Vasopressin increases Cerebral Perfusion Pressure but not Cerebral Blood Flow in Neurosurgical Patients with Norepinephrine-Refractory Hypotension: A Preliminary Evaluation using the non-invasive Quantix ND in Comparison to the Literature

Vasopressin increases Cerebral Perfusion Pressure but not Cerebral Blood Flow in Neurosurgical Patients with Norepinephrine-Refractory Hypotension: A Preliminary Evaluation using the non-invasive Quantix ND in Comparison to the Literature | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Vasopressin increases Cerebral Perfusion Pressure but not Cerebral Blood Flow in Neurosurgical Patients with Norepinephrine-Refractory Hypotension: A Preliminary Evaluation using the non-invasive Quantix ND in Comparison to the Literature Sylvia Bele, Elisabeth Bründl, Nils Ole Schmidt, Martin Kieninger This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3828021/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The maintenance of sufficient mean arterial pressure (MAP) to sustain perfusion and oxygen delivery to all major organs is important patients in intensive care but for neurosurgical patients after SAH or TBI it is essential to avoid secondary brain damage or delayed ischemia. So far most neurosurgical intensive care units use intracranial pressure (ICP) and cerebral perfusion pressure (CPP) as therapy guidance for those patients. Use of fluid resuscitation and norepinephrine is standard to achieve CPP between 50–70 mmHg. But sometimes norepinephrine-refractory hypotension occurs. In those cases, arginin-vasopressin (AVP) is often the drug of choice. AVP and its synthetic analogies are widely used in modern medicine and gained interest in treatment of septic shock or refractory hypotension after cardiac surgery or hypovolemic shock. Recent papers also showed a significant impact of AVP in resuscitation of after traumatic brain injury (TBI) and influence on CPP in TBI patients during ICU treatment. But little is known about the effects of AVP on cerebral perfusion and oxygenation. The present preliminary study was carried out to examine the influence of vasopressin administration on cerebral blood flow by using the non-invasive QuantixND® device. We found significantly increased MAP and CPP but no concomitant elevation in CBF. In contrast, in most patients the CBF even decreased despite elevation of CPP. We conclude that AVP is an alternative drug to maintain MAP and CPP but must be used with care in patients with already compromised cerebral perfusion. Subarachnoid hemorrhage norepinephrine-refractory hypotension vasopressin cerebral blood flow cerebral perfusion pressure Figures Figure 1 Introduction The means of treatment of ICU patients is to sustain perfusion and O 2 delivery to all major organs to avoid organ damage. Since it is not possible to influence the initial insult on neurosurgical ICUs it is crucial to prevent an additional neuronal damage. Thus, avoidance of early brain injury (EBI) following aneurysmal subarachnoid 1 , raised intracranial pressure (ICP) or low cerebral perfusion pressure (CPP) due to low mean arterial blood pressure (MAP) following traumatic brain injury is key. Especially in aSAH patients suffering from cerebral vasospasm (CV) often leads to sequelae like delayed cerebral ischemia (DCI) or low tissue oxygenation 2 . To minimize the risk of brain ischemia, standard treatment guidelines have been established including the maintenance of a CPP > 60 mmHg. The management of CPP normally includes the control of ICP and mean arterial pressure (MAP), since CPP = MAP-ICP. Despite many clinical trials so far, no level I evidence for an ideal CPP exists, but the guidelines of the Brain Trauma Foundation recommend a CPP between 50–70 mmHg in traumatic brain injury (TBI) patients, depending on the patient’s individual cerebral hemodynamic profile 3 . For patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) there might be completely different needs for CPP levels since the major cause of death after SAH is DCI often due to cerebral vasospasm and thus elevated vascular resistance 4 , 5 . For those patients among other treatment needs, a sufficient CCP is crucial 6 . To obtain CPP, fluid resuscitation can be used but, in most patients, additionally vasopressors are needed. Today catecholamines are the agent of choice. But with increasing dosage or prolonged duration, side effects like increased heart rate and increased myocardial oxygen consumption occur. Those side effects can potentiate the extracranial effects of SAH like intravascular volume depletion or cardiac impairment known as neurogenic myocardial injury (NMI) 7 , 8 . The elevation of systemic vascular resistance can also compromise end organ perfusion 9 , 10 . In addition, refractoriness to catecholamines exists 11 . For those patients, arginine-vasopressin (AVP) might be the drug of choice. Vasopressin is synthesized as a prehormone in the magnocellular neurons of paraventricular and supraoptic nuclei of the hypothalamus and is one of the key players for osmotic and cardiovascular hemostasis 12 . It is cleaved into the active hormone and released into systemic circulation from the posterior pituitary gland. The serum levels of this nonapeptide represent the interaction of AVP synthesis, release, and metabolism. Arginine vasopressin exerts its actions via a variety of receptors. The main three receptors are: AVPR1a (V1 receptor, mainly vascular functions), AVPR1b (V3 receptor, mostly central functions) and AVPR2 (V2 receptor, renal functions). In addition, AVP can act via oxytocin receptors as well as purinergic receptors 13 . The V3 receptor is expressed in the hippocampus and the anterior pituitary gland and V3 receptor stimulation by vasopressin leads to a release of adrenocorticotropic hormone (ACTH) and thus interacts with the corticosteroid axis in response to stress such as hypotension 14 , 15 . The regulation of the vasoconstrictive effects of AVP is an interplay of various actions and receptors. AVPR1a, a G-protein coupled receptor, is the main effector for the AVP associated vasocontraction and is expressed on the vascular smooth muscle cell, platelets, and hepatocytes for review see 16 . It stimulates a phosphatidyl-inositol-calcium signal pathway leading to smooth muscle contraction 13 . But on the other side AVPR1a stimulation also causes production of nitric oxide, a potent vasodilator in pulmonary 17 and coronary vessels 18 . Also, the stimulation of oxytocin receptors by low dose vasopressin can induce vasodilation 19 . Due to the mostly independently regulated pathways of the different AVP receptors, synthetic agonists of the AVP receptors are routinely used in modern medicine, e.g. desmopressin, a V2 receptor agonist is used in diagnostics and treatment of diabetes insipidus or used for treatment of coagulopathies 20 . Vasopressin or terlipressin (via V1 receptor) are used in postoperative bowel distention or refractory hypotension after cardiac surgery 21 . AVP gained more interest over the years in treatment of vasoplegic septic shock or other forms of refractory vasoplegic catecholamine resistant shock 13 , 16 . AVP can restore vascular tone by at least four different mechanisms: activation of AVPR1a, modulation of NO, modulation of ATP-sensitive K + channels and potentiation of adrenergic vasoconstrictive agents leading to contraction of small arterioles and increasing peripheral vascular resistance 22 . A review of literature by Russel in 2011 showed that in patients with septic shock the use of low dose vasopressin combined with corticosteroids had better patient outcome than norepinephrine and steroids but showed potential side effects such as peripheral ischemia or disturbances in microcirculation. Even though studies clearly showed that AVP is safe to use and can have beneficial effects in septic shock 13 , 16 or in traumatic shock resuscitation when combined with low fluid resuscitation 9 , 20 , 23 so far validated recommendations in clinical guidelines for the use of AVP in either septic shock or resuscitation fail to appear. The use of AVP in neurosurgical or neurological patients is even more controversial. After brain injury vasopressin is released leading to inflammatory reactions and cerebral edema 24 . Use of AVPR1a antagonists led to attenuation of secondary brain lesion and edema 25 , 26 . Interestingly in a model for blunt trauma to the head and chest showed that the use of AVP was as effective as phenylephrine to maintain CPP but improved ICP and cerebral tissue oxygenation 27 . In 2013 Van Haren et al. published a paper concerning the use of vasopressin for CPP management in patients with severe traumatic brain injury 28 . They concluded that vasopressin is safe to use and represents an effective alternative to catecholamines for maintaining CPP. Since the vasoconstrictive potency of AVP is well known and the study by Van Haren et al. didn’t measure cerebral blood flow (CBF) or brain tissue oxygenation (P bt O 2 ) the present preliminary study was carried out to evaluate the influence of AVP on CPP, ICP and CBF in neurosurgical patients suffering from catecholamine refractory hypotension. Materials and Methods Ethics/ IRB Statement This retrospective study was approved by the Local Ethics Committee University of Regensburg Approval Number 18-1059-104. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1975 Helsinki declaration and its later amendment. For the present retrospective study informed consent is not required. Patient selection and ICU therapy: We included 5 patients on our neurosurgical ward in this preliminary study. Four patients were treated for aSAH and one patient for severe TBI (for patient demographics see table 1). The localization of the aneurysm responsible for the SAH and severity of the bleeding was documented according to the classification of the World Federation of Neurological Surgeons (WFNS) who showed a norepinephrine refractory hypotension. All patients had continuous ICP monitoring (Raumedic Neurovent®, Raumedic AG, Helmbrechts, Germany) and intraarterial blood pressure measurement to continuously calculate CPP. Also, P bt O 2 values were measured using the Licox® probe (Integra Life Science, Tullamore, Ireland) according to our standard protocols when patients were under analgo-sedation for > 96 h or CV was suspected due to elevated transcranial doppler (TCD) values according to our standard operating procedures 29 . The last transcranial doppler (TCD) value before vasopressin administration was recorded to check for CV. Patients received volume and catecholamine therapy according to standard recommendations and in dependance on the occurrence of cerebral vasospasm. The goal was to keep CPP > 70 mmHg 5 . The TBI patient was treated according to the Brain Trauma Foundation guidelines 30 and actual literature 3 . During the ICU stay each of those patients suffered from at least one episode of refractory hypotension that could not be treated sufficiently by volume, hydrocortisone and catecholamines. Therapeutical Intervention und CBF monitoring: When the decision to try AVP was made a 3 I.U. bolus was applied and the effect on MAP, ICP and CPP was monitored. The goal was to establish a CPP > 70 mmHg. Since it was a preliminary study, we decided to measure CBF non-invasively using the Quantix ND® device. The Quantix ND® (Cardiosonix Ltd, Israel) uses an angle-independent doppler technique that employs two ultrasound heads placed in a defined angle to each other in one insonation probe (Fig. 1), projecting actual flow diagrams on a real time monitor. Probe was placed in the submandibular region of a supine positioned patient and internal carotid artery (ICA) was located by identifying its specific flow diagram on the real time monitor. On the real-time monitor the volume flow, both angles (θ1,θ2), the measured diameters of the vessel (D1, D2), both measured velocities as to the laminar flow (L1,L2) and finally the shear force were monitored (Fig. 1). This information is continuously stored on the computer and can be later replayed for offline reevaluation. The system was evaluated at our clinic comparing CBF values measured by the QuantixND® compared with rCBF values 31 – 35 . We measured the flow volume in the internal carotid artery (ICA) since it was shown that the flow volume has an almost linear correlation with the cerebral blood flow on the measured side 31 but showed an even better correlation when flow volume in both ICA was measured and compared to global CBF 31 . When decision to use vasopressin in a patient was made, in all SAH patients the last transcranial doppler value was noted and the Quantix ND® was used to establish the baseline flow volume and thus the CBF before vasopressin administration. Additional measurements were performed 2, 10 and 20 minutes after vasopressin. In addition, MAP, ICP, and CPP was documented at the same timepoints. Patient outcome was evaluated at hospital discharge using the Glasgow Outcome Score (GOS). GOS 0 represents death, GOS 1–3 poor outcome and GOS 4–5 favorable outcome. Results Between 2014 and 2018 seven patients fulfilled the criteria for using vasopressin to treat hypotension refractory to fluid, norepinephrine, and hydrocortisone. One patient was treated for TBI, six patients were treated for aSAH four of whom developed cerebral vasospasm. All but one patient received a bolus of 3 I.JU. vasopressin, in patient 2 another bolus of 5 I.U. was needed to improve MAP. The outcome using the GOS was favorable in 2 patients, 3 patients were in the poor outcome group at time of hospital discharge (GOS3), both improved to GOS 4 after rehabilitation. Two patients died during hospital stay due to multi-infarct syndrome as sequelae of CV (for patient demographics see table 1). In all examined patients robust external flow values in the internal carotid artery (ICA) values could be gathered before and 2, 10 and 20 minutes after vasopressin administration according to the standard evaluations of the Quantix ND® device. For detailed values of each measurement and each patient see table 2–8. Elevation of MAP combined with reduction in ICP and thus elevated CPP could be achieved within 2 minutes after AVP administration and was still valid 10 and 20 minutes after AVP bolus. Mean MAP before vasopressin was 56,51 mmHg (± 4,5 mmHg) and CPP was 40,14 mmHg (± 8,86; 6,86). The mean increase in all patients over the examined timepoints was 37,39 mmHg and 40,19 mmHg respectively. This increase in MAP and CPP was neither paralleled in an increase in blood flow volume nor P bt O 2 . Blood flow volume was decreased in 5 of the aSAH patients, especially in those with signs of CV. In the one patient with normal TCD values blood flow volume stayed within the normal error of measurement. The mean blood flow in both carotid arteries was 320,30 ml/min before vasopressin administration and the overall mean reduction was 23,45 ml/min. In patients with signs of CV at time of vasopressin administration (patient 1,3 and 4) the mean blood flow volume was 286,83 ml/min and decreased to a mean flow volume of 241,42 ml/min. In contrast, the TBI patient showed an increase of MAP and CPP following vasopressin which was accompanied by an increase in blood flow volume. Thus, decision was made to continue AVP administration continuously (0,03 I.U./min) for 12 h to preserve a CPP > 65 mmHg (for details see table 6). Unfortunately, no P bt O 2 probe was in place since this was not standard monitoring in TBI patients Patient was discharged after 23 days with good outcome. P bt O 2 in all patients measured showed no significant change except for patient 2 who had no signs of vasospasm and brain oxygenation improved slightly following vasopressin. Discussion In the present preliminary retrospective study, we found that administration of vasopressin does improve MAP and CPP in neurocritical care patients suffering from norepinephrine-refractory hypotension but failed to improve CBF, especially in patients with already compromised cerebral perfusion. Due to the mostly independently regulated pathways of the different AVP receptors, synthetic agonists of the AVP receptors are routinely used in modern medicine, e.g. desmopressin, a V2 receptor agonist is used in diagnostics and treatment of diabetes insipidus or used for treatment of different coagulopathies such as von Willebrand disease 32 or to counteract effects of acetyl salicylic acid 33 . The AVPR1a- agonist vasopressin (AVP) or terlipressin are used in postoperative bowel distention, refractory hypotension after cardiac surgery 34 or to treat intraoperative hypotension or treatment of portal hypertension 35 . AVP experienced a renaissance for treatment of hypovolemic 36 or septic shock, refractory hypotension or in resuscitation 16 , 37 . The finely tuned and independent work mechanisms of AVP on its different receptors make it the ideal drug for treatment of patients after cardiac surgery suffering from low systemic resistance concomitant with pulmonary hypertension since it elevates systemic resistance while parallel decreasing pulmonary hypertension 38 . Those different work mechanisms make AVP a possible target for use in neurosurgical patients. Despite the fact that AVP can enhance cerebral edema after ischemia 25 , 39 and also leads to an increased rebleeding rate in an animal model of SAH 40 , some studies demonstrated that AVP is safe to use after TBI using the increase in MAP and CPP as endpoints 28 , 41 , or in an animal model where cerebral oxygenation was also studied 27 . But to our knowledge this preliminary study is the first to measure not only the changes in MAP and CPP but put the focus of attention to changes in cerebral blood flow (CBF) after AVP administration. In the small number of patients included in our study we could clearly demonstrate a significant rise in MAP and CPP after administration of 3 I.U. AVP. Taken this as endpoint it would appear AVP is a safe to use alternative vasopressor in neurosurgical patients, especially after TBI and aSAH, giving the wanted results of an increased CPP. But the problem is the AVPR1a mediated contraction of smooth muscle cells that appears to happen also in cerebral vessels, reflected by the decrease or the lack of sufficient increase in CBF after AVP administration in our patients. This stands in contrast to norepinephrine which elevates systemic blood pressure without normally effecting cerebral vessels, making it the ideal catecholamine for aSAH patients. Those findings and our data rise two questions: first - is CPP alone really the ideal target for treatment guidance in TBI and aSAH patients and second- is vasopressin safe to use in those patients? The maintenance of sufficient MAP is important in all ICU patients but for neurosurgical patients after SAH or TBI it is essential to avoid delayed ischemia. So far, most neuro ICUs use MAP, ICP and CPP to guide their therapy for those patients. This still is considered sufficient, at least in TBI patients according to the Brain Trauma Foundation guidelines, but those simple treatment algorithms are nowadays challenged 42 , 43 . After TBI a dysfunction in cerebral autoregulation might occur 44 , and the microcirculation seems to be dysregulated leading to distended arterioles 45 and thus more intracerebral blood volume. As consequence ICP can be elevated. Several studies concluded that a dynamic CPP concept depending on each patient’s cerebrovascular autoregulatory capacities should be followed in ICU care after TBI 43 , 46 . Depreitere et al . also concluded that CPP alone is not sufficient for patient treatment and added the pressure reactivity index (PRx) defined by Czosnyka 47 to their monitoring. While current evidence regarding the use of P bt O 2 remains promising 48 but mixed, three ongoing clinical multicenter trials are expected to definitively answer the question of what role P bt O 2 monitoring plays in severe TBI (BOOST III, BONANZAand OXY-TC) 49 . In our neurosurgical ICU additional neuromonitoring (P bt O 2 and/or CBF) is used in addition to ICP and CPP to steer therapy after TBI since 2021 and aSAH since 2014. But this is no standard at all since there exists no level I evidence so far that even an ICP/CPP guided therapy has any beneficial effects on patient outcome after TBI 50 . The findings of Van Harren et al. 2013 suggest that the disturbances in normal autoregulation especially in peripheral arterioles and brain function after TBI are complex and may take effect on various levels 28 . The influence of vasopressin on oxytocin receptors leading to vasodilation 13 , 16 are overridden on a dose dependent manner by vasopressin related activation of AVPR1a and thus vasoconstriction. This might be the reason for the beneficial effect of vasopressin after TBI seen by Van Harren 2013 and Dudkiewicz 2008. The AVPR1a activation led to elevation in MAP and due to constriction of small cerebral vessels to lower intracranial blood volume and thus lower ICP. This was reflected in the results of the TBI patient in our own study. The AVP administration led to significant rise in MAP, lower ICP value and therefore increased CPP. From the concomitant elevation in CBF we conclude that AVP can at least partly counteract the autoregulatory dysfunction and optimize CPP and CBF without impairment of CBF. Thus, AVP seems to be safe to use for treatment of refractory hypotension in TBI patients. It might be even more beneficial than other vasopressors due to its potential effects on small cerebral vessels. Norepinephrine can only reduce ICP when autoregulation is intact, since it has no direct influence on cerebral vessels due to lack of passages through the blood brain barrier 51 . Hence the application of low dose AVP might be superior to catecholamines for ICU treatment of TBI patients regarding ICP and CPP management when signs of disturbed autoregulation are present. This hypothesis is supported by the findings of Dudkiewicz and Proctor in 2008 who could demonstrate that AVP maintained CPP but improved ICP and cerebral tissue oxygenation better that phenylephrine 27 . In addition, there is a new multicenter trial using a drug targeting the disturbed autoregulatory functions of small distended cerebral arterioles. Administration of the test drug ought to lead to small vessel contraction thus lowering ICP. The use of CPP as therapy guidance in patients with SAH is a completely different story. Depending on the severity of the initial bleeding patients can be awake and neurologically assessable or are analgo-sedated and on a ventilator for extended time periods. Cerebral vasospasm is still the major cause for mortality and morbidity after SAH. Vasospasm leads to a decrease in vascular diameter hence an increase in cerebrovascular resistance. The decreased blood flow is often followed by delayed cerebral ischemia leading to catastrophic neurological outcomes or even death 52 . The use of CPP as therapy guidance after SAH is problematic because one can only roughly estimate CBF since it doesn’t take vessel diameter, resistance, or blood viscosity into account 53 . But increased vascular resistance plays the key role in CBF after SAH. It is suggested to use at least brain oxygen measurements to avoid DCI due to non-optimal CPP or CBF 54 . It has been shown that P bt O 2 values can help to find the optimal CPP since patients with aSAH are at risk for insufficient CBF if CPP opt is not reached and might develop DCI 55 We suggest that multimodal neuromonitoring measuring P bt O 2 (Licox® or the Raumedic® PTO probe and if available CBF monitoring (Hemedex probe) should be used in addition to ICP/CPP measurement to optimize ICU treatment and to determine the needed MAP and CPP for each patient individually. This could save volume load and catecholamine administration since the ideal MAP level for each patient could be set (ranges often between 70–140 mmHg). In aSAH we use P bt O 2 and CBF monitoring regularly and have good outcome results (unpublished data and 29 ) but so far, no level I evidence exists showing that the use of additional neuromonitoring has a significant influence on patient outcome 6 . This is not due to lack of studies but due to the intraindividual variability of patients’ needs and therefore difficulties in finding standardized treatments settings that are used in equally in all participating clinics. The maintenance of a sufficient CPP according to dependent variables as P bt O 2 and CBF is normally done using hypertension therapy 4 . In cases when norepinephrine-refractory hypotension occurs, AVP could again be the drug of choice due to its vasoconstrictive effects. But our data clearly demonstrated that the increased MAP combined with decreased ICP leading to elevated CPP was not accompanied by a concomitant improvement of CBF in SAH patients. In addition, we did not see any improvement in P bt O 2 value in patients following vasopressin administration. This effect was especially seen in patients with elevated TCD velocities suggestive of cerebral vasospasm. This might be due to the dose dependent effects of AVP. The bolus administration of 3 I.U. vasopressin possibly leads to the stimulation of AVPR1a overriding the potential beneficial effects of oxytocin receptor stimulation and increased NO release in the brain. The possible modulation of NO release and thus vasodilation could be a very useful tool for prevention of severe cerebral vasospasm after SAH. New studies allude to the fact that cerebral vasospasm is not exclusively a disease of the larger vessels but might occur at early stages mainly in microcirculation. Terpolilli et al. showed promising data using NO-ventilation to prevent microcirculatory vasospasm after SAH (presentation at the 2014 annual DGNC meeting). Since AVP can also modulate and release NO, it could be useful at early timepoints after SAH to avoid occurrence of vasospastic events in microcirculation. But further studies must be done to exploit this possibility. So far, om our preliminary data show that AVP can counteract refractory hypotension in SAH patients but does not lead to sufficient improvement of CBF. In contrast, in three patients CBF was even decreased after AVP administration despite significantly increased CPP, pointing out that AVP possibly exerts a vasoconstrictive effect on cerebral blood vessels. That suggests that despite the beneficial effect on refractory hypotension AVP should be used with retentiveness in patients with impaired cerebral perfusion but further studies using continuous invasive CBF monitoring, and more patients need to be done to finally decide the fate of AVP in those patients. Conclusion Vasopressin is an alternative vasopressor for treatment of refractory hypotension to avoid organ hypoperfusion in ICU patients. It seems practicable for TBI patients, but our preliminary data showed that in general it should be used with care in neurosurgical patients, especially when cerebral blood flow might be compromised e.g. by cerebral vasospasm since it does neither improved CBF nor P bt O 2 values. When using vasopressin in those patients, CBF or at least P bt O 2 should be monitored to evaluate if the increase in CPP in accompanied by an increase in brain oxygenation to avoid cerebral ischemia. But studies with larger patient groups measuring cerebral tissue oxygenation and CBF by using intraparenchymal probes like the QFlow 500™ by Hemedex, Waldham USA® should be carried out to support these findings. References Helbok R, Schiefecker AJ, Beer R, et al. Early brain injury after aneurysmal subarachnoid hemorrhage: a multimodal neuromonitoring study. Crit Care. 2015;19(1):75. 10.1186/s13054-015-0809-9 . (In eng). Etminan N, Macdonald RL. Management of aneurysmal subarachnoid hemorrhage. Handb Clin Neurol. 2017;140:195–228. 10.1016/b978-0-444-63600-3.00012-x . (In eng). Vella MA, Crandall ML, Patel MB. Acute Management of Traumatic Brain Injury. Surg Clin North Am. 2017;97(5):1015–30. 10.1016/j.suc.2017.06.003 . (In eng). Wu CT, Wong CS, Yeh CC, Borel CO. Treatment of cerebral vasospasm after subarachnoid hemorrhage–a review. Acta anaesthesiologica Taiwanica: official journal of the Taiwan Society of Anesthesiologists. 2004;42(4):215–22. http://www.ncbi.nlm.nih.gov/pubmed/15679131 . Keyrouz SG, Diringer MN. Clinical review: Prevention and therapy of vasospasm in subarachnoid hemorrhage. Crit Care. 2007;11(4):220. 10.1186/cc5958 . (In eng). Treggiari MM, Rabinstein AA, Busl KM, et al. Guidelines for the Neurocritical Care Management of Aneurysmal Subarachnoid Hemorrhage. Neurocrit Care. 2023;39(1):1–28. 10.1007/s12028-023-01713-5 . Stevens RD, Nyquist PA. The systemic implications of aneurysmal subarachnoid hemorrhage. J Neurol Sci. 2007;261(1–2):143–56. 10.1016/j.jns.2007.04.047 . (In eng). Hall A, O'Kane R. The Extracranial Consequences of Subarachnoid Hemorrhage. World Neurosurg. 2018;109:381–92. 10.1016/j.wneu.2017.10.016 . (In eng). Albright TN, Zimmerman MA, Selzman CH. Vasopressin in the cardiac surgery intensive care unit. Am J Crit Care. 2002;11(4):326–30. quiz 331-2. (In eng). Farand P, Hamel M, Lauzier F, Plante GE, Lesur O. Review article: organ perfusion/permeability-related effects of norepinephrine and vasopressin in sepsis. Can J Anaesth. 2006;53(9):934–46. 10.1007/bf03022837 . (In eng). Yeh CC, Wu CT, Lu CH, Yang CP, Wong CS. Early use of small-dose vasopressin for unstable hemodynamics in an acute brain injury patient refractory to catecholamine treatment: a case report. Anesth Analg. 2003;97(2):577–9. 10.1213/01.Ane.0000070231.16378.A6 . (In eng). Marcinkowska AB, Biancardi VC, Winklewski PJ. Arginine Vasopressin, Synaptic Plasticity, and Brain Networks. Curr Neuropharmacol. 2022;20(12):2292–302. 10.2174/1570159x20666220222143532 . (In eng). Russell JA. Bench-to-bedside review: Vasopressin in the management of septic shock. Crit Care. 2011;15(4):226. 10.1186/cc8224 . (In eng). Antoni FA, Holmes MC, Makara GB, Kárteszi M, László FA. Evidence that the effects of arginine-8-vasopressin (AVP) on pituitary corticotropin (ACTH) release are mediated by a novel type of receptor. Peptides. 1984;5(3):519–22. 10.1016/0196-9781(84)90080-9 . (In eng). Birnbaumer M. Vasopressin receptors. Trends Endocrinol Metab. 2000;11(10):406–10. 10.1016/s1043-2760(00)00304-0 . (In eng). Russell JA. Vasopressor therapy in critically ill patients with shock. Intensive Care Med. 2019;45(11):1503–17. 10.1007/s00134-019-05801-z . (In eng). Evora PR, Pearson PJ, Schaff HV. Arginine vasopressin induces endothelium-dependent vasodilatation of the pulmonary artery. V1-receptor-mediated production of nitric oxide. Chest. 1993;103(4):1241–5. 10.1378/chest.103.4.1241 . (In eng). Okamura T, Ayajiki K, Fujioka H, Toda N. Mechanisms underlying arginine vasopressin-induced relaxation in monkey isolated coronary arteries. J Hypertens. 1999;17(5):673–8. 10.1097/00004872-199917050-00011 . (In eng). Thibonnier M, Conarty DM, Preston JA, Plesnicher CL, Dweik RA, Erzurum SC. Human vascular endothelial cells express oxytocin receptors. Endocrinology. 1999;140(3):1301–9. 10.1210/endo.140.3.6546 . (In eng). Akin M. Response to low-dose desmopressin by a subcutaneous route in children with type 1 von Willebrand disease. Hematology. 2013;18(2):115–8. 10.1179/1607845412y.0000000051 . (In eng). Datt V, Wadhhwa R, Sharma V, Virmani S, Minhas HS, Malik S. Vasoplegic syndrome after cardiovascular surgery: A review of pathophysiology and outcome-oriented therapeutic management. J Card Surg. 2021;36(10):3749–60. 10.1111/jocs.15805 . (In eng). Landry DW, Levin HR, Gallant EM, et al. Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation. 1997;95(5):1122–5. 10.1161/01.cir.95.5.1122 . (In eng). Feinstein AJ, Patel MB, Sanui M, Cohn SM, Majetschak M, Proctor KG. Resuscitation with pressors after traumatic brain injury. J Am Coll Surg. 2005;201(4):536–45. 10.1016/j.jamcollsurg.2005.05.031 . (In eng). Krieg SM, Trabold R, Plesnila N. Time-Dependent Effects of Arginine-Vasopressin V1 Receptor Inhibition on Secondary Brain Damage after Traumatic Brain Injury. J Neurotrauma. 2017;34(7):1329–36. 10.1089/neu.2016.4514 . (In eng). Liu X, Nakayama S, Amiry-Moghaddam M, Ottersen OP, Bhardwaj A. Arginine-vasopressin V1 but not V2 receptor antagonism modulates infarct volume, brain water content, and aquaporin-4 expression following experimental stroke. Neurocrit Care. 2010;12(1):124–31. 10.1007/s12028-009-9277-x . (In eng). Ameli PA, Ameli NJ, Gubernick DM, et al. Role of vasopressin and its antagonism in stroke related edema. J Neurosci Res. 2014;92(9):1091–9. 10.1002/jnr.23407 . (In eng). Dudkiewicz M, Proctor KG. Tissue oxygenation during management of cerebral perfusion pressure with phenylephrine or vasopressin. Crit Care Med. 2008;36(9):2641–50. 10.1097/CCM.0b013e3181847af3 . (In eng). Van Haren RM, Thorson CM, Ogilvie MP, et al. Vasopressin for cerebral perfusion pressure management in patients with severe traumatic brain injury: preliminary results of a randomized controlled trial. J Trauma Acute Care Surg. 2013;75(6):1024–30. 10.1097/TA.0b013e3182a99d48 . discussion 1030. (In eng). Bele S, Proescholdt MA, Hochreiter A, et al. Continuous intra-arterial nimodipine infusion in patients with severe refractory cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a feasibility study and outcome results. Acta Neurochir. 2015;157(12):2041–50. (In eng). Carney N, Totten AM, O'Reilly C, et al. Guidelines for the Management of Severe Traumatic Brain Injury. Fourth Ed Neurosurg. 2017;80(1):6–15. 10.1227/neu.0000000000001432 . (In eng). Soustiel JF, Glenn TC, Vespa P, Rinsky B, Hanuscin C, Martin NA. Assessment of cerebral blood flow by means of blood-flow-volume measurement in the internal carotid artery: comparative study with a 133xenon clearance technique. Stroke. 2003;34(8):1876–80. 10.1161/01.Str.0000080942.32331.39 . (In eng). Shortt J, Opat SS, Gorniak MB, Aumann HA, Collecutt MF, Street AM. A retrospective study of the utility of desmopressin (1-deamino-8-D-arginine vasopressin) trials in the management of patients with von Willebrand disorder. Int J Lab Hematol. 2010;32(1 Pt 1):e181–3. 10.1111/j.1751-553X.2008.01117.x . (In eng). Kam PC. Use of desmopressin (DDAVP) in controlling aspirin-induced coagulopathy after cardiac surgery. Heart Lung. 1994;23(4):333–6. (In eng). Ltaief Z, Ben-Hamouda N, Rancati V, et al. Vasoplegic Syndrome after Cardiopulmonary Bypass in Cardiovascular Surgery: Pathophysiology and Management in Critical Care. J Clin Med. 2022;11(21). 10.3390/jcm11216407 . (In eng). Saeki Y, Nagatomi N, Kobayashi T et al. Effects of vasopressin on gastric mucosal blood flow in portal hypertension. Gastroenterol Jpn. 1991;26 Suppl 3:90 – 2. (In eng). 10.1007/bf02779273 . Cossu AP, Mura P, De Giudici LM, et al. Vasopressin in hemorrhagic shock: a systematic review and meta-analysis of randomized animal trials. Biomed Res Int. 2014;2014:421291. 10.1155/2014/421291 . (In eng). Krismer AC, Dünser MW, Lindner KH, et al. Vasopressin during cardiopulmonary resuscitation and different shock states: a review of the literature. Am J Cardiovasc Drugs. 2006;6(1):51–68. 10.2165/00129784-200606010-00005 . (In eng). Tayama E, Ueda T, Shojima T, et al. Arginine vasopressin is an ideal drug after cardiac surgery for the management of low systemic vascular resistant hypotension concomitant with pulmonary hypertension. Interact Cardiovasc Thorac Surg. 2007;6(6):715–9. 10.1510/icvts.2007.159624 . (In eng). Rauen K, Trabold R, Brem C, Terpolilli NA, Plesnila N. Arginine vasopressin V1a receptor-deficient mice have reduced brain edema and secondary brain damage following traumatic brain injury. J Neurotrauma. 2013;30(16):1442–8. 10.1089/neu.2012.2807 . (In eng). Hockel K, Schöller K, Trabold R, Nussberger J, Plesnila N. Vasopressin V(1a) receptors mediate posthemorrhagic systemic hypertension thereby determining rebleeding rate and outcome after experimental subarachnoid hemorrhage. Stroke. 2012;43(1):227–32. 10.1161/strokeaha.111.626168 . (In eng). Earle SA, de Moya MA, Zuccarelli JE, Norenberg MD, Proctor KG. Cerebrovascular resuscitation after polytrauma and fluid restriction. J Am Coll Surg. 2007;204(2):261–75. 10.1016/j.jamcollsurg.2006.11.014 . (In eng). Bernard F. Neurotrauma and Intracranial Pressure Management. Crit Care Clin. 2023;39(1):103–21. 10.1016/j.ccc.2022.08.002 . (In eng). Tas J, Beqiri E, van Kaam RC, et al. Targeting Autoregulation-Guided Cerebral Perfusion Pressure after Traumatic Brain Injury (COGiTATE): A Feasibility Randomized Controlled Clinical Trial. J Neurotrauma. 2021;38(20):2790–800. 10.1089/neu.2021.0197 . (In eng). Engelborghs K, Haseldonckx M, Van Reempts J, et al. Impaired autoregulation of cerebral blood flow in an experimental model of traumatic brain injury. J Neurotrauma. 2000;17(8):667–77. 10.1089/089771500415418 . (In eng). Glushakova OY, Johnson D, Hayes RL. Delayed increases in microvascular pathology after experimental traumatic brain injury are associated with prolonged inflammation, blood-brain barrier disruption, and progressive white matter damage. J Neurotrauma. 2014;31(13):1180–93. 10.1089/neu.2013.3080 . (In eng). Depreitere B, Güiza F, Van den Berghe G, et al. Pressure autoregulation monitoring and cerebral perfusion pressure target recommendation in patients with severe traumatic brain injury based on minute-by-minute monitoring data. J Neurosurg. 2014;120(6):1451–7. 10.3171/2014.3.Jns131500 . (In eng). Czosnyka M, Czosnyka Z, Smielewski P. Pressure reactivity index: journey through the past 20 years. Acta Neurochir. 2017;159(11):2063–5. 10.1007/s00701-017-3310-1 . (In eng). Okonkwo DO, Shutter LA, Moore C, et al. Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase-II: A Phase II Randomized Trial. Crit Care Med. 2017;45(11):1907–14. 10.1097/ccm.0000000000002619 . (In eng). Leach MR, Shutter LA. How much oxygen for the injured brain - can invasive parenchymal catheters help? Curr Opin Crit Care. 2021;27(2):95–102. 10.1097/mcc.0000000000000810 . (In eng). Le Roux P. Intracranial pressure after the BEST TRIP trial: a call for more monitoring. Curr Opin Crit Care. 2014;20(2):141–7. 10.1097/mcc.0000000000000078 . (In eng). Strandgaard S, Sigurdsson ST. Point:Counterpoint: Sympathetic activity does/does not influence cerebral blood flow. Counterpoint: Sympathetic nerve activity does not influence cerebral blood flow. J Appl Physiol (1985) 2008;105(4):1366-7; discussion 1367-8. (In eng). 10.1152/japplphysiol.90597.2008a . Thomé C, Schubert GA, Schilling L. Hypothermia as a neuroprotective strategy in subarachnoid hemorrhage: a pathophysiological review focusing on the acute phase. Neurol Res. 2005;27(3):229–37. 10.1179/016164105x25252 . (In eng). Small C, Lucke-Wold B, Patel C, et al. What are we measuring? A refined look at the process of disrupted autoregulation and the limitations of cerebral perfusion pressure in preventing secondary injury after traumatic brain injury. Clin Neurol Neurosurg. 2022;221:107389. 10.1016/j.clineuro.2022.107389 . (In eng). Coppadoro A, Citerio G. Subarachnoid hemorrhage: an update for the intensivist. Minerva Anestesiol. 2011;77(1):74–84. (In eng). Johnson U, Engquist H, Lewén A, et al. Increased risk of critical CBF levels in SAH patients with actual CPP below calculated optimal CPP. Acta Neurochir. 2017;159(6):1065–71. 10.1007/s00701-017-3139-7 . (In eng). Tables Table 1 shows the relevant demographic data of the included patients. AL= aneurysm location, ACoA= anterior cerebral artery, GCS= Glasgow Coma Score, GOS= Glasgow Outcome Scale, MCA= middle cerebral artery, n= no, na= not applicable, SAH= Subarachnoid Hemorrhage, TBI= Traumatic Brain Injury, y= yes, WFNS World Federation of Neurosurgeons Score Table 1 Demographic data gender age diagnosis WFNS GCS AL vasospasm GOS Patient 1 f 57 SAH 2 13 MCA y 0 Patient 2 m 43 SAH 4 8 ACoA n 4 Patient 3 f 48 SAH 3 11 MCA y 3 Patient 4 m 61 SAH 1 15 ACoA y 0 Patient 5 m 40 TBI na 7 na na 4 Patient 6 f 42 SAH 3 9 MCA y 3 Patient 7 f 58 SAH 2 13 ACoA n 4 Table 2 shows all relevant measurements for patient 1 before (timepoint 1) and at the 3 timepoints after vasopressin. Timepoint 2 representing 2 minutes, timepoint 3=10 minutes and timepoint 4= 20 minutes following vasopressin administration. Table 2 Detailed measurement data Patient 1 Quantix ml/min TCD cm/sec Timepoints MAP ICP CPP PbtO2 ACI l ACI r LMCA RMCA 1 56 12 44 22 289 276 217 198 2 94 10 84 18 216 229 3 92 15 77 16 208 213 4 86 15 71 18 220 228 Mean 90,67 13,33 77,33 17,33 214,67 223,33 ACI l= left internal carotid artery, ACI r = right internal carotid artery, CPP=cerebral perfusion pressure in mmHg, ICP= intracranial pressure in mmHg, LMCA= left middle cerebral artery, MAP= mean arterial pressure in mmHg, P bt O 2 =brain tissue oxygenation in mmHg, Quantix = blood flow volume in ml/min, RMCA= right middle cerebral artery, TCD= transcranial doppler in cm/sec Table 3 shows all relevant measurements for patient 2 before (timepoint 1) and at the 3 timepoints after vasopressin. Timepoint 2 representing 2 minutes, timepoint 3=10 minutes and timepoint 4= 20 minutes following vasopressin administration. Table 3 Detailed measurement data Patient 2 Quantix ml/min TCD cm/sec Timepoints MAP ICP CPP PbtO2 ACI l ACIr LMCA RMCA 1 52 15 37 16 354 339 132 128 2 87 12 75 22 330 316 3 90 14 76 24 358 342 4 88 14 74 22 350 347 Mean 88,33 13,33 75,00 21,00 346,00 335,00 ACI l= left internal carotid artery, ACI r = right internal carotid artery, CPP=cerebral perfusion pressure in mmHg, ICP= intracranial pressure in mmHg, LMCA= left middle cerebral artery, MAP= mean arterial pressure in mmHg, P bt O 2 =brain tissue oxygenation in mmHg, Quantix = blood flow volume in ml/min, RMCA= right middle cerebral artery, TCD= transcranial doppler in cm/sec Table 4 shows all relevant measurements for patient 3 before (timepoint 1) and at the 3 timepoints after vasopressin. Timepoint 2 representing 2 minutes, timepoint 3=10 minutes and timepoint 4= 20 minutes following vasopressin administration. ACI l= left internal carotid artery, ACI r = right internal carotid artery, CPP=cerebral perfusion pressure in mmHg, ICP= intracranial pressure in mmHg, LMCA= left middle cerebral artery, MAP= mean arterial pressure in mmHg, P bt O 2 =brain tissue oxygenation in mmHg, Quantix = blood flow volume in ml/min, RMCA= right middle cerebral artery, TCD= transcranial doppler in cm/sec Table 4 Detailed measurement data Patient 3 Quantix ml/min TCD cm/sec Timepoints MAP ICP CPP PbtO2 ACI l ACIr LMCA RMCA 1 60 20 40 21 289 276 210 188 2 87 16 82 16 216 229 3 94 15 79 18 258 232 4 90 15 75 20 278 266 Mean 90,33 15,33 78,67 18,00 250,67 242,33 Table 5 shows all relevant measurements for patient 4 before (timepoint 1) and at the 3 timepoints after vasopressin. Timepoint 2 representing 2 minutes, timepoint 3=10 minutes and timepoint 4= 20 minutes following vasopressin administration. ACI l= left internal carotid artery, ACI r = right internal carotid artery, CPP=cerebral perfusion pressure in mmHg, ICP= intracranial pressure in mmHg, LMCA= left middle cerebral artery, MAP= mean arterial pressure in mmHg, n.a.= not applicable, P bt O 2 =brain tissue oxygenation in mmHg, Quantix = blood flow volume in ml/min, RMCA= right middle cerebral artery, TCD= transcranial doppler in cm/sec Table 5 Detailed measurement data Patient 4 Quantix ml/min TCD cm/sec Timepoints MAP ICP CPP PbtO2 ACI l ACIr LMCA RMCA 1 61 17 44 14 326 265 165 176 2 108 14 94 15 302 246 3 106 15 91 14 288 230 4 96 14 82 16 264 228 Mean 103,33 14,33 89,00 15,00 284,67 234,67 Table 6 shows all relevant measurements for patient 5 before (timepoint 1) and at the 3 timepoints after vasopressin. Timepoint 2 representing 2 minutes, timepoint 3=10 minutes and timepoint 4= 20 minutes following vasopressin administration. ACI l= left internal carotid artery, ACI r = right internal carotid artery, CPP=cerebral perfusion pressure in mmHg, ICP= intracranial pressure in mmHg, LMCA= left middle cerebral artery, MAP= mean arterial pressure in mmHg, P bt O 2 =brain tissue oxygenation in mmHg, Quantix = blood flow volume in ml/min, RMCA= right middle cerebral artery, TCD= transcranial doppler in cm/sec Table 6 Detailed measurement data Patient 5 Quantix ml/min TCD cm/sec Timepoints MAP ICP CPP PbtO2 ACI l ACIr LMCA RMCA 1 52 18 34 n.a. 387 341 n.a. n.a. 2 99 13 86 n.a. 442 386 3 98 12 86 n.a. 428 392 4 89 12 77 n.a. 402 366 Mean 95,33 12,33 83,00 424,00 381,33 Table 7 shows all relevant measurements for patient 6 before (timepoint 1) and at the 3 timepoints after vasopressin. Timepoint 2 representing 2 minutes, timepoint 3=10 minutes and timepoint 4= 20 minutes following vasopressin administration. ACI l= left internal carotid artery, ACI r = right internal carotid artery, CPP=cerebral perfusion pressure in mmHg, ICP= intracranial pressure in mmHg, LMCA= left middle cerebral artery, MAP= mean arterial pressure in mmHg, P bt O 2 =brain tissue oxygenation in mmHg, Quantix = blood flow volume in ml/min, RMCA= right middle cerebral artery, TCD= transcranial doppler in cm/sec Table 7 Detailed measurement data Patient 6 Quantix ml/min TCD cm/sec Timepoints MAP ICP CPP PbtO2 ACI l ACIr LMCA RMCA 1 60 20 49 15 312 310 172 130 2 92 17 75 17 308 312 3 100 15 85 17 310 298 4 92 16 76 16 308 366 Mean 94,67 16,00 78,67 16,67 308,67 325,33 Table 8 shows all relevant measurements for patient 7 before (timepoint 1) and at the 3 timepoints after vasopressin. Timepoint 2 representing 2 minutes, timepoint 3=10 minutes and timepoint 4= 20 minutes following vasopressin administration. ACI l= left internal carotid artery, ACI r = right internal carotid artery, CPP=cerebral perfusion pressure in mmHg, ICP= intracranial pressure in mmHg, LMCA= left middle cerebral artery, MAP= mean arterial pressure in mmHg, P bt O 2 =brain tissue oxygenation in mmHg, Quantix = blood flow volume in ml/min, RMCA= right middle cerebral artery, TCD= transcranial doppler in cm/sec Table 8 Detailed measurement data Patient 7 Quantix ml/min TCD cm/sec Timepoints MAP ICP CPP PbtO2 ACI l ACIr LMCA RMCA 1 55 22 33 12 402 328 143 165 2 96 17 79 15 387 324 3 98 15 83 15 390 298 4 96 16 80 14 394 300 Mean 96,67 16,00 80,67 14,67 390,33 307,33 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3828021","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":265638670,"identity":"59902891-0595-4818-8ed3-8cc0e0e98c84","order_by":0,"name":"Sylvia Bele","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3UlEQVRIie2PvQrCMBRGbwnEJTSO6aKvEBCcfJgEwbFLRx2UQrs5O/gQvoGVQrvkAQoFbXcHJ3ES4w+O3o4OOWTJJef7bgAcjr+ELEGBPT3wGsjsIEMV76MQILK7Am+Fik7KcKMT0Swg5IQUc2aO4JfL34qsrKIKiIKYzmpWRRAYpEYKHUtFQe9yNq7ZRdkQhS5mlTvofc6v0Us5NchnKr1qdGJbCKOEVc8WxJCmtcpaRCKno2BrFAsMtlg6zQ636yTkadxezoUa+GWG1PRfmeJ7Z8h7C8cyHQ6Hw/EApblH85isiuYAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0001-9887-3165","institution":"Universitatsklinikum Regensburg","correspondingAuthor":true,"prefix":"","firstName":"Sylvia","middleName":"","lastName":"Bele","suffix":""},{"id":265638671,"identity":"ded97704-4418-4e9e-a397-b2b5bd368bd8","order_by":1,"name":"Elisabeth Bründl","email":"","orcid":"","institution":"Universitätsklinikum Regensburg: Universitatsklinikum Regensburg","correspondingAuthor":false,"prefix":"","firstName":"Elisabeth","middleName":"","lastName":"Bründl","suffix":""},{"id":265638672,"identity":"1e9bec29-c973-4c4b-8a60-3909fee3a6e4","order_by":2,"name":"Nils Ole Schmidt","email":"","orcid":"","institution":"Universitätsklinikum Regensburg: Universitatsklinikum Regensburg","correspondingAuthor":false,"prefix":"","firstName":"Nils","middleName":"Ole","lastName":"Schmidt","suffix":""},{"id":265638673,"identity":"85345ba8-4b7a-463e-b23a-36a49d1f1086","order_by":3,"name":"Martin Kieninger","email":"","orcid":"","institution":"Universitätsklinikum Regensburg: Universitatsklinikum Regensburg","correspondingAuthor":false,"prefix":"","firstName":"Martin","middleName":"","lastName":"Kieninger","suffix":""}],"badges":[],"createdAt":"2024-01-01 19:54:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3828021/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3828021/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49383919,"identity":"00674286-9a44-46b1-b552-98dd554595d2","added_by":"auto","created_at":"2024-01-09 19:44:58","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":14445,"visible":true,"origin":"","legend":"\u003cp\u003eShows a schematic of the ICA using the Quantix ND\u003csup\u003e®\u003c/sup\u003e System with L1 representing the laminar flow beam 1, L2 the laminar flow beam 2. D represents the vessel diameter, V the volume and α the insonated angle to measure total flow volume within the carotid artery.\u003c/p\u003e","description":"","filename":"Figure1Neurocritcare.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3828021/v1/d98531ec854e44252df627a0.jpg"},{"id":49499517,"identity":"753c688e-87a6-457e-979b-95e6c10470f4","added_by":"auto","created_at":"2024-01-11 23:53:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":283690,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3828021/v1/20d808db-8ad7-4342-933e-9a1d974da039.pdf"}],"financialInterests":"","formattedTitle":"Vasopressin increases Cerebral Perfusion Pressure but not Cerebral Blood Flow in Neurosurgical Patients with Norepinephrine-Refractory Hypotension: A Preliminary Evaluation using the non-invasive Quantix ND in Comparison to the Literature","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe means of treatment of ICU patients is to sustain perfusion and O\u003csub\u003e2\u003c/sub\u003e delivery to all major organs to avoid organ damage. Since it is not possible to influence the initial insult on neurosurgical ICUs it is crucial to prevent an additional neuronal damage. Thus, avoidance of early brain injury (EBI) following aneurysmal subarachnoid \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e, raised intracranial pressure (ICP) or low cerebral perfusion pressure (CPP) due to low mean arterial blood pressure (MAP) following traumatic brain injury is key. Especially in aSAH patients suffering from cerebral vasospasm (CV) often leads to sequelae like delayed cerebral ischemia (DCI) or low tissue oxygenation \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. To minimize the risk of brain ischemia, standard treatment guidelines have been established including the maintenance of a CPP\u0026thinsp;\u0026gt;\u0026thinsp;60 mmHg. The management of CPP normally includes the control of ICP and mean arterial pressure (MAP), since CPP\u0026thinsp;=\u0026thinsp;MAP-ICP. Despite many clinical trials so far, no level I evidence for an ideal CPP exists, but the guidelines of the Brain Trauma Foundation recommend a CPP between 50\u0026ndash;70 mmHg in traumatic brain injury (TBI) patients, depending on the patient\u0026rsquo;s individual cerebral hemodynamic profile \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. For patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) there might be completely different needs for CPP levels since the major cause of death after SAH is DCI often due to cerebral vasospasm and thus elevated vascular resistance \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. For those patients among other treatment needs, a sufficient CCP is crucial \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. To obtain CPP, fluid resuscitation can be used but, in most patients, additionally vasopressors are needed. Today catecholamines are the agent of choice. But with increasing dosage or prolonged duration, side effects like increased heart rate and increased myocardial oxygen consumption occur. Those side effects can potentiate the extracranial effects of SAH like intravascular volume depletion or cardiac impairment known as neurogenic myocardial injury (NMI) \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. The elevation of systemic vascular resistance can also compromise end organ perfusion \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. In addition, refractoriness to catecholamines exists \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. For those patients, arginine-vasopressin (AVP) might be the drug of choice.\u003c/p\u003e \u003cp\u003eVasopressin is synthesized as a prehormone in the magnocellular neurons of paraventricular and supraoptic nuclei of the hypothalamus and is one of the key players for osmotic and cardiovascular hemostasis \u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. It is cleaved into the active hormone and released into systemic circulation from the posterior pituitary gland. The serum levels of this nonapeptide represent the interaction of AVP synthesis, release, and metabolism. Arginine vasopressin exerts its actions via a variety of receptors. The main three receptors are: AVPR1a (V1 receptor, mainly vascular functions), AVPR1b (V3 receptor, mostly central functions) and AVPR2 (V2 receptor, renal functions). In addition, AVP can act via oxytocin receptors as well as purinergic receptors \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. The V3 receptor is expressed in the hippocampus and the anterior pituitary gland and V3 receptor stimulation by vasopressin leads to a release of adrenocorticotropic hormone (ACTH) and thus interacts with the corticosteroid axis in response to stress such as hypotension \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe regulation of the vasoconstrictive effects of AVP is an interplay of various actions and receptors. AVPR1a, a G-protein coupled receptor, is the main effector for the AVP associated vasocontraction and is expressed on the vascular smooth muscle cell, platelets, and hepatocytes for review see \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. It stimulates a phosphatidyl-inositol-calcium signal pathway leading to smooth muscle contraction \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. But on the other side AVPR1a stimulation also causes production of nitric oxide, a potent vasodilator in pulmonary \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e and coronary vessels \u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Also, the stimulation of oxytocin receptors by low dose vasopressin can induce vasodilation \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDue to the mostly independently regulated pathways of the different AVP receptors, synthetic agonists of the AVP receptors are routinely used in modern medicine, e.g. desmopressin, a V2 receptor agonist is used in diagnostics and treatment of diabetes insipidus or used for treatment of coagulopathies \u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Vasopressin or terlipressin (via V1 receptor) are used in postoperative bowel distention or refractory hypotension after cardiac surgery \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. AVP gained more interest over the years in treatment of vasoplegic septic shock or other forms of refractory vasoplegic catecholamine resistant shock \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. AVP can restore vascular tone by at least four different mechanisms: activation of AVPR1a, modulation of NO, modulation of ATP-sensitive K\u003csup\u003e+\u003c/sup\u003echannels and potentiation of adrenergic vasoconstrictive agents leading to contraction of small arterioles and increasing peripheral vascular resistance \u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eA review of literature by Russel in 2011 showed that in patients with septic shock the use of low dose vasopressin combined with corticosteroids had better patient outcome than norepinephrine and steroids but showed potential side effects such as peripheral ischemia or disturbances in microcirculation. Even though studies clearly showed that AVP is safe to use and can have beneficial effects in septic shock \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e or in traumatic shock resuscitation when combined with low fluid resuscitation \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e so far validated recommendations in clinical guidelines for the use of AVP in either septic shock or resuscitation fail to appear.\u003c/p\u003e \u003cp\u003eThe use of AVP in neurosurgical or neurological patients is even more controversial. After brain injury vasopressin is released leading to inflammatory reactions and cerebral edema \u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. Use of AVPR1a antagonists led to attenuation of secondary brain lesion and edema \u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. Interestingly in a model for blunt trauma to the head and chest showed that the use of AVP was as effective as phenylephrine to maintain CPP but improved ICP and cerebral tissue oxygenation \u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. In 2013 Van Haren et al. published a paper concerning the use of vasopressin for CPP management in patients with severe traumatic brain injury \u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. They concluded that vasopressin is safe to use and represents an effective alternative to catecholamines for maintaining CPP.\u003c/p\u003e \u003cp\u003eSince the vasoconstrictive potency of AVP is well known and the study by Van Haren et al. didn\u0026rsquo;t measure cerebral blood flow (CBF) or brain tissue oxygenation (P\u003csub\u003ebt\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e) the present preliminary study was carried out to evaluate the influence of AVP on CPP, ICP and CBF in neurosurgical patients suffering from catecholamine refractory hypotension.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eEthics/ IRB Statement\u003c/p\u003e \u003cp\u003e This retrospective study was approved by the Local Ethics Committee University of Regensburg Approval Number 18-1059-104.\u003c/p\u003e \u003cp\u003eAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1975 Helsinki declaration and its later amendment. For the present retrospective study informed consent is not required.\u003c/p\u003e \u003cp\u003ePatient selection and ICU therapy:\u003c/p\u003e \u003cp\u003eWe included 5 patients on our neurosurgical ward in this preliminary study. Four patients were treated for aSAH and one patient for severe TBI (for patient demographics see table 1). The localization of the aneurysm responsible for the SAH and severity of the bleeding was documented according to the classification of the World Federation of Neurological Surgeons (WFNS) who showed a norepinephrine refractory hypotension. All patients had continuous ICP monitoring (Raumedic Neurovent\u0026reg;, Raumedic AG, Helmbrechts, Germany) and intraarterial blood pressure measurement to continuously calculate CPP. Also, P\u003csub\u003ebt\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e values were measured using the Licox\u0026reg; probe (Integra Life Science, Tullamore, Ireland) according to our standard protocols when patients were under analgo-sedation for \u0026gt;\u0026thinsp;96 h or CV was suspected due to elevated transcranial doppler (TCD) values according to our standard operating procedures \u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. The last transcranial doppler (TCD) value before vasopressin administration was recorded to check for CV.\u003c/p\u003e \u003cp\u003ePatients received volume and catecholamine therapy according to standard recommendations and in dependance on the occurrence of cerebral vasospasm. The goal was to keep CPP\u0026thinsp;\u0026gt;\u0026thinsp;70 mmHg \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. The TBI patient was treated according to the Brain Trauma Foundation guidelines \u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e and actual literature \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. During the ICU stay each of those patients suffered from at least one episode of refractory hypotension that could not be treated sufficiently by volume, hydrocortisone and catecholamines.\u003c/p\u003e \u003cp\u003eTherapeutical Intervention und CBF monitoring:\u003c/p\u003e \u003cp\u003eWhen the decision to try AVP was made a 3 I.U. bolus was applied and the effect on MAP, ICP and CPP was monitored. The goal was to establish a CPP\u0026thinsp;\u0026gt;\u0026thinsp;70 mmHg. Since it was a preliminary study, we decided to measure CBF non-invasively using the Quantix ND\u0026reg; device.\u003c/p\u003e \u003cp\u003eThe Quantix ND\u0026reg; (Cardiosonix Ltd, Israel) uses an angle-independent doppler technique that employs two ultrasound heads placed in a defined angle to each other in one insonation probe (Fig.\u0026nbsp;1), projecting actual flow diagrams on a real time monitor. Probe was placed in the submandibular region of a supine positioned patient and internal carotid artery (ICA) was located by identifying its specific flow diagram on the real time monitor. On the real-time monitor the volume flow, both angles (θ1,θ2), the measured diameters of the vessel (D1, D2), both measured velocities as to the laminar flow (L1,L2) and finally the shear force were monitored (Fig.\u0026nbsp;1). This information is continuously stored on the computer and can be later replayed for offline reevaluation. The system was evaluated at our clinic comparing CBF values measured by the QuantixND\u0026reg; compared with rCBF values \u003csup\u003e\u003cspan additionalcitationids=\"CR32 CR33 CR34\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e. We measured the flow volume in the internal carotid artery (ICA) since it was shown that the flow volume has an almost linear correlation with the cerebral blood flow on the measured side \u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e but showed an even better correlation when flow volume in both ICA was measured and compared to global CBF \u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eWhen decision to use vasopressin in a patient was made, in all SAH patients the last transcranial doppler value was noted and the Quantix ND\u0026reg; was used to establish the baseline flow volume and thus the CBF before vasopressin administration. Additional measurements were performed 2, 10 and 20 minutes after vasopressin. In addition, MAP, ICP, and CPP was documented at the same timepoints. Patient outcome was evaluated at hospital discharge using the Glasgow Outcome Score (GOS). GOS 0 represents death, GOS 1\u0026ndash;3 poor outcome and GOS 4\u0026ndash;5 favorable outcome.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eBetween 2014 and 2018 seven patients fulfilled the criteria for using vasopressin to treat hypotension refractory to fluid, norepinephrine, and hydrocortisone. One patient was treated for TBI, six patients were treated for aSAH four of whom developed cerebral vasospasm. All but one patient received a bolus of 3 I.JU. vasopressin, in patient 2 another bolus of 5 I.U. was needed to improve MAP. The outcome using the GOS was favorable in 2 patients, 3 patients were in the poor outcome group at time of hospital discharge (GOS3), both improved to GOS 4 after rehabilitation. Two patients died during hospital stay due to multi-infarct syndrome as sequelae of CV (for patient demographics see table 1).\u003c/p\u003e \u003cp\u003eIn all examined patients robust external flow values in the internal carotid artery (ICA) values could be gathered before and 2, 10 and 20 minutes after vasopressin administration according to the standard evaluations of the Quantix ND\u0026reg; device. For detailed values of each measurement and each patient see table 2\u0026ndash;8. Elevation of MAP combined with reduction in ICP and thus elevated CPP could be achieved within 2 minutes after AVP administration and was still valid 10 and 20 minutes after AVP bolus. Mean MAP before vasopressin was 56,51 mmHg (\u0026plusmn;\u0026thinsp;4,5 mmHg) and CPP was 40,14 mmHg (\u0026plusmn;\u0026thinsp;8,86; 6,86). The mean increase in all patients over the examined timepoints was 37,39 mmHg and 40,19 mmHg respectively. This increase in MAP and CPP was neither paralleled in an increase in blood flow volume nor P\u003csub\u003ebt\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e. Blood flow volume was decreased in 5 of the aSAH patients, especially in those with signs of CV. In the one patient with normal TCD values blood flow volume stayed within the normal error of measurement. The mean blood flow in both carotid arteries was 320,30 ml/min before vasopressin administration and the overall mean reduction was 23,45 ml/min. In patients with signs of CV at time of vasopressin administration (patient 1,3 and 4) the mean blood flow volume was 286,83 ml/min and decreased to a mean flow volume of 241,42 ml/min. In contrast, the TBI patient showed an increase of MAP and CPP following vasopressin which was accompanied by an increase in blood flow volume. Thus, decision was made to continue AVP administration continuously (0,03 I.U./min) for 12 h to preserve a CPP\u0026thinsp;\u0026gt;\u0026thinsp;65 mmHg (for details see table 6). Unfortunately, no P\u003csub\u003ebt\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e probe was in place since this was not standard monitoring in TBI patients Patient was discharged after 23 days with good outcome.\u003c/p\u003e \u003cp\u003eP\u003csub\u003ebt\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e in all patients measured showed no significant change except for patient 2 who had no signs of vasospasm and brain oxygenation improved slightly following vasopressin.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn the present preliminary retrospective study, we found that administration of vasopressin does improve MAP and CPP in neurocritical care patients suffering from norepinephrine-refractory hypotension but failed to improve CBF, especially in patients with already compromised cerebral perfusion.\u003c/p\u003e \u003cp\u003eDue to the mostly independently regulated pathways of the different AVP receptors, synthetic agonists of the AVP receptors are routinely used in modern medicine, e.g. desmopressin, a V2 receptor agonist is used in diagnostics and treatment of diabetes insipidus or used for treatment of different coagulopathies such as von Willebrand disease \u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e or to counteract effects of acetyl salicylic acid \u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e. The AVPR1a- agonist vasopressin (AVP) or terlipressin are used in postoperative bowel distention, refractory hypotension after cardiac surgery \u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e or to treat intraoperative hypotension or treatment of portal hypertension \u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e. AVP experienced a renaissance for treatment of hypovolemic \u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e or septic shock, refractory hypotension or in resuscitation \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e. The finely tuned and independent work mechanisms of AVP on its different receptors make it the ideal drug for treatment of patients after cardiac surgery suffering from low systemic resistance concomitant with pulmonary hypertension since it elevates systemic resistance while parallel decreasing pulmonary hypertension \u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThose different work mechanisms make AVP a possible target for use in neurosurgical patients. Despite the fact that AVP can enhance cerebral edema after ischemia \u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e,\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e and also leads to an increased rebleeding rate in an animal model of SAH \u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e, some studies demonstrated that AVP is safe to use after TBI using the increase in MAP and CPP as endpoints \u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e, or in an animal model where cerebral oxygenation was also studied \u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. But to our knowledge this preliminary study is the first to measure not only the changes in MAP and CPP but put the focus of attention to changes in cerebral blood flow (CBF) after AVP administration. In the small number of patients included in our study we could clearly demonstrate a significant rise in MAP and CPP after administration of 3 I.U. AVP. Taken this as endpoint it would appear AVP is a safe to use alternative vasopressor in neurosurgical patients, especially after TBI and aSAH, giving the wanted results of an increased CPP. But the problem is the AVPR1a mediated contraction of smooth muscle cells that appears to happen also in cerebral vessels, reflected by the decrease or the lack of sufficient increase in CBF after AVP administration in our patients. This stands in contrast to norepinephrine which elevates systemic blood pressure without normally effecting cerebral vessels, making it the ideal catecholamine for aSAH patients.\u003c/p\u003e \u003cp\u003eThose findings and our data rise two questions: first - is CPP alone really the ideal target for treatment guidance in TBI and aSAH patients and second- is vasopressin safe to use in those patients?\u003c/p\u003e \u003cp\u003eThe maintenance of sufficient MAP is important in all ICU patients but for neurosurgical patients after SAH or TBI it is essential to avoid delayed ischemia. So far, most neuro ICUs use MAP, ICP and CPP to guide their therapy for those patients. This still is considered sufficient, at least in TBI patients according to the Brain Trauma Foundation guidelines, but those simple treatment algorithms are nowadays challenged \u003csup\u003e\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e,\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e. After TBI a dysfunction in cerebral autoregulation might occur \u003csup\u003e\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e, and the microcirculation seems to be dysregulated leading to distended arterioles \u003csup\u003e\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e and thus more intracerebral blood volume. As consequence ICP can be elevated. Several studies concluded that a dynamic CPP concept depending on each patient\u0026rsquo;s cerebrovascular autoregulatory capacities should be followed in ICU care after TBI \u003csup\u003e\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e,\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e. Depreitere \u003cem\u003eet al\u003c/em\u003e. also concluded that CPP alone is not sufficient for patient treatment and added the pressure reactivity index (PRx) defined by Czosnyka \u003csup\u003e\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u003c/sup\u003e to their monitoring. While current evidence regarding the use of P\u003csub\u003ebt\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e remains promising \u003csup\u003e\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e but mixed, three ongoing clinical multicenter trials are expected to definitively answer the question of what role P\u003csub\u003ebt\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e monitoring plays in severe TBI (BOOST III, BONANZAand OXY-TC) \u003csup\u003e\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn our neurosurgical ICU additional neuromonitoring (P\u003csub\u003ebt\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e and/or CBF) is used in addition to ICP and CPP to steer therapy after TBI since 2021 and aSAH since 2014. But this is no standard at all since there exists no level I evidence so far that even an ICP/CPP guided therapy has any beneficial effects on patient outcome after TBI \u003csup\u003e\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e\u003c/sup\u003e. The findings of Van Harren et al. 2013 suggest that the disturbances in normal autoregulation especially in peripheral arterioles and brain function after TBI are complex and may take effect on various levels \u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. The influence of vasopressin on oxytocin receptors leading to vasodilation \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e are overridden on a dose dependent manner by vasopressin related activation of AVPR1a and thus vasoconstriction. This might be the reason for the beneficial effect of vasopressin after TBI seen by Van Harren 2013 and Dudkiewicz 2008. The AVPR1a activation led to elevation in MAP and due to constriction of small cerebral vessels to lower intracranial blood volume and thus lower ICP. This was reflected in the results of the TBI patient in our own study. The AVP administration led to significant rise in MAP, lower ICP value and therefore increased CPP. From the concomitant elevation in CBF we conclude that AVP can at least partly counteract the autoregulatory dysfunction and optimize CPP and CBF without impairment of CBF. Thus, AVP seems to be safe to use for treatment of refractory hypotension in TBI patients. It might be even more beneficial than other vasopressors due to its potential effects on small cerebral vessels. Norepinephrine can only reduce ICP when autoregulation is intact, since it has no direct influence on cerebral vessels due to lack of passages through the blood brain barrier \u003csup\u003e\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u003c/sup\u003e. Hence the application of low dose AVP might be superior to catecholamines for ICU treatment of TBI patients regarding ICP and CPP management when signs of disturbed autoregulation are present. This hypothesis is supported by the findings of Dudkiewicz and Proctor in 2008 who could demonstrate that AVP maintained CPP but improved ICP and cerebral tissue oxygenation better that phenylephrine \u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. In addition, there is a new multicenter trial using a drug targeting the disturbed autoregulatory functions of small distended cerebral arterioles. Administration of the test drug ought to lead to small vessel contraction thus lowering ICP.\u003c/p\u003e \u003cp\u003eThe use of CPP as therapy guidance in patients with SAH is a completely different story. Depending on the severity of the initial bleeding patients can be awake and neurologically assessable or are analgo-sedated and on a ventilator for extended time periods. Cerebral vasospasm is still the major cause for mortality and morbidity after SAH. Vasospasm leads to a decrease in vascular diameter hence an increase in cerebrovascular resistance. The decreased blood flow is often followed by delayed cerebral ischemia leading to catastrophic neurological outcomes or even death \u003csup\u003e\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e\u003c/sup\u003e. The use of CPP as therapy guidance after SAH is problematic because one can only roughly estimate CBF since it doesn\u0026rsquo;t take vessel diameter, resistance, or blood viscosity into account \u003csup\u003e\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e\u003c/sup\u003e. But increased vascular resistance plays the key role in CBF after SAH. It is suggested to use at least brain oxygen measurements to avoid DCI due to non-optimal CPP or CBF \u003csup\u003e\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e\u003c/sup\u003e. It has been shown that P\u003csub\u003ebt\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e values can help to find the optimal CPP since patients with aSAH are at risk for insufficient CBF if CPP\u003csub\u003eopt\u003c/sub\u003e is not reached and might develop DCI \u003csup\u003e\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eWe suggest that multimodal neuromonitoring measuring P\u003csub\u003ebt\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e (Licox\u0026reg; or the Raumedic\u0026reg; PTO probe and if available CBF monitoring (Hemedex probe) should be used in addition to ICP/CPP measurement to optimize ICU treatment and to determine the needed MAP and CPP for each patient individually. This could save volume load and catecholamine administration since the ideal MAP level for each patient could be set (ranges often between 70\u0026ndash;140 mmHg). In aSAH we use P\u003csub\u003ebt\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e and CBF monitoring regularly and have good outcome results (unpublished data and \u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e) but so far, no level I evidence exists showing that the use of additional neuromonitoring has a significant influence on patient outcome \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. This is not due to lack of studies but due to the intraindividual variability of patients\u0026rsquo; needs and therefore difficulties in finding standardized treatments settings that are used in equally in all participating clinics.\u003c/p\u003e \u003cp\u003eThe maintenance of a sufficient CPP according to dependent variables as P\u003csub\u003ebt\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e and CBF is normally done using hypertension therapy \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. In cases when norepinephrine-refractory hypotension occurs, AVP could again be the drug of choice due to its vasoconstrictive effects. But our data clearly demonstrated that the increased MAP combined with decreased ICP leading to elevated CPP was not accompanied by a concomitant improvement of CBF in SAH patients. In addition, we did not see any improvement in P\u003csub\u003ebt\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e value in patients following vasopressin administration. This effect was especially seen in patients with elevated TCD velocities suggestive of cerebral vasospasm. This might be due to the dose dependent effects of AVP. The bolus administration of 3 I.U. vasopressin possibly leads to the stimulation of AVPR1a overriding the potential beneficial effects of oxytocin receptor stimulation and increased NO release in the brain. The possible modulation of NO release and thus vasodilation could be a very useful tool for prevention of severe cerebral vasospasm after SAH. New studies allude to the fact that cerebral vasospasm is not exclusively a disease of the larger vessels but might occur at early stages mainly in microcirculation. Terpolilli et al. showed promising data using NO-ventilation to prevent microcirculatory vasospasm after SAH (presentation at the 2014 annual DGNC meeting). Since AVP can also modulate and release NO, it could be useful at early timepoints after SAH to avoid occurrence of vasospastic events in microcirculation. But further studies must be done to exploit this possibility. So far, om our preliminary data show that AVP can counteract refractory hypotension in SAH patients but does not lead to sufficient improvement of CBF. In contrast, in three patients CBF was even decreased after AVP administration despite significantly increased CPP, pointing out that AVP possibly exerts a vasoconstrictive effect on cerebral blood vessels. That suggests that despite the beneficial effect on refractory hypotension AVP should be used with retentiveness in patients with impaired cerebral perfusion but further studies using continuous invasive CBF monitoring, and more patients need to be done to finally decide the fate of AVP in those patients.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eVasopressin is an alternative vasopressor for treatment of refractory hypotension to avoid organ hypoperfusion in ICU patients. It seems practicable for TBI patients, but our preliminary data showed that in general it should be used with care in neurosurgical patients, especially when cerebral blood flow might be compromised e.g. by cerebral vasospasm since it does neither improved CBF nor P\u003csub\u003ebt\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e values. When using vasopressin in those patients, CBF or at least P\u003csub\u003ebt\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e should be monitored to evaluate if the increase in CPP in accompanied by an increase in brain oxygenation to avoid cerebral ischemia. But studies with larger patient groups measuring cerebral tissue oxygenation and CBF by using intraparenchymal probes like the QFlow 500\u0026trade; by Hemedex, Waldham USA\u0026reg; should be carried out to support these findings.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHelbok R, Schiefecker AJ, Beer R, et al. Early brain injury after aneurysmal subarachnoid hemorrhage: a multimodal neuromonitoring study. Crit Care. 2015;19(1):75. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s13054-015-0809-9\u003c/span\u003e\u003cspan address=\"10.1186/s13054-015-0809-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEtminan N, Macdonald RL. Management of aneurysmal subarachnoid hemorrhage. Handb Clin Neurol. 2017;140:195\u0026ndash;228. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/b978-0-444-63600-3.00012-x\u003c/span\u003e\u003cspan address=\"10.1016/b978-0-444-63600-3.00012-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVella MA, Crandall ML, Patel MB. Acute Management of Traumatic Brain Injury. Surg Clin North Am. 2017;97(5):1015\u0026ndash;30. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.suc.2017.06.003\u003c/span\u003e\u003cspan address=\"10.1016/j.suc.2017.06.003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu CT, Wong CS, Yeh CC, Borel CO. Treatment of cerebral vasospasm after subarachnoid hemorrhage\u0026ndash;a review. Acta anaesthesiologica Taiwanica: official journal of the Taiwan Society of Anesthesiologists. 2004;42(4):215\u0026ndash;22. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.ncbi.nlm.nih.gov/pubmed/15679131\u003c/span\u003e\u003cspan address=\"http://www.ncbi.nlm.nih.gov/pubmed/15679131\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKeyrouz SG, Diringer MN. Clinical review: Prevention and therapy of vasospasm in subarachnoid hemorrhage. Crit Care. 2007;11(4):220. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/cc5958\u003c/span\u003e\u003cspan address=\"10.1186/cc5958\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTreggiari MM, Rabinstein AA, Busl KM, et al. Guidelines for the Neurocritical Care Management of Aneurysmal Subarachnoid Hemorrhage. Neurocrit Care. 2023;39(1):1\u0026ndash;28. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s12028-023-01713-5\u003c/span\u003e\u003cspan address=\"10.1007/s12028-023-01713-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStevens RD, Nyquist PA. The systemic implications of aneurysmal subarachnoid hemorrhage. J Neurol Sci. 2007;261(1\u0026ndash;2):143\u0026ndash;56. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jns.2007.04.047\u003c/span\u003e\u003cspan address=\"10.1016/j.jns.2007.04.047\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHall A, O'Kane R. The Extracranial Consequences of Subarachnoid Hemorrhage. World Neurosurg. 2018;109:381\u0026ndash;92. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.wneu.2017.10.016\u003c/span\u003e\u003cspan address=\"10.1016/j.wneu.2017.10.016\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlbright TN, Zimmerman MA, Selzman CH. Vasopressin in the cardiac surgery intensive care unit. Am J Crit Care. 2002;11(4):326\u0026ndash;30. quiz 331-2. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFarand P, Hamel M, Lauzier F, Plante GE, Lesur O. Review article: organ perfusion/permeability-related effects of norepinephrine and vasopressin in sepsis. Can J Anaesth. 2006;53(9):934\u0026ndash;46. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/bf03022837\u003c/span\u003e\u003cspan address=\"10.1007/bf03022837\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYeh CC, Wu CT, Lu CH, Yang CP, Wong CS. Early use of small-dose vasopressin for unstable hemodynamics in an acute brain injury patient refractory to catecholamine treatment: a case report. Anesth Analg. 2003;97(2):577\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1213/01.Ane.0000070231.16378.A6\u003c/span\u003e\u003cspan address=\"10.1213/01.Ane.0000070231.16378.A6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarcinkowska AB, Biancardi VC, Winklewski PJ. Arginine Vasopressin, Synaptic Plasticity, and Brain Networks. Curr Neuropharmacol. 2022;20(12):2292\u0026ndash;302. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2174/1570159x20666220222143532\u003c/span\u003e\u003cspan address=\"10.2174/1570159x20666220222143532\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRussell JA. Bench-to-bedside review: Vasopressin in the management of septic shock. Crit Care. 2011;15(4):226. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/cc8224\u003c/span\u003e\u003cspan address=\"10.1186/cc8224\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAntoni FA, Holmes MC, Makara GB, K\u0026aacute;rteszi M, L\u0026aacute;szl\u0026oacute; FA. Evidence that the effects of arginine-8-vasopressin (AVP) on pituitary corticotropin (ACTH) release are mediated by a novel type of receptor. Peptides. 1984;5(3):519\u0026ndash;22. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/0196-9781(84)90080-9\u003c/span\u003e\u003cspan address=\"10.1016/0196-9781(84)90080-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBirnbaumer M. Vasopressin receptors. Trends Endocrinol Metab. 2000;11(10):406\u0026ndash;10. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s1043-2760(00)00304-0\u003c/span\u003e\u003cspan address=\"10.1016/s1043-2760(00)00304-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRussell JA. Vasopressor therapy in critically ill patients with shock. Intensive Care Med. 2019;45(11):1503\u0026ndash;17. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00134-019-05801-z\u003c/span\u003e\u003cspan address=\"10.1007/s00134-019-05801-z\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEvora PR, Pearson PJ, Schaff HV. Arginine vasopressin induces endothelium-dependent vasodilatation of the pulmonary artery. V1-receptor-mediated production of nitric oxide. Chest. 1993;103(4):1241\u0026ndash;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1378/chest.103.4.1241\u003c/span\u003e\u003cspan address=\"10.1378/chest.103.4.1241\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOkamura T, Ayajiki K, Fujioka H, Toda N. Mechanisms underlying arginine vasopressin-induced relaxation in monkey isolated coronary arteries. J Hypertens. 1999;17(5):673\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/00004872-199917050-00011\u003c/span\u003e\u003cspan address=\"10.1097/00004872-199917050-00011\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThibonnier M, Conarty DM, Preston JA, Plesnicher CL, Dweik RA, Erzurum SC. Human vascular endothelial cells express oxytocin receptors. Endocrinology. 1999;140(3):1301\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1210/endo.140.3.6546\u003c/span\u003e\u003cspan address=\"10.1210/endo.140.3.6546\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAkin M. Response to low-dose desmopressin by a subcutaneous route in children with type 1 von Willebrand disease. Hematology. 2013;18(2):115\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1179/1607845412y.0000000051\u003c/span\u003e\u003cspan address=\"10.1179/1607845412y.0000000051\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDatt V, Wadhhwa R, Sharma V, Virmani S, Minhas HS, Malik S. Vasoplegic syndrome after cardiovascular surgery: A review of pathophysiology and outcome-oriented therapeutic management. J Card Surg. 2021;36(10):3749\u0026ndash;60. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/jocs.15805\u003c/span\u003e\u003cspan address=\"10.1111/jocs.15805\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLandry DW, Levin HR, Gallant EM, et al. Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation. 1997;95(5):1122\u0026ndash;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/01.cir.95.5.1122\u003c/span\u003e\u003cspan address=\"10.1161/01.cir.95.5.1122\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFeinstein AJ, Patel MB, Sanui M, Cohn SM, Majetschak M, Proctor KG. Resuscitation with pressors after traumatic brain injury. J Am Coll Surg. 2005;201(4):536\u0026ndash;45. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jamcollsurg.2005.05.031\u003c/span\u003e\u003cspan address=\"10.1016/j.jamcollsurg.2005.05.031\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKrieg SM, Trabold R, Plesnila N. Time-Dependent Effects of Arginine-Vasopressin V1 Receptor Inhibition on Secondary Brain Damage after Traumatic Brain Injury. J Neurotrauma. 2017;34(7):1329\u0026ndash;36. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1089/neu.2016.4514\u003c/span\u003e\u003cspan address=\"10.1089/neu.2016.4514\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu X, Nakayama S, Amiry-Moghaddam M, Ottersen OP, Bhardwaj A. Arginine-vasopressin V1 but not V2 receptor antagonism modulates infarct volume, brain water content, and aquaporin-4 expression following experimental stroke. Neurocrit Care. 2010;12(1):124\u0026ndash;31. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s12028-009-9277-x\u003c/span\u003e\u003cspan address=\"10.1007/s12028-009-9277-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmeli PA, Ameli NJ, Gubernick DM, et al. Role of vasopressin and its antagonism in stroke related edema. J Neurosci Res. 2014;92(9):1091\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/jnr.23407\u003c/span\u003e\u003cspan address=\"10.1002/jnr.23407\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDudkiewicz M, Proctor KG. Tissue oxygenation during management of cerebral perfusion pressure with phenylephrine or vasopressin. Crit Care Med. 2008;36(9):2641\u0026ndash;50. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/CCM.0b013e3181847af3\u003c/span\u003e\u003cspan address=\"10.1097/CCM.0b013e3181847af3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVan Haren RM, Thorson CM, Ogilvie MP, et al. Vasopressin for cerebral perfusion pressure management in patients with severe traumatic brain injury: preliminary results of a randomized controlled trial. J Trauma Acute Care Surg. 2013;75(6):1024\u0026ndash;30. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/TA.0b013e3182a99d48\u003c/span\u003e\u003cspan address=\"10.1097/TA.0b013e3182a99d48\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. discussion 1030. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBele S, Proescholdt MA, Hochreiter A, et al. Continuous intra-arterial nimodipine infusion in patients with severe refractory cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a feasibility study and outcome results. Acta Neurochir. 2015;157(12):2041\u0026ndash;50. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCarney N, Totten AM, O'Reilly C, et al. Guidelines for the Management of Severe Traumatic Brain Injury. Fourth Ed Neurosurg. 2017;80(1):6\u0026ndash;15. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1227/neu.0000000000001432\u003c/span\u003e\u003cspan address=\"10.1227/neu.0000000000001432\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSoustiel JF, Glenn TC, Vespa P, Rinsky B, Hanuscin C, Martin NA. Assessment of cerebral blood flow by means of blood-flow-volume measurement in the internal carotid artery: comparative study with a 133xenon clearance technique. Stroke. 2003;34(8):1876\u0026ndash;80. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/01.Str.0000080942.32331.39\u003c/span\u003e\u003cspan address=\"10.1161/01.Str.0000080942.32331.39\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShortt J, Opat SS, Gorniak MB, Aumann HA, Collecutt MF, Street AM. A retrospective study of the utility of desmopressin (1-deamino-8-D-arginine vasopressin) trials in the management of patients with von Willebrand disorder. Int J Lab Hematol. 2010;32(1 Pt 1):e181\u0026ndash;3. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.1751-553X.2008.01117.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1751-553X.2008.01117.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKam PC. Use of desmopressin (DDAVP) in controlling aspirin-induced coagulopathy after cardiac surgery. Heart Lung. 1994;23(4):333\u0026ndash;6. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLtaief Z, Ben-Hamouda N, Rancati V, et al. Vasoplegic Syndrome after Cardiopulmonary Bypass in Cardiovascular Surgery: Pathophysiology and Management in Critical Care. J Clin Med. 2022;11(21). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/jcm11216407\u003c/span\u003e\u003cspan address=\"10.3390/jcm11216407\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaeki Y, Nagatomi N, Kobayashi T et al. Effects of vasopressin on gastric mucosal blood flow in portal hypertension. Gastroenterol Jpn. 1991;26 Suppl 3:90\u0026thinsp;\u0026ndash;\u0026thinsp;2. (In eng). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/bf02779273\u003c/span\u003e\u003cspan address=\"10.1007/bf02779273\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCossu AP, Mura P, De Giudici LM, et al. Vasopressin in hemorrhagic shock: a systematic review and meta-analysis of randomized animal trials. Biomed Res Int. 2014;2014:421291. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1155/2014/421291\u003c/span\u003e\u003cspan address=\"10.1155/2014/421291\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKrismer AC, D\u0026uuml;nser MW, Lindner KH, et al. Vasopressin during cardiopulmonary resuscitation and different shock states: a review of the literature. Am J Cardiovasc Drugs. 2006;6(1):51\u0026ndash;68. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2165/00129784-200606010-00005\u003c/span\u003e\u003cspan address=\"10.2165/00129784-200606010-00005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTayama E, Ueda T, Shojima T, et al. Arginine vasopressin is an ideal drug after cardiac surgery for the management of low systemic vascular resistant hypotension concomitant with pulmonary hypertension. Interact Cardiovasc Thorac Surg. 2007;6(6):715\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1510/icvts.2007.159624\u003c/span\u003e\u003cspan address=\"10.1510/icvts.2007.159624\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRauen K, Trabold R, Brem C, Terpolilli NA, Plesnila N. Arginine vasopressin V1a receptor-deficient mice have reduced brain edema and secondary brain damage following traumatic brain injury. J Neurotrauma. 2013;30(16):1442\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1089/neu.2012.2807\u003c/span\u003e\u003cspan address=\"10.1089/neu.2012.2807\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHockel K, Sch\u0026ouml;ller K, Trabold R, Nussberger J, Plesnila N. Vasopressin V(1a) receptors mediate posthemorrhagic systemic hypertension thereby determining rebleeding rate and outcome after experimental subarachnoid hemorrhage. Stroke. 2012;43(1):227\u0026ndash;32. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/strokeaha.111.626168\u003c/span\u003e\u003cspan address=\"10.1161/strokeaha.111.626168\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEarle SA, de Moya MA, Zuccarelli JE, Norenberg MD, Proctor KG. Cerebrovascular resuscitation after polytrauma and fluid restriction. J Am Coll Surg. 2007;204(2):261\u0026ndash;75. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jamcollsurg.2006.11.014\u003c/span\u003e\u003cspan address=\"10.1016/j.jamcollsurg.2006.11.014\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBernard F. Neurotrauma and Intracranial Pressure Management. Crit Care Clin. 2023;39(1):103\u0026ndash;21. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ccc.2022.08.002\u003c/span\u003e\u003cspan address=\"10.1016/j.ccc.2022.08.002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTas J, Beqiri E, van Kaam RC, et al. Targeting Autoregulation-Guided Cerebral Perfusion Pressure after Traumatic Brain Injury (COGiTATE): A Feasibility Randomized Controlled Clinical Trial. J Neurotrauma. 2021;38(20):2790\u0026ndash;800. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1089/neu.2021.0197\u003c/span\u003e\u003cspan address=\"10.1089/neu.2021.0197\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEngelborghs K, Haseldonckx M, Van Reempts J, et al. Impaired autoregulation of cerebral blood flow in an experimental model of traumatic brain injury. J Neurotrauma. 2000;17(8):667\u0026ndash;77. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1089/089771500415418\u003c/span\u003e\u003cspan address=\"10.1089/089771500415418\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGlushakova OY, Johnson D, Hayes RL. Delayed increases in microvascular pathology after experimental traumatic brain injury are associated with prolonged inflammation, blood-brain barrier disruption, and progressive white matter damage. J Neurotrauma. 2014;31(13):1180\u0026ndash;93. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1089/neu.2013.3080\u003c/span\u003e\u003cspan address=\"10.1089/neu.2013.3080\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDepreitere B, G\u0026uuml;iza F, Van den Berghe G, et al. Pressure autoregulation monitoring and cerebral perfusion pressure target recommendation in patients with severe traumatic brain injury based on minute-by-minute monitoring data. J Neurosurg. 2014;120(6):1451\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3171/2014.3.Jns131500\u003c/span\u003e\u003cspan address=\"10.3171/2014.3.Jns131500\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCzosnyka M, Czosnyka Z, Smielewski P. Pressure reactivity index: journey through the past 20 years. Acta Neurochir. 2017;159(11):2063\u0026ndash;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00701-017-3310-1\u003c/span\u003e\u003cspan address=\"10.1007/s00701-017-3310-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOkonkwo DO, Shutter LA, Moore C, et al. Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase-II: A Phase II Randomized Trial. Crit Care Med. 2017;45(11):1907\u0026ndash;14. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/ccm.0000000000002619\u003c/span\u003e\u003cspan address=\"10.1097/ccm.0000000000002619\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLeach MR, Shutter LA. How much oxygen for the injured brain - can invasive parenchymal catheters help? Curr Opin Crit Care. 2021;27(2):95\u0026ndash;102. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/mcc.0000000000000810\u003c/span\u003e\u003cspan address=\"10.1097/mcc.0000000000000810\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLe Roux P. Intracranial pressure after the BEST TRIP trial: a call for more monitoring. Curr Opin Crit Care. 2014;20(2):141\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/mcc.0000000000000078\u003c/span\u003e\u003cspan address=\"10.1097/mcc.0000000000000078\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStrandgaard S, Sigurdsson ST. Point:Counterpoint: Sympathetic activity does/does not influence cerebral blood flow. Counterpoint: Sympathetic nerve activity does not influence cerebral blood flow. J Appl Physiol (1985) 2008;105(4):1366-7; discussion 1367-8. (In eng). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1152/japplphysiol.90597.2008a\u003c/span\u003e\u003cspan address=\"10.1152/japplphysiol.90597.2008a\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThom\u0026eacute; C, Schubert GA, Schilling L. Hypothermia as a neuroprotective strategy in subarachnoid hemorrhage: a pathophysiological review focusing on the acute phase. Neurol Res. 2005;27(3):229\u0026ndash;37. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1179/016164105x25252\u003c/span\u003e\u003cspan address=\"10.1179/016164105x25252\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSmall C, Lucke-Wold B, Patel C, et al. What are we measuring? A refined look at the process of disrupted autoregulation and the limitations of cerebral perfusion pressure in preventing secondary injury after traumatic brain injury. Clin Neurol Neurosurg. 2022;221:107389. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.clineuro.2022.107389\u003c/span\u003e\u003cspan address=\"10.1016/j.clineuro.2022.107389\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCoppadoro A, Citerio G. Subarachnoid hemorrhage: an update for the intensivist. Minerva Anestesiol. 2011;77(1):74\u0026ndash;84. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJohnson U, Engquist H, Lew\u0026eacute;n A, et al. Increased risk of critical CBF levels in SAH patients with actual CPP below calculated optimal CPP. Acta Neurochir. 2017;159(6):1065\u0026ndash;71. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00701-017-3139-7\u003c/span\u003e\u003cspan address=\"10.1007/s00701-017-3139-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 shows the relevant demographic data of the included patients. AL= aneurysm location, ACoA= anterior cerebral artery, GCS= Glasgow Coma Score, GOS= Glasgow Outcome Scale, MCA= middle cerebral artery, n= no, na= not applicable, SAH= Subarachnoid Hemorrhage, TBI= Traumatic Brain Injury, y= yes, WFNS World Federation of Neurosurgeons Score\u003c/p\u003e\n\u003cp\u003eTable 1 Demographic data\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003egender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ediagnosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eWFNS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGCS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003evasospasm\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGOS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient 1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ef\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e57\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSAH\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e13\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMCA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ey\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;Patient 2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003em\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e43\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSAH\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eACoA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003en\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient 3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ef\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e48\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSAH\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e11\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMCA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ey\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient 4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003em\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e61\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSAH\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e15\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eACoA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ey\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient 5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003em\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e40\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTBI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ena\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ena\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ena\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient 6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ef\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e42\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSAH\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMCA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ey\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient 7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ef\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e58\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSAH\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e13\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eACoA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003en\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 2 shows all relevant measurements for patient 1 before (timepoint 1) and at the 3 timepoints after vasopressin. Timepoint 2 representing 2 minutes, timepoint 3=10 minutes and timepoint 4= 20 minutes following vasopressin administration. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 2 Detailed measurement data Patient 1 \u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"669\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"23.880597014925375%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eQuantix ml/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.044776119402986%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eTCD cm/sec\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003eTimepoints\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003eMAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003eICP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003eCPP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003ePbtO2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003eACI l\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003eACI r\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\n \u003cp\u003eLMCA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003eRMCA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e289\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e276\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\n \u003cp\u003e217\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e198\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003e94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e216\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e229\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003e92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e208\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e213\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003e86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e220\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e228\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Mean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003e90,67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003e13,33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e77,33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003e17,33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e214,67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e223,33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eACI l= left internal carotid artery, ACI r = right internal carotid artery, CPP=cerebral perfusion pressure in mmHg, ICP= intracranial pressure in mmHg, LMCA= left middle cerebral artery, MAP= mean arterial pressure in mmHg, P\u003csub\u003ebt\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e=brain tissue oxygenation in mmHg, Quantix = blood flow volume in ml/min, RMCA= right middle cerebral artery, TCD= transcranial doppler in cm/sec\u003c/p\u003e\n\u003cp\u003eTable 3 shows all relevant measurements for patient 2 before (timepoint 1) and at the 3 timepoints after vasopressin. Timepoint 2 representing 2 minutes, timepoint 3=10 minutes and timepoint 4= 20 minutes following vasopressin administration. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 3 Detailed measurement data Patient 2\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"669\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"23.880597014925375%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eQuantix ml/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.044776119402986%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eTCD cm/sec\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003eTimepoints\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003eMAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003eICP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003eCPP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003ePbtO2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003eACI l\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003eACIr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\n \u003cp\u003eLMCA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003eRMCA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e354\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e339\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\n \u003cp\u003e132\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e128\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003e87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e330\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e316\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003e90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e358\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e342\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003e88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e350\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e347\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003e88,33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003e13,33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e75,00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003e21,00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e346,00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e335,00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eACI l= left internal carotid artery, ACI r = right internal carotid artery, CPP=cerebral perfusion pressure in mmHg, ICP= intracranial pressure in mmHg, LMCA= left middle cerebral artery, MAP= mean arterial pressure in mmHg, P\u003csub\u003ebt\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e=brain tissue oxygenation in mmHg, Quantix = blood flow volume in ml/min, RMCA= right middle cerebral artery, TCD= transcranial doppler in cm/sec\u003c/p\u003e\n\u003cp\u003eTable 4 shows all relevant measurements for patient 3 before (timepoint 1) and at the 3 timepoints after vasopressin. Timepoint 2 representing 2 minutes, timepoint 3=10 minutes and timepoint 4= 20 minutes following vasopressin administration. \u0026nbsp;ACI l= left internal carotid artery, ACI r = right internal carotid artery, CPP=cerebral perfusion pressure in mmHg, ICP= intracranial pressure in mmHg, LMCA= left middle cerebral artery, MAP= mean arterial pressure in mmHg, P\u003csub\u003ebt\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e=brain tissue oxygenation in mmHg, Quantix = blood flow volume in ml/min, RMCA= right middle cerebral artery, TCD= transcranial doppler in cm/sec\u003c/p\u003e\n\u003cp\u003eTable 4 Detailed measurement data Patient 3\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"669\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"23.880597014925375%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eQuantix ml/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.044776119402986%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eTCD cm/sec\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003eTimepoints\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003eMAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003eICP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003eCPP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003ePbtO2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003eACI l\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003eACIr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\n \u003cp\u003eLMCA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003eRMCA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e289\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e276\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\n \u003cp\u003e210\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e188\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003e87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e216\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e229\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003e94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e258\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e232\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003e90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e278\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e266\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Mean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003e90,33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003e15,33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e78,67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003e18,00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e250,67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e242,33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 5 shows all relevant measurements for patient 4 before (timepoint 1) and at the 3 timepoints after vasopressin. Timepoint 2 representing 2 minutes, timepoint 3=10 minutes and timepoint 4= 20 minutes following vasopressin administration. \u0026nbsp;ACI l= left internal carotid artery, ACI r = right internal carotid artery, CPP=cerebral perfusion pressure in mmHg, ICP= intracranial pressure in mmHg, LMCA= left middle cerebral artery, MAP= mean arterial pressure in mmHg, n.a.= not applicable, P\u003csub\u003ebt\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e=brain tissue oxygenation in mmHg, Quantix = blood flow volume in ml/min, RMCA= right middle cerebral artery, TCD= transcranial doppler in cm/sec\u003c/p\u003e\n\u003cp\u003eTable 5 Detailed measurement data Patient 4\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"669\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.177347242921014%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.134128166915053%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.730253353204173%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.985096870342772%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.879284649776453%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"23.880597014925375%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eQuantix ml/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.044776119402986%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eTCD cm/sec\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\n \u003cp\u003eTimepoints\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.177347242921014%\" valign=\"bottom\"\u003e\n \u003cp\u003eMAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.134128166915053%\" valign=\"bottom\"\u003e\n \u003cp\u003eICP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.730253353204173%\" valign=\"bottom\"\u003e\n \u003cp\u003eCPP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.985096870342772%\" valign=\"bottom\"\u003e\n \u003cp\u003ePbtO2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\n \u003cp\u003eACI l\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.879284649776453%\" valign=\"bottom\"\u003e\n \u003cp\u003eACIr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\n \u003cp\u003eLMCA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\n \u003cp\u003eRMCA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.177347242921014%\" valign=\"bottom\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.134128166915053%\" valign=\"bottom\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.730253353204173%\" valign=\"bottom\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.985096870342772%\" valign=\"bottom\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\n \u003cp\u003e326\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.879284649776453%\" valign=\"bottom\"\u003e\n \u003cp\u003e265\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\n \u003cp\u003e165\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\n \u003cp\u003e176\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.177347242921014%\" valign=\"bottom\"\u003e\n \u003cp\u003e108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.134128166915053%\" valign=\"bottom\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.730253353204173%\" valign=\"bottom\"\u003e\n \u003cp\u003e94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.985096870342772%\" valign=\"bottom\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\n \u003cp\u003e302\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.879284649776453%\" valign=\"bottom\"\u003e\n \u003cp\u003e246\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.177347242921014%\" valign=\"bottom\"\u003e\n \u003cp\u003e106\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.134128166915053%\" valign=\"bottom\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.730253353204173%\" valign=\"bottom\"\u003e\n \u003cp\u003e91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.985096870342772%\" valign=\"bottom\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\n \u003cp\u003e288\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.879284649776453%\" valign=\"bottom\"\u003e\n \u003cp\u003e230\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.177347242921014%\" valign=\"bottom\"\u003e\n \u003cp\u003e96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.134128166915053%\" valign=\"bottom\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.730253353204173%\" valign=\"bottom\"\u003e\n \u003cp\u003e82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.985096870342772%\" valign=\"bottom\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\n \u003cp\u003e264\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.879284649776453%\" valign=\"bottom\"\u003e\n \u003cp\u003e228\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.177347242921014%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.134128166915053%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.730253353204173%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.985096870342772%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.879284649776453%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Mean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.177347242921014%\" valign=\"bottom\"\u003e\n \u003cp\u003e103,33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.134128166915053%\" valign=\"bottom\"\u003e\n \u003cp\u003e14,33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.730253353204173%\" valign=\"bottom\"\u003e\n \u003cp\u003e89,00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.985096870342772%\" valign=\"bottom\"\u003e\n \u003cp\u003e15,00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\n \u003cp\u003e284,67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.879284649776453%\" valign=\"bottom\"\u003e\n \u003cp\u003e234,67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 6 shows all relevant measurements for patient 5 before (timepoint 1) and at the 3 timepoints after vasopressin. Timepoint 2 representing 2 minutes, timepoint 3=10 minutes and timepoint 4= 20 minutes following vasopressin administration. \u0026nbsp;ACI l= left internal carotid artery, ACI r = right internal carotid artery, CPP=cerebral perfusion pressure in mmHg, ICP= intracranial pressure in mmHg, LMCA= left middle cerebral artery, MAP= mean arterial pressure in mmHg, P\u003csub\u003ebt\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e=brain tissue oxygenation in mmHg, Quantix = blood flow volume in ml/min, RMCA= right middle cerebral artery, TCD= transcranial doppler in cm/sec\u003c/p\u003e\n\u003cp\u003eTable 6 Detailed measurement data Patient 5\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"669\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.177347242921014%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.134128166915053%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.730253353204173%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.985096870342772%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.879284649776453%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"23.880597014925375%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eQuantix ml/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.044776119402986%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eTCD cm/sec\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\n \u003cp\u003eTimepoints\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.177347242921014%\" valign=\"bottom\"\u003e\n \u003cp\u003eMAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.134128166915053%\" valign=\"bottom\"\u003e\n \u003cp\u003eICP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.730253353204173%\" valign=\"bottom\"\u003e\n \u003cp\u003eCPP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.985096870342772%\" valign=\"bottom\"\u003e\n \u003cp\u003ePbtO2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\n \u003cp\u003eACI l\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.879284649776453%\" valign=\"bottom\"\u003e\n \u003cp\u003eACIr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\n \u003cp\u003eLMCA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\n \u003cp\u003eRMCA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.177347242921014%\" valign=\"bottom\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.134128166915053%\" valign=\"bottom\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.730253353204173%\" valign=\"bottom\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.985096870342772%\" valign=\"bottom\"\u003e\n \u003cp\u003en.a.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\n \u003cp\u003e387\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.879284649776453%\" valign=\"bottom\"\u003e\n \u003cp\u003e341\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\n \u003cp\u003en.a.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\n \u003cp\u003en.a.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.177347242921014%\" valign=\"bottom\"\u003e\n \u003cp\u003e99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.134128166915053%\" valign=\"bottom\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.730253353204173%\" valign=\"bottom\"\u003e\n \u003cp\u003e86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.985096870342772%\" valign=\"bottom\"\u003e\n \u003cp\u003en.a.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\n \u003cp\u003e442\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.879284649776453%\" valign=\"bottom\"\u003e\n \u003cp\u003e386\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.177347242921014%\" valign=\"bottom\"\u003e\n \u003cp\u003e98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.134128166915053%\" valign=\"bottom\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.730253353204173%\" valign=\"bottom\"\u003e\n \u003cp\u003e86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.985096870342772%\" valign=\"bottom\"\u003e\n \u003cp\u003en.a.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\n \u003cp\u003e428\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.879284649776453%\" valign=\"bottom\"\u003e\n \u003cp\u003e392\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.177347242921014%\" valign=\"bottom\"\u003e\n \u003cp\u003e89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.134128166915053%\" valign=\"bottom\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.730253353204173%\" valign=\"bottom\"\u003e\n \u003cp\u003e77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.985096870342772%\" valign=\"bottom\"\u003e\n \u003cp\u003en.a.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\n \u003cp\u003e402\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.879284649776453%\" valign=\"bottom\"\u003e\n \u003cp\u003e366\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.177347242921014%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.134128166915053%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.730253353204173%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.985096870342772%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.879284649776453%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Mean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.177347242921014%\" valign=\"bottom\"\u003e\n \u003cp\u003e95,33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.134128166915053%\" valign=\"bottom\"\u003e\n \u003cp\u003e12,33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.730253353204173%\" valign=\"bottom\"\u003e\n \u003cp\u003e83,00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.985096870342772%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.965722801788376%\" valign=\"bottom\"\u003e\n \u003cp\u003e424,00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.879284649776453%\" valign=\"bottom\"\u003e\n \u003cp\u003e381,33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.581222056631892%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 7 shows all relevant measurements for patient 6 before (timepoint 1) and at the 3 timepoints after vasopressin. Timepoint 2 representing 2 minutes, timepoint 3=10 minutes and timepoint 4= 20 minutes following vasopressin administration. \u0026nbsp;ACI l= left internal carotid artery, ACI r = right internal carotid artery, CPP=cerebral perfusion pressure in mmHg, ICP= intracranial pressure in mmHg, LMCA= left middle cerebral artery, MAP= mean arterial pressure in mmHg, P\u003csub\u003ebt\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e=brain tissue oxygenation in mmHg, Quantix = blood flow volume in ml/min, RMCA= right middle cerebral artery, TCD= transcranial doppler in cm/sec\u003c/p\u003e\n\u003cp\u003eTable 7 Detailed measurement data Patient 6\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"669\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"23.880597014925375%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eQuantix ml/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.044776119402986%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eTCD cm/sec\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003eTimepoints\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003eMAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003eICP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003eCPP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003ePbtO2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003eACI l\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003eACIr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\n \u003cp\u003eLMCA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003eRMCA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e312\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e310\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\n \u003cp\u003e172\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e130\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003e92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e308\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e312\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e310\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e298\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003e92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e308\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e366\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Mean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003e94,67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003e16,00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e78,67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003e16,67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e308,67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e325,33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 8 shows all relevant measurements for patient 7 before (timepoint 1) and at the 3 timepoints after vasopressin. Timepoint 2 representing 2 minutes, timepoint 3=10 minutes and timepoint 4= 20 minutes following vasopressin administration. \u0026nbsp;ACI l= left internal carotid artery, ACI r = right internal carotid artery, CPP=cerebral perfusion pressure in mmHg, ICP= intracranial pressure in mmHg, LMCA= left middle cerebral artery, MAP= mean arterial pressure in mmHg, P\u003csub\u003ebt\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e=brain tissue oxygenation in mmHg, Quantix = blood flow volume in ml/min, RMCA= right middle cerebral artery, TCD= transcranial doppler in cm/sec\u003c/p\u003e\n\u003cp\u003eTable 8 Detailed measurement data Patient 7\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"669\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"23.880597014925375%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eQuantix ml/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.044776119402986%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eTCD cm/sec\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003eTimepoints\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003eMAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003eICP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003eCPP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003ePbtO2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003eACI l\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003eACIr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\n \u003cp\u003eLMCA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003eRMCA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e402\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e328\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\n \u003cp\u003e143\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e165\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003e96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e387\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e324\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003e98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e390\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e298\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003e96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e394\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Mean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\n \u003cp\u003e96,67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\n \u003cp\u003e16,00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\n \u003cp\u003e80,67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\n \u003cp\u003e14,67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e390,33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\n \u003cp\u003e307,33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.985074626865671%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.194029850746269%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.149253731343284%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"11.940298507462687%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.298507462686567%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.746268656716419%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Subarachnoid hemorrhage, norepinephrine-refractory hypotension, vasopressin, cerebral blood flow, cerebral perfusion pressure","lastPublishedDoi":"10.21203/rs.3.rs-3828021/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3828021/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe maintenance of sufficient mean arterial pressure (MAP) to sustain perfusion and oxygen delivery to all major organs is important patients in intensive care but for neurosurgical patients after SAH or TBI it is essential to avoid secondary brain damage or delayed ischemia. So far most neurosurgical intensive care units use intracranial pressure (ICP) and cerebral perfusion pressure (CPP) as therapy guidance for those patients. Use of fluid resuscitation and norepinephrine is standard to achieve CPP between 50\u0026ndash;70 mmHg. But sometimes norepinephrine-refractory hypotension occurs. In those cases, arginin-vasopressin (AVP) is often the drug of choice. AVP and its synthetic analogies are widely used in modern medicine and gained interest in treatment of septic shock or refractory hypotension after cardiac surgery or hypovolemic shock. Recent papers also showed a significant impact of AVP in resuscitation of after traumatic brain injury (TBI) and influence on CPP in TBI patients during ICU treatment. But little is known about the effects of AVP on cerebral perfusion and oxygenation. The present preliminary study was carried out to examine the influence of vasopressin administration on cerebral blood flow by using the non-invasive QuantixND\u0026reg; device. We found significantly increased MAP and CPP but no concomitant elevation in CBF. In contrast, in most patients the CBF even decreased despite elevation of CPP. We conclude that AVP is an alternative drug to maintain MAP and CPP but must be used with care in patients with already compromised cerebral perfusion.\u003c/p\u003e","manuscriptTitle":"Vasopressin increases Cerebral Perfusion Pressure but not Cerebral Blood Flow in Neurosurgical Patients with Norepinephrine-Refractory Hypotension: A Preliminary Evaluation using the non-invasive Quantix ND in Comparison to the Literature","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-09 19:44:54","doi":"10.21203/rs.3.rs-3828021/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"99d6ce9a-7ffd-481d-b91b-04a336efdc56","owner":[],"postedDate":"January 9th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-01-11T23:45:47+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-09 19:44:54","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3828021","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3828021","identity":"rs-3828021","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}