Targeted Temperature Management following Traumatic Brain Injury: ESICM / NACCS Consensus Recommendations Guidelines

Targeted Temperature Management following Traumatic Brain Injury: ESICM / NACCS Consensus Recommendations Guidelines | 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 Targeted Temperature Management following Traumatic Brain Injury: ESICM / NACCS Consensus Recommendations Guidelines Andrea Lavinio, Jonathan P Coles, Chiara Robba, Marcel Aries, and 17 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4021300/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 Background The aim of this panel was to develop consensus recommendations and guidance on targeted temperature management (TTM) in patients with severe traumatic brain injury (TBI) and in patients with moderate TBI who deteriorate and require admission to the intensive care unit (ICU) for intracranial pressure (ICP) management. Methods A group of 18 international neuro-intensive care experts in the acute management of TBI participated in a modified Delphi process. An online anonymised survey was completed ahead of the meeting, before the group convened to explore the level of consensus on TTM following TBI. Outputs from the meeting were combined into a further anonymous online survey round to finalise recommendations. Thresholds of ≥ 16 out of 18 panel members in agreement (≥ 88%) for strong consensus and ≥ 14 out of 18 (≥ 78%) for moderate consensus were prospectively set for all statements. Results Strong consensus was reached on TTM being essential for high-quality TBI care. It was recommended that temperature should be monitored continuously, and that fever should be promptly identified and managed in patients perceived to be at risk of secondary brain injury. Controlled normothermia (36.0°C–37.5°C) was strongly recommended as a therapeutic option to be considered in tier 1 and 2 of the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC) ICP management protocol. Temperature management targets should be individualised based on the perceived risk of secondary brain injury and fever aetiology. Conclusions Based on a modified Delphi expert consensus process, this report aims to inform on best practices for TTM delivery for patients following TBI, and to highlight areas of need for further research to improve clinical guidelines in this setting. Traumatic Brain Injury Intensive Care Targeted Temperature Management Temperature Fever Intracranial Pressure Normothermia Hypothermia Figures Figure 1 Figure 2 Introduction Traumatic brain injury (TBI) is a complex and heterogeneous disease, and a major cause of death and disability globally. 1–3 Amongst other common neurological diseases (including stroke, Alzheimer’s disease, Parkinson’s disease and multiple sclerosis), TBI is estimated to have the highest prevalence and incidence, impacting up to 60 million people worldwide annually and representing a substantial public health burden. 4 TBI is defined as an alteration in brain function or other evidence of brain pathology caused by an external force, 5 and requires immediate and sustained management strategies to optimise clinical outcome. The injury processes that follow from a TBI are often divided into two stages: primary and secondary, 6 where primary injury refers to the damage caused by the original physical impact, which can trigger a pathophysiological cascade resulting in secondary injury with deleterious effects on neurological outcome and survival. 7,8 In order to prevent or mitigate secondary injury, immediate treatment following severe TBI focuses on the prevention of further brain damage. As the brain remains susceptible to secondary injury from processes that extend beyond the zone of primary injury such as ischaemia, oedema, herniation, seizures and altered metabolism, 9 immediate treatment following severe TBI focuses on prevention or mitigation of such injury. This is achieved through the control of intracranial pressure (ICP), and prompt treatment of systemic insults such as hypoxia, hypercapnia, and systemic hypotension. 10 In the neuro-intensive care unit (NICU), fever is a prevalent occurrence with heterogenous underlying causes, and it may contribute to secondary injury. Across patients with TBI, subarachnoid haemorrhage and stroke, 11–13 hyperthermia has been found to increase the risk of complications and is believed to be associated with unfavourable clinical outcome including death. 9,11,14,15 This work aims to utilise a Delphi approach to develop holistic consensus recommendations from international experts for the real-world application of TTM in severe TBI with ICP guided treatments. Methods A modified Delphi consensus method was employed, involving a combination of an online survey (Round 1), a face-to-face meeting (Round 2), an additional online survey containing the refined questions from the previous steps, (Round 3) and post-meeting reviews of the consensus results. The questions asked at Round 1 can be found in the supplementary materials, and the results following Round 3 are shown in Table 1 . Round 1 was conducted via the SmartSurvey® online platform, and Round 2 was held as a hybrid meeting in London, UK, on Tuesday 10th October 2023. AL acted as Chair, with an independent facilitator (ES) moderating the meeting. After the results from the final survey of Round 3 were received, the recommendations and final manuscript were developed, with documents shared by e-mail and feedback collected independently from each participant by the facilitator. The predefined agreed cut-off for strong consensus was to have ≥ 16 out of 18 (≥ 88%) of panel members in agreement, and for moderate consensus was to have ≥ 14 out of 18 (≥ 78%) of panel members in agreement. The Delphi methodology and process was adopted from the manuscript published by Lavinio et al. (2023). 17 The process for the Delphi panel and subsequent manuscript development is visualised in Fig. 1 . A detailed overview of the iterative Delphi process is provided in the supplementary materials. Participants The 18 expert attendees for the Delphi process were chosen from members of three professional societies: the Neuro Anaesthesia and Critical Care Society (NACCS), the European Society of Intensive Care Medicine (ESICM), and the European Society of Anaesthesiology and Intensive Care (ESAIC). Selection was based on a documented history of publications in the fields of traumatic brain injury and/or targeted temperature management, as well as their established professional profiles and expertise as leading intensive care practitioners in teaching university hospitals. We endeavoured to ensure balanced representation, covering the geographic areas of the EU, Switzerland, and the UK. Review of the literature and evidence quality assessment Statements and questions were informed by a systematic review of the literature, which identified observational studies, meta-analyses and randomised controlled trials (RCTs) relevant to the topics under discussion. This review search focused on evidence released since 2013. Following this first review, the methodology group of ESICM conducted an independent systematic review of the literature, considering only published RCTs regarding TTM in TBI patients with ICP monitoring. This review confirmed the paucity of RCTs and the substantial clinical heterogeneity between them, which precluded meta-analytical combination. The outputs from the reviews were shared with the expert panel members ahead of the Delphi process. A detailed reporting of the literature reviews is provided as supplementary material. Results The results of the final consensus agreements are presented in Table 1 . We highlight and expand upon statements in which consensus was reached in the discussion section. Some consideration is added to statements in which consensus was not reached, proposing them as potential areas for valuable future research. Table 1 Summary of panel recommendations. *Questions 16 and 17 explored what the lowest target temperature should be when therapeutic hypothermia is considered as a short-term and as a medium term ICP-control measure. Whilst no consensus was achieved, the majority of experts indicated 35.0°C as the lowest temperature in both scenarios. The breakdown of responses to questions 16 and 17 is provided in the table. Original question Topic Level of consensus Stage reached Pathophysiology 1 Temperature measurement and control is an essential aspect of high-quality care in patients with severe traumatic brain injury (TBI) Strong consensus (100%) Round 3 5 In patients with impending cerebral herniation, temperature control is essential Strong consensus (89%) Round 3 Monitoring 6 Continuous temperature monitoring is preferable over intermittent temperature measurements in patients with severe TBI Strong consensus (100%) Round 1 7 Monitoring core temperature (e.g., bladder, oesophageal, brain) is strongly recommended over measuring or monitoring superficial temperature (e.g., skin, tympanic) in severe TBI Strong consensus (94%) Round 3 8 Monitoring brain temperature is recommended in addition to monitoring core systemic temperature as a therapeutic target No consensus (61%) 9 When brain temperature monitoring is not immediately available, alternative sources of core temperature (oesophageal, bladder, intravascular) are acceptable Strong consensus (89%) Round 3 10 When brain temperature monitoring is in place, it is advisable to also assess core temperature Strong consensus (100%) Round 3 ICP 11 Temperature control is a key component of intracranial pressure (ICP) management in severe TBI cases Strong consensus (100%) Round 1 12 Controlled normothermia (i.e., target core temperature 36–37.5°C) should be included as an addition to the Tier 1 and Tier 2 treatments defined within the SIBICC 2019 guidelines. Moderate consensus (83%) Round 3 13 Therapeutic hypothermia (i.e., target core temperature ≤ 36.0°C) should be considered in cases where tier 1 and 2 treatments (as per SIBICC guidance) have failed to control ICP Moderate consensus (83%) Round 3 14 If hypothermia is considered to control ICP, target temperature should be managed as close to physiological temperature as possible Strong consensus (94%) Round 3 15 In patients with impending brain herniation, therapeutic hypothermia should be considered as a temporising strategy, and should be induced rapidly No consensus (61%) 16 In patients with impending herniation awaiting surgical evacuation or decompression, the lowest target core temperature at which hypothermia should be initiated as a short-term temporising strategy is No consensus * (61% – 35.0 °C; 17% – 34.0 °C; 6% – 33.0 °C; 17% – N/A) Round 3 17 In patients with exhausted intracranial volume buffering reserve and labile ICP with occasional spikes > 25 mmHg, the lowest target core temperature that a medium term ICP-control strategy should be implemented at is No consensus * (56% – 35.0 °C; 33% – 34.0 °C; 6% – 33.0 °C; 6% – N/A) Round 3 18 In tier 3 treatment in SIBICC guidelines, before considering decompressive craniectomy, hypothermia (< 36.0C) should be attempted No consensus (44%) 19 Before considering barbiturate burst suppression, hypothermia (< 36.0C) should be attempted No consensus (61%) Fever 2 Uncontrolled fever (neurogenic or secondary to inflammation or infection) can precipitate secondary brain injury in patients with severe TBI Strong consensus (100%) Round 3 3 Fever control is recommended in patients with severe TBI who have seizures or are perceived to be at high risk of seizures Strong consensus (94%) Round 3 4 Fever increases the risk of intracranial hypertension in patients with severe TBI Strong consensus (94%) Round 3 20 Neurogenic fever (core temperature > 37.5°C driven by neurological dysregulation in the absence of sepsis or clinically significant inflammatory process) is relatively common in traumatic brain injury cases, and it should be promptly detected and treated (i.e., with controlled normothermia targeting 36.0°C to 37.5°C), irrespective of ICP Moderate consensus (83%) Round 3 21 Controlled normothermia should be considered when pyrexia is secondary to sepsis or inflammatory processes, and when the patient is perceived to be at risk of secondary brain injury, especially in the acute phase of TBI Strong consensus (94%) Round 3 22 In patients with severe TBI who are sedated and ventilated, controlled normothermia, irrespective of ICP, should be initiated reactively when fever is detected Strong consensus (94%) Round 3 23 When neurogenic fever is detected in TBI cases, controlled normothermia should be continued for as long as the brain remains at risk of secondary brain damage Strong consensus (89%) Round 3 TTM induction 24 It is recommended that the rapid induction of hypothermia in TBI cases should be achieved with automated feedback-controlled temperature management devices Strong consensus (89%) Round 3 25 It is advisable that neurotrauma ICUs should stock readily available NaCl solutions of different concentrations stored at ice-cold temperature for the management of intracranial hypertension crises No consensus (50%) TTM maintenance 26 An automated feedback-controlled TTM device that enables precise temperature control is desirable for the initiation of TTM and maintenance at target temperature in patients with severe TBI Strong consensus (100%) Round 1 27 The maximum temperature variation that a patient should experience during normothermia is less than or equal to +/- 0.5°C per hour and ≤ 1°C per 24-h period Moderate consensus (78%) Round 3 28 When hypothermia is indicated, treatment should be continued for as long as the brain is considered to be at risk of secondary brain injury Strong consensus (89%) Round 3 TTM rewarming 29 Obtaining an interval scan and/or an alternative assessment of intracranial compliance, in addition to the absolute number of ICP, is recommended before rewarming Strong consensus (89%) Round 3 30 When rewarming a patient from therapeutic hypothermia, rewarming should be controlled by an automated feedback-controlled TTM device and should not exceed 1.0°C per 24-hour period No consensus (44%) 31 Rebound hyperthermia should be prevented whenever possible or promptly treated in cases when the brain is perceived to be at risk of secondary brain injury Strong consensus (100%) Round 3 Shivering 32 It is important to assess, document and manage shivering in severe TBI patients Strong consensus (100%) Round 3 33 Whenever ICP is labile and shivering is detected, neuromuscular blockers should be considered after ensuring appropriate depth of sedation Strong consensus (94%) Round 3 34 In self-ventilating patients in the subacute phase of severe TBI, an individualised risk-benefit assessment should be undertaken regarding the indications of controlled normothermia Strong consensus (100%) Round 3 35 Permissive hyperthermia should be considered in cases where risk of secondary brain injury resulting from pyrexia is thought to be low, and when shivering cannot be controlled with first line treatments such as NSAIDs, opiates, magnesium or counter warming Moderate consensus (83%) Round 3 Auditing 36 Time within target range, burden of fever and similar metrics can be considered as indicators of quality of temperature management Strong consensus (94%) Round 3 Discussion To date, a relatively small amount of homogenous data has been published regarding the use of TTM with an automated feedback-controlled device for managing temperature in severe TBI. This underlines the importance of consensus discussion in identifying areas of uncertainty where evidence is lacking, and to stimulate harmonisation of processes of care across different settings. To guide discussions, clinical terms were defined with the values as shown in table 2. Table 2: Definitions applied during the Delphi process. Clinical term Definition Mild hypothermia Core temperature 34.0°C–36.0°C Therapeutic hypothermia Core temperature 37.5°C Pathophysiology (i) Temperature measurement and control is an essential aspect of high-quality care in patients with severe TBI (ii) In patients with impending cerebral herniation, temperature control is essential As an introduction to the discussions, the group debated the recommendation for temperature measurement and control following severe TBI and, after extensive discussion, concluded that core temperature measurement and control is essential for the provision of high-quality care, especially in patients perceived to be at high risk of secondary brain injury. Noting the phrasing of ‘temperature control’ in the recent guidelines for temperature control following cardiac arrest, 18 the group agreed that as an entry point into high-quality care following TBI, the notion of temperature measurement and control is key, opening the door to the full practice of targeted temperature management. This nuanced phrasing was intended to set the scene for the group’s work, with the specifics of the TTM process such as temperature ranges and duration of control being addressed throughout the remainder of the discussions. Highlighting the wealth of physiological data available on the management of temperature in stroke and cardiac arrest, the group noted that the guidelines for temperature management in TBI are less specific. Fundamentally, the group agreed that high-quality TBI care does include monitoring temperature and implementing some form of temperature control, recognising its potential role in optimising outcome. The group highlighted the importance of treatment titration based on an individualised risk-benefit assessment and stratification. In particular, it was noted that in patients with exhausted intracranial compensatory reserve and at risk of cerebral herniation or ischaemia – there exists an extreme susceptibility to secondary brain injury precipitated by suboptimal temperature control. Cerebral herniation is a life-threatening event that requires early diagnosis and prompt management in order to prevent irreversible pathological cascades that can lead to death. 19 Increases in brain temperature have been linked to a linear rise in ICP, with the relationships between temperature, ICP and cerebral perfusion pressure (CPP) becoming more apparent with rapid temperature changes. The impact of temperature on ICP supports the recommendation from the group that temperature control is an essential aspect of care in patients at risk of herniation. 20 The group agreed that while control of ICP and prevention of herniation were important reasons for TTM in TBI, benefits of TTM in the acute phase of TBI also extended to patients without intracranial hypertension. During the discussions the group highlighted that different pathologies often dictate different patient management. For example, patients in whom fluctuations in ICP are well-tolerated (e.g., patients with high intracranial compliance) will be managed differently to patients with obliterated basal cisterns, obliterated cortical sulci, and midline shift (e.g., intracranial mass effect). In patients with exhausted intracranial volume-buffering reserve, strict control of physiological parameters such as CO 2 and temperature, is strongly recommended. Monitoring (i) Continuous temperature monitoring is preferable over intermittent temperature measurements in patients with severe TBI (ii) Monitoring core temperature (e.g., bladder, oesophageal, brain) is strongly recommended over measuring or monitoring superficial temperature (e.g., skin, tympanic) in severe TBI (iii) When brain temperature monitoring is in place, it is advisable to assess an additional source of core temperature monitoring (i.e. oesophageal, bladder) The group widely agreed, in line with supporting literature, that continuous temperature monitoring is preferable over intermittent temperature measurements with severe TBI. Intermittent monitoring and recording of temperature can result in large fluctuations in temperature being missed, as highlighted by supporting literature investigating the use of TTM following cardiac arrest, TBI and stroke. 17,21,22 Discussions amongst the group drew attention to the fact that inaccurately measured temperatures can negatively impact patient care and outcome. Several temperature monitoring sites are available for TTM, and the group widely agreed that core temperature measurements, i.e., bladder and oesophageal sites, are strongly preferred over superficial measurements such as those taken at skin and tympanic sites. Following acknowledgement of their limitations, 23 bladder and oesophageal were singled out as favoured core temperature measurements. The group acknowledged the widespread use of oesophageal probes due to their relative ease of insertion and the challenges of finding MRI compatible bladder probes. Confirmation of preference between the two was acknowledged as being beyond the scope of the group due to these nuances. Rectal temperature monitoring was widely regarded as impractical for reasons such as the lag time and a high rate of dislocation. 16,23 Peripheral sites were unanimously deemed to be insufficiently accurate to guide temperature treatment. 16 Some panel members argued that monitoring target organ (i.e. brain) temperature could add a layer of clinical safety, improve pathophysiological understanding and allow selective and individualised titration of treatment (i.e. selective brain cooling). It was, however, agreed by the group that more research is needed into optimum methods for measuring brain temperature and its interpretation from both a clinical and resource-availability perspective. In particular, it was highlighted that temperature thresholds for harm are less well defined for brain temperature than core temperature. When brain temperature monitoring is available and in place, the group advised that core temperature should also be assessed with bladder or oesophageal probes since this is part of routine practice and has been studied to a greater extent than brain temperature. The group noted the importance of having a dual source of temperature monitoring when using automated TTM devices to reduce the risk of probe malfunction and subsequent over or undercooling. 24 After TBI, brain temperature has often been shown to be higher than systemic temperature and can vary independently, with literature noting a difference of as much as 2°C depending on the individual characteristics of brain pathology and/or probe location, making a consistent and accurate link between the two challenging and possibly inaccurate. 25,26 The group highlighted that targeting brain temperature may allow precise titration of treatment dose, including titration of selective brain cooling with brain temperature management technologies, theoretically reducing side effects associated with systemic hypothermia, whilst delivering neuroprotection and brain temperature management. However, it was concluded that further research is needed in this regard and that not enough evidence exists to support practical recommendations. ICP management (i) Temperature control is a key component of ICP management in severe TBI (ii) Controlled normothermia (i.e., target core temperature 36.0–37.5°C) should be included as an addition to the Tier 1 and Tier 2 treatments defined within the SIBICC 2019 guidelines (iii) Therapeutic hypothermia (i.e., target core temperature ≤36.0°C) should be considered in cases where tier 1 and 2 treatments (as per SIBICC guidance) have failed to control ICP (iv) If hypothermia is considered to control ICP, target temperature should be managed as close to normothermia as possible ICP monitoring remains a critical component in the management of severe TBI. 27,28 The group unanimously agreed that temperature control is a key aspect of managing ICP, highlighting that an increase in temperature can lead to an increase in cerebral metabolism and augmented cerebral blood flow, and a simultaneous increase in cerebral blood volume. In cases of exhausted compensatory mechanisms, these factors can precipitate intracranial hypertension, 20 which in turn can have a deleterious effect on overall outcome. Because there is often no single pathophysiological pathway of ICP elevation, its management is complex. The most recent versions of the Brain Trauma Foundation TBI guidelines do not contain treatment protocols, in part due to a lack of solid evidence around the relative efficacy of available interventions. 27 To address this, the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC) developed a consensus-based practical algorithm for tiered management of severe TBI guided by ICP measurements. 28 One of the most impactful outcomes from this consensus meeting was the acknowledgement of the essential role of temperature control for ICP management in severe TBI, and the recommendation that controlled normothermia (i.e., target core temperature 36.0°C–37.5°C) should be considered in addition to Tier 1 and Tier 2 treatments. The group was keen to harmonise this output with SIBICC by suggesting a more aggressive and specific management with the addition of controlled normothermia in Tiers 1 and 2, adding a layer of clinical safety beyond merely the avoidance of fever over 38.0°C in Tier 0, as shown in Figure 2. In cases when hypothermia is considered (i.e., SIBICC Tier 3), the group recommended that target temperature be managed as close to normothermia as possible, based on an individualised risk-benefit assessment. 29 No consensus was reached on whether hypothermia was a viable temporising strategy in patients with impending cerebral herniation, in patients awaiting hematoma evacuation or decompression, or before consideration of barbiturate coma. Whilst the group acknowledged that therapeutic hypothermia can be effective in reducing ICP, there was no consensus on whether this could be induced rapidly enough in these circumstances, and it was felt that insufficient evidence was available to provide pragmatic recommendations on its indication in these extreme clinical circumstances. Whilst the majority of experts indicated 35.0°C as the lowest target temperature to be considered in these circumstances, no consensus was reached. The discussion highlighted that insufficient evidence exists to support practical recommendations and highlighted the importance of an individualised risk-benefit assessment. It was also noted that centres might have a varying degree of familiarity with different therapeutic options, including ease of access to neurosurgical options (i.e. ventricular drainage, decompression) and this may have an impact on clinician preference for hypothermia as a temporising therapeutic modality. The group also discussed the indication of barbiturates in the context of ICP control following severe TBI, not reaching consensus on whether therapeutic hypothermia should be attempted before considering barbiturates. The group noted that both barbiturate-induced burst-suppression and therapeutic hypothermia have distinctive side effects and concluded that no recommendations for standard clinical practice could be made beyond what was already stated in SIBICC guidance. Fever (i) Neurogenic fever (core temperature >37.5°C) driven by neurological dysregulation in the absence of sepsis or a clinically significant systemic inflammatory process is relatively common in TBI, and it should be promptly detected and treated (i.e., with controlled normothermia targeting 36.0°C to 37.5°C), irrespective of ICP level (ii) Controlled normothermia should be considered when pyrexia is secondary to sepsis or inflammatory processes, and when the patient is perceived to be at risk of secondary brain injury, especially in the acute phase of TBI (iii) Uncontrolled fever (neurogenic or secondary to inflammation or infection) can precipitate secondary brain injury in patients with severe TBI It was widely agreed that neurogenic fever, defined here as core temperature >37.5°C driven by neurological dysregulation in the absence of sepsis or a clinically significant inflammatory process is common in intensive care and it has been found to be associated with an increased risk of complications and unfavourable outcome. 9,14,15 In the setting of neurogenic fever developing in comatose patients with acute traumatic encephalopathies, controlled normothermia targeting 36.0– 37.5°C was recommended in tier 1 and 2 of the ICP management algorithm. Correctly differentiating central fever against fever of infectious origin is both challenging and clinically important due to the impact of failing to identify a treatable condition, the negative consequences of antibiotic overuse, and the detrimental effect of hyperthermia on brain-injured patients. 17,30,31 However, the group noted that physiological processes such as brain metabolic rate of oxygen, CO 2 control, P bt O 2 and ICP are directly related to temperature, and that the deleterious effects and likelihood of secondary injury may occur irrespective of whether temperature is raised due to infection or impaired thermoregulation. This therefore highlights the need for acute management of temperature regardless of the source of the pyrexia, although added focus must be placed on the management of nuanced patient characteristics such as those with severe TBI with impending herniation and/or obliterated basal cisterns, as opposed those with low ICP and preserved intracranial compliance. In line with current research, 9,11,32 it was agreed that the development of fever is common in TBI cases, and that it can precipitate secondary brain injury and adversely affect patient outcome. It is therefore of utmost importance to prevent or promptly treat fever when detected. The group agreed that while some degree of controlled pyrexia may be allowed during the subacute phase of disease, ‘uncontrolled’ fever requires urgent management in the acute phase as long as the patient is still perceived to be at significant risk of secondary brain injury. (i) Fever control is recommended in patients with severe TBI who have seizures or are perceived to be at high risk of seizures (ii) In patients with severe TBI who are sedated and ventilated, controlled normothermia, irrespective of ICP, should be initiated reactively when fever is detected (iii) When neurogenic fever is detected in TBI cases, controlled normothermia should be continued for as long as the brain remains at risk of secondary brain damage The group strongly recommended that fever control and controlled normothermia are of particular relevance in patients perceived to be at high risk of seizures and, more in general, secondary brain injury. The assessment of whether an individual patient should be considered ‘at risk of seizures’ or ‘at risk of secondary brain injury’ remains the responsibility of the managing physician. The group defined risk factors for seizures as a history of seizures, the presence of temporal contusions or depressed skull fractures. Features associated with a higher ‘risk of secondary brain injury’ included labile ICP, obliterated basal cisterns, midline shift or subfalcine herniation, and other signs of exhausted intracranial volume buffering reserve. While no consensus was reached on a specific temperature range to target during controlled normothermia, the group agreed that the reactive initiation of temperature control was important in sedated and ventilated TBI patients, with agreement on a pragmatic setting of a target core temperature range of 36.0–37.5°C to accommodate expected fluctuations of +/- 0.5°C while avoiding spikes over 38.0°C. 28 TTM induction (i) It is recommended that the rapid induction of hypothermia in traumatic brain injury cases should be achieved with automated feedback-controlled temperature management devices In line with previous research, 17 the group widely agreed on the reactive use of an automated feedback-controlled device for the application of optimal TTM. The TTM process can be divided into three phases: induction, maintenance, and rewarming. 9,16 As explained in existing literature, varying availability of devices and financial aspects may dictate choice, and while non-automated methods of temperature control are cheaper and easier to apply, the level of control offered is poor and their use should be limited to the induction phase, as adjuncts to automated devices. 17,33 The application of therapeutic hypothermia requires constant monitoring of core body temperature in order to achieve an accurate target temperature during induction to prevent overcooling, to assess variations during the maintenance phase, and to ensure a steady, controlled rewarming phase. 16 There was no agreed recommendation from the group as to whether ICUs should stock readily available ice-cold NaCl solutions of different concentrations for the management of ICP crises, citing a lack of clear evidence to draw upon. The group did however highlight the fact that the rapid infusion of ice-cold saline is an inexpensive and readily available option for lowering core body temperature, 9 with the rapidity of response to ice-cold infusions being regarded as a valuable aspect of TTM induction. TTM maintenance (i) An automated feedback-controlled TTM device that enables precise temperature control is desirable for the initiation of TTM and maintenance at target temperature in patients with severe TBI (ii) The maximum temperature variation that a patient should experience during normothermia is less than or equal to +/- 0.5°C per hour and ≤1°C per 24-hour period (iii) When hypothermia is indicated, treatment should be continued for as long as the brain is considered to be at risk of secondary brain injury Automated feedback-controlled devices for TTM are powerful tools, encouraging the delivery of quality care and aiming to improve neurological outcome, 13,17 minimising the chances of temperature variability. Temperature variability is the deviation of patient temperature outside of the goal, typically reported as mean deviation or percent of time outside of target. 9 The group noted that there is a level of pragmatism to be adopted in TTM maintenance, discussing that while more time spent in fever can negatively impact neurological outcome, fluctuations in temperature may also affect outcome, 17 and consensus was reached on the importance of maintaining temperature at as consistent a level as possible with the group settling on a fluctuation range of less than or equal to +/- 0.5°C per hour and ≤1°C per 24-h period. In instances where an automated feedback-controlled device is not available, the group noted the importance of increased staff awareness of patient status to ensure fluctuations outside of this range are appropriately managed. The group highlighted that a dedicated protocol for sedation, analgesia and shivering management might be helpful to ensure consistent application of optimal TTM. The group agreed that when indicated, hypothermia should be continued for as long as the individual practitioner considers the brain to be at risk of secondary injury. These considerations were supported with a suggestion that it should be maintained for as short a time as possible. TTM rewarming (i) Obtaining an interval scan and/or an alternative assessment of intracranial compliance, in addition to the absolute number of ICP, is recommended before rewarming (ii) Rebound hyperthermia should be prevented whenever possible or promptly treated in cases when the brain is perceived to be at risk of secondary brain injury In cases in which the patient is being rewarmed from therapeutic hypothermia (core temperature lower than 36.0°C), the group agreed that once ICP has been maintained within controlled limits and de-escalation of treatment intensity is considered, it is sensible to ensure the patient has sufficient intracranial volume buffering reserve through the use of an interval scan and/or an alternative measure of intracranial compliance, before commencing the rewarming process. The group also noted the high prevalence and potential risks associated with rebound hyperthermia when TTM is discontinued following therapeutic hypothermia, highlighting the importance of continued vigilance and careful temperature control in the rewarming phase. Whilst no consensus was reached on recommended rewarming rates, the group agreed that controlled rewarming with an automated feedback-controlled device may reduce the risk of rapid temperature variations and rebound pyrexia that can precipitate secondary brain injury and compromise care. 16,33 The group highlighted how controlled rewarming may improve the ability of clinicians to more effectively control important inter-dependent clinical variables such as PaCO 2 , ventilation settings and depth of sedation. TTM for shivering (i) It is important to assess, document and manage shivering in severe TBI patients (ii) Whenever ICP is labile and shivering is detected, neuromuscular blockers should be considered after ensuring appropriate depth of sedation (iii) In self-ventilating patients in the subacute phase of severe TBI, an individualised risk-benefit assessment should be undertaken regarding the strict indications of controlled normothermia (iv) Permissive hyperthermia should be considered in cases where risk of secondary brain injury resulting from pyrexia is thought to be low, and when shivering cannot be controlled with first line treatments such as NSAIDs, opiates, magnesium or counter warming In line with current literature, it was widely agreed that shivering should be managed in patients following severe TBI. Shivering can reduce brain tissue oxygenation leading to cerebral metabolic stress, which may therefore negate the neuroprotective benefits of TTM. 9,34–36 Titration of sedation and the use of neuromuscular blocking agents provides intensivists with readily available and effective options for shivering control in critically ill patients. 37 To ensure appropriate and effective use however, treating staff must be aware of the nuances of selecting the correct agent, monitoring the depth of neuromuscular blockade, and ensuring adequate skeletal muscle recovery once therapy with neuromuscular blockers has ceased. In cases of shivering when ICP is labile, the group agreed in line with current literature that ensuring depth of sedation before administering neuromuscular blockers is of utmost importance. 37, 38 When using pharmacologic agents for shivering management, treating staff must consider potential pharmacokinetic and pharmacodynamic variation and monitor for efficacy (i.e. shivering control) and safety (i.e. adverse events and drug-drug interactions). 9 The group agreed that in patients who are perceived to be at relatively lower risk of secondary brain injury (i.e. self-ventilating patients in the sub-acute phase of severe TBI), permissive hyperthermia may be considered over TTM, especially if the latter therapeutic option would require sedation or other invasive interventions. The group agreed that an individualised risk-benefit assessment should ultimately be undertaken before commencing controlled normothermia in such patients. Auditing (i) ‘Time within target range’, ‘burden of fever’ and similar metrics can be considered as indicators of quality of temperature management ‘Time within target range’ and ‘burden of fever’ were considered by the group to be appropriate metrics of quality temperature management. It was widely acknowledged that these metrics should be weighed by patient length of stay and/or duration of monitoring for appropriate statistical interpretation. The group was also careful to note that the administrative burden on physicians is already high and acknowledged the fact that some centres may not have access to electronic patient data management systems, so it was agreed that it was unrealistic for this group to issue prescriptive recommendations on auditing practices. In light of the high heterogeneity across centres, 9 here the group were keen to clarify that wherever possible, documenting metrics such as ‘time within target range’ and ‘burden of fever’ may improve their ability to deliver data-driven service improvement and temperature control. Summary This consensus review was undertaken to evaluate current evidence on the application of TTM in the management of severe TBI in a critical care setting, and to develop a set of practical recommendations to address identified gaps in current published evidence. As highlighted by the SIBICC 2020 group, the gap between published evidence and management protocols is bridged by expert opinion. 39 The optimal method for the provision of high-quality TTM remains unknown, and barriers to its consistent implementation include the lack of evidence-based treatment protocols, knowledge deficiencies, limited access to equipment, lack of financial resources and staff workload. This document aims to address key practice gaps and optimise patient care through multimodal assessment following TBI. Strengths and limitations The Delphi process has a number of strengths. Participants are able to reconsider their views in light of the evolving discussions, allowing for an element of reflection that isn’t regularly seen in other studies involving a single time point such as interviews or focus groups. 40 The element of anonymity offered to the panellists in the survey rounds avoids group conformity and promotes honesty, and the controlled and iterative discussions offer a flexible approach to gathering expert viewpoints on the set research questions. The Delphi method is an iterative process allowing the anonymous inclusion of a number of individuals across diverse locations and areas of expertise and avoiding dominance by any one individual. It uses a systematic progression of repeated rounds of voting and is an effective process for determining expert group consensus where there is little or no definitive evidence and where opinion is important. 41,42 The modified Delphi approach used here combined the early flow of structured information and submission of anonymous responses with the (hybrid) face-to-face discussion and further voting to gain consensus (or establish lack thereof) and expert insight into usual practice regarding non-pharmacological TTM with an automated feedback-controlled device. As cited in existing literature however, 13,17 the Delphi process has limitations. The process is vulnerable to drop-outs and technical issues, with the online voting process during our meeting seeing some participants unable to cast their votes on a number of questions, leading to the need for a final anonymous survey round. The group opinions during the meeting may have been impacted by social bias, and the voices across the in-person and online participants may not have been equally heard, highlighting a potential need to ensure consistency in attendance in the same format in future panel meetings. This report has been developed by an expert panel comprised of specialists in neuro-critical care experienced in the management of severe TBI, therefore the recommendations focus on patients managed in a critical care environment. An individualised risk-benefit assessment should be undertaken for each domain to accommodate the high levels of heterogeneity seen across TBI patients, local practice settings, staff training and equipment availability. 9 Conclusion TTM is a complex therapy that has a role in ICP management and may reduce secondary injury and improve long-term neurological outcome for victims of TBI. 9 Appropriate methods for the implementation of TTM across widely heterogenous clinical settings and patient populations are relatively understudied, and due to a lack of consistent and high-quality evidence, remain largely unknown. Areas of consensus emerging from the Delphi process included TTM being recognised as an essential aspect of high-quality TBI care. Controlled normothermia (36.0°C–37.5°C) was strongly recommended as a therapeutic option to be considered in Tier 1 and 2 of the SIBICC ICP management protocol. Temperature management targets should be individualised based on the perceived risk of secondary brain injury and fever aetiology. Declarations Acknowledgements The group would like to acknowledge the support of Page & Page in facilitating the Delphi meeting. Declaration of interest AL received consultancy and speaker fees from Beckton, Dickinson and Company (“BD”) for Chairing the Delphi panel and for contributing to the writing of the article. RH received speaker fees from BD and Zoll. This article contains the personal and professional opinions of the individual authors and does not necessarily reflect the views and opinions of Becton, Dickinson and Company (“BD”) or any Business Unit or affiliate of BD. The Delphi Panel meeting in October 2023 was facilitated (through the provision of travel costs, meeting space and refreshments) by Becton, Dickinson and Company. 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Journal of Hospital Administration , 3 (4), 1. https://doi.org/10.5430/jha.v3n4p1 Eubank, B. H., Mohtadi, N. G., Lafave, M. R., Wiley, J. P., Bois, A. J., Boorman, R. S., & Sheps, D. M. (2016). Using the modified Delphi method to establish clinical consensus for the diagnosis and treatment of patients with rotator cuff pathology. BMC Medical Research Methodology , 16 (1). https://doi.org/10.1186/s12874-016-0165-8 Supplementary Files AGREETTMTBIchecklist.docx SMDelphiprocessMethodology.docx SMESICMmethodologyTTMTBIsummaryofevidence.pdf SMTTMTBILiteratureReviewAugust2023master.xlsx SMesurveyquestionsRound1.pdf SMesurveyquestionsRound3.pdf 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. 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Hospital","correspondingAuthor":false,"prefix":"","firstName":"Fabio","middleName":"S","lastName":"Taccone","suffix":""},{"id":277255455,"identity":"edd3e483-3a4c-4ae9-9ee8-4b6647259fad","order_by":20,"name":"Riikka Takala","email":"","orcid":"","institution":"Turku University Hospital: TYKS Turu yliopistollinen keskussairaala","correspondingAuthor":false,"prefix":"","firstName":"Riikka","middleName":"","lastName":"Takala","suffix":""}],"badges":[],"createdAt":"2024-03-06 14:13:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4021300/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4021300/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":52537307,"identity":"7794c267-e223-414c-8250-b07e386b7d06","added_by":"auto","created_at":"2024-03-12 16:44:06","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":133917,"visible":true,"origin":"","legend":"\u003cp\u003eSummary of the Delphi process. \u003cem\u003e\u003cstrong\u003eESAIC, \u003c/strong\u003e\u003c/em\u003e\u003cem\u003eEuropean Society of\u003c/em\u003e \u003cem\u003eAnaesthesiology and Intensive Care;\u003c/em\u003e\u003cem\u003e\u003cstrong\u003e ESICM\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e, European Society of Intensive Care Medicine; \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eNACCS\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e, Neuro Anaesthesia and Critical Care Society.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4021300/v1/a35a6c9ee90d47020611ef2f.png"},{"id":52537309,"identity":"1ec2b7d2-65de-4c44-8937-c533f2a274ef","added_by":"auto","created_at":"2024-03-12 16:44:06","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":148674,"visible":true,"origin":"","legend":"\u003cp\u003eIntracranial pressure management algorithm for severe TBI edited from SIBICC 2019. \u003csup\u003e28\u003c/sup\u003e * Including TTM in tiers 1 and 2 is the suggested addition from the TTM-TBI group to the original SIBICC tiers (green bars).\u003c/p\u003e\n\u003cp\u003e*When possible, the lowest tier should be used. It is not necessary to use all modalities in a previous tier before moving to the next tier. Consider repeat CT and surgical options for space occupying lesions. \u003cem\u003e\u003cstrong\u003eCPP:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e cerebral perfusion pressure; \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eCT:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e computed tomography; \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eHg:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e haemoglobin;\u003c/em\u003e\u003cem\u003e\u003cstrong\u003e PaCO\u003c/strong\u003e\u003c/em\u003e\u003csub\u003e\u003cem\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/em\u003e\u003c/sub\u003e\u003cem\u003e\u003cstrong\u003e:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e arterial partial pressure of carbon dioxide; \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eSpO\u003c/strong\u003e\u003c/em\u003e\u003csub\u003e\u003cem\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/em\u003e\u003c/sub\u003e\u003cem\u003e\u003cstrong\u003e:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e arterial oxygen saturation.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4021300/v1/a57cb20545a71acaca1b2f6c.png"},{"id":53285838,"identity":"889a37b0-2452-49d9-a473-73ec0d808b3a","added_by":"auto","created_at":"2024-03-22 23:29:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":726941,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4021300/v1/8feaac2b-c711-4517-a65c-7221364bbd91.pdf"},{"id":52537985,"identity":"d5b8d842-7a89-418a-a4e9-0219573222b2","added_by":"auto","created_at":"2024-03-12 16:52:06","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":224469,"visible":true,"origin":"","legend":"","description":"","filename":"AGREETTMTBIchecklist.docx","url":"https://assets-eu.researchsquare.com/files/rs-4021300/v1/eecfdcf0035587853a7abc22.docx"},{"id":52537308,"identity":"89ad84de-a7bc-40dc-bdf6-25289556245c","added_by":"auto","created_at":"2024-03-12 16:44:06","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":17322,"visible":true,"origin":"","legend":"","description":"","filename":"SMDelphiprocessMethodology.docx","url":"https://assets-eu.researchsquare.com/files/rs-4021300/v1/e1fe1ecd976c0f5dfe08bdf4.docx"},{"id":52537313,"identity":"1761dbc1-61aa-4103-bee5-3362270ef7f4","added_by":"auto","created_at":"2024-03-12 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16:44:06","extension":"pdf","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":76281,"visible":true,"origin":"","legend":"","description":"","filename":"SMesurveyquestionsRound1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4021300/v1/8b6ccb8f41dbd3025e99c7fb.pdf"},{"id":52537310,"identity":"a2e2abdd-6aaf-4331-97a9-432c05fe00dc","added_by":"auto","created_at":"2024-03-12 16:44:06","extension":"pdf","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":77713,"visible":true,"origin":"","legend":"","description":"","filename":"SMesurveyquestionsRound3.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4021300/v1/70b42055c05e7db940266ebd.pdf"}],"financialInterests":"","formattedTitle":"Targeted Temperature Management following Traumatic Brain Injury: ESICM / NACCS Consensus Recommendations Guidelines","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTraumatic brain injury (TBI) is a complex and heterogeneous disease, and a major cause of death and disability globally. \u003csup\u003e1\u0026ndash;3\u003c/sup\u003e Amongst other common neurological diseases (including stroke, Alzheimer\u0026rsquo;s disease, Parkinson\u0026rsquo;s disease and multiple sclerosis), TBI is estimated to have the highest prevalence and incidence, impacting up to 60\u0026nbsp;million people worldwide annually and representing a substantial public health burden. \u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eTBI is defined as an alteration in brain function or other evidence of brain pathology caused by an external force, \u003csup\u003e5\u003c/sup\u003e and requires immediate and sustained management strategies to optimise clinical outcome. The injury processes that follow from a TBI are often divided into two stages: primary and secondary, \u003csup\u003e6\u003c/sup\u003e where primary injury refers to the damage caused by the original physical impact, which can trigger a pathophysiological cascade resulting in secondary injury with deleterious effects on neurological outcome and survival. \u003csup\u003e7,8\u003c/sup\u003e In order to prevent or mitigate secondary injury, immediate treatment following severe TBI focuses on the prevention of further brain damage. As the brain remains susceptible to secondary injury from processes that extend beyond the zone of primary injury such as ischaemia, oedema, herniation, seizures and altered metabolism, \u003csup\u003e9\u003c/sup\u003e immediate treatment following severe TBI focuses on prevention or mitigation of such injury. This is achieved through the control of intracranial pressure (ICP), and prompt treatment of systemic insults such as hypoxia, hypercapnia, and systemic hypotension. \u003csup\u003e10\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn the neuro-intensive care unit (NICU), fever is a prevalent occurrence with heterogenous underlying causes, and it may contribute to secondary injury. Across patients with TBI, subarachnoid haemorrhage and stroke, \u003csup\u003e11\u0026ndash;13\u003c/sup\u003e hyperthermia has been found to increase the risk of complications and is believed to be associated with unfavourable clinical outcome including death. \u003csup\u003e9,11,14,15\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e This work aims to utilise a Delphi approach to develop holistic consensus recommendations from international experts for the real-world application of TTM in severe TBI with ICP guided treatments.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eA modified Delphi consensus method was employed, involving a combination of an online survey (Round 1), a face-to-face meeting (Round 2), an additional online survey containing the refined questions from the previous steps, (Round 3) and post-meeting reviews of the consensus results. The questions asked at Round 1 can be found in the supplementary materials, and the results following Round 3 are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Round 1 was conducted via the SmartSurvey\u0026reg; online platform, and Round 2 was held as a hybrid meeting in London, UK, on Tuesday 10th October 2023. AL acted as Chair, with an independent facilitator (ES) moderating the meeting. After the results from the final survey of Round 3 were received, the recommendations and final manuscript were developed, with documents shared by e-mail and feedback collected independently from each participant by the facilitator. The predefined agreed cut-off for strong consensus was to have \u0026ge;\u0026thinsp;16 out of 18 (\u0026ge;\u0026thinsp;88%) of panel members in agreement, and for moderate consensus was to have \u0026ge;\u0026thinsp;14 out of 18 (\u0026ge;\u0026thinsp;78%) of panel members in agreement. The Delphi methodology and process was adopted from the manuscript published by Lavinio et al. (2023).\u003csup\u003e17\u003c/sup\u003e The process for the Delphi panel and subsequent manuscript development is visualised in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. A detailed overview of the iterative Delphi process is provided in the supplementary materials.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eParticipants\u003c/h2\u003e \u003cp\u003e The 18 expert attendees for the Delphi process were chosen from members of three professional societies: the Neuro Anaesthesia and Critical Care Society (NACCS), the European Society of Intensive Care Medicine (ESICM), and the European Society of Anaesthesiology and Intensive Care (ESAIC). Selection was based on a documented history of publications in the fields of traumatic brain injury and/or targeted temperature management, as well as their established professional profiles and expertise as leading intensive care practitioners in teaching university hospitals. We endeavoured to ensure balanced representation, covering the geographic areas of the EU, Switzerland, and the UK.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eReview of the literature and evidence quality assessment\u003c/h2\u003e \u003cp\u003eStatements and questions were informed by a systematic review of the literature, which identified observational studies, meta-analyses and randomised controlled trials (RCTs) relevant to the topics under discussion. This review search focused on evidence released since 2013. Following this first review, the methodology group of ESICM conducted an independent systematic review of the literature, considering only published RCTs regarding TTM in TBI patients with ICP monitoring. This review confirmed the paucity of RCTs and the substantial clinical heterogeneity between them, which precluded meta-analytical combination. The outputs from the reviews were shared with the expert panel members ahead of the Delphi process. A detailed reporting of the literature reviews is provided as supplementary material.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe results of the final consensus agreements are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. We highlight and expand upon statements in which consensus was reached in the \u003cspan refid=\"Sec6\" class=\"InternalRef\"\u003ediscussion\u003c/span\u003e section. Some consideration is added to statements in which consensus was not reached, proposing them as potential areas for valuable future research.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSummary of panel recommendations. *Questions 16 and 17 explored what the lowest target temperature should be when therapeutic hypothermia is considered as a short-term and as a medium term ICP-control measure. Whilst no consensus was achieved, the majority of experts indicated 35.0\u0026deg;C as the lowest temperature in both scenarios. The breakdown of responses to questions 16 and 17 is provided in the table.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOriginal question\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTopic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLevel of consensus\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStage reached\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003ePathophysiology\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTemperature measurement and control is an essential aspect of high-quality care in patients with severe traumatic brain injury (TBI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStrong consensus (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIn patients with impending cerebral herniation, temperature control is essential\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStrong consensus (89%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalicUnderline\" class=\"BoldItalicUnderline\" name=\"Emphasis\"\u003eMonitoring\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eContinuous temperature monitoring is preferable over intermittent temperature measurements in patients with severe TBI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStrong consensus (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMonitoring core temperature (e.g., bladder, oesophageal, brain) is strongly recommended over measuring or monitoring superficial temperature (e.g., skin, tympanic) in severe TBI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStrong consensus (94%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMonitoring brain temperature is recommended in addition to monitoring core systemic temperature as a therapeutic target\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eNo consensus (61%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWhen brain temperature monitoring is not immediately available, alternative sources of core temperature (oesophageal, bladder, intravascular) are acceptable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStrong consensus (89%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWhen brain temperature monitoring is in place, it is advisable to also assess core temperature\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStrong consensus (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalicUnderline\" class=\"BoldItalicUnderline\" name=\"Emphasis\"\u003eICP\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTemperature control is a key component of intracranial pressure (ICP) management in severe TBI cases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStrong consensus (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControlled normothermia (i.e., target core temperature 36\u0026ndash;37.5\u0026deg;C) should be included as an addition to the Tier 1 and Tier 2 treatments defined within the SIBICC 2019 guidelines.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eModerate consensus (83%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTherapeutic hypothermia (i.e., target core temperature\u0026thinsp;\u0026le;\u0026thinsp;36.0\u0026deg;C) should be considered in cases where tier 1 and 2 treatments (as per SIBICC guidance) have failed to control ICP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eModerate consensus (83%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIf hypothermia is considered to control ICP, target temperature should be managed as close to physiological temperature as possible\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStrong consensus (94%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIn patients with impending brain herniation, therapeutic hypothermia should be considered as a temporising strategy, and should be induced rapidly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eNo consensus (61%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIn patients with impending herniation awaiting surgical evacuation or decompression, the lowest target core temperature at which hypothermia should be initiated as a short-term temporising strategy is\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eNo consensus *\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(61% \u0026ndash; 35.0\u003c/em\u003e\u0026deg;C;\u003c/p\u003e \u003cp\u003e\u003cem\u003e17% \u0026ndash; 34.0\u003c/em\u003e\u0026deg;C;\u003c/p\u003e \u003cp\u003e\u003cem\u003e6% \u0026ndash; 33.0\u003c/em\u003e\u0026deg;C;\u003c/p\u003e \u003cp\u003e\u003cem\u003e17% \u0026ndash; N/A)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIn patients with exhausted intracranial volume buffering reserve and labile ICP with occasional spikes\u0026thinsp;\u0026gt;\u0026thinsp;25 mmHg, the lowest target core temperature that a medium term ICP-control strategy should be implemented at is\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eNo consensus *\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(56% \u0026ndash; 35.0\u003c/em\u003e\u0026deg;C;\u003c/p\u003e \u003cp\u003e\u003cem\u003e33% \u0026ndash; 34.0\u003c/em\u003e\u0026deg;C;\u003c/p\u003e \u003cp\u003e\u003cem\u003e6% \u0026ndash; 33.0\u003c/em\u003e\u0026deg;C;\u003c/p\u003e \u003cp\u003e\u003cem\u003e6% \u0026ndash; N/A)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIn tier 3 treatment in SIBICC guidelines, before considering decompressive craniectomy, hypothermia (\u0026lt;\u0026thinsp;36.0C) should be attempted\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eNo consensus (44%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBefore considering barbiturate burst suppression, hypothermia (\u0026lt;\u0026thinsp;36.0C) should be attempted\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eNo consensus (61%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalicUnderline\" class=\"BoldItalicUnderline\" name=\"Emphasis\"\u003eFever\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUncontrolled fever (neurogenic or secondary to inflammation or infection) can precipitate secondary brain injury in patients with severe TBI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStrong consensus (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFever control is recommended in patients with severe TBI who have seizures or are perceived to be at high risk of seizures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStrong consensus (94%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFever increases the risk of intracranial hypertension in patients with severe TBI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStrong consensus (94%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNeurogenic fever (core temperature\u0026thinsp;\u0026gt;\u0026thinsp;37.5\u0026deg;C driven by neurological dysregulation in the absence of sepsis or clinically significant inflammatory process) is relatively common in traumatic brain injury cases, and it should be promptly detected and treated (i.e., with controlled normothermia targeting 36.0\u0026deg;C to 37.5\u0026deg;C), irrespective of ICP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eModerate consensus (83%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControlled normothermia should be considered when pyrexia is secondary to sepsis or inflammatory processes, and when the patient is perceived to be at risk of secondary brain injury, especially in the acute phase of TBI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStrong consensus (94%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIn patients with severe TBI who are sedated and ventilated, controlled normothermia, irrespective of ICP, should be initiated reactively when fever is detected\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStrong consensus (94%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWhen neurogenic fever is detected in TBI cases, controlled normothermia should be continued for as long as the brain remains at risk of secondary brain damage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStrong consensus (89%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalicUnderline\" class=\"BoldItalicUnderline\" name=\"Emphasis\"\u003eTTM induction\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIt is recommended that the rapid induction of hypothermia in TBI cases should be achieved with automated feedback-controlled temperature management devices\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStrong consensus (89%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIt is advisable that neurotrauma ICUs should stock readily available NaCl solutions of different concentrations stored at ice-cold temperature for the management of intracranial hypertension crises\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo consensus \u003cem\u003e(50%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalicUnderline\" class=\"BoldItalicUnderline\" name=\"Emphasis\"\u003eTTM maintenance\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAn automated feedback-controlled TTM device that enables precise temperature control is desirable for the initiation of TTM and maintenance at target temperature in patients with severe TBI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStrong consensus (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe maximum temperature variation that a patient should experience during normothermia is less than or equal to +/- 0.5\u0026deg;C per hour and \u0026le;\u0026thinsp;1\u0026deg;C per 24-h period\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eModerate consensus\u003c/p\u003e \u003cp\u003e(78%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWhen hypothermia is indicated, treatment should be continued for as long as the brain is considered to be at risk of secondary brain injury\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStrong consensus (89%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalicUnderline\" class=\"BoldItalicUnderline\" name=\"Emphasis\"\u003eTTM rewarming\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eObtaining an interval scan and/or an alternative assessment of\u003c/p\u003e \u003cp\u003eintracranial compliance, in addition to the absolute number of ICP, is recommended before rewarming\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStrong consensus (89%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWhen rewarming a patient from therapeutic hypothermia, rewarming should be controlled by an automated feedback-controlled TTM device and should not exceed 1.0\u0026deg;C per 24-hour period\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eNo consensus (44%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRebound hyperthermia should be prevented whenever possible or promptly treated in cases when the brain is perceived to be at risk of secondary brain injury\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStrong consensus (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalicUnderline\" class=\"BoldItalicUnderline\" name=\"Emphasis\"\u003eShivering\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIt is important to assess, document and manage shivering in severe TBI patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStrong consensus (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWhenever ICP is labile and shivering is detected, neuromuscular blockers should be considered after ensuring appropriate depth of sedation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStrong consensus (94%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIn self-ventilating patients in the subacute phase of severe TBI, an individualised risk-benefit assessment should be undertaken regarding the indications of controlled normothermia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStrong consensus (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePermissive hyperthermia should be considered in cases where risk of secondary brain injury resulting from pyrexia is thought to be low, and when shivering cannot be controlled with first line treatments such as NSAIDs, opiates, magnesium or counter warming\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eModerate consensus (83%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalicUnderline\" class=\"BoldItalicUnderline\" name=\"Emphasis\"\u003eAuditing\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTime within target range, burden of fever and similar metrics can be considered as indicators of quality of temperature management\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStrong consensus (94%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRound 3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo date, a relatively small amount of homogenous data has been published regarding the use of TTM with an automated feedback-controlled device for managing temperature in severe TBI. This underlines the importance of consensus discussion in identifying areas of uncertainty where evidence is lacking, and to stimulate harmonisation of processes of care across different settings. To guide discussions, clinical terms were defined with the values as shown in table 2. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2:\u0026nbsp;\u003c/strong\u003eDefinitions applied during the Delphi process. \u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"601\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.08319467554077%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical term \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"49.91680532445923%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDefinition \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.08319467554077%\" valign=\"top\"\u003e\n \u003cp\u003eMild hypothermia \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"49.91680532445923%\" valign=\"top\"\u003e\n \u003cp\u003eCore temperature 34.0\u0026deg;C\u0026ndash;36.0\u0026deg;C \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.08319467554077%\" valign=\"top\"\u003e\n \u003cp\u003eTherapeutic hypothermia \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"49.91680532445923%\" valign=\"top\"\u003e\n \u003cp\u003eCore temperature \u0026lt;36.0\u0026deg;C \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.08319467554077%\" valign=\"top\"\u003e\n \u003cp\u003eControlled normothermia \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"49.91680532445923%\" valign=\"top\"\u003e\n \u003cp\u003eCore temperature 36.0\u0026deg;C\u0026ndash;37.5\u0026deg;C \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.08319467554077%\" valign=\"top\"\u003e\n \u003cp\u003eFever \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"49.91680532445923%\" valign=\"top\"\u003e\n \u003cp\u003eCore temperature \u0026gt;37.5\u0026deg;C \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003ch2\u003ePathophysiology \u0026nbsp;\u003c/h2\u003e\n\u003cp\u003e(i)\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Temperature measurement and control is an essential aspect of high-quality care in patients with severe TBI\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(ii)\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;In patients with impending cerebral herniation, temperature control is essential \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAs an introduction to the discussions, the group debated the recommendation for temperature measurement and control following severe TBI and, after extensive discussion, concluded that core temperature measurement and control is essential for the provision of high-quality care, especially in patients perceived to be at high risk of secondary brain injury. Noting the phrasing of \u0026lsquo;temperature control\u0026rsquo; in the recent guidelines for temperature control following cardiac arrest, \u003csup\u003e18\u003c/sup\u003e the group agreed that as an entry point into high-quality care following TBI, the notion of temperature measurement and control is key, opening the door to the full practice of targeted temperature management. This nuanced phrasing was intended to set the scene for the group\u0026rsquo;s work, with the specifics of the TTM process such as temperature ranges and duration of control being addressed throughout the remainder of the discussions. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHighlighting the wealth of physiological data available on the management of temperature in stroke and cardiac arrest, the group noted that the guidelines for temperature management in TBI are less specific. Fundamentally, the group agreed that high-quality TBI care does include monitoring temperature and implementing some form of temperature control, recognising its potential role in optimising outcome. The group highlighted the importance of treatment titration based on an individualised risk-benefit assessment and stratification. In particular, it was noted that in patients with exhausted intracranial compensatory reserve and at risk of cerebral herniation or ischaemia \u0026ndash; there exists an extreme susceptibility to secondary brain injury precipitated by suboptimal temperature control.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCerebral herniation is a life-threatening event that requires early diagnosis and prompt management in order to prevent irreversible pathological cascades that can lead to death. \u003csup\u003e19\u003c/sup\u003e Increases in brain temperature have been linked to a linear rise in ICP, with the relationships between temperature, ICP and cerebral perfusion pressure (CPP) becoming more apparent with rapid temperature changes. The impact of temperature on ICP supports the recommendation from the group that temperature control is an essential aspect of care in patients at risk of herniation. \u003csup\u003e20\u003c/sup\u003e The group agreed that while control of ICP and prevention of herniation were important reasons for TTM in TBI, benefits of TTM in the acute phase of TBI also extended to patients without intracranial hypertension.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDuring the discussions the group highlighted that different pathologies often dictate different patient management. For example, patients in whom fluctuations in ICP are well-tolerated (e.g., patients with high intracranial compliance) will be managed differently to patients with obliterated basal cisterns, obliterated cortical sulci, and midline shift (e.g., intracranial mass effect). In patients with exhausted intracranial volume-buffering reserve, strict control of physiological parameters such as CO\u003csub\u003e2\u003c/sub\u003e and temperature, is strongly recommended.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eMonitoring\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003e(i)\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Continuous temperature monitoring is preferable over intermittent temperature measurements in patients with severe TBI\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(ii)\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Monitoring core temperature (e.g., bladder, oesophageal, brain) is strongly recommended over measuring or monitoring superficial temperature (e.g., skin, tympanic) in severe TBI \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(iii) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;When brain temperature monitoring is in place, it is advisable to assess an additional source of core temperature monitoring (i.e. oesophageal, bladder)\u003c/p\u003e\n\u003cp\u003eThe group widely agreed, in line with supporting literature, that continuous temperature monitoring is preferable over intermittent temperature measurements with severe TBI. Intermittent monitoring and recording of temperature can result in large fluctuations in temperature being missed, as highlighted by supporting literature investigating the use of TTM following cardiac arrest, TBI and stroke. \u003csup\u003e17,21,22\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDiscussions amongst the group drew attention to the fact that inaccurately measured temperatures can negatively impact patient care and outcome. Several temperature monitoring sites are available for TTM, and the group widely agreed that core temperature measurements, i.e., bladder and oesophageal sites, are strongly preferred over superficial measurements such as those taken at skin and tympanic sites. Following acknowledgement of their limitations, \u003csup\u003e23\u003c/sup\u003e bladder and oesophageal were singled out as favoured core temperature measurements. The group acknowledged the widespread use of oesophageal probes due to their relative ease of insertion and the challenges of finding MRI compatible bladder probes. Confirmation of preference between the two was acknowledged as being beyond the scope of the group due to these nuances. Rectal temperature monitoring was widely regarded as impractical for reasons such as the lag time and a high rate of dislocation.\u003csup\u003e\u0026nbsp;16,23\u003c/sup\u003e Peripheral sites were unanimously deemed to be insufficiently accurate to guide temperature treatment.\u003csup\u003e\u0026nbsp;16\u0026nbsp;\u003c/sup\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eSome panel members argued that monitoring target organ (i.e. brain) temperature could add a layer of clinical safety, improve pathophysiological understanding and allow selective and individualised titration of treatment (i.e. selective brain cooling). It was, however, agreed by the group that more research is needed into optimum methods for measuring brain temperature and its interpretation from both a clinical and resource-availability perspective. In particular, it was highlighted that temperature thresholds for harm are less well defined for brain temperature than core temperature. When brain temperature monitoring is available and in place, the group advised that core temperature should also be assessed with bladder or oesophageal probes since this is part of routine practice and has been studied to a greater extent than brain temperature. The group noted the importance of having a dual source of temperature monitoring when using automated TTM devices to reduce the risk of probe malfunction and subsequent over or undercooling. \u003csup\u003e24\u003c/sup\u003e \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAfter TBI, brain temperature has often been shown to be higher than systemic temperature and can vary independently, with literature noting a difference of as much as 2\u0026deg;C depending on the individual characteristics of brain pathology and/or probe location, making a consistent and accurate link between the two challenging and possibly inaccurate. \u003csup\u003e25,26\u003c/sup\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003eThe group highlighted that targeting brain temperature may allow precise titration of treatment dose, including titration of selective brain cooling with brain temperature management technologies, theoretically reducing side effects associated with systemic hypothermia, whilst delivering neuroprotection and brain temperature management. However, it was concluded that further research is needed in this regard and that not enough evidence exists to support practical recommendations.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eICP management\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003e(i)\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Temperature control is a key component of ICP management in severe TBI\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(ii)\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Controlled normothermia (i.e., target core temperature 36.0\u0026ndash;37.5\u0026deg;C) should be included as an addition to the Tier 1 and Tier 2 treatments defined within the SIBICC 2019 guidelines\u003c/p\u003e\n\u003cp\u003e(iii)\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Therapeutic hypothermia (i.e., target core temperature \u0026le;36.0\u0026deg;C) should be considered in cases where tier 1 and 2 treatments (as per SIBICC guidance) have failed to control ICP\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(iv) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; If hypothermia is considered to control ICP, target temperature should be managed as close to normothermia as possible\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eICP monitoring remains a critical component in the management of severe TBI. \u003csup\u003e27,28\u003c/sup\u003e The group unanimously agreed that temperature control is a key aspect of managing ICP, highlighting that an increase in temperature can lead to an increase in cerebral metabolism and augmented cerebral blood flow, and a simultaneous increase in cerebral blood volume. In cases of exhausted compensatory mechanisms, these factors can precipitate intracranial hypertension, \u003csup\u003e20\u003c/sup\u003e which in turn can have a deleterious effect on overall outcome.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBecause there is often no single pathophysiological pathway of ICP elevation, its management is complex. The most recent versions of the Brain Trauma Foundation TBI guidelines do not contain treatment protocols, in part due to a lack of solid evidence around the relative efficacy of available interventions. \u003csup\u003e27\u003c/sup\u003e To address this, the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC) developed a consensus-based practical algorithm for tiered management of severe TBI guided by ICP measurements. \u003csup\u003e28\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOne of the most impactful outcomes from this consensus meeting was the acknowledgement of the essential role of temperature control for ICP management in severe TBI, and the recommendation that controlled normothermia (i.e., target core temperature 36.0\u0026deg;C\u0026ndash;37.5\u0026deg;C) should be considered in addition to Tier 1 and Tier 2 treatments. The group was keen to harmonise this output with SIBICC by suggesting a more aggressive and specific management with the addition of controlled normothermia in Tiers 1 and 2, adding a layer of clinical safety beyond merely the avoidance of fever over 38.0\u0026deg;C in Tier 0, as shown in Figure 2. In cases when hypothermia is considered (i.e., SIBICC Tier 3), the group recommended that target temperature be managed as close to normothermia as possible, based on an individualised risk-benefit assessment.\u0026nbsp;\u003csup\u003e29\u003c/sup\u003e\u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNo consensus was reached on whether hypothermia was a viable temporising strategy in patients with impending cerebral herniation, in patients awaiting hematoma evacuation or decompression, or before consideration of barbiturate coma. Whilst the group acknowledged that therapeutic hypothermia can be effective in reducing ICP, there was no consensus on whether this could be induced rapidly enough in these circumstances, and it was felt that insufficient evidence was available to provide pragmatic recommendations on its indication in these extreme clinical circumstances. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWhilst the majority of experts indicated 35.0\u0026deg;C as the lowest target temperature to be considered in these circumstances, no consensus was reached. The discussion highlighted that insufficient evidence exists to support practical recommendations and highlighted the importance of an individualised risk-benefit assessment. It was also noted that centres might have a varying degree of familiarity with different therapeutic options, including ease of access to neurosurgical options (i.e. ventricular drainage, decompression) and this may have an impact on clinician preference for hypothermia as a temporising therapeutic modality. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe group also discussed the indication of barbiturates in the context of ICP control following severe TBI, not reaching consensus on whether therapeutic hypothermia should be attempted before considering barbiturates. The group noted that both barbiturate-induced burst-suppression and therapeutic hypothermia have distinctive side effects and concluded that no recommendations for standard clinical practice could be made beyond what was already stated in SIBICC guidance.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eFever \u0026nbsp;\u003c/h2\u003e\n\u003cp\u003e(i) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Neurogenic fever (core temperature \u0026gt;37.5\u0026deg;C) driven by neurological dysregulation in the absence of sepsis or a clinically significant systemic inflammatory process is relatively common in TBI, and it should be promptly detected and treated (i.e., with controlled normothermia targeting 36.0\u0026deg;C to 37.5\u0026deg;C), irrespective of ICP level\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(ii) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Controlled normothermia should be considered when pyrexia is secondary to sepsis or inflammatory processes, and when the patient is perceived to be at risk of secondary brain injury, especially in the acute phase of TBI\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(iii) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Uncontrolled fever (neurogenic or secondary to inflammation or infection) can precipitate secondary brain injury in patients with severe TBI\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIt was widely agreed that neurogenic fever, defined here as core temperature \u0026gt;37.5\u0026deg;C driven by neurological dysregulation in the absence of sepsis or a clinically significant inflammatory process is common in intensive care and it has been found to be associated with an increased risk of complications and unfavourable outcome. \u003csup\u003e9,14,15\u0026nbsp;\u003c/sup\u003eIn the setting of neurogenic fever developing in comatose patients with acute traumatic encephalopathies, controlled normothermia targeting 36.0\u0026ndash; 37.5\u0026deg;C was recommended in tier 1 and 2 of the ICP management algorithm. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCorrectly differentiating central fever against fever of infectious origin is both challenging and clinically important due to the impact of failing to identify a treatable condition, the negative consequences of antibiotic overuse, and the detrimental effect of hyperthermia on brain-injured patients. \u003csup\u003e17,30,31\u003c/sup\u003e However, the group noted that physiological processes such as brain metabolic rate of oxygen, CO\u003csub\u003e2\u003c/sub\u003e control, P\u003csub\u003ebt\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e and ICP are directly related to temperature, and that the deleterious effects and likelihood of secondary injury may occur irrespective of whether temperature is raised due to infection or impaired thermoregulation. This therefore highlights the need for acute management of temperature regardless of the source of the pyrexia, although added focus must be placed on the management of nuanced patient characteristics such as those with severe TBI with impending herniation and/or obliterated basal cisterns, as opposed those with low ICP and preserved intracranial compliance. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn line with current research, \u003csup\u003e9,11,32\u003c/sup\u003e it was agreed that the development of fever is common in TBI cases, and that it can precipitate secondary brain injury and adversely affect patient outcome. It is therefore of utmost importance to prevent or promptly treat fever when detected. The group agreed that while some degree of controlled pyrexia may be allowed during the subacute phase of disease, \u0026lsquo;uncontrolled\u0026rsquo; fever requires urgent management in the acute phase as long as the patient is still perceived to be at significant risk of secondary brain injury. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(i) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Fever control is recommended in patients with severe TBI who have seizures or are perceived to be at high risk of seizures\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(ii) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; In patients with severe TBI who are sedated and ventilated, controlled normothermia, irrespective of ICP, should be initiated reactively when fever is detected\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(iii) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;When neurogenic fever is detected in TBI cases, controlled normothermia should be continued for as long as the brain remains at risk of secondary brain damage\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe group strongly recommended that fever control and controlled normothermia are of particular relevance in patients perceived to be at high risk of seizures and, more in general, secondary brain injury. The assessment of whether an individual patient should be considered \u0026lsquo;at risk of seizures\u0026rsquo; or \u0026lsquo;at risk of secondary brain injury\u0026rsquo; remains the responsibility of the managing physician. The group defined risk factors for seizures as a history of seizures, the presence of temporal contusions or depressed skull fractures. Features associated with a higher \u0026lsquo;risk of secondary brain injury\u0026rsquo; included labile ICP, obliterated basal cisterns, midline shift or subfalcine herniation, and other signs of exhausted intracranial volume buffering reserve. While no consensus was reached on a specific temperature range to target during controlled normothermia, the group agreed that the reactive initiation of temperature control was important in sedated and ventilated TBI patients, with agreement on a pragmatic setting of a target core temperature range of 36.0\u0026ndash;37.5\u0026deg;C to accommodate expected fluctuations of +/- 0.5\u0026deg;C while avoiding spikes over 38.0\u0026deg;C. \u003csup\u003e28\u0026nbsp;\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eTTM induction \u0026nbsp;\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003e(i) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; It is recommended that the rapid induction of hypothermia in traumatic brain injury cases should be achieved with automated feedback-controlled temperature management devices\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn line with previous research, \u003csup\u003e17\u003c/sup\u003e the group widely agreed on the reactive use of an automated feedback-controlled device for the application of optimal TTM. The TTM process can be divided into three phases: induction, maintenance, and rewarming. \u003csup\u003e9,16\u0026nbsp;\u003c/sup\u003eAs explained in existing literature, varying availability of devices and financial aspects may dictate choice, and while non-automated methods of temperature control are cheaper and easier to apply, the level of control offered is poor and their use should be limited to the induction phase, as adjuncts to automated devices. \u003csup\u003e17,33\u003c/sup\u003e The application of therapeutic hypothermia requires constant monitoring of core body temperature in order to achieve an accurate target temperature during induction to prevent overcooling, to assess variations during the maintenance phase, and to ensure a steady, controlled rewarming phase. \u003csup\u003e16\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere was no agreed recommendation from the group as to whether ICUs should stock readily available ice-cold NaCl solutions of different concentrations for the management of ICP crises, citing a lack of clear evidence to draw upon. The group did however highlight the fact that the rapid infusion of ice-cold saline is an inexpensive and readily available option for lowering core body temperature, \u003csup\u003e9\u003c/sup\u003e with the rapidity of response to ice-cold infusions being regarded as a valuable aspect of TTM induction. \u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eTTM maintenance \u0026nbsp; \u0026nbsp;\u003c/h2\u003e\n\u003cp\u003e(i) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;An automated feedback-controlled TTM device that enables precise temperature control is desirable for the initiation of TTM and maintenance at target temperature in patients with severe TBI\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(ii) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; The maximum temperature variation that a patient should experience during\u0026nbsp;\u003c/p\u003e\n\u003cp\u003enormothermia is less than or equal to +/- 0.5\u0026deg;C per hour and \u0026le;1\u0026deg;C per 24-hour period\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(iii) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;When hypothermia is indicated, treatment should be continued for as long as the brain is considered to be at risk of secondary brain injury\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAutomated feedback-controlled devices for TTM are powerful tools, encouraging the delivery of quality care and aiming to improve neurological outcome, \u003csup\u003e13,17\u003c/sup\u003e minimising the chances of temperature variability. Temperature variability is the deviation of patient temperature outside of the goal, typically reported as mean deviation or percent of time outside of target. \u003csup\u003e9\u003c/sup\u003e The group noted that there is a level of pragmatism to be adopted in TTM maintenance, discussing that while more time spent in fever can negatively impact neurological outcome, fluctuations in temperature may also affect outcome, \u003csup\u003e17\u003c/sup\u003e and consensus was reached on the importance of maintaining temperature at as consistent a level as possible with the group settling on a fluctuation range of less than or equal to +/- 0.5\u0026deg;C per hour and \u0026le;1\u0026deg;C per 24-h period. In instances where an automated feedback-controlled device is not available, the group noted the importance of increased staff awareness of patient status to ensure fluctuations outside of this range are appropriately managed. The group highlighted that a dedicated protocol for sedation, analgesia and shivering management might be helpful to ensure consistent application of optimal TTM. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe group agreed that when indicated, hypothermia should be continued for as long as the individual practitioner considers the brain to be at risk of secondary injury. These considerations were supported with a suggestion that it should be maintained for as short a time as possible.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eTTM rewarming \u0026nbsp;\u003c/h2\u003e\n\u003cp\u003e(i) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Obtaining an interval scan and/or an alternative assessment of intracranial compliance, in addition to the absolute number of ICP, is recommended before rewarming\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(ii) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Rebound hyperthermia should be prevented whenever possible or promptly treated in cases when the brain is perceived to be at risk of secondary brain injury\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn cases in which the patient is being rewarmed from therapeutic hypothermia (core temperature lower than 36.0\u0026deg;C), the group agreed that once ICP has been maintained within controlled limits and de-escalation of treatment intensity is considered, it is sensible to ensure the patient has sufficient intracranial volume buffering reserve through the use of an interval scan and/or an alternative measure of intracranial compliance, before commencing the rewarming process. The group also noted the high prevalence and potential risks associated with rebound hyperthermia when TTM is discontinued following therapeutic hypothermia, highlighting the importance of continued vigilance and careful temperature control in the rewarming phase.\u003c/p\u003e\n\u003cp\u003eWhilst no consensus was reached on recommended rewarming rates, the group agreed that controlled rewarming with an automated feedback-controlled device may reduce the risk of rapid temperature variations and rebound pyrexia that can precipitate secondary brain injury and compromise care. \u003csup\u003e16,33\u003c/sup\u003e The group highlighted how controlled rewarming may improve the ability of clinicians to more effectively control important inter-dependent clinical variables such as PaCO\u003csub\u003e2\u003c/sub\u003e, ventilation settings and depth of sedation. \u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eTTM for shivering \u0026nbsp;\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003e(i) \u0026nbsp; It is important to assess, document and manage shivering in severe TBI patients \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(ii) \u0026nbsp;Whenever ICP is labile and shivering is detected, neuromuscular blockers should be considered after ensuring appropriate depth of sedation\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(iii) \u0026nbsp; In self-ventilating patients in the subacute phase of severe TBI, an individualised risk-benefit assessment should be undertaken regarding the strict indications of controlled normothermia\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(iv) \u0026nbsp;Permissive hyperthermia should be considered in cases where risk of secondary brain injury resulting from pyrexia is thought to be low, and when shivering cannot be controlled with first line treatments such as NSAIDs, opiates, magnesium or counter warming\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn line with current literature, it was widely agreed that shivering should be managed in patients following severe TBI. Shivering can reduce brain tissue oxygenation leading to cerebral metabolic stress, which may therefore negate the neuroprotective benefits of TTM. \u003csup\u003e9,34\u0026ndash;36\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTitration of sedation and the use of neuromuscular blocking agents provides intensivists with readily available and effective options for shivering control in critically ill patients. \u003csup\u003e37\u003c/sup\u003e To ensure appropriate and effective use however, treating staff must be aware of the nuances of selecting the correct agent, monitoring the depth of neuromuscular blockade, and ensuring adequate skeletal muscle recovery once therapy with neuromuscular blockers has ceased. In cases of shivering when ICP is labile, the group agreed in line with current literature that ensuring depth of sedation before administering neuromuscular blockers is of utmost importance. \u003csup\u003e37, 38\u003c/sup\u003e When using pharmacologic agents for shivering management, treating staff must consider potential pharmacokinetic and pharmacodynamic variation and monitor for efficacy (i.e. shivering control) and safety (i.e. adverse events and drug-drug interactions). \u003csup\u003e9\u003c/sup\u003e \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe group agreed that in patients who are perceived to be at relatively lower risk of secondary brain injury (i.e. self-ventilating patients in the sub-acute phase of severe TBI), permissive hyperthermia may be considered over TTM, especially if the latter therapeutic option would require sedation or other invasive interventions. The group agreed that an individualised risk-benefit assessment should ultimately be undertaken before commencing controlled normothermia in such patients. \u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eAuditing\u003c/h2\u003e\n\u003cp\u003e(i) \u0026lsquo;Time within target range\u0026rsquo;, \u0026lsquo;burden of fever\u0026rsquo; and similar metrics can be considered as indicators of quality of temperature management\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026lsquo;Time within target range\u0026rsquo; and \u0026lsquo;burden of fever\u0026rsquo; were considered by the group to be appropriate metrics of quality temperature management. It was widely acknowledged that these metrics should be weighed by patient length of stay and/or duration of monitoring for appropriate statistical interpretation. The group was also careful to note that the administrative burden on physicians is already high and acknowledged the fact that some centres may not have access to electronic patient data management systems, so it was agreed that it was unrealistic for this group to issue prescriptive recommendations on auditing practices. In light of the high heterogeneity across centres, 9 here the group were keen to clarify that \u0026nbsp; wherever possible, documenting metrics such as \u0026lsquo;time within target range\u0026rsquo; and \u0026lsquo;burden of fever\u0026rsquo; may improve their ability to deliver data-driven service improvement and temperature control.\u003c/p\u003e\n\u003ch2\u003eSummary\u003c/h2\u003e\n\u003cp\u003eThis consensus review was undertaken to evaluate current evidence on the application of TTM in the management of severe TBI in a critical care setting, and to develop a set of practical recommendations to address identified gaps in current published evidence.\u003c/p\u003e\n\u003cp\u003eAs highlighted by the SIBICC 2020 group, the gap between published evidence and management protocols is bridged by expert opinion. \u003csup\u003e39\u003c/sup\u003e The optimal method for the provision of high-quality TTM remains unknown, and barriers to its consistent implementation include the lack of evidence-based treatment protocols, knowledge deficiencies, limited access to equipment, lack of financial resources and staff workload. This document aims to address key practice gaps and optimise patient care through multimodal assessment following TBI. \u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eStrengths and limitations\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eThe Delphi process has a number of strengths. Participants are able to reconsider their views in light of the evolving discussions, allowing for an element of reflection that isn\u0026rsquo;t regularly seen in other studies involving a single time point such as interviews or focus groups. \u003csup\u003e40\u003c/sup\u003e The element of anonymity offered to the panellists in the survey rounds avoids group conformity and promotes honesty, and the controlled and iterative discussions offer a flexible approach to gathering expert viewpoints on the set research questions. The Delphi method is an iterative process allowing the anonymous inclusion of a number of individuals across diverse locations and areas of expertise and avoiding dominance by any one individual. It uses a systematic progression of repeated rounds of voting and is an effective process for determining expert group consensus where there is little or no definitive evidence and where opinion is important. \u003csup\u003e41,42\u0026nbsp;\u003c/sup\u003eThe modified Delphi approach used here combined the early flow of structured information and submission of anonymous responses with the (hybrid) face-to-face discussion and further voting to gain consensus (or establish lack thereof) and expert insight into usual practice regarding non-pharmacological TTM with an automated feedback-controlled device. As cited in existing literature however, \u003csup\u003e13,17\u003c/sup\u003e the Delphi process has limitations. The process is vulnerable to drop-outs and technical issues, with the online voting process during our meeting seeing some participants unable to cast their votes on a number of questions, leading to the need for a final anonymous survey round. The group opinions during the meeting may have been impacted by social bias, and the voices across the in-person and online participants may not have been equally heard, highlighting a potential need to ensure consistency in attendance in the same format in future panel meetings.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis report has been developed by an expert panel comprised of specialists in neuro-critical care experienced in the management of severe TBI, therefore the recommendations focus on patients managed in a critical care environment. An individualised risk-benefit assessment should be undertaken for each domain to accommodate the high levels of heterogeneity seen across TBI patients, local practice settings, staff training and equipment availability. \u003csup\u003e9\u003c/sup\u003e \u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eTTM is a complex therapy that has a role in ICP management and may reduce secondary injury and improve long-term neurological outcome for victims of TBI. \u003csup\u003e9\u003c/sup\u003e Appropriate methods for the implementation of TTM across widely heterogenous clinical settings and patient populations are relatively understudied, and due to a lack of consistent and high-quality evidence, remain largely unknown. Areas of consensus emerging from the Delphi process included TTM being recognised as an essential aspect of high-quality TBI care. Controlled normothermia (36.0\u0026deg;C\u0026ndash;37.5\u0026deg;C) was strongly recommended as a therapeutic option to be considered in Tier 1 and 2 of the SIBICC ICP management protocol. Temperature management targets should be individualised based on the perceived risk of secondary brain injury and fever aetiology.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe group would like to acknowledge the support of Page \u0026amp; Page in facilitating the Delphi meeting.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of interest \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAL received consultancy and speaker fees from Beckton, Dickinson and Company (\u0026ldquo;BD\u0026rdquo;) for Chairing the Delphi panel and for contributing to the writing of the article. RH received speaker fees from BD and Zoll.\u003c/p\u003e\n\u003cp\u003eThis article contains the personal and professional opinions of the individual authors and does not necessarily reflect the views and opinions of Becton, Dickinson and Company (\u0026ldquo;BD\u0026rdquo;) or any Business Unit or affiliate of BD.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe Delphi Panel meeting in October 2023 was facilitated (through the provision of travel costs, meeting space and refreshments) by Becton, Dickinson and Company. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIf drugs and/or medical devices are cited in the article, please consult package insert and instructions for use of them to know indications, contraindications, and any other more detailed safety information.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCDC (2023) Moderate to Severe Traumatic Brain Injury is a Lifelong Condition. https://www.cdc.gov/traumaticbraininjury/pdf/moderate_to_severe_tbi_lifelong-a.pdfAccessed December 2023 \u003c/li\u003e\n\u003cli\u003eCenter TBI. Traumatic Brain Injury Fact sheets and Policy brief. https://www.centertbi.eu/files/news/21571f81-20b8-4860-a3dd-1f6e27d02b3d.pdfAccessed November 2023. \u003c/li\u003e\n\u003cli\u003eVrettou, C. S., \u0026amp; Mentzelopoulos, S. D. (2022). Second- and Third-Tier Therapies for Severe Traumatic Brain Injury. In \u003cem\u003eJournal of Clinical Medicine\u003c/em\u003e (Vol. 11, Issue 16). MDPI. https://doi.org/10.3390/jcm11164790 \u003c/li\u003e\n\u003cli\u003eMaas, A. I. R., Menon, D. K., Manley, G., et al. (2022). Traumatic brain injury: progress and challenges in prevention, clinical care, and research. In \u003cem\u003eThe Lancet Neurology\u003c/em\u003e (Vol. 21, Issue11, pp. 1004\u0026ndash;1060). Elsevier Ltd. https://doi.org/10.1016/S1474-4422(22)00309-X\u003c/li\u003e\n\u003cli\u003eMenon, D. K., Schwab, K., Wright, D. W., \u0026amp; Maas, A. I. (2010). Position statement: Definition of traumatic brain injury. In \u003cem\u003eArchives of Physical Medicine and Rehabilitation\u003c/em\u003e (Vol. 91, Issue 11, pp. 1637\u0026ndash;1640). W.B. Saunders. https://doi.org/10.1016/j.apmr.2010.05.017\u003c/li\u003e\n\u003cli\u003eWu, X., Tao, Y., Marsons, L., Dee, P., Yu, D., Guan, Y., \u0026amp; Zhou, X. (2021). The effectiveness of early prophylactic hypothermia in adult patients with traumatic brain injury: A systematic review and meta-analysis. In \u003cem\u003eAustralian Critical Care\u003c/em\u003e (Vol. 34, Issue 1, pp. 83\u0026ndash;91). Elsevier Ireland Ltd. https://doi.org/10.1016/j.aucc.2020.05.005 \u003c/li\u003e\n\u003cli\u003eHopkins Medicine (2023) Traumatic Brain Injury. https://www.hopkinsmedicine.org/health/conditions-and-diseases/traumatic-brain-injuryAccessed November 2023 \u003c/li\u003e\n\u003cli\u003eBMJ (2009) Rapid response to: Prehospital management of severe traumatic brain injury. https://www.bmj.com/rapid-response/2011/11/02/classifying-types-brain-injuryAccessed December 2023 \u003c/li\u003e\n\u003cli\u003eMadden, L. K., Hill, M., May, T. L., Human, T., Guanci, M. M. K., Jacobi, J., Moreda, M. V., \u0026amp; Badjatia, N. (2017). The Implementation of Targeted Temperature Management: An Evidence-Based Guideline from the Neurocritical Care Society. \u003cem\u003eNeurocritical Care\u003c/em\u003e, \u003cem\u003e27\u003c/em\u003e(3), 468\u0026ndash;487. https://doi.org/10.1007/s12028-017-0469-5 \u003c/li\u003e\n\u003cli\u003eNINDS (2023) Traumatic Brain Injury (TBI) https://www.ninds.nih.gov/healthinformation/disorders/traumatic-brain-injury-tbiAccessed December 2023 \u003c/li\u003e\n\u003cli\u003eHinson, H. E., Rowell, S., Morris, C., Lin, A. L., \u0026amp; Schreiber, M. A. (2018). Early fever after trauma: Does it matter? \u003cem\u003eJournal of Trauma and Acute Care Surgery\u003c/em\u003e, \u003cem\u003e84\u003c/em\u003e(1), 19\u0026ndash;24. https://doi.org/10.1097/TA.0000000000001627 \u003c/li\u003e\n\u003cli\u003eGreer, D. M., Funk, S. E., Reaven, N. L., Ouzounelli, M., \u0026amp; Uman, G. C. (2008). 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A management algorithm for adult patients with both brain oxygen and intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC). \u003cem\u003eIntensive Care Medicine\u003c/em\u003e, \u003cem\u003e46\u003c/em\u003e(5), 919\u0026ndash;929. https://doi.org/10.1007/s00134-019-05900-x \u003c/li\u003e\n\u003cli\u003eBarrett, D., \u0026amp; Heale, R. (2020). What are Delphi studies? In \u003cem\u003eEvidence-Based Nursing\u003c/em\u003e. BMJ Publishing Group. https://doi.org/10.1136/ebnurs-2020-103303 \u003c/li\u003e\n\u003cli\u003eMeshkat, B., Cowman, S., Gethin, G., Ryan, K., Wiley, M., Brick, A., Clarke, E., \u0026amp; Mulligan, E. (2014). Using an e-Delphi technique in achieving consensus across disciplines for developing best practice in day surgery in Ireland. \u003cem\u003eJournal of Hospital Administration\u003c/em\u003e, \u003cem\u003e3\u003c/em\u003e(4), 1. https://doi.org/10.5430/jha.v3n4p1 \u003c/li\u003e\n\u003cli\u003eEubank, B. H., Mohtadi, N. G., Lafave, M. R., Wiley, J. P., Bois, A. J., Boorman, R. S., \u0026amp; Sheps, D. M. (2016). Using the modified Delphi method to establish clinical consensus for the diagnosis and treatment of patients with rotator cuff pathology. \u003cem\u003eBMC Medical Research Methodology\u003c/em\u003e, \u003cem\u003e16\u003c/em\u003e(1). https://doi.org/10.1186/s12874-016-0165-8 \u003c/li\u003e\n\u003c/ol\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":"Traumatic Brain Injury, Intensive Care, Targeted Temperature Management, Temperature, Fever, Intracranial Pressure, Normothermia, Hypothermia","lastPublishedDoi":"10.21203/rs.3.rs-4021300/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4021300/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe aim of this panel was to develop consensus recommendations and guidance on targeted temperature management (TTM) in patients with severe traumatic brain injury (TBI) and in patients with moderate TBI who deteriorate and require admission to the intensive care unit (ICU) for intracranial pressure (ICP) management.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA group of 18 international neuro-intensive care experts in the acute management of TBI participated in a modified Delphi process. An online anonymised survey was completed ahead of the meeting, before the group convened to explore the level of consensus on TTM following TBI. Outputs from the meeting were combined into a further anonymous online survey round to finalise recommendations. Thresholds of \u0026ge;\u0026thinsp;16 out of 18 panel members in agreement (\u0026ge;\u0026thinsp;88%) for strong consensus and \u0026ge;\u0026thinsp;14 out of 18 (\u0026ge;\u0026thinsp;78%) for moderate consensus were prospectively set for all statements.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eStrong consensus was reached on TTM being essential for high-quality TBI care. It was recommended that temperature should be monitored continuously, and that fever should be promptly identified and managed in patients perceived to be at risk of secondary brain injury. Controlled normothermia (36.0\u0026deg;C\u0026ndash;37.5\u0026deg;C) was strongly recommended as a therapeutic option to be considered in tier 1 and 2 of the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC) ICP management protocol. Temperature management targets should be individualised based on the perceived risk of secondary brain injury and fever aetiology.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003e Based on a modified Delphi expert consensus process, this report aims to inform on best practices for TTM delivery for patients following TBI, and to highlight areas of need for further research to improve clinical guidelines in this setting.\u003c/p\u003e","manuscriptTitle":"Targeted Temperature Management following Traumatic Brain Injury: ESICM / NACCS Consensus Recommendations Guidelines","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-12 16:44:01","doi":"10.21203/rs.3.rs-4021300/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":"f3e6182a-bac0-4555-8acc-bc6132569f82","owner":[],"postedDate":"March 12th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-03-22T23:21:24+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-12 16:44:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4021300","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4021300","identity":"rs-4021300","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}