Vasopressin Infusion Induced Diabetes Insipidus, a Case Report and Literature Review

Vasopressin Infusion Induced Diabetes Insipidus, a Case Report and Literature Review | 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 Case Report Vasopressin Infusion Induced Diabetes Insipidus, a Case Report and Literature Review Samaneh Rabiei, Kaye-Anne Newton, Vitaly Kantorovich This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7124867/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 09 Feb, 2026 Read the published version in SN Comprehensive Clinical Medicine → Version 1 posted 4 You are reading this latest preprint version Abstract Introduction: Vasopressin infusion has a crucial role in treating critical care patients needing circulatory support or for maintaining cerebral perfusion in patients with cerebral vasospasm. However, one of the potential side effects of treatment with continuous, high dose of vasopressin is development of diabetes insipidus (DI) at the level of hypothalamus/pituitary and kidneys. Here, we present a case of DI after discontinuing vasopressin infusion in a patient admitted with subarachnoid hemorrhage. Case Presentation: Patient is a 46-year-old male admitted with subarachnoid hemorrhage who underwent emergent balloon-assisted aneurysm coiling and external ventricular drain placement. While in the ICU, he developed elevated intracranial cerebral pressure. Therefore, vasopressin infusion was started for vasospasm treatment with subsequent discontinuation seven days later. The patient then developed significant polyuria and hypernatremia (consistent with DI) shortly after vasopressin infusion discontinuation. Low dose IV DDAVP was then started but he subsequently required higher dosing as high as 1 mcg every 4 hours to maintain normal urine output and serum sodium. Over the next 15 days, DDAVP tapered off with no recurrence of the DI. Conclusions: Vasopressin infusion-induced DI can happen at the level of hypothalamus/pituitary or kidneys. This phenomenon can be explained by depletion of AVP storage in the pituitary gland and/or desensitization of renal ADH receptors due to continuous exposure to supraphysiologic dose of vasopressin. The latter could be overcome by administration of high doses of DDAVP followed by slow tapering to restore receptor sensitization as was the case with our patient. Diabetes insipidus vasopressin infusion Figures Figure 1 Introduction Arginine vasopressin (AVP) is a hormone, synthesized in hypothalamic nuclei and released from posterior pituitary gland. It plays a crucial role in osmoregulation and vascular smooth muscle tonus. Diabetes insipidus (DI) is a disorder characterized by either decreased synthesis/secretion of antidiuretic hormone (ADH) or reduced response to ADH, leading to excessive free water loss ( 1 ). The Therapeutic use of AVP is based on its physiological action on two receptor subtypes, including V1R-driven vasoconstriction and V2R-modulated expression of aquaporin-2. The first mechanism is used in treatment of vascular shock, as well as aneurysmal subarachnoid hemorrhage (aSAH) to treat delayed cerebral ischemia (DCI) through an increase in cerebral perfusion ( 2 ). The second mechanism is directed toward an increase in cell membrane permeability in the apical cells of the collecting duct in the kidney, increasing water reabsorption in patients with diabetes insipidus (DI). It is used for parenteral boluses or intranasal/PO delivery in DI, whereas in shock and aSAH, delivery usually involves continuous IV infusion ( 3 ). Prolonged AVP infusion exposes V2Rs to continuous, high levels of the hormone, potentially promoting receptor desensitization. There are increasing number of case reports of transient diabetes insipidus (tDI or post AVP infusion diabetes insipidus - PAIDI) following the withdrawal of vasopressin infusion in both neurosurgical and medical ICU patients ( 2 , 4 – 9 ). We report a case of transient diabetes insipidus that occurred after discontinuation of vasopressin infusion in a patient with subarachnoid hemorrhage complicated by vasospasm. Case Presentation A 46-year-old male patient was admitted with altered mental status after experiencing severe headache, neck pain, and vomiting at home. He had a past medical history of hyperlipidemia, anxiety, and substance use during methadone therapy CT revealed a right anterior communicating artery aneurysm associated with intraparenchymal and subarachnoid hemorrhage.. The patient underwent successful aneurysm coiling, and right frontal craniotomy. ICU stay complicated by elevated intracranial pressure (ICP) reaching as high as 35 mmHg (NL range: 7–15 mmHg). Head CTA revealed moderate to severe vasospasm of the anterior cerebral artery (ACA) branches. A vasopressin infusion was subsequently started to maintain perfusion. The patient was maintained on vasopressin infusion for seven days. During this time, there was no administration of pharmacological agents known to cause diabetes insipidus, including amphotericin, ofloxacin, demeclocycline, lithium or foscarnet. Calcium levels remained within the normal range. Vasopressin infusion was stopped on the 8th day after ICU admission. A few hours after discontinuation of vasopressin infusion, the patient developed significant polyuria with 1.3 liters of urine output in one hour, hypernatremia at 160 mmol/L (reference range 135–146 mmol/L) and elevated serum osmolality at 344 mOsm/kg (normal reference range: 278–305 mOsm/kg). The clinical picture was highly suggestive of diabetes insipidus. Treatment with intravenous desmopressin (DDAVP) injections of 0.5 mcg every eight hours was started with the impression of post-AVP infusion diabetes insipidus. Owing to the suboptimal response and persistent polyuria, DDAVP was titrated to 1 mcg IV DDAVP every 4 hours to achieve normal urine output (UOP) and plasma sodium. Over 15 days, the DDAVP dose tapered off, with the patient’s UOP and electrolytes remaining within the normal range (Fig. 1 ). (Please see the graphs below.) Discussion In the critical care setting, AVP infusion is used for treating various types of shock or cerebral vasospasm. This hormone increases sympathetic activity and baroreflex sensitivity, as well as aldosterone secretion both directly and indirectly through the renin angiotensin aldosterone system (RAAS) ( 10 ). The different types of DI are classified by where the alterations to normal ADH physiology occur. AVP deficiency (AVP-D) formerly known as central DI is due to inadequate synthesis, secretion or storage of vasopressin by the hypothalamus, neurohypophysis and posterior pituitary gland ( 11 ). Compression of the pituitary stalk by macroadenoma, hemorrhage into the area, surgical severing, and autoimmune, infiltrative or inflammatory diseases can all lead to enough neuronal destruction to cause acquired AVP-D ( 5 ) ( 12 ). Alternately, nephrogenic DI or AVP resistance is frequently driven by renal insensitivity to the antidiuretic effect of AVP due to mutations in vasopressin receptors or aquaporin genes in pediatric population ( 5 , 13 , 14 ). In adults, nephrogenic DI is associated with certain medications (lithium, cisplatin, antibiotics), renal failure, electrolyte abnormalities( 13 ), or liver dysfunction especially during pregnancy. Gestational DI usually occurs at the end of the second or third trimester, due to excessive vasopressinase activity expressed by placental trophoblasts. This disorder usually remits spontaneously 4–6 weeks after delivery ( 15 ). In addition to the more familiar categories of DI, increasing attention has been given to transient diabetes insipidus after vasopressin infusion. Ferenchick et al. reported that the incidence of DI after cessation was 1.53% in patients with shock ( 6 ). These cases have been reported in patients suffering from septic shock ( 16 ) ( 17 ) ( 18 ), hemorrhagic shock ( 19 ), and those with recent neurosurgical ( 18 , 20 ) or cardiothoracic surgery ( 8 ). During their treatment, they all received continuous AVP infusion resulting in symptoms after discontinuation. Levinsky et al reported changes in urine concentration during prolonged administration of AVP and reported a reduced response to infusion of supraphysiologic doses of AVP ( 21 ), a phenomenon known as renal escape from antidiuresis. Later studies suggested the downregulation of V2 receptors as a possible underlying mechanism for this phenomenon ( 22 ). After Sato et al reported that V2 receptors are expressed on AVP neurons in rats, others have postulated that downregulation of these receptors can cause a decreased release of AVP ( 19 , 23 ). This relationship is further supported by the relatively high incidence of transient diabetes insipidus in cardiothoracic surgery patients receiving higher concentrations of vasopressin infusion ( 6 ). An alternative explanation could be an independent or concomitant negative feedback effect of exogenous high dose AVP infusion on the patient’s own endogenous AVP production or release ( 17 ). The effort in discovering of possible etiology can be further complicated by the fact that SAH itself, as well as associated neurosurgical procedures, are well known causes of transient and permanent central diabetes insipidus ( 16 ) ( 24 ). Notably, two distinct clinical settings of tDI/PAIDI have been recognized. In one scenario, patients receive AVP infusion as an aid to circulatory support, usually in the absence of overt DI. In the other scenario, patients suffer from DI (usually AVP-D) and receive AVP infusion as a selective pharmacologic treatment. This latter category is comprised of neurosurgical patients. We believe it is important to monitor any patient who has been receiving AVP infusion for clinical and laboratory signs of DI upon discontinuation of AVP infusion. Another possible strategy is gradual tapering of the infusion instead of abrupt discontinuation. However, there are no widely acceptable guidelines regarding the details of optimal tapering of AVP infusion. Owing to the paucity of literature on PAIDI, it is not known which discontinuation strategy has a lower rate of PAIDI. It is not known which group is more susceptible to PAIDI and which AVP infusion discontinuation strategy is associated with a lower risk of PAIDI. Regardless of the intent of AVP infusion, close monitoring of patients for signs of early DI appears to be the most reliable strategy for diagnosing PAIDI. Bohl et al reported on a series of six neurosurgical patients receiving AVP infusions who developed PAIDI ( 20 ). They recommended that any neurosurgical patient who is being treated with an AVP infusion should have all hypertonic sodium replacement and medications that induce DI (i.e., demeclocycline) held for 12 to 24 hours before discontinuation of the AVP infusion. After the AVP infusion is discontinued, urine output should be closely monitored, and any patient with a urine output greater than 200 mL/hr should have urine specific gravity and serum sodium levels checked every 2 hours. A dose of 2 mcg desmopressin should be administered twice a day to any patient who develops DI after discontinuation of AVP, and patients who develop severe hypernatremia refractory to desmopressin should restart AVP. This process should be repeated until the patient’s condition can be controlled on desmopressin alone ( 1 ). Our patient did not demonstrate recurrence of DI after gradual taper of IV DDAVP. To our knowledge, none of the reports on PAIDI that we reviewed described recurrence of DI after appropriate treatment of PAIDI. Therefore, after resolution of PAIDI, no further monitoring would be necessary. In conclusion we believe that increased awareness regarding transient diabetes insipidus after vasopressin infusion is important and that providers should be mindful of this potential complication to monitor patients’ urine output and electrolytes upon discontinuation of vasopressin infusion. Declarations Ethics approval and consent to participate This report was reviewed in our department ethic committee and was approved from an ethical standpoint for publication. Consent for publication This is an anonymous case report. The authors have not obtained a written consent from the patient for the purpose of this study as patient’s identification information will not be shared. Code availability No custom code was used in this study; hence, there is no code available. The datasets generated and/or analyzed during the current study are not publicly available because the datasets are within an electronic medical record system protected by HIPPA but de-identified datasets are available from the corresponding author on reasonable request. Data Availability The data included in this study is only comprised of primary data and cannot be shared openly to protect study participant privacy. The data is stored in our institution’s electronic medical record system and is available in a de-identified form upon request sent to the corresponding author. Competing interests The authors declare that they have no competing interests. Funding This study did not require any funding. Authors & contributions All authors made substantial contributions to the conception of the report. SR collected, analyzed, and interpreted the data. SR drafted the report. KAN and VC made substantial contributions to revising the report. All authors have agreed both to be personally accountable for the author’s own contributions and to ensure that questions related to the accuracy or integrity of any part of the work. All authors read and approved the final manuscript. Acknowledgements Not applicable References Boone M, Deen PM. Physiology and pathophysiology of the vasopressin-regulated renal water reabsorption. Pflugers Archiv : European journal of physiology. 2008;456(6):1005-24. Yousef KM, Crago E, Chang Y, Lagattuta TF, Mahmoud K, Shutter L, et al. Vasopressor Infusion After Subarachnoid Hemorrhage Does Not Increase Regional Cerebral Tissue Oxygenation. The Journal of neuroscience nursing : journal of the American Association of Neuroscience Nurses. 2018;50(4):225-30. Holt NF, Haspel KL. Vasopressin: a review of therapeutic applications. J Cardiothorac Vasc Anesth. 2010;24(2):330-47. Kristeller JL, Sterns RH. Transient diabetes insipidus after discontinuation of therapeutic vasopressin. Pharmacotherapy. 2004;24(4):541-5. Hui C, Khan M, Khan Suheb MZ, Radbel JM. Diabetes Insipidus. StatPearls. Treasure Island (FL): StatPearls Publishing Copyright © 2023, StatPearls Publishing LLC.; 2023. Ferenchick H, Cemalovic N, Ferguson N, Dicpinigaitis PV. Diabetes Insipidus After Discontinuation of Vasopressin Infusion for Treatment of Shock. Crit Care Med. 2019;47(12):e1008-e13. Bohl MA, Forseth J, Nakaji P. Transient Diabetes Insipidus After Discontinuation of Vasopressin in Neurological Intensive Care Unit Patients: Case Series and Literature Review. World Neurosurgery. 2017;97:479-88. Peskey CS, Mauermann WJ, Meyer SR, Abel MD. Vasopressin withdrawal associated with massive polyuria. The Journal of thoracic and cardiovascular surgery. 2009;138(2):491-2. Statlender L, Fishman G, Hellerman M, Kagan I, Bendavid I, Gorfil D, et al. Transient diabetes insipidus in critically ill COVID19 patients. J Crit Care. 2023;74:154211. Bankir L, Bichet DG, Morgenthaler NG. Vasopressin: physiology, assessment and osmosensation. J Intern Med. 2017;282(4):284-97. Persico RS, Viana MV, Viana LV. Diabetes Insipidus after Vasopressin Withdrawal: A Scoping Review. Indian J Crit Care Med. 2022;26(7):846-52. Tomkins M, Lawless S, Martin-Grace J, Sherlock M, Thompson CJ. Diagnosis and Management of Central Diabetes Insipidus in Adults. J Clin Endocrinol Metab. 2022;107(10):2701-15. Moeller HB, Rittig S, Fenton RA. Nephrogenic diabetes insipidus: essential insights into the molecular background and potential therapies for treatment. Endocr Rev. 2013;34(2):278-301. Robertson GL. Diabetes insipidus: Differential diagnosis and management. Best Pract Res Clin Endocrinol Metab. 2016;30(2):205-18. Marques P, Gunawardana K, Grossman A. Transient diabetes insipidus in pregnancy. Endocrinol Diabetes Metab Case Rep. 2015;2015:150078. Carman N, Kay C, Petersen A, Kravchenko M, Tate J. Transient Central Diabetes Insipidus after Discontinuation of Vasopressin. Case reports in endocrinology. 2019;2019:4189525. Pata R, Nway N, Logvinsky IK, Lutaya I, Chowdhury T. Sudden Vasopressin Withdrawal Causing Transient Central Diabetes Insipidus: A Case Report. Cureus. 2022;14(5):e24966. Urban JA, Zirille F, Kiser TH, Aschner Y. Why So Salty? Transient Diabetes Insipidus After Discontinuation of Vasopressin. Ann Intern Med Clin Cases. 2022;1. Cristiano EA, Harris A, Grdinovac K. Transient Central Diabetes Insipidus Occurring After Vasopressin Infusion. AACE clinical case reports. 2022;8(1):8-10. Bohl MA, Forseth J, Nakaji P. Transient Diabetes Insipidus After Discontinuation of Vasopressin in Neurological Intensive Care Unit Patients: Case Series and Literature Review. World Neurosurg. 2017;97:479-88. Levinsky NG, Davidson DG, Berliner RW. Changes in urine concentration during prolonged administration of vasopressin and water. Am J Physiol. 1959;196(2):451-6. Tian Y, Sandberg K, Murase T, Baker EA, Speth RC, Verbalis JG. Vasopressin V2 receptor binding is down-regulated during renal escape from vasopressin-induced antidiuresis. Endocrinology. 2000;141(1):307-14. Sato K, Numata T, Saito T, Ueta Y, Okada Y. V(2) receptor-mediated autocrine role of somatodendritic release of AVP in rat vasopressin neurons under hypo-osmotic conditions. Sci Signal. 2011;4(157):ra5. Qureshi AI, Suri MF, Sung GY, Straw RN, Yahia AM, Saad M, et al. Prognostic significance of hypernatremia and hyponatremia among patients with aneurysmal subarachnoid hemorrhage. Neurosurgery. 2002;50(4):749-55; discussion 55-6. Additional Declarations No competing interests reported. Supplementary Files SamanehRabieiCAREchecklistEnglishField.pdf Cite Share Download PDF Status: Published Journal Publication published 09 Feb, 2026 Read the published version in SN Comprehensive Clinical Medicine → Version 1 posted Editorial decision: Revision requested 28 Jul, 2025 Editor assigned by journal 24 Jul, 2025 Submission checks completed at journal 24 Jul, 2025 First submitted to journal 14 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7124867","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":491814734,"identity":"629942ec-e0f8-4fe6-8a88-ea62cd3a2e28","order_by":0,"name":"Samaneh Rabiei","email":"data:image/png;base64,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","orcid":"","institution":"Hartford Hospital Hartford","correspondingAuthor":true,"prefix":"","firstName":"Samaneh","middleName":"","lastName":"Rabiei","suffix":""},{"id":491814735,"identity":"364f4df9-3d42-4cae-ad57-2ee4122a5d89","order_by":1,"name":"Kaye-Anne Newton","email":"","orcid":"","institution":"Hartford Hospital Hartford","correspondingAuthor":false,"prefix":"","firstName":"Kaye-Anne","middleName":"","lastName":"Newton","suffix":""},{"id":491814736,"identity":"a9478eec-fcd8-4d86-88f1-0882107fd745","order_by":2,"name":"Vitaly Kantorovich","email":"","orcid":"","institution":"Hartford Hospital Hartford","correspondingAuthor":false,"prefix":"","firstName":"Vitaly","middleName":"","lastName":"Kantorovich","suffix":""}],"badges":[],"createdAt":"2025-07-15 00:08:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7124867/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7124867/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s42399-025-02173-y","type":"published","date":"2026-02-09T15:58:04+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":88646058,"identity":"2347332e-60f0-454d-8f24-6fd171d7321c","added_by":"auto","created_at":"2025-08-08 16:32:40","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":266358,"visible":true,"origin":"","legend":"\u003cp\u003eConcurrent timeline of serum sodium level and urine output VPI: vasopressin infusion\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7124867/v1/86fe02c85aba3ce91c1c46bf.png"},{"id":102785769,"identity":"deef1a68-22bb-4579-9d45-0876a08bb284","added_by":"auto","created_at":"2026-02-16 16:09:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":571722,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7124867/v1/167fc600-5177-4ee9-a44b-796c84dc1c4e.pdf"},{"id":88646059,"identity":"a36a5a38-fbd9-4a36-ad1b-0d8f33dcac0f","added_by":"auto","created_at":"2025-08-08 16:32:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":706240,"visible":true,"origin":"","legend":"","description":"","filename":"SamanehRabieiCAREchecklistEnglishField.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7124867/v1/68a4b254bd91b4fbc7bbb373.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Vasopressin Infusion Induced Diabetes Insipidus, a Case Report and Literature Review","fulltext":[{"header":"Introduction","content":"\u003cp\u003eArginine vasopressin (AVP) is a hormone, synthesized in hypothalamic nuclei and released from posterior pituitary gland. It plays a crucial role in osmoregulation and vascular smooth muscle tonus. Diabetes insipidus (DI) is a disorder characterized by either decreased synthesis/secretion of antidiuretic hormone (ADH) or reduced response to ADH, leading to excessive free water loss (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe Therapeutic use of AVP is based on its physiological action on two receptor subtypes, including V1R-driven vasoconstriction and V2R-modulated expression of aquaporin-2. The first mechanism is used in treatment of vascular shock, as well as aneurysmal subarachnoid hemorrhage (aSAH) to treat delayed cerebral ischemia (DCI) through an increase in cerebral perfusion (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The second mechanism is directed toward an increase in cell membrane permeability in the apical cells of the collecting duct in the kidney, increasing water reabsorption in patients with diabetes insipidus (DI). It is used for parenteral boluses or intranasal/PO delivery in DI, whereas in shock and aSAH, delivery usually involves continuous IV infusion (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eProlonged AVP infusion exposes V2Rs to continuous, high levels of the hormone, potentially promoting receptor desensitization. There are increasing number of case reports of transient diabetes insipidus (tDI or post AVP infusion diabetes insipidus - PAIDI) following the withdrawal of vasopressin infusion in both neurosurgical and medical ICU patients (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e–\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eWe report a case of transient diabetes insipidus that occurred after discontinuation of vasopressin infusion in a patient with subarachnoid hemorrhage complicated by vasospasm.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 46-year-old male patient was admitted with altered mental status after experiencing severe headache, neck pain, and vomiting at home. He had a past medical history of hyperlipidemia, anxiety, and substance use during methadone therapy CT revealed a right anterior communicating artery aneurysm associated with intraparenchymal and subarachnoid hemorrhage..\u003c/p\u003e\u003cp\u003eThe patient underwent successful aneurysm coiling, and right frontal craniotomy. ICU stay complicated by elevated intracranial pressure (ICP) reaching as high as 35 mmHg (NL range: 7–15 mmHg). Head CTA revealed moderate to severe vasospasm of the anterior cerebral artery (ACA) branches. A vasopressin infusion was subsequently started to maintain perfusion. The patient was maintained on vasopressin infusion for seven days. During this time, there was no administration of pharmacological agents known to cause diabetes insipidus, including amphotericin, ofloxacin, demeclocycline, lithium or foscarnet. Calcium levels remained within the normal range.\u003c/p\u003e\u003cp\u003eVasopressin infusion was stopped on the 8th day after ICU admission. A few hours after discontinuation of vasopressin infusion, the patient developed significant polyuria with 1.3 liters of urine output in one hour, hypernatremia at 160 mmol/L (reference range 135–146 mmol/L) and elevated serum osmolality at 344 mOsm/kg (normal reference range: 278–305 mOsm/kg). The clinical picture was highly suggestive of diabetes insipidus. Treatment with intravenous desmopressin (DDAVP) injections of 0.5 mcg every eight hours was started with the impression of post-AVP infusion diabetes insipidus. Owing to the suboptimal response and persistent polyuria, DDAVP was titrated to 1 mcg IV DDAVP every 4 hours to achieve normal urine output (UOP) and plasma sodium. Over 15 days, the DDAVP dose tapered off, with the patient’s UOP and electrolytes remaining within the normal range (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). (Please see the graphs below.)\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn the critical care setting, AVP infusion is used for treating various types of shock or cerebral vasospasm. This hormone increases sympathetic activity and baroreflex sensitivity, as well as aldosterone secretion both directly and indirectly through the renin angiotensin aldosterone system (RAAS) (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe different types of DI are classified by where the alterations to normal ADH physiology occur. AVP deficiency (AVP-D) formerly known as central DI is due to inadequate synthesis, secretion or storage of vasopressin by the hypothalamus, neurohypophysis and posterior pituitary gland (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Compression of the pituitary stalk by macroadenoma, hemorrhage into the area, surgical severing, and autoimmune, infiltrative or inflammatory diseases can all lead to enough neuronal destruction to cause acquired AVP-D (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Alternately, nephrogenic DI or AVP resistance is frequently driven by renal insensitivity to the antidiuretic effect of AVP due to mutations in vasopressin receptors or aquaporin genes in pediatric population (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). In adults, nephrogenic DI is associated with certain medications (lithium, cisplatin, antibiotics), renal failure, electrolyte abnormalities(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e), or liver dysfunction especially during pregnancy. Gestational DI usually occurs at the end of the second or third trimester, due to excessive vasopressinase activity expressed by placental trophoblasts. This disorder usually remits spontaneously 4\u0026ndash;6 weeks after delivery (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn addition to the more familiar categories of DI, increasing attention has been given to transient diabetes insipidus after vasopressin infusion. Ferenchick et al. reported that the incidence of DI after cessation was 1.53% in patients with shock (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). These cases have been reported in patients suffering from septic shock (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e), hemorrhagic shock (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), and those with recent neurosurgical (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) or cardiothoracic surgery (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). During their treatment, they all received continuous AVP infusion resulting in symptoms after discontinuation. Levinsky et al reported changes in urine concentration during prolonged administration of AVP and reported a reduced response to infusion of supraphysiologic doses of AVP (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e), a phenomenon known as renal escape from antidiuresis. Later studies suggested the downregulation of V2 receptors as a possible underlying mechanism for this phenomenon (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). After Sato et al reported that V2 receptors are expressed on AVP neurons in rats, others have postulated that downregulation of these receptors can cause a decreased release of AVP (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). This relationship is further supported by the relatively high incidence of transient diabetes insipidus in cardiothoracic surgery patients receiving higher concentrations of vasopressin infusion (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). An alternative explanation could be an independent or concomitant negative feedback effect of exogenous high dose AVP infusion on the patient\u0026rsquo;s own endogenous AVP production or release (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). The effort in discovering of possible etiology can be further complicated by the fact that SAH itself, as well as associated neurosurgical procedures, are well known causes of transient and permanent central diabetes insipidus (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eNotably, two distinct clinical settings of tDI/PAIDI have been recognized. In one scenario, patients receive AVP infusion as an aid to circulatory support, usually in the absence of overt DI. In the other scenario, patients suffer from DI (usually AVP-D) and receive AVP infusion as a selective pharmacologic treatment. This latter category is comprised of neurosurgical patients. We believe it is important to monitor any patient who has been receiving AVP infusion for clinical and laboratory signs of DI upon discontinuation of AVP infusion. Another possible strategy is gradual tapering of the infusion instead of abrupt discontinuation. However, there are no widely acceptable guidelines regarding the details of optimal tapering of AVP infusion. Owing to the paucity of literature on PAIDI, it is not known which discontinuation strategy has a lower rate of PAIDI. It is not known which group is more susceptible to PAIDI and which AVP infusion discontinuation strategy is associated with a lower risk of PAIDI. Regardless of the intent of AVP infusion, close monitoring of patients for signs of early DI appears to be the most reliable strategy for diagnosing PAIDI. Bohl et al reported on a series of six neurosurgical patients receiving AVP infusions who developed PAIDI (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). They recommended that any neurosurgical patient who is being treated with an AVP infusion should have all hypertonic sodium replacement and medications that induce DI (i.e., demeclocycline) held for 12 to 24 hours before discontinuation of the AVP infusion. After the AVP infusion is discontinued, urine output should be closely monitored, and any patient with a urine output greater than 200 mL/hr should have urine specific gravity and serum sodium levels checked every 2 hours. A dose of 2 mcg desmopressin should be administered twice a day to any patient who develops DI after discontinuation of AVP, and patients who develop severe hypernatremia refractory to desmopressin should restart AVP. This process should be repeated until the patient\u0026rsquo;s condition can be controlled on desmopressin alone (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eOur patient did not demonstrate recurrence of DI after gradual taper of IV DDAVP. To our knowledge, none of the reports on PAIDI that we reviewed described recurrence of DI after appropriate treatment of PAIDI. Therefore, after resolution of PAIDI, no further monitoring would be necessary.\u003c/p\u003e\u003cp\u003eIn conclusion we believe that increased awareness regarding transient diabetes insipidus after vasopressin infusion is important and that providers should be mindful of this potential complication to monitor patients\u0026rsquo; urine output and electrolytes upon discontinuation of vasopressin infusion.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis report was reviewed in our department ethic committee and was approved from an ethical standpoint for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis is an anonymous case report. The authors have not obtained a written consent from the patient for the purpose of this study as patient\u0026rsquo;s identification information will not be shared.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCode availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo custom code was used in this study; hence, there is no code available.\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available because the datasets are within an electronic medical record system protected by HIPPA but de-identified datasets are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data included in this study is only comprised of primary data and cannot be shared openly to protect study participant privacy. The data is stored in our institution\u0026rsquo;s electronic medical record system and is available in a de-identified form upon request sent to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study did not require any funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors \u0026amp; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors made substantial contributions to the conception of the report.\u003c/p\u003e\n\u003cp\u003eSR collected, analyzed, and interpreted the data.\u003c/p\u003e\n\u003cp\u003eSR drafted the report.\u003c/p\u003e\n\u003cp\u003eKAN and VC made substantial contributions to revising the report.\u003c/p\u003e\n\u003cp\u003eAll authors have agreed both to be personally accountable for the author\u0026rsquo;s own contributions and to ensure that questions related to the accuracy or integrity of any part of the work. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003cbr\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBoone M, Deen PM. Physiology and pathophysiology of the vasopressin-regulated renal water reabsorption. Pflugers Archiv : European journal of physiology. 2008;456(6):1005-24.\u003c/li\u003e\n\u003cli\u003eYousef KM, Crago E, Chang Y, Lagattuta TF, Mahmoud K, Shutter L, et al. Vasopressor Infusion After Subarachnoid Hemorrhage Does Not Increase Regional Cerebral Tissue Oxygenation. The Journal of neuroscience nursing : journal of the American Association of Neuroscience Nurses. 2018;50(4):225-30.\u003c/li\u003e\n\u003cli\u003eHolt NF, Haspel KL. Vasopressin: a review of therapeutic applications. J Cardiothorac Vasc Anesth. 2010;24(2):330-47.\u003c/li\u003e\n\u003cli\u003eKristeller JL, Sterns RH. Transient diabetes insipidus after discontinuation of therapeutic vasopressin. Pharmacotherapy. 2004;24(4):541-5.\u003c/li\u003e\n\u003cli\u003eHui C, Khan M, Khan Suheb MZ, Radbel JM. Diabetes Insipidus. StatPearls. Treasure Island (FL): StatPearls Publishing Copyright \u0026copy; 2023, StatPearls Publishing LLC.; 2023.\u003c/li\u003e\n\u003cli\u003eFerenchick H, Cemalovic N, Ferguson N, Dicpinigaitis PV. Diabetes Insipidus After Discontinuation of Vasopressin Infusion for Treatment of Shock. Crit Care Med. 2019;47(12):e1008-e13.\u003c/li\u003e\n\u003cli\u003eBohl MA, Forseth J, Nakaji P. Transient Diabetes Insipidus After Discontinuation of Vasopressin in Neurological Intensive Care Unit Patients: Case Series and Literature Review. World Neurosurgery. 2017;97:479-88.\u003c/li\u003e\n\u003cli\u003ePeskey CS, Mauermann WJ, Meyer SR, Abel MD. Vasopressin withdrawal associated with massive polyuria. The Journal of thoracic and cardiovascular surgery. 2009;138(2):491-2.\u003c/li\u003e\n\u003cli\u003eStatlender L, Fishman G, Hellerman M, Kagan I, Bendavid I, Gorfil D, et al. Transient diabetes insipidus in critically ill COVID19 patients. J Crit Care. 2023;74:154211.\u003c/li\u003e\n\u003cli\u003eBankir L, Bichet DG, Morgenthaler NG. Vasopressin: physiology, assessment and osmosensation. J Intern Med. 2017;282(4):284-97.\u003c/li\u003e\n\u003cli\u003ePersico RS, Viana MV, Viana LV. Diabetes Insipidus after Vasopressin Withdrawal: A Scoping Review. Indian J Crit Care Med. 2022;26(7):846-52.\u003c/li\u003e\n\u003cli\u003eTomkins M, Lawless S, Martin-Grace J, Sherlock M, Thompson CJ. Diagnosis and Management of Central Diabetes Insipidus in Adults. J Clin Endocrinol Metab. 2022;107(10):2701-15.\u003c/li\u003e\n\u003cli\u003eMoeller HB, Rittig S, Fenton RA. Nephrogenic diabetes insipidus: essential insights into the molecular background and potential therapies for treatment. Endocr Rev. 2013;34(2):278-301.\u003c/li\u003e\n\u003cli\u003eRobertson GL. Diabetes insipidus: Differential diagnosis and management. Best Pract Res Clin Endocrinol Metab. 2016;30(2):205-18.\u003c/li\u003e\n\u003cli\u003eMarques P, Gunawardana K, Grossman A. Transient diabetes insipidus in pregnancy. Endocrinol Diabetes Metab Case Rep. 2015;2015:150078.\u003c/li\u003e\n\u003cli\u003eCarman N, Kay C, Petersen A, Kravchenko M, Tate J. Transient Central Diabetes Insipidus after Discontinuation of Vasopressin. Case reports in endocrinology. 2019;2019:4189525.\u003c/li\u003e\n\u003cli\u003ePata R, Nway N, Logvinsky IK, Lutaya I, Chowdhury T. Sudden Vasopressin Withdrawal Causing Transient Central Diabetes Insipidus: A Case Report. Cureus. 2022;14(5):e24966.\u003c/li\u003e\n\u003cli\u003eUrban JA, Zirille F, Kiser TH, Aschner Y. Why So Salty? Transient Diabetes Insipidus After Discontinuation of Vasopressin. Ann Intern Med Clin Cases. 2022;1.\u003c/li\u003e\n\u003cli\u003eCristiano EA, Harris A, Grdinovac K. Transient Central Diabetes Insipidus Occurring After Vasopressin Infusion. AACE clinical case reports. 2022;8(1):8-10.\u003c/li\u003e\n\u003cli\u003eBohl MA, Forseth J, Nakaji P. Transient Diabetes Insipidus After Discontinuation of Vasopressin in Neurological Intensive Care Unit Patients: Case Series and Literature Review. World Neurosurg. 2017;97:479-88.\u003c/li\u003e\n\u003cli\u003eLevinsky NG, Davidson DG, Berliner RW. Changes in urine concentration during prolonged administration of vasopressin and water. Am J Physiol. 1959;196(2):451-6.\u003c/li\u003e\n\u003cli\u003eTian Y, Sandberg K, Murase T, Baker EA, Speth RC, Verbalis JG. Vasopressin V2 receptor binding is down-regulated during renal escape from vasopressin-induced antidiuresis. Endocrinology. 2000;141(1):307-14.\u003c/li\u003e\n\u003cli\u003eSato K, Numata T, Saito T, Ueta Y, Okada Y. V(2) receptor-mediated autocrine role of somatodendritic release of AVP in rat vasopressin neurons under hypo-osmotic conditions. Sci Signal. 2011;4(157):ra5.\u003c/li\u003e\n\u003cli\u003eQureshi AI, Suri MF, Sung GY, Straw RN, Yahia AM, Saad M, et al. Prognostic significance of hypernatremia and hyponatremia among patients with aneurysmal subarachnoid hemorrhage. Neurosurgery. 2002;50(4):749-55; discussion 55-6.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Diabetes insipidus, vasopressin, infusion","lastPublishedDoi":"10.21203/rs.3.rs-7124867/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7124867/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIntroduction: Vasopressin infusion has a crucial role in treating critical care patients needing circulatory support or for maintaining cerebral perfusion in patients with cerebral vasospasm. However, one of the potential side effects of treatment with continuous, high dose of vasopressin is development of diabetes insipidus (DI) at the level of hypothalamus/pituitary and kidneys. Here, we present a case of DI after discontinuing vasopressin infusion in a patient admitted with subarachnoid hemorrhage.\u003c/p\u003e\u003cp\u003eCase Presentation: Patient is a 46-year-old male admitted with subarachnoid hemorrhage who underwent emergent balloon-assisted aneurysm coiling and external ventricular drain placement. While in the ICU, he developed elevated intracranial cerebral pressure. Therefore, vasopressin infusion was started for vasospasm treatment with subsequent discontinuation seven days later. The patient then developed significant polyuria and hypernatremia (consistent with DI) shortly after vasopressin infusion discontinuation. Low dose IV DDAVP was then started but he subsequently required higher dosing as high as 1 mcg every 4 hours to maintain normal urine output and serum sodium. Over the next 15 days, DDAVP tapered off with no recurrence of the DI.\u003c/p\u003e\u003cp\u003eConclusions: Vasopressin infusion-induced DI can happen at the level of hypothalamus/pituitary or kidneys. This phenomenon can be explained by depletion of AVP storage in the pituitary gland and/or desensitization of renal ADH receptors due to continuous exposure to supraphysiologic dose of vasopressin. The latter could be overcome by administration of high doses of DDAVP followed by slow tapering to restore receptor sensitization as was the case with our patient.\u003c/p\u003e","manuscriptTitle":"Vasopressin Infusion Induced Diabetes Insipidus, a Case Report and Literature Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-08 16:32:35","doi":"10.21203/rs.3.rs-7124867/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-28T08:22:08+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-24T15:06:53+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-24T12:28:38+00:00","index":"","fulltext":""},{"type":"submitted","content":"SN Comprehensive Clinical Medicine","date":"2025-07-15T00:05:22+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"d1f72332-5d5b-47af-8b32-ed0404aba0cb","owner":[],"postedDate":"August 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-16T16:07:54+00:00","versionOfRecord":{"articleIdentity":"rs-7124867","link":"https://doi.org/10.1007/s42399-025-02173-y","journal":{"identity":"sn-comprehensive-clinical-medicine","isVorOnly":false,"title":"SN Comprehensive Clinical Medicine"},"publishedOn":"2026-02-09 15:58:04","publishedOnDateReadable":"February 9th, 2026"},"versionCreatedAt":"2025-08-08 16:32:35","video":"","vorDoi":"10.1007/s42399-025-02173-y","vorDoiUrl":"https://doi.org/10.1007/s42399-025-02173-y","workflowStages":[]},"version":"v1","identity":"rs-7124867","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7124867","identity":"rs-7124867","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}