Perioperative Diabetes Insipidus Caused by Anesthetic Medications

A Review of the Literature

Lauren M. Van Decar, MD; Emily G. Reynolds, BS; Emily E. Sharpe, MD; Monica W. Harbell, MD; Heidi E. Kosiorek, MS; Molly B. Kraus, MD

Disclosures

Anesth Analg. 2022;134(1):82-89.

Abstract and Introduction

Abstract

Diabetes insipidus (DI) is an uncommon perioperative complication that can occur secondary to medications or surgical manipulation and can cause significant hypovolemia and electrolyte abnormalities. We reviewed and evaluated the current literature and identified 29 cases of DI related to medications commonly used in anesthesia such as propofol, dexmedetomidine, sevoflurane, ketamine, and opioids. This review summarizes the case reports and frequency of DI with each medication and presents possible pathophysiology. Medication-induced DI should be included in the differential diagnosis when intraoperative polyuria is identified. Early identification, removal of the agent, and treatment of intraoperative DI are critical to minimize complications.

Introduction

Diabetes insipidus (DI) is a rare condition associated with the inability to effectively autoregulate water balance resulting in polyuria, polydipsia, and electrolyte abnormalities. This disease process is generally classified into either central or nephrogenic dysfunction with either decreased release or ineffective response to antidiuretic hormone (ADH), respectively.

DI has many known etiologies including genetics, medications, and surgical manipulation. However, little data are available regarding DI associated with medications commonly used for anesthesia or sedation, and no previous reviews have been published. Many surgeries are several hours in duration and require prolonged medication infusions or administration. DI presenting during anesthesia is marked by significant urine output of >125 mL/h in adults, while other symptoms might be masked intraoperatively and become evident in the recovery room.^[1] This significant change in total body water content characteristically produces hypernatremia that, if not identified and corrected, can lead to potentially serious neurological symptoms including weakness, lethargy, myalgias, and coma. As patients receiving anesthesia or sedation are unable to adjust their fluid intake to compensate, it is the responsibility of the anesthesiologist to replete the volume and manage any electrolyte abnormalities.

To our knowledge, there has not been a review evaluating DI associated with anesthetic agents. Due to the serious complications associated with DI, it is imperative that anesthesiologists are able to identify signs of DI in their patients and consider all possible etiologies, including anesthetics. In this review, we have compiled and analyzed published cases of DI related to commonly used anesthetic medications. The aim is to determine whether DI is more commonly associated with certain anesthetics.

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Abstract and Introduction
Methods
Results
Discussion
Conclusions
References

Table 1. Reported Cases in the Literature of DI and Polyuria Related to an Anesthetic Agents
	First author	Patient (age/gender)	Surgery/procedure	Anesthetic agents administered					Presumed causative agent	Start of presumed causative agent to onset of signs of DI (h)	Return to normal UOP after end of exposure (h)	Full recovery in no. of days postexposure	DDAVP/vasopressin and dose	Length of anesthetic exposure (h)	Length of sedation exposure (d)
	First author	Patient (age/gender)	Surgery/procedure	Ketamine	Dexmedetomidine	Remifentanil	Sevoflurane	Propofol infusion	Presumed causative agent		Return to normal UOP after end of exposure (h)	Full recovery in no. of days postexposure	DDAVP/vasopressin and dose	Length of anesthetic exposure (h)	Length of sedation exposure (d)
1	Soo et al²	66/male	Posterior laminectomy with instrumentation from L2–L5 (spine/ortho)				X	X	Propofol	<1	<1	0	None	8
2	Kassebaum et al³	13/male	Parathyroidectomy (neuro/ENT)			X		X	Propofol	<1		1	DDAVP-unknown dose-responsive	5
3	Hong et al⁴	48/male	EDAS (vascular)			X	X		Inconclusive	3		1	DDAVP^a-5 μg divided doses-responsive
4	Hong et al⁴	46/female	Surgical revascularization for Moya Moya disease (vascular)			X	X		Inconclusive	3		1	DDAVP^a-2 μg divided doses-responsive
5	Granger and Ninan⁵	23/male	Anterior and posterior discectomy and spinal fusion (spine/ortho)		X	X		X	Dexmedetomidine	1		1	None	9
6	Ji and Liu⁶	71/female	Posterior spinal decompression and fusion (spine/ortho)		X	X	X		Dexmedetomidine	<1		0	None	7
7	Haldar et al⁷	25/female	Endoscopic endonasal excision of tuberculum sellae meningioma (neuro/ENT)		X		X		Dexmedetomidine	"Initial stages of surgery"	<1	2	None	6
8	Adams and Cassara⁸	12/female	Posterior spinal fusion (spine/ortho)	X	X	X		X	Dexmedetomidine	<1	<1	0	None	4.5
9	Greening et al⁹	40/male	Posterior spinal fusion (spine/ortho)	X	X				Dexmedetomidine	<1	<2	1	None	6
10	Pratt et al¹⁰	50/male	Sedation in ICU		X			X	Dexmedetomidine	2 h of increased dose (24 h after initial dose)	<1	0	None
11	Selvaraj and Panneerselvam¹¹	45/female	Mandibulectomy and free flap for carcinoma of buccal mucosa (neuro/ENT)		X			X	Dexmedetomidine	0.5		0	None
12	Xu and Wan¹²	72/male	Sarcoma resection (spine/ortho)		X	X	X		Dexmedetomidine	<1		1	None	7
13	Chow et al¹³	67/male	Sedation in ICU		X			X	Dexmedetomidine	Unclear		2	DDAVP^a-unknown dose
14	Muyldermans et al¹⁴	34/male	Sedation in ICU		X		X		Sevoflurane	"During the next 7 d"		5	DDAVP-2 μg		7
15	Schirle¹⁵	18/male	Free flap of left latissimus dorsi to left lower extremity (general)				X		Sevoflurane	<1	<1	0	None	1.5
16	Maussion et al¹⁶	34/male	Sedation in ICU	X			X	X	Sevoflurane	48		4	None		2
17	Cabibel et al¹⁷	27/male	Sedation in ICU	X			X	X	Sevoflurane	Unclear	Days	8	DDAVP^a-4 μg Nonresponsive		13
18	Cabibel et al¹⁷	43/male	Sedation in ICU	X			X	X	Sevoflurane	Unclear	Days	16	DDAVP-4 μg three times daily for 3 d (36 μg) Nonresponsive		4
19	Cabibel et al¹⁷	64/male	Sedation in ICU				X		Sevoflurane	Unclear	Days	>6	DDAVP^a-unknown dose Nonresponsive		6
20	Otsuka et al¹⁸	60/female	Left upper lobectomy (general)				X		Sevoflurane	Unclear	Days	14	DDAVP-unknown dose-responsive	4
21	Gaffar et al¹⁹	18/female	Internal carotid artery bypass (vascular)	X		X	X	X	Ketamine	2		0	DDAVP^a-4 μg
22	Kataria et al²⁰	42/male	Exploratory laparotomy and splenectomy (general)	X					Ketamine	"Shortly after initiation"	Days	5	DDAVP-2 μg daily-responsive	7
23	Hatab et al²¹	2/female	Sedation in PICU	X	X				Ketamine	7		Unclear	Vasopressin^a-180 mU over 12 h		7
24	Sakai et al²²	28/male	Sedation in ICU	X					Ketamine			1	DDAVP^a-30 μg divided doses-responsive		8
25	Herity et al²³	59/female	Sedation in ICU	X				X	Ketamine	32		1	Vasopressin^a DDAVP-10 μg		2
26	Herity et al²³	23/male	Sedation in ICU	X	X				Ketamine	55		0	Vasopressin^a		2
27	Ansar et al²⁴	29/male	Sinus surgery (neuro/ENT)				X		Inconclusive	2		1	DDAVP^a-2 μg	5
28	Chen et al²⁵	62/male	Neck dissection and free flap (neuro/ENT)		X		X	X	Dexmedetomidine	0.5	<2	0	Vasopressin	15
29	Kirschen et al²⁶	30/female	Cervical fusion (spine/ortho)	X	X			X	Dexmedetomidine	0.5	<2	0	DDAVP^a-23 μg Responsive

Blank spaces indicate insufficient data obtained from the case report.
Abbreviations: DDAVP, desmopressin; DI, diabetes insipidus; EDAS, encephaloduroarteriosynangiosis; ENT, otolaryngology; ICU, intensive care unit; neuro, neurosurgery; ortho, orthopedic surgery; PICU, pediatric intensive care unit; UOP, urine output.
^aDDAVP/vasopressin was administered intraoperatively or concurrently with sedation.

Table 2. Summary of Case Reports of Diabetes Insipidus or Polyuria Due to Anesthesia or Sedation
Demographics (N = 29)
Age (y)	39.7 (19.6), range: 2–72
Male	19 (65.5%)
Female	10 (34.5%)
Procedure type
Sedation	11 (37.9%)
Spine/ortho	7 (24.1%)
Neurosurgery/ENT	5 (17.2%)
Vascular	3 (12.5%)
General	3 (12.5%)
Exposure duration
Surgical cases (N = 18)
Mean (h)	6.5 (3.2), range: 1.5–15
Unspecified	5
Sedation cases (N = 11)
Mean (d)	5.67 (3.6), range 2–13
Unspecified	2
Treatment
DDAVP	15 (51.7%)
Vasopressin	4 (13.8%)
None	11 (37.9%)
Symptom resolution (no. of days postexposure)
Surgical cases (N = 18)
0	8 (44.4%)
1	7 (38.9%)
≥2	3 (16.7%)
Sedation cases (N = 11)
Unclear	1 (9.1%)
0	2 (18.2%)
1	2 (18.2%)
≥2	6 (54.5%)
Agents (present in report)
Sevoflurane	16 (55.2%)
Propofol	14 (48.2%)
Dexmedetomidine	14 (48.2%)
Ketamine	12 (41.4%)
Remifentanil	8 (27.6%)
Offending agent (as concluded by author)
Dexmedetomidine	11 (37.9%)
Sevoflurane	7 (24.1%)
Ketamine	6 (20.7%)
Inconclusive	3 (10.3%)
Propofol	2 (6.9%)
Remifentanil	0 (0%)

Data are expressed as mean (standard deviation) or count (%) where appropriate.
Abbreviations: DDAVP, desmopressin; ENT, otolaryngology; ortho, orthopedic surgery.