Is there an increased risk for malignant hyperthermia with use of dexmedetomidine?

Comment by InpharmD Researcher

Published evidence describing an association between dexmedetomidine and malignant hyperthermia (MH) is extremely limited. A comprehensive literature search identified a single case of suspected MH with dexmedetomidine use, requiring treatment with dantrolene and targeted temperature management for fever resolution (Table 1). In contrast, multiple reports describe successful use of dexmedetomidine as part of the sedation regimen in patients with known risk for MH without triggering adverse events. Additional literature has described drug-associated hyperthermia in critically ill patients receiving dexmedetomidine, with some studies suggesting a potentially higher incidence in obese patients or those undergoing cardiac surgery. Overall, the available evidence does not support an association between dexmedetomidine and MH, and the literature more commonly describes drug-related hyperthermia along with the safe use of dexmedetomidine in MH-susceptible patients.

Background

A 2021 systematic review evaluated the occurrence of fever or hyperthermia induced by dexmedetomidine in adult patients.. The systematic review identified 488 citations, narrowing down to 17 eligible studies, including 4 retrospective cohort studies, 1 case series, and 12 case reports. The evidence ranged from very low to low quality, with patient-level data indicating the uncommon nature of dexmedetomidine-associated fever. The median Naranjo score was 4, and dexmedetomidine doses varied from 0.1 to 2 μg/kg/h, highlighting obesity and cardiac surgery as potential risk factors. The 2021 review underscored the importance of clinicians considering dexmedetomidine-associated fever when evaluating elevated body temperature in critically ill patients, given that the true incidence remains unclear. Notably, the review revealed that patients receiving dexmedetomidine were significantly more likely to develop hyperthermia compared to those on standard sedatives like propofol. The findings also point to a higher incidence of thermodysregulation in cardiothoracic intensive care unit patients. Despite the lack of high-quality randomized controlled trials, the review suggests a need for heightened awareness and monitoring of this adverse effect within clinical settings, encouraging stewardship programs to factor in dexmedetomidine-associated fever in their patient evaluations. [1]

References: [1] Schurr JW, Ambrosi L, Lastra JL, McLaughlin KC, Hacobian G, Szumita PM. Fever Associated With Dexmedetomidine in Adult Acute Care Patients: A Systematic Review of the Literature. J Clin Pharmacol. 2021;61(7):848-856. doi:10.1002/jcph.1826
Relevant Prescribing Information

WARNINGS AND PRECAUTIONS

Hyperthermia or Pyrexia
Dexmedetomidine may induce hyperthermia or pyrexia, which may be resistant to traditional cooling methods, such as administration of cooled intravenous fluids and antipyretic medications. Discontinue dexmedetomidine if drug-related hyperthermia or pyrexia is suspected and monitor patients until body temperature normalizes. [2]

References: [2] Dexmedetomidine injection (solution, concentrate). Prescribing information. WG Critical Care, LLC. 2026
Literature Review

A search of the published medical literature revealed 6 studies investigating the researchable question:

Is there an increased risk for malignant hyperthermia with use of dexmedetomidine?

Level of evidence

B - One high-quality study or multiple studies with limitations  Read more→


Please see Tables 1-6 for your response.

Hex of the Dex: Dexmedetomidine Induced Malignant Hyperthermia in Myotonic Dystrophy

Design

 Case report

Case presentation

 A 40-year-old woman with morbid obesity and myotonic dystrophy type 1 (DM1) was hospitalized with pneumonia, fluid overload, presumed obesity hypoventilation syndrome, and chronic obstructive pulmonary disease. Despite treatment with antibiotics, high-flow nasal oxygen, and intermittent noninvasive ventilation, she developed respiratory decompensation on hospital day 3 requiring intubation and sedation with fentanyl and propofol. After gradual improvement, dexmedetomidine was initiated on the fourth day of mechanical ventilation to facilitate weaning from propofol and preparation for extubation. Approximately 24 hours after starting dexmedetomidine, the patient developed severe hyperthermia with a peak temperature of 42.2°C, raising concern for malignant hyperthermia. Dexmedetomidine was immediately discontinued, and treatment included acetaminophen, external cooling measures, ice packs, and cold intravenous fluids; however, the hyperthermia remained refractory. The patient subsequently received dantrolene and was placed on a noninvasive targeted temperature management system (Arctic Sun®). Her fever resolved without recurrence, and the authors concluded that dexmedetomidine was the likely cause of malignant hyperthermia in this patient with underlying myotonic dystrophy, with complete resolution occurring within 24 hours of drug discontinuation.

Study Author Conclusions

 This case emphasizes the temporal correlation between dexmedetomidine initiation and the onset of hyperthermia, along with its resolution following discontinuation, suggesting a causative link. This case also raises questions about the potential sensitivity of patients with DM1 to dexmedetomidine-induced hyperthermia, underscoring the need for vigilant monitoring and prompt intervention when using this medication in similar patient populations.
References:
[1] [1] Almerico K, Salimnia T, Dogra S. Hex of the Dex: Dexmedetomidine Induced Malignant Hyperthermia in Myotonic Dystrophy. Am J Respir Crit Care Med. 2022; 205(S1):A1575. Doi: 10.1164/ajrccm-conference.2022.205.1_MeetingAbstracts.A1575

Dexmedetomidine as the primary anesthetic agent during cardiac surgery in an infant with a family history of malignant hyperthermia

Design

  Case report

Case presentation

A 5-month-old infant (5.5 kg) with a strong maternal family history of malignant hyperthermia (MH) underwent surgical repair of a perimembranous ventricular septal defect and pulmonary stenosis using a non-triggering anesthetic regimen. Anesthesia included dexmedetomidine (1 mcg/kg loading dose followed by 1–2 mcg/kg/hr infusion), midazolam, ketamine, fentanyl, rocuronium, clonidine, and morphine. Cardiopulmonary bypass, hemodynamics, bispectral index monitoring, lactate concentrations, and glucose concentrations remained stable throughout the procedure. Separation from bypass was uneventful, the patient was extubated at the end of surgery, and postoperative analgesia was managed with fentanyl nurse-controlled analgesia. The patient was discharged home on postoperative day 4 without reported anesthetic complications or malignant hyperthermia.

Study Author Conclusions

Although anecdotal, our case provides further evidence for the role of dexmedetomidine in pediatric cardiac surgery and its role as the primary agent of a nontriggering anesthetic for patients with history of MH.
References:
[1] [1] Naguib A, McKee C, Phillips A, Tobias JD. Dexmedetomidine as the primary anesthetic agent during cardiac surgery in an infant with a family history of malignant hyperthermia. Saudi J Anaesth. 2011;5(4):426-429. doi:10.4103/1658-354X.87276

Dexmedetomidine as Part of Balanced Anesthesia Care in Children With Malignant Hyperthermia Risk and Egg Allergy

Design

 Case series

Case presentation 1

A 6-year-old boy weighing 27 kg with a family history of biopsy-confirmed malignant hyperthermia and a documented egg protein allergy underwent adenotonsillectomy using a dexmedetomidine-based anesthetic regimen. Premedication consisted of oral ketamine 5 mg/kg and oral midazolam 0.5 mg/kg, followed by administration of nitrous oxide (70%) in oxygen and dexmedetomidine at a loading dose of 1 mcg/kg over 10 minutes and a continuous infusion of 1 mcg/kg/hour. Tracheal intubation was facilitated with rocuronium 0.3 mg/kg, and maintenance anesthesia included nitrous oxide, morphine 0.1 mg/kg IV, and dexmedetomidine infusion. Additional medications included dexamethasone 0.5 mg/kg IV, ondansetron 0.15 mg/kg IV, and acetaminophen 40 mg/kg per rectum. Following the 40-minute procedure, dexmedetomidine and nitrous oxide were discontinued, morphine 0.05 mg/kg IV was administered, neuromuscular blockade was reversed with glycopyrrolate and neostigmine, and the patient was extubated 10 minutes later. His postoperative course was uneventful, with no evidence of malignant hyperthermia, and he was discharged home after 2 hours of postoperative monitoring.

Case presentation 2

A 12-year-old boy weighing 52 kg with a family history of biopsy-confirmed malignant hyperthermia and documented anaphylaxis to egg and soybean proteins underwent femoral nail placement for a traumatic femur fracture. After premedication with IV midazolam 2 mg, dexmedetomidine was administered as a loading dose of 1 mcg/kg over 10 minutes followed by a continuous infusion of 1 mcg/kg/hour, resulting in a decrease in BIS from 84–90 to 50–60. Supplemental oxygen (2 L/min) was provided, and spinal anesthesia was performed at the L3–4 interspace using isobaric bupivacaine 7.5 mg with epinephrine, achieving a bilateral T8 sensory block. During the 80-minute procedure, the dexmedetomidine infusion was maintained at 0.7–1 mcg/kg/hour to keep the BIS between 50 and 70, and the patient remained asleep throughout surgery with end-tidal CO₂ values ranging from 42–48 mmHg. At the conclusion of the procedure, the dexmedetomidine infusion was discontinued, and the patient was transferred to the post-anesthesia care unit. His postoperative course was uneventful, with no evidence of malignant hyperthermia or anesthetic complications, and he was discharged to the inpatient ward after 2 hours of temperature monitoring.

Case presentation 3

A 4-year-old boy weighing 22 kg with a family history of malignant hyperthermia and documented egg protein anaphylaxis underwent craniotomy and resection of a medulloblastoma. After premedication with oral ketamine 0.5 mg/kg and midazolam 0.5 mg/kg, anesthesia was induced using dexmedetomidine (1 mcg/kg loading dose over 10 minutes followed by 1 mcg/kg/hr infusion) and remifentanil (3 mcg/kg loading dose followed by 0.2 mcg/kg/min infusion), with rocuronium 1 mg/kg administered for tracheal intubation. Maintenance anesthesia consisted of 50% nitrous oxide in oxygen, remifentanil 0.2–0.5 mcg/kg/min, and dexmedetomidine 1 mcg/kg/hr, maintaining a BIS index of 36–54 during the 4-hour 20-minute procedure. At the conclusion of surgery, dexmedetomidine, remifentanil, and nitrous oxide were discontinued, postoperative analgesia was provided with morphine 0.05 mg/kg IV, and neuromuscular blockade was reversed with glycopyrrolate and neostigmine. The patient was extubated 10 minutes later and transferred to the pediatric intensive care unit, where his postoperative course was uneventful without evidence of malignant hyperthermia.

Study Author Conclusions

We report our anecdotal experience using dexmedetomidine as part of intraoperative anesthetic management in three pediatric patients with a family history of malignant hyperthermia and personal history of egg or soybean allergy, in whom propofol was avoided. In two cases, dexmedetomidine was incorporated into balanced general anesthesia alongside nitrous oxide and an opioid (morphine or remifentanil), while in the third case it was used as the primary sedative for monitored anesthesia care during spinal anesthesia. These cases suggest that dexmedetomidine may be a useful alternative sedative in selected pediatric patients when conventional agents such as propofol are contraindicated, although propofol remains an appropriate option in broader anesthesia practice.
References:
[1] [1] Dewhirst E, Naguib A, Tobias JD. Dexmedetomidine as part of balanced anesthesia care in children with malignant hyperthermia risk and egg allergy. J Pediatr Pharmacol Ther. 2011;16(2):113-117. doi:10.5863/1551-6776-16.2.113

General anesthesia with dexmedetomidine in a malignant hyperthermia-susceptible woman

Design

 Case report 

Case presentation

A 59-year-old woman with known malignant hyperthermia (MH) susceptibility, previously confirmed by muscle biopsy and with a strong family history of MH crisis in her mother and sister, underwent surgery using a dexmedetomidine-based, MH-safe anesthetic technique. After appropriate MH precautions were implemented (removal of triggering agents, anesthesia machine decontamination with circuit and CO₂ absorbent changes, and oxygen flushing at 10 L/min for 8 hours), the patient underwent standard monitoring including ECG, noninvasive blood pressure, oxygen saturation, and BIS. Dexmedetomidine was administered as a loading dose of 1 mcg/kg over 10 minutes followed by an infusion of 0.6 mcg/kg/h, during which a transient rise in blood pressure to 150/96 mmHg was observed; anesthesia was supplemented with fentanyl (50 mcg) and propofol titrated to effect (total 160 mg initially, then infusion 100–200 mcg/kg/min) along with 50% nitrous oxide to maintain BIS 40–55. Intraoperative and postoperative hemodynamics remained stable, propofol was discontinued 10 minutes prior to completion of surgery, and the patient awoke promptly with continuation of dexmedetomidine at 0.4 mcg/kg/h in the PACU for 30 minutes. She received hydromorphone 3 mg during her 1-day hospital stay and experienced no perioperative complications or adverse effects at 1-month follow-up.

Study Author Conclusions

We used dexmedetomidine in this patient based on our institutional experience with the agent, its favorable safety profile in MH–susceptible patients, and its pharmacologic mechanism, including inhibition of norepinephrine and epinephrine release, which are potential MH triggers. We also considered its anesthetic-sparing effects, which may reduce exposure to other agents while maintaining adequate depth of anesthesia. In this case, dexmedetomidine combined with MH-safe anesthetics was well tolerated, and our experience suggests that this approach may warrant further investigation in MH-susceptible patients.
References:
[1] [1] Unger RJ. General anesthesia with dexmedetomidine in a malignant hyperthermia-susceptible woman. Acta Anaesthesiol Scand. 2006;50(10):1312-1313. doi:10.1111/j.1399-6576.2006.01155.x
The Effect of Early Sedation With Dexmedetomidine on Body Temperature in Critically Ill Patients
Design

Post hoc analysis

N= 703
Objective To assess whether early sedation with dexmedetomidine in critically ill, mechanically ventilated ICU patients increases body temperature, the prevalence of mild body temperature elevations (≥ 38.3°C), and severe body temperature elevations (≥ 39°C)
Study Groups

Dexmedetomidine (n= 351)

Usual care (n= 352)
Inclusion Criteria Intubated, receiving mechanical ventilation, expected to remain on ventilatory support beyond the calendar day following randomization, and requiring immediate sedatives for comfort and safety
Exclusion Criteria Age under 18 years old, invasive ventilation in the ICU for longer than 12 hours before enrollment, and suspected or proven acute, primary brain or spinal cord injury
Methods Patients were randomly assigned to dexmedetomidine or usual care. Dexmedetomidine group received it as the primary sedative with a starting dose of 1 µg/kg/hr, up to 1.5 µg/kg/hr. Usual care group received propofol or other sedatives. Temperature data were collected for 5 days post-randomization
Duration November 2013 to February 2018
Outcome Measures

Primary: Mean daily body temperature

Secondary: Proportions of patients with body temperatures ≥ 38.3°C and ≥ 39°C
Baseline Characteristics   Dexmedetomidine (n= 351) Usual Care (n= 352)
Age, years 62.5 ± 15.5 63.6 ± 14.8
Male 212 (60.4%) 222 (63.1%)
Weight, kg 84.2 ± 25.7 86.5 ± 27.6
Weight > 120 kg 24 (6.8%) 32 (9.1%)
APACHE-II score 22.3 ± 7.91 21.4 ± 7.02
Suspected or proven sepsis 235 (67%) 232 (65.9%)
Body temperature, °C 36.7 (36.2–37.5)  36.6 (36.1–37.3)
Results Temperatures (n = 703) Dexmedetomidine (n= 351) Usual Care (n= 352) Estimate (95% CI) Interaction p
Mean daily temperature, °C 37.06 36.88 0.18 (0.00–0.36) 0.65
Highest daily temperature, °C 37.62 37.37 0.25 (0.05–0.45) 0.58
Highest temperature in the first 5 d in ICU ≥ 38.3°C 79 (50%) 58 (37.4%) 1.67 (1.07–2.62) 0.76
Highest temperature in the first 5 days in ICU ≥ 39°C 39 (24.7%) 26 (16.8%) 1.63 (0.93–2.83) 0.83
Adverse Events Potentially important elevations in body temperature associated with dexmedetomidine use. No statistically significant increase in mortality was observed, but a higher proportion of patients in the dexmedetomidine group experienced hyperthermia.
Study Author Conclusions Our study suggests potentially important elevations in body temperature are associated with early dexmedetomidine sedation in adults who are mechanically ventilated in the ICU.
Critique The study provides valuable insights into the effects of dexmedetomidine on body temperature, but the post hoc nature and limited power to detect clinical consequences are limitations. The open-label design may have introduced bias, and the lack of standardization in temperature measurement could affect results. The study's findings are consistent with previous case reports, but further research is needed to confirm clinical implications.
References:
[1] Grayson KE, Bailey M, Balachandran M, et al. The Effect of Early Sedation With Dexmedetomidine on Body Temperature in Critically Ill Patients. Crit Care Med. 2021;49(7):1118-1128. doi:10.1097/CCM.0000000000004935
Dexmedetomidine-associated hyperthermia: a retrospective cohort study of intensive care unit admissions between 2009 and 2016
Design

Retrospective cohort study

N= 9,782
Objective To examine the association between dexmedetomidine and temperature ≥39.5°C, including patient characteristics, temporality, and potential risk factors
Study Groups

Dexmedetomidine exposure (n= 611)

No dexmedetomidine exposure (n= 9,171)
Inclusion Criteria All ICU admissions between 1 July 2009 and 31 May 2016 with available temperature data
Exclusion Criteria Patients with missing temperature data
Methods Retrospective analysis of ICU admissions using electronic clinical information systems. Dexmedetomidine was administered intravenously at a dose of 0 to 1.5 g/kg/hour. Temperature data was analyzed for association with dexmedetomidine exposure. Multivariate analysis was conducted to adjust for confounders
Duration 1 July 2009 to 31 May 2016
Outcome Measures

Primary: Association between dexmedetomidine and temperature ≥39.5°C

Secondary: Risk factors such as open heart surgery and obesity
Baseline Characteristics   All Exposed Unexposed P-value
Age, years  61.8 ± 16.3 55.8 ± 16 61.7 ± 16.3 <0.001
Male 63.8% 74.6% 63.1% <0.001
Temperature ≥39.5°C 3.5% 12% 2.9% <0.001
BMI >35 kg/m2 12.8% 17.8% 12.3% <0.001
Ventilated 64.5% 91.5% 62.7% <0.001
Noradrenaline 48.3% 71.9% 46.8% <0.001
Proven infection 32.6% 59.6% 30.8% <0.001
Results   OR 95% CI P-value
Dexmedetomidine 1.61 1.1–2.3 <0.01
Obesity (BMI >35 kg/m2) 0.67 0.4–1.1 0.133
Dexmedetomidine and obesity 3.44 1.5–7.9 0.004
OHS admission 0.30 0.2–0.6 <0.001
Dexmedetomidine and OHS 2.72 1.1–6.9 0.035
Adverse Events Dexmedetomidine exposure is associated with an increased risk of hyperthermia. Possible risk factors are open heart surgery and obesity.
Study Author Conclusions Dexmedetomidine use is independently associated with high temperatures in ICU patients. Cessation of dexmedetomidine is recommended for patients with temperatures ≥39.5°C, especially those with risk factors such as obesity or post-open heart surgery.
Critique The study provides valuable insights into the association between dexmedetomidine and hyperthermia, highlighting potential risk factors. However, as an observational study, it can only infer associations, not causality. The single-center design and reliance on retrospective data may limit generalizability. Further research is needed to confirm findings and explore mechanisms.
References:
[1] Grayson K, Tobin AE, Lim TK, Reid DE, Ghani M. Dexmedetomidine-associated hyperthermia: a retrospective cohort study of intensive care unit admissions between 2009 and 2016. Anaesth Intensive Care. 2017;45(6):727-736. doi:10.1177/0310057X1704500613