The Effect of Early Sedation With Dexmedetomidine on Body Temperature in Critically Ill Patients*

Abstract

OBJECTIVES: Previous case series reported an association between dexmedetomidine use and hyperthermia. Temperature data have not been systematically reported in previous randomized controlled trials evaluating dexmedetomidine. A causal link between dexmedetomidine administration and elevated temperature has not been demonstrated. DESIGN: Post hoc analysis. SETTING: Four ICUs in Australia and New Zealand. PATIENTS: About 703 mechanically ventilated ICU patients. INTERVENTIONS: Early sedation with dexmedetomidine versus usual care. MEASUREMENTS AND MAIN RESULTS: The primary outcome was mean daily body temperature. Secondary outcomes included the proportions of patients with body temperatures greater than or equal to 38.3°C and greater than or equal to 39°C, respectively. Outcomes were recorded for 5 days postrandomization in the ICU. The mean daily temperature was not different between the dexmedetomidine (n = 351) and usual care (n = 352) groups (36.84°C ± sd vs 36.78°C ± sd; p = 0.16). Over the first 5 ICU days, more dexmedetomidine group (vs usual care) patients had a temperature greater than or equal to 38.3°C (43.3% vs 32.7%, p = 0.004; absolute difference 10.6 percentage points) and greater than or equal to 39.0°C (19.4% vs 12.5%, p = 0.013; absolute difference 6.9 percentage points). Results were similar after adjusting for diagnosis, admitting temperature, age, weight, study site, sepsis occurrence, and the time from dexmedetomidine initiation to first hyperthermia recorded. There was a significant dose response relationship with temperature increasing by 0.30°C ±0.08 for every additional 1 μg/kg/hr of dexmedetomidine received p < 0.0002. 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.

A Retrospective Characterization of Dexmedetomidine-Suspected Fever and Its Consequences in Adult Critically Ill Patients

“…18 In contrast to our study, this analysis reported a high rate of hyperthermia, with a number needed to harm of 15 for patients with a temperature ≥39°C. 18 One potential explanation for this discrepancy is the use of strict selection criteria in our study, minimizing the possibility of potential confounders on elevations in body temperature. Another finding of the aforementioned study was that patients greater than 120 kg were more likely to develop increases in body temperature ( P = .02), which is consistent with a previous study conducted by the same group that identified obesity as a potential risk factor for DSF.…”

“…The findings of our study echo the results reported by Grayson and colleagues in a post-hoc analysis of the SPICE III Trial, in which significantly more patients treated with dexmedetomidine versus other sedatives had temperatures greater than or equal to 38.3°C (43.3% vs. 32.7%, P = .004) and 39.0°C (19.4% vs. 12.5%, P = .013). 18 In contrast to our study, this analysis reported a high rate of hyperthermia, with a number needed to harm of 15 for patients with a temperature ≥39°C. 18 One potential explanation for this discrepancy is the use of strict selection criteria in our study, minimizing the possibility of potential confounders on elevations in body temperature.…”

“…Another finding of the aforementioned study was that patients greater than 120 kg were more likely to develop increases in body temperature ( P = .02), which is consistent with a previous study conducted by the same group that identified obesity as a potential risk factor for DSF. 18,19 While our sample size was too small to determine any significant impact of weight on DSF, the median weight of patients in our study was 91.2 kg, which supports the idea of a potential dose-related response as our institution does not use a dose cap for patients >100 kg. Finally, the Grayson study did not observe a difference in culture acquisition or duration of antimicrobials in the dexmedetomidine group; however, no specific analysis was conducted on those who developed fever on dexmedetomidine.…”

“…Finally, the Grayson study did not observe a difference in culture acquisition or duration of antimicrobials in the dexmedetomidine group; however, no specific analysis was conducted on those who developed fever on dexmedetomidine. 18…”

“…1,[8][9][10][11][12]17 In a recent post-hoc analysis of a randomized controlled trial evaluating dexmedetomidine as a sedative agent, patients receiving dexmedetomidine experienced mild (≥38.3°C, 43.3%) and severe (≥39.0°C, 19.4%) temperature elevations more frequently than control patients. 18 The pathogenesis of dexmedetomidine-suspected fever (DSF) is largely unknown but may be due to suppression of neurotransmitters central to hypothalamic regulation of body temperature or hypersensitivity to the drug. 8,19 Due to the lack of recognition of this possible adverse effect, it is likely that potentially unnecessary, harmful, or costly interventions, including infectious diagnostic examinations and medical management, are occurring.…”