Buspirone and dexmedetomidine synergistically reduce the shivering threshold in humans
KeywordsRespiratory Depression Tympanic Membrane Dexmedetomidine Buspirone Therapeutic Hypothermia
Hypothermia may be therapeutically beneficial in stroke victims; however, it provokes vigorous shivering. Buspirone, a partial serotonin 1A antagonist, and dexmedetomidine, an α2 agonist, linearly reduce the shivering threshold (triggering core temperature) with minimal sedation and respiratory depression. We tested the hypothesis that buspirone and dexmedetomidine synergistically reduce the shivering threshold without producing substantial sedation or respiratory depression.
We studied four healthy male volunteers (18–40) on 4 days: (1) control (no drug); (2) buspirone only (60 mg orally); (3) dexmedetomidine only (target plasma concentration 0.6 ng/ml); and (4) combined buspirone and dexmedetomidine in the same doses. Lactated Ringer's solution (3°C) was infused via a central venous catheter to decrease tympanic membrane temperature by ≈2.2°C/hour; the mean skin temperature was maintained at 31°C.
An increase in oxygen consumption more than 25% of baseline identified the shivering threshold. Sedation was evaluated using the Observer's Assessment Sedation/Alertness scale. Two-way repeated-measures analysis of variance was used to identify interactions between drugs. Data are presented as means ± SDs; P < 0.05 was statistically significant.
The shivering thresholds were 36.4 ± 0.5°C on the control day; 34.9 ± 0.6°C (P < 0.01 from control) on the buspirone only day; 36.1 ± 0.6°C (P < 0.01 from control) on the dexmedetomidine only day; and 34.2 ± 0.5°C (P < 0.01 from control) on the combined buspirone and dexmedetomidine day. The calculated mean difference between the thresholds on the combined and the control days was 1.9 ± 0.4°C, while the measured mean difference derived from the difference between the combined and control days was 2.3 ± 0.4°C. There was only trivial sedation with either drug alone or in combination. The respiratory rate and end-tidal PCO2 were well preserved on all days.
Buspirone and dexmedetomidine act synergistically to reduce the shivering threshold with only mild sedation and no respiratory depression. This combination might be a valid treatment to prevent shivering in stroke patients during therapeutic hypothermia.