Dantrolene reduces the threshold and gain for shivering.
Dantrolene is used for treatment of life-threatening hyperthermia, yet its thermoregulatory effects are unknown. We tested the hypothesis that dantrolene reduces the threshold (triggering core temperature) and gain (incremental increase) of shivering. Healthy volunteers were evaluated on 2 random days: control and dantrolene (approximately 2.5 mg/kg plus a continuous infusion). In Study 1, 9 men were warmed until sweating was provoked and then cooled until arteriovenous shunt constriction and shivering occurred. Sweating was quantified on the chest using a ventilated capsule. Absolute right middle fingertip blood flow was quantified using venous-occlusion volume plethysmography. A sustained increase in oxygen consumption identified the shivering threshold. In Study 2, 9 men were given cold lactated Ringer's solution i.v. to reduce core temperature approximately 2 degrees C/h. Cooling was stopped when shivering intensity no longer increased with further core cooling. The gain of shivering was the slope of oxygen consumption versus core temperature regression. In Study 1, sweating and vasoconstriction thresholds were similar on both days. In contrast, shivering threshold decreased 0.3 +/- 0.3 degrees C, P = 0.004, on the dantrolene day. In Study 2, dantrolene decreased the shivering threshold from 36.7 +/- 0.2 to 36.3 +/- 0.3 degrees C, P = 0.01 and systemic gain from 353 +/- 144 to 211 +/- 93 mL.min(-1).degrees C(-1), P = 0.02. Thus, dantrolene substantially decreased the gain of shivering, but produced little central thermoregulatory inhibition.


CONCLUSIONS
Dantrolene substantially decreases the gain of shivering but produces relatively little central thermoregulatory inhibition. It thus seems unlikely to prove more effective than conventional muscle relaxants for treatment of life-threatening hyperthermia.
Lin
Chun-Ming
CM
Outcomes Research Institute, University of Louisville, Louisville, Kentucky 40202, USA.
Neeru
Sharma
S
Doufas
Anthony G
AG
Liem
Edwin
E
Muneer Shah
Yunus
Y
Wadhwa
Anupama
A
Lenhardt
Rainer
R
Bjorksten
Andrew
A
Taguchi
Akiko
A
Kabon
Barhara
B
Sessler
Daniel I
DI
Kurz
Andrea
A
D000293:Adolescent; D000328:Adult; D001831:Body Temperature / Q000502:physiology; D002245:Carbon Dioxide / Q000097:blood; D003620:Dantrolene / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D010108:Oxyhemoglobins / Q000378:metabolism; D012768:Shivering / Q000187:drug effects*; D012881:Skin Temperature / Q000187:drug effects / Q000502:physiology; D013546:Sweating / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D009125:Muscle Relaxants, Central; D010108:Oxyhemoglobins; D002245:Carbon Dioxide; D003620:Dantrolene