Nefopam and Alfentanil Additively Reduce the Shivering Threshold in Humans whereas Nefopam and Clonidine Do Not

Abstract

Nefopam and alfentanil additively reduce the shivering threshold, but nefopam and clonidine do not.

Optimal Management of Shivering During Therapeutic Hypothermia After Cardiac Arrest

“…Numerous pharmacological agents 7,10,[16][17][18][19][20][21][22][23][24][25] (Table 2) that reduce the vasoconstriction and shivering thresholds have been used to manage shivering during therapeutic hypothermia. According to the ILCOR, 3 sedative and hypnotic agents are often used to decrease metabolic demand and facilitate mechanical ventilation in comatose patients who lack signs of awakening within the first 5 to 10 minutes after return of spontaneous circulation.…”

“…Alfonsi et al 10 found that the combination of nefopam and clonidine reduced the shivering threshold by 0.7ºC (SD, 0.4ºC), to 35.7ºC (SD, 0.2ºC). This drug combination was no better than either drug alone, but the combination of nefopam and alfentanil additively reduced the shivering threshold by 1.8ºC (SD, 0.6ºC), to 34.5ºC (SD, 0.7ºC).…”

“…Shivering can cause thermal discomfort as well as sympathetic nervous system activation resulting in tachycardia and hypertension. 10 Shivering results in increased resting energy expenditure and oxygen consumption, impeding the induction of hypothermia and eliminating any potential benefits. 11 When shivering is uncontrolled, consequences include increased tissue ischemia.…”

“…22 Of note, buspirone is available only for oral administration and therefore is inappropriate for comatose patients. Nefopam and alfentanil additively reduced the shivering threshold by 1.8ºC, to 34.5ºC, 10 but nefopam is unavailable for use in the United States.…”

The Thermoregulation Story

“…Other areas of interest included neuraxial anesthesia, [31][32][33] fever, [34][35][36][37] and blunting thermoregulatory responses to facilitate induction of therapeutic hypothermia. [38][39][40] Recognition that halothane impairs thermoregulatory defenses, but does not obliterate them, was thus the first step in understanding why and how surgical patients become hypothermic. That, in turn, led to an appreciation of just how harmful even mild hypothermia can be, and subsequently to good methods of preventing hypothermia.…”