The effects of nefopam on the gain and maximum intensity of shivering in healthy volunteers.

Mild hypothermia has been shown to improve neurologic outcome after cardiac arrest. Nefopam, a centrally acting, nonsedative analgesic, decreases the threshold of shivering, but not vasoconstriction, and thus might be a suitable drug for induction of therapeutic hypothermia. However, not only the threshold but also the gain and maximum intensity of shivering define the thermoregulatory properties of a drug and thus are clinically important. Therefore, we evaluated the gain and maximum intensity of shivering at 2 different doses of nefopam and placebo. Seven healthy volunteers were randomly assigned to 3 study days: (1) control (saline), (2) small-dose nefopam (50 ng/mL), and (3) large-dose nefopam (100 ng/mL). On all study days volunteers were cooled using central venous infusion of cold IV fluid while mean skin temperature was maintained at 31 degrees C. Core temperature was recorded at the tympanic membrane. Threshold, gain, and maximum intensity of shivering were evaluated using oxygen consumption. Both 50 and 100 ng/mL nefopam significantly reduced the shivering threshold as well as the gain of shivering: shivering threshold: 35.6 degrees C + or - 0.2 degrees C (control); 35.2 degrees C + or - 0.3 degrees C (small dose); 34.9 degrees C + or - 0.5 degrees C (large dose), P = 0.004; gain of shivering: 597 + or - 235 mL x min(-1) x degrees C(-1) (control); 438 + or - 178 mL x min(-1) x degrees C(-1) (small dose); 301 + or - 134 mL x min(-1) x degrees C(-1) (large dose), P = 0.028. Maximum intensity of shivering did not differ among the 3 treatments. Nefopam significantly reduced the gain of shivering. This reduction, in combination with a reduced shivering threshold, will allow clinicians to cool patients even further when therapeutic hypothermia is indicated.