Alfonsi Pascal, Passard Andrea, Gaude-Joindreau Valérie, Guignard Bruno, Sessler Daniel I, Chauvin Marcel
Department of Anesthesia, Hôpital Ambroise Paré, Boulogne France.
Anesthesiology. 2009 Jul;111(1):102-9. doi: 10.1097/ALN.0b013e3181a979c1.
Induction of therapeutic hypothermia is often complicated by shivering. Nefopam reduces the shivering threshold with minimal side effects. Consequently, nefopam is an attractive component for induction of therapeutic hypothermia. However, nefopam alone is insufficient; it will thus need to be combined with another drug. Clonidine and alfentanil each reduce the shivering threshold. This study, therefore, tested the hypothesis that nefopam, combined either with clonidine or alfentanil, synergistically reduces the shivering threshold.
For each combination, ten volunteers were studied on 4 days. Combination 1: (1) control (no drug); (2) nefopam (100 ng/ml); (3) clonidine (2.5 microg/kg); and (4) nefopam plus clonidine (100 ng/ml and 2.5 microg/kg, respectively). Combination 2: (1) control (no drug); (2) nefopam (100 ng/ml); (3) alfentanil (150 ng/ml); and (4) nefopam plus alfentanil (100 ng/ml and 150 ng/ml, respectively). Lactated Ringer's solution (approximately 4 degrees C) was infused to decrease core temperature. Mean skin temperature was maintained at 31 degrees C. The core temperature that increased oxygen consumption to more than 25% of baseline identified the shivering threshold.
With nefopam and clonidine, the shivering thresholds were significantly lower than on the control day. The shivering threshold decreased significantly less than would be expected on the basis of the individual effects of each drug (P = 0.034). In contrast, the interaction between nefopam and alfentanil on shivering was additive, meaning that the combination reduced the shivering threshold as much as would be expected by the individual effect of each drug.
Nefopam and alfentanil additively reduce the shivering threshold, but nefopam and clonidine do not.
治疗性低温诱导常因寒战而复杂化。奈福泮能降低寒战阈值且副作用极小。因此，奈福泮是治疗性低温诱导的一个有吸引力的成分。然而，单独使用奈福泮并不充分；因此需要与另一种药物联合使用。可乐定和阿芬太尼均可降低寒战阈值。因此，本研究检验了奈福泮与可乐定或阿芬太尼联合使用能协同降低寒战阈值的假设。
对于每种联合用药，10名志愿者在4天内接受研究。联合用药1：（1）对照组（无药物）；（2）奈福泮（100纳克/毫升）；（3）可乐定（2.5微克/千克）；（4）奈福泮加可乐定（分别为100纳克/毫升和2.5微克/千克）。联合用药2：（1）对照组（无药物）；（2）奈福泮（100纳克/毫升）；（3）阿芬太尼（150纳克/毫升）；（4）奈福泮加阿芬太尼（分别为100纳克/毫升和150纳克/毫升）。输注乳酸林格液（约4℃）以降低核心体温。平均皮肤温度维持在31℃。将使耗氧量增加至超过基线25%的核心体温确定为寒战阈值。
使用奈福泮和可乐定时，寒战阈值显著低于对照日。寒战阈值的降低显著小于基于每种药物单独作用所预期的降低幅度（P = 0.034）。相比之下，奈福泮和阿芬太尼对寒战的相互作用是相加的，这意味着联合用药降低寒战阈值的程度与每种药物单独作用所预期的降低程度相同。
奈福泮和阿芬太尼相加可降低寒战阈值，但奈福泮和可乐定则不然。
