Department of Outcomes Research, Anesthesia Institute, Cleveland Clinic, Cleveland, OH 43195, USA.
Anesth Analg. 2010 Aug;111(2):409-14. doi: 10.1213/ANE.0b013e3181e332bb. Epub 2010 Jun 7.
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.
轻度低温已被证明可改善心脏骤停后的神经功能预后。奈福泮是一种中枢作用的非镇静性镇痛药，可降低寒战的阈值，但不引起血管收缩，因此可能是诱导治疗性低温的合适药物。然而，不仅阈值，而且寒战的增益和最大强度也定义了药物的体温调节特性，因此具有临床重要性。因此，我们评估了奈福泮和安慰剂两种不同剂量的寒战增益和最大强度。
7 名健康志愿者随机分为 3 个研究日：（1）对照（生理盐水），（2）小剂量奈福泮（50ng/ml）和（3）大剂量奈福泮（100ng/ml）。在所有研究日，志愿者通过中心静脉输注冷 IV 液冷却，同时保持平均皮肤温度在 31°C。鼓膜核心温度记录。使用耗氧量评估寒战的阈值、增益和最大强度。
奈福泮 50 和 100ng/ml 均显著降低寒战阈值和寒战增益：寒战阈值：35.6°C ± 0.2°C（对照）；35.2°C ± 0.3°C（小剂量）；34.9°C ± 0.5°C（大剂量），P=0.004；寒战增益：597 ± 235mL×min-1×°C-1（对照）；438 ± 178mL×min-1×°C-1（小剂量）；301 ± 134mL×min-1×°C-1（大剂量），P=0.028。三种治疗方法的寒战最大强度无差异。
奈福泮显著降低了寒战的增益。这种降低，结合降低的寒战阈值，将使临床医生在需要治疗性低温时能够进一步冷却患者。
