Doufas Anthony G, Lin Chun-Ming, Suleman Mohammad-Irfan, Liem Edwin B, Lenhardt Rainer, Morioka Nobutada, Akça Ozan, Shah Yunus M, Bjorksten Andrew R, Sessler Daniel I
Outcomes Research Institute and the Department of Anesthesiology, Louisville, KY, USA.
Stroke. 2003 May;34(5):1218-23. doi: 10.1161/01.STR.0000068787.76670.A4. Epub 2003 Apr 10.
Hypothermia might prove to be therapeutically beneficial in stroke victims; however, even mild hypothermia provokes vigorous shivering. Meperidine and dexmedetomidine each linearly reduce the shivering threshold (triggering core temperature) with minimal sedation. We tested the hypothesis that meperidine and dexmedetomidine synergistically reduce the shivering threshold without producing substantial sedation or respiratory depression.
We studied 10 healthy male volunteers (18 to 40 years) on 4 days: (1) control (no drug); (2) meperidine (target plasma level 0.3 microg/mL); (3) dexmedetomidine (target plasma level 0.4 ng/mL); and (4) meperidine plus dexmedetomidine (target plasma levels of 0.3 microg/mL and 0.4 ng/mL, respectively). Lactated Ringer's solution (approximately 4 degrees C) was infused through a central venous catheter to decrease tympanic membrane temperature by approximately 2.5 degrees C/h; mean skin temperature was maintained at 31 degrees C. An increase in oxygen consumption >25% of baseline identified the shivering threshold. Sedation was evaluated by using the Observer's Assessment of Sedation/Alertness scale. Two-way repeated-measures ANOVA was used to identify interactions between drugs. Data are presented as mean+/-SD; P<0.05 was statistically significant.
The shivering thresholds on the study days were as follows: control, 36.7+/-0.3 degrees C; dexmedetomidine, 36.0+/-0.5 degrees C (P<0.001 from control); meperidine, 35.5+/-0.6 degrees C (P<0.001); and meperidine plus dexmedetomidine, 34.7+/-0.6 degrees C (P<0.001). Although meperidine and dexmedetomidine each reduced the shivering threshold, their interaction was not synergistic but additive (P=0.19). There was trivial sedation with either drug alone or in combination. Respiratory rate and end-tidal Pco2 were well preserved on all days.
Dexmedetomidine and meperidine additively reduce the shivering threshold; in the small doses tested, the combination produced only mild sedation and no respiratory toxicity.
低温疗法可能对中风患者具有治疗益处；然而，即使是轻度低温也会引发剧烈寒战。哌替啶和右美托咪定均可在最小程度镇静的情况下线性降低寒战阈值（触发核心体温）。我们检验了以下假设：哌替啶和右美托咪定可协同降低寒战阈值，且不会产生显著的镇静作用或呼吸抑制。
我们在4天内对10名健康男性志愿者（18至40岁）进行了研究：（1）对照组（未用药）；（2）哌替啶组（目标血浆浓度0.3μg/mL）；（3）右美托咪定组（目标血浆浓度0.4ng/mL）；（4）哌替啶加右美托咪定组（目标血浆浓度分别为0.3μg/mL和0.4ng/mL）。通过中心静脉导管输注乳酸林格氏液（约4℃），以使鼓膜温度每小时降低约2.5℃；平均皮肤温度维持在31℃。氧耗量增加超过基线水平的25%即确定为寒战阈值。使用观察者镇静/警觉性评估量表评估镇静情况。采用双向重复测量方差分析来确定药物之间的相互作用。数据以平均值±标准差表示；P<0.05具有统计学意义。
研究各日的寒战阈值如下：对照组，36.7±0.3℃；右美托咪定组，36.0±0.5℃（与对照组相比P<0.001）；哌替啶组，35.5±0.6℃（P<0.001）；哌替啶加右美托咪定组，34.7±0.6℃（P<0.001）。虽然哌替啶和右美托咪定各自均降低了寒战阈值，但它们的相互作用并非协同作用而是相加作用（P=0.19）。单独使用或联合使用这两种药物时均仅有轻微镇静作用。所有日子的呼吸频率和呼气末二氧化碳分压均保持良好。
右美托咪定和哌替啶相加可降低寒战阈值；在测试的小剂量下，联合用药仅产生轻度镇静作用，且无呼吸毒性。
