Brown R H, Wagner E M
Environmental Health Sciences/Division of Physiology, Johns Hopkins School of Public Health, Baltimore, Maryland 21205, USA.
Anesthesiology. 1999 Mar;90(3):822-8. doi: 10.1097/00000542-199903000-00025.
Propofol and ketamine have been purported to decrease bronchoconstriction during induction of anesthesia and intubation. Whether they act on airway smooth muscle or through neural reflexes has not been determined. We compared propofol and ketamine to attenuate the direct activation of airway smooth muscle by methacholine and limit neurally mediated bronchoconstriction (vagal nerve stimulation).
After approval from the institutional review board, eight sheep were anesthetized with pentobarbital, paralyzed, and ventilated. After left thoracotomy, the bronchial artery was cannulated and perfused. In random order, 5 mg/ml concentrations of propofol, ketamine, and thiopental were infused into the bronchial artery at rates of 0.06, 0.20, and 0.60 ml/min. After 10 min, airway resistance was measured before and after vagal nerve stimulation and methacholine given via the bronchial artery. Data were expressed as a percent of baseline response before infusion of drug and analyzed by analysis of variance with significance set at P< or =0.05.
Systemic blood pressure was not affected by any of the drugs (P>0.46). Baseline airway resistance was not different among the three agents (P = 0.56) or by dose (P = 0.96). Infusion of propofol and ketamine into the bronchial artery caused a dose-dependent attenuation of the vagal nerve stimulation-induced bronchoconstriction to 26+/-11% and 8+/-2% of maximum, respectively (P<0.0001). In addition, propofol caused a significant decrease in the methacholine-induced bronchoconstriction to 43+/-27% of maximum at the highest concentration (P = 0.05)
The local bronchoprotective effects of ketamine and propofol on airways is through neurally mediated mechanisms. Although the direct effects on airway smooth muscle occur at high concentrations, these are unlikely to be of primary clinical relevance.
丙泊酚和氯胺酮据称可在麻醉诱导和插管期间减轻支气管收缩。它们是作用于气道平滑肌还是通过神经反射起作用尚未确定。我们比较了丙泊酚和氯胺酮减轻乙酰甲胆碱对气道平滑肌的直接激活并限制神经介导的支气管收缩（迷走神经刺激）的效果。
经机构审查委员会批准后，对八只绵羊用戊巴比妥麻醉、使其麻痹并进行通气。左胸开胸后，将支气管动脉插管并灌注。以随机顺序，将浓度为5mg/ml的丙泊酚、氯胺酮和硫喷妥钠以0.06、0.20和0.60ml/min的速率注入支气管动脉。10分钟后，在迷走神经刺激和通过支气管动脉给予乙酰甲胆碱之前和之后测量气道阻力。数据表示为药物输注前基线反应的百分比，并通过方差分析进行分析，显著性设定为P≤0.05。
所有药物均未影响全身血压（P>0.46）。三种药物之间的基线气道阻力无差异（P = 0.56），剂量之间也无差异（P = 0.96）。向支气管动脉内注入丙泊酚和氯胺酮导致迷走神经刺激诱导的支气管收缩分别剂量依赖性地减弱至最大值的26±11%和8±2%（P<0.0001）。此外，丙泊酚在最高浓度时使乙酰甲胆碱诱导的支气管收缩显著降低至最大值的43±27%（P = 0.05）。
氯胺酮和丙泊酚对气道的局部支气管保护作用是通过神经介导机制实现的。虽然在高浓度下对气道平滑肌有直接作用，但这些作用不太可能具有主要临床相关性。
