Davis Jennifer J, Swenson Jeffrey D, Hall Robert H, Dillon Jeffrey D, Johnson Ken B, Egan Talmage D, Pace Nathan L, Niu Su-Yi
Department of Anesthesiology at the University of Utah Medical Center, Salt Lake City, Utah.
Anesth Analg. 2005 Aug;101(2):389-395. doi: 10.1213/01.ANE.0000156563.25878.19.
When opioids are used for postoperative pain control, it is useful to define the dose-response relationship for analgesia and respiratory depression. We studied 20 chronically opioid-consuming patients having elective multilevel spine fusion. Preoperatively, each patient received a fentanyl infusion of 2 microg x kg(-1) x min(-1) until the respiratory rate was <5 breaths/min. Pharmacokinetic simulations were used to estimate the effect site concentration at the time of respiratory depression and to predict the patient-controlled analgesia settings that would provide an effect-site fentanyl concentration that was 30% of the concentration associated with respiratory depression. Postoperatively, patient-controlled analgesia settings were adjusted to achieve 2-3 demand doses per hour. At steady-state patient-controlled analgesia settings, arterial blood gases and plasma fentanyl levels were measured. Sixteen patients required no adjustment or one patient-controlled analgesia adjustment. The median arterial Pco(2) level was 41 mm Hg and the interquartile range was 39-46 mm Hg. Plasma fentanyl levels demonstrated a significant correlation to the estimated effect-site concentration associated with respiratory depression determined during the preoperative fentanyl challenge. A preoperative fentanyl challenge used with pharmacokinetic simulations may be a useful tool to individualize the administration of analgesics to chronically opioid-consuming patients.
In chronically opioid-consuming patients, doses causing respiratory depression and analgesia may differ from those in opioid-naive individuals. A preoperative infusion of fentanyl, used in conjunction with pharmacokinetic simulation, may be a valuable tool for identifying clinical end-points, such as respiratory depression and analgesia, and individualizing postoperative treatment of pain in patients who chronically consume opioids.
当使用阿片类药物进行术后疼痛控制时，明确镇痛和呼吸抑制的剂量反应关系很有用。我们研究了20例长期使用阿片类药物的择期多节段脊柱融合手术患者。术前，每位患者接受2微克·千克⁻¹·分钟⁻¹的芬太尼输注，直至呼吸频率<5次/分钟。使用药代动力学模拟来估计呼吸抑制时效应部位浓度，并预测患者自控镇痛设置，该设置可提供与呼吸抑制相关浓度30%的效应部位芬太尼浓度。术后，调整患者自控镇痛设置以达到每小时2 - 3次按需剂量。在稳态患者自控镇痛设置下，测量动脉血气和血浆芬太尼水平。16例患者无需调整或仅需一次患者自控镇痛调整。动脉血二氧化碳分压中位数为41毫米汞柱，四分位间距为39 - 46毫米汞柱。血浆芬太尼水平与术前芬太尼激发试验期间确定的与呼吸抑制相关的估计效应部位浓度显著相关。术前芬太尼激发试验结合药代动力学模拟可能是一种有用的工具，可用于为长期使用阿片类药物的患者个体化给予镇痛药。
在长期使用阿片类药物的患者中，导致呼吸抑制和镇痛的剂量可能与未使用过阿片类药物的个体不同。术前输注芬太尼并结合药代动力学模拟，可能是识别临床终点（如呼吸抑制和镇痛）以及为长期使用阿片类药物的患者个体化术后疼痛治疗的有价值工具。
