Lu J K, Schafer P G, Gardner T L, Pace N L, Zhang J, Niu S, Stanley T H, Bailey P L
Department of Anesthesiology, University of Utah Health Sciences Center, Salt Lake City 84132, USA.
Anesth Analg. 1997 Aug;85(2):372-9. doi: 10.1097/00000539-199708000-00023.
The pharmacologic effects of intrathecal sufentanil (ITS) beyond what is clinically administered (10 microg) are not known. We observed 18 healthy, young, adult female volunteers who received 12.5, 25, or 50 microg of ITS in a randomized, double-blind fashion for 11 h. Analgesia was assessed by pressure algometry at the tibia. Respiratory function was assessed by pulse oximetry, respiratory rate, arterial blood gas, the ventilatory response to CO2, and a respiratory intervention score (RIS). The incidence and severity of side effects also were documented. Serum sufentanil levels were measured for 4 h after ITS administration. We found that ITS produced statistically significant changes in algometry, doubling the pressure required to produce moderate pain. However, doses of ITS greater than 12.5 microg failed to produce proportionate increases in the duration or intensity of analgesia. All doses of ITS produced significant respiratory depression, but only the RIS was significantly related to ITS dose. Neither respiratory rate nor sedation reliably predicted hypoxemia. Supplemental oxygen by nasal cannula consistently prevented pulse oximeter readings below 90%. Serum sufentanil concentrations were related to ITS dose in a statistically significant manner, reached clinically significant concentrations, and followed a time course similar to analgesia and measures of respiratory depression. However, there was no significant increase in measured analgesia associated with the increases in serum sufentanil concentrations. We conclude that in our volunteer model of lower extremity pain, administering ITS in doses larger than 12.5 microg does not improve the speed of onset, magnitude, or duration of analgesia and only causes dose-related increases in serum sufentanil concentrations, which may augment respiratory depression.
鞘内注射舒芬太尼（ITS）超出临床常用剂量（10微克）后的药理作用尚不清楚。我们观察了18名健康、年轻的成年女性志愿者，她们以随机、双盲的方式接受了12.5微克、25微克或50微克的ITS，持续11小时。通过胫骨压力测痛法评估镇痛效果。通过脉搏血氧饱和度测定、呼吸频率、动脉血气分析、对二氧化碳的通气反应以及呼吸干预评分（RIS）评估呼吸功能。同时记录副作用的发生率和严重程度。在注射ITS后4小时测量血清舒芬太尼水平。我们发现，ITS在压力测痛法上产生了具有统计学意义的变化，使产生中度疼痛所需的压力增加了一倍。然而，大于12.5微克的ITS剂量未能使镇痛持续时间或强度成比例增加。所有剂量的ITS均产生了显著的呼吸抑制，但只有RIS与ITS剂量显著相关。呼吸频率和镇静程度均不能可靠地预测低氧血症。经鼻导管补充氧气可始终防止脉搏血氧饱和度读数低于90%。血清舒芬太尼浓度与ITS剂量呈统计学显著相关，达到了临床显著浓度，且其时间进程与镇痛及呼吸抑制指标相似。然而，血清舒芬太尼浓度升高并未伴随实测镇痛效果的显著增加。我们得出结论，在我们的下肢疼痛志愿者模型中，给予大于12.5微克的ITS剂量并不能改善镇痛的起效速度、程度或持续时间，只会导致血清舒芬太尼浓度与剂量相关的增加，这可能会加重呼吸抑制。
