Objectives: Obstructive sleep apnea syndrome (OSAS) is associated with increased risk of postoperative complications, which is possibly related to increased sensitivity to opioid. However, the effect of increased sensitivity to opioids in patients with OSAS remains controversial. This study aims to investigate whether male patients with moderate to severe OSAS have increased sensitivity to opioid remifentanil and its related predictive factors, so as to provide a reference for the rational use of opioids in patients with OSAS.
Methods: This study was a prospective study. From December 28, 2021 to October 15, 2022, a total of 61 male patients aged 22 to 60 years old, American Society of Anesthesiologists (ASA) status I and II, who underwent nasopharyngeal surgery under general anesthesia, were selected. According to STOP-BANG questionnaire score and apnea-hypopnea index (AHI), the patients were divided into an OSAS group (n=39) and a control group (n=22). The pupil diameter (PD) of the patients was measured by hand-held monocular pupillometer, and the perception threshold (PT) and pain tolerance threshold (PTT) of the patients were measured by somatosensory evoked potential stimulator. The initial PD, PT, and PTT were measured in a quiet environment and recorded as PD0, PT0, and PTT0. Changes in PD, PT, PTT, respiration, and consciousness were recorded after remifentanil infusion. Age, body mass index (BMI), smoking, AHI, minimal oxygen saturation, and percentage of sleep time spent with oxygen saturation <90% (T90) were included as independent variables in multiple linear regression equations to analyze the possible predictors of increased opioid sensitivity in patients with moderate to severe OSAS.
Results: There were no significant differences in PD0, PT0 and PTT0 between the OSAS group and the control group (all P>0.05). After remifentanil infusion, there was no significant difference in the rate of PT change between the 2 groups (P>0.05). The change rate of PTT and PD in the OSAS group was significantly higher than that in the control group (P<0.05 and P<0.001, respectively), PD in the OSAS group was significantly lower than that in the control group (P<0.001). During remifentanil infusion, there were no significant differences in the incidence of respiratory depression and the distribution of observer's assessment of alertness/sedation (OAA/S) scores between the 2 groups (both P>0.05), and there were no changes in mental status and airway support in the patients of the 2 groups. Multiple linear regression showed that T90 was positively correlated with miosis rate (β=0.597, 95% CI 0.269 to 0.924, P<0.05) and the rate of PTT change (β=0.458, 95% CI 0.116 to 0.800, P<0.05). However, minimal oxygen saturation, age, BMI, smoking, and AHI were not correlated with PD change rate and PTT change rate in the OSAS patients (all P>0.05).
Conclusions: Male patients with moderate to severe OSAS have increased sensitivity to remifentanil, the duration of nocturnal desaturation may be its predictive factor. Male patients with moderate to severe OSAS with a longer duration of nocturnal hypoxia are more sensitive to remifentanil, and the use of opioids in these patients should be more cautious in clinical.
目的: 阻塞型睡眠呼吸暂停综合征(obstructive sleep apnea syndrome，OSAS)患者围手术期并发症发生率高，可能与OSAS患者对阿片类药物的敏感性增加有关。然而，OSAS患者对阿片类药物的敏感性是否增加，目前尚有争议。本研究探讨男性中重度OSAS患者对阿片类药物瑞芬太尼的敏感性是否增加及其预测因素，旨在为OSAS患者合理使用阿片类药物提供参考。方法: 本研究是前瞻性研究。选取2021年12月28日至2022年10月15日在全身麻醉下行鼻咽部手术的男性患者61例，年龄22~60岁，美国麻醉医师协会(American Society of Anesthesiologists，ASA)分级I~II级，根据OSAS初筛问卷STOP-BANG量表评分和呼吸暂停低通气指数(apnea-hypopnea index，AHI)分为OSAS组(n=39)和对照组(n=22)。采用手持式单目瞳孔测量仪测量2组患者的瞳孔直径(pupil diameter，PD)，体感诱发电位刺激仪测量2组患者的感觉阈值(perception threshold，PT)和耐痛阈值(pain tolerance threshold，PTT)。在安静的环境下，测量患者初始PD、PT、PTT，并记为PD0、PT0、PTT0。在输注瑞芬太尼后，记录PD、PT、PTT、呼吸和意识的变化情况。将年龄、体重指数(body mass index，BMI)、吸烟、AHI、睡眠期间最低血氧饱和度、血氧饱和度<90%的时间占总监测时间的百分比(percentage of sleep time spent with oxygen saturation <90%，T90)作为自变量纳入多元线性回归方程，分析中重度OSAS患者对瑞芬太尼敏感性增加的预测因素。结果: OSAS组与对照组之间PD0、PT0和PTT0的差异均无统计学意义(均P>0.05)；在输注瑞芬太尼后，2组间PT变化率差异无统计学意义(P>0.05)，OSAS组PTT和PD的变化率明显大于对照组(分别为P<0.05和P<0.001)，PD显著小于对照组(P<0.001)；在瑞芬太尼输注过程中，2组的呼吸抑制发生率、警觉/镇静评分分布差异均无统计学意义(均P>0.05)，2组患者均无精神状态改变和气道支持。多元线性回归结果显示：T90与PD变化率(β=0.597，95% CI 0.269~0.924)和PTT变化率(β=0.458，95% CI 0.116~0.800)均呈正相关(均P<0.05)，但睡眠期间最低血氧饱和度、年龄、BMI、吸烟、AHI与PD变化率和PTT变化率均无相关性(均P>0.05)。结论: 成年男性中重度OSAS患者对瑞芬太尼的敏感性增加，夜间缺氧持续时间可能是其预测因素。夜间缺氧持续时间越长的男性中重度OSAS患者对瑞芬太尼越敏感，在临床上对该类患者使用阿片类药物需要更加谨慎。.
Keywords: duration of nocturnal desaturation; obstructive sleep apnea syndrome; pain; pupil; remifentanil.