Department of Surgery, Anesthesia and Operative Service, Walter Reed Army Medical Center, Washington, DC, USA.
Anesth Analg. 2010 Feb 1;110(2):630-4. doi: 10.1213/ANE.0b013e3181c76a33. Epub 2009 Dec 2.
Ropivacaine is a long-acting local anesthetic used frequently for peripheral nerve blocks and continuous peripheral nerve block catheters. Combat trauma patients at Walter Reed Army Medical Center often receive continuous peripheral nerve block catheters as part of their pain regimen. These catheters remain in situ for several days to weeks. In this study, we evaluated the free ropivacaine drug levels over time in trauma patients by measuring the serum concentration of bound and unbound local anesthetic. The corresponding alpha(1)-acid glycoprotein concentration in patients with prolonged ropivacaine infusions was also measured.
Fifteen patients were enrolled in the study; 2 patients were excluded because only a single ropivacaine level was obtained. Of the remaining 13 patients in the study, 2 had peripheral nerve catheters placed at the time of enrollment; the remaining 11 patients had catheters placed before enrollment. These patients were already receiving 0.2% ropivacaine infusions for a period of 18-126 h before the first assessment of local anesthetic level. Catheters infused 0.2% ropivacaine at a rate of 6-14 mL/h; catheter boluses were administered with 0.5% ropivacaine. Local anesthetic blood concentrations were scheduled to be measured on Days 1, 3, 5, 7, and 10 and every 3 days thereafter until all catheters were removed, although not all patients underwent each assessment. Specimens were assayed using high-performance liquid chromatography for total and free serum ropivacaine concentrations. Alpha(1)-acid glycoprotein was also measured.
Thirteen patients remained in the study, for a total of 59 blood samples. The median number of days catheters remained in situ for the duration of acute pain therapy was 7 days (range: 6-27 days). The median number of days catheters remained in situ after enrollment into the study was 7 days (range: 4-25 days). The median number of blood samples collected per patient was 4 (range: 2-10 samples). Two patients had isolated increased concentrations of free ropivacaine into a previously identified toxic range with no obvious mitigating factors; both patients had received a 300-mg bolus of 0.5% ropivacaine approximately 24 h before that blood collection. The median ropivacaine concentration over the length of the study was 0.11 mg/L (range: undetectable to 0.63 mg/L). During the first week of the study, the median change in ropivacaine concentration per patient was 0.00 mg/L (range: -0.35 to 0.47 mg/L).
Although 2 patients demonstrated isolated serum ropivacaine concentration spikes into a previously identified toxic range, continuous peripheral nerve block catheter management and local anesthetic doses as practiced at Walter Reed Army Medical Center did not result in clinically evident systemic ropivacaine toxicity. There was no correlation between free ropivacaine concentration and alpha(1)-acid glycoprotein concentration except in patients who had already been receiving ropivacaine infusions before entering the study. Despite this lack of correlation, the total duration of local anesthetic infusion did not seem to influence the free concentration of the drug.
罗哌卡因是一种长效局部麻醉剂,常用于周围神经阻滞和连续外周神经阻滞导管。沃尔特·里德陆军医疗中心的创伤患者经常接受连续外周神经阻滞导管作为其疼痛治疗方案的一部分。这些导管在原位停留数天至数周。在这项研究中,我们通过测量结合和未结合局部麻醉剂的血清浓度来评估创伤患者的游离罗哌卡因药物水平。还测量了接受长时间罗哌卡因输注患者的相应α(1)-酸性糖蛋白浓度。
15 名患者入组本研究;2 名患者因仅获得单次罗哌卡因水平而被排除。在研究中的 13 名患者中,有 2 名患者在入组时放置了外周神经导管;其余 11 名患者在入组前放置了导管。这些患者在首次评估局部麻醉剂水平前已经接受 0.2%罗哌卡因输注 18-126 小时。导管以 6-14 mL/h 的速度输注 0.2%罗哌卡因;导管推注用 0.5%罗哌卡因。计划在第 1、3、5、7 和 10 天以及此后每 3 天测量一次局部麻醉剂血药浓度,直到所有导管被移除,尽管并非所有患者都进行了每次评估。使用高效液相色谱法测定总血清罗哌卡因浓度和游离血清罗哌卡因浓度。还测量了α(1)-酸性糖蛋白。
13 名患者继续留在研究中,共采集了 59 份血样。导管在急性疼痛治疗期间原位停留的中位数天数为 7 天(范围:6-27 天)。入组研究后导管在原位停留的中位数天数为 7 天(范围:4-25 天)。每位患者采集的中位数血样数为 4 份(范围:2-10 份)。有 2 名患者的游离罗哌卡因浓度单独升高至先前确定的毒性范围,没有明显的缓解因素;这两名患者在那次采血前约 24 小时接受了 300 毫克 0.5%罗哌卡因的推注。整个研究期间罗哌卡因的中位数浓度为 0.11 毫克/升(范围:未检出至 0.63 毫克/升)。在研究的第一周,每位患者的罗哌卡因浓度中位数变化为 0.00 毫克/升(范围:-0.35 至 0.47 毫克/升)。
尽管有 2 名患者的血清罗哌卡因浓度单独出现了先前确定的毒性范围内的峰值,但沃尔特·里德陆军医疗中心实施的连续外周神经阻滞导管管理和局部麻醉剂剂量并未导致临床明显的全身罗哌卡因毒性。游离罗哌卡因浓度与α(1)-酸性糖蛋白浓度之间除了在入组前已经接受罗哌卡因输注的患者外,没有相关性。尽管没有这种相关性,但局部麻醉剂输注的总持续时间似乎并没有影响药物的游离浓度。