The risk of local anesthetic toxicity is a concern for the use of continuous blocks performed in the ambulatory setting.1 The use of continuous blocks to reduce postsurgical pain has been demonstrated in children, but limited data are currently available to demonstrate local anesthetic safety.2 The risk of exceeding potentially toxic levels of the local anesthetic might discourage the use of peripheral nerve catheters in children. It remains to be determined whether blood levels of bupivacaine are safe in adolescents receiving continuous femoral blocks.
The main objective of the current investigation was to evaluate blood bupivacaine concentrations in pediatric patients having an ultrasound-guided single-shot sciatic and continuous femoral blocks after anterior cruciate ligament (ACL) repair.
This was a prospective, observational study, with reporting performed according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) consensus.3 Approval for the study was received by the institutional review board of the Ann & Robert H. Lurie Children’s Hospital of Chicago. Written informed consent was obtained from parents or legal guardians of all participating subjects. Eligible subjects were children (<18 years of age) undergoing ACL repair with a continuous femoral nerve block. Subjects were excluded if they had significant cardiovascular, renal, or liver disease.
A femoral nerve catheter was inserted by one of the investigators (S.S.) using ultrasound guidance after induction of general anesthesia. The dose of bupivacaine was 0.3 mL/kg of 0.25% bupivacaine, not to exceed 25 mL for the initial injection, followed by a continuous infusion of 4 mL/h of 0.1% bupivacaine (Elastomeric ON-Q Pump; Halyard Inc, Alpharetta, Ga). The dose selected is consistent with commonly utilized local anesthetic doses in children.4 A single-shot sciatic block was also performed using ultrasound probe (SonoSite, Bothell, Wash) and adopting an in-plane approach to the sciatic nerve in the popliteal fossa. Injection around the nerve was confirmed with the complete spread of local anesthetic around the nerve bundle. A total volume of 0.2 mL/kg of 0.25% bupivacaine was utilized for the sciatic nerve block.
Whole blood samples were collected on a piece of Whatman Protein Saver 903 filter paper from either a peripheral line or a finger stick. Blood samples were obtained at 0, 5, 15, 30, 60, and 120 minutes and 4, 24, and 48 hours after the initial local anesthetic infusion. Parents collected the samples in cases in which the children were already discharged from the hospital. We followed the same methodology for handling the samples as recently demonstrated by our group.5
Five subjects would allow estimating an upper 99% confidence interval (CI) of 151 ng/dL using the sample mean of 71 ng/dL and a standard deviation (SD) of 39 ng/dL. Normally distributed interval data are reported as mean and SD. Non-normally distributed interval and ordinal data are reported as median, range, or interquartile range. The Shapiro-Wilk test was used for the values from each subject at all points to confirm that the data followed a normal distribution (all P > .05). The 99% upper CI limits for the blood bupivacaine levels across subsequent times were calculated.
A convenience sample of 9 subjects was enrolled in the study. Patients’ characteristics are presented in Table 1. All pediatric patients underwent uncomplicated ultrasound-guided single-shot sciatic block and a femoral nerve continuous block. The time course of total plasma bupivacaine concentration is shown in Figure 1 (median, 25th and 75th percentile values). The highest 99% upper CI occurred at the 4-hour point, with a mean (99% upper confidence limit) of 72 ng/ mL (135 ng/mL). More important, the 99% upper confidence limit was below potentially toxic levels (1500 ng/mL) across all times (Table 2).6 The highest blood levels for individual patients occurred at various times (1 at 5 minutes, 2 at 15 minutes, 2 at 30 minutes, 1 at 60 minutes, 1 at 4 hours, and 2 at 24 hours), but none crossed potentially toxic plasma levels. The highest individual concentration was 180 ng/mL, and it occurred at the 4-hour interval. None of the children demonstrated any potential signs of local anesthetic toxicity (Figure 2).
The most important finding of the current investigation was the lack of toxic blood levels of bupivacaine when a single-shot sciatic nerve block and femoral nerve catheters were utilized in pediatric patients undergoing orthopedic procedures. The 99% upper CI for blood bupivacaine levels did not cross potentially toxic bupivacaine plasma levels up to 48 hours after the local anesthetic injection. Our results suggest a low risk of local anesthetic toxicity when femoral nerve catheters were used in children using an infusion consistent with recommended dose of bupivacaine per kilogram.
Our results are clinically important because acute pain in children undergoing orthopedic surgery is difficult to control.7,8 The use of ambulatory continuous nerve blocks in pediatric patients can be a viable strategy to improve analgesic outcomes in this patient population, but the potential for the development of local anesthetic toxicity may reduce the use of ambulatory catheters in the pediatric population. To the best of our knowledge, this is the first study to prospectively evaluate local anesthetic plasma levels in pediatric patients having a continuous femoral block technique.
We noted significant variability in the blood levels, and we studied only 9 subjects. This is a pilot, single-center study in a small cohort of patients without cardiovascular, renal, or liver disease, which limits the generalizability of our results and suggests the need for larger sample sizes in future studies. Nonetheless, our study can be used to plan larger studies on the topic.
The authors thank Jeffrey Galinkin, MD, Christians Uwe, and Keith Hoffman (Children’s Hospital of Colorado) for help with sample analysis and interpretation of the results, and Angela Cambic, MD, for help conducting the study.
Name: Santhanam Suresh, MD.
Contribution: This author helped design the study, conduct the study, and prepare the manuscript.
Name: Gildasio S. De Oliveira Jr, MD, MSCI.
Contribution: This author helped analyze the statistics and prepare the manuscript.
This manuscript was handled by: James A. DiNardo, MD, FAAP.
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