The median (95% range) for the local anesthetic dose per weight for caudal blocks was 1.4 mg (0.78–2.51 mg) of bupivacaine equivalents/kg representing a large variation in clinical practice. There was a direct linear relationship between the total local anesthetic dose and patients’ weights; however, subjects’ weight was not sufficient to explain much of the variability in dose (Fig. 1). Variation in the local anesthetic dose was not better explained by variations in age of subjects (slope of regression line 0.32 ± 0.00; goodness of fit r2 = 0.41 and slope significantly different from 0, P < 0.0001. Examination of a residual plot demonstrated a fairly random pattern).
The median (IQR) local anesthetic dose per weight was larger when epinephrine was used as a block adjunct compared to when no epinephrine was used, 1.4 mg (1.2–1.6 mg) and 1.3 mg (1.2–1.6 mg) of bupivacaine equivalents/kg, respectively (P < 0.001). After adjusting for different local anesthetic potencies, subjects who had a caudal block with ropivacaine received a greater dose of local anesthetics than those who had a caudal block with bupivacaine, median (IQR) of 1.66 mg (1.25–2.31 mg) and 1.34 mg (1.13–1.4 mg) of bupivacaine/kg equivalents, respectively, P < 0.001.
Four thousand four hundred-six of 17,867 (24.6%; 95% CI, 24%–25.2%) subjects received larger doses than 2 mg of bupivacaine equivalents/kg that potentially could have been unsafe. When a less conservative limit of 2.5 mg/kg dose of bupivacaine was evaluated, 968 of 17,867 (5.4%; 95% CI, 5.0%–5.4%) subjects received potentially toxic doses. Subjects who received doses larger than the maximal safe local anesthetic doses were younger than subjects who did not receive potentially unsafe doses, 11 (6–20) months and 15 (7–36) months, respectively (P < 0.001).
The most important finding of the current investigation was the low rate of complications when the caudal block was performed in pediatric patients undergoing surgical procedures. The upper incidence limit of severe complications such as cardiac arrest and seizure was 0.02%. More importantly, no cases of long-term sequelae were detected in any of the 18,650 patients in this cohort. Taken together, our results suggest that caudal block is a safe regional anesthesia technique when performed in children undergoing surgery.
Our results are clinically important since reports of complications associated with the performance of caudal block in the literature have questioned its safety in children.22–24 In addition, prior safety studies that specifically examined caudal block were limited by a small number of patients and the evaluation of only a single center.25,26 In Europe, a large study on the safety of several regional anesthesia techniques in children demonstrated a low incidence of complications for 8493 caudal blocks.14 Our study establishes the safety of caudal block in children across multiple pediatric hospitals in the United States. The current study is, to the best of our knowledge, the largest study to demonstrate safety of a single regional anesthesia technique in children.
Another important finding of the current investigation was the detection of a large variation in local anesthetic dose used in caudal blocks (IQR, 1.23 mg of bupivacaine/kg to 1.98 mg of bupivacaine/kg). In addition, the dose variation was not largely explained by changes in weight of the subjects R2 (95% CI) = 0.5 (0.48 to 0.52). Current data suggest that approximately 25% of patients undergoing a caudal block receive a local anesthetic dose that has the potential to cause local anesthetic toxicity.27–31 Younger children seem to be at greatest risk for receiving a toxic dose. Quality improvement projects should be implemented across different institutions to detect and avoid unsafe local anesthetic doses when caudal block is performed in pediatric patients.
We did not detect a beneficial role in the use of ultrasound to minimize complications of caudal block in children. It was also interesting that the use of ultrasound decreased across the years. The use of ultrasound assistance has been shown to minimize complications and/or improve efficacy of peripheral regional anesthesia techniques in adults when compared to nerve stimulation.32–35 Although the current data do not suggest that ultrasound improves safety of caudal block, future studies examining the role of ultrasound guidance on the efficacy of caudal blocks are still needed.
The efficacy of caudal block to minimize postoperative pain in specific surgical procedures has yet to be established.2 In addition, optimal dose regimens also need to be determined to help reduce the large variation in clinical practice we observed. Given the safety of caudal blocks in children demonstrated by the current analysis, the performance of randomized controlled trials is justified not only to establish procedure-specific efficacy but also to detect optimal local anesthetic dose regimens.
Our study should only be interpreted within the context of its limitations. We evaluated the safety of caudal block but did not examine its efficacy. Since the PRAN database does not capture type of surgical procedure, we were not able to investigate if specific types of surgical procedures carry a greater risk for patients to receive potentially toxic doses of local anesthetics or to have postoperative complications. Similar to other national quality improvement programs, site-specific contributions were not available and could not be incorporated into the analysis.36–39
In summary, we established a safety profile for caudal block in children using data from >20 pediatric hospitals in the United States in 18,650 pediatric patients. However, we detected a large variation in clinical practice regarding dose of local anesthetics for caudal block that may lead to local anesthetic toxicity. Safety concerns should not be a barrier to the development of randomized trials in order to test the efficacy of caudal block on analgesic outcomes in children pending the appropriate selection of local anesthetic doses.
We would like to acknowledge the PRAN steering committee members: Drs. Martin, Polaner, Krane, Bosenberg, Walker, and Taenzer for their dedication in conceptually forming the PRAN database, all sites that have contributed data to the consortium, and Christie Wolf from Axio Research whose contributions to the database are invaluable.
1. Shah RD, Suresh S. Applications of regional anaesthesia in paediatrics. Br J Anaesth. 2013;111(Suppl 1):i114–24
2. Suresh S, Schaldenbrand K, Wallis B, De Oliveira GS. Regional anaesthesia to improve pain outcomes in pediatric surgical patients: a qualitative systematic review of randomized controlled trials. Br J Anaesth. 2014;113:375–90
3. Krane EJ, Polaner D. The safety and effectiveness of continuous peripheral nerve blockade in children. Anesth Analg. 2014;118:499–500
4. Varughese AM, Rampersad SE, Whitney GM, Flick RP, Anton B, Heitmiller ES. Quality and safety in pediatric anesthesia. Anesth Analg. 2013;117:1408–18
5. Kahn MG, Bailey LC, Forrest CB, Padula MA, Hirschfeld S. Building a common pediatric research terminology for accelerating child health research. Pediatrics. 2014;133:516–25
6. Kim EM, Lee JR, Koo BN, Im YJ, Oh HJ, Lee JH. Analgesic efficacy of caudal dexamethasone combined with ropivacaine in children undergoing orchiopexy. Br J Anaesth. 2014;112:885–91
7. Gurnaney H, Kraemer FW, Maxwell L, Muhly WT, Schleelein L, Ganesh A. Ambulatory continuous peripheral nerve blocks in children and adolescents: a longitudinal 8-year single center study. Anesth Analg. 2014;118:621–7
8. Naja ZM, Ziade FM, Kamel R, El-Kayali S, Daoud N, El-Rajab MA. The effectiveness of pudendal nerve block versus caudal block anesthesia for hypospadias in children. Anesth Analg. 2013;117:1401–7
9. Muhly W, Gurnaney H, Hosalkar H, Kraemer F, Davidson R, Ganesh A. Continuous perineural infusion after lower extremity osteotomies in children: a feasibility and safety analysis. Br J Anaesth. 2013;110:851–2
10. Hall Burton DM, Boretsky KR. A comparison of paravertebral nerve block catheters and thoracic epidural catheters for postoperative analgesia following the Nuss procedure for pectus excavatum repair. Paediatr Anaesth. 2014;24:516–20
11. Campbell MF. Caudal anesthesia in children. Am J Urol. 1933;30:245–9
12. Schnabel A, Poepping DM, Kranke P, Zahn PK, Pogatzki-Zahn EM. Efficacy and adverse effects of ketamine as an additive for paediatric caudal anaesthesia: a quantitative systematic review of randomized controlled trials. Br J Anaesth. 2011;107:601–11
13. Jöhr M, Berger TM. Caudal blocks. Paediatr Anaesth. 2012;22:44–50
14. Ecoffey C, Lacroix F, Giaufré E, Orliaguet G, Courrèges PAssociation des Anesthésistes Réanimateurs Pédiatriques d’Expression Française (ADARPEF). . Epidemiology and morbidity of regional anesthesia in children: a follow-up one-year prospective survey of the French-Language Society of Paediatric Anaesthesiologists (ADARPEF). Paediatr Anaesth. 2010;20:1061–9
15. Jagannathan N, Sohn L, Sawardekar A, Ambrosy A, Hagerty J, Chin A, Barsness K, Suresh S. Unilateral groin surgery in children: will the addition of an ultrasound-guided ilioinguinal nerve block enhance the duration of analgesia of a single-shot caudal block? Paediatr Anaesth. 2009;19:892–8
16. Polaner DM, Taenzer AH, Walker BJ, Bosenberg A, Krane EJ, Suresh S, Wolf C, Martin LD. Pediatric Regional Anesthesia Network (PRAN): a multi-institutional study of the use and incidence of complications of pediatric regional anesthesia. Anesth Analg. 2012;115:1353–64
17. Divine G, Norton HJ, Hunt R, Dienemann J. Statistical grand rounds: a review of analysis and sample size calculation considerations for Wilcoxon tests. Anesth Analg. 2013;117:699–710
18. Dexter F. Wilcoxon-Mann-Whitney test used for data that are not normally distributed. Anesth Analg. 2013;117:537–8
19. Dann RS, Koch GG. Review and evaluation of methods for computing confidence intervals for the ratio of two proportions and considerations for non-inferiority clinical trials. J Biopharm Stat. 2005;15:85–107
20. Lee YY, Ngan Kee WD, Fong SY, Liu JT, Gin T. The median effective dose of bupivacaine, levobupivacaine, and ropivacaine after intrathecal injection in lower limb surgery. Anesth Analg. 2009;109:1331–4
21. Cox B, Durieux ME, Marcus MA. Toxicity of local anaesthetics. Best Pract Res Clin Anaesthesiol. 2003;17:111–36
22. Na EH, Han SJ, Kim MH. Delayed occurrence of spinal arachnoiditis following a caudal block. J Spinal Cord Med. 2011;34:616–9
23. Lin EP, Aronson LA. Successful resuscitation of bupivacaine-induced cardiotoxicity in a neonate. Paediatr Anaesth. 2010;20:955–7
24. Symons JA, Palmer GM. Neuropathic pain and foot drop related to nerve injury after short duration surgery and caudal analgesia. Clin J Pain. 2008;24:647–9
25. Beyaz SG, Tokgöz O, Tüfek A. Caudal epidural block in children and infants: retrospective analysis of 2088 cases. Ann Saudi Med. 2011;31:494–7
26. Aprodu GS, Munteanu V, Filciu G, Goţia DG. [Caudal anesthesia in pediatric surgery]. Rev Med Chir Soc Med Nat Iasi. 2008;112:142–7
27. Hessian EC, Evans BE, Woods JA, Taylor DJ, Kinkel E, Bjorksten AR. Plasma ropivacaine concentrations during bilateral transversus abdominis plane infusions. Br J Anaesth. 2013;111:488–95
28. Griffiths JD, Le NV, Grant S, Bjorksten A, Hebbard P, Royse C. Symptomatic local anaesthetic toxicity and plasma ropivacaine concentrations after transversus abdominis plane block for Caesarean section. Br J Anaesth. 2013;110:996–1000
29. Barreveld A, Witte J, Chahal H, Durieux ME, Strichartz G. Preventive analgesia by local anesthetics: the reduction of postoperative pain by peripheral nerve blocks and intravenous drugs. Anesth Analg. 2013;116:1141–61
30. McAlvin JB, Reznor G, Shankarappa SA, Stefanescu CF, Kohane DS. Local toxicity from local anesthetic polymeric microparticles. Anesth Analg. 2013;116:794–803
31. Li B, Yan J, Shen Y, Li B, Hu Z, Ma Z. Association of sustained cardiovascular recovery with epinephrine in the delayed lipid-based resuscitation from cardiac arrest induced by bupivacaine overdose in rats. Br J Anaesth. 2012;108:857–63
32. Schnabel A, Meyer-Frießem CH, Zahn PK, Pogatzki-Zahn EM. Ultrasound compared with nerve stimulation guidance for peripheral nerve catheter placement: a meta-analysis of randomized controlled trials. Br J Anaesth. 2013;111:564–72
33. Kent ML, Hackworth RJ, Riffenburgh RH, Kaesberg JL, Asseff DC, Lujan E, Corey JM. A comparison of ultrasound-guided and landmark-based approaches to saphenous nerve blockade: a prospective, controlled, blinded, crossover trial. Anesth Analg. 2013;117:265–70
34. Bhatia A, Brull R. Review article: is ultrasound guidance advantageous for interventional pain management? A systematic review of chronic pain outcomes. Anesth Analg. 2013;117:236–51
35. Taha AM, Abd-Elmaksoud AM. Lidocaine use in ultrasound-guided femoral nerve block: what is the minimum effective anaesthetic concentration (MEAC90)? Br J Anaesth. 2013;110:1040–4
36. Mascha EJ, Dalton JE, Kurz A, Saager L. Statistical grand rounds: understanding the mechanism: mediation analysis in randomized and nonrandomized studies. Anesth Analg. 2013;117:980–94
37. Maile MD, Engoren MC, Tremper KK, Jewell E, Kheterpal S. Worsening preoperative heart failure is associated with mortality and noncardiac complications, but not myocardial infarction after noncardiac surgery: a retrospective cohort study. Anesth Analg. 2014;119:522–3
38. Sharifpour M, Moore LE, Shanks AM, Didier TJ, Kheterpal S, Mashour GA. Incidence, predictors, and outcomes of perioperative stroke in noncarotid major vascular surgery. Anesth Analg. 2013;116:424–34
39. Long JB, Birmingham PK, De Oliveira GS Jr, Schaldenbrand KM, Suresh S. Transversus abdominis plane block in children: a multicenter safety analysis of 1994 cases from the PRAN (Pediatric Regional Anesthesia Network) database. Anesth Analg. 2014;119:395–9