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The Ropivacaine Concentration Required for Ultrasound-Guided Ilioinguinal/Iliohypogastric Nerve Block in Pediatric Patients

Yamada, Kumiko MD; Inomata, Shinichi MD; Tanaka, Makoto MD

doi: 10.1213/ANE.0000000000001329
Pediatric Anesthesiology: Research Report

BACKGROUND: To the best of our knowledge, the ropivacaine concentration required for ultrasound-guided ilioinguinal and iliohypogastric nerve block (INB) has not been reported. We designed this study to examine the 50% effective concentration (EC50) of ropivacaine for ultrasound-guided INB in children anesthetized with 2% sevoflurane.

METHODS: We studied 30 consecutive children (age range, 6 months to 11 years) ASA physical status I to II undergoing unilateral open inguinal hernia repair. General anesthesia was induced by sevoflurane and maintained with 2% end-tidal concentration of sevoflurane in air and oxygen (FIO2 = 0.4). Ultrasound-guided INB was performed using a 3 mL ropivacaine solution. The first child received 0.3% ropivacaine, and subsequent concentrations were determined by the response of the previous patient to initial skin incision using Dixon up-and-down method. The testing interval was set at 0.1%, and the lowest concentration was 0.05% (0.05%, 0.1%, 0.2%, 0.3%, 0.4%, or 0.5%). The EC50 for INB of ropivacaine was analyzed using probit test.

RESULTS: The concentration at which all patients showed complete block was 0.50%, according to the up-and-down method. The EC50 was 0.21% (95% confidence interval, 0.03–0.34).

CONCLUSIONS: The EC50 of ropivacaine for ultrasound-guided INB was 0.21% (95% confidence interval, 0.03–0.34), in pediatric patients anesthetized with 2% sevoflurane.

From the Faculty of Medicine, Division of Clinical Medicine, Department of Anesthesiology, University of Tsukuba, Tsukuba, Ibaraki, Japan.

Accepted for publication February 27 2016.

Funding: Departmental.

The authors declare no conflicts of interest.

Reprints will not be available from the authors.

Address correspondence to Shinichi Inomata, MD, Faculty of Medicine, Division of Clinical Medicine, Department of Anesthesiology, University of Tsukuba, Tsukuba City, Ibaraki 305, Japan. Address e-mail to inomatas@md.tsukuba.ac.jp.

Ilioinguinal and iliohypogastric nerve block (INB) is a commonly used technique in inguinal surgery.1,2 Ultrasound guidance improves the quality of INB.3

Ropivacaine is a long-acting local anesthetic, is less cardiotoxic, and causes less central nervous system toxicity than bupivacaine.4–6 Ropivacaine has been reported to provide effective analgesia when given as a single INB in 1- to 12-year-old children.7,8 The concentration of ropivacaine used in INB ranges from 0.2% to 0.75% in children.7–9 The concentration of local anesthetics required for INB in children anesthetized with sevoflurane without nitrous oxide has not yet been determined. The concentration is very important in judging the success rate of regional anesthesia.

We designed this prospective study to examine the 50% effective concentration (EC50) of ropivacaine for ultrasound-guided INB in children anesthetized with 2% sevoflurane. Primary outcome was the concentration at which all patients showed complete block. Secondary outcome was the EC50 of ropivacaine for INB under general anesthesia with 2% sevoflurane in oxygen.

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METHODS

The study was approved by the Ethics Committee of the University of Tsukuba in 2006. (H24-047). Trial registration was performed via the university hospital Medical Information Network Center Clinical Trials Register (registration number: UMIN 000012907; principal investigator’s name: Shinichi Inomata; date of registration: January 21, 2014). When beginning our study, registration in the University of Tsukuba system was not required. Written informed consent was obtained from parents.

The study comprised 30 ASA physical status I to II children, age ranging from 6 months to 11 years, who were scheduled for elective unilateral open inguinal hernia repair under general anesthesia. Patients with any contraindication to INB, a history of allergy to study drugs, or parental refusal were excluded from the study.

After a perioperative fasting period of a minimum of 3 hours, all patients received oral midazolam 0.5 mg kg−1. In the theatre, electrocardiography, noninvasive blood pressure, and pulse oximeter were monitored. General anesthesia was induced with sevoflurane (5%) in oxygen through facemask without neuromuscular relaxants and IV anesthetics. After tracheal intubation and INB, anesthesia was maintained with 2% (1 minimum alveolar concentration [MAC])10,11 end-tidal concentration of sevoflurane in oxygen and air (FIO2, 0.4). The lungs were mechanically ventilated using a pressure-controlled mode to maintain ETCO2 between 35 and 45 mm Hg.

Patients received an INB under ultrasound guidance using S-Nerve ultrasound unit (Sonosite, Bothell, WA) and linear probe (HFL 38 X, 6–13 MHz) after general anesthesia was induced. We used a 25-gauge 22-mm needle (B. Braun, Melsungen, Germany). The needle was advanced with the ultrasound beam until the needle tip was placed adjacent to each target nerve. Once the tip of the needle was placed, and negative aspiration was achieved, 3 mL ropivacaine was administered under direct ultrasound guidance. The first child received 0.3% ropivacaine, and subsequent concentrations were determined by the response of the previous patient to the initial skin incision by the use of Dixon up-and-down method. The testing interval was set at 0.1%, and the lowest concentration was 0.05%. Local anesthetic solution was 3 mL. Blocks were performed by residents with 6 months to 1 year of experience in anesthesiology. The surgical procedure was started at least 15 minutes after the nerve block. The patients were maintained at 2% end-tidal sevoflurane for 15 to 20 minutes before the skin incision. After skin incision, patients’ body movement and hemodynamic changes were observed for 5 minutes. Patients who showed body movements, an increase in systolic blood pressure, and/or heart rate changes of >20% of the baseline value just before, during, and/or after the skin incision were immediately given 1 μg kg−1 fentanyl. These patients’ blocks were regarded as “failed.” Painful traction of the peritoneum was not relieved by INB during surgery, and fentanyl was used if necessary after the assessment.

The anticipated number of “failed − complete” pairs was calculated with power analysis based on the results of Sebel et al.12 Six pairs of patients are necessary to provide 80% power (1 − β = 0.80), with a 5% 2-sided type I error (α = 0.05). For sample size, we continued data sampling until we had obtained 6 or more mid-points of pairs of concentration.13

Data are presented as mean (range) as appropriate. The EC50 with 95% confidence intervals (CIs) was analyzed using probit test (SAS System, version 6.12, SAS Institute Inc., Cary, NC). The probit analysis was as follows:

Probit equation:

CV

CV

and

CV

CV

We analyzed the ropivacaine concentration required for a successful block by using probit test in which P, the probability of a successful block, was defined by the above equation, where X1 is the ropivacaine concentration, β0 is the regression intercept constant, and β1 is the coefficient for ropivacaine concentration.

To determine the concentration of ropivacaine required for a successful block in 50% of children, the probability of success was assigned the value 0.5, and the equation was solved for the ropivacaine concentration as follows:

CV

CV

CV

CV

For instance, EC50 = −(−2.13)/10.06 = 0.21.

Likewise, for 95% CI, the equation was

CV

CV

where variance for β0 is ν00, variance for β1 is ν11, and covariance for β0 and β1 is ν01. All values were calculated using probit test.

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RESULTS

Table 1

Table 1

Figure 1

Figure 1

Figure 2

Figure 2

Figure 3

Figure 3

Thirty children were enrolled in the study (Fig. 1). Their mean age was 4 years (6 months to 11 years), mean weight was 16 kg (9 to 34 kg), and mean height was 98 cm (66 to 144 cm). There were no surgical or anesthetic complications. Sequential patient response to initial skin incision with “up-and-down” method is shown in Figure 2. Table 1 shows ropivacaine concentrations and percentages of patients who had a complete INB. The dose-response curve for this patient population is shown in Figure 3. The EC50 was 0.21% (95% CI, 0.03%–0.34%). The highest ropivacaine concentration in this study was 0.5%, which we selected using the up-and-down method. No adverse effect related to INB was observed.

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DISCUSSION

The EC50 of ropivacaine for ultrasound-guided INB was 0.21% (95% CI, 0.03%–0.34%) in pediatric patients anesthetized with 2% sevoflurane. The highest ropivacaine concentration was 0.5%, which we selected using the up-and-down method.

INB is a commonly used technique in inguinal surgery.1,2 Ultrasound guidance improves the quality of INB.3 Ropivacaine is a long-acting local anesthetic. It is less cardio toxic and causes less central nervous system toxicity than bupivacaine.4–6 Ropivacaine has been reported to provide effective analgesia when given as a single INB in 1- to 12-year-old children.7,8 Although the concentration of ropivacaine used in INB ranges from 0.2% to 0.75% in children,7–9 the exact concentration has not been determined. We designed this prospective study to examine the EC50 of ropivacaine for ultrasound-guided INB in children under general anesthesia.

The important factors in assessing the effectiveness of regional anesthesia are the volume and concentration of the local anesthetic solution.14 Weintraud et al.15 reported a volume of 0.25 mL kg−1 (16 kg: 4 mL) of 0.5% ropivacaine provided sufficient analgesia in 94% of pediatric patients with ultrasound-guided INB. On the other hand, Willschke et al.16 reported that a volume of only 0.075 mL kg−1 of local anesthetic provided sufficient analgesia with ultrasound-guided INB in pediatric anesthesia. Starting at the middle of these values, we began research with 3 mL. In addition, nerve dimension may be larger in older children than in younger children. With respect to the volume of local anesthetic, Eichenberger et al.17 established an effective dose of 1% mepivacaine to accomplish an adequate ulnar nerve sensory block and measured the ulnar nerve at the proximal forearm by ultrasound image in volunteers. The ED95 volume of mepivacaine was 0.11 mL mm−2 (SD, 0.03 mL mm−2). The mean cross-sectional area of the nerve was 6.2 mm2 (SD, 1.0 mm2). Eichenberger et al.’s report indicates that a volume of 0.68 mL can accomplish ulnar nerve block, and a volume of 3 mL can block a nerve area of 30 mm2 (from 3 to 4 mm in diameter). In addition, Willschke et al.16 reports that a volume of 0.075 mL kg−1 of local anesthetic provides sufficient analgesia in ultrasound-guided INB in pediatric anesthesia. The patients’ body weight in this study ranged from 9 to 34 kg, and a volume of 3 mL was, therefore, >0.075 mL kg−1 in all cases and considered sufficient. We performed these blocks at our hospital under ultrasound guidance. We chose a volume of 3 mL because ultrasound shows that it sufficiently covers the essential neural region.

The concentration and volume of local anesthetic used for a nerve block affect its success. If both are changed, it may complicate the study unnecessarily. Therefore, we started research with a constant volume while determining the concentration required for a successful block. That is, we first aimed to determine a concentration that was successful in all patients in this study and then determined the required volume.

Dalens et al.7 reported that a dose of 3 mg kg−1 ropivacaine, given as a single INB (landmark-based technique) in 1- to 12-year old children, is well tolerated and has no local anesthetic toxicity. The dose of ropivacaine in the study was <3 mg kg−1 in all. Conversely, Weintraud et al.15 reported that plasma concentrations of ropivacaine are higher when using an ultrasound-guided technique than when using a landmark-based technique for INB in children. Thus, a reduction in the volume and concentration of local anesthetic should be considered when using ultrasound-guided INB, especially when done on the both sides for small patients. Although a larger volume might have covered more of the field, we used a fixed volume to mitigate the risk of local anesthetic toxicity.

Our study has several limitations. First, for the purposes of this study, we determined the success or failure of the block based on hemodynamic change and movement on skin incision. Our criteria for the success of the block did not include the response to surgery of deeper tissue. Second, the investigators were not blinded to the concentration of ropivacaine. Third, determination of the minimum concentration of local anesthetic may be affected by various elements. In this study, premedication with midazolam and inhaled anesthetic (2% sevoflurane) might have affected our results. A concentration of 2% sevoflurane is equal to MAC value of approximately 1. Although some children may not move under a 2% concentration of sevoflurane, more may move at lower concentrations. At lower concentrations, complications such as strong motion and bronchospasm are feared. We selected the 2% concentration of sevoflurane as the safest and most commonly used in clinical situations. We recognize that MAC changes with age and affects the study results. However, we chose a simple protocol to avoid dropout by mistake during a long study. Fourth, it is possible that 15 minutes was insufficient in some patients, especially at low concentrations of local anesthetic. With respect to the elapsed time after a block, Butterworth et al.18 report that it takes almost 40 minutes for a median nerve block to become fully effective when using 0.33% bupivacaine and that 1% mepivacaine and 0.33% bupivacaine show different onset times (10–15 minutes and 25–30 minutes, respectively) according to a pinprick test in adults. Conversely, Klein et al.19 reported that the mean onset time of sensory blockade during an interscalene block was shorter than 6 minutes under 0.5% and 0.75% ropivacaine, and that there was no difference between the 0.5% and 0.75% groups. Fifth, the subgroup that received ropivacaine at a concentration of 0.4% seemed to be an outlier and, therefore, might have a wide CI.

In conclusion, the EC50 of ropivacaine for ultrasound-guided INB was 0.21% (95% CI, 0.03%–0.34%) in children anesthetized with 2% sevoflurane.

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DISCLOSURES

Name: Kumiko Yamada, MD.

Contribution: This author helped with the study design, conduct of this study, data collection, data review and analysis, manuscript preparation, and is one of the archival authors.

Attestation: Kumiko Yamada approved the final version of the manuscript.

Name: Shinichi Inomata, MD.

Contribution: This author helped with the study design, conduct of this study, data collection, data review and analysis, manuscript preparation, and is one of the archival authors.

Attestation: Shinichi Inomata approved the final version of the manuscript.

Name: Makoto Tanaka, MD.

Contribution: This author helped with the manuscript preparation.

Attestation: Makoto Tanaka approved the final version of the manuscript.

This manuscript was handled by: James A. DiNardo, MD.

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REFERENCES

1. Shandling B, Steward DJRegional analgesia for postoperative pain in pediatric outpatient surgery.J Pediatr Surg198015477–80
2. Scott AD, Phillips A, White JB, Stow PJAnalgesia following inguinal herniotomy or orchidopexy in children: a comparison of caudal and regional blockade.J R Coll Surg Edinb198934143–5
3. Willschke H, Marhofer P, Bösenberg A, Johnston S, Wanzel O, Cox SG, Sitzwohl C, Kapral SUltrasonography for ilioinguinal/iliohypogastric nerve blocks in children.Br J Anaesth200595226–30
4. Scott DB, Lee A, Fagan D, Bowler GM, Bloomfield P, Lundh RAcute toxicity of ropivacaine compared with that of bupivacaine.Anesth Analg198969563–9
5. McClure JHRopivacaine.Br J Anaesth199676300–7
6. Knudsen K, Beckman Suurküla M, Blomberg S, Sjövall J, Edvardsson NCentral nervous and cardiovascular effects of i.v. infusions of ropivacaine, bupivacaine and placebo in volunteers.Br J Anaesth199778507–14
7. Dalens B, Ecoffey C, Joly A, Giaufré E, Gustafsson U, Huledal G, Larsson LEPharmacokinetics and analgesic effect of ropivacaine following ilioinguinal/iliohypogastric nerve block in children.Paediatr Anaesth200111415–20
8. Ala-Kokko TI, Karinen J, Räihä E, Kiviluoma K, Alahuhta SPharmacokinetics of 0.75% ropivacaine and 0.5% bupivacaine after ilioinguinal-iliohypogastric nerve block in children.Br J Anaesth200289438–41
9. Tanaka HSafe use of ropivacaine for regional anesthesia in young children.J Jpn Soc Clin Anesth200929718–23
10. Inomata S, Watanabe S, Taguchi M, Okada MEnd-tidal sevoflurane concentration for tracheal intubation and minimum alveolar concentration in pediatric patients.Anesthesiology19948093–6
11. Inomata S, Nishikawa TDetermination of end-tidal sevoflurane concentration for tracheal intubation in children with the rapid method.Can J Anaesth199643806–11
12. Sebel PS, Glass PS, Fletcher JE, Murphy MR, Gallagher C, Quill TReduction of the MAC of desflurane with fentanyl.Anesthesiology19927652–9
13. Aantaa R, Jaakola ML, Kallio A, Kanto JReduction of the minimum alveolar concentration of isoflurane by dexmedetomidine.Anesthesiology1997861055–60
14. Fredrickson MJ, Smith KR, Wong ACImportance of volume and concentration for ropivacaine interscalene block in preventing recovery room pain and minimizing motor block after shoulder surgery.Anesthesiology20101121374–81
15. Weintraud M, Lundblad M, Kettner SC, Willschke H, Kapral S, Lönnqvist PA, Koppatz K, Turnheim K, Bsenberg A, Marhofer PUltrasound versus landmark-based technique for ilioinguinal-iliohypogastric nerve blockade in children: the implications on plasma levels of ropivacaine.Anesth Analg20091081488–92
16. Willschke H, Bösenberg A, Marhofer P, Johnston S, Kettner S, Eichenberger U, Wanzel O, Kapral SUltrasonographic-guided ilioinguinal/iliohypogastric nerve block in pediatric anesthesia: what is the optimal volume?Anesth Analg20061021680–4
17. Eichenberger U, Stöckli S, Marhofer P, Huber G, Willimann P, Kettner SC, Pleiner J, Curatolo M, Kapral SMinimal local anesthetic volume for peripheral nerve block: a new ultrasound-guided, nerve dimension-based method.Reg Anesth Pain Med200934242–6
18. Butterworth J, Ririe DG, Thompson RB, Walker FO, Jackson D, James RLDifferential onset of median nerve block: randomized, double-blind comparison of mepivacaine and bupivacaine in healthy volunteers.Br J Anaesth199881515–21
19. Klein SM, Greengrass RA, Steele SM, D’Ercole FJ, Speer KP, Gleason DH, DeLong ER, Warner DSA comparison of 0.5% bupivacaine, 0.5% ropivacaine, and 0.75% ropivacaine for interscalene brachial plexus block.Anesth Analg1998871316–9
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