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Abstract
Background This study assessed the effect of perineural dexamethasone on block duration, opioid requirement, blood glucose levels, and stress response to surgery as measured by the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), following pediatric foot and ankle surgery.
Methods In this parallel, double-blinded randomized controlled trial, 90 children (ages 2–5 years, >5 kg) scheduled for foot or ankle surgery under spinal anesthesia with ultrasound-guided single-shot popliteal sciatic nerve block were randomized into 3 groups: 0.5% ropivacaine with saline (control), 0.5% ropivacaine plus dexamethasone 0.1 mg/kg (DEX0.1), and 0.5% ropivacaine plus dexamethasone 0.05 mg/kg (DEX0.05). Primary outcome was the time to first rescue opioid analgesia. Secondary outcomes included motor block duration, pain scores, NLR, PLR, and blood glucose levels.
Results Time to first rescue opioid analgesia was significantly longer in the DEX0.1 group compared with the DEX0.05 group (18.4 hours, SD 2.6 hours vs 16 hours, SD 2.8 hours), with a mean difference of 2.2 hours (95% CI 0.7 to 3.6), p<0.01; and the control group (8.5 hours, SD 1.5 hours), with a mean difference of −9.9 (95% CI −11.4 to −8.4), p<0.001. Motor block was significantly longer in the DEX0.1 group (17.3 hours, SD 2.5 hours) compared with the DEX0.05 (15.2 hours, SD 2.7 hours; p<0.01) and control groups (7.8±1.1, p<0.001). Total opioid consumption was significantly lower in the DEX0.1 group compared with the control group (p=0.01). NLR, PLR, and glucose levels did not differ significantly between the groups at baseline, 24 hours, and 48 hours post surgery.
Conclusions Perineural dexamethasone significantly prolonged postoperative motor block duration and did not influence blood glucose, NLR, or PLR levels.
Trial registration number NCT06086418.
- Nerve Block
- Pain, Postoperative
- Lower Extremity
- Acute Pain
- Pediatrics
Data availability statement
Data are available upon reasonable request. The study datasets are available from the corresponding author at reasonable request.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, an indication of whether changes were made, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
Dexamethasone as an adjuvant to local anesthetics is known to prolong the duration of nerve blocks in adults, but its efficacy and safety in young children, particularly regarding systemic effects such as blood glucose levels and inflammatory responses, were not well documented.
WHAT THIS STUDY ADDS
This study demonstrates that perineural dexamethasone significantly prolongs the duration of ropivacaine-induced sciatic nerve blocks in children aged 2–5 years without affecting blood glucose levels or stress markers like neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
The findings support the use of dexamethasone as an effective adjuvant in pediatric nerve blocks to enhance postoperative analgesia, potentially reducing the need for opioid consumption, and could inform guidelines for pediatric anesthesia practice.
Introduction
Pediatric foot and ankle surgery can result in moderate-to-severe postoperative pain. The popliteal sciatic nerve block is frequently performed to provide postoperative analgesia and has been shown to improve pain management.1 Ropivacaine is one of the most popular local anesthetics used for peripheral nerve blocks in children due to its long duration of action and favorable safety profile compared with bupivacaine or lidocaine.2 In adults, the duration of action of a popliteal sciatic nerve block without adjunctive agents is approximately 10 hours, providing significant analgesia.3 However, many patients experience rebound pain once the sciatic nerve block wears off.4 Many adjuvants to local anesthetics have been tested to prolong the duration of peripheral nerve blocks in adults, with dexmedetomidine and dexamethasone being the most effective5 and showing similar durations of action.6 However, dexmedetomidine can cause hypotension, bradycardia, and sedation, whereas dexamethasone is associated with fewer adverse effects.
Dexamethasone is a glucocorticoid with minimal mineralocorticoid activity, frequently used during general anesthesia to prevent postoperative nausea and vomiting and in pediatric anesthesia to reduce intubation-associated edema. It reduces ectopic neuronal discharge, inhibits potassium channel-mediated firing of nociceptive C fibers, and attenuates the release of inflammatory mediators.7 The potential mechanism of action of perineural dexamethasone is to stimulate glucocorticoid receptors on neurons, increase the expression of inhibitory K+ channels, and decrease the excitability of and neuronal transmission in unmyelinated nociceptive C fibers. Importantly, especially for children, dexamethasone must be administered without preservatives such as benzyl alcohol and propylene, which can cause neurolysis.8
Dexamethasone has been associated with increased postoperative glycemia in both adults with and without diabetes.9 However, issues with wound healing and systemic or wound infections have not been documented in adults.10 There is a lack of studies on the adverse effects of perineural dexamethasone in children, particularly in younger children.
Several randomized controlled trials (RCTs) have demonstrated that dexamethasone is safe and effective in caudal blocks for children.11–14 However, intravenous dexamethasone did not enhance the duration of peripheral nerve blocks in infants and children.15 Perineural dexamethasone, at a dose of 0.1 mg/kg, showed promise in prolonging the duration of femoral nerve block in adolescents undergoing knee arthroscopy.16 In adults, perineural dexamethasone was shown to be effective at doses of 0.05 mg/kg17 and higher.18 Therefore, we examined the efficacy of 0.05 mg/kg and 0.1 mg/kg of perineural dexamethasone in children undergoing foot or ankle surgery, considering the possible side effects of higher doses. The aim of this study, without anticipating any specific result, was to evaluate the impact of perineural dexamethasone in children. The primary outcome was the time to first rescue opioid analgesia, and secondary outcomes included Face, Legs, Activity, Cry, and Controllability Scale (FLACC) scores, total opioid consumption, neutrophile-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), and blood glucose levels.
Materials and methods
Study design
This RCT was conducted in Poland and was registered at www.clinicaltrials.gov (NCT06086418) on 16 October 2023, prior to recruitment. Written informed consent was obtained from all patients’ caregivers prior to enrollment. Enrollment occurred from 17 October 2023 to 23 February 2024.
Participants
We proposed enrollment to patients meeting the inclusion criteria: <18 years old, scheduled for foot or ankle surgery under spinal anesthesia, and a body weight >5 kg. The exclusion criteria included infection at the site of the regional block, coagulation disorders, immunodeficiency, American Society of Anesthesiologists physical status of IV or higher, and a history of regular steroid medication.
Randomization and concealment
Patients were randomized using computer software in a 1:1:1 ratio, with blocks of 6 or 9 in random order, to receive ultrasound-guided popliteal sciatic nerve block with 0.2% ropivacaine (control group), 0.2% ropivacaine with 0.1 mg/kg dexamethasone (DEX0.1 group), or 0.2% ropivacaine with 0.05 mg/kg dexamethasone (DEX0.05 group). The randomization list was generated by the nQuery Advisor program (Statistical Solutions, Boston, Massachusetts, USA). Following the allocation sequence, the anesthetic nurse, who was not involved in the study, prepared the trial medication in identical opaque syringes placed in sequentially numbered containers. The anesthesia team, surgeons, operating room staff, patients and their caregivers were blinded to the study group assignments. The group blinding was unmasked after the completion of statistical analysis.
All patients underwent foot or ankle surgery under spinal anesthesia performed by a single surgical team at our institution. Patients underwent at least 2 days of active follow-up after surgery. An independent researcher collected the primary and secondary outcomes during inpatient hospital visits.
Procedures
All patients received standardized spinal anesthetic management under mild sedation, following the common practice in our hospital. In all three groups, patients received midazolam 0.25 mg/kg p.o. a half hour before the surgery as part of the multimodal preemptive analgesia protocol. Mild sedation was maintained with continuous propofol infusion at 5 mg/kg/hour throughout the surgery. Spontaneous ventilation was maintained with an oxygen mask at 2 L/min. Spinal anesthesia (L3/4; Sprotte needle 27 G × 70 mm, PAJUNK, Geisingen, Germany) was performed using 0.1 mL/kg of 0.5% ropivacaine. Pediatric patients with failed spinal anesthesia or conversion to general anesthesia were excluded from this study. No surgeon-delivered infiltration was performed before, during, or after surgery. Two anesthesiologists, each with at least 5 years of experience in post-specialty clinical expertise in pediatric regional anesthesia, performed the popliteal sciatic nerve block.
Ultrasound-guided popliteal sciatic nerve block
The popliteal sciatic nerve block was performed after the spinal anesthesia and before the surgical incision. We used a linear, high-frequency 4–8 Hz probe and a 22-gage needle (Stimuplex Ultra 360, 50 mm). The transducer was placed in a transverse orientation above the popliteal fossa between the biceps femoris and semimembranosus and semitendinosus tendons. The needle was inserted in-plane, and the tip was placed into the sciatic nerve sheath between the tibial and common peroneal nerves. Needle tip placement was ascertained using hydrolocation with 0.5 mL of 0.9% isotonic saline. After negative aspiration, 0.5 mL/kg of 0.2% ropivacaine was injected to separate the tibial and common peroneal nerves. According to random group allocation, perineural 0.5 mL/kg saline, 0.05 mg/kg dexamethasone, or 0.1 mg/kg dexamethasone was also added to the local anesthetic.19
Postoperative analgesia management
Postoperative analgesia included administering acetaminophen 15 mg/kg every 6 hours, metamizole 15 mg/kg every 6 hours, and ibuprofen 10 mg/kg every 8 hours. Additionally, if the patient’s FLACC score was 4 or above, a 0.1 mg/kg nalbuphine bolus injection was administered for rescue analgesia.
Assessment of postoperative outcomes
Primary outcome
The time to first rescue opioid analgesia was assessed by residents not involved in the study from the postoperative and orthopedic wards.
Secondary outcomes
A blinded observer contacted the study subjects’ caregivers, who were also blinded to the study group allocation, for toe movement data collection at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 hours after surgery. The pain score was also assessed using the FLACC score (0 meaning no pain and 10 meaning the worst pain imaginable) at all these postoperative time points. Two independent physicians examined each subject, and the final score was agreed on at the end of the assessment. Total opioid consumption was assessed from the postoperative and orthopedic ward records by residents not involved in the study.
Blood samples for PLR, NLR, and blood glucose were obtained 24 hours and 48 hours after surgery. Two researchers who were blinded to the group allocation assessed these outcomes.
Data regarding nerve injury, identified as nerve deficits, were collected post hoc retrospectively from the orthopedic wards on the day of discharge. Nerve deficits were defined as sensory findings: 0—no nerve damage, 1—minor sensory paresthesias, 2—complete sensory anesthesia, 3—complete motor defect with or without sensory paresthesia, and 4—complex regional pain syndrome. Two researchers who were blinded to the group allocation assessed these outcomes.
Statistical analysis
The sample size was based on our primary hypothesis that the time to first rescue opioid analgesia would be significantly longer in the DEX0.1 group than that in the DEX0.05 group. Our null hypothesis was that there would be no significant difference in the time to first rescue analgesia between these two groups. The time to first rescue opioid analgesia was the primary variable. Based on a pilot study on 10 patients, not included in the final analysis, the time to first rescue opioid analgesia was 19.00±2.03 hours (mean±SD) in the DEX0.1 group and 15.90±2.97 hours (mean±SD) in the DEX0.05 group. Using pairwise comparison, we calculated the sample size required to detect a difference in the time to first rescue opioid analgesia among the three groups. Bonferroni correction was performed to adjust for the increased type I error rate in multiple comparisons. Accordingly, 28 subjects were required in each group to achieve a statistical power of 95% at a p value of <0.05. To facilitate block randomization and account for loss to follow-up, 30 pediatric patients per group (90 in total) were recruited.
Statistical analysis was performed using GraphPad Prism V.10.1.1 (270) software (GraphPad Software, San Diego, California, USA). The parametric distribution of numerical variables was evaluated using the Shapiro-Wilk normality test. Differences between groups were assessed using the analysis of variance with post hoc Tukey’s test. Categorical variables were compared with the Kruskal-Wallis test, and contingency analysis between groups was conducted using Fisher’s exact test. A p value of <0.05 was considered statistically significant and was calculated with 95% CIs.
Results
Summary of participation
Out of the 101 children assessed for eligibility, 8 did not meet the inclusion criteria, and the caregivers of 4 children refused to participate. The remaining 90 children were randomly allocated to 3 groups and analyzed, as depicted in figure 1. No clinically relevant differences were observed among the group characteristics, as shown in table 1.
Baseline characteristics
Consolidated Standards of Reporting Trials 2010 flow diagram.
Primary outcomes
The time to first rescue opioid analgesia was significantly longer in the DEX0.1 group compared with both the DEX0.05 and control groups, as shown in table 2.
Time to first rescue opioid analgesia, motor block, and total opioid consumption
Secondary outcomes
Time to first toe movement
The time to first toe movement was significantly longer in the DEX0.1 group compared with both the DEX0.05 and control groups. Additionally, the time to first toe movement was significantly longer in the DEX0.05 compared with the control group, as shown in table 2.
Total opioid consumption
Total opioid consumption within 48 hours after surgery, expressed in nalbuphine mg/kg, was significantly lower in the DEX0.1 group compared with the control group. However, there was no significant difference in total opioid consumption between the DEX0.1 and the DEX0.05 groups, nor between the DEX0.05 and the control groups.
The number of patients requiring opioid analgesia differed significantly between the DEX0.1 and the control groups but not between the DEX0.05 and the control groups or between the DEX0.1 and DEX0.05 groups, as shown in table 2.
FLACC score
The FLACC scores differed significantly between the DEX0.1 and the DEX0.05 groups only 4 hours after surgery. However, as shown in table 3, there were no significant differences in FLACC scores between the DEX0.1 and the DEX0.05 groups at other time points. Additionally, FLACC scores did not significantly differ between the DEX0.1 and the control groups or between the DEX0.05 and the control groups 4 hours after surgery.
FLACC scores
However, FLACC scores significantly differed between the DEX0.1 and the control groups and between the DEX0.05 and the control groups up to 20 hours after surgery.
Blood glucose levels
Blood glucose levels (mg/dL) did not statistically differ among the three groups before surgery, 24 hours after surgery, and 48 hours after surgery. Furthermore, blood glucose levels did not significantly differ between the DEX0.1 group and the DEX0.05 group before surgery, 24 hours after surgery, and 48 hours after surgery (table 4).
Biochemical values
NLR and PLR levels
We found no significant differences in NLR and PLR levels among the groups (table 4).
Nerve deficits
No occurrences of nerve damage were observed in any of the three groups.
Discussion
This RCT compared the effect of two concentrations of perineural dexamethasone, 0.1 mg/kg and 0.05 mg/kg, on pediatric ultrasound-guided popliteal sciatic nerve block. Our results suggest that perineural dexamethasone prolongs the mean time to first rescue opioid analgesia by 10 hours compared with a placebo. In addition, 0.1 mg/kg perineural dexamethasone prolongs the mean time to first rescue opioid analgesia and motor block duration by 2 hours compared with 0.05 mg/kg dexamethasone. Consequently, perineural dexamethasone lowered the FLACC pain scores. Importantly, administering perineural dexamethasone at doses of 1.0 mg/kg and 0.05 mg/kg did not affect blood glucose levels or alter the surgical stress response in children undergoing foot or ankle surgery.
Our study is one of the few to examine the use of perineural dexamethasone as an adjuvant to ropivacaine when performing blocks in pediatric populations. Two other RCTs have investigated perineural dexamethasone in children.16 20 Veneziano et al16 studied children aged 10–18 years undergoing femoral nerve block for knee arthroscopy, while Arafa et al20 examined children aged 6–12 years undergoing Quadratus Lumborum Block for renal surgeries.
Similar to these two studies, our trial demonstrated prolonged time to first rescue analgesia and motor block duration with the addition of perineural dexamethasone to the local anesthetic. Arafa et al20 reported that perineural dexamethasone (0.1 mg/kg) prolonged the time to first rescue opioid analgesia for up to 7 hours post surgery, and Veneziano et al16 found that the same dosage extended time to first rescue analgesia up to 29 hours post surgery. However, in our study, dexamethasone at 0.1 mg/kg prolonged the time to first rescue opioid analgesia up to 10 hours post surgery and at 0.05 mg/kg by up to 7.5 hours, possibly due to variations in patient age and types of peripheral nerve blocks.
Consistent with the findings of those two studies, our study also showed a reduction in postoperative opioid consumption and pain scores. Veneziano et al16 used the Visual Analogue Scale (VAS) score, and Arafa et al20 used the Pediatric Objective Pain Score, whereas our study employed the FLACC score because all our patients were younger than seven years old.
This study is the first to compare two doses of dexamethasone regarding their influence on blood glucose levels and surgical stress response, as measured by NLR and PLR levels in children. Our findings are similar to findings in studies on adults, where the addition of dexamethasone to local anesthetics in peripheral nerve blocks did not influence blood glucose levels,21 22 suggesting that dexamethasone at 0.1 mg/kg or lower doses has no systematic effect on stress response or blood glucose levels.
Previous studies in adults have shown that regional anesthesia reduces the stress response caused by surgery23–26 or opioids.27 28 However, no studies have investigated the influence of perineural adjuvants on surgery stress response when added to local anesthetics used in regional anesthesia. Thus, our study addressed this gap by showing that perineural dexamethasone does not affect stress response as measured by NLR and PLR levels.
Limitations
The main limitation of this study is that the duration of motor block (toe movement) and time to first opioid rescue analgesia inherently depended on caregivers' recall. However, this limitation would similarly impact all three study groups, hence minimizing the potential recall bias on study findings. Data on nerve injury were collected retrospectively, carrying a risk of under-reporting. Additionally, blood glucose, NLR, and PLR levels were not measured at 6 and 12 hours post surgery. Finally, hospital discharge times and subsequent adverse effects were not monitored. Future trials are necessary to explore different local anesthetic solutions and doses.
To conclude, the addition of dexamethasone at doses of 0.05 mg/kg and 0.1 mg/kg to ropivacaine significantly prolonged the mean time to first rescue opioid analgesia and the mean duration of postoperative motor block compared with ropivacaine alone in pediatric popliteal sciatic nerve block. Furthermore, dexamethasone did not influence blood glucose levels or the surgical stress response as measured by the NLR and PLR levels.
Data availability statement
Data are available upon reasonable request. The study datasets are available from the corresponding author at reasonable request.
Ethics statements
Patient consent for publication
Ethics approval
Ethics approval was obtained on 13 September 2023, from the Bioethics Committee at the Poznan University of Medical Sciences, Poznan, Poland (protocol number 539/23). The study was conducted according to the Declaration of Helsinki. Participants gave informed consent to participate in the study before taking part.
Footnotes
Contributors Conceptualization, methodology: MR and TR. Software: PD and MS. Validation: MR, MS, and TR. Formal analysis: TR and PD. Investigation: MR, GK, MS, and TR. Resources: GK. Data curation: PD, PJ and TR. Writing—original draft preparation: MR. Writing—review and editing: MR, PJ, TK, KW-T, and TR. Visualization: KW-T. Supervision, project administration, acquisition: KW-T and TK. Guarantor: M.R.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.