European Journal of Cardiovascular Medicine

The management of pediatric pain, especially in the postoperative period, has undergone significant advancements, yet it remains an area fraught with challenges such as the risk of opioid-induced respiratory depression and the potential for addiction. The evolution of pediatric analgesia has been marked by a better understanding of pediatric neurobiology and the advent of novel analgesics, fostering a multimodal approach that integrates systemic opioids, non-steroidal anti-inflammatory drugs (NSAIDs), and regional anesthesia techniques, with or without adjuvants, either alone or in combination[1].

Among the regional anesthesia techniques, the caudal block stands out as a cornerstone for providing postoperative analgesia in children undergoing infraumbilical surgeries[2]. This popularity owes to its effectiveness in managing postoperative pain with a relatively low side-effect profile. The advent of combining local anesthetics with adjuvants in caudal blocks has significantly enhanced the quality of analgesia, thereby reducing side effects and facilitating early discharge[3].

Local anesthetics such as Bupivacaine, Levobupivacaine, and Ropivacaine, in various concentrations and combined with additives like fentanyl, midazolam, morphine, and others, have been explored to improve efficacy and prolong the duration of analgesia[4]. Levobupivacaine, an S [–] enantiomer of racemic bupivacaine, exhibits similar anesthetic properties but with reduced cardiotoxicity, a critical advantage given the potentially fatal cardiovascular side effects associated with racemic bupivacaine[5]. Ropivacaine, another S-enantiomer of an amide local anesthetic, is distinguished by its differential neural blockade, favoring sensory over motor blockade, and its lower propensity for cardiovascular and neurological toxicity. These attributes make Ropivacaine particularly suitable for day-care surgeries in the pediatricpopulation[6].

Despite these advances, the literature reveals a scarcity of studies directly comparing the effectiveness of Ropivacaine with different adjuvants for both intraoperative and postoperative analgesia. The current study aims to fill this gap by evaluating the efficacy of Ropivacaine combined with either fentanyl or midazolam in pediatric single-shot caudal blocks. Such a comparative analysis is pivotal for elucidating the optimal adjuvant for enhancing caudal block analgesia while minimizing adverse effects, thereby guiding clinical practice towards safer, more effective pain management strategies in pediatric surgeries.

The choice of adjuvants like fentanyl, a potent opioid analgesic, and midazolam, a benzodiazepine with anxiolytic, amnestic, and sedative properties, for combination with Ropivacaine in caudal blocks, reflects a strategic approach to leverage the synergistic effects of these drugs. Fentanyl can enhance the analgesic efficacy of local anesthetics while potentially shortening the onset time of the block[7]. Conversely, midazolam, when used as an adjuvant, not only prolongs the duration of analgesia but also provides sedation and anxiolysis, which are beneficial in the pediatric surgical context[8].

In conducting this comparative study, it becomes imperative to systematically assess the analgesic effectiveness, onset and duration of action, and the incidence of side effects associated with each combination. This involves a rigorous methodological framework that ensures the reliability and validity of the findings, thereby contributing valuable insights into pediatric analgesia practice.

Aims and Objectives

The aim of the study was to compare the effectiveness of 0.25% Ropivacaine with Fentanyl and 0.25% Ropivacaine with Midazolam in pediatric single-shot caudal blocks for providing intraoperative and postoperative analgesia. The objective was to evaluate and document the analgesic efficacy, onset and duration of analgesia, and the incidence of side effects associated with each combination to identify the optimal adjuvant for enhancing caudal block analgesia in children undergoing infraumbilical surgeries.

The methodology employed in this study was designed to ensure a rigorous and comprehensive evaluation of the comparative effectiveness of the two drug combinations. The study was conducted as a double-blinded, prospective, randomized clinical trial. Ethical approval was obtained from the Institutional Ethics Committee before the commencement of the study. The study population consisted of children aged 2 to 5 years, classified as ASA (American Society of Anesthesiologists) I&II, who were scheduled for infraumbilical surgeries at MLB Medical College and Hospital, Jhansi, India.

The sample size was determined based on a preliminary literature review and power analysis to ensure adequate statistical power to detect a significant difference between the two groups. A total of 80 children were enrolled in the study, with 40 children randomly assigned to each group. Randomization was achieved using a computer-generated random number table to ensure the allocation concealment.

Inclusion criteria for the study were children aged 2 to 5 years, ASA I&II, scheduled for elective infraumbilical surgeries.

Exclusion criteria included children with known allergies to the study medications, contraindications to caudal block, coagulopathy, infection at the injection site, and chronic analgesic therapy.

Group 1 consisted of patients who received 1ml/kg of 0.25% Ropivacaine combined with 1µg/kg Fentanyl for the caudal block. Group 2 consisted of patients who received 1ml/kg of 0.25% Ropivacaine combined with 50µg/kg Midazolam for the caudal block. After the induction of anesthesia with titrated doses of propofol and facilitation of intubation with atracurium (0.5mg/kg), patients were maintained on N2O and O2 (50% each) with 2% Sevoflurane. The caudal block was performed in the left lateral position using a 22 G needle under strict aseptic conditions. The surgical procedure commenced 15 minutes post-block to allow for the onset of analgesia.

The primary outcomes measured were the analgesic efficacy as determined by intraoperative heart rate and blood pressure monitoring at 10-minute intervals, including pre and post-induction, and postoperative pain assessment using the Children’s and Infant’s Postoperative Pain Scale (CHIPPS) at 2, 4, 6, 12, and 24 hours post-surgery. Secondary outcomes included the onset and duration of analgesia and the incidence of side effects such as nausea, vomiting, and pruritus.

Data analysis was conducted using Fisher's exact p-test, chi-square test, and student's paired t-test to compare the effectiveness, onset and duration of analgesia, and side effects between the two groups. The statistical significance was set at a p-value of less than 0.05.

The study meticulously documented the clinical parameters and employed a structured working proforma for each participant, encompassing demographic details, clinical examination findings, ASA grading, airway assessment, diagnosis, details of the operation, and anesthetic management. This comprehensive approach ensured the collection of relevant and detailed data to support the objectives of the study.

The comparative study of 0.25% Ropivacaine with Fentanyl versus 0.25% Ropivacaine with Midazolam in pediatric single-shot caudal blocks aimed to evaluate the efficacy and safety of these analgesic combinations in children undergoing infraumbilical surgeries. The study included a total of 80 participants, evenly divided into two groups based on the adjuvant used with Ropivacaine for the caudal block.

Baseline characteristics of the participants, including age, sex, weight, ASA classification, and type of surgery, were comparable between the two groups. The mean age was 3.5 ± 1.0 years in the Ropivacaine + Fentanyl group and 3.6 ± 1.1 years in the Ropivacaine + Midazolam group, with a p-value of 0.76, indicating no significant difference. Similarly, there were no significant differences in sex distribution, weight, ASA classification, or type of surgery between the two groups, with p-values of 0.70, 0.82, 0.65, respectively, and 0.73, 0.69, and 1.00 for the types of surgeries performed.

Intraoperative monitoring parameters were closely monitored and compared between the two groups. Heart rate, systolic blood pressure, diastolic blood pressure, and SpO2 levels were recorded at baseline (T0), before incision (T1), and at 10-minute intervals after incision (T2, T3, T4). There were no significant differences in heart rate, systolic or diastolic blood pressure, or SpO2 levels between the two groups at any of the time points, with p-values ranging from 0.65 to 0.98, indicating similar intraoperative hemodynamic stability under both analgesic regimens.

Postoperative pain assessment using the CHIPPS scale revealed significant differences in pain scores between the two groups at 2, 4, 6, 12, and 24 hours post-surgery. The Ropivacaine + Fentanyl group demonstrated lower pain scores at all time points compared to the Ropivacaine + Midazolam group, with p-values of 0.03, 0.04, 0.01, 0.05, and 0.02, respectively. This suggests a superior analgesic effect of Ropivacaine when combined with Fentanyl in the immediate postoperative period.

The duration of analgesia also differed significantly between the two groups. The mean duration was longer in the Ropivacaine + Fentanyl group (8 ± 1.5 hours) compared to the Ropivacaine + Midazolam group (6 ± 1.7 hours), with a p-value of <0.001, indicating the addition of Fentanyl may prolong the analgesic effect of Ropivacaine in pediatric caudal blocks.

The incidence of side effects, including nausea, vomiting, pruritus, and respiratory depression, was monitored, showing no significant differences between the two groups. The percentages of patients experiencing nausea, vomiting, and pruritus were low and similar across both groups, with p-values of 0.45, 0.31, and 0.68, respectively. There were no instances of respiratory depression in either group.

Postoperative analgesic requirements were assessed, revealing a non-significant trend towards higher use of Paracetamol and Tramadol in the Ropivacaine + Midazolam group compared to the Ropivacaine + Fentanyl group, with p-values of 0.15 and 0.11, respectively. This trend suggests that the combination of Ropivacaine with Fentanyl may be more effective in reducing the need for additional postoperative analgesia.

In summary, the study findings indicate that 0.25% Ropivacaine combined with Fentanyl provides better postoperative analgesia with a longer duration of action and does not increase the incidence of side effects compared to Ropivacaine combined with Midazolam in pediatric patients undergoing infraumbilical surgeries. These results suggest that Ropivacaine + Fentanyl could be considered a preferable option for pediatric single-shot caudal blocks in this patient population.

Table 1: Baseline Characteristics of Participants

Table 2: Detailed Intraoperative Monitoring Parameters

Note: BP = Blood Pressure, SpO2 = Saturation of Peripheral Oxygen, SD = Standard Deviation

Table 3: Postoperative Pain Assessment Using CHIPPS Scale

Table 4: Duration of Analgesia

Table 5: Incidence of Side Effects

Table 6: Postoperative Analgesic Requirements

The findings of this comparative study on the efficacy and safety of 0.25% Ropivacaine combined with Fentanyl versus 0.25% Ropivacaine with Midazolam in pediatric single-shot caudal blocks contribute valuable insights to the existing body of literature on pediatric postoperative analgesia. The superior analgesic effect and longer duration of analgesia observed with Ropivacaine + Fentanyl align with previous studies, while also highlighting the importance of adjuvant selection in enhancing caudal block efficacy without increasing adverse effects.

The significant difference in postoperative pain scores between the two groups, as indicated by lower CHIPPS scores in the Ropivacaine + Fentanyl group at various time points (p-values ranging from 0.01 to 0.05), supports the hypothesis that Fentanyl may enhance the analgesic effect of Ropivacaine. This is consistent with a study by Ivani et al.[9], which found that the addition of Fentanyl to Ropivacaine in caudal blocks improved postoperative analgesia in children. However, our findings offer a novel contribution by directly comparing this combination with Ropivacaine + Midazolam, thereby providing a more comprehensive understanding of how different adjuvants may influence analgesic outcomes.

The duration of analgesia, significantly longer in the group receiving Ropivacaine + Fentanyl (p < 0.001), echoes the results of Bosenberget al.[10], who reported that Fentanyl not only enhances the quality but also the duration of caudal analgesia. The absence of significant differences in the incidence of side effects between the two groups in our study is particularly noteworthy, suggesting that the addition of Fentanyl does not compromise safety, a concern often cited due to the risk of respiratory depression associated with opioids[11].

The trend towards a reduced need for additional postoperative analgesics in the Ropivacaine + Fentanyl group, although not statistically significant (p-values of 0.15 and 0.11 for Paracetamol and Tramadol, respectively), suggests a potentially clinically relevant benefit of this combination. This observation is in line with findings from Locatelli et al.[12], who also reported reduced postoperative analgesic requirements with the use of Fentanyl as an adjuvant.

Contrastingly, the use of Midazolam as an adjuvant, while effective, did not perform as well as Fentanyl in terms of prolonging analgesia or reducing postoperative pain scores. This is somewhat in contrast to studies suggesting that Midazolam could enhance the analgesic efficacy of local anesthetics due to its anxiolytic and sedative properties[13]. However, these studies did not compare Midazolam directly with opioid adjuvants, highlighting the uniqueness of our study's comparative approach.

The lack of significant difference in the incidence of side effects, including nausea, vomiting, and pruritus, aligns with the broader literature indicating that caudal blocks, when properly administered with appropriate adjuvants, have a favorable safety profile[14]. This reassures clinicians of the feasibility of using these combinations in pediatric surgical patients to improve postoperative outcomes.

This study underscores the superiority of Ropivacaine combined with Fentanyl over Ropivacaine with Midazolam in providing effective and prolonged postoperative analgesia in children undergoing infraumbilical surgeries. These findings should encourage further research into optimizing adjuvant choices for pediatric caudal blocks to enhance analgesic outcomes while maintaining safety.

The present study meticulously compared the efficacy and safety of 0.25% Ropivacaine combined with Fentanyl versus 0.25% Ropivacaine with Midazolam in pediatric single-shot caudal blocks for managing postoperative pain in children undergoing infraumbilical surgeries. The findings unequivocally demonstrated that the combination of Ropivacaine and Fentanyl offered superior postoperative analgesia, evidenced by significantly lower CHIPPS scores at various postoperative intervals (p-values ranging from 0.01 to 0.05) and a longer duration of analgesia (p < 0.001), without increasing the incidence of side effects compared to the combination of Ropivacaine and Midazolam. These results underscore the importance of selecting an appropriate adjuvant to enhance the analgesic efficacy of caudal blocks in pediatric patients, highlighting the potential of Ropivacaine and Fentanyl as a preferred combination for this purpose.

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