|Year : 2018 | Volume
| Issue : 4 | Page : 239-244
Prospective randomized study comparing the efficacy of caudal bupivacaine versus bupivacaine–neostigmine in children undergoing congenital inguinal hernia repair
Omnia A.H El-Miseery, Lobna M. Abo El-Nasr, Ahmed S Bassouni, Hesham I El-Tatwey
Department of Anesthesia and Surgical Intensive Care, Faculty of Medicine, Tanta University, Tanta, Egypt
|Date of Submission||11-Mar-2017|
|Date of Acceptance||25-Feb-2018|
|Date of Web Publication||02-Aug-2019|
M.Sc Omnia A.H El-Miseery
Department of Anesthesia and Surgical, Intensive Care, Faculty of Medicine, Tanta University, El-Gharbia, El-Mahalla El-Kobra, El-Sheteewy Street, Tanta
Background Posthernioraphy pain in children is an unpleasant subjective sensation. The concept of postoperative pain relief and its utilization in the pediatric age group has improved dramatically over the recent years. Caudal block is one of the most common regional anesthetic techniques used in children that reduce the amount of inhaled and intravenous anesthetic administration, alter the stress response to surgery, and facilitate a rapid and smooth postoperative analgesia. Neostigmine is one of the additives known for significant analgesic prolongation, and it has been used safely in both adults and children.
Aim The aim of the present study was to evaluate the effect of neostigmine as an additive for caudal analgesia in congenital inguinal hernia repair in pediatrics.
Patients and methods This study was carried out on 70 children, with age range from 1 month to 6 years, having ASA status I–II, and scheduled for elective congenital inguinal hernia repair. Patients were randomized into two equal groups (35 patients in each group): group I, as bupivacaine group, where patients received 1 ml/kg bupivacaine 0.25%, and group II, as bupivacaine–neostigmine group, where patients received 1 ml/kg bupivacaine 0.25% and neostigmine 2 μg/kg. Heart rate and mean arterial blood pressure were recorded intraoperatively and postoperatively. Postoperative pain was assisted by face legs activity cry consolability pain scale, and the number of patients who needed postoperative rescue analgesia, total amount of rescue analgesia, and any undesirable adverse effects have been recorded.
Results Heart rate and mean arterial blood pressure were statistically significantly lower in group II than in group I. Similarly, the face legs activity cry consolability behavioral pain score was significantly lower in group II than in group I. Moreover, the total number of patients who needed rescue analgesia and the total amount of rescue analgesia were significantly lower in group II than in group I. Patients who developed bradycardia were significantly higher in group II. There was no difference between both the groups in the incidence of pruritus or vomiting. None of our patients developed urine retention.
Conclusion Addition of neostigmine to bupivacaine in a dose of 2 μg/kg results in superior analgesia than bupivacaine alone.
Keywords: bupivacaine, caudal block, congenital inguinal hernia, neostigmine
|How to cite this article:|
El-Miseery OA, El-Nasr LM, Bassouni AS, El-Tatwey HI. Prospective randomized study comparing the efficacy of caudal bupivacaine versus bupivacaine–neostigmine in children undergoing congenital inguinal hernia repair. Tanta Med J 2018;46:239-44
|How to cite this URL:|
El-Miseery OA, El-Nasr LM, Bassouni AS, El-Tatwey HI. Prospective randomized study comparing the efficacy of caudal bupivacaine versus bupivacaine–neostigmine in children undergoing congenital inguinal hernia repair. Tanta Med J [serial online] 2018 [cited 2020 Jun 6];46:239-44. Available from: http://www.tdj.eg.net/text.asp?2018/46/4/239/263917
| Introduction|| |
Posthernioraphy pain in children is an unpleasant subjective sensation that can only be experienced by their parents or caregivers. Till date, various methods including opioids, NSAIDs, acetaminophen, and regional anesthesia techniques have been evaluated for providing postoperative pain relief in pediatric population .
Caudal block is one of the most common regional anesthetic techniques used in children .
The biggest disadvantage of caudal anesthesia is the relatively short duration of action, even with the use of long-acting local anesthetics such as bupivacaine. To improve the duration of action and quality of analgesia of a single-shot caudal block with bupivacaine, various additives have been used ,.
Neostigmine has been safely used in adults and children. It is one of the additives known for significant analgesic prolongation; in addition, respiratory depression, sedation, and pruritus ascribed to the use of caudal opioids are not encountered with caudal neostigmine ,,.
| Aim|| |
The aim of this present study was to evaluate the effect of neostigmine as an additive for caudal analgesia in congenital inguinal hernia repair in pediatrics.
| Patients and methods|| |
After obtaining the research ethics committee approval of Tanta Faculty of Medicine (approval code: 2878/11/14) and the informed and written consent from parents, a double-blinded randomized prospective study was carried out at Tanta University Hospital, in Pediatric Surgery Department, on 70 children of both sex, aged from 1 month to 6 years, ASA I and II, and scheduled for congenital inguinal hernia repair. Patients with refusal by the guardians, history of allergy to local anesthetics, local infection, or anatomic malformation at the site of the block or coagulopathies were excluded from the study. Patients were randomized into two equal groups by using sealed opaque envelope (35 patients in each group) according to local anesthetic used: group I as bupivacaine group, where patients received 1 ml/kg bupivacaine 0.25%, and group II as bupivacaine–neostigmine group, where patients received 1 ml/kg bupivacaine 0.25% and neostigmine 2 μg/kg. Group allocation was done by a sealed opaque envelope technique. The measurements were taken by another anesthetist who had no subsequent involvement in the study.
Preoperative assessment was done by history taking, clinical examination, and laboratory investigations. Patients fasted according to ASA guidelines. On the arrival to operating room (OR), the patients were attached with electrodes to the monitor displaying the following: ECG, pulse oximetry, non invasive blood pressure (NIBP), and temperature. Anesthesia was induced by 2–5% halothane according to patient age in 100% O2 followed by insertion of an intravenous line and administration of fentanyl intravenous (1 μg/kg). Endotracheal intubation was facilitated by atracurium (0.5 mg/kg) intravenous. Capnometer was connected to the tube after intubation. Maintenance of anesthesia was done by isoflurane 1–2% in 100% O2. They were mechanically ventilated using a tidal volume of 6–8 ml/kg and respiratory rate of 14–30 according to age to maintain end-tidal carbon dioxide between 30 and 35 mmHg. After induction of anesthesia, left lateral position was obtained with the upper hip flexed 90° and the lower one only 45°. The investigator sterilized her hands, wore sterilized gloves and gown, and swabbed the patient’s lower back in a craniocaudal direction with betadine solution. The back of the patient was covered with sterile drapes leaving the area over sacral hiatus which was felt as a groove or notch above the coccyx and between two bony prominences, the sacral cornu. The index finger of the left hand was put over the upper part of the sacral hiatus, and epidural puncture was done with the right hand in the most proximal region of the sacral hiatus with the needle inclined 45°–60° to the skin. The peneteration of the sacrococcygeal ligament that occludes the sacral hiatus was identified by sensing a release as the needle passes into the epidural space. Once in the epidural space, the needle was minimally advanced, no more than 1–3 mm to avoid a bloody puncture or an intrathecal injection. Negative aspiration was done to exclude presence of the needle tip in a vessel or the medication was administered incrementally every 20–30 s over a few minutes while monitoring vital signs for evidence of intravenous or intrathecal administration. Any resistance to injection was interpreted as incorrect position of the needle. The index finger of the left hand was palpating the skin cephalad to the needle to ensure that local anesthetic was not injected subcutaneously.
Demographic data, including age, sex, weight, ASA physical status, site of surgery, associated comorbidities, duration of surgery, heart rate, and mean arterial blood pressure (MAP), were recorded before induction of anesthesia (baseline); at 15, 30, and 60 min after induction of anesthesia; and 5, 30, 60, and 120 min after recovery. Pain score was recorded at 1, 2, 4, 6, and 24 h after recovery using the face legs activity cry consolability (FLACC). Behavioral scale was as follows: 0 indicates no pain and 10 indicates the worst pain . Table 1 shows the number of patients who needed rescue analgesia in the first 24 h postoperatively. Rescue analgesia was administered at FLACC score of at least 4 in the form of acetaminophen suppository 15 mg/kg every 6 h. Total amount of acetaminophen within the first 24 h was recorded, and any undesirable adverse effects like bradycardia, pruritus, vomiting, or urine retention were recorded and managed.
Statistical analysis was performed using statistical package for the social sciences, version 23 (SPSS) created by IBM, Illinois, Chicago, USA. Data were presented as mean±SD or number (percentage) where appropriate. Numerical data were compared using paired t-test in the same group. χ2-Test was used for comparison of qualitative data. Data were considered significant when P value was less than 0.05.
| Results|| |
Regarding the demographic data (Table 2) such as age, sex, weight, ASA physical status, associated medical comorbidities, site of surgery, and the duration of surgery, there was no significant difference between both the groups.
Regarding heart rate, there was no statistically significant difference between both groups before induction of anesthesia; at 15, 30, and 60 min after induction of anesthesia; and at 5, 30, and 60 min after recovery of anesthesia (P<0.05). At 120 min postoperatively, heart rate was significantly lower in group II compared with group I (P<0.05) ([Figure 1]).
|Figure 1 Comparison of heart rate (HR) (beats/min) changes between both groups.|
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Regarding MAP, there was no statistically significant difference between both groups before induction of anesthesia; 15, 30, and 60 min after induction of anesthesia; and 5 and 30 min after recovery of anesthesia (P<0.05). At 60 and 120 min postoperatively, MAP was significantly lower in group II compared with group I (P<0.05) ([Figure 2]).
|Figure 2 Comparison of mean arterial blood pressure (MAP) changes between both groups.|
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Comparison of both groups showed no statistically difference in the FLACC pain score value at the first hour postoperatively, but it was significantly lower in group II at 2, 4, 6, 12, and 24 h postoperatively (P>0.05) ([Figure 3]).
The total number of patients who needed rescue analgesia (acetaminophen suppository) and total amount of analgesia were statistically significantly lower in group II than in group I ([Figure 4] and [Figure 5]).
Regarding postoperative complications, patients who developed bradycardia were significantly higher in group II. There was no difference between both groups in the incidence of pruritus or vomiting. None of our patients developed urine retention ([Figure 6]).
| Discussion|| |
Although the use of neostigmine as an adjuvant to bupivacaine has been shown to be beneficial, only few studies have investigated its analgesic effect ,,,,,,.
Our study found that addition of neostigmine to caudal bupivacaine resulted in superior analgesia compared with bupivacaine alone. Moreover, it significantly reduced the amount of rescue analgesia during the first postoperative 24 h, and the percentage of patients required rescue analgesia to 23%. This was in accordance with the results of Kumar et al. , Abdulatif et al. , Karaaslan et al. , and Mahajan et al. ; these studies used different pain scores including objective pain score, verbal pain score, and an observational scoring system modified from Hannallah, respectively. In the present study, we used FLACC pain score because it is known to be used in young children aged from 2 months to 7 years. FLACC pain score has been reported to be valid and reliable score for evaluation of pain .
In contrast to these results, Memiş et al.  and Karaaslan et al. , who assessed the severity of postoperative pain by using Toddler, Preschooler, Postoperative Pain Scale and Children’s and Infant’s Postoperative Pain Scale  respectively, found that addition of neostigmine neither caused significant decrease in pain scores nor resulted in decrease in the amount of rescue analgesia given to the patients. This may be owing to the usage of different doses of neostigmine in these studies.
The analgesic effects of caudal neostigmine observed in our study may be attributed to either the direct action at the spinal cord level after transdural diffusion to the cerebrospinal fluid or a peripheral antinociceptive effect at the surgical site after systemic absorption. The direct effect of neostigmine was attributed to its inhibition to the breakdown of the acetylcholine in the dorsal horn of the spinal cord . Spinal muscarinic M1 receptors are believed to be involved in the analgesic properties of spinal neostigmine . Different previous studies support the hypothesis of a peripheral antinociceptive effect of neostigmine ,,,. However, the dose required to achieve analgesia after peripheral administration of neostigmine, for example, intra-articular injection, is ∼10–100 times its analgesic neuraxial dose (500 μg for peripheral vs. 5–50 μg for spinal or epidural) ,. Therefore, we suggest that the effectiveness of the small dose of caudal neostigmine (2 μg/kg) used in the present study could be attributed to its spinal rather than its peripheral mechanism of action. A future pharmacokinetic evaluation of serum and cerebrospinal fluid concentrations of neostigmine after its epidural administration is required to confirm a neuraxial site of action.
The results of our study showed lower values of heat rate and MAP in group II patients who received caudal bupivacaine 0.25% with neostigmine 2 μg/kg compared with group I patients who received bupivacaine 0.25% only in the postextubation period. This was in agreement with Abdulatif et al.  and Taheri et al. , who reported better perioperative hemodynamics with addition of neostigmine.
In contrast to our results, Kumar et al. , Memiş et al. , and Mahajan et al.  found no significant differences in heart rate or MAP between groups.
Regarding the postoperative complications, our results showed higher incidence of vomiting (three patients in group I and five patients in group II) and bradycardia (six patients in group II) in the bupivacaine/neostigmine group. No hypotension, respiratory depression, or urine retention was reported in our patients, and only two patients in group II developed pruritus. Our results were in agreement with those of Taheri et al.  and Karaaslan et al. .
However, Kumar et al.  reported that the incidence of vomiting was the same in those who received bupivacaine only, bupivacaine–neostigmine, bupivacaine–ketamine, and bupivacaine–midazolam.
Neostigmine preparations used in the present study included methyl and propylparabens as preservatives. Early experimental and clinical trials used preservative-free neostigmine ,. Although preservative-free neostigmine is not associated with neurotoxicity , it is no longer marketed. Two investigations have confirmed that chronically administered intrathecal neostigmine containing methyl and propylparabens is not associated with any behavioral, chemical, or histopathological evidence of neurotoxicity ,.
Comparing neostigmine with other local anesthetics adjuvants, Engelman et al. , in their meta-analysis study to calculate postoperative analgesia of three additives, clonidine, neostigmine, and tramadol, to bupivacaine, ropivacaine, or levobupivacaine used for single-dose caudal extradural blockade in children found that neostigmine increased the duration of analgesia by 9.96 h, as compared with 3.68 h with clonidine and 4.45 h with tramadol. There was 95% probability that neostigmine increases the duration of postoperative analgesia by more than 8 h, clonidine by more than 2.8 h and tramadol by more than 3.25 h, as compared with local anesthetic alone. All three additives reduced the amounts of postoperative analgesic drugs. Neostigmine and tramadol increased the probability for postoperative nausea and vomiting. They concluded that neostigmine provides the longest postoperative analgesia.
| Conclusion|| |
From the previous data, we can conclude that addition of neostigmine to bupivacaine in a dose of 2 μg/kg results in superior analgesia than bupivacaine alone.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]