In children effective analgesia after herniotomy is essential and several techniques are used such as administration of opioids, nonsteroidal inflammatory drugs, peripheral nerve block, caudal block and wound infiltration with local anaesthetics [1,2]. These are based on the hypothesis that the most effective way to eliminate or to reduce postoperative pain is to prevent the development of pain rather than simply treat it.
Levobupivacaine, the S (−)-enantiomer of racemic bupivacaine, is associated with greater safety with regard to cardiotoxicity and neurotoxicity than the dex-enantiomer or racemic bupivacaine [3,4]. Levobupivacaine is long-acting with an onset of action of 15 min or less. The duration of action is dose-dependent and varies according to anaesthetic techniques . Wound infiltration has been advocated as a simple and safe technique to minimize pain following abdominal surgery . Wound infiltration with levobupivacaine 0.5% after inguinal hernia surgery and presurgical cutaneous levobupivacaine infiltration in patients undergoing laparoscopic gynaecological surgery diminished postoperative pain and decreased analgesic consumption [6,7]. Matsota et al. showed that postincisional wound infiltration with levobupivacaine prolonged the duration of postoperative analgesia and increased early mobilization in children. But few data are available regarding wound infiltration with levobupivacaine in children.
Another concern of the anaesthesiologist is the suppression of the surgical stress response. Stress responses to surgical trauma and postoperative pain elicit diffuse changes in hormonal secretion of cortisol and prolactin [9,10]. Control of postoperative pain with regional anaesthesia by local anaesthetics and high-dose intravenous (i.v.) opioids is associated with attenuated stress responses [11,12]. It has also been suggested that stress response hormone levels can be used as an objective method to assess the analgesic efficacy of the anaesthetic techniques used in children as the assessment of pain in children can be difficult and unreliable .
The aim of this study was to compare the postoperative analgesic effects of preincisional and postincisional wound infiltration with levobupivacaine in children following inguinal hernia repair and also the postoperative cortisol and prolactin levels.
Patients and methods
The study was approved by the local ethics committee (Sisli Etfal Teaching and Research Hospital) and written informed parental consent was obtained in every case. Ninety-six children, whose ages varied between 2 and 10 years, undergoing unilateral inguinal hernia repair and with ASA physical status I were included. The study was designed as a prospective, single-blinded and randomized trial. Children who had bilateral or recurrent hernia or a neurological, neuromuscular, psychiatric or blood clotting disorder or any drug allergy were excluded.
No premedication was administered. Routine monitoring was used, including continuous ECG, noninvasive blood pressure, pulse oximetry, capnography and inhalation agents (Julian, Drager, Lubeck, Germany). Local anaesthetic cream was placed on the back of the left hand for painless i.v. cannula insertion. General anaesthesia was induced with thiopentone 5 mg kg−1. A laryngeal mask airway was inserted after induction of anaesthesia. Intravenous fentanyl 1 μg kg−1 and 2–2.5% sevoflurane with 70/30% air/oxygen was used for maintenance of anaesthesia. Standard i.v. fluid as a 5% dextrose–0.2% NaCl solution (Isolayt P) was administered. Fentanyl 0.5–1 μg kg−1 was added when the heart rate (HR) and blood pressure were 20% above baseline values. Fentanyl consumption was recorded perioperatively. A decrease in HR below 80 bpm was treated with incremental doses of atropine 0.01 mg kg−1 i.v. Oxygen saturation was not permitted below 96%.
Patients were randomly assigned to three groups using a computer-generated random numbers table. Levobupivacaine (Chirocaine, Abbott S.p.A, Latina, Italy) 0.25 ml kg−1 at a concentration of 5 mg ml−1 was used as a local anaesthetic solution for subcutaneous infiltrative analgesia. The study included the following groups: preincisional group (group A, n = 32) was infiltrated with levobupivacaine after induction of general anaesthesia; postincisional group (group B, n = 32) was infiltrated with levobupivacaine before the end of the surgery; and the control group (group C, n = 32) received no levobupivacaine infiltration at all. Infiltration before the end of surgery was performed on the subcutaneous wound after closure of the external aponeurosis, but before the skin suture. The surgery was done by the same surgical team in all cases and also a 23-gauge needle was used for wound infiltration. Thereafter, general anaesthesia was discontinued; patients were extubated in the operating room following adequate breathing. All patients were then admitted to the paediatric surgery ward after a 4 h stay in the postanaesthesia care unit (PACU).
Upon arrival in the PACU, mean arterial pressure (MAP), HR and objective pain score (OPS) were recorded at 15 min intervals for the first 1 h, followed by every 1 h for the next 4 h by another investigator who was not present during the period of anaesthesia and surgery in the operating room and who was unaware of the group assignment. A modified Hannallah et al.  10-point objective pain scale was used (five criteria: crying, movement, agitation, posture and localization of pain; each scored 0–2 to give a total score of 0–10). The first pain assessment was performed 10 min after the arrival in the PACU. A standardized plan for postoperative analgesia was prepared. Patients with a pain score of at least 4 or upon parents' request were treated with 20 mg kg−1 paracetamol orally. Patients were discharged from the ward by the paediatric surgeon. An OPS was taught to parents the same day before surgery. Adverse effects (hypotension, bradycardia, flushing) were recorded up to 4 h in the PACU. Parents were contacted by telephone the day after the surgery at 24 h for assessment of OPS, nausea, vomiting and pruritus, if any, and these were recorded over the 24 h. The number of rescue analgesics and the time of giving the first dose of paracetamol were recorded.
Blood samples were obtained from each patient for determination of cortisol and prolactin levels before induction of anaesthesia and at 40 min after the end of the surgery. Blood samples were collected in plasma tubes containing ethylenediaminetetraacetic acid (EDTA) and centrifuged and stored at −20°C until assayed. Plasma concentrations of prolactin (normal range for a girl 3.2–25.3 ng ml−1 and for a boy 2.9–17.1 ng ml−1) and cortisol (normal range 1–39 μg dl−1 a.m. and 3–18 μg dl−1 p.m.) were measured by electrochemiluminescence immunoassay (ECLIA) on an Elecsys E-170 analyser (Roche Diagnostic Systems, Basel, Switzerland).
The sample size was estimated using the data from literature for biochemical markers and pain scores. To detect a difference of 1 SD between the hormone levels, it was calculated that 16 patients per group were required for the study to have power of 80% and a type I error of 0.05. A difference of 1 in the mean increase of OPS between the groups and a SD of 0.8 were used for the calculation. Seventeen patients were required to give a 95% power to demonstrate this difference at the 0.05 significance level.
Data were evaluated using SPSS 10 for windows. Data were expressed as means ± SD or number (%), as appropriate. Statistical analysis was performed with the χ2 test for nominal data, the Kruskal–Wallis test followed by the Mann–Whitney U-test for OPS and the Wilcoxon sign test for pairwise comparisons among the three groups. Log-rank tests were applied to compare time to first analgesic among the three groups. One-way analysis of variance was used to compare the groups and also to determine the significant difference, and the Tukey honestly significant difference (HSD) test was applied for multiple comparison within the groups. Parametric data were analysed by Student's t-test. A value of P less than 0.05 was considered statistically significant.
A total of 96 children (32 in each group) were included in this study. There were no differences among the three groups according to age, sex, weight, the amount of opioid dose, duration of surgery and duration of general anaesthesia (P > 0.05) (Table 1).
Oral paracetamol as a rescue analgesic in 24 h postoperatively was required in six patients in group A, seven patients in group B and 10 patients in group C. The rescue analgesic administration was higher in group C than in group A and in group B (P < 0.05). The average time to the first analgesia was significantly shorter in group C (1.40 ± 0.67 h) than in either group A (5.96 ± 0.88 h) or group B (6.20 ± 1.21 h; P < 0.001), whereas no difference between group A and group B was detected (Table 1).
Within each group independently, the HR of the patients at 4 h was found to be significantly lower in all the groups than at baseline (P < 0.05, P < 0.01). The HR of the patients at 1, 2 and 3 h was also found to be significantly lower in group B than at baseline (P < 0.01).
Among the three groups, the HR of the patients at 15, 30 and 45 min and at 2 h was significantly higher in group C than in group A and in group B (P < 0.01). The HR of the patients at 60 min was significantly higher in group C than in group A (P < 0.01) and the HR of the patients at 3 and 4 h was significantly higher in group C than in group B (P < 0.01, P < 0.05).
No significant differences were observed in MAP at any of the observation points in each independent group or among the three groups (P > 0.05).
The pain scores of the patients at baseline, 15, 30, 45 and 60 min and at 2, 3 and 4 h were significantly higher in group C than in group A and in group B (P < 0.01), whereas there were no differences between group A and group B (Table 2).
There were no significant differences among the three groups with regard to preoperative plasma cortisol and prolactin levels. These values were within the normal ranges of our laboratory results for children of this age group. Postoperative plasma cortisol and prolactin levels were significantly higher in the three groups than the preoperative plasma cortisol and prolactin levels (P < 0.001). However, postoperative plasma cortisol and prolactin levels were significantly higher in group C than in either group A or group B (P < 0.001), whereas there was no difference between group A and group B (Table 3).
There was no difference among the three groups regarding adverse effects. One child in group A and one child in group C had pruritus. In addition, one child in group C had nausea (P > 0.05).
Our study confirms that both routes of levobupivacaine infiltration produce effective analgesia after inguinal hernia repair operations in children during the postoperative period. In this study, it was observed that plasma stress hormones increased in patients in the control group more than in those in the levobupivacaine treatment groups.
In children, the optimal methods to achieve analgesia after inguinal hernia repair are not clear. Many studies [15,16] have shown that wound infiltration and wound instillation with a local anaesthetic produced effective postoperative analgesia after inguinal hernia repair in children.
Some clinical studies have indicated in children that effective postoperative pain relief was achieved with wound instillation of 0.5% bupivacaine 0.25 ml kg−1 with epinephrine 5 μg ml−1 after inguinal hernia repair . Dahl et al. found that, in children, a smooth recovery with little need for opioids postoperatively after hernioplasty was observed with preoperative infiltration with 0.25% bupivacaine 1 mg kg−1, whereas they did not find any difference between infiltration before and after surgery. The studies by Bay-Nielsen et al. and Kingsnorth et al. showed that levobupivacaine has similar anaesthetic and analgesic efficacies to 0.25% racemic bupivacaine when used intraoperatively and postoperatively by the infiltration technique in patients having inguinal hernia repair.
In children, very few reports in the literature compare the anaesthetic efficacy of the wound infiltration of levobupivacaine. One clinical study by Matsota et al. reported that postincisional levobupivacaine infiltration for inguinal hernia repair showed an increased duration of postoperative analgesia and early recovery, whereas in their other study preincisional levobupivacaine infiltration for circumcision showed cardiovascular stability and faster recovery . The postoperative analgesia tended to be longer and adequate in both studies, although no significant difference was noted between infiltration groups and the group receiving paracetamol 30 mg kg−1 rectally. We also observed in our study that there was not any superiority in the preincisional group over the postincisional group. Moreover, we found that blocking of the painful stimuli by the use of wound infiltration with levobupivacaine reduces postoperative pain and analgesic consumption. The mean dose of local anaesthetic used in our study was well tolerated and had no side effects. Patients who received either the preincisional wound infiltration or the postincisional wound infiltration had significant low OPS differences compared with control group. These groups also had a lower rescue analgesic consumption than the control group. We did not observe any decrease in MAP during the observational period, whereas HR was significantly lower in both the treatment groups than in the control group.
Lower abdominal operations generally cause severe pain, leading to agitation. This pain stimulus increases stress hormone levels . Neuroendocrine response attenuation has been frequently investigated by measuring levels of plasma cortisol and prolactin . Bozkurt  found that a single dose of 0.1 mg kg−1 epidural morphine compared with intraoperative i.v. morphine combined with postoperative patient-controlled morphine administration provided adequate analgesia and attenuated neuroendocrine response to lower abdominal and genitourinary operations in children. Solak et al. assessed the effects of caudal anaesthesia with 0.25% bupivacaine in addition to general anaesthesia on plasma cortisol and prolactin levels in children who underwent lower abdominal and genitourinary surgery during the early postoperative period. They suggested that in children caudal anaesthesia attenuated the postoperative cortisol and prolactin responses to surgery and pain compared with general anaesthesia alone. The study of Sakellaris et al. measured cortisol and prolactin levels in children who received preincisional and postincisional infiltration at the surgical area with ropivacaine in addition to general anaesthesia during inguinal hernia repair. They also demonstrated that wound infiltration with ropivacaine decreased the stress response to surgery and to postoperative pain in children. In our study, cortisol and prolactin levels increased among the three groups and this was statistically significant compared with preoperative levels but the increase was less in the infiltration groups than in the control group. Moreover, we found low postoperative pain scores in the infiltration groups. These results indicate that control of postoperative pain is effective on stress hormones. We also believe that pain could not be the main reason for increasing stress hormone levels postoperatively. Emotional factors such as anxiety about the stay in the PACU or being separated from parents might play a role in the increase in postoperative cortisol and prolactin levels.
In conclusion, preincisional and postincisional wound infiltrations of levobupivacaine are effective in reducing postoperative pain and rescue analgesic consumption. However, wound infiltration with levobupivacaine may relatively attenuate or make partial changes to the postoperative cortisol and prolactin response to surgery. This regional anaesthetic technique is simple, relatively noninvasive and quickly performed. We conclude that levobupivacaine infiltration regardless of preincisional or postincisional period may be a good choice for postoperative analgesia in children having inguinal hernia repair.
Financial support was provided by departmental sources.
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