Effect of Dexmedetomidine as an Adjuvant to Ropivacaine in Ilioinguinal-Iliohypogastric Nerve Blocks for Inguinal Hernia Repair in Pediatric Patients: A Randomized, Double-Blind, Control Trial.

BACKGROUND: Bulk of published data support the efficacy of dexmedetomidine for prolongation of peripheral nerve block; but most of the studies are in adults. Ample data regarding use of dexmedetomidine in setting of paediatric peripheral nerve blocks is scarce. AIM AND
OBJECTIVE: To determine whether adding dexmedetomidine to ropivacaine in ilioinguinal-iliohypogastric nerve block prolongs postoperative analgesia in children undergoing inguinal hernia repair.
MATERIAL AND METHODS: Sixty children of American Society of Anesthesiologist (ASA) grade I - II aged between 2-11 years scheduled for elective hernitomy were randomly allocated to receive an ultrasound guided ilioinguinal-iliohypogastric nerve block (IINB) with 0.2 ml/kg dose of plain ropivacaine 0.2% (group R; n = 30) or ropivacaine 0.2% with adjunct dexmedetomidine 1 μg/kg (group RD; n = 30). Time to first post-operative need for supplemental analgesia triggered by pain score ≥4 according to Children's and infants postoperative pain scale (CHIPPS scale) was the primary end point of study. Number of analgesic doses during first 24 hours; intraoperative hemodynamic changes; sedation; postoperative adverse effects were noted.
RESULTS: The mean duration of analgesia was significantly prolonged in group RD (970.23 ± 46.71minutes) as compared to group R (419.56 ± 60.6 minutes). Children in group RD had significantly lower CHIPPS score, and less number of rescue analgesic requirements during first 24 hours postoperatively. No adverse effects were recorded in any group.
CONCLUSION: The present study concluded that combined use of ropivacaine and dexmedetomidine in IINB provided profound prolongation of post operative analgesia in children following inguinal hernia repair.

INTRODUCTION

Ilioinguinal-iliohypogastric nerve block (IINB) is a simple and widely used regional anesthesia technique in pediatric patients to provide intraoperative as well as postoperative pain relief for inguinal hernia surgery. However, prolonging the duration of these blocks to treat postoperative pain effectively is a key issue. Clonidine (α2-agonist) has been administered with regional anesthesia for decades, and meta-analyses based on adult studies have shown clonidine to prolong duration of peripheral nerve blocks when given as adjuvant to local anesthetics.[123] However, evidence base in children is less conclusive.

Modern α2-agonist dexmedetomidine appears as an attractive new option as adjunct in peripheral nerve blocks in adults and children.[45] Much like clonidine, dexmedetomidine has been shown in a rat model to prolong duration of analgesia by blocking hyperpolarization-activated cation current without any signs of peripheral nerve neurotoxicity.[6] Recent meta-analysis by Abdallah and Brull examined studies of dexmedetomidine as additive to brachial plexus blocks and found significant prolongation of motor block and time to the first analgesia.[7] Volunteer studies have also demonstrated efficacy of dexmedetomidine.[8] Of note, a recent study found that duration of sensory and motor block of the posterior tibial nerve was prolonged by adding dexmedetomidine to ropivacaine.[9] In children, most studies have described successful use of dexmedetomidine as an adjunct to caudal blockade,[1011121314] but so far, data regarding its use in peripheral nerve blocks in children are scarcely available. Thus, the aim of our study was to investigate the analgesic effect of dexmedetomidine when used as an adjunct to ropivacaine in IINB for pediatric inguinal hernia repair.

METHODS

Following institutes' Ethical Committee approval and informed parental consent, 60 American Society of Anesthesiologists' physical status Classes I and II children, aged 2–11 years scheduled for elective herniotomy were recruited for the study. Exclusion criteria included patients with known allergy to study drugs, coagulopathy, infection at injection site, or body mass index >30 kg/m2.

A standardized anesthesia protocol was followed. A peripheral venous cannula was inserted before bringing patients to operating theater. General anesthesia was induced by intravenous propofol (3–5 mg/kg) and fentanyl (1 μg/kg) in children with venous access. For children, whose venous access could not be given preoperatively were induced with sevoflurane increasing concentration from 1% to 5% in 100% oxygen, and Laryngeal mask airway (LMA) of appropriate size was introduced. Then, fentanyl (1 μg/kg) was given to them. All children were monitored for baseline heart rate (HR), noninvasive blood pressure, oxygen saturation (SpO2), continuous electrocardiography, and end-tidal carbon dioxide. Subsequently, anesthesia was maintained with sevoflurane 1–1.5 minimum alveolar concentration and 40% air and oxygen mixture with children breathing spontaneously. All patients received paracetamol rectally (30 mg/kg) just after induction. Ultrasound-guided IINB was performed under aseptic conditions using a sterile linear high frequency (7–13 MHz) transducer, portable ultrasound machine (SonoSite, Micromax Bothell, Washington, USA), and a 22-G 1.5-inch Stimuplex needle with an out of plane approach. Tip of needle was advanced to reach the nerves in the space between internal oblique and transversus abdominis muscle where 0.2 ml/kg of study drug was injected under direct visualization. Patients were recruited into one of the two treatment groups by the use of computer-generated random numbers. Group R received 0.2 ml/kg of 0.2% plain ropivacaine in IINB and Group RD received 0.2 ml/kg of 0.2% plain ropivacaine with 1 μg/kg dexmedetomidine. All drugs were prepared by pharmacist who opened the randomization envelope and accordingly provided drugs. In Group R, saline was mixed with drug to keep the experimenter blind. Junior residents of anesthesia and nurses who monitored the patients in recovery room and ward were blinded to the treatment groups.

Block success was measured by assessment of hemodynamic stability, as indicated by absence of an increase in HR and systolic blood pressure (SBP) of more than 20% from baseline values, at surgical incision which was allowed 15 min after giving nerve block.

HR, mean arterial pressure (MAP), and SpO2 were recorded before surgery as the baseline values. Intraoperatively HR, MAP, Spo2 were recorded at 5,20,40,60 min intervals. Postoperatively, HR and MAP were recorded at 1, 2, 6, 12, and 24 h. Intraoperative hypotension requiring fluid boluses or vasopressors and bradycardia requiring atropine were recorded. Emergence time (the time from end of surgery to opening the eyes on calling name) was also noted.

Postoperatively, patients were assessed upon arrival in postanesthetic care unit (PACU) by junior residents of our department who were trained to assess pain scores in children by Children's and Infants' Postoperative Pain Scale (CHIPPS). Supplemental analgesia in the form of intravenous paracetamol (20 mg/kg) was administered when CHIPPS score ≥4. If further analgesia was required intravenous diclofenac (0.3mg/kg) was administered. If still pain persisted intravenous fentanyl was administered at 1 μg/kg. Time to first administration of supplemental analgesia was noted. Duration of postoperative analgesia was from the time of extubation to the first use of rescue analgesia. After discharge from PACU, pain score was assessed at 0, 1, 2, and 4 h and then at 6, 8, 12, and 24 h. The total number of doses of paracetamol was recorded.

Any potential adverse events such as postoperative nausea and vomiting (PONV) defined as any nausea, retching, or vomiting was retrieved by staff nurses in a yes or no format every 4-h intervals, till 24 h postoperatively. Sedation was evaluated during the 1st h in PACU by using a 3-point sedation scale based on eye opening, alert with spontaneous eye opening = 0, drowsy with eye opening in response to speech = 1, and sedation with eye opening in response to physical stimulation = 2.[15]

Statistical analysis

Categorical variables are expressed as number of patients and percentage of patients and compared across the groups using Pearson's Chi-square test for independence of attributes/Fisher's exact test as appropriate.

Continuous variables are expressed as mean, median, and standard deviation and compared across the groups using Mann–Whitney U-test.

The statistical software SPSS version 20 (IBM) has been used for the analysis.

An alpha level of 5% has been taken, i.e., if any P < 0.05, it has been considered as significant.

RESULTS

In total, 65 patients were recruited in the study and 60 patients were subsequently enrolled. Thirty patients were randomized to Group R and 30 patients to Group RD. The CONSORT flow diagram is displayed in Figure 1. The patient demographics, duration of surgery, and emergence times were similar in both the groups [Table 1].

Figure 1

CONSORT flow diagram of participants

Table 1

Demographic data

Intraoperative and postoperative hemodynamics were compared and found to be similar in both the groups at all time intervals [Figures 2 and 3] except at 5-min interval when HR came out to be significantly decreased in group RD.

Figure 2

Mean blood pressure variation between two groups

Figure 3

Heart rate variation between two groups

Adequate block success was achieved in both the groups. The duration of analgesia as studied by the time to the first administration of rescue paracetamol dose was significantly longer in Group RD (16.17 ± 0.77 h) compared to Group R (6.9 ± 1.01 h) with P < 0.001. The percentage of patients needing rescue analgesia within 24 h in Group RD was much less as compared to the other group, as tabulated in Table 2.

Table 2

Comparison of analgesic requirements

The total number of analgesic doses administered was less in Group RD than in Group R [Table 3]. In Group R, 43% of the patients did not need rescue drug, whereas in Group RD, 83% patients needed no rescue dose.

Table 3

Rescue analgesic requirements in 24 h

The median pain scores [Table 4] were significantly lower in Group RD compared to Group R at 6 and 8 h. At 24 h, pain scores were higher in Group RD than in Group R (P < 0.001) as shown in Figure 4.

Table 4

Children's and Infants' Postoperative Pain Scale pain scores in 24 h

Figure 4

Comparision of pain scores between two groups

There were no complications attributed to the IINB. There was no incidence of bradycardia or hypotension requiring treatment in the Group RD. Two patients had nausea in Group RD and 1 patient in Group R had vomiting. However, on comparison, this was insignificant. Both the groups had similar mean postoperative sedation scores.

DISCUSSION

Dexmedetomidine was first used as an additive in 2004 to supplement intravenous regional anesthesia.[16] Idea of perineural administration of dexmedetomidine was conceived in the last decade, following successful use of clonidine in nerve blocks. Dexmedetomidine being a congener of clonidine could have similar effects. After multiple randomized controlled trials, it has been found that adding dexmedetomidine as an additive to peripheral nerve block not only prolonged mean block durations but provided good postoperative analgesia. The analgesic sparing effect observed after preoperative or an intraoperative administration usually lasts up to 24 h, with anxiolytic, sedative, and thymoanaleptic properties implicated as being partly responsible for this effect.[17] Animal and clinical studies reported that the use of dexmedetomidine as an adjunct with local anesthetics improved peripheral nerve block by reducing onset time and efficacy of nerve block during surgery with no recorded neurotoxicity.[18] A bulk of published data make it a viable option as an additive to ropivacaine or bupivacaine for peripheral nerve block more commonly in adults. However, experience of this drug in pediatric population is limited to intravenous use for periprocedural sedation in a dose of 1 μg/kg and sometimes as an adjunct to caudal anesthesia.[19] However, studies relating to the use of dexmedetomidine in peripheral nerve block in children are scarce and nonconcluding. Since peripheral nerve blocks are thought to be effective and safe method for postoperative analgesia and has attained wide use in pediatric patient, there was a need to evaluate effect of dexmedetomidine as an additive to peripheral nerve block in children.

In our study, we compared 1 μg/kg dexmedetomidine against a control group receiving plain ropivacaine in ultrasound-guided IINB given to patients undergoing inguinal hernia repair. We found that time of adequate analgesia (CHIPPS score <4) without the use of supplemental analgesia was significantly higher in group receiving dexmedetomidine–ropivacaine mixture (16.17 ± 0.77 h) than group receiving plain ropivacaine (6.9 ± 1.01 h). The number of patients needing rescue analgesic drug was much less in Group RD (16.67%) as compared to Group R. In our study, the pain scores were significantly higher in Group R at 6 and 8 h. Almost 57% of patients in Group R had received rescue analgesics out of which 40% received it by the 6th h. At 24 h, Group RD had higher pain scores than Group R as maximum patients in Group R had already received rescue analgesics by that time.

There are many studies regarding the use of dexmedetomidine with various local anesthetics in various kinds of nerve blocks. In one study on brachial blocks, a dose of 0.75–1.5 μg/kg had been used, and a significant prolongation of block duration and an analgesia ranging from 400 to over 1000 min was observed.[20212223] In a study where dexmedetomidine was used in greater palatine nerve block in children undergoing cleft palate repair, postoperative analgesia duration of 22 h was noted as against 14 h with plain bupivacaine.[24] In parallel with main result of the current study, a previous study by Lundblad et al. reported that 0.5 μg/kg of dexmedetomidine used in IINB in children undergoing inguinal hernia repair prolonged duration of analgesia by 88% over plain ropivacaine, but this observation was not statistically significant, the reason being lower dose of dexmedetomidine used.[25] Since we used a higher dose of 1 μg/kg dexmedetomidine in our study which was in accordance to a volunteer study by Keplinger et al.,[26] our results were statistically significant. They reported 60% extension of block duration with the use of 20 μg of perineural dexmedetomidine in their initial study.[8] In their recent study, they found that dexmedetomidine produces a dose-dependent prolongation of sensory block in ulnar nerve blocks. About 100 μg of dexmedetomidine when given perineurally had better efficacy than doses less than this. Another dose finding study on femoral nerve blocks[27] got negative results with the use of low-dose level as 25 μg. This difference in efficacy of dexmedetomidine as an adjuvant in peripheral nerve blocks was attributed to the type and size of nerve to be blocked and type of study population as well. Our study on pediatric IINB and role of dexmedetomidine in this block is only second study of such type and was much needed to support the use of dexmedetomidine as additive in children for IINB. The first study was conducted by Lundblad et al. with a lower dose of (0.5 μg/kg) dexmedetomidine.

A randomized controlled trial by El-Hennawy et al.[11] reported that addition of dexmedetomidine in a dose of 2 μg/kg as adjuvant to bupivacaine caudally in pediatric patients significantly increased duration of postoperative analgesia without any undesirable side effects. In our study, dexmedetomidine was used in a dose of 1 μg/kg, without any side effects or any significant delay in recovery from general anesthesia. There was no difference in incidence of PONV. Moreover, magnitude of hemodynamic changes between the groups was similar except at 5-min interval where HR was significantly decreased in group receiving dexmedetomidine. This might have occurred due to systemic absorption of the drug from block site. Such changes in HR and blood pressure were also noted in a study by Agarwal et al.[28] The dose-dependent side effects such as bradycardia and hypotension were not evident in any of the groups in our study. Further studies with higher doses of dexmedetomidine can be done to evaluate the dose-dependent side effects of perineural dexmedetomidine. We did not identify any significant difference in sedation in postanesthesia recovery unit between the two groups. This could help us to conclude that dexmedetomidine at 1 μg/kg when given perineurally does not result in significant sedation.

Dexmedetomidine seems to possess neuroprotective effects and attenuates neurocognitive impairment (mainly delirium and agitation) following anesthesia.[29] This could have led to decreased agitation in patients which might have resulted in lower pain scores in Group RD. Although in our study, we did not document postoperative delirium score, since most of our patients were >4 years of age, it was easy to differentiate between pain and delirium. Thus, the low pain scores could be attributed to direct action of dexmedetomidine over peripheral nerves leading to prolongation of analgesia rather than its neurocognitive effects.

CONCLUSION

The use of dexmedetomidine at 1 μg/kg dose as an additive in IINB in children undergoing herniotomy could achieve prolonged duration of postoperative analgesia of 16.17 ± 0.77 h without any significant side effects. Thus, it can be a promising method of increasing the pain free period postoperatively without any undesirable complications.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.