Comparison between preemptive gabapentin and paracetamol for pain control after adenotonsillectomy in children.

BACKGROUND: Tonsillectomy is the most commonly performed surgical procedure in ENT practice. Postoperative pain remains the major problem following tonsillectomy, if not treated. Different methods and many drugs have been used to control the postoperative pain. In this study, we evaluate the role of gabapentin premedication vs paracetamol in management of postoperative pain following adenotonsillectomy in children.
MATERIALS AND METHODS: In a double blind randomized study, 70 children were subjected for adenotonsillectomy classified into two equal groups. Group I: Gabapentin 10 mg/kg was given orally 2 hours before induction of anesthesia (Gabapentin syrup 250 mg/5 ml); Group II: Oral paracetamol 20 mg/kg was given orally 2 hours before induction of anesthesia. All children underwent general anesthesia. Pain score was assisted postoperatively 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, and 18 hours after recovery using visual analogue scale (VAS). RESULT: Pain score in gabapentin group was significantly less in 2 hours, 4 hours, 6 hours, and 8 hours postoperatively than in paracetamol group (P=0.0003, <0.0001, 0.0004, <0.0001, respectively). The time to first analgesia was longer in the gabapentin group than paracetamol group (7.95±2.06 hours vs 5.85±1.87 hours; P<0.0001) and the total amount of pethedine was less in gabapentin group than in paracetamol group (8±10.05 mg vs 16.25±11.57 mg; P=0.002).
CONCLUSION: Gabapentin premedication improves postoperative analgesia following adenotonsillectomy in children and reduce analgesic requirements in comparison with paracetamol premedication, with no reported side effects.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Tonsillectomy is one of the most commonly performed children's surgeries and produces a considerable degree of pain postoperatively.[1] These characters make this surgery ideal for the investigation of pain-relieving medications.[2]

Opiates, which provide the most effective pain relief, are associated with a high incidence of nausea and vomiting, respiratory depression, and sedation.[3] These side effects are hazardous in children; thus, alternatives to opiates have been sought for postoperative analgesia in tonsillectomy. Gabapentin was introduced in 1993 and had been used in the treatment of children's seizures and chronic pain syndromes.[4]

Gabapentin has been used in management of acute conditions in the perioperative period. Gabapentin has role in postoperative analgesia, preoperative anxiolysis, prevention of chronic postoperative neuropathic pain, attenuation of hemodynamic changes during intubation, and prevention of postoperative nausea, vomiting, and delirium.[5] This clinical study compares effect of gabapentin premedication with paracetamol premedication on postoperative pain following adenotonsillectomy in children.

MATERIALS AND METHODS

This study was carried out on 70 children ASA I and II who underwent adenotonsillectomy after obtaining approval from the hospital ethics committee and written informed consent from the parents of each child.

Age group was between 4 and 6 years. Exclusion criteria included diabetes, liver and/or kidney disease, hypersensitivity to drugs used, peritonsillar abscess, swallowing disorder, epilepsy or previous treatment with gabapentin or opioids analgesia. Tonsillectomy dissection was done using the bipolar diathermy and was performed in all patients by the four surgeons with the same experience and qualifications. Patients were randomly allocated equally (35 patients) in each group as follows:

Group I: Gabapentin 10 mg/kg was given orally 2 hours before induction of anesthesia (Gabapentin syrup 250 mg/5 ml).[6]

Group II: Oral paracetamol 20 mg/kg was given orally 2 hours before induction of anesthesia.[7]

The randomization was performed using sealed numbered envelopes indicating the group of each patient. A blind nurse who did not participate in patients’ follow up read the number and made group assignments.

A blinded chief nurse who did not participate in data collection confirmed that each patient ingested the medications as was scheduled. The process of inclusion in the study went on until the required number of patients was reached.

Anesthesia technique

General anesthesia was induced by sevoflurane (7 vol.%,). After the patients′ loss of consciousness, intravenous line was inserted. Central orotracheal intubation was performed with 1 μg/kg fentanyl and rocronium 0.6 mg/Kg. Anesthesia was maintained with sevoflurane 2 to 3 vol.% in N2O/O2 (70:30 vol.%) and ventilation was controlled to maintain normocapnia. Standard patient monitoring (electrocardiogram, non-invasive arterial pressure, heart rate, pulse oximetry, and end-tidal CO2) were used during anesthesia.

After the surgeon had completed the operation, residual neuromuscular blockade was antagonized with atropine 0.01 mg/kg and neostigmine 0.05 mg/kg. Oropharyngeal suction was done under direct vision, all patients were extubated in tonsillectomy position with or without nasopharyngeal or oropharyngeal airway in place to prevent airway obstruction, and were transported to the post-anesthesia recovery room.

Metoclopramide 0.15 mg/kg was administered for treatment of postoperative nausea and vomiting (PONV). If PONV still persisted, ondansetron 0.1 mg/kg was administered.

Measurements

The pain intensity was assisted by a person who was blind to study by using visual analogue scale graded from 0 to 10 (0 = no pain, 10 = the worst possible pain) in the following time in the post-anesthesia recovery room 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, and 18 hours after recovery.

During the preoperative visit, all children were shown the visual analogue toy containing different animal figures increasing in size from bird (0, bottom = no pain) to elephant (10, top = worst pain), in ten steps.

Postoperative analgesia was given in all patients depending on VAS score.

If the VAS value was less than 5 rectal, paracetamol 20 mg/kg was given; if VAS value was more than 5, pethedine 0.5 mg/kg was given intra-muscular and recorded. The time to first dose of analgesia and total amount of pethedine used was recorded in all patients.

Patients will be discharged postoperative when they had no or mild pain (VAS around 3), were able to tolerate clear fluids and soft food, and had no bleeding or nausea and vomiting.

Primary outcome measure of this study was the total postoperative pethedine consumption (from the time of extubation). Secondary outcome measures were pain scores, presence of nausea/vomiting, and sedation.

Sample size was chosen based on the previous study in our institute, which had determined that 35 patients in each group were enough for detection of significant changes in analgesic requirements.[8]

Statistical analysis

All data are expressed as mean±SD. To study the pattern of changes in individual variables in each group during various phase of study, an analysis of variance for repeated measure was performed. P value <0.05 was regarded as statistically significant. Unpaired t-test was used to compare between both groups and Mann-Whitney U test was used for pain scores.

RESULTS

This study was carried out on 70 patients divided into two groups, 35 in each group. The groups were comparable with regards to demographic data including age, gender, weight, and duration of anesthesia [Table 1].

Table 1

Demographic data; pethedine consumption; time of first analgesic requirement; and duration of anesthesia

Time to first request for analgesia was significantly longer in group I than group II (7.95±2.06 hours vs 5.85±1.87 hours; P<0.0001) [Table 1].

The amount of pethedine was less in group I than group II (8±10.05 mg vs 16.25±11.57 mg; P=0.002) [Table 1].

Pain score in gabapentin group was significantly less in 2 hours, 4 hours, 6 hours, and 8 hours postoperatively than in paracetamol group (P=0.0003, <0.0001, 0.0004, <0.0001, respectively). At 12 hours, VAS score was comparable between groups and patients received analgesia (pethedine in dose 0.5 mg/kg). Also, at 18 hours, the VAS was comparable between groups [Table 2].

Table 2

Visual analogue scale

Incidence of nausea, vomiting, and sedation was comparable in both groups. Six patients in group I received metoclopramide for controlling vomiting vs four patients in group II.

DISCUSSION

Tonsillectomy is one of the most common operation performed in children; it is associated with significant postoperative pain which if not treated well can cause significant risk including increasing heart rate, blood pressure, respiratory rate, difficulty swallowing, increased risk of postoperative bleeding, and prolong hospital stay.

In our study, we use either gabapentin 10 mg/kg 2 hours before anesthesia or oral paracetamol 20 mg/kg for controlling the postoperative pain following adenotonsillectomy in children and revealed that gabapentin premedication reduced VAS, prolonged the time for first analgesic requirement, and decreased its requirements.

The mechanism of gabapentin on pain is thought to involve voltage-gated N-type calcium ion channels. It is thought to bind to the alpha 2_ delta subunit of the voltage-dependent calcium channel in the central nervous system. This reduces calcium influx into the nerve terminals and decreases the release of neurotransmitters such as glutamate.[910]

These findings are consistent with that of Jeon et al. who concluded that premedication with gabapentin decreased post-tonsillectomy pain during swallowing in adult patients.[11]

A number of reports from many groups have revealed that preemptive gabapentin may play a considerable role in controlling postoperative pain. However, many of these studies used it preoperatively and postoperatively.[12-14]

The present study showed that the total pethedine requirements were less in gabapentin group. This is concordant with the findings of other studies.[1214] Mikkelsen et al.[15] reported that gabapentin reduced opioid consumption in the first 24 hours after tonsillectomy. However, the benefits of reduced opioid intake were overwhelmed by side effects of large doses of gabapentin used. They were unable to demonstrate any reduction in postoperative pain scores and postulated the lack of effect of gabapentin in post-tonsillectomy pain.

On the other hand, gabapentin is expensive and may increase the incidence of postoperative dizziness which may limit its use in day case surgery. However, incidence of nausea, vomiting, and sedation was comparable in both groups.

CONCLUSION

Gabapentin 10 mg/kg administrated orally 2 hours before adenotonsillectomy in children significantly decreased postoperative pain score and pethedine requirements vs paracetamol premedication, with no reported side effects.