Comparison of preoperative rectal paracetamol with paracetamol - diclofenac combination for postoperative analgesia in pediatric surgeries under general anesthesia.

CONTEXT: Traditionally, pain in children is a topic that has received only minimal attention. However, in the recent times, considerable progress has been made in the field of neonatal and pediatric pharmacology. The concept of preemptive analgesia is important in combating postoperative pain in children. In this study, we sought to compare the effectiveness of preemptive analgesia provided by paracetamol alone and by its combination with diclofenac when administered per rectum. AIMS: To compare the efficacy of preoperative rectal paracetamol with paracetamol - diclofenac combination for postoperative analgesia in pediatric surgeries under general anesthesia. SETTINGS AND
DESIGN: Prospective randomized double-blind study. SUBJECTS AND METHODS: Sixty children scheduled for various surgeries under general anesthesia were randomly allocated into two Groups A and B, with 30 in each. Children in Group A received paracetamol suppository 20 mg/kg and those in Group B received paracetamol 20 mg/kg + diclofenac 2 mg/kg as suppository immediately after tracheal intubation. All the children were assessed for 24 h from the time of extubation. The pain was measured using numerical rating scale in children above 7 years and face-legs-activity-cry-consolability scale in children below 7 years. The time interval between extubation and the administration of the first dose of rescue analgesic was taken as the duration of postoperative analgesia. STATISTICAL ANALYSIS USED: Descriptive and inferential statistical methods were used to analyze the data.
RESULTS: The duration of postoperative analgesia was significantly longer in paracetamol + diclofenac group (21.13 ± 2.68 h) as compared to paracetamol alone group (10.18 ± 2.39 h).
CONCLUSIONS: The combination of paracetamol and diclofenac administered per rectum preoperatively is more effective than paracetamol alone in providing postoperative analgesia in children.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Postoperative pain is usually an acute pain, sharp in character which starts with the surgical trauma and ends with tissue healing. Unrelieved acute pain results in potentially life-threatening adverse physiological effects and may also cause psychological disturbances. In the modern day concept, postoperative care essentially includes an effective relief from pain, suffering, anxiety, and sleeplessness. Thus, the outcome of postoperative recovery is greatly influenced by effective pain management. Traditionally, pain in children is a topic that has received only minimal attention. However, in the recent times, considerable progress has been made in the field of neonatal and pediatric pharmacology. Multi-disciplinary pain trails are being developed. The concept of preemptive analgesia is important in combating postoperative pain in children. In this study, we sought to compare the effectiveness of preemptive analgesia provided by paracetamol alone and by its combination with diclofenac when administered rectally.

SUBJECTS AND METHODS

After obtaining the approval from Institutional Ethics Committee and written informed consent from the parents, all the pediatric patients aged between 1 and 14 years, scheduled for various elective surgeries from June 2005 to May 2006 were included in the study. Preanesthetic evaluation included detailed history and examination. Children with known drug allergy, bleeding disorders, heart disease, anorectal complaints, liver, and kidney disorders and those on treatment with anticoagulants, lithium or phenytoin were excluded from the study. Intravenous (IV) premedication was given with midazolam 0.05 mg/kg, glycopyrrolate 5µg/kg, and fentanyl 2 µg/kg 5 min before induction of general anesthesia. Induction was achieved with IV pentathol sodium 5 mg/kg and IV succinylcholine 2 mg/kg followed by tracheal intubation. All children enrolled in the study were randomly allocated into two Groups A and B, by a computer generated randomization program. Children in Group A received paracetamol suppository 20 mg/kg and those in Group B received paracetamol 20 mg/kg + diclofenac 2 mg/kg as suppository immediately after tracheal intubation. Anesthesia was maintained by IV veccuronium loading dose of 0.1 mg/kg followed by top-ups as required and 1:1 mixture of nitrous oxide and oxygen in halothane. After the surgery, the residual neuromuscular block was reversed with IV neostigmine 0.05 mg/kg and glycopyrrolate 0.01 mg/kg. Time of extubation was recorded. All the children were assessed for 24 h from the time of extubation. The pain was measured using numerical rating scale (NRS) in children who could verbally communicate (>7 years of age). In children under 7 years of age who cannot effectively communicate verbally, face-legs-activity-cry-consolability (FLACC) scale [Table 1] was used to measure the pain. IV tramadol 0.75 mg/kg was administered as rescue analgesic when NRS read more than 3 or FLACC read more than 5 and the time was noted. The time interval between extubation and the administration of the first dose of rescue analgesic was taken as the duration of postoperative analgesia. Simultaneously patients were monitored for any complaints of nausea, vomiting, or other gastrointestinal disorders.

Table 1

FLACC scale for measuring pain

Statistical analysis

Descriptive and inferential statistical methods were used to analyze the data. In descriptive statistics, calculation of means, the standard deviation was done with the help of Microsoft Excel. In inferential statistics, Student's t-test of difference between two means was used to test the difference in the quantitative parameters viz., age, weight and duration of postoperative analgesia. Chi-square test was used to test the difference between the qualitative parameters viz., gender, type of surgery, and side effects. The power of the study was calculated using online power calculator for two independent sample study.

RESULTS

A total of 60 patients were enrolled in the study during the said duration of 1 year with 30 in each group. The power of the study calculated based on “duration of postoperative analgesia” was 100%. There was no statistically significant difference between the two groups in the demographic profile, nature of surgical procedures and the type of side effects [Tables 2 and 3]. However, a very highly significant difference was observed between the two groups in the duration of postoperative analgesia which was significantly longer in paracetamol + diclofenac group (21.13 ± 2.68 h) as compared to paracetamol alone group (10.18 ± 2.39 h) [Table 2].

Table 2

Analysis of variation of age, weight and duration of postoperative analgesia

Table 3

Analysis of variation in gender, type of surgery and side effects

DISCUSSION

Millions of patients undergo surgery each year and benefit from the knowledge, skills, and sophisticated technology that characterize most aspects of modern surgical treatment. Though essential, effective pain control is sadly suffering a lacuna despite advances in pathophysiology, pharmacology, and development of newer modalities of pain management. Postoperative pain is undertreated for varied reasons viz., lack of knowledge regarding effective dose ranges, duration of action of opioids and unfounded fear of respiratory depression and addiction. However, strong opioids viz., morphine,[1] fentanyl,[2] alfentanyl,[3] etc., have always been the gold standard in the management of postoperative pain. The major hindrance to the liberal use of strong opioids in the postoperative zone is the threat of respiratory depression[4] especially in children where the optimal dose for effective pain control is higher than in adults because of a larger volume of distribution[5] posing a relatively narrow margin of safety. Nonsteroidal anti-inflammatory drugs (NSAIDs) occupy a pivotal role in the arena of postoperative pain management because of their opioid sparing property. Paracetamol is the most widely used centrally acting NSAID in pediatric age group because of its wide margin of safety. There is evidence in the literature that paracetamol[6] was safely used up to a dose of 90 mg/kg/day. Diclofenac is a potent NSAID, which marks the first line of defense in combating acute pain even today. Diclofenac inhibits the release of prostaglandins which sensitize the nociceptors to other inflammatory mediators. Thus administering diclofenac before surgical incision will increase the pain threshold and decrease the analgesic requirement in the postoperative period. There is abundant evidence in the literature proving the effectiveness of diclofenac in postoperative pain management.[789] When two different agents targeted at a single pharmacological effect are used in synergism, the said combination allows the reduction in the dose of individual drugs without compromising on the quality of the effect, rendering a wider margin of safety. Thus in our study, we sought to compare the effectiveness of the combination of paracetamol and diclofenac with that of paracetamol alone in combating postoperative pain. We opted for the rectal route of administration as it is painless and well-tolerated in children. In this study, we had to use two different pain scales to objectively evaluate the postoperative pain, as there was a wide variation in the age of the subjects ranging from infancy to late childhood. NRS is an objective pain scale of 0–10, where “0” is no pain and “10” is the worst pain ever experienced by the subject. This scale was employed in our study to measure the pain in children more than 7-year-old, who could comprehend well and rate their pain effectively on the scale. In younger children below 7-year-old, we employed FLACC scale.[10] In our study, it was observed that preemptive administration of NSAIDs effectively spared the requirement of opioids in the postoperative period. Rescue analgesia was required after an average of 10.18 h postoperatively in children who were given paracetamol alone, which itself is an impressive duration of postoperative analgesia. This was even outweighed by the combination of paracetamol and diclofenac that effectively spared the opioid requirement for up to an average of 21.13 h postoperatively [Figure 1].

Figure 1

Variation of the duration of postoperative analgesia

CONCLUSION

We conclude that the combination of paracetamol and diclofenac administered per rectum preoperatively is more effective than paracetamol alone in providing postoperative analgesia in children.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest