Evaluation of the treatments to manage postoperative pain in children undergoing dental procedures under general anaesthesia

The combination of Ibuprofen and Paracetamol, administered preoperatively and intravenously, has been shown to provide superior postoperative pain relief, enhance patient comfort, reduce the need for additional pain medications, and support quicker recovery in children.

Postoperative pain accounts for the most prevalent complication in American Society of Anaesthesiologists (ASA) I, II and III groups of children. Over 80% of individuals experience acute postoperative pain. It has been reported that maximum number of paediatric patients undergoing comprehensive dental treatment under general anaesthesia (GA) report discomfort from persistent bleeding and nausea, in addition to experiencing sore mouth, trouble eating, emotional distress, nightmares, mental discomfort, high anxiety, enuresis and altered behaviour. In order to reduce the financial burden, increase patient satisfaction, and avoid extended hospital stays, children receiving dental treatment under general anaesthesia (GA) must have their post-operative pain effectively managed. It is recommended by the American Society of Anaesthesiologists (ASA) that actions be taken "before, during, and after a procedure to reduce or eliminate postoperative pain before discharge."  Additionally, research has demonstrated that factors such as the patient's age, anxiety level, kind of operation, and pre-existing preoperative pain all predict postoperative pain. Therefore, it is essential to assess various pharmacological interventions for effective post-operative pain relief.

RATIONALE BEHIND RESEARCH

Post-operative pain has been known to result in prolonged hospitalization and increased distress in 80-95% of the children receiving dental treatment under GA. Therefore, it is necessary to compare the multiple modalities used to control the post-operative pain in children so that the results presented can be employed by physicians to make an informed decision.

OBJECTIVE

The study aimed to explore the use of various pharmacological modalities to manage postoperative pain in children receiving general anaesthesia for dental treatment.

Literature search

The systematic review adhered to the PRISMA criteria for systematic research and meta-analysis. Keywords like “children,” “general anaesthesia,” “postoperative pain,” and “dental extraction” were used in searches on Web of Science, Scopus, and PubMed for articles published up to June 2021. 131 abstracts were eliminated from the total of 191 abstracts based on the inclusion-exclusion criteria. Out of 60 shortlisted abstracts for full length reading and only 21 were selected for the systematic review after removing 39 duplicates.

Inclusion criteria

• Children and adolescents aged 0-18 years who underwent comprehensive dental treatment under GA, including preventive, restorative, and exodontia procedures.
• Randomized control trials and case-control interventional studies involving postoperative pain management modalities or interventions.
• Children in groups I, II, and III of the ASA physical status.
• Articles written exclusively in English were selected.

Exclusion criteria

• Studies involving adults or a combination of adults and children were excluded, along with those involving children exclusively treated under local anesthesia or conscious sedation.
• The study excluded various types of studies including observational, cohort studies, narrative reviews, systematic reviews, case reports, editorials, conference proceedings, book chapters, and commentaries.

Study Selection and Data extraction

The data was collected by two separate reviewers, and the third reviewer rectified any discrepancies. The data gathered included authors' names, publication year, country of origin, study type, demographic characteristics, treatment modalities, pharmacological agents used, frequency, procedure duration, postoperative pain intensity, analgesia, administration route, and outcomes.

The different pharmacological treatments to cure post-operative pain included the use of NSAIDs alone or in combination with opioid analgesics and local anaesthesia (LA). All the included studies utilized rescue analgesics by evaluating the pain score of the patient or as a routine regimen except for one RCT. 

Data and Statistical Analysis

N/A

Risk of Bias and Quality assessment

The Joanna Briggs analysis was used to assess the risk of bias. The score of analysis >9 indicates low RoB, moderate if score is between 7-9 and high for score <7. The high RoB studies (2 studies) included the patients not randomized or systematically allotted into different analgesic groups. The post-operative pain assessment varied among the studies. The earliest assessments were made 15 minutes after recovery, while others observed pain levels for several hours post-anesthesia, with some extending follow-ups up to a week.

Outcomes

Study and participant characteristics:

• Children undergoing dental treatment under GA who received pharmaceutical treatment to alleviate post-operative pain.
• Children receiving dental care under GA without any modalities comprised the control group.
• The outcome of the study focused on the frequency, incidence, and need for intervention with rescue analgesics in children receiving dental treatment under GA.

Study quality:

Effect of intervention on the outcome:

Administration of NSAIDs alone or in combination with postoperative analgesia

• A study by Gazal et al. demonstrated that preoperative Ibuprofen alone or in combination with Paracetamol has been shown to provide better pain relief than groups where only Paracetamol was administered.
• In an RCT conducted by El Batawi, Diclofenac was superior to Acetaminophen in relieving postoperative pain in children.
• A study by O’ Donnell et al. reported better pain relief in children after preoperative administration of rectal Voltarol than preoperative oral Paracetamol.
• Marshall et al. found that combining Paracetamol with NSAIDs, as recommended by APA, resulted in lower postoperative pain.
• Preoperative intravenous (IV) Paracetamol lowered the pain score as compared to the administration of IV Paracetamol postoperatively as reported in a randomized study by Kharouba et al.
• A contradictory study by Jensen reported no difference in postoperative pain scores among intra-operative Paracetamol alone, NSAIDs, opioids and combination groups.

Use of NSAIDs with opioid analgesics in postoperative analgesia

• A prospective study by Alohali et al. reported that a short-acting opioid IV Fentanyl, in combination with Paracetamol decreased postoperative pain when compared to IV Fentanyl, IV Paracetamol and control group.
• A study by Littlejohn et al. revealed no significant difference in the pain scores between IV Nalbuphine, IV Diclofenac suppositories and the control groups.

Use of opioids in postoperative pain management

• An RCT conducted by Sheta et al. reported decreased postoperative pain with intranasal Dexmedetomidine as compared to preoperative intranasal Midazolam.
• An RCT by Roelofse et al. found that intranasal Sufentanil and Midazolam group experienced less postoperative pain compared to intranasal Ketamine and Midazolam group.
• Roelofse et al.'s randomized control trial found IV Tramadol improved postoperative analgesia, while McIntyre et al.'s trial found no difference in pain scores between Dexamethasone and normal saline.

Use of local anaesthesia alone or in combination with Paracetamol and NSAIDs in postoperative analgesia

• Coulthard et al.'s randomized control trial found that LA, compared to saline, was ineffective in reducing postoperative pain in children.
• McWilliams et al.'s randomized control study found no significant difference in postoperative pain scores between LA and the group without LA.
• Townsend et al.'s randomized prospective study found no significant difference in pain scores between groups receiving IV Ketorolac with oral infiltration of LA and the IV Ketorolac group alone.
• Jürgens et al. found that LA injections, when compared with IV Fentanyl alone or in combination with Paracetamol, provided a superior postoperative analgesic effect.
• An RCT by Leong et al. comparing LA administration techniques, including intra-ligamental injection with infiltration, to a control group, found no significant difference in postoperative pain despite a decrease in pain scores.
• Sammons et al.'s randomized control trial found a reduction in pain scores in the intra-ligamental injection group compared to the control group, but this reduction was only noticeable in the first hour postoperatively, suggesting that LA's role in pain reduction was insignificant.

Use of topical local anaesthesia alone in postoperative analgesia

• Andrzejowski et al. conducted a randomized control trial which found no difference in pain scores between the topical Bupivacaine and saline group.
• A randomized control trial by Gazal et al. revealed topical Bupivacaine did not effectively provide postoperative analgesic relief.

Multiple studies suggest that preoperative administration of NSAIDs like Ibuprofen alone or in combination with Paracetamol effectively reduces postoperative pain scores due to the inhibition of prostaglandin release centrally and peripherally at the site of injury.

Children aged 2-7 years, experience higher pain scores and distress after teeth extractions compared to those aged 8-12. Two studies found that NSAIDs, such as rectal Voltarol and oral Diclofenac, significantly reduced postoperative pain scores compared to acetaminophen.

Another study involving a comparison among Ibuprofen, Ketoprofen, and Acetaminophen revealed that intravenous (IV) administration of Diclofenac improved postoperative analgesia, particularly in cases with multiple traumatic dental extractions. Diclofenac's action onsets in rectal administration at 20-24 minutes, avoiding first-pass metabolism, while oral Paracetamol has an onset of at least 1 hour and only 60% bioavailability after first-pass metabolism

Administration of Paracetamol preoperatively or IV Paracetamol intra-operatively instead of oral and rectal route has been shown to decrease the pain score rapidly. Preoperative oral Acetaminophen patients have been shown to require less rescue morphine postoperatively compared to rectal acetaminophen patients. Paracetamol's better preoperative analgesic effect is due to its serotonergic pain pathway mechanism, which interrupts the repeated firing of neurons from the surgical site.

A study reported that Rofecoxib administration required less postoperative analgesics than intra-operative administration, and rectal Diclofenac had peak analgesic effect at 30 minutes. However, a meta-analysis found no sufficient evidence to support preoperative analgesics for children under LA in dental clinics, as side effects include asthma, gastric bleeding, hepatotoxicity, and nephrotoxicity, warranting caution.

A short-acting opioid called Fentanyl when combined with NSAIDs was shown to decrease the pain score postoperatively in children. However, the use of IV Fentanyl is restricted in children receiving comprehensive dental treatment as it causes respiratory depression. In contrast, Sufentanil, an opioid agonist analgesic was found to be twice as potent as Fentanyl with no side effects. Another opioid agonist, Nalbuphine hydrochloride was shown to have superiority over morphine, however few side effects have been reported from its use as compared to NSAIDs.

Tramadol is a centrally acting opioid which functions by inhibiting the noradrenaline and serotonin (5HT) reuptake and providing analgesia from 20 minutes up to nine hours. However, its role in reducing postoperative pain is controversial due to no significant evidence and multiple side effects such as nausea, vomiting and respiratory reactions.

Intranasal analgesia is recommended using Dexmedetomidine and Midazolam due to rapid absorption and increased bioavailability compared to oral dosing. Dexmedetomidine is rapid, non-invasive, and has a has higher compliance rate but its use is limited by adverse effects like hypotension, bradycardia, and hemodynamic disturbances.

Long anaesthesia (LA), a pain reliever, may cause distress in young children due to its numbing effect. Intraligamental techniques are recommended for younger children to alleviate numbness and potential self-injury of lips, while morphine with or without IV NSAIDs is reported to cause less distress in postanaesthesia care unit nurses. The analgesic effect of LA only lasts for one hour, therefore rescue analgesics are needed to overcome postoperative pain. LA is essential for reducing haemorrhage in children, but it's inefficient for pain control. Furthermore, the topical use of bupivacaine did not alleviate postoperative discomfort.

FUTURE RECOMMENDATIONS

• Future studies could incorporate post-operative inflammatory markers like C-reactive protein to prevent bias by addition to subjective measurements.
• Separate subgroup analysis could be done based on the age of the children, as pain perception varies between 6 and 14 years old.
• The postoperative pain follow-up period should be extended until the recall visit to fully understand the patients' post-operative co-morbidities.
• Further research is needed in paediatric dentistry to effectively manage postoperative pain in children receiving general anaesthesia using short-acting opioids like Fentanyl in combination with Paracetamol.