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REVIEW ARTICLE
Year : 2023  |  Volume : 17  |  Issue : 1  |  Page : 65-71

Buprenorphine for acute post-surgical pain: A systematic review and meta-analysis


1 Department of Anesthesia, College of Medicine, Majmaah University, Al Majma'ah, 11952, Saudi Arabia
2 Department of Anesthesia, College of Medicine, King Saud University, Riyadh, Saudi Arabia
3 College of Medicine, Majmaah University, Al Majma'ah, 11952, Saudi Arabia

Correspondence Address:
Musab S Alabeesy
College of Medicine, Majmaah University, Al Majma'ah, 11952
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sja.sja_822_22

Rights and Permissions
Date of Submission16-Nov-2022
Date of Acceptance18-Nov-2022
Date of Web Publication02-Jan-2023
 

  Abstract 


Our study was designed to evaluate the efficacy of buprenorphine for the management of acute post-surgical pain reported in published studies in the years 2015–2022. Comprehensive research was performed by using online resources like PUBMED and the Wiley Library database to gather the relevant literature. Two authors were assigned to independently collect the information. Cochran's Q-test and I square statistic were used to determine the heterogeneity across the studies. Publication bias was estimated by using the Egger regression analysis and found to be significantly present once the P value <0.05. In this review, 15 studies were included. The pooled ratio of pain reduction after 12 hours of surgery was reported as 11.2% with 97% heterogeneity. Day one shows 5.9 reductions in pain with 98% heterogeneity. The 3% more pain was reduced on day 2. The day 3 pooled pain reduction score was observed as 1.9%. The overall pool prevalence of pain reduction was noted as 6.2% at different time duration with significant heterogeneity of 100%. Buprenorphine transdermal and sublingual both have significant pain relief scores. The analgesic drug consumption was reduced at the end of the follow-up duration.

Keywords: Acute pain, buprenorphine, post-surgical pain


How to cite this article:
Albaqami MS, Alqarni AA, Alabeesy MS, Alotaibi AN, Alharbi HA, Alshammari MM, Aldhfery AH. Buprenorphine for acute post-surgical pain: A systematic review and meta-analysis. Saudi J Anaesth 2023;17:65-71

How to cite this URL:
Albaqami MS, Alqarni AA, Alabeesy MS, Alotaibi AN, Alharbi HA, Alshammari MM, Aldhfery AH. Buprenorphine for acute post-surgical pain: A systematic review and meta-analysis. Saudi J Anaesth [serial online] 2023 [cited 2023 Feb 3];17:65-71. Available from: https://www.saudija.org/text.asp?2023/17/1/65/364884




  Introduction Top


Post-surgical pain is still very common globally despite many treatments that have been introduced in markets. Patients reported moderate-to-severe pain during a postoperative hospital stay. An estimated 20–40% of patients suffered from severe postoperative pain.[1] The pain reported on the day first of surgery can cause delayed ambulation and raised cardiopulmonary and thrombotic morbidity.[1],[2] Chronic pain can also be seen if day first pain is not treated well.[2] Currently, multimodal analgesia is considered the best suitable method of pain relief; however, opioid therapy is still most practiced in many clinical settings.[3],[4] Despite effective outcomes, these therapies also become a reason for adverse drug effects with frequently reported cases of nausea, vomiting, constipation, and urinary retention. High doses of opioids enhanced the risk of drug side effects and were vastly reported in previous studies.[5],[6]

Effective management of early postoperative acute pain is highly associated with patient satisfaction, early mobilization, and reduced duration of hospital stay. Oral opioids are widely used for early management.[5] Recently, in acute pain settings, buprenorphine gained attention due to its full-agonist analgesic and partial-agonist respiratory depression properties.[6] Research revealed that buprenorphine has a ceiling effect and is 75 to 100 times more potent than morphine.[7],[8] It can be used for renal dysfunction cases but need special attention when used for patients impaired with liver functions.[5],[7],[9] This systematic review and meta-analysis were designed to evaluate the efficacy of buprenorphine for the management of acute post-surgical pain reported in published studies in the years 2015–2022.


  Methodology Top


This systematic review and meta-analysis were conducted according to the PRISMA guideline.[10] This study aimed to evaluate the effect of buprenorphine on acute post-surgical pain.

Literature sources

Comprehensive research was performed by using online resources like PUBMED and the Wiley Library database to gather the relevant literature produced from the years 2015–2022.

Search strategy

The following guideline keywords with various combinations were used to access the data: pain score, analgesic score, acute pain, sublingual buprenorphine, transdermal buprenorphine, etc. To identify the additional studies, we also hand-searched the reference list of selected articles.

Inclusion and exclusion criteria

All the studies exploring the effect of buprenorphine before or after surgery were included. Studies considering patients aged above 18 years were included. No restriction was made on surgery type. Both prospective and retrospective studies were included. Studies using fentanyl and tramadol in the control group were considered eligible as fentanyl and tramadol are well studied in clinical trials and understood opioids. Studies investigating the use of buprenorphine for the management of chronic pain or opioid substitution were excluded. Case reports and previous systematic reviews were excluded.

Data extraction

Authors XYZ and MO were assigned to collect the relevant information including the author's name, region of study, study design, dosage, publication year, sample size, postoperative pain, postoperative analgesia, and drug-related side effects. In case of disagreement, third reviewer was asked to resolve the matter with consensus. After the data collection process, two independent authors processed the quality assessment of included articles.

Risk of bias

Cochran's risk of bias was used to assess the quality of included studies. The main items of this scoring include title, abstract, sample size calculations, allocation of patients, and allocation concealment.

Statistical analysis

Excel sheets were formed. Meta-Mar software was used for data analysis. Mean and standard deviations were used to describe the parameters. Pool prevalence was estimated by using the Wald test with a fixed-effects model. Pool prevalence was used to generate proportions with 95% confidence intervals (CI) and model-fitted weights. Cochran's Q test and I square statistic were used to determine the heterogeneity across the studies. I2 > 50% and P < 0.10 were considered significant. Publication bias was estimated by using the Egger regression analysis and found to be significantly present once the P value <0.05.


  Results Top


During the study timeframe, a total of 390 potential studies were found. In the final stage, 15 studies were included. Out of these 15, four studies were on sublingual buprenorphine [Figure 1]. Five studies were reported from India while three were from Iran, three were from the Chinese region, and a single study was reported from Mexico, Korea, UK, and Australia while in one study the region was unclear. Most of the studies used a double-blind procedure. Five studies performed abdominal surgeries while 10 orthopedic-related types of research were included (lower limb, spinal surgery, knee arthroplasty, lumber discectomy, hip fractures, and hallux valgus surgery). The sample size of included studies ranged from 50 to 150 patients with an average age of 18 to 75 years. In the control group, tramadol, fentanyl, celecoxib, and midazolam were used. Buprenorphine was induced before the surgical intervention for an average of 10 days. [Table 1] shows detailed information.
Figure 1: Flowchart on PRISMA guidelines

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Table 1: Characteristics

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Characteristics of individual studies

Side effects like nausea, vomiting, headache, sedation, and urinary retention were observed. [Table 2] reflects the outcomes of included studies. [Table 2] presents the complete outcomes of included studies.
Table 2: Outcomes of included studies

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A study by Soltani et al. reported significantly high pain in the morphine group when compared to buprenorphine (P < 0.001). However, the buprenorphine group reported four beats lower pulse rate than morphine along with a high level of sedation. No significant difference was reported between both groups in terms of side effects. Arshad's study reported no significant difference in incidents of nausea, urinary retention, and constipation between both groups (p-value = 1.0000). Kumar's study measured the systolic and diastolic blood pressure in both the placebo and treatment groups. They divided their treatment group into two main categories of low- and high-dose transdermal buprenorphine (10 mg vs. 20 mg). High systolic blood pressure was reported in the low-dose group than high dose while diastolic blood rate was observed high in the placebo group along with a high pain score. On the other side, the Desai study reported acute pain in patients with hip fractures. They reported significantly lower side effects of transdermal buprenorphine than oral tramadol (P < 0.01). No case of skin rash was reported in the buprenorphine group. Kim's study observed no significant difference between both groups when comparing back pain [Table 2].

Risk of bias

Cochran risk of bias was used to assess the quality of included studies. The main items of this scoring include title, abstract, sample size calculations, allocation of patients, and allocation concealment. The risk of bias was low in all studies; only sample size calculation was performed in a study of Desai et al. only while other lacked this point of interest [Table 3]. Desai study scored 6 points while study conducted by Narozi et al., and Nayogi et al. scored 5 points. Both of these studies not reported their sample size calculation format. Two studies scored lowest 2 points.
Table 3: Subgroup analysis of pain reduction score

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Meta-analysis

For conducting a meta-analysis, standard mean difference was used to evaluate the 12-hour, 24-hour, 48-hour, and 3rd-day pain. Only six studies represented the mean score. Study by Kumar evaluates two different dosages of buprenorphine (10 mg and 20 mg). The pooled ratio of pain reduction after 12 hours of surgery was reported as 11.2% with 97% heterogeneity. Day one shows 5.9 reductions in pain with 98% heterogeneity. The 3% more pain was reduced on day 2 [Figure 2]. The day 3 pooled pain reduction score was observed as 1.9%. The overall pool prevalence of pain reduction was noted as 6.2% at different time duration with significant heterogeneity of 100%. However, Egger regression analysis for publication bias was insignificant a P value observed as 0.1 > 0.05 [Figure 3]. A complete subgroup analysis is described in [Table 3].
Figure 2: Wald test of pain score at the different time duration

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Figure 3: Egger regression asymmetry funnel plot

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  Discussion Top


To our knowledge, this is the first systematic review and meta-analysis which evaluate the efficacy of transdermal buprenorphine and sublingual buprenorphine for postoperative pain management. Transdermal buprenorphine was initiated 6–48 hours before surgery in majority consistent with the previous studies using transdermal buprenorphine patch prior to 12–24 hour latency time.[5],[6],[9] Preoperative achievement of stable plasma concentrations is considered ideal; however, ethical concerns (in terms of unnecessary usage before pain stimuli) occur when it comes to preoperative usage of opioids. Large variation was observed in buprenorphine dosage ranges from 5 mcg h−1 to 52.5 mcg h−1. Many studies used 5–10 mg patches with oral doses of up to 30 mg day−1. The quantity of these dosages is in agreement with the postoperative opioid protocol and can be attained even after using weak opioids.[26],[27] Comparative cases control placebo clinical trials observed a significant decline in pain score and lower postoperative analgesic consumption in the buprenorphine groups.[13],[16],[18] Meanwhile, somnolence[13] and nausea[16] incidents were increased in two studies while one study[18] reported no difference in drug-related side effects. Pain relief and reduction in analgesic consumption are common outcomes of opioids with high drug-related side effects.[26],[27] The present review also demonstrates that buprenorphine reduces pain more efficiently than the placebo with documented side effects like nausea, vomiting and somnolence, and sedation without any significant difference between both groups. Placebo groups also reported cases of respiratory depression, urinary retention, vomiting, and constipation.

Studies also reported patient satisfaction and significant pain relief in the buprenorphine group when compared with weak opioid tramadol.[14],[15] Moreover, buprenorphine-favoring studies were reported in this analysis. One study initiates a patch before 12 hours of surgery while another initiated it after 36 hours of surgical procedure. Both of these studies used patient-controlled analgesia with fentanyl. The analgesia onset of buprenorphine was slower than tramadol; however, the similar pain score favored the buprenorphine opioid.

Comparing the results of two studies[17],[19] using NSAIDS control and buprenorphine, similar postoperative outcomes were observed in terms of pain. Meanwhile, the consumption of celecoxib reported less pain relief than buprenorphine. Postoperative analgesic consumption was also similar in both groups; except in one study low dosage of buprenorphine was consumed.[19] The drug effect was also similar in both groups; however, both studies reported higher satisfaction in the buprenorphine group. These results indicate that buprenorphine has equivalent or superior analgesic efficacy than flurbiprofen, parecoxib, and celecoxib.

Despite the significant outcomes, one study[12] failed to reduce the pain score. This study used 10 mcg h−1 buprenorphine compared with 25 mcg h−1 fentanyl. This study also reported high sedation scores, while postoperative opioid consumption was similar in both groups. In two studies, patches were applied before 6 hours while previous studies also reported non-equivalent dosages of buprenorphine and fentanyl.[28],[29],[30] Three studies[13],[16],[18] consumed different dosages of buprenorphine while in one study[13] that used 10 mg and 20 mg buprenorphine researchers observed more pain scores in the 10 mg group than in the other. Out of these three, two studies used a high buprenorphine dosage of 17.5 mcg h−1 to 52.5 mcg h−1 but failed to observe any significant difference in pain score and patient satisfaction.[16],[18] Higher buprenorphine dosages reported an increased rate of somnolence[13] and sedation.[16] All these results indicate that transdermal buprenorphine provides pain relief and reduces postoperative analgesic requirements. Results also summarize that the higher doses do not provide increased analgesic benefits. Moreover, no life-threatening adverse side effects were observed in the literature.


  Conclusion Top


In conclusion, buprenorphine either transdermal or sublingual both have significant pain relief scores. The analgesic drug consumption was reduced at the end of the follow-up duration. However, buprenorphine had more adverse effects than other NSAIDs and placebo which may irritate patients and affect their surgical experience of patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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