Pain Medicine Section Editor: Spencer S. Liu
Transversus Abdominis Plane Block to Ameliorate Postoperative Pain Outcomes After Laparoscopic Surgery: A Meta-Analysis of Randomized Controlled Trials Gildasio S. De Oliveira Jr, MD, MSCI, Lucas Jorge Castro-Alves, MD, Autoun Nader, MD, Mark C. Kendall, MD, and Robert J. McCarthy, PharmD BACKGROUND: Transversus abdominis plane (TAP) block has been used as a multimodal strategy to optimize postoperative pain outcomes; however, it remains unclear which type of surgical procedures can benefit from the administration of a TAP block. Several studies have examined the effect of the TAP block on postoperative pain outcomes after laparoscopic surgical procedures and generated conflicting results. Our main objective in the current investigation was to evaluate the effect of TAP block on postoperative analgesia outcomes for laparoscopic surgical procedures. METHODS: A search was performed to identify randomized controlled trials that evaluated the effects of the TAP block compared with an inactive group (placebo or “no treatment”) on postoperative pain outcomes in laparoscopic surgical procedures. Primary outcomes included early (0–4 hours) and late (24 hours) postoperative pain at rest and on movement and postoperative opioid consumption (up to 24 hours). Meta-analysis was performed using a random-effects model. Publication bias was evaluated by examining the presence of asymmetric funnel plots using Egger regression test. Meta-regression analysis was performed to establish an association between the local anesthetic dose and the evaluated outcomes. RESULTS: Ten randomized clinical trials with 633 subjects were included in the analysis. The weighted mean difference (99% confidence interval) of the combined effects favored TAP block over control for pain at rest (≤4 hours, −2.41 [−3.6 to −1.16]) and (at 24 hours, −1.33 [−2.19 to −0.48]) (0–10 numerical scale). Postoperative opioid consumption was decreased in the TAP block group compared with control, weighted mean difference (99% confidence interval) of −5.74 (−8.48 to −2.99) mg morphine IV equivalents. Publication bias was not present in any of the analysis. Preoperative TAP block administration resulted in greater effects on early pain and opioid consumption compared with postoperative administration. Meta-regression analysis revealed an association between local anesthetic dose and the TAP block effect on late pain at rest and postoperative opioid consumption. None of the studies reported symptoms of local anesthetic toxicity. CONCLUSIONS: TAP block is an effective strategy to improve early and late pain at rest and to reduce opioid consumption after laparoscopic surgical procedures. In contrast, the TAP block was not superior compared with control to reduce early and late pain during movement. Preoperative administration of a TAP block seems to result in greater effects on postoperative pain outcomes. We also detected a local anesthetic dose response on late pain and postoperative opioid consumption. (Anesth Analg 2014;118:454–63)
T
he advance in surgical techniques and the development of anesthetics with low side effect profiles have enabled the current rapid growth of outpatient surgical procedures.1,2 Recently, larger procedures such as
From the Department of Anesthesiology, Northwestern University, Chicago, Illinois. Accepted for publication November 15, 2013. Funding: Department of Anesthesiology, Northwestern University, Chicago, IL. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Gildasio S. De Oliveira Jr, MD, MSCI, Department of Anesthesiology, Northwestern University, 241 East Huron St., F 5-704, Chicago, IL. Address e-mail to [email protected]. Copyright © 2014 International Anesthesia Research Society DOI: 10.1213/ANE.0000000000000066
454 www.anesthesia-analgesia.org
prostatectomy and gynecological cancer surgeries have been performed laparoscopically allowing a better and faster postoperative recovery to patients.3,4 Nevertheless, postoperative pain seems to remain a very important factor that can deteriorate the overall quality of recovery after laparoscopic procedures.5,6 Transversus abdominis plane (TAP) block has been used as a multimodal strategy to optimize postoperative pain outcomes. However, in recent reviews evaluating the clinical effectiveness of TAP block, the investigators were not able to identify the surgical procedures, dosing, techniques, and timing that provide optimal analgesia after TAP block.7,8 Since then, evidence suggested an effective role for TAP block to minimize postoperative pain in certain procedures such as cesarean deliveries that do not include February 2014 • Volume 118 • Number 2
intrathecal morphine.9 In contrast, it remains to be determined whether TAP block can improve analgesic outcomes after laparoscopic surgical procedures. The main objective of the current investigation was to examine the effect of TAP block on postoperative pain outcomes after laparoscopic surgeries. We also sought to investigate the effect of block timing and local anesthetic dose on the evaluated outcomes.
METHODS
We performed a quantitative systematic review following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.10
Systematic Search
Published reports of randomized trials evaluating the effects of TAP block on surgical postoperative pain were searched using the National Library of Medicine’s PubMed database, the Cochrane Database of Systematic Reviews, and Google Scholar inclusive of April 21, 2013. Free text and MeSH terms “transversus,” “pain,” “postoperative,” “preoperative,” “analgesia,” and “opioid” were used individually and in all pairwise combinations. No language restriction was used. The search was limited to human subjects aged >18 years. An attempt to identify additional studies not found by the primary search methods was made by reviewing the reference lists from identified studies. No search was performed for unpublished studies. This initial search yielded 115 randomized clinical trials.
Selection of Included Studies
The study’s inclusion and exclusion criteria were determined before the systematic search. Two authors independently evaluated the abstract and results of the 115 articles obtained by the initial search. Articles that were clearly not relevant based on our inclusion and exclusion criteria were excluded at this phase. Disagreements on inclusion of the articles were resolved by discussion among the evaluators. If an agreement could not be reached, the dispute was resolved with the help of a third investigator. The third investigator was blinded regarding evaluation of the first 2 authors.
Inclusion and Exclusion Criteria
We included randomized controlled trials that compared perioperative TAP blocks with local anesthetics and an inactive (placebo or “no treatment”) control group in patients undergoing laparoscopic surgical procedures under general anesthesia. Trials that evaluated the effect of the TAP block in patients undergoing a different surgical procedure than laparoscopy were excluded to optimize clinical homogeneity. Studies containing a concurrent use of an alternative multimodal analgesia regimen were excluded if a direct comparison of TAP block and control (sham or no block) could not be established. Included studies had to report at least on pain scores or opioid consumption as postoperative pain outcomes. No minimum sample size was required for inclusion in the meta-analysis.
Validity Scoring
Two authors independently read the included reports and assessed their methodological validity using a modified
February 2014 • Volume 118 • Number 2
Jadad 5-point quality scale.11 The scale evaluates the study for the following: randomization, double-blind evaluation, concealment of study group to evaluator, valid randomization method, and completeness of data at follow-up. Discrepancies in rating of the trials were resolved by discussion among the evaluators. If an agreement could not be reached, the dispute was resolved with the help of a third investigator. Because only randomized trials were included in the analysis, the minimum possible score of an included trial was 1 and the maximum was 5. Trials were not excluded or weighted in the analysis based on quality assessment scores.
Data Extraction
Two authors independently evaluated the full manuscripts of all included trials and performed data extraction using a data collection form specifically developed for this review. Discrepancies were resolved by discussion between the investigators. If an agreement could not be reached between the 2 investigators, the decision was made by a third investigator. Data extracted from trials included the local anesthetic type and dose, sample size, number of subjects in treatment groups, follow-up period, type of surgery, early pain scores (≤4 hours) at rest and at movement, late pain scores (24 hours) at rest and at movement, cumulative opioid consumption, time to rescue analgesic administration (minutes), and adverse events. Postoperative opioid consumption was converted to the equivalent dose of IV morphine.12 A visual analog scale or numeric rating scale for pain was converted to a 0 to 10 numeric rating scale. Data were initially extracted from tables or text. For data not available in tables, the data were abstracted from available figures. Dichotomous data on the presence or absence of adverse effects were extracted and converted to incidence, whereas continuous data were recorded using mean and standard deviation. Data presented only as median and range were converted to means and standard deviation using previously described methodology.13 In studies that involved >1 independent dose group compared with a single control group, the control group was split according to the number of comparisons. When required, the standard deviation for pain scores was estimated using the most extreme values. The most conservative value was used when the same outcome was reported more than once for a determined period.
Definition of Relevant Outcome Data
The primary outcomes were early acute postoperative pain scores (visual analog scale or numeric rating scale) at rest and at movement (0–4 hours postoperatively), late acute postoperative pain scores (visual analog scale or numeric rating scale) at rest and at movement (24 hours postoperatively), and cumulative opioid consumption (24 hours) in the postoperative period. The secondary outcomes were the time to first analgesic administration (minutes); adverse events included postoperative hypotension, nausea, and/or vomiting.
Meta-Analyses
The weighted mean differences (WMDs) with 99% confidence interval (CI) were determined and reported for
www.anesthesia-analgesia.org
455
Tap block laparoscopic surgery
continuous data. For dichotomous data (adverse effects), the Peto odds ratio (to account for the potential of 0 counts in the cells for low-frequency outcomes) and 99% CI are reported. For primary outcomes, a significant effect compared with placebo required that the 99% CI for continuous data did not include 0, and for dichotomous secondary data, the 95% CI did not include 1.0. Due to the different surgical procedures, we used a random effect model in an attempt to generalize our findings to studies not included in our meta-analysis.14 Publication bias was evaluated by examining for asymmetric funnel plots using the Egger regression test.15,16 A 1-sided P < 0.05 was considered an indication of an asymmetric funnel plot. A file drawer analysis described by Rosenthal17 was performed in the case of an asymmetric funnel plot. The test estimates the lowest number of additional studies that if they would become available would reduce the combined effect to nonsignificance, assuming the average z value of the combined P values of these missing studies would be 0. Heterogeneity of the included studies was further evaluated if the I2 statistic was >50%. The I2 statistic is a test of heterogeneity that measures the variability between studies included in a quantitative analysis regarding an evaluated outcome. I2 values range between 0% and 100%, where 0 represents perfect homogeneity among included studies and 100% represents the highest degree of heterogeneity. Further analysis was planned a priori to explore nontrivial heterogeneity of the treatment effect across the included studies, including time of block administration (preoperatively versus postoperatively) and quality of included studies evaluated by the Jadad score. Subgroup analysis was performed to test whether the overall effect of TAP block on evaluated outcomes changed when lower quality studies (Jadad ≤3) were removed from the analysis. The proportion of the total variance explained by the covariates (R2) was calculated by dividing the random-effects pooled estimates of variance (τ2) within studies by the total variance (total τ2). The value obtained was then subtracted from 1. When values were outside the range of 0% to 100%, they were set to the closest value (0% or 100%). A meta-regression analysis was performed to evaluate a possible association between total local anesthetic dose and the effect size on evaluated outcomes. Equipotent doses of ropivacaine were converted to bupivacaine (0.7 mg bupivacaine = 1 mg ropivacaine).18,19 Because we prespecified 5 primary outcomes (2 pain states at 2 times each, plus opioids), we assessed a P value
Transversus Abdominis Plane Block to Ameliorate Postoperative Pain Outcomes After Laparoscopic Surgery: A Meta-Analysis of Randomized Controlled Trials Gildasio S. De Oliveira Jr, MD, MSCI, Lucas Jorge Castro-Alves, MD, Autoun Nader, MD, Mark C. Kendall, MD, and Robert J. McCarthy, PharmD BACKGROUND: Transversus abdominis plane (TAP) block has been used as a multimodal strategy to optimize postoperative pain outcomes; however, it remains unclear which type of surgical procedures can benefit from the administration of a TAP block. Several studies have examined the effect of the TAP block on postoperative pain outcomes after laparoscopic surgical procedures and generated conflicting results. Our main objective in the current investigation was to evaluate the effect of TAP block on postoperative analgesia outcomes for laparoscopic surgical procedures. METHODS: A search was performed to identify randomized controlled trials that evaluated the effects of the TAP block compared with an inactive group (placebo or “no treatment”) on postoperative pain outcomes in laparoscopic surgical procedures. Primary outcomes included early (0–4 hours) and late (24 hours) postoperative pain at rest and on movement and postoperative opioid consumption (up to 24 hours). Meta-analysis was performed using a random-effects model. Publication bias was evaluated by examining the presence of asymmetric funnel plots using Egger regression test. Meta-regression analysis was performed to establish an association between the local anesthetic dose and the evaluated outcomes. RESULTS: Ten randomized clinical trials with 633 subjects were included in the analysis. The weighted mean difference (99% confidence interval) of the combined effects favored TAP block over control for pain at rest (≤4 hours, −2.41 [−3.6 to −1.16]) and (at 24 hours, −1.33 [−2.19 to −0.48]) (0–10 numerical scale). Postoperative opioid consumption was decreased in the TAP block group compared with control, weighted mean difference (99% confidence interval) of −5.74 (−8.48 to −2.99) mg morphine IV equivalents. Publication bias was not present in any of the analysis. Preoperative TAP block administration resulted in greater effects on early pain and opioid consumption compared with postoperative administration. Meta-regression analysis revealed an association between local anesthetic dose and the TAP block effect on late pain at rest and postoperative opioid consumption. None of the studies reported symptoms of local anesthetic toxicity. CONCLUSIONS: TAP block is an effective strategy to improve early and late pain at rest and to reduce opioid consumption after laparoscopic surgical procedures. In contrast, the TAP block was not superior compared with control to reduce early and late pain during movement. Preoperative administration of a TAP block seems to result in greater effects on postoperative pain outcomes. We also detected a local anesthetic dose response on late pain and postoperative opioid consumption. (Anesth Analg 2014;118:454–63)
T
he advance in surgical techniques and the development of anesthetics with low side effect profiles have enabled the current rapid growth of outpatient surgical procedures.1,2 Recently, larger procedures such as
From the Department of Anesthesiology, Northwestern University, Chicago, Illinois. Accepted for publication November 15, 2013. Funding: Department of Anesthesiology, Northwestern University, Chicago, IL. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Gildasio S. De Oliveira Jr, MD, MSCI, Department of Anesthesiology, Northwestern University, 241 East Huron St., F 5-704, Chicago, IL. Address e-mail to [email protected]. Copyright © 2014 International Anesthesia Research Society DOI: 10.1213/ANE.0000000000000066
454 www.anesthesia-analgesia.org
prostatectomy and gynecological cancer surgeries have been performed laparoscopically allowing a better and faster postoperative recovery to patients.3,4 Nevertheless, postoperative pain seems to remain a very important factor that can deteriorate the overall quality of recovery after laparoscopic procedures.5,6 Transversus abdominis plane (TAP) block has been used as a multimodal strategy to optimize postoperative pain outcomes. However, in recent reviews evaluating the clinical effectiveness of TAP block, the investigators were not able to identify the surgical procedures, dosing, techniques, and timing that provide optimal analgesia after TAP block.7,8 Since then, evidence suggested an effective role for TAP block to minimize postoperative pain in certain procedures such as cesarean deliveries that do not include February 2014 • Volume 118 • Number 2
intrathecal morphine.9 In contrast, it remains to be determined whether TAP block can improve analgesic outcomes after laparoscopic surgical procedures. The main objective of the current investigation was to examine the effect of TAP block on postoperative pain outcomes after laparoscopic surgeries. We also sought to investigate the effect of block timing and local anesthetic dose on the evaluated outcomes.
METHODS
We performed a quantitative systematic review following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.10
Systematic Search
Published reports of randomized trials evaluating the effects of TAP block on surgical postoperative pain were searched using the National Library of Medicine’s PubMed database, the Cochrane Database of Systematic Reviews, and Google Scholar inclusive of April 21, 2013. Free text and MeSH terms “transversus,” “pain,” “postoperative,” “preoperative,” “analgesia,” and “opioid” were used individually and in all pairwise combinations. No language restriction was used. The search was limited to human subjects aged >18 years. An attempt to identify additional studies not found by the primary search methods was made by reviewing the reference lists from identified studies. No search was performed for unpublished studies. This initial search yielded 115 randomized clinical trials.
Selection of Included Studies
The study’s inclusion and exclusion criteria were determined before the systematic search. Two authors independently evaluated the abstract and results of the 115 articles obtained by the initial search. Articles that were clearly not relevant based on our inclusion and exclusion criteria were excluded at this phase. Disagreements on inclusion of the articles were resolved by discussion among the evaluators. If an agreement could not be reached, the dispute was resolved with the help of a third investigator. The third investigator was blinded regarding evaluation of the first 2 authors.
Inclusion and Exclusion Criteria
We included randomized controlled trials that compared perioperative TAP blocks with local anesthetics and an inactive (placebo or “no treatment”) control group in patients undergoing laparoscopic surgical procedures under general anesthesia. Trials that evaluated the effect of the TAP block in patients undergoing a different surgical procedure than laparoscopy were excluded to optimize clinical homogeneity. Studies containing a concurrent use of an alternative multimodal analgesia regimen were excluded if a direct comparison of TAP block and control (sham or no block) could not be established. Included studies had to report at least on pain scores or opioid consumption as postoperative pain outcomes. No minimum sample size was required for inclusion in the meta-analysis.
Validity Scoring
Two authors independently read the included reports and assessed their methodological validity using a modified
February 2014 • Volume 118 • Number 2
Jadad 5-point quality scale.11 The scale evaluates the study for the following: randomization, double-blind evaluation, concealment of study group to evaluator, valid randomization method, and completeness of data at follow-up. Discrepancies in rating of the trials were resolved by discussion among the evaluators. If an agreement could not be reached, the dispute was resolved with the help of a third investigator. Because only randomized trials were included in the analysis, the minimum possible score of an included trial was 1 and the maximum was 5. Trials were not excluded or weighted in the analysis based on quality assessment scores.
Data Extraction
Two authors independently evaluated the full manuscripts of all included trials and performed data extraction using a data collection form specifically developed for this review. Discrepancies were resolved by discussion between the investigators. If an agreement could not be reached between the 2 investigators, the decision was made by a third investigator. Data extracted from trials included the local anesthetic type and dose, sample size, number of subjects in treatment groups, follow-up period, type of surgery, early pain scores (≤4 hours) at rest and at movement, late pain scores (24 hours) at rest and at movement, cumulative opioid consumption, time to rescue analgesic administration (minutes), and adverse events. Postoperative opioid consumption was converted to the equivalent dose of IV morphine.12 A visual analog scale or numeric rating scale for pain was converted to a 0 to 10 numeric rating scale. Data were initially extracted from tables or text. For data not available in tables, the data were abstracted from available figures. Dichotomous data on the presence or absence of adverse effects were extracted and converted to incidence, whereas continuous data were recorded using mean and standard deviation. Data presented only as median and range were converted to means and standard deviation using previously described methodology.13 In studies that involved >1 independent dose group compared with a single control group, the control group was split according to the number of comparisons. When required, the standard deviation for pain scores was estimated using the most extreme values. The most conservative value was used when the same outcome was reported more than once for a determined period.
Definition of Relevant Outcome Data
The primary outcomes were early acute postoperative pain scores (visual analog scale or numeric rating scale) at rest and at movement (0–4 hours postoperatively), late acute postoperative pain scores (visual analog scale or numeric rating scale) at rest and at movement (24 hours postoperatively), and cumulative opioid consumption (24 hours) in the postoperative period. The secondary outcomes were the time to first analgesic administration (minutes); adverse events included postoperative hypotension, nausea, and/or vomiting.
Meta-Analyses
The weighted mean differences (WMDs) with 99% confidence interval (CI) were determined and reported for
www.anesthesia-analgesia.org
455
Tap block laparoscopic surgery
continuous data. For dichotomous data (adverse effects), the Peto odds ratio (to account for the potential of 0 counts in the cells for low-frequency outcomes) and 99% CI are reported. For primary outcomes, a significant effect compared with placebo required that the 99% CI for continuous data did not include 0, and for dichotomous secondary data, the 95% CI did not include 1.0. Due to the different surgical procedures, we used a random effect model in an attempt to generalize our findings to studies not included in our meta-analysis.14 Publication bias was evaluated by examining for asymmetric funnel plots using the Egger regression test.15,16 A 1-sided P < 0.05 was considered an indication of an asymmetric funnel plot. A file drawer analysis described by Rosenthal17 was performed in the case of an asymmetric funnel plot. The test estimates the lowest number of additional studies that if they would become available would reduce the combined effect to nonsignificance, assuming the average z value of the combined P values of these missing studies would be 0. Heterogeneity of the included studies was further evaluated if the I2 statistic was >50%. The I2 statistic is a test of heterogeneity that measures the variability between studies included in a quantitative analysis regarding an evaluated outcome. I2 values range between 0% and 100%, where 0 represents perfect homogeneity among included studies and 100% represents the highest degree of heterogeneity. Further analysis was planned a priori to explore nontrivial heterogeneity of the treatment effect across the included studies, including time of block administration (preoperatively versus postoperatively) and quality of included studies evaluated by the Jadad score. Subgroup analysis was performed to test whether the overall effect of TAP block on evaluated outcomes changed when lower quality studies (Jadad ≤3) were removed from the analysis. The proportion of the total variance explained by the covariates (R2) was calculated by dividing the random-effects pooled estimates of variance (τ2) within studies by the total variance (total τ2). The value obtained was then subtracted from 1. When values were outside the range of 0% to 100%, they were set to the closest value (0% or 100%). A meta-regression analysis was performed to evaluate a possible association between total local anesthetic dose and the effect size on evaluated outcomes. Equipotent doses of ropivacaine were converted to bupivacaine (0.7 mg bupivacaine = 1 mg ropivacaine).18,19 Because we prespecified 5 primary outcomes (2 pain states at 2 times each, plus opioids), we assessed a P value
