BREAST Preemptive Analgesia with Bupivacaine in Reduction Mammaplasty: A Prospective, Randomized, Double-Blind, PlaceboControlled Trial Denis S. Valente, M.D. Porto Alegre, Brazil
Background: Preincisional analgesia is an antinociceptive treatment that prevents altered central excitability from high-intensity noxious stimuli. To determine the analgesic efficacy of preoperative infiltration with bupivacaine for reduction mammaplasty, a randomized, double-blind, placebo-controlled trial was designed. Methods: Women with mammary hypertrophy were allocated randomly to one of two study groups. Patients in group I received preincision infiltration with bupivacaine into each breast after general anesthesia. Group II patients received similar injections of saline injection alone after general anesthesia. Results: Visual analogue pain score, verbal pain score, and short-form McGill Pain Questionnaire scores were higher in group II patients until 22 hours after surgery (p < 0.008). Patients in the saline group had higher intravenous meperidine consumption for 22 hours postoperatively and solicited opioids before the patients in the bupivacaine group (p < 0.001). The difference between groups was statistically significant. Conclusion: Preincisional infiltration with bupivacaine results in reduced pain and lower postoperative opioid requirements in the early postoperative phase of pain following breast reduction. (Plast. Reconstr. Surg. 134: 581, 2014.) CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.
W
omen who suffer from breast hypertrophy commonly have physical symptoms such as back pain and psychosocial problems. Breast reduction surgery is performed to relieve these problems. Reduction mammaplasty significantly improves satisfaction with breast appearance and psychosocial, sexual, and physical well-being.1–3 Pain control is pertinent for optimal care in surgical patients. Pain is one of the main postoperative adverse outcomes causing distress to patients, prolonging hospital stay, and increasing the incidence of admissions after surgery. Preemptive analgesia has been proposed to result in better pain management, reduced analgesic consumption, and improved patient satisfaction. From the Division of Plastic Surgery and Reconstructive Microsurgery, Santa Casa Hospital; and the Division of Plastic Surgery, Mãe de Deus Health System. Received for publication January 19, 2014; accepted February 13, 2014. Copyright © 2014 by the American Society of Plastic Surgeons DOI: 10.1097/PRS.0000000000000522
Preemptive analgesia is defined as an antinociceptive treatment that prevents the establishment of altered central processing of afferent input, which amplifies postoperative pain.4–6 The objective of this study is to verify whether the preincisional infiltration with bupivacaine alters the sensation of pain in the immediate postoperative period following reduction mammaplasty, under general anesthesia.
PATIENTS AND METHODS This study was designed as a randomized, double-blind, placebo-controlled clinical trial. The design of the research protocol was accepted by the research ethics committee and is registered Disclosure: The author has no commercial associations or financial disclosures that might pose or create a conflict of interest with information presented in this study. The author has no financial interest in any of the products, devices, or drugs mentioned in this article. This study has not received any supporting funds.
www.PRSJournal.com
581
Plastic and Reconstructive Surgery • October 2014 with the Brazilian Information System on Research Ethics Involving Humans (Sistema Nacional de Informações sobre Ética em Pesquisa envolvendo Seres Humanos) under no. 0081.0.005.000-03. All patients gave written informed consent. Table 1 lists the criteria for inclusion in the study and Table 2 lists the exclusion criteria. Each patient was allocated into one of two groups by randomization. In group I, beyond the standard technique, 20 ml of bupivacaine at 0.75% was infiltrated. In group II, the patients received the standard infiltration with another 20 ml of saline solution at 0.9% (placebo considered as local anesthetics).6–10 At the time of surgery, all patients underwent general anesthesia. Preincisional infiltration was performed with a solution consisting of 200 ml of saline solution at 0.9% with 0.5 mg of epinephrine, and attempting to achieve local vasoconstriction before incision. On receiving a spreadsheet generated by the computer program, the pharmacist of the supply center of the hospital provided numbered sterile syringes containing either 20 ml of bupivacaine at 0.75% or saline solution at 0.9% in the same volume. The syringes were prepared at a laminar flow cabinet and were sent to the surgical center with sequential Arabic numerals placed outside the sterilized package. Thus, no participant of the medical staff knew which solution was infiltrated and therefore could not compare results. The infiltration began in the inframammary fold, infiltrating the retroglandular space, waiting 10 minutes to obtain the vasoconstriction effect.11 Approximately 110 ml of the solution was injected into each side. For postoperative analgesic, dipyrone 8 mg/kg body weight administered intravenously was used every 6 hours and tenoxicam 0.3 mg/kg body Table 1. Inclusion Criteria Age between 18 and 70 yr Bearer of hypermastia or mammary ptosis Pass the screening tests and evaluation by the medical committee of the staff with reduction mammaplasty being indicated Sign the informed consent form agreeing to its items after explanation of the study by the resident physician
Table 2. Exclusion Criteria History of previous breast surgery Depression Moderate or severe liver disease Moderate or severe renal failure Use of psychoactive medication in the past 6 mo Use of alcohol or drugs in the past 2 mo
582
weight was administered intravenously every 12 hours. If the patients thought it was necessary, they could request more analgesia (meperidine 0.5 mg/kg of body weight intravenously up to every 3 hours).12 The time between the end of surgery and the first request for analgesia, and the requests for analgesics administered at the request of the patient was noted. Twenty-two hours after surgery, three tests were applied: the verbal pain scale scored on a scale of 0 to 6; the visual analogue scale, which shows distances between 0 and 10 cm; and the McGill Pain Questionnaire, showing a score of 0 to 45. These five tests together constitute an excellent tool for measuring postoperative pain for the purposes of research.12,13 The pain assessments were performed by an independent analyst posing exactly the same questions to all of the patients. At the end of data collection, the pharmacist revealed the contents of each syringe for statistical analysis. We estimated the sample size based on a difference between groups in postoperative pain of 30 percent, with a variation of 35 to 40 percent. On the basis of these assumptions, we calculated that 15 patients per group were required to achieve 80 percent power at 5 percent alpha error. The calculation of sample size was based on α = 0.05, with an estimation power of 0.8014 using PS software: Power and Sample Size (Vanderbilt University Medical Center, Nashville, Tenn.). Each patient was allocated into one of two groups by randomization using SAS 8.2 software (SAS Institute, Inc., Cary, N.C.), at a ratio of 5 and to calculate n = 70. A value of p < 0.05 was considered statistically significant. All p values reported were two-tailed. We used IBM SPSS Version 20 (IBM Corp., Armonk, N.Y.) for all statistical analyses. The Mann-Whitney U was used when the two samples had the same scale parameter value, the t test was used when the statistical units underlying the two samples being compared were nonoverlapping, and the chisquare test was used to examine differences with categorical variables.
RESULTS Thirty-nine patients were part of this study. Being allocated by lottery were, as a result, 18 patients in group I and 20 patients in group II. The two groups showed no statistically significant difference in terms of age, distance between the papilla and point A, duration of surgery, resection volume, or surgical technique (Table 3). No liposuction procedures were performed in these
Volume 134, Number 4 • Bupivacaine in Reduction Mammaplasty Table 3. Average Variables Where No Difference between the Groups Was Observed Age, yr Papilla-to–point A distance, cm Duration of surgery, min Resected volume, g Wise-pattern technique, %
Average
SD
p
35.57 7.25 168.75 621.23 71.1
15.17 2.69 42.70 487.28 —
0.325* 0.105* 0.177* 0.141* 0.670†
*t test. †χ2.
patients. The surgical techniques performed were Wise pattern and Arie-Pitanguy. Figure 1 shows the Consolidated Standards of Reporting Trials flow chart.15 Regarding the analysis of postoperative pain, group I showed statistically significant lower rates compared with group II in all tests performed (Table 4). Regarding the McGill Pain Questionnaire, group I had half the score of group II. Regarding the visual analogue scale score, the
difference between the groups was 2.38 cm. Regarding the verbal pain scale, the group that did not receive bupivacaine had more than double the score compared with the bupivacaine group. The patients who received bupivacaine requested the first dose of analgesia, approximately 70 minutes after those who did not receive it, despite having comparatively used 1.5 fewer doses of analgesic. No major complications were seen.
DISCUSSION Although pain can protect us by forcing us to rest an injury or to stop doing something, the experience of being in a state of uncontrolled pain is horrible and frightening, and can have a profound effect on our quality of life. Persistent pain in the postoperative period usually increases the incidence of nausea and vomiting and unplanned readmissions and results in a longer hospital stay. Tissue damage caused by surgery
Fig. 1. Consolidated Standards of Reporting Trials flow chart.
583
Plastic and Reconstructive Surgery • October 2014 Table 4. Average Results ± SD Obtained in Each Group Time from surgery to first analgesic requested dose, min No. of doses McGill Pain Questionnaire Visual analogue scale, cm Verbal pain scale
Group I
Group II
p*
232.22 ± 78.25 1.55 ± 0.61 7.77 ± 4.72 2.95 ± 1.62 0.83 ± 0.85
162.51 ± 47.33 3.05 ± 0.60 16.95 ± 4.44 5.33 ± 1.08 1.71 ± 0.47
0.008
Background: Preincisional analgesia is an antinociceptive treatment that prevents altered central excitability from high-intensity noxious stimuli. To determine the analgesic efficacy of preoperative infiltration with bupivacaine for reduction mammaplasty, a randomized, double-blind, placebo-controlled trial was designed. Methods: Women with mammary hypertrophy were allocated randomly to one of two study groups. Patients in group I received preincision infiltration with bupivacaine into each breast after general anesthesia. Group II patients received similar injections of saline injection alone after general anesthesia. Results: Visual analogue pain score, verbal pain score, and short-form McGill Pain Questionnaire scores were higher in group II patients until 22 hours after surgery (p < 0.008). Patients in the saline group had higher intravenous meperidine consumption for 22 hours postoperatively and solicited opioids before the patients in the bupivacaine group (p < 0.001). The difference between groups was statistically significant. Conclusion: Preincisional infiltration with bupivacaine results in reduced pain and lower postoperative opioid requirements in the early postoperative phase of pain following breast reduction. (Plast. Reconstr. Surg. 134: 581, 2014.) CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.
W
omen who suffer from breast hypertrophy commonly have physical symptoms such as back pain and psychosocial problems. Breast reduction surgery is performed to relieve these problems. Reduction mammaplasty significantly improves satisfaction with breast appearance and psychosocial, sexual, and physical well-being.1–3 Pain control is pertinent for optimal care in surgical patients. Pain is one of the main postoperative adverse outcomes causing distress to patients, prolonging hospital stay, and increasing the incidence of admissions after surgery. Preemptive analgesia has been proposed to result in better pain management, reduced analgesic consumption, and improved patient satisfaction. From the Division of Plastic Surgery and Reconstructive Microsurgery, Santa Casa Hospital; and the Division of Plastic Surgery, Mãe de Deus Health System. Received for publication January 19, 2014; accepted February 13, 2014. Copyright © 2014 by the American Society of Plastic Surgeons DOI: 10.1097/PRS.0000000000000522
Preemptive analgesia is defined as an antinociceptive treatment that prevents the establishment of altered central processing of afferent input, which amplifies postoperative pain.4–6 The objective of this study is to verify whether the preincisional infiltration with bupivacaine alters the sensation of pain in the immediate postoperative period following reduction mammaplasty, under general anesthesia.
PATIENTS AND METHODS This study was designed as a randomized, double-blind, placebo-controlled clinical trial. The design of the research protocol was accepted by the research ethics committee and is registered Disclosure: The author has no commercial associations or financial disclosures that might pose or create a conflict of interest with information presented in this study. The author has no financial interest in any of the products, devices, or drugs mentioned in this article. This study has not received any supporting funds.
www.PRSJournal.com
581
Plastic and Reconstructive Surgery • October 2014 with the Brazilian Information System on Research Ethics Involving Humans (Sistema Nacional de Informações sobre Ética em Pesquisa envolvendo Seres Humanos) under no. 0081.0.005.000-03. All patients gave written informed consent. Table 1 lists the criteria for inclusion in the study and Table 2 lists the exclusion criteria. Each patient was allocated into one of two groups by randomization. In group I, beyond the standard technique, 20 ml of bupivacaine at 0.75% was infiltrated. In group II, the patients received the standard infiltration with another 20 ml of saline solution at 0.9% (placebo considered as local anesthetics).6–10 At the time of surgery, all patients underwent general anesthesia. Preincisional infiltration was performed with a solution consisting of 200 ml of saline solution at 0.9% with 0.5 mg of epinephrine, and attempting to achieve local vasoconstriction before incision. On receiving a spreadsheet generated by the computer program, the pharmacist of the supply center of the hospital provided numbered sterile syringes containing either 20 ml of bupivacaine at 0.75% or saline solution at 0.9% in the same volume. The syringes were prepared at a laminar flow cabinet and were sent to the surgical center with sequential Arabic numerals placed outside the sterilized package. Thus, no participant of the medical staff knew which solution was infiltrated and therefore could not compare results. The infiltration began in the inframammary fold, infiltrating the retroglandular space, waiting 10 minutes to obtain the vasoconstriction effect.11 Approximately 110 ml of the solution was injected into each side. For postoperative analgesic, dipyrone 8 mg/kg body weight administered intravenously was used every 6 hours and tenoxicam 0.3 mg/kg body Table 1. Inclusion Criteria Age between 18 and 70 yr Bearer of hypermastia or mammary ptosis Pass the screening tests and evaluation by the medical committee of the staff with reduction mammaplasty being indicated Sign the informed consent form agreeing to its items after explanation of the study by the resident physician
Table 2. Exclusion Criteria History of previous breast surgery Depression Moderate or severe liver disease Moderate or severe renal failure Use of psychoactive medication in the past 6 mo Use of alcohol or drugs in the past 2 mo
582
weight was administered intravenously every 12 hours. If the patients thought it was necessary, they could request more analgesia (meperidine 0.5 mg/kg of body weight intravenously up to every 3 hours).12 The time between the end of surgery and the first request for analgesia, and the requests for analgesics administered at the request of the patient was noted. Twenty-two hours after surgery, three tests were applied: the verbal pain scale scored on a scale of 0 to 6; the visual analogue scale, which shows distances between 0 and 10 cm; and the McGill Pain Questionnaire, showing a score of 0 to 45. These five tests together constitute an excellent tool for measuring postoperative pain for the purposes of research.12,13 The pain assessments were performed by an independent analyst posing exactly the same questions to all of the patients. At the end of data collection, the pharmacist revealed the contents of each syringe for statistical analysis. We estimated the sample size based on a difference between groups in postoperative pain of 30 percent, with a variation of 35 to 40 percent. On the basis of these assumptions, we calculated that 15 patients per group were required to achieve 80 percent power at 5 percent alpha error. The calculation of sample size was based on α = 0.05, with an estimation power of 0.8014 using PS software: Power and Sample Size (Vanderbilt University Medical Center, Nashville, Tenn.). Each patient was allocated into one of two groups by randomization using SAS 8.2 software (SAS Institute, Inc., Cary, N.C.), at a ratio of 5 and to calculate n = 70. A value of p < 0.05 was considered statistically significant. All p values reported were two-tailed. We used IBM SPSS Version 20 (IBM Corp., Armonk, N.Y.) for all statistical analyses. The Mann-Whitney U was used when the two samples had the same scale parameter value, the t test was used when the statistical units underlying the two samples being compared were nonoverlapping, and the chisquare test was used to examine differences with categorical variables.
RESULTS Thirty-nine patients were part of this study. Being allocated by lottery were, as a result, 18 patients in group I and 20 patients in group II. The two groups showed no statistically significant difference in terms of age, distance between the papilla and point A, duration of surgery, resection volume, or surgical technique (Table 3). No liposuction procedures were performed in these
Volume 134, Number 4 • Bupivacaine in Reduction Mammaplasty Table 3. Average Variables Where No Difference between the Groups Was Observed Age, yr Papilla-to–point A distance, cm Duration of surgery, min Resected volume, g Wise-pattern technique, %
Average
SD
p
35.57 7.25 168.75 621.23 71.1
15.17 2.69 42.70 487.28 —
0.325* 0.105* 0.177* 0.141* 0.670†
*t test. †χ2.
patients. The surgical techniques performed were Wise pattern and Arie-Pitanguy. Figure 1 shows the Consolidated Standards of Reporting Trials flow chart.15 Regarding the analysis of postoperative pain, group I showed statistically significant lower rates compared with group II in all tests performed (Table 4). Regarding the McGill Pain Questionnaire, group I had half the score of group II. Regarding the visual analogue scale score, the
difference between the groups was 2.38 cm. Regarding the verbal pain scale, the group that did not receive bupivacaine had more than double the score compared with the bupivacaine group. The patients who received bupivacaine requested the first dose of analgesia, approximately 70 minutes after those who did not receive it, despite having comparatively used 1.5 fewer doses of analgesic. No major complications were seen.
DISCUSSION Although pain can protect us by forcing us to rest an injury or to stop doing something, the experience of being in a state of uncontrolled pain is horrible and frightening, and can have a profound effect on our quality of life. Persistent pain in the postoperative period usually increases the incidence of nausea and vomiting and unplanned readmissions and results in a longer hospital stay. Tissue damage caused by surgery
Fig. 1. Consolidated Standards of Reporting Trials flow chart.
583
Plastic and Reconstructive Surgery • October 2014 Table 4. Average Results ± SD Obtained in Each Group Time from surgery to first analgesic requested dose, min No. of doses McGill Pain Questionnaire Visual analogue scale, cm Verbal pain scale
Group I
Group II
p*
232.22 ± 78.25 1.55 ± 0.61 7.77 ± 4.72 2.95 ± 1.62 0.83 ± 0.85
162.51 ± 47.33 3.05 ± 0.60 16.95 ± 4.44 5.33 ± 1.08 1.71 ± 0.47
0.008
