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Transversus Abdominis Plane Block Versus Surgical Site Infiltration for Pain Management After Open Total Abdominal Hysterectomy

Gasanova, Irina MD*; Alexander, John MD*; Ogunnaike, Babatunde MD*; Hamid, Cherine MD; Rogers, David MD; Minhajuddin, Abu PhD; Joshi, Girish P. MB BS, MD, FFARCSI*

doi: 10.1213/ANE.0000000000000909
Regional Anesthesia: Research Report

BACKGROUND: Surgical site infiltration and transversus abdominis plane (TAP) blocks are commonly used to improve pain relief after lower abdominal surgery. This randomized, observer-blinded study was designed to compare the analgesic efficacy of TAP blocks with surgical site infiltration in patients undergoing open total abdominal hysterectomy via a Pfannenstiel incision.

METHODS: Patients were randomized to receive either bilateral ultrasound-guided TAP blocks using bupivacaine 0.5% 20 mL on each side (n = 30) or surgical site infiltration with liposomal bupivacaine 266 mg diluted to 60 mL injected in the preperitoneal, subfascial, and subcutaneous planes (n = 30). The remaining aspects of the perioperative care were standardized. An investigator blinded to the group allocation documented pain scores at rest and with coughing, opioid requirements, nausea, vomiting, and rescue antiemetics in the postanesthesia care unit and at 2, 6, 12, 24, and 48 hours postoperatively. The primary outcome measure was pain scores on coughing at 6 hours postoperatively.

RESULTS: One patient in each group was excluded from the analysis because of reoperation within 24 hours in the TAP block group and change of incision type in the infiltration group. The pain scores at rest and with coughing were significantly lower in the surgical site infiltration group at all postoperative time points (P < 0.0001) except at rest in the postanesthesia care unit. The opioid requirements between 24 and 48 hours were significantly lower in the infiltration group (P = 0.009). The nausea scores, occurrence of vomiting, and need for rescue antiemetics were similar.

CONCLUSIONS: Surgical site infiltration provided superior pain relief at rest and on coughing, as well as reduced opioid consumption for up to 48 hours. Future studies need to compare TAP blocks with liposomal bupivacaine with surgical site infiltration with liposomal bupivacaine.

Published ahead of print August 6, 2015

From the Departments of *Anesthesiology and Pain Management, Obstetrics and Gynecology, and Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas.

Accepted for publication June 8, 2015.

Published ahead of print August 6, 2015

Funding: Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, Dallas, TX.

Conflict of Interest: See Disclosures at the end of the article.

Address correspondence to Irina Gasanova, MD, Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390. Address e-mail to irina.gasanova@utsouthwestern.edu.

Local and/or regional analgesia techniques are critical components of an optimal multimodal analgesia technique, as they have been shown to improve pain relief, as well as reduce opioid requirements.1 Surgical site local anesthetic infiltration has been shown to provide excellent analgesia and is recommended, when appropriate.1,2 In recent years, transversus abdominis plane (TAP) blocks have been increasingly used in patients undergoing lower abdominal surgical procedures because of improved pain relief and reduced opioid requirements.3–5 However, surgical site local anesthetic infiltration has not previously been compared with TAP blocks in patients undergoing open abdominal hysterectomy.3

Therefore, we designed a study to compare bilateral TAP blocks with surgical site infiltration in combination with a basic nonopioid analgesic regimen, such as acetaminophen and nonsteroidal antiinflammatory drug (NSAID), in patients undergoing open total abdominal hysterectomy. For surgical site infiltration, we used a liposomal formulation of bupivacaine (Exparel®, Pacira Inc, San Diego, CA), which is reported to provide a therapeutic benefit for up to 72 hours after a single injection.6,7 This would address one of the limitations of local/regional analgesia related to the relatively short duration of action of bupivacaine and ropivacaine, which is typically 6 to 8 hours.4,5 However, for TAP blocks, we used bupivacaine HCl because when the study was designed the Food and Drug Administration had approved liposomal bupivacaine only for administration into the surgical site.8

We hypothesized that ultrasound-guided bilateral TAP blocks would provide superior pain relief when compared with surgical site infiltration at 6 hours after open total abdominal hysterectomy. The primary outcome measure of this prospective, randomized trial was pain scores on coughing at 6 hours postoperatively, and the secondary objectives included pain scores, opioid requirements, incidence of nausea and vomiting, and need for rescue antiemetics for 48 hours, postoperatively.

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METHODS

This study was approved by the IRB at the University of Texas Southwestern Medical Center at Dallas, Texas. The trial was registered with the United States National Clinical Trials Registry (registration number: NCT02074709). After written informed consent was obtained, women 18 to 80 years, ASA physical status I to III, scheduled for open abdominal hysterectomy via a Pfannenstiel incision at Parkland Hospital, Dallas, Texas, were enrolled in this study. Participants were excluded if they had a history of relevant drug allergy, significant psychiatric disturbance, history of alcohol, or drug addiction; were currently using analgesics; or had current acute or chronic pain. In addition, patients with contraindication to acetaminophen (e.g., significant hepatic dysfunction) and ketorolac and ibuprofen (e.g., significant renal dysfunction and reactive airway disease) were excluded. Patients were randomized according to a computer-generated randomization schedule to 1 of 2 groups: bilateral TAP blocks or surgical site infiltration. Randomization group allocations were concealed in sealed opaque envelopes until all the entry criteria for the study had been verified.

All patients received a standardized general anesthetic technique consisting of premedication with midazolam 1 to 2 mg, IV, induction with fentanyl (1–2 μg/kg), propofol (approximately 2 mg/kg), and rocuronium (0.6 mg/kg) and maintenance with oxygen/nitrous/desflurane or sevoflurane. Fentanyl 25 to 50 μg, IV, bolus was administered to maintain mean arterial blood pressure and/or heart rate within 20% of baseline values. All patients received antiemetic prophylaxis with dexamethasone 4 mg IV given after the induction of anesthesia and ondansetron 4 mg IV given approximately 30 minutes before the emergence from anesthesia. For pain prophylaxis all patients received acetaminophen 1 g, IV during fascia closure, and ketorolac 30 mg, IV during skin closure. Hydromorphone 0.02 to 0.03 mg/kg was titrated over 15 to 20 minutes at the end of the surgery, as needed.

At the end of surgery, but before emergence from anesthesia, patients randomized to the TAP group received bilateral ultrasound-guided TAP blocks performed by one of the authors with significant previous experience in ultrasound-guided techniques. An ultrasound transducer (linear 6–13 MHz; SonoSite M-Turbo®, Bothell, WA) was placed transversely in the flank between the anterior superior iliac spine and the costal margin. Using real-time ultrasound imaging, the external oblique, internal oblique, and transverse abdominis muscles were identified. After aseptic preparation of the injection site, a 22-gauge 100-mm insulated needle (Stimuplex® A, B-Braun Medical, Melsungen, Germany) was introduced medially and in the plane of the ultrasound beam until its tip was between internal oblique and transverse abdominal muscles. After negative aspiration, 20-mL bupivacaine 0.5% was injected in 5-mL increments. Distribution of the injectate between the internal oblique and the transverse abdominal muscles was observed under real-time imaging. Because the blocks were performed bilaterally, a total of 40-mL bupivacaine 0.5% was used.

Patients randomized to the surgical site infiltration group received infiltration with liposomal bupivacaine, which was performed by the surgical faculty familiar with the meticulous infiltration technique described later. All layers of the surgical incision were infiltrated with a 22-gauge, 40-mm needle in a controlled and systematic manner under direct visualization in fanlike fashion on each side of the incision. Liposomal bupivacaine 20 mL (266 mg) was diluted with 40 mL of normal saline to total volume of 60 mL, of which 20 mL was infiltrated in the preperitoneal plane, 20 mL in the subfascial plane, and 20 mL into the subcutaneous plane.

In the postanesthesia care unit (PACU), patients complaining of pain (visual analog scale [VAS] >4/10) received hydromorphone 0.1 to 0.2 mg IV bolus until VAS scores of ≤3/10 were achieved. After discharge from the PACU, all patients received IV patient-controlled analgesia (IV-PCA) morphine 1-mg bolus and 5-minute lockout period as rescue analgesia (Table 1). In the first 24 hours postoperatively, all patients received ketorolac 30 mg, IV and acetaminophen 1 g, orally, every 6 hours. After 24 hours, all patients received ibuprofen 800 mg, orally and acetaminophen 1 g, orally every 8 hours. In addition, combination of hydrocodone 5 mg/acetaminophen 325 mg, 1 to 2 tablets every 6 hours was allowed, as needed.

Table 1

Table 1

Data collected included patient demographics (i.e., age, gender, weight, and height), duration of surgery, and duration of PACU stay. In addition, an investigator blinded to group allocation assessed the intensity of pain at rest and on coughing using a VAS (0 = no pain to 10 = worst pain), opioid consumption (i.e., intraoperative period, PACU, IV-PCA morphine, and oral opioids), severity of nausea (none = 0, mild = 1, moderate = 2, severe = 3), episodes of vomiting, and the need for rescue antiemetics in the PACU and at 2, 6, 12, 24, and 48 hours, postoperatively.

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Statistical Analyses

Sample size calculations were based on previous studies involving the use of TAP block in patients undergoing lower abdominal surgery.3,5 A mean VAS pain score at 6 hours postoperatively was assumed to be 4/10 (SD 2/10), and a 2-point reduction from this is considered clinically significant. Based on the formula for normal theory and assuming a 2-sided type 1 error of 0.05 and power of 0.90, a minimum sample size of 23 patients per group was required. We decided to enroll 30 patients in each group to account for potential exclusions after randomization and loss to follow-up.

Statistical analyses were performed using SAS software (version 9.3, Cary, NC). Demographic and categorical data were compared using 2 independent sample Student t tests. The end points of resting and coughing VAS pain scores were evaluated using a repeated measure mixed linear model with intervention group, time, and group × time interaction in the model followed by post hoc comparison of groups at each time point. Normal probability plots were used to assess the assumption of normality of the residuals of the 2 statistical models. No substantial violation of the assumptions of normality of the model residuals was observed as the corresponding normal probability plots displayed data points on a reasonably straight line. For post hoc comparisons, t tests with Bonferroni correction (6 paired comparisons) were used. Presence of any nausea, vomiting, and use of rescue antiemetics at each time point were reported as number and percentage. All tests were 2-tailed with a type I error rate of 0.05.

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RESULTS

Sixty-seven patients were assessed as eligible for the study. The CONSORT flow diagram is presented in Figure 1. The groups were comparable with respect to patient demographics (i.e., age, height, weight, and body mass index), duration of surgery, and duration of PACU stay (Table 2).

Table 2

Table 2

Figure 1

Figure 1

The pain scores at rest and on coughing were significantly lower in the surgical site infiltration group across time (VAS rest, F statistic [df1, df2] = 50.98 [1, 335], P < 0.0001 and VAS cough, F statistic [df1, df2] = 78.62 [1, 336], P < 0.0001). Post hoc comparisons showed that the pain scores at rest and with coughing were significantly lower in the surgical site infiltration group at every time point except at rest in the PACU (Figs. 2 and 3).

Figure 2

Figure 2

Figure 3

Figure 3

Both patient groups initially experienced a gradual increase in pain scores over time, which started a downward trend in the latter half of the 48-hour study period (VAS rest, F statistic [df1, df2] = 4.08 [5, 335], P = 0.0013, and VAS cough, F statistic [df1, df2] = 15.97 [5, 336], P < 0.0001). However, a nonsignificant group × time interaction (P = 0.7735 for VAS rest, and P = 0.9351 for VAS coughing) suggested similar changes over time for both patient groups (Figs. 2 and 3).

Intraoperative fentanyl and hydromorphone requirements, as well as PACU hydromorphone requirements, were similar in the 2 study groups (Table 3). The IV-PCA morphine consumption over the first 24-hour postoperative period was probably statistically significantly higher in the TAP block group compared with the surgical site infiltration group (P = 0.0497; Table 3). The number of oral hydrocodone/acetaminophen tablets consumed in the TAP block group was significantly higher than the surgical site infiltration group (P = 0.009; Table 3).

Table 3

Table 3

The overall incidence of nausea between the 2 groups across all the time points was not statistically significantly different. Fifteen patients (51.7%) in the TAP block group experienced nausea (nausea score > 0) over the 48-hour study period compared with 14 (48.3%) patients in the surgical site infiltration group (z-statistic = 0.26, P = 0.793). Only 1 patient in the TAP block group complained of severe nausea. Overall, the incidence of vomiting was not significantly different among the groups across the study time points over 48 hours: (8 [27.6%] patients in TAP block group versus 5 [17.2%] in surgical site infiltration group; z = 0.95, P = 0.345). One patient in each group had emesis and required an antiemetic in the PACU. The 2 groups were similar in terms of any use of rescue antiemetic medications: (15 [51.7%] patients in TAP block group versus 11 [37.9%] in surgical site infiltration group; z = 1.06, P = 0.291] over the 48-hour study period.

All patients resumed oral intake, were able to walk the morning after surgery, and were discharged home within 48 to 60 hours postoperatively.

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DISCUSSION

This is the first randomized trial investigating the analgesic effects of ultrasound-guided bilateral TAP blocks with a meticulous surgical site infiltration technique, which included injection in the peritoneal, subfascial, and subcutaneous planes, in patients undergoing open total abdominal hysterectomy via a Pfannenstiel incision. One of the strengths of our study is that we included a well-recognized multimodal analgesic regimen, such as acetaminophen and NSAID as well as dexamethasone, as part of our analgesic technique in both groups, thus making the results clinical applicable.1,5

In contrast to previously published studies evaluating surgical site infiltration techniques, which essentially involved subcutaneous local anesthetic injections, we also performed subfascial and preperitoneal infiltration. It is suggested that the peritoneum is a metabolically active organ, which responds to surgical insult by manifesting a local and systemic immunologic and inflammatory response.9 Therefore, peritoneal infiltration may provide added benefit, as it blocks the “silent nociceptors” that are activated by surgical injury and intraperitoneal inflammation.10 This is evident from recent studies that report excellent pain relief after intraperitoneal local anesthetic injection or nebulization in patients undergoing abdominal surgery.11–13 Similarly, preperitoneal local anesthetic infusion has been shown to provide excellent pain relief after abdominal surgery.14,15

Our observations can be explained by the fact that although TAP blocks may influence the parietal pain through blockade of the nerves between the internal oblique and the transversus abdominis muscles, it does not influence the peritoneal contribution to pain perception. Also, despite the performance of the TAP blocks with real-time ultrasound, the spread of local anesthetic may not be uniformly consistent because of the presence of anatomical variations.16 In addition, nerves located between the costal margin and the inguinal ligament in the anterior axillary line have variable segmental origin from T9-L1, which may influence the efficacy of TAP blocks.17 It is possible that the addition of basic analgesic regimen, such as acetaminophen, NSAIDs, and dexamethasone, may, at least partially, compensate for these limitation of TAP blocks.

Of note, one would assume that the shorter duration of action of bupivacaine HCl (i.e., the TAP block group) would result in higher pain scores in the 24- to 48-hour postoperative period. However, the data from this study show that the pain scores (on coughing and at rest) remained stable after 24 hours (Figs. 2 and 3), perhaps because the patients in the TAP block group had higher opioid consumption, which may have compensated for the loss of analgesic effects of bupivacaine HCl. Furthermore, it is suggested that blockade of the parietal and visceral afferents may reduce sensitization of the dorsal horn neurons, resulting in analgesic benefits beyond the duration of action of the local anesthetic.14,18

Preclinical and clinical data studies have assessed the systemic absorption of liposomal bupivacaine and bupivacaine HCl. Hu et al19 reported the pharmacokinetics of liposomal bupivacaine (106–532 mg) and bupivacaine HCl (100–150 mg) after a single local injection at the surgical site. After infiltration with liposomal bupivacaine, an initial peak in bupivacaine concentration occurs within 1 hour, most likely resulting from a small amount (approximately 3%) of bupivacaine HCl included in the formulation. This is followed by a second peak after about 12 to 36 hours (i.e., the time to maximum plasma concentration [Tmax]), which is because of the gradual release of bupivacaine from the liposomes. With respect to bupivacaine HCl, the Tmax is achieved in about 30 to 45 minutes. The maximum plasma bupivacaine concentrations (Cmax) produced by bupivacaine HCl 100 mg was similar to that produced by liposomal bupivacaine 266 mg (the maximum recommended dose).19 It is important to note that the correlation between the plasma concentration of bupivacaine and the clinical efficacy at the site of administration is unknown. Although the liposomal bupivacaine is not bioequivalent to bupivacaine HCl, once bupivacaine is released from the liposomes, the distribution, metabolism, and excretion follows the same kinetics as bupivacaine HCl. A 532-mg dose of liposomal bupivacaine produced a Cmax of 935 ng/mL,19 which is significantly below the threshold range (2000–4000 ng/mL) at which central nervous system and cardiovascular toxicity of bupivacaine can occur.20,21

A study in healthy volunteers reported that time to onset of pain relief with liposomal bupivacaine was similar to that of bupivacaine HCl, with clinically meaningful analgesia occurring within 2 minutes and substantial analgesia within 5 minutes.22 This may be because of a small amount (about 3%) of extraliposomal bupivacaine (i.e., bupivacaine HCl) available in the liposomal bupivacaine formulation.8

This study has several limitations. One is that a double-blind design was not used or a placebo group was not included, as it was considered unethical by our IRB to perform a sham-TAP blocks or sham surgical site infiltration, particularly because a previous study from our institution reported the benefits of performing TAP blocks.5 Nevertheless, an investigator blinded to the group allocation collected postoperative data. Also, we did not assess sensory blockade after TAP blocks. However, it is well recognized that the spread of sensory blockade does not necessarily reflect the analgesic effectiveness of a TAP block. Also, the bupivacaine formulations for the 2 groups were different (i.e., bupivacaine for TAP blocks and liposomal bupivacaine for surgical site infiltration). However, we chose a primary outcome measure of pain scores at 6 hours because both the formulations of bupivacaine (i.e., bupivacaine HCl and liposomal bupivacaine) should provide equivalent analgesia at least for 6 hours after administration. Thus, the differences in analgesia between TAP blocks and surgical site infiltration at 6 hours should not be because of the differences in the bupivacaine formulations. Furthermore, this study could be criticized because we did not assess blood levels of bupivacaine. However, as discussed earlier, this has already been studied in several previous trails.19 Future trials are necessary to compare TAP blocks and surgical site infiltration both performed using liposomal bupivacaine. Of note, the Food and Drug Administration has not yet approved liposomal bupivacaine for perineural administration.

In conclusion, in patients undergoing open total abdominal hysterectomy, surgical site infiltration including injections in the subfascial and preperitoneal planes provided superior analgesia compared with bilateral TAP blocks.

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DISCLOSURES

Name: Irina Gasanova, MD.

Contribution: This author helped design and conduct the study and prepare the manuscript.

Attestation: Irina Gasanova approved the final manuscript and attests the integrity of the original data and the analysis reported in this manuscript.

Conflict of interest: This author declares no conflicts of interest.

Name: John Alexander, MD.

Contribution: This author helped design and conduct the study and review the manuscript.

Attestation: John Alexander approved the final manuscript and attests the integrity of the original data and the analysis reported in this manuscript.

Conflict of interest: This author declares no conflicts of interest.

Name: Babatunde Ogunnaike, MD.

Contribution: This author helped conduct the study and review the manuscript.

Attestation: Babatunde Ogunnaike approved the final manuscript and attests the integrity of the original data and the analysis reported in this manuscript.

Conflict of interest: This author declares no conflicts of interest.

Name: Cherine Hamid, MD.

Contribution: This author helped conduct the study and review the manuscript.

Attestation: Cherine Hamid approved the final manuscript and attests the integrity of the original data and the analysis reported in this manuscript.

Conflict of interest: This author declares no conflicts of interest.

Name: David Rogers, MD.

Contribution: This author helped conduct the study and review the manuscript.

Attestation: David Rogers approved the final manuscript and attests the integrity of the original data and the analysis reported in this manuscript.

Conflict of interest: This author declares no conflicts of interest.

Name: Abu Minhajuddin, PhD.

Contribution: This author helped analyze the data and review the manuscript.

Attestation: Abu Minhajuddin approved the final manuscript and attests the integrity of the original data and the analysis reported in this manuscript.

Conflict of interest: This author declares no conflicts of interest.

Name: Girish P. Joshi, MB BS, MD, FFARCSI.

Contribution: This author helped design and conduct the study, write the manuscript, and review the manuscript.

Attestation: Girish P. Joshi approved the final manuscript and attests the integrity of the original data and the analysis reported in this manuscript.

Conflict of interest: This author has received honoraria from Baxter, Cadence, and Pacira Pharmaceuticals.

This manuscript was handled by: Terese Horlocker, MD.

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ACKNOWLEDGMENTS

The authors thank Olutoyosi Ogunkua, MD, Anesthesiology Resident and Emine Babar-Melik, Research Assistant for their assistance with data collection.

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