Can J Anesth/J Can Anesth (2014) 61:631–640 DOI 10.1007/s12630-014-0162-5

REPORTS OF ORIGINAL INVESTIGATIONS

Transversus abdominis plane block does not improve early or late pain outcomes after Cesarean delivery: a randomized controlled trial Le bloc dans le plan du muscle transverse de l’abdomen n’ame´liore pas les douleurs pre´coces ou tardives apre`s ce´sarienne : un essai randomise´ controˆle´ Dolores M. McKeen, MD • Ronald B. George, MD John Colin Boyd, MSc • Victoria M. Allen, MD • Aaron Pink, MD

•

Received: 14 June 2013 / Accepted: 31 March 2014 / Published online: 24 April 2014 Ó Canadian Anesthesiologists’ Society 2014

Abstract Objectives Cesarean delivery is a common surgical procedure with anticipated substantial postoperative pain. The addition of a transversus abdominis plane block (TAPB) to a multimodal analgesic regimen that includes intrathecal morphine may provide improved early pain outcomes and decrease the risk of chronic postsurgical pain. The purpose of this research was to assess the ability of an ultrasound-guided TAPB with low-dose ropivacaine to decrease early postoperative pain, opioid consumption, and risk of developing persistent pain when compared with a placebo block.

Author contributions Dolores M. McKeen, Ronald B. George, Victoria M. Allen, and Aaron Pink contributed to the study design. Dolores M. McKeen, Ronald B. George, and Aaron Pink contributed to data collection. Dolores M. McKeen and Ronald B. George contributed to data analysis. Dolores M. McKeen, Ronald B. George, J. Colin Boyd, and Victoria M. Allen contributed to the interpretation of results. Dolores M. McKeen, Ronald B. George, and J. Colin Boyd contributed to drafting the manuscript. All authors provided feedback. D. M. McKeen, MD (&)
R. B. George, MD
J. C. Boyd, MSc Department of Women’s & Obstetric Anesthesia, Dalhousie University, IWK Health Centre, 5850/5980 University Avenue, P.O. Box 9700, Halifax, NS B3K 6R8, Canada e-mail: [email protected] V. M. Allen, MD Department of Obstetrics & Gynaecology, Dalhousie University, IWK Health Centre, 5850/5980 University Avenue, P.O. Box 9700, Halifax, NS B3K 6R8, Canada A. Pink, MD Faculty of Medicine, Dalhousie University, Halifax, NS, Canada

Methods Eighty-three women were randomly assigned to either a treatment (0.25% ropivacaine) or control group (0.9% saline) in this double-blind trial, and 74 women were included in the final analysis. Ultrasound-guided TAPBs were performed with an injection of 20 mL of study solution per side. The primary outcome measures of this study were: pain at rest and pain after movement measured with a numeric rating scale, results of the Quality of Recovery-40 (QoR-40) questionnaire, and opioid consumption at 24 hr. These were used with an a priori sample size calculation to detect a 30% reduction in pain scores, a 10% improvement in QoR-40 score, and a 50% reduction in opioid consumption. Health quality and physical functioning were assessed using the Short Form 36 (SF-36Ò) Health Survey at 30 days and six months. Results Assessment at 24 hr after Cesarean delivery revealed no clinically important differences between groups in postoperative pain, QoR-40, or opioid consumption. There were no clinically important differences between groups regarding measures of nausea, pruritus, vomiting, urine retention (2, 24, and 48 hr postoperatively), 24-hr QoR-40 sub-dimensions, or the SF36 Health Survey (30 days and six months postoperatively). Conclusions Ultrasound-guided TAPB did not improve postoperative pain, quality of recovery, or opioid consumption 24 hr following surgery. Similar health and functioning (SF-36) at 30 days and six months were reported by both groups. This trial was registered at ClinicalTrials.gov number: NCT01261637. Re´sume´ Objectifs L’accouchement par ce´sarienne est une proce´dure chirurgicale courante ou l’on anticipe une

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importante douleur postope´ratoire. L’ajout d’un bloc dans le plan du muscle transverse de l’abdomen (TAP) a` un protocole antalgique multimodal incluant la morphine intrathe´cale pourrait ame´liorer les douleurs pre´coces et diminuer le risque de douleur postope´ratoire chronique. L’objectif de cette e´tude e´tait d’e´valuer la capacite´ d’une TAP guide´e par e´chographie, utilisant une faible dose de ropivacaı¨ne, a` diminuer la douleur postope´ratoire pre´coce, la consommation de morphinique et le risque de de´veloppement de douleur persistante comparativement a` un bloc avec un placebo. Me´thodes Quatre-vingts-trois femmes ont e´te´ randomise´es dans le groupe de traitement (ropivacaı¨ne 0,25 %) ou dans le groupe te´moin (se´rum physiologique 0,9 %) dans une e´tude a` double insu et 74 femmes ont e´te´ incluses dans l’analyse de´finitive. Les TAPB guide´es par e´chographie ont e´te´ pratique´es par injection de 20 mL de ˆ te´. Les crite`res la solution e´tudie´e de chaque co d’e´valuation principaux de cette e´tude e´taient les suivants : douleur au repos et douleur apre`s mouvement mesure´es avec une e´chelle d’e´valuation nume´rique, les re´sultats du questionnaire de la Qualite´ de la convalescence-40 (QoR-40) et la consommation de morphinique a` 24 h. Ces crite`res ont e´te´ utilise´s avec un calcul de taille d’e´chantillon a priori conc¸u pour de´tecter une re´duction de 30 % des scores de douleur, une ame´lioration de 10 % du score du QoR-40 et une baisse de 50 % de la consommation de morphinique. La qualite´ de la sante´ et le fonctionnement physique ont e´te´ e´value´s a` l’aide d’une enqueˆte de sante´ avec le Formulaire abre´ge´ 36 (SF-36Ò) a` 30 jours et six mois. Re´sultats L’e´valuation effectue´e 24 heures apre`s l’accouchement par ce´sarienne n’a re´ve´le´ aucune diffe´rence cliniquement importante entre les groupes pour la douleur postope´ratoire, le QoR-40 ou la consommation de morphinique. Il n’y a pas eu de diffe´rence cliniquement importante entre les groupes concernant les mesures de nause´es, prurit, vomissements, re´tention d’urine (a` 2 h, 24 h et 48 h postope´ratoires), QoR-40 a` 24 h ou de l’enqueˆte de sante´ avec le Formulaire abre´ge´ 36 (30 jours et 6 mois postope´ratoires). Conclusions La TAP guide´e par e´chographie n’a pas ame´liore´ la douleur postope´ratoire, la qualite´ de la convalescence ou la consommation de morphinique 24 h apre`s l’intervention chirurgicale. Des scores similaires de sante´ et de fonctionnement (SF-36) ont e´te´ de´crits dans les deux groupes a` 30 jours et 6 mois. Cette e´tude a e´te´ enregistre´e sur le site www.clinicaltrials.gov: NCT01261637. It is recognized that pain during childbirth contributes significantly to the occurrence of acute and chronic pain experienced by women worldwide.1 Evidence suggests that

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severe acute pain, particularly after Cesarean delivery (CD), may contribute to the development of chronic postsurgical pain (CPSP) and postpartum depression.2 Cesarean delivery is a common surgical intervention in Canada. The rate of (CD) in Canada has increased from 21.9% (2001/2002) to 27.8% (2009/2010),3 and while CD rates in Canada have recently stabilized, the incidence of obesity and advanced maternal age, both risk factors for CD, continue to increase.4-6 Women are known to be at higher risk for severe postoperative pain.7 In recent publications, there has been an attempt to characterize the scope of the problem, i.e., to define, assess the incidence, and investigate the neurobiological mechanisms of acute post-surgical pain and the development of CPSP after CD.1,8,9 These observations emphasize the need to optimize acute pain management during delivery as well as to identify individual risk factors to prevent the development of CPSP.10 Optimal postoperative analgesia regimens for CD require safe and effective analgesia to prevent postoperative morbidity so as to facilitate early mobilization and infant care (breastfeeding and maternalinfant bonding).11 Pain management achieved solely through opioids may contribute to adverse maternal and perinatal events, especially in breastfeeding infants. Optimal multimodal analgesia regimens and local anesthesia techniques may minimize or eliminate these adverse outcomes.12,13 Despite the use of neuraxial opioids in routine care in Canada, women still experience significant breakthrough pain and have associated side effects of nausea, vomiting, and pruritus.14,15 Recently, use of the transversus abdominis plane block (TAPB) with local anesthetics (e.g., bupivacaine, ropivacaine) and either a landmark technique (triangle of Petit) or ultrasound guidance to block the T6-L1 sensory nerve roots that innervate the lower anterior abdominal wall have emerged as an effective way to limit initial postoperative pain after a variety of abdominal surgeries.16 Despite a number of publications with varying methodologies on TAPB in CD, the efficacy of TABP in this population is uncertain.17-21 Interpretation of current publications may be confounded by differences in block technique and success, type and total dose of local anesthetic, and inclusion of co-analgesics, including multimodal analgesics and neuraxial opioids (i.e., intrathecal morphine [ITM]). While TAPB alone has been found to be inferior with respect to acute pain outcomes when compared with ITM, it was associated with decreased side effects.22 In two studies that assessed the benefit of TAPB amongst patients who received ITM, Costello et al. used an ultrasound-guided approach, while McMorrow et al. used the originally described landmark

US guided tap block in cesarean delivery

approach.18,21 Neither group found benefit; however, block failure and its impact was not assessed, and only one study evaluated chronic pain six weeks postoperatively.18,21 Consequently, additional studies are needed to determine whether low doses of local anesthetic in TAPB can be effective as well as to consider success rates of TAPB using ultrasound, the benefit of TAPB with co-analgesics inclusive of ITM / multimodal analgesia, and the impact on CPSP outcomes. We hypothesized that the addition of bilateral ultrasound TAPB using low-dose 0.25% ropivacaine as part of routine multimodal postoperative analgesia, inclusive of ITM, would significantly decrease acute surgical pain as measured by lower pain scores, opioid consumption, and improved quality of recovery in the first 24 hr postoperatively. We also planned to explore the impact of TAPB on the development of CPSP by assessing physical functioning at 30 days and six months postoperatively. Accordingly, patients undergoing elective CD with spinal anesthesia were recruited for the study, and to test this hypothesis, all patients were to receive 0.1 mg ITM and multimodal analgesia with ultrasound-guided TAPB and either 0.25% ropivacaine or 0.9% saline placebo.

Methods Patients Research Ethics Board (REB) approval was obtained (IWK Health Centre REB #1004605 April 15th, 2009). Clinical Trial registration for this research can be found at www. ClinicalTrials.Gov (NCT01261637).A Patients scheduled to undergo CD with planned spinal anesthesia were approached by research personnel and recruited to participate. Eligibility criteria included all patients who were non-labouring, C 18 yr old, minimum 37 weeks gestational age, American Society of Anesthesiologists (ASA) status I or II, and English speaking. Exclusion criteria included morbid obesity (body mass index C 45 kg
m-2), emergency CD, severe maternal cardiac disease, significant obstetric comorbidities, failed spinal anesthesia, and enrolment in any other studies. A screening log based on the suggested format in the CONSORT Statement was maintained to document the number of patients approached for study enrolment and reasons for refusal.23 After providing informed consent, patients were assigned a study number in order of recruitment.

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Randomization into either the control (0.9% saline placebo) or treatment (0.25% ropivacaine) group was achieved by opening sealed opaque envelopes labelled with the sequential study numbers. Blinded study group allocation (A or B) was indicated inside the sealed envelope. Blinding and matching of the group allocation was determined by the IWK Health Centre Pharmacy Department using a computer-generated block randomized table. Blocks were permuted at ten patients per block with equal allocation of patients between the two groups. On a monthly basis (or as needed if supply was exhausted earlier), the pharmacy supplied sterile blinded study drug syringes labelled TAP Block Study Drug ‘‘A’’ or ‘‘B’’.24 Study protocol Prior to the CD, all patients received antacid prophylaxis, and standard monitors were applied. The spinal anesthetic technique was standardized and consisted of hyperbaric bupivacaine 12 mg, fentanyl 15 lg, and preservative-free morphine 100 lg. Anesthetic management, including adequacy of spinal block and subsequent operative delivery, was performed in the usual manner. At the conclusion of the procedure, each patient received ketorolac 30 mg, ondansetron 4 mg, acetaminophen 1,000 mg, as well as bilateral TAPBs from one of two investigators (D.M. or R.G.). Bilateral TAPBs were performed under ultrasound guidance using a 38-mm linear high-resolution ultrasound probe (M-Turbo Ultrasound, SonoSite, Hitchin, UK) and a 100-mm 20G Tuohy needle. Using aseptic precautions, the Tuohy needle was inserted in an anteroposterior direction along the long axis of the probe (in plane). The appropriate tissue plane was identified and observed distending (deep to the fascial plane between the interior oblique and transversus abdominis) with an incremental injection of 20 mL of study solution.24 Bandages were placed over the injection sites. Postanesthesia care unit (PACU) and ward orders included routine neuraxial opioid protocol for monitoring respiratory rate, sedation scores, and hemodynamic variables, and standardized orders for postoperative analgesia included Naprosyn 250 mg q8 h, acetaminophen 1,000 mg q6 h, and oxycodone 2.5-5 mg q6 h prn. Prior to each patient’s discharge from the PACU (once spinal motor block had regressed), one of the investigators (D.M. or R.G.) assessed the adequacy of the TAPB. Evidence of inadequate TAPB was unilateral or bilateral sensation to cold (ice) below T10. Measures

A

www.ClinicalTrials.Gov (NCT01261637) trial registration was not congruent with the final study protocol and did not include cumulative opioid consumption at 24 hr postoperatively as a primary outcome.

Research personnel unaware of the patients’ randomization or adequacy of block assessment collected data until the

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patients left the PACU (minimum two hours), then 24 hr and 48 hr postoperatively via a ward visit. In accordance with IMMPACT guidelines, pain intensity was measured with an 11-point numeric rating scale (NRS) (0 = no pain; 10 = pain ‘‘as bad as you can imagine’’) and a verbal rating scale (VRS) (none, mild, moderate, or severe).25,26 Pain intensity was measured at rest (supine) and after movement (log roll). Nausea intensity was assessed using an NRS anchored at 0 (no nausea) and 10 (nausea ‘‘as bad as you can imagine’’).26 Vomiting episodes were recorded separately. Pruritus was assessed at 24 hr and 48 hr with a four-point scale.27 At 24 hr, patients were asked to complete a Quality of Recovery-40 (QoR-40) questionnaire that provides an extensive efficient evaluation of a patient’s quality of recovery after anesthesia and surgery.28 The QoR-40 scores can range from 40-200, with higher scores representing better recovery. Data regarding cumulative oxycodone tablet consumption were recorded at two, 24, and 48-hr intervals and converted to oral morphine equivalents at a ratio of 1:1.5 oxycodone to morphine.29,30 Forty-eight hours after surgery, patients were asked about their satisfaction with postoperative pain relief using an NRS anchored at 0 (totally unsatisfied) and 10 (totally satisfied). After discharge, research personnel contacted patients via telephone at 30 days and six months to complete a fiveminute Short Form-36 Health Survey (SF-36Ò). The SF-36, an 11-question (36 item) measure of health-related quality of life, is the most commonly used generic measure of health-related quality of life.25

D. M. McKeen et al.

Based on data from Eisenach et al., parturients who underwent CD reported a maximum (SD) NRS (worst pain) of 7.1 (2.3) at 24 hr.2 Assuming a 30% reduction in NRS, 19 subjects per group were required for an estimation of maximum NRS pain at 24 hr postoperatively. Based on personal communication and data from Myles et al., an average (SD) postoperative QoR score of 167 (23) was expected.28 Assuming a reduction in QoR score of 10%, 29 subjects per group were required to estimate QoR at 24 hr postoperatively. Using the largest sample size estimate and accounting for attrition, violations, and block failure (10%), we planned to recruit a minimum of 34 patients per group (total sample size = 68). Student’s two-sample t test was used for comparison of the means of continuous normally distributed data. Categorical data were analyzed using the mid-P variant of Fisher’s exact test.32 Odds ratios were estimated using conditional maximum likelihood estimation, and midP exact confidence limits were calculated.33 Most statistical analyses were performed using GraphPad Prism version 5.0 (GraphPad Software, San Diego, CA, USA). The mid-P exact tests were performed using OpenEpi version 2 (open source calculator). For each of the four primary outcomes, P \ 0.05 was considered statistically significant. A value of P \ 0.001 was used for the analyses relating to other outcomes to account for multiple other outcomes and repeated testing over time.

Results Statistical analysis Patients The superiority of pain scales vs opioid consumption as a surrogate measure of acute pain is unclear.25 For this reason, we have chosen four primary outcomes; the two pain scores, the QoR, and cumulative opioid consumption at 24 hr. As the multiple primary outcomes were to be interpreted individually, no adjustment for multiplicity was necessary (i.e., all were required to reach statistical significance at 0.05). Sample size calculations An a priori two-tailed sample size calculation with a significance level of a = 0.05 and b = 0.20 was completed for all four measurements at the 24-hr postoperative assessments. Based on data from Girgin et al., where intravenous patient-controlled analgesia postoperative opioid was used for 24 hr following CD with 0.1 mg ITM, parturients consumed an average (SD) of 28 (18) mg of morphine.31 Assuming a 50% reduction in opioid consumption, 28 subjects per group were required for an estimation of opioid consumption at 24 hr postoperatively.

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One hundred thirty-seven patients were approached to participate in this study; 83 patients consented, 51 declined, and three were further excluded based on study inclusion and exclusion criteria. Data from nine patients were withdrawn/not collected due to deviations from the study protocol: failed spinal (n = 4); no investigator available (n = 1); surgical complication requiring general anesthesia (n = 1); abnormal blood work (n = 1); standardized postoperative analgesia protocol not followed (n = 1); attrition at follow-up (n = 1). As a result, data from 74 patients were available for protocol analyses (placebo n = 39; treatment n = 35, Figure).24 All patients were similar in anthropometric measures, ASA status, and gravidity/parity at baseline (Table 1). Among participants, intraoperative spinal anesthesia levels were determined to be T4-T6, with no patient requiring additional intraoperative analgesia supplementation. The primary outcome measures of pain, opioid consumption, and quality of recovery assessed at 24 hr are summarized in Table 2. Pain scores at 24 hr were

US guided tap block in cesarean delivery

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Figure CONSORT 2010 Flow diagram of patient enrolment, allocation, follow-up, and analysis

Table 1 Patient characteristics Measure

Ropivacaine 0.25% (n = 35)

Placebo (n = 39)

Age (yr)

32.1 (5.3)

31.4 (5.8)

Weight (kg)

87.7 (18.5)

87.4 (14.8)

Height (cm)

162.6 (6.4)

164.0 (5.2)

I

20 (57.1%)

27 (69.2%)

II

15 (42.9%)

12 (30.8%)

ASA Status Gravidity (n) Parity (n)

1/2/3/4/5

1 / 1 / 11 / 16 / 6

2 / 1 / 12 / 15 / 9

%

2.9 / 2.9 / 31.4 / 45.7 / 17.1

5.1 / 2.6 / 30.8 / 38.5 / 23.1

0/1/2/3

7 / 21 / 7 / 0

10 / 18 / 10 / 1

%

20 / 60 / 20 / 0

25.6 / 46.2 / 25.6 / 2.6

ASA = American Society of Anesthesiologists. Data are presented as mean (SD); median [interquartile range]; n (%)

slightly higher in the TAPB 0.25% ropivacaine group. These differences were not statistically significant, and the confidence interval ranges rule out clinically important decreases in pain (C 2 points) with the use of ropivacaine. Opioid consumption (expressed as morphine equivalents) at 24 hr was slightly higher in the TAPB 0.25% ropivacaine group; these differences were not statistically or clinically significant. The global QoR-40 scores at 24 hr postoperatively were also clinically similar. The secondary outcome measures of health-related quality of life collected at a time distant from surgery are also summarized in Table 2. Total scores in the SF-36 Health Survey were similar between groups at both 30 days and six months postoperatively.

Additional information regarding pain intensity, opioid consumption, and quality of recovery at two different time periods is summarized in Table 3. The group receiving ropivacaine reported less pain at rest, less pain with movement, and had lower morphine consumption at two hours than the placebo group. This situation was reversed at 24 and 48 hr. Given the likely non-Gaussian distribution of data related to morphine equivalents, median values were also considered. At two hours, the median use was zero for both groups. At 48 hr, the median [IQR] quantity of morphine equivalents consumed was 15 [0.0-30.0] mg in the 0.25% ropivacaine group and 0.0 [0.0-7.5] mg in the placebo group. Nevertheless, all of the differences were small and none were statistically significant.

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Table 2 Primary and secondary outcomes at 24 hr postoperatively Measure

n (R/P)

Ropivacaine 0.25%

Placebo

Estimated Difference

95% Confidence Interval

P value

Primary Outcomes NRS Pain at Rest

33/39

2.2 (1.5)

1.7 (1.6)

0.4 (0.4)

-1.16 to 0.30

0.24

NRS Pain after Movement

33/39

4.7 (2.2)

3.8 (2.3)

0.9 (0.5)

-2.0 to 0.13

0.08

Morphine Equivalents

35/39

15.5 (20.2)

13.4 (14.6)

2.1 (4.1)

-10.21 to 6.02

0.61

Quality of Recovery-40

34/39

173 (12)

177 (10)

3.6 (2.6)

-1.65 to 8.89

0.17

Secondary Outcomes SF-36 Total 30 days

34/38

68 (13)

72 (16)

4.16 (3.48)

-2.78 to 11.10

0.24

SF-36 Total 6 months

35/36

86 (15)

87 (16)

0.73 (3.62)

-6.50 to 7.95

0.84

NRS = numeric rating scale; R/P = ropivacaine/placebo. Data are presented as mean (SD) unless otherwise indicated. All data analyzed by Student’s two-sample t test

Table 3 Secondary outcomes of pain and morphine consumption at 2 and 48 hr postoperatively

Table 5 Secondary outcomes of sub-dimensions of SF-36 and Quality of Recovery-40

Measure

Category

n (R/P)

Time (hr)

Ropivacaine 0.25%

Placebo

NRS

n (R/P)

Ropivacaine 0.25%

Placebo

Quality of Recovery-40

Pain at Rest

35/39

2

2.0 (2.1)

3.5 (2.4)

Emotional State

34/39

40 (4)

41 (3)

35/39

48

2.1 (1.9)

1.1 (1.5)

Physical Comfort

34/39

50 (5)

52 (4)

Pain after Movement

34/38 35/39

2 48

3.6 (2.7) 4.3 (2.1)

4.7 (3.0) 3.2 (2.0)

Psychological Support Physical Independence

33/39 34/39

34 (2) 18 (2)

34 (2) 18 (3)

Morphine Equivalents

35/39

2

Pain

34/39

31 (3)

32 (2)

35/39

48

1.4 (2.9)

2.9 (4.3)

(0.0 - 7.5)

(0.0 - 17.5)

18.6 (21.4)

6.8 (12.0)

Physical

34/38

61 (2)

66 (3)

(0.0 - 42.5)

Mental

34/38

75 (2)

77 (2)

(0.0 - 107.5)

NRS = numeric rating scale; R/P = ropivacaine/placebo. Data presented as mean (SD) and (min - max)

Nausea

Vomiting

n Time Rating (R/P) (hr) (/10) 35/39

2

0/1-4/5-8 26/5/4

33/5/1

0/1-4/5-8 28/4/1

38/0/1

34/39 48

0/1-4/5-8 27/4/3

37/1/1

2

2 (5.7%)

2 (5.1%)

35/39 24

2 (5.7%)

2 (5.1%)

1 (2.9%)

1 (2.6%)

35/39 48 Pruritus

Ropivacaine Placebo 0.25%

33/39 24 35/39

34/39

SF-36 6 months Physical

35/36

84 (2)

85 (3)

Mental

35/36

82 (3)

83 (3)

Data presented as mean (SD). R/P = ropivacaine/placebo

Table 4 Nausea, pruritus, vomiting, and urine retention Measure

SF-36 30 days

2

0/1/2/3

11/11/10/2

13/14/10/2

33/39 24

0/1/2/3

12/9/11/1

17/13/9/0

35/39 48

0/1/2/3

28/4/3/0

37/0/2/0

Urine Retention 29/28 24

3 (10.3%)

1 (3.6%)

29/28 48

3 (10.3%)

1 (3.6%)

of urine retention (Table 4). While sub-dimensions of the QoR-40 were similar, at 24 hr postoperatively, lower physical comfort scores were observed in the 0.25% ropivacaine group compared with placebo, but these were not clinically different. The SF-36 scores on both the physical and mental dimensions were similar at 30 days and six months postoperatively (Table 5). Severe pain (NRS [ 6) at rest and after movement is summarized in Table 6. At 48 hr, 20% of patients in the 0.25% ropivacaine TABP group reported severe pain (NRS [ 6), 17.4% more than those who received placebo TAPB. Patient satisfaction 48 hr following surgery was similar between groups (data not shown).

Data presented as rating / n or n (%). R/P = ropivacaine/placebo

Discussion We observed no difference in the occurrence of adverse outcomes of nausea, vomiting, and pruritus and observed a small, not clinically important difference in the occurrence

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In this study, we assessed the effect of the addition of ultrasound-guided TAPB with 0.25% ropivacaine to a

US guided tap block in cesarean delivery

637

Table 6 Secondary outcomes of incidence of severe pain (numeric rating scale [ 6/10) Measure Pain at Rest

Pain After Movement

n (R/P)

Time (hr)

Ropivacaine 0.25%

Placebo

Risk Difference

95% confidence interval

35/39

2

1 (2.9%)

4 (10.3%)

-7.4%

-18.4 to 3.6

33/39

24

0 (0%)

1 (2.6%)

-2.6%

-7.5 to 2.4

35/39

48

0 (0%)

0 (0%)

0.0%

0.0 to 0.0 -32.9 to 4.5

34/38

2

5 (14.7%)

11 (28.9%)

-14.2%

33/39

24

9 (27.3%)

6 (15.4%)

11.9%

-7.1 to 30.8

35/39

48

7 (20.0%)

1 (2.6%)

17.4%

3.3 to 31.6

Data presented as n (%). R/P = ropivacaine/placebo

multimodal approach (inclusive of ITM) to postoperative CD analgesia. At 24 hr, the pre-specified time point of interest, the TAPB group had higher pain scores and opioid consumption and poorer physical functioning compared with placebo; however, the differences were small and not clinically important. The confidence intervals for the between-group differences suggest that clinically important advantages of TAPB with 0.25% ropivacaine are unlikely. Scores on the secondary endpoint SF-36 questionnaire assessing CPSP outcomes at 30 days and six months were similar and, while exploratory, do not support any benefit in terms of long-term improvement in functional health and wellbeing. Similar rates of side effects, including nausea, pruritus, vomiting, and urine retention, were observed among all patients. It was reassuring that there were relatively few occurrences of these adverse outcomes. Studies of the TAPB technique have reported varying degrees of success in improving opioid consumption, and results similar to the current findings have been shown.17,19,21,34,35 Several studies inclusive of ITM reported the inability of TAPB to improve pain scores in the initial 24 hr after surgery.18,21,22 Specifically, Singh et al. completed an ultrasound-guided TAPB study using low-dose 0.25% and 0.5% ropivacaine inclusive of ITM that showed no benefit in pain scores at 24 hr and up to six weeks with TAPB at either local anesthetic dose.36 We observed slightly higher pain scores in the 0.25% ropivacaine TAPB group at 24 and 48 hr. This may be a chance occurrence or may represent a real phenomenon. In keeping with the duration of action of ropivacaine, the 0.25% ropivacaine TAPB likely delayed return of abdominal wall pain sensation for up to two to six hours after initial return of sensation from spinal anesthesia.B This may have allowed TAPB patients to reduce or delay early (2-24 hr) opioid use (the desired TAPB effect), yet with a possible undesired higher opioid consumption secondary to ‘‘rebound pain’’. Rebound pain phenomenon has been reported after knee reconstruction with femoral B

NAROPINÒ Prescribing Information, Table 7. Data on file. 451112E/ Revised: November 2012. Available from URL: http://www.naropin-us. com/pdf/Naropin_PI_451112E_Nov_2012.pdf (accessed March 2014).

nerve block, and this was further confirmed with ropivacaine perineural block in rats.37,38 After perineural block regression, patients may take larger doses of opioids to ‘‘catch up’’ to attain therapeutic opioid levels. Two other alternative explanations can be considered. Patient expectations may influence their pain perceptions and postoperative recovery. Transversus abdominis plane block regression occurs when patients are comfortable and expecting pain to improve over time rather than worsen. Transversus abdominis plane block may allow patients to start to mobilize earlier (desired effect), yet this increased mobility after TAPB regression may result in an increased perception of pain. Regardless of the cause, our findings suggest that TAPB with 0.25% ropivacaine produces no benefit at 24 hr postoperatively and a possible disadvantage at 48 hr postoperatively in this population. The current findings are relevant to the diverse body of data in the literature related to TAPB following CD. Differences in block technique and success rates, local anesthetic type and total dose, as well as the inclusion of co-analgesics, including multimodal analgesics and neuraxial opioids, confound interpretation of current TAPB publications in this CD population. As accurate placement of local anesthetic in the transversus abdominis facial plane is critical to its ultimate success, the technique used to determine its location warrants consideration. While the first descriptions of the TAPB technique used anatomical landmarks to locate the Triangle of Petit, anatomical differences, the gravid abdomen, and an increasing prevalence of obesity contribute to difficulties with palpation, particularly in the pregnant population.16,17,39,40 First described by Hebbard et al., the use of ultrasound to guide and confirm needle position is a promising addition to the TAPB technique to improve block accuracy, efficiency, and safety.41-43 There have been suggestions that negative studies failing to show TAPB benefit in CD studies may in fact be due to TAPB failure itself secondary to inaccurate needle placement or inability of TAPB, particularly the ultrasound approach to cover L1 nerve roots.44 It has been recommended that success of TAPB be routinely assessed in further studies.44,45

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This current study attempted to assess TAPB duration and failure rates by dermatome sensory testing to cold using ice.46 This assessment was conducted after regression of spinal anesthesia and after the patient was evaluated as discharge ready (two hours after PACU admission). Spinal anesthesia block regression, as part of PACU dischargeready criteria, includes a modified Bromage score of 5 (knee flexion / hip extension allowing five-second pelvic lift).47 We found 56% and 76% block success rates in the placebo and 0.25% ropivacaine groups, respectively. The success of TAPB in 56% of the placebo group indicates that this assessment technique was confounded by residual spinal sensory block. We therefore cannot accurately report TAPB failure rates. We can comment that TAPB failure designation was liberal (lack of cold sensation had to be bilateral for block success), and the two-hour improvement in the ropivacaine within group NRS/VRS suggests likely high rates of TAPB success. Subgroup analysis with removal of TAPB failures (0.25% ropivacaine group n = 26, data not shown) was similar to the per protocol analysis and did not reveal any relevant differences for pain at rest (95% confidence interval [CI]: -1.26 to 0.36), pain after movement (95% CI: -2.31 to 0.06), morphine equivalent consumption (95% CI: -11.77 to 6.87), or QoR (95% CI: -2.61 to 9.04). To evaluate the duration of TAPB, the patients selfassessed numbness of the abdominal wall and location of postoperative pain by means of shading a dermatome diagram in a self-recorded paper diary at six, 12, and 24 hr after delivery. On the initial 24-hr ward visit, research personnel found \ 25% compliance. While the patient diary itself and data related to the duration of TAPB were collected, data analysis was not undertaken due to attrition and missing data points. Special attention should be paid to reduce the dose of local anesthetic given its increased potential to induce systemic toxicity in this highly vascularized and ‘‘at risk’’ pregnant population.48-50 The higher concentration (0.5% ropivacaine) used for TAPB usually approximates 3 mg
kg-1, exceeds manufacturers’ recommendations, and may result in plasma concentration levels capable of causing central nervous system toxicity.B Seizures have occurred following TAPB in ‘‘at risk’’ patient populations.B,48 While preliminary reports using high-dose local anesthetic TAPB (0.75% bupivacaine) showed success in improving pain management and opioid consumption, the authors acknowledge that the dose used was higher than that recommended by the manufacturer, but they insist on its safety.17,51 Follow-up studies attempting to improve on those findings with lower doses of bupivacaine and ropivacaine have yielded less promising results, suggesting the effectiveness of the block may be intimately linked to dosage.18,21,22,34,50 Several reports of

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TAPB with varying levels of bupivacaine (0.25-0.75%)— known to be more potent than ropivacaine—following CD have not shown consistent improvement in postoperative analgesia.17,20-22,52,53 Three reports using moderate- to high-dose local anesthetic in TAPB (0.5% and 0.375% ropivacaine) were unable to show an improvement in pain management following CD up to 48 hr postoperatively.18,19,34 Considering the threat of neurotoxicity presented by TAPB using 0.5% ropivacaine, elicitation of the minimum effective dose of local amino amide anesthetic is important, and consensus is needed on the optimal dosage of ropivacaine for the efficacy of ultrasound-guided TAPB.18,19,34-36 Meta-analyses by Mishriky et al. and Abdulla et al., both published in 2012, stratified for the impact of including ITM on the efficacy of TAPB.54,55 Further meta-analysis of additional recent publications stratifying for technique, local anesthetic dosage, multimodal analgesia, and ITM is needed as these mixed methodologies currently confound interpretation of TAPB publications in this CD population. In the study by Costello et al., residual abdominal pain was assessed at six weeks, and TAPB did not reduce the incidence of chronic pain.18 Importantly, our study provides an assessment of TAPB for long-term health benefits and prevention of persistent pain at 30 days and six months. While this study was not powered to detect significant differences and was considered exploratory, we can state that we observed no differences in SF-36 followup data at either time point, with almost identical scores six months postoperatively (Table 5). There were several limitations recognized in this study. An alternative strategy to assess block success needs to be determined. Block success was confirmed by bilateral lack of cold sensation to ice below T10 after motor block regression. We did not attempt to assess the lower level, i.e., L1 coverage of the block. Residual spinal sensory block and occasional unilateral block (assigned as TAPB block failure) confounded the assessment of TAPB adequacy. Unfortunately, this was not discovered until data analysis and un-blinding of group allocation. Singh et al. utilized a ‘‘satisfactory review’’ by two anesthesia staff confirming the ultrasound image of correct needle placement and local anesthetic spread, which, as a surrogate marker of block success, is an alternate yet unvalidated approach. The relatively low values of pain intensity at rest (NRS* 1-3 /10) reported by the majority of women through 48 hr of recovery (in association with multimodal analgesia inclusive of ITM) may have affected the evaluation of the clinical impact of the TAPB technique. We emphasize that almost one-third of women in both groups reported severe pain after movement. Additionally,

US guided tap block in cesarean delivery

measures capable of isolating psychological and social influences on the experience of pain associated with childbirth may be beneficial in future research. In our study, the use of only one treatment group and a placebo group limits our ability to discuss specific effect of anesthetic dose compared with the general effectiveness of the TAPB technique. As TAPB is relatively new, general recommendations, including type of local anesthetic and dosage and standards of practice, e.g., the optimal TAPB approach, have yet to be established.56 In conclusion, amongst women undergoing CD inclusive of ITM and multimodal analgesia, ultrasoundguided TAPB with 0.25% ropivacaine does not improve self-reported pain, QoR, and opioid consumption when compared with placebo in the first 24 hr postoperatively. Transversus abdominis plane block may be associated with greater pain and opioid consumption later in recovery at 24-48 hr. Continued evaluation of anesthetic dosage is needed for further exploration of the dose-response relationship as well as ongoing assessment of the effectiveness of the ultrasound-guided vs the landmark technique to improve postoperative analgesia in this CD population. Acknowledgements We are grateful to Dr. Colleen O’Connell and Dr. Christy Woolcott for their assistance with statistical analyses. This study was completed at the IWK Health Centre. Dr. McKeen acknowledges the support of the Canadian Anesthesiologists’ Society (CAS) GE Healthcare Canada Research Award in Perioperative Imaging Operating Grant. Dr. George held an IWK Recruitment & Establishment Grant and acknowledges the support of a CAS Career Scientist Award. Dr. Allen held a Canadian Institutes of Health Research New Investigator Award and a Dalhousie University Clinical Research Scholar Award. Dr. Pink acknowledges Dalhousie University Medical Research Foundation Summer Research Studentship Funding.

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18. Conflicts of interest

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References 1. Lavand’homme P. Chronic pain after vaginal and cesarean delivery: a reality questioning our daily practice of obstetric anesthesia. Int J Obstet Anesth 2010; 19: 1-2. 2. Eisenach JC, Pan PH, Smiley R, Lavand’homme P, Landau R, Houle TT. Severity of acute pain after childbirth, but not type of delivery, predicts persistent pain and postpartum depression. Pain 2008; 140: 87-94. 3. Public Health Agency of Canada. Ottawa. Perinatal Health Indicators for Canada 2011. Available from URL: http:// publications.gc.ca/site/eng/412027/publication.html (accessed March 2014). 4. Joseph KS, Young DC, Dodds L, et al. Changes in maternal characteristics and obstetric practice and recent increases in primary cesarean delivery. Obstetc Gynecol 2003; 102: 791-800. 5. Public Health Agency of Canada. Ottawa. Obesity in Canada: A Joint Report from the Public Health Agency of Canada and the Canadian Institute for Health Information; 2011. Available from

19.

20.

21.

22.

23.

URL: www.phac-aspc.gc.ca/hp-ps/hl-mvs/oic-oac/assets/pdf/oicoac-eng.pdf (accessed March 2014). Kelly S, Sprague A, Fell DB, et al. Examining caesarean section rates in Canada using the robson classification system. J Obstet Gynaecol Can 2013; 35: 206-14. Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet 2006; 367: 1618-25. Flood P, Wong CA. Chronic pain secondary to childbirth: does it exist? Anesthesiology 2013; 118: 16-8. Johansen A, Romundstad L, Nielsen CS, Schirmer H, Stubhaug A. Persistent postsurgical pain in a general population: prevalence and predictors in the Tromso study. Pain 2012; 153: 1390-6. Landau R, Bollag L, Ortner C. Chronic pain after childbirth. Int J Obstet Anesth 2013; 22: 133-45. McDonnell NJ, Keating ML, Muchatuta NA, Pavy TJ, Paech MJ. Analgesia after caesarean delivery. Anaesth Intensive Care 2009; 37: 539-51. U.S. Food and Drug Administration. Use of Codeine by Some Breastfeeding Mothers May Lead to Life-Threatening Side Effects in Nursing Babies - 2007. Available from URL: http://www.fda.gov/ drugs/drugsafety/postmarketdrugsafetyinformationforpatientsand providers/drugsafetyinformationforheathcareprofessionals/public healthadvisories/ucm054717.htm (accessed March 2014). Wheeler M, Oderda GM, Ashburn MA, Lipman AG. Adverse events associated with postoperative opioid analgesia: a systematic review. J Pain 2002; 3: 159-80. Dahl JB, Jeppesen IS, Jorgensen H, Wetterslev J, Moiniche S. Intraoperative and postoperative analgesic efficacy and adverse effects of intrathecal opioids in patients undergoing cesarean section with spinal anesthesia: a qualitative and quantitative systematic review of randomized controlled trials. Anesthesiology 1999; 91: 1919-27. Wong JY, Carvalho B, Riley ET. Intrathecal morphine 100 and 200 lg for post-cesarean delivery analgesia: a trade-off between analgesic efficacy and side effects. Int J Obstet Anesth 2013; 22: 36-41. McDonnell JG, O’Donnell B, Curley G, Heffernan A, Power C, Laffey JG. The analgesic efficacy of transversus abdominis plane block after abdominal surgery: a prospective randomized controlled trial. Anesth Analg 2007; 104: 193-7. McDonnell JG, Curley G, Carney J, et al. The analgesic efficacy of transversus abdominis plane block after cesarean delivery: a randomized controlled trial. Anesth Analg 2008; 106: 186-91. Costello JF, Moore AR, Wieczorek PM, Macarthur AJ, Balki M, Carvalho JC. The transversus abdominis plane block, when used as part of a multimodal regimen inclusive of intrathecal morphine, does not improve analgesia after cesarean delivery. Reg Anesth Pain Med 2009; 34: 586-9. Belavy D, Cowlishaw PJ, Howes M, Phillips F. Ultrasoundguided transversus abdominis plane block for analgesia after caesarean delivery. Br J Anaesth 2009; 103: 726-30. Baaj JM, Alsatli RA, Majaj HA, Babay ZA, Thallaj AK. Efficacy of ultrasound-guided transversus abdominis plane (TAP) block for postcesarean section delivery analgesia—a double-blind, placebo-controlled, randomized study. Middle East J Anesthesiol 2010; 20: 821-6. McMorrow RC, Ni Mhuircheartaigh RJ, Ahmed KA, et al. Comparison of transversus abdominis plane block vs spinal morphine for pain relief after caesarean section. Br J Anaesth 2011; 106: 706-12. Kanazi GE, Aouad MT, Abdallah FW, et al. The analgesic efficacy of subarachnoid morphine in comparison with ultrasound-guided transversus abdominis plane block after cesarean delivery: a randomized controlled trial. Anesth Analg 2010; 111: 475-81. Schulz KF, Altman DG, Moher D; CONSORT Group. CONSORT. Statement: Updated guidelines for reporting parallel group randomised trials. J Clin Epidemiol 2010; 2010(63): 834-40.

123

640 24. Altman DG. Practical Statistics for Medical Research. Chapman & Hall/CRC; 1991. 25. Dworkin RH, Turk DC, Farrar JT, et al. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain 2005; 113: 9-19. 26. Gan TJ, Meyer TA, Apfel CC, et al. Society for Ambulatory Anesthesia guidelines for the management of postoperative nausea and vomiting. Anesth Analg 2007; 105: 1615-28. 27. Horta ML, Morejon LC, da Cruz AW, et al. Study of the prophylactic effect of droperidol, alizapride, propofol and promethazine on spinal morphine-induced pruritus. Br J Anaesth 2006; 96: 796-800. 28. Myles PS, Weitkamp B, Jones K, Melick J, Hensen S. Validity and reliability of a postoperative quality of recovery score: the QoR40. Br J Anaesth 2000; 84: 11-5. 29. Mercadante S, Caraceni A. Conversion ratios for opioid switching in the treatment of cancer pain: a systematic review. Palliat Med 2011; 25: 504-15. 30. Bruera E, Belzile M, Pituskin E, et al. Randomized, double-blind, cross-over trial comparing safety and efficacy of oral controlledrelease oxycodone with controlled-release morphine in patients with cancer pain. J Clin Oncol 1998; 16: 3222-9. 31. Girgin NK, Gurbet A, Turker G, Aksu H, Gulhan N. Intrathecal morphine in anesthesia for cesarean delivery: dose-response relationship for combinations of low-dose intrathecal morphine and spinal bupivacaine. J Clin Anesth 2008; 20: 180-5. 32. Agresti A. An Introduction to Categorical Data Analysis - Second Edition. Wiley; 2007. 33. Martin D, Austin H. An efficient program for computing conditional maximum likelihood estimates and exact confidence limits for a common odds ratio. Epidemiology 1991; 2: 359-62. 34. Loane H, Preston R, Douglas MJ, Massey S, Papsdorf M, Tyler J. A randomized controlled trial comparing intrathecal morphine with transversus abdominis plane block for post-cesarean delivery analgesia. Int J Obstet Anesth 2012; 21: 112-8. 35. De Oliveira GS, Jr Fitzgerald PC, Marcus RJ, Ahmad S, McCarthy RJ. A dose-ranging study of the effect of transversus abdominis block on postoperative quality of recovery and analgesia after outpatient laparoscopy. Anesth Analg 2011; 113: 1218-25. 36. Singh S, Dhir S, Marmai K, Rehou S, Silva M, Bradbury C. Efficacy of ultrasound-guided transversus abdominis plane blocks for post-cesarean delivery analgesia: a double-blind, dosecomparison, placebo-controlled randomized trial. Int J Obstet Anesth 2013; 22: 188-93. 37. Williams BA, Bottegal MT, Kentor ML, Irrgang JJ, Williams JP. Rebound pain scores as a function of femoral nerve block duration after anterior cruciate ligament reconstruction: retrospective analysis of a prospective, randomized clinical trial. Reg Anesth Pain Med 2007; 32: 186-92. 38. Kolarczyk LM, Williams BA. Transient heat hyperalgesia during resolution of ropivacaine sciatic nerve block in the rat. Reg Anesth Pain Med 2011; 36: 220-4. 39. Rafi AN. Abdominal field block: a new approach via the lumbar triangle. Anaesthesia 2001; 56: 1024-6. 40. Reid SA. The transversus abdominis plane block. Anesth Analg 2007; 105: 282; author reply 282-3.

123

D. M. McKeen et al. 41. Hebbard P, Fujiwara Y, Shibata Y, Royse C. Ultrasound-guided transversus abdominis plane (TAP) block. Anaesth Intensive Care 2007; 35: 616-7. 42. Koscielniak-Nielsen ZJ. Ultrasound-guided peripheral nerve blocks: what are the benefits? Acta Anaesthesiol Scand 2008; 52: 727-37. 43. Liu SS, Ngeow JE, Yadeau JT. Ultrasound-guided regional anesthesia and analgesia: a qualitative systematic review. Reg Anesth Pain Med 2009; 34: 47-59. 44. Factor D, Chin KJ. Transversus abdominis plane block in lower segment cesarean section: a question of block failure or lack of efficacy? Reg Anesth Pain Med 2010; 35: 404-5. 45. Hebbard PD, Royse CF. Lack of efficacy with transversus abdominis plane block: is it the technique, the end points, or the statistics? Reg Anesth Pain Med 2010; 35: 324. 46. Hebbard P. Subcostal transversus abdominis plane block under ultrasound guidance. Anesth Analg 2008; 106: 674-5; author reply 675. 47. Breen TW, Shapiro T, Glass B, Foster-Payne D, Oriol NE. Epidural anesthesia for labor in an ambulatory patient. Anesth Analg 1993; 77: 919-24. 48. Landy C, Gagnon N, Boulland P, Raynaud L, Plancade D. Seizures associated with local anaesthetic intoxication. Br J Anaesth 2012; 109: 463-4; author reply 464. 49. Griffiths JD, Barron FA, Grant S, Bjorksten AR, Hebbard P, Royse CF. Plasma ropivacaine concentrations after ultrasoundguided transversus abdominis plane block. Br J Anaesth 2010; 105: 853-6. 50. Onishi Y, Kato R, Okutomi T, Tabata K, Amano K, Unno N. Transversus abdominis plane block provides postoperative analgesic effects after cesarean section: additional analgesia to epidural morphine alone. J Obstet Gynaecol Res 2013; 39: 1397-405. 51. Sweetman SC. Martindale: The Complete Drug Reference. 35th ed. London, UK: Pharmaceutical Press; 2007 . 52. Tan TT, Teoh WH, Woo DC, Ocampo CE, Shah MK, Sia AT. A randomised trial of the analgesic efficacy of ultrasound-guided transversus abdominis plane block after caesarean delivery under general anaesthesia. Eur J Anaesthesiol 2012; 29: 88-94. 53. Eslamian L, Jalili Z, Jamal A, Marsoosi V, Movafegh A. Transversus abdominis plane block reduces postoperative pain intensity and analgesic consumption in elective cesarean delivery under general anesthesia. J Anesth 2012; 26: 334-8. 54. Mishriky BM, George RB, Habib AS. Transversus abdominis plane block for analgesia after cesarean delivery: a systematic review and meta-analysis. Can J Anesth 2012; 59: 766-78. 55. Abdallah FW, Halpern SH, Margarido CB. Transversus abdominis plane block for postoperative analgesia after caesarean delivery performed under spinal anaesthesia? A systematic review and meta-analysis. Br J Anaesth 2012; 109: 679-87. 56. Bonnet F, Berger J, Aveline C. Transversus abdominis plane block: what is its role in postoperative analgesia? Br J Anaesth 2009; 103: 468-70.