The Effect of Enhanced Recovery after Surgery Pathway Implementation on Abdominal-Based Microvascular Breast Reconstruction

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The Effect of Enhanced Recovery after Surgery Pathway Implementation on Abdominal-Based Microvascular Breast Reconstruction Banafsheh Sharif-Askary, BS,a Eliza Hompe, AB,a Gloria Broadwater, MS,b Rachel Anolik, MD,c and Scott T. Hollenbeck, MD, FACSc,* a

Duke University School of Medicine, Durham, North Carolina Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina c Division of Plastic and Reconstructive Surgery, Duke University Medical Center, Durham, North Carolina b

article info

abstract

Article history:

Background: Although Enhanced Recovery after Surgery (ERAS) pathways are becoming the

Received 9 September 2018

standard of care in microvascular breast reconstruction, evidence supporting their use is

Received in revised form

limited or based on small sample sizes. We hypothesized that improvements in post-

23 February 2019

operative outcomes would persist when examining the largest cohort of patients under-

Accepted 24 April 2019

going abdominal-based microvascular breast reconstruction, to date.

Available online 21 May 2019

Materials and methods: Data were retrospectively reviewed for 276 consecutive patients who underwent abdominal-based free flap breast reconstruction before and after ERAS imple-

Keywords:

mentation (pre-ERAS, n ¼ 138 patients; post-ERAS, n ¼ 138 patients). Primary outcomes

Breast reconstruction

were postoperative opioid use measured in oral morphine equivalents (OMEs), median

Enhanced Recovery after Surgery

hospital length of stay (LOS) in days, and incidence of postoperative complications.

ERAS

Results: Postoperative opioid requirements were significantly lower in the post-ERAS cohort

Microvascular breast reconstruction

compared with the pre-ERAS cohort (57.3 OME, [interquartile range 20.0-115.5] versus 297.3

Fast-track surgery

OME [interquartile range 138.6-437.7], P < 0.0001). There was no significant difference in hospital LOS when controlling for variables that differed between the groups. In addition, there were no differences in the rate of postoperative complications, return to operating room, or readmission after ERAS pathway implementation. Conclusions: ERAS improves specific aspects of recovery for patients undergoing microvascular breast reconstruction, most notably postoperative opioid use. Patient selection and a shift toward less invasive procedures may explain a nonsignificant impact on hospital LOS. ª 2019 Elsevier Inc. All rights reserved.

Introduction Recently, there has been a heightened focus on multimodal evidence-based protocols in perioperative care. Enhanced Recovery After Surgery (ERAS) protocols or fasttrack

perioperative care pathways are quickly becoming the standard of care across a number of surgical domains. These protocols combine and streamline care items that improve postoperative outcomes by reducing the physiological burden of surgery.1 From preoperative clinic visits to discharge, every

* Corresponding author. Division of Plastic, Maxillofacial and Oral Surgery, Duke University Hospital, Box 3974, Durham, NC 27710. Tel.: þ1 919 681-5079; fax: þ1 919 681-2670. E-mail address: [email protected] (S.T. Hollenbeck). 0022-4804/$ e see front matter ª 2019 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jss.2019.04.062

sharif-askary et al  eras in breast reconstruction

phase of care involves distinct protocol items delivered by different members of an integrated, multidisciplinary team. The objectives of ERAS protocols are to accelerate postoperative recovery, improve patient satisfaction, and promote cost-effective care. Although ERAS protocols were originally developed for colorectal surgery, their positive impact has led to implementation across various surgical specialties.2-6 The first “fasttrack” surgical pathways designed for abdominal-based microvascular breast reconstruction shortened hospital length of stay (LOS) without increasing complication rates.7,8 These initial pathways were less comprehensive than current ERAS protocols, lacking key components such as preoperative carbohydrate loading and perioperative goal-directed fluid management. When complete ERAS pathways for breast reconstruction were introduced, they led to shorter hospital LOS and decreased postoperative opioid requirements.9,10 The promising results documented in these studies were the basis for widespread adoption of ERAS protocols in microvascular breast reconstruction. ERAS protocols, however, are not without their shortcomings. Although they aim to accelerate recovery, early discontinuation of specific aspects of care, and restrictions on others, can be problematic. Thus, regular safety assessments and audit are important aspects of ERAS implementation. The aim of this study was to critically evaluate the effects of a comprehensive ERAS protocol in the largest abdominal-based free flap reconstruction cohort published to date. We hypothesized that ERAS-associated improvements in postoperative outcomes, observed in prior studies with smaller sample sizes, would persist in a larger cohort.

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Methods Study design and data collection This study was approved by the Duke University Institutional Review Board. We conducted a retrospective chart review of 276 consecutive patients who underwent abdominal-based free flap breast reconstruction before and after ERAS implementation (pre-ERAS, n ¼ 138; post-ERAS, n ¼ 138) between August 2012 and June 2017. There were no exclusion criteria for the study, as all patients who consented to microvascular breast reconstruction were enrolled in the ERAS pathway. Thus, attempts to meet full pathway criteria were made for all patients. Of note, at our institution, exclusion criteria for undergoing microvascular breast reconstruction include current smoking status, body mass index above 35 kg/m2, and poorly managed medical comorbidities.

ERAS pathway The ERAS protocol for abdominal-based microvascular breast reconstruction was developed by a multidisciplinary team of plastic surgeons, general surgeons, anesthesiologists, and nursing leadership (Figure; see Text Document, Supplemental Content 1, for detailed ERAS protocol). It was adapted from an existing ERAS pathway for colorectal surgery at our institution11 to include key items identified in a recent consensus review of optimal perioperative care in breast reconstruction outlined by the ERAS society.12

Fig e The ERAS protocol for abdominal-based microvascular breast reconstruction at our institution. (Color version of figure is available online.)

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Preoperative pathway Patients first entered the ERAS pathway during clinic visits, where they received preoperative counseling. On the morning of their procedure, patients received a carbohydrate drink, multimodal pain management, and postoperative nausea and vomiting prophylaxis. Before ERAS implementation, patients did not receive standardized counseling, pain management, or a carbohydrate drink preoperatively.

Intraoperative pathway Intraoperatively, multimodal pain management was administered. Patients also received local anesthesia with liposomal bupivacaine (Exparel; Pacira Pharmaceuticals, Inc, San Diego, CA) administered as a single-injection transversus abdominis plane (TAP) block. Before ERAS was implemented, dosage and timing of anesthetic administration were left to the anesthesiologist’s discretion, and patients did not receive TAP blocks. The goals of intraoperative fluid management within the ERAS protocol were to maintain euvolemia and reduce the risk of postsurgical complications associated with fluid overload.13 Phenylephrine and ephedrine use was permitted to optimize intraoperative blood pressure. Before ERAS implementation, administration of intraoperative fluids was based on blood pressure, heart rate, and urine output at the anesthesiologist’s discretion.

Postoperative pathway Postoperatively, patients were taken to the postanesthesia care unit and subsequently transferred to a floor staffed with nurses trained in flap monitoring. Surgical flaps were monitored until discharge using implantable Doppler probes and, after 2013, real-time tissue oxygenation monitoring (ViOptix, Fremont, CA). Patients were immediately started on a postsurgical bland diet. Patients’ level of activity increased gradually until they were ambulating freely on postoperative day 2 (POD 2). First-line pain management included a multimodal nonnarcotic pain regimen, supplemented with opioids for breakthrough pain. By protocol, urinary catheters were removed on the morning of POD 2. Fluid optimization continued postoperatively until intravenous fluids (IVFs) were discontinued on POD 1. Patients were discharged on POD 3 or when they met all predefined discharge criteria. Before ERAS pathway implementation, nearly all patients received patient-controlled analgesia (PCA) postoperatively. Urinary catheters were removed between POD 3 and POD 4 based on clinician judgment. IVFs were discontinued once patients were tolerating a regular diet. Transition to normal diet depended on patient request and timing of IVF discontinuation. Generally, patients were transitioned to clear liquids on POD 1 and a regular diet on POD 2.

Surgical technique Abdominal-based microvascular breast reconstruction was performed by one of two microsurgeons at our institution. Patients underwent muscle-sparing transverse rectus abdominis

myocutaneous (msTRAM) or deep inferior epigastric perforator (DIEP) flap surgery. Before ERAS pathway implementation, neither surgical approach nor postoperative management was standardized between the two microsurgeons. Under the ERAS protocol, postoperative management was uniform for all patients. Intraoperative bilateral TAP blocks were administered under direct visualization by the surgeon. For select patients who underwent an msTRAM flap surgery, a mesh product was used for abdominal wall reinforcement. Postoperative flap monitoring was performed using clinical examination, CookSwartz Doppler probes, tissue oximetry, or a combination of these techniques. Patients were kept in the step-down unit for the duration of their hospital course.

Outcomes Primary outcomes were median hospital LOS in days, postoperative opioid use, and the incidence of postoperative complications. Hospital LOS was measured as the number of nights the patient spent in the hospital with POD 0 being the day of surgery. Postoperative opioid use was measured in milligrams of oral morphine equivalents (OMEs) as a cumulative 48-h total. To assess whether patients were experiencing adequate pain relief, pain scores were recorded using a visual analog scale with values ranging from 0 to 10 (0 ¼ no pain; 10 ¼ worst pain). Preoperative pain scores or “pain score goals” were collected for baseline assessment. Postoperatively, pain scores were collected at 4-h intervals, beginning when the patient arrived in the postanesthesia care unit and continuing until they were 72 h after surgery. All complications were measured up to 30 d postoperatively except for deep and superficial surgical site infections (SSIs), which were measured up to 90 d from surgery. Postoperative complications included pulmonary embolism (PE) or deep vein thrombosis (DVT), need for increased level of care, urinary tract infection (UTI), acute kidney injury (AKI), deep and superficial SSI, unplanned return to the operating room (OR), and unplanned hospital readmission. Need for increased level of care was defined as admission to the surgical intensive care unit. Length of time, in hours, spent in the intensive care unit was also recorded. UTIs were defined using the National Surgical Quality Improvement Program (NSQIP) definition. This required one of six criteria (fever >38 C, urgency, frequency, dysuria, suprapubic tenderness, costovertebral angle pain, or tenderness) and a urine culture of >100,000 colonies/mL urine with no more than two separate species of organisms, all within 30 d after the principal operative procedure. Alternatively, patients could have two of the six criteria and at least one of the following: dipstick test positive for leukocyte esterase and/or nitrate, pyuria (>10 white blood cells per mm3), or organisms seen on gram stain.14 AKI was defined as a rise in postoperative creatinine by more than 1.5 times a patient’s preoperative baseline value. Deep and superficial SSIs were classified based on location: abdominal donor site, native breast, or breast flap. SSIs were considered “deep” if they required surgical drainage and “superficial” if they were managed with systemic antibiotics alone. Return to OR and unplanned readmissions related to the initial reconstructive surgery within 30 d postoperatively were recorded. Reasons for return to OR included infection, venous

sharif-askary et al  eras in breast reconstruction

congestion, seroma, hematoma, wound dehiscence or delayed wound healing, or breast flap necrosis. Intraoperative flap loss was subclassified as partial or total; partial flap loss was defined as tissue necrosis requiring surgical debridement with residual viable flap, whereas total flap loss necessitated surgical removal of the entire flap. Secondary outcome measures were indicators of ERAS protocol compliance. Intraoperative data collected included total opioid dose administered, total volume of IVF administered, and estimated blood loss (EBL). Postoperative secondary outcomes were PCA utilization and duration of PCA use, in hours. Day of ambulation was defined as the postoperative day that patients were walking on the hospital floor, beyond simply moving out of bed to a chair in their hospital room. Day of urinary catheter removal, first oral intake, IVF discontinuation, and first bowel movement were also recorded. Total IVF administration for 48-h postoperatively was collected. Blood glucose levels were measured using a 48-h postoperative average. Need for urinary catheter reinsertion was used as a surrogate measure of postoperative urinary retention (UR).15 Patients were deemed to require urinary catheter reinsertion based on failure of an 8-h voiding trial with >250 mL residual urine volume on ultrasound. Both intermittent catheterization and short-term catheterization were classified as need for urinary catheter reinsertion.

Statistical analysis Descriptive statistics were used to summarize the data. Normally, distributed continuous variables are summarized

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using mean and standard error of the mean (SEM). Nonparametric continuous variables are summarized using median and interquartile range (IQR). Categorical variables are summarized with frequency and percent. Chi-square or Fisher’s exact tests were used to compare categorical variables, and t-tests or Wilcoxon rank-sum tests were used to compare continuous variables. For comparison of pre- versus post-ERAS postoperative outcomes, adjusted P values are associated with the type 3 sum of squares from analysis of covariance (ANCOVA) models controlling for the patient characteristics and intraoperative factors, which were significantly different between the pre- and post-ERAS groups (age, surgery length, liposomal bupivacaine, abdominal wall mesh, IVFs intraoperative total, and flap procedure type). Logistic regression modeling was used to determine if catheter reinsertion or preepost ERAS were predictive of UTI incidence. Statistical analyses were conducted using SAS v. 9.4 software (SAS Institute, Inc, Cary NC).

Results Demographics Demographic and baseline patient characteristics are shown in Table 1. There were 276 consecutive patients identified between August 2012 and June 2017. No patients were excluded. The final study cohort included 138 women who underwent reconstruction before ERAS implementation and 138 women receiving reconstruction after ERAS

Table 1 e Baseline patient characteristics. Variable

Cohort Pre-ERAS, n ¼ 138

P value Post-ERAS, n ¼ 138

Age

50.9 (0.69)

45.5 (1.08)

BMI

29.3 (0.39)

29.0 (0.32)

Race 101 (76.52)

Black

25 (18.94)

24 (17.78)

Other

6 (4.55)

10 (7.41)

101 (74.81)

91 (65.94)

88 (63.77)

Smoking history

Current

0.60 0.61

White

Never

<0.001

0.81

3 (2.17)

2 (1.45)

44 (31.88)

48 (34.78)

History of chest wall radiation

80 (57.97)

89 (64.49)

0.27

History of chemotherapy

81 (58.70)

86 (62.32)

0.54

Chronic pain diagnosis

12 (8.70)

5 (3.62)

0.08

Chronic opioid use

11 (7.97)

4 (2.90)

0.06

COPD/asthma

10 (7.25)

15 (10.87)

0.29

Hypertension

31 (22.46)

35 (25.36)

0.57

Type 2 diabetes mellitus

13 (9.42)

11 (7.97)

0.67

Chronic kidney disease

0 (0)

3 (2.17)

0.25

Hypercoagulable disorder

0 (0)

2 (1.45)

0.50

Past

Data are represented as mean (SEM) or n (% of patients). P-values < 0.05 are in bold. BMI ¼ body mass index; COPD ¼ chronic obstructive pulmonary disease.

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Table 2 e Compliance data for ERAS protocol items. ERAS protocol item

Cohort Pre-ERAS, N ¼ 138

Post-ERAS, N ¼ 138

Preoperative counseling

0 (0%)

130 (94.2%)

Preoperative carbohydrate drink (ClearFast, 12 oz)

0 (0%)

124 (89.9%)*

0 (0%)

138 (100%)

Preoperative multimodal pain management Intraoperative multimodal pain management

51 (40.0%)

137 (99.3%)

Foley catheter removed on POD 2

19 (13.8%)

128 (92.8%)

Oral fluid intake on POD 0

20 (14.5%)

Discontinuation of IVFs on POD 0

94 (68.1%)*

2 (1.5%)

Ambulated on POD 2

60 (43.5%)*

56 (40.6%)

112 (81.2%)

Data are represented as n (% of patients) who completed protocol items. * n ¼ 1 (<1%) patient missing data in the post-ERAS cohort.

implementation. As mentioned previously, all patients who consented to microvascular breast reconstruction were enrolled in the ERAS pathway. Compliance data for ERAS protocol items that were available through retrospective chart review are shown in Table 2. Between both groups, the study included 419 flaps (143 bilateral). Patients in the post-ERAS group were significantly younger than patients in the pre-ERAS group (45.5  1.08 versus 50.9  0.69, P < 0.001). Otherwise, there were no group differences with regards to demographic or baseline patient characteristics. Of note, there were no differences in rates of chronic pain diagnoses between groups.

Reconstructive and intraoperative data Reconstructive and intraoperative data are shown in Table 3. Length of surgery was significantly longer in the pre-ERAS cohort compared with the post-ERAS cohort (592.5 min [IQR 469-649] versus 502.5 min [IQR 434-566]; P < 0.001). There were no significant group differences in the laterality of reconstructions. Similarly, there were no group differences with regards to timing of reconstruction in relation to mastectomy surgery. There was a significant difference in flap types (P ¼ 0.0004) with more single msTRAMs (25.4% versus 8.7%), double msTRAMs (9.4% versus 7.3%), and cases with one

Table 3 e Reconstructive and intraoperative data. Variable

Cohort Pre-ERAS, n ¼ 138

Surgery length

592.5 (469-649)

P value Post-ERAS, n ¼ 138 502.5 (434-566)

Reconstruction laterality

0.55

Unilateral

69 (50)

64 (46.38)

Bilateral

69 (50)

74 (53.62)

Reconstruction timing

0.15

Immediate

91 (65.94)

102 (73.91)

Delayed

47 (34.06)

36 (26.09) 0.0004

Flap type Single msTRAM

35 (25.4)

12 (8.7)

Single DIEP

31 (22.5)

52 (37.7)

Double msTRAM

13 (9.4)

10 (7.3)

Double DIEP

40 (29.0)

53 (38.4)

One msTRAM and one DIEP

16 (11.6)

11 (8.0)

Other

3 (2.2)

0 (0)

Liposomal bupivacaine infiltration

51 (37.0)

137 (99.3)

Abdominal wall mesh

56 (40.58)

Total intraoperative IVF, mL Total intraoperative opioid, mg OME

<0.001

38 (27.54)

<0.001 0.02 <0.001

4725 (3750-5600)

3475 (2850-4000)

205.85 (127-316.66)

204.43 (165.11-240)

0.64

150 (100-250)

175 (100-200)

0.46

EBL (mL) Data are represented as median (IQR) or n (% of patients). P-values < 0.05 are in bold.

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Table 4 e Postoperative outcomes. Outcome

Cohort Pre-ERAS, n ¼ 138

Hospital LOS, d Postoperative opioid dose, mg OME Pain score goal

4.0 (4.0-5.0) 297.3 (138.6-437.4) 0 (0-0)

Post-ERAS, n ¼ 138

Wilcoxon rank Sum P value

Multivariate ANCOVA P value*

<0.0001

0.87

<0.0001

<0.0001

0 (0-0)

0.71

0.33

4.0 (3.0-4.0) 57.3 (20.0-115.5)

Highest postoperative pain score 0-4 h

4.0 (1.5-6.0)

4.0 (0-5.0)

0.05

0.85

4-8 h

4.0 (1.0-6.0)

4.0 (0-7.0)

0.59

0.018

8-12 h

4.0 (2.0-6.0)

3.0 (0-6.0)

0.09

0.39

12-18 h

4.0 (2.0-6.0)

4.0 (2.0-6.0)

0.18

0.79

18-24 h

5.0 (3.0-7.0)

4.0 (0.0-7.0)

0.06

0.63

24-48 h

5.0 (4.0-7.0)

5.0 (4.0-7.0)

0.92

0.73

48-72 h

6.0 (4.0-8.0)

5.0 (3.0-8.0)

0.09

0.60

<0.0001

y y

PCA use

129 (93.5)

Duration of PCA use

62.0 (58.0-65.0)

29.5 (10.5-53.0)

0.07

Day of first ambulation

2.0 (2.0-3.0)

2.0 (2.0-2.0)

<0.0001

0.13

Day of PO fluid intake

1.0 (1.0-1.0)

0 (0-1.0)

<0.0001

<0.0001

Day of IVF discontinuation

3.0 (2.0-3.0)

1 (0-1.0)

<0.0001

<0.0001

Total postoperative IVF, mL Day of urinary catheter removal Need for catheter reinsertion

4561.0 (3269.5-5643.4) 3.0 (3.0-3.0) 3 (2.2)

4 (2.9)

909.6 (515.0-1952.3) 2.0 (2.0-2.0) 6 (4.4)

<0.0001

<0.0001

<0.0001

<0.0001

0.50

0.45

Data are represented as median (IQR) or n (% of patients). P-values < 0.05 are in bold. * P value from multivariate ANCOVA model after adjusting for group differences including age, length of surgery, use of liposomal bupivacaine, use of abdominal wall mesh, volume of intraoperative IVF administration, and flap procedure type. y P value not provided due to small sample size in post-ERAS cohort.

msTRAM and one DIEP in the pre-ERAS cohort (11.6% versus 8.0%) relative to the post-ERAS cohort. On the other hand, there were fewer cases of single DIEPs (22.5% versus 37.7%) and double DIEPs (29.0% versus 38.4%) in the pre-ERAS compared with the post-ERAS cohort. Intraoperative local anesthesia was administered more often in patients in the post-ERAS group (37.0% versus 99.3%, P < 0.001). A significantly higher proportion of patients had abdominal wall mesh before ERAS implementation (41% versus 28%, P ¼ 0.02). Intraoperative IVF administration was significantly higher in the pre-ERAS (4725 mL, IQR 3750-5600) cohort compared with the post-ERAS cohort (3475 mL, IQR 2850-4000, P < 0.001). Neither cumulative intraoperative opioid administration nor intraoperative EBL differed between groups.

Postoperative outcomes: univariate analysis Postoperative outcomes are shown in Table 4. Without controlling for variables, which were different between the groups, the univariate analysis demonstrated that cumulative postoperative opioid requirements were significantly lower in the post-ERAS cohort (57.3 OME [IQR 20.0-115.5] versus 297.3 OME [IQR 138.6-437.7], P < 0.0001). Similarly, the median hospital LOS was significantly shorter in the post-ERAS cohort (4.0 d, IQR 3.0-4.0) compared with the pre-ERAS cohort (4.0 d, IQR 4.0-5.0; P < 0.0001). Preoperative pain score goals were comparable

between groups. With regards to postoperative pain scores, patients in the post-ERAS group reported significantly less pain at the 0- to 4-h time interval (4.0 max pain score [IQR 0.0-5.0]) compared with the patients in the pre-ERAS group (4.0 max pain score [IQR 1.5-6.0], P ¼ 0.05). Almost all patients in the pre-ERAS cohort used PCAs (93.5%), whereas nearly none of the patients in the postERAS cohorts did so (2.9%, P < 0.0001). However, for patients requiring PCAs, median duration of PCA use was not significantly different between the two groups (P ¼ 0.07). Post-ERAS patients had shorter time to ambulation than pre-ERAS patients (median 2 d [IQR 2-2], mean  SEM days 2.1  0.05 versus median of 2 d [IQR 2-3], mean  SE days 2.5  0.12, Wilcoxon rank sum P < 0.0001). Patients in the pre-ERAS cohort had IVF discontinued significantly later (3 d, IQR 2-3) compared with patients enrolled in the postERAS cohort (1 d, IQR 0-1, P < 0.0001). Accordingly, patients in the post-ERAS cohort were administered a significantly lower volume of postoperative IVF (909.6 mL [IQR 515.0-1952.3] versus 4561.0 mL [IQR 3269.5-5643.4], P < 0.001). Day of PO intake was earlier in the post-ERAS cohort (0 d, IQR 0-1) compared with the pre-ERAS group (1 d, IQR 1-1, P < 0.0001). Urinary catheters were removed earlier in the post-ERAS cohort (2 d, IQR 2-2) compared with the pre-ERAS cohort (3 d, IQR 3-3, P < 0.0001). The proportion of patients needing urinary catheter reinsertion was not significantly different between the pre- and post-ERAS groups (2.2% versus 4.4%, P ¼ 0.50).

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Table 5 e Postoperative complications. Complication

Cohort

P value

Pre-ERAS, n ¼ 138

Post-ERAS, n ¼ 138

Hospital readmission, 30 d

15 (11.0)

16 (11.6)

1.0

11 (73.3)

9 (56.3)

0.46

Venous congestion

1 (6.7)

2 (12.5)

Seroma

2 (13.3)

Hematoma

3 (20.0)

2 (12.5)

0

0

d

1 (6.7)

4 (25.0)

0.33

Infection

Delayed wound healing Necrosis Return to OR, 30 d

0 (0)

1.0 0.23 0.65

15 (10.9)

16 (11.6)

1.0

Infection

4 (26.7)

0

0.04

Venous congestion

6 (40.0)

7 (43.8)

1.0

Seroma

2 (13.3)

0

0.23

Hematoma

5 (33.3)

8 (50.0)

0.47

Necrosis

3 (20.0)

3 (18.8)

1.0

3 (2.2)

4 (2.9)

1.0

0

1 (25.0)

3 (100)

3 (75.0)

UTI

3 (2.2)

9 (6.5)

0.14

AKI

5 (3.7)

7 (5.3)

0.57

0

1 (0.72)

1.0

28 (20.4)

19 (13.8)

0.15

8 (5.8)

3 (2.2)

0.22 1.0

Flap loss Partial Total

PE/DVT Superficial SSI, 90 d Native breast Breast flap

6 (4.4)

7 (5.1)

18 (13.1)

11 (8.0)

0.24

4 (2.9)

5 (3.6)

1.0

Native breast

1 (0.73)

0

0.50

Breast flap

1 (0.73)

0

0.50

Abdominal donor site

2 (1.5)

5 (3.6)

0.45

Abdominal donor site Deep SSI, 90 d

Data are represented as n (% of patients).

Postoperative outcomes: multivariate analysis

Postoperative complications

Postoperative outcomes, when controlling for variables that differed between the groups in multivariate analysis, are also depicted in Table 4. The difference in postoperative opioid use between the pre- and post-ERAS cohorts remained significant (P < 0.0001), even after adjusting for age, surgery length, intraoperative liposomal bupivacaine, abdominal wall mesh, and intraoperative IVF total. The same is true for day of IVF discontinuation (P < 0.0001), day of PO fluid intake (P < 0.0001), IVF postoperative total (P < 0.001), and day of urinary catheter removal (P < 0.0001). However, median hospital LOS (P ¼ 0.87) and day of ambulation (P ¼ 0.13) were not significantly different between pre- and post-ERAS cohorts after adjusting for covariates. With regards to postoperative pain scores, the difference in pain scores did not persist at 0 to 4 h when controlling for group differences. A multivariate analysis, controlling for covariates, did reveal that post-ERAS patients reported significantly less pain at the 4- to 8-h time interval (4.0 max pain score [IQR 1.0-6.0]) compared with the patients in the preERAS group (4.0 max pain score [IQR 0-7.0], P ¼ 0.018).

Postoperative complications are shown in Table 5. Of note, there were no significant differences in the rate of hospital readmission, return to OR, or flap loss (all P values ¼ 1.0). Similarly, there were no group differences in other complications including AKI, PE/DVT, or deep and superficial SSI. Of note, the incidence of UTIs increased threefold after ERAS implementation, although this did not reach statistical significance (2.2% versus 6.5%, P ¼ 0.14). When examining the pre- and post-ERAS groups combined, univariate logistic regression showed that catheter reinsertion was a univariate significant predictor of UTI (odds ratio ¼ 25.9, 95% confidence interval [CI] 5.8-115.1, P < 0.0001), whereas pre- and post-ERAS status were not (odds ratio ¼ 3.1, 95% CI 0.8-11.9, P ¼ 0.09). In a multivariate model containing both urinary catheter reinsertion and pre- and post-ERAS status, only catheter reinsertion was a significant predictor of UTI (odds ratio ¼ 24.0, 95% CI 5.2-110.3, P < 0.0001). Due to no patients having both catheter reinsertion and postoperative UTI in the pre-ERAS group, the interaction between catheter reinsertion and ERAS could not be tested. In addition, a subset analysis in the pre-ERAS group

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could not be conducted for the same reason. A univariate logistic regression model predicting UTI in the post-ERAS group demonstrates that the need for urinary catheter reinsertion is a significant predictor of the development of postoperative UTI (odds ratio ¼ 50.8, 95% CI 7.5-345.9, P < 0.0001). The width of the CIs is attributable to the low incidence of catheter reinsertions and UTIs.

Discussion A key component of ERAS pathway implementation is the evaluation of its impact on postoperative outcomes.2-6,12 Our study examines the effects of a comprehensive ERAS protocol on the largest cohort of patients undergoing abdominal-based free flap breast reconstruction at a single institution to date. Decreased hospital LOS is one of the most celebrated ERAS outcomes as it lowers healthcare costs and removes patients from the risks of the hospital setting.16 Using smaller cohorts of patients undergoing microvascular breast reconstruction, Batdorf et al. previously observed a mean reduction in hospital LOS, from 5.5 to 3.9 d, and Afonso et al. similarly observed a mean reduction in hospital LOS, from 5.0 to 4.0 d.9,10 Neither study showed an increase in postoperative complications, return to OR, or hospital readmissions with ERAS implementation, suggesting that ERAS protocol items that hasten recovery are not only effective but also safe. In contrast to these prior studies, we did not find a significant reduction in hospital LOS in the post-ERAS cohort when controlling for covariates.9,10 This suggests that the decreased LOS we observed with the ERAS protocol in our univariate analysis could be attributable to group differences, specifically in patient age and surgery length. Post-ERAS patients were significantly younger, on average. It has been demonstrated that hospital utilization and cost vary according to age, with younger patients generally experiencing shorter hospital LOS.17 In addition, patients in the post-ERAS cohort experienced shorter surgical length, and thus shorter duration of exposure to general anesthetics. These medications have commonly been linked to delayed ambulation and delayed return of bowel function, both of which may extend hospital LOS.15,18 Another possible explanation is that our pre-ERAS hospital LOS was already shorter than that of other groups, leaving less room for improvement after ERAS implementation. It may also be that, at some point, the reduction in hospital stay reaches a limit. Reduction in postoperative opioid requirements represents another success of ERAS pathway implementation across surgical specialities.2-4,9,10,19,20 Although opioids contribute to patient comfort and help reduce pain postoperatively, they are also accompanied by a wide array of adverse events ranging from nausea and vomiting to constipation, respiratory events, and even substance use disorders in the long term.18 These adverse events can slow progress related to spontaneous voiding and ambulation, key metrics required for discharge. The multimodal approach to pain management in ERAS protocols has helped to reduce reliance on opioids as the primary option for pain management. Indeed, in our cohort, we observed a significant decrease in postoperative opioid requirements even when controlling for group differences. This went hand-in-hand with a drastically smaller proportion of

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patients in the post-ERAS group requiring PCAs postoperatively. There was, however, no difference in duration of PCA use between pre- and post-ERAS for patients who required a PCA. This may be because, after a PCA is started, it may be difficult to discontinue; therefore, providers are more inclined to allow time for it to work before considering an oral opioid trial. A more appropriate protocol would be to taper PCA use while increasing the use of other multimodal medications with frequent pain score assessments for improvement. The reduction in overall opioid utilization may be attributed to our use of intraoperative TAP blocks and a multimodal nonnarcotic regimen. Several randomized controlled trials have demonstrated that TAP blocks reduce donor-site pain in patients undergoing abdominal-based reconstruction.13,21 The use of TAP blocks also likely facilitated multimodal nonnarcotic pain management directly because a single injection has been demonstrated to reduce morphine requirements for the first 48-h postoperatively.22 Although the cost of Exparel may be a limiting factor for some institutions, several studies in noneplastic surgery literature have found no difference in mean hospitalization costs between patients receiving PCAs and those receiving Exparel as part of multimodal analgesia.23 Furthermore, a recent cost analysis of TAP blocks with Exparel in microvascular reconstruction found no significant difference in hospital expenses between patients who did and did not receive TAP blocks.24 The relative reduction in postoperative opioid use in our study (72%) was higher than previously reported in the literature. This may be due to our diverse preoperative regimen of acetaminophen, celecoxib, and gabapentin. Lending credence to this hypothesis, Batdorf et al. premedicated with a similar regimen and observed a comparable reduction in postoperative opioid requirements (71%), unlike Afonso et al., who relied solely on ketorolac and saw a smaller (35%) reduction.9,10 Our protocol also uniquely uses gabapentin both pre- and post-operatively, which has been demonstrated to reduce postoperative narcotic requirements substantially.25-27 Taken together, these findings prove that a combination of nonopioid medications with different modalities of action alleviates pain most effectively.28-31 One possible explanation for the greater opioid requirement in the pre-ERAS cohort is that a significantly higher proportion of these patients required abdominal mesh placement during surgery. Although mesh use is associated with discomfort and pain, this is generally observed further out from surgery, as opposed to in the immediate postoperative period.32 In addition, results of our ANCOVA controlling for group differences accounted for the differential use of abdominal mesh pre- and post-ERAS, and the decrease in postoperative opioid requirements remained significant. Although it is important to reduce unnecessary opioid intake in the postoperative period, adequate pain management is vital to avoid adverse events such as impaired sleep, reduced physical mobility, and the development of hypersensitization and eventual chronic pain.33 Post-ERAS patients demonstrated lower pain score ratings at the 4- to 8-h interval postoperatively. For the remainder of the hospital stay, there were no differences in pain scores at any postoperative time interval. This suggests that this shift away from opioidcentered pain medication is not countered by inadequate pain management and increased patient suffering.

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j o u r n a l o f s u r g i c a l r e s e a r c h  o c t o b e r 2 0 1 9 ( 2 4 2 ) 2 7 6 e2 8 5

Similar to Batdorf et al., we noted a higher percentage of DIEP flaps (both single and double) in the post-ERAS cohort. This shift toward muscle-sparing techniques may have biased our primary outcomes, as DIEP flaps have been associated with decreased postoperative morphine requirements and reduced hospital LOS.34 Despite this, differences in postoperative opioid requirements persisted when controlling for group differences with flap procedure type among them. These findings similarly persisted when Batdorf et al. controlled for group difference and suggests that ERAS implementation alone decreases opioid requirements, irrespective of the invasiveness of flap dissection. Although previous studies have reported no increase in overall 30-d complication rates with ERAS implementation, we anecdotally observed a higher rate of postoperative UTIs in our post-ERAS cohort. Our study confirmed this finding, demonstrating a threefold increase in UTI incidence after ERAS implementation. That this rise in UTIs did not reach statistical significance may be attributed to the fact that we used strict NSQIP UTI criteria, while clinically diagnosed UTIs requiring antibiotic treatment may occur more commonly. These would be instances of UTI where patients were symptomatic (i.e., fever/chills, suprapubic pain, frequency, urgency) with suspect UAs (e.g., leukocyte esterase and nitrites, but not at threshold), without available urine culture to sufficiently meet NSQIP criteria.9 Examining other postoperative complications (Table 5), we did not see any rise to the same degree as the rate of UTIs. Given that UTIs are an important metric by which hospital quality of care is measured, and that they pose significant risk and discomfort to our patients, this finding merited further investigation. Given the risk of UTI with indwelling urinary catheters, ERAS guidelines call for early postoperative removal.35 Accordingly, patients in the post-ERAS cohort had catheters removed significantly earlier compared with those in the pre-ERAS cohort. One drawback of early urinary catheter removal, however, is postoperative UR requiring repeat catheterization.36,37 In our study, the rate of urinary catheter reinsertion for UR was higher in the post-ERAS group compared with the pre-ERAS group, although this, too, did not reach statistical significance. When examining this more closely, we found that urinary catheter reinsertion was a significant predictor of UTI in both the combined pre- and post-ERAS group as well as when looking at the post-ERAS group alone. Clearly, the relationship between urinary catheter management and UTIs is multifaceted; although early catheter removal has been demonstrated to reduce the risk of UTI, our findings indicate that this protocol item may also contribute to UR requiring repeat catheterization, and thus increased risk of UTI, in a key subset of patients. Given the extensive literature linking length of urinary catheterization to risk for UTI, it would be inappropriate to endorse prolonging catheterization for all patients.35 Rather, clinicians could take a more tailored approach to urinary catheter management based on a patient’s specific risk factors for UR.

approximately equally between two surgeons (52% and 48%). However, under the standardized ERAS pathway, postoperative management would have theoretically been the same despite a difference in surgeon. Although our study was retrospective, diligent documentation by two independent reviewers with frequent quality check of one another’s work ensured reliable data collection. Ultimately, we believe that none of these limitations is meaningful enough to prevent our work from adding to the current literature examining the effects of ERAS in abdominal-based free flap breast reconstruction.

Conclusions Our study uses the largest single-institution cohort to date to show that ERAS pathways improve certain aspects of recovery for patients undergoing abdominal-based microvascular breast reconstruction. Specifically, decreased postoperative opioid requirements were accompanied by no increase in complications and a slight reduction in pain scores in the early postoperative period. On the other hand, we failed to find a significant reduction in hospital LOS as has been reported in other studies of ERAS implementation in microvascular breast reconstruction. This may be attributed to more careful patient selection and a shift toward less invasive methods of flap harvest. Nonetheless, we believe our 5-y study provides further evidence that the ERAS protocol is an effective and sustainable perioperative care pathway in microvascular breast reconstruction.

Acknowledgment This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Authors’ contributions: B.S.-A. led all stages of project design, methodological setup, data acquisition, interpretation of data, and article preparation. E.H. contributed to methodological setup, data acquisition, interpretation of results, as well as article preparation. G.B. led data analysis and contributed to interpretation of the results. R.A. was involved with project design, interpretation of the results, and article preparation and subsequent revision. All the above was performed under direct supervision of the principal investigator, S.T H. S.T.H. was also directly involved in initial project design, interpretation of the data, article preparation, and final approval of the version to be submitted.

Disclosure The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article.

Limitations

Supplementary data An important limitation of this study is that one microsurgeon performed the majority of the post-ERAS breast reconstructions, whereas the pre-ERAS cases were split

Supplementary data to this article can be found online at https://doi.org/10.1016/j.jss.2019.04.062.

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