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The impact of an enhanced recovery after minimally invasive surgery program on opioid use in gynecologic oncology patients undergoing hysterectomy
YGYNO-977832; No. of pages: 7; 4C: Gynecologic Oncology xxx (xxxx) xxx
Contents lists available at ScienceDirect
Gynecologic Oncology journal homepage: www.elsevier.com/locate/ygyno
The impact of an enhanced recovery after minimally invasive surgery program on opioid use in gynecologic oncology patients undergoing hysterectomy☆ Erica Weston a, Margarita Noel b, Kara Douglas b, Kelsey Terrones b, Francis Grumbine b, Rebecca Stone a, Kimberly Levinson a,b,⁎ a b
The Kelly Gynecologic Oncology Service, Johns Hopkins University School of Medicine, Baltimore, MD, USA Greater Baltimore Medical Center, Towson, MD, USA
H I G H L I G H T S • • • •
An enhanced recovery protocol reduced inpatient post-operative opioid use after minimally invasive hysterectomy. An enhanced recovery after minimally invasive surgery protocol reduced intra-operative opioid use. Despite reductions in opioid use, post-operative pain scores were lower after enhanced recovery protocol implementation. Protocol compliance exceeded 80% for multimodal pain management interventions and was 75% overall.
a r t i c l e
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Article history: Received 5 January 2020 Accepted 31 January 2020 Available online xxxx Keywords: Enhanced recovery after surgery (ERAS) Opioids Minimally invasive hysterectomy Analgesia Pain management Post-operative care
a b s t r a c t Objectives. To evaluate the effects of an enhanced recovery after minimally invasive surgery (MIS-ERAS) protocol on opioid requirements and post-operative pain in patients undergoing minimally invasive hysterectomy on a gynecologic oncology service. Methods. For this retrospective study, opioid use (oral morphine equivalents (OME)) and post-operative pain scores were compared between patients undergoing minimally invasive hysterectomy pre and post MIS-ERAS protocol implementation. Patients with chronic opioid use or chronic pain were excluded. Opioid use and pain scores were compared between groups using Wilcoxon Rank Sum, Student's t-test, and multiple linear regression. Compliance and factors associated with opioid use and pain scores were assessed. Results. The MIS-ERAS cohort (n = 127) was compared to the historical cohort (n = 99) with no differences in patient demographic, clinical or surgical characteristics observed between groups. Median intra-operative and inpatient post-operative opioid use were lower among the MIS-ERAS cohort (12.0 vs 32.0 OME, p b .0001 and 20.0 vs 35.0 OME, p = .02, respectively). Pain scores among MIS-ERAS patients were also lower (mean 3.6 vs 4.1, p = .03). After controlling for age, BMI, operative time, length of stay, cancer diagnosis, and surgical approach, the MIS-ERAS cohort used 10.43 fewer OME intra-operatively (p b .001), 10.97 fewer OME post-operatively (p = .019) and reported pain scores 0.56 points lower than historical controls (p = .013). Compliance was ≥81% for multimodal analgesia elements and ≥75% overall. Conclusions. Enhanced recovery after minimally invasive surgery protocol implementation is an effective means to reduce opioid use, both in the intra-operative and post-operative phases of care, among gynecologic oncology patients undergoing minimally invasive hysterectomy. © 2020 Elsevier Inc. All rights reserved.
1. Introduction
☆ The findings of this manuscript were presented as a poster at the Society of Gynecologic Oncology Annual Meeting in Honolulu, Hawaii in March 17, 2019. ⁎ Corresponding author at: 600 N. Wolfe Street/Phipps 277, Baltimore, MD, USA. E-mail address: [email protected] (K. Levinson).
Enhanced recovery after surgery (ERAS) is a multifaceted approach to peri-operative care, designed to mitigate peri-operative stress and shorten surgical recovery time, and is standard of care at many centers [1,2]. These protocols aim to lower the physiologic stress response of surgery and shorten time to return to normal function by utilizing
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Please cite this article as: E. Weston, M. Noel, K. Douglas, et al., The impact of an enhanced recovery after minimally invasive surgery program on opioid use in gynecol..., Gynecologic Oncology, https://doi.org/10.1016/j.ygyno.2020.01.041
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E. Weston et al. / Gynecologic Oncology xxx (xxxx) xxx
components such as elimination of routine bowel preparation, physiologic euvolemia, early post-operative feeding, and multimodal pain management [1]. ERAS pain management protocols aim to minimize opioid consumption in order to reduce side effects of opioids such as constipation, sedation, and urinary retention, while achieving adequate pain control which, in turn, facilitates ambulation and return to normal functioning after surgery [3,4]. While ERAS protocols involve several different pre-operative, intraoperative, and post-operative interventions, multimodal pain management is a key component of ERAS programs [5], and includes preoperative administration of oral non-opioid analgesics, and postoperative scheduled dosing of acetaminophen, non-steroidal antiinflammatory agents (NSAIDs) and gabapentin [3,6,7]. ERAS protocols have been shown to decrease post-operative opioid consumption after laparotomy by 46% in gynecologic oncology patients; they similarly decrease post-operative pain scores [8] and improve patient satisfaction with pain control in benign gynecologic surgery patients [9]. ERAS programs have been most extensively evaluated after exploratory laparotomy in gynecologic oncology patients [2,8,10,11]. Few studies have investigated enhanced recovery after minimally invasive surgery (MIS-ERAS) programs in gynecologic oncology patients [9,12–15] and the data are limited in that they evaluate ERAS protocols that utilize regional analgesia [13], are restricted to patients undergoing laparoscopic bowel surgery [12], do not report on opioid use outcomes [9,15], or report limited or no compliance data with multimodal analgesia elements [14]. The addition of regional analgesia to an MIS-ERAS protocol adds cost without definitive benefit in MIS patients [3,16–18] and is an added barrier to protocol implementation. The assessment of protocol compliance is essential in order to assess the effectiveness of the interventions and is recommended by the ERAS Society [11]. In the era of the opioid epidemic, reducing exposure to opioid medications is key in reducing the potential for prolonged inappropriate opioid use after surgery [19]. Reducing inpatient opioid use in post-surgical patients is particularly imperative because inpatient opioid use is the strongest predictor of post-discharge opioid use in gynecologic oncology patients and other surgical cohorts [20,21]. While ERAS protocols significantly reduce inpatient opioid consumption for gynecologic oncology patients undergoing laparotomy [8,9] the impact of MIS-ERAS on opioid consumption among minimally invasive hysterectomy patients remains understudied. To bridge this gap, we evaluated the implementation of an MIS-ERAS program to determine its impact on inpatient intra-operative and post-operative opioid use and postoperative pain in gynecologic oncology patients after minimally invasive hysterectomy. We hypothesized that intra-operative and postoperative opioid use would be lower, and pain control maintained after the implementation of an MIS-ERAS program. 2. Methods 2.1. Study design This is a retrospective cohort study, with a historical control comparison group, which was approved by the Institutional Review Board at Greater Baltimore Medical Center, a 342-bed hospital. The MIS-ERAS cohort includes patients who underwent minimally invasive hysterectomy after implementation of a minimally invasive surgery specific ERAS protocol, while the historical control group includes patients who underwent surgery prior to ERAS implementation (pre-ERAS). 2.2. Enhanced recovery after surgery protocol An MIS-ERAS protocol was implemented for all women undergoing minimally invasive hysterectomy in the division of gynecologic oncology at our institution starting July 1, 2017. A multidisciplinary team consisting of anesthesiology, gynecologic oncology, nursing, and colorectal surgery designed this quality improvement initiative to improve
surgical recovery for patients undergoing minimally invasive surgery and exploratory laparotomy. The minimally invasive surgery ERAS protocol includes pre-operative, intra-operative, and post-operative interventions restricted to those relevant to recovery specifically from minimally invasive surgery (Fig. 1). The MIS-ERAS protocol was adopted for all minimally invasive hysterectomy patients operated on by one of the two gynecologic oncologists after the start date of July 1, 2017. Of note, the surgeons remained the same during the entire study period with no major changes in referral pattern or surgical volume. Both surgeons routinely admitted patients undergoing minimally invasive hysterectomy for 23-h observation both prior to and after the implementation of the ERAS protocol. Thus, length of stay was not anticipated to change with the implementation of ERAS and therefore was not a primary outcome in this study. 2.3. Inclusion and exclusion criteria Inclusion criteria for this retrospective cohort study were patients who had a minimally invasive hysterectomy (straight stick laparoscopic, single incision laparoscopic, or robotic assisted) with one of the two gynecologic oncologists in the division of gynecologic oncology during the 14 months immediately following the initiation of the MISERAS protocol (July 1, 2017 to September 4, 2018). Of note, only one of the two surgeons performed single incision laparoscopy during the study period. Patients who underwent minimally invasive hysterectomy during the 9 months prior to the MIS-ERAS protocol initiation (October 1, 2016 to June 30, 2017) were included as historical controls (pre MIS-ERAS). The pre MIS-ERAS group was restricted to this 9-month period due to a change in electronic medical record (EMR) in October 2016, making prior peri-operative data inaccessible. Patients with a history of chronic pain and/or chronic opioid use, defined as a documentation in the electronic health record medical history and/or the preoperative history and physical note (20 patients excluded), and those who underwent any other type of surgery, including those converted to exploratory laparotomy from a planned MIS approach, were excluded from the analysis. 2.4. Outcomes Our primary outcomes were intra-operative opioid use and inpatient post-operative opioid use. Intra-operative opioid use was defined as any opioid received from the anesthesia start time to the surgical stop time recorded in the EMR. Post-operative opioid use was defined as any opioid received from the surgical stop time recorded in the EMR until hospital discharge. All opioids were converted to oral morphine milligram equivalents (OME) using standard conversion tables [22]. The secondary outcome was mean post-operative pain score. Pain scores were obtained at routine intervals by nursing staff (at least every 4 h and as needed on post-operative day one) and recorded as numeric scores (0–10 scale) in the EMR from surgery stop time until hospital discharge. All outcome data and demographic, clinical and surgical characteristics were abstracted from the EMR and were subject to a data field consistency and range check for verification. Compliance with the MIS-ERAS protocol was formally assessed starting 1/17/2018 through the implementation of two EMR checklists 1) the pre-operative checklist completed by nursing staff assessing whether the patient received pre-operative education, patient warming, and chlorhexidine wipes, and 2) the anesthesia checklist completed by anesthesia providers assessing type of anesthesia (total intravenous anesthesia with propofol or a combination of intravenous and volatile anesthetic gas), use of anti-emetic prophylaxis (yes/no), fluid management per guidelines (yes/no), use of multimodal pain management (yes/no), antiemetic prophylaxis (yes/no), and venous thromboembolism chemoprophylaxis (yes/no). Compliance with multimodal analgesia use pre, intra, and post-operatively was further assessed via EMR review.
Please cite this article as: E. Weston, M. Noel, K. Douglas, et al., The impact of an enhanced recovery after minimally invasive surgery program on opioid use in gynecol..., Gynecologic Oncology, https://doi.org/10.1016/j.ygyno.2020.01.041
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Fig. 1. Enhanced recovery after minimally invasive surgery protocol details MAC = minimum alveolar concentration, PO = by mouth, IV = intravenous ⁎ Patient reported history of postoperative nausea/vomiting or a history of motion sickness. † Extended venous thrombo-embolism (VTE) prophylaxis was prescribed at the provider's discretion for 14 days for patients with known malignancy after sentinel lymph node dissection, and 28 days for patients after full pelvic or pelvic and para-aortic lymph node dissections or for patients with a history of VTE or risk of VTE for other reasons (i.e. history of unprovoked VTE).
2.5. Statistical analysis Patient age, race, and BMI, operative time, hospital length of stay, cancer diagnosis (benign or premalignant/malignant), and surgical approach (robotic/laparoscopic/single incision laparoscopic) were compared between the pre and post MIS-ERAS protocol implementation groups using Chi squared, Fisher's Exact, and Student's t-test for dichotomous and continuous variables respectively. The underlying distributions of the outcome variables were evaluated. To compare intra-operative and post-operative opioid use between the MIS-ERAS and pre-ERAS historical controls Wilcoxon Rank Sum analysis was used, and group medians are presented, due to the non-normal distribution of the opioid use data. To compare inpatient pain scores between the cohorts Student's t-test was used, and means are presented as the pain score data were normally distributed. Linear regression was used to quantify the effects of ERAS group status on intra-operative and post-operative opioid use, to obtain
confidence intervals for those effects, and to control for potential confounders. The adequate sample size allowed for the use of parametric tests despite the non-normally distributed opioid use data. Both the non-parametric Wilcoxon Rank Sum and parametric linear regression results are presented for comparison. The following potential confounding factors, that could arise over time were included in the multiple linear regression models: patient characteristics, surgical approach (laparoscopic/robotic assisted/single incision laparoscopic), procedure length, hospital length of stay, cancer diagnosis (benign/malignant). Simple and multiple linear regression were also used to evaluate the effect of ERAS protocol implementation on average inpatient pain scores, controlling for the above patient, clinical, and surgical factors. The associations between patient demographic, clinical, and surgical factors and intra-operative and post-operative opioid use and average inpatient pain scores were also evaluated using simple and multiple linear regression in these models. Protocol compliance was assessed by proportion compliant with protocol individual items.
Please cite this article as: E. Weston, M. Noel, K. Douglas, et al., The impact of an enhanced recovery after minimally invasive surgery program on opioid use in gynecol..., Gynecologic Oncology, https://doi.org/10.1016/j.ygyno.2020.01.041
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Sample size was fixed due to the retrospective nature of this analysis. Two tailed P values of b0.05 were considered statistically significant. All analyses were performed using Stata 15 software (StataCorp, College Station, Texas). 3. Results The pre-ERAS group included 99 patients who underwent minimally invasive hysterectomy prior to the implementation of the MIS-ERAS protocol, and the MIS-ERAS group included 127 patients who underwent minimally invasive hysterectomy after the implementation of the protocol. Overall, the mean age of participants was 58 years, mean BMI was obese at 32 kg/m2, the majority of participants identified as Caucasian/White (72%), and half had a diagnosed malignancy (50%). The most common surgical approach was robotic assisted laparoscopic hysterectomy (43.4%), while 33.6% of surgeries were performed with traditional laparoscopy, and 23% of surgeries were performed via single incision laparoscopy. The average operative time was 169 min. The preERAS and MIS-ERAS groups did not differ on any examined baseline demographic or surgical characteristics including age, body mass index (BMI), race, diagnosis of malignancy, surgical approach, operative time, or use of local anesthetic intra-operatively. Hospital length of stay also remained constant during the study period (Table 1). Compliance with the tracked MIS-ERAS protocol items are displayed in Table 2. Pre-operatively, celecoxib was administered to 82.8% of patients, while 94.5% received gabapentin and 94.5% acetaminophen. Intra-operatively, 95.8% percent of patients received multimodal analgesia and 99% received local anesthetic injection into port-sites. Postoperatively, 92.9% of patients received acetaminophen and 81.9% of patients were administered either ibuprofen or ketorolac per protocol recommendations (Table 2). Prior to MIS-ERAS protocol implementation five patients received pre-operative multimodal analgesia (three patients received all medications, two patients received acetaminophen alone). After protocol implementation, patients more often received post-operative acetaminophen (66.7 vs 92.9%, p b .001), ketorolac (19.2% vs 45.5% p = .047), or either ketorolac or ibuprofen (71.7 vs 81.9% p = .07). Patients had their pain assessed a median of 13 times (IQR 10-17) during the post-operative period. Median intra-operative opioid use was significantly lower in the MIS-ERAS group, 32 OME for the pre-ERAS group and 12 OME for the MIS-ERAS group (p b .0001) (Fig. 2A). Median opioid use was also lower in the immediate post-operative period (between the end of surgery and discharge), with a median of 35 OME pre-ERAS and 20 OME in the MIS-ERAS group (p = .02) (Fig. 2B). Despite using fewer opioids
Table 1 Demographic and clinical characteristics of gynecologic oncology patients undergoing minimally invasive hysterectomy pre and post enhanced recovery after surgery (ERAS) protocol implementation. Characteristic Age (y) BMI (kg/m2) Race Caucasian/White Black/African American Asian Other/decline to answer Diagnosis Malignancy Benign/pre-malignant Surgical approach Robot assisted Laparoscopic Single incision laparoscopic Operative time (min) Hospital length of stay (hours)
Pre-ERAS (n = 99)
Post-ERAS (n = 127)
p value
58.83 31.91
±11.92 ± 9.13
58.25 32.61
±12.88 ±9.54
0.73 0.58
73 25 1 0
(73.7) (25.3) (1) (0)
90 29 4 4
(70.9) (22.9) (3.1) (3.1)
0.47
46 53
(46.5) (53.5)
67 60
(52.8) (47.2)
0.35
(44.1) (36.2) (19.7) ±60.58 ±9.7
0.36
42 30 27 173.12 26.70
Data are mean ± SD, n (%), or median (IQR).
(42.4) (30.3) (27.3) ±66.91 ±13.9
56 46 25 165.69 26.33
0.38 0.82
Table 2 Enhanced recovery after minimally invasive surgery protocol compliance. Item
Compliant Missing
Pre-operative checklista (n = 84) Patient education Patient warming Chlorhexidine wipes Pre-operative medications administered (n = 127)
63 (75.0) 74 (88.1) 81 (96.4)
Celecoxib PO Gabapentin PO Acetaminophen PO Intraoperative anesthesia checklistb (n = 71) TIVA or combination TIVA and volatile gas anesthesia Fluid management plan in placec Anti-emetic prophylaxis Multi-modal pain management Venous thromboembolism chemoprophylaxis prior to incision Intra-operative local anesthetic usedd (n = 127)
105 (82.8) 120 (94.5) 120 (94.5) 65 (91.6) 67 (94.4) 68 (95.8) 68 (95.8)
3 (3.6) 8 (9.5) 2 (2.4) 0 (0) 0 (0) 0 (0) 2 (2.8) 0 (0) 2 (2.8) 1 (1.4)
69 (97.2)
0 (0)
126 (99.2)
0 (0)
Post-operative multimodal analgesia administered (n = 127) Acetaminophen PO Either ibuprofen PO or ketorolac IV Ibuprofen PO Ketorolac IV
118 (92.9) 104 (81.9) 64 (50.4) 58 (45.7)
0 (0) 0 (0) 0 (0) 0 (0)
TIVA = total intravenous anesthesia (i.e. propofol), PO = by mouth, IV = intravenous. Data are n (%). a Completed by pre-operative nursing staff with the above items to monitor compliance with pre-operative interventions, implemented 1/17/18. Only includes patients with checklists activated in the electronic medical record. b Completed by anesthesia staff with the above items to monitor compliance with intraoperative interventions, implemented 1/17/18. Only includes patients with checklists activated in the electronic medical record. c Defined as documenting a fluid management plan on the anesthesia checklist. d Infiltration of incision site pre or post-incision.
both intra-operatively and post-operatively, patients who underwent surgery after MIS-ERAS implementation reported lower inpatient post-operative pain scores (mean = 4.1 vs 3.6, 95% CI for difference: 0.06–0.97, p = .03) (Fig. 2C). After controlling for age, BMI, procedure length, hospital length of stay, cancer diagnosis (benign/malignant), and surgical approach (laparoscopic/robotic assisted/single incision laparoscopic), patients who had surgery after MIS-ERAS protocol implementation used 10.43 fewer OME intra-operatively (95% CI: −13.74, −7.12, p b .001), and 10.97 fewer OME post-operatively (95% CI: −20.09, −1.84, p = .019). The difference in mean post-operative pain score among patients after MIS-ERAS implementation was 0.56 lower than the mean in the preERAS group (95% CI for difference: −0.97, −0.09, p = .013) (Table 3). After controlling for all other variables in the model, age, operative time, and cancer diagnosis also remained associated with intraoperative opioid use, though the magnitude of these effects were small (Table 3). For every 10 year increase in age, patients received 2.5 fewer OME of opioids intra-operatively (p b .001), for every 30 min increase in procedure length, patients received an additional 1.2 OME of opioids intra-operatively (p = .005), and patients with a malignancy received 4.7 OME fewer opioids intra-operatively than those with benign pathology (p = .019). Similar patterns were observed for the relationship between post-operative opioid use with both age and length of stay in the multiple linear regression model. After controlling for all other variables in the model, for every 10 year increase in age, patients used 11 fewer OME of opioids post-operatively (p b .001). For every 10 h increase in length of stay, patients used 10.6 more MME of opioids post-operatively (p b .001) (Table 3). Older age was also associated with lower average post-operative pain scores, after controlling for
Please cite this article as: E. Weston, M. Noel, K. Douglas, et al., The impact of an enhanced recovery after minimally invasive surgery program on opioid use in gynecol..., Gynecologic Oncology, https://doi.org/10.1016/j.ygyno.2020.01.041
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Fig. 2. Differences in median intra-operative and post-operative opioid use and mean pain scores before and after enhanced recovery after minimally invasive surgery protocol implementation MIS-ERAS = enhanced recovery after minimally invasive surgery A) Median intra-operative opioid use during minimally invasive hysterectomy pre and post MISERAS protocol Implementation, *p b .0001. B) Median post-operative inpatient opioids consumed pre and post MIS-ERAS protocol Implementation, ⁎p = .02. C) Mean inpatient postoperative pain scores pre and post implementation of an MIS-ERAS protocol, ⁎p = .03.
all other factors in the model. For every 10 year increase in age, average pain scores were 0.4 points lower (p b .001) (Table 3). Neither intraoperative nor post-operative opioid consumption differed by surgical approach by either simple or multiple linear regression. 4. Discussion In the era of the opioid epidemic, with a public health focus on opioid reduction [23,24], surgical specialties are obligated to explore means to reduce opioid medication utilization. Our study adds to the growing body of literature demonstrating that ERAS protocols are effective at inpatient opioid use reduction. Our findings support the adoption of MISERAS protocols in gynecologic oncology, and more broadly in minimally invasive gynecologic surgery. Patient satisfaction also remains at the
forefront of healthcare and, importantly, our results demonstrate that an MIS-ERAS protocol not only reduces opioid consumption, but adequately maintains (and even slightly improves) pain control in this setting. These findings are a novel contribution to the literature, in that while ERAS protocols have been shown to reduce post-operative opioids in patients undergoing laparotomy [3,8], this protocol uniquely demonstrates reduced opioid consumption and lower pain scores among gynecologic oncology patients undergoing minimally invasive hysterectomy, does not use epidural or TAP block, and tracks compliance with multimodal analgesia protocol items. In the setting of MIS surgery with regional analgesia, Chapman and colleagues demonstrated decreased opioid use post-operatively in a cohort of gynecologic oncology patients who underwent MIS after the implementation of an ERAS protocol,
Please cite this article as: E. Weston, M. Noel, K. Douglas, et al., The impact of an enhanced recovery after minimally invasive surgery program on opioid use in gynecol..., Gynecologic Oncology, https://doi.org/10.1016/j.ygyno.2020.01.041
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Table 3 Simple and multiple linear regressions examining the relationships between ERAS cohort status, patient demographics, and surgical characteristics and the outcomes of intra-operative opioid use, post-operative opioid use, and post-operative pain scores. Unadjustedc
Intra-operative opioid use (OME) ERAS status (pre-ERAS vs ERAS) Age (years) BMI (mg/kg2) Operative time (min) Hospital length of stay (hours) Cancer diagnosis (benign vs malignant) Surgical approacha Robotic assisted Single incision laparoscopic Post-operative opioid use (OME) ERAS status (pre-ERAS vs ERAS) Age (years) BMI (mg/kg2) Operative time (min) Hospital length of stay (hours) Cancer diagnosis (benign vs malignant) Surgical approachb Robotic assisted Single incision laparoscopic Post-operative pain scores (mean) ERAS status (pre-ERAS vs ERAS) Age (years) BMI (mg/kg2) Operative time (min) Hospital length of stay (hours) Cancer diagnosis (benign vs malignant) Surgical approachb Robotic assisted Single incision laparoscopic
Adjustedd
Slopea
(95% CI)
P
Slopea
(95% CI)
P
−11.45 −0.30 0.09 0.03 0.09 −7.47
(−14.93, −7.97) (−0.45, −0.16) -(0.12, 0.29) (0.004, 0.06) (−0.07, 0.25) (−11.10, −3.85)
b0.001 b0.001 0.40 0.03 0.26 b0.001
−10.43 −0.25 0.07 0.04 0.09 −4.73
(−13.74, −7.12) (−0.41, −0.09) (−0.12, 0.26) (0.01, 0.07) (−0.06, 0.24) (−8.66, −0.80)
b0.001 0.002 0.50 0.005 0.24 0.019
−0.53 3.96
(−4.82, 3.77) (−1.10, 9.01)
0.81 0.12
−1.74 1.66
(−6.09, 2.60) (−2.86, 6.18)
0.43 0.47
−12.07 −0.98 0.35 0.10 0.97 −15.60
(−22.18, −1.96) (−1.37, −0.60) (−0.20, 0.90) (0.02, 0.18) (0.56, 1.38) (−25.54, −5.66)
0.019 b0.001 0.21 0.012 b0.001 0.002
−10.97 −1.10 0.06 0.08 1.06 −7.43
(−20.09, −1.84) (−1.53, −0.67) (0.46, 0.59) (−0.001, 0.17) (0.65, 1.47) (−18.29, 3.42)
0.019 b0.001 0.81 0.053 b0.001 0.18
4.55 6.14
(−7.11, 16.22) (−7.59, 19.88)
0.44 0.38
1.22 −1.07
(−10.76, 13.21) (−13.55, 11.41)
0.84 0.87
−0.52 −0.04 0.03 0.001 −0.001 −0.15
(−0.97, −0.06) (−0.06, −0.02) (0.01, 0.06) (−0.002, 0.005) (−0.02, 0.02) (−0.60, 0.31)
0.03 b0.001 0.005 0.48 0.92 0.53
−0.56 −0.04 0.02 0.0002 0.001 0.19
(−0.97, −0.09) (−0.06, −0.02) (−0.003, 0.05) (−0.004, 0.004) (−0.02, 0.02) (−0.33, 0.71)
0.013 b0.001 0.08 0.93 0.93 0.48
0.55 0.65
(0.03, 1.07) (0.04, 1.26)
0.04 0.04
0.39 0.40
(−0.19, 0.96) (−0.20, 0.99)
0.08 0.19
ERAS, Enhanced Recovery After Surgery; CI, Confidence Interval; BMI, body mass index; OME, oral morphine milligram equivalents. a Change in outcome (intra-operative opioid use, post-operative opioid use, and post-operative pain scores respectively) per 1 unit change in ERAS cohort status, age, BMI, operative time, hospital length of stay, cancer diagnosis, or surgical approach. b Laparoscopic (reference group) versus robotic assisted or single incision laparoscopic. c N = 226 for unadjusted models, N = 219 for adjusted models due to 7 patients with missing BMI data. d Mutually adjusted for all characteristics listed under each outcome.
however, the majority of patients (58%) had TAP block in the ERAS cohort while no patients had this intervention in the historical control cohort [13]. While opioid use was lower in the ERAS group in this prior study [13], the reduction could be attributed to the use of TAP block alone and limits generalizability to centers which include this procedure in their MIS-ERAS protocols. Despite protocolization of post-operative pain medication administration, we observed an improvement in subjective pain management, which adds support for the use of ERAS protocols in MIS patients. Our study shows that even in the setting of not performing a TAP block procedure, both intra-operative and post-operative opioid use was decreased with an ERAS protocol, and patients reported lower pain scores in the MIS-ERAS cohort compared to historical controls in our study. The finding of post-operative pain reduction, despite using fewer opioids, is consistent with data from laparotomy patients [8]. Limitations of our study include our retrospective design, which restricts the available data on post-operative recovery outcomes. Specifically, we are unable to accurately compare return of bowel function, ambulation, or patient satisfaction with our retrospective design, which are important outcomes when evaluating post-operative recovery. Additionally, by limiting our cohort to patients without chronic pain or chronic opioid use we limit generalizability to this group of patients who may specifically benefit from multimodal pain control. Generalizability may also be limited based on similarities or differences in the patient demographics in this sample. The use of a historical control also limits our findings given there could be unmeasured patient, clinical, or surgical factors that differed over time. Strengths of our study include the stability of our patient population, hospital length of stay, surgical approaches, operative time, and use of
local anesthetic over time with no differences noted between the preERAS and MIS-ERAS cohorts. Additionally, there were no major changes in hospital or division policy with regards to post-operative care during the study period, which emphasizes the strength of the observed impact of the MIS-ERAS protocol on opioid consumption and pain management in our study. Importantly, protocol compliance was high (81% or above) for multimodal analgesia elements and 75% or above overall. However, formal compliance tracking with the pre-operative nursing and anesthesia checklists was not implemented until six months after MISERAS protocol implementation with differing compliance in the use of these checklists (Table 2), thus limiting the amount of data available for this assessment. Additional compliance monitoring tools have since been implemented including a post-anesthesia care unit and a post-operative checklist to further assess protocol compliance moving forward. Hospital length of stay remained constant in our MIS-ERAS cohort compared to historical controls as the standard procedure for 23-h observation after minimally invasive hysterectomy was not altered with the implementation of the ERAS protocol. Length of stay was unaffected likely due to the short length of stay (with typical discharge on postoperative day one) that was already standard of care, and routine practice, in our center. While prior published data suggests that an ERAS protocol may reduce hospital length of stay among MIS patients [13], our MIS-ERAS protocol was not designed to reduce hospital length of stay, and discharge on the same day of surgery is not currently part of routine practice at our center. However, these findings invite future research on surgical care milestones such as opioid utilization and/or pain scores to determine patient eligibility for same-day hospital discharge. Nonetheless, our findings of decreased opioid consumption and lower
Please cite this article as: E. Weston, M. Noel, K. Douglas, et al., The impact of an enhanced recovery after minimally invasive surgery program on opioid use in gynecol..., Gynecologic Oncology, https://doi.org/10.1016/j.ygyno.2020.01.041
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pain scores in the MIS-ERAS cohort, while maintaining an established baseline short hospital length of stay, provide support for the benefits of ERAS protocols in gynecologic MIS patients. Though not yet proven, the implications of our findings may reach even beyond the inpatient stay to reduce opioid use in the full postoperative recovery period. Despite the risks associated with opioid use (including diversion of unused pills from prescriptions) [25,26], opioids are commonly used to treat post-operative pain. By improving inpatient pain control with multimodal analgesia, there is potential to also reduce post-discharge opioid use (as inpatient opioid use has been shown to predict post-discharge opioid use in general [21] and gynecologic surgical patients [20]). In conclusion, ERAS protocols not only improve outcomes in laparotomy patients but also reduce opioid consumption in patients undergoing minimally invasive gynecologic surgery. Our high compliance with protocol elements demonstrates that MIS-ERAS is an accessible intervention that could be implemented to improve post-operative recovery among gynecologic MIS patients. Looking ahead, leveraging ERAS multimodal analgesia protocols to design a precision medicine approach to post-discharge pain control could have a broad impact on opioid prescribing practices in surgical patients. Author contributions Erica Weston, MD MHS (corresponding author): Research study design, data collection, manuscript preparation and editing and approval of submitted manuscript. Margarita Noel, MS: Data collection, manuscript revising, and approval of submitted manuscript. Kara Douglas, CRNA: Research study design, manuscript revising, and approval of submitted manuscript. Kelsey Terrones, MS FNP: Research study design, manuscript revising, and approval of submitted manuscript. Francis Grumbine, MD: Research study design, manuscript revising, and approval of submitted manuscript. Rebecca Stone, MD MS: Research study design, manuscript revising, and approval of submitted manuscript. Kimberly Levinson, MD MPH: Research study design, manuscript revising, and approval of submitted manuscript. Funding The authors received no funding to complete this research. Declaration of competing interest The authors have no conflicts of interest to disclose and received no funding to complete this research. References [1] E. Miralpeix, A.M. Nick, L.A. Meyer, et al., A call for new standard of care in perioperative gynecologic oncology practice: impact of enhanced recovery after surgery (ERAS) programs, Gynecol. Oncol. 141 (2) (2016) 371–378, https://doi.org/10. 1016/j.ygyno.2016.02.019. [2] G. Nelson, E. Kalogera, S.C. Dowdy, Enhanced recovery pathways in gynecologic oncology, Gynecol. Oncol. 135 (3) (2014) 586–594, https://doi.org/10.1016/j.ygyno. 2014.10.006. [3] E. Kalogera, S.C. Dowdy, Enhanced recovery pathway in gynecologic surgery: improving outcomes through evidence-based medicine, Obstet. Gynecol. Clin. N. Am. 43 (3) (2016) 551–573, https://doi.org/10.1016/j.ogc.2016.04.006. [4] American College of Obstetricians and Gynecologists’’ Committee on Gynecologic Practice, Perioperative pathways: enhanced recovery after surgery, Obstet. Gynecol. 132 (3) (2018) 120–130, https://doi.org/10.1111/jth.12999.
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[5] E.C. Wick, M.C. Grant, C.L. Wu, Postoperativemultimodal analgesia pain management with nonopioid analgesics and techniques, A Review. JAMA Surg. 152 (7) (2017) 691–697, https://doi.org/10.1001/jamasurg.2017.0898. [6] E. Maund, C. McDaid, S. Rice, K. Wright, B. Jenkins, N. Woolacott, Paracetamol and selective and non-selective non-steroidal anti-inflammatory drugs for the reduction in morphine-related side-effects after major surgery: a systematic review, Br. J. Anaesth. 106 (3) (2011) 292–297, https://doi.org/10.1093/bja/aeq406. [7] L. Ajori, L. Nazari, M.M. Mazloomfard, Z. Amiri, EVects of gabapentin on postoperative pain, nausea and vomiting after abdominal hysterectomy: a double blind randomized clinical trial, Arch. Gynecol. Obstet. 285 (3) (2012) 677–682, https://doi. org/10.1007/s00404-011-2023-6. [8] J.E. Bergstrom, M.E. Scott, Y. 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Gynecol. 128 (3) (2016) 457–466, https://doi.org/10.1097/AOG.0000000000001555. [15] E. Lambaudie, A. De Nonneville, C. Brun, et al., Enhanced recovery after surgery program in gynaecologic oncological surgery in a minimally invasive techniques expert center, BMC Surg. 17 (1) (2017) 1–9, https://doi.org/10.1186/s12893-017-0332-9. [16] G. Nelson, A.D. Altman, A. Nick, et al., Guidelines for pre- and intra-operative care in gynecologic/oncology surgery: Enhanced Recovery after Surgery (ERAS®) society recommendations - part I, Gynecol. Oncol. 140 (2) (2016) 313–322, https://doi. org/10.1016/j.ygyno.2015.11.015. [17] C.M. Johnson, G.E.H. Makai, A systematic review of perioperative opioid management for minimally invasive hysterectomy, J. Minim. Invasive Gynecol. 26 (2) (2019) 233–243, https://doi.org/10.1016/j.jmig.2018.08.024. [18] M. Wong, S. Morris, K. Wang, K. Simpson, Managing postoperative pain after minimally invasive gynecologic surgery in the era of the opioid epidemic, J. Minim. 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Contents lists available at ScienceDirect
Gynecologic Oncology journal homepage: www.elsevier.com/locate/ygyno
The impact of an enhanced recovery after minimally invasive surgery program on opioid use in gynecologic oncology patients undergoing hysterectomy☆ Erica Weston a, Margarita Noel b, Kara Douglas b, Kelsey Terrones b, Francis Grumbine b, Rebecca Stone a, Kimberly Levinson a,b,⁎ a b
The Kelly Gynecologic Oncology Service, Johns Hopkins University School of Medicine, Baltimore, MD, USA Greater Baltimore Medical Center, Towson, MD, USA
H I G H L I G H T S • • • •
An enhanced recovery protocol reduced inpatient post-operative opioid use after minimally invasive hysterectomy. An enhanced recovery after minimally invasive surgery protocol reduced intra-operative opioid use. Despite reductions in opioid use, post-operative pain scores were lower after enhanced recovery protocol implementation. Protocol compliance exceeded 80% for multimodal pain management interventions and was 75% overall.
a r t i c l e
i n f o
Article history: Received 5 January 2020 Accepted 31 January 2020 Available online xxxx Keywords: Enhanced recovery after surgery (ERAS) Opioids Minimally invasive hysterectomy Analgesia Pain management Post-operative care
a b s t r a c t Objectives. To evaluate the effects of an enhanced recovery after minimally invasive surgery (MIS-ERAS) protocol on opioid requirements and post-operative pain in patients undergoing minimally invasive hysterectomy on a gynecologic oncology service. Methods. For this retrospective study, opioid use (oral morphine equivalents (OME)) and post-operative pain scores were compared between patients undergoing minimally invasive hysterectomy pre and post MIS-ERAS protocol implementation. Patients with chronic opioid use or chronic pain were excluded. Opioid use and pain scores were compared between groups using Wilcoxon Rank Sum, Student's t-test, and multiple linear regression. Compliance and factors associated with opioid use and pain scores were assessed. Results. The MIS-ERAS cohort (n = 127) was compared to the historical cohort (n = 99) with no differences in patient demographic, clinical or surgical characteristics observed between groups. Median intra-operative and inpatient post-operative opioid use were lower among the MIS-ERAS cohort (12.0 vs 32.0 OME, p b .0001 and 20.0 vs 35.0 OME, p = .02, respectively). Pain scores among MIS-ERAS patients were also lower (mean 3.6 vs 4.1, p = .03). After controlling for age, BMI, operative time, length of stay, cancer diagnosis, and surgical approach, the MIS-ERAS cohort used 10.43 fewer OME intra-operatively (p b .001), 10.97 fewer OME post-operatively (p = .019) and reported pain scores 0.56 points lower than historical controls (p = .013). Compliance was ≥81% for multimodal analgesia elements and ≥75% overall. Conclusions. Enhanced recovery after minimally invasive surgery protocol implementation is an effective means to reduce opioid use, both in the intra-operative and post-operative phases of care, among gynecologic oncology patients undergoing minimally invasive hysterectomy. © 2020 Elsevier Inc. All rights reserved.
1. Introduction
☆ The findings of this manuscript were presented as a poster at the Society of Gynecologic Oncology Annual Meeting in Honolulu, Hawaii in March 17, 2019. ⁎ Corresponding author at: 600 N. Wolfe Street/Phipps 277, Baltimore, MD, USA. E-mail address: [email protected] (K. Levinson).
Enhanced recovery after surgery (ERAS) is a multifaceted approach to peri-operative care, designed to mitigate peri-operative stress and shorten surgical recovery time, and is standard of care at many centers [1,2]. These protocols aim to lower the physiologic stress response of surgery and shorten time to return to normal function by utilizing
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components such as elimination of routine bowel preparation, physiologic euvolemia, early post-operative feeding, and multimodal pain management [1]. ERAS pain management protocols aim to minimize opioid consumption in order to reduce side effects of opioids such as constipation, sedation, and urinary retention, while achieving adequate pain control which, in turn, facilitates ambulation and return to normal functioning after surgery [3,4]. While ERAS protocols involve several different pre-operative, intraoperative, and post-operative interventions, multimodal pain management is a key component of ERAS programs [5], and includes preoperative administration of oral non-opioid analgesics, and postoperative scheduled dosing of acetaminophen, non-steroidal antiinflammatory agents (NSAIDs) and gabapentin [3,6,7]. ERAS protocols have been shown to decrease post-operative opioid consumption after laparotomy by 46% in gynecologic oncology patients; they similarly decrease post-operative pain scores [8] and improve patient satisfaction with pain control in benign gynecologic surgery patients [9]. ERAS programs have been most extensively evaluated after exploratory laparotomy in gynecologic oncology patients [2,8,10,11]. Few studies have investigated enhanced recovery after minimally invasive surgery (MIS-ERAS) programs in gynecologic oncology patients [9,12–15] and the data are limited in that they evaluate ERAS protocols that utilize regional analgesia [13], are restricted to patients undergoing laparoscopic bowel surgery [12], do not report on opioid use outcomes [9,15], or report limited or no compliance data with multimodal analgesia elements [14]. The addition of regional analgesia to an MIS-ERAS protocol adds cost without definitive benefit in MIS patients [3,16–18] and is an added barrier to protocol implementation. The assessment of protocol compliance is essential in order to assess the effectiveness of the interventions and is recommended by the ERAS Society [11]. In the era of the opioid epidemic, reducing exposure to opioid medications is key in reducing the potential for prolonged inappropriate opioid use after surgery [19]. Reducing inpatient opioid use in post-surgical patients is particularly imperative because inpatient opioid use is the strongest predictor of post-discharge opioid use in gynecologic oncology patients and other surgical cohorts [20,21]. While ERAS protocols significantly reduce inpatient opioid consumption for gynecologic oncology patients undergoing laparotomy [8,9] the impact of MIS-ERAS on opioid consumption among minimally invasive hysterectomy patients remains understudied. To bridge this gap, we evaluated the implementation of an MIS-ERAS program to determine its impact on inpatient intra-operative and post-operative opioid use and postoperative pain in gynecologic oncology patients after minimally invasive hysterectomy. We hypothesized that intra-operative and postoperative opioid use would be lower, and pain control maintained after the implementation of an MIS-ERAS program. 2. Methods 2.1. Study design This is a retrospective cohort study, with a historical control comparison group, which was approved by the Institutional Review Board at Greater Baltimore Medical Center, a 342-bed hospital. The MIS-ERAS cohort includes patients who underwent minimally invasive hysterectomy after implementation of a minimally invasive surgery specific ERAS protocol, while the historical control group includes patients who underwent surgery prior to ERAS implementation (pre-ERAS). 2.2. Enhanced recovery after surgery protocol An MIS-ERAS protocol was implemented for all women undergoing minimally invasive hysterectomy in the division of gynecologic oncology at our institution starting July 1, 2017. A multidisciplinary team consisting of anesthesiology, gynecologic oncology, nursing, and colorectal surgery designed this quality improvement initiative to improve
surgical recovery for patients undergoing minimally invasive surgery and exploratory laparotomy. The minimally invasive surgery ERAS protocol includes pre-operative, intra-operative, and post-operative interventions restricted to those relevant to recovery specifically from minimally invasive surgery (Fig. 1). The MIS-ERAS protocol was adopted for all minimally invasive hysterectomy patients operated on by one of the two gynecologic oncologists after the start date of July 1, 2017. Of note, the surgeons remained the same during the entire study period with no major changes in referral pattern or surgical volume. Both surgeons routinely admitted patients undergoing minimally invasive hysterectomy for 23-h observation both prior to and after the implementation of the ERAS protocol. Thus, length of stay was not anticipated to change with the implementation of ERAS and therefore was not a primary outcome in this study. 2.3. Inclusion and exclusion criteria Inclusion criteria for this retrospective cohort study were patients who had a minimally invasive hysterectomy (straight stick laparoscopic, single incision laparoscopic, or robotic assisted) with one of the two gynecologic oncologists in the division of gynecologic oncology during the 14 months immediately following the initiation of the MISERAS protocol (July 1, 2017 to September 4, 2018). Of note, only one of the two surgeons performed single incision laparoscopy during the study period. Patients who underwent minimally invasive hysterectomy during the 9 months prior to the MIS-ERAS protocol initiation (October 1, 2016 to June 30, 2017) were included as historical controls (pre MIS-ERAS). The pre MIS-ERAS group was restricted to this 9-month period due to a change in electronic medical record (EMR) in October 2016, making prior peri-operative data inaccessible. Patients with a history of chronic pain and/or chronic opioid use, defined as a documentation in the electronic health record medical history and/or the preoperative history and physical note (20 patients excluded), and those who underwent any other type of surgery, including those converted to exploratory laparotomy from a planned MIS approach, were excluded from the analysis. 2.4. Outcomes Our primary outcomes were intra-operative opioid use and inpatient post-operative opioid use. Intra-operative opioid use was defined as any opioid received from the anesthesia start time to the surgical stop time recorded in the EMR. Post-operative opioid use was defined as any opioid received from the surgical stop time recorded in the EMR until hospital discharge. All opioids were converted to oral morphine milligram equivalents (OME) using standard conversion tables [22]. The secondary outcome was mean post-operative pain score. Pain scores were obtained at routine intervals by nursing staff (at least every 4 h and as needed on post-operative day one) and recorded as numeric scores (0–10 scale) in the EMR from surgery stop time until hospital discharge. All outcome data and demographic, clinical and surgical characteristics were abstracted from the EMR and were subject to a data field consistency and range check for verification. Compliance with the MIS-ERAS protocol was formally assessed starting 1/17/2018 through the implementation of two EMR checklists 1) the pre-operative checklist completed by nursing staff assessing whether the patient received pre-operative education, patient warming, and chlorhexidine wipes, and 2) the anesthesia checklist completed by anesthesia providers assessing type of anesthesia (total intravenous anesthesia with propofol or a combination of intravenous and volatile anesthetic gas), use of anti-emetic prophylaxis (yes/no), fluid management per guidelines (yes/no), use of multimodal pain management (yes/no), antiemetic prophylaxis (yes/no), and venous thromboembolism chemoprophylaxis (yes/no). Compliance with multimodal analgesia use pre, intra, and post-operatively was further assessed via EMR review.
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Fig. 1. Enhanced recovery after minimally invasive surgery protocol details MAC = minimum alveolar concentration, PO = by mouth, IV = intravenous ⁎ Patient reported history of postoperative nausea/vomiting or a history of motion sickness. † Extended venous thrombo-embolism (VTE) prophylaxis was prescribed at the provider's discretion for 14 days for patients with known malignancy after sentinel lymph node dissection, and 28 days for patients after full pelvic or pelvic and para-aortic lymph node dissections or for patients with a history of VTE or risk of VTE for other reasons (i.e. history of unprovoked VTE).
2.5. Statistical analysis Patient age, race, and BMI, operative time, hospital length of stay, cancer diagnosis (benign or premalignant/malignant), and surgical approach (robotic/laparoscopic/single incision laparoscopic) were compared between the pre and post MIS-ERAS protocol implementation groups using Chi squared, Fisher's Exact, and Student's t-test for dichotomous and continuous variables respectively. The underlying distributions of the outcome variables were evaluated. To compare intra-operative and post-operative opioid use between the MIS-ERAS and pre-ERAS historical controls Wilcoxon Rank Sum analysis was used, and group medians are presented, due to the non-normal distribution of the opioid use data. To compare inpatient pain scores between the cohorts Student's t-test was used, and means are presented as the pain score data were normally distributed. Linear regression was used to quantify the effects of ERAS group status on intra-operative and post-operative opioid use, to obtain
confidence intervals for those effects, and to control for potential confounders. The adequate sample size allowed for the use of parametric tests despite the non-normally distributed opioid use data. Both the non-parametric Wilcoxon Rank Sum and parametric linear regression results are presented for comparison. The following potential confounding factors, that could arise over time were included in the multiple linear regression models: patient characteristics, surgical approach (laparoscopic/robotic assisted/single incision laparoscopic), procedure length, hospital length of stay, cancer diagnosis (benign/malignant). Simple and multiple linear regression were also used to evaluate the effect of ERAS protocol implementation on average inpatient pain scores, controlling for the above patient, clinical, and surgical factors. The associations between patient demographic, clinical, and surgical factors and intra-operative and post-operative opioid use and average inpatient pain scores were also evaluated using simple and multiple linear regression in these models. Protocol compliance was assessed by proportion compliant with protocol individual items.
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Sample size was fixed due to the retrospective nature of this analysis. Two tailed P values of b0.05 were considered statistically significant. All analyses were performed using Stata 15 software (StataCorp, College Station, Texas). 3. Results The pre-ERAS group included 99 patients who underwent minimally invasive hysterectomy prior to the implementation of the MIS-ERAS protocol, and the MIS-ERAS group included 127 patients who underwent minimally invasive hysterectomy after the implementation of the protocol. Overall, the mean age of participants was 58 years, mean BMI was obese at 32 kg/m2, the majority of participants identified as Caucasian/White (72%), and half had a diagnosed malignancy (50%). The most common surgical approach was robotic assisted laparoscopic hysterectomy (43.4%), while 33.6% of surgeries were performed with traditional laparoscopy, and 23% of surgeries were performed via single incision laparoscopy. The average operative time was 169 min. The preERAS and MIS-ERAS groups did not differ on any examined baseline demographic or surgical characteristics including age, body mass index (BMI), race, diagnosis of malignancy, surgical approach, operative time, or use of local anesthetic intra-operatively. Hospital length of stay also remained constant during the study period (Table 1). Compliance with the tracked MIS-ERAS protocol items are displayed in Table 2. Pre-operatively, celecoxib was administered to 82.8% of patients, while 94.5% received gabapentin and 94.5% acetaminophen. Intra-operatively, 95.8% percent of patients received multimodal analgesia and 99% received local anesthetic injection into port-sites. Postoperatively, 92.9% of patients received acetaminophen and 81.9% of patients were administered either ibuprofen or ketorolac per protocol recommendations (Table 2). Prior to MIS-ERAS protocol implementation five patients received pre-operative multimodal analgesia (three patients received all medications, two patients received acetaminophen alone). After protocol implementation, patients more often received post-operative acetaminophen (66.7 vs 92.9%, p b .001), ketorolac (19.2% vs 45.5% p = .047), or either ketorolac or ibuprofen (71.7 vs 81.9% p = .07). Patients had their pain assessed a median of 13 times (IQR 10-17) during the post-operative period. Median intra-operative opioid use was significantly lower in the MIS-ERAS group, 32 OME for the pre-ERAS group and 12 OME for the MIS-ERAS group (p b .0001) (Fig. 2A). Median opioid use was also lower in the immediate post-operative period (between the end of surgery and discharge), with a median of 35 OME pre-ERAS and 20 OME in the MIS-ERAS group (p = .02) (Fig. 2B). Despite using fewer opioids
Table 1 Demographic and clinical characteristics of gynecologic oncology patients undergoing minimally invasive hysterectomy pre and post enhanced recovery after surgery (ERAS) protocol implementation. Characteristic Age (y) BMI (kg/m2) Race Caucasian/White Black/African American Asian Other/decline to answer Diagnosis Malignancy Benign/pre-malignant Surgical approach Robot assisted Laparoscopic Single incision laparoscopic Operative time (min) Hospital length of stay (hours)
Pre-ERAS (n = 99)
Post-ERAS (n = 127)
p value
58.83 31.91
±11.92 ± 9.13
58.25 32.61
±12.88 ±9.54
0.73 0.58
73 25 1 0
(73.7) (25.3) (1) (0)
90 29 4 4
(70.9) (22.9) (3.1) (3.1)
0.47
46 53
(46.5) (53.5)
67 60
(52.8) (47.2)
0.35
(44.1) (36.2) (19.7) ±60.58 ±9.7
0.36
42 30 27 173.12 26.70
Data are mean ± SD, n (%), or median (IQR).
(42.4) (30.3) (27.3) ±66.91 ±13.9
56 46 25 165.69 26.33
0.38 0.82
Table 2 Enhanced recovery after minimally invasive surgery protocol compliance. Item
Compliant Missing
Pre-operative checklista (n = 84) Patient education Patient warming Chlorhexidine wipes Pre-operative medications administered (n = 127)
63 (75.0) 74 (88.1) 81 (96.4)
Celecoxib PO Gabapentin PO Acetaminophen PO Intraoperative anesthesia checklistb (n = 71) TIVA or combination TIVA and volatile gas anesthesia Fluid management plan in placec Anti-emetic prophylaxis Multi-modal pain management Venous thromboembolism chemoprophylaxis prior to incision Intra-operative local anesthetic usedd (n = 127)
105 (82.8) 120 (94.5) 120 (94.5) 65 (91.6) 67 (94.4) 68 (95.8) 68 (95.8)
3 (3.6) 8 (9.5) 2 (2.4) 0 (0) 0 (0) 0 (0) 2 (2.8) 0 (0) 2 (2.8) 1 (1.4)
69 (97.2)
0 (0)
126 (99.2)
0 (0)
Post-operative multimodal analgesia administered (n = 127) Acetaminophen PO Either ibuprofen PO or ketorolac IV Ibuprofen PO Ketorolac IV
118 (92.9) 104 (81.9) 64 (50.4) 58 (45.7)
0 (0) 0 (0) 0 (0) 0 (0)
TIVA = total intravenous anesthesia (i.e. propofol), PO = by mouth, IV = intravenous. Data are n (%). a Completed by pre-operative nursing staff with the above items to monitor compliance with pre-operative interventions, implemented 1/17/18. Only includes patients with checklists activated in the electronic medical record. b Completed by anesthesia staff with the above items to monitor compliance with intraoperative interventions, implemented 1/17/18. Only includes patients with checklists activated in the electronic medical record. c Defined as documenting a fluid management plan on the anesthesia checklist. d Infiltration of incision site pre or post-incision.
both intra-operatively and post-operatively, patients who underwent surgery after MIS-ERAS implementation reported lower inpatient post-operative pain scores (mean = 4.1 vs 3.6, 95% CI for difference: 0.06–0.97, p = .03) (Fig. 2C). After controlling for age, BMI, procedure length, hospital length of stay, cancer diagnosis (benign/malignant), and surgical approach (laparoscopic/robotic assisted/single incision laparoscopic), patients who had surgery after MIS-ERAS protocol implementation used 10.43 fewer OME intra-operatively (95% CI: −13.74, −7.12, p b .001), and 10.97 fewer OME post-operatively (95% CI: −20.09, −1.84, p = .019). The difference in mean post-operative pain score among patients after MIS-ERAS implementation was 0.56 lower than the mean in the preERAS group (95% CI for difference: −0.97, −0.09, p = .013) (Table 3). After controlling for all other variables in the model, age, operative time, and cancer diagnosis also remained associated with intraoperative opioid use, though the magnitude of these effects were small (Table 3). For every 10 year increase in age, patients received 2.5 fewer OME of opioids intra-operatively (p b .001), for every 30 min increase in procedure length, patients received an additional 1.2 OME of opioids intra-operatively (p = .005), and patients with a malignancy received 4.7 OME fewer opioids intra-operatively than those with benign pathology (p = .019). Similar patterns were observed for the relationship between post-operative opioid use with both age and length of stay in the multiple linear regression model. After controlling for all other variables in the model, for every 10 year increase in age, patients used 11 fewer OME of opioids post-operatively (p b .001). For every 10 h increase in length of stay, patients used 10.6 more MME of opioids post-operatively (p b .001) (Table 3). Older age was also associated with lower average post-operative pain scores, after controlling for
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Fig. 2. Differences in median intra-operative and post-operative opioid use and mean pain scores before and after enhanced recovery after minimally invasive surgery protocol implementation MIS-ERAS = enhanced recovery after minimally invasive surgery A) Median intra-operative opioid use during minimally invasive hysterectomy pre and post MISERAS protocol Implementation, *p b .0001. B) Median post-operative inpatient opioids consumed pre and post MIS-ERAS protocol Implementation, ⁎p = .02. C) Mean inpatient postoperative pain scores pre and post implementation of an MIS-ERAS protocol, ⁎p = .03.
all other factors in the model. For every 10 year increase in age, average pain scores were 0.4 points lower (p b .001) (Table 3). Neither intraoperative nor post-operative opioid consumption differed by surgical approach by either simple or multiple linear regression. 4. Discussion In the era of the opioid epidemic, with a public health focus on opioid reduction [23,24], surgical specialties are obligated to explore means to reduce opioid medication utilization. Our study adds to the growing body of literature demonstrating that ERAS protocols are effective at inpatient opioid use reduction. Our findings support the adoption of MISERAS protocols in gynecologic oncology, and more broadly in minimally invasive gynecologic surgery. Patient satisfaction also remains at the
forefront of healthcare and, importantly, our results demonstrate that an MIS-ERAS protocol not only reduces opioid consumption, but adequately maintains (and even slightly improves) pain control in this setting. These findings are a novel contribution to the literature, in that while ERAS protocols have been shown to reduce post-operative opioids in patients undergoing laparotomy [3,8], this protocol uniquely demonstrates reduced opioid consumption and lower pain scores among gynecologic oncology patients undergoing minimally invasive hysterectomy, does not use epidural or TAP block, and tracks compliance with multimodal analgesia protocol items. In the setting of MIS surgery with regional analgesia, Chapman and colleagues demonstrated decreased opioid use post-operatively in a cohort of gynecologic oncology patients who underwent MIS after the implementation of an ERAS protocol,
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E. Weston et al. / Gynecologic Oncology xxx (xxxx) xxx
Table 3 Simple and multiple linear regressions examining the relationships between ERAS cohort status, patient demographics, and surgical characteristics and the outcomes of intra-operative opioid use, post-operative opioid use, and post-operative pain scores. Unadjustedc
Intra-operative opioid use (OME) ERAS status (pre-ERAS vs ERAS) Age (years) BMI (mg/kg2) Operative time (min) Hospital length of stay (hours) Cancer diagnosis (benign vs malignant) Surgical approacha Robotic assisted Single incision laparoscopic Post-operative opioid use (OME) ERAS status (pre-ERAS vs ERAS) Age (years) BMI (mg/kg2) Operative time (min) Hospital length of stay (hours) Cancer diagnosis (benign vs malignant) Surgical approachb Robotic assisted Single incision laparoscopic Post-operative pain scores (mean) ERAS status (pre-ERAS vs ERAS) Age (years) BMI (mg/kg2) Operative time (min) Hospital length of stay (hours) Cancer diagnosis (benign vs malignant) Surgical approachb Robotic assisted Single incision laparoscopic
Adjustedd
Slopea
(95% CI)
P
Slopea
(95% CI)
P
−11.45 −0.30 0.09 0.03 0.09 −7.47
(−14.93, −7.97) (−0.45, −0.16) -(0.12, 0.29) (0.004, 0.06) (−0.07, 0.25) (−11.10, −3.85)
b0.001 b0.001 0.40 0.03 0.26 b0.001
−10.43 −0.25 0.07 0.04 0.09 −4.73
(−13.74, −7.12) (−0.41, −0.09) (−0.12, 0.26) (0.01, 0.07) (−0.06, 0.24) (−8.66, −0.80)
b0.001 0.002 0.50 0.005 0.24 0.019
−0.53 3.96
(−4.82, 3.77) (−1.10, 9.01)
0.81 0.12
−1.74 1.66
(−6.09, 2.60) (−2.86, 6.18)
0.43 0.47
−12.07 −0.98 0.35 0.10 0.97 −15.60
(−22.18, −1.96) (−1.37, −0.60) (−0.20, 0.90) (0.02, 0.18) (0.56, 1.38) (−25.54, −5.66)
0.019 b0.001 0.21 0.012 b0.001 0.002
−10.97 −1.10 0.06 0.08 1.06 −7.43
(−20.09, −1.84) (−1.53, −0.67) (0.46, 0.59) (−0.001, 0.17) (0.65, 1.47) (−18.29, 3.42)
0.019 b0.001 0.81 0.053 b0.001 0.18
4.55 6.14
(−7.11, 16.22) (−7.59, 19.88)
0.44 0.38
1.22 −1.07
(−10.76, 13.21) (−13.55, 11.41)
0.84 0.87
−0.52 −0.04 0.03 0.001 −0.001 −0.15
(−0.97, −0.06) (−0.06, −0.02) (0.01, 0.06) (−0.002, 0.005) (−0.02, 0.02) (−0.60, 0.31)
0.03 b0.001 0.005 0.48 0.92 0.53
−0.56 −0.04 0.02 0.0002 0.001 0.19
(−0.97, −0.09) (−0.06, −0.02) (−0.003, 0.05) (−0.004, 0.004) (−0.02, 0.02) (−0.33, 0.71)
0.013 b0.001 0.08 0.93 0.93 0.48
0.55 0.65
(0.03, 1.07) (0.04, 1.26)
0.04 0.04
0.39 0.40
(−0.19, 0.96) (−0.20, 0.99)
0.08 0.19
ERAS, Enhanced Recovery After Surgery; CI, Confidence Interval; BMI, body mass index; OME, oral morphine milligram equivalents. a Change in outcome (intra-operative opioid use, post-operative opioid use, and post-operative pain scores respectively) per 1 unit change in ERAS cohort status, age, BMI, operative time, hospital length of stay, cancer diagnosis, or surgical approach. b Laparoscopic (reference group) versus robotic assisted or single incision laparoscopic. c N = 226 for unadjusted models, N = 219 for adjusted models due to 7 patients with missing BMI data. d Mutually adjusted for all characteristics listed under each outcome.
however, the majority of patients (58%) had TAP block in the ERAS cohort while no patients had this intervention in the historical control cohort [13]. While opioid use was lower in the ERAS group in this prior study [13], the reduction could be attributed to the use of TAP block alone and limits generalizability to centers which include this procedure in their MIS-ERAS protocols. Despite protocolization of post-operative pain medication administration, we observed an improvement in subjective pain management, which adds support for the use of ERAS protocols in MIS patients. Our study shows that even in the setting of not performing a TAP block procedure, both intra-operative and post-operative opioid use was decreased with an ERAS protocol, and patients reported lower pain scores in the MIS-ERAS cohort compared to historical controls in our study. The finding of post-operative pain reduction, despite using fewer opioids, is consistent with data from laparotomy patients [8]. Limitations of our study include our retrospective design, which restricts the available data on post-operative recovery outcomes. Specifically, we are unable to accurately compare return of bowel function, ambulation, or patient satisfaction with our retrospective design, which are important outcomes when evaluating post-operative recovery. Additionally, by limiting our cohort to patients without chronic pain or chronic opioid use we limit generalizability to this group of patients who may specifically benefit from multimodal pain control. Generalizability may also be limited based on similarities or differences in the patient demographics in this sample. The use of a historical control also limits our findings given there could be unmeasured patient, clinical, or surgical factors that differed over time. Strengths of our study include the stability of our patient population, hospital length of stay, surgical approaches, operative time, and use of
local anesthetic over time with no differences noted between the preERAS and MIS-ERAS cohorts. Additionally, there were no major changes in hospital or division policy with regards to post-operative care during the study period, which emphasizes the strength of the observed impact of the MIS-ERAS protocol on opioid consumption and pain management in our study. Importantly, protocol compliance was high (81% or above) for multimodal analgesia elements and 75% or above overall. However, formal compliance tracking with the pre-operative nursing and anesthesia checklists was not implemented until six months after MISERAS protocol implementation with differing compliance in the use of these checklists (Table 2), thus limiting the amount of data available for this assessment. Additional compliance monitoring tools have since been implemented including a post-anesthesia care unit and a post-operative checklist to further assess protocol compliance moving forward. Hospital length of stay remained constant in our MIS-ERAS cohort compared to historical controls as the standard procedure for 23-h observation after minimally invasive hysterectomy was not altered with the implementation of the ERAS protocol. Length of stay was unaffected likely due to the short length of stay (with typical discharge on postoperative day one) that was already standard of care, and routine practice, in our center. While prior published data suggests that an ERAS protocol may reduce hospital length of stay among MIS patients [13], our MIS-ERAS protocol was not designed to reduce hospital length of stay, and discharge on the same day of surgery is not currently part of routine practice at our center. However, these findings invite future research on surgical care milestones such as opioid utilization and/or pain scores to determine patient eligibility for same-day hospital discharge. Nonetheless, our findings of decreased opioid consumption and lower
Please cite this article as: E. Weston, M. Noel, K. Douglas, et al., The impact of an enhanced recovery after minimally invasive surgery program on opioid use in gynecol..., Gynecologic Oncology, https://doi.org/10.1016/j.ygyno.2020.01.041
E. Weston et al. / Gynecologic Oncology xxx (xxxx) xxx
pain scores in the MIS-ERAS cohort, while maintaining an established baseline short hospital length of stay, provide support for the benefits of ERAS protocols in gynecologic MIS patients. Though not yet proven, the implications of our findings may reach even beyond the inpatient stay to reduce opioid use in the full postoperative recovery period. Despite the risks associated with opioid use (including diversion of unused pills from prescriptions) [25,26], opioids are commonly used to treat post-operative pain. By improving inpatient pain control with multimodal analgesia, there is potential to also reduce post-discharge opioid use (as inpatient opioid use has been shown to predict post-discharge opioid use in general [21] and gynecologic surgical patients [20]). In conclusion, ERAS protocols not only improve outcomes in laparotomy patients but also reduce opioid consumption in patients undergoing minimally invasive gynecologic surgery. Our high compliance with protocol elements demonstrates that MIS-ERAS is an accessible intervention that could be implemented to improve post-operative recovery among gynecologic MIS patients. Looking ahead, leveraging ERAS multimodal analgesia protocols to design a precision medicine approach to post-discharge pain control could have a broad impact on opioid prescribing practices in surgical patients. Author contributions Erica Weston, MD MHS (corresponding author): Research study design, data collection, manuscript preparation and editing and approval of submitted manuscript. Margarita Noel, MS: Data collection, manuscript revising, and approval of submitted manuscript. Kara Douglas, CRNA: Research study design, manuscript revising, and approval of submitted manuscript. Kelsey Terrones, MS FNP: Research study design, manuscript revising, and approval of submitted manuscript. Francis Grumbine, MD: Research study design, manuscript revising, and approval of submitted manuscript. Rebecca Stone, MD MS: Research study design, manuscript revising, and approval of submitted manuscript. Kimberly Levinson, MD MPH: Research study design, manuscript revising, and approval of submitted manuscript. Funding The authors received no funding to complete this research. Declaration of competing interest The authors have no conflicts of interest to disclose and received no funding to complete this research. References [1] E. Miralpeix, A.M. Nick, L.A. Meyer, et al., A call for new standard of care in perioperative gynecologic oncology practice: impact of enhanced recovery after surgery (ERAS) programs, Gynecol. Oncol. 141 (2) (2016) 371–378, https://doi.org/10. 1016/j.ygyno.2016.02.019. [2] G. Nelson, E. Kalogera, S.C. Dowdy, Enhanced recovery pathways in gynecologic oncology, Gynecol. Oncol. 135 (3) (2014) 586–594, https://doi.org/10.1016/j.ygyno. 2014.10.006. [3] E. Kalogera, S.C. Dowdy, Enhanced recovery pathway in gynecologic surgery: improving outcomes through evidence-based medicine, Obstet. Gynecol. Clin. N. Am. 43 (3) (2016) 551–573, https://doi.org/10.1016/j.ogc.2016.04.006. [4] American College of Obstetricians and Gynecologists’’ Committee on Gynecologic Practice, Perioperative pathways: enhanced recovery after surgery, Obstet. Gynecol. 132 (3) (2018) 120–130, https://doi.org/10.1111/jth.12999.
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