key: cord-0869088-av6s3xvw
authors: Peng, Terrance; Shemanski, Kimberly A.; Ding, Li; David, Elizabeth A.; Kim, Anthony W.; Kim, Michael; Lieu, Dustin K.; Wightman, Sean C.; Zhao, Jasmine; Atay, Scott M.
title: Enhanced Recovery After Surgery Protocol Minimizes Intensive Care Unit Utilization and Improves Outcomes Following Pulmonary Resection
date: 2021-08-04
journal: World J Surg
DOI: 10.1007/s00268-021-06259-1
sha: a020abb6a82cee1cd6f7a84341dee5d003c847d2
doc_id: 869088
cord_uid: av6s3xvw

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols have been associated with improved postoperative outcomes but require further validation in thoracic surgery. This study evaluated outcomes of patients undergoing pulmonary resection before and after implementation of an ERAS protocol. METHODS: Electronic medical records were queried for all patients undergoing pulmonary resection between April 2017 and April 2019. Patients were grouped into pre- and post-ERAS cohorts based on dates of operation. The ERAS protocol prioritized early mobilization, limited invasive monitoring, euvolemia, and non-narcotic analgesia. Primary outcome measures included intensive care unit (ICU) utilization, postoperative pain metrics, and perioperative morbidity. Regression analyses were performed to identify predictors of morbidity. Subgroup analyses were performed by pulmonary risk profile and surgical approach. RESULTS: A total of 64 pre- and 67 post-ERAS patients were included in the study. ERAS implementation was associated with reduced postoperative ICU admission (pre: 65.6% vs. post: 19.4%, p < 0.0001), shorter ICU median length of stay (LOS) (pre: 1 vs. post: 0, p < 0.0001), and decreased opioid usage measured by median morphine milligram equivalents (pre: 40.5 vs. post: 20.0, p < 0.0001). Post-ERAS patients also reported lower visual analog scale (VAS) pain scores on postoperative days (POD) 1 and 2 (pre: 6.3/5.6 vs. post: 5.3/4.2, p = 0.04/0.01) as well as average VAS pain score over POD0-2 (pre: 6.2 vs. post: 5.2, p = 0.005). CONCLUSIONS: Implementation of an ERAS protocol for pulmonary resection, which dictated reduced ICU admissions, did not increase major postoperative morbidity. Additionally, ERAS-enrolled patients reported improved postoperative pain control despite decreased opioid utilization. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00268-021-06259-1.

The first iteration of an enhanced recovery after surgery (ERAS) protocol led to decreased intensive care unit (ICU) and overall length of stay (LOS), employing many facets of Terrance Peng and Kimberly A. Shemanski contributed equally to the creation and submission of this manuscript. modern protocols, such as preoperative patient and family education, early extubation, and early mobilization [1] . Early protocols utilizing ERAS verbiage focused on colorectal surgery but were quickly implemented across surgical disciplines [2, 3] . While specifics of the protocols differ across specialties and institutions, the goal is to create a multidisciplinary, evidence-based approach to optimizing perioperative patient care and improving outcomes [4] [5] [6] . This includes an emphasis on minimally invasive surgery (MIS), non-narcotic analgesia, and early mobilization.

Similar protocols have been advantageous for patients undergoing pulmonary resection, utilizing techniques such as shortened preoperative fasting periods, thoracic epidural or subarachnoid analgesia, and intercostal nerve blockades [7] [8] [9] [10] . Numerous clinical benefits have been reported following protocol implementation, including but not limited to decreased postoperative pulmonary complications, shortened LOS, and reduced opioid usage [7] [8] [9] . In addition to improving postoperative outcomes, ERAS protocols have also been shown to significantly reduce hospital costs [8, 11] . ERAS protocols remain largely institution-specific in the USA, with variability in outcomes when implemented for thoracic surgery [12] . Consequently, further research is required to support the development of consensus ERAS guidelines in thoracic surgery and further optimize perioperative care.

The objective of this study was to evaluate outcomes of patients undergoing pulmonary resection before and after implementation of an ERAS protocol at a single academic institution. We hypothesized that employing an ERAS protocol would lead to decreased resource utilization, including ICU admissions, as well as improved postoperative pain management with reduced opioid requirements.

Electronic medical records were queried for all patients undergoing anatomic lung resection between April 2017 and April 2019. The institutional ERAS protocol was rolled out at the midpoint of the study in April 2018. Patients were organized into pre-and post-ERAS groups based on date of operation. All post-ERAS patients were enrolled in the ERAS protocol. There was no transitional period after introduction of the institutional ERAS protocol, and all surgeons immediately and unanimously participated in its use. Exclusion criteria included incomplete data sets, extended resections (pneumonectomy), or non-resectional operations. Consistent with modalities presented in previous literature, the ERAS protocol prioritized early mobility, limited invasive monitoring, euvolemia, and nonnarcotic analgesia, including intraoperative regional blocks instead of thoracic epidurals [7-9, 11, 12] . For minimally invasive approaches, regional blocks were administered at the start of the operation, typically extending one level superior to the highest port site and one level inferior to the lowest port site. The complete institutional protocol is described in Online Resource 1.

Descriptive statistics were performed for demographic variables. Primary outcome measures included ICU utilization, perioperative pain metrics, and perioperative complications. Logistic and linear regression analyses were performed to compare groups. Beta estimates for morphine milligram equivalent (MME) usage were calculated as square root values to account for linearity assumption violations. A mediation analysis was performed to characterize the potential influence of pain score modulation on the relationship between ERAS protocol implementation and MME usage. Cohorts were further divided based on pulmonary risk profile and approach (MIS vs. open). Patients were considered increased risk if they had a postoperative predicted forced expiratory volume in 1 second or a postoperative predicted diffusing capacity of the lungs for carbon monoxide \ 50%. MIS included robotic or video-assisted thoracic surgery (VATS) approaches. All VATS and robotic anatomic lung resections were performed without rib-spreading. Robotic approaches employed closed port techniques with CO2 insufflation, while VATS approaches employed open port techniques without insufflation. Between 1 and 4 port sites were used during robotic and VATS anatomic lung resections at the discretion of the operating surgeon. Staging in this study was performed in accordance with the contemporaneous edition of the American Joint Committee on Cancer staging manual [13, 14] . Significance level for twosided tests was defined as p \ 0.05. All statistical analyses were performed with SAS v9.4 (SAS Institute Inc., Cary, NC).

A total of 64 pre-ERAS and 67 post-ERAS patients met inclusion criteria and comprised the final cohorts. Groups were well balanced with respect to demographic and preoperative variables (Table 1 ). Median ages of the pre-and post-ERAS cohorts were 64.5 (26-89) years and 64.0 (21-86) years, respectively (p = 0.91). There were no significant differences between cohorts regarding sex, ethnicity, or body mass index. Groups were also well balanced with respect to comorbidities, including Charlson Comorbidity Scores. No significant differences were found in preoperative pulmonary function, American Society of Anesthesiologists classification, surgery type, or operative approach.

There were no significant differences in blood transfusions, intraoperative fluid balance, or invasive line use between pre-and post-ERAS groups ( Table 1 ). The post-ERAS group experienced reduced postoperative ICU admissions (65.6% vs. 19.4%, p \ 0.0001) and median ICU LOS (1 vs. 0 days, p \ 0.0001). There were no significant differences in chest tube duration, ventilator duration, prolonged air leak, hospital LOS, or readmissions \ 30 days.

Patients were stratified into standard and increased-risk cohorts based on pulmonary function test results. There were 7/64 and 9/67 increased-risk patients in the pre-and post-ERAS cohorts, respectively. Compared to the standard-risk pre-ERAS reference group, both standard-risk and increased-risk post-ERAS groups experienced significantly decreased postoperative ICU admissions (post-ERAS standard-risk: OR 0.14, 95% CI [0.06, 0.34], p \ 0.0001; post-ERAS increased-risk: OR 0.20, 95% CI [0.05, 0.84], p = 0.03) (Fig. 1) . No significant differences were observed with respect to new-onset atrial fibrillation or LOS when stratifying by risk.

When grouped by surgical approach, post-ERAS patients who underwent either MIS (OR 0.06, p \ 0.0001) or open surgery (OR 0.36, p = 0.04) had significantly lower odds of ICU admission compared to pre-ERAS MIS patients ( Table 2) . Irrespective of ERAS, patients who underwent open surgery had increased chest tube duration (pre-ERAS: IRR 2.33, p \ 0.0001; post-ERAS: IRR 2.30, p \ 0.0001) and longer LOS (pre-ERAS: IRR 1.70, p \ 0.0001; post-ERAS: IRR 1.69, p \ 0.0001) relative to the pre-ERAS MIS group. No significant difference in either outcome was noted between pre-and post-ERAS MIS cohorts.

VAS pain scores were improved for the post-ERAS cohort compared to the pre-ERAS cohort. This included timepoint-specific VAS scores on POD1 and POD2 as well as average VAS scores over POD0-2 (Table 3) . Median pain medication usage in MME was reduced in post-ERAS as compared to pre-ERAS patients Mediation analysis demonstrated that ERAS protocol implementation had a total effect of b -2.19 on MME consumption (standard error 0.46, p \ 0.0001). Average VAS pain scores over POD0-2 accounted for 42.4% of the total mediation (p = 0.0002); the remaining 57.7% represents unknown pathways through which the ERAS protocol reduced MME consumption (b -1.26, standard error 0.37, p = 0.0005). Every unit increase in average VAS pain score over POD0-2 for any given patient led to a mean increase of 0.87 (p \ 0.0001) in MME usage, whereas ERAS protocol implementation contributed a mean reduction of -1.06 (p = 0.004) in average VAS pain score. A summary of the mediation analysis is presented in Online Resource 2.

This study demonstrates that implementation of our ERAS protocol for patients undergoing pulmonary resection is associated with decreased ICU utilization, improved pain control, and reduced opioid consumption. In the absence of consensus guidelines, these findings offer critical evidence to characterize the advantages of ERAS in thoracic surgery using clinical algorithms consistent with current medical literature. Furthermore, the benefit of reduced resource utilization with ERAS protocol implementation is especially poignant in this era of increased ICU needs during the COVID-19 pandemic. These results are consistent with previously studied non-thoracic ERAS protocols as well as the largest published series of thoracic ERAS patients by Van Haren and colleagues. [9] In our study, the pre-ERAS MIS cohort was primarily used as the reference group, given prior studies demonstrating the efficacy of VATS with respect to perioperative outcome metrics; the authors believe this design minimizes the potential to overestimate the benefits of ERAS protocol implementation [15] . For example, patients who underwent open surgery-with or without ERAS implementation-had an increased LOS compared to pre-ERAS MIS patients, whereas LOS was similar between pre-ERAS and post-ERAS MIS patients [6, [8] [9] [10] . Patients in the post-ERAS cohort experienced clear advantages over the pre-ERAS cohort with respect to postoperative pain control. These benefits were detected in VAS pain scores on POD1, POD2, and overall (Table 3) . Although decreased VAS pain scores were observed in the post-ERAS MIS cohort relative to the pre-ERAS MIS cohort, no differences in VAS pain scores were detected between pre-ERAS MIS and post-ERAS open patients either overall or on any individual postoperative day Fig. 2a ). This would support the utility of open operations, when appropriate, under ERAS protocol with the expectation that postoperative pain control would be equivalent to a non-ERAS MIS operation. Our findings are consistent with prior studies comparing thoracotomy and VATS, where no differences in pain scores were observed on POD 1-3 when enrolled on an ERAS protocol [17] . In addition to reductions in self-reported pain, the post-ERAS cohort also benefitted from decreased opioid consumption (Table 3 ). This finding is consistent with reports of decreased opioid use with enhanced recovery programs in previous literature [8, 18] . Interestingly, post-ERAS open surgery patients used fewer opioids than the pre-ERAS MIS reference group, despite our observation that the two cohorts did not differ significantly with respect to VAS pain scores. This finding may reflect disparate opioid requirements originating from differences in postoperative pain between the pre-ERAS MIS and post-ERAS open cohorts. Maintaining equivalent pain control, as noted by similar VAS pain scores despite a 50% reduction in overall opioid utilization, would support broad implementation of ERAS even in the absence of effect on standard perioperative metrics such as LOS and re-admission. This may be the most valuable effect noted, as patients undergoing chest surgery for cancer are particularly vulnerable to long-term opioid dependence [19, 20] . Although we did not specifically compare post-ERAS MIS with post-ERAS open patients, similar pain scores and MME usage have been reported between ERAS patients receiving VATS and open surgery [17] .

It is also possible that differences in opioid usage were driven by pathways other than pain. Mediation analysis demonstrated that only 42.4% of the impact of ERAS protocol implementation on opioid consumption occurred via reductions in average VAS pain score. While pain reduction constituted an undoubtedly substantial contribution, the remaining 57.7% influence in this relationship could be accounted for by several different factors, including but not limited to early mobilization, improved overall patient satisfaction, and perception of a better patient-physician relationship. However, these pathways were not examined in the present study. These observations are reflective of the well-described nature of ERAS protocols as multifaceted models with synergistic components that enhance recovery through a cascade of improved perioperative outcomes [3] . As such, it can be difficult to characterize the total value of ERAS protocol implementation, let alone fully assess the contribution of each individual component. For example, postoperative pain is a critically important factor that our institutional ERAS protocol seeks to address through multiple avenues, but it represents just one element of a patient's perioperative experience. This study has several limitations, including those inherent to retrospective designs. Certain true disparities in perioperative outcomes, such as hospital LOS, between pre-ERAS and post-ERAS cohorts may not have been detected due to small sample size. Sample size limitations precluded a subgroup analysis of patients who experienced an ICU LOS [ 1 day, which may have otherwise provided valuable insight into the impacts of our institutional ERAS protocol. In comparing opioid usage between cohorts stratified by protocol and surgical approach, the square root of MME was identified as the relevant variable due to a linearity assumption violation. While this modified the terminology used to describe our results, introduction of this proxy (i.e., rather than MME, directly) did not alter the core finding: Decreased opioid consumption was observed in both the post-ERAS MIS and post-ERAS open cohorts relative to the pre-ERAS MIS reference group. The costs associated with each patient's hospital stay were not specifically investigated, and comments pertaining to the potential financial advantages of ERAS protocol implementation in this study are therefore limited to inference only. However, the decrease in ICU utilization alone is likely to account for cost reductions easily offsetting the cost of protocol implementation. Martin et al. estimated cost-savings of $5,299 and $15,861 with ERAS implementation for each patient undergoing VATS and thoracotomy, respectively [8] . In their investigation of the economic implications of enhanced recovery pathways, Paci and colleagues similarly described significant cost reductions with respect to both ICU and pharmacy utilization [11] .

This study demonstrates that our institutional ERAS protocol, which dictates reduced postoperative ICU admissions, offers significant benefits for pulmonary resection patients, including improved VAS pain scores and decreased opioid consumption. Nearly half the reduction in opioid usage observed in ERAS patients is attributable to amelioration of postoperative pain, but the remainder of this impact occurs through undescribed pathways. In addition to patient-centered benefits, ERAS protocols may present opportunities for significant reductions in perioperative healthcare costs, thereby providing a supplementary financial advantage for healthcare providers and institutions. Continued research efforts are necessary to further characterize the utility of ERAS protocol implementation in thoracic surgery and ultimately contribute to the development of consensus guidelines in the USA. 

Fast-track recovery of the coronary bypass patient

Enhanced recovery after surgery: a consensus review of clinical care for patients undergoing colonic resection

Enhanced recovery after surgery: a review

Evidence-based surgical care and the evolution of fast-track surgery

Enhanced recovery pathways in gynecologic oncology

An enhanced recovery pathway reduces duration of stay and complications after open pulmonary lobectomy

Reduction of postoperative pulmonary complications after lung surgery using a fast track clinical pathway

Implementing a thoracic enhanced recovery program: lessons learned in the first year

Enhanced recovery decreases pulmonary and cardiac complications after thoracotomy for lung cancer

Thoracic enhanced recovery after surgery: single Academic Center Observations after implementation

Economic impact of an enhanced recovery pathway for lung resection

Enhanced recovery pathway versus standard care in patients undergoing video-assisted thoracoscopic lobectomy

Video-assisted thoracic surgery and open chest surgery in lung cancer treatment: present and future

Enhancing the study of enhanced recovery after thoracic surgery: methodology and population-based approaches for the future

Is less really more? Reexamining video-assisted thoracoscopic versus open lobectomy in the setting of an enhanced recovery protocol

Enhanced recovery after thoracic surgery reduces discharge on highly dependent narcotics

Opioid use and abuse following video-assisted thoracic surgery (VATS) or thoracotomy lung cancer surgery

Opioid Use After Open Resection or Video-Assisted Thoracoscopic Surgery for Early-Stage Lung Cancer

Acknowledgements This project was deemed exempt by the Institutional Review Board at the University of Southern California.Funding Funding was provided by grants UL1TR001855 and UL1TR000130 from the National Center for Advancing Translational Science (NCATS) of the US National Institutes of Health for Dr. Ding.

Conflict of interest The authors have no conflicts of interest to disclose.