J Gastrointest Surg (2015) 19:387–399 DOI 10.1007/s11605-014-2712-0
REVIEW ARTICLE
Enhanced Recovery After Surgery Protocols for Open Hepatectomy—Physiology, Immunomodulation, and Implementation Andrew J. Page & Aslam Ejaz & Gaya Spolverato & Tiffany Zavadsky & Michael C. Grant & Daniel J. Galante & Elizabeth C. Wick & Matthew Weiss & Martin A. Makary & Christopher L. Wu & Timothy M. Pawlik
Received: 7 October 2014 / Accepted: 19 November 2014 / Published online: 4 December 2014 # 2014 The Society for Surgery of the Alimentary Tract
Abstract There has been recent interest in enhanced-recovery after surgery (ERAS®) or “fast-track” perioperative protocols in the surgical community. The subspecialty field of colorectal surgery has been the leading adopter of ERAS protocols, with less data available regarding its adoption in hepato-pancreato-biliary surgery. This review focuses on available data pertaining to the application of ERAS to open hepatectomy. We focus on four fundamental variables that impact normal physiology and exacerbate perioperative inflammation: (1) the stress of laparotomy, (2) the use of opioids, (3) blood loss and blood product transfusions, and (4) perioperative fasting. The attenuation of these inflammatory stressors is largely responsible for the improvements in perioperative outcomes due to the implementation of ERAS-based pathways. Collectively, the data suggest that the implementation of ERAS principles should be strongly considered in all patients undergoing hepatectomy. Keywords Enhanced recovery . Hepatectomy . Epidural anesthesia . Low-CVP surgery
Introduction There has been recent interest in enhanced-recovery after surgery (ERAS®) or “fast-track” perioperative protocols in the surgical community. Formally introduced in the 1990s, the primary goal of the ERAS paradigm has been to incorporate evidence-based perioperative care in a standardized fashion to A. J. Page : A. Ejaz : G. Spolverato : T. Zavadsky : D. J. Galante : E. C. Wick : M. Weiss : M. A. Makary : T. M. Pawlik Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA M. C. Grant : C. L. Wu Department of Anesthesiology, Johns Hopkins Hospital, Baltimore, MD, USA T. M. Pawlik (*) Department of Surgery, John L. Cameron Professor of Alimentary Tract Surgery, Blalock 688, 600 N. Wolfe Street, Baltimore, MD 21287, USA e-mail:
[email protected]
restore baseline preoperative physiology as quickly as possible while attenuating the negative sequelae of surgical inflammation. In doing so, ERAS protocols have the potential to improve outcomes such as length of stay (LOS), value, patient satisfaction, and morbidity. The subspecialty field of colorectal surgery has been the leading adopter of ERAS protocols – within general surgery.1 4 Recent data from prospective studies and meta-analyses demonstrate an overall improvement in LOS of up to 3 days and a decrease in perioperative compli– cations of up to 3–20 %.4 12 These studies have demonstrated the feasibility and impact of ERAS protocols in general surgery, with potential for application to other subspecialties. Postoperative recovery from open hepatic surgery has historically been fraught with a high incidence of complications including perioperative hemorrhage, infections, poor pain , control, and prolonged ICU and hospital stays.12 13 However, recent developments in the perioperative surgical and anesthetic management of patients undergoing hepatectomy have led to improvements in these outcomes. Specifically, improvements in surgical technique and patient selection, minimization of narcotics, and the adoption of low central venous pressure (CVP) techniques have been routinely demonstrated to reduce overall perioperative morbidity and LOS while possibly improving survival – after open hepatic resection.13 16
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Despite the expanding indications and subsequent overall improved clinical outcomes for open hepatectomy, there are limited data evaluating the implementation of standardized best practices for perioperative care. Furthermore, there are even fewer studies evaluating ERAS protocols following open , hepatectomy.17 18 In fact, there are less than ten studies to date evaluating the implementation of ERAS protocols in patients following open hepatectomy. Despite the small number of studies, all of these reports have demonstrated improvements – in perioperative outcomes (Tables 1, 2, and 3).18 22 While the proposed ERAS-based perioperative pathways in these studies are not uniform, all address and attempt to minimize four fundamental perioperative variables that exacerbate perioperative inflammation during open hepatectomy: (1) the stress of laparotomy, (2) the use of opioids, (3) blood loss and blood product transfusions, and (4) perioperative fasting.23 Minimization and downregulation of these inflammatory stressors have been proposed as the likely causative mechanism for improvements in perioperative outcomes. The growing field that integrates physiology and the immune response to surgery has been coined “perioperative immunomodulation.” In particular, most of the research in this field has been on the effects of surgical stressors on the
Table1
cytokine response and adaptive immunity. This review focuses on the available data pertaining to these aforementioned four primary immunomodulating factors associated with open hepatectomy. We also present ERAS-based solutions in the context of preservation of normal preoperative physiology and immunity.
Surgery as a Stressor: The Laparotomy The stress of surgery alone has been a well-recognized inflammatory trigger that may have many negative physiologic and immunologic consequences. One of the earliest mechanistic demonstrations of this phenomenon was the effect of surgery on perioperative immunomodulation described by Colacchio et al.24 In their rodent model of liver cancer, the authors compared the cytotoxicity of natural killer (NK) cells (an endogenous lymphocyte with cancer-protective immune function) in animals that underwent laparotomy with control animals that did not undergo laparotomy. Those animals undergoing laparotomy were found to have depressed NK cytotoxicity and an overall increased tumor burden compared with animals that did not have surgery. The depressed function of
Individual reports examining the role of ERAS in patients undergoing hepatectomy van Dam et al.19 ERAS/S
Jones et al.20 ERAS/S
Ni et al.89 ERAS/S
Schultz et al.18 ERAS/S
Lin et al.21 ERAS/S
Dunne et al.22 ERAS(e)/ERAS(l)d
Year Type of study Patients
2008 Case–control 61/100
2013 RCT 46/45
2013 RCT 80/80
2012 Case–control 100/NR
2011 Case–control 56/61
2013 Case–control 143/161
Age (years/median) Extent of resection (%) ≥3 segments
