Enhanced Recovery After Surgery in Laparoscopic Surgery

Abstract

Background:

As part of an effort to maximize value in the perioperative setting, a paradigm shift is underway in the way that patients are cared for preoperatively, on the day of surgery, and postoperatively—a setting collectively known as the perioperative care. Enhanced Recovery After Surgery (ERAS^®) is an evidence-based, patient-centered team approach to delivering high-quality perioperative care to surgical patients.

Methods:

This review focuses on anesthesiologists, with their unique purview of perioperative setting, who are important drivers of change in the delivery of valuable perioperative care. ERAS care pathways begin in the preoperative setting by both preparing the patient for the psychological stress of surgery and optimizing the patient's medical and physiologic status so the body is ready for the physical demands of surgery.

Results:

Minimization of perioperative fasting is important to maintain volume status—decreasing reliance on intravenous fluid administration, and to reduce protein catabolism around the time of surgery. Intraoperative management in ERAS pathways relies on goal-directed fluid therapy and opioid-sparing multimodal analgesia. Postoperatively, early feeding and ambulation, as well as discontinuation of extraneous lines and catheters facilitate patients' functional recovery.

Conclusion:

The laparoscopic approach to surgery, when possible, compliments ERAS techniques by reducing abdominal wall trauma and the resultant milieu of inflammatory, neurohumoral, and pain responses. Anesthesiologists driving change in the perioperative setting, in collaboration with surgeons and other disciplines, can improve value in healthcare and provide optimal outcomes that matter most to patients and healthcare providers alike.

Introduction

Laparoscopic surgery has helped to minimize surgical trauma in an increasing number of surgical procedures, and thus has together with improvements in anesthetic techniques helped to reduce complications and pain after surgery. Despite these advances, postsurgical complications remain a major disadvantage of surgical intervention for a patient and to the medical system in general. Long-term survival of a surgical patient and perioperative costs are directly dependent on complications.^1,2 Enhanced Recovery After Surgery (ERAS^®) pathways represent a paradigm shift in perioperative care aimed to replace traditional practices with evidence-based practices when necessary, in an interdisciplinary multimodal approach to accelerate convalescence and reduce general morbidity by simultaneously applying several interventions.^3–5 ERAS pathways are comprehensive in scope, covering all areas of the patient's journey through the perioperative process. Despite institutional differences, ERAS pathways include several key elements aimed to attenuate surgical stress, maintain physiologic homeostasis, and return the patient to presurgical functional baseline. These key elements include standardization of care, reduction of care variability, functional and hemodynamic optimization, early oral intake, early ambulation, and multimodal opioid-sparing analgesic regiments.⁶ ERAS protocols incorporate previous discoveries into clinical practice, and a fast growing body of research has thus far shown that such protocols can significantly reduce perioperative opioid use, morbidity, and mortality, as well as hospital length of stay. Institutional implementation of ERAS protocols accelerates the evolution of value-based healthcare as both cost reduction and improved outcomes are ERAS goals.^5,7–9 Achieving high value for patients must become the overarching goal in healthcare delivery as this goal is what matters most to patients and unites the interests of all stakeholders in the medical field.⁹ Cost reduction in ERAS pathways is contingent on good outcomes, which produces cost reduction not at the expense of quality.^5,7,10

ERAS pathways have been successfully implemented in many surgical specialties, including gastrointestinal, hepatobiliary, pancreatic, urologic, gynecologic, and urologic surgery.^7,11–16 The strongest evidence so far has been described in patients undergoing open colorectal procedures.^5,17–23 Combining minimally invasive laparoscopic surgery and ERAS protocols has the potential to further improve patient outcomes and is becoming the optimal strategy for colorectal surgery when technically feasible.^24–26

The Role of the Anesthesiologist and Surgeon in Implementing ERAS

The unique footprint of the anesthesiologist in a hospital predisposes the anesthesiologist to become the driving force in the hospital-wide ERAS implementation as a multidisciplinary approach is necessary to combine and coordinate all elements of ERAS care, while avoiding the common “silo mentality.” Anesthesiologists not only provide care in the operating room (OR) but also work in non-OR procedure rooms, preoperative clinics, intensive care units, and recovery rooms, as acute and chronic pain physicians on the wards, and have built valuable relationships with nurses, pharmacists, nutritionists, physical therapists, radiology staff, information technologists, and the hospital administration, which helps to promote open communication. In many places, the anesthesiologists are now fulfilling the role of the perioperative physician.⁶ The surgeon has traditionally considered himself or herself as the “captain of the ship.” However, this mentality is less conducive to the multidisciplinary approach needed for ERAS; a more successful model is a close partnership with the anesthesiologist and other team members, where each team member has an equally important component to perform. Rivalries between the anesthesiology and surgical specialties of the past have little space in the multidisciplinary team approach of the ERAS era.^5–7 Each specialist will contribute significantly in the preoperative, intraoperative, and postoperative care of a patients and the more coordinated the approach, the more likely that successful outcomes will be achieved. The components of ERAS are demonstrated in Figure 1.

FIG. 1.

Common components of ERAS pathways. ERAS, Enhanced Recovery After Surgery; ETOH, ethanol.

The Preoperative Visit: Preparing the Patient for Enhanced Recovery

All patients included in ERAS protocols for open and laparoscopic surgery should undergo a multidisciplinary preoperative evaluation with focus on preoperative medical and functional optimization. The term “prehabilitation” refers to improvement in presurgical physiological and functional status through enhanced ambulation, exercise, nutrition, smoking and alcohol cessation, and medical optimization, such as diabetes and anemia treatment.²⁷ Patient education, perioperative instructions and setting achievable expectation, incorporating the patient as a vital component in his/her own well-being, and recovery are of utmost importance. Patients need to understand that unless they contribute to the care path presented to them by the ERAS team, optimal surgical outcome and recovery will not be achievable. The patient needs to understand that they have “skin in the game.”^5–7,27

All surgeries, including laparoscopic surgery, represent a major stressor to the patient with possible sequelae for postoperative well-being, including decline in functional capacity, cognitive ability, and even cancer spread. Comorbidities such as diabetes, ischemic heart and vascular disease, stroke, and others have a larger impact on postoperative morbidity and mortality than age.¹⁹ In addition, frailty and low physical functional status such as a 6-minute walking distance <350 m predict poor outcomes, more than coronary artery disease alone.^20,21 The aim of prehabilitation is to optimally condition the patient for the stress of surgery, thus mitigating the risk of postoperative morbidity and mortality in patients undergoing surgery in the near future.

Control of Surgical Stress and Maintenance of Homoeostasis

Controlling surgical stress

The enhanced recovery concept is based on the principles to reduce surgically induced stress and minimize negative responses such as fasting, ileus, pain, opioid consumption, hemorrhage, hypoxia, fluid shifts and edema, inability to ambulate, and cognitive decline.^6,28 Laparoscopic surgery has advantages compared to open surgery as common metabolic stress responses, such as hematological, immunological, inflammatory, hormonal, and endocrine disturbances, are reduced. A laparoscopic ERAS protocol aims to further reduce these stress responses caused by surgery and maintain homeostasis.²⁶

Abdominal wall trauma is decreased by laparoscopic surgery, especially when modern ports are used, which split rather than divide muscle fibers. The intra-abdominal part of the surgery may be similar whether performed open or laparoscopically; however, the surgical technique can contribute to decreased peritoneal and serosal injury, resulting in less gut motility reduction, bleeding, and adhesion formation.^29–31

Insulin resistance and postoperative hyperglycemia are major problems in the perioperative period and the observed degree correlates with hospital length of stay³² and other complications.^33–36 Furthermore, postoperative protein catabolism and decrease in muscle mass may correlate with insulin resistance³⁷ and contribute to poorer wound healing, immune response, and muscular strength, leading to decreased coughing, mobilization, and functional recovery.

ERAS interventions reducing insulin resistance: preoperative carbohydrate, early postoperative feeding, analgesia, and glycemic control

Animal studies have demonstrated that after trauma-fed animals do better than starved ones.³⁸ Oral clear carbohydrate liquids are used in ERAS pathways to and may improve insulin sensitivity by 50%, shifting cellular metabolism to a more anabolic state,³⁹ and thus decreasing insulin resistance with decreased protein and muscle loss. Data for preoperative carbohydrate loading have been suggestive of reducing length of stay (LOS) in major surgery, but these studies have generally been conducted in small populations and impact other than patient satisfaction is unknown for minor surgery.^40–43 Poorly controlled diabetics may demonstrate significant hyperglycemia after preoperative carbohydrate loading requiring insulin treatment, and future research will need to establish improved protocols for this patient population.

ERAS protocols utilize early mobilization and oral feeding to avoid metabolic imbalance. Regional anesthesia such as thoracic epidural analgesia or transverse abdominis plane (TAP) blocks help to spare opioids, which slow down gut motility and contribute to ileus. Improved blood glucose levels and a decreased catabolic response have been described.^44,45 Therapeutic insulin administration is recommended to avoid sequelae by hyperglycemia, should it occur.^46,47 Minimally invasive laparoscopic surgery benefits the patient by typically allowing enhanced mobilization, decreased opioid requirement, and a more rapid return of gut function resulting in reduced LOS.⁴⁸

Intestinal dysfunction, ileus, and fluid balance

Despite the decrease of an immune-inflammatory and hormonal response in laparoscopic compared to open surgery, the overall effect on the gut leads to an inhibition of bowel function, decreased gut motility, and increased vascular permeability, which can lead to interstitial edema, especially after excessive fluid administration. The net result is delayed recovery of gastrointestinal function and impaired anastomotic healing.⁴⁹ Risk factors for postoperative ileus have previously been described and include increased age, opioid use, long duration and emergency surgery, excessive fluid and salt overload, and a low serum albumin level.^3,4,6,28 Strategies to reduce ileus are multifactorial and include¹ avoidance of fluid and salt overload,² avoidance of opioids by multimodal analgesia, including nonsteroidal anti-inflammatory drugs (NSAIDs), magnesium sulfate, alvimopan, and epidural or regional anesthesia,³ chewing gum and early enteral nutrition,⁴ early mobilization, and⁵ laparoscopic surgery.^3,4,6,28

Avoidance of a traditional bowel preparation in favor of no bowel preparation except for a 5-day residual free diet or a combined mechanical and oral antibiotic bowel preparation has reduced preoperative osmotic dehydration with the need for significant intraoperative fluid resuscitation, which avoids intestinal edema formation, while decreasing ileus and anastomotic leaks.^17,18,50 Nasogastric and bladder catheters may be placed before surgical incision, but should be removed in the operating room or as soon as possible thereafter. Moreover, goal-directed fluid therapy (GDFT) is one of several modalities in ERAS pathways to further reduce fluid and electrolyte, as well as hormonal and inflammatory responses.^6,51 Moreover, GDFT aims to maintain normovolemia and avoid weight gains due to excessive fluid administration. In addition, adequate preoperative oral hydration and avoidance of bowel preparation, as well as perioperative normothermia, help in achieving the goal of keeping a favorable range of normovolemia, cardiac output, and tissue perfusion/oxygenation.^6,51 The anesthesiologist may use clinical skill or use technologies such as esophageal Doppler, pulse pressure variation, or pulse contour wave analysis to guide the intraoperative GDFT.^6,52–55

Multimodal Analgesia, Central Neuraxial, Regional, and Local Analgesia Techniques

All surgical incisions, including minimally invasive laparoscopic surgery, lead to tissue trauma, cell disruption, and nociceptive impulses with subsequent neurohormonal stress response and release of chemical mediators. Proinflammatory cytokines, insulin resistance, acute pain, and other clinical pathophysiological changes such as hyperalgesia, allodynia, and persistent postsurgical pain can become significant problems.⁵⁶ Opioids have been the traditional method to provide perioperative analgesia, but significant problems are associated with opioid use such as postoperative nausea and vomiting (PONV), pruritus, respiratory depression, delirium, hyperalgesia, constipation, ileus, immunosuppression, and addiction even after short-term opioid use.^6,56 Multiple articles have reported an increase in tumor recurrence or decreased long-term survival in cancer patients who received opioid therapy compared to regional anesthesia techniques.^57–61 Depression of natural killer cells or mu receptor activation of tumor cells has been described.^62,63 The prevalence of persistent postsurgical pain and opioid addition may surpass traditionally reported surgical complications such as infections or hemorrhage in many surgeries (Table 1).^56,64 One study found that the risk of persistent pain, regardless of the suspected mechanism, was not substantially greater after open mesh than laparoscopic surgery for inguinal hernia repair.⁶⁴

Table 1.

The Incidence of Chronic Pain Following Common Procedures

	Incidence of chronic postsurgical pain, %	U.S. surgical volumes (in 1000s)
Amputation	57–62	159
Breast surgery	27–48	479
Thoracotomy	52–61	Unknown
Inguinal hernia repair	19–40	609
Coronary artery bypass	23–39	598
Caesarean section	12	220
Laparoscopic nephrectomy	3.7–11	Unknown
Laparoscopic cholecystectomy	1–5	1200

Kehlet et al.,⁵⁶ Alper et al.,¹⁰⁵ Harju et al.,¹⁰⁶ and Stiff et al.¹⁰⁷

Central neuraxial techniques (epidural and spinal analgesia)

Epidural and spinal anesthesia are part of many ERAS protocols and can achieve excellent analgesia, while accelerating return of bowel function. In addition to the desired analgesic effects of neuraxial analgesia, a reduction of surgical stress, cardiopulmonary events, and renal injury, as well as thromboembolic events with an overall reduction of morbidity and mortality have been described.^65–67 Adverse events include technical difficulties and block failure, inadvertent postdural puncture headache, infection, motor block, and systemic hypotension. A systematic review has concluded that neuraxial analgesia is effective in both open and laparoscopic surgeries; however, the risk–benefit ratio for laparoscopic surgery needs to be evaluated for each individual patient.^66–70 Regional analgesia techniques such as paravertebral blocks or transversus abdominis plane blocks (TAP) are becoming increasingly popular by anesthesiologists as ultrasound techniques have increased the speed and success rates of peripheral nerve blocks, while decreasing complications.⁷¹ Incorporation of bilateral TAP blocks to ERAS protocols for abdominal laparoscopic surgery has shown to reduce PONV, opioid requirements, and postoperative pain. Some studies suggest comparable efficacy of bilateral TAP blocks with epidural analgesia in laparoscopic surgery. TAP catheters are an option for continuous infusion of local anesthesia, should analgesia for a longer duration be desired.

Surgical site infiltration with local anesthetics has been shown to decrease opioid requirements after abdominal laparoscopic surgery such as appendectomy, cholecystectomy, hernia repair, and fundoplication.⁷² However, the evidence that local administration produces effective postsurgical analgesia is lacking likely due to inadequate dosing, variable application method, and the relative short duration of local anesthetics.⁷³ Modern, longer acting local anesthetics, such as liposomal bupivacaine, may improve analgesia for local infiltration, TAP blocks, and possibly nerve blocks, eliminating the need for block catheters; however, further studies in this area are required.^74–76

Systemic Analgesia

Opioids

Opioids have been used as the foundation for postoperative pain; however, their use is recommended only for moderate to severe pain. Multimodal analgesia is not a new concept; however, perioperative physicians have in recent years expanded the use of nonopioid medications to decrease opioid adverse events. Dose-related side effects include PONV, urinary retention, constipation, ileus, and most dangerously respiratory depression, which especially in patients with known or unknown sleep apnea can be causative for morbidity and mortality.⁶ Opioid addiction may not be dose related as even short-term postoperative opioid therapy might lead to chronic use and opioid use disorder.⁷⁷ The aim of ERAS protocols is to restrict opioid use to moderate to severe pain, while fully implementing multimodal analgesia and regional anesthesia.

Acetaminophen (paracetamol)

Acetaminophen is an effective analgesic for mild to moderate pain and an important component in most ERAS protocols as its use has shown to decrease opioid use by 30%.^78,79 Preoperative oral acetaminophen is a cost-effective alternative to intravenous dosing; however, well-designed studies comparing efficacy of oral versus intravenous acetaminophen are lacking. Intravenous acetaminophen has an accelerated dose to peak effect time and hence may be preferred, if painful stimulus is expected soon, whereas the delayed onset of analgesia of oral acetaminophen may correlate well with surgical incision, if given in the holding area before the operation. Acetaminophen has a favorable safety profile; however, doses may need to be reduced or eliminated in patients with liver disease.⁸⁰ Acetaminophen may be combined with NSAIDs. In one Cochrane database, the combination was more effective than opioids to reduce pain.⁸¹

NSAIDs and cyclooxygenase-2 inhibitors

NSAIDs, including cyclooxygenase-2 inhibitors, have shown to be effective analgesics for multimodal pain regiments and reduce perioperative opioid requirements.⁸² One case–control study suggested that ketorolac, in particular, was associated with an increase in anastomotic leaks; however, this study had several significant flaws, including selection bias, inadequate control for other risk factors, and it was underpowered.⁸³ Other studies had similar problems; however, when combined with experimental data, these concerns for anastomotic leak suggest that caution is needed when prescribing NSAIDs to patients with preexisting risk factors for leak until more definitive evidence emerges and selective NSAIDs may be preferred in these patients.⁸⁴

N-methyl-D-aspartate receptor antagonists

Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist and a potent analgesic that has been shown to reduce postoperative opioid use and to be helpful in patients with opioid use disorder, in opioid-refractory pain, and in repeated painful stimuli such as dressing changes in burn victims.^85,86 Ketamine is widely used in Europe and is gaining popularity in the United States in enhanced recovery protocols such as for joint replacement and spine surgery.^85,86 It can be used in laparoscopic surgery with the potential of avoiding opioids altogether. Other NMDA receptor antagonists are dextromethorphan and magnesium sulfate.⁸⁷ Adverse side effects, such as psychosis or hallucinations, can occur, but are less common in low-dose ketamine and dextromethorphan.⁸⁸

Anticonvulsants (gamma-aminobutyric acid analogues)

Gabapentin and pregabalin are gamma-aminobutyric acid analogues that have shown to reduce acute and chronic postoperative pain and opioid requirements in a wide range of surgeries when used in a multimodal pain regimen.^89,90 The mechanism of action involves binding alpha 2-d subunits of voltage-dependent presynaptic calcium channels, which leads to a decrease in postsynaptic excitatory neurotransmitters and postsynaptic calcium influx.⁷³ The optimal doses for gabapentin and pregabalin in the perioperative period are not known and more research is needed to guide the clinician. Side effects include sedation, visual disturbances, dizziness, and headache. Lower doses should be used for patients with renal failure.⁹⁰

Beta-blockers and Alpha 2 agonists

Beta-blockers such as esmolol may reduce intraoperative and postoperative pain and opioid consumption by their antinociceptive properties.⁹¹ Blunting cardiovascular sympathetic responses may also lead to less opioids given intraoperatively and may prevent perioperative cardiac events.⁶⁹ Alpha 2 agonists such as clonidine and dexmedetomidine produce analgesia and have shown to reduce postoperative opioid needs, and can be part of a multimodal pain regiment.^91–95

Glucocorticoids

Glucocorticoids such as dexamethasone can assist in pain management and reduce opioid use by several mechanisms, including antinociceptive effects at the spinal level, and reduction of inflammation and inflammatory cytokines, prostaglandins, and leukotrienes.⁷³ The optimal dose for dexamethasone is unknown, but a single dose of 4–8 mg can reduce PONV as well as provide opioid-sparing effects, and enhance recovery without significantly increasing the risk for hyperglycemia, wound healing, and infection.^96–98

Lidocaine infusions

Intravenous lidocaine can significantly reduce acute pain sensation after surgery and reduce opioid usage.^99,100 Lidocaine has an anti-inflammatory component and has better results in surgeries with soft tissue damage and less effect in joint replacement surgery. In laparoscopic and bariatric surgery, intravenous lidocaine can easily be used intraoperatively, resulting in improved quality of recovery, and can be combined with postoperative TAP blocks for prolonged pain relief.¹⁰¹ Intraoperative intravenous lidocaine infusion has been shown to decrease hospital length of stay in patients having intra-abdominal surgery and is an excellent option for patients in whom epidural anesthesia is contraindicated.¹⁰²

Surgery, Cognitive Dysfunction, and Postoperative Deconditioning

Surgical trauma may produce neuroinflammatory changes that may lead to postoperative cognitive dysfunction, including delirium. Reduction of proinflammatory cytokines by laparoscopic surgery with less tissue trauma, multimodal pain regimens, and avoiding medications that impair cognition such as opioids and benzodiazepines may lead to an overall reduction of cognitive decline after surgery and hasten recovery.

Postoperative early mobilization with avoidance of prolonged bed rest is part of all enhanced recovery protocols. Early ambulation reduces skeletal muscle atrophy, avoids decreased insulin sensitivity, attenuates microvascular dysfunction, and reduces the risk of atelectasis, pulmonary complications, and thromboembolic complications.^103,104 While there is no clear evidence of how early mobilization should be optimally structured, it has been suggested to develop specific targets for patients such as the number of times per day and total hours a patient should ambulate following surgery. If feasible, ambulation on the day of surgery is recommended.

Conclusion

Laparoscopic surgery is compatible with enhanced recovery principles, which employ evidence-based approaches to surgery starting in the preoperative phase with improved patient education, expectation setting, and medical optimization. Perioperative paradigm shifts incorporate preoperative carbohydrate loading, early postoperative nutrition, and mobilization. Perioperative reduction in surgically induced stress includes smaller tissue trauma because of minimally invasive laparoscopic approaches but also reduction in stress mediators by multimodal, opioid-sparing analgesia, as well as regional anesthesia. The adoption and the implementation of ERAS protocol for laparoscopic surgery may allow an immediate significant reduction of length of stay, improving perioperative management and postoperative outcomes. Dedicated multidisciplinary teams and strict application of ERAS items are likely to be crucial to obtain the desired improvement compared to the traditional care pathways.

Future studies must expand the boundaries of ERAS principles in increasingly complex scenarios and focus on the patient's perspective and satisfaction as a benchmark for recovery.

Footnotes

Acknowledgment

ERAS^® is a registered trademark of the ERAS^® Society.

Disclosure Statement

No competing financial interests exist.

References

Khuri

, Henderson

, DePalma

, Mosca

, Healey

, Kumbhani

. Participants in the VA National Surgical Quality Improvement Program. Determinants of long-term survival after major surgery and the adverse effect of postoperative complications. Ann Surg, 2005; 242:326–341.

Dimick

, Chen

, Taheri

, Henderson

, Khuri

, Campbell

Jr . Hospital costs associated with surgical complications: A report from the private-sector National Surgical Quality Improvement Program. J Am Coll Surg, 2004; 199:531–537.

Mattei

, Rombeau

. Review of the pathophysiology and management of postoperative ileus. World J Surg, 2006; 30:1382–1391.

Person

, Wexner

. The management of postoperative ileus. Curr Probl Surg, 2006; 43:6–65.

Varadhan

, Neal

, Dejong

, Fearon

, Ljungqvist

, Lobo

. The enhanced recovery after surgery (ERAS) pathway for patients undergoing major elective open colorectal surgery: A meta-analysis of randomized controlled trials. Clin Nutr, 2010; 29:434–440.

Scott

, Baldini

, Fearon

, Feldheiser

, Feldman

, Gan

, Ljungqvist

, Lobo

, Rockall

, Schricker

, Carli

. Enhanced recovery after surgery (ERAS) for gastrointestinal surgery, part 1: Pathophysiological considerations. Acta Anaesthesiol Scand, 2015; 59:1212–1231.

Varadhan

, Lobo

, Ljungqvist

. Enhanced recovery after surgery: The future of improving surgical care. Crit Care Clin, 2010; 26:527–547.

Porter

, Lee

. From volume to value in health care: The work begins. JAMA, 2016; 316:1047–1048.

Porter

ME.

What is value in health care?. N Engl J Med, 2010; 363:2477–2481.

10.

Porter

, Kaplan

. How to pay for health care. Harv Bus Rev, 2016; 94:88–98.

11.

Lassen

, Coolsen

, Slim

. Guidelines for perioperative care for pancreaticoduodenectomy: Enhanced recovery after surgery (ERAS®) society recommendations. World J Surg, 2013; 37:240–258.

12.

Mortensen

, Nilsson

, Slim

. Consensus guidelines for enhanced recovery after gastrectomy: Enhanced recovery after surgery (ERAS®) society recommendations. Br J Surg, 2013; 101:1209–1229.

13.

Cerantola

, Valerio

, Persson

. Guidelines for perioperative care after radical cystectomy for bladder cancer: Enhanced recovery after surgery (ERAS®) society recommendations. Clin Nutr, 2013; 32:879–887.

14.

Nelson

, Altman

, Nick

. Guidelines for postoperative care in gynecologic/oncology surgery: Enhanced recovery after surgery (ERAS®) society recommendations—Part II. Gynecol Oncol, 2016; 140:323–332.

15.

Nelson

, Altman

, Nick

. Guidelines for pre- and intra-operative care in gynecologic/oncology surgery: Enhanced recovery after surgery (ERAS®) society recommendations—Part I. Gynecol Oncol, 2016; 140:313–322.

16.

Liang

, Ying

, Wang

, et al. Enhanced recovery program versus traditional care in laparoscopic hepatectomy. Medicine (Baltimore), 2016; 95:e2835.

17.

Nygren

, Thacker

, Carli

. Guidelines for perioperative care in elective rectal/pelvic surgery: Enhanced recovery after surgery (ERAS®) society recommendations. World J Surg, 2013; 37:285–305.

18.

Gustafsson

, Scott

, Schwenk

. Guidelines for perioperative care in elective colonic surgery: Enhanced recovery after surgery (ERAS®) society recommendations. Clin Nutr, 2012; 31:783–800.

19.

Bona

, Molteni

, Rosati

. Introducing an enhanced recovery after surgery program in colorectal surgery: A single center experience. World J Gastroenterol, 2014; 20:17578–17587.

20.

Gustafsson

, Hausel

, Thorell

. Adherence to the enhanced recovery after surgery protocol and outcomes after colorectal cancer surgery. Arch Surg, 2011; 146:571–577.

21.

Spanjersberg

, van Sambeeck

, Bremers

. Systematic review and meta-analysis for laparoscopic versus open colon surgery with or without an ERAS programme. Surg Endosc, 2015; 29:3443–3453.

22.

Wind

, Polle

, Fung Kon Jin

. Systematic review of enhanced recovery programmes in colonic surgery. Br J Surg, 2016; 93:800–809.

23.

Zhuang

, Ye

, Zhang

, et al. Enhanced recovery after surgery programs versus traditional care for colorectal surgery: A meta-analysis of randomized controlled trials. Dis Colon Rectum, 2013; 56:667–678.

24.

Vlug

, Wind

, Hollmann

, et al. Laparoscopy in combination with fast track multimodal management is the best perioperative strategy in patients undergoing colonic surgery: A randomized clinical trial (LAFA-study). Ann Surg, 2011; 254:868–875.

25.

Wind

, Hofland

, Preckel. Perioperative strategy in colonic surgery; LAparoscopy and/or FAst track multimodal management versus standard care (LAFA trial). BMC Surg, 2006; 6:16.

26.

Brescia

, Tomassini

, Berardi

, Sebastiani

, Pezzatini

, Dall'Oglio

, Laracca

, Apponi

, Gasparrini

Development of an enhanced recovery after surgery (ERAS) protocol in laparoscopic colorectal surgery: Results of the first 120 consecutive cases from a university hospital. Updates Surg, 2017. [Epub ahead of print]; DOI: 10.1007/s13304-017-0432-1.

27.

Miller

, Thacker

, White

, Mantyh

, Migaly

, Jin

, Roche

, Eisenstein

, Edwards

, Anstrom

, Moon

, Gan

; Enhanced Recovery Study Group. Reduced length of hospital stay in colorectal surgery after implementation of an enhanced recovery protocol. Anesth Analg, 2014; 118:1052–1061.

28.

Feldheiser

, Aziz

, Baldini

, Cox

, Fearon

, Feldman

, Gan

, Kennedy

, Ljungqvist

, Lobo

, Miller

, Radtke

, Ruiz Garces

, Schricker

, Scott

, Thacker

, Ytrebø

, Carli

. Enhanced recovery after surgery (ERAS) for gastrointestinal surgery, part 2: Consensus statement for anaesthesia practice. Acta Anaesthesiol Scand, 2016; 60:289–334.

29.

Schwenk

, Haase

, Neudecker

, Muller

. Short term benefits for laparoscopic colorectal resection. Cochrane Database Syst Rev, 2005; CD003145.

30.

Dowson

, Bong

, Lovell

, Worthington

, Karanjia

, Rockall

. Reduced adhesion formation following laparoscopic versus open colorectal surgery. Br J Surg, 2008; 95:909–914.

31.

Levy

, Dowson

, Fawcett

, Scott

MJP

, Stoneham

, Zuleika

, Rockall

. The effect of regional anaesthesia on haemodynamic changes occurring during laparoscopic colorectal surgery. Anaesthesia, 2009; 64:810.

32.

Thorell

, Nygren

, Ljungqvist

. Insulin resistance: A marker of surgical stress. Curr Opin Clin Nutr Metab Care, 1999; 2:69–78.

33.

Sato

, Carvalho

, Sato

, Lattermann

, Matsukawa

, Schricker

. The association of preoperative glycemic control, intraoperative insulin sensitivity, and outcomes after cardiac surgery. J Clin Endocrinol Metab, 2010; 95:4338–4344.

34.

Krinsley

JS.

Association between hyperglycemia and increased hospital mortality in a heterogeneous population of critically ill patients. Mayo Clin Proc, 2003; 78:1471–1478.

35.

McAlister

, Man

, Bistritz

, Amad

, Tandon

. Diabetes and coronary artery bypass surgery: An examination of perioperative glycemic control and outcomes. Diabetes Care, 2003; 26:1518–1524.

36.

Kiran

, Turina

, Hammel

, Fazio

. The clinical significance of an elevated postoperative glucose value in nondiabetic patients after colorectal surgery: Evidence for the need for tight glucose control?. Ann Surg, 2013; 258:599–604; discuss 604–605.

37.

Donatelli

, Corbella

, Di Nicola

, Carli

, Lorini

, Fumagalli

, Biolo

. Preoperative insulin resistance and the impact of feeding on postoperative protein balance: A stable isotope study. J Clin Endocrinol Metab, 2011; 96:E1789–E1797.

38.

Ljungqvist

Modulating postoperative insulin resistance by preoperative carbohydrate loading. Best Pract Res Clin Anaesthesiol, 2009; 23:401.

39.

Wang

, Wang

, Qin

. Randomized clinical trial to compare the effects of preoperative oral carbohydrate versus placebo on insulin resistance after colorectal surgery. Br J Surg, 2010; 97:317–327.

40.

Hausel

, Nygren

, Thorell

, Lagerkranser

, Ljungqvist

. Randomized clinical trial of the effects of oral preoperative carbohydrates on postoperative nausea and vomiting after laparoscopic cholecystectomy. Br J Surg, 2005; 92:415–421.

41.

Yagci

, Can

, Ozturk

, Dag

, Ozgurtas

, Cosar

, Tufan

. Effects of preoperative carbohydrate loading on glucose metabolism and gastric contents in patients undergoing moderate surgery: A randomized, controlled trial. Nutrition, 2008; 24:212–216.

42.

Awad

, Varadhan

, Ljungqvist

, Lobo

. A meta-analysis of randomised controlled trials on preoperative oral carbohydrate treatment in elective surgery. Clin Nutr, 2013; 32:34–44.

43.

Smith

, McCall

, Plank

, Herbison

, Soop

, Nygren

. Preoperative carbohydrate treatment for enhancing recovery after elective surgery. Cochrane Database Syst Rev, 2014; 8:CD009161.

44.

Lewis

, Andersen

, Thomas

. Early enteral nutrition within 24 h of intestinal surgery versus later commencement of feeding: A systematic review and meta-analysis. J Gastrointest Surg, 2009; 13:569–575.

45.

Soop

, Carlson

, Hopkinson

, Clarke

, Thorell

, Nygren

, Ljungqvist

. Randomized clinical trial of the effects of immediate enteral nutrition on metabolic responses to major colorectal surgery in an enhanced recovery protocol. Br J Surg, 2004; 91:1138–1145.

46.

van den Berghe

, Wouters

, Weekers

, Verwaest

, Bruyninckx

, Schetz

, Vlasselaers

, Ferdinande

, Lauwers

, Bouillon

. Intensive insulin therapy in critically ill patients. N Engl J Med, 2001; 345:1359–1367.

47.

Investigators

N-SS

, Finfer

, Chittock

, Su

, Blair

, Foster

, Dhingra

, Bellomo

, Cook

, Dodek

, Henderson

, Hebert

, Heritier

, Heyland

, McArthur

, McDonald

, Mitchell

, Myburgh

, Norton

, Potter

, Robinson

, Ronco

. Intensive versus conventional glucose control in critically ill patients. N Engl J Med, 2009; 360:1283–1297.

48.

Haverkamp

, de Roos

, Ong

. The ERAS protocol reduces the length of stay after laparoscopic colectomies. Surg Endosc, 2012; 26:361–367.

49.

Chowdhury

, Lobo

. Fluids and gastrointestinal function. Curr Opin Clin Nutr Metab Care, 2011; 14:469–476.

50.

Kiran

, Murray

, Chiuzan

, Estrada

, Forde

. Combined preoperative mechanical bowel preparation with oral antibiotics significantly reduces surgical site infection, anastomotic leak, and ileus after colorectal surgery. Ann Surg, 2015; 262:416–425.

51.

Gan

, Soppitt

, Maroof

, el-Moalem

, Robertson

, Moretti

, Dwane

, Glass

. Goal-directed intraoperative fluid administration reduces length of hospital stay after major surgery. Anesthesiology, 2002; 97:820–826.

52.

Brandstrup

, Svendsen

, Rasmussen

, Belhage

, Rodt

, Hansen

, Moller

, Lundbech

, Andersen

, Berg

, Thomassen

, Andersen

, Simonsen

. Which goal for fluid therapy during colorectal surgery is followed by the best outcome: Near-maximal stroke volume or zero fluid balance?. Br J Anaesth, 2012; 109:191–199.

53.

Pearse

, Harrison

, MacDonald

, Gillies

, Blunt

, Ackland

, Grocott

, Ahern

, Griggs

, Scott

, Hinds

, Rowan

, Group

. Effect of a perioperative, cardiac output-guided hemodynamic therapy algorithm on outcomes following major gastrointestinal surgery: A randomized clinical trial and systematic review. JAMA, 2014; 311:2181–2190.

54.

Srinivasa

, Taylor

, Singh

, Lemanu

, MacCormick

, Hill

. Goal-directed fluid therapy in major elective rectal surgery. Int J Surg, 2014; 12:1467–1472.

55.

Pestana

, Espinosa

, Eden

, Najera

, Collar

, Aldecoa

, Higuera

, Escribano

, Bystritski

, Pascual

, Fernandez-Garijo

, de Prada

, Muriel

, Pizov

. Perioperative goal-directed hemodynamic optimization using noninvasive cardiac output monitoring in major abdominal surgery: A prospective, randomized, multicenter, pragmatic trial: POEMAS study (PeriOperative goal-directed thErapy in Major Abdominal Surgery). Anesth Analg, 2014; 119:579–587.

56.

Kehlet

, Jensen

, Woolf

. Persistent postsurgical pain: Risk factors and prevention. Lancet, 2006; 367:1618–1625.

57.

de Oliveira

Jr , Ahmad

, Schink

, Singh

, Fitzgerald

, McCarthy

. Intraoperative neuraxial anesthesia but not postoperative neuraxial analgesia is associated with increased relapse-free survival in ovarian cancer patients after primary cytoreductive surgery. Reg Anesth Pain Med, 2011; 36:271–277.

58.

Exadaktylos

, Buggy

, Moriarty

, Mascha

, Sessler

. Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis?. Anesthesiology, 2006; 105:660–664.

59.

Biki

, Mascha

, Moriarty

, Fitzpatrick

, Sessler

, Buggy

. Anesthetic technique for radical prostatectomy surgery affects cancer recurrence: A retrospective analysis. Anesthesiology, 2008; 109:180–187.

60.

Lennon

, Mirzapoiazova

, Mambetsariev

, Poroyko

, Salgia

, Moss

, Singleton

. The Mu opioid receptor promotes opioid and growth factor-induced proliferation, migration and epithelial mesenchymal transition (EMT) in human lung cancer. PLoS One, 2014; 9:e91577.

61.

Gupta

, Björnsson

, Fredriksson

, Hallböök

, Eintrei

. Reduction in mortality after epidural anaesthesia and analgesia in patients undergoing rectal but not colonic cancer surgery: A retrospective analysis of data from 655 patients in central Sweden. Br J Anaesth, 2011; 107:164–170.

62.

Byrne

, Levins

, Buggy

. Can anesthetic-analgesic technique during primary cancer surgery affect recurrence or metastasis?. Can J Anaesth, 2016; 63:184–192.

63.

Plein

, Rittner

. Opioids and the immune system—friend or foe. Br J Pharmacol, 2017.

64.

Niccolaï

, Ouchchane

, Libier

, Beouche

, Belon

, Vedrinne

, El Drayi

, Vallet

, Ruiz

, Biermann

, Duchêne

, Chirat

, Soule-Sonneville

, Dualé

, Dubray

, Schoeffler

. Persistent neuropathic pain after inguinal herniorrhaphy depending on the procedure (open mesh v. laparoscopy): A propensity-matched analysis. Can J Surg, 2015; 58:114–120.

65.

Rodgers

, Walker

, Schug

, et al. Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: Results from overview of randomised trials. BMJ, 2000; 321:1493.

66.

Popping

, Elia

, Van Aken

, et al. Impact of epidural analgesia on mortality and morbidity after surgery: Systematic review and meta-analysis of randomized controlled trials. Ann Surg, 2014; 259:1056–1067.

67.

Vaghadia

, McLeod

, Mitchell

, Merrick

, Chilvers

. Small-dose hypobaric lidocaine-fentanyl spinal anesthesia for short duration outpatient laparoscopy. I. A randomized comparison with conventional dose hyperbaric lidocaine. Anesth Analg, 1997; 84:59–64.

68.

Lennox

, Vaghadia

, Henderson

, Martin

, Mitchell

. Small-dose selective spinal anesthesia for short-duration outpatient laparoscopy: Recovery characteristics compared with desflurane anesthesia. Anesth Analg, 2002; 94:346–350.

69.

Bettelli

Anaesthesia for the elderly outpatient: Preoperative assessment and evaluation, anaesthetic technique and postoperative pain management. Curr Opin Anaesthesiol, 2010; 23:726–731.

70.

Joshi

, Bonnet

, Kehlet

; PROSPECT Collaboration. Evidence-based postoperative pain management after laparoscopic colorectal surgery. Colorectal Dis, 2013; 15:146–155.

71.

Jankovic

, Ahmad

, Ravishankar

, Archer

. Transversus abdominis plane block: How safe is it?. Anesth Analg, 2008; 107:1758–1759.

72.

Moiniche

, Jorgensen

, Wetterslev

, Dahl

. Local anesthetic infiltration for postoperative pain relief after laparoscopy: A qualitative and quantitative systematic review of intraperitoneal, port-site infiltration and mesosalpinx block. Anesth Analg, 2000; 90:899–912.

73.

Pyati

, Gan

. Perioperative pain management. CNS Drugs, 2007; 21:185–211.

74.

Fayezizadeh

, Majumder

, Neupane

, Elliott

, Novitsky

. Efficacy of transversus abdominis plane block with liposomal bupivacaine during open abdominal wall reconstruction. Am J Surg, 2016; 212:399–405.

75.

McGraw-Tatum

, Groover

, George

, Urse

, Heh

. A prospective, randomized trial comparing liposomal bupivacaine vs fascia iliaca compartment block for postoperative pain control in total hip arthroplasty. J Arthroplasty, 2017; 32:2181–2185.

76.

Hamilton

, Athanassoglou

, Trivella

, Strickland

, Mellon

, Murray

, Pandit

. Liposomal bupivacaine peripheral nerve block for the management of postoperative pain. Cochrane Database Syst Rev, 2016:CD011476.

77.

Callinan

, Neuman

, Lacy

, Gabison

, Ashburn

. The initiation of chronic opioids: A survey of chronic pain patients. J Pain, 2017; 18:360–365.

78.

Wong

, St John-Green

, Walker

. Opioid-sparing effects of perioperative paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) in children. Paediatr Anaesth, 2013; 23:475–495.

79.

Cobby

, Crighton

, Kyriakides

, Hobbs

. Rectal paracetamol has a significant morphine-sparing effect after hysterectomy. Br J Anaesth, 1999; 83:253–256.

80.

Zukowski

, Kotfis

. Safety of metamizole and paracetamol for acute pain treatment (Polish). Anestezjol Intens Ter, 2009; 41:170–175.

81.

Moore

, Wiffen

, Derry

, Maguire

, Roy

, Tyrrell

. Non-prescription (OTC) oral analgesics for acute pain—an overview of Cochrane reviews. Cochrane Database Syst Rev, 2015:CD010794.

82.

Cepeda

, Carr

, Miranda

, Diaz

, Silva

, Morales

. Comparison of morphine, ketorolac, and their combination for postoperative pain: Results from a large, randomized, double-blind trial. Anesthesiology, 2005; 103:1225–1232.

83.

Subendran

, Siddiqui

, Victor

, McLeod

, Govindarajan

. NSAID use and anastomotic leaks following elective colorectal surgery: A matched case-control study. J Gastrointest Surg, 2014; 18:1391–1397.

84.

Bhangu

, Singh

, Fitzgerald

, Slesser

, Tekkis

. Postoperative nonsteroidal anti-inflammatory drugs and risk of anastomotic leak: Meta-analysis of clinical and experimental studies. World J Surg, 2014; 38:2247–2257.

85.

Remerand

, Le Tendre

, Baud

, et al. The early and delayed analgesic effects of ketamine after total hip arthroplasty: A prospective, randomized, controlled, double-blind study. Anesth Analg, 2009; 109:1963–1971.

86.

Loftus

, Yeager

, Clark

, et al. Intraoperative ketamine reduces perioperative opiate consumption in opiate-dependent patients with chronic back pain undergoing back surgery. Anesthesiology, 2010; 113:639–646.

87.

McCartney

, Sinha

, Katz

. A qualitative systematic review of the role of N-methyl-D-aspartate receptor antagonists in preventive analgesia. Anesth Analg, 2004; 98:1385–1400.

88.

Tan

, Law

, Gan

. Optimizing pain management to facilitate enhanced recovery after surgery pathways. Can J Anaesth, 2015; 62:203–218.

89.

Khan

, Rahimi

, Makarem

, Khan

. Optimal dose of pre-incision/post-incision gabapentin for pain relief following lumbar laminectomy: A randomized study. Acta Anaesthesiol Scand, 2011; 55:306–312.

90.

Zhang

, Ho

, Wang

. Efficacy of pregabalin in acute postoperative pain: A meta-analysis. Br J Anaesth, 2011; 106:454–462.

91.

Chia

, Chan

, Ko

, Liu

. Role of beta-blockade in anaesthesia and postoperative pain management after hysterectomy. Br J Anaesth, 2004; 93:799–805.

92.

Blaudszun

, Lysakowski

, Elia

, Tramer

. Effect of perioperative systemic alpha2 agonists on postoperative morphine consumption and pain intensity: Systematic review and meta-analysis of randomized controlled trials. Anesthesiology, 2012; 116:1312–1322.

93.

, Jao

, Borel

, et al. The effect of epidural clonidine on perioperative cytokine response, postoperative pain, and bowel function in patients undergoing colorectal surgery. Anesth Analg, 2004; 99:502–509.

94.

Ramadhyani

, Park

, Carollo

, Waterman

, Nossaman

. Dexmedetomidine: Clinical application as an adjunct for intravenous regional anesthesia. Anesthesiol Clin, 2010; 28:709–722.

95.

Tufanogullari

, White

, Peixoto

, et al. Dexmedetomidine infusion during laparoscopic bariatric surgery: The effect on recovery outcome variables. Anesth Analg, 2008; 106:1741–1748.

96.

Waldron

, Jones

, Gan

, Allen

, Habib

. Impact of perioperative dexamethasone on postoperative analgesia and side-effects: Systematic review and meta-analysis. Br J Anesth, 2013; 110:191–200.

97.

Karanicolas

, Smith

, Kanbur

, Davies

, Guyatt

. The impact of prophylactic dexamethasone on nausea and vomiting after laparoscopic cholecystectomy: A systematic review and meta-analysis. Ann Surg, 2008; 248:751–762.

98.

Colin

, Gan

. Cancer recurrence and hyperglycemia with dexamethasone for postoperative nausea and vomiting prophylaxis: More moot points?. Anesth Analg, 2014; 118:1154–1156.

99.

Vigneault

, Turgeon

, Cote

, et al. Perioperative intravenous lidocaine infusion for postoperative pain control: A meta-analysis of randomized controlled trials. Can J Anesth, 2011; 58:22–37.

100.

Farag

, Ghobrial

, Sessler

, Dalton

, Liu

, Lee

, Zaky

, Benzel

, Bingaman

, Kurz

. Effect of perioperative intravenous lidocaine administration on pain, opioid consumption, and quality of life after complex spine surgery. Anesthesiology, 2013; 119:932–940.

101.

De Oliveira

Jr , Duncan

, Fitzgerald

, Nader

, Gould

, McCarthy

. Systemic lidocaine to improve quality of recovery after laparoscopic bariatric surgery: A randomized double-blinded placebo-controlled trial. Obes Surg, 2014; 24:212–218.

102.

Kang

, Kim

, Lee

. Intraoperative intravenous lidocaine reduces hospital length of stay following open gastrectomy for stomach cancer in men. J Clin Anesth, 2012; 24:465–470.

103.

Brower

RG.

Consequences of bed rest. Crit Care Med, 2009; 37:S422–S428.

104.

Convertino

, Bloomfield

, Greenleaf

. An overview of the issues: Physiological effects of bed rest and restricted physical activity. Med Sci Sports Exerc, 1997; 29:187–190.

105.

Alper

, Yüksel

. Comparison of acute and chronic pain after open nephrectomy versus laparoscopic nephrectomy: A prospective clinical trial. Medicine (Baltimore), 2016; 95:e3433.

106.

Harju

, Aspinen

, Juvonen

, Kokki

, Eskelinen

. Ten-year outcome after minilaparotomy versus laparoscopic cholecystectomy: A prospective randomised trial. Surg Endosc, 2013; 27:2512–2516.

107.

Stiff

, Rhodes

, Kelly

, Telford

, Armstrong

, Rees

. Long-term pain: Less common after laparoscopic than open cholecystectomy. Br J Surg, 1994; 81:1368–1370.