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Guidelines for pre- and intra-operative care in gynecologic/oncology surgery: Enhanced Recovery After Surgery (ERAS®) Society recommendations — Part I

Open AccessPublished:November 18, 2015DOI:https://doi.org/10.1016/j.ygyno.2015.11.015

      Highlights

      • We provide evidence supporting pre- and intra-operative management of patients undergoing gynecologic/oncology surgery.
      • This guideline will help integrate knowledge into practice, align perioperative care, and encourage future investigations.

      Keywords

      1. Introduction

      The systematic implementation of an evidence-based perioperative care protocol (or “enhanced recovery pathway,” ERP), such as that developed by the Enhanced Recovery After Surgery (ERAS®) Society, has resulted in an average reduction in length of stay of 2.5 days and a decrease in complications by as much as 50% for patients undergoing colorectal surgery [
      • Gustafsson U.O.
      • Scott M.J.
      • Schwenk W.
      • Demartines N.
      • Roulin D.
      • Francis N.
      • et al.
      Guidelines for perioperative care in elective colonic surgery: Enhanced Recovery After Surgery (ERAS) Society recommendations.
      ,
      • Greco M.
      • Capretti G.
      • Beretta L.
      • Gemma M.
      • Pecorelli N.
      • Braga M.
      Enhanced recovery program in colorectal surgery: a meta-analysis of randomized controlled trials.
      ]. These benefits are achieved by reducing surgical stress, maintaining normal physiological function postoperatively, and enhancing mobilization after surgery [
      • Ljungqvist O.
      • Jonathan E.
      Rhoads lecture 2011: insulin resistance and enhanced recovery after surgery.
      ]. Furthermore, use of ERP has resulted in a mean savings of $2245 (1651€) per patient [
      • Adamina M.
      • Kehlet H.
      • Tomlinson G.A.
      • Senagore A.J.
      • Delaney C.P.
      Enhanced recovery pathways optimize health outcomes and resource utilization: a meta-analysis of randomized controlled trials in colorectal surgery.
      ]. ERAS® protocols have been published for rectal, urological, pancreatic and gastric surgeries [
      • Nygren J.
      • Thacker J.
      • Carli F.
      • Fearon K.C.
      • Norderval S.
      • Lobo D.N.
      • et al.
      Guidelines for perioperative care in elective rectal/pelvic surgery: Enhanced Recovery After Surgery (ERAS) Society recommendations.
      ,
      • Cerantola Y.
      • Valerio M.
      • Persson B.
      • Jichlinski P.
      • Ljungqvist O.
      • Hubner M.
      • et al.
      Guidelines for perioperative care after radical cystectomy for bladder cancer: Enhanced Recovery After Surgery (ERAS®) Society recommendations.
      ,
      • Lassen K.
      • Coolsen M.M.
      • Slim K.
      • Carli F.
      • de Aguilar-Nascimento J.E.
      • Schäfer M.
      • et al.
      Guidelines for perioperative care for pancreaticoduodenectomy: Enhanced Recovery After Surgery (ERAS®) Society recommendations.
      ,
      • Mortensen K.
      • Nilsson M.
      • Slim K.
      • Schäfer M.
      • Mariette C.
      • Braga M.
      • et al.
      Consensus guidelines for enhanced recovery after gastrectomy: Enhanced Recovery After Surgery (ERAS®) Society recommendations.
      ]. Given the proven benefit to both the patient and the healthcare system, several international groups are currently working with the ERAS® Society to develop protocols specific for breast and reconstructive surgery, head and neck cancer, thoracic, hepatobiliary, and orthopedic surgery.
      A recent review of ERP in gynecologic oncology [
      • Nelson G.
      • Kalogera E.
      • Dowdy S.C.
      Enhanced recovery pathways in gynecologic oncology.
      ] showed marked dissimilarities among the protocols and highlighted the need to develop a standardized, evidence-based guideline for our specialty. Standardizing perioperative care helps to ensure that all patients receive optimal treatment and is required to measure compliance. Auditing compliance has proven to be a key factor to successfully implement and sustain an ERAS® protocol. The goal of this article is to critically review existing evidence and make recommendations for elements of pre- and intra-operative care in our specialty. This effort forms the basis of the ERAS® Guideline for pre- and intra-operative care in gynecologic/oncology surgery.

      2. Methods

      2.1 Literature search

      The authors convened in July 2014 to discuss topics for inclusion — the topic list was based on the ERAS® colonic surgery [
      • Gustafsson U.O.
      • Scott M.J.
      • Schwenk W.
      • Demartines N.
      • Roulin D.
      • Francis N.
      • et al.
      Guidelines for perioperative care in elective colonic surgery: Enhanced Recovery After Surgery (ERAS) Society recommendations.
      ] and rectal/pelvic [
      • Nygren J.
      • Thacker J.
      • Carli F.
      • Fearon K.C.
      • Norderval S.
      • Lobo D.N.
      • et al.
      Guidelines for perioperative care in elective rectal/pelvic surgery: Enhanced Recovery After Surgery (ERAS) Society recommendations.
      ] guidelines which were used as templates. After the topics were agreed upon they were then allocated among the group according to expertise. The literature search (1966–2014) used Embase and PubMed to search medical subject headings including “gynecology”, “gynecologic oncology” and all pre- and intra-operative ERAS® items (see Table 1). Reference lists of all eligible articles were crosschecked for other relevant studies.
      Table 1Guidelines for pre- and intraoperative care in gynecologic/oncology surgery: Enhanced Recovery After Surgery (ERAS®) Society recommendations.
      ItemRecommendationEvidence levelRecommendation grade
      Preoperative information education and counselingPatients should routinely receive dedicated preoperative counselingLowStrong
      Preoperative optimizationSmoking and alcohol consumption (alcohol abusers) should be stopped four weeks before surgerySmoking: HighStrong
      Alcohol: ModerateStrong
      Anemia should be actively identified, investigated, and corrected preoperativelyHighStrong
      Preoperative bowel preparationMechanical bowel preparation should not be used routinely even when bowel resection is plannedModerateStrong
      Preoperative fasting and carbohydrate treatmentClear fluids should be allowed up to 2 h and solids up to 6 h hours prior to induction of anesthesiaSolids/fluids: HighStrong
      Carbohydrate loading reduces postoperative insulin resistance and should be used routinelyCarb loading: Mod (outcome insulin resistance)

      Carb loading: Mod (other outcomes)
      Strong
      Preanesthetic medicationRoutine administration of sedatives to reduce anxiety preoperatively should be avoidedLowStrong
      Thromboembolism prophylaxisPatients at risk of VTE should receive prophylaxis with either LMWH or heparin, commenced preoperatively, combined with mechanical methodsHigh (Preop admin: Mod)Strong
      Patients should be advised to consider stopping HRT or consider alternative preparations before surgeryLowWeak
      Patients should discontinue oral contraception prior to surgery and switch to another formHighStrong
      Antimicrobial prophylaxis and skin preparationIV antibiotics (1st generation cephalosporin or amoxi–clav) should be administered routinely within 60 min before skin incision; additional doses should be given during prolonged operations, severe blood loss and obese patientsHighStrong
      Hair clipping is preferred if hair removal is mandatoryHighStrong
      Chlorhexidine–alcohol is preferred to aqueous povidone-iodine solution for skin cleansingHighStrong
      Standard anesthetic protocolShort acting anesthetic agents should be used to allow rapid awakeningLowStrong
      A ventilation strategy using tidal volumes of 5–7 ml/kg with a PEEP of 4–6 cm H2O should be employed to reduce postoperative pulmonary complicationsModerateStrong
      Postoperative nausea and vomitingA multimodal approach to PONV with >2 antiemetic agents should be used for patients undergoing gynecologic proceduresModerateStrong
      Minimally invasive surgery (MIS)MIS is recommended for appropriate patients when expertise and resources are availableMorbidity: Low

      Recovery: High
      Strong
      Nasogastric intubationRoutine nasogastric intubation should be avoidedHighStrong
      Nasogastric tubes inserted during surgery should be removed before reversal of anesthesia
      Preventing intraoperative hypothermiaMaintenance of normothermia with suitable active warming devices should be used routinelyHighStrong
      Perioperative fluid managementVery restrictive or liberal fluid regimes should be avoided in favor of euvolemiaHighStrong
      In major open surgery and for high risk patients where there is large blood loss (>7 ml/kg) or a SIRS response the use of advanced hemodynamic monitoring to facilitate individualized fluid therapy and optimize oxygen delivery during the perioperative period is recommendedModerateStrong

      2.2 Study selection

      Titles and abstracts were screened by individual reviewers to identify potentially relevant articles. Discrepancies in judgment were resolved by the lead (GN) and senior authors (OL, SD). Meta-analyses, systematic reviews, randomized controlled studies, non-randomized controlled studies, reviews, and case series were considered for each individual topic.

      2.3 Quality assessment and data analyses

      The quality of evidence and recommendations were evaluated according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system (see Table 2a, Table 2b) [
      • Guyatt G.H.
      • Oxman A.D.
      • Vist G.E.
      • Kunz R.
      • Falck-Ytter Y.
      • Alonso-Coello P.
      • et al.
      GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.
      ] whereby recommendations are given as follows: Strong recommendations indicate that the panel is confident that the desirable effects of adherence to a recommendation outweigh the undesirable effects. Weak recommendations indicate that the desirable effects of adherence to a recommendation probably outweigh the undesirable effects, but the panel is less confident. Recommendations are based on quality of evidence: high, moderate, low and very low, but also on the balance between desirable and undesirable effects. As such, consistent with other ERAS® Guideline Working groups [
      • Gustafsson U.O.
      • Scott M.J.
      • Schwenk W.
      • Demartines N.
      • Roulin D.
      • Francis N.
      • et al.
      Guidelines for perioperative care in elective colonic surgery: Enhanced Recovery After Surgery (ERAS) Society recommendations.
      ,
      • Cerantola Y.
      • Valerio M.
      • Persson B.
      • Jichlinski P.
      • Ljungqvist O.
      • Hubner M.
      • et al.
      Guidelines for perioperative care after radical cystectomy for bladder cancer: Enhanced Recovery After Surgery (ERAS®) Society recommendations.
      ], in some cases strong recommendations may be reached from low-quality data and vice versa. Of note, this would be considered a modified GRADE evaluation since we did not consider resource utilization when making our recommendations [
      • Brunetti M.
      • Shemilt I.
      • Pregno S.
      • Vale L.
      • Oxman A.D.
      • Lord J.
      • et al.
      GRADE guidelines: 10. Considering resource use and rating the quality of economic evidence.
      ].
      Table 2aGRADE system for rating quality of evidence.
      Evidence levelDefinition
      High qualityFurther research unlikely to change confidence in estimate of effect
      Moderate qualityFurther research likely to have important impact on confidence in estimate of effect and may change the estimate
      Low qualityFurther research very likely to have important impact on confidence in estimate of effect and likely to change the estimate
      Very low qualityAny estimate of effect is very uncertain
      Ref.
      • Guyatt G.H.
      • Oxman A.D.
      • Vist G.E.
      • Kunz R.
      • Falck-Ytter Y.
      • Alonso-Coello P.
      • et al.
      GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.
      .
      Table 2bGRADE system for rating strength of recommendations.
      Recommendation strengthDefinition
      StrongWhen desirable effects of intervention clearly outweigh the undesirable effects, or clearly do not
      WeakWhen trade-offs are less certain — either because of low quality evidence or because evidence suggests desirable and undesirable effects are closely balanced
      Ref.
      • Guyatt G.H.
      • Oxman A.D.
      • Vist G.E.
      • Kunz R.
      • Falck-Ytter Y.
      • Alonso-Coello P.
      • et al.
      GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.
      .

      3. Results

      The evidence base, recommendations, evidence level, and recommendation grade are provided for each individual ERAS® item below.

      3.1 Preadmission information, education and counseling

      Preoperative counseling helps to set expectations about surgical and anesthetic procedures and may diminish fear, fatigue, pain, and enhance recovery and early discharge [
      • Egbert L.D.
      • Battit G.E.
      • Welch C.E.
      • Bartlett M.K.
      Reduction of postoperative pain by encouragement and instruction of patients. A study of doctor–patient rapport.
      ]. Verbalized education, leaflets, and multimedia information containing explanations of the procedure and cognitive interventions may improve pain control, nausea and anxiety after surgery [
      • Ridgeway V.
      • Mathews A.
      Psychological preparation for surgery: a comparison of methods.
      ]. It is uncertain if formal education is superior to informal education [
      • Gurusamy K.S.
      • Vaughan J.
      • Davidson B.R.
      Formal education of patients about to undergo laparoscopic cholecystectomy.
      ], but ideally patients should receive information in both written and oral form. The patient and a relative or care provider should meet with all members of the team including the surgeon, anesthetist and nurse. Studies show that patients with gynecologic cancer prefer to be well informed, and support from a nurse at the time of diagnosis reduced stress levels for up to 6 months [
      • Stewart D.E.
      • Wong F.
      • Cheung A.M.
      • Dancey J.
      • Meana M.
      • Cameron J.I.
      • et al.
      Information needs and decisional preferences among women with ovarian cancer.
      ].
      Summary and recommendation:
      Although quality evidence is lacking, most studies show that counseling provides beneficial effects with no evidence of harm. It is recommended that patients should routinely receive dedicated preoperative counseling.
      Evidence level:
      Low.
      Recommendation grade:
      Strong.

      3.2 Preadmission optimization

      Use of tobacco, alcohol, and the presence of anemia should be routinely assessed preoperatively. Also, previously undiagnosed diabetes/hyperglycemic states are becoming increasingly common. Evidence that interventions addressing these factors prior to elective surgery reduce perioperative morbidity and mortality is presented below. For patients with gynecologic cancer, the risk of delaying surgery in order to complete preoperative optimization must be carefully considered.

      3.2.1 Smoking

      Smoking is associated with a high risk of postoperative complications, but the pulmonary effects of smoking can be improved within four weeks of cessation [
      • Sorensen L.T.
      Wound healing and infection in surgery: the pathophysiological impact of smoking, smoking cessation, and nicotine replacement therapy: a systematic review.
      ]. While smoking cessation interventions such as behavioral support and nicotine replacement therapy are known to result in short term smoking cessation, there is weak evidence to show that these measures decrease postoperative morbidity. A trial of varenicline showed an increase in long term smoking cessation but no evidence of a reduction in postoperative morbidity [
      • Thomsen T.
      • Villebro N.
      • Møller A.M.
      Interventions for preoperative smoking cessation.
      ].

      3.2.2 Alcohol

      The chronic effects of alcohol on the liver, pancreas and neurologic system are well known. In the perioperative period, effects of alcohol on cardiac function, blood clotting, immune function, and response to surgical stress contribute to excess morbidity. Intensive preoperative interventions aimed at complete alcohol cessation for at least four weeks reduces postoperative complications, but does not significantly reduce mortality or length of stay. However, only a small number of studies are available, the mechanism by which such interventions reduce complications is unknown, and the optimal timing of the interventions has yet to be determined [
      • Oppedal K.
      • Møller A.M.
      • Pedersen B.
      • Tønnesen H.
      Preoperative alcohol cessation prior to elective surgery.
      ].

      3.2.3 Preoperative hyperglycemia

      A report by the American Society of Anesthesiologists in 2012 noted that up to 40% of preoperative patients may have an abnormal blood glucose level and of the 13% with diabetes, 40% were undiagnosed [
      • Apfelbaum J.L.
      • Connis R.T.
      • Nickinovich D.G.
      American Society of Anesthesiologists Task Force on preanesthesia evaluation. Practice advisory for preanesthesia evaluation: an updated report by the American Society of Anesthesiologists Task Force on preanesthesia evaluation.
      ]. For the group with previously unrecognized hyperglycemia, the risk of adverse perioperative events was higher than the risks for patients with a known diagnosis of diabetes [
      • Kotagal M.
      • Symons R.G.
      • Hirsch I.B.
      • Umpierrez G.E.
      • Dellinger E.P.
      • Farrokhi E.T.
      • et al.
      Perioperative hyperglycemia and risk of adverse events among patients with and without diabetes.
      ]. In a small study of 120 patients undergoing colorectal surgery, elevated hemoglobin A1c (HbA1c) was associated with an increased risk of postoperative complications [
      • Gustafsson U.O.
      • Thorell A.
      • Soop M.
      • Ljungqvist O.
      • Nygren J.
      Haemoglobin A1c as a predictor of postoperative hyperglycaemia and complications after major colorectal surgery.
      ]. The benefit of tight glycemic control has not been shown conclusively but the authors of one review suggest that “it seems prudent to control blood glucose to a reasonable level preoperatively”, while acknowledging that “recommendations for exact targets cannot be made” [
      • Sheehy A.
      • Gabbay R.
      An overview of pre-operative glucose evaluation, management, and perioperative impact.
      ]. The results of a number of studies on tight glycemic control (TGC) are contradictory. Complicated and variable protocols are used to achieve glycemic control, the duration of TCG varies between studies, and there are persistent concerns with hypoglycemia. Delaying surgery to correct hyperglycemia has not been shown to improve surgical outcomes in existing larger observational datasets [
      • Holman R.R.
      • Paul S.K.
      • Bethel M.A.
      • Matthews D.R.
      • Neil H.A.
      10-year follow-up of intensive glucose control in type 2 diabetes.
      ].

      3.2.4 Anemia

      Preoperative anemia is associated with postoperative morbidity and mortality. A comprehensive review of blood management in Europe and the NHS Blood Transfusion Committee Guidelines in the UK advocate for preoperative screening for anemia. Anemia should be identified and corrected for iron deficiency and any underlying disorder before elective surgery [
      • NHS Blood Transfusion Committee
      Patient blood management — an evidence-based approach to patient care.
      ]. Treating anemia preoperatively helps to avoid adverse effects from anemia, transfusion or both. The risks are increased with the severity of the anemia [
      • Kotzé A.
      • Harris A.
      • Baker C.
      • Iqbal T.
      • Lavies N.
      • Richards T.
      • et al.
      British committee for standards in haematology guidelines on the identification and management of pre-operative anaemia.
      ]. The speed of response to iron therapy (oral or intravenous) is greater in more severe iron deficiency anemia and therefore prompt identification and treatment is important to reduce the need for erythropoiesis-stimulating agents or transfusion. Although not gynecological-cancer specific, both erythropoiesis-stimulating agents and perioperative transfusion have been associated with poorer outcomes for cancer patients, with a Cochrane review showing an increase in cancer recurrence following perioperative transfusion [
      • Amato A.
      • Pescatori M.
      Perioperative blood transfusions for the recurrence of colorectal cancer.
      ,
      • Tonia T.
      • Mettler A.
      • Robert N.
      • Schwarzer G.
      • Seidenfeld J.
      • Weingart O.
      • et al.
      Erythropoietin or darbepoetin for patients with cancer.
      ].
      The recent guideline from the British Committee for Hematology showed no strong evidence of benefit from preoperative transfusion to improve surgical outcomes (in cardiac surgery patients) and, in the absence of other blood management measures, did not reduce total transfusion requirements. Where transfusion is considered to be unavoidable there is no evidence to suggest advantages of pre- over intraoperative transfusion [
      • Kotzé A.
      • Harris A.
      • Baker C.
      • Iqbal T.
      • Lavies N.
      • Richards T.
      • et al.
      British committee for standards in haematology guidelines on the identification and management of pre-operative anaemia.
      ]. If possible, the focus should be on preventing further blood loss intraoperatively.
      Summary and recommendations:
      Smoking is associated with increased postoperative morbidity and should be stopped at least four weeks before surgery.
      Alcohol is associated with increased perioperative morbidity and mortality and should be avoided for at least four weeks before surgery in patients who abuse alcohol.
      Anemia is associated with an increase in postoperative morbidity and mortality and should be identified, investigated, and corrected preoperatively. Iron therapy is the preferred first line treatment for the correction of iron deficiency anemia.
      Evidence level:
      Smoking: High.
      Alcohol: Moderate (small number of studies).
      Anemia: High.
      Recommendation grade:
      Smoking: Strong.
      Alcohol: Strong.
      Anemia: Strong.

      3.3 Preoperative mechanical bowel preparation

      Mechanical bowel preparation (MBP) often results in patient distress, may cause dehydration, and evidence of benefit to the patient is lacking. A systematic review of 18 randomized clinical trials (5805 patients) found no statistically significant evidence that patients benefit from either bowel preparation or rectal enemas [
      • Guenaga K.F.
      • Matos D.
      • Wille-Jorgensen P.
      Mechanical bowel preparation for elective colorectal surgery.
      ] — the infection and anastomotic leak rates in patients with a bowel preparation was 9.6% and 4.4%, respectively, compared to 8.5% and 4.5% for those without. The authors concluded that in colonic surgery, bowel cleansing may be safely omitted. Recently, a number of large retrospective studies have suggested that oral antibiotic bowel preparation may be associated with decreased infection rates [
      • Toneva G.D.
      • Deierhoi R.J.
      • Morris M.
      • Richman J.
      • Cannon J.A.
      • Altom L.K.
      • et al.
      Oral antibiotic bowel preparation reduces length of stay and readmissions after colorectal surgery.
      ]. This, however, has not been verified in randomized trials investigating oral antibiotics alone (without MBP) in sufficient numbers of patients. There is some debate currently as to the benefit of bowel preparation in patients undergoing low anterior resection. In a single-blind, RCT of rectal cancer patients undergoing low anterior resection, patients were randomized to preoperative MBP versus no preparation [
      • Bretagnol F.
      • Panis Y.
      • Rullier E.
      • Rouanet P.
      • Berdah S.
      • Dousset B.
      • et al.
      Rectal cancer surgery with or without bowel preparation: the French GRECCAR III multicenter single-blinded randomized trial.
      ]. Overall and infectious morbidity were higher in the no MBP group. However, there was no significant difference in the rate of anastomotic leakage between groups. Further studies are required in this area.
      Finally, the routine use of mechanical bowel preparation before minimally invasive gynecologic surgery has not been shown to improve intraoperative visualization, bowel handling, or ease of performing the procedure [
      • Arnold A.
      • Aitchison L.P.
      • Abbott J.
      Preoperative mechanical bowel preparation for abdominal, laparoscopic, and vaginal surgery: a systematic review.
      ,
      • Kantartzis K.L.
      • Shepherd J.P.
      The use of mechanical bowel preparation in laparoscopic gynecologic surgery: a decision analysis.
      ,
      • Ryan N.A.
      • Ng V.S.
      • Sangi-Haghpeykar H.
      • Guan X.
      Evaluating mechanical bowel preparation prior to total laparoscopic hysterectomy.
      ].
      Summary and recommendation:
      Routine oral mechanical bowel preparation should not be used in gynecologic/oncology surgery, including patients with a planned enteric resection.
      Evidence level:
      Moderate (extrapolated from results in colorectal patients).
      Recommendation grade:
      Strong.

      3.4 Preoperative fasting and carbohydrate treatment

      Scientific evidence has shown that intake of clear fluids until 2 h before surgery does not increase gastric content, reduce gastric fluid pH, or increase complication rates. Hence, in patients without conditions associated with delayed gastric emptying, the intake of clear fluids until 2 h before the induction of anesthesia as well as a 6 h fast for solid food is now recommended [
      • Smith I.
      • Kranke P.
      • Murat I.
      • Smith A.
      • O'Sullivan G.
      • Soreide E.
      • et al.
      Perioperative fasting in adults and children: guidelines from the European Society of Anaesthesiology.
      ].
      In order to reduce postoperative insulin resistance and associated increased risks for complications, carbohydrate loading before surgery has been advocated to achieve a metabolically fed state. In the last decade an increasing number of original studies, systematic reviews, and meta-analyses have shown that carbohydrate loading attenuates the increase in insulin resistance related to surgery, and hence should be used routinely in major abdominal surgery [
      • Gustafsson U.O.
      • Scott M.J.
      • Schwenk W.
      • Demartines N.
      • Roulin D.
      • Francis N.
      • et al.
      Guidelines for perioperative care in elective colonic surgery: Enhanced Recovery After Surgery (ERAS) Society recommendations.
      ,
      • Smith M.D.
      • McCall J.
      • Plank L.
      • Herbison G.P.
      • Soop M.
      • Nygren J.
      Preoperative carbohydrate treatment for enhancing recovery after elective surgery.
      ]. Carbohydrate drinks for preoperative use should be properly tested as not all carbohydrate drinks have the same effects on gastric emptying. Although no studies have been performed in patients undergoing major gynecological surgery, these findings are considered valid for gynecologic patients given similarities in patient characteristics. Randomized trials have demonstrated that preoperative carbohydrates improve wellbeing and reduce nausea and vomiting [
      • Hausel J.
      • Nygren J.
      • Thorell A.
      • Lagerkranser M.
      • Ljungqvist O.
      Randomized clinical trial of the effects of oral preoperative carbohydrates on postoperative nausea and vomiting after laparoscopic cholecystectomy.
      ]. No studies have specifically addressed diabetic patients, although limited data indicate it is likely to be safe in well controlled diabetics.
      Summary and recommendation:
      Patients should be permitted to drink clear fluids until 2 h before anesthesia and surgery.
      Patients should abstain from solids 6 h prior to induction of anesthesia.
      Oral carbohydrate loading reduces postoperative insulin resistance, improves preoperative wellbeing, and should be used routinely.
      Insufficient data is available for diabetic patients.
      Evidence level:
      Solids and fluids: High.
      Carbohydrate loading, primary outcome insulin resistance: Moderate.
      Carbohydrate loading other outcomes: Moderate.
      Recommendation grade:
      Fasting guidelines: Strong.
      Carbohydrate loading: Strong.

      3.5 Preanesthetic medication

      Preoperative medications are widely used in major gynecological surgery to decrease anxiety. However, routine administration of long-acting sedatives within 12 h of surgery should be avoided due to its effects on immediate postoperative recovery [
      • Walker K.J.
      • Smith A.F.
      Premedication for anxiety in adult day surgery.
      ]. In 2009, a Cochrane review of short-acting oral anxiolytics for outpatient surgery concluded that patients were successfully discharged. However, an impairment in psychomotor function was observed in some studies up to 4 h postoperatively, which may negatively influence the patient's ability to ambulate, eat and drink [
      • Walker K.J.
      • Smith A.F.
      Premedication for anxiety in adult day surgery.
      ]. The use of short acting anxiolytics to address severe preoperative anxiety may be appropriate on a case by case basis.
      Summary and recommendation:
      Routine administration of sedatives to reduce anxiety preoperatively should be avoided in order to hasten postoperative recovery.
      Evidence level:
      Low.
      Recommendation grade:
      Strong.

      3.6 Thromboembolism prophylaxis

      Venous thromboembolism (VTE) is a major risk in gynecologic oncology patients with rates as high as 8% in endometrial cancer [
      • Matsuo K.
      • Yessaian A.A.
      • Lin Y.G.
      • Pham H.Q.
      • Muderspach L.I.
      • Liebman H.A.
      • et al.
      Predictive model of venous thromboembolism in endometrial cancer.
      ] and 38% in ovarian cancer [
      • Levitan N.
      • Dowlati A.
      • Remick S.C.
      • Tahsildar H.I.
      • Sivinski L.D.
      • Beyth R.
      • et al.
      Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy. Risk analysis using medicare claims data.
      ]. An analysis from the Million Women study showed an increased risk of VTE 12 weeks postoperatively, with a risk of 1/85 for oncologic surgery and 1/365 for gynecologic surgery [
      • Sweetland S.
      • Green J.
      • Liu B.
      • Berrington de González A.
      • Canonico M.
      • Reeves G.
      • et al.
      Duration and magnitude of the postoperative risk of venous thromboembolism in middle aged women: prospective cohort study.
      ]. Patients undergoing oncologic surgery were at over 90 times the risk of VTE in the first 6 weeks. All gynecologic oncology patients with major surgery >30 min should receive VTE prophylaxis with either low molecular weight heparin (LMWH) or heparin [
      • Baykal C.
      • Al A.
      • Demirtas E.
      • Ayhan A.
      Comparison of enoxaparin and standard heparin in gynaecologic oncologic surgery: a randomised prospective double-blind clinical study.
      ]. Prophylaxis should be commenced preoperatively, combined with mechanical methods, and continued post-operatively [
      • Lyman G.H.
      • Khorana A.A.
      • Kuderer N.M.
      • Lee A.Y.
      • Arcelus J.I.
      • Balaban E.P.
      • et al.
      Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology Clinical Practice guideline update.
      ].

      3.6.1 Preoperative anticoagulation

      Only one retrospective study has examined preoperative versus postoperative anticoagulation in gynecologic oncology, showing a decreased rate of DVT (8% vs. 1.9%; p = 0.04) and a decreased rate of DVT associated deaths (0 vs. 2; p < 0.001) when given preoperatively; all patients in this study received combined prophylaxis with medical and mechanical methods [
      • Whitworth J.M.
      • Schneider K.E.
      • Frederick P.J.
      • Finan M.A.
      • Reed E.
      • Fauci J.M.
      • et al.
      Double prophylaxis for deep venous thrombosis in patients with gynecologic oncology who are undergoing laparotomy: does preoperative anticoagulation matter?.
      ].

      3.6.2 Intraoperative prophylaxis

      Prophylactic anticoagulation has not been shown to increase risks of hemorrhage, thrombocytopenia or epidural hematoma. Low dose prophylactic heparin has been commonly used with less than 10 cases of reported spinal hematomas; however given the serious sequelae associated with spinal hematomas, epidural catheters and spinal anesthetics should not be placed or removed 12 h before or after the last dose of therapeutic heparin [
      • Horlocker T.T.
      • Wedel D.J.
      • Rowlingson J.C.
      • Enneking F.K.
      • Kopp S.L.
      • Benzon H.T.
      • et al.
      Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-based guidelines (third edition).
      ].
      Pneumatic compression stockings reduce the rate of VTE when compared to observation within the first 5 days postoperatively [
      • Clarke-Pearson D.L.
      • Synan I.S.
      • Dodge R.
      • Soper J.T.
      • Berchuck A.
      • Coleman R.E.
      A randomized trial of low-dose heparin and intermittent pneumatic calf compression for the prevention of deep venous thrombosis after gynecologic oncology surgery.
      ]. Their efficacy is equivalent to heparin [
      • Maxwell G.L.
      • Synan I.
      • Dodge R.
      • Carroll B.
      • Clarke-Pearson D.L.
      Pneumatic compression versus low molecular weight heparin in gynecologic oncology surgery: a randomized trial.
      ] and improved when combined with heparin [
      • Einstein M.H.
      • Kushner D.M.
      • Connor J.P.
      • Bohl A.A.
      • Best T.J.
      • Evans M.D.
      • et al.
      A protocol of dual prophylaxis for venous thromboembolism prevention in gynecologic cancer patients.
      ] in gynecologic oncology patients.

      3.6.3 Special circumstances

      3.6.3.1 Hormone replacement therapy (HRT)

      A Cochrane review on long term hormone therapy for perimenopausal and postmenopausal women showed an elevated risk of thromboembolism in women treated with continuous combined HRT or estrogen used alone [
      • Marjoribanks J.
      • Farquhar C.
      • Roberts H.
      • Lethaby A.
      Long term hormone therapy for perimenopausal women.
      ]. Extrapolating from this evidence, the use of HRT is viewed as a perioperative risk factor for thromboembolism [
      • Panay N.
      • Hamoda H.
      • Arya R.
      • Savvas M.
      The 2013 British Menopause Society and Women's Health Concern recommendations on hormone replacement therapy.
      ]. In the United Kingdom both the National Institute for Health and Clinical Excellence (NICE) and the Royal College of Obstetricians and Gynecologists (RCOG) suggest that patients discontinue HRT 4 weeks before surgery, but stop short of a direct recommendation [
      • NICE
      Clinical Guideline 92. Reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in patients admitted to hospital.
      ,
      Venous Thromboembolism and Hormone Replacement Therapy.
      ]. These recommendations acknowledge the paucity of direct evidence of HRT as a risk factor and emphasize the importance of discussing the risks and benefits of stopping HRT. Changing from an oral to a transdermal estrogen preparation may reduce thromboembolic risk; of note, most patients taking HRT will meet criteria to receive thromboprophylaxis.

      3.6.3.2 Combined oral hormonal contraception

      Combined oral hormonal contraception is a risk factor for postoperative thromboembolism. The risk of thromboembolism varies according to progesterone type, with levonorgestrel, norethisterone, and norgestimate associated with the lowest risk. Women should be encouraged to use an alternative form of contraception preoperatively. Continued use of combined oral hormonal contraception is an indication for thromboprophylaxis [
      • NICE
      Clinical Guideline 92. Reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in patients admitted to hospital.
      ,
      Venous Thromboembolism and Hormone Replacement Therapy.
      ].
      Summary and recommendation:
      Patients at risk of VTE should receive prophylaxis with either LMWH or heparin, commenced preoperatively, combined with mechanical methods, and continued post-operatively.
      HRT is a relative risk factor for postoperative thromboembolism and patients should be advised to consider stopping or switching to alternative preparations before surgery, taking into account the risks and benefits. If HRT is continued, thromboprophylaxis should be considered.
      Combined oral hormonal contraception is a risk factor for thromboembolism. Patients should change to another form of contraception prior to surgery. If continued to the time of surgery, thromboprophylaxis should be prescribed.
      Evidence level:
      Stockings, pneumatic compression, LMWH: High.
      Preoperative administration: Moderate.
      HRT: Low.
      Combined oral hormonal contraception: High.
      Recommendation grade:
      Pre-operative DVT prophylaxis: Strong.
      HRT: Weak.
      Combined oral hormonal contraception: Strong.

      3.7 Antimicrobial prophylaxis and skin preparation

      Most surgical interventions for gynecologic malignancies include total hysterectomy which is classified as a clean contaminated, or type II incision. Surgical site infections (SSI) in gynecology involve skin flora, vaginal flora, or enteric bacteria when the colon is entered. Prophylactic antibiotics should therefore be broad spectrum. Many studies and meta-analyses have demonstrated the benefits of antibiotic prophylaxis in reducing surgical site infection after vaginal or abdominal hysterectomy [
      • Tanos V.
      • Rojansky N.
      Prophylactic antibiotics in abdominal hysterectomy.
      ]. Cephalosporins are the most commonly recommended antibiotic class given their broad spectrum, low cost, and low allergenic potential [
      • Bulletins–Gynecology, A.C.o.P.
      ACOG Practice Bulletin No. 104: antibiotic prophylaxis for gynecologic procedures.
      ]. Cefazolin is generally recommended for gynecologic interventions where antibiotic prophylaxis is mandatory. Amoxicillin–clavulanic acid has been shown to be equivalent to cefazolin and can also be used [
      • Gadducci A.
      • Cosio S.
      • Spirito N.
      • Genazzani A.R.
      The perioperative management of patients with gynaecological cancer undergoing major surgery: a debated clinical challenge.
      ]. Antibiotics are administered intravenously within 1 h [
      • Hawn M.T.
      • Richman J.S.
      • Vick C.C.
      • Deierhoi R.J.
      • Graham L.A.
      • Henderson W.G.
      • et al.
      Timing of surgical antibiotic prophylaxis and the risk of surgical site infection.
      ] before skin incision (usually at the time of anesthesia induction). The dose should be increased in obese patients (BMI > 35 or >100 kg) [
      • Forse R.A.
      • Karam B.
      • MacLean L.D.
      • Christou N.V.
      Antibiotic prophylaxis for surgery in morbidly obese patients.
      ], and repeated after 1–2 times the half-life of the chosen medication in prolonged operations (eg. 3 h for cefazolin, half-life: 1.8 h) and in case of blood loss >1500 ml [
      • Swoboda S.M.
      • Merz C.
      • Kostuik J.
      • Trentler B.
      • Lipsett P.A.
      Does intraoperative blood loss affect antibiotic serum and tissue concentrations?.
      ]. For patients allergic to penicillin/cephalosporin, a combination of clindamycin and gentamycin IV or a quinolone (eg. ciprofloxacin) can be used. Laparoscopic operations not contaminated by the genitourinary or digestive tracts do not require antimicrobial prophylaxis [
      • Morrill M.Y.
      • Schimpf M.O.
      • Abed H.
      • Carberry C.
      • Margulies R.U.
      • White A.B.
      • et al.
      Antibiotic prophylaxis for selected gynecologic surgeries.
      ].
      Skin preparation before surgery traditionally includes a shower, hair removal and the use of skin antiseptic solution. One Cochrane review addressed the topic of showering or bathing with different antiseptic solutions before surgery [
      • Webster J.
      • Osborne S.
      Preoperative bathing or showering with skin antiseptics to prevent surgical site infection.
      ]. Showering using plain soap is as effective as chlorhexidine in reducing surgical site infection. Compared to shaving, hair clipping in the operating room immediately prior to surgery is associated with lower rates of SSI [
      • Tanner J.
      • Norrie P.
      • Melen K.
      Preoperative hair removal to reduce surgical site infection.
      ]. However, there is no clear evidence that hair removal reduces SSI, irrespective of the method chosen (shaving, hair clipping or depilatory cream). Therefore, hair removal should be avoided and if deemed necessary hair clipping is preferred.
      Skin antiseptic is highly recommended. A RCT showed a 40% reduction in SSI when using chlorhexidine gluconate and isopropyl alcohol 70% compared to an aqueous solution of 10% povidone-iodine for skin cleansing in different clean-contaminated interventions [
      • Darouiche R.O.
      • Wall Jr., M.J.
      • Itani K.M.
      • Otterson M.F.
      • Webb A.L.
      • Carrick M.M.
      • et al.
      Chlorhexidine–alcohol versus povidone-iodine for surgical-site antisepsis.
      ]. Chlorhexidine–alcohol therefore is preferred over aqueous povidone-iodine solution although care must be taken to avoid ignition when electrocautery is used [
      • Rocos B.
      • Donaldson L.J.
      Alcohol skin preparation causes surgical fires.
      ].
      Summary and recommendation:
      IV antibiotics should be administered routinely within 60 min before skin incision. The dose should be repeated in case of prolonged operations or severe blood loss and increased in obese patients.
      Hair clipping is preferred if hair removal is mandatory.
      Chlorhexidine–alcohol is preferred to aqueous povidone-iodine solution for skin cleansing.
      Evidence level:
      Antibiotic prophylaxis: High.
      Hair clipping: High.
      Chlorhexidine–alcohol: High.
      Recommendation grade:
      Antibiotic prophylaxis: Strong.
      Hair clipping: Strong.
      Chlorhexidine–alcohol: Strong.

      3.8 Standard anesthetic protocol

      To allow rapid awakening, anesthesia should be maintained with short-acting agents such as sevoflurane or desflurane, or continuous target controlled infusions of propofol. When combined with short-acting opioid analgesics such as remifentanil, this may allow a consistently rapid recovery. Propofol-based total intravenous anesthesia has fewer postoperative side effects and the advantage of producing less postoperative nausea and vomiting [
      • Bailie R.
      • Craig C.
      • Restall J.
      Total intravenous anesthesia for laparoscopy.
      ]. Nitrous oxide is associated with postoperative nausea and vomiting (PONV) when the baseline risk of vomiting is high [
      • Tramer M.
      • Moore A.
      • McQuay H.
      Omitting nitrous oxide in general anaesthesia: meta-analysis of intraoperative awareness and postoperative emesis in randomized controlled trials.
      ]. Both laparoscopic procedures and gynecological surgery are independent predictors of PONV [
      • Apfel C.C.
      • Heidrich F.M.
      • Jukar-Rao S.
      • Jalota L.
      • Hornuss C.
      • Whelan R.P.
      • et al.
      Evidence-based analysis of risk factors for postoperative nausea and vomiting.
      ], so it is reasonable to omit N2O during laparoscopic gynecologic surgery to prevent PONV and prophylaxis with a combination of at least 2 antiemetics should be standard. Use of bispectral index (BIS) to guide anesthetic depth may allow reduction of anesthetic dose and hence facilitate rapid awakening [
      • Punjasawadwong Y.
      • Phongchiewboon A.
      • Bunchungmongkol N.
      Bispectral index for improving anaesthetic delivery and postoperative recovery.
      ]. Regional anesthetic techniques are opioid sparing, reducing PONV and allowing more rapid awakening [
      • Guay J.
      The benefits of adding epidural analgesia to general anesthesia: a meta-analysis.
      ]. Recent studies have shown a reduction in pulmonary complications in patients undergoing open abdominal surgery when a lung protective ventilation strategy is utilized (TV5-7 ml/kg with PEEP 4–6 cm H2O) [
      • Futier E.
      • Constantin J.M.
      • Paugam-Burtz C.
      • Pascal J.
      • Eurin M.
      • Neuschwander A.
      • et al.
      A trial of intraoperative low-tidal-volume ventilation in abdominal surgery.
      ].
      Summary and recommendation:
      Short acting anesthetic agents should be used to allow rapid awakening. The addition of regional anesthesia to general anesthesia is opioid sparing, helps reduce PONV, and allows more rapid awakening.
      A ventilation strategy using tidal volumes of 5–7 ml/kg with a PEEP of 4–6 cm H2O reduces postoperative pulmonary complications.
      Evidence level:
      Short acting general anesthesia: Low (lack of data).
      Lung protective ventilation (5–7 ml/kg): Moderate.
      Recommendation:
      Short acting general anesthesia: Strong.
      Lung protective ventilation: Strong.

      3.9 Prevention of postoperative nausea and vomiting

      Postoperative nausea and vomiting (PONV) is very common and troubling for patients undergoing gynecologic surgery. Vomiting occurs in 12–30% and nausea in 22–80% [
      • Gan T.J.
      • Diemunsch P.
      • Habib A.S.
      • Kovac A.
      • Kranke P.
      • Meyer T.A.
      • et al.
      Consensus guidelines for the management of postoperative nausea and vomiting.
      ], potentially leading to prolonged hospitalization and distress. Several risk factors have been identified for PONV including: age <50 years, gynecologic surgery, laparoscopic surgery, female gender, history of PONV or motion sickness, non-smoking, use of volatile anesthetics, long duration of anesthesia, postoperative opioid use, obesity, and use of nitrous oxide [
      • Apfel C.C.
      • Heidrich F.M.
      • Jukar-Rao S.
      • Jalota L.
      • Hornuss C.
      • Whelan R.P.
      • et al.
      Evidence-based analysis of risk factors for postoperative nausea and vomiting.
      ,
      • Gan T.J.
      • Diemunsch P.
      • Habib A.S.
      • Kovac A.
      • Kranke P.
      • Meyer T.A.
      • et al.
      Consensus guidelines for the management of postoperative nausea and vomiting.
      ]. A patient's risk of PONV may be assessed using a validated risk score [
      • Gan T.J.
      • Diemunsch P.
      • Habib A.S.
      • Kovac A.
      • Kranke P.
      • Meyer T.A.
      • et al.
      Consensus guidelines for the management of postoperative nausea and vomiting.
      ,
      • Apfel C.C.
      • Laara E.
      • Koivuranta M.
      • Greim C.A.
      • Roewer N.
      A simplified risk score for predicting postoperative nausea and vomiting: conclusions from cross-validations between two centers.
      ], allowing the clinician to give prophylaxis to patients deemed to be at high risk.
      Strategies for reducing PONV include administration of antiemetic prophylaxis to all patients receiving abdominal surgery and emetogenic anesthetics/analgesics; this would likely include a large proportion of gynecologic or gynecologic oncology patients. The second strategy is to decrease PONV risk by avoiding general anesthesia, using propofol infusions, avoiding nitrous oxide and volatile anesthetics, reducing opioid use, and decreasing the neostigmine dose [
      • Gan T.J.
      • Diemunsch P.
      • Habib A.S.
      • Kovac A.
      • Kranke P.
      • Meyer T.A.
      • et al.
      Consensus guidelines for the management of postoperative nausea and vomiting.
      ,
      • Apfel C.C.
      • Korttila K.
      • Abdalla M.
      • Kerger H.
      • Turan A.
      • Vedder I.
      • et al.
      A factorial trial of six interventions for the prevention of postoperative nausea and vomiting.
      ]. Although regional interventions (e.g. transversus abdominis plane block) may decrease opioid use and postoperative pain, this may not directly translate into a PONV advantage in all cases [
      • Charlton S.
      • Cyna A.M.
      • Middleton P.
      • Griffiths J.D.
      Perioperative transversus abdominis plane (TAP) blocks for analgesia after abdominal surgery.
      ].
      A multimodal approach to PONV prevention is quickly becoming standard of care. Antiemetics are classified into the following categories: 5HT3 antagonists, NK-1 antagonists, corticosteroids, butyrophenones, antihistamines, anticholinergics and phenothiazines [
      • Gan T.J.
      • Diemunsch P.
      • Habib A.S.
      • Kovac A.
      • Kranke P.
      • Meyer T.A.
      • et al.
      Consensus guidelines for the management of postoperative nausea and vomiting.
      ,
      • Carlisle J.B.
      • Stevenson C.A.
      Drugs for preventing postoperative nausea and vomiting.
      ]. Combinations of two or more classes of antiemetics may enhance potency (e.g. aprepitant, ondansetron, midazolam, or haloperidol combined with dexamethasone) [
      • Gan T.J.
      • Diemunsch P.
      • Habib A.S.
      • Kovac A.
      • Kranke P.
      • Meyer T.A.
      • et al.
      Consensus guidelines for the management of postoperative nausea and vomiting.
      ,
      • Habib A.S.
      • El-Moalem H.E.
      • Gan T.J.
      The efficacy of the 5-HT3 receptor antagonists combined with droperidol for PONV prophylaxis is similar to their combination with dexamethasone. A meta-analysis of randomized controlled trials.
      ,
      • Pan P.H.
      • Lee S.C.
      • Harris L.C.
      Antiemetic prophylaxis for postdischarge nausea and vomiting and impact on functional quality of living during recovery in patients with high emetic risks: a prospective, randomized, double-blind comparison of two prophylactic antiemetic regimens.
      ,
      • Karanicolas P.J.
      • Smith S.E.
      • Kanbur B.
      • Davies E.
      • Guyatt G.H.
      The impact of prophylactic dexamethasone on nausea and vomiting after laparoscopic cholecystectomy: a systematic review and meta-analysis.
      ,
      • Gan T.J.
      • Meyer T.A.
      • Apfel C.C.
      • Chung F.
      • Davis P.J.
      • Habib A.S.
      • et al.
      Society for Ambulatory Anesthesia guidelines for the management of postoperative nausea and vomiting.
      ]. Although dexamethasone has good efficacy for PONV and pain control, its long term effects as an immunosuppressant are unknown [
      • Gan T.J.
      • Diemunsch P.
      • Habib A.S.
      • Kovac A.
      • Kranke P.
      • Meyer T.A.
      • et al.
      Consensus guidelines for the management of postoperative nausea and vomiting.
      ]. If nausea and vomiting occurs postoperatively, an antiemetic drug from a different class should be selected. A 5-HT3 antagonist should be administered first since it is the only category that has been well studied for existing PONV [
      • Gan T.J.
      • Diemunsch P.
      • Habib A.S.
      • Kovac A.
      • Kranke P.
      • Meyer T.A.
      • et al.
      Consensus guidelines for the management of postoperative nausea and vomiting.
      ,
      • Gan T.J.
      • Meyer T.A.
      • Apfel C.C.
      • Chung F.
      • Davis P.J.
      • Habib A.S.
      • et al.
      Society for Ambulatory Anesthesia guidelines for the management of postoperative nausea and vomiting.
      ,
      • Meyer T.A.
      • Roberson C.R.
      • Rajab M.H.
      • Davis J.
      • McLeskey C.H.
      Dolasetron versus ondansetron for the treatment of postoperative nausea and vomiting.
      ]. Transdermal scopolamine has also been shown to decrease the rate of PONV with application the night before or on the same day as surgery [
      • Orhan-Sungur M.
      • Kranke P.
      • Sessler D.
      • Apfel C.C.
      Does supplemental oxygen reduce postoperative nausea and vomiting? A meta-analysis of randomized controlled trials.
      ].
      Supplemental oxygen may reduce the risk of early vomiting, but has no overall effect on PONV, and is therefore no longer recommended for the prevention of PONV [
      • Gan T.J.
      • Diemunsch P.
      • Habib A.S.
      • Kovac A.
      • Kranke P.
      • Meyer T.A.
      • et al.
      Consensus guidelines for the management of postoperative nausea and vomiting.
      ,
      • Orhan-Sungur M.
      • Kranke P.
      • Sessler D.
      • Apfel C.C.
      Does supplemental oxygen reduce postoperative nausea and vomiting? A meta-analysis of randomized controlled trials.
      ]. P6 acupoint stimulation has also been shown to decrease PONV regardless of timing of administration [
      • Frey U.H.
      • Scharmann P.
      • Lohlein C.
      • Peters J.
      P6 acustimulation effectively decreases postoperative nausea and vomiting in high-risk patients.
      ]. Other therapies including music therapy, isopropyl alcohol, aromatherapy, ginger, NG decompression, proton pump inhibitor and nicotine patches have been proposed, but are not supported by current evidence [
      • Gan T.J.
      • Diemunsch P.
      • Habib A.S.
      • Kovac A.
      • Kranke P.
      • Meyer T.A.
      • et al.
      Consensus guidelines for the management of postoperative nausea and vomiting.
      ,
      • Reza N.
      • Ali S.M.
      • Saeed K.
      • Abul-Qasim A.
      • Reza T.H.
      The impact of music on postoperative pain and anxiety following cesarean section.
      ,
      • Teran L.
      • Hawkins J.K.
      The effectiveness of inhalation isopropyl alcohol vs. granisetron for the prevention of postoperative nausea and vomiting.
      ,
      • Weilbach C.
      • Kahler K.
      • Thissen U.
      • Rahe-Meyer N.
      • Piepenbrock S.
      Esomeprazole for the prevention of postoperative nausea and vomiting. A randomized, placebo-controlled trial.
      ,
      • Ernst E.
      • Pittler M.H.
      Efficacy of ginger for nausea and vomiting: a systematic review of randomized clinical trials.
      ,
      • Czarnetzki C.
      • Schiffer E.
      • Lysakowski C.
      • Haller G.
      • Bertrand D.
      • Tramèr M.R.
      Transcutaneous nicotine does not prevent postoperative nausea and vomiting: a randomized controlled trial.
      ]. Alternative non-pharmacologic therapies are not commonly used due to difficulties with access and efficacy of existing drug therapies.
      Summary and recommendations:
      Patients undergoing gynecologic procedures should receive prophylaxis using a multimodal approach to PONV using more than two antiemetic agents.
      The risk of PONV is reduced with increased utilization of regional anesthesia, decreasing or eliminating opioids, neostigmine, volatile anesthetics, and increasing propofol use.
      Evidence level:
      Moderate.
      Recommendation grade:
      Strong.

      3.10 Minimally invasive surgery

      The introduction of laparoscopy and, more recently, robotic surgery, has led to substantial improvements in patient outcomes by decreasing intraoperative blood loss, length of stay, analgesic requirements, return of bowel function, length of hospitalization, and return to normal daily activities [
      • Obermair A.
      • Baker J.M.
      • Kondalsamy-Chennakesavan S.
      • Brand A.
      • Hogg R.
      • Jobling T.W.
      • et al.
      Improved surgical safety after laparoscopic compared to open surgery for apparent early stage endometrial cancer: results from a randomised controlled trial.
      ,
      • Walker J.L.
      • Piedmonte M.R.
      • Spirtos N.M.
      • Eisenkop S.M.
      • Schlaerth J.B.
      • et al.
      Laparoscopy compared with laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group Study LAP2.
      ]. However, the perioperative benefits of this approach may be reduced by a number of elements, including uncontrolled pain, nausea and vomiting, fluid overload, limited ambulation, fatigue, and deconditioning, irrespective of the existence of postoperative complications. Age, blood loss, perioperative blood transfusion, and postoperative complications have been associated with prolonged length of stay after laparoscopic surgery [
      • Zand B.
      • Frumovitz M.
      • Jofre M.F.
      • Nick A.M.
      • Dos Reis R.
      • Munsell M.F.
      • et al.
      Risk factors for prolonged hospitalization after gynecologic laparoscopic surgery.
      ].
      While most investigations of ERAS programs have been performed in open surgery, there is mounting evidence that ERAS programs are also beneficial for patients undergoing laparoscopic surgery. The LAFA (LAparoscopy and/or FAst track multimodal management vs. standard of care) trial evaluated patients requiring segmental colectomy for colon cancer. The study included four arms (laparoscopy/ERAS vs. laparoscopy/traditional vs. open/ERAS vs. open/traditional). The investigators in this study concluded that the optimal perioperative treatment for patients requiring segmental colectomy for colon cancer was laparoscopic resection in combination with an ERAS program [
      • Vlug M.S.
      • Wind J.
      • Hollman M.W.
      • Ubbink D.T.
      • Cense H.A.
      • Engel A.F.
      • 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).
      ]. Furthermore, several reports have shown that implementation of an ERAS program may also be of benefit in the setting of vaginal hysterectomy, including a shorter length of hospital stay and higher patient satisfaction scores [
      • Relph S.
      • Bell A.
      • Sivashanmugarajan V.
      • Munro K.
      • Chigwidden K.
      • Lloyd S.
      • et al.
      Cost effectiveness of enhanced recovery after surgery programme for vaginal hysterectomy: a comparison of pre and post-implementation expenditures.
      ,
      • Yoong W.
      • Sivashanmugarajan V.
      • Relph S.
      • Bell A.
      • Fajemirokun E.
      • Davies T.
      • et al.
      Can enhanced recovery pathways improve outcomes of vaginal hysterectomy? Cohort control study.
      ].
      Elements of particular value for an ERAS program in minimally invasive surgery include avoidance of prolonged nasogastric intubation (see Nasogastric intubation, below), maintenance of normothermia, normovolemia with maintenance of adequate cardiac output (impacted in minimally invasive surgery by head-down position and pneumoperitoneum), prevention of postoperative ileus, and early mobilization [
      • Gustafsson U.O.
      • Scott M.J.
      • Schwenk W.
      • Demartines N.
      • Roulin D.
      • Francis N.
      • et al.
      Guidelines for perioperative care in elective colonic surgery: Enhanced Recovery After Surgery (ERAS) Society recommendations.
      ].
      Summary and recommendation:
      Minimally invasive surgery (MIS), including vaginal surgery is preferred for appropriate patients when feasible.
      Evidence level:
      Morbidity: Low.
      Recovery: High.
      Recommendation grade:
      Strong.

      3.11 Nasogastric intubation

      Meta-analyses have concluded that nasogastric intubation increases the risk of postoperative pneumonia (6% vs. 3%) after elective abdominal surgery. Moreover, nasogastric decompression does not reduce the risk of wound dehiscence or intestinal leaks [
      • Cheatham M.L.
      • Chapman W.C.
      • Key S.P.
      • Sawyers J.L.
      A meta-analysis of selective versus routine nasogastric decompression after elective laparotomy.
      ]. In a prospective randomized trial comparing early feeding to nasogastric decompression after major open gynecologic oncology surgery, the authors found no significant difference in postoperative nausea and vomiting between the two groups. Only 10% of the early feeding arm required nasogastric tube insertion because of sub-occlusive symptoms. Conversely, 88% of patients who had a nasogastric tube experienced moderate to severe discomfort. Time to passage of flatus or stools and length of hospital stay was significantly shorter in the early diet group [
      • Cutillo G.
      • Maneschi F.
      • Franchi M.
      • Giannice R.
      • Scambia G.
      • Benedetti-Panici P.
      Early feeding compared with nasogastric decompression after major oncologic gynecologic surgery: a randomized study.
      ].
      One exception where gastric decompression by oro- or nasogastric intubation may be of benefit is during laparoscopic or robotic surgery, whereby decompression may be used to reduce risk of gastric perforation by trochar or Veress needle insertion. The tube, however, should be removed at extubation.
      Summary and recommendation:
      Routine nasogastric intubation should be avoided. Nasogastric tubes inserted during surgery should be removed before reversal of anesthesia.
      Evidence level:
      High.
      Recommendation grade:
      Strong.

      3.12 Preventing intraoperative hypothermia

      During anesthesia and major surgery there is a high risk of hypothermia due to exposure and impairment of the normal thermoregulatory response, resulting in accelerated heat loss [

      Warttig S, Alderson P, Campbell G, Smith AF. Interventions for treating inadvertent postoperative hypothermia. Warttig S. Cochrane Database Syst. Rev. Nov 20 2014;11:CD009892. http://dx.doi.org/10.1002/14651858.CD009892.pub2.

      ]. Hypothermia has been shown to impair drug metabolism, adversely affect coagulation, and increase bleeding, cardiac morbidity, and wound infection [

      Warttig S, Alderson P, Campbell G, Smith AF. Interventions for treating inadvertent postoperative hypothermia. Warttig S. Cochrane Database Syst. Rev. Nov 20 2014;11:CD009892. http://dx.doi.org/10.1002/14651858.CD009892.pub2.

      ,
      • Scott E.M.
      • Buckland R.
      A systematic review of intraoperative warming to prevent postoperative complications.
      ,
      • Rajagopalan S.
      • Mascha E.
      • Na J.
      • Sessler D.I.
      The effects of mild perioperative hypothermia on blood loss and transfusion requirement.
      ]. Postoperative shivering also increases oxygen consumption at a critical time and can worsen pain [
      • Scott E.M.
      • Buckland R.
      A systematic review of intraoperative warming to prevent postoperative complications.
      ]. It is important to maintain normothermia by active methods throughout the perioperative period, including prewarming patients to avoid an initial drop in body temperature [
      • Wong P.F.
      • Kumar S.
      • Bohra A.
      • Whetter D.
      • Leaper D.J.
      Randomized clinical trial of perioperative systemic warming in major elective abdominal surgery.
      ]. Wound infections are significantly less common with the use of active warming compared to conventional methods, with an absolute risk reduction of 13% [
      • Scott E.M.
      • Buckland R.
      A systematic review of intraoperative warming to prevent postoperative complications.
      ]. During surgery, warming using forced air blanket devices are effective and widely used [
      • Galvão C.M.
      • Liang Y.
      • Clark A.M.
      Effectiveness of cutaneous warming systems on temperature control: meta analysis.
      ]. Underbody warming mattresses are also effective and avoid the use of a blanket that may interfere with surgical access, particularly in robotic surgery [
      • Perez-Protto S.
      • Sessler D.I.
      • Reynolds L.F.
      • Bakri M.H.
      • Mascha E.
      • Cywinski J.
      • et al.
      Circulating-water garment or the combination of a circulating-water mattress and forced-air cover to maintain core temperature during major upper-abdominal surgery.
      ]. Intravenous fluids should be warmed using a suitable device to avoid lowering body temperature [
      • Campbell G.
      • Alderson P.
      • Smith A.F.
      • Warttig S.
      ]. Temperature monitoring should be used to guide therapy and to avoid hyperthermia, which also has deleterious effects on homeostasis. Patients who have prolonged surgery with a likelihood of a Systemic Inflammatory Response (SIRS), such as open debulking procedures, are at a higher risk of developing hyperpyrexia as surgery progresses if warming is not monitored. The most convenient site to measure core temperature during gynecological surgery is the nasopharynx. Warming should be continued into the postoperative period to ensure the patient leaves the post anesthetic care unit with a temperature >36.0 °C.
      Summary and recommendation:
      Patient temperature monitoring is mandatory to titrate warming devices and avoid hypo- and hyperpyrexia. Maintenance of normothermia with suitable active warming devices should be used routinely.
      Evidence level:
      Continuous measurement of core temperature for efficacy and compliance: High.
      Use of active warming devices: High.
      Recommendation grade:
      Strong.

      3.13 Principles of perioperative fluid balance

      The aim of intravenous fluid therapy is to maintain normovolemia and reduce flux across the extracellular space. Enhanced recovery protocols and modern surgical techniques reduce the need for both total volume and duration of intravenous fluid therapy [
      • Raghunathan K.
      • Singh M.
      • Lobo D.N.
      Fluid management in abdominal surgery: what, when, and when not to administer.
      ]. While salt and fluid overload in the postoperative period is a major cause of morbidity [
      • Lobo D.N.
      • Bostock K.A.
      • Neal K.R.
      • Perkins A.C.
      • Rowlands B.J.
      • Allison S.P.
      Effect of salt and water balance on recovery of gastrointestinal function after elective colonic resection: a randomised controlled trial.
      ], very restrictive fluid regimes also lead to increased morbidity and mortality. There have been very few randomized trials investigating fluid therapy and hemodynamic monitoring in major gynecologic surgery. Hence recommendations are based on extrapolations from evidence in major intra-abdominal surgery. Patients undergoing colorectal resections randomized to a zero balance fluid regimen had fewer cardiopulmonary complications (7% vs. 24%; p < 0.001) compared to standard perioperative fluid management [
      • Brandstrup B.
      • Tonnesen H.
      • Beier-Holgersen R.
      • Hjortso E.
      • Ording H.
      • Lindorff-Larsen K.
      • et al.
      Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial.
      ]. A meta-analysis of 9 randomized trials from nearly 1000 patients demonstrated that restrictive fluid therapy reduced morbidity (OR 0.41; p = 0.005) [
      • Rahbari N.N.
      • Zimmermann J.B.
      • Schmidt T.
      • Koch M.
      • Weigand M.A.
      • Weitz J.
      Meta-analysis of standard, restrictive and supplemental fluid administration in colorectal surgery.
      ]. Importantly, these improvements in morbidity were not observed if fluid restriction was initiated only in the post-operative period.
      Summary and recommendation:
      Very restrictive or liberal fluid regimes should be avoided in favor of euvolemia.
      Evidence level:
      High.
      Recommendation grade:
      Strong.

      3.14 Intraoperative fluid therapy and advanced hemodynamic monitoring

      Anesthetic drugs, intermittent positive pressure ventilation, and the use of regional anesthetic techniques all have different effects on vasomotor tone causing arteriolar and venous dilatation leading to hypotension. Therefore, once intravascular volume is normalized during surgery, vasopressors should be used to maintain mean arterial pressure when needed to avoid fluid excess. Central venous catheters may be needed to administer vasopressors and can be used in the immediate post-operative period to guide fluid administration by deriving oxygen extraction from the SCVO2. The head down position and pneumo-peritoneum used during MIS can cause difficulty in interpreting monitoring. The fluid requirements during MIS in gynecology surgery are reduced as compared with open surgery.
      Arterial lines can be used to measure arterial blood gases giving important information about oxygenation, effective ventilation, blood pH, and lactate as a marker for cellular perfusion. Dynamic changes in arterial waveform derived values such as systolic pressure, pulse pressure and stroke volume can be useful as predictors of fluid responsiveness [
      • Marik P.E.
      • Cavallazzi R.
      • Vasu T.
      • Hirani A.
      Dynamic changes in arterial waveform derived variables and fluid responsiveness in mechanically ventilated patients: a systematic review of the literature.
      ], but when noradrenaline infusions are used the fluid response does not concur with the Esophageal Doppler Monitor (EDM) [
      • Feldheiser A.
      • Hunsicker O.
      • Krebbel H.
      • Weimann K.
      • Kaufner L.
      • Wernecke K.-D.
      • et al.
      Oesophageal Doppler and calibrated pulse contour analysis are not interchangeable within a goal-directed haemodynamic algorithm in major gynaecological surgery.
      ]. There have been two studies in gynecology patients within an ERP using EDM. The first showed minimal improvement, with a reduction in length of stay from 7 to 6 days [
      • McKenny M.
      • Conroy P.
      • Wong A.
      • Farren M.
      • Gleeson N.
      • Walsh C.
      • et al.
      A randomised prospective trial of intra-operative oesophageal Doppler-guided fluid administration in major gynaecological surgery.
      ], but the second study showed a benefit in patients with advanced cancer including an earlier return to gut function as well as reduced length of stay [
      • Chattopadhyay S.
      • Mittal S.
      • Christian S.
      • Terblanche A.L.
      • Patel A.
      • Biliatis I.
      • et al.
      The role of intraoperative fluid optimization using the esophageal Doppler in advanced gynecological cancer: early postoperative recovery and fitness for discharge.
      ]. The benefit from the use of EDM in fit elective patients undergoing uncomplicated surgery within an ERAS Protocol is presently unclear [
      • Minto G.
      • Scott M.J.
      • Miller T.E.
      Monitoring needs and goal-directed fluid therapy within an enhanced recovery program.
      ] and regular fluid challenges in anaerobically fit patients without an endpoint may lead to harm [
      • Challand C.
      • Struthers R.
      • Sneyd J.R.
      • Erasmus P.D.
      • Mellor N.
      • Hosie K.B.
      • et al.
      Randomized controlled trial of intraoperative goal-directed fluid therapy in aerobically fit and unfit patients having major colorectal surgery.
      ]. High risk patients benefit most from optimization of oxygen delivery using inotropes in addition to fluid [
      • Hamilton M.A.
      • Cecconi M.
      • Rhodes A.
      A systematic review and meta-analysis on the use of preemptive hemodynamic intervention to improve postoperative outcomes in moderate and high-risk surgical patients.
      ].
      Summary and recommendation:
      In major open surgery and for high-risk patients where there is large blood loss (>7 ml/kg) or a SIRS response, the use of advanced hemodynamic monitoring to facilitate individualized fluid therapy and optimize oxygen delivery through the perioperative period is recommended.
      Evidence level:
      Moderate.
      Recommendation grade:
      Strong.

      4. Discussion

      This guideline outlines the recommendations of the ERAS Group for the pre- and intraoperative management of patients undergoing gynecologic and gynecologic oncology surgery, and is based on the best available evidence. However, in some instances good quality data was not available for gynecologic/oncology patients. In these instances recommendations were made based on findings from other surgical disciplines, including colorectal surgery, in which major abdominal surgery is routinely utilized. We are hopeful that individuals and groups of surgeons will use these guidelines to help integrate existing knowledge into practice, align perioperative care, and encourage future investigations of optimal perioperative care for patients undergoing gynecologic/oncology surgery.

      Conflict of interest statement

      Dr. Acheson reports personal fees from Baxter UK Ltd., outside the submitted work. In addition, Dr. Acheson has a commercial (future royalties on a medical device in development) relationship with Mediplus Ltd. He has also held the following appointments: Joint National Clinical Advisor (Gynaecology) to the Enhanced Recovery Partnership Programme, Department of Health (2010–2011), and continued under NHS Improvement (2011–2013); Member of Steering Board, Enhanced Recovery ERAS (UK) (2011–2013).
      Dr. Scott received honoraria for lecturing and travel expenses from Baxter Healthcare, Merck, and Deltex. He is an Executive Committee member of the ERAS Society.
      Dr. Ljungqvist has an appointment with Nutricia Advisory Board, has received speakers honoraria from Nutricia, MSD, BBraun and Fresenius-Kabi. He is the current Chairman of the ERAS Society (www.erassociety.org). He founded, serves on the Board and owns stock in Encare AB that runs the ERAS Society Interactive Audit System (EIAS).

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