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Preoperative Evaluation and Management of Patients With Select Chronic Gastrointestinal, Liver, and Renal Diseases

      Abstract

      Patients with chronic gastrointestinal, hepatic, and renal disease are frequently encountered in clinical practice. This is due in part to the rising prevalence of risk factors associated with these conditions. These patients are increasingly being considered for surgical intervention and are at higher risk for multiple perioperative complications. Many are able to safely undergo surgery but require unique considerations to ensure optimal perioperative care. In this review, we highlight relevant perioperative physiology and outline our approach to the evaluation and management of patients with select chronic gastrointestinal, hepatic, and renal diseases. A comprehensive preoperative evaluation with a multidisciplinary approach is often beneficial, and specialist involvement should be considered. Intraoperative and postoperative plans should be individualized based on the unique medical and surgical characteristics of each patient.

      Abbreviations and Acronyms:

      AGA (American Gastroenterology Association), ASA (American Society of Anesthesiologists), CTP (Child-Turcotte-Pugh (score)), ECG (electrocardiogram), ESA (erythropoiesis-stimulating agent), ESRD (end-stage renal disease), IBD (inflammatory bowel disease), INR (international normalized ratio), MELD (Model for End-Stage Liver Disease), NGS (non-gastroenterological surgery), VTE (venous thromboembolism)
      Patients with chronic gastrointestinal, hepatic, and renal disease are frequently encountered in clinical practice. These patients are increasingly being considered for surgical intervention and are at increased risk for multiple perioperative complications due to underlying comorbidities. Most patients can safely undergo surgery but require unique considerations to ensure optimal perioperative care. In this review, we highlight relevant perioperative physiology, disease-specific pathophysiology, and outline our approach to the preoperative evaluation and management of patients with select chronic gastrointestinal, hepatic, and renal diseases. Common postoperative gastrointestinal and renal complications will be reviewed in a subsequent paper in the series.

      Gastrointestinal Physiology in the Perioperative Period

      In the perioperative setting, alterations to gastrointestinal physiology can occur for a variety of reasons. These include expected and compensatory physiological changes, direct gut stimulation (mechanical effects from the surgery itself), medication effects, and effects due to the underlying gastrointestinal disease. Delayed gastric emptying and alterations in peristalsis may occur due to neurotransmitter effects (eg, acetylcholine, serotonin, and dopamine) on the central nervous system, specifically the chemoreceptor trigger zone in the area postrema, dorsal pons, amygdala, and thalamus.
      • Wiesmann T.
      • Kranke P.
      • Eberhart L.
      Postoperative nausea and vomiting — a narrative review of pathophysiology, pharmacotherapy and clinical management strategies.
      These physiologic changes may lead to postoperative nausea and vomiting, interference with medication absorption from the gastrointestinal tract, and delayed advancement to an oral diet.
      Effects of the surgical procedure on the gastrointestinal tract are most common in abdominal and pelvic surgeries, where the gut is directly manipulated or subjected to pressurization during pneumoperitoneum, resulting in postoperative gut hypomotility or reduced perfusion. Furthermore, excessive fluid administered perioperatively has been associated with gut wall edema, which can contribute to the development of ileus.
      • VandeHei M.S.
      • Papageorge C.M.
      • Murphy M.M.
      • Kennedy G.D.
      The effect of perioperative fluid management on postoperative ileus in rectal cancer patients.
      • Nisanevich V.
      • Felsenstein I.
      • Almogy G.
      • Weissman C.
      • Einav S.
      • Matot I.
      Effect of intraoperative fluid management on outcome after intraabdominal surgery.
      • 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.
      Patients with chronic liver disease may have difficulty metabolizing medications with high hepatic clearance such as opioids, ketamine, neuromuscular blockers (including rocuronium and vecuronium), sedatives (such as benzodiazepines), and amide local anesthetics.
      • Hunter J.M.
      • Parker C.J.
      • Bell C.F.
      • Jones R.S.
      • Utting J.E.
      The use of different doses of vecuronium in patients with liver dysfunction.
      ,
      • Magorian T.
      • Wood P.
      • Caldwell J.
      • et al.
      The pharmacokinetics and neuromuscular effects of rocuronium bromide in patients with liver disease.
      Chronic liver disease can lead to reduced protein synthesis (which can alter drug binding), impaired wound healing, and altered clotting factor production. Portal hypertension contributes to excess collateral circulation, splenic sequestration, and renal dysfunction. Vasodilation from impaired arterial autoregulation can be exacerbated by anesthetics, leading to hypotension.
      • Northup P.G.
      • Friedman L.S.
      • Kamath P.S.
      AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review.

      Perioperative Management of Non-Cirrhotic Liver Disease

      There are limited data on the perioperative management of non-cirrhotic chronic liver disease. Many previous studies were performed before modern surgical and diagnostic techniques.
      • Friedman L.S.
      The risk of surgery in patients with liver disease.
      In patients with acute hepatic injury, perioperative morbidity and mortality is increased (Table 1).
      • Harville D.D.
      • Summerskill W.H.
      Surgery in acute hepatitis. Causes and effects.
      • Greenwood S.M.
      • Leffler C.T.
      • Minkowitz S.
      The increased mortality rate of open liver biopsy in alcoholic hepatitis.
      • Powell-Jackson P.
      • Greenway B.
      • Williams R.
      Adverse effects of exploratory laparotomy in patients with unsuspected liver disease.
      • Lee W.M.
      • Stravitz R.T.
      • Larson A.M.
      Introduction to the revised American Association for the Study of Liver Diseases Position Paper on acute liver failure 2011.
      Although these results have not been replicated in modern cohorts, the preponderance of data suggest that the risks (eg, infection, bleeding, clotting, wound healing, and wound fragility) of proceeding with elective surgery in these patients are significantly greater than the harm from delaying surgery.
      • Frye J.W.
      • Perri R.E.
      Perioperative risk assessment for patients with cirrhosis and liver disease.
      Patients needing urgent or emergency surgery should receive individualized care with input from surgical, hepatobiliary, and anesthesia specialists.
      Table 1Acute Hepatic Diseases and Complications Associated With Significant Perioperative Risk
      Compiled from resources noted in the reference list.9-12
      ConditionPerioperative implicationsManagement considerations
      Acute alcoholic hepatitisLaparotomy associated with morbidity and mortality >50%.Studies predate modern medical management of liver disease. Resolution can take up to 12 weeks if patient abstains from alcohol. Once resolved, evaluate for baseline hepatic disease.
      Acute liver failure (fulminant hepatitis)
      Defined as the development of jaundice, coagulopathy, and hepatic encephalopathy within 26 weeks in a patient with acute liver injury in the absence of preexisting liver disease.
      Mortality approached 85% before transplantation.Medical management of liver disease takes precedence. Consider referral for liver transplantation.
      Acute viral or drug-induced hepatitisDiagnostic laparotomy associated with significant risk of morbidity (12% to 60%) and mortality (9.5% to 30%) in studies performed when that practice was common.Underlying conditions are treatable or self-limited. Surgical risk may be reduced if delayed to allow hepatic recovery.
      Severe extrahepatic complications (hepatorenal syndrome, hypoxemia, hepatopulmonary syndrome, portopulmonary hypertension, and cardiomyopathy)Significant mortality risk exists even in non-perioperative settings.Optimize medical therapy per clinical practice guidelines. Consider liver transplantation evaluation.
      Coagulopathy
      Defined as platelets <50,000 or international normalized ration >1.5.
      Severe bleeding may not be controllable. Bleeding risk does not correlate with degree of coagulopathy due to upregulation of procoagulant factors.Very limited data on outcomes in patients. Consider liver transplantation evaluation.
      a Compiled from resources noted in the reference list.
      • Harville D.D.
      • Summerskill W.H.
      Surgery in acute hepatitis. Causes and effects.
      • Greenwood S.M.
      • Leffler C.T.
      • Minkowitz S.
      The increased mortality rate of open liver biopsy in alcoholic hepatitis.
      • Powell-Jackson P.
      • Greenway B.
      • Williams R.
      Adverse effects of exploratory laparotomy in patients with unsuspected liver disease.
      • Lee W.M.
      • Stravitz R.T.
      • Larson A.M.
      Introduction to the revised American Association for the Study of Liver Diseases Position Paper on acute liver failure 2011.
      b Defined as the development of jaundice, coagulopathy, and hepatic encephalopathy within 26 weeks in a patient with acute liver injury in the absence of preexisting liver disease.
      c Defined as platelets <50,000 or international normalized ration >1.5.
      Patients with chronic, non-cirrhotic liver disease generally have a lower risk of perioperative complications compared with patients with cirrhosis.
      • Runyon B.A.
      Surgical procedures are well tolerated by patients with asymptomatic chronic hepatitis.
      ,
      • Cheung R.C.
      • Hsieh F.
      • Wang Y.
      • Pollard J.B.
      The impact of hepatitis C status on postoperative outcome.
      There are unique considerations that should be taken into account perioperatively due to the underlying physiology of the disease or its associated treatments (Table 2).
      • O'Leary J.G.
      • Yachimski P.S.
      • Friedman L.S.
      Surgery in the patient with liver disease.
      • Villanova N.
      • Moscatiello S.
      • Ramilli S.
      • et al.
      Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty liver disease.
      • Prenner S.
      • Ganger D.
      Risk stratification and preoperative evaluation of the patient with known or suspected liver disease.
      • Huxtable C.A.
      • Roberts L.J.
      • Somogyi A.A.
      • MacIntyre P.E.
      Acute pain management in opioid-tolerant patients: a growing challenge.
      • Yarze J.C.
      • Martin P.
      • Munoz S.J.
      • Friedman L.S.
      Wilson's disease: current status.
      • Bacon B.R.
      • Adams P.C.
      • Kowdley K.V.
      • et al.
      Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases.
      Patients with chronic, active hepatitis without cirrhosis undergoing hepatic resection for hepatocellular carcinoma may be at higher risk for postoperative complications, such as death or liver failure, than those without active hepatitis.
      • Higashi H.
      • Matsumata T.
      • Adachi E.
      • Taketomi A.
      • Kashiwagi S.
      • Sugimachi K.
      Influence of viral hepatitis status on operative morbidity and mortality in patients with primary hepatocellular carcinoma.
      This may be due to decreased hepatic synthetic function and increased risk for portal hypertension.
      • Friedman L.S.
      The risk of surgery in patients with liver disease.
      Table 2Non-cirrhotic Chronic Liver Disease
      CT = computed tomography.
      ,
      Compiled from resources in the reference list.16-21,23,24
      ConditionPerioperative implicationsManagement considerations
      Acute and chronic viral hepatitisDisease severity correlates with perioperative risk. Non-cirrhotic chronic viral hepatitis is not associated with increased perioperative risk. Ribavirin and peginterferon can cause thrombocytopenia.Antiviral therapy should be initiated before elective surgery with a goal to lower viral load. Patients on antiviral therapy should continue the medications perioperatively to prevent hepatitis relapse and drug resistance.
      Non-alcoholic fatty liver diseaseIncreased risk for cardiovascular disease and diabetes. Higher risk of perioperative myocardial infarction after liver transplantation.Consider enhanced cardiac risk stratification and close monitoring for perioperative myocardial injury (as detailed in previous publication from this series).
      • Raslau D.
      • Bierle D.M.
      • Stephenson C.R.
      • Mikhail M.A.
      • Kebede E.B.
      • Mauck K.F.
      Preoperative cardiac risk assessment.
      HemochromatosisIncreased risk for diabetes, pituitary dysfunction, and cardiomyopathy.Check preoperative fasting glucose, ferritin, and hemoglobin. Echocardiography is required if cardiac symptoms or low functional capacity are present. Consider endocrine referral if diabetic or pituitary symptoms (headache, visual changes, growth changes, or Cushinoid features) are present.
      Autoimmune hepatitisFrequently exposed to corticosteroids. Infection risk may be increased due to chronic immunosuppression.Continue immunosuppressant medications to prevent relapse. Evaluate corticosteroid exposure and administer stress dose steroids if indicated (dosing tailored individually based on indication, duration of use, and surgical type).
      Primary biliary cholangitis/primary sclerosing cholangitisPruritus may be treated with naltrexone. Naltrexone complicates opioid analgesia through competitive antagonism and patients may be very sensitive to opioid analgesia due to an increase in central opioid receptor concentration. Hyperlipidemia is common but it is unclear if this affects cardiac risk without the presence of other risk factors.Naltrexone should be stopped preoperatively (2-3 days for immediate release, 24-30 days for extended-release).
      • O'Rourke M.J.
      • Keshock M.C.
      • Boxhorn C.E.
      • et al.
      Preoperative management of opioid and nonopioid analgesics: Society for Perioperative Assessment and Quality Improvement (SPAQI) consensus statement.
      Multimodal analgesia should be considered. The risk for coronary artery disease may be increased if additional risk factors besides hyperlipidemia are present.
      Wilson diseaseIncreased risk of delirium. D-penicillamine may impact wound healing.May benefit from delirium prevention or early intervention strategies. D-penicillamine can impair wound healing.
      Alpha-1 antitrypsin deficiencyIncreased risk for chronic obstructive pulmonary disease.Consider preoperative pulmonary assessment (chest x-ray, CT scan, oxygen saturation, pulmonary function testing) if pulmonary symptoms are present.
      a CT = computed tomography.
      b Compiled from resources in the reference list.
      • O'Leary J.G.
      • Yachimski P.S.
      • Friedman L.S.
      Surgery in the patient with liver disease.
      • Villanova N.
      • Moscatiello S.
      • Ramilli S.
      • et al.
      Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty liver disease.
      • Prenner S.
      • Ganger D.
      Risk stratification and preoperative evaluation of the patient with known or suspected liver disease.
      • Huxtable C.A.
      • Roberts L.J.
      • Somogyi A.A.
      • MacIntyre P.E.
      Acute pain management in opioid-tolerant patients: a growing challenge.
      • Yarze J.C.
      • Martin P.
      • Munoz S.J.
      • Friedman L.S.
      Wilson's disease: current status.
      • Bacon B.R.
      • Adams P.C.
      • Kowdley K.V.
      • et al.
      Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases.
      • Raslau D.
      • Bierle D.M.
      • Stephenson C.R.
      • Mikhail M.A.
      • Kebede E.B.
      • Mauck K.F.
      Preoperative cardiac risk assessment.
      • O'Rourke M.J.
      • Keshock M.C.
      • Boxhorn C.E.
      • et al.
      Preoperative management of opioid and nonopioid analgesics: Society for Perioperative Assessment and Quality Improvement (SPAQI) consensus statement.

      Perioperative Management of Cirrhotic Liver Disease

      Patients with cirrhosis are at increased risk of perioperative complications, including bleeding, thromboembolism, poor wound healing, pulmonary complications, delirium, hepatic failure, renal dysfunction, and death.
      • Northup P.G.
      • Friedman L.S.
      • Kamath P.S.
      AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review.
      General perioperative risk assessment principles discussed in previous entries in this series should be applied.
      • Raslau D.
      • Bierle D.M.
      • Stephenson C.R.
      • Mikhail M.A.
      • Kebede E.B.
      • Mauck K.F.
      Preoperative cardiac risk assessment.
      Early evaluation by a multispecialty team may be beneficial for patients being considered for elective or semi-urgent surgery. Patients being considered for urgent or emergency surgery may benefit from the expertise at a facility experienced in cirrhosis management, such as a transplant-based medical center.
      • Parikh N.D.
      • Chang Y.H.
      • Tapper E.B.
      • Mathur A.K.
      Outcomes of patients with cirrhosis undergoing orthopedic procedures: an analysis of the Nationwide Inpatient Sample.

      Baseline Assessment

      The primary goals of the baseline cirrhosis assessment are to identify the presence of complications of cirrhosis and evidence of portal hypertension.
      • Northup P.G.
      • Friedman L.S.
      • Kamath P.S.
      AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review.
      Perioperative risk correlates directly with the severity of the underlying liver disease, as seen in non-cirrhotic chronic liver disease.
      • Teh S.H.
      • Nagorney D.M.
      • Stevens S.R.
      • et al.
      Risk factors for mortality after surgery in patients with cirrhosis.
      Because cirrhosis represents the final common pathway of various disease processes, there is less heterogeneous data and more evidence to guide preoperative evaluation. Nevertheless, it is still imperative to understand the underlying etiology and severity of the patient’s cirrhosis, as there may be disease-specific aspects with unique perioperative considerations (Table 2).
      A focused history aims to identify the etiology, duration, and severity of cirrhosis, any previous or current interventions directed at the underlying cause, and the use of any medications or substances that could affect the liver perioperatively. An accurate medication history, including herbs and supplements, is essential. Complications of portal hypertension or decreased hepatic synthetic dysfunction, such as ascites, esophageal varices, renal dysfunction, hepatic encephalopathy, and coagulopathy have significant clinical impact in the perioperative setting and should be investigated as recommended by established clinical practice guidelines.
      • Northup P.G.
      • Friedman L.S.
      • Kamath P.S.
      AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review.
      Patients may not be aware of disease manifestations, so physical examination findings suggestive of portal hypertension (eg, ascites, shifting abdominal dullness, gynecomastia, spider angioma, caput medusae, splenomegaly, jugular venous distension, jaundice, edema, etc) should prompt further evaluation.
      • Northup P.G.
      • Friedman L.S.
      • Kamath P.S.
      AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review.
      Preoperative diagnostic studies are useful in assessing hepatic function (Table 3). Many of these studies provide the information necessary to perform cirrhosis-specific perioperative risk stratification using tools such as the Model for End-Stage Liver Disease (MELD) score, Child-Turcotte-Pugh (CTP) score, or the Mayo Postoperative Surgical Risk calculator.
      • Teh S.H.
      • Nagorney D.M.
      • Stevens S.R.
      • et al.
      Risk factors for mortality after surgery in patients with cirrhosis.
      Advanced imaging such as ultrasound or computed tomography can be helpful in patients with symptoms, examination findings, or laboratory abnormalities suggestive of cirrhotic complications. Invasive diagnostic procedures such as liver biopsy should be performed as indicated by clinical practice guidelines for general cirrhosis management.
      • Chalasani N.
      • Younossi Z.
      • Lavine J.E.
      • et al.
      The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases.
      Markers that exclude clinically significant portal hypertension include a hepatic vein portal gradient less than 10 mm Hg, the absence of venous abdominal collaterals on cross-sectional imaging, the lack of esophageal varices on endoscopy, peripheral blood platelet count greater than 100,000/mL, and hepatic transient elastography values of less than 22 kPa.
      • Northup P.G.
      • Friedman L.S.
      • Kamath P.S.
      AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review.
      Overall, for patients with symptomatic, decompensated, or previously undiagnosed liver disease, our practice is to postpone any elective surgical procedure until further evaluation and optimization has been performed.
      Table 3Preoperative Testing
      CBC = complete blood count; CT = computed tomography; EGD = esophagogastroduodenoscopy; MELD = Model for End-stage Liver Disease; MRI = magnetic resonance imaging.
      TestClinical utility
      CBCAnemia; thrombocytopenia
      ElectrolytesAbnormalities may be seen due to cirrhosis or complications of its treatment
      CreatinineNecessary component of MELD score
      AlbuminAssessment of hepatic synthetic function
      Liver enzymesMay reflect active hepatitis; often low/normal in cirrhosis due to reduction in number of hepatocytes
      Prothrombin timeNecessary component of MELD score
      BilirubinNecessary component of MELD score
      B vitaminsDeficiencies common in cirrhosis
      ZincDeficiencies common in cirrhosis; may impact wound healing
      SeleniumDeficiencies common in cirrhosis; may impact wound healing
      ThromboelastogramFunctional test of coagulopathy that better correlates with bleeding risk and can identify interventions to reduce bleeding risk
      ElastographyLower stiffness associated with lower risk of portal hypertension
      EGDTest of choice for screening for esophageal varices
      Ultrasound/CT/MRICan demonstrate objective evidence of portal hypertension and sarcopenia
      Handgrip strengthObjective measure of frailty
      DensitometryObjective measure of sarcopenia
      a CBC = complete blood count; CT = computed tomography; EGD = esophagogastroduodenoscopy; MELD = Model for End-stage Liver Disease; MRI = magnetic resonance imaging.

      Perioperative Risk Assessment in Cirrhosis

      The American Gastroenterology Association (AGA) recently published the first clinical practice guidelines on perioperative risk assessment in cirrhosis.
      • Northup P.G.
      • Friedman L.S.
      • Kamath P.S.
      AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review.
      These guidelines recognize the predictive performance of the MELD score, CTP score, Mayo Postoperative Surgical Risk Score, and the American Society of Anesthesiologists (ASA) score. The CTP score (Table 4) was initially developed to predict survival after esophageal resection in variceal bleeding.
      • Pugh R.N.
      • Murray-Lyon I.M.
      • Dawson J.L.
      • Pietroni M.C.
      • Williams R.
      Transection of the oesophagus for bleeding oesophageal varices.
      It grades ascites, encephalopathy, hypoalbuminemia, hyperbilirubinemia, and prothrombin time (subsequently modified to include international normalized ratio [INR]) on a 3-point scale. The scores are summed and classified as A (score 5–6), B (score 7–9), and C (score 10–15). The MELD score was initially developed to predict mortality after transjugular portosystemic shunt placement.
      • Malinchoc M.
      • Kamath P.S.
      • Gordon F.D.
      • Peine C.J.
      • Rank J.
      • ter Borg P.C.
      A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts.
      It incorporates bilirubin, INR, and creatinine into an equation that produces a score from 6 to 40 points. The MELD-Na, which adds serum sodium to the original MELD components, is currently used for organ transplant prioritization but has not been evaluated for perioperative risk assessment. The Mayo Postoperative Surgical Risk Score combines the original MELD with ASA status, age, and the underlying etiology of cirrhosis to provide a mortality estimate at 7 days, 30 days, 90 days, 1 year, and 5 years postoperatively.
      • Teh S.H.
      • Nagorney D.M.
      • Stevens S.R.
      • et al.
      Risk factors for mortality after surgery in patients with cirrhosis.
      Table 4Child-Turcotte-Pugh Classification for Severity of Cirrhosis
      Total score obtained by adding points for each parameter. Class A, 5-6 points; class B, 7-9 points; class C,10-15 points.
      Clinical and lab parametersPoints
      123
      AscitesNoneMild to moderateSevere
      EncephalopathyNoneMild to moderate (grade 1 or 2)Severe (grade 3 or 4)
      Albumin, g/dL>3.52.8-3.5<2.8
      Bilirubin, mg/dL<22-3>3
      Prothrombin time prolongation (s)

      International normalized ratio
      <4

      <1.7
      4-6

      1.7-2.3
      >6

      >2.3
      a Total score obtained by adding points for each parameter. Class A, 5-6 points; class B, 7-9 points; class C,10-15 points.
      There are unique strengths and limitations with each of the above scoring systems.
      • Northup P.G.
      • Friedman L.S.
      • Kamath P.S.
      AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review.
      The CTP score incorporates clinical factors in addition to laboratory values. Two of these factors, ascites and encephalopathy, are subjectively graded, which increases interobserver variability. Scores are grouped into risk classes, which do not reflect the continuous (rather than categorical) nature of risk. The MELD score incorporates only laboratory measures of hepatic dysfunction but does not capture other hepatic complications, such as ascites. The Mayo risk score showed improved predictive performance over the MELD in the derivation study, in part by incorporating clinical factors.
      • Teh S.H.
      • Nagorney D.M.
      • Stevens S.R.
      • et al.
      Risk factors for mortality after surgery in patients with cirrhosis.
      However, the study population was highly selective, excluding patients with significant nonhepatic comorbidities, which could affect generalizability and predictive value. Although the Mayo risk score derivation population included gastrointestinal, orthopedic, and cardiovascular surgeries, it has not been formally evaluated in other surgery types nor has it been validated outside of the institution where it was developed.
      Current studies generally show better performance of the MELD score than CTP score in modern cohorts, but this is not definitive.
      • Northup P.G.
      • Friedman L.S.
      • Kamath P.S.
      AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review.
      For example, some patients with severe ascites have relatively preserved hepatic synthetic function leading to a discrepancy between the CTP and MELD scores. The AGA recommends using both systems to overcome this limitation. A limitation with both scoring systems is that they do not incorporate surgery-specific factors, such as the type of surgery or the need for emergency surgery. Table 5 lists surgeries with uniquely associated risk in patients with cirrhosis.
      Table 5Surgeries Associated With Increased Risk in Patients With Cirrhosis
      MELD = Model for End-stage Liver Disease.
      ProcedureComplications
      Hepatic resectionElevated risk of postoperative hepatic failure
      CholecystectomyElevated risk of mortality and conversion to open procedure
      Abdominal wall hernia repairPoor wound healing and dehiscence in the presence of ascites
      Cardiovascular surgeryTechnically complex management of extracorporeal circulation; increased morbidity and mortality if MELD >7
      Bariatric surgeryRoux-en-Y gastric bypass may make liver transplant technically complicated
      a MELD = Model for End-stage Liver Disease.
      Perioperative mortality risk increases continuously. However, there is no universal cutoff where surgery is absolutely contraindicated.
      • Northup P.G.
      • Friedman L.S.
      • Kamath P.S.
      AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review.
      Patients with CTP class A or MELD score less than 10 points can typically undergo elective surgery safely. Patients with MELD score from 10 to 15 points or CTP score of class B may be able to safely undergo elective surgery depending on the degree of portal hypertension and the specific surgery being considered.
      • Northup P.G.
      • Friedman L.S.
      • Kamath P.S.
      AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review.
      Multiple studies of different surgery types have shown an increased risk in patients with a MELD score greater than 15 points; mortality may be as high as 50% at 90 days postoperatively.
      • Teh S.H.
      • Nagorney D.M.
      • Stevens S.R.
      • et al.
      Risk factors for mortality after surgery in patients with cirrhosis.
      Patients with CTP class C cirrhosis or MELD greater than 20 points have a very high risk of perioperative morbidity and mortality, and the AGA recommends against elective surgery in this population.
      Postoperative liver failure is a potential indication for liver transplantation, although eligibility for liver transplantation is ideally determined preoperatively. The AGA recommends delaying non-urgent surgery to facilitate this evaluation in patients with a MELD score greater than 15 points or a liver-related 3-month postoperative mortality risk greater than 15%.
      • Northup P.G.
      • Friedman L.S.
      • Kamath P.S.
      AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review.
      Delaying elective surgery until after liver transplantation should also be considered in this population. Patients with severely advanced cirrhosis who develop an urgent or emergent surgical need may encounter a situation of medical futility; Teh et al
      • Teh S.H.
      • Nagorney D.M.
      • Stevens S.R.
      • et al.
      Risk factors for mortality after surgery in patients with cirrhosis.
      identified a 100% 90-day mortality rate in patients with cirrhosis and an ASA status of 5.
      • Teh S.H.
      • Nagorney D.M.
      • Stevens S.R.
      • et al.
      Risk factors for mortality after surgery in patients with cirrhosis.
      Advanced care planning is crucial to ensure patients’ wishes are identified.

      Perioperative Management of Cirrhotic Complications

      Infection

      Preoperative infections such as pneumonia or spontaneous bacterial peritonitis are associated with increased postoperative mortality in patients with cirrhosis. Spontaneous bacterial peritonitis can present subtly, and diagnostic paracentesis is recommended for any patient with ascites who suffers a clinical deterioration. Empiric antimicrobial therapy appropriate for the suspected site of infection should be initiated early and tailored based on the results of cultures.
      • Ziser A.
      • Plevak D.J.
      • Wiesner R.H.
      • Rakela J.
      • Offord K.P.
      • Brown D.L.
      Morbidity and mortality in cirrhotic patients undergoing anesthesia and surgery.

      Ascites

      Ascites can be managed via restricting dietary sodium and using diuretics such as furosemide and spironolactone.
      • Runyon B.A.
      AASLD Practice Guidelines Committee
      Management of adult patients with ascites due to cirrhosis: an update.
      Symptomatic ascites is best treated with a large-volume paracentesis followed by the intravenous administration of 6 to 8 g albumin per liter of ascitic fluid removed. Large-volume paracentesis should ideally be performed the day before the planned surgery, as this could help to decrease infection risk (especially spontaneous bacterial peritonitis), decrease abdominal girth, improve ventilatory mechanics, and achieve better overall volume control. Thoracentesis is recommended for patients with hepatic hydrothorax if the effusion is affecting ventilatory mechanics. Intravenous fluid and blood products should be used in a goal-directed manner (such as targeting a mean arterial pressure of >65 mm Hg or a hemoglobin of >7 g/dL) as excessive resuscitation may lead to extracellular volume overload and increase portal venous pressure.
      • O'Leary J.G.
      • Greenberg C.S.
      • Patton H.M.
      • Caldwell S.H.
      AGA Clinical practice update: coagulation in cirrhosis.
      Although transjugular intrahepatic portosystemic shunts may be used to treat medically refractory ascites or recurrent variceal bleeding, their role in reducing the risk of perioperative complications has been poorly studied. There are inconsistent data on reducing blood transfusions and limited data on complications such as hepatic encephalopathy. The AGA currently does not recommend placement of preoperative transjugular intrahepatic portosystemic shunt unless it is indicated independent of surgical status.
      • Northup P.G.
      • Friedman L.S.
      • Kamath P.S.
      AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review.

      Coagulopathy

      Patients with cirrhosis are at risk for both bleeding and thrombosis. These risks are difficult to predict due to variations in pro- and anticoagulant factors.
      • Tripodi A.
      • Salerno F.
      • Chantarangkul V.
      • et al.
      Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests.
      ,
      • Tripodi A.
      • Primignani M.
      • Chantarangkul V.
      • et al.
      Global hemostasis tests in patients with cirrhosis before and after prophylactic platelet transfusion.
      Reduced platelet counts and impaired production of clotting factors (except factor VIII, which is also produced in vascular endothelial cells) and fibrinogen contribute to bleeding risk, whereas reduced protein C and S levels and activation contribute to thrombotic risk. Vascular endothelial dysfunction leads to increased von Willebrand factor production, which is accompanied by an increase in factor VIII.
      • Forkin K.T.
      • Colquhoun D.A.
      • Nemergut E.C.
      • Huffmyer J.L.
      The coagulation profile of end-stage liver disease and considerations for intraoperative management.
      The INR counterintuitively does not correlate with bleeding risk.
      • O'Leary J.G.
      • Greenberg C.S.
      • Patton H.M.
      • Caldwell S.H.
      AGA Clinical practice update: coagulation in cirrhosis.
      Rather, pro-coagulant effects dominate in later stages of cirrhosis due to reduced protein C activity, increases in factor VIII levels, and increased platelet aggregation mediated by Von Willebrand factor.
      • Lisman T.
      • Bongers T.N.
      • Adelmeijer J.
      • et al.
      Elevated levels of von Willebrand Factor in cirrhosis support platelet adhesion despite reduced functional capacity.
      Low fibrinogen levels (<120 mg/dL) are associated with increased bleeding risk.
      • Drolz A.
      • Horvatits T.
      • Roedl K.
      • et al.
      Coagulation parameters and major bleeding in critically ill patients with cirrhosis.
      Platelet counts greater than 50,000/μL are adequate in most patients undergoing invasive procedures, although platelet counts greater than 100,000/μL are recommended for intracranial or intraspinal procedures and neuraxial anesthesia.
      • Northup P.G.
      • Friedman L.S.
      • Kamath P.S.
      AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review.
      Regarding coagulopathic changes associated with cirrhosis, there are several potential treatment agents that could be used in the perioperative setting. Cryoprecipitate infusion to satisfy fibrinogen levels is reasonable for patients with hypofibrinogenemia, although controlled trials have not shown the clinical efficacy of replacement strategies. Vitamin K may be helpful in cases of malnutrition or biliary obstruction.
      • Frye J.W.
      • Perri R.E.
      Perioperative risk assessment for patients with cirrhosis and liver disease.
      Fresh frozen plasma transfusion based on INR alone is not recommended as it does not reduce bleeding and the additional volume may worsen portal hypertension.
      • Northup P.G.
      • Friedman L.S.
      • Kamath P.S.
      AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review.
      ,
      • O'Leary J.G.
      • Greenberg C.S.
      • Patton H.M.
      • Caldwell S.H.
      AGA Clinical practice update: coagulation in cirrhosis.
      Thrombopoietin analogues have not been approved for use in cirrhosis. However, thrombopoietin receptor agonists have been approved for thrombocytopenia due to cirrhosis from hepatitis C (eltrombopag) and cirrhosis from any cause (avatrombopag and lusutrombopag) in patients with platelet counts less than 50,000/ μL before invasive procedures.
      • O'Leary J.G.
      • Greenberg C.S.
      • Patton H.M.
      • Caldwell S.H.
      AGA Clinical practice update: coagulation in cirrhosis.
      Although these agents were effective in raising platelet counts, bleeding events were not reduced and thrombotic events still occurred. Until further data are available, thrombopoietin receptor agonists should be used cautiously; the AGA recommends limiting their use to selected patients with platelet counts less than 50,000/μL undergoing procedures with high risk for bleeding.
      • Northup P.G.
      • Friedman L.S.
      • Kamath P.S.
      AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review.
      Because of the above-stated changes in various coagulation factors, patients with cirrhosis are often found to be at increased risk for perioperative bleeding and thromboembolic events simultaneously. A recent meta-analysis showed an increased risk for venous thromboembolism in patients with cirrhosis, particularly in men.
      • Ambrosino P.
      • Tarantino L.
      • Di Minno G.
      • et al.
      The risk of venous thromboembolism in patients with cirrhosis. A systematic review and meta-analysis.
      As a result, patients with cirrhosis should be considered for venous thromboembolism prophylaxis guided by existing practice guidelines,
      • Anderson D.R.
      • Morgano G.P.
      • Bennett C.
      • et al.
      American Society of Hematology 2019 guidelines for management of venous thromboembolism: prevention of venous thromboembolism in surgical hospitalized patients.
      which should be tailored accordingly. Consideration could be given for the use of sequential compression devices as well as unfractionated heparin (given its reversibility and shorter duration of activity).

      Encephalopathy

      Multiple perioperative factors increase the risk for hepatic encephalopathy, including analgesics, protein catabolism, hypovolemia, electrolyte disturbances, bleeding, infection, constipation, and ileus. The diagnosis of encephalopathy (defined as transient cognitive impairment in the setting of cirrhosis, presenting as a spectrum of neurological or psychiatric abnormalities) is made clinically, although a serum ammonia level may be helpful if there is uncertainty. An evaluation for potential precipitating factors should be completed; most common etiologies include infection, electrolyte disorder, gastrointestinal bleeding, constipation, medication side effect, and dehydration.
      • Vilstrup H.
      • Amodio P.
      • Bajaj J.
      • et al.
      Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver.
      Treatment includes minimizing sedating medications, optimizing volume status, electrolyte repletion, controlling infection and bleeding, and ensuring an adequate bowel regimen. Oral or rectal lactulose titrated to two to three bowel movements a day is commonly recommended.
      • Vilstrup H.
      • Amodio P.
      • Bajaj J.
      • et al.
      Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver.
      Rifaximin can be used as second line therapy. Treatment response should be monitored clinically; trending ammonia levels is not recommended.

      Malnutrition

      Protein depletion, micronutrient deficiency, electrolyte derangement, and malnutrition are frequently seen in cirrhosis. The prevalence of protein-calorie malnutrition increases with increasing severity of liver disease. Alcohol consumption further exacerbates catabolism, leading to greater malnutrition. Malnutrition and sarcopenia are associated with higher rates of perioperative morbidity and mortality in patients with cirrhosis who undergo abdominal surgery or liver transplantation. Although prospective evidence is limited in malnourished patients with cirrhosis, observational evidence from other malnourished populations would suggest delaying elective surgery to optimize nutritional status if sarcopenia (via detection of muscle mass loss in radiographic studies) or decreased muscle function (via exercise testing or 6-minute walk testing) is identified.
      • Plauth M.
      • Bernal W.
      • Dasarathy S.
      • et al.
      ESPEN guideline on clinical nutrition in liver disease.
      Changes in glucose metabolism have perioperative implications in cirrhosis. Hepatic glucose production decreases due to reduced hepatic glycogen storage and an inability to increase gluconeogenesis to compensate. This results in a metabolic state similar to prolonged starvation after an overnight fast. Fasting should be kept to a minimum perioperatively and glucose monitoring is advisable. Enhanced recovery after surgery protocols are encouraged.
      • Plauth M.
      • Bernal W.
      • Dasarathy S.
      • et al.
      ESPEN guideline on clinical nutrition in liver disease.
      Specialized diets or regimens have not shown consistent benefit over standard regimens in adults. Calorie requirements are similar to non-cirrhotic patients, but protein needs are increased. Approximately 1.2 to 1.5 g protein/kg body weight/day is recommended to facilitate nitrogen balance and protein accretion. Protein restriction should be avoided as it increases catabolism and does not reduce the risk of encephalopathy. Enteral nutrition is preferred over parenteral nutrition in patients unable to tolerate oral intake. There may be benefit to initiating parenteral therapy if oral intake will be delayed more than 12 to 24 hours postoperatively. Percutaneous endoscopic gastric tubes are associated with a higher risk of complications in patients with ascites or varices. If necessary, nasogastric or nasojejunal tubes are preferred over percutaneous gastric tubes for most patients.
      • Plauth M.
      • Bernal W.
      • Dasarathy S.
      • et al.
      ESPEN guideline on clinical nutrition in liver disease.

      Renal Dysfunction

      Renal dysfunction directly correlates with mortality risk in cirrhosis, as shown by its inclusion in the MELD score. Common causes of postoperative renal dysfunction in cirrhosis include intravascular volume depletion, acute tubular necrosis, and hepatorenal syndrome.
      • O'Leary J.G.
      • Yachimski P.S.
      • Friedman L.S.
      Surgery in the patient with liver disease.
      Avoiding nephrotoxic agents and ensuring adequate intravascular volume are recommended.
      • Northup P.G.
      • Friedman L.S.
      • Kamath P.S.
      AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review.
      The use of albumin, especially after large-volume paracentesis or as part of the treatment for spontaneous bacterial peritonitis, can help maintain renal perfusion, although trials have not shown universal benefit of colloid over crystalloid fluids.
      • Navarro L.H.
      • Bloomstone J.A.
      • Auler Jr., J.O.
      • et al.
      Perioperative fluid therapy: a statement from the international Fluid Optimization Group.
      Renal function should be closely monitored postoperatively. The cause of deteriorating renal function should be rapidly identified; a targeted workup could include a complete blood count, serum extended electrolytes (including calcium, magnesium, and phosphorus), urinalysis with microscopy, urine electrolytes, and a renal ultrasound. If hepatorenal syndrome is identified, rapid treatment is vital as this condition is often fatal if not treated. Vasoactive medications may be necessary to treat hepatorenal syndrome and early specialist consultation should be considered in such cases.
      • O'Leary J.G.
      • Yachimski P.S.
      • Friedman L.S.
      Surgery in the patient with liver disease.

      Medication Management

      Significant alterations in drug metabolism, protein binding, and elimination occur in cirrhosis, increasing the risk of medication toxicity. General principles include starting at lower doses with longer dosing intervals, particularly for sedating medications such as opioids and benzodiazepines. Short-acting medications are preferred to long-acting medications, especially in the early perioperative period.
      • Frye J.W.
      • Perri R.E.
      Perioperative risk assessment for patients with cirrhosis and liver disease.
      Hydromorphone and fentanyl have favorable hepatic metabolism compared to with other opioids. Acetaminophen is safe in cirrhosis at doses of up to 2 g per day.
      • Northup P.G.
      • Friedman L.S.
      • Kamath P.S.
      AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review.
      Nonsteroidal anti-inflammatory medications are generally avoided to lessen the risk for kidney injury and platelet dysfunction in the setting of coagulopathy. All current anesthetic agents may be safely used in the setting of acute or chronic liver disease.
      Patients who have received a liver transplant deserve special attention with respect to medication management to avoid compromising immunosuppression or inducing toxicity. The prescribed regimen should be identified, ideally with goal drug levels. In most cases, post-transplantation immunosuppressive medications should be continued preoperatively as closely as possible to their normal schedule. Calcineurin inhibitors such as tacrolimus and cyclosporine are prescribed to most patients after liver transplantation and have several properties that can lead to altered drug levels perioperatively. They are metabolized by CYP3A4/5 enzymes; any new medications should be screened for potential drug interactions. In addition, disruptions in gastrointestinal motility can affect absorption, with increased absorption potentially occurring in situations that prolong transit time (eg, ileus, opioid use). Monitoring trough levels of calcineurin inhibitors postoperatively is reasonable and a liver transplantation expert should be consulted if significant drug level alterations are anticipated or identified.
      • Lucey M.R.
      • Terrault N.
      Reply: to PMID 23281277.

      Management of Inflammatory Bowel Disease in the Perioperative Setting

      Patients with inflammatory bowel disease (IBD) require careful preoperative evaluation, with particular focus on assessment of disease severity and current activity, potential IBD-related complications (nutritional deficiencies, anemia, venous thromboembolic [VTE] risk, and chronic pain), and IBD-specific medication management. Recommended perioperative IBD management depends on whether the patient is undergoing gastroenterological surgery or non-gastroenterological surgery.
      In non-gastroenterological surgery, assessment for an IBD flare is a key element of the preoperative evaluation. Pertinent history includes the presence of fevers, chills, bowel habit change, oral intake, weight loss, bleeding, pain level, and current medications. Preoperative inflammatory markers (such as erythrocyte sedimentation rate or C-reactive protein) may assist the clinical evaluation. In the case of elective and non-urgent surgery, patients with suspected active or flared IBD should be referred to their gastroenterologist as part of the preoperative assessment. All patients with IBD merit preoperative laboratory studies to include a complete blood count, metabolic panel, and serologic nutritional markers (eg, albumin and prealbumin) if there is concern for malnutrition.
      If severe malnutrition is present, surgery should be delayed for nutritional optimization. Weight loss greater than 10%, albumin less than 3 g/dL, and body mass index less than 18.5 kg/m2 are associated with postoperative complications.
      • Lazarev M.
      • Ullman T.
      • Schraut W.H.
      • Kip K.E.
      • Saul M.
      • Regueiro M.
      Small bowel resection rates in Crohn's disease and the indication for surgery over time: experience from a large tertiary care center.
      In mild cases, patients should be referred to a dietician to optimize oral nutrition. In cases of severe malnutrition unresponsive to optimized oral nutrition, patients may require enteral (preferred route) or parenteral nutrition.
      Anemia is the most common systemic complication of IBD and is usually due to iron deficiency.
      • Lightner A.L.
      • Shen B.
      Perioperative use of immunosuppressive medications in patients with Crohn's disease in the new “biological era.”.
      Alternatively, it may be related to chronic systemic inflammatory burden, malabsorption, other nutritional deficiencies, and gastrointestinal blood loss. If anemia is present, evaluation for gastrointestinal blood loss and nutritional deficiencies is required. Patients with iron deficiency anemia should be given iron supplementation, although the optimal timing, route of administration, and effect on perioperative transfusion requirements are unknown.
      • Froessler B.
      • Palm P.
      • Weber I.
      • Hodyl N.A.
      • Singh R.
      • Murphy E.M.
      The important role for intravenous iron in perioperative patient blood management in major abdominal surgery: a randomized controlled trial.
      ,
      • Richards T.
      • Baikady R.R.
      • Clevenger B.
      • et al.
      Preoperative intravenous iron to treat anaemia before major abdominal surgery (PREVENTT): a randomised, double-blind, controlled trial.
      Patients with IBD are at increased VTE risk in both inpatient and outpatient settings, highlighting the need for aggressive perioperative VTE prophylaxis.
      • Lightner A.L.
      • Shen B.
      Perioperative use of immunosuppressive medications in patients with Crohn's disease in the new “biological era.”.
      The presence of IBD is incorporated into the commonly used Caprini risk assessment model, which guides perioperative VTE prophylaxis in many non-orthopedic surgeries.
      • Gould M.K.
      • Garcia D.A.
      • Wren S.M.
      • et al.
      Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.
      Patients with IBD undergoing gastroenterological and non-gastroenterological surgery should receive prophylaxis based on current clinical guidelines for VTE prevention in both orthopedic and non-orthopedic surgery.
      • Gould M.K.
      • Garcia D.A.
      • Wren S.M.
      • et al.
      Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.
      ,
      • Falck-Ytter Y.
      • Francis C.W.
      • Johanson N.A.
      • et al.
      Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.
      Because of the additional VTE risk associated with IBD, some practices extend postoperative VTE prophylaxis to 30 days in patients undergoing gastroenterological surgery.
      • Lightner A.L.
      • Shen B.
      Perioperative use of immunosuppressive medications in patients with Crohn's disease in the new “biological era.”.
      In individuals with IBD and chronic abdominal pain or taking opioids, a pain management plan and associated expectations should be addressed preoperatively. If possible, it is ideal to wean opioids before surgery due to increased risk for postoperative constipation, ileus, respiratory complications, and possible increased risk for overall mortality.
      • Burr N.E.
      • Smith C.
      • West R.
      • Hull M.A.
      • Subramanian V.
      Increasing prescription of opiates and mortality in patients with inflammatory bowel diseases in England.
      Involvement of pain medicine specialists is beneficial.
      Chronic corticosteroids and other immunosuppressive medications are frequently used in IBD treatment. Associated perioperative concerns, due to the use of chronic corticosteroids or other immunosuppressants, include impaired wound healing, infection, hyperglycemia, fluid retention, and delirium. In patients receiving chronic corticosteroids who are undergoing gastroenterological surgery, there may be concerns about increased risk of intra-abdominal sepsis and anastomotic healing.
      • Beddy D.
      • Dozois E.J.
      • Pemberton J.H.
      Perioperative complications in inflammatory bowel disease.
      In general for non-gastroenterological surgery, the lowest dose of corticosteroids should be used and need for supplemental steroids addressed on a case-by-case basis.
      • Nickerson T.P.
      • Merchea A.
      Perioperative considerations in crohn disease and ulcerative colitis.
      Perioperative glucocorticoid supplementation is based on both surgery type and patient-specific factors (including steroid dose and duration of therapy). Purine analogues including azathioprine and 6-mercaptopurine are generally held the day of surgery but otherwise continued throughout the perioperative timeframe.
      • Lightner A.L.
      • Shen B.
      Perioperative use of immunosuppressive medications in patients with Crohn's disease in the new “biological era.”.
      ,
      • Beddy D.
      • Dozois E.J.
      • Pemberton J.H.
      Perioperative complications in inflammatory bowel disease.
      • Nickerson T.P.
      • Merchea A.
      Perioperative considerations in crohn disease and ulcerative colitis.
      • Pfeifer K.J.
      • Selzer A.
      • Whinney C.M.
      • et al.
      Preoperative management of gastrointestinal and pulmonary medications: Society for Perioperative Assessment and Quality Improvement (SPAQI) consensus statement.
      Aminosalicylates can be continued through surgery, unless there is concern for renal insufficiency.
      • Lightner A.L.
      • Shen B.
      Perioperative use of immunosuppressive medications in patients with Crohn's disease in the new “biological era.”.
      ,
      • Pfeifer K.J.
      • Selzer A.
      • Whinney C.M.
      • et al.
      Preoperative management of gastrointestinal and pulmonary medications: Society for Perioperative Assessment and Quality Improvement (SPAQI) consensus statement.
      In patients undergoing non-gastroenterological surgery, biologics are typically held preoperatively (length of time depends on the specific medication) and surgery should occur at the end of the dosing cycle. Biologics are typically resumed 2 weeks postoperatively or after wound healing is complete. The decision to hold these medications is complex and must be balanced with the potential risk of IBD flare. Risks should be discussed with the patient and the primary gastroenterologist. The evidence regarding continuation of biologic agents in patients undergoing gastroenterological surgery for IBD is mixed and depends on the surgical procedure, the severity and type of underlying disease, and other factors. This is best deferred to the patient’s gastroenterologist.

      Renal Physiology in the Perioperative Period

      Renal function can be affected during the perioperative period due to hemodynamic changes and medication selection, leading to a reversible decrease in renal blood flow and secondary decrease in glomerular filtration rate. Renal blood flow may be indirectly affected by anesthesia-related sympatholysis and intraoperative hypotension.
      • Sun L.Y.
      • Wijeysundera D.N.
      • Tait G.A.
      • Beattie W.S.
      Association of intraoperative hypotension with acute kidney injury after elective noncardiac surgery.
      The physiologic response to surgery further impacts renal perfusion as catecholamines released in response to noxious stimuli activate the renin-angiotensin system as well as directly constrict the renal circulation, thus directly decreasing renal blood flow. During surgery, there is additional antidiuretic hormone release, which promotes fluid retention and transient hyponatremia.
      • Butterworth J.F.M.D.
      • Wasnick J.D.
      Morgan and Mikhail's Clinical Anesthesiology.
      In patients with pre-existing renal impairment, consideration should be given to the direct renal effects of medications as well as renal clearance of medication. Most medications can be used safely in patients with renal disease, although some require dose adjustments based on renal function.
      • Butterworth J.F.M.D.
      • Wasnick J.D.
      Morgan and Mikhail's Clinical Anesthesiology.

      Fluid Management in the Perioperative Period

      The ideal preoperative fluid management strategy continues to be debated. Traditional liberal fluid strategies are associated with intravascular expansion and improved end organ perfusion.
      • Prowle J.R.
      • Chua H.R.
      • Bagshaw S.M.
      • Bellomo R.
      Clinical review: volume of fluid resuscitation and the incidence of acute kidney injury — a systematic review.
      This strategy, however, is associated with a higher incidence of volume overload complications, including interstitial edema and poor tissue healing.
      • Al-Ghamdi A.A.
      Intraoperative fluid management: past and future, where is the evidence?.
      More restrictive fluid strategies have also been used. These have been successful in reducing the length of hospital stays, but have been associated with an increased incidence of acute kidney injury.
      • Nisanevich V.
      • Felsenstein I.
      • Almogy G.
      • Weissman C.
      • Einav S.
      • Matot I.
      Effect of intraoperative fluid management on outcome after intraabdominal surgery.
      Most current enhanced recovery after surgery protocols incorporate the use of goal-directed fluid management in the perioperative period, wherein the goal is to maintain tissue perfusion without causing the deleterious effects of volume overload.
      • Al-Ghamdi A.A.
      Intraoperative fluid management: past and future, where is the evidence?.
      This is achieved by closely matching intravenous fluid therapy to predetermined hemodynamic goals.

      Perioperative Assessment and Management of Patients With End-Stage Renal Disease

      Preoperative Assessment for Patients With End-stage Renal Disease

      The perioperative management of patients with chronic kidney disease is covered in a separate entry in this perioperative series.
      • Stephenson C.
      • Mohabbat A.
      • Raslau D.
      • Gilman E.
      • Wight E.
      • Kashiwagi D.
      Management of common postoperative complications.
      Patients with end-stage renal disease (ESRD (glomerular filtration rate less than15 mL/min or dialysis-dependent) require special perioperative consideration. These patients have a significantly higher risk of perioperative morbidity and all-cause mortality spanning multiple types of surgery,
      Erratum Regarding “US Renal Data System 2017 Annual Data Report: Epidemiology of Kidney Disease in the United States” (Am J Kidney Dis. 2018;71[3][suppl 1]:Svii,S1-S676).
      • Gajdos C.
      • Hawn M.T.
      • Kile D.
      • et al.
      The risk of major elective vascular surgical procedures in patients with end-stage renal disease.
      • Lin J.C.
      • Liang W.M.
      Mortality and complications after hip fracture among elderly patients undergoing hemodialysis.
      • Moran-Atkin E.
      • Stem M.
      • Lidor A.O.
      Surgery for diverticulitis is associated with high risk of in-hospital mortality and morbidity in older patients with end-stage renal disease.
      • Parikh D.S.
      • Swaminathan M.
      • Archer L.E.
      • et al.
      Perioperative outcomes among patients with end-stage renal disease following coronary artery bypass surgery in the USA.
      likely related to an increased rate of cardiovascular disease, electrolyte disturbances, and blood pressure lability. A large retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program database compared patients with ESRD with matched controls undergoing common general surgery procedures. End-stage renal disease was associated with increased mortality (odds ratio, 9.05; 95% CI, 4.09 to 20.00), as well as increased rates of return to the operating room, postoperative infection, and pulmonary complications.
      • Brakoniecki K.
      • Tam S.
      • Chung P.
      • Smith M.
      • Alfonso A.
      • Sugiyama G.
      Mortality in patients with end-stage renal disease and the risk of returning to the operating room after common general surgery procedures.
      End-stage renal disease is not a contraindication to elective surgery, but special preoperative planning and counseling is indicated.
      During the preoperative assessment, the patient’s renal function and regular dialysis regimen should be clarified and the plan for perioperative dialysis discussed. In particular, it is useful to know the patient’s current dry weight to help assess volume status in the perioperative period. Whether the patient continues to produce urine should also be established as this may influence medication decisions. Residual renal function, with even minimal urine production, is associated with better prognosis; as such, it is worthwhile to preserve any renal function, if at all possible.
      • Shemin D.
      • Bostom A.G.
      • Laliberty P.
      • Dworkin L.D.
      Residual renal function and mortality risk in hemodialysis patients.
      The preoperative physical examination should include a volume assessment and evaluation of the dialysis access site to ensure there is no evidence of infection. Preoperative labs should include a complete blood count (to assess for anemia) and a full set of extended electrolytes, including calcium, phosphorus, and magnesium (to help guide perioperative dialysis).

      Perioperative Management of Patients with ESRD

      Timing of Dialysis

      Dialysis is necessary to correct electrolyte abnormalities (particularly potassium and urea), acid-base imbalance, and volume status. The goal is to reach the patient’s dry weight before surgery. For patients on hemodialysis, it is recommended that patients dialyze 12 to 24 hours before elective surgery, ideally the day before surgery.
      • Carlo J.O.
      • Phisitkul P.
      • Phisitkul K.
      • Reddy S.
      • Amendola A.
      Perioperative implications of end-stage renal disease in orthopaedic surgery.
      Logistically, elective surgical procedures should not be scheduled on Monday as most outpatient dialysis centers are closed on Sunday. There is no evidence to suggest that an additional hemodialysis session (besides the normal routine) improves outcomes. If dialysis must be performed within 4 to 6 hours of surgery, heparin should be avoided to decrease perioperative bleeding risk.
      • Carlo J.O.
      • Phisitkul P.
      • Phisitkul K.
      • Reddy S.
      • Amendola A.
      Perioperative implications of end-stage renal disease in orthopaedic surgery.
      ,
      • Kanda H.
      • Hirasaki Y.
      • Iida T.
      • et al.
      Perioperative management of patients with end-stage renal disease.
      For patients on peritoneal dialysis, some nephrologists recommend increasing the dialysis time for a few days to a week before surgery in anticipation that postoperative peritoneal dialysis may be delayed or complicated by ileus or constipation. This may be achieved by adding an additional exchange per day for patients on continuous ambulatory peritoneal dialysis or adding an additional couple of hours on the cycler for patients on continuous cycling peritoneal dialysis.

      Sanghani NS, Soundararajan R, Golper TA. Medical management of the dialysis patient undergoing surgery. In:Post TW, ed. UptoDate. UpToDate. Accessed February 20, 2020. https://www.uptodate.com/contents/medical-management-of-the-dialysis-patient-undergoing-surgery

      ,
      • Kleinpeter M.A.
      • Krane N.K.
      Perioperative management of peritoneal dialysis patients: review of abdominal surgery.
      However, there are no published data on the outcomes of this practice, and increased preoperative peritoneal dialysis is not uniformly endorsed.

      Hyperkalemia

      In the perioperative setting, hyperkalemia is the electrolyte derangement of greatest concern, given the potential effects on cardiac membrane stability. It is prudent to check the plasma potassium level on the day of surgery to re-evaluate an unexpectedly elevated potassium level because pseudohyperkalemia can result from mechanical trauma related to venipuncture, prolonged tourniquet time, or blood drawn through the intravenous line. Although there is no clear consensus regarding an ideal preoperative potassium level, it is recommended that potassium be less than 5.5 mEq/L before elective surgery.
      • Carlo J.O.
      • Phisitkul P.
      • Phisitkul K.
      • Reddy S.
      • Amendola A.
      Perioperative implications of end-stage renal disease in orthopaedic surgery.
      In the case of nonelective surgery, patients with hyperkalemia should have a preoperative electrocardiogram (ECG). In their usual sequence of appearance, hyperkalemia results in peaked T waves, prolonged PR intervals, loss of the P wave amplitude, widening of the QRS complex, sine wave configuration, and eventually ventricular fibrillation and asystole.
      • Ahmed J.
      • Weisberg L.S.
      Hyperkalemia in dialysis patients.
      Serum potassium greater than 6.5 mEq/L is usually associated with ECG changes, although it is also possible for a patient to directly enter ventricular fibrillation or asystole without prior ECG disturbances.
      • Ahmed J.
      • Weisberg L.S.
      Hyperkalemia in dialysis patients.
      Furthermore, it has been recommended that a patient be dialyzed preoperatively if there are any hyperkalemia-associated ECG changes or if the serum potassium is greater than 6.0 to 6.2 mEq/L.
      • Weisberg L.S.
      The risk of preoperative hyperkalemia.

      Anemia

      Before elective surgery, the goal is to bring hemoglobin to target levels using erythropoiesis-stimulating agents (ESAs) and intravenous iron supplementation to reduce the need for red blood cell transfusion. It is particularly important to minimize transfusions in patients anticipating renal transplantation given the concern for alloimmunization and subsequent increased risk of graft rejection. Patients with anemia are at risk for bleeding. Lower concentrations of red blood cells result in positioning of platelets within the bloodstream further from the subendothelium, which makes them less likely to induce clotting. Red blood cells release adenosine diphosphate and thromboxane A2, which trigger platelet aggregation, and are reduced in the setting of anemia.
      • Hedges S.J.
      • Dehoney S.B.
      • Hooper J.S.
      • Amanzadeh J.
      • Busti A.J.
      Evidence-based treatment recommendations for uremic bleeding.
      Therefore, it is recommended that hemoglobin and iron studies be assessed and optimized with ESAs and iron supplementation before elective surgery. The 2012 Kidney Disease Improving Global Outcomes guidelines recommend achieving a hemoglobin between 10 and 11.5 g/dL, transferrin saturation greater than 30%, and ferritin greater than 500 ng/mL.
      Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group
      KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease.
      If hemoglobin is less than 10 g/dL and transferrin saturation and ferritin are not above these goals, iron should first be repleted before initiating the ESA. Typically, 1000 mg intravenous iron is given as a single dose or as repeated smaller doses at consecutive hemodialysis sessions. Transferrin saturation and ferritin levels can be rechecked 1 week after the last iron infusion.
      Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group
      KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease.

      Coagulation Abnormalities

      Patients with ESRD are at increased risk of bleeding.
      • Boccardo P.
      • Remuzzi G.
      • Galbusera M.
      Platelet dysfunction in renal failure.
      ,
      • Acedillo R.R.
      • Shah M.
      • Devereaux P.J.
      • et al.
      The risk of perioperative bleeding in patients with chronic kidney disease: a systematic review and meta-analysis.
      There are several underlying reasons for this, including uremia-induced platelet dysfunction, abnormal platelet-endothelial interaction, and anemia. Therefore, preoperative dialysis is important to reduce urea levels and reduce platelet dysfunction. However, heparin should be avoided if dialysis is performed within 4 to 6 hours of surgery.
      • Carlo J.O.
      • Phisitkul P.
      • Phisitkul K.
      • Reddy S.
      • Amendola A.
      Perioperative implications of end-stage renal disease in orthopaedic surgery.
      ,
      • Kanda H.
      • Hirasaki Y.
      • Iida T.
      • et al.
      Perioperative management of patients with end-stage renal disease.
      As noted above, optimizing hemoglobin to target levels also decreases bleeding risk.
      • Hedges S.J.
      • Dehoney S.B.
      • Hooper J.S.
      • Amanzadeh J.
      • Busti A.J.
      Evidence-based treatment recommendations for uremic bleeding.
      Desmopressin, which assists platelet aggregation by increasing release of von Willebrand factor, can be considered for patients with a history of excessive bleeding.
      • Lee H.K.
      • Kim Y.J.
      • Jeong J.U.
      • Park J.S.
      • Chi H.S.
      • Kim S.B.
      Desmopressin improves platelet dysfunction measured by in vitro closure time in uremic patients.
      ,
      • Mannucci P.M.
      • Remuzzi G.
      • Pusineri F.
      • et al.
      Deamino-8-D-arginine vasopressin shortens the bleeding time in uremia.
      This can be given intravenously, subcutaneously, or intranasally immediately before or during surgery. The intravenous and the subcutaneous dose is 0.3 μg/kg and the intranasal dose if 3 μg/kg. Desmopressin takes effect in approximately 1 hour and lasts for at least 4 hours.
      • Mannucci P.M.
      • Remuzzi G.
      • Pusineri F.
      • et al.
      Deamino-8-D-arginine vasopressin shortens the bleeding time in uremia.
      However, there is no clear evidence that desmopressin significantly impacts clinical outcomes and there is some potential increased risk of thrombotic events.
      • Levy J.H.
      Pharmacologic methods to reduce perioperative bleeding.

      Malnutrition

      Malnutrition is common in ESRD, in part related to changes in taste and appetite, loss of nutrients during hemodialysis, dialysis-induced catabolism, inflammation, and dietary restrictions.
      • Trainor D.
      • Borthwick E.
      • Ferguson A.
      Perioperative management of the hemodialysis patient.
      Before elective surgery, it is recommended that nutritional status be assessed and optimized orally as much as possible.
      • Evans D.C.
      • Martindale R.G.
      • Kiraly L.N.
      • Jones C.M.
      Nutrition optimization prior to surgery.
      ,
      • Weimann A.
      • Braga M.
      • Carli F.
      • et al.
      ESPEN guideline: clinical nutrition in surgery.
      Surgical patients with a body mass index less than 18.5 kg/m2, more than 10% weight loss within 6 months, or 5% over 3 months are considered to be malnourished as per the European Society for Parenteral and Enteral Nutrition guidelines. Involving a dietician is especially helpful in these circumstances. Oral nutritional supplements are preferred over intravenous supplements.
      • Weimann A.
      • Braga M.
      • Carli F.
      • et al.
      ESPEN guideline: clinical nutrition in surgery.
      Renal specific supplements that are high protein, low volume, and have reduced potassium and phosphorus are preferred in patients with a history of hyperkalemia, hyperphosphatemia, or volume overload.
      • Sabatino A.
      • Regolisti G.
      • Karupaiah T.
      • et al.
      Protein-energy wasting and nutritional supplementation in patients with end-stage renal disease on hemodialysis.

      Conclusion

      Patients with chronic gastrointestinal, hepatic, or renal disease are at risk for multiple perioperative complications and require a comprehensive preoperative evaluation. A multidisciplinary approach is often beneficial and specialist involvement should be considered. The intraoperative and postoperative plans should be individualized based on the unique medical and surgical characteristics of each patient.

      Potential Competing Interests

      The authors report no potential competing interests.

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