PERIOPERATIVE ISSUES
Selections from the University of California, San Francisco, School of Medicine’s Postgraduate Course in General Surgery, March 17-19, 2005
| INDICATIONS FOR BLOOD TRANSFUSION IN ANEMIC SURGICAL PATIENTS —Eugene Shafton, MD, Clinical Professor of Medicine, University of California, San Francisco, School of Medicine |
| Potential adverse effects of transfusion: volume overload—difficult to assess adequate volume; microvascular perfusion impairment—in patients with conditions such as acute coronary syndrome, where more blood and more O2 transport would appear beneficial, transfusion may, in fact, impair tissue perfusion; studies show most patients with acute coronary syndrome can function with hemoglobin of ≈7 g/dL, and that transfusion would be detrimental unless continued pain or evidence of adequate hypoperfusion present; febrile reactions—cause delay and increase cost; mismatched blood— estimated that 1 in 14,000 units mismatched or given to wrong patient; platelet transfusion—primary cause of bacterial contamination; cytomegalovirus—problematic with delayed febrile reactions and for patients with immune incompetence; prevented by appropriate testing and ultraviolet irradiation; graft vs host reactions—activation of lymphocytes, particularly in immunologically impaired patients; hemolytic reactions—transmitted antibodies can hemolyze patient’s own blood; transmitted infections—hepatitis B most commonly transmitted viral infection; prevention of West Nile virus (WNV) transmission hindered by delay between infection and production of antibodies and insensitivity of testing; trypanosomiasis largely excluded by patient’s history (endemic to Central and South America) |
| Assessment of blood volume: target should be normovolemia, using crystalloids and colloids before considering blood products; urine output not accurate measurement; intravascular volume difficult to assess (changes in central venous, superior vena cava, and inferior vena cava pressures useful, but absolute numbers not useful); use of pulmonary artery lines (Swan- Ganz catheter) decreasing due to complications; echocardiography has many limitations; clinical tests important, eg, changes in heart rate and blood pressure (BP) with volume fluctuations |
| Ischemia: transfusion has been used to target ischemia of heart, brain, and kidney tissue; still important but difficult to assess, especially in patients who may have altered mental status and brain ischemia; erythropoietin may be valuable in maximizing brain recovery after stroke |
| Preoperative transfusions: appears to be no hemoglobin threshold for safety; short- and long-term mortality of anemic patients likely due to comorbidity associated with anemia; most nontransfused anemic patients can undergo surgery safely; speaker recommends increasing preoperative hemoglobin levels with techniques other than transfusion, such as erythropoietin with iron |
| Intra- and postoperative transfusions: transfusion rarely indicated unless hemoglobin <6 to 7 g/dL or patient has active tissue ischemia; study—357 patients with cardiovascular disease in intensive care; if hemoglobin ≤7 g/dL, patient transfused and maintained at 7 to 9 g/dL; if level reached 10 g/dL, patient transfused and maintained at 10 to 12 g/dL; 30-day mortality rate same for both groups; more liberal transfusion favored patients with active ongoing acute myocardial infarction (MI) or ischemia, but numbers not significant |
| Heart failure (HF): anemia (defined by speaker as hemoglobin 12 g/dL for men, 11 g/dL for women) major risk factor for HF; 79% of patients with class IV HF anemic, and many have associated chronic renal failure; transfusion rarely indicated, despite anemia; erythropoietin may prove useful treatment |
| New therapies: erythropoietin—effects include stimulation of hemoglobin synthesis, anti-inflammatory effects, stimulation of nitric oxide, and O2 release in endothelium; risks include hypertension and impairment of tissue perfusion; recombinant factor VIIa—potent, short-acting thrombin stimulator; small studies have shown significant reductions in perioperative bleeding; artificial O2 carriers—largely studied in trauma situations; release O2 at endothelium, which can lead to vasoconstriction |
| Erythropoietin: has potential to aid recovery of ischemic central nervous system (CNS) tissue; timing important factor because it stimulates erythropoiesis if administered for too long, which could be resolved by using derivatives with more specific actions; indicated for patients with chronic renal failure, chemotherapy-induced anemia, preoperative stimulation of erythropoiesis, and chronic HF |
| Retropubic prostatectomy study: patients randomized to receive 20 µg/kg or 40 µg/kg of recombinant factor VIIa or placebo; less bleeding in patients receiving recombinant factor VIIa, especially 40 µg/kg dose; patients receiving 40-µg/kg dose did not require transfusions |
| PERIOPERATIVE CARDIAC RISK REDUCTION STRATEGIES FOR THE SURGICAL PATIENT —Arthur Wallace, MD, PhD, Associate Professor of Anesthesiology and Perioperative Care, University of California, San Francisco, School of Medicine |
| Definition of perioperative cardiac morbidity: consists of cardiac death, MI, unstable angina, HF, and life-threatening dysrhythmias |
| Risk factors: Goldman study—9 independent risk factors identified, including congestive heart failure, MI, arrhythmias, old age, major operations, aortic stenosis, and poor general medical condition; Mangano study—40% of patients in study had episode of myocardial ischemia (episodes defined as Holter monitor-recorded, 1-mm ST changes for 1 min during 1 perioperative week); myocardial episode increases risk for perioperative cardiac morbidity tenfold, and increases 2-yr mortality twofold |
| Assessing risk: Mangano et al study—dipyridamole thallium-201 (201Tl) scintigraphy performed on 60 patients undergoing vascular surgery; results showed no association between redistribution defects and perioperative ischemia; test appears to have no predictive value; Baron et al study—in 457 patients, 201Tl scintigraphy had no predictive value for perioperative MI |
| Prophylactic coronary artery bypass grafting (CABG): study—patients undergoing vascular surgery randomized to receive or not receive preoperative prophylactic CABG; results showed prophylactic CABG had no benefit |
| Avoiding myocardial ischemia: risk factors include tachycardia, hypotension, hypertension, pain, vasospasm, and tissue injury; after many trials involving many agents, atenolol and clonidine shown to reduce mortality risk by 50% |
 | Atenolol study: double-blind placebo-controlled randomized trial involving 200 patients undergoing noncardiac surgery; history, physical examination, and Holter monitoring performed; inclusion criteria—patients undergoing noncardiac surgery, and had coronary disease, vascular disease, or 2 risk factors (age, smoking, hypertension, cholesterol, diabetes); method—trial performed using Intensive Care Information System (ICIS) protocols for acute MI; 10 mg intravenous (IV) atenolol administered in postanesthesia care unit before surgery if heart rate >55 bpm, BP >100 mm Hg, and no evidence of acute congestive failure, third-degree heart block, or bronchospasm; protocol repeated postoperatively for 1 wk; cost of therapy—with IV medications, $18 per patient; with oral medications, $1 per patient; results—50% decrease in episodes of myocardial ischemia during postoperative week; 31 patients died during >2-yr follow-up, 21 in placebo group and 9 in atenolol group; 19 days to first death in placebo group, compared to 237 days in atenolol group |
| Poldermans et al data: initial study—1300 patients undergoing surgery for abdominal aortic aneurysm or aortofemoral bifurca tion graft received history and physical examination; 700 patients identified as having high risk for coronary disease received dobutamine stress echocardiography, which identified 300 patients with significant coronary disease who underwent surgery; surgical mortality rate 30%; bisoprolol study—patients randomized as in previous study, but half of patients with significant coronary disease received bisoprolol for 1 wk preoperatively (metoprolol used where IV drug indicated); bisoprolol decreased mortality rate 90%; suggests preoperative medication can reduce mortality rate 90%; note—patients deemed too sick for randomization underwent CABG before randomization; CABG mortality rate 50%; interpretation— patients without risk factors can undergo surgery; patients with risk factors should receive preoperative β-blocker, then undergo surgery; mortality rate in highest-risk group in bisoprolol study less than risk associated with cardiology work-up |
| Preoperative CABG: study data—patients randomized to CABG, percutaneous coronary intervention (PCI), or medical therapy; mortality rate at 1 yr for CABG 4%, compared to 4.5% for PCI group and 1.5% for medical therapy; advantage from CABG seen only if patient survives 5 yr; therefore, stable patient not likely to benefit from cardiology work-up |
| Clonidine as alternative to β-blockers: study data—double-blind placebo-controlled trial of 200 patients at risk for coronary disease randomized to receive 0.2 mg clonidine night before surgery and day of surgery or placebo; clonidine decreased risk for ischemia 50%; outcomes—30-day mortality reduced sevenfold; 2-yr mortality reduced 50%; mechanism of action—reduces release of catecholamines from CNS ( β-blockers block effects of catecholamines); reduces epinephrine and norepinephrine |
| American College of Cardiology protocol: study—ability of physicians in preoperative clinic to follow protocol assessed; results show guidelines never agreed on need for noninvasive testing; in practice, protocol did not work |
| Recommendations: perform careful history and physical examination; perform additional work-up if indicated, but do not use surgical experience as reason for CABG; preoperative testing should be guided by history and physical examination; no suggestion that prophylactic tests have benefit; prophylactic perioperative β-blockade indicated for patients with known coronary disease or risk factors; use clonidine if patient unable to take β-blocker |
| MANAGING THE CIRRHOTIC WHO NEEDS ABDOMINAL SURGERY —Karen Deveney, MD, Professor of Surgery and Program Director in Surgery, Oregon Health and Science University, Portland |
| Case example: 58-yr-old man presented with painful leaking abdominal hernia; hernia tender and overlying skin red and ulcerated; hernia leaking acidic fluid; patient jaundiced and discombobulated, smelled of alcohol, and had obvious ascites; unsuccessful attempt made to stitch hernia; laboratory tests revealed Child’s class C cirrhosis |
| Morbidity and mortality: simple hernia repair has increased morbidity and mortality if ascites present; Child’s class B patients—mortality rate 30%; Child’s class C patients—mortality rate prohibitively high; emergency operations— especially high risk; colon operations—high risk due to increased colonic bacteria; others—patients with acute alcoholic hepatitis or hepatorenal syndrome at high risk |
| Preoperative assessment: important to perform full assessment and have frank discussion with patient and family; for some patients with serious conditions, providing comfort care only may be best approach; important to assess all risk factors for underlying liver disease during thorough physical examination; patient with known liver disease—assess physiologic status ahead of time; preoperative preparation can reduce complications and mortality |
| Portal hypertension: speaker frequently operates on patients with ulcerative colitis who have sclerosing cholangitis; in these patients, assessment of portal hypertension important in deciding which operation suitable if patient presents with colon cancer or high-grade dysplasia in colon; physical signs include caput medusa; ensure referring gastroenterologist has evaluated patient for varices using endoscopy; computerized tomography (CT) can reveal collateral veins; if patient has portal hypertension and no history of variceal hemorrhage, β-blocker indicated; patient with history of bleeding more likely to undergo banding or sclerotherapy; transjugular intrahepatic portosystemic shunt (TIPS) occasionally required, which treats ascites but increases risk for encephalopathy |
| Ascites: preoperative evaluation and treatment helpful in preventing infection, dehiscence, and leak; treatment includes sodium and water restriction or more extreme measures in severe cases; culture, cell count, and cytology required if operation cancer-related; diurese using spironolactone or furosemide; preventing prerenal azotemia and electrolyte problems—begin with spironolactone at usual dose (can be increased to 600 mg/day); furosemide may be added if spironolactone dose not adequate or if patient develops hyperkalemia, hyperchloremia, or acidosis; treat until creatinine increases; paracentesis and replacement with albumin may be necessary in extreme cases |
| Hepatic encephalopathy: if present preoperatively, document, then stop and avoid drugs with CNS effects; treat with lactulose and neomycin |
| Coagulopathies: need to be corrected before surgery using vitamin K, fresh frozen plasma, and platelets if count <50,000/µL |
| Malnourishment: protein restriction no longer recommended; enteral feeding preferred to parenteral |
| Hemostasis: perform slow, deliberate dissection with liberal use of electrocautery; use suture ligation for abdominal wall collateral blood vessels; minimize risk for ascites by not dividing large collateral blood vessels; close abdomen in layers, with continuous suturing |
| Anesthetic management: use of central venous or Swan-Ganz catheters results in minimal need for fluid replacement; minimize crystalloid and sodium intraoperatively and postoperatively; use anesthetic that increases hepatic blood flow, eg, isoflurane, desflurane, or sevoflurane; use neuromuscular blocking agents not metabolized by liver, eg, atracurium; request anesthesiologist who has experience with this group of patients; use short-acting narcotics to avoid prolonged effects; beneficial to use sedatives eliminated by glucuronidation, rather than hepatic metabolism |
| Postoperative management: minimize formation of ascites; short-acting analgesics minimize encephalopathy; resume lactulose and neomycin treatment as quickly as possible if patient at high risk for delirium tremens; take steps to prevent infection, maintain nutrition, and optimize coagulation |
| Case-example outcome: patient received fresh frozen plasma and perioperative antibiotics; postoperatively, patient developed encephalopathy and ascites reaccumulated, but patient survived |
Educational Objectives
| The goal of this program is to educate the listener about perioperative issues. After hearing and assimilating this program, the clinician will be better able to: |
| 1. Review the indications for blood transfusion in anemic surgical patients. |
| 2. Discuss the potential applications for erythropoietin and recombinant coagulation factors in anemic surgical patients. |
| 3. Review cardiac risk reduction strategies for surgical patients. |
| 4. Prescribe atenolol and clonidine to reduce cardiac risk in surgical patients. |
| 5. Apply appropriate strategies for the management of cirrhotic patients who need abdominal surgery. |
Discussed on This Program
Atenolol [Tenormin] Atracurium besylate [Tracrium] Bisoprolol fumarate [Zebeta] Clonidine HCl [Catapres, Duraclon] Desflurane [Suprane] Epoetin alfa (erythropoietin; EPO) [Epogen, Procrit] Furosemide [Lasix] Isoflurane [Forane] Lactulose [several trade names] Metoprolol succinate [Lopressor, Metoprolol Tartrate, Toprol XL] Neomycin sulfate [Mycifradin, Neo-fradin, Neo-Tabs] Recombinant activated coagulation factor VII (rFVIIa) [NovoSeven] Sevoflurane [Ultane] Spironolactone [Aldactone]
Suggested Reading
Azoulay D et al: Neoadjuvant transjugular intrahepatic portosystemic shunt: a solution for extrahepatic abdominal operation in cirrhotic patients with severe portal hypertension. J Am Coll Surg 193(1):46, 2001; Baker JE: Erythropoietin mimics ischemic preconditioning. Vascul Pharmacol 42(5-6):233, 2005; Farnsworth N et al: Child-Turcotte-Pugh versus MELD score as a predictor of outcome after elective and emergent surgery in cirrhotic patients. Am J Surg 188(5):580, 2004; Friederich PW et al: Effect of recombinant activated factor VII on perioperative blood loss in patients undergoing retropubic prostatectomy: a double-blind placebo-controlled randomised trial. Lancet 361(9353):201, 2003; Friederich PW et al: The effect of the administration of recombinant activated factor VII (NovoSeven) on perioperative blood loss in patients undergoing transabdominal retropubic prostatectomy: the PROSE study. Blood Coagul Fibrinolysis 11(Suppl 1):S129, 2000; Fuster J et al: Abdominal drainage after liver resection for hepatocellular carcinoma in cirrhotic patients: a randomized controlled study. Hepatogastroenterology 51(56):536, 2004; Goodnough LT: Autologous blood donation. Anesthesiol Clin North America 23(2):263, 2005; Kallergis EM et al: Anaemia and heart failure: is its correction a therapeutic target? The role of erythropoietin. Hell J Cardiol 46(3):222, 2005; Kertai MD et al: The prognostic value of dobutamine stress echocardiography in patients with abdominal aortic aneurysm and concomitant coronary artery disease. J Cardiovasc Surg (Torino) 44(3):423, 2003; Maddox TM: Preoperative cardiovascular evaluation for noncardiac surgery. Mt Sinai J Med 72(3):185, 2005; Mahdy AM, Webster NR: Perioperative systemic haemostatic agents. Br J Anaesth 93(6):842, 2004; Mangano DT et al: Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. Multicenter Study of Perioperative Ischemia Research Group. N Engl J Med 335(23):1713, 1996; Maull KI, Turnage B: Trauma in the cirrhotic patient. South Med J 94(2):205, 2001; Merli M et al: Malnutrition is a risk factor in cirrhotic patients undergoing surgery. Nutrition 18(11-12):978, 2002; O'Meara E et al: Anemia and heart failure. Curr Heart Fail Rep 1(4):176, 2004; Poldermans D et al: Bisoprolol reduces cardiac death and myocardial infarction in high-risk patients as long as 2 years after successful major vascular surgery. Eur Heart J 22(15):1353, 2001; Poldermans D et al: The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group. N Engl J Med 341(24):1789, 1999; Pomier-Layrargues G et al: Transjugular intrahepatic portosystemic shunt (TIPS) versus endoscopic variceal ligation in the prevention of variceal rebleeding in patients with cirrhosis: a randomised trial. Gut 48(3):390, 2001; Romney R et al: Usefulness of routine analysis of ascitic fluid at the time of therapeutic paracentesis in asymptomatic outpatients. Results of a multicenter prospective study. Gastroenterol Clin Biol 29(3):275, 2005; Silverberg DS et al: The importance of anemia and its correction in the management of severe congestive heart failure. Eur J Heart Fail 4(6):681, 2002; Stasi R et al: Management of cancer-related anemia with erythropoietic agents: doubts, certainties, and concerns. Oncologist 10(7):539, 2005; Wallace A et al: Prophylactic atenolol reduces postoperative myocardial ischemia. McSPI Research Group. Anesthesiology 88(1):7, 1998; Wallace AW et al: Effect of clonidine on cardiovascular morbidity and mortality after noncardiac surgery. Anesthesiology 101(2):284, 2004.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial relationship with the manufacturer or provider of any commercial product or service discussed. For this issue, the following has been reported: Dr. Shafton is a consultant for Reliant Pharmaceuticals, Inc. and is a member of the Speakers’ Bureau for Abbott Laboratories, Boehringer Ingelheim Corp, and Pfizer Inc.
Drs. Shafton, Wallace, and Deveney were recorded March 17, 2005, in San Francisco at the University of California, San Francisco, School of Medicine’s Postgraduate Course in General Surgery. The Audio-Digest Foundation thanks the speakers and the University of California, San Francisco, School of Medicine for their cooperation in the production of this program.
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