Failure to Separate From Cardiopulmonary Bypass 

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Key action points in managing failure to separate from cardiopulmonary bypass (CPB) include the following:

Safe and successful weaning from CPB is a process that requires careful coordination between the surgeon and the anesthesiologist in close collaboration with the perfusionist. ^{[1, 2]}

Despite many improvements in CPB technology and circuit design, patients still undergo an intense inflammatory response when their blood comes in contact with the nonendothelial surfaces involved in extracorporeal circulation. Platelets, endothelial cells and leukocytes become activated and, in turn, initiate the coagulation cascade while releasing various mediators. The ensuing vasoplegia, coagulopathy, and depressed myocardial function present numerous challenges during the weaning process, as well as during the following hours in the intensive care unit (ICU).

In a study investigating difficult and complex separation from CPB in high-risk cardiac surgical patients, ^[3]  Denault et al described difficult (or pharmacologically assisted) separation from bypass (DSB) as the requirement for at least both vasoactive and inotropic agents from the end of CPB until the end of surgery. They defined complex or very difficult separation from CPB as at least one failure of the first separation attempt or the need for mechanical support (an IABP or ventricular assist device) to leave the operating room (OR). An increased requirement for pharmacologic or mechanical support in the weaning process was associated with higher morbidity and mortality and longer times on CPB.

Adequate planning for specific patient variables and predictable problems often encountered in cardiac surgery, though essential, cannot fully eliminate the necessity of intervening and even urgently returning to CPB. The severity of the inflammatory response from CPB cannot always be anticipated, and rare mechanical or technical problems can arise that contribute to a difficult transition off CPB. Preoperative risk stratification can facilitate the identification of patients at increased risk for perioperative morbidity and mortality, but it does not take into account significant intraoperative factors.

For the past several decades, the Society of Thoracic Surgeons (STS) has been leading the development of risk models and quality improvement monitoring with the STS National Cardiac Database. The more than 5.8 million surgical records in this database have helped create surgical risk calculators and led to improvements in perioperative care for cardiac surgery patients. The anesthesiology module now included in the Adult Cardiac Surgery Database (ACSD) component of the STS database, created through a partnership with the Society of Cardiovascular Anesthesiologists (SCA), will only further enhance perioperative care. 

Undoubtedly, improved risk modeling and preoperative planning can help anesthesiologists deliver better patient care. Nevertheless, it is essential to maintain vigilance in the OR, especially when faced with an aging population at increased risk for surgical morbidity and mortality.   Anesthesiologists will continue to play primary roles in optimizing patients’ medical condition and safely guiding them through cardiac surgery with CPB. By integrating preoperative data with intraoperative factors, anesthesiologists will be best prepared to convert a failure to wean from CPB into a complex separation from CPB, thereby reducing morbidity and mortality.

Preparation for any transition from CPB, even one that appears straightforward, first requires open communication among the surgeon, the anesthesiologist, and the perfusionist. Ideally, the transition is led by the anesthesiologist, who then allows the surgeon to focus on the surgical field, the suture lines, gross cardiac function, and hemostasis. If communication among the members of the cardiac team is not open and free, there is a risk that their independent actions may compete with each other and even prove counterproductive. In this way, what could have been an easy transition can turn into one that is difficult or complex. 

As mentioned above, CPB creates numerous insults to normal physiology. Expected affronts to homeostasis during standard CPB include the following:

It is a fortunate occurrence when patients transition off CPB effortlessly as ventilation is reestablished and arterial pump use gradually decreased. Such good fortune should not be automatically expected. It is better to be surprised by an easy transition after having prepared for a more difficult one than to be surprised by a difficult transition after having prepared for an easy one. 

Various mnemonics have been created and used by anesthesiologists as reminders of the steps required in safely transitioning patients from CPB back to their native circulation. The following are two common examples:

At many institutions, weaning protocols are standardized to help minimize errors of omission. Just as preparation for and execution of weaning are often standardized, investigation and management of problems encountered during and after weaning should be carried out in a systematic fashion to ensure thoroughness.  

Hypothermia occurs to varying degrees as a consequence of heat loss, even if active cooling is not employed during CPB. Temperatures are measured at multiple locations as surrogates for brain, core, and shell temperature.

Gradual warming is required to avoid cerebral injury induced by hyperthermia. The proximity of the aortic cannula to the great vessels creates a positive gradient between nasopharyngeal and core temperature measured at the bladder or rectum. A nasopharyngeal temperature in the range of 36.5-37.0º is targeted during warming; core temperature is typically 2-3º lower. A larger gradient or a lower temperature can create shivering, hypertension, and instability after cessation of CPB as pulsatile blood flow opens up relatively colder vascular beds. This can occur during chest closure or can even present after transfer into the ICU.

The venous intake line carries true mixed venous blood. Inadequate tissue perfusion and oxygenation will manifest in the form of increased lactate production and decreased pH. A mixed venous saturation of approximately 75% and a venous oxygen tension (PO₂) higher than 35 mm Hg are satisfactory for transitioning from CPB.

Hemodilution during CPB facilitates tissue perfusion and oxygen delivery through enhancement of blood flow by reducing blood viscosity and oncotic pressure. Hemoconcentration achieved by means of diuretics or  CPB devices helps in restoring adequate oxygen-carrying capacity after CPB. Blood conservation measures (eg, antifibrinolytics, cell salvage, prebypass sequestration, miniaturized bypass circuitry, and retrograde autologous circuit priming) also play a significant role in patient management.

Although there is no longer an accepted target hematocrit (Hct) to be maintained for transitioning from CPB, a number of well-designed randomized controlled trials (RCTs) have shown increased morbidity and mortality with liberal transfusion strategies in critically ill patients. There are risks associated with blood product transfusion, as well as risks associated with anemia.

Loor et al ^[4]  found that patients who had a single-negative exposure to either anemia or RBC transfusion experienced less morbidity than patients who had a double-negative exposure (ie, to both anemia and RBC transfusion). A context-specific meta-analysis by Hovaguimian et al ^[5] showed that in patients undergoing cardiac or vascular procedures, restrictive strategies appear to increase the risk of events that reflect inadequate oxygen supply (eg, myocardial, cerebral, renal, mesenteric, and peripheral ischemic injury; arrhythmia; and unstable angina).

When it is not possible to achieve ideal optimization of the Hct of cardiac surgical patients preoperatively, avoidance of a double-negative exposure to anemia and RBC transfusion can decrease patient morbidity.  

It is imperative to address and correct acidosis before the patient is weaned from CPB. Any degree of acidosis depresses myocardial contractility, increases pulmonary vascular resistance, and decreases the efficacy of endogenous and exogenously administered catecholamine medications.

Bilateral lung expansion is visually confirmed by carrying out multiple recruitment maneuvers before continuing regular mechanical ventilation at a fraction of inspired oxygen (FiO₂) of 100%. Care must be taken to avoid overdistention of the lungs, especially for patients in whom internal mammary arteries have been used in coronary artery bypass grafting (CABG). 

Abnormal concentrations of potassium and calcium are the most common electrolyte derangements encountered during cardiac surgery and CPB.  Hyperkalemia typically occurs from the use of cardioplegic solutions but usually resolves on its own. Because hyperkalemia does result in atrioventricular block, it should be addressed before the cessation of CPB.

Air will always be present in the left-side cardiac chambers when they are opened during a procedure. It may also accumulate in the ventricles or the aortic root during surgery. Upon reestablishment of ventilation, pulmonary blood flow can carry air bubbles trapped in the pulmonary veins into the left cardiac chambers. Left-side air may embolize to the coronary or cerebral arteries after removal of the aortic cross-clamp. Coronary embolization causes ischemia, arrhythmias, and ventricular dysfunction; cerebral embolization can potentiate neurologic dysfunction. 

Cannulas placed to decompress the left heart or anterograde cardioplegia catheters placed in the aortic root can act as vents for removal of air before the cessation of CPB. The surgeon may massage the heart while the patient is in the Trendelenburg position to assist in deairing while simultaneously reducing the risk of cerebral embolization. Increased inotropic support of the heart may be required to facilitate the deairing process, especially if air emboli are suspected of causing ventricular dysfunction.

A perfusing rhythm is required before the transition from CPB. Intrinsic conduction may spontaneously return with rewarming, or it may first require direct defibrillation. Normal sinus rhythm is ideal in all patients, especially those with significantly impaired ventricular compliance. Atrial kick can supply as much as 40% of cardiac output in stiff post-CPB ventricles with baseline diastolic dysfunction.

If the underlying rhythm is inadequate, epicardial pacing wires can be placed by the surgeon to achieve pacing. Atrioventricular blockade may be present or may become a concern later, so that atrial and ventricular wires would be needed to attain synchronized atrioventricular pacing.

Decreased systemic vascular resistance (SVR) is common after CPB and often necessitates the use of exogenous vasoconstrictors. This is a concern when hypotension is observed alongside normal or increased cardiac output and pump flow rate. Patients who are taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) can be especially prone to low SVR while undergoing cardiac surgery with CPB.

If administration of increasing doses of standard catecholamine medications with alpha antagonism is ineffective, a vasopressin infusion may be added to achieve adequate SVR. Methylene blue has also been used in patients with catecholamine-refractory vasoplegia on the basis of its ability to inhibit NO production through guanylate cyclase inhibition; some studies have shown it to decrease mortality in these patients. ^{[6, 7]}

CPB gives rise to myocardial injury and dysfunction that are superimposed onto any preexisting chronic myocardial dysfunction. Myocardial protection strategies center on the use of hypothermia and potassium for cardioplegia-induced cardiac arrest. Ischemia-reperfusion injury is, unfortunately, unavoidable and exacerbates CPB-induced ventricular dysfunction during the weaning process. 

Simple visual observation of cardiac function, correlated with findings from transesophageal echocardiography (TEE), can often provide enough information to allow prediction of the ease or difficulty of terminating CPB in a given patient. Rate and rhythm are assessed through visualization and electrocardiography (ECG). Preload and contractility are also assessed and optimized in preparation for transitioning off CPB.  Regional myocardial wall-motion abnormalities can give clues to supply-demand imbalances in coronary blood flow or can indicate technical problems with surgical repairs (see below).

Preoperative left ventricular (LV) dysfunction and a history of a previous myocardial infarction (MI) are independent risk factors for complex separation from CPB. ^[3]  Pre-CPB right ventricular (RV) dysfunction is also associated with increased morbidity (prolonged mechanical ventilation, longer ICU stay, and increased duration of hospitalization), as well as with increased early and late mortality in patients with severe LV dysfunction who undergo CABG. ^{[8, 9]}

Diastolic dysfunction of both the RV (RVDD) and the LV (LVDD) is increasingly being appreciated as an independent predictor of difficulty in separating from CPB. Bernard et al found that patients with LVDD had a fourfold increase in the need for inotropic or vasoactive drugs to separate from CPB. ^[10]  Denault et al found that moderate-to-severe LVDD and RVDD were associated with a lower cardiac index and an increased risk of DSB. ^[8]

Phosphodiesterase inhibitors improve diastolic function through several mechanisms and are classified as lusitropic agents, they can be a beneficial therapeutic option in patients with known diastolic dysfunction. ^[11]

Technical problems with repairs can occur during the transition off CPB, after chest closure, or even when the patient is transported to the ICU. TEE is a valuable tool for assessing surgical repairs. Valve repairs and replacements are interrogated for stenosis, residual regurgitation, or paravalvular leaks. The patency of coronary bypass grafts is evaluated by assessing gross ventricular systolic function and regional wall-motion abnormalities.

The use of TEE by the anesthesiologist is an integral adjunct to cardiac procedures requiring CPB. It is essential during the transition on and off CPB and can be paramount in the evaluation and diagnosis of problems during these periods of a cardiac procedure.

An obese 57-year-old man with hypertension, hyperlipidemia, type 2 diabetes mellitus, and coronary artery disease (CAD) with mild biventricular systolic dysfunction is undergoing CABG involving placement of the left internal mammary artery (LIMA) to the left anterior descending artery (LAD), a saphenous vein graft (SVG) to the circumflex artery, and an SVG to the right coronary artery. Moderate collateralization is seen on coronary angiography after stress echocardiography identifies inducible regional wall-motion abnormalities. The operative course before and during CPB is uneventful, with average CPB and aortic cross-clamp times.

After the achievement of normothermia and normal sinus rhythm by gradual occlusion of the venous cannula, the weaning process is initiated. The patient’s biventricular systolic function is much poorer than expected. Calcium chloride is given intravenously (IV), and a low-dose epinephrine infusion is initiated.

A second attempt is made to transition off CPB but is also unsuccessful, with persistent biventricular dysfunction and worsened ventricular distention. ST-segment elevation is noted in lead II with a subsequent elevation in pulmonary arterial pressures, raising a strong suspicion of coronary vasospasm associated with CPB.

The differential diagnosis in this scenario includes ischemia-reperfusion injury and inadequate cardioprotective maneuvers, acute myocardial thrombosis, mechanical occlusion of bypass grafts, coronary vasospasm, and coronary air embolism.

An IV infusion of nitroglycerin was begun while the surgeon inspected the three bypass grafts for kinking or occlusion. The ST changes improved with the administration of nitroglycerin, and no surgical graft occlusion was found; however, the LV systolic dysfunction was still concerning with regard to successful transition from CPB.

A phenylephrine infusion was then added to increase the coronary perfusion pressure, and the surgeon applied papaverine-soaked gauze to the bypass grafts while waiting for an IABP to be brought to the OR. The higher coronary perfusion pressure and the application of papaverine allowed  successful discontinuance of CPB, confirming the presence of severe coronary vasospasm. The IABP was subsequently placed as an additional aid for coronary perfusion and LV augmentation.

A 32-year-old man with Marfan syndrome is undergoing a valve-sparing aortic root replacement (Tirone David procedure) to treat the progression of his aortic root aneurysm. Because he has yet to develop severe aortic insufficiency affecting the LV, the procedure is scheduled while he still maintains normal LV size and systolic function.

The operative course before and during CPB is uneventful. Cold-blood cardioplegia is used, initially retrograde via a coronary sinus catheter and then directly anterograde into the coronary vessels after the aortotomy. Replacement is accomplished by using a composite vein graft with reimplantation of the coronary arteries with coronary buttons into the graft. One external defibrillation is needed to achieve sinus rhythm, and biventricular function appears normal while the heart is filled to assess for the presence of air in the LV and aortic root. The patient is taken out of the Trendelenburg position in preparation for transition off CPB.

As the CPB flow is decreased and the venous return cannula flow is incrementally restricted, the patient becomes increasingly hypotensive. The anesthesiologist reports mild LV systolic dysfunction with marked RV dilation and systolic dysfunction. The surgeon also notes RV dilation and decreased free wall motion on visual inspection. As the perfusionist initiates a return to full CPB, the anesthesiologist informs the team that there are new ST-segment changes on the ECG, notably ST-segment elevation in the inferior leads.

The differential diagnosis in this scenario includes occlusion of the reimplanted coronary buttons or coronary dissection from complications with surgical repair, coronary vasospasm, acute coronary thrombosis, and coronary air or particulate embolism.

With the patient back on full CPB, Doppler assessment of the coronary buttons and proximal coronary arteries was carried out; the findings made acute dissection or thrombosis unlikely. Further evaluation by the anesthesiologist with TEE guidance revealed the presence of significant LV and aortic root air, which made coronary air embolism the most likely cause of the biventricular dysfunction. The right coronary artery is often the most susceptible to air emboli in that air rises to its anterior aortic ostium in a supine patient.

To minimize further air entrainment into the coronary ostia, the patient was put back into the Trendelenburg position. Maneuvers to enhance ejection of intracardiac air focus on increasing cardiac inotropy, which in this case was accomplished by administering calcium chloride and small intermittent boluses of epinephrine. Manipulation of the LV by the surgeon also aided in directing intracardiac air into the ascending aorta. Distal systemic embolization was minimized by keeping the LV and aortic root vent on high suction to allow the intracardiac air to be directed to the venous reservoir of the CPB machine.

After 10 minutes of vigorous deairing, biventricular function slowly improved, and the ST-segment abnormalities resolved. The second attempt at weaning from CPB was successful, with minimal need for exogenous inotropic support. The Tirone David procedure was then completed without further complications.

A 63-year-old woman with New York Heart Association (NYHA) class IV heart failure from nonischemic cardiomyopathy (NICM) is admitted to the cardiac critical care unit for IV inotropic support after maximal medical therapy fails to manage her condition. She is deemed by the mechanical circulatory support and transplant teams to be an ideal candidate for LV assist device (LVAD) implantation as a bridge to transplant.

Preoperative transthorascic echocardiography (TTE) shows severe LV dilation and dysfunction with an ejection fraction (EF) of 20%. The RV is mildly enlarged and exhibits a mild-to-moderate reduction in systolic function. Mild-to-moderate tricuspid regurgitation, moderate mitral regurgitation, and mild aortic insufficiency are noted in the report. Additional pertinent findings include the presence of mild pulmonary hypertension on the basis of the tricuspid regurgitant jet and the absence of a patent foramen ovale on the bubble study.

The preoperative milrinone infusion is continued on induction and through the pre-CPB period, with the addition of a low-dose epinephrine infusion. After implantation of the LVAD’s inflow cannula and outflow graft, echocardiography confirms satisfactory placement of the inflow cannula in the LV. Epicardial pacing wires are placed for atrioventricular pacing, and inotrope doses are moderately increased in anticipation of the subsequent need during weaning from CPB. Appropriate deairing is achieved in the aorta and LV with needle vents, and the LVAD is then started at the appropriate initial speed.

Upon partial occlusion of the venous line, the interventricular septum is observed to be shifted to the left, with a distended RV and a nearly empty LV. Electrolyte balance and acid-base status are further optimized while inotrope doses are incrementally increased. Despite these therapeutic changes, RV function is severely decreased with volume loading, signifying RHF.

Despite improvements in LVAD design, RHF still occurs in 9-40% of LVAD recipients. ^[12]  RHF is also associated with a high (>70%) in-hospital mortality. ^[13]

In this scenario, inhaled epoprostenol was added to reduce pulmonary vascular resistance, and an IABP was placed to augment RV coronary perfusion pressure. These therapeutic additions were sufficient to provide adequate RV systolic function, allowing LVAD speed to be increased slowly and the patient to be weaned from CPB, with the interventricular septum midline on TEE. Placement of a temporary RV assist device (RVAD) would have been another choice for allowing transition off CPB.

Nguyen L, Roth DM, Shanewise JS, Kaplan JA. Discontinuing cardiopulmonary bypass. Kaplan JA, Agoustides JGT, Manecke Jr GR, Maus T, Reich DL, eds. Kaplan’s Cardiac Anesthesia: In Cardiac and Noncardiac Surgery. 7th ed. Philadelphia: Elsevier; 2017. 1291-312.

Fitzsimons MG. Weaning from cardiopulmonary bypass (CPB). UpToDate. Available at https://www.uptodate.com/contents/weaning-from-cardiopulmonary-bypass-cpb?source=search_result&search=cardiopulmonary%20bypass&selectedTitle=2~150. November 29, 2016; Accessed: February 20, 2017.

Denault AY, Tardif JC, Mazer CD, Lambert J, BART Investigators. Difficult and complex separation from cardiopulmonary bypass in high-risk cardiac surgical patients: a multicenter study. J Cardiothorac Vasc Anesth. 2012 Aug. 26 (4):608-16. [Medline].

Loor G, Rajeswaran J, Li L, Sabik JF 3rd, Blackstone EH, McCrae KR, et al. The least of 3 evils: exposure to red blood cell transfusion, anemia, or both?. J Thorac Cardiovasc Surg. 2013 Dec. 146 (6):1480-1487.e6. [Medline].

Hovaguimian F, Myles PS. Restrictive versus Liberal Transfusion Strategy in the Perioperative and Acute Care Settings: A Context-specific Systematic Review and Meta-analysis of Randomized Controlled Trials. Anesthesiology. 2016 Jul. 125 (1):46-61. [Medline].

Leyh RG, Kofidis T, Strüber M, Fischer S, Knobloch K, Wachsmann B, et al. Methylene blue: the drug of choice for catecholamine-refractory vasoplegia after cardiopulmonary bypass?. J Thorac Cardiovasc Surg. 2003 Jun. 125 (6):1426-31. [Medline].

Evora PR, Levin RL. Methylene blue as drug of choice for catecholamine-refractory vasoplegia after cardiopulmonary bypass. J Thorac Cardiovasc Surg. 2004 Mar. 127 (3):895-6; author reply 896. [Medline].

Denault AY, Couture P, Buithieu J, Haddad F, Carrier M, Babin D, et al. Left and right ventricular diastolic dysfunction as predictors of difficult separation from cardiopulmonary bypass. Can J Anaesth. 2006 Oct. 53 (10):1020-9. [Medline].

Maslow AD, Regan MM, Panzica P, Heindel S, Mashikian J, Comunale ME. Precardiopulmonary bypass right ventricular function is associated with poor outcome after coronary artery bypass grafting in patients with severe left ventricular systolic dysfunction. Anesth Analg. 2002 Dec. 95 (6):1507-18, table of contents. [Medline].

Bernard F, Denault A, Babin D, Goyer C, Couture P, Couturier A, et al. Diastolic dysfunction is predictive of difficult weaning from cardiopulmonary bypass. Anesth Analg. 2001 Feb. 92 (2):291-8. [Medline].

Hardy JF, Belisle S. Inotropic support of the heart that fails to successfully wean from cardiopulmonary bypass: the Montreal Heart Institute experience. J Cardiothorac Vasc Anesth. 1993 Aug. 7 (4 Suppl 2):33-9. [Medline].

Fida N, Loebe M, Estep JD, Guha A. Predictors and management of right heart failure after left ventricular assist device implantation. Methodist Debakey Cardiovasc J. 2015 Jan-Mar. 11 (1):18-23. [Medline].

Haddad F, Couture P, Tousignant C, Denault AY. The right ventricle in cardiac surgery, a perioperative perspective: II. Pathophysiology, clinical importance, and management. Anesth Analg. 2009 Feb. 108 (2):422-33. [Medline].

Jacob Ryan Pletcher, MD Cardiothoracic Anesthesiologist and Intensivist

Jacob Ryan Pletcher, MD is a member of the following medical societies: American Society of Anesthesiologists, California Society of Anesthesiologists, Society of Critical Care Anesthesiologists

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Sheela Pai Cole, MD Clinical Associate Professor of Cardiothoracic Anesthesiology and Critical Care Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine

Sheela Pai Cole, MD is a member of the following medical societies: American Medical Association, American Society of Anesthesiologists, American Society of Echocardiography, California Society of Anesthesiologists, International Anesthesia Research Society, Pennsylvania Society of Anesthesiologists, Society of Cardiovascular Anesthesiologists, Society of Critical Care Anesthesiologists, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Failure to Separate From Cardiopulmonary Bypass 

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