Weaning a patient off cardiopulmonary  bypass (CPB) is an important step of cardiac surgical procedures.  Emergence from CPB is a time for planned action and cooperation among  the cardiac operating team. Returning heart and lungs to the circulation  after CPB may represent a potential stress to the heart.
Most techniques, conduction and management of CPB are well standardized; however, separating patients from perfusion occasionally involves decisions based on empirical therapies. Weaning off CPB is a straightforward process that requires no particular measures other than reestablishing ventilation to the lungs and slowly turning the arterial pump off. In a number of cases however, weaning may be specially difficult, and in a few situations simply impossible.
Most techniques, conduction and management of CPB are well standardized; however, separating patients from perfusion occasionally involves decisions based on empirical therapies. Weaning off CPB is a straightforward process that requires no particular measures other than reestablishing ventilation to the lungs and slowly turning the arterial pump off. In a number of cases however, weaning may be specially difficult, and in a few situations simply impossible.
 Separation of CPB may require special  protocols, in accordance to the status of the patients, to their  particular age group and the conduction of bypass. Weaning off small  children after prolonged, difficult and complex operations may represent  a challenge to the surgical team.
 Weaning off CPB is always conducted in a  coordinate fashion. The surgeon directs the weaning process with some  input from anesthesia and perfusion. A skillful anesthesiologist usually  shares the control of weaning with the surgeon. This allows the surgeon  to direct full attention to the grafts position, valve function,  security of suture lines and final gross hemostasis. When this  arrangement fails or there is no free communication in the team, it is  not unusual while separating a patient from bypass to observe a  perfusionist retaining more volume into a hypotensive patient while the  anesthesiologist administers a vasopressor, both ignoring the surgeon's  observation that the heart is distending.
 Inadequate weaning and separation from CPB  can prolong recovery and increase morbidity and mortality. 
PREPARING FOR WEANING
  CPB is associated with various insults to  normal physiology. These include anticoagulation, hemodilution,  hypothermia, ischemic or chemical cardiac arrest, increased release of  endogenous cathecolamine, vasopressin and other vasoactive substances,  electrolyte disturbances, platelet activation, aggregation and  destruction, and activation of complement and other plasma protein  systems. These multiple interacting factors represent a number of  potential routes for myocardial dysfunction or injury [1]. 
 Weaning process is initiated after  adjustment of certain patient variables, such as temperature, tissue  oxygenation, hematocrit level, acid-base and electrolytes status, and  cardiac function. Requirements of analgesic, narcotic and paralyzing  drugs usually increase during rewarming and the necessary adjustments  are made with avoidance of myocardial and circulatory depressant agents  [2].
Weaning process is initiated after  adjustment of certain patient variables, such as temperature, tissue  oxygenation, hematocrit level, acid-base and electrolytes status, and  cardiac function. Requirements of analgesic, narcotic and paralyzing  drugs usually increase during rewarming and the necessary adjustments  are made with avoidance of myocardial and circulatory depressant agents  [2]. While most steps of weaning are standard  and common to all cases, evaluation of cardiac function may disclose  situations which will require specific measures such as the use of  temporary pacemaker, inotropic or vasoactive drugs or mechanical  support.
Temperature
 Cardiopulmonary bypass is systematically  accompanied by heat loss to the environment, even when hypothermia is  not employed. Preparation for terminating CPB includes rewarming of  patients to the normal or near normal temperature. Rewarming should be  initiated as early as necessary so that its completion coincides with  completion of the surgical procedure or soon afterwards. Patient  temperature is monitored in at least two sites such as nasopharingeal,  tympanic, esophageal, rectal or bladder. The most common combination is  nasopharingeal and rectal temperatures. 
 As nasopharingeal temperature reaches 36.5  to 370C, rectal temperature is usually two to three degrees  lower. A larger than four degrees gradient between the nasopharingeal  and rectal temperatures is indicative of inadequate rewarming or  increased vasoconstriction. In these situations there may occur a two to  three degrees decrease in nasopharingeal  temperature during sternal  closure and transfer to intensive care unit, which may predispose the  patients to unstable cardiac rhythm, shivering, and hypertension [3,4].  This afterdrop results from redistribution of heat within the body as  the normal pulsatile blood flow opens up some relatively colder and  constricted vascular beds [1,2]. 
 A slow infusion of vasodilators (sodium  nitroprusside) may provide a more homogenous rewarming and reduce the  occurrence of significant temperature gradients. Pulsatile flow may  promote the same results [5].  Warming blankets will not always be effective to correct the temperature  drift, due to the increased peripheral constriction; small children may  better benefit from warming blankets and ventilation with heated and  humidified gases. 
 Hohn et cols [6] investigated 86 patients  to draw the influence of warming the skin during weaning. Patients  warmed through a water blanket and a blow of warm air to the head, in  addition to the heat exchanger, had a better thermal balance and a lower  blood loss, when compared to a control group.
Tissue oxygenation
  Metabolic abnormalities are corrected  before initiating the weaning process. Venous line carries true mixed  venous blood, and venous oxygen saturation and PO2 are satisfactory  indicators of tissue metabolism. Arterial PO2 and saturation  best  reflect the oxygenator performance.
 Increased lactate production, decreased  pH, and decreased mixed venous saturation and PO2 are indicators of  inadequate tissue perfusion or oxygenation. A venous oxygen saturation  of 75% and a minimum venous PO2 of 35mmHg are satisfactory to start  weaning from CPB.
Hematocrit
  Hemodilution is universally accepted as an  important adjunct to cardiopulmonary bypass. Blood viscosity and  oncotic pressure are reduced while tissue perfusion and oxygenation and  cerebral flow are enhanced by the levels of hemodilution commonly used  in clinical settings. Hematocrit values from 20 to 25% are usual with  most perfusion protocols. By the end of rewarming, depending on renal  function and the use of diuretics hematocrit may reach 24 to 30%. 
 Hearts with severe preoperative myocardial  dysfunction will perform better immediately after termination of CPB  with a hematocrit level above 34%. Red cells transfusion during  rewarming may be necessary to adjust the hematocrit prior to  discontinuing perfusion [7]. Under special circumstances or while  perfusing small babies, a very low hematocrit can be corrected by   transoperative ultrafiltration.   
Acid base status
  Regardless of the lowest temperature  attained or the acid-base management protocol used (alpha or pH stat)  during CPB, by the end of rewarming a pH of 7.4 and a PCO2 higher than  35 mmHg are mandatory to safely disconnect a patient from the pump. 
 Any degree of acidosis should promptly be  corrected because it depresses myocardial contraction, diminishes the  action of inotropes, and increases pulmonary vascular resistance.
Electrolytes
Potassium is the critical ion that may present acute changes during CPB, followed by calcium. Others ions rarely show significant changes and their correction is less demanding for the weaning to take place.
 Hyperkalemia may result in  atrioventricular block. Blood cardioplegia usually produces a higher  potassium level at the end of perfusion. In the presence of a normal  renal function, a mild hyperkalemia represented by a serum level of  6  mEq/L or less, will not require special treatment and resolve  spontaneously. In the presence of a heart block or bradicardia, a more  regular rhythm should be secured with temporary pacemaker wires. The  hyperkalemia should be treated with insulin, glucose and furosemide  [2,3].
 Hypokalemia may predispose to atrial and  ventricular arrhythmias, and shall be treated. During CPB it is  preferable to administer potassium chloride in small frequent doses  instead of continuous infusion. Doses of 5 mEq may be repeated after  proper evaluation of serum levels. 
 Ionized calcium levels usually decrease  during CPB and appears to recover fast thereafter. Administration of  calcium chloride was widely employed in the past during separation from  perfusion, because of its positive inotropic effect. Elevated serum  calcium levels have been associated with increased vascular resistance  on the peripheral, coronary, renal and cerebral microcirculation [1,8].  Calcium chloride administration has been associated with coronary  arteries and mammary grafts spasms and is usually avoided in the  revascularized patient. Some concern exists as to the potential role of  an elevated serum calcium level in the aggravation of reperfusion injury  [9].  
 Valvular and pediatric patients with a  sluggish myocardial contraction frequently show some transient  improvement after a small bolus (10 to 15mg/Kg) of calcium chloride  immediately before discontinuing CPB. 
Cardiac action
  Several interacting factors of perfusion  predispose the myocardium to injury and dysfunction. A certain amount of  myocardial injury may be added after aortic unclamping, during the  reperfusion phase. The period immediately before complete separation from bypass is  critical; its duration is conditioned by myocardial recovery. Regardless  of the myocardial protection strategy and method, even short periods of  aortic cross-clamping can be followed by temporary functional  depression.
 Usually there is a mild and transient  functional impairment shortly followed by resumption of effective  cardiac action. Most hearts will benefit from a short period of  supportive CPB, usually from 15 to 20 minutes for each hour of clamping.  This is easily accomplished by properly timing surgery and rewarming  [1,3,10].
 When normal temperature is reached and  preparations for weaning are completed, maximal myocardial recovery from  the arrest period has usually been attained.
 Cardiac function immediately prior to  discontinuing perfusion is usually assessed by visual observation,  electrocardiogram, ventricular filling pressures and afterload, and  transesophageal echocardiography if available. Simple visual observation  of heart action can provide valuable information on myocardial  performance. Experienced teams can accurately predict the chances of  immediate difficulties to terminate CPB by visually inspecting the heart  action alone.
 All clinical variables involved with  cardiac performance (heart rate, preload and afterload, and  contractility) are assessed in order to optimize cardiac output.
 Cardiac rhythm and the adequacy of  ventricular rate are evaluated by the electrocardiogram. Slow  ventricular rates are adjusted by ventricular pacing; atrioventricular  dissociation is corrected by atrioventricular sequential pacing.
  Preload is evaluated by ventricular  filling pressures. Left ventricular preload is inferred from left atrial  mean pressure or pulmonary artery diastolic pressure; right atrial  pressure reflects the preload conditions of right ventricle. During  weaning preload is pump-dependent and can be adjusted by balancing blood  volume between patient and oxygenator. 
 Ventricular afterload is evaluated by the  status of peripheral vascular resistance. This is represented by the  ratio between mean systemic arterial pressure and pump flow. Elevated  peripheral resistance may require vasodilators. An occasional patient  will present in a state of deep vasodilation and hypotension even when  pump flow is adequate or elevated [11]. These will require a  vasoconstrictor infusion to restore a normal peripheral resistance.  
 Transesophageal echocardiography (TEE) is  useful to verify the adequacy of surgical repair in congenital and  valvular cases; it can also offer valuable information on ventricular  volumes and the quality of myocardial contractility [12]. 
 Ninomiya et cols [13] assessed continuous  transesophageal echocardiography monitoring during weaning from CPB in  41 children. They measured left ventricular ejection fraction, wall  motion and end-diastolic volume. In the presence of severe heart  failure, the authors could adjust drugs and mechanical support oriented  by the TEE information. Shankar et cols [14] found epicardial ultrasound  examination of paramount importance to detect less than perfect  coronary translocations after Jatene's operation. 
TERMINATION OF CPB
 After adjusting cardiac rhythm and rate,  preload and systemic arterial resistance, the assessment of cardiac  function immediately before terminating CPB allows the patients to be  classified into 3 groups. The proportion of patients on each group will  depend on case distribution. According to our retrospective experience  [15], a general surgical service dealing with the broadest spectrum of  patients, which includes elderly, reoperations, emergencies and neonates  will result in an approximate 70% of patients in group A, 25% in group B  and 5% in group C.
  Group A: Patients that will obviously offer no difficulty to disconnect from  perfusion. For these patients, after reestablishing ventilation to the  lungs, pump flow can be gradually reduced while venous return to the  oxygenator is decreased until bypass is minimal. Arterial pump is  stopped and venous line is clamped. Final adjustment of cardiac  performance is made off pump, by slowly administering residual volume  from the oxygenator until ideal preload is attained. These patients  maintain an adequate cardiac output, as can be confirmed by normal  atrial and arterial pressures, arterial and venous blood gases and pH  and adequate spontaneous diuresis.
 Most teams will administer a slow infusion  of an inotrope (dopamine or dobutamine) or, less frequently a  vasodilator, based only on "routine" protocol or "past" experience. This  infusion is usually discontinued as the patient arrives to the  intensive care area or is maintained for a few hours thereafter.
   Group B:   Patients with a mild to moderate degree of cardiac dysfunction that  will require some support to disconnect from the pump. This support may  be physiological (Starling law) or pharmacological (inotropes,  vasodilators or both). Some patients in this group can benefit from  intra-aortic balloon pumping [16,17].
 Group B patients require a more elaborated  protocol for CPB termination. Final preparations are made on partial  bypass.
 Before turning pump off all clinical  determinants of cardiac performance are evaluated and adjusted, in order  to optimize cardiac output. Blood volume is adjusted according to left  atrial or pulmonary artery pressures and inotropes are commenced.  Peripheral resistance is estimated and vasodilators or constrictors are  instituted as required. After the drugs effectiveness is assessed, pump  flow is decreased in small increments while venous return in  proportionately adjusted to maintain a constant filling pressure.  Arterial pump is stopped and venous line is clamped.  
 Most patients in group B will perform as  well as group A patients. Some patients may have to return to pump for  better adjustment of drugs, or to have an intra-aortic balloon inserted  if a marginal cardiac output is present, as demonstrated by atrial and  arterial pressures, arterial and venous blood gases and pH, and  spontaneous diuresis. 
 Children with preoperative high pulmonary  blood flow, children after a heart transplant, and some adults with long  standing congestive heart failure may present with pulmonary  hypertension that precludes successful weaning. Inhalation of nitric  oxide (NO) has been demonstrated as dramatically improving cardiac  output and allowing a smooth discontinuance of CPB [18, 19].
 Bauer et cols [20] evaluated the efficacy  of prostaglandin E1 as a poweful adjunt to wean difficult transplanted  children with right ventricular failure.
 The association of epinephrin in a slow  infusion and nitroprusside or another vasodilator drug, possibly  represents the strongest available stimulus to improve myocardial  contractility.  
 A recently introduced inotrope (enoximone)  is under evaluation to provide phrmacological support during weaning of  patients with severe ventricular dysfunction [21,22].
 An occasional patient in group B will not  tolerate CPB termination even after a few trials. These few exceptions  turn into group C patients.
   Group C: Patients with severe cardiac dysfunction that will prove difficult to be  removed from CPB, despite physiologic and pharmacological support. For  these patients CPB will have to be prolonged. A few hours of circulatory  assistance and intensive inotropic and vasodilator drugs therapy may  turn some of these patients into group B. The remaining patients are  candidates to a form of total circulatory mechanical support (if  available) or they will not likely survive disconnection from pump  [23,24,25].
 Group C patients are by definition the  hardest cases to manage. A few of these patients by the end of rewarming  will have minimal or no cardiac activity which precludes any trial of  disconnection from pump. The remaining patients may be given a short  trial off pump after optimization of preload, afterload and  contractility by a criterious combination of inotropes and vasoactive  agents. Some of these patients will tolerate CPB removal, under maximal  physiological and pharmacological support, and a few in the group may be  further improved by an intra-aortic balloon pump. The patients with  minimal cardiac activity and those in whom the trial off pump was  unsuccessful are temporarily maintained on cardiac support with the  heart-lung machine. A few hours on pump support may be a sufficient rest  period to allow recovery of cardiac function and removal of CPB support  in a small number of cases. For the others, a decision has to be made  as to either advance to a mechanical device for prolonged support or  terminate the efforts to recover cardiac action.
 Children supported by full veno-arterial  extracorporeal membrane oxygenation (ECMO) post cardiotomy, have a poor  long term survival rate [26] when compared with children managed with  centrifugal ventricular assist devices [27]. 
CONCLUSION
 Weaning and disconnecting CPB is a team  effort and requires clear planning and integrated performance. Despite  being a simple procedure, interrupting perfusion can be elaborated,  extremely difficult or virtually impossible. Resources for prolonged  supportive bypass and mechanical devices shall be made available and  their application to the difficult situations should be a part of CPB  protocols.   
SUMMARY
  Weaning off cardiopulmonary bypass is a  simple process; however, it may occasionally prove very difficult and  sometimes virtually impossible. Preparation for weaning includes the  adjustment of several patient related variables such as temperatures,  tissue oxygenation, hematocrit, pH, electrolytes, and cardiac rhythm and  rate. Cardiac action as routinely assessed will allow patients to be  classified into 3 groups. Group A includes patients which will obviously  offer no difficulties to remove from CPB. Group B comprises patients  with mild to moderate dysfunction; they will require some physiological  (Starling law) or pharmacological (inotropes, vasoactive drugs) support  to be disconnected from pump. Group C are the patients with poor or no  cardiac action, which will require either an aggressive pharmacological  support or prolonged mechanical support as alternatives to sustain  life.< p align=justify> Resources for prolonged supportive bypass and mechanical devices shall  be available and their application to difficult situations should be  part of CPB protocols. 

