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Weaning, the process of transition from cardiopulmonary bypass (CPB) to normal, physiological circulation, requires excellent communication and teamwork between perfusionist, surgeon and anesthetist. Electrolyte abnormalities should be corrected before separation from CPB in order to optimize myocyte function. Cardiac function should be assessed as far as possible prior to weaning from CPB. This assessment should concentrate on three main areas: rate, rhythm and contractility. During CPB the lungs are allowed to deflate fully or to remain slightly inflated at low levels of positive end expiratory pressure (PEEP). Effective mechanical ventilation of the lungs must be ensured prior to commencing weaning from CPB. Epicardial pacing is commonly required in the immediate and early post-CPB period. The pacing system and pacing and sensing thresholds should be tested prior to weaning. Establishment of an appropriate mode of epicardial pacing is specifically intended to improve cardiac performance.