Individualized, perioperative, hemodynamic goal-directed therapy in major abdominal surgery (iPEGASUS trial): study protocol for a randomized controlled trial.

BACKGROUND: Postoperative morbidity and mortality in patients undergoing surgery is high, especially in patients who are at risk of complications and undergoing major surgery. We hypothesize that perioperative, algorithm-driven, hemodynamic therapy based on individualized fluid status and cardiac output optimization is able to reduce mortality and postoperative moderate and severe complications as a major determinant of the patients' postoperative quality of life, as well as health care costs. METHODS/DESIGN: This is a multi-center, international, prospective, randomized trial in 380 patients undergoing major abdominal surgery including visceral, urological, and gynecological operations. Eligible patients will be randomly allocated to two treatment arms within the participating centers. Patients of the intervention group will be treated perioperatively following a specific hemodynamic therapy algorithm based on pulse-pressure variation (PPV) and individualized optimization of cardiac output assessed by pulse-contour analysis (ProAQT© device; Pulsion Medical Systems, Feldkirchen, Germany). Patients in the control group will be treated according to standard local care based on established basic hemodynamic treatment. The primary endpoint is a composite comprising the occurrence of moderate or severe postoperative complications or death within 28 days post surgery. Secondary endpoints are: (1) the number of moderate and severe postoperative complications in total, per patient and for each individual complication; (2) the occurrence of at least one of these complications on days 1, 3, 5, 7, and 28 in total and for every complication; (3) the days alive and free of mechanical ventilation, vasopressor therapy and renal replacement therapy, length of intensive care unit, and hospital stay at day 7 and day 28; and (4) mortality and quality of life, assessed by the EQ-5D-5L™ questionnaire, after 6 months. DISCUSSION: This is a large, international randomized controlled study evaluating the effect of perioperative, individualized, algorithm-driven ,hemodynamic optimization on postoperative morbidity and mortality. TRIAL REGISTRATION: Trial registration: NCT03021525 . Registered on 12 January 2017.

Positive end-expiratory pressure does not compromise myocardial contractility in myocardial ischemia/reperfusion.

Therapy for severe myocardial ischemia/reperfusion sometimes necessitates intermittent positive pressure ventilation, which may impair left ventricular function by reduction of ventricular loading. It is unknown today whether positive airway pressure also affects contractile force after myocardial ischemia/reperfusion. The authors tested whether positive end-expiratory pressure (PEEP) impairs myocardial contractility in acute ischemic heart failure. In 11 anesthetized mechanically ventilated pigs (28 +/- 3 kg), cardiac output (CO, aortic flow probe), load-independent parameters of left ventricular contractility (conductance method: preload recruitable stroke work [PRSW] and end-systolic elastance [E(es)]) and preload (end-diastolic volume [EDV] conductance) were assessed before and after myocardial ischemia and reperfusion (left anterior descending artery occlusion, 60 min). Data were taken during PEEP 0, 5, and 10 cm H2O. Before myocardial ischemia, both PEEP 5 and 10 cm H2O reduced CO (P < 0.05) because of a reduction of EDV (P < 0.05, PEEP 10 cm H2O). The PRSW remained unchanged (not significant [NS]) and E(es) increased (P < 0.05, PEEP 10 cm H2O). After myocardial ischemia/reperfusion, CO and PRSW, but not E(es) (NS), deteriorated markedly. At the same time, PEEP 10 cm H2O reduced CO (P < 0.05) and, slightly, EDV (NS). Now, both PRSW (P < 0.05, PEEP 5 cm H2O) and E(es) (P < 0.05, PEEP 10 cm H2O) improved upon ventilation with PEEP. In our model, the administration of PEEP impaired global left ventricular function before and after myocardial ischemia/reperfusion. The observed impairment is not attributable to compromised contractility.