O2 delivery and CO2 production during cardiopulmonary bypass as determinants of acute kidney injury: time for a goal-directed perfusion management?

INTRODUCTION: Acute kidney injury (AKI) is common after cardiac operations. There are different risk factors or determinants of AKI, and some are related to cardiopulmonary bypass (CPB). In this study, we explored the association between metabolic parameters (oxygen delivery (DO2) and carbon dioxide production (VCO2)) during CPB with postoperative AKI. METHODS: We conducted a retrospective analysis of prospectively collected data at two different institutions. The study population included 359 adult patients. The DO2 and VCO2 levels of each patient were monitored during CPB. Outcome variables were related to kidney function (peak postoperative serum creatinine increase and AKI stage 1 or 2). The experimental hypothesis was that nadir DO2 values and nadir DO2/VCO2 ratios during CPB would be independent predictors of AKI. Multivariable logistic regression models were built to detect the independent predictors of AKI and any kind of kidney function damage. RESULTS: A nadir DO2 level < 262 mL/minute/m2 and a nadir DO2/VCO2 ratio < 5.3 were independently associated with AKI within a model including EuroSCORE and CPB duration. Patients with nadir DO2 levels and nadir DO2/VCO2 ratios below the identified cutoff values during CPB had a significantly higher rate of AKI stage 2 (odds ratios 3.1 and 2.9, respectively). The negative predictive power of both variables exceeded 90%. The most accurate predictor of AKI stage 2 postoperative status was the nadir DO2 level. CONCLUSIONS: The nadir DO2 level during CPB is independently associated with postoperative AKI. The measurement of VCO2-related variables does not add accuracy to the AKI prediction. Since DO2 during CPB is a modifiable factor (through pump flow adjustments), this study generates the hypothesis that goal-directed perfusion management aimed at maintaining the DO2 level above the identified critical value might limit the incidence of postoperative AKI.

Sulforaphane pretreatment prevents systemic inflammation and renal injury in response to cardiopulmonary bypass.

OBJECTIVES: Systemic inflammatory responses are a major cause of morbidity and mortality in patients undergoing cardiac surgery with cardiopulmonary bypass. However, the underlying molecular mechanisms for systemic inflammation in response to cardiopulmonary bypass are poorly understood. METHODS: A porcine model was established to study the signaling pathways that promote systemic inflammation in response to cardiac surgery with cardiopulmonary bypass under well-controlled experimental conditions. The influence of sulforaphane, an anti-inflammatory compound derived from green vegetables, on inflammation and injury in response to cardiopulmonary bypass was also studied. Intracellular staining and flow cytometry were performed to measure phosphorylation of p38 mitogen-activated protein kinase and the transcription factor nuclear factor-κB in granulocytes and mononuclear cells. RESULTS: Surgery with cardiopulmonary bypass for 1 to 2 hours enhanced phosphorylation of p38 (2.5-fold) and nuclear factor-κB (1.6-fold) in circulating mononuclear cells. Cardiopulmonary bypass also modified granulocytes by activating nuclear factor-κB (1.6-fold), whereas p38 was not altered. Histologic analyses revealed that cardiopulmonary bypass promoted acute tubular necrosis. Pretreatment of animals with sulforaphane reduced p38 (90% reduction) and nuclear factor-κB (50% reduction) phosphorylation in leukocytes and protected kidneys from injury. CONCLUSIONS: Systemic inflammatory responses after cardiopulmonary bypass were associated with activation of p38 and nuclear factor-κB pathways in circulating leukocytes. Inflammatory responses to cardiopulmonary bypass can be reduced by sulforaphane, which reduced leukocyte activation and protected against renal injury.

Feasibility and safety of minimized cardiopulmonary bypass in major aortic surgery.

OBJECTIVES: Conventional cardiopulmonary bypass causes haemodilution and is a trigger of systemic inflammatory reactions, coagulopathy and organ failure. Miniaturized cardiopulmonary bypass has been proposed as a way to reduce these deleterious effects of conventional cardiopulmonary bypass and to promote a more physiological state. The use of miniaturized cardiopulmonary bypass has been reported in low-risk patients undergoing valve and coronary artery bypass graft (CABG) surgery. However, little is known about its application in major aortic surgery. METHODS: From February 2007 to September 2010, 49 patients underwent major aortic surgery using the Hammersmith miniaturized cardiopulmonary bypass (ECCO, Sorin). Data were extracted from medical records to characterize preoperative comorbidities (EuroSCORE), perioperative complications and the use of blood products. The same data were collected and described for 328 consecutive patients having similar surgery with conventional cardiopulmonary bypass at the Bristol Heart Institute, our twinned centre, during the same period. RESULTS: The miniaturized cardiopulmonary bypass group had a median EuroSCORE of 8 [inter-quartile range (IQR): 5-11], 13% had preoperative renal dysfunction and 20% of operations were classified as emergency or salvage. Thirty-day mortalities were 6.4; and 69, 67 and 74% had ≥ 1 unit of red cells, fresh frozen plasma (FFP) and platelets transfused, respectively. Eight percent of patients experienced a renal complication, and 8% a neurological complication. The conventional cardiopulmonary bypass group was similar, with a EuroSCORE of 8 (IQR: 6-10); 30-day mortalities were 9.4; and 68, 62 and 74% had ≥ 1 unit of red cells, FFP and platelets transfused, respectively. The proportions experiencing renal and neurological complications were 14 and 5%. CONCLUSIONS: Our experience suggests that miniaturized cardiopulmonary bypass is safe and feasible for use in major aortic cardiac surgery. A randomized trial is needed to evaluate miniaturized cardiopulmonary bypass formally.

Aortic surgery using total miniaturized cardiopulmonary bypass.

PURPOSE: Few centers have attempted aortic surgery using miniaturized cardiopulmonary bypass (MCPB) systems due to concerns of air handling. The extra corporeal circuit optimized (ECCO) total MCPB system uses a venous air removal device and a parallel soft-shell reservoir that allows for venting of the heart. At our institution, total MCPB is used for all coronary artery bypass graft patients. Our objective was to assess the suitability of the ECCO total MCPB system during aortic surgery. DESCRIPTION: Fifty consecutive and unselected aortic procedures using the ECCO system were undertaken. Surgical feasibility, air removal ability, and blood transfusion requirements were audited to determine the efficacy of this technique. EVALUATION: The bypass time was 81.6 +/- 28.0 minutes and the ischemic time was 56.7 +/- 18.9 minutes. Total MCPB handled 1,910 +/- 404 mL of vented blood with 96 venous air removal device activations noted. The blood product transfusion rate was 12%, which was below the surgical transfusion rate for our unit. There were no complications. CONCLUSIONS: Aortic surgery can be undertaken safely and effectively using the ECCO total MCPB system.