Renal perfusion, function and oxygenation after major surgery and in septic shock

Abstract

Acute kidney injury (AKI) is a common and dreaded complication to severe illness and major surgery, with major impact on mor- bidity and mortality. The aim of this doctoral thesis was to increase the knowledge on renal pathophysiology and to explore potential interventions for treatment and prevention of AKI after cardiac surgery, liver transplantation and in early clinical septic shock. Patients and methods: Patients were studied in the intensive care unit (ICU) immediately after surgery, and in septic shock patients within 24 hours from admission to ICU. We studied the renal effects of a crystalloid (Ringers-acetate®) and a col- loid (Venofundin®) fluid as plasma volume expanders after uncomplicated cardiac surgery (paper I, n=30), renal pathophysiology and the renal effects of target mean arterial pressure (tMAP) after liver trans- plantation (paper II n=12, and II, respec- tively, n=10), and renal pathophysiology in early clinical septic shock (paper IV, n=8). Renal blood flow (RBF) and glomerular fil- tration rate (GFR) were measured by renal vein thermodilution and renal extraction of 51Cr-EDTA, respectively. In paper IV, RBF was measured by infusion clearance for para-aminohippurate (PAH). Results: RBF is increased by both crystalloid and colloid fluid when used as plasma volume expander after cardiac surgery, but due to hemodilution, neither of the fluids increases renal oxygen delivery (RDO2). The crystalloid-induced increase in GFR is associated with impaired renal oxygenation, which is not seen with the colloid. After liver transplantation, vasodilation of the efferent arterioles causes a renal vasodilation and a fall in GFR. Renal oxygen consumption (RVO2) is considerably in- creased early after liver transplantation, despite the lower GFR. The increased RBF seen after liver transplantation is not sufficient to meet the increased RVO2, result- ing in an impaired renal oxygenation. Early after liver transplantation, a tMAP of 75 mmHg, compared to 60 mmHg, improves RBF and GFR without impairing renal oxygenation. In early clinical septic shock, there is a fall in GFR and RDO2 caused by a constriction of renal afferent arterioles, ac- companied by a sodium reabsorption at a high oxygen cost, which together with the reduced RDO2 impairs renal oxygenation, causing renal tubular injury. Conclusions: Treatment of hypovolemia with a bolus dose of crystalloid fluid impairs renal oxygenation after uncomplicated cardiac surgery. In liver transplant recipients, renal function is severely reduced and renal oxygenation is impaired due to a high RVO2 not matched by a proportional increase in RDO2. In liver recipients, RBF and GFR are pressure-dependent due to the loss of renal autoregulation at a MAP < 75 mmHg. In early clinical septic shock, GFR and RDO2 are reduced because of renal vasoconstriction, causing impaired renal oxygenation and a tubular injury.