Cardiopulmonary bypass and the kidney - studies on patients undergoing cardiac surgery
Acute kidney injury is a common complication after cardiac surgery with cardiopulmonary bypass (CPB), and has a major impact on morbidity, mortality and costs. The mechanism of CPB-related renal impairment is not fully understood. The aim of this thesis was to describe how CPB affects the kidneys, and whether increased CPB flow might improve renal oxygenation. In addition, we compared the systemic and renal effects of two inotropes in patients with impaired cardiac and renal function. Methods: In patients undergoing cardiac surgery we used urine measurement of N-acetyl-ß-D-glucosaminidase (NAG) to assess tubular cell injury (n=61). Renal vein catheterization was used to study renal blood flow, oxygenation, and filtration during normothermic CPB at 2.5 L/min/m2 (n=18), and at different CPB flow levels (2.4, 2.7 and 3.0 L/min/m2) applied in a randomized order (n=17). In 32 patients with cardiac and renal impairment, pulmonary artery and renal vein catheters were used to study the differential effects of levosimendan and dobutamine in a randomized blinded trial. Results: NAG was elevated already after 30 minutes of CPB, and increased to a six-fold peak early after discontinuation of CPB. In a multivariate analysis, the duration of CPB and the degree of rewarming were independent predictors of peak NAG excretion. Renal oxygenation was impaired during CPB, mainly through reduced oxygen delivery due to hemodilution and renal vasoconstriction. After CPB, renal oxygenation was further impaired due to increased oxygen consumption and inefficient sodium transport. At higher than normal CPB flow rates, renal oxygen extraction was reduced by 12–23 % at an unchanged filtration fraction, indicating that renal oxygenation was improved. In contrast to dobutamine, levosimendan did not only increase cardiac output and renal blood flow, but also increased the glomerular filtration rate by 22%. Conclusions: Cardiopulmonary bypass impairs renal oxygenation due to renal vasoconstriction and hemodilution during and after cardiopulmonary bypass, accompanied by increased release of a tubular injury marker. The postoperative tubular injury is increased after longer CPB times and higher degree of rewarming. Increasing the CPB flow rate may ameliorate the impaired oxygenation seen during CPB. In patients with heart failure and renal impairment, levosimendan may be the inotrope of choice.
Parts of work
I. Lannemyr L, Lundin E, Reinsfelt B, Bragadottir G, Redfors B, Oras J, Ricksten SE. Renal tubular injury during cardiopulmonary bypass as assessed by urinary release of N-acetyl-ß-D-glucosaminidase. Acta Anaesthesiologica Scandinavica. 2017;61(9):1075-1083. ::doi::10.1111/aas.12946II. Lannemyr L, Bragadottir G, Krumbholz V, Redfors B, Sellgren J, Ricksten SE. Effects of Cardiopulmonary Bypass on Renal Perfusion, Filtration, and Oxygenation in Patients Undergoing Cardiac Surgery. Anesthesiology, 2017;126(2):205-213. ::doi::10.1097/ALN.0000000000001461III. Lannemyr L, Bragadottir G, Hjärpe A, Redfors B, Ricksten SE. Impact of cardiopulmonary bypass flow on renal oxygenation in patients undergoing cardiac surgery. Accepted for publication, Annals of Thoracic Surgery, August 2018IV. Lannemyr L, Ricksten SE, Rundqvist B, Andersson B, Bartfay SE, Ljungman C, Dahlberg P, Bergh N, Hjalmarsson C, Gilljam T, Bollano E, Karason K. Differential effects of levosimendan and dobutamine on glomerular filtration rate in patients with heart failure and renal impairment: A randomized double-blind controlled trial. Journal of the American Heart Association. 2018;7: e008455. ::doi::10.1161/JAHA.117.008455
Doctor of Philosophy (Medicine)
University of Gothenburg. Sahlgrenska Academy
Institute of Clinical Sciences. Department of Anesthesiology & Intensive Care Medicine
Fredagen den 30 november 2018, kl. 9.00, sal Kammaren, Sahlgrenska Universitetssjukhuset, Blå Stråket 5, Göteborg.
Date of defence
glomerular filtration rate
renal blood flow