Background
In ovine hyperdynamic sepsis there is a large increase in cardiac output to maintain arterial pressure, and despite increased renal blood flow (RBF) acute kidney injury (AKI) develops. Sepsis is associated with large changes in SNA to the heart and kidney. Determining the effects of increased SNA on individual organs is important in view of proposals to use sympatholytics in sepsis.
Methods
The effects of sepsis were examined in control conscious sheep, during infusion of atenolol (10 mg then 0.125 mg/kg/h for 16 hours), and 2 weeks following surgical renal denervation. Mean arterial pressure (MAP), cardiac output (CO) and renal blood flow (RBF) were continuously monitored during a 24 hour baseline period and 24 h infusion of live E. coli to induce sepsis. Urine was collected hourly and arterial blood was collected at set intervals.
Results
Sepsis decreased MAP and increased heart rate, CO and RBF. There was a fall in creatinine clearance, and an initial diuresis was followed by oliguria. Atenolol reduced HR (157±9 to 111±4 bpm) and CO (6.2±0.6 to 5.0±0.5 L/min), but there was no significant effect on MAP due to less peripheral vasodilatation, and renal function was unchanged. Following renal denervation, MAP had decreased to 67±3 mmHg at 24 h of sepsis, compared with 82±5 mmHg in the control group. Renal denervation abolished the sepsis induced initial diuresis, but had no effect on the development of oliguria. The abolition of the diuresis by renal denervation was independent of changes in plasma AVP levels.
Conclusions
In sepsis, treatment with atenolol did not cause further hypotension or reduce renal function. Renal denervation caused a greater fall in MAP and prevented the initial diuresis, but did not prevent development of AKI. Further studies are required to determine the safety of sympatholytics such as clonidine in sepsis.
Disclosure: none.