Abstract
Background and AimsAlthough terlipressin (TP) may improve renal function in cirrhotic patients, its use in sepsis remains controversial due to concerns about regional ischemia. We investigated the effects of TP on regional hemodynamics and kidney function in experimental hyperdynamic sepsis.MethodsWe studied thirteen merino ewes in a university physiology laboratory using a randomized controlled cross over design. We implanted flow probes around the pulmonary, circumflex coronary, superior mesenteric, renal and iliac arteries. We injected live Escherichia coli and induced hyperdynamic sepsis. We treated animals with either bolus vehicle or a single dose of TP (sTP = 1 mg). In a second group, after 1 mg of TP, two additional bolus injections (mTP) of 0.5 mg were given at 2 hourly intervals.Main ResultssTP (1 mg) significantly increased mean arterial pressure (MAP) (74 to 89 mmHg; P<0.0001) creatinine clearance (31 to 85 mL/min; P<0.0001) and urine output (24 to 307 mL/hr) (P<0.0001). However, it decreased CO (5.7 to 3.9 L/min; p<0.0001), coronary blood flow (CBF) (43 to 32 mL/min; p<0.0001) and mesenteric blood flow (MBF) (944 to 625 mL/min; p = 0.004) and increased blood lactate (2.1 to 4.0 mmol/L; p<0.0001). Extra doses of TP caused little additional effect.ConclusionsIn hyperdynamic sepsis, bolus TP transiently improves MAP and renal function, but reduces CO, CBF and MBF, and increases blood lactate. Caution should be applied when prescribing bolus TP in septic patients at risk of coronary or mesenteric ischemia.
Highlights
Severe sepsis is a major cause of death in critically ill patients and its incidence is increasing [1]
After the bolus injection of live E.coli, prior to the intervention with single dose TP (s-TP) or vehicle, all sheep reached the predefined criteria for hyperdynamic sepsis within 10 hours
Hyperdynamic sepsis was indicated by a 23% fall in mean arterial pressure (MAP) (93612 to 74612 mmHg, p,0.05), peripheral vasodilatation (TPC increased from 4567 to 80628 mL/min/mmHg, p,0.05), a 40% increase in CO (4.060.3 to 5.660.8 L/min, p,0.05) a doubling in HR (73611 to 14469 beats/min, p,0.05), a 29% decrease in SV (5569 to 3965 mL/beats, p,0.05) a halving in urine output, a 60% decrease in creatinine clearance, a 37% increase in serum creatinine and a 300% increase in blood lactate levels (Table 1, Figure 1)
Summary
Severe sepsis is a major cause of death in critically ill patients and its incidence is increasing [1]. Arginine vasopressin (AVP), which acts on vascular smooth muscle via V1 receptors [6], has been used as an additional vasoactive drug in patients with septic shock [2,7]. Such addition is postulated to improve kidney dysfunction in patients with septic shock [8]. Terlipressin (TP) may improve renal function in cirrhotic patients, its use in sepsis remains controversial due to concerns about regional ischemia. We investigated the effects of TP on regional hemodynamics and kidney function in experimental hyperdynamic sepsis
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