The Effects of Terlipressin on Regional Hemodynamics and Kidney Function in Experimental Hyperdynamic Sepsis

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.

Sepsis-Induced Acute Kidney Injury

“…19 Finally, infusion of efferent arteriolar vasoconstrictors, such as angiotensin II and vasopressin, during experimental hyperdynamic sepsis improve MAP, GFR, and urine output despite reduced global RBF. 20,21 This observation further supports the role of prevailing efferent arteriolar relaxation in septic AKI.…”

A Selective V1A Receptor Agonist, Selepressin, Is Superior to Arginine Vasopressin and to Norepinephrine in Ovine Septic Shock*

“…Renal function was better preserved by selepressin, particularly when administered early. In experimental and clinical studies of septic shock, AVP, terlipressin, or [Phe 2 ,Orn 8 ]vasotocin was shown to increase urine output and creatinine clearance ( 14 , 41 , 42 ). Because selepressin cannot induce V 2 receptor-mediated antidiuresis, due to its very high selectivity for the V 1A receptor ( 8 , 10 ), restoration of arterial pressure may have contributed to the preserved renal perfusion and the increased urine output.…”

Sepsis-Associated Acute Kidney Injury: Macrohemodynamic and Microhemodynamic Alterations in the Renal Circulation

“…77 These findings from the Vasopressin and Septic Shock Trial are largely consistent with large mammal preclinical studies of SA-AKI. 75,78 CONCLUSIONS In adult human beings, early septic shock is associated more commonly with hyperdynamic circulation and is likely to be associated with high-flow-low-pressure renal circulation. Timely reversal of these circulatory abnormalities with vasoconstrictors may reverse early hemodynamically mediated renal dysfunction, and higher blood pressure targets may be justified in patients with pre-existing hypertension.…”