Vasoactive drugs and acute kidney injury.
ABSTRACT The use of norepinephrine, and probably vasopressor therapy in general, in intensive care patients with hypotensive vasodilatation despite fluid resuscitation and evidence of acute kidney injury remains the subject of much debate and controversy. Although there is concern about the use of these drugs, these concerns are unfounded. At this time, the experimental and human data strongly suggest that, in these patients, vasopressor therapy is safe and probably beneficial from a renal, and probably general, point of view. On the basis of currently available evidence, in hypotensive vasodilated patients with acute kidney injury, restoration of blood pressure within autoregulatory values should occur promptly with noradrenaline and be sustained until such vasodilatation dissipates. The additional role of other vasopressors in these situations remains unclear. The addition of vasopressin may be helpful in individual patients, but widespread use is not supported by evidence. Alpha-dose dopamine has no advantages over noradrenaline and is not as reliably effective in restoring blood pressure and urine output. Its widespread use cannot be supported in patients with vasodilatation and acute kidney injury. Other vasopressor drugs such as epinephrine and phenylephrine may be similar in efficacy to noradrenaline. However, experience and available data with their use is vastly less than with noradrenaline. Adrenaline, in addition, is associated with hyperglycemia, hyperlactatemia, acidosis, and hypokalemia. Terlipressin appears useful in patients with acute kidney injury secondary to hepatorenal syndrome. Whether it is superior to noradrenaline in this setting remains uncertain, and more studies are needed before recommendations can be made.
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ABSTRACT: Arginine vasopressin is a promising systemic vasopressor in settings such as vasodilatory shock and cardiopulmonary resuscitation. The evidence that arginine vasopressin may also have a pulmonary vasodilatory effect makes it an attractive drug for the treatment of circulatory shock secondary to right ventricular failure and pulmonary hypertension. In the present study, we evaluated the effects of arginine vasopressin on right ventricular function and ventriculovascular coupling in the setting of moderate acute pulmonary hypertension and compared these effects with those of phenylephrine. Prospective laboratory investigation using an established model of acute pulmonary hypertension. University hospital laboratory. Seven adult beagle dogs weighing 8-14 kg. After acute instrumentation to measure right ventricular pressure and volume with the conductance technique and pulmonary artery flow and pressure with high-fidelity transducers, the stable thromboxane analogue U46619 was infused continuously to obtain stable pulmonary hypertension. Phenylephrine and arginine vasopressin were administered consecutively in continuous infusions at doses titrated to achieve a 25% increase in aortic pressure. Phenylephrine and arginine vasopressin both increased total pulmonary vascular resistance and arterial elastance without influencing characteristic impedance. Both drugs decreased cardiac output and stroke volume. Right ventricular hydraulic power output was reduced by arginine vasopressin but not by phenylephrine. Most importantly, arginine vasopressin caused a 31% decrease in right ventricular contractility measured as the slope of the preload recruitable stroke work relationship, whereas contractility was preserved during phenylephrine infusion. In the present model, arginine vasopressin causes pulmonary vascular constriction and exerts an important negative inotropic effect on the right ventricle. These findings suggest that one should be cautious in the use of arginine vasopressin when right ventricular function is compromised.Critical Care Medicine 12/2002; 30(11):2548-52. · 6.12 Impact Factor
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ABSTRACT: Terlipressin is a vasopressin analog that may improve renal function in hepatorenal syndrome by mechanisms as yet unknown. The authors investigated the effect of the drug on systemic, hepatic and renal hemodynamics in cirrhosis. Six patients with cirrhosis and ascites were studied (five Child's B and one Child's C). Heart rate (HR), mean arterial pressure (MAP), cardiac output (CO), systemic vascular resistance (SVR), hepatic venous pressure gradient (HVPG), reverse thermodilution unilateral real-time renal blood flow (RBF), urinary flow, and sodium concentrations were measured before and 1 h after an intravenous bolus of 2 mg of terlipressin. Following terlipressin administration, HR fell significantly (84.2 +/- 6 to 70.8 +/- 4.9, P = 0.013), MAP increased (72.7 +/- 3.6 to 87 +/- 5.3 mmHg, P = 0.027), CO fell (7.4 +/- 0.8 to 6.4 +/- 0.8 L/min, P = 0.02) and SVR increased (1368.5 +/- 236 to 2079.7 +/- 458, P = 0.04). There were no significant differences in HVPG (12.3 +/- 1.6 to 14 +/- 0.9 mmHg, P-value not significant [NS]), RBF (255 +/- 0.02 compared with 249 +/- 0.02 mL/min, P-value NS), urinary volume (49.1 +/- 8.9 compared with 49.6 +/- 16.7 mL/ h, P-value NS) and urinary sodium excretion (4 +/- 1.1 compared with 5.9 +/- 3.5 mmol/ h). In the present small study, the authors were able to demonstrate that a bolus injection of terlipressin produced an increase in MAP and SVR, along with a reduction in cardiac output without a reduction in renal blood flow. Further studies are necessary to define the effects of terlipressin on renal hemodynamics and sodium excretion.Journal of Gastroenterology and Hepatology 02/2004; 19(1):73-7. · 3.33 Impact Factor
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ABSTRACT: The present study investigated the protective effect of acute volume expansion (25%) with isotonic saline, isotonic mannitol, and hypertonic mannitol in a model of unilateral norepinephrine-induced acute renal failure (ARF). Three hours following a 40-min intrarenal infusion of norepinephrine (NE) (0.75 microgram/kg/min), inulin clearance had fallen from a control value of 54.1 +/- 6.5 to 1.3 +/- 1.3 ml/min in untreated dogs and fell similarly (P = NS) to 3.3 +/- 1.5 ml/min in animals preexpanded with 0.9% saline (0.75 ml/kg/min). In contrast, as compared to the untreated animals, inulin clearance 3 hr post NE infusion was significantly greater in dogs preexpanded with 5% mannitol (9.2 +/- 2.5 ml/min, P less than 0.01), or 20% mannitol (16.6 +/- 3.9 ml/min, P less than 0.01). The protective effects of 5% and 20% mannitol were not statistically different from each other. Recovery of renal excretory function in all groups, expressed as 3-hr post NE inulin clearance, correlated with the magnitude of pre NE solute excretion rate (r = 0.612, P less than 0.001) and osmolar clearance rate (r=0.593, P less than 0.001), but not with pre insult inulin clearance (r = 0.233, P = NS) or renal blood flow (r = 0.249, P = NS). In the presence of a profound fall in inulin clearance, proximal tubular (PT) pressures in untreated dogs 3 hr post NE infusion achieved a value equal to control (26 +/- 11 vs. 25 +/- 2 mm Hg). In contrast, pretreatment with isotonic mannitol produced a rise in PT pressure both before (45 +/- 4 mm Hg, P less than 0.05) and 3 hr post NE infusion (38 +/- 5 mm Hg, P less than 0.05). In all groups of animals, at both 3 and 24 hr post NE, tubular injury was observed but glomerular architecture remained normal by light and electron microscopy. Conclusion. the protective effect of mannitol in this reversible model of ARF did not correlate with inulin clearance, renal blood flow, extracellular fluid (ECF) volume, ECF hypertonicity, or renal histologic changes but did correlate with the solute excretion rate. The increased PT pressures with mannitol both before and after the NE insult could contribute to the protective effect of attenuating any relative intratubular obstruction.Kidney International 09/1978; 14(2):115-25. · 7.92 Impact Factor