Terlipressin: a new therapeutic for calcium-channel blockers overdose.
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Biomedical subjects
Anne Delmas
Publications and source records attributed to Anne Delmas.
Increasing mean arterial pressure in patients with septic shock: effects on oxygen variables and renal function.
OBJECTIVE: To measure the effects of increasing mean arterial pressure on oxygen variables and renal function in septic shock. DESIGN: Prospective, open-label, randomized, controlled study. SETTING: Medical-surgical intensive care unit of a tertiary care teaching hospital. PATIENTS: Twenty-eight patients with a diagnosis of septic shock who required fluid resuscitation and pressor agents to increase and maintain mean arterial pressure > or =60 mm Hg. INTERVENTIONS: Patients were treated with fluid and norepinephrine to achieve and maintain a mean arterial pressure of 65 mm Hg. Then they were randomized in two groups: In the first group (control group, n = 14), mean arterial pressure was maintained at 65 mm Hg, and in the second group (n = 14), mean arterial pressure was increased to 85 mm Hg by increasing the dose of norepinephrine. MEASUREMENTS AND MAIN RESULTS: Hemodynamic variables (mean arterial pressure, heart rate, mean pulmonary artery pressure, pulmonary artery occlusion pressure, cardiac index, systemic vascular resistance index, pulmonary vascular resistance index, left and right ventricular stroke indexes), metabolic variables (oxygen delivery, oxygen consumption-calorimetric method, arterial lactate), and renal function variables (urine flow, serum creatinine, creatinine clearance) were measured. After introduction of norepinephrine, similar values of hemodynamic, metabolic, and renal function variables were obtained in both groups. No changes were observed in group 1 during the study period. Increasing mean arterial pressure from 65 to 85 mm Hg with norepinephrine in group 2 resulted in a significant increase in cardiac index from 4.8 (3.8-6.0) to 5.8 (4.3-6.9) L.min.m. Arterial lactate and oxygen consumption did not change. No changes were observed in renal function variables: urine flow, 63 (14-127) and 70 (15-121) mL; serum creatinine, 170 (117-333) and 153 (112-310) mumol.L; and creatinine clearance, 50 (12-77) and 67 (13-89) mL.min.1.73 m. CONCLUSIONS: Increasing mean arterial pressure from 65 to 85 mm Hg with norepinephrine neither affects metabolic variables nor improves renal function.
Adult↗
Terlipressin or norepinephrine in hyperdynamic septic shock: a prospective, randomized study.
OBJECTIVE: To compare, in patients with hyperdynamic septic shock, the effects of norepinephrine or terlipressin on hemodynamic variables and renal function. DESIGN: Prospective, randomized, open-label study. SETTING: Intensive care unit of a university, tertiary, and referral center. PATIENTS: Twenty adult patients with hyperdynamic septic shock, after fluid resuscitation. INTERVENTIONS: Patients were randomized to receive norepinephrine or terlipressin. Global hemodynamic variables, oxygen consumption, urine flow, creatinine clearance, and arterial blood lactate levels were measured. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure, systemic vascular resistance, pulmonary vascular resistance, and left and right ventricular stroke work were significantly increased with both drugs. With terlipressin, but not with norepinephrine, a significant decrease in heart rate (from 113 +/- 17 to 104 +/- 11 beats.min(-1), p < .01) and cardiac index (from 5.1 +/- 1.7 to 4.2 +/- 1.6 L.min(-1).m(-2)) was observed, with no change in stroke volume. Oxygen delivery index (from 784 +/- 131 to 701 +/- 92 mL.min(-1).m(-2)) and consumption index (from 244 +/- 69 to 210 +/- 54 mL.min(-1).m(-2)) were significantly decreased with terlipressin, but not with norepinephrine. Blood lactate concentrations were significantly decreased with both drugs. Urine flow and creatinine clearance were increased with both drugs. CONCLUSIONS: In patients with hyperdynamic septic shock, both norepinephrine and terlipressin were effective to raise mean arterial blood pressure. With terlipressin, but not norepinephrine, the improvement in blood pressure was achieved at the expense of cardiac index and oxygen consumption, which were significantly decreased. Renal function was improved with both drugs. In further studies, alternative strategies to maintain cardiac index should be explored, such as a synergy between low-dose terlipressin and dobutamine.
Adult↗
Clinical review: Vasopressin and terlipressin in septic shock patients.
Vasopressin (antidiuretic hormone) is emerging as a potentially major advance in the treatment of septic shock. Terlipressin (tricyl-lysine-vasopressin) is the synthetic, long-acting analogue of vasopressin, and has comparable pharmacodynamic but different pharmacokinetic properties. Vasopressin mediates vasoconstriction via V1 receptor activation on vascular smooth muscle. Septic shock first causes a transient early increase in blood vasopressin concentrations; these concentrations subsequently decrease to very low levels as compared with those observed with other causes of hypotension. Infusions of 0.01-0.04 U/min vasopressin in septic shock patients increase plasma vasopressin concentrations. This increase is associated with reduced need for other vasopressors. Vasopressin has been shown to result in greater blood flow diversion from nonvital to vital organ beds compared with adrenaline (epinephrine). Of concern is a constant decrease in cardiac output and oxygen delivery, the consequences of which in terms of development of multiple organ failure are not yet known. Terlipressin (one or two boluses of 1 mg) has similar effects, but this drug has been used in far fewer patients. Large randomized clinical trials should be conducted to establish the utility of these drugs as therapeutic agents in patients with septic shock.
Adult↗
Terlipressin in catecholamine-resistant septic shock patients.
To determine the effects on hemodynamics, laboratory parameters, and renal function of terlipressin used in septic-shock patients with hypotension not responsive to high-dose norepinephrine (>2.0 microg x kg(-1) x min(-1)) and dopamine (25 microg x kg(-1) x min(-1)), a prospective, open-label study was carried out in 17 patients. Patients received one or two boluses of 1 mg of terlipressin. In all patients terlipressin induced a significant increase in mean arterial pressure (MAP), systemic vascular resistance, pulmonary vascular resistance, and left and right ventricular stroke work. The increase in MAP was accompanied by a significant decrease in heart rate and cardiac index, but stroke volume remained unchanged. Oxygen delivery and consumption were significantly decreased. Blood lactate concentrations significantly decreased over the study period. Bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were significantly increased. Thrombocytes were significantly decreased. No change in prothrombin time was observed. Renal function, assessed by urine flow and creatinine clearance, was significantly improved. Pulmonary function assessed by Pao2/Fio2 ratio was not affected. A significant reduction in norepinephrine and dopamine infusion rates was observed in all patients. Eight patients died during their ICU stay from late multiple organ failure. Within the limitations of the present study (open-label design, small group of patients), it can be concluded that in septic shock patients with hypotension nonresponsive to fluid resuscitation and high-dose vasopressors, terlipressin can be effective to restore MAP. Cardiac index should be closely monitored because it was significantly decreased by terlipressin. Renal function was significantly improved. Mesenteric circulation was not evaluated, but hepatic function was altered during the study period. Further studies are required to determine whether terlipressin is safe in terms of outcome in septic shock patients.
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