14 Feb 09
Posted in Inotropic support at 6:55 by Laci
BY L Tritapepe, V De Santis, D Vitale, F Guarracino, F Pellegrini, P Pietropaoli and M. Singer
BJA 2009;102:198-204
The calcium sensitizer levosimendan has anti-ischaemic effects mediated via the opening of sarcolemmal and mitochondrial ATP-sensitive potassium channels. These properties suggest potential application in clinical situations where cardioprotection would be beneficial, such as cardiac surgery. We thus decided to investigate whether pharmacological pre-treatment with levosimendan reduces intensive care unit (ICU) length of stay in patients undergoing elective myocardial revascularization under cardiopulmonary bypass.
Methods
One hundred and six patients undergoing elective coronary artery bypass grafting were randomly assigned in a double-blind manner to receive levosimendan or placebo. Levosimendan (24 µg kg–1) or placebo was administered as a slow i.v. bolus over a 10 min period before the initiation of bypass.
Results
Tracheal intubation time and the length of ICU stay were significantly reduced in the levosimendan group (P<0.01). The number of patients needing inotropic support for >12 h was significantly higher in the control group (18.0% vs 3.8%; P=0.021). Compared with control patients, levosimendan-treated patients had lower postoperative troponin I concentrations (P<0.0001) and a higher cardiac power index (P<0.0001).
Conclusions
Pre-treatment with levosimendan in patients undergoing surgical myocardial revascularization resulted in less myocardial injury, a reduction in tracheal intubation time, less requirement for inotropic support, and a shorter length of ICU stay.
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18 Jan 09
Posted in Acid-Base disorders, Inotropic support at 0:35 by Laci
By J A Myburgh, A Higgins, A Jovanovska, J Lipman, N Ramakrishnan, J Santamaria and the CAT Study investigators
Intensive Care Med 2008:34;2226-2234
To determine whether there was a difference between epinephrine and norepinephrine in achieving a mean arterial pressure (MAP) goal in intensive care (ICU) patients.
Design
Prospective, double-blind, randomised-controlled trial.
Setting
Four Australian university-affiliated multidisciplinary ICUs.
Patients and participants
Patients who required vasopressors for any cause at randomisation. Patients with septic shock and acute circulatory failure were analysed separately.
Interventions
Blinded infusions of epinephrine or norepinephrine to achieve a MAP =70 mmHg for the duration of ICU admission.
Measurements
Primary outcome was achievement of MAP goal >24 h without vasopressors. Secondary outcomes were 28 and 90-day mortality. Two hundred and eighty patients were randomised to receive either epinephrine or norepinephrine. Median time to achieve the MAP goal was 35.1 h (interquartile range (IQR) 13.8ñ70.4 h) with epinephrine compared to 40.0 h (IQR 14.5ñ120 h) with norepinephrine (relative risk (RR) 0.88; 95% confidence interval (CI) 0.69ñ1.12; P = 0.26). There was no difference in the time to achieve MAP goals in the subgroups of patients with severe sepsis (n = 158; RR 0.81; 95% CI 0.59ñ1.12; P = 0.18) or those with acute circulatory failure (n = 192; RR 0.89; 95% CI 0.62ñ1.27; P = 0.49) between epinephrine and norepinephrine. Epinephrine was associated with the development of significant but transient metabolic effects that prompted the withdrawal of 18/139 (12.9%) patients from the study by attending clinicians. There was no difference in 28 and 90-day mortality.
Conclusions
Despite the development of potential drug-related effects with epinephrine, there was no difference in the achievement of a MAP goal between epinephrine and norepinephrine in a heterogenous population of ICU patients.
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12 Jan 09
Posted in IABP, Inotropic support, Sepsis at 0:05 by Laci
By SB Solomon, PC Minneci, KJ Deans, J Feng, PQ Eichacker, SM Banks, RL Danner, C Natanson and MA Solomon
Critical Care Med 2008;37:7-18
Fluid refractory septic shock can develop into a hypodynamic cardiovascular state in both children and adults. Despite management of these patients with empirical inotropic therapy (with or without a vasodilator), mortality remains high.
Objectives
The effect of cardiovascular support using intra-aortic balloon counterpulsation was investigated in a hypodynamic, mechanically ventilated canine sepsis model in which cardiovascular and pulmonary support were titrated based on treatment protocols.
Methods
Each week, three animals (n = 33, 10-12 kg) were administered intrabronchial Staphylococcus aureus challenge and then randomized to receive intra-aortic balloon counterpulsation for 68 hrs or no intra-aortic balloon counterpulsation (control). Bacterial doses were increased over the study (4-8 x 109 cfu/kg) to assess the effects of intra-aortic balloon counterpulsation during sepsis with increasing risk of death.
Main results
Compared with lower bacterial doses (4-7 x 109 colony-forming units/kg), control animals challenged with the highest dose (8 x 109 colony-forming units/kg) had a greater risk of death (mortality rate 86% vs. 17%), with worse lung injury ([A - a]o2), and renal dysfunction (creatinine). These sicker animals required higher norepinephrine infusion rates to maintain blood pressure (and higher Fio2) and positive end-expiratory pressure levels to maintain oxygenation (p <= 0.04 for all). In animals receiving the highest bacterial dose, intra-aortic balloon counterpulsation improved survival time (23.4 +/- 10 hrs longer; p = 0.003) and lowered norepinephrine requirements (0.43 +/- 0.17 [mu]g/kg/min; p = 0.002) and systemic vascular resistance index (1.44 +/- 0.57 dynes/s/cm5/kg; p = 0.0001) compared with controls. Despite these beneficial effects, intra-aortic balloon counterpulsation was associated with an increase in blood urea nitrogen (p = 0.002) and creatinine (p = 0.12). In animals receiving lower doses of bacteria, intra-aortic balloon counterpulsation had no significant effects on survival or renal function.
Conclusions
In a canine model of severe septic shock with a low cardiac index, intra-aortic balloon counterpulsation prolongs survival time and lowers vasopressor requirements.
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07 Sep 08
Posted in Coronary artery disease, Heart failure/Cardiogenic shock, Inotropic support at 19:27 by Laci
By JT Fuhrmann, A Schmeisser, MR Schulze, C Wunderlich, SP Schoen, T Rauwolf, C Weinbrenner, RH Strasser
Critical Care Medicine 2008:36:2257-2266
Cardiogenic shock is the leading cause of death in patients hospitalized for acute myocardial infarction. The objectives were to investigate the effects of levosimendan, a novel inodilator, compared with the phosphodiesterase-III inhibitor enoximone in refractory cardiogenic shock complicating acute myocardial infarction, on top of current therapy.
Design
Prospective, randomized, controlled single-center clinical trial.
Setting
Medical and coronary intensive care unit in a university hospital.
Patients
Thirty-two patients with refractory cardiogenic shock for at least 2 hrs requiring additional therapy.
Interventions
Infusion of either levosimendan (12 ug/kg over 10 min, followed by 0.1 ug/kg/min over 50 min, and of 0.2 ug/kg/min for the next 23 hrs) or enoximone (fractional loading dose of 0.5 mg/kg, followed by 2-10 ug/kg/min continuously) after initiation of current therapy, always including revascularization, intra-aortic balloon pump counterpulsation, and inotropes.
Measurements and main results
Survival rate at 30 days was significantly higher in the levosimendan-treated group (69%, 11 of 16) compared with the enoximone group (37%, 6 of 16, p = 0.023). Invasive hemodynamic parameters during the first 48 hrs were comparable in both groups. Levosimendan induced a trend toward higher cardiac index, cardiac power index, left ventricular stroke work index, and mixed venous oxygen saturation. In addition, lower cumulative values for catecholamines at 72 hrs and for clinical signs of inflammation were seen in the levosimendan-treated patients. Multiple organ failure leading to death occurred exclusively in the enoximone group (4 of 16 patients).
Conclusions
In severe and refractory cardiogenic shock complicating acute myocardial infarction, levosimendan, added to current therapy, may contribute to improved survival compared with enoximone.
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