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      The relationship between inotrope exposure, six-hour postoperative physiological variables, hospital mortality and renal dysfunction in patients undergoing cardiac surgery

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          Abstract

          Introduction

          Acute haemodynamic complications are common after cardiac surgery and optimal perioperative use of inotropic agents, typically guided by haemodynamic variables, remains controversial. The aim of this study was to examine the relationship of inotrope use to hospital mortality and renal dysfunction.

          Material and methods

          A retrospective cohort study of 1,326 cardiac surgery patients was carried out at two university-affiliated ICUs. Multivariable logistic regression analysis and propensity matching were performed to evaluate whether inotrope exposure was independently associated with mortality and renal dysfunction.

          Results

          Patients exposed to inotropes had a higher mortality rate than those not exposed. After adjusting for differences in Parsonnet score, left ventricular ejection fraction, perioperative intraaortic balloon pump use, bypass time, reoperation and cardiac index, inotrope exposure appeared to be independently associated with increased hospital mortality (adjusted odds ratio (OR) 2.3, 95% confidence interval (95% CI) 1.2 to 4.5) and renal dysfunction (adjusted OR 2.7, 95% CI 1.5 to 4.6). A propensity score-matched analysis similarly demonstrated that death and renal dysfunction were significantly more likely to occur in patients exposed to inotropes ( P = 0.01).

          Conclusions

          Postoperative inotrope exposure was independently associated with worse outcomes in this cohort study. Further research is needed to better elucidate the appropriate use of inotropes in cardiac surgery.

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          Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group.

          M. Packer, J R Carver, R J Rodeheffer … (1991)
          Milrinone, a phosphodiesterase inhibitor, enhances cardiac contractility by increasing intracellular levels of cyclic AMP, but the long-term effect of this type of positive inotropic agent on the survival of patients with chronic heart failure has not been determined. We randomly assigned 1,088 patients with severe chronic heart failure (New York Heart Association class III or IV) and advanced left ventricular dysfunction to double-blind treatment with (40 mg of oral milrinone daily (561 patients) or placebo (527 patients). In addition, all patients received conventional therapy with digoxin, diuretics, and a converting-enzyme inhibitor throughout the trial. The median period of follow-up was 6.1 months (range, 1 day to 20 months). As compared with placebo, milrinone therapy was associated with a 28 percent increase in mortality from all causes (95 percent confidence interval, 1 to 61 percent; P = 0.038) and a 34 percent increase in cardiovascular mortality (95 percent confidence interval, 6 to 69 percent; P = 0.016). The adverse effect of milrinone was greatest in patients with the most severe symptoms (New York Heart Association class IV), who had a 53 percent increase in mortality (95 percent confidence interval, 13 to 107 percent; P = 0.006). Milrinone did not have a beneficial effect on the survival of any subgroup. Patients treated with milrinone had more hospitalizations (44 vs. 39 percent, P = 0.041), were withdrawn from double-blind therapy more frequently (12.7 vs. 8.7 percent, P = 0.041), and had serious adverse cardiovascular reactions, including hypotension (P = 0.006) and syncope (P = 0.002), more often than the patients given placebo. Our findings indicate that despite its beneficial hemodynamic actions, long-term therapy with oral milrinone increases the morbidity and mortality of patients with severe chronic heart failure. The mechanism by which the drug exerts its deleterious effects is unknown.
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            Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE Randomized Trial.

            P Põder, Roopal Thakkar, Alexandre Mebazaa … (2007)
            Because acute decompensated heart failure causes substantial morbidity and mortality, there is a need for agents that at least improve hemodynamics and relieve symptoms without adversely affecting survival. To assess the effect of a short-term intravenous infusion of levosimendan or dobutamine on long-term survival. The Survival of Patients With Acute Heart Failure in Need of Intravenous Inotropic Support (SURVIVE) study was a randomized, double-blind trial comparing the efficacy and safety of intravenous levosimendan or dobutamine in 1327 patients hospitalized with acute decompensated heart failure who required inotropic support. The trial was conducted at 75 centers in 9 countries and patients were randomized between March 2003 and December 2004. Intravenous levosimendan (n = 664) or intravenous dobutamine (n = 663). All-cause mortality at 180 days. All-cause mortality at 180 days occurred in 173 (26%) patients in the levosimendan group and 185 (28%) patients in the dobutamine group (hazard ratio, 0.91; 95% confidence interval, 0.74-1.13; P = .40). The levosimendan group had greater decreases in B-type natriuretic peptide level at 24 hours that persisted through 5 days compared with the dobutamine group (P<.001 for all time points). There were no statistical differences between treatment groups for the other secondary end points (all-cause mortality at 31 days, number of days alive and out of the hospital, patient global assessment, patient assessment of dyspnea at 24 hours, and cardiovascular mortality at 180 days). There was a higher incidence of cardiac failure in the dobutamine group. There were higher incidences of atrial fibrillation, hypokalemia, and headache in the levosimendan group. Despite an initial reduction in plasma B-type natriuretic peptide level in patients in the levosimendan group compared with patients in the dobutamine group, levosimendan did not significantly reduce all-cause mortality at 180 days or affect any secondary clinical outcomes. clinicaltrials.gov Identifier: NCT00348504.
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              Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial.

              Robert Bourge, Mihai Gheorghiade, Ileana L Piña … (2002)
              Little randomized evidence is available to guide the in-hospital management of patients with an acute exacerbation of chronic heart failure. Although intravenous inotropic therapy usually produces beneficial hemodynamic effects and is labeled for use in the care of such patients, the effect of such therapy on intermediate-term clinical outcomes is uncertain. To prospectively test whether a strategy that includes short-term use of milrinone in addition to standard therapy can improve clinical outcomes of patients hospitalized with an exacerbation of chronic heart failure. Prospective, randomized, double-blind, placebo-controlled trial conducted from July 1997 through November 1999. Seventy-eight community and tertiary care hospitals in the United States. A total of 951 patients admitted with an exacerbation of systolic heart failure not requiring intravenous inotropic support (mean age, 65 years; 92% with baseline New York Heart Association class III or IV; mean left ventricular ejection fraction, 23%). Patients were randomly assigned to receive a 48-hour infusion of either milrinone, 0.5 microg/kg per minute initially (n = 477), or saline placebo (n = 472). Cumulative days of hospitalization for cardiovascular cause within 60 days following randomization. The median number of days hospitalized for cardiovascular causes within 60 days after randomization did not differ significantly between patients given milrinone (6 days) compared with placebo (7 days; P =.71). Sustained hypotension requiring intervention (10.7% vs 3.2%; P<.001) and new atrial arrhythmias (4.6% vs 1.5%; P =.004) occurred more frequently in patients who received milrinone. The milrinone and placebo groups did not differ significantly in in-hospital mortality (3.8% vs 2.3%; P =.19), 60-day mortality (10.3% vs 8.9%; P =.41), or the composite incidence of death or readmission (35.0% vs 35.3%; P =.92) These results do not support the routine use of intravenous milrinone as an adjunct to standard therapy in the treatment of patients hospitalized for an exacerbation of chronic heart failure.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Crit Care
                Journal ID (iso-abbrev): Crit Care
                Title: Critical Care
                Publisher: BioMed Central
                ISSN (Print): 1364-8535
                ISSN (Electronic): 1466-609X
                Publication date (Print): 2011
                Publication date (Electronic): 7 July 2011
                Volume: 15
                Issue: 4
                Page: R162
                Affiliations
                [1 ]Division of Critical Care, McGill University Health Centre, 687 Pine Avenue West, Montreal, QC, H3A 1A1, Canada
                [2 ]Division of Cardiac Surgery, McGill University Health Centre, 687 Pine Avenue West, Montreal, QC, H3A 1A1, Canada
                [3 ]McGill University Faculty of Medicine, 845 Sherbrooke Street West, Montreal, QC, H3A 2T5, Canada
                [4 ]Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University Health Centre, 3650 St-Urbain, Montreal, QC, H2X 2P4, Canada
                [5 ]Department of Critical Care, SMBD-Jewish General Hospital, McGill University, 845 Sherbrooke Street West, Montreal, QC, H3A 2T5, Canada
                Article
                Publisher ID: cc10302
                DOI: 10.1186/cc10302
                PMC ID: 3387599
                PubMed ID: 21736726
                SO-VID: 4e2bd09e-f702-4fcf-9886-f1ffbcf355c9
                Copyright © Copyright ©2011 Shahin et al.; licensee BioMed Central Ltd.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 20 January 2011
                Date revision received : 27 March 2011
                Date accepted : 7 July 2011
                Categories
                Subject: Research

                ScienceOpen disciplines: Emergency medicine & Trauma
                Data availability:
                ScienceOpen disciplines: Emergency medicine & Trauma

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