Elsevier

Journal of Critical Care

Volume 26, Issue 1, February 2011, Pages 15-21
Journal of Critical Care

Airway/Ventilation
Weaning difficult-to-wean chronic obstructive pulmonary disease patients: A pilot study comparing initial hemodynamic effects of levosimendan and dobutamine

https://doi.org/10.1016/j.jcrc.2010.01.002Get rights and content

Abstract

Purpose

To compare the short-term hemodynamic effects of levosimendan and dobutamine in chronic obstructive pulmonary disease (COPD) patients experiencing weaning difficulties in relation with increased left ventricular filling pressure.

Materials and Methods

This prospective, sequential, pilot study included 10 COPD patients experiencing weaning difficulties in relation with increased left ventricular filling pressure ascertained by an increase >10 mm Hg of pulmonary artery occlusion pressure (PAOP) at the shift from mechanical to spontaneous breathing (SB). Patients received 1 h infusion of 7 μg/kg per minute of dobutamine, followed by 24-hour infusion of 0.2 μg/kg per minute levosimendan. Hemodynamic variables were measured under MV and 15 to 30 minutes after SB at baseline, at the end of dobutamine infusion, at a washout period, and after levosimendan infusion.

Results

At baseline, the shift from mechanical ventilation to spontaneous ventilation was associated with a significant increase in PAOP from a median of 15 (interquartile range [IQR], 6) to 29 (9) mm Hg. Both drugs reduced significantly the level of PAOP increase at SB, but levosimendan had a greater effect than dobutamine [median PAOP increase (IQR): 5 (2) vs 9 (4) mm Hg, respectively; P < .01].

Conclusions

Both drugs reduced the magnitude of PAOP increase at SB in difficult-to-wean COPD patients. PAOP increase was reduced to a greater extent by levosimendan.

Introduction

Chronic obstructive pulmonary disease (COPD) and congestive heart failure (CHF) have common determinants (smoking, and chronic inflammation), and might coexist in the same patients with underdiagnosis and misclassification [1]. Unrecognized congestive heart failure may coexist in stable COPD condition [2], [3], [4], [5], and in acute exacerbation with a prevalence varying between 21% in moderate exacerbation [6], [7], and 31.1% in severe acute exacerbation requiring intensive care unit (ICU) admission and ventilator assistance [8]. In COPD patients, unrecognized CHF might reveal either as a cause of exacerbation [6], [8], or as a cause of weaning difficulties raised by severe cardiopulmonary interactions [9], [10], [11].

Weaning difficulties in COPD are usually ascribed to fatigue of respiratory muscles and a worsening of respiratory mechanics [12]. However, the occurrence of overt increase in left ventricular (LV) filling pressure evoking acute pulmonary edema has been invoked with increasing frequency in this setting. The increase in LV filling pressure upon switching from mechanical ventilation (MV) to spontaneous breathing (SB) is usually ascribed to acute left heart failure [13], but it might also be due to major cardiopulmonary interactions occurring abruptly in this condition [14]. Left ventricular dysfunction and elevated LV filling pressure in this setting are due to an increase in venous return and LV preload, myocardial ischemia, decrease in LV ejection fraction, or ventricular interdependence [9], [11], [15], [16], [17].

Optimal treatments of LV dysfunction occurring during weaning from mechanical ventilation are debated. Although the use of drugs aiming at optimizing LV load conditions (vasodilators, diuretics, ultrafiltration) represents the most appropriate choice in such condition, positive inotropes such as dobutamine remain commonly used in these patients although evidence of impaired LV contractility during weaning failure is not constant and the fact that dobutamine infusion is usually associated with increased myocardial oxygen demand, cardiac arrhythmias, and even mortality [11], [18], [19], [20], [21], [22]. Nonetheless, short-term administration of inotropes may be necessary in a subset of patients, as a bridge therapy to ease weaning by supporting dysfunctioning heart during this transient period.

Levosimendan an inodilator acting independently of cyclic Adenosinemonophosphate (AMPc) production, might be an attractive alternative in the particular setting of weaning induced LV dysfunction and pulmonary edema. Levosimendan enhances LV contractility without promoting neither arrhythmias nor oxygen consumption [23]. Short-term hemodynamic effects in left heart failure consist in an increase in stroke volume and cardiac index, and a decrease in LV and right ventricular (RV) filling pressures [24], [25], [26]. In conditions characterized by RV overload, levosimendan has also been shown to improve RV performance through pulmonary vasodilator effects [27], [28]. Two recent reports suggest that levosimendan may be successful to ease weaning of difficult-to-wean ICU patients [13], [29].

We hypothesized that combined systemic and pulmonary effects of levosimendan might be of greater benefit than those of dobutamine in difficult-to-wean COPD patients in relation with major cardiopulmonary interactions. Accordingly, we conducted the present pilot study in order to examine the short-term hemodynamic effects of levosimendan in comparison with those of dobutamine in COPD patients experiencing weaning difficulties in relation with increased LV filling pressure.

Section snippets

Patients and methods

In this prospective sequential study conducted between February 2005 and February 2007, all patients suffering from acute exacerbation and receiving endotracheal mechanical ventilation were considered for enrolment in the study. The study protocol was approved by our institutional review board and all included patients or relatives gave informed consent to participate in the study.

When weaning criteria were fulfilled, patients who experienced weaning difficulties ascribed to LV dysfunction were

Results

During the study period 164 patients were admitted to the ICU because of acute exacerbation of COPD. Of these 100 were ventilated with noninvasive ventilation and 64 were intubated and had conventional mechanical ventilation. Twenty-three out of these 64 conventionally ventilated patients exhibited weaning difficulties; 10 of them had weaning difficulties ultimately ascribed to LV dysfunction and thus included in the study.

Demographic characteristics of the included patients are depicted in

Discussion

The present study shows that both dobutamine and levosimendan reduced the magnitude of PAOP increase induced by the shift from mechanical ventilation to spontaneous ventilation in COPD patients exhibiting weaning difficulties related to cardiac dysfunction. In comparison to dobutamine, levosimendan reduced to a greater extent the weaning-induced PAOP increase.

More favorable effects of levosimendan on LV function appears to be mostly related to its effects on myocardial oxygen consumption

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