Nitroglycerin can facilitate weaning of difficult-to-wean chronic obstructive pulmonary disease patients: a prospective interventional non-randomized study

Christina Routsi, Ioannis Stanopoulos, Epaminondas Zakynthinos, Panagiotis Politis, Vassilios Papas, Demetrios Zervakis, Spyros Zakynthinos, Christina Routsi, Ioannis Stanopoulos, Epaminondas Zakynthinos, Panagiotis Politis, Vassilios Papas, Demetrios Zervakis, Spyros Zakynthinos

Abstract

Introduction: Both experimental and clinical data give convincing evidence to acute cardiac dysfunction as the origin or a cofactor of weaning failure in patients with chronic obstructive pulmonary disease. Therefore, treatment targeting the cardiovascular system might help the heart to tolerate more effectively the critical period of weaning. This study aims to assess the hemodynamic, respiratory and clinical effects of nitroglycerin infusion in difficult-to-wean patients with severe chronic obstructive pulmonary disease.

Methods: Twelve difficult-to-wean (failed ≥ 3 consecutive trials) chronic obstructive pulmonary disease patients, who presented systemic arterial hypertension (systolic blood pressure ≥ 140 mmHg) during weaning failure and had systemic and pulmonary artery catheters in place, participated in this prospective, interventional, non-randomized clinical trial. Patients were studied in two consecutive days, i.e., the first day without (Control day) and the second day with (Study day) nitroglycerin continuous intravenous infusion starting at the beginning of the spontaneous breathing trial, and titrated to maintain normal systolic blood pressure. Hemodynamic, oxygenation and respiratory measurements were performed on mechanical ventilation, and during a 2-hour T-piece spontaneous breathing trial. Primary endpoint was hemodynamic and respiratory effects of nitroglycerin infusion. Secondary endpoint was spontaneous breathing trial and extubation outcome.

Results: Compared to mechanical ventilation, mean systemic arterial pressure, rate-pressure product, mean pulmonary arterial pressure, and pulmonary artery occlusion pressure increased [from (mean ± SD) 94 ± 14, 13708 ± 3166, 29.9 ± 4.8, and 14.8 ± 3.8 to 109 ± 20 mmHg, 19856 ± 4877 mmHg b/min, 41.6 ± 5.8 mmHg, and 23.4 ± 7.4 mmHg, respectively], and mixed venous oxygen saturation decreased (from 75.7 ± 3.5 to 69.3 ± 7.5%) during failing trials on Control day, whereas they did not change on Study day. Venous admixture increased throughout the trial on both Control day and Study day, but this increase was lower on Study day. Whereas weaning failed in all patients on Control day, nitroglycerin administration on Study day enabled a successful spontaneous breathing trial and extubation in 92% and 88% of patients, respectively.

Conclusions: In this clinical setting, nitroglycerin infusion can expedite the weaning by restoring weaning-induced cardiovascular compromise.

Figures

Figure 1
Figure 1
Variations of systolic blood pressure (sBP) and pulmonary artery occlusion pressure (PAOP) during weaning trials. Individual values of systolic blood pressure (sBP) (left) and pulmonary artery occlusion pressure (PAOP) (right) obtained on mechanical ventilation (MV) and at the 10th minute (Start) and last minute (End) of the spontaneous breathing trial on Control day (upper panel) and Study day (lower panel).
Figure 2
Figure 2
Variations of arterial oxygen saturation (SaO2) and mixed venous oxygen saturation (SaO2) during weaning trials. Individual values of arterial oxygen saturation (SaO2) (left) and mixed venous oxygen saturation (SvO2) (right) obtained on mechanical ventilation (MV) and at the 10th minute (Start) and last minute (End) of the spontaneous breathing trial on Control day (upper panel) and Study day (lower panel).
Figure 3
Figure 3
Mean pulmonary arterial pressure and mean arterial blood pressure versus cardiac output during mechanical ventilation (circles) and at the start (triangles) and end (squares) of spontaneous breathing trials on Control day (closed symbols) and Study day (open symbols). Substantial increases in mean pulmonary arterial pressure and mean arterial blood pressure on Control day were cancelled by nitroglycerin infusion on Study day and a similar increase in cardiac output occurred on both days, strongly suggesting that nitroglycerin infusion on Study day abandoned the increased right and left ventricular afterload on Control day.

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