Inhaled NO and sildenafil combination in cardiac surgery patients with out-of-proportion pulmonary hypertension: acute effects on postoperative gas exchange and hemodynamics.

BACKGROUND: The goal of this study was to examine the effects of coadministration of sildenafil and inhaled nitric oxide (iNO) in patients with out-of-proportion pulmonary hypertension who underwent cardiac valve replacement surgery. METHODS AND RESULTS: Twenty consecutive cardiac surgery patients with out-of-proportion pulmonary hypertension were randomly assigned postoperatively into 2 groups: group A received 10 ppm of iNO followed by sildenafil (100 mg) orally 30 minutes later, and group B initially received sildenafil (100 mg) orally followed by 10 ppm of iNO 60 minutes later. Hemodynamic and gas exchange data were obtained at baseline, after administration of either iNO or sildenafil alone, and at 90 minutes from baseline. In group A, iNO resulted in a significant reduction in mean pulmonary artery pressure (MPAP) and pulmonary vascular resistance index (PVRI) (by 9.6% and 20.8%, respectively). In group B, sildenafil administration also resulted in a significant decrease in mean arterial pressure, MPAP, pulmonary artery occlusive pressure, PVRI, and systemic vascular resistance index but also in the PaO(2)/inspired fraction of oxygen ratio (by 18.7%, 22.0%, 15.7%, 31.6%, 21.3%, and 14%, respectively). In both groups, the coadministration of the 2 drugs resulted in a significant further reduction of mean arterial pressure, MPAP, pulmonary artery occlusive pressure, systemic vascular resistance index, and PVRI, whereas cardiac index and mixed venous oxygen saturation remained unchanged. The hypoxemia after sildenafil administration in group B improved after the coadministration of iNO, and thus PaO(2)/inspired fraction of oxygen returned to values near baseline. CONCLUSION: In this study, the postoperative coadministration of iNO and oral sildenafil in patients with out-of-proportion pulmonary hypertension undergoing cardiac surgery is safe and results in an additive favorable effect on pulmonary arterial pressure and pulmonary vascular resistance, without systemic hypotension and ventilation/perfusion mismatch.

Respiratory, metabolic and hemodynamic effects of clonidine in ventilated patients presenting with withdrawal syndrome.

OBJECTIVE: To investigate the respiratory, metabolic and hemodynamic effects of clonidine in ventilated patients presenting with withdrawal syndrome after sedation interruption. DESIGN: Prospective, interventional, single-center study in 30 ventilated ICU patients. INTERVENTIONS: Metabolic [oxygen consumption (VO(2)), CO(2) production (VCO(2)), resting energy expenditure (REE)], respiratory [minute ventilation (V (E)), tidal volume (V (T)), respiratory rate (RR)] and hemodynamic (HR, SAP, MAP) parameters were measured in 30 ventilated ICU patients. Measurements were performed first under sedation with remifentanil-propofol, then after sedation interruption, and finally after clonidine administration (0.9-1.8 mg of clonidine in two doses of 10 min interval). RESULTS: Sedation interruption produced significant increases in the hemodynamic parameters (SAP and MAP by 33%, HR by 37%), and metabolic rate (increase in VO(2) by 70%, VCO(2) by 88% and REE by 74%), leading to high respiratory demands (increase in V (E) from 9 to 15 l/min). The V (E) was increased due to a twofold increase in the RR; V (T) remained constant. In 25 out of 30 patients, clonidine administration decreased the hemodynamic (SAP, MAP and HR), metabolic (VO(2), VCO(2), REE) and respiratory parameters to values close to those observed with sedation. Clonidine induced mild sedation and patients became more cooperative with the ventilator. All patients responding to clonidine were weaned from the ventilator in 2 days (median, range 1-18 days). CONCLUSION: Patients with withdrawal syndrome had significantly elevated hemodynamic, metabolic and respiratory demands. Clonidine significantly decreased these demands, induced mild sedation and facilitated patient cooperation with the ventilator, enabling ventilator weaning.