I CASE REPORTS Sildenafil Can Increase the Response to Inhaled Nitric Oxide

INHALED nitric oxide (NO) reduces pulmonary artery pressure and increases arterial oxygen tension (Pao2) in many patients with pulmonary hypertension',* and acute respiratory failure.' Not all patients, however, manifest an equally effective r e~p o n s e ,~ and investigators have sought to enhance the physiologic effects of inhaled NO.5 One possible strategy is to increase the availability of cyclic guanosine monophosphate (cGMP), an intracellular messenger of NO, by blocking its degradation by cGMP-specific phosphodiesterase (PDE-5). Dipyridamole, a PDE-5 inhibitor, has been used in combination with inhaled NO to decrease pulmonary artery pressure in patients with pulmonary hypertension of various etiologies."~' However, the results of these small series have been inconsistent, possibly because of the multiple pharmacologic actions of this drug. ' Sildenafil is a newer PDE-5 inhibitor used in the management of erectile dysfunction" that acts by increasing the local availability of endogenous NO. Sildenafil has a higher PDE-5 selectivity than dipyridamole and a predict- [email protected] able gastrointestinal absorption,9 which make it an attractive complement to inhaled NO for the management of acute pulmonary hypertension in critically ill patients. Rather than simply adding the effect of a second vasodilator, sildenafil may enhance the selective pulmonary vasodilator effect of inhaled NO by making more messenger cGMP available locally. For example, the administration of sildenafil was recently reported to attenuate the acute pullnonary hypertension associated with the withdrawal of inhaled NO in two infants treated for pulmonary hypertension. lo We report the case of a patient with severe hypoxemia caused by pulmonary hypertension and venous blood shunting through a patent foramen ovale (PFO) that was reversed using inhaled NO in association with systemic sildenafil administration. Case Report A 52-yr-old woman with severe interstitial piilmonary fibrosis, Crohn disease, and previous pulmonary thromboembolism developed acute respiratory failure while being evaluated for a living related-donor lung transplant. The likely cause of her exacerbation was infectious. Chest radiograms showed her chronic diffuse pattern of pulmonary infiltrates and a new parenchymal consolidation iit the right lung base. Gram stains of bronchial secretions showed abundant neutrophils without predominant organisms. She was administered broad-spectrum antibiotics, her trachea was intubated, and mechanical ventilation was begun. A norepinephrine infusion (1-3 pg/min) was used to treat hypotension. Pulmonaiy artery (PA) catheterization revealed a niran PA pressure of 50 mmHg, a cardiac output of 4.8 I/min with a stroke volume of 47 ml, a pulmonary artery occlusion pressure of 14 nimHg, and a central venous pressure of 9 mmHg. An echocardiogram showed normal left ventricular function, mild right ventricular (RV) dilation, mild tricuspid regurgitation, and a PFO. The latter was not present in a study performed a year earlier, when the systolic RV pressure had been estimated at 41 mmHg. To confirm the presence of a hemodynamically significant shunt, an indocyanine dilution study was performed, which showed a pattern of early dye recirculation compatible with a right-to-left intracardiac shunt

Intubation Practices and Adverse Peri-intubation Events in Critically Ill Patients from 29 Countries

Importance: Tracheal intubation is one of the most commonly performed and high-risk interventions in critically ill patients. Limited information is available on adverse peri-intubation events. Objective: To evaluate the incidence and nature of adverse peri-intubation events and to assess current practice of intubation in critically ill patients. Design, Setting, and Participants: The International Observational Study to Understand the Impact and Best Practices of Airway Management in Critically Ill Patients (INTUBE) study was an international, multicenter, prospective cohort study involving consecutive critically ill patients undergoing tracheal intubation in the intensive care units (ICUs), emergency departments, and wards, from October 1, 2018, to July 31, 2019 (August 28, 2019, was the final follow-up) in a convenience sample of 197 sites from 29 countries across 5 continents. Exposures: Tracheal intubation. Main Outcomes and Measures: The primary outcome was the incidence of major adverse peri-intubation events defined as at least 1 of the following events occurring within 30 minutes from the start of the intubation procedure: cardiovascular instability (either: systolic pressure <65 mm Hg at least once, <90 mm Hg for >30 minutes, new or increase need of vasopressors or fluid bolus >15 mL/kg), severe hypoxemia (peripheral oxygen saturation <80%) or cardiac arrest. The secondary outcomes included intensive care unit mortality. Results: Of 3659 patients screened, 2964 (median age, 63 years; interquartile range [IQR], 49-74 years; 62.6% men) from 197 sites across 5 continents were included. The main reason for intubation was respiratory failure in 52.3% of patients, followed by neurological impairment in 30.5%, and cardiovascular instability in 9.4%. Primary outcome data were available for all patients. Among the study patients, 45.2% experienced at least 1 major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 42.6% of all patients undergoing emergency intubation, followed by severe hypoxemia (9.3%) and cardiac arrest (3.1%). Overall ICU mortality was 32.8%. Conclusions and Relevance: In this observational study of intubation practices in critically ill patients from a convenience sample of 197 sites across 29 countries, major adverse peri-intubation events - in particular cardiovascular instability - were observed frequently

Effect of Intraoperative High Positive End-Expiratory Pressure (PEEP) With Recruitment Maneuvers vs Low PEEP on Postoperative Pulmonary Complications in Obese Patients: A Randomized Clinical Trial (vol 321, pg 2292, 2019)

status: publishe