A phase I trial of low-dose inhaled carbon monoxide in sepsis-induced ARDS.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a prevalent disease with significant mortality for which no effective pharmacologic therapy exists. Low-dose inhaled carbon monoxide (iCO) confers cytoprotection in preclinical models of sepsis and ARDS. METHODS: We conducted a phase I dose escalation trial to assess feasibility and safety of low-dose iCO administration in patients with sepsis-induced ARDS. Twelve participants were randomized to iCO or placebo air 2:1 in two cohorts. Four subjects each were administered iCO (100 ppm in cohort 1 or 200 ppm in cohort 2) or placebo for 90 minutes for up to 5 consecutive days. Primary outcomes included the incidence of carboxyhemoglobin (COHb) level ≥10%, prespecified administration-associated adverse events (AEs), and severe adverse events (SAEs). Secondary endpoints included the accuracy of the Coburn-Forster-Kane (CFK) equation to predict COHb levels, biomarker levels, and clinical outcomes. RESULTS: No participants exceeded a COHb level of 10%, and there were no administration-associated AEs or study-related SAEs. CO-treated participants had a significant increase in COHb (3.48% ± 0.7% [cohort 1]; 4.9% ± 0.28% [cohort 2]) compared with placebo-treated subjects (1.97% ± 0.39%). The CFK equation was highly accurate at predicting COHb levels, particularly in cohort 2 (R2 = 0.9205; P < 0.0001). Circulating mitochondrial DNA levels were reduced in iCO-treated participants compared with placebo-treated subjects. CONCLUSION: Precise administration of low-dose iCO is feasible, well-tolerated, and appears to be safe in patients with sepsis-induced ARDS. Excellent agreement between predicted and observed COHb should ensure that COHb levels remain in the target range during future efficacy trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT02425579. FUNDING: NIH grants P01HL108801, KL2TR002385, K08HL130557, and K08GM102695.

Safety of Propofol for Oxygenator Exchange in Extracorporeal Membrane Oxygenation.

The purpose of this analysis is to describe the safety of propofol administration in adult extracorporeal membrane oxygenation (ECMO) patients. We performed a prospective cohort analysis of patients using ECMO at Brigham and Women's Hospital between February 2013 and October 2015. Patients were included if they used ECMO for at least 48 hours. The major end-point of the analysis was the median oxygenator lifespan. Oxygenator exchanges were analyzed by the number of patients requiring an oxygenator exchange and the number of oxygenator exchanges per ECMO day. A priori analysis was performed by comparing the outcomes between patients who did and did not receive propofol during their ECMO course. During the study, 43 patients were included in the analysis. Sixteen patients used propofol during their ECMO course. There were 12 oxygenator exchanges during therapy. Oxygenator exchange occurred on 1.8% of ECMO days. The median oxygenator lifespan was 7 days. Patients who used propofol had a significantly longer oxygenator lifespan (p = 0.02). Among patients who received propofol, patients who required oxygenator exchange used a significantly lower median daily dose of propofol (p < 0.001). The use of propofol appears safe in ECMO with regards to oxygenator viability. Contrary to expected, oxygenator lifespan was significantly longer among patients who received propofol.

Clinical and Economic Impact of Formulary Conversion From Inhaled Flolan to Inhaled Veletri for Refractory Hypoxemia in Critically Ill Patients.

BACKGROUND: Flolan (iFLO) and Veletri (iVEL) are 2 inhaled epoprostenol formulations. There is no published literature comparing these formulations in critically ill patients with refractory hypoxemia. OBJECTIVE: To compare efficacy, safety, and cost outcomes in patients who received either iFLO or iVEL for hypoxic respiratory failure. METHODS: This was a retrospective, single-center analysis of adult, mechanically ventilated patients receiving iFLO or iVEL for improvement in oxygenation. The primary end point was the change in the PaO2/FiO2 ratio after 1 hour of pulmonary vasodilator therapy. Secondary end points assessed were intensive care unit (ICU) length of stay (LOS), hospital LOS, duration of study therapy, duration of mechanical ventilation, mortality, incidence of adverse events, and cost. RESULTS: A total of 104 patients were included (iFLO = 52; iVEL = 52). More iFLO patients had acute respiratory distress syndrome compared with the iVEL group (61.5 vs 34.6%; P = 0.01). There was no difference in the change in the PaO2/FiO2 ratio after 1 hour of therapy (33.04 ± 36.9 vs 31.47 ± 19.92; P = 0.54) in the iFLO and iVEL groups, respectively. Patients who received iVEL had a shorter duration of mechanical ventilation (P < 0.001) and ICU LOS (P < 0.001) but not hospital LOS (P = 0.86) and duration of therapy (P = 0.36). No adverse events were attributed to pulmonary vasodilator therapy, and there was no difference in cost. CONCLUSIONS: We found no difference between iFLO and iVEL when comparing the change in the PaO2/FiO2 ratio, safety, and cost in hypoxic, critically ill patients. There were differences in secondary outcomes, likely a result of differences in underlying indication for inhaled epoprostenol.

Inhaled epoprostenol vs inhaled nitric oxide for refractory hypoxemia in critically ill patients.

PURPOSE: The purpose of this is to compare efficacy, safety, and cost outcomes in patients who have received either inhaled epoprostenol (iEPO) or inhaled nitric oxide (iNO) for hypoxic respiratory failure. MATERIALS AND METHODS: This is a retrospective, single-center analysis of adult, mechanically ventilated patients receiving iNO or iEPO for improvement in oxygenation. RESULTS: We evaluated 105 mechanically ventilated patients who received iEPO (52 patients) or iNO (53 patients) between January 2009 and October 2010. Most patients received therapy for acute respiratory distress syndrome (iNO 58.5% vs iEPO 61.5%; P=.84). There was no difference in the change in the partial pressure of arterial O2/fraction of inspired O2 ratio after 1 hour of therapy (20.58±91.54 vs 33.04±36.19 [P=.36]) in the iNO and iEPO groups, respectively. No difference was observed in duration of therapy (P=.63), mechanical ventilation (P=.07), intensive care unit (P=.67), and hospital lengths of stay (P=.26) comparing the iNO and iEPO groups. No adverse events were attributed to either therapy. Inhaled nitric oxide was 4.5 to 17 times more expensive than iEPO depending on contract pricing. CONCLUSIONS: We found no difference in efficacy and safety outcomes when comparing iNO and iEPO in hypoxic, critically ill patients. Inhaled epoprostenol is associated with less drug expenditure than iNO.

Tracheostomy care: a clinician's guide.

Tracheostomies have become a typical component of the management of patients with prolonged respiratory failure. There are, however, relatively few studies from which to establish an accepted standard of care with regard to the specific features, daily care, and removal of tracheostomy tubes. Consequently, these decisions are sometimes guided by myth and misconception. In this article, we review the different types of tracheostomy tubes with their respective advantages and disadvantages, basic principles of care, recognition of complications, speech with a tracheostomy tube, and the process by which they may sometimes be removed.

Tracheostomy tube malposition in patients admitted to a respiratory acute care unit following prolonged ventilation.

BACKGROUND: Tracheostomy tube malposition is a barrier to weaning from mechanical ventilation. We determined the incidence of tracheostomy tube malposition, identified the associated risk factors, and examined the effect of malposition on clinical outcomes. METHODS: We performed a retrospective study on 403 consecutive patients with a tracheostomy who had been admitted to an acute care unit specializing in weaning from mechanical ventilation between July 1, 2002, and December 31, 2005. Bronchoscopy reports were reviewed for evidence of tracheostomy tube malposition (ie, > 50% occlusion of lumen by tissue). The main outcome parameters were the incidence of tracheostomy tube malposition; demographic, clinical, and tracheostomy-related factors associated with malposition; clinical response to correct the malposition; the duration of mechanical ventilation; the length of hospital stay; and mortality. RESULTS: Malpositioned tracheostomy tubes were identified in 40 of 403 patients (10%). The subspecialty of the surgical service physicians who performed the tracheostomy was most strongly associated with malposition. Thoracic and general surgeons were equally likely to have their patients associated with a malpositioned tracheostomy tube, while other subspecialty surgeons were more likely (odds ratio, 6.42; 95% confidence interval, 1.82 to 22.68; p = 0.004). Malpositioned tracheostomy tubes were changed in 80% of cases. Malposition was associated with prolonged mechanical ventilation posttracheostomy (median duration, 25 vs 15 d; p = 0.009), but not with increased hospital length of stay or mortality. CONCLUSION: Tracheostomy tube malposition appears to be a common and important complication in patients who are being weaned from mechanical ventilation. Surgical expertise may be an important factor that impacts this complication.