Robert W. Taylor

Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome : Results of a randomized phase II trial

OBJECTIVESnTo evaluate the safety and physiologic response of inhaled nitric oxide (NO) in patients with acute respiratory distress syndrome (ARDS). In addition, the effect of various doses of inhaled NO on clinical outcome parameters was assessed.nnnDESIGNnProspective, multicenter, randomized, double-blind, placebo-controlled study.nnnSETTINGnIntensive care units of 30 academic, teaching, and community hospitals in the United States.nnnPATIENTSnPatients with ARDS, as defined by the American-European Consensus Conference, were enrolled into the study if the onset of disease was within 72 hrs of randomization.nnnINTERVENTIONSnPatients were randomized to receive placebo (nitrogen gas) or inhaled NO at concentrations of 1.25, 5, 20, 40, or 80 ppm.nnnMEASUREMENTS AND MAIN RESULTSnAcute increases in PaO2, decreases in mean pulmonary arterial pressure, intensity of mechanical ventilation, and oxygenation index were examined. Clinical outcomes examined were the dose effects of inhaled NO on mortality, the number of days alive and off mechanical ventilation, and the number of days alive after meeting oxygenation criteria for extubation. A total of 177 patients were enrolled over a 14-month period. An acute response to treatment gas, defined as a PaO2 increase > or =20%, was seen in 60% of the patients receiving inhaled NO with no significant differences between dose groups. Twenty-four percent of placebo patients also had an acute response to treatment gas during the first 4 hrs. The initial increase in oxygenation translated into a reduction in the FIO2 over the first day and in the intensity of mechanical ventilation over the first 4 days of treatment, as measured by the oxygenation index. There were no differences among the pooled inhaled NO groups and placebo with respect to mortality rate, the number of days alive and off mechanical ventilation, or the number of days alive after meeting oxygenation criteria for extubation. However, patients receiving 5 ppm inhaled NO showed an improvement in these parameters. In this dose group, the percentage of patients alive and off mechanical ventilation at day 28 (a post hoc analysis) was higher (62% vs. 44%) than the placebo group. There was no apparent difference in the number or type of adverse events reported among those patients receiving inhaled NO compared with placebo. Four patients had methemoglobin concentrations >5%. The mean inspired nitrogen dioxide concentration in inhaled NO patients was 1.5 ppm.nnnCONCLUSIONSnFrom this placebo-controlled study, inhaled NO appears to be well tolerated in the population of ARDS patients studied. With mechanical ventilation held constant, inhaled NO is associated with a significant improvement in oxygenation compared with placebo over the first 4 hrs of treatment. An improvement in oxygenation index was observed over the first 4 days. Larger phase III studies are needed to ascertain if these acute physiologic improvements can lead to altered clinical outcome.

Endotracheal intubation and mechanical ventilation in severe asthma

Objective:To determine the occurrence rate of complications and mortality in patients with severe asthma requiring endotracheal intubation and mechanical ventilation. Design:Retrospective review of medical records from September 1982 to July 1988. Setting:Urban, teaching hospital serving primarily indigent patients. Patients:Fifty-seven adult patients with asthma requiring tracheal intubation and mechanical ventilation.Interventions: None. Measurements and Main Results:Fifty-seven patients requiring tracheal intubation and mechanical ventilation during 69 hospital admissions were identified. Medication noncompliance and upper respiratory tract infections were recorded as the most frequent precipitating events for exacerbation of asthma. Forty-nine intubations were initiated because of a clinical diagnosis of respiratory distress, but multiple indications were present in 42 admissions. One or more complications occurred in 31 episodes of endotracheal intubation and mechanical ventilation (45%). Death occurred in four (6%) of 69 admissions. Three of the four deaths occurred in patients who had a cardiorespiratory arrest before hospital admission. Conclusions:While complications occurred in 45% of patients with severe asthma requiring intubation and mechanical ventilation, the mortality rate was low. We conclude that intubation and mechanical ventilation in patients with life-threatening asthma are safe and beneficial interventions. (Crit Care Med 1993; 21:1727–1730)

Activated protein C in septic shock: a propensity-matched analysis

IntroductionThe use of human recombinant activated protein C (rhAPC) for the treatment of severe sepsis remains controversial despite multiple reported trials. The efficacy of rhAPC remains a matter of dispute. We hypothesized that patients with septic shock who were treated with rhAPC had an improved in-hospital mortality compared to patients with septic shock with similar acuity who did not receive rhAPC.MethodsThis retrospective cohort study was completed at a large university-affiliated hospital. All patients with septic shock admitted to a 50-bed ICU between July 2003 and February 2009 were included. Patients were treated according to sepsis management guidelines.ResultsA total of 563 septic shock patients were included (110 received rhAPC and 453 did not). Treated and untreated groups were matched in patient characteristics, comorbidities, and physiologic variables in a 1:1 propensity-matched analysis (108 received rhAPC, 108 did not). Mean Acute Physiology And Chronic Health Evaluation II (APACHE II) scores were 24.5 for the matched treated and 23.9 for the matched untreated group (P = 0.54). Receipt of rhAPC was associated with reduced in-hospital mortality (35.2% vs. 53.8%, P = 0.005), similar mean days on vasopressors (2 vs. 2, P = 0.90), similar mean days on mechanical ventilation (9 vs. 8.7, P = 0.80), similar mean length of ICU stay in days (11.0 vs. 11.3, P = 0.90), and similar mean length of hospital stay in days (19.5 vs 27, P = 0.11). No patients in either group had intracranial bleeding; differences in gastrointestinal bleeding and transfusion requirements were not statistically significant.ConclusionsPatients in our institution with septic shock who were treated with rhAPC had a reduced in-hospital mortality compared with patients with septic shock with similar acuity who were not treated with rhAPC. In addition, time on mechanical ventilation, time on vasopressors, lengths of stay and bleeding complications did not differ between the groups.

Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial—PROSPECT: a pilot trial

BackgroundProbiotics are live microorganisms that may confer health benefits when ingested. Randomized trials suggest that probiotics significantly decrease the incidence of ventilator-associated pneumonia (VAP) and the overall incidence of infection in critically ill patients. However, these studies are small, largely single-center, and at risk of bias. The aim of the PROSPECT pilot trial was to determine the feasibility of conducting a larger trial of probiotics to prevent VAP in mechanically ventilated patients in the intensive care unit (ICU).MethodsIn a randomized blinded trial, patients expected to be mechanically ventilated for ≥72xa0hours were allocated to receive either 1u2009×u20091010 colony-forming units of Lactobacillus rhamnosus GG or placebo, twice daily. Patients were excluded if they were at increased risk of L. rhamnosus GG infection or had contraindications to enteral medication. Feasibility objectives were: (1) timely recruitment; (2) maximal protocol adherence; (3) minimal contamination; and (4) estimated VAP rate ≥10xa0%. We also measured other infections, diarrhea, ICU and hospital length of stay, and mortality.ResultsOverall, in 14 centers in Canada and the USA, all feasibility goals were met: (1) 150 patients were randomized in 1xa0year; (2) protocol adherence was 97xa0%; (3) no patients received open-label probiotics; and (4) the VAP rate was 19xa0%. Other infections included: bloodstream infection (19.3xa0%), urinary tract infections (12.7xa0%), and skin and soft tissue infections (4.0xa0%). Diarrhea, defined as Bristol type 6 or 7 stools, occurred in 133 (88.7xa0%) of patients, the median length of stay in ICU was 12xa0days (quartile 1 to quartile 3, 7–18 days), and in hospital was 26xa0days (quartile 1 to quartile 3, 14–44 days); 23 patients (15.3xa0%) died in the ICU.ConclusionsThe PROSPECT pilot trial supports the feasibility of a larger trial to investigate the effect of L. rhamnosus GG on VAP and other nosocomial infections in critically ill patients.Trial registrationClinicaltrials.gov NCT01782755. Registered on 29 January 2013.

Risk factors for and prediction of mortality in critically ill medical-surgical patients receiving heparin thromboprophylaxis

AbstractBackgroundnPrevious studies have suggested that prediction models for mortality should be adjusted for additional risk factors beyond the Acute Physiology and Chronic Health Evaluation (APACHE) score. Our objective was to identify risk factors independent of APACHE II score and construct a prediction model to improve the predictive accuracy for hospital and intensive care unit (ICU) mortality.nMethodsWe used data from a multicenter randomized controlled trial (PROTECT, Prophylaxis for Thromboembolism in Critical Care Trial) to build a new prediction model for hospital and ICU mortality. Our primary outcome was all-cause 60-day hospital mortality, and the secondary outcome was all-cause 60-day ICU mortality.ResultsWe included 3746 critically ill non-trauma medical–surgical patients receiving heparin thromboprophylaxis (43.3xa0% females) in this study. The new model predicting 60-day hospital mortality incorporated APACHE II score (main effect: hazard ratio (HR)xa0=xa00.97 for per-point increase), body mass index (BMI) (main effect: HRxa0=xa00.92 for per-point increase), medical admission versus surgical (HRxa0=xa01.67), use of inotropes or vasopressors (HRxa0=xa01.34), acetylsalicylic acid or clopidogrel (HRxa0=xa01.27) and the interaction term between APACHE II score and BMI (HRxa0=xa01.002 for per-point increase). This model had a good fit to the data and was well calibrated and internally validated. However, the discriminative ability of the prediction model was unsatisfactory (C indexxa0<xa00.65). Sensitivity analyses supported the robustness of these findings. Similar results were observed in the new prediction model for 60-day ICU mortality which included APACHE II score, BMI, medical admission and invasive mechanical ventilation.ConclusionCompared with the APACHE II score alone, the new prediction model increases data collection, is more complex but does not substantially improve discriminative ability.n Trial registration: ClinicalTrials.gov Identifier: NCT00182143

Foreign-body pneumonitis associated with tracheostomy.

Foreign-body aspiration in adults is usually associated with asphyxiation after aspiration of food particles. The present report documents a case of foreign-body aspiration that resulted from poor tracheostomy care in an alcoholic patient, and caused fulminant pneumonitis.

Gut Motility Issues in Critical Illness.

Acute gastrointestinal injury (AGI) is common in critical illness and negatively affects outcome. A variety of definitions have been used to describe AGI, which has led to clinical confusion and hampered comparison of research studies across institutions. An international working group of the European Society of Intensive Care Medicine was convened to standardize definitions for AGI and provide current evidence-based understanding of its pathophysiology and management. This disorder is associated with a wide variety of signs and symptoms and may be difficult to detect, therefore a high index of suspicion is warranted.