Acute effect of inhaled iloprost on exercise dynamic hyperinflation in COPD patients: A randomized crossover study.

BACKGROUND AND OBJECTIVE: We tested whether the prostacyclin analog inhaled iloprost modulates dead space, dynamic hyperinflation (DH), and systemic inflammation/oxidative stress during maximal exercise in subjects with chronic obstructive pulmonary disease (COPD) who were not selected based on pulmonary hypertension (PH). METHODS: Twenty-four COPD patients with moderate-severe obstruction (age 59 ± 7 years, FEV1 53 ± 13% predicted) participated in a randomized, double-blind, placebo-controlled crossover trial. Each subject received a single nebulized dose of 5.0 µg iloprost or placebo on non-consecutive days followed by maximal cardiopulmonary exercise tests. The primary outcome was DH quantified by end-expiratory lung volume/total lung capacity ratio (EELV/TLC) at metabolic isotime. RESULTS: Inhaled iloprost was well-tolerated and reduced submaximal alveolar dead-space fraction but did not significantly reduce DH (0.70 ± 0.09 vs 0.69 ± 0.07 following placebo and iloprost, respectively, p = 0.38). Maximal exercise time (9.1 ± 2.3 vs 9.3 ± 2.2 min, p = 0.31) and peak oxygen uptake (17.4 ± 6.3 vs 17.9 ± 6.9 mL/kg/min, p = 0.30) were not significantly different following placebo versus iloprost. CONCLUSIONS: A single dose of inhaled iloprost was safe and reduced alveolar dead space fraction; however, it was not efficacious in modulating DH or improving exercise capacity in COPD patients who were not selected for the presence of PH.

A Multicenter Randomized Trial of a Checklist for Endotracheal Intubation of Critically Ill Adults.

BACKGROUND: Hypoxemia and hypotension are common complications during endotracheal intubation of critically ill adults. Verbal performance of a written, preintubation checklist may prevent these complications. We compared a written, verbally performed, preintubation checklist with usual care regarding lowest arterial oxygen saturation or lowest systolic BP experienced by critically ill adults undergoing endotracheal intubation. METHODS: A multicenter trial in which 262 adults undergoing endotracheal intubation were randomized to a written, verbally performed, preintubation checklist (checklist) or no preintubation checklist (usual care). The coprimary outcomes were lowest arterial oxygen saturation and lowest systolic BP between the time of procedural medication administration and 2 min after endotracheal intubation. RESULTS: The median lowest arterial oxygen saturation was 92% (interquartile range [IQR], 79-98) in the checklist group vs 93% (IQR, 84-100) with usual care (P = .34). The median lowest systolic BP was 112 mm Hg (IQR, 94-133) in the checklist group vs 108 mm Hg (IQR, 90-132) in the usual care group (P = .61). There was no difference between the checklist and usual care in procedure duration (120 vs 118 s; P = .49), number of laryngoscopy attempts (one vs one attempt; P = .42), or severe life-threatening procedural complications (40.8% vs 32.6%; P = .20). CONCLUSIONS: The verbal performance of a written, preprocedure checklist does not increase the lowest arterial oxygen saturation or lowest systolic BP during endotracheal intubation of critically ill adults compared with usual care. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02497729; URL: www.clinicaltrials.gov.

A Multicenter, Randomized Trial of Ramped Position vs Sniffing Position During Endotracheal Intubation of Critically Ill Adults.

BACKGROUND: Hypoxemia is the most common complication during endotracheal intubation of critically ill adults. Intubation in the ramped position has been hypothesized to prevent hypoxemia by increasing functional residual capacity and decreasing the duration of intubation, but has never been studied outside of the operating room. METHODS: Multicenter, randomized trial comparing the ramped position (head of the bed elevated to 25°) with the sniffing position (torso supine, neck flexed, and head extended) among 260 adults undergoing endotracheal intubation by pulmonary and critical care medicine fellows in four ICUs between July 22, 2015, and July 19, 2016. The primary outcome was lowest arterial oxygen saturation between induction and 2 minutes after intubation. Secondary outcomes included Cormack-Lehane grade of glottic view, difficulty of intubation, and number of laryngoscopy attempts. RESULTS: The median lowest arterial oxygen saturation was 93% (interquartile range [IQR], 84%-99%) with the ramped position vs 92% (IQR, 79%-98%) with the sniffing position (P = .27). The ramped position appeared to increase the incidence of grade III or IV view (25.4% vs 11.5%, P = .01), increase the incidence of difficult intubation (12.3% vs 4.6%, P = .04), and decrease the rate of intubation on the first attempt (76.2% vs 85.4%, P = .02), respectively. CONCLUSIONS: In this multicenter trial, the ramped position did not improve oxygenation during endotracheal intubation of critically ill adults compared with the sniffing position. The ramped position may worsen glottic view and increase the number of laryngoscopy attempts required for successful intubation. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02497729; URL: www.clinicaltrials.gov.

Missed Opportunities for Health Promotion Intervention in the Management of Alcohol Withdrawal Syndrome.

OBJECTIVE: We aimed to characterize utilization of evidence-based health promotion practices not included in Alcohol Withdrawal Syndrome (AWS) guidelines, such as vaccinations and counseling services, hypothesizing that missed opportunities for health promotion intervention would abound. METHODS: Retrospective medical record review of 99 patients presenting to a safety-net academic medical center with AWS between August 1, 2012 and March 31, 2013. RESULTS: Thiamine replacement (70%), tobacco cessation counseling (28%), influenza or pneumonia vaccination (25% and 28% respectively), psychiatric counseling (70%), referral to alcohol support group or treatment center(40%), and screening for viral hepatitis and HIV (39% and 44%, respectively) were documented by healthcare providers at lower than optimal frequency. CONCLUSIONS: Provision of health promotion interventions was not consistent with evidence-based practices. Integration of these measures into AWS protocols and guidelines could help clinicians provide consistent, cost-effective, evidence- based care.

Persistent fever in the ICU.

Disorders of elevated body temperature may be classified as either fever or hyperthermia. Fever is caused by a pyrogen-mediated upward adjustment of the hypothalamic thermostat; hyperthermia results from a loss of physiologic control of temperature regulation. Fever in the ICU can be due to infectious or noninfectious causes. The initial approach to a febrile, critically ill patient should involve a thoughtful review of the clinical data to elicit the likely source of fever prior to the ordering of cultures, imaging studies, and broad-spectrum antibiotics. Both high fever and prolonged fever have been associated with increased mortality; however, a causal role for fever as a mediator of adverse outcomes during non-neurologic critical illness has not been established. Outside the realm of acute brain injury, the practice of treating fever remains controversial. To generate high-quality, evidence-based guidelines for the management of fever, large, prospective, multicenter trials are needed.

Enteral omega-3 fatty acid, gamma-linolenic acid, and antioxidant supplementation in acute lung injury.

CONTEXT: The omega-3 (n-3) fatty acids docosahexaenoic acid and eicosapentaenoic acid, along with γ-linolenic acid and antioxidants, may modulate systemic inflammatory response and improve oxygenation and outcomes in patients with acute lung injury. OBJECTIVE: To determine if dietary supplementation of these substances to patients with acute lung injury would increase ventilator-free days to study day 28. DESIGN, SETTING, AND PARTICIPANTS: The OMEGA study, a randomized, double-blind, placebo-controlled, multicenter trial conducted from January 2, 2008, through February 21, 2009. Participants were 272 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. All participants had complete follow-up. INTERVENTIONS: Twice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants compared with an isocaloric control. Enteral nutrition, directed by a protocol, was delivered separately from the study supplement. MAIN OUTCOME MEASURE: Ventilator-free days to study day 28. RESULTS: The study was stopped early for futility after 143 and 129 patients were enrolled in the n-3 and control groups. Despite an 8-fold increase in plasma eicosapentaenoic acid levels, patients receiving the n-3 supplement had fewer ventilator-free days (14.0 vs 17.2; P = .02) (difference, -3.2 [95% CI, -5.8 to -0.7]) and intensive care unit-free days (14.0 vs 16.7; P = .04). Patients in the n-3 group also had fewer nonpulmonary organ failure-free days (12.3 vs 15.5; P = .02). Sixty-day hospital mortality was 26.6% in the n-3 group vs 16.3% in the control group (P = .054), and adjusted 60-day mortality was 25.1% and 17.6% in the n-3 and control groups, respectively (P = .11). Use of the n-3 supplement resulted in more days with diarrhea (29% vs 21%; P = .001). CONCLUSIONS: Twice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants did not improve the primary end point of ventilator-free days or other clinical outcomes in patients with acute lung injury and may be harmful. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00609180.

Plasma adiponectin and mortality in critically ill subjects with acute respiratory failure.

OBJECTIVE: : Adiponectin, an anti-inflammatory cytokine produced by adipose tissue, has been shown to modulate survival in animal models of critical illness. We examined the association between plasma adiponectin and clinical outcomes in critically ill patients with acute respiratory failure. DESIGN: : Secondary analysis of a single-center, randomized controlled trial. SETTING: : Medical intensive care unit of a university-based, tertiary medical center. PATIENTS: : One hundred seventy-five subjects with acute respiratory failure enrolled in randomized, controlled pilot trial of Early versus Delayed Enternal Nutrition (EDEN pilot study). INTERVENTIONS: : None. MEASUREMENTS AND MAIN RESULTS: : Adiponectin measured within 48 hrs of respiratory failure (Apn1) was inversely correlated with body mass index (r=-0.25, p=.007) and was higher in females (median, 12.6 µg/mL; interquartile range, 7.6-17.1) than males (9.45 µg/mL; 6.2-14.2; p=.02). Adiponectin increased at day 6 (Apn1: 11.4 µg/mL [6.6-15.3] vs. Apn6: 14.1 µg/mL [10.3-18.6], p<.001). This increase was significant only in survivors (Δ adiponectin in survivors: 3.9±6 µg/mL, n=80, p<.001 vs. Δ in nonsurvivors: 1.69±4.6 µg/mL, n=14, p=.19). Higher Apn1 was significantly associated with 28-day mortality (odds ratio 1.59 per 5-µg/mL increase; 95% confidence interval 1.15-2.21; p=.006). No measured demographic, clinical, or cytokine covariates, including interleukin-6, interleukin-8, interleukin-10, interleukin-1ß, interleukin-12, tumor necrosis factor-α, and interferon-γ, were confounders or effect modifiers of this association between adiponectin and mortality. CONCLUSIONS: : Independent of measured covariates, increased plasma adiponectin levels measured within 48 hrs of respiratory failure are associated with mortality. This finding suggests that factors derived from adipose tissue play a role in modulating the response to critical illness.

Percutaneous dilational tracheostomy techniques.

In summary, PDT is a bedside procedure that can be performed with very low morbidity by skilled practitioners. Established methods are undergoing constant evolution and we hope that technical adjuncts are improving patient safety. Evaluation of procedural modifications will require evaluation in randomized clinical trials.