Association of Elevated Plasma Interleukin-18 Level With Increased Mortality in a Clinical Trial of Statin Treatment for Acute Respiratory Distress Syndrome.

OBJECTIVE: A high plasma level of inflammasome mediator interleukin-18 was associated with mortality in observational acute respiratory distress syndrome cohorts. Statin exposure increases both inflammasome activation and lung injury in mouse models. We tested whether randomization to statin therapy correlated with increased interleukin-18 in the ARDS Network Statins for Acutely Injured Lungs from Sepsis trial. DESIGN: Retrospective analysis of randomized controlled clinical trial. SETTING: Multicenter North American clinical trial, the ARDS Network Statins for Acutely Injured Lungs from Sepsis. PATIENTS: Six hundred eighty-three subjects with infection-related acute respiratory distress syndrome, representing 92% of the original trial population. INTERVENTIONS: Random assignment of rosuvastatin or placebo for up to 28 days or 3 days after ICU discharge. MEASUREMENTS AND MAIN RESULTS: We measured plasma interleukin-18 levels in all Statins for Acutely Injured Lungs from Sepsis patients with sample available at day 0 (baseline, n = 683) and day 3 (after randomization, n = 588). We tested the association among interleukin-18 level at baseline, rising interleukin-18, and the impact of statin therapy on 60-day mortality, adjusting for severity of illness. Baseline plasma interleukin-18 level greater than or equal to 800 pg/mL was highly associated with 60-day mortality, with a hazard of death of 2.3 (95% CI, 1.7-3.1). Rising plasma interleukin-18 was also associated with increased mortality. For each unit increase in log2 (interleukin-18) at day 3 compared with baseline, the hazard of death increased by 2.3 (95% CI, 1.5-3.5). Subjects randomized to statin were significantly more likely to experience a rise in plasma interleukin-18 levels. Subjects with acute kidney injury, shock, low baseline interleukin-18, and those not receiving systemic corticosteroids were more likely to experience rising interleukin-18. Randomization to statin therapy was associated with rising in interleukin-18 in all of those subsets, however. CONCLUSIONS: Elevated baseline plasma interleukin-18 was associated with higher mortality in sepsis-induced acute respiratory distress syndrome. A rise in plasma interleukin-18 was also associated with increased mortality and was more common in subjects randomized to statin therapy in this clinical trial.

Randomized trial of initial trophic versus full-energy enteral nutrition in mechanically ventilated patients with acute respiratory failure.

OBJECTIVE: Enteral nutrition is provided to mechanically ventilated patients who cannot eat normally, yet the amount of support needed is unknown. We conducted this randomized, open-label study to test the hypothesis that initial low-volume (i.e., trophic) enteral nutrition would decrease episodes of gastrointestinal intolerance/complications and improve outcomes as compared to initial full-energy enteral nutrition in patients with acute respiratory failure. DESIGN: Randomized, open-label study. PATIENTS: A total of 200 patients with acute respiratory failure expected to require mechanical ventilation for at least 72 hrs. INTERVENTIONS: Patients were randomized to receive either initial trophic (10 mL/hr) or full-energy enteral nutrition for the initial 6 days of ventilation. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was ventilator-free days to day 28. Baseline characteristics were similar between the 98 patients randomized to trophic and the 102 patients randomized to full-energy nutrition. At enrollment, patients had a mean Acute Physiology and Chronic Health Evaluation II score of 26.9 and a PaO2/FiO2 ratio of 182 and 38% were in shock. Both groups received similar durations of enteral nutrition (5.5 vs. 5.1 days; p = .51). The trophic group received an average of 15.8% ± 11% of goal calories daily through day 6 compared to 74.8% ± 38.5% (p < .001) for the full-energy group. Both groups had a median of 23.0 ventilator-free days (p = .90) and a median of 21.0 intensive-care-unit-free days (p = .64). Mortality to hospital discharge was 22.4% for the trophic group vs. 19.6% for the full-energy group (p = .62). In the first 6 days, the trophic group had trends for less diarrhea (19% vs. 24% of feeding days; p = .08) and significantly fewer episodes of elevated gastric residual volumes (2% vs. 8% of feeding days; p < .001). CONCLUSION: Initial trophic enteral nutrition resulted in clinical outcomes in mechanically ventilated patients with acute respiratory failure similar to those of early full-energy enteral nutrition but with fewer episodes of gastrointestinal intolerance.

Assessment of post-operative opioid prescribing practices in a community hospital ambulatory surgical center.

OBJECTIVE: To evaluate the prescribing practices and opioid consumption in an ambulatory setting to inform the development of evidence-based guidelines. DESIGN: A prospective study of adults undergoing outpatient open and laparoscopic surgeries over 3 months. One week after discharge, a telephonic interview quantified the number of opioids prescribed and consumed, degree of pain control and satisfaction, and whether additional pain medication was requested. SETTING: Community hospital ambulatory surgery center in Westchester County, New York. PARTICIPANTS: This study included 304 adults undergoing a variety of procedures by surgeons from multiple specialties. MAIN OUTCOME MEASURES: Quantify surgeons' postoperative opioid prescribing compared with patient opioid consumption. RESULTS: Eighty-one percent (N = 245) responded to the survey, of which 64 percent were prescribed opioids. Males and females were equally represented with the mean age of 59.4 years. Of those prescribed opioids, 92 percent filled the prescription. The most commonly prescribed opioids reported by the patients that filled their prescription (N = 145) were oxycodone (36.5 percent), oxycodone/acetaminophen (28.9 percent), and tramadol (22.7 percent). The mean number of opioid pills prescribed was 20 and the mean consumption was 6.7 pills, resulting in an average of 13 retained pills. Only 3.8 percent of the patients prescribed opioids at discharge called their provider for additional analgesia. Despite the low opioid consumption patients reported high satisfaction (4.5 on scale of 0-5) with pain control. Only 10.4 percent reported that the surgeon recommended an over the counter (OTC) analgesic option. There was variability in the amount of opioids prescribed within each surgical category. CONCLUSIONS: One week after outpatient surgery, patients consumed one-third of physician-prescribed opioids, yet they reported high pain management satisfaction. Our study will inform the development of a patient-centered interdisciplinary perioperative education program to more effectively tailor multimodal pain management in ambulatory surgical patients and collaterally reduce the number of retained opioids.