CCR-Newsletter-Banner

 

 

American Thoracic Society Meeting Update / May 19th 2019

Welcome

 

Hello

Welcome to a supplemental Critical Care Reviews Newsletter, bringing you the major research studies presented at the 2014 American Thoracic Society meeting in San Diego, and contemporaneously published in JAMA and NEJM.

SAILS

 
The ARDSnet group performed a blinded, multicenter, randomized, controlled trial comparing rosuvastatin with placebo in 745 critically ill, mechanically ventilated patients with sepsis-associated ARDS, and found:
  1. the study was stopped early for futility
    • 745 out of a planned 1000 patients were recruited
  2. both groups were similar for
    • demographics
    • physiology
  3. there were no significant differences in
    • 60-day in-hospital mortality
      • rosuvastatin: 28.5% vs placebo 24.9% (P=0.21) 
    • ventilator-free days (mean ±SD)
      • rosuvastatin: 15.1±10.8 vs placebo 15.1±11.0 (P=0.96)
    • serum creatine kinase levels above 10 times the upper limit of normal
  4. rosuvastatin was associated with fewer days free of
    • renal failure to day 14
      • 10.1±5.3 vs. 11.0±4.7 (P=0.01)
    • hepatic failure to day 14
      • 10.8±5.0 vs. 11.8±4.3 (P=0.003)

Full Text:  The National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome (SAILS). New Engl J Med 2014;epublished May 18th

Back to Top ↑ 

OPTIMISE

Pearse and colleagues completed a pragmatic, multicenter, randomized, observer-blinded trial of 734 high-risk UK patients aged 50 years or older, undergoing major gastrointestinal surgery, comparing the effectiveness of a perioperative, cardiac output–guided hemodynamic therapy algorithm consisting of IV fluid and dopexamine infusion during and 6 hours following surgery (n=368) with standard care (n=366), as well as a systematic review and meta analysis evaluating perioperative goal directed care, and found:

  1. in the randomized controlled trial
    • groups were similar at baseline
    • nonadherence was < 10% in each group
    • the hemodynamic therapy algorithm was associated with
      • a trend towards a reduction in composite outcome of 30-day complications and mortality (1° outcome)
        • 36.6% vs 43.4% (RR 0.84, 95% CI 0.71 to 1.01; absolute risk reduction 6.8%, 95% CI −0.3% to 13.9%; P = 0.07)
      • no significant difference between groups for any secondary outcomes.
        • morbidity on day 7
          • 66.2% vs 67.9%; RR 0.97, 95% CI 0.87 to 1.09; P=0.72
        • infectious complications at day 30
          • 23.8% vs 29.7%; RR 0.80, 95% CI 0.63 to 1.02; P=0.08
        • critical care–free days at day 30
          • 27 vs 28; P=0.98
        • all-cause mortality at 30 days following surgery
          • 3.3% vs 3.0%; RR 1.08, 95% CI 0.48 to 2.43; P>0.99
        • all-cause mortality at 180 days following surgery
          • 7.7% vs 11.6%; RR 0.66, 95% CI 0.42 to 1.05; P=0.08
        • duration of acute hospital length of stay
          • 10 vs 11; P=0.05
        • a trend for increased cardiovascular serious adverse events within 24 hours (1.4% (n=5) vs 0) (P = 0.06)
  2. in the meta analysis (38 studies, n=6,595)
    • perioperative goal-directed therapy was associated with
      • fewer complications
        • 31.5% vs 41.6%; RR 0.77, 95% CI 0.71 to 0.83
      • nonsignificant reductions in mortality
        • hospital / 28-day / 30-day 
          • 4.9% vs 6.5%; RR 0.82, 95% CI 0.67 to 1.01
        • at longest follow-up
          • 8.3% vs 10.3%; RR 0.86, 95% CI 0.74 to 1.00

Full Text:  Pearse. Effect of a Perioperative, Cardiac Output–Guided Hemodynamic Therapy Algorithm on Outcomes Following Major Gastrointestinal SurgeryA Randomized Clinical Trial and Systematic Review (OPTIMISE). JAMA 2014;epublished May 19th

Back to Top ↑

Contribution of Sepsis to Mortality

Liu and colleagues quantified the contribution of sepsis to mortality in 2 complementary inpatient cohorts from Kaiser Permanente Northern California (n=482,828) and the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (n=6,500,000), and found:

  1. the number of sepsis hospitalizations were
    • KPNC cohort
      • 55,008 explicit (11.4% of total; 95% CI 11.3% to 11.5%) 
      • 80,678 implicit (16.7%; 95% CI 16.6% to 16.8%)
    • NIS cohort
      • 280 663 explicit  (4.3%; 95% CI  4.3% to 4.3%)
      • 717,718 implicit (10.9%; 95% CI 10.9% to 11.0%)
  2. the numbers of inpatients dying with a diagnosis of sepsis were
    • KPNC cohort
      • of 14, 206 inpatient deaths
        • explicit sepsis: 36.9% (95% CI 36.1% to 37.7%)
        • implicit sepsis: 55.9% (95% CI 55.1% to 56.7%)
        • nearly all present on admission. 
    • NIS cohort
      • of 143,312 deaths
        • explicit sepsis: 34.7% (95% CI 34.4% to 34.9%) 
        • implicit sepsis: 52.0% (95% CI 51.7% to 52.2%)
  3. In the 2012 linked KPNC subset
    • patients with sepsis meeting criteria for EGDT (n = 2,536)
      • comprised 32.6% (95% CI 30.4% to 34.7%) of sepsis deaths
    • patients with sepsis, normal blood pressure, and measured lactate levels of less than 4 mmol/L (n = 15,095)
      • comprised 55.9% (95% CI 53.6% to 58.1%) of sepsis deaths

Full Text:  Liu.  Hospital Deaths in Patients With Sepsis From 2 Independent Cohorts. JAMA 2014;epublished May 18th

Back to Top ↑

PANTHER-IPF

The Idiopathic Pulmonary Fibrosis Clinical Research Network conducted a randomized, double-blind, placebo-controlled trial, initially comparing three groups consisting of (1) a three-drug regimen of prednisone, azathioprine, and acetylcysteine; (2) acetylcysteine alone; or (3) placebo, but later reduced to a 2 group comparison (acetylcysteine (n=133) vs placebo (n=131)), after safety concerns with the three-drug regimen, and found:

  1. at 60 weeks, there were no significant differences in the
    • change in FVC
      • acetylcysteine group: −0.18 liters and placebo group: −0.19 liters (P=0.77)
    • rates of
      • death
        • acetylcysteine group: 4.9% vs. placebo group: 2.5% (P=0.30 by the log-rank test)
      • acute exacerbation
        • 2.3% in each group (P > 0.99)

Full Text:  The Idiopathic Pulmonary Fibrosis Clinical Research Network. Randomized Trial of Acetylcysteine in Idiopathic Pulmonary Fibrosis. New Eng J Med 2014;epublished May 18th

Back to Top ↑

INPULSIS-1 and INPULSIS-2

Richeldi and colleagues completed two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 and INPULSIS-2) comparing nintedanib, a tyrosine kinase inhibitor, 150 mg twice daily with placebo in a 3:2 ratio, in 1,066 patients with idiopathic pulmonary fibrosis, and found:

  1. nintedanib was associated with
    • a smaller adjusted annual rate of change in FVC
      • INPULSIS-1: −114.7 ml vs −239.9 ml; difference 125.3 ml; 95% CI 77.7 to 172.8; P<0.001
      • INPULSIS-2: −113.6 ml vs −207.3 ml; difference 93.7 ml per year; 95% CI 44.8 to 142.7; P<0.001
    • increased time to the first acute exacerbation in IMPULSIS-2 only
      • INPULSIS-2: hazard ratio with nintedanib 0.38; 95% CI 0.19 to 0.77; P=0.005
      • INPULSIS-1: hazard ratio with nintedanib 1.15; 95% CI 0.54 to 2.42; P=0.67
  2. The most frequent adverse event in the nintedanib groups was diarrhoea
    • INPULSIS-1: 61.5% vs 18.6%
    • INPULSIS-2: 63.2% vs 18.3%
      • necessitating drug discontinuation in 5%

Full Text:  Richeldi. Nintedanib in Idiopathic Pulmonary Fibrosis. New Eng J Med 2014;epublished May 18th

Back to Top ↑

ASCEND

King and colleagues performed a randomized, phase 3 study, comparing oral pirfenidone (2,403 mg per day) with placebo for 52 weeks, in 555 patients with idiopathic pulmonary fibrosis, and found:

  1. pirfenidone was associated with
    • a reduction in patients who had an absolute decline of ≥10% of the predicted FVC or who died
      • 16.5%  vs. 31.8%
    • an increase in number of patients with no decline in FVC (P<0.001)
      • 22.7% vs. 9.7%
    • a reduced decline of ≥ 50 meters in the 6-minute walk distance
      • 25.9% vs 35.7% (P=0.04)
    • improved progression-free survival (P<0.001)
    • no significant between-group differences in
      • dyspnea scores (P=0.16)
      • rates of death from
        • any cause (P=0.10)
        • idiopathic pulmonary fibrosis (P=0.23)
  2. in a prespecified pooled analysis incorporating results from two previous phase 3 trials
    • pirfenidone reduced death from
      • any cause (P=0.01)
      • from idiopathic pulmonary fibrosis (P=0.006)

Full Text:  King. Pirfenidone in Idiopathic Pulmonary Fibrosis. New Eng J Med 2014;epublished May 18th

Back to Top ↑

 

I hope you find this brief conference update useful.


Until the weekend

Rob

 

Search