Ferguson ND, Cook DJ, Guyatt GH, Mehta S, Hand L, Austin P, et al. High-frequency oscillation in early acute respiratory distress syndrome. N Engl J Med. 2013 Feb 28; 368(9): 795-805. This international, multicenter, randomized, controlled trial examined the use of high-frequency oscillatory ventilation (HFOV) versus standard ventilation with a low-tidal-volume, high-positive-end-expiratory-pressure (PEEP) approach in the treatment of early acute reparatory distress syndrome (ARDS). A total of 273 patients were included in the “control” arm—those receiving standard ventilation as described above—while 275 patients were included in the “experimental” HFOV arm of the trial. Sample populations were well matched at baseline. The intended primary outcome of the study was all-cause, in-hospital mortality; however, the study was terminated prematurely due to a significant mortality difference between the groups. 129 patients (47%) in the HFOV group versus 96 patients (35%) in the control group expired in the hospital throughout the course of the trial (p=0.005). Subgroup analysis demonstrated an increased use of vasopressors (p=0.001) as well as an increased use of neuromuscular blockers (p<0.001) in the HFOV group within the first day of therapy. There was no association between mortality and baseline severity of hypoxemia, respiratory compliance, body-mass index, use of vasopressors, or center experience. This study concludes a positive association between HFOV and mortality when applied early in the treatment of moderate-to-severe ARDS compared to ARDS-directed standard ventilation. The major limitations of this study include reliance on an HFOV protocol that is based on minimal human-derived evidence in addition to the early termination of the study, which decreases its statistical power and may overinflate the scale of its results.

- Emel


Glaser NS, Wootton-Gorges SL, Buonocore MH, et al. Subclinical cerebral edema in children with diabetic ketoacidosis randomized to 2 different rehydration protocols. Pediatrics. January 2013; 131(1):E73-80.  This single center randomized pilot study evaluated differences in the development of subclinical cerebral edema in pediatric patients with DKA randomized to either slower or more rapid fluid rehydration.  Patients were between the ages of 8-18 years of age with type 1 DM who presented to the Emergency Department in DKA.  DKA was defined as serum glucose >300 mg/dL, venous pH <7.25 or serum bicarb <15 mEq/L, and a positive test for urine ketones.  The degree of subclinical cerebral edema was determined using Diffusion weighted MRI imaging, comparing their apparent diffusion coefficients.  MRIs were performed at 3 time points: 3-6 hours after treatment initiation, 9-12 hours after treatment initiation, and after recovery from DKA.  A total of 20 DKA events were included from 18 patients (2 patients were enrolled twice, for separate DKA events).  18 events were included in the final analysis as 2 patients in the rapid resuscitation group were unable to complete their MRI studies, one due to severe claustrophobia and one due to clinical instability.  Investigators found no significant difference between the groups in ADC at any of the time periods evaluated.  Additionally, there were no significant differences in the rates of change for various biochemical values including pH, pCO2, serum glucose, serum sodium, and osmolality. 

This study effectively shows that the rate of fluid resuscitation does not directly correlate with the development of cerebral edema.  That being said, there are several limitations.  This was a small study which made detections of small differences between groups difficult.  It is also unknown whether ADC changes correlate with risk of clinically apparent cerebral edema.  This study should re-assure clinicians treating patients in DKA that rapid fluid resuscitation is safe and does not directly result in cerebral edema.  It remains to be seen from larger studies of other various fluid resuscitation strategies, whether the choice of fluids is associated with cerebral edema.

-  Chenoweth