Decra
- Included 155 adult patients (15-59 yrs) with severe, nonpenetrating traumatic brain injury (GCS 3 to 8) and elevated ICP despite first-tier medical therapy
- Elevated ICP defined as spontaneous ICP > 20 for at least 15 minutes (note that this is a low threshold and a short duration for intracranial hypertension)
- Excluded patients with dilated, unreactive pupils and mass lesions that would normally require surgical intervention
- Randomized to bifrontotemporoparietal decompressive craniectomy (without division of sagittal sinus and falx cerebri) plus standard of care or standard of care alone
- Baseline characteristics were balanced with the exception of pupil reactivity (surgical group with worse baseline)
- Primary endpoint (6-month functional outcome) was worse with craniectomy than standard of care alone (median 3 vs. 4, OR 1.84, p=0.03)
- Unfavourable outcome (death, vegetative state, severe disability) was more common with craniectomy (70% vs. 51%, OR 2.21, p=0.02, NNH 5). Vegetative state was the primary driver for the difference in the composite score
- After post-hoc adjustment for imbalanced pupil reactivity, neither functional (p=0.15) or unfavorable outcomes (p=0.07) were significantly different
- Craniectomy resulted in reduced ICP (14.4 vs. 19.1, p<0.001) and fewer interventions for elevated ICP
- Patients in the craniectomy group had shorter duration of mechanical ventilation (11 vs. 15 days, p<0.001) and shorter ICU length of stay (13 vs. 18 days, p<0.001)
- Hydrocephalus was more common with craniectomy
- Over 95% of screened patients were ineligible for study inclusion (155 of 3478), most commonly due to mass lesion or positive response to first-tier therapy — limits external validity
- The RESCUEicp study appears to conflict with DECRA, but RESCUEicp actually had a very different design. In RESCUEicp, craniectomy was used later (more of a last-line modality) among more severely ill patients (as demonstrated by a 6-month mortality of about 19% vs. 38%).
- DECRA and RESCUEicp highlight the importance of selecting the appropriate patient for craniectomy.
TBL
Early bifrontotemporoparietal decompressive craniectomy reduces ICP in patients with severe traumatic brain injury without mass lesions, but does not improve (and may worsen) functional or unfavorable outcomes.
Dose
- Included 308 patients with acute decompensated heart failure and a history of home oral furosemide 80-240 mg/day
- Excluded patients with systolic BP < 90 mmHg, creatinine > 3 mg/dL, and those receiving IV vasodilators or inotropic agents (other than digoxin)
- Randomized in 2×2 factorial design to low-dose furosemide (daily IV dose equal to daily home PO dose) or high-dose furosemide (daily IV dose equal to 2.5 times daily home PO dose), and randomized to either bolus (dosed Q12h) or continuous infusion for 72 hours. A 50% dose increase was optional at 48 hours.
- Primary efficacy endpoint (patient’s subjective global assessment of symptoms at 72 hrs) was not different between any group comparison, although there was a trend towards improvement with high-dose over low-dose strategy (mean AUC 4430 vs. 4171, p=0.06)
- Bolus dosing was associated with a higher incidence of a dose increase at 48 hrs (21% vs. 11%, p=0.01)
- High-dose strategy was more likely to switch to oral diuretics at 48 hrs (31% vs. 17%, p<0.001) and was less likely to have a dose increase at 48 hrs (24% vs. 9%, p=0.003)
- Primary safety endpoint (change in creatinine at 72 hrs) was not different between any group comparisons
- A pre-defined secondary safety endpoint of serum creatinine increase of 0.3 mg/dL or more at 72 hrs occurred more frequently with the high-dose strategy (23% vs. 14%, p=0.04, NNH 11), although the clinical significant of this endpoint is unknown
- There was no difference in any group comparison for duration of hospitalization, the composite endpoint of death, rehospitalization, or ED visit within 60 days, or days alive and out of the hospital.
TBL
There is no clinical advantage to a high-dose vs. low-dose furosemide strategy or bolus vs. continuous infusion furosemide. There may be a small signal of subjective benefit in high-dose patients, but high dose was more associated with a small increase in serum creatinine.
Devlin
- Three-center study including 36 patients with delirium (ICDSC >= 4) with a standing order for haloperidol and able to take enteral nutrition
- Randomized patients to quetiapine or placebo until delirium has resolved, 10 days had elapsed, or ICU discharge
- Quetiapine dosing regimen:50 mg PO Q12h increased daily by 50 every 12 hours up to a maximum of 200 mg PO Q12h
- Subjects allowed to receive open-label haloperidol 1-10 mg IV Q2h PRN
- Primary endpoint (time to first resolution of delirium (ICSDC <= 3)) was shorter with quetiapine therapy (1.0 vs. 4.5 days, p=0.001)
- Patients receiving quetiapine spent less time in delirium (36 vs. 120 hrs, p=0.006) and less percent time in delirium (53% vs. 69%, p=0.02, NNT 6)
- Duration of mechanical ventilation, ICU/hospital length of stay, and mortality were not difference between treatment groups
- Quetiapine was not associated with a higher incidence of QTc prolongation (>60 msec increase or > 500 msec)
- Excluded 86% of screened patients (222/258) limiting external validity and potentially underpowering any secondary efficacy or safety analyses
TBL
Quetiapine may result in a faster resolution of delirium and prevent additional episodes of delirium, although this effect does not translate to a shorter length of stay or mortality benefit.
Draculovic
- Single-center study included 86 mechanically ventilated patients
- Excluded recent abdominal surgery, neurosurgery, shock refractory to vasoactive therapy, and previous intubation in the past 30 days
- Randomized patients to semirecumbent (45° head of bed) or supine (0°)
- Suspected pneumonia was defined as new chest radiograph infiltrates with two of the following: fever (≥ 38.3 °C), leukopenia or leukocytosis (≤ 4 or ≥ 12×109/L), purulent tracheal secretions
- Primary endpoint (suspected pneumonia) was reduced with semirecumbent positioning (34% vs. 8%, p=0.003, NNT 4, RRR 76%)
- Secondary endpoint (suspected pneumonia with positive respiratory culture) was reduced with semirecumbent positioning (5% vs. 23%, p=0.018, NNT 6, RRR 78%)
- The incidence rate of suspected pneumonia over time was also reduced with semirecumbent positioning (10.9 per 1000 vent days vs. 41.2 per 1000 vent days)
- About 80% of the cases of suspected pneumonia were late-onset, occurring after 96 hours of mechanical ventilation
- There was no difference in mortality between semirecumbent and supine positions (18% vs. 28%, p=0.289), although this was likely an underpowered analysis
- Multivariate analysis showed that supine body position (OR 6.8), enteral feeding (OR 5.7), mechanical ventilation ≥ 7 days (OR 10.9), and GCS < 9 on admission (OR 4.0) were all independently associated with nosocomial pneumonia
- The largest benefit was seen in patients receiving enteral feeding. Suspected pneumonia with supine positioning and enteral feeding was 50% (14/28) compared to 9% (2/22) with semirecumbent positioning and enteral feeding
TBL
Raising the head of bed to a semirecumbent position reduced suspected and proven nosocomial pneumonia in mechanically ventilated patients.
Key Points
DeGans
- Included 301 patients with suspected meningitis with supporting clinical signs
- Randomized patients to receive dexamethasone 10 mg IV Q6h or placebo x 4 days.
- Treatment was started 0-20 minutes PRIOR to antibiotic administration
- Primary endpoint (unfavorable Glasgow Outcome Scale score of <= 4 at 8 weeks) was lower with dexamethasone (15% vs. 25%, p=0.03, NNT 10)
- The effect on unfavorable outcome was shown with S. pneumoniae meningitis (OR 0.5, p=0.006), but not with N. meningitidis, other bacteria, or a negative CSF culture
- Mortality was reduced with dexamethasone (7% vs. 14%, p=0.04, NNT 14), but was only seen with S. pneumoniae
TBL
Early, empiric treatment with dexamethasone in patients with suspected meningitis improved discharge outcome and mortality, but this effect was only seen among patients with confirmed S. pneumoniae meningitis.
