Kress 2000

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Daily interruption of sedative infusions

  • Included 128 mechanically ventilated patients in a single-center medical ICU
  • All patients received morphine infusions for analgesia, randomized to either midazolam or propofol infusions for sedation, and again randomized to either “daily interruption” or standard of care
  • Daily interruption protocol: Each day, morphine and sedative infusions were stopped until the patient was awake and could follow commands or became agitated. “Awake” was defined as following 3 of the 4 actions: open eyes to voice, use eyes to follow investigator on request, squeeze hand on request, stick out tongue on request.
  • Primary endpoints were duration of mechanical ventilation, ICU and hospital length of stay
  • Daily awakening decreased duration of mechanical ventilation (4.9 vs. 7.3 days, p=0.004) and ICU length of stay (6.4 vs. 9.9 days, p=0.02).
  • There was no difference in hospital length of stay or mortality.
  • The benefit of time on the vent and ICU length of stay was significant in both midazolam and propofol arms
  • Patients with daily interruption had fewer diagnostic scans to assess mental status (6 vs. 16 tests, p=0.02) and did not have a higher incidence of self-extubation or self removal of central lines


Medical ICU patients receiving continuous infusion sedation with daily interruption were liberated from mechanical ventilation and left the ICU quicker, but this effect did not translate to a shorter hospital course or a mortality benefit.

See the paper here

Kumar 2006

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Delay in antibiotics increases septic shock mortality

  • Retrospective cohort of 2,731 septic shock patients from the US and Canada
  • Study spanned from 1989-2004 (long time period introduces temporal confounding with changes in practice)
  • Onset of hypotension to first appropriate antibiotic very delayed (median 6 hrs, mean 13.5 hrs)
  • Overall mortality rate of 56.2% (very high for septic shock)
  • Every hour of delay resulted in a mean 7.6% increase in mortality (range 3.6-9.9%)
  • Interestingly, in patients who initiated antimicrobial before the onset of shock, mortality rates were quite high (52.2%) –roughly the same mortality rate as waiting 5-6 hours after the onset of shock


Among patients with septic shock, every hour of delay in appropriate antibiotic administration was associated with a significant increase in mortality.

See the paper here


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