UMEM Educational Pearls - By Quincy Tran

Settings: multicenter, double-blind, phase 3 trial (apparently vitamin D worked in phase 2 trials).

  • Patients:
    • 1059 patients were enrolled within 12 hours of ICU admission.  The patients had to have risk factors warranted ICU admisions (pneumonia, sepsis, mechanical ventilation, shock, pancreatitis, etc.).
    • Vitamin D deficiency was defined as plasma level < 20 ng/ml
  • Intervention:
    • 531 patients received a single oral dose of 540,000 IU of vitamin D3 within 2 hours after randomization
  • Comparison
    • 528 patients received placebo
  • Outcome
    • 90-day all-cause mortality

Study Results:

  • Total SOFA score was similar in both groups (5.6 vs. 5.4).               
  • On day 3, mean plasma vitamin D was higher (47 ng/ml) in treatment group vs 11 ng/ml in placebo group
  • 90-day all cause mortality was similar.  Treatment group was 23.5% vs. 20.6% for placebo (95% CI, −2.1 to 7.9; P = 0.26).
  • Vitamin D-related adverse events were similar in both groups.

Discussion:

  • This trial enrolled patients early in their critical illness compared to phase 2 trial which enrolled patients after 3 days in the ICU.
  • This phase 3 trial also enrolled mostly medical-related illness, whereas 75% of patients in phase 2 had either surgical or neurology-related illnesses.

Conclusion:

Early administration of high dose vitamin D did not improve 90-day all cause mortality.

 

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Category: Critical Care

Title: Conservative oxygenation during mechanical ventilation

Keywords: conservative oxygenation (PubMed Search)

Posted: 11/26/2019 by Quincy Tran, MD (Updated: 1/24/2020)
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Settings

  • Patients: mechanical ventilation in the ICU. Randomization of 1000 patients.
  • Intervention: conservative oxygen therapy, if spO2 reached 97%, then FiO2 was lowered to 0.21
  • Comparison: no specific limits for FiO2 or SpO2.
  • Outcome: number of ventilator-free days at 28 days after randomization.

Study Results:

  • 484 conservative-oxygen group vs  481 to the usual oxygen group
  • Comparing to the conservative-oxygen group had:
  • more time at FiO2 21 (29 hours vs. 28 hours),
  • less time with SpO2 > 97% (27 hours vs. 49 hours)
  • Similar ventilator-free days: 21 days vs. 22 days.

Discussion:

This study’s results differed from previous single center study (Girardis JAMA 2016) or meta analysis (Chu DK, Lancer 2018), which showed mortality benefit in patients with conservative oxygen (Girardis & Chu) and more ventilator-free days (Girardis).

Conclusion: Conservative oxygen did not significantly affect the ventilator free days of mechanically ventilated patients.

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Rationale: Data regarding temperature management in patients suffered from cardiac arrest with nonshockable rhythm was inconclusive.

Objective: whether moderate hypothermia at 33C, compared with normothermia at 37C would improve neurologic outcome in patients with coma after cardiac arrest with nonshockable rhythm.

Outcome: survival with favorable 90-day neurologic outcome (Cerebral Performance Category scale 1-2/5)

SummaryThere was higher percentage of patients achieving CPC 1-2 in the hypothermia group (10.2%) vs normothermia group (5.7%, Hazard Ratio 4.5, 95% CI 0.1-8.9, p=0.04)

This randomized multicenter trial involved 581 patients with cardiac arrest and nonshockable rhythm.  Hypothermia group included 284 patients vs. 297 in the normothermia group.  Median GCS at enrollment = 3.

Majority of patients was cooled with the use of a basic external cooling device: 37% for hypothermia and 50.8% for normothermia group.

There was higher percentage of patients achieving CPC 1-2 in the hypothermia group (10.2%) vs normothermia group (5.7%, Hazard Ratio 4.5, 95% CI 0.1-8.9, p=0.04)

Limitation:

A. The study used strict enrollment criteria:

  1. CPR initiation within 10 minutes;
  2. CPR to ROSC within 60 minutes;
  3. epinephrine or norepinephrine infusion at < 1 ug/kg/min;
  4. No Child-Pugh class C liver cirrhosis

B. normothermia group had higher proportion of patients with temperature at 38C.

C. Hypothermia group underwent temperature management of 56 hours vs. 48 hours for normothermia patients.

Take home points:

In a selected group of patients with cardiac arrest and nonshockable rhythm, moderate hypothermia at 33C may improve neurologic outcome.

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Category: Critical Care

Title: Torsades de pointes and QT prolongation Associated with Antibiotics

Keywords: Torsades de pointes, QT prolongation, antibiotics (PubMed Search)

Posted: 8/20/2019 by Quincy Tran, MD (Updated: 1/24/2020)
Click here to contact Quincy Tran, MD

A new study confirmed the previously-known antibiotics to be associated with Torsades de pointes and QT prolongation (Macrolides, Linezolid, Imipenem and Fluoroquinolones). However, this study found new association between amikacin and Torsades de pointes/QT prolongation.

Methods

The authors queried the United States FDA Adverse Event Reporting System (FAERS) from 01/01/2015 to 12/31/2017 for reports of Torsade de points/QT prolongation (TdP/QT).

Reporting Odd Ratio (ROR) was calculated as the ratio of the odds of reporting TdP/QTP versus all other ADRs for a given drug, compared with these reporting odds for all other drugs present in FAERS

Results

FAERS contained 2,042,801 reports from January 1, 2015 to December 31, 2017. There were 3,960 TdP/QTP reports from the study period (0.19%).

 

Macrolides               ROR 14 (95% CI 11.8-17.38)

Linezolid                  ROR 12 (95% CI 8.5-18)

Amikacin                 ROR 11.8 (5.57-24.97)

Imipenem-cilastatin ROR 6.6 (3.13-13.9)

Fluoroquinolones   ROR 5.68 (95% CI 4.78-6.76)

 

Limitations:

These adverse events are voluntary reports

There might be other confounded by concomitant drugs such as ondansetron, azole anti-fungals, antipsychotics.

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Category: Critical Care

Title:

Keywords: amikacin, Torsades de pointes, QT prolongation (PubMed Search)

Posted: 8/20/2019 by Quincy Tran, MD (Emailed: 1/24/2020)
Click here to contact Quincy Tran, MD

Torsades de pointes and QT prolongation Associated with Antibiotics

 

Methods

The authors queried the United States FDA Adverse Event Reporting System (FAERS) from 01/01/2015 to 12/31/2017 for reports of Torsade de points/QT prolongation (TdP/QT).

Reporting Odd Ratio (ROR) was calculated as the ratio of the odds of reporting TdP/QTP versus all other ADRs for a given drug, compared with these reporting odds for all other drugs present in FAERS

Results

FAERS contained 2,042,801 reports from January 1, 2015 to December 31, 2017. There were 3,960 TdP/QTP reports from the study period (0.19%).

 

Macrolides               ROR 14 (95% CI 11.8-17.38)

Linezolid                  ROR 12 (95% CI 8.5-18)

Amikacin                 ROR 11.8 (5.57-24.97)

Imipenem-cilastatin ROR 6.6 (3.13-13.9)

Fluoroquinolones   ROR 5.68 (95% CI 4.78-6.76)

 

Limitations:

These adverse events are voluntary reports

There might be other confounded by concomitant drugs such as ondansetron, azole anti-fungals, antipsychotics.

 

Bottom Line:

This study confimed the previously-known antibiotics to be associated with Torsades de pointes and QT prolongation (Macrolides, Linezolid, Imipenem and Fluoroquinolones). However, this study  found new association between amikacin and Torsades de pointes/QT prolongation.

Show References