UMEM Educational Pearls - By Quincy Tran

Background:

Lung-protective ventilation with low-tidal volume improves outcome among patients with Acute Respiratory Distress Syndrome.  The use of low tidal volume ventilation in the Emergency Departments has been shown to provide early benefits for critically ill patients.

Methodology:

A systemic review and meta-analysis of studies comparing outcomes of patients receiving low tidal volume ventilation vs. those who did not receive low tidal volume ventilation.

The authors identified 11 studies with approximately 11000 patients.  The studies were mostly observational studies and there was no randomized trials.

The authors included 10 studies in the analysis, after excluding a single study that suggested Non-low tidal volume ventilation was associated with higher mortality than low tidal volume ventilation (1).

Results:

Comparing to those with NON-Low tidal volume ventilation in ED, patients with Low-Tidal volume ventilation in ED were associated with:

  • Significant lower risk of death (OR 0.80, 95% CI 0.72-0.88, I2 = 0%),
  • Lower risk of ARDS (OR 0.57, 95% CI 0.44-0.75, I2 = 21%),
  • Shorter ICU length of stay (Mean Difference -1.19 days [-2.38, -0.11]),
  • Shorter ventilator-free days (-1.03 days, [-1,74, -0.32]).

Discussion:

  • If the outlying study by Prekker et al was included, there as no significant difference in mortality.
  • Tidal volume in ED has been steadily decreased.  It was approximately 9 ml/kg of predicted body weight when reported in 2009, and was approximately 6.5 mg/kg PBW in 2018.
  • Most ventilator settings in the ED would be continued in the ICU.

Conclusion:

Although there was low quality of evidence for low tidal volume ventilation in the ED, Emergency clinicians should continue to consider this strategy.

Show References


Category: Critical Care

Title: APRV or Low Tidal Volume Strategy for patients with COVID-19

Keywords: APRV, low tidal volume, COVID-19 (PubMed Search)

Posted: 4/5/2022 by Quincy Tran, MD (Updated: 6/25/2022)
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During the height of the pandemic, a large proportion of patients who were referred to our center for VV-ECMO evaluation were on Airway Pressure Release Ventilation (APRV).  Does this ventilation mode offer any advantage?  This new randomized control trial attempted to offer an answer.

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1.Settings: RCT, single center

2. Patients: 90 adults patients with respiratory failure due to COVID-19

3. Intervention: APRV with maximum allowed high pressure of 30 cm H20, at time of 4 seconds.  Low pressure was always 0 cm H20, and expiratory time (T-low) at 0.4-0.6 seconds. This T-low time can be adjusted upon analysis of flow-time curve at expiration.

4. Comparison: Low tidal volume (LTV)  strategy according to ARDSNet protocol.

5. Outcome: Primary outcome was Ventilator Free Days at 28 days.

6.Study Results:

  • Baseline characteristics were similar. At randomization, PF ratio for APRV group = 140 (SD 42) vs. 149 (SD 50) for LTV group.
  • Median Ventilator Free Day for APRV group: 3.7 [0-15] days vs. 5.2 [0-19] for LTV group ( P = 0.28)
  • APRV group had higher PaO2/FiO2 ratio during first 7 days (mean difference = 26, P<0.001)
  • ICU length of stay for APRV group: 9 [7-16] vs. 12 [8-17] days (P = 0.17)
  • Severe hypercapnia (Pco2 at ≥ 55 along with a pH < 7.15): APRV group = 19 (42%) vs. LTV = 7 (15%), P = 0.009.
  • Death at 28 days: 35 (78%) for APRV group, vs. 27 (60%) for LTV group ( P = 0.07)

7.Discussion:

  • Hypercapnea was transient and was mostly due to implementation of the ventilator settings.  The protocol recommended reduction of T-high to allow more ventilation, but most clinicians did not want to shorten the T-High, but instead opted for higher T-low.
  • Although the number of barotrauma were similar in both group, all 4 cases of barotrauma in the APRV group occurred within a very short period of time (3 weeks), prompted the safety monitoring board to recommend stopping recruitment for COVID-19 patients.

8.Conclusion:

APRV was not associated with more ventilator free days or other outcomes among patients with COVID-19, when compared to Low Tidal Volume strategies in this small RCT.

 

Show References


Category: Critical Care

Title: Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults

Keywords: Saline, balanced fluid, critically ill, mortality (PubMed Search)

Posted: 2/8/2022 by Quincy Tran, MD (Updated: 6/25/2022)
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The debate is still going on: Whether we should give balanced fluids or normal saline.  

Settings: PLUS study involving 53 ICUs in Australia and New Zealand. This was a double-blinded Randomized Control trial.

  • Patients: A total of 5037 adults who were admitted to any ICU.
  • Intervention: Balanced multielectrolyte solutions (BMES). Once patient is outside the ICU, the type of fluid was decided by the treating physicians.
  • Comparison: Normal saline
  • Outcome: 90-day all cause mortality.

Study Results:

  • Patient characteristics:
    • 2515 patients in BMES group vs. 2522 in Saline group.  Characteristics were similar in both groups.
    • Median fluid amount = 3.9L (BMES group) vs. 3.7L (Saline group).
  • Primary outcome:
    • Mortality = 21.8% (BMES group) vs. 22.0 (Saline), (OR 0.99, 95% CI 0.86-1.14)
  • Secondary outcomes:
    • Requiring Dialysis: OR 0.98 (95% CI 0.83-1.16)
    • Requiring vasopressor: OR 0.92 (95% CI 0.78-1.09)
    • Maximum creatinine level: similar between groups (155.5 umol/L for BMES vs. 154.5 umol/L for Saline group)

Discussion:

  • Treatment with saline increased serum chloride, and lower pH than BMES, but kidney function was not affected.
  • An updated meta-analysis including this trial was also published in January 2022. This updated meta-analysis showed that the risk ratio for 90-day mortality for BMES was 0.96 (95% CI 0.91-1.01).  This data suggested that using BMES could reduce risk of death (up to 9%) or increase risk of death (up to 1%).
  • Appropriate volume resuscitation is still more important than the type of fluid.

 

Conclusion:

 

  • BME treatment was not associated with improved mortality.

Show References


Category: Critical Care

Title: Likelihood of Bacterial Infection in Patients Treated With Broad-Spectrum IV Antibiotics in the Emergency Department

Keywords: bacterial infection, sepsis, Emergency Department, broad spectrum antibiotics (PubMed Search)

Posted: 12/14/2021 by Quincy Tran, MD (Updated: 6/25/2022)
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When we initiate the sepsis bundle in the ED for patients with suspected sepsis, what probability that those patients who received broad spectrum antibiotics in the ED would have bacterial infection.

This study (Shappell et al) provides us with a glimpse of those number.

 

Settings: Retrospective study of adults presenting to 4 EDs in Massachusetts.

Patients: patients with suspected serious bacterial infection in ED, defined as blood cultures and initiation of at least one broad spectrum antibiotics.  Random selection of 75 patients per hospital.

Patients were categorized in 4 groups:

  • Definite bacterial infection: clinical syndrome, pathologic diagnosis of infection (positive cultures from blood, urine; pus; radiographic evidence of abscess, consolidations in lungs)
  • Likely bacterial infection: not meeting criteria for definite infection, but having a compatible clinical syndrome responsive to antibiotics and no clear etiology or reason for clinical improvement.
  • Unlikely bacterial infection: clinical syndrome consistent with infection, but an alternate diagnosis is more likely.
  • Definitely no bacterial infection: there was clear non-infectious diagnosis and no evidence of concurrent bacterial process.

Outcome: Prevalence of each category.

Study Results: 300 patients who received broad spectrum antibiotics.

  1. Prevalence of bacterial infection:
    1. 81 (27%) had definite bacterial infection
    2. 104 (34.7%) had likely bacterial infection
    3. 55 (18.3%) had unlikely bacterial infection
    4. 49 (16.3%) with definitely no bacterial infection
  2. For 96 patients with suspicion of sepsis vs. the rest of the cohort (P = 0.36)
    1. Definite 42.7%
    2. Likely 29.2%
    3. Unlikely 16.7%
    4. Definitely no 11.5%

       3. For patients who were admitted to the ICU (P = 0.26)

  a.   Definite 16.5%

                b.   Likely 8.6%

  c.   Unlikely 16.4%

                d.   Definitely no 20.4%

4. Source of infection

  1.  Definite/Likely bacterial infection
    1. GU = 69 (35%)
    2. Respiratory = 48 (24.4%)
    3. Skin or soft tissue = 45 (22.8%)
    4. Bacteremia or endovascular = 42 (21.3%)
    5. Abdominal = 24 (12.2%) 
  2. Unlikely/definitely not bacterial infection
  1. Viral = 27%
  2. Volume overload/cardiac disease = 10%
  3. Hypovolemia = 8%

 

Discussion:

  1. Slightly more than half of the patient we covered with broad spectrum antibiotics would have definitely or likely bacterial infection.
  2. This study agreed with previous studies (2), which suggested that for patients treated prophylactically for sepsis, 13% had a “none” likelihood, 30% of only "possible" likelihood for bacterial infection.
  3. The study highlighted that it was not easy for Emergency clinicians to recognize bacterial infection when we operate on a limited source of information and a limited timeline (think about the bundle of sepsis).
  4. However, overtreatment is also bad, so we just need to be cognizant.

Conclusion:

Approximately 30% of patients who had blood cultures drawn and received broad spectrum antibiotics in ED have low likelihood of bacterial infection.

Reference:

1. Shappell CN, Klompas M, Ochoa A, Rhee C; CDC Prevention Epicenters Program. Likelihood of Bacterial Infection in Patients Treated With Broad-Spectrum IV Antibiotics in the Emergency Department. Crit Care Med. 2021 Nov 1;49(11):e1144-e1150. doi: 10.1097/CCM.0000000000005090. PMID: 33967206; PMCID: PMC8516665.

2. Klein Klouwenberg PM, Cremer OL, van Vught LA, Ong DS, Frencken JF, Schultz MJ, Bonten MJ, van der Poll T. Likelihood of infection in patients with presumed sepsis at the time of intensive care unit admission: a cohort study. Crit Care. 2015 Sep 7;19(1):319. doi: 10.1186/s13054-015-1035-1. PMID: 26346055; PMCID: PMC4562354.


Category: Critical Care

Title: Simultaneous Use of Hypertonic Saline and IV Furosemide for Fluid Overload: A Systematic Review and Meta-Analysis

Keywords: decompensated heart failure, hypertonic saline, furosemide (PubMed Search)

Posted: 10/19/2021 by Quincy Tran, MD (Updated: 6/25/2022)
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Settings & Designs: a meta-analysis of 11 randomized controlled trials among patients with fluid overload.

Patients: This meta-analysis included 2987 patients with acute decompensated heart failure.

Intervention: intravenous hypertonic saline + intravenous furosemide.

Comparison: intravenous furosemide

Outcome: all-cause mortality, hospital length of stay

Study Results:

·       Hypertonic saline + furosemide treatment was associated with lower relative risk of mortality (RR 0.55, 95% CI 0.33-0.76%, P< 0.05, I-square = 12%).

·       Hypertonic saline + furosemide treatment was also associated with 3.8 shorter hospital length of stay (mean difference = -3.38 days, 95% CI -4.1 to -2.4, P< 0.05, I-square = 93%). 

·       Sodium creatine also decreased about 0.46 mg/dl (mean difference, -0.46, 95% CI -051, -0.41, P<0.05, I-square 89%) for patients received both hypertonic saline and furosemide.

Discussion:

·       Most studies only included patients with advanced heart failure (NYHA class IV, EF < 35%)

·       For these patients with advanced heart failure, most studies infused 150 ml of 1.5%-3% saline.  However, all studies used very high doses of furosemide (500mg -1000mg BID).

Conclusion:

In patients with acute decompensated heart failure, a combination of hypertonic saline and intravenous furosemide was associated with improved outcomes, compared with a single therapy of furosemide.

 

Show References


Background: SOFA score has been used as a predictor for poor outcomes in patients with sepsis.  However, the original SOFA score utilizes PaO2/FiO2 ratio to calculate the SOFA’s respiratory component.  When there are no ABG, thus no PaO2, we have to convert patients’ spO2 to PaO2, and the amount of oxygen support to FiO2 (for example, 2 liters of oxygen via nasal cannula = 0.27).  This is cumbersome.

Objective: This study assessed whether spO2 can be used instead of PaO2/FiO2 ratio for SOFA’s respiratory score.

Settings: 8 hospitals across Sweden and Canada

Patients: Adults with sepsis.  19396 patients were included for the derivation group while there were 10586 patients for the validation cohort.

Study Results:

  • When PaO2 was not measured, assigning respiratory SOFA score of 1 for spO2 94% and respiratory SOFA score of 2 for spO2 < 90% had good discriminatory capability.
  • The AUROC with SOFA score using spO2 threshold as above was 0.783 (0.767-0.798), which was slightly increased from the model using previous methods to calculate respiratory SOFA scores (0.781 [0.765-0.796]).

Discussion:

  • For Emergency Medicine, using a cut-off threshold  for spO2 of 94% (respiratory SOFA of 1) and 90% (respiratory SOFA of 2) can simplify how to calculate the SOFA score.  
  • It’s also simpler to do research when we collect SOFA score retrospectively.

Show References


Category: Critical Care

Title: Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

Keywords: OHCA, hypothermia, normothermia (PubMed Search)

Posted: 6/29/2021 by Quincy Tran, MD (Updated: 6/25/2022)
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Settings: International multicenter trials; 1:1 randomization, blinded assessment of outcomes.

Patients: adults with witnessed OHCA, regardless of initial rhythm.  Patients had more than 20 minutes of CPR.  Eligible patients were unconscious, not able to follow command, no verbal responses to painful stimuli.

Intervention: hypothermia to target of 33C for 28 hours, then rewarming at rate of 1/3C every hour until  37C.

Comparison: maintaining temperature at 37.5C or less.  Cooling if body temperature reached 37.8C to 37.5C

Outcome: primary outcome was Any cause mortality at 6 months; secondary outcome was poor functional outcome at 6 months (modified Rankin Scale 4-6).

Study Results:

1. 930 hypothermia, mortality 465/925 (50%, RR 1.04, 95%CI 0.94-1.14); 488/881 (55%) had mRS 4-6 (RR 1.0, 95%CI 0.92-1.09).

2. 931 normothermia, mortality 446/925 (48%); 479/866 (55%) had mRS 4-6.

Discussion Points:

  • Hypothermia would lead to higher rates of arrhythmia-related hemodynamic instability.
  • More studies reinforced that preventing fever is beneficial.
  • ED clinicians will not have to rush to cool patients while awaiting for ICU beds (Yay).

Conclusion:

Normothermia in coma patients after OHCA did not lead to higher morality or worse neurologic outcomes.

Show References


Background:

Cardiac arrest from massive pulmonary embolism (PE) can be up to 90% (1). A recent systemic review evaluated the efficacy of Venoarterial-Extracorporeal Membrane Oxygenation (VA-ECMO) for PE-related cardiac arrest.

Results:

The authors screened 1115 articles and included 77 articles, including gray literature.  The authors performed a quantitative analysis of a total of 301 patients.

Overall, 183/301 (61%) patients survived to hospital discharge, a significant improvement from 90%.

Patients who were cannulated during chest compression were associated with 7x higher odds of death (OR, 6.84; 95% CI, 1.53–30.58; p = 0.01), compared to those who were cannulated after ROSC.  However, cannulation in the ED was not associated with improved outcomes, compared with other cannulation site.

No increased risk of death among patients who received tPA prior to VA-ECMO vs. those who did not (OR, 0.78; 95% CI, 0.39–1.54; p = 0.48).

Patients whose age > 65 years of age were associated with 3X risk of death, compared to those with age < 65 years (OR, 3.56; 95% CI, 1.29–9.87; p = 0.02).

Take-home points

Please consider “early” VA-ECMO for eligible patients who have cardiac arrest from massive PE.  However, it will take great convincing to push the PERT team to cannulate for VA-ECMO while the patient is still receiving chest compression.

Show References


Background:

Cardiac arrest from massive pulmonary embolism (PE) can be up to 90% (1). A recent systemic review evaluated the efficacy of Venoarterial-Extracorporeal Membrane Oxygenation (VA-ECMO) for PE-related cardiac arrest.

Results:

The authors screened 1115 articles and included 77 articles, including gray literature.  The authors performed a quantitative analysis of a total of 301 patients.

Overall, 183/301 (61%) patients survived to hospital discharge, a significant improvement from 90%.

Patients who were cannulated during chest compression were associated with 7x higher odds of death (OR, 6.84; 95% CI, 1.53–30.58; p = 0.01), compared to those who were cannulated after ROSC.  However, cannulation in the ED was not associated with improved outcomes, compared with other cannulation sites.

No increased risk of death among patients who received tPA prior to VA-ECMO vs. those who did not (OR, 0.78; 95% CI, 0.39–1.54; p = 0.48).

Patients whose age > 65 years of age were associated with 3X risk of death, compared to those with age < 65 years (OR, 3.56; 95% CI, 1.29–9.87; p = 0.02).

Take-home points

Please consider “early” VA-ECMO for eligible patients who have cardiac arrest from massive PE.  However, it will take great convincing to push the PERT team to cannulate for VA-ECMO while the patient is still receiving chest compression.

Show References


Background:

The association between time intervals of ED antibiotic administration and outcome has been controversial.  While single studies showed there was increased mortality associated with delayed antibiotic administration (1-3). A meta-analysis of 13 studies and 33000 patients showed that there was no mortality difference between septic patients receiving immediate Abx (< 1 hour) vs. those receiving early abx (1-3 hours) (4).

Since delay in recognition of sepsis (defined as ED triage to Abx order) and delay in antibiotics delivery (Abx order to administration) contribute to total delay of Abx administration, a new retrospective study (3) attempted to investigate the contributions of either factor to hospital mortality.

Results:

The study used generalized linear mixed models and involved 24000 patients.

For All patients and outcome of hospital mortality:

Recognition delay (ED triage to Abx order): OR 2.7 (95% CI 1.5-4.7)*

Administration delay at 2-2.5 hours (Abx order to administration): OR 1.5 (1.1-2.0)

These results was associated with non-statistical significance in patients with septic shocks.

Conclusion:

Delayed recognition of sepsis was associated with higher hospital mortality.  Longer delay of abx administration was also associated with increased risk of hospital mortality.

Show References


A single center (Nebraska, USA), retrospective analysis investigated the prevalence of intubation during hospital stay for 105 patients who had COVID-19 between March 24 to May 5, 2020 (1).   40 patients underwent awake proning vs. 60 patients did not undergo awake proning.

After adjusting for either SOFA or APACHE scores, patients with awake proning were associated with lower Hazard Ratios of intubation for SOFA (HR 0.30, 95% CI 0.09-0.96, p=0.043) and APACHE (HR 0.30, 95%CI 0.1-0.91, p=0.034).

 

 

Discussion

While this US study seemed promising, another Brazilian study being published earlier in July 2020 showed no difference in the prevalence of intubation between COVID-19 patients with proning or without proning (2).

These 2 studies highlighted the nature of this disease: high practice variability, uncertainty of therapeutic modalities.  However, the complications from awake proning had been very low.

Conclusion:

Awake proning for hypoxic COVID-19 patients is a promising intervention but we will need more studies.  In the meanwhile, we can try this therapeutic modality as the risk is low.

Show References


Summary

Our group performed a meta-analysis to assess whether it is safe to infuse vasopressor through peripheral venous catheters.  We identified 9 studies with a total of 1835 patients.  The prevalence of complications among the pooled patient population was 9%.  Up to 96% of the complications was extravasation and almost no complications required any treatment.

A few studies reported safe infusion of norepinephrine up to 0.1 mcg/kg/min for up to 24 hours.

In exploratory meta-regression, catheter size 20 or larger was negatively associated with the rate of complications.

We also observed that studies that were published within the past 5 years reported significantly lower rate of complications from older studies.  This suggested that with careful planning and monitoring, it is safe to start vasopressor through peripheral IV.

Limitation

most of the included studies were observational. No studies had enough power to statistically analyze any variables that could predict complications.

Bottom line: we should start vasopressor as soon as indicated, if we have good, reliable IV access.

 

 

 

Show References


A retrospective study analyzed data from 757 patients with spontaneous intraparenchymal hemorrhage.

Within the first 6 hours of admission, patients who had systolic blood pressure reduction between 40 – 60 mm Hg (OR 1.9, 95% CI 1.1-3.5) or reduction ≥ 60 mm Hg (OR 1.9, 95%CI 1.01-3.8) were associated with almost double likelihood of poor discharge functional outcome (defined as modified Rankin Scale 3-6).

Additionally, large systolic blood pressure reduction ≥ 60 mm Hg in patients with large hematoma (≥ 30.47 ml) was associated with higher likelihood of very poor functional outcome (mRS 5-6).

Take home points: while more studies are still needed to confirm these observations, perhaps we may not want to drop blood pressure in patients with spontaneous intraparenchymal hemorrhage too much and too fast.

Show References


Patient 

  • Single Center, double-blinded, randomized trial. 

  • Patients with cancer and septic shock 

Intervention 

  • 4% albumin + lactate ringer bolus in 10 minutes 

  • 180 patients 

Comparison 

  • Lactate ringer bolus in 10 minutes 

  • 180 patients 

Outcome 

  • Primary: Any mortality within 7 days of randomization. 

  • Secondary: Mortality within 28 days, renal replacement therapy (RRT) 

Results: 

  • 7-day mortality: 46 (25%) for LR + albumin vs. 40 (22%) for LR only 

  • 28-day mortality: 96 (53%) for LR + albumin vs. 83 (46%) for LR only 

  • RRT: 16 (9%) for LR + albumin vs. 12 (7) for LR only 

Conclusion: 

Adding albumin for early resuscitation to crystalloids did not improve mortality in cancer patients with septic shock. 

 

Show References


Patient

·         A North America multicenter study involving 821 asymptomatic patients who had exposure to Covid-19-positive patients.  The study was double-blind, placebo-controlled randomized trial.

Intervention

·         Within 4 days of exposure, participants were randomized to receive hydroxychloroquine.  Dose of hydroxychloroquine was 800 mg once then 600 mg in 6-8 hours then 600 mg daily for 4 more days.

·         There were 414 patients in this arm. Median age 41 years [IQR 33-51]

Comparison:

·         Placebo treatment.  There were 407 patients in this arm. Median age 40years [IQR 32-50]

Outcome:

·         Incidence of either laboratory-confirmed Covid-19 or Covid-19 symptoms within 14 days.

Results:

·         49 (11.8%) patients with treatment had Covid-19 findings (positive tests or symptoms)

·         58 (14.3%) patients with placebo had Covid-19 findings (p=0.35). 

·         The absolute difference was -2.4%.  The number need to treat (NNT) to prevent one infection is 42 patients.  Number needed to harm is 50 patients.

·         Symptoms were fatigue (49.5%), cough (44.9%), sore throat (40.2%) myalgia (37.4%), fever (34.6%), anosmia (23.4%), shortness of breath (18.7%).

 

Conclusion:

Hydroxychloroquine prophylaxis did not prevent post-exposure Covid-19 infection.

Show References


Category: Critical Care

Title: What anticonvulsant medication to administer for status epilepticus

Keywords: status epilepticus, anticonvulsant medications, fosphenytoin, levetiracetam, valproate (PubMed Search)

Posted: 4/21/2020 by Quincy Tran, MD (Updated: 6/25/2022)
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Title: Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus

 

Settings:

  • 57 US hospitals: 26 sites for adults only, 18 sites enrolling only children, 13 sites enroll both.

Patients:

  • 384 patients whose ages were 2 years and older. 
  • Patients who continued to have generalized seizure for at least 5 minutes after “accepted” cumulative dose of benzodiazepines.

Intervention:

  • levetiracetam at a dose of 60 mg per kilogram (maximum, 4500 mg),
  • Fosphenytoin at a dose of 20 mg PE per kilogram (maximum, 1500 mg PE),
  • valproate at a dose of 40 mg per kilogram (maximum 3000 mg)

Comparison:

  • Patients > 32 kg total body weight:  diazepam of 10 mg; Lorazepam 4mg Intravenously; midazolam 10 mg intravenously or intramuscularly.
  • Patients < 32 kg total body weight: diazepam at a dose of 0.3 mg per kilogram (administered intravenously or rectally), lorazepam at a dose of 0.1 mg per kilogram (administered intravenously), or midazolam at a dose of 0.3 mg of per kilogram (administered intramuscularly) or 0.2 mg per kilogram (administered intravenously)

Outcome: absence of clinical seizure at 60 minutes after infusion of medication.

Study Results:

  • Rates of cessation of status epilepticus were similar in all 3 groups: 47% of levetiracetam vs. 45% Fosphenytoin vs. 46% for valproate.
  • Fosphenytoin was associated with non-significantly higher rate of hypotension (3.2%) vs other drugs.
  • Levetiracetam was associated with non-significantly higher rate of death (4.7%) vs. other drugs.
  • All three medication was associated with similar rate of intubation within 60 minutes of drug infusion.

Discussion:

  • The median time interval from start to cessation of status epilepticus appeared to be shorter for valproate but there was no formal analysis yet,
  • Valproate (7.0 minutes) vs. levetiracetam (11.7 minutes) vs. Fosphenytoin (11.7 minutes)

Conclusion:

  • Three medications, Fosphenytoin, levetiracetam, valproate were equally effective.

Show References


Category: Critical Care

Title: Nonsedation or Light Sedation in Critically Ill, Mechanically Ventilated Patients

Keywords: sedation, light sedation, no sedation, mechanically ventilated patients (PubMed Search)

Posted: 2/26/2020 by Quincy Tran, MD (Emailed: 3/3/2020) (Updated: 3/3/2020)
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Settings: Multicenter randomized controlled trial

Patients: 710 patients

Intervention: 345 patients.  no sedative but only boluses of morphine as clinically indicated (Sedation group)

Comparison: 356 patients.  light sedation with daily interruption (Nonsedation group)

Outcome: all-cause mortality at 90 days after randomization

Study Results:

42.4% of nonsedation group died vs 37% of sedation group (95% confidence interval [CI], −2.2 to 12.2; P = 0.65). 

Number of ventilator-free days for nonsedation group was 27 days vs. 26 for sedation group. 

Discussion:

This study did not agree with previous studies that lighter sedation was associated with shorter length of stay on mechanical ventilation , ICU or hospital.  The authors attributed to the findings that RASS score was not significantly different between the 2 groups.

Conclusion:

Critically ill adult patients receiving mechanical ventilation, there was no difference in 90-day mortality between patients receiving light sedation or no sedation.

Show References


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.

 

Show References


Category: Critical Care

Title: Conservative oxygenation during mechanical ventilation

Keywords: conservative oxygenation (PubMed Search)

Posted: 11/26/2019 by Quincy Tran, MD (Updated: 6/25/2022)
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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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