UMEM Educational Pearls - By Quincy Tran

Settings: this is a meta-analysis of 17 observational studies about boarding of critically ill patients in US Emergency Departments. All studies were from urban, academic centers.

Participants:

• There was a total of 407,178 patients, 194,814 (485) were boarding vs. 212,364 (52%) non-boarding patients.
• 355,86 (87%) patients were at centers with the presence of a resuscitation service.
• Ther was a mixture of critical illnesses: trauma (29.4 %), medical conditions (29.4 %) and mixed critical illness (41.2 %).

Outcome measurement: all cause mortality, as reported by the authors of the original studies.

Study Results:

• Overall, boarding patients were not associated with higher mortality, than non-boarding patients (Odd ratios 1.06, 95 % CI 0.94–1.19 p=0.383).
• Boarding patients were not associated with longer hospital length of stay (mean difference 0.38 days, 95%CI 0.94-1.50, P=0.51).
• However, among subgroup analyses, boarding patient population with mixed critical illnesses was associated with higher odds for mortality (OR 1.2, CI 1.04–1.4, p = 0.02 ) and longer HLOS (difference = 1.9, 95 % CI 0.81–3.1, I2 = 0 %, p = 0.001).

Discussion:

• All studies were observational so there was risk of bias and there was a presence of a small publication bias. This means that there were a few unpublished studies out there that showed that Boarding patients might have better outcomes.
• The findings that patient population with mixed illnesses were associated with higher odds for mortality, compared with Trauma-only or medical-only patients, might suggest that ED are not well equipped to take care of a wide spectrum of disease states. We seem to do better with populations with protocols such as sepsis, stroke, trauma.
• There was no clear consensus about how researchers approach this topic. A few studies did not even report their patient populations’ age (I cannot understand how these got published). Researchers used different thresholds for boarding, likely reflecting their institutional variabilities. There was quite a significant heterogeneity about patients’ acuity: some studies used SOFA, others used mSOFA.
• All of the studies were from urban academic centers so their results may not be applicable to non-academic centers which may not have many boarding issues

Conclusion: 

Critically ill patients boarding in the U.S. Emergency Departments were associated with a non-statistically signi?cant increase in odds of mortality and hospital length of stay compared to non-boarded patients

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Delirium is common among critically ill patients. Some of the common Acetylcholinesterase inhibitors (AChEI), rivastigmine, donepezil, have been used to prevent delirium in ICU patients. However, their efficacy was just recently re-examined in a meta-analysis of only Randomized Control Trials.

Ten studies and 731 patients were included- 365 in the treatment (AChEI) group and 366 in the control group.

AChEI was associated with lower occurrence of delirium (RR 0.68, 95% CI 0.47-0.98, p=0.039. However, there was no significant difference in the delirium duration (mean difference -0.16 day, 95% CI -0.95 to 0.62 day, p=0.23). There was no difference in delirium severity nor length of hospital stay.

Among the medication, interestingly, rivastigmine 4.5 mg/day  significantly reduced  delirium occurrence  (RR = 0.61 [0.39– 0.97]) and severity  (SMD = –0.33 [–0.58  to –0.08]), as well as  length of hospital stay  (MD = –1.29 [–1.87  to –0.72]).

Discussion:

This meta-analysis was well-conducted.

The cholinergic dysregulation—especially elevated acetylcholinesterase activity—can lead to the imbalance between attention and cognition, contributing to delirium in ICU patients. Thus, the use of AChEI and reduction of occurrence of delirium proves that acetylcholine deficiency may be associated with delirium among ICU patients.

Subgroup analysis showed that prophylactic use of AChEI was associated with significant reduction of delirium duration. Thus, further studies are needed to define which populations will benefit from AChEI.

Conclusion:

AChEIs are effective in reducing occurrence of delirium, but they did not affect delirium duration, severity or hospital LOS.

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Settings: multinational, randomized, double- blind, placebo-controlled clinical trial conducted in 17 centers in Italy, Russia, and Kazakhstan

Participants: A total of 307 ICU patients with sepsis or septic shock. Patients who were likely to die (APACHE II > 65 points) were excluded.

Treatment group: 80 mg bolus of omeprazole at randomization, at 12 hours and infusion of 12 mg/hour for 72 hours. Total dose of 1024 mg.

Outcome measurement: primary outcome of the study was organ dysfunction measured as the mean daily SOFA score during the first 10 days. Secondary outcomes were antibiotics-free days at 28 days; all-cause mortality at 28 days

Study Results:

• At 10 days, there was no difference in the median mean daily SOFA score: 5 (IQR, 3–10) in the mega- dose esomeprazole and 5 (IQR, 3–9) in the placebo groups (risk difference [RD], 0.1; 95% CI, –0.8 to 1.0; p > 0.99).
• At day 28, the median antibiotic-free days were 15 (IQR, 0–21) in the mega-dose esomeprazole group vs. 13 (IQR, 0–21) in the placebo group (p = 0.62).
• All-cause mortality at 28 days was 25% in the mega- dose esomeprazole group and 20% in the placebo group (RD, 4.9; 95% CI, –4.5 to 14.2; p = 0.31).

Discussion:

• The authors also did in vitro assays and they detected reduced levels of anti-inflammatory cytokines among patients receiving megadose of omeprazole. However, these in vitro results did not translate into clinical benefits in these patients with sepsis.
• Apparently, this study is another example that animal studies may not translate into clinical benefits in human studies, especially sepsis , as this condition is highly heterogeneous.

Conclusion: 

In sepsis patients, Esomeprazole did not re- duce organ dysfunction, despite demonstrating in vivo immunomodulatory effects

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Have you ever wondered what happened to your mechanically ventilated patients who developed diarrhea. Apparently, a multicenter study involving 2650 patients from 44 ICUs in the US, Canada and Saudi Arabia investigated the prevalence of diarrhea among these patients.
This study was the Editor’s choice for June 2025.

Results:

The mean age for the population was 59.8 (16.5) years, with APACHE II Score of 22.0 (7.8). Up to 61% of the patients received vasopressors or inotropes on day 1, which mean these patients are relatively ill.

Up to 60% of patients had diarrhea during their ICU stay, with 15% had diarrhea on day 1 or 2.
Initiating laxatives and antibiotics (who in the ICU would not receive vitamin V and Vitamin Z?) were associated with increased risk of diarrhea: HR for laxatives 1.28 (1.13–1.44), p<0.001; HR for antibiotics 1.41 (1.20–1.67), P< 0.001.

Furthermore, enteral feeding with high/moderate protein concentration was also associated with diarrhea (HR 1.13, 1.00-1.28, P=0.045.
Not surprisingly, diarrhea was associated with higher number of C. Diff testing.
Although patients with diarrhea were associated with longer ICU stay (15 [10-23] days) vs. those without diarrhea (8 [6-12] days), it was not associated with higher mortality (HR 0.70, 95% CI 0.57-0.86, P<0.001)

Discussion:
1. The authors did not report the rates of positive C. Diff. infection in these patients during ICU stay, although they did report that for another study in this population, the rate of positive C. Diff. infection during ICU stay was 2.2%.  If only 2.2% had C. Diff. infection while up to 60% had diarrhea. Consequently, for every 30 patients with diarrhea, only one patient had C. Diff. infection.  Therefore, do we have to check C. Diff. in those ICU patients with diarrhea every time?
2. The authors hypothesized that patients with diarrhea had longer ICU stay and lower mortality because they survived long enough to develop diarrhea. Thus, diarrhea is bad for clinicians, but may not be too bad for patients?

Conclusion: 
Diarrhea is common among invasively ventilated patients. Patients who received laxatives, antibiotics, enteral feeding with high protein amount are at higher risk for diarrhea.

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We have known that resuscitation with balanced crystalloids was associated with better outcomes, than normal saline.  However, I have believed that in the early phase of resuscitation, volume of any crystalloids is still better than little volume. Thus, a couple of liters of normal saline (0.9% saline) would not hurt. However, the recent secondary analysis from the Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) trial might have changed my practice.
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Settings:

60 ICU in the United States between 2018 to 2022. This is the secondary analysis of the Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) trial population
Participants: Patients with sepsis-induced hypotension after receiving fluid resuscitation (from 1-3 litters). Participants who received lactate ringers (622 patients) were compared with patients who received normal saline (690 patients).
Outcome measurement:
Death before discharge home by day 90.
Hospital-free days at 28 days
Study Results:
Dead occurred in 12.2% of LR group (76/622) vs. 15.9% (110/690) patients of the NS group, Adjusted Hazard Ratio 0.71 (95% CI 0.51-0.99, p=0.043)
Patients receiving LR had more hospital-free days at 28 days than those receiving 0.9% saline (16.6 ± 10.8 vs. 15.4 ± 11.4 d, respectively). The mean difference was 1.6 days (95% CI, 0.4–2.8; p = 0.009).
Discussion:
This study confirms that not only early resuscitation is important, but the fluid choice during the early resuscitation phase is also important, especially in patients with signs and symptoms of sepsis.

Thus, even during pre-hospital phase and in the ED, clinicians should consider to use LR or other balanced solutions if available.
Conclusion:
Among patients with sepsis-induced hypotension, resuscitation with Lactate Ringer was associated with better outcomes than normal saline.

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If you watch those medical drama (House MD, ER, Grey’s Anatomy, Resident…), the doctors and residents are always faced with a dilemma – is it a rare autoimmune disorder or is it an infection? They are worried that if they give steroid to a patient with infections, that would kill the patients.
Well, it might not be the case for Community acquired pneumonia.

A meta-analysis of randomized control trials involving 3224 patients to look into the efficacy of adjuvant corticosteroids for CAP. The authors assessed the heterogeneity of treatment effect (different groups should have different response to treatment).
For patients who were anticipated to benefit (those who had CRP > 240 mg/L), corticosteroids were associated with lower odds of 30-day mortality (OR 0·43 [0·25–0·76], p=0·026).

When stratifying by risk, there was no significant effect between those with Pneumonia Severity Index (PSI) I-III versus those with PSI IV-V. 
However, corticosteroids increased odds of hyperglycemia (OR 2·50 [95% CI 1·63–3·83], p<0·0001), odds of hospital readmissions (1·95 [1·24–3·07], p=0·0038)

Discussion:
There were different regiments for corticosteroids in the included studies. However, hydrocortisone appeared to be more effective than other corticosteroids.
Furthermore, the time intervals for treatment is still debatable. The data suggested that the ideal treatment is within 24 hours of hospital admission, but patients can still benefit from treatment in up to 48 hours.
A response-dependent treatment is also recommended: 8 days or 14 days, depending on how patients respond to treatment by day 4.
Conclusion:
Adjuvant treatment with corticosteroids among hospitalized patients with CAP was significantly associated with reduction of 30-day mortality. The treatment effect, however, varied according to patients CRP concentrations at baseline.

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Delirium in the ICU means badness as delirious ICU patients are associated with longer stay and higher mortality. While medications are not proven to prevent delirium, certain environmental interventions such as window access, light and sound levels have been recognized as legit interventions to prevent ICU delirium.

Settings: This is a retrospective study at Massachusetts General Hospital 
Participants: 3527 patients admitted to a surgical ICU between 2020 and 2023.
Outcome measurement: This study hypothesized that patients in a windowed ICU room will have lower rates of delirium, decreased ICU length of stay, hospital LOS. Multivariable logistic regressions were performed for the association of clinical variables and the presence of delirium.
Study Results: 
Delirium was observed in 460 patients (21%) of the windowed rooms group and 206 patients (16%) of the nonwindowed rooms group. Multivariable logistic regression showed that patients in windowed rooms were associated with higher odds of delirium (aOR, 1.29; 95% CI, 1.07–1.56; p = 0.008), although they were not associated with longer ICU LOS or longer HLOS
Discussion:
The study’s findings added to the literature that natural lighting might not be the effective prevention of delirium. The presence of windows might not be the answer. 
In this study, all the windows were facing another building, and there was no view of other natural scenes, with a limited view of the sky. Therefore, the authors suggested that the overall quality of the windows would be more important.

Conclusion: 
The ICU environment is more important for patients’ delirium than just the presence of windows.

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It’s the age-old question. We’ve read studies comparing propofol vs. etomidate, ketofol vs. etomidate, and now a meta-analysis about ketamine vs. etomidate.  Etomidate is the staple induction agent for RSI, mostly used by Emergency Medicine, and to a degree in the Intensive Care Unit. However, the question about adrenal suppression was initiated in the early 2000s and researchers have been looking for other alternatives. This meta analysis attempted to look for another answer.

Settings: A meta-analysis of randomized controlled trials

Participants: 2384 patients who needed emergent intubation were included.

Outcome measurement: Peri-intubation instability

Study Results:

Compared with etomidate, ketamine was associated with higher risk of hemodynamic instability and moderate certainty (RR 1.29, 95% CI 1.07-1.57). 

Ketamine was associated with lower risk of adrenal suppression, again, with moderate uncertainty (RR 0.54, 95% CI 0.45-0.66).

Ketamine was not associated with differences and risk of first successful intubation nor mortality.

Discussion:

Most studies were single center and involved small-moderate sample size, ranging from 20 patients to 700 patients.

For adrenal suppression, there were only 3 studies and a total of 1280 patients, thus, the results are still not definitive.

For an academic exercise, the Number Needed to Harm for both hemodynamic instability and adrenal suppression are calculated here.

Number Needed to Harm for hemodynamic instability: 25.

Number needed to harm for adrendal suppression: 11.

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Title: Albumin Versus Balanced Crystalloid for the Early Resuscitation of Sepsis: An Open Parallel-Group Randomized Feasibility Trial— The ABC-Sepsis Trial

Settings: 15 ED in the United Kingdom. This study is a feasibility study but it looked at mortality as a primary outcome.
Participants: 
•    Patients with Sepsis, with their National Early Warning Score (NEWS) ? 5 (These patients have estimated mortality of 20%). IV fluid resuscitation needs to be within 1 hour of assessment.
•    300 Patients were randomized to receive balanced crystalloids or 5% human albumin solution (HAS) only, within 6 hours of randomization.
Outcome measurement: 30-day mortality, Hospital length of stay (HLOS)
Study Results:
•    The median time for receiving IV fluid from randomization was 41 minutes (HAS) vs. 36 minutes (crystalloids).
•    Total volume of IV fluid per Kg  in first 6 hours 14.5 ml/kg  (HAS) vs. 18.8 ml/kg (crystalloids).
•    Other interventions (vasopressor, Renal replacement therapy, invasive ventilation) were similar.
•    Complications (AKI, pulmonary edema, allergy) were lower for Crystalloids group
•    Median hospital LOS = 6 days for both groups.
•    90-day mortality: 31 (21.1%) (HAS) vs. 22 (14.8%) (Crystalloids), OR 1.54 (95% 0.8-2.8)
Discussion:
•    Total volumes for resuscitation in the first 6 hours was 750 ml (HAS) and 1250 ml (crystalloids). This signified a trend toward lower total volume of resuscitation (remember that 30 ml/kg recommendation)
•    The 2024 guidelines from Chest (REF 2) suggested that: “In Critically ill adult patients (excluding patients with thermal injuries and ARDS), intravenous albumin is not suggested for first line volume replacement or to increase serum albumin levels. Therefore, we should not give patients (except for cirrhosis or spontaneous bacterial peritonitis) albumin just to reduce the volume of fluid.
•    The authors suggested that even a definitive trial in the future will not be able to demonstrate a significant benefit of using 5% albumin.
Conclusion: 
There is lower mortality (numerical but not statistically) among the group with balanced crystalloids.

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We heard it before. Continuous administration of antibiotics might be associated with better outcomes. However, results from smaller randomized controlled trials of beta-lactam showed inconsistent conclusions. Therefore, a large RCT was conducted

Settings: 31 ICUs in Croatia, Italy, Kazakhstan, Russia between June 2018 – August 2022.

Randomized, double-blind control trial.

Participants:

• Patients with sepsis or septic shock who were given meropenem by their clinicians. 
• A total of 607 patients were enrolled: 303 continuous meropenem vs. 304 intermittent administration of meropenem.

Outcome measurement: 

• Primary outcome: all cause mortality at day 28.
• Secondary outcome: emergency of pan-drug resistant bacteria at day 28.

Study Results:

• 369 (61%) had septic shock, while 33% had low respiratory tract infection. There were 442 (73%) had invasive mechanical ventilation. 
• Median SOFA score was 9 [6-11]; the median daily meropenem dose was 0.04 g/kg/day (total of 3 g/day).
• The all cause mortality at 28 days was 91 (30%) for continuous group vs. 99 (33%) (P = 0.50) for intermittent group.
• The rate of emergence of pandrug resistant bacteria was 68/288 (24%) vs. 70/280 (25%) (P= 0.70)

Discussion:

• The current study involved more high risk patients, as the median SOFA was high at 9
• There was no therapeutic monitoring in this study, so the minimal inhibitory concentration was not known.
• Continuous meropenem might be less labor-intensive than intermittent meropenem, which required administration every 8 hours.

Conclusion: 

In critically ill patients with sepsis, continuous administration of meropenem did not improve mortality nor reduce the emergence of pandrug resistant bacteria.

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Title: Antipsychotics in the Treatment of Delirium in Critically Ill Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

We all do it. When our patients in the ICU develop delirium, we would give them an antipsychotic, commonly quetiapine (Brand name Seroquel), and all is good. However, results from this most recent meta-analysis may suggest otherwise. 

Settings: This is a meta-analysis from 5 Randomized Control Trials. Intervention was antipsychotic vs. placebo or just standard of care.

Participants: The 5 trials included A total of 1750 participants. All trials used Confusion Assessment Method for the ICU or Intensive Care Delirium Screening Checklist to measure delirium.

Outcome measurement: Delirium – and Coma-Free days

Study Results:

The use of any antipsychotic (typical or atypical) did not result in a statistically significant difference in delirium- and coma-free days among patients with ICU delirium (Mean Difference of 0.9 day; 95% CI -0.32 to 2.12).

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Similarly, atypical antipsychotic medication also did not result in difference of delirium- and coma-free days: Mean difference of 0.56 day; 95% CI -0.85 to 1.97).

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ICU length of stay was also not different in the group receiving antipsychotic: Mean difference -0.47 day, 95% CI -1.89 to 0.95).

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Discussion:

The authors used both delirium -free and coma-free days as a composite outcome because they reasoned that delirium cannot be evaluated in unresponsive patients. This composite outcome might have affected the true incidence of delirium and the outcome of delirium-free days. 

This meta-analysis would be different from previous ones that aimed to answer the same question. Previous studies compared either haloperidol vs a broader range of other medication (atypical antipsychotic, benzodiazepines) (Reference 2) or included all ICU patients  with or without delirium who received haloperidol vs. placebo (Reference 3). Overall, those previous studies also reported that the use of haloperidol has not resulted in improvement of delirium-free days.

Conclusion: 

There is evidence that the use of anti-psychotic medication does not result in difference of delirium- or coma-free days among critically ill patients with delirium.

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Title: Safety and Efficacy of Reduced-Dose Versus Full-Dose Alteplase for Acute Pulmonary Embolism: A Multicenter Observational Comparative Effectiveness Study

Settings: Retrospective observational study from a combination of Abbott Northwestern Hospital and 15 others as part of the Mayo Health system.

Participants: Patients between 2012 – 2020 who were treated for PE. Patients were propensity-matched according to the probability of a patient receiving a reduced- dose of alteplase.

Outcome measurement: 

• Primary outcome: all-cause and PE-related mortality or hemorrhage within 7 days of alteplase administration.
• Secondary outcomes: shock index at 8 hours after alteplase administration, LOS.

Study Results:

• A total of 284 patients were included in the retrospective analysis; 98 were treated with the full-dose and 186 with the reduced-dose alteplase regimen.
• Primary outcome was similar in both groups:
  • 7-day all-cause (5.6% in full- dose vs. 8% in reduced-dose, p = 0.45) 
  • PE-related (4% in full-dose vs. 4.2% in reduced-dose, p = 0.93)
• All other secondary outcomes were similar between both groups
• overall rates of hemorrhagic complications were significantly lower in the reduced-dose group than in the full-dose group (13% vs. 24.5%, respectively, p = 0.014).
• Major intracranial hemorrhage was higher, but not statistically significant, for full-dose group: 1.3% in reduced-dose vs. 7.1% in full-dose for major, (p = 0.067)

Discussion:

• Overall, there was more risk for full-dose. However, this is a retrospective study so whether it will be factored into clinical practice remains to be seen.
• The PERT team at UMMC still recommends full dose for hemodynamic unstable patients. Perhaps for those with somewhat instability, a half dose should be considered?
• There is still not enough data regarding the newer ones, as UMMS hospitals are starting to use TNK more frequently nowadays.

Conclusion: 

In this retrospective, Propensity-score matching study, the full-dose regimen but is associated with a lower risk of bleeding.

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Background: There is no clear guidelines regarding whether norepinephrine or epinephrine would be the preferred agent to maintain hemodynamic stability after cardiac arrest. In recent years, there has been more opinions about the use of norepinephrine in this situation.

Settings: retrospective multi-site cohort study of adult patients who presented to emergency departments at Mayo Clinic hospitals in Minnesota, Florida, Arizona with out-of-hospital-cardiac arrest (OHCA). Study period was May 5th, 2018, to January 31st, 2022

Participants: 18 years of age and older

Outcome measurement: tachycardia, rate of re-arrest during hospitalization, in-hospital mortality.

Multivariate logistic regressions were performed.

Study Results:

• The study included 221 patients, 151 patients received norepinephrine infusion vs. 70 patients received epinephrine infusion.
• The maximum dose of epinephrine = 0.28 mcg/kg/min vs. 0.15 mcg/kg/min for norepinephrine.
• The Odds for clinically significant tachyarrhythmia was the same between both groups (OR 1.34, 95% CI 0.6802.62, P=0.40).
• Epinephrine infusion was associated with higher odds of in-hospital mortality (OR 6.21, 95% CI 2.37–16.25, P <0.001)
• Epinephrine infusion was associated with higher odds of re-arrest ( OR 5.77, 95% CI 2.74–12.18, P < 0.001)

Discussion:

It was retrospective study that uses electronic health records. Thus, other important factors from the pre-hospital settings might not be accurate.

On the other hand, the patient population came from multiple hospitals with varying practices so the patient population is more generalizable.

Conclusion: 

Although the rate of tachyarrhythmia was not different between patients receiving norepinephrine vs. epinephrine after ROSC. This study would add more data to the current literature that norepinephrine might be more beneficial for patients with post-cardiac arrest shock.

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Hot of the press from the Society of Critical Care Medicine (But most of us would know it already)

Settings: This is a prospective observational population-based study design with non-contemporaneous, nonrandomized clinical trial direct (unadjusted) head- to-head evaluations
Propensity score–matched comparisons of non-shockable cardiac arrest (NS-OHCA) patient survivor using conventional CPR (C-CPR) vs. C-CPR plus Automated Head/thorax up positioning-CPR (AHUP-CPR).

Participants: patients with non-traumatic, non-shockable out of hospital cardiac arrest (NS-OHCA).

Outcome measurement: primary outcome = survival, secondary outcome = survival with good neurologic outcome (Cerebral Performance Category score of 1–2 or modified Rankin Score less than or equal to 3).

Study Results:
•    There was a total of 380 AHUP-CPR vs. 1852 C-CPR patients. After 1:1 matching, there were 353 AHUP-CPR patients and 353 C-CPR patients.
•    In unadjusted analysis
o    AHUP-CPR was associated with higher odds of survival (Odds ratio 2.46, 95% CI 1.55-3.92) and higher odds of survival with good neurologic function (Odds ratio 3.09 (95% CI 1.64-5.81)
•    In matched groups
o    AHUP-CPR was associated with higher odds of survival (Odds ratio 2.84, 95% CI 1.35-5.96) and higher odds of survival with good neurologic function [Odds ratio 3.87 (95% CI 11.27-11.78]

Discussion:
•    There was no difference in rates of ROSC between groups.  The authors argued that there was “neuroprotective effects” for the AHUP-CPR group.
•    Although randomized controlled trials are usually required before clinical interventions are adopted, the aurthors argued that it would be difficult to randomize OHCA patients, and that the risk vs benefits may facilitate early adoption of this strategy.
•    AHUP-CPR should be used first by well-trained clinicians to ensure its benefits.

Conclusion: 
OHCA patients with NS presentations will have a much higher likelihood of surviving with good neurologic function when chest compressions are augmented by expedient application of the noninvasive tools to elevated head and thorax used in this study.

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Settings: systemic review and meta-analysis

Participants: 2 RCTs, 21 observational studies. Fifteen studies were published between 2020-2023.

There was a total of 25721 patients with septic shock

Outcome measurement: Primary outcome was short-term mortality (ICU, hospital, 28-day, 30-day). Secondary outcomes included ICU LOS, Hospital LOS, time to achieve MAP > 65 mm Hg,

Study Results:

Composite outcome of short term mortality: 

• 20 studies and 17470 patients. Early initiation of vasopressors was associated with lower odds of short term mortality (OR 0.775, 95% CI 0.673-0.893, P<0.001, I2 = 68%).
• Early initiation of norepinephrine was associated with lower odds of short term mortality (OR 0.656, 95% CI = 0.544 to 0.790, P <0.001, I2 = 57.2%)
• Early initiation of vasopressin was also associated with lower odds of short term mortality (OR 0.685, 95% CI 0.558-0.840, P < 0.001, I2= 57%)

 Secondary outcome:

• Early vasopressor group was associated with lower odds of RRT use (OR 0.796, 95% CI 0.654-0.968, P = 0.022, I2 = 0%)
• Mean Serum lactate levels at 6 hours was similar in early vasopressor group (Mean Difference 0.218, 95% CI -0.642 to 1.079, P = 0.619).
• However, mean serum lactate levels at 6 hours was lower in early norepinephrine subgroup (mean difference -0.489, 95% CI -0.863 to -0.115, P = 0.01).

Discussion:

• This appears to be a hot topic. When our group did this topic in 2020, there were 8 or 9 studies. Since 2020, there has been a significant increase in the number of publications, although most publications were observation studies.
• Early initiation of norepinephrine may reduce fluid overload, not by reducing fluid input, but by improving host inflammatory response, improving endothelial cell barrier stability.
• Counter-intuitively, early vasopressor was also found to be associated with lower incidence of arrhythmia, which the authors attributed to shorter duration of vasopressors and lower total dosage.

Conclusion: 

More and more studies, although a RCT is still necessary, are showing that early initiation of vasopressor within 1-6 hours of septic shock would be more beneficial to patients with septic shock.

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Settings: Retrospective study of a national inpatient database (Japan).

Participants:

• All patients who were admitted between April 1, 2018 and March 31, 2021 with a SOFA score > 2 on admission day.
• Propensity score matching using SOFA score at admission was used to group patients according to the first unit of admission. The units of admissions were: ICU, High-dependency unit (HDU, which is also called Intermediate care unit), general ward.

Outcome measurement: Primary outcome was in-hospital mortality, after propensity score matching.

Study Results:

• There were 19770 patients admitted to the IC, 23066 patients in the HDU and 54,234 patients in the ward.
• There were no significant differences in in-hospital mortality among cohorts with SOFA scores of 3–5.
• Patients with SOFA => 6 and admitted to the ICU or HDU were associated with lower mortality than patients with same SOFA score but admitted to the ward (Risk difference -2.3 (95% CI -4.6 to -0.1, P=0.041).
• Patients who had SOFA > 12 and was admitted to the ICU group were associated with significantly lower in-hospital mortality than those with similar SOFA score but was admitted to the HDU (Risk difference -4.3, 95% CI -7.5 to -1.0, P = 0.010)

Discussion:

• Most of the high SOFA scores among ICU patients were due to norepinephrine or mechanical ventilation.
• Patients with SOFA 2-5 and were admitted to the ICU/HDU were associated with higher mortality than those admitted to the ward. This was mostly from patients who needed intensive monitoring, and not support for organ failure.
• ICU admission is also associated with certain adverse events (2).

Conclusion:

Risk-stratifying patients according to SOFA score is a potential strategy for appropriate admission strategies.

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Settings: Single ICU in Poland, randomized trial

Participants: intubated patients who needed arterial catheter placement. Patients who had adequate access to one axillary and one femoral artery were eligible.

Patients were randomized 1:1 for axillary or femoral artery cannulation.

Outcome measurement: Primary outcome was cannulation success rate. Secondary outcomes were first pass success rate, number of attempts.

Study Results:

• A total of 109 patients with data: 55 patients in the Axillary group vs. 54 for femoral group.
• Cannulation success rate for axillary group was 96.4% vs. 96% for femoral group
• First pass success rate for Axillary group was 69% vs. Femoral group of 74% (p=0.56)
• Total number of procedural complications (puncture of opposite wall of artery, puncture of adjacent vein, periarterial extravasation, ischemia of extremity) was non-statistically different between groups.

Discussion:

• There was higher rate of dysfunction of arterial pressure curve among Axillary group (15%) vs. femoral group (2%, P = 0.016).  The reason for this finding is not quite clear.
• Needle visibility was worse with the femoral group. There were 75% patients with excellent and good view for the Axillary group, vs. 24% for the femoral group. This could be due to the difference between out-of-plane cannulation for femoral group vs. in-plane cannulation for axillary group.
• There was overall low rate of complications.

Conclusion:

Ultrasound-guided cannulation of the axillary artery via the infraclavicular route is non-inferior to the cannulation of the common femoral artery. When cannulation of the radial or femoral artery is not available, we can consider axillary artery via the infraclavicular approach.

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Settings: Retrospective data from 3 Dutch EDs (development of the score), 2 Denmark ED (for validation of the score). The novel score (International Early Warning Score) will be composed of the National Early Warning Score (NEWS) + Age +Sex

Components of the National Early Warning Score:

• Respiratory rate,
• oxygen saturation,
• supplemental oxygen (yes/no),
• Temperature,
• Systolic blood pressure,
• heart rate,
• level of consciousness (Alert vs. not).

Participants: All adult patients in the Netherlands Emergency department Evaluation Database (NEED) and Danish Multicenter Cohort (DMC).

Outcome measurement: in-hospital mortality, including death in EDs.

Study Results:

• 95553 (2314, 2.5% died) patients were used for development of the score, 14809 patients (365, 2.5% died) were in the validation cohort.
• The IEWS provides higher AUROC (0.87, 95% CI 0.85-0.88) than the NEWS (AUROC 0.82, 95% CI 0.80-0.84) in the validation cohort.
• The IEWS for the age group 18-65 years (AUROC 0.86, 95% CI 0.80-0.91) had the most improvement, compared to NEWS (AUROC 0.82, 95% CI 0.75-0.89).

Discussion:

• The study excluded patients whom did not have 2 sets of vital signs, thus, “very sick” or “not sick” patients would be excluded.
• This novel score was not compared with the updated NEWS2, which incorporates hypercapnia and confusion. Additionally, this novel score was also not compared with another popular score, Modified Early Warning Score (MEWS). Both the NEWS and MEWS scores have been studied extensively in the literature, thus, have been adopted in clinical use.

Conclusion:

This multicenter study showed that IEWS perform better than the NEWS for predicting in-hospital mortality for ED patients.

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As emergency physicians, we use etomidate to intubate patients most of the time, although there was controversy whether etomidate would suppress critically ill patients’ cortisol production. Whether etomidate was associated with mortality was controversial. A recent meta-analysis investigated the issue again.

Methods: meta-analysis of randomized trials using etomidate for intubation versus other agents. Outcome = mortality as defined by the authors. Mortality was defined from 24 hours to 30 days by study’s authors.

Results: 11 RCTs, including one new RCT in 2022

319 (1359, 23%) patients received etomidate died vs. 267 (1345, 20%) receiving other agents died; Risk Ratio 1.16, 95% CI 1.01-1.33, P = 0.03.

Etomidate was also associated with higher risk ratio for adrenal insufficiency, when compared with other control agents (147/695, 21% vs. 69/686, 10%, RR 2.01, 95% CI (1.59-2.56), P < 0.01.

Etomidate was also associated with higher risk ratio of mortality, when compared with ketamine, for mortality, as defined by each study’s author (273/1201, 23% vs. 226/1198. 19%. RR 1.18, 95% CI 1.02-1.37, P = 0.03).

Discussion:

The authors used fixed effects model, as they claimed that their meta-analysis had low heterogeneity (I2 =0%). However, fixed effects model should only be used when there is no difference among patient population. In this study, the outcome definitions were different, the patient populations were different (trauma, pre-hospital, ED, ICU). Therefore, random effects model should be used. Random effects models tend to yield larger 95% CI, thus, more likely yield non-statistically significant results.

The authors claimed a Number Needed To Treat (NNT) for etomidate of 31, so basically many ED patients would die, while most of patients being intubated by Anesthesiology, regarding settings, would not die, as anesthesiologists mostly use propofol.

Title: Electrocardiographic Changes at the Early Stage of Status Epilepticus: First Insights From the ICTAL Registry.

As the song goes: “the thigh bone is connected to the hip bone, the hip bone is connected to the back bone.” It turns out that the brain electrical activities are also connected to the heart conduction activities.

In a multi-center (23 French ICUs) retrospective analysis of 155 critically ill patients with status epilepticus, ECGs were done within 24 hours of onset of status epilepticus, and were independently reviewed by cardiologists showed abnormalities in 145 (93.5%) of patients.

Below is a list of events that occurred more than 10% of events.

Abnormal rate (<60 or > 100 beats/min         64 (44%)

Negative T-waves                                           61 (42%)

Flattened T-waves                                           18 (12%)

ST elevation                                                    24 (16.6%)

ST depression                                                 26 (17.9%)

Left axis deviation                                          22 (15.9%)

Discussion:

Major ECG abnormalities were not associated with 90-day functional outcome in multivariable logistic regression.

The brain-heart axis could be affected by antiseizure medication. For example, phenytoin, lacosamide are sodium channel blockers while benzodiazepines, propofol, barbiturates with their GABAnergic effects will also display cardiac side effects.  This current study was not able to tease out whether the cardiac effects were from medication. Therefore, further studies are needed to figure out the cardiac effect for patients with status epilepticus.

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