UMEM Educational Pearls - By Quincy Tran

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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Title:

The Impact of Thoracic Ultrasound on Clinical Management of Critically Ill Patients (UltraMan): An International Prospective Observational Study

Settings: 4 hospitals (3 in Netherlands and 1 in Italy)

Participants: All adults patients who were admitted to the ICU but patients who died within 8 hours of thoracic ultrasound were excluded.

Thoracic ultrasound procedure: cardiac, lung, diaphragm, inferior vena cava. The main indicators were Respiratory, Cardiac and Volume status.

Study Results:

725 thoracic ultrasound examinations and 534 patients.  Clinical management occurred in 247 (88.5%) patients within 8 hours of ultrasound.

Thoracic ultrasound was performed by 111 operators, ranging from inexperienced to very experienced.

Common findings from thoracic ultrasound among these ICU patients.

• Atelectasis 233 (32.1%)
• Pleural effusion 221 (30.5%)
• Pulmonary edema 120 (16.6%)
• Pneumonia 107 (14.8%)

Discussion:

• There was a major impact in fluid management.
  • Patients who needed more fluid (N=63) would have a balance of +907 ml within 8 hours.
  • Patients who need euvolemia (N = 28) would have a balance of +80ml within 8 hours.
  • Patients who need less fluid (N=45) would have a balance of -411ml within 8 hours.
• There was no information regarding management change according the experience of the operators.
• The authors did not assess patient-centered outcomes from these management changes.

Conclusion: Thoracic ultrasound provided a significant change in management of critically ill patients.

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This was a cross-sectional survey for the Diversity-Related Research Committee of the Women in Critical Care (WICC) Interest Group of the American Thoracic Society.

Settings: 62 sites in Canada and the US

Participants: Attending physicians who worked in ICUs

Questionaire:

·         Measure of Moral Distress for healthcare professionals (27 items),

·         Maslach burnout inventory (2 items),

·         Stanford Professional Fulfilment Index (14-items), Brief Cope scale (14-items)

Study Results:

1.       Demographics:

·         431 participants (approximately 43.3% response rate).

·         334 (65%) participants worked at University-affiliated hospitals

·         387 (89.0%) worked in Adult ICUs.

·         Pre-pandemic, clinical days/months was 10.1 (± 14) days, and increased to 13.1 (± 16) days during the pandemic.

2.       Measure of moral distress: Average score 95.6 ± 66.9 (maximum 417).

·         The highest score (mean 8.5 ± 4.8), for distress, came from the item: “Follow the family insistence to continue aggressive treatment even though it is not in the best interest of the patient.” ((Family wanted to do everything).

3.       Stanford Fulfillment Index:

·         387 (91.9%) intensivists found their work meaningful and 365 (86.5%) felt worthwhile at work, although most felt physically (297, 71.6%), emotionally (266 [63.8%]) exhausted.

4.       Coping strategies:

·         Participants resorted to a wide variety of scoping strategies ranging from Acceptance (90%), Self-distraction (85%) to Substance abuse (32%) and Denial (18%).

·         Most physicians (231 [55.9%]) reported that their coping remained the same before and during the pandemic.

Discussion:

·         Physicians are quite resilient. The authors found that physicians who worked more days experienced significantly more moral distress but with similar Stanford Professional Fulfillment score.

·         This finding was similar to an exploratory analysis from a meta-analysis that showed physicians, among other healthcare workers, were less likely to have severe symptoms of PTSD (2).

·         Women and physicians who were persons of color experienced significantly higher moral distress and burn-out.

Conclusion:

There was moderate moral distress and burn-out, although physicians who worked in ICUs still achieved moderate professional fulfillment.  Up to 20% of ICU physicians used a maladaptive coping strategy

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Have you ever encountered an ESRD patient who missed dialysis because the patient "felt too sick to go to dialysis"? The patient then had hypotension from an infected catheter line? Do we give 30 ml/kg of balanced fluid now?

__________________________

Title: Outcomes of CMS-mandated ?uid administration among ?uid-overloaded patients with sepsis: A systematic review and meta-analysis.

Settings: This is a meta-analysis

Patients: Septic patients who have underlying fluid overload conditions (CHF or ESRD).

Intervention: intravenous fluid administration according to the mandate by the Center for Medicare/Medicaid as 30 ml per kilograms of bodyweight.

Comparison: fluid administration at less than 30 ml/kg of body weight.

Outcome: 30-day mortality, rates of vasopressor requirement, rates of invasive mechanical ventilation

Study Results:

• Random-effects meta-analysis of 5 studies, including 5804 patients.  There were 5260 (91%) patients receiving non-aggressive IVF at < 30 ml/kg versus 544 (9%) patients received aggressive IVF at rates > 30 ml/kg.
• Patients who received aggressive IVF > 30 ml/kg were associated with 30-day all-cause mortality OR 1.42 (95% CI 0.88-2.3, P = 0.15, I² =35%).
• The need for vasopressor during stay was similar: OR 0.69 (95%CI 0.42-1.15, P=0.21, I² = 33%)
• The need for invasive mechanical ventilation during hospitalization was similar: OR 0.85 (95% CI 0.57-1.26, P = 0.42, I² = 0)
• Both groups had similar ICU length of stay: Standard Difference in Means -0.002 (Very small magnitude), 95% CI -0.35 to 0.34, P= 0.99, I² = 53)
• Similar hospital length of stay: Standard Difference in means -0.11 (small magnitude), 95% CI -0.62 to 0.38), P= 0.67, I²=77%

Discussion:

• All studies were retrospective studies, as it’s hard to do RCT when the treatment is required by guidelines.  Although the studies were graded as high quality but there was still risk of bias.
• Until there is significant evidence to change the guidelines, please document thoroughly in your charts if you do not give sepsis patients who have fluid overload the required volume of IVF at 30 ml/kg.
• Consider early vasopressor.

Conclusion:

• Patients who have fluid overload and sepsis had similar outcomes when they were given IVF at rates < 30 ml/kg, compared to those given IVF > 30 ml/kg as required by CMS.

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Have you ever wonder what patients feel after being intubated in the ED?

The study " Awareness With Paralysis Among Critically Ill Emergency Department Patients: A Prospective Cohort Study" aimed at answering just that.

Settings: Emergency Departments from 3 hospitals; This was a secondary analysis of a prospective trial.

Patients:

Patients who received neuromuscular blockade in ED

Intervention: None.

Comparison: None.

Outcome: Primary outcome was Awareness while paralyzed, secondary outcome was Perceived threat, which is considered the pathway for PTSD.

Study Results:

The study evaluated 388 patients.  There were 230 (59%) patients who received rocuronium.

Patients who received rocuronium (5.5%, 12/230) were more likely to experience awareness than patients receiving other neuromuscular blockade (0.6%, 1/158).

Patients who experienced awareness during paralysis had a higher threat perception score that those who did not have awareness (15.6 [5.8] vs. 7.7 [6.0], P<0.01).

A multivariable logistic regression, after adjustment for small sample size, showed that Rocuronium in the ED was significantly associated with awareness (OR 7.2 [1.39-37.58], P = 0.02). 

Discussion:

With the increasing use of rocuronium for rapid sequence intubation in the ED, clinicians should start to pay more attention to the prevalence of awareness during paralysis.  According to the study, patients reported pain from procedures, being restrained, and worst of all feelings of impending death.

One of the risk factors for awareness during paralysis would be the long half-life of rocuronium, compared to that of succinylcholine.  Therefore, clinicians should consider prompt and appropriate dosage of sedatives for post-intubation sedation.  Previous studies showed that a mean time from intubation till sedatives was 27 minutes (2), and propofol was started at a low dose of 30 mcg/kg/min for ED intubation (3). 

Conclusion:

Approximately 5.5% of all patients or 4% of survivors of patients who had invasive mechanical ventilation in the ED experienced awareness during paralysis.  They also were at high risk for PTSD.

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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.

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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.

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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.

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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

5.  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%) 
6. 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.