UMEM Educational Pearls - By Quincy Tran

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?

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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