UMEM Educational Pearls

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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• Electronic cigarette (E-cigs) smoking (vaping) continues to be a major concern among adolescents and teens, who mistakenly think it is safer than smoking traditional cigarettes or don't consider it as smoking at all.
• Typically, they contain nicotine which is highly addictive and can cause harm in the developing brain, but can also contain other dangerous chemicals, flavorings and drugs.
• They often contain higher amounts and concentrations of nicotine. 1 JUUL pod can contain the equivalent of 20 packs of nicotine cigarettes.
• Inhaled aerosols of the various chemicals, flavorings, and heavy metals have resulted in lung disease and acute respiratory failure. Bilateral infiltrates on chest imaging is a common finding.
• Nicotine toxicity can also occur. Symptoms include vomiting, diarrhea, abdominal pain, salivation, headache, dizziness, confusion, and seizures. Hypertension and tachycardia acutely, followed by hypotension and bradycardia can be expected.
• Bottom Line: Ask specifically about electronic cigarette use in adolescents and teens who present with acute complaints. One study found that of those who regularly used and presented for evaluation of symptoms, 98% were respiratory, 81% were gastrointestinal, and 100% were constitutional in nature.

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• Functional neurological disorders (FND) are unintentional and involuntary. 
• Imaging and electrophysiological studies have shown cerebral dysfunctions in attention and perception, which may explain why symptoms often improve with distraction. 
• Diagnosis requires demonstration of inconsistency and/or incongruency with recognized neurological or medical conditions. 
  • No clinical sign alone is diagnostic. 
  • Patients may have comorbidities such as multiple sclerosis, stroke, or epilepsy. 
• Hoover’s sign and drift without pronation have been described as positive signs for FND. 
  • These can also be seen in patients with pain, neglect, or apraxia. 
• Avoid maneuvers that may harm the patient, such as dropping their arm onto their face. 
  • A high-pitched tuning fork applied to the nostrils is an effective stimulus to assess responsiveness.  
• Avoid using terms like non-organic, psychogenic, or pseudoseizure. 
• When counseling a patient, avoid only explaining what conditions they do not have or attributing symptoms to psychological problems or stress. 
  • Instead, name the diagnosis, explain that their symptoms are real and common, and emphasize that symptoms are potentially reversible. 
• Early diagnosis of FND is associated with improved physical and psychological outcomes. 

Bottom Line: Functional neurological disorders (FND) are commonly encountered in the ED. A thorough neurological exam may reveal positive signs suggestive of FND. Early diagnosis and referral to specialists may improve outcomes. 

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Erythrocyte sedimentation rate (ESR) for spinal infection

Sensitive for spinal infection but not specific

Elevated ESR is observed in greater than 80% of patients with vertebral osteomyelitis and epidural abscess

ESR is the most sensitive and specific serum marker for spinal infection

               Usually elevated in acute presentations of SEA and vertebral osteomyelitis

ESR was elevated in 94-100% of patients with SEA vs. only 33% of non-SEA patients

Mean ESR in patients with SEA was significantly elevated (51-77mm/hour)

Infection is unlikely in patients with an ESR less than 20 mm/h.

Incorporating ESR into an ED decision guideline may improve diagnostic delays and help distinguish patients in whom MRI may be performed on a non-emergent basis

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Supplemental oxygen therapy is frequently required for patients presenting with acute respiratory distress and COPD exacerbation. Over-oxygenation can derail compensatory physiologic responses to hypoxia,¹ resulting in worsening VQ mismatch and, to a lesser degree, decreases in minute ventilation, that cause worsened respiratory failure.

The 2012 DECAF (Dyspnea, Eosinopenia, Consolidation, Acidaemia, and Atrial Fibrillation) score was found to predict risk of in-hospital mortality in patients admitted with acute COPD exacerbation.^2,3 Data from the DECAF study’s derivation and external validation cohorts were examined specifically to look at outcome associated with varying levels of oxygen saturation.

• 1027 patients from 6 UK hospitals receiving supplemental oxygen at admission

• Lowest in-hospital mortality seen in the 88-92% cohort 

• Adj OR for in-hospital mortality in ≥97% vs 88-92% group: 2.97 (95% CI 1.58-5.58, p=0.001)

• Adj OR for in-hospital mortality in 93-96% vs 88-92% group: 1.98 (95% CI 1.09-3.60, p=0.025)

• Surprisingly, mortality risk seen more in normocapnic than hypercapnic patients

• Association between admission SpO2 and mortality persisted after adjusting for baseline risk and disease severity using the DECAF and NEWS 2 score

Bottom Line

In patients presenting to the ED with acute COPD exacerbation requiring oxygen supplementation, a target oxygen saturation of 88-92% is associated with the lowest in-hospital mortality, and higher oxygen saturations should be avoided independent of patients' PCO2 levels.

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• Alteplase administration in acute ischemic stroke (AIS) has been associated with errors.
• A recent study looked at the types of errors that occurred at regional hospitals and Comprehensive Stroke Centers.
• 19.8% (133/676) of patients had an error associated with alteplase administration with the majority occurring at regional hospitals without stroke certification.
  • The most common error was over-dosage of alteplase, occurring in 5% (36) of patients.
  • Other common errors included under-dosage, infusion errors, and apparent contraindications.
• The most common contributing factor leading to the error was incorrect calculation.
• Administration error was associated with higher rate of hemorrhagic conversion (12.7% vs. 7.1%, p=0.04).

Bottom Line: Alteplase administration in acute ischemic stroke is associated with errors, most commonly with over-dosage of the medication.

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Study Question:  A recent study investigated whether adult patients presenting to the ED with a diagnosis of mTBI prescribed light exercise were less likely to develop persistent postconcussion symptoms.

Setting:  Randomized controlled trial conducted in three Canadian EDs. Consecutive, adults (18–64 years) seen in ED with a mTBI sustained within the preceding 48 hours.

The intervention group received discharge instructions prescribing 30 minutes of daily light exercise.

The control group was given standard mTBI instructions advising gradual return to exercise following symptom resolution.

Outcome:  The primary outcome was the proportion of patients with postconcussion symptoms at 30 days,

A total of 367 patients were enrolled. Median age was 32 years Male 43%/Female 57%.

Result:  There was no difference in the proportion of patients with postconcussion symptoms at 30 days. There were no differences in median change of concussion testing scores, median number of return PCP visits, median number of missed school or work days, or unplanned return ED visits within 30 days. Participants in the control group reported fewer minutes of light exercise at 7 days (30 vs 35).

Conclusion

Prescribing light exercise for acute mTBI, demonstrated no differences in recovery or health care utilization outcomes.

Extrapolating from studies in the athletic population, there may be a patient benefit for light exercise prescription.

Make sure that the patient is only exercising to their symptomatic threshold as we recommend with concussed athletes. Previous studies have shown that athletes with the highest post injury activity levels had poorer visual memory and reaction time scores than those with moderate activity levels.

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There are three commonly household spices that can be abuse/misused or cause toxicity after exposure.

Pure vanilla extract contains at least 35% ethanol by volume per US Food and Drug Administration standards

• Results in alcohol intoxication
• Ingestion of 1.3 mL/kg in child will result in blood ethanol concentration of 100 mg/dL

Nutmeg contains myristicin – serotonergic agonist that possess psychomimetic properties. 

• Typical recreational dose: 5-30 gm. (tablespoon of ground nutmeg: 7 gm).

Clinical effects:

• GI symptoms: nausea, vomiting and abdominal pain
• Cardiovascular: hypertension and tachycardia
• CNS: hallucination, paranoia, seizure
• Others: flushing, mydriasis

Cinnamon contains cinnamaldehyde and eugenol – local irritants.

• Can cause contact dermatitis and ulceration from topical application
• Inhalation of cinnamon can result in chronic and significant pulmonary inflammation and fibrosis

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Two items from the recent INSPIRATION trial UMEM pearl were very well pointed out by our own Dr. Michael Scott and require clarification.  Thank you to all our readers for their close attention, and please know that we always appreciate you reaching out with questions/comments.  

• Dosing Correction - The "standard-dose" prophylactic dosing of enoxaparin in this trial was 40 milligrams/day.  Please excuse the error in the prior post stating 40 mg/kg/day (we will revise the post).  Standard dosing of enoxaparin for DVT/VTE prophylaxis was a flat 40 mg/day, and was not weight based.

• Major Bleeding - While the difference in major bleeding (2.5% vs 1.4%) was relatively small, this endpoint DID NOT meet non-inferiority.  In other words, the study appeared to detect a statistically significant difference in major bleeding between the dosing regimens.  Given that this is a single study and there are concerns with this finding (the authors themselves describe this as "exploratory"), I would interpret this with caution, but this supports the very intuitive notion that the intermediate (higher) dose regimen of enoxaparin would be associated with more bleeding than the standard dose regimen.  

COVID-19 is generally regarded as a hypercoagulable state, and the role of pulmonary emboli and other VTE in COVID remains unclear.  As a result, how to optimally provide prophylactic anticoagulation in COVID-19 patients who are not known to have VTE has been a point of debate.  

The INSPIRATION trial looked at 600 patients admitted to academic ICUs in Iran, and compared what is often-referred to as "intermediate-dose" prophylaxis (in this case 1 mg/kg daily of enoxaparin) to standard dose prophylaxis (40 mg/day of enoxaparin).  The study utilized a combined endpoint of venous thromboembolism, arterial thromboembolism, need for ECMO, or mortality.  As a reminder, composite endpoints can skew results.  However, the dose and type of anticoagulant chosen is similar to many academic centers around the world, and pharmacy guidelines often recommend providing this type of "intermediate-dose" prophylaxis in COVID-19 patients, sometimes based on clinical status, d-dimer or other coagulation-related patient-data.  As with many things with COVID-19, this practice is based on limited data.

There was no significant difference between groups in the primary outcome (45.7% in intermediate ppx group vs 44.1% in standard group), and while safety outcomes were similar (major bleeding in 2.5% in the intermediate ppx group vs 1.4% in standard group), the intermediate regimen failed to demonstrate non-inferiority to the standard regimen for major bleeding.

Intermediate vs standard-dose ppx was similar in this study with a small, but statistically significant increase in major bleeding in the intermediate-dose group.

Bottom Line: Although this study had methodologic flaws and there are external validity concerns, the INSPIRATION trial supports the notion that standard dose (e.g. 40 mg/g/kg/day enoxaparin) and intermediate-dose (e.g. 1 mg/kg/day enoxaparin) VTE prophylaxis are equivalent in critically ill COVID-19 patients who do not already have a known VTE in terms of preventing negative VTE outcomes.  Intermediate-dose may be associated with increased bleeding.  As more critically ill patients require ED boarding, the dose of VTE prophylaxis may remain controversial, but the need to start it remains an important consideration.

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While fluoroquinolones have fallen out of favor for many indications due to the ever growing list of adverse effects, they still play an important role in the outpatient treatment of pyelonephritis. Fluoroquinolones and TMP-SMX are the preferred agents due to higher failure rates with beta-lactams.

Preferred Therapies:
Ciprofloxacin 500 mg PO BID*
Levofloxacin 750 mg PO daily*
TMP-SMX 1 DS tab PO BID**

*Consider a single dose of long-acting parenteral agent, such as ceftriaxone, if community prevalence of fluoroquinolone resistance >10%.
**Consider a single dose of long-acting parenteral agent, such as ceftriaxone, if using TMP-SMX.

Alternative Therapies#:
Cefpodoxime 200 mg PO BID
Cefdinir 300 mg PO BID

#Beta-lactams are not preferred agents due to higher failure rates when compared to fluoroquinolones. Consider a single dose of long-acting parenteral agent, such as ceftriaxone, if using beta-lactams.

Duration of Therapy: 10-14 days

Take Home Point:
Utilize ciprofloxacin, levofloxacin, or TMP-SMX over beta-lactams when discharging patients with oral antibiotics for pyelonephritis.

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Improving Compliance with Lung-Protective Ventilation

• Approximately 250,000 ED patients are intubated and receive mechanical ventilation each year in the United States.
• While emergency physicians understand the importance of providing lung-protective ventilation, current studies demonstrate that more than 40% of ED patients are placed on initial tidal volumes > 8 ml/kg of predicted body weight (PBW).
• In many cases, this may be due to the inaccurate estimation of patient height when determining PBW.
• In a recent single-center study, Tallman and colleagues evaluated a quality improvement intiative, whereby respiratory therapists were provided with a tape measure and an EHR BPA that reminded them to measure the patient's height for PBW.
• In this study, these simple, low-cost interventions significantly increased compliance with lung-protective ventilation.
• Take Home Pearl: Be sure to measure your intubated patient to accurately determine PBW and set the correct tidal volume.

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Diphenhydramine is commonly involved in overdose or misused. Although it is primarily used for its anti-histamine property, it also has significant antimuscarinic effect.

A recent retrospective study investigated the clinical characteristics associated with severe outcomes in diphenhydramine overdose using the multi-center Toxicology Investigators Consortium (ToxIC) Registry. 

Severe outcomes were defined as any of the following:

• Seizure
• Ventricular dysrhythmia
• Intubation

Results

863 cases of isolated diphenhydramine ingestion were identified between Jan 1, 2010 to Dec 31, 2016

• Females: 59.1% 
• Age < 18 years: 51.3%
• Intentional ingestion: 86.0%
  • Self-harm: 37.5%
  • Abuse/misuse: 11.5%

Most common symptoms:

• Delirium/toxic psychosis: 40.1% (n=346)
• Agitation: 33.1% (n=286)
• Severe outcome: 15.6% (n=135)

Factors associated with severe outcome

• Intubation: self-harm ingestion and male
• Acidemia: pH <7.2
• QRS prolongation: QRS > 120 msec
• Elevated anion gap: AG >20

Conclusion

• Acidemia, QRS prolongation and elevated anion gap was associated with severe outcome in diphenhydramine toxicity

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Even though acute myocardial ischemia (AMI) does not present as commonly in the pediatric patient as in the adult and the literature is limited, it is reasonable to obtain a troponin when acute cardiac ischemia is suspected based on the history and physical exam. 

Recreational drugs including cocaine, amphetamine, cannabis, Spice, and K2 (cannabis derivatives) have been shown to result in myocardial injury including AMI. Coronary vasospasm secondary to drug use is well documented in the pediatric population. While cocaine use is a known risk factor for coronary vasospasm, the same condition has been reported in pediatric patients after marijuana use.

In a study of pediatric patients with blunt chest trauma, 3 of 4 patients with electrocardiographic or echocardiographic evidence of cardiac injury had elevations in troponin I above 2.0 ng/mL. Cardiac troponins are an accurate tool for screening for cardiac contusion after blunt chest trauma in pediatric patients even with limited data.

Cardiac troponins are also useful in the evaluation for myocarditis. In one study, myocarditis was the most common diagnosis (27%) in pediatric ED patients presenting with chest pain and an increased troponin. Eisenberg et al showed a 100% sensitivity and an 85% specificity for myocarditis using a troponin of 0.01 ng/mL or greater as a cut off.  A normal troponin using this cutoff can be used to exclude myocarditis. Abnormal troponin in the first 72 hours of hospitalization in pediatric patients with viral myocarditis is associated with subsequent need for extracorporeal membrane oxygenation and IVIg.

Bottom line: Troponin can be used in pediatric patients with clinical concern for cardiac ischemia, cardiac contusion and myocarditis

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There are different occupational hazards depending on the nature of one’s trade/skill/employment. Although healthcare providers may not always inquire about patient’s occupation, knowledge of a patient’s occupation may provide insightful information when caring for patients with acute poisoning.

From a recent retrospective study of National Poison Data System, the top 10 occupational toxicants were:

1. Caustics (acids & alkalis)
2. Chlorines/hypochlorites
3. Carbon monoxide
4. Hydrocarbons
5. Cleansers/detergents
6. Ammonia
7. Cement
8. Hydrofluoric acid
9. Disinfectants
10. Hydrogen sulfide

Top 10 occupational toxicants associated with fatalities were:

1. Hydrogen sulfide
2. Ammonia
3. Carbon Monoxide
4. Simple asphyxiants
5. Chlorine/hypochlorites
6. Alkalis
7. Pyrethrins/pyrethroids
8. Toluene/xylene
9. Methane
10. Methylene chloride 

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Question

The PARAMEDIC2 trial in NEJM 2018 studied the outcomes of the use of epinephrine in outside hospital cardiac arrest (OHCA) on survival and neurological outcome. 

Methods: Conducted in Britain, randomized 8007 patients to receive either epinepherine 1mg (n=4012) or placebo (n=3995) as part of standard CPR for out-of-hosptial arrest. Their primary outcome was survival at 30 days and their secondary outcomes included length of stay as well as neurological outcomes at 30 days and 3 months.

Results: The epinepherine group had improved survival to hospital admission (23% vs. 8%), at 30 days (3.2% vs. 2.4%) or at 3 months (3% vs. 2.2%). Favourable neurological outcomes, however, had no statistical difference at both hospital discharge and at 3 months.

Bottom line: Epinephrine improves ROSC, though with poor neurological outcomes. 

Important facts: 

• Demographics: Mean age 69 years, 35% female
• Initial cardiac rhythm: shockable 19%, Non-shockable 78%, Undetermined 2%
• Cause of Cardiac Arrest: Medical 91% Traumatic 2%, Drowning 0.2%, substance overdose 2%, Asphyxia 3%, missing data 2%
• Witness of cardiac arrest: none 37%, Paramedic 11%, Bystander 50%, missing data 1%
• CPR Performed by: Paramedic 11%, bystander 59%, missing data 2%
• Time from: emergency call to ambulance arrival 6min, emergency call to administration of drug 22 min, arrival to ambulance departure 50 min

Recently, a follow up of the PARAMEDIC2 trial was completed in Resuscitation. 

They reported long-term survival, quality of life, functional and cognitive outcomes at 3, 6 and 12-months.

Results:  At 6 months, 78 (2.0%) of the patients in the adrenaline group and 58 (1.5%) of patients in the placebo group had a favourable neurological outcome (adjusted odds ratio 1.35 [95% confidence interval: 0.93, 1.97]). 117 (2.9%) patients were alive at 6-months in the adrenaline group compared with 86 (2.2%) in the placebo group (1.43 [1.05, 1.96], reducing to 107 (2.7%) and 80 (2.0%) respectively at 12-months (1.38 [1.00, 1.92]). Measures of 3 and 6-month cognitive, functional and quality of life outcomes were reduced, but there was no strong evidence of differences between groups.

Bottom line: Epinephrine improves survival at 12 months, but poor neurological outcomes remain. 

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Bottom Line: In a recent meta-analysis the risk factors for patellofemoral syndrome are weak hip abduction strength, quadricep weakness in military recruits, and increased hip strength in adolescence.

PatelloFemoral Syndrome: Patellofemoral pain is not clearly understood and is believed to be multi-factorial.  Numerous factors have been proposed including muscle weakness, damage to cartilage, patella maltracking, as well as others.  Patient often complain of anterior knee that is aggravated by walking up and down stairs or squatting. Patellofemoral pain is extremely common. In the general population the annual prevalence for patellofemoral pain is approximately 22.7%, and in adolescents it is 28.9%.

Though commonly taught, the following have no evidence to support that they are a risk factor for patellofemoral syndrome: Age, Height, Weight, BMI, Body Fat or Q Angle of patella

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• Idiopathic intracranial hypertension (IIH) predominantly affects women of childbearing age and is strongly associated with obesity.
• Patients can have high rates of healthcare utilization due to their chronic disabling headaches, multiple diagnostic tests and specialist consultations, and potential complications related to treatments.
• A recent study looked at trends in the incidence, prevalence, and healthcare outcomes of IIH in the 3.1 million Welsh population over a 14-year period.
  • Incidence of IIH increased from 2.3/100,000 to 7.8/100,000 (p<0.001).
  • Prevalence of IIH increased from 12/100,000 to 76/100,000 (p<0.001).
  • Obesity (BMI >30 kg/m2) also increased from 29% to 40% of the population (p<0.001), with IIH incidence and prevalence strongly associated with BMI.
  • Outcomes included blindness (0.78%), moderate visual impairment (1.9%), CSF diversion (9%) with 44% of these patients requiring at least 1 revision surgery.
  • IIH patients also had 5.28 times higher rate of unscheduled hospital visits during this time period.

Bottom Line: The incidence and prevalence of IIH is increasing, likely related to rising rate of obesity. This has also been associated with more healthcare utilization compared to the general population.

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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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