UMEM Educational Pearls

Many patients are treated in the emergency room for non-fatal opioid overdose. However, it is unknown what proportion of these patient population experience subsequent fatality after their ED visit. 

A recent study investigated the 1-year mortality rate among Massachusetts ED patients who were treated and discharged from ED for non-fatal opioid overdose.

Results

• 11,557 patients were identified between July 1, 2011 and September 30, 2015.
• There were 635 fatalities (5.5%) within 1 year in this cohort.
  • Of these, 428 (67.4%) died due to opioid overdose

Of those who died, 

• 130 (20.5%) died within 1 month
• 29 (4.6%) died within 2 days.

Manner of death

• Natural causes: 121 (19.1%)
• Accidental: 460 (72.4%)
• Suicide: 13 (2.0%)
• Other/pending investigation: 41 (6.5%)

Place of death

• Hospital: 310 (48.8%)
• Residence: 146 (23.0%)
• Other/unknown/nursing home: 179 (28.2%)

Conclusion

• There is high rate of fatality within 1 month (20.5%) after non-fatal opioid overdose ED visits.
• Subsequent fatal opioid overdose was observed in 428 (67.4%) of the cohort.

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Settings: multicenter, double-blind, phase 3 trial (apparently vitamin D worked in phase 2 trials).

• Patients:
  • 1059 patients were enrolled within 12 hours of ICU admission.  The patients had to have risk factors warranted ICU admisions (pneumonia, sepsis, mechanical ventilation, shock, pancreatitis, etc.).
  • Vitamin D deficiency was defined as plasma level < 20 ng/ml
• Intervention:
  • 531 patients received a single oral dose of 540,000 IU of vitamin D3 within 2 hours after randomization
• Comparison
  • 528 patients received placebo
• Outcome
  • 90-day all-cause mortality

Study Results:

• Total SOFA score was similar in both groups (5.6 vs. 5.4).               
• On day 3, mean plasma vitamin D was higher (47 ng/ml) in treatment group vs 11 ng/ml in placebo group
• 90-day all cause mortality was similar.  Treatment group was 23.5% vs. 20.6% for placebo (95% CI, −2.1 to 7.9; P = 0.26).
• Vitamin D-related adverse events were similar in both groups.

Discussion:

• This trial enrolled patients early in their critical illness compared to phase 2 trial which enrolled patients after 3 days in the ICU.
• This phase 3 trial also enrolled mostly medical-related illness, whereas 75% of patients in phase 2 had either surgical or neurology-related illnesses.

Conclusion:

Early administration of high dose vitamin D did not improve 90-day all cause mortality.

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Known effects and side effects of prescribed medicines may masquerade as cauda equina syndrome (CES) .

Analgesic medicines used by patients with chronic back pain may also cloud the diagnosis of CES.

Cholinergic medications (glaucoma/myasthenia) may lead to voiding issues.

Anticholinergic medications (COPD/urinary incontinence) may lead to urinary retention.

Opioids – Constipation, reduced bladder sensation

Anticonvulsants (Gabapentin/Pregabalin)- Urinary incontinence

Antidepressants (Amitriptyline) – Urinary retention, sexual dysfunction, reduced awareness of need to pass urine

NSAIDs – Urinary retention.

• 2.3 fold greater risk versus non users.  Higher in those aged 45 years or older, Highest risk (3.3 fold) was observed in patients who had recently started using NSAIDs. Dose dependent association.  

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Adequate treatment of adrenal crisis (AC) is often delayed, even when a h/o adrenal insufficiency is known.

• most important predictor of AC is a h/o of AC

Besides refractory hypotension, also consider in pts with:

• critically ill pts with eosinophilia (cortisol typically suppresses eosinophil counts)
• cancer patients who are on check-point inhibitor immunotherapy (they can cause severe hypophysitis or adrenalitis)
• (inhaled glucocorticoids and topical creams also cause a degree of adrenal insufficiency)

Beware of triggers:

• trauma, recent surgery, even emotional stress/exercise
• recent initiation of medications that increase hydrocortisone metabolism (avasimibe, carbamazepine, rifampicin, phenytoin, and St. John’s wort extract)
• recent withdrawal of medications that decrease hydrocortisone metabolism (voriconazole, grapefruit juice, itraconazole, ketoconazole, clarithromycin, lopinavir, nefazodone, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, and conivaptan)

Treatment:

• 100 mg IV hydrocortisone STAT as a loading dose, followed by 50 mg IV hydrocortisone q6h
• can also give 40 mg IV methylprednisolone if hydrocortisone is not immediately available
• can also give 4-6 mg IV decadron instead (will preserve integrity of ACTH stim test to diagnose adrenal insufficiency if it is performed later)

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Influenza is a common cause of community-acquired pneumonia and invasive bacterial coinfection may occur.  In addition, secondary bacterial pneumonia due to MRSA is becoming more prevalent.  Due to the higher incidence of MRSA, it is recommended that antibiotics with activity against MRSA (vancomycin or linezolid) be included in the empiric treatment regimen, especially if the patient is critically ill.

Take Home Point: Don’t forget to add MRSA coverage to your empiric treatment regimen in those influenza patients with severe disease or secondary bacterial pneumonia.

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Pharmacobezoars (clumps of medication/pills) formation has been demonstrated in few medications such as aspirin, and ferrous sulfate tablets. Their presence can alter management due to prolonged absorption and may cause GI obstruction.

Acetaminophen (APAP) is a commonly available over-the-counter medication that is often implicated in an acute overdose event. A recently published in-vitro study (using pig stomach) investigated whether APAP can form a pharmacobezoar.

APAP group/dosage

• 25 gm (50 tablets)
• 37.5 gm (75 tablets)
• 50 gm (100 tablets)

Positive control group

• ferrous sulfate (15 gm/50 tablets)

Negative control group

• chlorpheniramine (200 mg (50 tablets)

Results

• APAP formed clumps in 37.5 gm and 50 gm groups
• 83% (5 out of 6) of the 25 gm APAP group did not form clumps.

• Dissolution profile: APAP clumps released more slowly (over 60 min tested) compared to individual tablet without reaching a peak.

Conclusion

• APAP can form pharmacobezoar at doses greater than 37.5 gm (in-vitro model) and can result in prolonged or delayed toxicity due to pharmacobezoar formation.

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The arrival of a critically ill pregnant patient to the ED can be anxiety-provoking for emergency physicians as two lives and outcomes must be considered.

Some basic tenets of care, regardless of underlying issue, include:

• Obtain IV access above the diaphragm to avoid delay/prevention of administered products reaching central circulation due to compression of the IVC by the gravid uterus. 

• Provide supplemental oxygen as needed to maintain a saturation of >95% which corresponds to a PaO2 >70 mmHg. A PaO2 <60 mmHg is associated with fetal hypoxemia which will quickly lead to fetal acidosis and bradycardia. 

• Goal maternal PaCO2 is 28-32 mmHg; this respiratory alkalosis maintains a CO2 gradient to help shift offload fetal CO2 into the maternal circulation for clearance. 

• Hypotensive pregnant patients with a large uterus (20+ weeks) should be turned to the left lateral decubitus position or tilted leftward by at least 15 degrees to offload aortocaval compression and minimize secondary decrease in venous return) by the gravid uterus. 

• In cases of maternal cardiac arrest, the patient should be kept supine for chest compressions with the gravid uterus manually displaced to the left.

• Keeping the mother alive is the best way to keep the fetus alive. Standard sedatives, vasopressors, and inotropes are okay if they are needed. Exception for ketamine, which has mixed effects in existing studies and while low doses are probably safe if needed, use as a firstline agent is not recommended. Notify the NICU team of medications given to mother if there is a precipitous delivery.

• Fetal tococardiometry monitoring if available, or regular POCUS assessment of FHR, in all viable pregnancies.

Finally, once critical illness is identified the OB and NICU teams should be consulted immediately. Fetal distress in a viable pregnancy may be an indication for delivery, and initiation of the transfer process should occur if the supportive specialties are not in-house.

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Non-opioid medications such as gabapentin are frequently prescribed for the management of pain. 

A retrospective study of the National Poison Data System (data collected by the U.S. Poison Centers) from 2013 – 2017 showed increasing trend of gabapentin exposure.

Gabapentin exposure increased between 2013 and 2017 by:

• Total exposure: 72.3% 
• Isolated intentional suicide attempt: 80.5%
• Isolated exposure: 67.1%
• Isolated intentional abuse/misuse: 119.9%

5 most commonly co-ingested substances with gabapentin

• Sedative-hypnotic: 22.9%
• Antidepressant: 12.7%
• Antihypertensive: 9.9%
• Opioid: 9.0%
• Antipsychotics: 6.3%

16.7% of the isolated gabapentin exposure required hospitalization.

Conclusion:

• Gabapentin abuse/misuse and ingestion with self-harm intent is increasing in the U.S.

Hemophagocytic Lymphohistiocytosis (HLH) – Part I

A rare, but important disease that is becoming more widely recognized and more frequently diagnosed. This disease, while uncommon, is rapidly progressive and caries a high mortality rate.

Causes are not completely understood, but involve abnormal activation of the immune response due to a failure of the typical downregulation in hyperinflammatory processes.

Two types exist:

            Congenital/Familial – genetic predisposition which usually requires a triggering event to occur

            Acquired – occurs in adults with no known predisposition (often have underlying genetic predispositions) – triggering events include infections , immunodeficiency, rheumatologic disorders, and malignancy in addition to many others.

Diagnosis is challenging due to the wide variety of symptoms and constellation of symptoms, which often mimic more common infections/sepsis presentations.  Common symptoms include the following:

• Fever – 95 percentSplenomegaly – 89 percent 
• Bicytopenia – 92 percent (most often anemia and thrombocytopenia) 
• Hypertriglyceridemia or hypofibrinogenemia – 90 percent

Symptoms can, and do, occur in any body system – rashes, conjunctivitis, DIC, LFT abnormalities,  hypotension/shock, and respiratory failure are all common concomitant findings in the presentation of HLH

More on the specific diagnosis and treatment to follow in part II...

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Urinary retention in pediatrics is defined as the inability to void for more than 12 hours in the presence of a palpable bladder or a urine volume greater than expected for age.

Maximum urine volume calculation for age:  (age in years + 2) x 30ml.

Causes of urinary retention include mechanical obstruction, infection, fecal impaction, neurological disorders, gynecological disorders and behavioral problems.

The distribution is bimodal occurring between 3 and 5 years and 10 to 13 years.

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There are few conditions that can be as dramatic or difficult to control as variceal GI bleeding in a cirrhotic patient.  It is important to be familiar with all options in these cases, from Blakemore/Minnesota tube placement to massive transfusion to when and which consultants to get involved.  In cases that are refractory or not amenable to endoscopic intervention, emergent interventional radiology consultation for Transjugular Intrahepatic Portosystemic Shunt (TIPS) may be a consideration.  In high risk cases, think about getting IR on the phone at the same time as you engage GI, in case endoscopic management fails.  Variceal bleed patients can decompensate rapidly, get your consultants involved early!

Generally accepted indications for emergent TIPS (both of the following should be true):

-GI bleeding not amenable or not controllable by endoscopy

-Cause is felt to be variceal. May also consider in portal hypertensive gastropathy

Contraindications:

-Right heart failure or pulmonary hypertension

-Severe liver failure (MELD > 22, T Bili > 3 or Child-Pugh C. In these cases TIPS may not confer a significant survival benefit)

-Hepatic encephalopathy (relative contradindication.  HE may be worsened by TIPS).

-Polycystic liver disease (makes TIPS technically challenging)

-Chronic portal vein thrombus (makes TIPS technically challenging. Acute PV thrombus is NOT considered a contraindication)

Bottom Line: In cases of variceal GI bleeding from portal hypertension, consider getting IR on the phone early to discuss emergent TIPS.

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Slipped Capital Femoral Epiphysis (SCFE)

• Progressive, posterior medial displacement (slipping) of the proximal femoral epiphysis
  • Complicated by AVN and premature physis closure

http://www.raymondliumd.com/images/SCFE%20illustrated%20and%20cropped.jpg

Early Diagnosis:

• Allows best chance for intervention and good functional outcome

• Subtle and difficult with X-ray

• Classic teaching is Klein’s line

Klein’s Line on AP view

• A line drawn from the superior aspect of the femoral neck will not intersect the femoral head epiphysis

• Modified line
  • >2mm difference in width lateral to line between each side

https://pedemmorsels.com/wp-content/uploads/2018/01/Slipped-Capital-Femoral-Epiphysis-3.png

Another virtual line may assist in diagnosis

S-sign

• The S-sign is a curvilinear line drawn on the inferior margin of the proximal femoral head neck junction along the proximal femoral physis.
•  Discontinuity or an abrupt sharp turn are abnormal

https://images.squarespace-cdn.com/content/v1/562149a6e4b0bca6fa53cb35/1530197888065-AOF0LA079Y81Q6M89RJU/ke17ZwdGBToddI8pDm48kE2XMWnCJSZ3ROkmIxQ7DdsUqsxRUqqbr1mOJYKfIPR7LoDQ9mXPOjoJoqy81S2I8N_N4V1vUb5AoIIIbLZhVYxCRW4BPu10St3TBAUQYVKcIZH9X6Fb-UKi0lvZd9RVmtFt1P_lj4JzgsdTxe78uiejbzfgXQaCWxJNArJhpf7P/Screen+Shot+2018-06-26+at+10.09.17+AM.png?format=1500w

Klein's line and S-sign

• A group of 20 orthopedic surgeons, radiologists, and pediatricians viewed 35 radiographs of SCFE using Klein's line on the AP view and the S-sign on frog-leg lateral view to make the diagnosis. 

• Overall diagnostic accuracy was better with the S-sign than Klein's line, 92% vs 79%.
  • Sensitivity of the S-sign was 89%, specificity 95%. 
  • Sensitivity of Klein's line was 68%, specificity 89%. 

• Combined S-sign + Klein's line sensitivity was 96%, specificity 85%.

Consider adding both of these virtual lines/signs to your review of the pediatric hip plain film

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Pearl: consider desmopressin (DDAVP) for patients with an intracranial hemorrhage who are taking an antiplatelet. Caution, this is not for patients with an ischemic stroke with hemorrhagic conversion and it was not specifically evaluated for patients on anticoagulation or going to the OR with neurosurgery.

How strong is this evidence? International guidelines already give cautious approval for this practice, and now there is a retrospective review to support it. Though there were only 124 patients in the trial, the rate of hemorrhage expansion was much lower in the DDAVP group (10.9% vs 36.2%, P = .002) and there was no increased risk of hyponatremia (no events reported).

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Adenosine is an atrioventricular nodal blocking agent that is commonly used in the treatment of supraventricular tachycardia.  It is dosed as 6 mg IV Push x 1, followed by dose escalation to 12 mg IV Push if the initial dose was unsuccessful.  In patients with central access or prior orthotopic heart transplantation, the initial recommended dose is 3 mg.

Due to its short half-life (< 10 seconds) it is imperative to administer in the most proximal access and follow with a 20 mL bolus of saline.  Traditionally this is done using a two-way stopcock. 

A new study compared single syringe (adenosine 6mg + 18 mL saline) vs two syringes (adenosine 6mg in one, 20 mL saline in the other) in 53 patients with SVT.  The single syringe arm converted to NSR 73.1% after one dose compared to 40.7% in the two-syringe arm (p=0.0176).  After up to three doses, the single syringe arm had 100% conversion compared to 70.4% in the two-syringe arm (p=0.0043).

Single syringe adenosine has been recommended in FOAM for several years.  Although small, this study is the first to compare the two methods.  This method simplifies administration and may improve cardioversion rates.

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After many years of national shortage and FDA’s black box warning in 2001 (QT prolongation) droperidol is slowing becoming available.

In 2015, a prospective observational study was published involving ED patients who received droperidol for agitation (acute behavioral disturbance). 

Method

• Study period: August 2009 to April 2013 in 6 EDs in Australia
• Intervention: droperidol 10 – 20 mg IM or IV (if available)
• EKG performed within 2 hours of droperidol administration.
• QT was manually measured and plotted against the heart rate on the QT nomogram – if above “at-risk line” = abnormal

Results

• Droperidol was administered in 1,403 ED patients
• EKG available in 1,009 ED patients
• Median age: 34 years (IQR: 25-44)
• Men: 59.9%

Four leading reason for ED presentation

1. Alcohol intoxication: 421
2. Deliberate or threatened self-harm: 200
3. Psychostimulant use: 130
4. Mental illness/psychosis: 142

• Median droperidol dose: 10 mg (IQR: 10 to 17.5 mg) 
• Abnormal QT interval: 13 (1.3%, 95% CI: 0.3% to 2.3%)
  • 7 patient had other potential contributing factors: methadone, escitalopram, Amiodarone or preexisting condition. 
• Median time to sedation: 20 min (IQR: 10 to 30 min)

Adverse events

• Desaturation (<90%): 22 (1.6%)
• Airway obstruction: 8 (0.6%)
• Hypotension: 28 (2.0%)
• Extrapyramidal symptoms: 7 (0.5%)
• Arrhythmia: 1 (0.1%)
• Hypoventilation (RR < 12 breaths/min): 4 (0.2%)
• Seizure: 1 (0.1%)
• No adverse events: 1,333 (95.0%)

Conclusion

• Droperidol is a safe sedating agent with no evidence of increased risk for QT prolongation with the doses used. 

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Interventions Shown to Reduce Mortality in RCTs

• Santacruz and colleagues recently performed a systematic review to determine which multicenter RCTs in critically ill patients have shown that an intervention was associated with a reduction in mortality.
• Approximately 13% of the 212 trials included in this review reported a statistically significant reduction in mortality.  Unfortunately, many of the interventions were not associated with reduced mortality in subsequent studies.
• Interventions consistently shown to reduce mortality in multicenter RCTs in critically ill patients were limited tidal volume in patients with ARDS, noninvasive ventilation in acute hypercapnic respiratory failure, and noninvasive ventilation following extubation in complex cases.
• Corticosteroids in septic shock, selective digestive decontamination, and prone positioning in ARDS remain controversial.

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Antibiotic stewardship has led various organizations such as the AAP, AAFP, and IDSA to introduce two different approaches to the treatment of acute otitis media (AOM):

• Immediate treatment with antibiotics versus
• initial observation for 48-72 hours without antibiotics.

Immediate treatment with antibiotics should always include the following patients:

• Children <6 months old
• Toxic appearing
• Severe signs/symptoms: otorhea, persistent pain, fever>39C, bilateral ear disease

The observation approach can be considered in the following very slect patient group:

• Otherwise healthy children >2 years of age
• Non-severe illness
• Unilateral ear disease
• Access to follow up within 48-72 hours
• Parental comfort / Shared decision making

Often the issue with pediatric AOM isn't necessarily the overprescribing of antibiotics, but the inaccurate/inappropriate over diagnosis of acute otitis media.  An erythematous tympanic membrane does not equal AOM.  Crying and fever can result in a red TM. Fluid seen behind the TM, is often just serous otitis media, which isn't AOM. 

When antibiotics are warranted, first-line treatment is with high dose amoxicillin, 90 mg/kg per day divided into two doses; unless the child has received beta-lactam antibiotics in the previous 90 days and/or also has puruent conjunctivitis mandating amoxicillin-clavulanate instead.  In the later case, prescribing the Augment ES, 600 mg/5mL formlation with a lower clavulanic concentration lessening GI upset and diarrhea is prefered.

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• Up to 1/3 of status epilepticus do not respond to benzodiazepines.
• Fosphenytoin, valproate, and levetiracetam are 3 antiepileptic medications commonly used to treat benzodiazepine-resistant status epilepticus, though it is unclear which is more effective.
• Results from the long awaited Established Status Epilepticus Treatment Trial (ESETT) has just been released.
• Fosphenytoin, valproate, and levetiracetam each achieved seizure cessation within 1 hour in approximately 50% of patients.
  • 80% of responders had seizure cessation within 20 minutes.
• Seizure recurrence was observed in 10% of each treatment group.
• It is important to note the dosages of antiepileptic medications used were:
  • Fosphenytoin 20 mg PE/kg, max 1500 mg 
  • Valproate 40 mg/kg, max 3000 mg
  • Levetiracetam 60 mg/kg, max 4500 mg

Bottom Line: Fosphenytoin, valproate, and levetiracetaim have similar efficacy in treatment of benzodiazepine-resistant status epilepticus.

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Settings

• Patients: mechanical ventilation in the ICU. Randomization of 1000 patients.
• Intervention: conservative oxygen therapy, if spO2 reached 97%, then FiO2 was lowered to 0.21
• Comparison: no specific limits for FiO2 or SpO2.
• Outcome: number of ventilator-free days at 28 days after randomization.

Study Results:

• 484 conservative-oxygen group vs  481 to the usual oxygen group
• Comparing to the conservative-oxygen group had:
• more time at FiO2 21 (29 hours vs. 28 hours),
• less time with SpO2 > 97% (27 hours vs. 49 hours)
• Similar ventilator-free days: 21 days vs. 22 days.

Discussion:

This study’s results differed from previous single center study (Girardis JAMA 2016) or meta analysis (Chu DK, Lancer 2018), which showed mortality benefit in patients with conservative oxygen (Girardis & Chu) and more ventilator-free days (Girardis).

Conclusion: Conservative oxygen did not significantly affect the ventilator free days of mechanically ventilated patients.

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Question

A ~55 year-old female with a history of ESRD and diabetes who presented to the ED with progressively worsening foot odor. An x-ray was performed. The picture below shows the right foot.

What is the diagnosis?

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