Valproic acid (VPA) is often used to treat seizure disorder and mania as a mood stabilizer. The mechanism of action involves enhancing GABA effect by preventing its degradation and slows the recovery from inactivation of neuronal Na⁺ channels (blockade effect).

VPA normally undergoes beta-oxidation (same as fatty acid metabolism) in the liver mitochondria, where VPA is transported into the mitochondria by carnitine shuttle pathway.

In setting of an overdose, carnitine is depleted and VPA undergoes omega-oxidation in the cytosol, resulting in a toxic metabolite.

Elevation NH₃ occurs as the toxic metabolite inhibits the carbomyl phosphate synthase I, preventing the incorporation of NH₃ into the urea cycle.

Signs and symptoms of acute toxicity include:

• GI: nausea/vomiting, hepatitis
• CNS: sedation, respiratory depression, ataxia, seizure and coma/encephalopathy (with serum concentration VPA: > 500 mg/mL)

Laboratory abnormalities

• Serum VPA level: signs of symptoms of toxicity does not correlate well with serum level.
• NH₃: elevated
• Liver function test: elevated AST/ALT
• Basic metabolic panel: hypernatremia, metabolic acidosis
• Complete blood count: pancytopenia

Treatment: L-carnitine

• Indication: hyperammonemia or hepatotoxicity
• Symptomatic patients: 100 mg/kg (max 6 gm) IV (over 30 min) followed by 15 mg/kg IV Q 4 hours until normalization of NH3 or improving LFT
• Asymptomatic patients: 100 mg/kg/day (max 3 mg) divided Q 6 hours.

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During rapid sequence intubation (RSI) we endeavor to avoid positive pressure ventilation, prior to securing a definitive airway. As such, an adequate buffer of oxygen is necessary to ensure a safe apneic period. This process involves replacing the residual nitrogen in the lung with oxygen. It has been demonstrated that a standard nonrebreather (NRB) mask alone does not provide a high enough fractional concentration of oxygen (FiO2) to optimally denitrogenate the lungs (1). Even when a nasal cannula at 15L/min is utilized in addition to the NRB, the resulting FiO2 is not ideal. A bag-valve mask (BVM) with a one-way-valve or PEEP valve has been demonstrated to provide oxygen concentrations close to that of an anesthesia circuit. But its effectiveness is drastically reduced if a proper mask seal is not maintained during the entire pre-oxygenation period (1). This is not always logistically possible in the chaos of an Emergency Department intubation.

A standard NRB with the addition of flush-rate oxygen appears to be a viable alternative. Recently published in Annals of Emergency Medicine, Driver et al demonstrated that a NRB with wall oxygen flow rates increased to maximum levels, rather than the standard 15L/min, provided end-tidal O2 (ET-O2) levels similar to an anesthesia circuit (2). 

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Takeaways

In a study of alarms from 77 monitored ICU beds over the course of a month at the University of California, San Francisco, false alarms were common. Accellerated Ventircular Rhythms (AVRs) made up roughly one third of the alarms, and of the more than 4,361 AVRs, 94.9% were false while the remaining 5.1% did not result in a clinical action.

While this study had a majority of patients in the Med/Surg ICUs, a minority were from the cardiac and neurologic ICUs giving it some broad applicability. This study adds to the literature indicating there are subsets of alarms which may not be necessary or which may require adjustment to increase specificity.

Suba S, Sandoval CS, Zegre-Hemsey J, et al. Contribution of Electrocardiographic Accelerated Ventricular Rhythm Alarms to Alarm Fatigue. American Journal of Critical Care. 2019; 28(3):222-229

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The pattern of prescription drug abuse continues to center around semisynthetic opioids like oxycodone and hydrocodone. Federal regulations have now raised hydrocodone to a schedule II drug like oxycodone. Despite efforts, the slope for natural and semisynthetic opioids remains steep.  The ED measures of education, limit prescriptions for acute pain, minimize number of days/pills prescribed and utlize the prescription drug monitoring program are some basics that can assist you in better prescribing habits.

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Question

A 3 year old is bitten by a spider on his right ear which is causing him intense pain, tachycardia, and muscle cramping. Identify the spider.  What is the treatment?

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Sports Hernia/Athletic pubalgia

Hx: Gradually increasing lower abdominal/proximal adductor pain. Usually activity related, resolves with rest. Frequent return despite rest when sports activity resumes.

Most common in athletes who perform cutting/maneuvers in addition to frequent acceleration/deceleration. Think ice hockey and soccer.

Bilateral symptoms not uncommon.

PE:  Resisted sit up with palpation of the inferolateral edge of the distal rectus may recreate symptoms. Similarly, resisted hip adduction may elicit symptoms. 

If for no other reason than to make the diagnosis harder to make, valsalva induced pain may also occur.

Fluoroscopic guided injections can be helpful to isolate the site of pain generation.

First line therapy is rest, non-narcotic analgesia and physical therapy.

With surgery, >80% return to pre injury level of play.

http://atlantasportsmedicine.com/orthopedic-surgeon/wp-content/uploads/2009/11/groin-injuries.jpg

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Question

23 year-old female presents complaining of progressive right lower quadrant pain after doing "vigorous" pushups. CT abdomen/pelvis below. What’s the diagnosis? (Hint: it’s not appendicitis)

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The Prehospital Acute Neurological Treatment and Optimization of Medical Care in Stroke Study (PHANTOM-S) was a randomized prehospital  clinical trial. On certain days, a dedicated Stroke Emergency Mobile (STEMO) responded to possible ischemic stroke incidents. Outcomes measured included time to thrombolysis and adverse events such as intracerebral hemorrhage. As opposed to usual prehospital care, a STEMO ambulance was equipped with a CT scanner, point of care laboratory, and a neurologist. According to the study, STEMO use resulted in reduced time to treatment (tPA) without adverse events. 

Though this trial did not specifically measure clinical endpoints, it addresses issues central to the delivery of specialized prehospital care:

1) Are there certain conditions which might warrant a tailored, super-specialized EMS response?
2) Are EMS systems capable of delivering definitive care to the patient as opposed to delivering the patient to definitive care? 

Stateside study has already started.  The Houston Fire Department, in partnership with UTHeath, has already loosed a "Mobile Stroke Unit" on the streets. Like the STEMO, the specialized ambulance will be University hospital based, carry a neurologist, and have the capability to administer tPA. 

STEMO pictures courtesy of the "NeuroEMS Blog"
http://www.neuroems.com/2014/05/14/tpa-in-the-truck-results-of-the-phantom-s-trial/

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Pulmonary Embolism 

• In patients with high pretest probability and abnormal vital signs think about cardiac evaluation for pulmonary embolism. McConnell’s sign is most specific but can also be found in acute RCA infarct. TAPSE < 1.8 cm is also a good identifier of RV strain. Remember that patients with COPD or Pulm Htn may have RV dilation at baseline. You may also want to risk stratify patients with PE with labs as well as lower extremity dvt studies. 
• Let’s give a shout out to Ashley Pickering who recently took some awesome echo images of a patient with a known saddle embolism. 

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Oxygenation goals

• In recent pearls we have talked about 'lung protective' ventilation strategies to reduce volutrauma, barotrauma, and oxygen toxicity.
• Using 'lung protective' strategies, such as low tidal volumes, results in higher levels of CO₂ and a lower pH.  These are tolerated in favor of lower and safer alveolar pressures.
• In addition to higher pCO₂ values and lower pH, oxygenation goals are slightly lower than conventional teaching.
• In these patients, you want to maintain S_pO₂ > 88% and P_aO₂ > 55 mm Hg.

D-Dimer levels are known to be elevated in pregnancy. But how high is too high and can this test be used in the workup of VTE in pregnant patients?

Recent literature indicates that D-dimer levels in each of the three trimesters are approximately 39% higher: 700, 1000, and 1400 ng/dL for each trimester (normal cutoff 500 ng/dL). So, figure out what trimester your patient is in and use the corresponding D-Dimer level for that trimester.

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Question

An alcoholic patient presents with a cough, fever, and very foul smelling breath (worse than usual)

What's the diagnosis? And what are the risk factors?

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Methods: A large retrospective case series evaluated 121 children under 6 years old with hypoglycemia from a sulfonylurea ingestion.

Results:

• In addition to dextrose, patients who received octreotide had a median of zero hypoglycemic episodes after octreotide (compared to 2 before treatment, p < 0.0001).
• Median blood glucose concentrations after receiving octreotide were also higher (62 mg/dL vs 44, p < 0.001).
• Most required only 1 dose of octreotide with no reported adverse effects.

Authors' Conclusion: Octreotide administration decreases the number of hypoglycemic events and increases blood glucose concentrations in children with sulfonylurea ingestion.

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General Information:

-As of April 5^th, 14 confirmed cases of a new influenza A virus (H7N9) have occurred in China.  Six of those have died. 

-Presumed transmission via infected poultry in bird markets, and thus far no person-to-person transmission has occurred.

-Likely susceptible to oseltamavir or inhaled zanamivir

Area of the world affected:

-China

Relevance to the US physician:

- Suspect in patients with a respiratory illness and appropriate travel history.

- Refer to CDC within 24 hours if test positive for flu A but cannot be subtyped

- If H7N9 is suspected, patients should be under droplet and airborne precautions

Bottom Line:

No human-to-human transmission from H7N9 thus far, but the possibility exists.  Any unsubtypeable influenza A patient should be placed on droplet and airborne precautions and oseltamavir or zanamivir started immediately.

University of Maryland Section of Global Emergency Health
Author: Andi Tenner, MD, MPH

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