Toxicology Expert: Poisoning Of Harvard University Scientists "No Accident"

• 6 scientists in a Boston area lab drank coffee that was laced with sodium azide
• Presented with hypotension, nausea and vomiting - one had a syncopal episode
• Sodium Azide is a chemical compound (NaN3) that is used as a preservative at very low concentrations but in higher concentrations can be lethal. It is even found in the propellant that is found in automobile airbag mechanisms
• It acts similiar to cyanide where it inhibits cytochrome oxidase and presents like a cyanide poisoning.
• No antidote, cyanide antidote kit will not work

• In 1976, vaccination with the swine flu vaccine was associated with a small risk of developing Guillain Barre Syndrome (GBS), approximately 1 additional case per 100,000 people who received the swine flu vaccine, which was slightly higher than the background rate for GBS.

• Since then, numerous studies have been done to evaluate if other flu vaccines were associated with GBS. In most studies, no association was found, but two studies suggested that approximately 1 additional person out of 1 million vaccinated people may be at risk for GBS associated with the seasonal influenza vaccine.

• It is important to keep in mind that severe illness and possible death can be associated with influenza, and that vaccination is the best way to prevent influenza infection and its complications.

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This week's pearl is courtesy of Dr. Evie Marcolini.  Thanks Evie!

Abdominal Compartment Syndrome in Burn Patients

• Patients who receive > 250 ml/kg of fluid in the the 24 hours after burn injury will most likely require abdominal decompression.
• In light of this, bladder pressure monitoring should be part of your practice in resuscitation of the patient with >30% TBSA burns.
• The simple act of placing the bladder probe will increase awareness of the possibility of ACS and prompt measurement of abdominal compartment pressures. 
• ACS can be treated with decompressive laparotomy, or in some cases, percutaneous abdominal decompression.

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A handful of lab abnormalities occur as a normal part of aging. Elderly patients will often demonstrate the following lab abnormalities without these indicating pathology:
1. ESR increases...use the following correction factor: top normal ESR < (age + 10)/2
2. creatinine falls
3. alkaline phosphatase may be elevated 2-3 fold
4. urinalysis may show asymptomatic pyuria or bacteriuria
5. ABGs demonstrate lower PaO2s and elevated A-a gradients
6. the top normal D-dimer level elevates slightly
7. the top normal BNP level elevates slightly
8. the ECG may show a first degree AV block, poor R-wave progression, leftward axis, and PVCs

Winged scapula is caused by muscular injury or damage to corresponding muscular innervation. Mechanism can be due to blunt or penetating thoracic trauma.

• Trapezius muscle
  • Long thoracic nerve
• Serratus Anterior muscle
  • Spinal Accessory Nerve

Clinical findings include

• Protruding medial edge of the scapula
• Exacerbation by pushing against resistance
• Difficulty lifting arm over head

Treatments

• Initial splinting and orthopedic referral
• Depending on mechanism - trial of physical therapy
• Surgical treatments include fascial grafts or adjacent muscle attachment

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• characterized by paroxysms of severe vomiting without apparent cause separated by periods of complete health
• typically begins between 3 and 7 years of age
• family or patient history of migraine or irritable bowel syndrome often noted
• intentse vomiting with lethargy, fever, and headache preceding the onset of emesis
• episodes last up to 48 hours (but may last up to one week) with 4-12 episodes per hour, and end suddenly often after sleep
• two thirds of children become so dehydrated they require intravenous fluids
• most patients have stereotypic patterns of onset and triggering events
• rapid treatment with IVF and glucose, along with migraine treatments such as cyproheptadine, propanolol, and TCA's
• antiemetics often not effective

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Zanamivir (Relenza) is another neuraminidase inhibitor effective against influenza strains A and B. We are currently reserving its use for patients with H1N1 that may develop resistance to oseltamivir (Tamiflu) since it has been effective in these situations with past influenza strains.

• Zanamivir is given by inhalation only (powder) and can therefore not be given to ventilated patients
• Treatment dose is 10 mg (two blister packs) BID for 5 days
• Prophylaxis is 10 mg (two blister packs) once daily for 10 days
• Most common adverse effects are respiratory related and include bronchospasm and cough
• Pregnancy category C (same as Tamiflu) and should be used in pregnant patients with suspected/confirmed H1N1 due to the increased risk of morbidity/mortality
  • In fact, zanamivir may be the preferable antiviral for pregnant women because of its limited systemic absorption

• Guillain-Barre’ Syndrome (GBS) is a group of immune mediated processes characterized by motor, sensory, and autonomic dysfunction of peripheral nerves.

• Classically, GBS is an acute inflammatory demyelinating polyneuropathy (AIDP) consisting of progressive, symmetric, ascending muscle weakness and paralysis, associated with diminished deep tendon reflexes.

• This rare condition, affecting 3,000 to 6,000 Americans annually (1 to 2 out of 100,00 per year), can lead to respiratory failure in severe cases, requiring vigilance in pro-actively administering mechanical ventilation as needed.

Extracorporeal Membrane Oxygenation

• In last week's pearl pertaining to critically ill patients with H1N1, I mentioned the use of ECMO as a potentially life-sustaining treatment for refractory respiratory failure.
• Essentially, ECMO removes blood from the patient and circulates it through an artificial lung with a pump.  For patients with respiratory failure, this is usually accomplished via cannulation of the femoral and internal jugular veins.
• General guidelines to consider ECMO in severe, refractory respiratory failure include:
  • P_aO₂ / F_iO₂ ratio < 100 on 100% F_iO₂ or A-a gradient > 600 mm Hg
  • Age < 65 years
  • No known contraindication to anticoagulation
  • Lack of significant co-morbidities (due to prolonged recovery after weaning from ECMO)

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Got some interesting info today on the costs of some commonly used antihypertensive medications. Keep in mind that in patients with severe hypertension, your options of IV drips are limited.

Here is some info from our hospital:

Fenoldopam - $113.28
Nicardipine - $94.67
Esmolol - $82.15
Nitroprusside - $20.86
Labetalol - $14.40
Nitroglycerin - $2.90

Although Fenoldopam (Corlopam), which has been around for years, is more expensive than Nitroprusside, it is just as effective and without the side effects.

A new drug on the market that we don't have yet, Clevidipine, is just as effective as the big guns Nipride and Fenoldopam. Costs at this point are unknown.

More on antihypertensive medications next week....

It's no secret that the elderly are at high risk for adverse drug effects. The average elderly patient takes 5 prescribed medications plus two over-the-counter medications. As many as 5% of admissions in the elderly are attributable to adverse drug effects. 

Anytime you prescribe a new medication to an elderly patient, ALWAYS check for the possibility of drug interactions.

Snuff Box Tenderness:

It has become the standard of care that individuals with snuff box tenderness, or pain with axial loading of the thumb, be placed in a thumb spica splint for 1-2 weeks until follow up x-rays can be done.  This is done to rule out an occult scaphoid fracture.  However, this practice can be hugely inconvenient to the patient and result in some atrophy of their forearm.

An alternative approach is to obtain a CT scan through the wrist to look specifically at the scaphoid bone.  If the CT scan is negative you can send them home with some pain control, RICE (Rest, Ice, Compression, Elevation) treatment and let them use thier thumb.  No splint is needed.  If it is positive then you can splint them and have them follow up with orthopedics or hand surgery.

This is a semi-synthetic opiate with partial agonist activity at the mu receptor. For an example of what a partial agonist is - see attached illustration. It is used in opioid addiction but is not as regulated as methadone clinics. Take a small course and you are licensed to prescribed it.  Primary caregivers are now able to administer buprenorphine to assist addicts though it is not recommended if the patient is requiring more than 40mg of methadone (rules out everyone in Baltimore).

The tablets (Suboxone) also contain naloxone to prevent intravenous injection which would induce withdrawal. Naloxone is not orally bioavailable and thus can be mixed into the pill.

Overdose is treated like any other opioid and naloxone should work.

Buprenorphine can illicit an opioid withdrawal response if the patient is currently on an opioid and then takes buprenorphine. 

Suppose to be safer than methadone - no QT prolongation and less respiratory depression

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• 0910152041_PartialAgonistBup.jpg (35 Kb)

• Pregnant patients presenting with their first seizure, should essentially be managed in the same way as any other adult patient (i.e. Is the source of the seizure due to a reversible systemic condition, and if not, is the patient at risk for recurrent unprovoked seizures; specialist follow-up arrangement).

• Additional pregnancy-related conditions that can be associated with seizure, such as eclampsia and cerebral venous thrombosis, should be considered.

• While the safety of all anti-epileptic drugs in pregnancy is questionable, the use of valproate (Depakote) should definitely be avoided, given its compelling association with fetal malformations.

Critically Ill Patients with H1N1

• Three recent reports published online in the Journal of the Americal Medical Association (JAMA) detail the potential problems of H1N1 infection in the critically ill.
• The three studies (Mexico, Canada, Australia/New Zealand) seem to have recurring themes:
  • shock and multisystem organ failure were common
  • many were healthy, young adults who developed rapid respiratory failure
  • hypoxemia was prolonged and often refractory to conventional modes of mechanical ventilation
• Newer modes of ventilation and therapies were required to treat refractory hypoxemia.  These included high frequency oscillatory ventilation, prone positioning, neuromuscular blockade, nitric oxide, and extracorporeal membrane oxygenation.
• Take Home Point: Involve your intensivist early in the management of ED patients with respiratory failure and suspected H1N1 infection, as non-conventional methods of ventilation may be needed to treat hypoxemia.

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Management of Heparin-Induced Thrombocytopenia (HIT)

HIT occurs when antibodies form to a Heparin-Platelet Factor 4 (PF4) complex in patients who have been exposed to Heparin. 

The main clinical manifestation is thrombosis (arterial/venous). Treatment is unique in that only certain medications can be used.

Medical Management options in HIT:

• Direct thrombin inhibitors (DTI). The main ones used in clinical practice include Argatroban and Hirudin. These drugs work by directly binding to thrombin (fibrin bound) and inhibiting it. The drugs are reliable and safe. Hirudin may initiate an allergic reaction in patients who have been exposed and is renally cleared (so shouldn't be used in ESRD or lower GFRs)
• Fondaparinux (Arixtra). Can be given subcutaneously. More expensive. Also approved for once daily treatment of DVT/PE

So, when a patient with a history of HIT shows up in the ED with a DVT/PE or other thrombotic problem, these are your mainstay drugs.

The recent Baltimore City Marathon served as a nice reminder in a few cases that long-distance running and other ultra-endurance events can produce elevations in troponin levels. To review the non-cardiac-disease causes of troponin elevations:

sepsis, PE, COPD, carbon monoxide, intracranial abnormalities (including SAH, stroke, IC hemorrhage, seizures), ESRD, rhabdomyolysis, eclampsia and preeclampsia, extreme endurance exercises, UGI bleeding, LVH, catecholamine toxicity 

Reimburshment Pearls:

Often charts are down coded as it is not clear from the documentation that your medical decision making was complex.

For instance, if your final diagnosis is GERD, and you do not document that you were also concerned about angina or a pneumothorax your level 5 chart could be coded as a level 3, since the final diganosis does not seem that complex.  In order to prevent this document:

• Your differential diagnosis and ideally why you were concerned about them
• Instead of just checking a box stating that you reviewed old records take 5 seconds to summarize their last visit.  (i.e.: Admitted in May for CHF exacarebation, EF 50% by Echo, discharge on lasix).  This helps the coders prove that you looked at the chart and gives you 2 points for medical decision making.
• Document the response or initial lack of response to therapy. (i.e.: Asthmatics might get discharged home and still qualify for critical care time or a level 5 chart if you document how they initially responded to nebulizers and it was the magnesium that finally broke the cycle.)

I realize that when you are busy this might be the last thing on your mind, but the difference between a level III chart and a level V chart is about $100, and the only additional work is the 3 minutes it would take to document what you did for the patient.

More to come...

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While it is often ok to defer removal of pesky nasal foreign bodies until ENT follow up, if the foreign body may be a button battery, emergent identification and removal is indicated.

Damage can occur in 3 hours, and by 24 hours, near complete necrosis of turbinates and ala has been described.

• If the object may be a button battery, consider a plain film - if it doesn't show up, it isn't a battery, and you are in the clear.
• If you can clearly see the button battery, you can try to remove it - consider using a magnet if one is available - more on that in a future pearl.
• Lastly, if you cannot visualize the battery, if there is any evidence of content leakage, or if there is any tissue damage, emergently consult ENT for assistance - this is a surgical emergency.

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A 34 y/o m presents to the ED agitated and combative with the following vitals signs: T 104.6, P 136, BP 198/124. His urine toxicology screen is positive for amphetamines. 

• Controlled animal experience clearly contraindicates the use of phenothiazines (e.g. prochlorperazine, chlorpromazine) and butyrophenones (e.g. haloperidol, droperidol).
• In animal models, these drugs enhance toxicity (seizures) or lethality, or both.
• Additional concerns regarding these drugs include their ability to interfere with heat dissipation, exacerbate tachycardia, prolong the QTc interval, and induce torsades de pointes, or precipitate dystonic reactions.