• Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, previously named “anticonvulsant hypersensitivity syndrome,” is a severe adverse drug reaction which occurs in approximately 1 of every 1,000–10,000 uses of anticonvulsants.

• Characterized by triad of fever, rash, and internal organ involvement.

• Usually involves aromatic anticonvulsants such as phenytoin, carbamazepine, phenobarbital, primidone, lamotrigine, and possibly oxcarbazepine.

• DRESS occurs most frequently within the first 2 months of therapy and is not related to dose or serum concentration.

• Treatment includes prompt discontinuation of the offending agent. Patients should be admitted to the hospital and receive methylprednisolone 0.5–1 mg/kg/d divided in four doses. Other promising therapies include use of IVIG.

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As we go through the problems of national drug shortages it is important to remember the old drugs but to also remember why they became old and seldom used drugs. Prime example is many hospitals are beginning to develop shortages of rocuronium - the nondepolarizing paralytic that has a fast onset. This shortage has caused many to switch back to succinylcholine. The following case report should serve as reminder of how succinylcholine - due to its depolarizing nature and fasciculations - can cause a transient but significant hyperkalemia.

Never be the first or last person to use a drug 

Vioxx was once touted to be the drug that would be the new standard for anti-inflammatories until it was found to increase your chance of MI by 33% and cause hypertension.

Dabigatran was recently pulled from Japan markets and now is dealing with an impressive meta-analysis by Uchino et al. It showed that dabigatran was significantly associated with higher risk of MI or ACS than other agents.

Control arms (included warfarin, enoxaparin or placebo): MI rate 83 per 10,514

Dabigatran arms: MI rate 237 per 20,000

OR 1.33; 95% CI, 1.03-1.71; p=0.03

The rush for what is perceived as a panaceae for all that is wrong with coumadin could actually cause an MI while it tries to prevent a stroke in nonvalvular a-fib.

Look at the study and decide for yourself and remember Vioxx:

http://archinte.ama-assn.org/cgi/content/full/archinternmed.2011.1666v1

• Suboxone = buprenorphine and naloxone in a 4:1 ratio, respectively. Formulated in 2 mg or 8mg tablets and film.

• Buprenorphine acts as a partial agonist on the mu receptor and an antagonist at the kappa receptor.

• If > 2 mg are ingested or age < 2 years old, these patients should be evaluated in an ED as ALL children with > 4 mg ingestion had symptoms.

• There is a ceiling effect with respiratory depression however no ceiling with analgesia. This gives buprenorphine a better safety profile compared to methadone.

• Onset of symptoms is about an hour and onset of respiratory depression is about 2-3 hours.

• Increased doses of naloxone starting at 0.1 mg/kg may be needed to overcome high receptor affinity of buprenorphine. Remember, most children are opioid-naive and will not experience withdrawal symptoms. Repeat doses of naloxone and even infusions may be needed.

• In the ED, a minimum of 6 hours observation is necessary. If no clinical effects are noted at 6 hours the patient can safely be discharged, although one small case series recommended 24 hours observation.

• Unintentional overdose is common in toddlers, so advise family to keep prescriptions including family pet prescriptions locked (buprenorphine in the IV form is used for veterinary pain control).

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Another great example of the generic drug name being so difficult to pronounce you have no choice but to say - Xarelto. The drug touts ease of use and no need for hematologic monitoring like Pradaxa. This drug has the same indication for stroke prevention in nonvalvular atrial fibrillation. It also is being used in DVT prophylaxis in hip and knee surgeries.

Differences:

- Selective Factor Xa inhibitor unlike Pradaxa which is a competetive direct thrombin inhibitor

- Once a day dosing instead of twice a day for Pradaxa

Same concerns:

- No real reversal but can use FFP in a pinch

- Recommend waiting 24 hrs DC med to perform surgical procedure - this includes LP. I am personally waiting for the first case report of LP performed in ED on a patient taking either Xarelto or Pradaxa with subsequent epidural hematoma. Someone is bound to miss this on the med list. Be careful.

Even if your hospital has not added it to its formulary, you will see patients on this drug in the ED.

Generally H2O2 is available OTC at a concentration of 3-9% and used as an antiseptic. Toxicity is by two methods: local irritation like a caustic and gas formation - both directly correlating with the % concentration. Some interesting findings have occurred with this ingestion including:

1) Portal vein gas seen on CT

2) Arterialization of O2 resulting in CVA

3) Encephalopathy with cortical visual impairment

4) MRI showing b/l hemispheric CVAs

Even use of 3% H2O2 for wound irrgation has caused subcutaneous emphysema and O2 emboli.

Treatment: XR/CT/MRI may detect gas, if present in RV should be placed in Tredelenburg and carefully aspirated through a central venous catheter. Anectdotal case reports have used HBO therapy when patients were critically ill.(1)

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A recent study highlighted the challenges we face managing ED patients on warfarin therapy. Some key observations about how we're doing: 

• Only 71% of patients on warfarin had an INR checked
• Nontherapeutic INRs were recorded for 49%; ED providers intervened to address these results in 21% of cases
• 71% of patients with a supratherapeutic INR received an intervention compared with 9% of patients with a subtherapeutic INR
• 30% of patients received or were prescribed potentially interacting medications
• Recommendations for specific anticoagulation follow-up were documented for only 19% of all patients

Literature continues to show warfarin is the most dangerous medication for our patients. Meticulous monitoring and follow up will help us potentially avoid serious interactions and adverse events.

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High dose insulin is recommended in treatment of beta-blocker and calcium channel blocker overdose. In a recent observational case series of cardiogenic shock, high dose insulin was evaluated for efficacy and safety.

• Insulin doses were given at a maximum of 10 units/kg/hour.

• Seven patients who were on vasopressors when enrolled were tapered off when placed on high dose insulin.

• 11/12 patients lived and were discharged from the hospital.

• Adverse effects included hypoglycemia (19 events) and hypokalemia (8).

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TEN is a rare, life-threatening dermatologic emergency characterized initially by erythema and tenderness. It is followed by a severe exfoliation that resembles a severe burn patient. Classically occurs within days of the exposure of the drug. Nikolsky's sign may be present - not pathognomonic.

The following is a short list of medications that can cause this lethal reaction:

allopurinol, bactrim, nitrofurantoin, NSAIDs, penicillin, phenytoin, lamotrigine, sulfasalazine

Treatment: transfer to a burn center may be needed, steroids are not generally recommended however immunomodulators are beginning to show promise - IVIG, cyclosporine and cyclophosphamide

See pic that is attached for example of the sloughing

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• 1111172057_TENPic.jpg (95 Kb)

Several medications have been linked to causing idiopathic intracranial hypertension (pseudotumor cerebri). Be sure to record an accurate medication history in patients you suspect of having this diagnosis.

• Excessive doses of vitamin A
  • Other retinoids too: retinol, isotretinoin, and tretinoin
• Tetracyclines (tetracycline, doxycycline, minocycline)
• Growth hormone

Withdrawal of the offending agent will generally resolve the symptoms.

Salicylates:

• stimulate the respiratory center in the brainstem, causing respiratory alkalosis
• interfere with the Krebs cycle, limiting ATP production, leading to an anaerobic metabolism
• uncouple oxidative phosphorylation, causing accumulation of pyruvic and lactic acid and heat production, resulting in acidosis and hyperthermia
• increase fatty acid metabolism, generating ketone bodies

Overall, this results in a mixed respiratory alkalosis and metabolic acidosis. 

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Methotrexate is a chemotherapeutic that is utilized in non-Hodgkin lymphoma and breast CA. It is also used as an immunosuppressant for rheumatoid arthritis and psoriasis. Finally, we see it used in the ED for the treatment of ectopic pregnancy. Overdose, often unintentional, can have a lethal outcome.

Toxicity: LFTs rise, N/V, stomatitis, mucositis, leukopenia, thrombocytopenia, renal failure

Antidote: Leukovorin (Folinic Acid)

Other Tx: Carboxypeptidase G2, Charcoal Hemoperfusion, HD (possible)

Carbon Monoxide Toxicity and Hyperbaric Oxygen Treatment

CO disrupts cellular function by several mechanisms at a
cellular/mitochondrial level.  Ultimately, these disruptions are
manifested as tissue hypoxia and hypoperfusion.
Initial symptoms may be subtle and nonspecific.  Be sure to ask about
CO exposure when evaluating “viral syndrome” or patients that present
with non-specific neurological complaints especially during fall and
winter months, when people first start using their heating, or after
power outages and generator use. Dysrhythmias, cardiomopathy, MI and
sudden cardiac arrest are reported in severe CO poisoning.

Lab studies- COHb, base excess, lactate and any other studies based on
presentation.

Supplemental oxygen is the cornerstone of treatment.   Oxygen
delivered at hyperbaric pressure (as opposed to sea-level) will
increase the rate of CO dissociation from hemoglobin, and mitigate
damage to cellular and mitochondrial function.

Definite Indications for HBOT:  Current evidence supports the use for
HBOT to reduce cognitive sequelae in CO poisoned patients who have:
LOC , seizure, exposure >23 hours, COHb of 25% or more, and age >36.
Relative Indications:  persistent symptoms after 100% O2 or change in
mental status, pregnancy, persistent cardiac ischemia, increased COHb
levels.

 Disposition:  Clinical judgment should guide your decision.  Most
patients with mild symptoms can be discharged after treatment. If
patient has a more concerning presentation with several risk factors
(extremes of age, CAD, unconscious at arrival in the ED, etc…)
consider admission.

A growing trend in EDs is to have a dedicated ED Pharmacist present to assist with the evaluation of a patient's medication list, appropriate and safe drug administration and to improve drug delivery times. To date, it has been difficult for hospitals to determine if this was a cost-effective measure. There has been increasing research that has shown the proven benefits that physicians feel when they have an ED Pharmacist. With the aging population, increasing polypharmacy, core measure and national patient safety goals all rising to the top of hospital initiatives, the ED pharmacist will be proven to be a valuable cog of the ED - as UofMd already knows

1) Improved safety - this study showed an ED pharmacist caught 2.9 errors/100 medications, very important considering the cost of just one severe reaction can cause a hospitalization or even litigation(1)

2) Improved time to delivery of medication - this study showed improved time of delivery of medications not found in a Pyxis from 61 min with no pharmacist  decreased  to 47 min with ED pharmacist.(2)

Further studies will be needed to determine the true cost:benefit however with core measures like 6hr time to administration of antibiotics and the safe/timely adminstration of tPA combined with patient safety/quality goals - the value of an ED pharmacist will only be accentuated.

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Every so often a patient arrives in PSVT with their only intravenous access being through a hemodialysis port.

Initial dose of adenosine should be reduced to 3 mg if administered through a central line.  Remember a central line delivers the adenosine right where you need it.  This recommendation is supported by the 2010 ACLS guidelines.  Second and third doses should be 6 mg (instead of 12 mg).

Cases of prolonged bradycardia and severe side effects have been reported after full-dose adenosine through a central line.  Other situations to consider lower doses include patients currently receiving carbamazepine or dipyridamole or in those with a transplanted heart.

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End Tidal CO2 continuous capnography is being utilized more in the ED for procedural sedation. One of the best studies is a randomized control trial using propofol that showed you could see signs of hypoventiliation prior to hypoxia by about 60 seconds - which can be plenty of time to get your BVM and airway cart ready.

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If you think the controversy was just heating up for propofol use in the Emergency Department, just wait until the new agent begins arriving to an ED near you - fospropofol. A new water soluble version of propofol, this agent will remove the problems of pain at the injection site, an easier/wider therapeutic window for sedation and allowing of long-term sedation without the heavy lipid load.

Currently, there is limited FDA approval in the US for monitored anesthesia care. I am waiting for the first paper showing its use in the ED for procedural sedation. Safety data is still growing.

     Mini-pearl: Patients allergic to soybean should either avoid propofol or undergo skin testing since the emulsion is made of soybean oil and egg lecithin. There have been reported cases of anaphylaxis after administration of propofol in patients with food allergies, peanut and birch.

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Caffeine can interfere with the successful reversion of paroxysmal supraventricular tachycardia (SVT) by adenosine.

Caffeine is an adenosine receptor blocker.

Ingestion of caffeine less than 4 hours before a 6-mg adenosine bolus significantly reduced its effectiveness in the treatment of SVT.  Theophylline is similar but not many patients are prescribed it anymore.

An increased initial adenosine dose may be indicated for these patients. A first dose of 12 mg (instead of 6), followed by 2nd and 3rd doses of 18 mg (instead of 12) may be indicated.

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o   The FDA is now asking manufacturers to limit the amount of acetaminophen in combination products to 325 mg per dose.

o   The higher dose formulations will be phased out by 2014.

o   The FDA is also considering lowering the maximum total to 3 gm per day, and a maximum dose of 650 mg per dose

o   This does not pertain to OTC, but this is likely to change in the near future; Johnson & Johnson (manufacturer of Tylenol) has already adopted these recommendations.

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The incidence of tendon rupture related to fluoroquinolone use is reported to be in the range of 1 in 6000.

The risk of tendon rupture associated with FQ use is increased in those older than 60 years of age, those taking steroids, and in patients who have received heart, renal, or pulmonary transplants.

There is no evidence that tendon rupture is more likely for patients taking levofloxacin compared to other FQs.

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