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)

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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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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There are increasing reports of bath salts which are crushed and then either injected, insufflated or taken orally. The actual substance has been found to be mephedrone as well as MDPV.(1)  Both are amphetamine derivatives and the psychosis seen can appear like schizophrenia to the point that some of these patients have been admitted to the psychiatric wards. (2)(3)  For those who have seen methamphetamine patients "tweaking" - where they use the drug for several days in a row without sleep - the presentation is quite similiar.

Synthetic drugs continue to present legal and regulatory problems since the compound is a "designer" synthesized drug that may not be on the DEA Schedule list.  The product is labeled "Not for human consumption". Head shops and the internet remain primary sources of the drug. Bath salts present a serious and dangerous public health risk.

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  1) Centers for Disease Control and Prevention (CDC). Emergency department visits after use of a drug sold as "bath salts"--Michigan, November 13, 2010-March 31,2011. MMWR Morb Mortal Wkly Rep. 2011 May 20;60(19):624-7. 

  2) Antonowicz JL, Metzger AK, Ramanujam SL. Paranoid psychosis induced by  consumption of methylenedioxypyrovalerone: two cases. Gen Hosp Psychiatry. 2011 May 25.  

  3) Penders TM, Gestring R. Hallucinatory delirium following use of MDPV: "Bath  Salts". Gen Hosp Psychiatry. 2011 Jul 13. [Epub ahead of print] PubMed PMID:  21762997.      

The mounting evidence on the use of 20% lipid emulsion or intrlipid has been growing for  any patient that is hemodynamically unstable due to a drug exposure. There is now a recent case report of a verapamil overdose patient that received intralipid and did well. They were able to measure verapamil levels before and after administration. They were able to remove the lipid from the serum to appropriately measure the level and found effective removal. This adds to the theory of the "lipid sink" where the lipid actually is binding/surrounding a lipophilic molecule effectively removing it from interaction.

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The true incidence of drug-induced seizure is very difficult to determine, however, a nice poison center study attempted to determine clinical factors associated with complications (potentially life-threatening) of drug-induced seizures. They found 3 predictors that demonstrated statistically significant associations:

1. Stimulant Exposure (i.e. cocaine, amphetamines etc)
2. Initial acidosis
3. Hyperglycemia (limitation they do not give incidence of DM)

They found a 60% complication rate in drug-induced seizures which is much higher than epileptic seizures. Makes sense since these patients are often sedated/altered or vomiting.

Stimulant Exposure is much more prominent in this population and has increased in mortality.

Interesting point with hyperglycemia, may be a novel marker for poor prognosis. Several studies have confirmed an association between hyperglycemia and increased neuronal injury and mortality in other settings like CVA and TBI.

Take home point - Drug-induced Seizure has a high complication rate in the ED. Watch for the 3 predictors as that may clue you in to the increased risk.

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Certain medications can cause a certain dermatologic pattern. Many fall into a generic waste basket of "contact dermatitis" but here are some more characteristic findings and the drugs that can cause them:

Alopecia - anticoagulants, chemo, phenytoin, retinoids, selenium, thallium

Erythema multiforme - allopurinol, barbiturates, carbamazepine, cimetidine, some antibiotics

Toxic Epidermal Necrolysis (TEN) - allopurinol, bactrim (sulfonamides), mithramycin, PCN, sulfasalazine, nitrofurantoin, phenytoin, prazocin

The following list of medications have been associated with the development of Lupus Anticoagulants. Though it sounds like they should anticoagulate, they interfere with the Protein C system which means that they could induce a pro-thrombotic state - good short list to know:

Chlorpromazine (Thorazine

Procainamide (sorry Amal, I know you love that drug)

Hydralazine

Quinidine

Phenytoin

Treating a patient with clinical hypoglycemia (neuroglycopenia if you want to sound cool) is with "1 amp of D50". Then some are starting D5 drips and D10 drips. Here is the actual breakdown of what you are giving:

1 amp of D50 = 50% dextrose = 50g/100mL = 25g x 4Kcal/g carbs = 100 calories bolus

1 L D5W at 100mL/hr = 5% Dextrose = 5g/100mL x 1L = 50g x (4Kcal/g) = 200 cal infusion of 20 cal/hr!

1 L D10W at 100mL/hr = 10%D= 10g/100mLx1L= 100g x (4Kcal/g)= 400 cal at infusion of 40 cal/hr!

Snickers Bar = 271 calories in one serving - most people will eat in 5 minutes =  54.2cal/min

Take home message is feed your patient once they are awake and alert. Much more effective.

The ability to determine whether or not a patient is an alcoholic or will go into alcohol withdrawal syndrome (AWS) is not amenable to a clinical decision rule though many attempts have been made. The strongest predictor that a patient can develop AWS is a positive family history of AWS. Some clinical and biochemical predictors are:

ALT >50 U/L

K <3.6

These two in one study have had an odds ratio of 9.0 and 5.7 respectively though specificity was quite low. Ethanol levels has also found to be contradictory. Being able to predict AWS does not currently seem plausible but the treatment of AWS should and can involve a clinical decision rule like CIWA-Ar which is a scoring system that takes into account N/V, tremor, sweats, anxiety, agitation, hallucinations, headache and sensorium. Take a look at the scoring system that is most validated and utilized for symptom triggered therapy - often considered the most effective treatment for alcohol withdrawal.

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• 1104212257_CIWA-Ar.pdf (10 Kb)

Extravasation from radiocontrast, phenytoin and promethazine have resulted in significant tissue necrosis sometimes requiring surgical debridement and reconstructive plastic surgery. 

Pearl: Keep the infiltrated peripheral IV in and inject hyaluronidase 3-5mL (150U/mL) into the same subcutaneous pocket of medication. Hyaluronidase will increase the systemic absorption of the drug, decreasing its time in the SQ tissue. Extremely safe drug (we have the enzyme in our body) and has been used in neonates as well as adults. Also used for SQ hydration in palliative care and pediatrics.

Controversy: Hot vs Cold - Heat will cause vasodilation and hopefully increase systemic absorption but will likely also increase SQ spread possibly increasing the surface area of injury. Cold will cause vasoconstriction and decrease size of injury however will concentrate drug and possibly worsen the local injury.

Show References

  1: Sokol DK, Dahlmann A, Dunn DW. Hyaluronidase treatment for intravenous  phenytoin extravasation. J Child Neurol. 1998 May;13(5):246-7.     2: Cochran ST, Bomyea K, Kahn M. Treatment of iodinated contrast material  extravasation with hyaluronidase. Acad Radiol. 2002 Aug;9 Suppl 2:S544-6.     3: Few BJ. Hyaluronidase for treating intravenous extravasations. MCN Am J Matern Child Nurs. 1987 Jan-Feb;12(1):23.     4: Kuensting LL. Treatment of intravenous infiltration in a neonate. J Pediatr  Health Care. 2010 May-Jun;24(3):184-8. Epub 2010 Mar 20.     5: Raszka WV Jr, Kueser TK, Smith FR, Bass JW. The use of hyaluronidase in the  treatment of intravenous extravasation injuries. J Perinatol. 1990  Jun;10(2):146-9. 

Could this be another risk factor for DVT/PE. Maybe not yet but it is worth mention. A recent observatioal study in BMJ showed that there was  an associated increase with DVT or PE. From a database of 25,532 patients over a 3 year period of time and finding match controls, the results were:

1. 32% overall increase risk of DVT/PE in patient who were taking antipsychotics
2. Recent initiation of therapy within 3 months increased risk 2-fold
3. Risk was greater with atypical antipsychotics (Odds Ratio 1.73 Atypical vs 1.23 Old)
4. Risk was greater with lower dose than higher dose

Limitations were this is was an observational study with missing data. BMI was missing in these records and it is always difficult to tease out the multiple medications these patients are on.  Also don't have a great biological mechanism (yet). Still makes you go hmm....

Antipsychotic drugs and risk of venous thromboembolism, Parker, BMJ, 2010.

Most have converted from succinylcholine to rocuronium for their choice of paralytic in RSI. Succinylcholine-induced hyperkalemia secondary to muscle fasciculations is considered usually clinically insignificant though there may be a hyperkalemic renal patient that this may tip them over. The fasciculations also may worsen traumatic long bone fractures.  Here is the argument in a head to head comparison:

Duration = injection of drug to 25% recovery of single twitch height (clinically relevant recovery in ED - essentially breathing may return)

Recovery Index = time from 25% to 75% recovery of single twitch height

The main reason succinylcholine was utilized was because of its fast onset and short duration. Rocuronium is comparable enough to succinylcholine in these characteristics tilting the overall benefits to rocuronium. If the FDA ever approves it, suggamadex is a possible reversal agent for rocuronium - currently used in Europe. Imagine having that in your RSI kit.
 

Continuing with the synthetic/designer drug theme. Last time we were discussing synthetic marijuana.  Another old drug making a resurgence under the designer drug category is mephedrone.This amphetamine-like drug has been purportedly the active substance in "bath salts". It has also been sold as "plant food" - still trying to figure that one out.

Sold in head shops under the name Bliss or Cloud 9 - they have been reported to be available in Baltimore, MD recently. They can also be bought over the internet. Crushed, snorted or ingested, the effect is similiar to cocaine with a largely sympathomimetic toxidrome. Mephedrone has been labeled an entactogen with users behaving similiar to an MDMA ingestion. A Baltimore news station incorrectly called it "synthetic cocaine" - though the effect may be similiar, completely different molecular structure.

Treatment is cooling, check lytes (especially sodium), check for rhabdomyolysis and sedation with benzodiazepines. Below is one link from a Denver News Station. Attached is a picture of a bath salt product.

The latest and greatest on the street - synthetic marijuana and bath salts!

http://www.thedenverchannel.com/news/26567376/detail.html

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• 1102241706_bath-salts.jpg (38 Kb)

Sold under the name of K2, Spice. Patients exposed to this will present with dry mouth, paranoia, tachycardia, hallucinations but will resolved rather quickly over several hours. Observation in the ED and supportive care is usually all that is needed. A little history about synthetic marijuana:

• JWH-018 is a synthetic cannabinoid (SC) that acts at cannabinoid receptors.
• Synthetic cannabinoids were created s in the 1960’s and continued to be developed as appetite stimulants (e.g., dronabinol).
• The JWH series of SCs are named for the chemist who first synthesized them, John W. Huffman, Ph.D. (thus the JWH prefix).
• SCs recently appeared for sale in smoke shops and other outlets (such as gas stations) as herbal incense.
• These products contain plant material that mimics smell and appearance of marijuana but is adulterated with one or more SCs.

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• 1102180659_Spice_drug.jpg (558 Kb)

Dabigatran (Pradaxa), an antithrombin medication, was discussed in an earlier pearl and thought I would play devil's advocate and explain the possible concerns:

• Yes you don't need INRs to evaluate therapeutic levels but the problem is also don't know if its subtherapeutic or supratherapeutic. This can be an issue during times of transition fromLWMH or coumadin. There are specific protocols to follow for "bridging".
• Though not clinically significant, there was an increase in myocardial infarction in thedabigatran (Pradaxa) group when compared to coumadin - remember vioxx?
• FDA approved dabigatran for stroke prevention, embolism, in AF patients. Though people will automatically translate all of the indications coumadin has that cannot be done yet.
• No reversal agent so in an acute (ED) setting, you are in trouble and are depending on the relatively short half-life to get you out of trouble.

Toxicology Mantra: You never want to be the first person or the last person to use a drug

Naloxone is the epitomy of an antidote with complete reversal of opioid toxicity within 60 seconds of administration. Remember your clinical endpoint should be respiratory effort. If you utilize "the vial" of either 0.4mg or 2mg and there is a higher probability of withdrawal and for acute lung injury. Here are some tips for administration:

1) IV Access: Try 0.1 mg or even 0.05 mg - anesthesiology typically doses naloxone in micrograms. Reversal is slower so you have to be patient. It is also not as dramatic so closely monitor respirations to see if you have improvement, that may be all that you get. These are probably patients that you don't want that awake anyways.

2) No IV Access: advantage of naloxone is it is bioavailable IV, intranasal and even by nebulizer.  Here you want the dose to be 0.4mg to start for intranasal. Nebulizer is difficult to measure and probably safe to start with 2mg in the nebulizer container.

There is a difference when you know it is an opioid overdose and are reversing apnea versus a diagnostic administration to determine if it is opioid toxicity. In the latter instance you can rationalize the large dose - just be ready and be sure you are not in line of the possible projectile vomiting.