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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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.      

Levamisole is an antihelminthic agent used in humans to treat certain parasitic infections and cancers.  It is more commonly used for veterinary purposes.  It has recently seen increasing use as a cutting agent for cocaine and heroin, found in up to 70% of cocaine sample seized by the DEA.  It adds bulk and weight to powdered cocaine and is even theorized to increase the stimulant effects.

Toxicity of levamisole includes agranulocytosis and vasculitis (see attached document for recent image from NEJM).

Trivia: Levamisole was found in DJ AM and Andrew Koppel (Ted Koppel’s son), who both died of drug overdoses.

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Attachments

• 1106231638_levamisole.doc (526 Kb)

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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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Dehydration and subsequent prerenal acute kidney injury can result when temperatures begin to rise in the summer months.  As a result, medications with narrow therapeutic indices that are primarily renally excreted may accumulate.  Here are the specific ones to look out for:

• Digoxin
• Lithium
• Colchicine
• Phenobarbital and theophylline (partially eliminated unchanged by the kidneys)

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

Several patients have recently presented with a medication history including tapentadol (Nucynta), the newest opioid formulation.  It is approved for treatment of acute moderate-severe pain.  Here are some key points:

• Mechanism similar to tramadol: mu-receptor agonist, also inhibits norepinephrine reuptake
• Potency stronger than tramadol, but less then morphine
• Usual dose is same as tramadol 50-100 mg every 4-6 hours prn pain
• Schedule II controlled substance, similar to morphine/oxycodone (tramadol is not a controlled substance)
• Overdose should present like other opioids, but potentially also including tachycardia, serotonergic effects, and seizures (similar to tramadol)

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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Attachments

• 1104212257_CIWA-Ar.pdf (10 Kb)

Kiwi fruit and latex share several antigens in common.  Thus, individuals who are allergic to either kiwi or latex may also suffer hypersensitivity reactions to the other material.

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·      In the event a nuclear power plant accident, people may be exposed to a mixture of radioactive products. The main radionuclides representing health risk are radioactive caesium and radioactive iodine.

·      Iodine-131 is concentrated in the thyroid gland and may eventually lead to development of thyroid nodules and thyroid cancer.

·      Radioiodine uptake by the thyroid can be blocked by taking potassium iodide (KI) pills or solution, preventing these effects.

·      KI should not be taken in the absence of a clear risk of exposure to a potentially dangerous level of radioactive iodine because KI can cause allergic reactions, skin rashes, salivary gland inflammation, hyperthyroidism or hypothyroidism.

·      Since radioactive iodine decays rapidly, current estimates indicate there will not be a hazardous level of reaching the United States from this accident.

·      There are three FDA approved KI products: Iosat, Thyrosafe and ThyroShield.

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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.

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  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.