Over the last few decades, the rate of breastfeeding has increased steadily in the developed countries of the world. During this time, opioid use in the general population has steadily increased as well. Despite this, clinicians remain unclear whether opioid use is safe during breastfeeding.
In a recent multicenter, double-blind, randomized, non-inferiority trial, vancomycin was compared to fidaxomixin for Clostridium difficile infection.
Location: 45 sites in Europe and 41 sites in the USA and Canada
Patients: Age 16 years or older with acute toxin-positive C difficile infection.
Treatment: Oral fidaxomicin (200 mg every 12 h) or oral vancomycin (125 mg every 6 h) for 10 days.
Endpoint: Clinical cure, defined as resolution of diarrhea and no further need for treatment.
Results: 198 (91.7%) of 216 patients in the per-protocol population given fidaxomicin achieved clinical cure, compared with 213 (90.6%) of 235 given vancomycin (one-sided 97·5% CI -4·3%). Occurrence of treatment-emergent adverse events did not differ between groups.
Author conclusions: Fidaxomicin could be an alternative treatment for infection with C difficile, with similar efficacy and safety to vancomycin.
Funding: Optimer Pharmaceuticals.
Pressure immobilization involves wrapping the entire extremity with a bandage and then immobilizing the extremity with a splint. It is a technique routinely employed in the pre-hospital management of neurotoxic snakes in Australia.
A position statement was recently published by several international toxicology societies regarding the utility of pressure immobilization after North American Crotalinae snake envenomation (e.g., Copperheads, Timber rattlesnakes, Cottonmouths).
"Available evidence fails to establish the efficacy of pressure immobilization in humans, but indicates the possibility of serious adverse events arising from its use. The use of pressure immobilization for the pre-hospital treatment of North American Crotalinae envenomation is NOT recommended."
The seasonal influenza vaccine is produced in chicken eggs. Ovalbumin, an egg protein, is often listed as a component of the purified vaccine on most drug-package inserts. The concentration of ovalbumin indicates the potential egg-allergen content of a vaccine.
Earlier ACIP guidelines recommended against giving the influenza vaccine to people with egg allergy, including those with a history of mild symptoms. However, several studies showed that influenza vaccine containing inactivated, or killed, virus is safe to give to people with egg allergy, especially those with a history of mild allergic reactions.
Influenza vaccines are now made with much lower ovalbumin concentrations than in the past; therefore, the level of potential egg protein allergens in a single dose of vaccine is extremely low.
The following are ACIP recommendations for the 2011 to 2012 influenza season:
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.
In the setting of critical drug shortages of ondansetron, prochlorperazine, and metoclopramide, consider droperidol as a viable option for the treatment of nausea and vomiting.
Although it is similar to haloperidol, it is actually FDA-approved for “prevention and/or treatment of nausea and vomiting from surgical and diagnostic procedures” (unlike haloperidol). Ironically, it is not approved for agitation, although it can be used for that indication.
Dosing for antiemesis is 1.25 to 2.5 mg IV/IM. Additional doses of 0.625 to 1.25 mg can be administered to achieve desired effect. Onset is 3-5 minutes and duration of effect is 2-4 hours. It should be administered via slow IV push over 2 minutes.
Why is it not commonly used? Black Box Warning for QTc prolongation. An ECG is a must prior to administration. Also be cautious in patients who are on other medications that can prolong the QT interval (www.qtdrugs.org).
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).
In 2011, updated treatment guidelines were published for acute uncomplicated cystitis and pyelonephritis in women. The recommendations differ from the previous iteration due to increased E. Coli resistance. The good news is we have been ahead of the curve in changing our prescribing habits.
Cystitis (recommendations in order of preference)
Take home points:
A recent study highlighted the challenges we face managing ED patients on warfarin therapy. Some key observations about how we're doing:
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.
A recent article estimated 100,000 emergency hospitalizations for adverse drug events in U.S. adults 65 years of age or older each year. Nearly half of these hospitalizations were among adults ≥80 years old and two-thirds were due to unintentional overdoses.
Four medications or medication classes were implicated alone or in combination in 67% of hospitalizations:
Opioids were #5. Digoxin was #7 and resulted in the highest percentage of hospitalizations per ED visit at 80%.
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.
Withdrawal of the offending agent will generally resolve the symptoms.
A recent randomized trial compared nicardipine as a continuous infusion to labetalol boluses to determine which one was more effective at lowering blood pressure to a target range within 30 minutes.
Median initial SBP for the 226 patients was 212 mm Hg. Within 30 minutes, nicardipine patients more often reached target range than labetalol (91.7 vs. 82.5%, P = 0.039). Of 6 BP measures (taken every 5 minutes) during the study period, nicardipine patients had higher rates of five and six instances within target range than labetalol (47.3% vs. 32.8%, P = 0.026).
What this means: Nicardipine is a reasonable choice for patients needing acute lowering of blood pressure (e.g., ischemic stroke with tPa). Nicardipine seems to achieve faster and smoother lowering of blood pressure than labetalol therapy with less blood pressure readings outside the target range.
An acute increase in the INR over 3 in patients with chronic kidney disease (CKD) is often associated with an unexplained acute increase in serum creatinine and an accelerated progression of CKD.
Kidney biopsy in a subset of these patients showed obstruction of the renal tubule by red blood cell casts, and this appears to be the dominant mechanism of the acute kidney injury. This has been termed warfarin-related nephropathy (WRN).
In 15,258 patients who initiated warfarin therapy during a 5-year period, 4006 had an INR over 3 and creatinine measured at the same time. A presumptive diagnosis of WRN was made if the creatinine increased by over 0.3 mg/dl within 1 week after the INR exceeded 3 with no record of hemorrhage. WRN occurred in 20.5% of the entire cohort, 33.0% of the CKD cohort, and 16.5% of the no-CKD cohort. Other risk factors included age, diabetes mellitus, hypertension, and cardiovascular disease. The 1-year mortality was 31.1% in patients with WRN compared with 18.9% in those without WRN, an increased risk of 65%.
Take home message: Although the mechanisms are not clear, be very wary of even a small creatinine bump in patients presenting with an INR > 3 on warfarin therapy. Yet another reason to fear warfarin...
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.
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.
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.
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.
Patients requiring anticoagulation for HIT or with a history of HIT may be initiated on argatroban. We have recently been seeing increased utilization. Here are some important points to remember.
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:
