UMEM Educational Pearls - By Ellen Lemkin

• Naloxone has technically always been able to be prescribed by physicians to individual patients.
   
• New laws however, make it acceptable for prescribers in many states to prescribe naloxone to “third parties,” e.g parents, friends, etc. of patients, with the assumption that the overdosed patient will not be capable of administering the antidote to themselves.

• Many states are offering short 10-20 minute training sessions on how bystanders can administer the reversal agent to the patient who has overdosed.

• If prescribed, it should be prescribed to the individual who completed the training, not the intended patient, and may be written for intranasal or intramuscular administration.

• Intranasal (IN) is “off label” and an approved intranasal preparation is not commercially available, but the intramuscular preparation can be prescribed along with an atomizer device. The usual IN dose is 1 mg per nostril which may be repeated in 3-5 minutes.

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Aseptic meningitis is meningitis with negative bacterial cultures. Overall, viral infections are the most common etiology, however medications can also cause this illness.

Well known causes of aseptic meningitis include: antimicrobials (particularly sulfamethoxazole/trimethoprim), NSAIDS, antivirals (valacyclovir), and antiepileptics.

Recently an abstract was published that suggests that patients on levetiracetam have a higher risk of developing aseptic meningitis than those on topiramate and gabapentin. Lamotrigine has also been implicated, but appears to have a lower risk than levetiracetam, topiramate and gabapentin.

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Tranexamic Acid (TXA) topically applied was compared to anterior nasal packing in 216 patients with acute anterior epistaxis. Cotton pledgets (15 cm) soaked in injectable TXA (500 mg/5 ml) were inserted into the bleeding nostril and removed after bleeding had arrested. This was compared to standard anterior packing.

RESULTS

Bottom line: topical tranexamic acid looks promising for control of uncomplicated anterior epistaxis.

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Tranexamic acid (TXA) is an antifibrinolytic that prevents clot breakdown by inhibiting plasminogen activation and plasmin activity

The CRASH-2 trial enrolled 20,211 adult trauma patients with significant hemorrhage (SBP <90 or HR 110) or at significant risk of hemorrhage

Patients were randomized to 1 gram TXA over 10 minutes followed by an infusion of 1 gm over 8 hours vs placebo

There was a significant reduction in the relative risk off all cause mortality of 9% (14.5% vs 16%, RR 0.91, CI 0.85-0.97, p = 0.0035)

The patients that benefited most were those most severely injured, and in those treated in less than 3 hours of injury.

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It has linear, predictable pharmacokinetics, achieves maximal concentration within 1-2 hours, is 50% renally excreted, and has a half life is 9-11 hours.

Edoxaban was evaluated in a recent trial comparing warfarin in patients with atrial fibrillation.

The primary end point or first stroke or systemic pulmonary embolic event occurred in 1.5% with warfarin, compared with 1.18% in the high dose edoxaban (HR 0.79; 97.5% CI 0.63-0.99, P<0.001). In the intention to treat there were trends favoring high dose edoxaban and unfavorable trends with the lower dose.

The principal safety end point of major bleeding occurred in 3.43% with warfarin versus 2.75% with high dose edoxaban (HR 0.86; 95% CI 0.71-0.91, P<0.001). 

Bottom line: Both high dose (60 mg) and low dose (30 mg) edoxaban were non-inferior to warfarin with prevention of stroke or systemic emboli, and were associated with significantly lower rates of bleeding and death from cardiovascular causes.

Currently it is approved for use in Japan.

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When patients with severe allergies to penicillin (urticarial, bronchospasm, anaphylaxis, angioedema) are excluded, the cross reactivity to cephalosporins is very low (approximately 0.1%)

The reaction is related to structures in the side chain, not the cyclical structure as thought in the past.

There are several cephalosporins with IDENTICAL side chains that should not be given to patients with allergies to specific penicillins, namely:

• Penicillin:   do not give cefoxitin
• Ampicillin:   do not give cefaclor or cephalexin
• Amoxicillin: do not give cefadroxil or cefprozil

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ACLS recommendation for procainamide in tachycardic rhythms is:

Loading dose 20 mg/minute (up to 50 mg/minute for more urgent situations) until:

• Arrhythmia is controlled
• Hypotension occurs
• QRS complex widens by 50% of its original width
• or total of 17 mg/kg is given

Maintenance infusion is 1 to 4 mg/min.

An easier method for dosing acute onset atrial fibrillation in stable patients was used in the Ottawa Aggressive Protocol, in which they administered 1 gm over 60 min, which was interrupted if BP < 100 mmHg; if corrected by a 250 ml IV bolus, the infusion was resumed. This was not used, however if the patient was to be admitted.

A strategy for treating stable monomorphic VT with procainamide used:

100 mg IV over 1-2 minutes, repeat as necessary until an endpoint of

• Termination of tachycardia
• Drug induced hemodynamic deterioration
• Completion of 800 mg maximal dose

If no slowing of the tachycardia occurred with a dose of 400 mg, the administration was ceased.

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NMS is most often seen with the typical high potency neuroleptic agents (e.g haldol, fluphenazine)

All classes of antipsychotics can cause NMS, including low potency and newer atypical agents; antiemetics can cause this as well.

Symptoms usually occur after the first 2 weeks of therapy, but may occur after years of use

Signs and symptoms include:

mental status changes

muscular rigidity (“lead pipe”)

hyperthermia (>38 - 40 degrees).

Autonomic instability (tachycardia, tachycardia and diaphoresis)

Treatment includes discontinuation of the offending agent and providing supportive care.

While no clinical trials have ever been undertaken, dantrolene (muscle relaxant) is commonly used.

Bromocriptine (dopamine agonist) may also be used, and amantadine (dopaminergic and anticholinergic agent) is used as an alternative to bromocriptone

Recently, several case reports have documented the successful use of diazepam as a sole pharmacologic agent. This may be an alternative or a supplement to the above agents

A recent article was published in the Journal of Medical Toxicology reviewing the use of sodium acetate for treatment of overdoses and poisonings.

Acetate is metabolized to bicarbonate, causing a net increase in cations; this increased strong anion difference leads to alkalemia.

It has been used to treat acidosis in uremia, diarrhea, and in trauma patients.

Although no studies have been conducted using sodium acetate as an antidote, if bicarbonate is unavailable this is a viable option for management of salicylate overdose, and for qrs widening or arrhythmias due to overdoses.

Sodium acetate, if given rapidly (in animals and hemodialysis patients), causes myocardial depression, hypotension, and hypopnea.

The bolus dose should be given as 1-2 mEq/L given over 15-20 minutes. For the maintenance infusion, dilute 150 mEq diluted to 1 L in dextrose 5%, infuse at 2X the maintenance rate.

It must be diluted in dextrose 5% and NOT normal saline.

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• Hold metformin if the patient is at risk for dehydration (eg. vomiting, diarrhea) due to the risk of lactic acidosis
• Medications that stimulate insulin secretion (eg. sulfonylureas, repaglinide, or nateglinide) should be held if the patient is at risk for hypoglycemia
• Patients usually should continue their basal insulin, but may decrease or hold their bolus dosing.
• Finger sticks should be checked every 2-4 hours for those on insulin, or 2-4 times per day for type II diabetics not on insulin.

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• Opioid analgesia can actually INCREASE sensitivity to pain in some cases

• The exact cause is unclear, but may be due to up-regulation of NDMA receptors in spinal cord dorsal horn neurons

• Pain tends to be DIFFERENT and DIFFUSE from the underlying condition for which the narcotics were prescribed

• Switching from shorter acting opiates to methadone may be effective, as it is a weak NDMA antagonist and has only partial cross tolerance with other opioids

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• Prothrombin Complex Concentrate (PCC) Kcentra™ has been approved for urgent reversal of major bleeding in patients taking vitamin K antagonists (e.g. warfarin).

• It contains factors 2,7,9 and 10, and antithrombotic Proteins C and S.

• Both fatal and non-fatal arterial and venous thromboembolic complications have occurred with Kcentra™. Thrombotic events occurred more frequently in the PCC group compared to plasma, although the differences were not statistically significant.

• Volume overload occurred less frequently in the PCC group, as there is a smaller volume  administered with PCC compared to that of plasma.

• Percentage of INR ≤ 1.3 at 30 minutes was 62% in the PCC group and 9.6% in the plasma group.

Approval of Kcentra™ may open the door for studying treatment of the bleeding patient on newer oral anticoagulants.

• Although Keppra has been used more frequently in clinical practice, there is little evidence for its use in status epilepticus.
• It has a wide spectrum of action and few drug interactions.
• Initially, case series appeared to be highly successful in terminating seizures as an add-on agent.
• A review of 2 prospective studies found efficacies of 44% as an add- on agent, and 75% as a primary agent. The studies had markedly different populations.
• In a retrospective study, the treatment failure rates were 3X higher than that of intravenous valproic acid as an add-on agent in terminating status epilepticus.
• Therefore, although it is used frequently, the evidence for use is limited and inconclusive in terminating status epilepticus.

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• A recent Cochrane review examined the use of early statin therapy in patients with ACS.

• They evaluated 18 studies (14,303 patients), which compared early statin therapy (within 14 days) to placebo or usual care.

• The conclusion was that initiation of early statin therapy does not reduce death, myocardial infarction of stroke up to four months, but reduces the occurrence of unstable angina by 24% at 4 months following ACS.

• Many smaller studies previously noted benefits with early statin initiation prior to this meta-analysis.

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• Found as adulterant in street drugs

• Used in bodybuilding and for weight loss

• Long acting beta-2 agonist

• Has specific anabolic activity and increases lipolysis

• Toxicity presents with tachycardia, palpitations, tremor, and myocardial ischemia

Creatine

• is the most popular nutritional supplement, accounting for $400 million in sales annually
• a nonessential amino acid
• has been shown to improve performance in short, high intensity exercises, including weight lifting

Adverse effects: weight gain, edema, GI cramping, fatigue and diarrhea

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• Serum total tryptase measurements may be useful for confirmation of venom or drug induced anaphylaxis (not as useful for food induced)
• Can send serial tryptase levels at the time of presentation, 1-2 hours later, and at resolution
• This is NOT helpful for confirmation at the time of the episode, as it takes several hours to perform

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A slight correction: The correct AUTHOR in the referenced article is:

Wilkerson, R. Gentry, MD. Angioedema in tthe Emergency Department: An Evidence-Based Review. Emergency Medicine Practice, Nov 2012;14(11).

• Angioedema is induced by elevated levels of bradykinin.

• Bradykinin is noramlly degraded by angiotensin-1 converting enzyme and several other enzymes (including aminipeptidase–P)

• A deficiency in aminopeptidase-P likely leads to ACE induced angioedema.

• Treatment typically starts with discontinuing ACE inhibitors, administering H1 and H2 antagonists, and corticosteroids (all Class indeterminate). 

• Another consideration may be FFP 10-15 ml/kg IV or the off label use of icatibant (both Class II recommendations).

• Icatibant inhibits the bradykin B2 receptor. It is a sythetic decapeptide structurally similar to bradykin.

• Icatibant has been effective in case reports and case series in ACE induced angioedema. There is a prospective, double blind randomized placebo controlled trial underway.

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• Is associated with chronic use of marijuana

• Patients typically present with severe, recurrent nausea, vomiting, and abdominal pain, usually in the morning

• Temporary relief of symptoms is achieved by taking hot showers or baths

• Diagnostic work up is negative

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