UMEM Educational Pearls

Cyanide poisoning, while uncommon, is frequently fatal. Current antidotes include methemoglobinemia inducers (nitrites), sulfur donators (thiosulfate), and hydroxocobalamin. Each has risks and benefits that must be considered. Three new potential antidotes, including sodium tetrathionate, have recently been evaluated in swine models.

 
Intramuscular sodium tetrathionate¹

• Sodium tetrathionate can bind and eliminate two cyanide molecules compared to one cyanide molecule by thiosulfate.
• Studied in a large (50 kg) female swine model of cyanide poisoning.
• All pigs were given cyanide via IV until 6 minutes post-onset of apnea, then given an approximately 1.5 mL IM injection of sodium tetrathionate (18 mg/kg).
• Survival at 90 minutes was 100% (6/6) in the treated group and 16% in the control arm (1/6). 

Advantages:

• Small volume injection (~1.5-2 mL in humans)
• No interference with routine laboratory tests.
• Ease of administration in pre-hospital or potential mass casulty setting.

Bottom line:

• New cyanide antidotes are being developed.
• The FDA does NOT require human trials of efficacy for cyanide antidotes.
• It is unclear where these drugs are in the approval process at this time, but look for them in the future.

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Primary headaches (not secondary to a life-threatening disease) can be challenging to manage. Remember the following pearls:

• Things that DO NOT work: IV fluids, 5-HT3 Antagonists (aka Zofran), diphenhydramine (aka Benadryl), opioids

• Things that KINDA work: oxygen for all headaches, sphenopalatine ganglion block (4% lido spray) 

• Things that REALLY work: ketorolac, metoclopramide, prochlorperazine, triptans and ergots, oxygen for cluster headaches

• Things that PREVENT recurrence: dexamethasone for migraine headaches 

Children are prone to inflammation and infection of the intervertebral discs

-Mean age 3-5years at presentation.

Lumbar region frequently involved

Although disc biopsy is not necessary for diagnosis, as many as 60% of biopsied discs grow bacteria

-Usually Staphylococcus aureus.

Untreated - may spontaneously resolve or progress to vertebral osteomyelitis or abscess

Chief complaint: Back pain and irritability, often associated with a limp or refusal to crawl or walk.

Fever is absent or low grade. 

Physical examination findings are nonspecific and may include a tendency to lie still and percussion tenderness over the involved spine.

Blood culture is generally sterile,

WBC count can be normal early in the disease course

However, the ESR is elevated in >90% of patients.

Plain radiographs are normal at the start of the illness, and generally take 2-3 weeks to demonstrate narrowing of the intervertebral space.

Therefore imaging study of choice is MRI.

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Naloxone distribution programs have been expanding to promote the naloxone adminstration by laypersons, usually intranasal (IN) device, to victims of opioid overdose. A recent study analyzed the reports of prehospital naloxone administration reported to a regional poison center.

• 1139 cases of prehospital naloxone administrations were identified between 2015 and 2017.
• 98.2% had ventilatory depression
• 97% were unresponsive
• Law enforcement officers administered 91% of the naloxone, 97.9% via IN route

Opioid toxicity revesal:

• Opioid-induced ventilatory or CNS depression was reversed in 79.2% after administering a mean naloxone dose of 3.12 mg. 
• EMS administered additional naloxone (mean dose: 2.2 mg) to 291 due to lack of or partial reversal of opioid toxicity. 
• 254 out of 291 (92.4%) regained normal/improved mental and ventilatory status.  
• 95.9% of the overdose victims survived.

However, between 2015 and 2017, the reversal rate decreased (82.1% to 76.4%) while mean administered naloxone dose increased (2.12 mg to 3.63 mg). The cause of this trend is unknown but the dose of commercially available IN naloxone kit increased from 2 mg to 4 mg in 2016.

Bottom line:

• IN naloxone administration is an effective intervention to reverse opioid toxicity.
• However, larger naloxone doses were administered between 2015 and 2017 while the reversal rate decreased.
• It is essential for bystander/witness of overdose to notify EMS as overdose victims may require additional naloxone administration/medical attention.

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Post-Arrest Prophylactic Antibiotics?

• Pneumonia is the most common infective complication in post-cardiac arrest patients. It may develop in up to 60% of patients and is associated with an increased ICU length of stay.
• Given the challenges in diagnosing pneumonia in the post-cardiac arrest patient, many clinicians consider prophylactic antibiotic administration.
• A recent systematic review and meta-analysis sought to evaluate the effect of early antibiotic use on survival and survival with good neurologic outcome in adult patients resuscitated from cardiac arrest. Key study results include:
  • 11 studies (3 RCTs, 8 observational trials)
  • 6149 patients
  • No change in overall survival or survival with good neurologic outcome
• Take Home Point: Current data does not support the prophylactic administration of antibiotics to adults resuscitated from cardiac arrest.

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Since 2013, the availability of fentanyl has been increasing in the illicit drug supply, especially in heroin supply. Fentanyl and its analogs have been responsible for the dramatic increase in opioid overdose death over the past 5 years. 

Two recent cross-sectional studies screened ED patients with opioid use disorder for fentanyl exposure.

Study 1:

• Of 165 patients, urine samples were obtained from 129 participants.
• 80.6% tested positive for fentanyl from urine sample when over 95% reported preference for heroin in the fentanyl positive group.
• 85.7% of the overdose group (n=42) was positive for fentanyl.
• Over 84% recognized fentanyl’s high potency and high risk of death in overdose.
• 29.7% (n=49 of 165) intentionally purchased fentanyl for use.  
• Intentional fentanyl purchase was more common in non-overdose group(34.1% vs. 16.7%).

Study 2: 

• 76 ED patients were screened.
• 83% showed presence of fentanyl in urine.
• 5% reported knowledge of using fentanyl (i.e. intentional use).

Bottom line:

• Fentanyl exposure is common among opioid users in Baltimore
• Up to 30% of ED patients with opioid use disorder intentionally purchase fentanyl although majority recognize the higher risk of overdose death from fentanyl compared to other opioids.

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• Benzodiazepines are first-line treatment for status epilepticus.
• Guidelines for the treatment of status epilepticus recommend dosing as:
  • 10 mg midazolam IM for patients > 40 kg or 5 mg midazolam IM for patients 13-40 kg
  • 0.1 mg/kg lorazepam IV (max 4 mg/dose), can repeat x 1
  • 0.15-0.2 mg/kg diazepam IV (max 10 mg/dose), can repeat x 1
• The recent Established Status Epilepticus Treatment Trial (ESETT) compared the treatment of patients who did not respond to benzodiazepines.
  • Overall, 29.8% of the first dose of benzodiazepines given in the ED met minimum dose recommendations.
  • Dosing for patients < 40 kg more frequently met minimum dose recommendations.
  • This study found a pattern of multiple, small doses instead of a single full dose of benzodiazepine as recommended by guidelines.

Bottom Line: Underdosing of benzodiazepines in status epilepticus may contribute to treatment failure.

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Little people (patients with achondroplasia or "dwarfism") have little lungs. Even though the trunk may appear to be a normal size with small limbs, the vital capacity is actually about 75% the predicted value based on the patient's sitting height. Macrocephaly and a decreased anterior-posterior depth are the cause for this. When you want to mechanically ventilate a little person, you can estimate their height based on a typical person with the same sitting height, but their actual volume will be about 3/4 the tidal volume predicted.

When intubating, remember these patients also have a high risk of basicranial hypoplasia (the foramen magnum may be small and key-hole shaped). These patients will be predisposed to compress the vertebral arteries when you tilt the head back and this itself can cause ischemia of the medulla and pons leading to central apnea.

Stokes DC, Wohl ME, Wise RA, et al. The lungs and airways in Achondroplasia. Do little people have little lungs? CHEST. 1990; 98(1):145-52

Pauli RM. Achondroplasia: A comprehensive review. Orphanet Journal of Rare Diseases. 2019; 14(1): 

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Acute transverse myelitis (ATM) refers to inflammation of gray and white matter in one or more adjacent spinal cord segments leading to acute/subacute dysfunction of all cord functions (i.e., motor, sensory, and autonomic).

There is a bimodal peak between ages 10-19 years and ages 30-39 years.

Most cases are idiopathic

Some patients may have had a preceding viral infection or autoimmune disorder.

The thoracic cord is most commonly involved.

Onset is characterized by acute/subacute development of neurologic signs and symptoms consistent with motor weakness, sensory changes or autonomic dysfunction.

Pain in the head, neck, and/or back may occur.

Motor and sensory changes occur below the level of the lesion and are more likely to be bilateral.

Motor symptoms include a rapidly progressing paraparesis.

Autonomic dysfunction may include urinary urgency or difficulty voiding, bowel or bladder incontinence, tenesmus, constipation, and sexual dysfunction.

Despite its low incidence, consider in a patient presents with a classic constellation of symptoms,

Rapid identification, and early initiation of treatment predicts the best outcomes

Diagnosis: whole spine MRI with and without gadolinium

Management: goals include reducing cord inflammation (IV glucocorticoids), alleviating symptoms (pain management, bladder decompression), and treating underlying causes (e.g., infections, autoimmune) as appropriate.

Many chemicals and substances - both legal and illegal - can be purchased from an online retailer. A recent study searched Amazon.com to see if any of the "extremely hazardaous substances" identified by Environmental Protection Agency (EPA) were available for purchase.

Amazon.com was searched over 10-month period.

Result:

• 79 of 340 substances listed as "extremely hazardous by the EPA were available for purchse. 
• 1/3 of the products/substances possess sufficient dose to be considered toxic in single unit purchase
• Only 4 substances required a bussiness account to be purchase. 

Bottom line:

Toxic substances are readily available from many online retailers that can potentially cause serious toxicity. Online retailers should consult with experts and governmental agencies to limit the availability of such products.

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Some patients with severe pulmonary hypertension receive continuous infusions at home of prostacyclins, such as epoprostanol (flolan).  These are generally delivered via a pump that the patient wears, which is attached to an indwelling catheter.  As with any indwelling device, they are at risk for infection and other complications, including malfunction.

Interruption of delivery of the medication can result in rapid cardiovascular collapse, sometimes within minutes.  In this instance, the medication should be resumed as quickly as possible (by a traditional IV if the catheter is not functional), and the patients should be treated as one would approach a patient with decompensated right heart failure.

I once saw a patient in the ED whose listed chief complaint was "medication refill", but was actually there for dislodgement of her prostacyclin catheter (thankfully she was ok).  With more patients receiving devices they are dependent upon (insulin pumps, AICDs, prostacyclin catheters), be wary of chief complaints such as "medication refill" or "device malfunction."

Bottom Line: Interruption of continuous prostacyclin therapy for pulmonary hypertension can be rapidly fatal and should be addressed immediately.

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For patients with bleeding due to warfarin, prothrombin complex concentrate (PCC) is the recommended antidote. Historically, PCC has been dosed on weight and INR:

·         INR 2 - 4: 25 units/kg, max 2500 units

·         INR 4 - 6: 35 units/kg, max 3500 units

·         INR > 6: 50 units/kg, max 5000 units

New data demonstrates that fixed dosing offers several advantages with similar efficacy outcomes:

·         Standardized dosing

·         Improved time to administration

·         Decreased cost

The University of Maryland Health System has adopted a fixed dose strategy for all patients with warfarin-associated critical bleeding:

·         Bleeding site other than intracranial hemorrhage AND INR 1.4 - 6 AND weight ≤ 100 kg = 1500 units

·         Intracranial hemorrhage OR > 100 kg OR INR >6 = 2000 units

**Note: PCC is also the antidote of choice for reversing critical bleeding due to factor Xa inhibitors (rivaroxaban, apixaban, edoxaban).  All critical bleeds due to these agents should receive 50 units/kg, max 5000 units.

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Bone tumors can present as MSK pain!

Pain may be activity related initially (can lead to misdiagnosis)

Over time will progress to rest pain and night pain

1) Primary osteosarcoma - most common primary malignant bone tumor

Adolescents, male > female

70% occur about the knee (also in hip/pelvis and upper arm)

pain, swelling, tenderness to palpation

Consider in the presentation of non traumatic knee pain!

2) Ewing's sarcoma

Peak incidence ages 10-20, male > female

pain, swelling, tendernes to palpation

Elevated temps and ESR

Consider in the differential of osteomyelitis!!

Variable location - lusually the extremities but also pelvis, scapula, ribs

Presentation:

- Prepubertal females are especially susceptible to urethral prolapse

- Can present incidentally is a painless mass found during bathing or on exam

- More commonly presents as urogenital bleeding, dysuria, or (rarely) urinary retention

Evaluation:

- Appears as a partial or circumferential "donut" of bright red, often friable prolapsed mucosa

- Typically occurs in the setting of UTI, cough, or constipation

- Need to rule out complications: UTI, urethral necrosis, and urinary retention

Treatment:

- Medical management start with sitz baths twice daily and addressing causative factors (treatment constipation, UTI, etc.)

- Can add either topical corticosteroid (hydrocortisone) or estrogen (Estrace or Premarin 0.01% twice daily)

- Urology follow-up necessary as many will require surgical resection of prolapsed mucosa

In a study of alarms from 77 monitored ICU beds over the course of a month at the University of California, San Francisco, false alarms were common. Accellerated Ventircular Rhythms (AVRs) made up roughly one third of the alarms, and of the more than 4,361 AVRs, 94.9% were false while the remaining 5.1% did not result in a clinical action.

While this study had a majority of patients in the Med/Surg ICUs, a minority were from the cardiac and neurologic ICUs giving it some broad applicability. This study adds to the literature indicating there are subsets of alarms which may not be necessary or which may require adjustment to increase specificity.

Suba S, Sandoval CS, Zegre-Hemsey J, et al. Contribution of Electrocardiographic Accelerated Ventricular Rhythm Alarms to Alarm Fatigue. American Journal of Critical Care. 2019; 28(3):222-229

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Remember to evaluate for any rotational deformity when evaluating patients with a phalanx fracture.

The easiest way to do this is to have the patient flex all their fingers. They should all point to the scaphoid. If a finger deviates or overlaps another finger there is a rotational deformity.  One should also make sure that all the nailbeds align.

This video shows how to evaluate for rotation https://www.youtube.com/watch?v=Dhp25UVn7RQ

Even if the finger is reduced otherwise, persistent rotational deformities should be referred to a hand surgeon for consideration of corrective surgery.

Washington state was one of the first states to legalize recreational marijuana use.  Toxicology call center data was collected on patient's 9 years old and younger with marijuana exposure between July 2010 and July 2016.  There were 161 cases during that time frame and of those 130 occurred after the legalization of recreational marijuana (over a 2.5 year period).  The median age range was 2 years old.  There were increasing cases noted after recreational marijuana was legalized and again after marijuana shops became legal.

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Drug-induced hypoglycemia is an important cause of hypoglycemia which should be considered in any patient presenting with altered mental status. In one study, drug-induced hypoglycemia represented 23% of all hospital admissions attributed to adverse drug events. Risk factors for developing hypoglycemia include older age, renal or hepatic insufficiency, concurrent use of insulin or sulfonylureas, infection, ethanol use, or severe comorbidities. The most commonly cited drugs associated with hypoglycemia include:

• Quinolones
• Sulfonylureas* either alone or with a potentiating drug 
• Insulin
• Pentamidine
• Quinine
• B-blockers
• ACE Inhibitors
• Tramadol**

*In Glipizide users, there was 2-3 fold higher odds of hypoglycemia with concurrent use of sulfamethoxale-trimethoprim, fluconazole, and levofloxacin compared with patients using Cephalexin.

**Tramadol potentially induces hypoglycemia by effects on hepatic gluconeogenesis and increasing insulin release and peripheral utlizilation. Was seen in elderly at initiation of therapy within first 30 days.

BOTTOM LINE:

Take care in prescribing drugs known to increase risk of hypoglycemia in elderly patients, with comorbidities, or those already taking medications associated with hypoglycemia. 

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• ANDROMEDA-SHOCK compared using capillary refill time versus lactate clearance as a guide for resuscitation in septic shock patients
• The cap refill group showed better SOFA scores at 72 hours, and a trend to lower mortality
• In the study, cap refill was performed by pressing a glass microscope slide to the ventral surface of the second finger distal phalanx, holding until blanched for 10 seconds, and releasing.  Cap refill > 3 seconds was considered abnormal.

Bottom Line: Consider using capillary refill as an alternate (or complimentary) endpoint to lactate clearance when resuscitating your septic shock patients.

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