Center for Disease Control and Prevention (CDC) recently issued alerts regarding cases of pulmonary illnesses that may be linked to "vaping" (in 15 states with 149 possible cases). These cases are still under investigation but all cases reported vaping weeks/months prior to hospitalization.

Most cases involve young adults who have been using THC-containing products

Common complaints included

• Gradual onset of shortness of breath, cough, and chest pain
• GI symptoms: nausea, vomiting and diarrhea
• Fever, fatigue

Imaging studies:

• Chest x-ray can show bilateral opacity
• CT lung demonstrates ground-glass opacities with sub-pleural sparing.

Clinical course

• Some cases required mechanical intubation
• Corticosteroid treatment appears to improve clinical course
• Infectious evaluation was negative in almost all cases.
• No clear causative etiology has been identified
• No death has been reported 

What to do:

• Inquire about vaping history when treating patients with suspected cases.
• Providers should contact their local health department, poison center or CDC (VapingAssocIllness@cdc.gov) to report possible case of vaping associated pulmonary injury 

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A new study confirmed the previously-known antibiotics to be associated with Torsades de pointes and QT prolongation (Macrolides, Linezolid, Imipenem and Fluoroquinolones). However, this study found new association between amikacin and Torsades de pointes/QT prolongation.

Methods

The authors queried the United States FDA Adverse Event Reporting System (FAERS) from 01/01/2015 to 12/31/2017 for reports of Torsade de points/QT prolongation (TdP/QT).

Reporting Odd Ratio (ROR) was calculated as the ratio of the odds of reporting TdP/QTP versus all other ADRs for a given drug, compared with these reporting odds for all other drugs present in FAERS

Results

FAERS contained 2,042,801 reports from January 1, 2015 to December 31, 2017. There were 3,960 TdP/QTP reports from the study period (0.19%).

Macrolides               ROR 14 (95% CI 11.8-17.38)

Linezolid                  ROR 12 (95% CI 8.5-18)

Amikacin                 ROR 11.8 (5.57-24.97)

Imipenem-cilastatin ROR 6.6 (3.13-13.9)

Fluoroquinolones   ROR 5.68 (95% CI 4.78-6.76)

Limitations:

These adverse events are voluntary reports

There might be other confounded by concomitant drugs such as ondansetron, azole anti-fungals, antipsychotics.

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Gunshot injuries are a leading cause of morbidity and mortality in the pediatric population.  The Pediatric Trauma Society supports the use of tourniquets in severe extremity trauma.  The Combat Application Tourniquet (CAT) that is commonly used in adults has not been prospectively tested in children.  This study used 60 children ages 6 through 16 years and applied a CAT to the upper arm and thigh while monitoring the peripheral pulse pressure by Doppler.  The CAT was successful in occluding arterial blood flow in all of the upper extremities and in 93% of the lower extremities.

Bottom line: The combat application tourniquet can stop arterial bleeding in the school aged child.

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Direct hepatotoxicity from a drug is predictable and dose-dependent.

Most commonly implicated agents include:

• Acetaminophen
• Niacin
• Aspirin
• Cocaine
• IV Amiodarone
• IV methotrexate
• Cancer chemotherapy

On the contrary, idiosyncratic prescription drug-induce liver injury is rare, unpredictable and not related to dose.

Most commonly implicated agents are:

1. Amoxicillin-clavulanate
2. Isoniazid
3. Nitrofurantoin
4. TMP-SMZ
5. Miocycline
6. Cefazolin
7. Azithromycin

Bottom line:

• Drug-induced liver injury is uncommon and can be a diagnostic challenge.
• Recognition of commonly implicated agents can help recognize/identify drug-induced liver injury. 

The Kidney Transplant Patient in Your ED

• Acute bacterial graft pyelonephritis is the most frequent type of sepis (bacterial pneumonia is the second most common source)
• Obtain renal transplant imaging to evaluate for sources of infection (i.e. urinary tract obstruction, renal abscess, or urine leakage)
• BK polyomavirus may reactivate and lead to nephritis, ureteral stenosis, or hemorrhagic cystitis
• Pneumocystis pneumonia is the most common fungal infection in patients without prophylaxis and after prophylaxis discontinuation (adjunctive steroids for treatment is controversial)
• Vascular access may be challenging. Avoid subclavian lines or femoral venous acess on the side of the graft
• Cardiovascular disease is the leading cause of mortality (accounts for 40-50% of deaths after the first year following renal transplant)

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Plica Syndrome

-A painful impairment of knee function resulting from thickened and inflamed synovial folds

Plicae are embryologic remnant inward folds of the synovial lining present in most knees

Most plica are asymptomatic

A pathological synovial plica can become inelastic, thickened and fibrotic. It may bowstring across the femoral trochlea at 70 to 100 degrees of knee flexion

Can be a cause of anterior knee pain/mechanical Sxs

Medial patellar plica most commonly involved

Hx: Snapping sensation, pain w/ sitting or repetitive activity

Anterior knee pain, clicking, clunking, and a popping sensation on knee loading activity such as squatting/stairs or with prolonged sitting

Many present with history of blunt trauma to the anterior knee

PE: A taut band of tissue that reproduces concordant pain with palpation

Tenderness in the medial parapatellar region

Painful, palpable medial parapatellar cord

-This can be rolled and popped beneath the examiners finger

The knee may be tender to the touch, swollen, and stiff 

Can be difficult to distinguish from other intra-articular conditions such as meniscal tears, articular cartilage injuries, or osteochondral lesions,

The examiner can then palpate for the plica by rolling one finger over the plica fold, which is located around the joint lines in anterior knee compartment

https://www.ortho.com.sg/wp-content/uploads/2018/04/medial-plica-syndrome-31-e1478966479644.jpg

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Managing the intubated patient with exacerbation of severe obstructive lung disease, especially asthma, can be very challenging as it carries higher risks of barotrauma due to higher pulmonary pressures and circulatory collapse due to auto-PEEP and decreased venous return. When measures such as medical therapy and noninvasive positive-pressure ventilation fail to prevent intubation, here are some tips to help:

1. Utilize a volume control ventilation mode to ensure a set tidal volume delivery / minute ventilation, as pressure-targeted modes will be more difficult due to the high pulmonary pressures in acute obstructive lung disease.

2. Set a low RR in order to allow for full exhalation, avoiding air-trapping / breath-stacking and circulatory collapse due to decreased venous return. This may require deep sedation and potentially paralysis.

• Permissive hypercapnea to >7.2 is generally well-tolerated except for pregnant patients, patients with high ICP, or patients with severe pulmonary hypertension

3. Increase your inspiratory flow by shortening your inspiratory time (thereby increasing your time for exhalation.

4. Monitor for auto-PEEP:

• Check your flow curve -- the waveform should return to zero before the start of the next inhalation, otherwise the next breath has been given before the patient has fully exhaled.
• Perform an expiratory hold at the end of exhalation. PEEP greater than set PEEP = auto-PEEP.

5. Peak inspiratory pressures will be high -- what is more important is the plateau pressure, measured by performing an inspiratory hold at the end of inspiration. Provided your plateau pressure remains <30, you don't need to worry as much about the peak pressure alarms.

6. If your patient acutely decompensates in terms of hemodynamics and oxygenation -- first attempt to decompress their likely auto-PEEPed lungs by popping them off the ventilator and manually press on their chest to assist with exhalation of stacked breaths allowing venous return to the heart.

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The American Diabetes Association requires a plasma glucose concentration greater than 250 mg/dL to diagnose diabetic ketoacidosis (DKA).  However, with the new diabetic agents this is not always the case. With the introduction of SGLT2 inhibitors (canagliflozin [Invokana], dapagliflozin [Farxiga], empagliflozin [Jardiance]) there have been reported cases of DKA and patients being euglycemic. 

Take Home Point

Patients with a low/normal blood glucose can still have DKA.  Especially if they are taking newer medications, such as the SGLT2 inhibitors.

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Hematologic toxicity (coagulopathy/bleeding) can occur with pit viper envenomation. Copperhead is the most commonly implicated pit viper envenomation in the U.S. However, the prevalence of hematologic toxicity from copperhead envenomation is variable, possibly due to regional variation in venom potency and species misidentification. 

An observation study was performing using multi-center (Virginia Commonweath university, University of Virginia Medical Center and Eastern Virginia Medical medical center) electronic hospital/medical records (Jan 1, 2006 to Dec 31, 2016) of suspected copperhead bites. Authors state that copperhead snakes are "nearly exclusively endemic" to the VCU and UVA medical center region.

Results:

388 patients were identified but 244 met inclusion/exclusion criteria.

• Mean age: 34 years
• Male: 59%
• Antivenom administration: 76%
• No bleeding was reported.

Hematologic toxicity: 14%

• Elevated PT: 10.0%
• Elevated PTT: 3.9%
• Thrombocytopenia: 1.2%
• Hypofibrinogenemia: 0.7%

Conclusion

In a small sample of copperhead envenomation in Virginia, “subtle” hematologic abnormalities were observed but clinically significant hematologic toxicity was not observed (i.e. bleeding)

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With increasing critical care boarding and the opioid crisis leading to more intubations for overdose, extubation - which was once a very rare event in the ED - is taking place downstairs more often.  Prolonged mechanical ventilation is associated with a ton of complications, so it's important for the ED physician to be comfortable assessing extubation readiness.  There is no single accepted set of criteria, but most commonly used are some variant of the following:

• Reason for intubation (e.g. overdose, pneumonia, pulmonary edema, AMS, etc) has resolved
• Minimal vent settings - Typically FiO2 < 40%, PEEP <= 5
• Spontaneous breathing present (i.e. pt breathes with reasonable rate on PS, SIMV, VS, PPS, etc) and able to maintain reasonable pH and pCO2 on these settings
• Neuromuscular function adequate - Ask patient to lift head off bed
• Mental status adequate - Ask patient to give thumbs up or squeeze hands
• Secretions tolerable - Ask RN or RT for frequency of suctioning and sputum character.  Think twice about extubation if getting purulent, thick secretions every 15 minutes.
• Clinical course does not require further intubation (i.e. no immediate trips planned to OR, MRI; pt not hemodynamically unstable, etc.)

If the above criteria are met, two additional tests are frequently considered:

• Spontaneous Breathing Trial (SBT) - Typically done by placing pt on PS with low settings (0/0 to 5/5).  Let pt equilibrate (time of SBT is variable) on these settings, then calculate RSBI (RR/Vt). RSBI < 105 is traditionally considered acceptable for extubation.  Remember - lower is better.  Ask RT for this. 
• Cuff Leak Test - becoming less popular, but may consider in patients at risk for laryngeal edema (e.g. prolonged intubation, angioedema, etc). Historically thought to predict airway swelling, but data is mixed.  Ask RT for this.

And don't forget to consider extubating high risk patients directly to BiPAP or HFNC!

Bottom Line: For conditions requiring intubation where significant clinical improvement may be expected while in the ED (e.g. overdose, flash pulmonary edema, etc), be vigilant about, and have a system for, assessing readiness for extubation.

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Bone stress injury (BSI) in Adolescents

A BSI occurs along a pathology continuum that begins with a stress reaction and may progress all the way to a stress fracture.

Difficult to diagnose clinically.

Identifying risk factors as part of the history is very important.

Common sites for BSI are most frequently in the lower extremity and include the tibia, fibula, tarsals and metatarsals, calcaneus, and femur.

When considering this in an ED setting, image the involved area and if there is no fracture, advise discontinuing the activity until time of PCP/sports medicine follow up. For those with rest pain, pain with minimal weight bearing or in whom a fracture was suspected but not present, consider providing a walking boot or crutches.

BSIs occur more frequently in young athletes than in adults.         

          Almost 50% of BSIs occur in those younger than 20 years of age

Primary care and sports medicine providers are seeing more of these patients due to many factors.

Year-round training, sports specialization at younger ages and increase in training intensity/duration contribute to the increase incidence in adolescents.

Not surprisingly, participation in organized sports as an adolescent is a known risk factor.

Just as a change in sporting level from high school to college is a known risk factor for BSI, young “gifted” athletes who are promoted to competing with the varsity team may be at similar risk.

Shin pain lasting more than 4 weeks may represent a unique subset of MSK pain complaints increasing risk of BSI.

A prior history of BSI is a strong predictor of future BSI.

Inquire about night pain, pain with ambulation, and pain affecting performance.

Athletes with BSIs have a significantly lower BMI than controls (<21.0 kg/m2).

Athletes with BSIs sleep significantly less than controls.

Athletes with BSIs have significantly lower dairy intake than controls.

Inquire about components of the female athlete triad (low energy availability, menstrual dysfunction and low bone mineral density)

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The incidence of empyema as a complication of pneumonia has been increasing since the 1990's and source control requires removing the pus from the chest as soon as possible, but how large should the drain be? The American Association for Thoracic Surgery (AATS) released the most recent guidelines for identifying and managing empyema in June 2017 and at the time had no certain evidence to guide the choice of large-bore vs small-bore catheters. Most studies to guide us are flawed (not randomized), but no recently published randomized studies exist to provide a definitive answer. 

Bottom line: a small-bore pigtail catheter is a reasonable choice to drain empyema and flushing it every 6 hours has been shown to prevent clogging.

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-Benzodiazepines alone are effective in terminating status epilepticus in 40 to 60% of pediatric patients

-The guidelines for second line agents are based on observational studies and expert opinion

-Adverse effects of phenytoin include hepatotoxicity, pancytopenia, Stevens-Johnson syndrome, extravasation injuries, hypotension and arrhythmias

- Levetiracetam has a reduced risk of serious adverse events, greater compatibility with IV fluids and can be given in 5 minutes versus 20 minutes for phenytoin.

Bottom line: In a recent randomized control trial they found that levetiracetam was not superior to phenytoin as a second line agent for management of convulsive status epilepticus in children.  There was no difference between efficacy or safety outcomes between the two groups.

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Pulmonary complications - aspiration, pulmonary edema, etc. are frequently reported in both heroin intoxication and in reversal of opioid overdose with naloxone. 

Suspected opioid overdose victims (N=1831) who received naloxone from EMS providers were studied retrospectively. Pulmonary complications were defined as pulmonary edema, aspiration pneumonia and aspiration pneumonitis.

Results

• Out of hospital naloxone dose > 4.4 mg – 62% more likely of experiencing pulmonary complication (OR 2.14, 95% CI: 1.44 to 3.18) 
• Increased risk of pulmonary complication if initial naloxone dose is > 0.4 mg (OR 2.57, 95% CI 1.45 to 4.54)

Conclusion

Higher out of hospital naloxone administration is associated with increased odds of developing pulmonary complications

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POCUS in the Critically Ill Pregnant Patient

• POCUS can be a valuable tool in the assessment and management of critically ill pregnant patients.
• Conditions to consider in the critically ill pregnant patient who presents with acute RUQ pain include acute fatty liver of pregnancy (AFLP), liver infarction, liver hematoma, and Budd-Chiari Syndrome.
• POCUS findings for these conditions include:
  • AFLP: a "bright" liver
  • Infarction: a wedge-shaped hypoechoic area (late finding)
  • Hematoma: a heterogeneous fluid collection below the capsule or intraparenchymal
  • Budd-Chiari Syndrome: lack of blood flow or thrombus in a hepatic vein or within the IVC.

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Long head of biceps tendon (LHBT) Testing

Overhead activities can cause anterior shoulder pain due to LHBT instability. A review of 3 physical exam maneuvers for bedside evaluation.

Speed test

Shoulder at 90° of flexion with arm fully supinated and elbow extended

Patient attempts to fwd. elevate arm against a downward force

Positive test is pain localized to bicipital groove.

Sensitivity 54% and specificity 81% for biceps pathology

https://youtu.be/N00gA4Pvsbw

Yergason test

Elbow at 90° of flexion with arm fully pronated and held against thoracic wall. Examiner grips patient’s hand and resists attempts at supination.

Positive test is pain localized to bicipital groove or LHBT subluxation.

Sensitivity 41% and specificity 79% for biceps pathology

https://youtu.be/_ot2S75mZ3o

Upper Cut test

Shoulder neutral with Elbow at 90° of flexion, arm fully supinated and hand in a fist. Patient moves hand toward chin in an uppercut motion like a boxer. Examiner places hand over patient’s fist and resists upward movement.

Positive test is pain localized to bicipital groove or LHBT subluxation.

Sensitivity 73%, specificity 78%, +LR 3.38 for biceps pathology

https://youtu.be/EE-WhlWFZvk

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“Push dose pressors” – administration of small doses of vasopressors in the emergency room has become a common practice. A recently published study investigated the incidence of human error and adverse hemodynamic events.

Push dose pressors were defined as:

• Phenylephrine (any dose)
• Epinephrine (<= 100 mcg) 

Adverse hemodynamic event was defined as:

• Extreme tachycardia (HR > 140 bmp)
• New bradycardia (HR < 60 bmp)
• Hypertension (SBP > 180 mmHg)
• Ventricular tachycardia

249 out of 1522 patients were identified and analyzed from Jan 2010 to November 2017

• median initial epinephrine dose (20 mcg; IQR: 10-100; range 1-100)
  • recieved more than one dose: 78 (57%)
• median initial phenylephrine dose (100 mcg; IQR: 100-100; range 25 to 10,000)
  • received more than one dose: 62 (56%)

Adverse event

• Phenylephrine group (n=110): 30 (27%; 95% CI: 19-36%)
• Epinephrine group (n=139): 68 (50%; 95% CI: 41-58%)

Errors

• Human error: 47 (19%) - similar proportion of human error between two agents.
• Dosing error: 7 (3%; 2.5 to 100-fold)
• Documentation error: 43 (17%)
• Only one dosing error occurred when a pharmacist was present

Conclusion

• Human errors and adverse hemodynamic event were common when “push dose pressors” were administered.
• Consultation with a pharmacist can/may reduce dosing error.

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• Symptoms/signs that suggest serious underlying conditions causing headaches are summarized by the mnemonic SNOOP:
  • S - Systemic symptoms/signs/disease
    • e.g. fever, weight loss, HIV, malignancy, pregnancy
  • N - Neurologic symptoms/signs
    • e.g. altered mental status, diplopia, pulsatile tinnitus, loss of consciousness
  • O - Onset sudden, abrupt, thunderclap
    • i.e. pain reaches maximal intensity instantly after onset
  • O - Older age of onset, especially > 50 years
  • P - Pattern change
    • e.g. change in frequency, severity, clinical features, precipitated by Valsalva, aggravated by postural change
• Consider structural pathologies, vascular disorders, infectious and inflammatory conditions in the evaluation of secondary headache syndromes.

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With a shortage of push dose epi, this may be an opportune time to review alternative options (see also Ashley's email on the subject).

The dose of vasopressor required to reverse hypotension has been most studied in pregnant women undergoing c-section who get epidurals and experience spinal-induced vasoplegia and hypotension (not necessarily our patient population, but we can extrapolate...)  

Phenylephrine was found to reverse hypotension 95% of the time at a dose of 159 micrograms (a neo stick has 100 ug/mL, so around 1-2 mL out of the stick)

Norepinephrine reversed hypotension in 95% of patients at a dose of 5.8 ug.  The starting dose for our norepi order in Epic is 0.01 ug/kg/min, so if you have a levophed drip hanging and have an acutely hypotensive patient, you may want to briefly infuse at a higher rate such as 0.1 ug/kg/min (for a typical weight patient), or bolus approximately 3-7 ug for a typical patient.  Of course the degree of hypotension, particular characteristics of your patient and clinical context should be taken into consideration.  When your a lucky enough to have this resource, always consult your pharmacist.

Bottom Line: To reverse acute transient hypotension you may consider:

-A bolus of phenylephrine 50-200 ug (0.5-2 mL from neo-stick)

-A bolus of norepinephrine 3-7 ug

-Briefly increasing your norepinephrine drip (if you have one) to something around 0.1 ug/kg/min in a typical weight patient

-Always search for other causes of hypotension and consider clinical context.

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Alteplase may be considered in some patients with a presumed or confirmed pulmonary embolism.  Below is a list of the different patient populations and the associated alteplase dosing.

-Hemodynamically Stable/Submassive: Alteplase usually not indicated.

-Hemodynamically Unstable/Massive: Alteplase IV 100 mg as an infusion over 2 hours.

-Cardiac Arrest: Alteplase IV/IO 50 mg bolus over 2 minutes.  Can repeat a second 50 mg bolus 15 minutes later if unable to achieve return of spontaneous circulation.

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