UMEM Educational Pearls

Extracorporeal membrane oxygenation use is increasing in the US for acute poisoning. 

A retrospective study of the National Poison Data System from 2000 to 2018 identified 407 ECMO cases (332 adults – age > 12 years, 75 pediatric – age < 12 years). Increase in ECMO use were more notable in adult population.

Characteristics

• Median age: 27 years (IQR: 15-39)
• Male: 52.6%
• Single substance exposure: 51.5%
• Median number of exposures: 3 (IQR: 2-4)
• Overall survival: 70%

Intentional exposure

• Age > 12 years: 72.6%
• Age < 12 years: 9.3%

Most common class of drug/poison exposure in adults

• Sedative/hypnotic: 26%
• Antidepressants: 25%
• Calcium channel blockers: 19%
• Opioids: 17%

Most common class of drug/poison exposure in children

• Hydrocarbons: 37%
• Antiarrhythmics: 15%
• Antihistamine: 8%
• Unknown: 8%

Most common states that used ECMO for poisoning

• Pennsylvania: 45
• Texas: 27
• Minnesota: 24
• Maryland: 22
• Michigan: 20
• New York: 20

Conclusion

• Increase in EMCO use was most notable in patients with age > 12 years
• There was no significant trend in mortality during the study period
• ECMO cases were mostly reported from urban areas 

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While the invasive monitoring of central venous pressure (CVP) in the critically ill septic patient has gone the way of also transfusing them to a hemoglobin of 10 mg/dL, it remains that an elevated CVP is associated with higher mortality^1,2 and renal failure.^2,3

Extrapolating from existing data looking at hepatic vein, portal vein, and renal vein pulsatility as measures of systemic venous hypertension and congestion,^4,5,6 Beaubien-Souligny et al. developed the venous excess ultrasound (VExUS) grading system incorporating assessment of all 3, plus the IVC, using US to stage severity of venous congestion in post-cardiac surgery patients.⁷ They evaluated several variations, determining that the VExUS-C grading system was most predictive of subsequent renal dysfunction.

(Image from www.pocus101.com)
 

High Points

       VExUS Grade 3 (severe) venous congestion:

• Correlated with higher CVP & NTproBNP levels, as well as overall fluid balance
• Had a 96% specificity for development of subsequent AKI

Caveats

• Evaluating all parameters yields the most benefit to avoid false positives
• Can be difficult to obtain all views (>25% of subjects excluded due to poor US image quality)
• Studied in a limited population, notably not primarily RV failure patients

Clinical Uses

• To limit harmful fluid administration in shock
• To help answer the prerenal vs cardiorenal AKI question in CHF
• To indicate when volume removal (diuresis) should be the strategy, even in patients with vasopressor-dependent shock

A great how-to can be found here:

https://www.pocus101.com/vexus-ultrasound-score-fluid-overload-and-venous-congestion-assessment/

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Ingestion of a button battery is a can't-miss diagnosis with a very high risk for causing severe esophageal injury. There are about 3000 button battery ingestions per year, and this is increasing because electronics are becoming more and more prevalent.

Severe damage to the esophagus occurs within 2 hours. On your lateral view, the end with narrowing is the negative end, which triggers a hydrolysis reaction that results in an alkaline caustic injury and, ultimately, liquefactive necrosis.

Children can present with nonspecific symptoms and if the ingestion was not witnessed, they are at high risk for delays in diagnosis. Additionally, in the community setting, there can be further delays in definitive treatment (endoscopic removal) due to difficulty in calling teams in or transporting to other facilities.

Anfang et al. looked into ways to mitigate damage to esophageal tissue. They did an in vitro study on porcine esophageal tissue, measuring the pH with different substances applied. They tried apple juice, orange juice, gatorade, powerade, pure honey, pure maple syrup, and carafate. They then repeated the study in vivo on piglets with button batteries left in the esophagus and ultimately did gross and histological examination of the esophageal tissue.

Honey and carafate demonstrated protective effects both in vitro and in vivo. They neutralized pH changes, decreased full-thickness esophageal injury, and decreased outward extension of injury into deep muscle.

Take Home Point: If a child is found to have a button battery in the esophagus, while definitive management is still emergent endoscopic removal, early and frequent ingestion of honey (outside of the hospital) and Carafate (in the hospital) may help reduce the damage done to the tissue in the interim. The authors recommend 10ml every 10 minutes.

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STARRT-AKITrial

The Standard versus Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury

The development of acute kidney injury (AKI) in the critical care setting portends a greater morbidity and mortality for patients. Additionally, it places the patient at high risk of complications and requires a greater use of resources. Several studies in the past have examined if the timing of initiation of renal replacement therapy (RRT) would result in a mortality benefit, but have failed to demonstrate consistent outcomes.

The STARRT-AKI trial was a multinational, randomized controlled trial designed to determine if early initiation of RRT in critically ill adult patients with AKI lowered the risk of 90-day mortality. The Kidney Disease Improving Global Outcomes (KDIGO) classification was used to define AKI and over 2900 patients were randomly assigned to two groups over a 4 year period. Exclusion criteria included: recent RRT, a renal transplant within the preceding year, advanced CKD, an overdose necessitating RRT, or a strong suspicion of obstruction or autoimmune/vascular cause of their AKI.

Groups:

• The accelerated strategy group
  • Initiation of RRT within 12 hours of meeting eligibility criteria (AKI based on KDIGO definition)
• The standard strategy group –
  • General goal of withholding RRT unless the patient met the following specific parameters:
  • K+ >6.0,  pH <7.20,  HCO3 <12mmol/L,  moderate ARDS with clinical picture concerning for volume overload, or persistent AKI >72hr after randomization

Outcomes/Results:

• The study’s primary outcome measure was all cause mortality at 90 days
  •  There was no significant difference between the groups
  •  P=0.92 with RR 1.00
• Secondary outcomes evaluated several things including ventilator and vasoactive free days, hospital length of stay, number of days without RRT at 90 days as well as adverse events directly related to RRT
  • Interestingly, at 90 days, the patients in the accelerated strategy group were more likely to have ongoing RRT needs at 10.4% compared to the standard strategy group at 6.0% (not statistically significant).
  •  Overall, no significant difference between the groups when assessed for death in the ICU, major adverse events, or with regard to hospital length of stay.

Take home points:

• This was a well done, well randomized trial from many countries and ICU settings
• No significant mortality benefit between groups at 90 days
• Interestingly, the patients in the accelerated group were more likely to have suffered adverse events related to RRT and were more likely to be dependent on RRT at 90 days
  • It is unclear why this is, but suggestive that early initiation of RRT may compromise the intrinsic healing of the kidney
  • Emphasizes a greater risk for adverse events without clear benefit
• Ultimately, the decision to initiate RRT should be based on the patient’s clinical picture, acid/base status, electrolyte abnormalities, and volume status and NOT on a general trend of their renal indices.

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• Trigeminal neuralgia is diagnosed by:
  • Pain in 1 or more divisions of the trigeminal nerve
  • Paroxysms of pain that are sudden, intense, usually few seconds in duration
  • Pain triggered by innocuous stimuli in the trigeminal nerve territory (91-99% patients)
• 24-49% of patients experience continuous or long-lasting pain
• Exam may reveal forceful contraction of the facial muscles during a paroxysm (tic convulsif)
• Causes include:
  • Intracranial vascular compression of the trigeminal nerve root (most common)
  • Multiple sclerosis, cerebellopontine angle tumor
  • Idiopathic (10% of cases)
• Carbamazepine and oxcarbazepine are first-line treatments
  • They may be poorly tolerated due to side effects including dizziness, diplopia, ataxia, CNS depression, and hyponatremia
  • They also have limited efficacy on continuous pain
• Acute exacerbations may warrant admission for hydration, acute pain control, and titration of antiepileptic drugs
  • Botulinum toxin A was recently added as a treatment option

Bottom Line: New onset trigeminal neuralgia needs workup for its etiology. Carbamazepine and oxcarbazepine can be effective for symptom management though continuous or long-lasting pain exacerbations are difficult to treat.

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Ketamine In the Critically Ill Patient

• Ketamine has become a popular agent in the ED for both RSI and procedural sedation.
• Given the sedative, analgesic, dissociative, antidepressant, and anti-inflammatory properties, ketamine has also been used in a number of other critical illness conditions including:
  • Acute pain management
  • Status asthmaticus
  • Alcohol withdrawal syndrome
  • Status epilepticus
  • Acute agitated delirium
• The authors of a recent review in Critical Care Medicine found that the evidence supporting the use of ketamine in the critically ill is most robust for adjunctive analgesia in the intubated patient.  Surprisingly, the data is very limited to support the use of ketamine in these other conditions.
• Pearl: ketamine does have a myocardial depressant effect, which can be unmasked in states of catecholamine depletion and result in hypotension and bradycadia.

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Diagnostic performance of Ultrasonography for detection of pediatric elbow fracture

Elbow fractures account for approximately 15% of pediatric fractures

Fat pads are traditionally taught as a marker of fracture

In a cadaveric study:

Elbow effusions of 1-3 mL could be identified with ultrasound

Elbow effusions of 5-10 mL could be identified with plain film

Pediatric plain films are sometimes challenging to obtain and interpret compared to adults

              -More likely to be uncooperative in obtaining required views

              -Non-ossified epiphyses

Ultrasound may be used to detect

              -Cortical disruption and irregularity

              -Growth plate widening

              -Hematoma interposed between fracture fragments

              -Elevated posterior fat pad

Absence of elbow fracture was indicated by

              -Lack of cortical disruption

              -Absence of posterior fat pad sign

Meta-analysis of 10 articles totaling 519 patients using ultrasonography to detect elbow fractures

              Sensitivity 96%

              Specificity 89%

              False negative rate 3.7%             

For comparison, plain radiographs

Interpreted by peds EM physicians (87.5% sensitive and 100% specific)

Interpreted by radiology (96% sensitive, 100% specific)

Consider using ultrasound as a noninvasive, radiation-free modality for accurate diagnosis of pediatric elbow fractures.

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Definition: Congenital anomaly where the hymen is completely obstructing the vaginal opening

Demographic: Incidence 0.05-0.1% of females

History:  Most are asymptomatic and diagnosed on physical exam or incidentally when there is lack of menarche. Symptoms in adolescents can include: Abdominal pain (50%), urinary retention (20%), abnormal menstruation (14%), dysuria (10%), frequency, renal failure, UTI and back pain.

Physical exam: bulging, blueish hymenal membrane

Complications: Late detection can lead to infections, fertility problems, endometriosis, hydronephrosis, and rarely renal failure

ED treatment: If abdominal pain is significant or there is urinary obstruction, a urinary foley can be placed.  GYN should be consulted.

Definitive treatment: Hymenectomy, hymenotomy, carbon dioxide laser treatments or foley insertion through the hymen (done by a specialist).

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Baclofen is a presynaptic GABA-B receptor agonist in the spinal cord that is primarily used for muscle spasms/spasticity. In large overdose, baclofen can produce CNS depression, respiratory depression, bradycardia/hypotension, hypothermia, seizure and coma.

Baclofen is primarily eliminated by the kidney. In patients with end-stage kidney disease/acute kidney failure, hemodialysis (HD) has been used to enhance baclofen clearance. However, it is unclear if there is a benefit of using HD in patients with normal kidney function. 

In a recently published case report, HD was implemented in an attempt to shorten the anticipated prolonged ICU course. 

Case: 14 year old (51 kg) woman ingested 60 tablets of baclofen (20 mg tablets)

Her symptoms were:

• Coma/CNS depression
• Tonic-clonic seizure
• Transient hypotension (95/47 mmHg – resolved with IV fluids)
• Flaccid extremities
• Initially intubated for airway protection --> no spontaneous breathing on mech. ventilation.

Baclofen level: 882 ng/mL (therapeutic range: 80 – 400 ng/mL)

Baclofen clearance from hemodialysis vs. urine

• 24 hour urine output: 2810 mL --> total baclofen urinary elimination: 42 mg
• 3 hours of HD #1: 3.05 mg removed. Total of 3 HD session performed.

Patient’s mental status improved on hospital day 6 and was extubated. She was discharged to psychiatry on hospital day 14.

 Conclusion:

• Although this is a single case report, it appears that hemodialysis does not remove baclofen effectively.

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Another week, another COVID-19 study...

On August 12th, the Metcovid study was e-published ahead of print in Clinical Infectious Diseases.  This was another study looking at steroids in COVID-19 pneumonia, this time performed in Brazil.  Metcovid was a parallel, double-blind, randomized, placebo-controlled phase IIb clinical trial which enrolled 416 patients at a single academic center for the evaluation of methylprednisolone (MP; 0.5 mg/kg BID x 5 days) vs placebo.  As with all COVID studies, Metcovid has some significant limitations, and some equivocal findings.  However, Metcovid was largely in line with RECOVERY and other trials looking at steroids in COVID-19, which lends it some face validity.  Metcovid found no significant difference in the primary outcome (mortality at day 28), but did find a difference in mortality in patients over 60 years old (a post-hoc analysis).  Metcovid was probably underpowered (sample size was based on a 50% reduction in mortality), and did have a very small trend towards reduced mortality in the MP group (37.1% vs 38.2%, p=0.629).

Bottom Line: 

• Steroids (methylprednisolone 0.5 mg/kg BID x 5 days in this case) may have some mild benefit in severe cases of COVID-19 pneumonia, especially in patients who are elderly or have more aggressive inflammatory responses (as measured by CRP here).  
• Steroids in COVID-19 may be associated with some theoretical downsides like reduced viral clearance, but are relatively safe.  Main side effect is the well known hyperglycemia induced by corticosteroids.
• When using steroids in COVID pneumonia, both to stick with the evidence and for theoretical pharmacologic reasons, it may make sense to use dexamethasone or methylprednisolone, as these medications have a higher glucocorticoid:mineralocorticoid activity ratio.  It is hypothesized that using high mineralocorticoid steroids (like cortisone or hydrocortisone) may lead to increased water retention, which could be deterimental in ARDS.  This is purely theoretical.
• There was a signal towards harm in younger and less sick patients in this study, and it probably remains prudent to reserve steroids for older, sicker COVID-19 pneumonia patients, similar to the RECOVERY trial.

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What physical exam findings are associated with nitrous oxide abuse?

Nitrous oxide (NO) inhalation abuse, also called “whip-its” or “whippets”, inactivates vitamin B12 and create a vitamin B12 deficiency state. Chronic abuse of nitrous oxide can result in neurologic deficits/findings affecting the posterior/dorsal column of the spinal cord. 

Physical exam findings: 

1. Truncal ataxia
2. Decreased vibratory sensation and proprioception in lower extremities
3. Impaired coordination and rapid alternative movements
4. Lhermitte’s sign: paresthesia of the upper and lower extremities associated with flexion of the head/neck.
5. Rossolimo’s sign: exaggerated flexion of the toes when the tips of the toes are percussed

• Spontaneous cerebrospinal fluid (CSF) rhinorrhea is rare and usually related to a combination of thinning of the bone and dura and fluctuating intracranial pressure.
• CSF rhinorrhea can be associated with idiopathic intracranial hypertension, skull base tumors, neurosurgical and otolaryngology procedures, and trauma.
• Trauma with fracture of the anterior skull base is the most common cause of CSF rhinorrhea.
• CT and MRI can identify bony defects, whereas cisternography can diagnose occult leaks.
• Fluid containing CSF is classically described to make a “halo” or “double-ring” pattern on gauze or linen.

• However, this sign is not specific to CSF, as mixtures of blood with saline, tears, or rhinorrhea can also produce halos.
• Beta-2 transferrin is a protein found almost exclusively in CSF* thus can be used to diagnose CSF rhinorrhea.

Bottom Line: Beta-2 transferrin is more accurate than the halo sign to identify CSF containing fluid.

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Pronator Teres Syndrome

A compressive neuropathy of the median nerve in the region of the elbow

The median nerve passes through the cubital fossa and passes between the superficial and deep heads of the pronator teres muscle.

Rare compared to other compressive neuropathies such as carpal tunnel syndrome.

More common in women and in fifth decade of life

May be seen with weight lifters, arm wrestlers, rowers, tennis, archery, professional cyclists, dentists, fiddlers, pianists, harpists

Also associated with well-developed forearm muscles  

History:

Forearm pain – unlike carpal tunnel

Paresthesias in median distribution

No night symptoms – unlike carpal tunnel

Physical exam:

Sensory loss in medial nerve distribution.

Involves the thenar eminence!

Unlike carpal tunnel syndrome which doesn’t involve sensory loss in thenar eminence.

Pain may be made worse with resisted forearm pronation

Compression/Tinel’s sign over pronator mass reproduces symptoms

Treatment:

Splinting which limits pronation and NSAIDs

Steroid injection

Surgical nerve decompression is non operative treatment fails after greater than 6 months (rare)

Prior to this study, a Cochrane review and meta-analysis of TXA for upper GI bleeds with 7 trials (1654 patients), showed a large reduction in mortality with TXA (RR 0.61, 95% CI 0.42-0.98, p=0.01)

Design:

-Randomized, international, multicentre, placebo-controlled trial at 164 hospitals in 15 countries Juy 2013-2019

->16/18 years old with upper or lower GI bleeding

-1 g TXA IV over 10 minutes followed by maintenance dose 3 g TXA over 24 hours 

Results:

-Main outcome death due to bleeding within 5 days 

-4% (222/5994) died in TXA group vs 4% (226/5981) placebo risk ratio RR 0.99, 95% CI 0.82-1.18 

-Arterial thromboembolic events MI/CVA similar in both groups (0.7% vs 0.8%)

-Venous thromboembolic events PE/DVT higher in TXA group (0.8% vs 0.4%)

Pitfalls:

-Initially calculated all cause mortality until realization that over half deaths were due to non-bleeding causes, changed to death related to bleeding, allowing study appropriate power to detect difference 

-Majority of patients had UGIB/variceal bleeding due to liver disease, over 75% deaths in those with liver disease 

-Only 16% patients randomized in <3 hours, most >8 hours (CRASH-2 trial found benefit TXA in trauma patients only <3 hrs to administration) 

Takeaway:

-TXA should not be used in the management of GI bleeds

-Increased venous thromboembolic events associated with TXA administration for GI bleeds

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The liver performs an essential role in the metabolism and clearance of many drugs. Liver damage due to cirrhosis can decrease first-pass metabolism of oral medications and increase free-drug concentrations of protein-bound medications due to decreased albumin production. In the absence of cirrhosis, patients with chronic hepatitis or hepatic cancer may only have a small decrease in drug clearance. Hepatic dose adjustments are not as prevalent or readily available as renal dose adjustments, which can create difficulty in finding the balance between pain relief and adverse effects.

The most common medications used for pain control in the emergency department are acetaminophen, NSAIDs, and opioids.

Acetaminophen

It is sometimes misconceived that acetaminophen should never be used in patients with cirrhosis due to the common knowledge that acetaminophen overdoses can cause hepatotoxicity. Alcoholics may have an increased risk of hepatotoxicity due to induction of CYP2E1 and decreased glutathione stores. However, acetaminophen is safe in patients with cirrhosis when used at appropriate doses. Limit the total daily dose of acetaminophen to 2 g daily in patients with cirrhosis and avoid acetaminophen in patients that are actively drinking.  Also, educate patients that over-the-counter (OTC) and prescription medications may contain acetaminophen.

NSAIDs

In patients with cirrhosis, NSAIDs have increased bioavailability due to decreased CYP metabolism and decreased protein binding. In addition, prostaglandin inhibition can precipitate renal failure and sodium retention, worsening ascites and increasing the risk of hepatorenal syndrome, and increase the risk of gastrointestinal bleeding. Thrombocytopenia from NSAID use can further increase the risk of bleeding. Thus, avoid NSAID use in patients with cirrhosis. Topical NSAIDs can be considered.

Opioids

Opioid metabolism is altered in patients with cirrhosis and can contribute to complications with cirrhosis, such as precipitating encephalopathy. Generally, the bioavailability is increased and half-life is extended; thus, lower doses of immediate-release (IR) formulations at extended dosing intervals should be utilized. Common opioids for acute pain control in the emergency department are fentanyl, hydrocodone/oxycodone, hydromorphone, and morphine.

• Fentanyl: Largely unaffected by cirrhosis. High potency so utilize only in appropriate clinical situations.
• Hydrocodone/Oxycodone: Metabolized by CYP to active metabolites (hydromorphone/oxymorphone). Due to decreased CYP metabolism, analgesia may be less potent and clearance decreased. Also, be aware that some formulations are combined with acetaminophen.
• Hydromorphone: Metabolized by glucuronidation to inactive metabolite. Metabolism and clearance less affected by cirrhosis.
• Morphine: Increased bioavailability and concentration due to decreased first-pass metabolism. Decreased clearance and longer half-life. Avoid use in renal impairment and hepatorenal syndrome due to risk of neurotoxic metabolite accumulation.
• Tramadol, codeine, meperidine, methadone, and buprenorphine not recommended for acute pain control in the emergency department.

Take Home Points

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There is no well validated clinical decision rule similar to NEXUS or the Canadian Cervical Spine rule in children for clearing the cervical spine.  Clinical clearance versus imaging first is a complicated decision.  Certain risk factors may predispose children to injury and should be taken into account when deciding about clinical clearance versus imaging (XR).

High Risk Criteria for Cervical Spine Injury in Pediatrics

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Tianeptine is an antidepressant with mu-opioid receptor agonism. It is available in several European countries for therapeutic use, but not available in the US.

There has been an increase in tianeptine exposure in the US since August 2019. Recently a retrospective observation study was done to characterize the clinical features associated with tianeptine exposure. 

Result

• 48 cases of tianeptine exposure were identified from January 1, 2015 to March 15, 2020 from a single poison center
• 37 cases (77%) occurred from May 2019 to March 2020.

Conclusion

• Tianeptine exposure is increasing in the US .
• Intoxication frequently results in lethargy and/or agitation.

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