UMEM Educational Pearls

Question

What medication ingestion can lead to black urine?

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• 2009241429_Black_urine.docx (115 Kb)

• We've talked about the rising incidence of cerebral venous thrombosis (CVT) and choice of neuroimaging studies before, now let’s talk about presentation and treatment.
• Symptoms range from headache to coma with cerebral edema and intracranial hypertension depending on the veins and sinuses involved.
  • Superior sagittal sinus is most frequently affected (62%) and can cause headache, hemiparesis, hemisensory loss, hemianopia, and seizures.
  • Transverse sinus is also commonly involved (45%) and can cause headache, aphasia, and seizures.
  • Thrombosis of the deep veins is seen in 18% of cases and can cause altered mental status, coma, and gaze palsy.
• Management includes anticoagulation, treatment of underlying cause, seizures, and intracranial hypertension.
  • LMWH is preferred unless in patients with renal dysfunction or need for rapid reversal of anticoagulation.
  • Endovascular intervention may be considered in severe cases that do not improve or deteriorate despite anticoagulation.
• Poor prognostic factors are: 
  • 2 points each - malignancy, coma, deep venous thrombosis
  • 1 point each - mental status disturbances, male, intracranial hemorrhage
  • Score ≥3 suggests high risk of poor outcome

Bottom Line: Severity of CVT presentation depends on the location and clot burden. Anticoagulation is key, though consider endovascular intervention if patient does not improve or deteriorates despite anticoagulation.

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A retrospective study analyzed data from 757 patients with spontaneous intraparenchymal hemorrhage.

Within the first 6 hours of admission, patients who had systolic blood pressure reduction between 40 – 60 mm Hg (OR 1.9, 95% CI 1.1-3.5) or reduction ≥ 60 mm Hg (OR 1.9, 95%CI 1.01-3.8) were associated with almost double likelihood of poor discharge functional outcome (defined as modified Rankin Scale 3-6).

Additionally, large systolic blood pressure reduction ≥ 60 mm Hg in patients with large hematoma (≥ 30.47 ml) was associated with higher likelihood of very poor functional outcome (mRS 5-6).

Take home points: while more studies are still needed to confirm these observations, perhaps we may not want to drop blood pressure in patients with spontaneous intraparenchymal hemorrhage too much and too fast.

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Systematic review and meta-analysis of 5 studies with a total of 929 patients comparing early vs. late initiation of norepinephrine in patients with septic shock

• all were single-center studies
• included RCTs, prospective and retrospective cohort studies

Primary outcome:

• short-term mortality of the early group was lower than that of the late group ([OR] = 0.45; 95% CI, 0.34 to 0.61)

Secondary outcome:

• no difference in ICU LOS
• time to achieved target MAP of the early group was shorter than that of the late group (mean difference = − 1.39; 95% CI, −1.81 to −0.96)
• in the three studies that assessed the volume of intravenous fluids within 6 h, the volume of intravenous fluids within 6 h of the early group was less than that of the late group (mean difference = − 0.50L; 95% CI, −0.68 to −0.3)

Caveat:

• no clear definition of “early” initiation (ranged from within 1 to 6 hrs)

Take home point:

Early norepinephrine usage may improve mortality in septic shock

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- Urethral prolapse will appear as a protrusion of the distal urethra through the urinary meatus causing a “doughnut” sign.

- Risk factors include trauma, UTI, anatomical differences, and increased intraabdoiminal pressure from cough or constipation.  There is a higher incidence in people of African descent.

- The chief complaint may include urethral mass and vaginal bleeding.

- There is a bimodal age distribution (prepuberty and postmetapause) due to a relative estrogen deficiency.

-Treatment is with estrogen cream and sitz baths for 4- 6 weeks.

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A recent study looked at thoracic spinal fractures in the era of the trauma panscan

NEXUS Chest CT Study from 2011 to 2014 at 9 Level I trauma centers.

Goal: To describe the identification rate and types of thoracic spine fractures.

Inclusion: age over 14 years, blunt trauma occurring within 6 hours of ED presentation, and chest CT imaging during ED evaluation.

11,477 subjects, 217 (1.9%) had a thoracic spine fracture

The majority of spine fractures in patients who had both chest x-ray and CT were observed on CT only (91%). 50% had more than 1 thoracic spinal level involved (mean 2.1). 22% had associated cervical fractures and 25% had associated lumbar fractures.

               64% had vertebral body fractures

               45% had posterior column fractures

               28% had compression fractures

               6% had burst fractures

Many patients (62%) had associated thoracic injuries such as

               Rib fractures (45%)

               PTX (36%)

               Clavicle fracture (18%)

               Scapular fracture (17%)

               Hemothorax (15%)

100 patients had clinically significant thoracic spine fractures.

Thoracic spine fractures are relatively uncommon in adult patients with blunt trauma.

If thoracic spine fracture is suspected clinically, radiography is not an effective screen and clinician should consider CT. If not suspected, guidelines discourage ordering CT to screen for this injury because of effective screening instruments, the diagnosis of clinically insignificant injuries and radiation exposure.

All clinically significant thoracic spine fractures would have been detected by the NEXUS Chest CT decision instrument.

https://www.mdcalc.com/nexus-chest-ct-decision-instrument-ct-imaging

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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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