UMEM Educational Pearls

In September 2013, an international group representing major societies in toxicology and nutrition support began collaborating on a comprehensive review of lipid use in poisoning. Six total papers will be published, with the most recent two made available online this week. Here are the available (and forthcoming) papers:

1. Gosselin S, et al. Methodology for AACT evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning. Clin Toxicol 2015;53(6):557-64. [PMID 26059735]

2. Grunbaum AM, et al. Review of the effect of intravenous lipid emulsion on laboratory analyses. Clin Toxicol 2016:54(2):92-102. [PMID 26623668]

3. Levine M, et al. Systematic review of the effect of intravenous lipid emulsion therapy for non-local anesthetics toxicity. Clin Toxicol. 2016;54(3):194-221. [PMID 26852931]

4. Hoegberg LC, et al. Systematic review of the effect of intravenous lipid emulsion therapy for local anesthetic toxicity. Clin Toxicol. 2016;54(3):167-93. [PMID 26853119]

5. Hayes BD, et al. Systematic Review of Clinical Adverse Events Reported After Acute Intravenous Lipid Emulsion Administration. Clin Toxicol. 2016 Apr 1. [Epub ahead of print] [PMID 27035513]

6. The final paper, which is in process, is the consensus recommendations from the workgroup based on the 4 systematic reviews.

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• Cerebral venous thrombosis (CVT) is a rare but potentially life-threatening disease.
• Mortality in CVT is largely attributed to herniation.
• The diagnosis of CVT is made on the basis of clinical presentation and imaging studies.
• When you are concerned about CVT in a patient, which neuroimaging modality should you obtain?  CT or MRI?
• Non-contrast CT
  • Often the first neuroimaging obtained as it can evaluate for other processes such as cerebral infarct, intracranial hemorrhage, and cerebral edema.
  • Dense delta sign, dense clot sign and cord sign all refer to hyperattenuation of the clot. 
  • However, these findings are only seen in 20-25% of cases and disappear within 1-2 weeks.
• MRI
  • Clot appears hyperintense in the subacute phase.
  • In the acute phase, clot can mimic normal venous flow signal and result in potential diagnostic error.
• CT venography
  • Detailed depiction of cerebral venous system.
  • Timing of contrast bolus affect quality of evaluation.
  • Reconstruction may be difficult to subtract all of the adjacent bone.
• MR venography (MRV)
  • Unenhanced time-of-flight (TOF) MR venography has excellent sensitivity to slow flow.  It is useful in detection of large occlusions (e.g. jugular venous thrombosis), but susceptible to flow artifacts.
  • Contrast enhanced MR venography improves visualization of small vessels, thus preferred to TOF MR venography.

Bottom Line:  CT venography is good for diagnosing CVT, but MRI/MRV is superior for detection of isolated cortical venous thromboses and assessing parenchymal damage.

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• Transthoracic echocardiography (TTE) is an essential tool during cardiac arrest because it identifies potentially reversible causes (e.g., tamponade, massive PE, etc.).
• One of the limitations of TTE is that it is sometimes difficult to assess the heart in less than ten seconds (i.e., during a pulse check) and good views of the heart sometimes hard to obtain. Transesophageal echocardiography (TEE) offers the potential to overcome these obstacles.
• TEE not only allows continuous visualization and better imaging of the heart during arrest, but it also allows the assessment of compression depth, and whether the heart is being correctly compressed during CPR.
• Here is what a TEE probe looks like, here is an example of a TEE during arrest, and here is a podcast by @ultrasoundpodcast on the literature for using TEE during cardiac arrest.

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An interesting new study was published looking at in-hospital mortality in TBI patients who received succinylcholine or rocuronium for RSI in the ED.

What They Did

• Retrospective cohort study
• 233 patients (149 received succinylcholine, 84 received rocuronium)
• Groups were well matched overall (roc group was older, more hypotension in sux group)
• Within the two groups, patients were separated based on head Abbreviated Injury Score (scores of 4 or 5 were considered severe)
• The authors controlled for a lot of confounding factors

What They Found

• Overall, mortality was the same in each group (23%)
  • Mortality within the roc group was the same irrespective of head AIS
  • Mortality within the sux group was significantly higher in the subset of patients with higher head AIS (OR 4.1, 95% CI 1.18-14.12, p = 0.026)

Application to Clinical Practice

• Succonylcholine may increase mortality in severe TBI patients undergoing RSI in the ED compared to rocuronium
• The confidence interval was wide and these findings need to be confirmed in a prospective study
• Though the patients were well matched and the authors controlled for many variables, it still is difficult to pinpoint one intervention as the cause for mortality in critically ill patients (eg, etomidate + sepsis)
• With proper rocuronium dosing, intubating conditions are similar to succinylcholine. So if there is a potential for increased mortality in severe TBI patients with sux, rocuronium seems to provide a safer alternative.

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Throughout medical history one of the basic tenets of poisoning therapy is to remove the poison from the patient. For hundreds of years, gastric decontamination has been the cornerstone treatment for acute poisonings by ingestion. This commonsense approach endeavors to remove as much of the the ingested toxin as possible before systemic absorption and organ toxicity occurs. Multiple GI decontamination methods have been utilized including gastric emptying by lavage and ipecac, toxin binding by activated charcoal, and increasing GI transit time with cathartics and bowel irrigation. Numerous studies have been conducted to assess the effectiveness of GI decontamination including measurement of amount of toxin removed by gastric retrieval, reduction of bioavailability by measuring blood levels, and finally comparison of clinical outcomes of patients treated with and without GI decontamination. Controlled studies have failed to show conclusive evidence of benefit and have even demonstrated resultant harm especially with use of gastric lavage. Activated charcoal has a tremendous surface area capable of binding many substances. Although viewed as relatively safe it does have risks in certain subsets of patients, pulmonary aspiration the most common, and is no longer routinely recommended.

Considerations for use of Activated charcoal (AC) use in acutely poisoned patients:

• AC does not bind alcohols, hydrocarbons, heavy metals
• Contraindications include diminished level of consciousness, seizure, emesis, unprotected airway, and intestinal obstruction
• Consider AC use in cases where there is potential for toxin to remain in the gut longer such as with delayed-release formulations or slowed gastric emptying
• Consider AC use in cases of expected severe toxicity with lack of effective antidote

The decision to use activated charcoal is no longer standard of care but should be individualized to each clinical situation weighing the risk versus clinical benefits.

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On February 1^st, the World Health Organization declared that Zika was an international public health emergency.  As noted in the Pearl from January 20^th, 2016, Zika is a mosquito-borne RNA flavivirus that is usually asymptomatic.  However, congenital malformations have been seen in pregnant women infected with Zika.

While it is clear that the decision to declare an international public health is a judgement call, what are the criteria for considering this declaration?

Per the WHO, the term Public Health Emergency of International Concern is defined in the IHR (2005) as “an extraordinary event which is determined, as provided in these Regulations:

·         to constitute a public health risk to other States through the international spread of disease; and

·         to potentially require a coordinated international response”. This definition implies a situation that: is serious, unusual or unexpected; carries implications for public health beyond the affected State’s national border; and may require immediate international action.

The responsibility of determining whether an event is within this category lies with the WHO Director-General and requires the convening of a committee of experts – the IHR Emergency Committee.

For Zika, the sequalae of concern are the clusters of microcephaly and Guillain-Barré syndrome suspected to have resulted from Zika infection.

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• AKI can be seen in up to 40% of ICU patients
• Around 5-10% require treatment with renal replacement therapies
• The most common cause is acute tubular necrosis
• Definition by KDIGO:

1. Increase in Creatinine by 0.3 or more within 48 hours OR
2. Increase in Cr to >1.5 x baseline, presumed to have occured within the prior 7 days
3. Urine volume <0.5 mL/kg/hr x 6 hours

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Diverticulitis

It seems like the standard treatment course for patients with suspected diverticulitis in the ED is to obtain a CT of the Abdomen and pelvis and then to start antibiotics. A CT scan is really only needed if you suspect that they have an abscess, micro perforation, are not responding to conventional treatment, or you suspect an alternative diagnosis.

However, what should the conventional treatment be? Several recent studies from Sweden, Iceland and the Netherlands have shown that patients treated with antibiotics did not fair any better then patients who were just observed. There was no difference in time to resolution of symptoms, complications, recurrence rate, or duration of hospitalization.  

Several national societies (Dutch, Danish, German, and Italian) now recommend withholding antibiotics in patients free of risk factors who have uncomplicated disease, but these patients will need close follow up.

TAKE HOME POINT: Patients with diverticulitis can be treated supportively and probably do not require antibiotics unless you suspect they have complicated disease or are immunosuppressed.

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Airway management is an integral part of caring of critically ill patients, but is there anything that should be done differently in the neurologically injured patient?

• Injured brains are particularly sensitive to hypoxia. Avoid it by appropriate positioning and preoxygenation.
• Consider fentanyl and/or ketamine for sedation for RSI, as fentanyl can blunt the hemodynamic response to intubation, while ketamine is hemodynamically neutral and safe.
• Consider Esmolol (1.5mg/kg) prior to intubation to prevent sympathomimetic surge during intubation in the absence of multiple injuries.
• There is no role for the use of a defasciculating dose of neuromuscuclar blockade during RSI

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Shock Index

• The shock index (SI) is calculated as the ratio of heart rate to systolic blood pressure and is often used in the assessment of critically ill patients.
• A SI > 0.8 has been shown to be an independent predictor of post-intubation hypotension during emergency airway management.
• Kristensen and colleagues performed a retrospective review in a single-center in Denmark to evaluate the ability of SI to predict 30-day mortality.
• In over 110,000 patients, they found a weaker association of SI with 30-day mortality in patients > 65 years of age, those taking a beta-blocker or calcium channel blocker, or those with a history of hypertension.
• Notwithstanding, a SI > 1 was a significant predictor of mortality across all patient populations and should be considered a warning of serious illness.

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Recommended follow-up for common orthopedic injuries

Lead is a ubiquitous metal in the environment partly due to decades of using leaded gasoline (organic lead) and lead-based paint (inorganic lead). Outside of occupational exposure, children are disproportionately affected from environmental lead exposure.

Common route of exposure are:

1. Ingestion (common in children): soil, water, lead-based paint chips, toys, certain folk remedies.
   • Absorption: adult: 3 – 10% vs. children: 40 – 50%
2. Inhalation (mostly occupational exposure): lead dust
   • Absorption: 30 – 40%
3. Dermal (minor): cosmetic products
   • Absorption: < 1%

Majority of the absorbed lead are stored in bone (years) > soft tissue (months) > blood (30-40 days) (half-life). Thus blood lead level does not accurately reflect the true body lead burden.

Incidence of elevated blood lead level (EBLL > 5 microgram/dL) in children increased from 2.9 to 4.9% in Flint, MI before and after water source change. In the area with the highest water lead level, the incidence increased by 6.6%.

Clinical manifestation in children

Evaluation for lead poisoning

1. Blood lead level (BLL)
2. CBC: hypochromic microcytic anemia, basophilic stippling
3. Imaging: abdominal XR – check for foreign bodies in GI tract; long-bone XR – lead lines

Management of children with EBLL

1. Removal from exposure
2. Environmental investigation/intervention (BLL: 15 - 44 ug/dL)
3. Chelation
   • Asymptomatic (BLL: 45 – 69 ug/dL): Succimer (PO)
   • Symptomatic (BLL: > 70 ug/dL): Dimercaprol (IM) and CaNa₂EDTA (IV)

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Zika virus is a mosquito-borne flavivirus. 

• The flavivirus genus includes multiple other human viral infections, including yellow fever, West Nile, dengue and tick-borne encephalitis.
• The primary vector for Zika virus is Aedes aegypti, though Aedes albopictus can also transmit it.

While outbreaks have been previously reported in Africa, Asia and the islands of the Pacific, it was first reported in the Western Hemisphere in May 2015. 

• Per the CDC, as of January 15, 2016, local transmission had been identified in at least 14 countries or territories in the Americas. 
• There has been no local transmission (yet) in the Continental US.

Clinical Disease:

• One in five infected become symptomatic
• Clinical illness is usually mild and lasts for several days or a week
  • Severe disease is uncommon, though Guillain-Barre syndrome has been reported in patients following suspected Zika infection
  • Fatalities are rare
  • Of note: congenital malformations have been seen in pregnant women infected with Zika
• Characteristic clinical findings can include:
  • acute onset of fever,
  • maculopapular rash,
  • arthralgia,
  • conjunctivitis

Diagnosis and Treatment

• Consider the diagnosis in symptomatic travels returning from affected areas
• RT-PCR can be used on serum specimens from the first week of illness
• There is no current commercial test available
• Treatment is symptomatic and supportive
  • No specific antiviral therapy

Prevention

• Avoid mosquito bites
  • Wear long sleeves and pants
  • Use insect repellents when outdoors (such as DEET)
  • Delay travel to known affected areas if you are pregnant

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What classifies "submassive PE"?

• Echocardiographic signs of RV strain (RV dilation/systolic dyfunction, decreased TAPSE)
• Hemodynamic stability (SBP >90)
• Patients may or may not have abnormal cardiac biomarkers (elevated troponin, BNP)

Submassive PE has early benefit from systemic thrombolysis at the cost of increased bleeding [1].

Ultrasound-accelerated, catheter-directed thrombolysis (USAT) [the EKOS catheters] has been shown to be safe, with low mortality and bleeding risk, as well as immediately improved RV dilation and clot burden [2-4]. USAT may improve pulmonary hypertension [4].

USAT is superior to heparin/anti-coagulation alone for submassive PE at reversing RV dilation at 24 hours without increased bleeding risk [5].

Long-term studies evaluating chronic thromboembolic pulmonary hypertension (CTEPH) need to be done, comparing USAT with systemic thrombolysis and surgical thombectomy.

Take-home: In patients with submassive PE, USAT should be considered over systemic thombolysis or anti-coagulation alone.

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Question

23 year-old female presents complaining of progressive right lower quadrant pain after doing "vigorous" exercise. CT abdomen/pelvis below. What’s the diagnosis? (Hint: it’s not appendicitis)

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The Salter Harris Classification System is used in pediatric epiphyseal fractures. The higher the type of fracture the greater the risk of complications and growth disturbance.

Some common exam facts about Salter Harris Fractures are:

• The type II fracture is the most common.
• The small metaphyseal fragment in Salter Harris type II and IV fractures is called the Thurston Holland Sign.
• Type III and IV fractures often require open reduction and internal fixation due to the fracture extending into the joint.
• Type V fractures may appear normal, but the epiphyseal plate is crushed and the blood supply is interrupted.

The Classification system as listed by Type:

• Type I: A fracture through the physeal growth plate. Typically can not be seen on x-ray unless they growth plate is widened or displaced..
• Type II: A fracture through the physeal growth plate and metaphysis.
• Type III: A fracture through the physeal growth plate and epiphysis.
• Type IV: A fracture through the epiphysis, physeal growth plate and metaphysis.
• Type V: A crush injury of the physeal growth plate.

For Maite, a helpful mnemonic is SALTR , Slipped (Type I), Above (Type II), Lower (Type III), Through (Type IV), and Ruined or Rammed (Type V)

A image of the fractures can be found on FP Notebook at http://www.fpnotebook.com/ortho/fracture/ephyslfrctr.htm

ED study of 60 pediatric patients for procedural sedation

• Fentanyl 1 mcg/kg was followed by 0.1 to 0.2 mg/kg of etomidate IV.
• One dose of 0.2 mg/kg IV etomidate was adequate for 39/60 patients
• 16.4% had respiratory depression
• Desaturation occured in 23 patients
• No patient required positive pressure ventilation
• Average recovery in 21 minutes

Bottom line: Etomidate can achieve effective sedation in children for a short procedure. Although respiratory effects were noted, none of them required assisted ventilation.

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The three-bag IV acetylcysteine regimen for acetaminophen overdose is complicated and can result in medication/administration errors. [1] Two recent studies have attempted simplifying the regimen using a two-bag approach and evaluated its effect on adverse effects. [2, 3]

Study 1 [2]

Prospective comparison of cases using a 20 h, two-bag regimen (200 mg/kg over 4 h followed by 100 mg/kg over 16 h) to an historical cohort treated with the 21 h three-bag IV regimen (150 mg/kg over 1 h, 50 mg/kg over 4 h and 100 mg/kg over 16 h).

The two-bag 20 h acetylcysteine regimen was well tolerated and resulted in significantly fewer and milder non-allergic anaphylactic reactions than the standard three-bag regimen.

Study 2 [3]

Prospective observational study of a modified 2-phase acetylcysteine protocol. The first infusion was 200 mg/kg over 4-9 h. The second infusion was 100 mg/kg over 16 h. Pre-defined outcomes were frequency of adverse reactions (systemic hypersensitivity reactions or gastrointestinal); proportion with ALT > 1000 U/L or abnormal ALT.

The 2-phase acetylcysteine infusion protocol resulted in fewer reactions in patients with toxic paracetamol concentrations.

Final word: Two-bag regimens seem to offer advantages compared to the traditional three-bag regimen with regard to reduced adverse drug reactions. Look for more data, particularly on effectiveness, and a potential transition to a two-bag approach in the future.

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• A recent systematic review looked at the prevalence of psychiatric disorders such as anxiety and depressive disorders in patients with traumatic brain injury (TBI).
• They found a substantial number of patients had a history of anxiety disorders (19%) or depressive disorders (13%) prior to their TBI.
• In the first year after TBI, pooled prevalence of anxiety and depressive disorders increased to 21% and 17%.
• Prevalence continued to increase over time, with longterm prevalence of anxiety and depressive disorders of 36% and 43%.
• Females, those without employment, and those with a history of psychiatric disorders or substance abuse prior to TBI were at higher risk for anxiety or depressive disorders following TBI.

Bottom Line: 

• Early recognition and treatment of psychiatric disorders in patients after TBI may improve their outcome, psychosocial functioning and health-related quality of life. 
• Thus we should consider providing appropriate discharge instructions that include psychiatric resources for patients after TBI.

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There are so many variables to monitor during CPR; speed and depth of compressions, rhythm analysis, etc. But how much attention do you give to the ventilations administered?

The right ventricle (RV) fills secondary to the negative pressure created during spontaneously breathing. However, during CPR we administer positive pressure ventilation (PPV), which increase intra-thoracic pressure thus reducing venous return to the RV, decreasing cardiac output, and coronary filling. PPV also increases intracranial pressure by reducing venous return from the brain.

So our goal for ventilations during cardiac arrest should be to minimize the intra-thoracic pressure (ITP); we can do this by remembering to ventilate "low (tidal volumes) and slow (respiratory rates)"

• Low: Use only one-hand while bagging, this will give the patient 500-600cc per breath. Using two-hands provides ~900-1,000cc per squeeze (more than we normally ventilate patients who have a pulse).
• Slow: Ventilate patients at 8-10 breaths per minute. The less you ventilate the less time the patient spends with positive ITP. Observational studies have demonstrated that providers ventilate too fast during code so the use of a metronome or timing light provides critical feedback.

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