Grand Rounds Recap 5/4

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Acetaminophen toxicity siM - Drs. LaFollette, Nelson and Toth

Take a read through our Cases If It Bleeds it Leads..., Seeing is Believing..., and Belly Pain Bonanza. Curated commentary to follow

Acetaminophen Toxicity

  • 60,000 poisonings / year
  • ~500 deaths per year, evenly split therapeutic / suicide
  • Mechanism - acetaminophen to NAPQI by P450, overwhelming gluthathione stores
  • Alcohol, phenytoin, isoniazid all induce P450 and may increase NAPQI production. Chronic alcohol use will worsen toxicity when acute ingestion will competitively inhibit and can be preventative at producing the toxic metabolite

Our sim case was obvious in the fulminant presentation, and coagulopathy is shown to happen in a minority of these patients (63%), however it is important to remember how to resuscitate the advanced coagulopathic hepatotoxic patient.

One measure of the severity of Acute Liver Failure (ALF) is the degree of resultant encephalopathy. Somnolence or even coma is a marker or worse outcome, but these neurologic derangements can be reversible if the liver recovers.

N-acetyslcysteine (NAC) is a mainstay of treatment in acetominophen induced hepatoxicity, and there is little downside to administration of it regardless of the etiology. Mortality benefit is debatable in non-acetominophen etiologies of ALF, but indications include toxic acetominphen levels dictated by nomogram levels, any signs of transaminitis from acetaminophen, and hepatic encephalopathy.

Infections, both bacterial and fungal are common during the course of hospitalization for a patient with severe ALF, and broad spectrum antibiotics are indicated in a patient such as the one in the simulation that is severely ill and in multi system organ failure.

Early initiation of transplant evaluation may be the only chance for survivial in an ill ALF patient. Transferring the patient to a transplant center and early engagement of the transplant team are often overlooked in the ED, but shouldn't be. There are multiple scoring systems for liver failure, but one commonly used for acetominophen toxicity is the King's College Criteria.

Coagulopathy in Liver Failure

Specifically we will discuss ESLD from viral, ethanol, combination, we will discuss some exceptions

‘Rebalanced Hemostasis’ - these patients should not be thought of as intrinsically anticoagulated but rather always at a tipping point between hypercoagulation and hypocoagulation.

A review of the derangements by stages of coagulation

  • Platelets
    • Decreased number
    • Multiple mechanisms of thrombocytopenia: Impaired thrombopoetin, marrow suppression, splenic sequestration
    • Correlation weak between amount of thrombocytopenia and risk of bleeding except when <50K
    • Decreased adherence if concomitant uremia, infection, and endothelial dysfunction
  • Coagulation Cascade
    • Coagulopathic due to lack of factors I,II,V,VII,XI,X,XI
    • Only VIII and XIIIa made by endothelium and bone marrow, respectively, and their amounts should be normalized.
    • Prothrombic factors also down including protein S, protein C, AT
    • INR/PT only measure coagulation cascade therefore is inaccurate measure of true bleeding risk
    • Increased Plasminogen Activator 1 and decreased ADAMST13 (less cleaved vWF)
  • Fibrinolysis
    • 30-45% of chronic liver disease patients (5-10% clinically significant)
    • Parallels amount of hepatic dysfunction as hepatocytes clear results of fibrinolysis
    • Increased tPA
    • Decreased alpha 2 antiplasmin, XIII, and thrombin-activatable fibrinolysis inhibitor (TAFI)
    • Elevated degradation components (d-dimer)

Enter: TEG: check out this review for a summary

  • R time - initial fibrin formation (Reaction) - give FFP/PCC
  • K time - time taken to achieve clot strength (20mm) (Kinetics)
  • Alpha - R/K angle - indicates clot formation speed - Give cryoprecipitate
  • MA - strength of the clot (Max Amplitude - give platelets/DDAVP
  • LY30 - % lysis in 30 minutes - give TXA/ACA
  • CLT - clot length time - until completely lysed

Exceptions:

  • Cholestatic disease (PBC, PSC) less likely to see coagulopathic derangements and more likely to be hypercoagulable
  • NASH have greater risk of prothrombotic disease
  • Acute liver failure have lower incidence of platelet dysfunction

References

 

Leadership Curriculum: The Finances of Leadership Part 1

Financial costs are no longer just isolated to the business gurus. It applies to our clinical roles (home linezolid? maybe not) and educational goals as well.

Some terms...

  • Return on Investment (ROI) - a marker of a relative profitability in regards to costs spent to achieve that goal
  • Capital Budget - an allocation of resources within a fixed overall budget
  • Fiscal Year - Health systems can define as they will, with the academics tending towards July-June

Quantification of your benefits and costs to articulate your ROI on educational goals is difficult, but esprit de corps is a hard argument to make - look for long term benefits and quantify if possible.

Pelvic Ultrasound - Dr. McKee

Check out her dedicated post to pelvic ultrasonography here