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Propofol Infusion Syndrome (PRIS)

5/18/2015

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Propofol basics:
  • Short acting, intravenous general anesthetic
  • Sedation dose typically 0.3-4 mg/kg/hr
  • Anesthesia dose 4-12 mg/kg/hr
  • Rapid onset and short duration
  • Propofol infusion syndrome first described in 1990
 
Mechanism PRIS:
  • Propofol inhibits transport of fatty acids into the mitochondria and inhibits electron transport chain causing build up of fatty acid metabolites and decreased ATP
  • Made worse by a patient who is critically ill, has depleted carbohydrate stores, and thus relies on fatty acid breakdown for energy
 
Clinical features:
  • Metabolic acidosis
  • Cardiovascular collapse: Hypotension, treatment resistant bradycardia, and Brugada pattern on EKG
  • Rhabdomyolysis/acute renal failure
  • Elevated triglycerides
  • Hepatomegaly
  • Elevated lactate
  • 30% mortality
 
Risk factors:
  • Younger age (think higher doses propofol and less carbohydrate stores)
  • People on high doses/long duration of propofol
  • Exogenous glucocorticoids and vasopressors
 
Prevention:
  • Limit propofol to 4 mg/kg/hr for less than 48 hours
  • Note: cases of PRIS have still been described even with short duration/doses of propofol
  • Consider screening high risk patients with lactate, CPK, EKG, or triglycerides
 
Treatment:
  • Stop the propofol
  • Provide carbohydrates
  • Hemodialysis for acidosis
  • ECMO if all else fails
 
References:
Diedrick, D, Brown D. Propofol Infusion Syndrome in the ICU. Journal of  Intensive Care Medicine. 2011; 26 (2) 59-72. .
 
Rosen DJ, Nicoara A, Koshy N, Wedderburn RV. Too much of a good thing? Tracing the history of the propofol infusion syndrome.  J Trauma. 2007;63(2):443-447.
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SSRI And Bleeding Risk In Pregnancy

5/1/2015

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SSRIs and Bleeding Risk:
Is there increased bleeding risk with pregnancy, GI, CVA?

SSRI Definition:
  • Selective serotonin reuptake inhibitor
  • Inhibition of serotonin uptake in neurons
  • Allows serotonin to repeatedly stimulate receptors 

Bleeding Mechanism:
  • Platelet aggregation dysfunction
  • Blocking uptake of serotonin from blood into platelets
  • Subsequent impairment in platelet hemostatic response
  • Decreased platelet aggregability and increased bleeding time

Directly increase gastric acidity:
Fluoxetine and sertraline both increase gastric acid secretion - completely eliminated by vagotomy .  Synergistic with aspirin

Potent CYP450 inhibitor:
Subsequently raises blood levels of NSAIDs, antiplatelet drugs
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Bleeding in Pregnancy:
SSRI use 1-2% of all pregnant females

Large Swedish study looking at pregnancy registry, unblinded
n = 500 with SSRI use, 39,000 controls
2.6/2.1 OR elevated risk for PPH/PP anemia
484 mL mean blood loss with SSRI vs 398 mL without SSRI

Clinical Implications:
No overwhelmingly convincing evidence available as of yet
Given bleeding state of pregnancy as well as predilection of SSRIs for bleeding, risk/benefits should be weighed

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GI Bleeding
  • 2014 Systematic Review with 15 case-control studies, four cohorts
  • NNH was 3,177 and 881 in low and high risk groups
  • Increased risk was 1.66-1.68 in the case control and cohort 
  • studies
  • With NSAID use the risk of upper GI bleeding was increased to OR of 4.25

Clinical Implications:
Although flawed, pathophysiology and studies combine for reasonable mechanism.  Likely should be avoided if possible.

PPI Therapy:
  • Multiple studies - case controls - reporting decreased bleeding with SSRI w/ PPI use de Abajo et al found 9.1 OR SSRI and no PPI, 1.3 WITH PPI
  • Targownik hospitalized GI bleeding OR ratio of 0.39 with use of PPI with SSRI

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CVA Risks:
  • Danish medical registry study, 5833 SSRI users compared to 1:1 number of control
  • HR 0.77, lower risk of MI or ischemic stroke 
  • HR 1.89 (CI 0.97-3.66) for bleeding death
  • HR 1.13 for overall mortality increase

Clinical Implications:
  • SSRI use likely still advantageous to treat post CVA depression given overall mortality rate HR 1.1
  • Bleeding risk technically statistically insignificant

Summary:
Do we need to consider bleeding risk when prescribing SSRIs? 
  • Keep SSRI in mind when looking at medication list and assessing bleeding risk
Greatest risk for SSRI 
  • When used in conjunction with NSAIDs
Should PPIs be prescribed in conjunction with SSRIs?
  • If NSAIDs are frequently used by patient then reasonable to also prescribe PPI
Do any recent studies provide strong enough evidence against use for pregnancy, CVA?
  • Evidence suggest tendencies towards increased bleeding but only minimally statistically significant, except for combined SSRI and PPI use.
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  • RESIDENCY
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