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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

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

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

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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Propofol Infusion Syndrome (PRIS)

SSRI And Bleeding Risk In Pregnancy

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