Drugs as Innocent Bystanders
by Andrea Sikora Newsome, PharmD
“The patient is thrombocytopenic at 134, so I think we should switch off the Pepcid to a PPI,” the resident says to the team.
A wince briefly passes over my face. The attending catches my expression knowingly, and when the resident finishes, he speaks. “What are this patient’s risk factors for thrombocytopenia? Why don’t we have the students go around in a circle until we can’t anymore.”
The students are able to go around three times before they start grasping at straws and this was a question just focused on this one patient. If the question had been opened up to any risk factor or cause, we may have been there all morning. Patients in the intensive care unit (ICU) have multiple risk factors for thrombocytopenia and this patient was no exception.
This is an example of what I have started calling the “drugs as innocent bystanders” phenomenon that can occur in the intensive care unit. This is where we blame a drug for something that it probably has nothing to do with and then switch to a less optimal therapy to avoid this purported interaction.
Thrombocytopenia is one of the most common laboratory abnormalities observed in the ICU; by some estimates, more than half of patients are thrombocytopenic at some point in their ICU stay. Indeed, it is so common that once, as a resident, a pharmacist asked me what a “normal” platelet count was. I guessed, “Over 100?” They chuckled at my answer, “I guess for the ICU that is normal.”
Thrombocytopenia is generally defined as a platelet count less than 150 x 103 /µL. Critically ill patients will frequently dip below 100 x 103 /µL. Severe thrombocytopenia, less than 50 x 103 /µL, occurs in about 5-20% of patients; at that level, many surgeries are deferred and thromboprophylaxis with heparin is withheld. Histamine-2 blockers – especially cimetidine – have been associated with thrombocytopenia. However, the numbers are extremely low and most reports are individual case reports in which patients had multiple other risk factors in addition to drug therapy.
Thus, we are faced with a risk-benefit analysis. Should we switch from famotidine, a H2 blocker, to pantoprazole, a proton pump inhibitor (PPI)? Stress ulcer prophylaxis (SUP), previously discussed in this column, is such a rich example of evidence-based medicine (or lack thereof) it is worth revisiting. PPIs have demonstrated superiority in the treatment of gastrointestinal bleeding due to their superior acid inhibition properties; however, this benefit has not translated to SUP in the unit. When it comes to SUP, there is a goldilocks effect. Too little acid suppression (as with antacids) is not as effective in prevention of bleeding. However, too much acid suppression (as with PPIs) is associated with increased infection because the stomach can no longer neutralize bacterial threats.
H2 blockers seem to have the “just right” amount of acid suppression that minimizes bleeding but causes fewer infections. However, an aggressive marketing campaign, among other factors, has led many prescribers to believe that PPIs are superior - despite increased adverse effects and higher costs. As a result, everyone looks for a reason not to use famotidine and thrombocytopenia is an easy target. Ironically, PPIs also have thrombocytopenia listed as an adverse effect but somehow have avoided this bad rap.
“So tell me why you’re making our pharmacist make that face?” The attending jokes with the resident. He has heard my speech on this before and takes the lead.
“Because it is probably all those things and not the famotidine?” The resident replies.
“Exactly,” I say, “famotidine is probably just an innocent bystander in all this.”
Andrea Sikora Newsome, PharmD, is a Clinical Faculty Member at the University of Georgia in Augusta, Georgia.