A colleague in upstate New York reports that Acetaminophen 325 mg. p.o and Benadryl 50 mg. p.o. are used by their Medicine faculty routinely just before infusion of RBC and Platelets in order to avoid febrile non-hemolytic transfusion reactions. In their experience, they are unaware of any ill effects of this approach, which may avoid some febrile non-hemolytic reactions. What is the policy at other institutions, and what has been the experience of those who do administer antipyretics and antihistamines to patients just before transfusion?

The following responses were received.

ADDENDA Nov. 19, 2003

1. A physician in Oklahoma reports that at his institution there is no policy regarding pretreatment of patients with medications to mitigate mild transfusion reactions. When asked by colleagues in his hospital, he advises against it as he is concerned that acetaminophen might mask a fever associated with a hemolytic transfusion reaction. However, his institution uses prestorage leukoreduced blood components which, in his opinion, makes recommending against acetaminophen an easier sell. He also does not recommend routine pretreatment with diphenhydramine either. However, on occasion he will agree to pretreat some patients; he has seen a few patients who were receiving plasma exchanges for TTP who would always develop hives. He would pretreat those patients.

ADDENDA Nov. 20, 2003

2. A very experienced transfusion medicine physician in Florida reports that in his experience the reason that studies of the incidence of transfusion reactions are so unreliable is that many clinicians routinely premedicate their patients before blood transfusions. The Florida physician comments that when attempting to determine the true incidence of reactions, the diligent researcher who actually reviews the charts of patients who DO have adverse responses should review the charts of those patients who do NOT have reactions in order to obtain a baseline. Unfortunately, the Florida physician believes this baseline analysis is not done frequently enough. On a historical note, the Florida physician comments on one oncologist who actually gave an injection of steroids before platelet transfusion. Finally, back in the days of glass bottles (pre-FDA), the Florida physician remembers that it was possible to buy vials of antipyretic intended for injection through the rubber stopper into the blood product before beginning the transfusion!

ADDENDA Nov. 28, 2003

3. A transfusion medicine physician who practices in the eastern USA wishes to comment on and offer a reference for review. At the responding physician's institution, the administration of premedication is left to the discretion of the physician ordering the blood products. The frequency with which this occurs is unknown, though the responding colleague's impression is that it is relatively common. His hospital does not provide universal leukocyte reduction at this time (it will be implemented in a few months). While the physician from Oklahoma who replied in #1 above voiced concern that acetaminophen could mask a hemolytic transfusion reaction, the physician providing this response is not convinced that this would be the case. At the responding physician's previous place of employment he was asked by a small hospital to assist with a patient who received both acetaminophen premedication and a single unit of ABO-incompatible red blood cells. The patient had pain at the site of infusion as well as a fever of 104 F (which resulted in the identification of the problem). The cytokine storm resulting from intravascular hemolysis made itself apparent despite 325 mg of acetaminophen! The responding physician would similarly suspect that the same would be true of anaphylactic reactions in spite of the administration of diphenhydramine. In the end, however, administering or not administering premedication may be irrelevant, at least in the setting of prestorage leukocyte reduction. As evidence, the responding physician refers interested readers to the following article: Wang SE et al. Acetaminophen and diphenhydramine as premedication for platelet transfusions: A prospective randomized double-blind placebo-controlled trial. Am J Hematol 2002;70:191-194.

In this study, Wang et al found no difference in the rate of non-hemolytic transfusion reactions among patients receiving prestorage leukocyte-reduced apheresis platelets between those premedicated with a placebo (15.2%) and those premedicated with acetaminophen and diphenhydramine (15.4%).

The study was a prospective randomized double-blind placebo-controlled trial involving approximately 50 patients in each arm. The responding physician concluded, stating (quote) "If I ever need a transfusion, give me a little acetaminophen and diphenhydramine just in case."

ADDENDA Apr. 12, 2005

4. A transfusion medicine physician in Ohio reports that one of the hospitals in her institution's network wonders about the advisability of the following standing orders which are being written by a new orthopedic surgeon for his patients who are undergoing hip and knee cases, when they require blood transfusion:

Before each unit give:
Tylenol 650 mg PO
Benadryl 25 mg PO

After each unit give:
Lasix 10 mg IV

The chairman of the Department of Medicine asked that this practice be reviewed as he is concerned that the symptoms of a transfusion reaction might be masked.

5. A colleague in Texas reports that her hospital's Blood Utilization Review Committee has asked her to find out how many other places have doctors who routinely premedicate their patients before a transfusion. The medications routinely administered before transfusions at her hospital are Tylenol and Benadryl. She reports that their oncologists "always" premedicate their patients and that other practitioners do so at least half the time.

6. A transfusion medicine physician in the Sacramento area agrees with the Eastern USA transfusion medicine physician (posting #3 above) that administering or not administering premedication may be irrelevant, at least in the setting of pre-storage leukocyte reduction, and also refers colleagues to the information published in 2002 by Wang SE et al. Acetaminophen and diphenhydramine as premedication for platelet transfusions: A prospective randomized double-blind placebo-controlled trial. Amer J Hem 2002;70:191-194. In this prospective trial, transfusions in patients receiving pre-storage leukocyte-reduced single-donor apheresis platelets (SDP) were randomized to premedication with either acetaminophen 650 mg PO and diphenhydramine 25 mg IV, or placebo. Fifty-one patients received 98 transfusions. Thirteen patients had 15 Non Hemolytic Transfusion Reactions (NHTR):15.4% (8/52) in the treatment arm and 15.2% (7/46) in the placebo arm. Based on these data the authors concluded that premedication prior to transfusion of pre-storage leukocyte reduced SDP does not significantly lower the incidence of NHTR as compared to placebo.

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Ira A. Shulman, MD
CBBS e-Network Forum Editor & Moderator