Steroid Induced Bradycardia in Acute Lymphoblastic Leukemia Patients

Background :

Systemic corticosteroids are widely used for treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma. There are anecdotal case reports of bradycardia in pediatric patients receiving corticosteroids, but a more extensive analysis of this side effect is needed.

Methods :

We performed an retrospective chart review of all 170 newly diagnosed patients with ALL/Lymphoblastic lymphoma who received corticosteroids during induction chemotherapy treated at Monroe Carell Jr Children's Hospital at Vanderbilt between 2010 and 2016 in order to determine the incidence, time of onset, and degree of bradycardia. Patients were treated with three or four drug induction chemotherapy which included dexamethasone 3-5mg/m²/dose or prednisone 30mg/m²/dose administered orally or intravenously twice a day for 14 to 28 days. Patients were excluded if they had a pre-existing cardiac abnormality or if they received corticosteroid treatment prior to diagnosis. Of the remaining 153 children, we determined the 24 hour mean heart rate prior to initiating steroid therapy, the 24 hour mean heart rate surrounding nadir, the heart rate after completion of induction chemotherapy, and assessed the degree and timing of steroid induced bradycardia. Additionally, adverse patient events and concomitant medication use was documented to identify other contributing factors to bradycardia.

Results :

A total of 153 children (80 females and 73 males, ages 16 months-27 years) were included in the analysis with 150 demonstrating a decrease in mean heart rate following steroid administration. Median heart rate decrease was 22.9 beats per minute (quartiles: 12.5 to 32.0) from prior to initiating steroids to surrounding nadir. 61% (94/153) developed bradycardia less than or equal to the 1^st percentile for their age range. Nadir occurred 7 doses (range 5 to 10) into treatment, which corresponded to 79 hours (55 to 109) after initiation of therapy. Of 94 patients who experienced bradycardia, 78% (73/94) were associated with dexamethasone rather than prednisone. Heart rate nadir was not associated with other vital sign abnormalities. After completion of induction chemotherapy, 87% (82/94) of patients had documented resolution of bradycardia with heart rates greater than the 5^th percentile for age. It was observed that the children who continued to have relatively low heart rate were often younger, ranging 20 months old - 5 years old. Examination of nadir heart rates during subsequent hospitalizations in which steroids were not being administered (excluding heart rates during procedural sedation) did not demonstrate a significant incidence of bradycardia. Concomitant opioid, beta-blocker, or other medication exposure did not contribute to the incidence of bradycardia.

Conclusions:

Corticosteroid-induced bradycardia is extremely common in children, teenagers, and young adults with ALL receiving induction chemotherapy. Bradycardia was not associated with clinical adverse events, and resolved after completion of corticosteroid treatment. Therefore, further cardiac assessment may not be warranted in the presence of bradycardia suspected to be secondary to steroid administration.