BOSTON Establishing a treatment protocol and seeking the collaboration of cardiologists who treat children may limit the potential for serious complications associated with the off-label use of propranolol for the treatment of severe infantile hemangiomas, according to Dr. Elaine C. Siegfried.
In her own practice, Dr. Siegfried, professor of pediatrics and dermatology at St. Louis University, has developed such a protocol. However, she said she continues to use first-line prednisolone for infants with severe hemangiomas.
Prednisolone "really is the path of least resistance, and it's the treatment we know the most about," said Dr. Siegfried. "For children who don't respond to the prednisolone or who cannot tolerate it, I consider propranolol."
Interest in the treatment rose after a report of serendipitous improvement of severe hemangiomas in two infants treated with propranolol for cardiac arrhythmias and hypertension as well as good responses in nine infants who were subsequently treated with propranolol alone (N. Engl. J. Med. 2008;358:2649-51).
Although the report was "the most exciting news in pediatric dermatology in the past year," there are limited data about propranolol's potential risks as well as about best practices for initiating and monitoring the therapy for this unapproved indication, Dr. Siegfried said at the American Academy of Dermatology's Academy 2009 meeting.
Before using propranolol for severe hemangiomas, "work with the subspecialists who know the most about the drug and come up with a consensus approach to using it," she recommended.
The treatment protocol developed by Dr. Siegfried and her colleagues includes obtaining a baseline pulse, respiration rates, blood pressure measurement, and echocardiography and 48-hour monitoring (inpatient or outpatient with home nursing visits) of vital signs and blood glucose levels. An initial propranolol dose of 0.16 mg/kg of body weight is given every 8 hours and doubled incrementally to a maximum of 0.67 mg/kg (a maximum daily dose of 2 mg/kg), as long as vital signs and glucose levels remain normal, she said, noting that the drug is gradually tapered over a 2-week period.
Reports of complications have included hypothermia and bradycardiaknown side effects of propranololand subclinical hypoglycemia, according to Dr. Siegfried. She and her associates noted their concerns about complications and protocols in a letter written in response to the original publication (N. Engl. J. Med. 2008;359:2846-7).
Parents need to be carefully trained regarding administration of the drug. The formulation is highly concentrated, and children need to be fed frequently to prevent hypoglycemia, Dr. Siegfried said. "Sustained hypoglycemia has been associated with long-term neurodevelopmental outcomes." Further, the clinical features of complications such as tachypnea, jitteriness, and hypohidrosis can be blunted by propranolol.
Complication risks could be high in infants with large hemangiomas and in those with miliary hemangiomatosis, which puts them at risk for high-output cardiac compromise. Infants with PHACES syndrome have arterial abnormalities that put them at risk for hypo-perfusion and ischemic infarct. There have been no reports of propranolol complications in infants with PHACES, "but it's something you have to watch," she said.
Close monitoring is critical in high-risk subsets, Dr. Siegfried said. In infants with hemangiomatosis, for example, "you want to look very closely at the hepatic artery and portal vein [via abdominal ultrasound] because dilatation can be an early sign of cardiac compromise." In infants with PHACES syndrome, propranolol "may be absolutely contraindicated" if there is evidence of arterial hyperplasia or stenosis. Additional studies are probably warranted before the drug can be used in this population.
A multicenter, prospective trial is planned to address the efficacy, risks, and appropriate use of propranolol in patients with infantile hemangioma; Dr. Siegfried disclosed that she will be a principal investigator.