A 2 1/2 -year-old boy became deaf after receiving an overdose of cancer chemotherapy two months ago at the Johns Hopkins Children's Center, the state health department said yesterday.
The child, who was given twice the correct dose on three successive days, was one of two pediatric cancer patients given accidental overdoses in late May, the agency said. In the other case, which involved a young girl, the dose was corrected after one treatment and before any harm was done.
Carol Benner, director of the state's Office of Health Care Quality, said hearing loss is a known risk of the medication, so it was not certain whether the child's deafness was a result of receiving too much. But she said the overdose was a serious and tragic mistake that significantly increased the risk of hearing loss.
"It's clear their systems broke down," said Benner. "They miscalculated the amount of the drug, gave the wrong dose three days in a row, and we have a bad outcome."
In a brief statement yesterday, a Hopkins spokesman expressed regret and said the institution was taking steps to prevent such mistakes from happening again.
"Hopkins deeply regrets the accidental dosing error with an anti-cancer drug being used to prepare a critically ill 3-year-old child for a bone marrow transplant," said Gary Stephenson.
The spokesman said the hospital had "multiple systems in place" to ensure correct dosing and discovered the overdose given to boy during a routine check.
The discovery prompted hospital officials to review dosages for five other patients, and that review turned up the second overdose.
The overdoses occurred about a year after Ellen Roche, a healthy 23-year-old lab worker, died after inhaling a chemical in an asthma experiment. The federal government subsequently suspended more than 2,000 trials at Hopkins and required the institution to shore up its system of protecting research subjects.
In contrast, the chemotherapy overdoses stemmed from standard care. Neither patient was enrolled in a research protocol.
The 2 1/2 -year-old suffered from neuroblastoma, the third-most common cancer in children, and was receiving chemotherapy in preparation for a bone marrow transplant. The disease typically attacks the adrenal glands or nerves in the back of the abdomen, but can also occur in the brain, neck or chest.
Dr. Walter Hall, a neurosurgeon with the University of Minnesota, said hearing loss and kidney damage are the two main risks of carboplatin overdoses. The drug causes deafness by destroying nerve cells of the inner ear that transmit sound impulses to the brain.
Benner, the state official, said the child may be regaining some hearing, but it remains unclear what level of auditory function he will achieve.
Neither state nor Hopkins officials would identify the patients or the staff responsible for the error, though Benner did say the miscalculation was a physician error. She said the boy eventually did receive the bone marrow transplant and seems to be recovering.
The health department began an investigation last month after receiving an inquiry from The Sun. Hopkins did not initially report the error to the agency, but hospitals are not required by Maryland or federal law to report injuries that arise from standard, as opposed to experimental treatments.
The two children received an approved drug called carboplatin, in which platinum is the central ingredient.
After the state started looking into the incidents, Hopkins cooperated fully and submitted an analysis of what went wrong along with a plan to prevent similar errors, Benner said.
"There was no attempt to cover up," she said. "This is certainly a tragedy, but I think we have to recognize ... that things will happen and what's important is what people do about it."
Doctors used a formula for calculating dosage that factors in the patient's age, weight and the kidneys' efficiency in flushing toxins from the blood. Generally, younger and smaller patients receive lower doses, as do patients with impaired kidneys that place them at risk for accumulating dangerous levels of the drug.
Benner said she was not sure what part of the calculation went wrong.
"Quite honestly, when our nurse calculated [the dose] for the first time, she came up with the same amount that was given," Benner said. "It was an easy mistake, but also a tragic error."
Stephenson said Hopkins began tightening its medication-checking system before the state investigation began.
The new plan includes redesign of all documentation and chemotherapy orders for patients with advanced neuroblastoma, and checks by two physicians and two pharmacists of each patient's dose. The doses will also be checked by the nursing staff, he said.
The hospital's corrective plan is under review by the health department, which could require changes.
Medical errors have been a topic of intense scrutiny in the past decade, but especially so since the National Academy of Science's Institute of Medicine estimated in a 1999 report that 44,000 to 98,000 people die each year from mistakes made in hospitals. More than 7,000 of the hospital deaths resulted from medication errors, the panel said.
To avoid mistakes, the panel called upon hospitals to make pharmacists available in nursing units and on doctors' rounds, to use computers that would alert doctors to abnormal lab results, and to track not only errors but "near misses" in medication orders.
Benner estimated that over the past 13 years, her office has investigated medication errors involving half the state's hospitals. Complaints of medication errors have increased markedly in recent years, due in large part to increased national attention, she said.
The issue was widely publicized in 1993, when chemotherapy overdoses at the Harvard-affiliated Dana Farber Cancer Institute killed Boston Globe writer Betsy A. Lehman and injured another patient.
Though Benner said she did not detect a pattern of chemotherapy errors at Hopkins, the hospital did report a chemotherapy overdose in January 1998 to the federal agency that regulates medical experiments.
In that report, a 7-year-old who was being treated as an outpatient for Wilms tumor, a type of kidney cancer, received 10 times the correct dose of a drug called vincristine. The hospital realized the error when the child went home, then called him back to the emergency room for evaluation.
The child did not suffer any ill effects from the overdose, which had been given once, according to the report. Hospital officials told the agency that the dosage had been correctly calculated, but that someone had accidentally picked up the wrong vial.
The hospital pledged to take preventive measures, including better labeling of chemotherapy vials so they can be matched with patients. Two nurses were to check each chemotherapy bag each morning.