A 33-year-old Tucson man, the subject of a medical drama spurring considerable discussion and a government investigation, was reported in critical condition with "less than 25 percent chance of recovery" last night after receiving a second human heart transplant at a University of Arizona hospital earlier yesterday.
Thomas Creighton, a Tucson auto mechanic and divorced father of two, underwent three heart operations in as many days, and surgeons' use of a highly experimental artificial heart in the second operation has prompted debate about the propriety of violating federal law to save a life.
Dr. Jack Copeland, head of the university's transplant program, told reporters that Creighton's condition had improved slightly but said, "The chances are probably less than 25 percent" that he will recover.
Dr. Allan Beigel, a university vice president and chief hospital spokesman, said doctors were trying to treat complications, including fluid accumulation in the lungs. He said the problem was caused by the time Creighton spent on a heart-lung bypass machine after his original heart transplant failed.
Stopgap use of the experimental artificial heart, which was under development in nearby Phoenix and had never been tested in a human, was done knowingly Wednesday without approval from the federal Food and Drug Administration, Beigel said.
In an interview, he defended the implant as a justified "emergency medical decision" that offered the "only viable chance of maintaining the patient's life."
Copeland told reporters, "I don't view this as an experiment. I view it as use of what's available to keep a man alive."
FDA officials said an investigation is under way because federal law was violated when the unsanctioned Phoenix heart was implanted. "From what we know, it is unlikely that we will take any major action," agency spokesman William Grigg said last night.
He said an Arizona hospital administrator told the FDA yesterday that Creighton's artificial-heart implant was "seen as a one-time livesaving measure" and promised "to apply to FDA if they do any further efforts along this line."
"If they recognize the law and plan to abide by it" in the future, Grigg added, the agency is "not in the business of putting surgeons in jail and bulldozing hospitals."
A carefully worded FDA statement noted earlier that the "agency's role is not to second-guess the practice of medicine."
It added that federal law determines that "our society and people would not be well served if every physician in the country took it upon himself to use untried devices on patients . . . . FDA's mission is to ensure patient safety."
The temporary implant was done Wednesday afternoon because Creighton's body had rejected a human heart transplanted Tuesday and doctors were concerned about possible damage if he were left too long on the heart-lung machine.
Creighton remained on the artificial heart for 11 hours until a second human heart was located late Wednesday and transplanted early yesterday.
Hospital officials said Creighton had been treated there since last May for heart problems including a cardiac attack, artery disease and left ventricle damage.
Officials said the state will pay for the two transplants but has not decided whether to pay for implanting the artificial device.
Members of the medical community expressed mixed reactions to the implant. While some doctors said they would have used the artificial device, others expressed concern that failure to follow standard experimental procedures could create problems.
Arthur Caplan, associate director of New York's Hastings Center, which specializes in medical ethics, said he is worried that it may set "a dangerous precedent that jeopardizes the integrity of human-experimentation protection."
Under the 1976 Medical Devices Act, institutions seeking to use experimental devices in humans must have FDA permission for an "investigational device exemption" before testing.
Application for an exemption must provide details about the experimental device and indicate what tests have been conducted with it in animals, who is to perform the procedure, how patients will be selected and what safeguards are included for informed patient consent.
Spokesmen for the Arizona hospital said permission for the mechanical heart implant was obtained from Creighton's family, but they provided no other details.
They also did not respond to a reporter's question as to whether the matter was taken on an emergency basis to the head of the hospital institutional review board, charged by law with local review of experimentation in humans.
Dr. William C. DeVries, who has performed three heart-implant operations, is the only physician with FDA permission to implant artificial hearts.
He placed one in the late Dr. Barney B. Clark in 1982 at the University of Utah, and his other patients -- William J. Schroeder and Murray P. Haydon -- are recuperating at Humana Heart Institute in Louisville.
Last December, the Hershey Medical Center of Pennsylvania State University sought permission to use its version of a mechanical heart as a temporary device to sustain patients awaiting human heart transplants.
The FDA responded with a questionnaire in mid-January, which was answered last month, and approval is expected soon, sources said yesterday.
A Hershey spokesman said the medical center has not faced an emergency similar to that in Tucson. He declined to comment on the Tucson situation.
Dr. John Burnside, Hershey's assistant vice president of health affairs, told reporters yesterday that doctors there have discussed using the device without permission should the problem arise but that they reached no conclusion.
"Not having encountered the situation, it would be unwise to speculate what would happen in those circumstances . . . . It's at this point hypothetical," he said. He added that, if necessary, the center would call the FDA and ask for emergency approval to implant on a one-time basis.
FDA sources said it is uncertain whether such an exemption could be granted. Therapeutic exemptions generally have applied to "custom-built" devices specially developed to treat an individual patient.
Artificial heart devices have been implanted at least twice in this country without FDA permission by Dr. Denton Cooley of the Texas Heart Institute in Houston, in 1969 and 1981.
In the latter case, the patient reportedly remained alive for 54 hours until a transplant could be performed but died a week later of complications.
The FDA reprimanded Cooley, and the FDA's Grigg said yesterday that the Texas group agreed not to attempt an illegal implant again.
Grigg also said the FDA was told yesterday by a University of Arizona hospital administrator that another artificial heart implant would not be attempted there without federal permission.
Possible FDA sanctions include a letter of reprimand to the doctors or institution, the most likely action at present, FDA sources said. Other possible penalties include restrictions on medical research dependent on federal funds or regulations, court action or criminal charges.
An FDA official had told a university attorney Wednesday afternoon that federal permission for the implant was required, but none was sought.
The FDA said it will assess the Arizona medical team's capabilities and those of the artificial Phoenix heart and assess whether Creighton's rights were "fully protected."
Hastings ethicist Caplan said yesterday that the agency should "be aggressive" in probing several major unanswered ethical questions.
"In certain emergency situations where it is not possible to anticipate a problem or the availability of a solution, it may be ethically justifiable to violate existing regulations," he said. In the Arizona case, he said it appeared that "the problem could have been anticipated."
Caplan said implanting the Phoenix heart raised several "major dangers," including failure to obtain informed consent from the patient, "bad science" in researching in an "unsystematic, uncontrolled way" an untested device, and "bad public policy" in that the patient received two heart transplants "when other people are in need and may not have received any."
University spokesman Beigel, describing his hospital as "one of the leading heart-transplant centers in the United States," said 63 such transplants have been performed there since 1979.
He cited instances in which two of the recipients died of cardiac arrest after acute failure of their transplanted hearts. He quoted surgeon Copeland as saying earlier that, if he had a transplant patient who faced certain death, "I will do everything in my power to see this does not occur again."
When Wednesday's transplant failed and a second heart could not be located immediately, Copeland contacted teams at St. Luke's Hospital in Phoenix and at the University of Utah for help with a temporary artificial heart implant.
The Phoenix team, headed by surgeon Cecil Vaughn, arrived first with two mechanical devices, including a total heart replacement developed by Kevin Cheng, a dentist specializing in reconstructive surgery. The replacement device had been tested for less than two years and reportedly implanted in two calves. Cheng told reporters that he had not sought government approval because he did not have funds to test the device.
Beigel said the device had operated continuously for as long as 12 hours in the animal tests, one hour more than it remained in Creighton Wednesday. He said yesterday that the doctors observed "no problems in its use."
In contrast, the Jarvik-7 total artificial heart used by DeVries and the "Penn State" heart have undergone extensive animal testing over many years. Although the mechanics of the three hearts differ, all are air-driven devices that replace the natural heart with a mechanical pump attached by hoses to an exterior drive system