If one were to graph these tests, and others commonly used, against the total time course of medical history, one would see a flat line for more than two thousand years, followed by a slight rise beginning about 1850, and then an ever sharper rise to the present time.
That is the meaning of technological innovation. It has struck medicine like a thunderbolt: far more advances have occurred in medicine in the last hundred years than occurred in the previous two thousand. There is no mystery why this should be so. Most research scientists in history are alive today; therefore most of the discoveries in history are being made today. But the consequences of this vast outpouring of information and technology have yet to be grasped. Major questions are raised in such widely diverse subjects as medical education and euthanasia.
What makes the case of Mr. O'Connor so interesting is the way it illustrates the vast web of technological advances which make diagnostic techniques and treatment today so radically different from what they were only thirty years ago.
PRESUMABLY, Mr. O'Connor had an infection. The treatment of infectious disease is considered one of the triumphs of modern medicine, crowned by the introduction of antibiotics. But as the bacteriologist René Dubos had pointed out, "The decrease in mortality caused by infection began nearly a century ago and has continued ever since at a fairly constant rate irrespective of the use of any specific therapy." He says, further, "These triumphs of modern chemotherapy have transformed the practice of medicine and are changing the very pattern of disease in the western world, but there is no reason to believe that they spell the conquest of microbial diseases."
In this light, consider Mr. O'Connor's antibiotic "cocktail," given shortly after admission. It was later the subject of some heated discussion when, during the first two or three days, he failed to improve. The use of antibiotics is more sophisticated now than it was twenty years ago, corresponding to a better appraisal of the benefits and limitations of the drugs. Generally speaking, the antibiotic cocktail, a mixture of drugs given before one has diagnosed the nature of the infection, is frowned upon.
The arguments against it are simple enough. For Mr. O'Connor, the mixture of antibiotics might not eliminate the primary site of infection, but it would certainly kill all free bacteria in the blood, thus making identification of the organisms impossible. Without identification, one cannot treat specifically, by matching the organism with the single most effective antibiotic. Further, the inability to identify the organism deprives doctors of an important clue to the location of the infection, since different organisms are more likely to infect different parts of the body.
The arguments in favor of the cocktail are equally simple: that Mr. O'Connor's fever was, in itself, dangerous and constituted a medical emergency. As they saw it, the first duty of the EW residents was to lower that fever by every possible means, even if this hampered further diagnostic efforts. As one resident said, "He could have died while we waited for the cultures to grow out."
It all comes back to Hippocrates: does one treat with a grave remedy, or a specific one? The MGH chose a grave remedy, a strong antibiotic cocktail. The residents did so with the full knowledge that it might impair further work.
Let us now see what happened to Mr. O'Connor.
Mr. O'Connor survived the night. The following morning his blood pressure was normal and his temperature was 99°, but he remained severely agitated and unresponsive. He was sedated with morphine, continued on intravenous fluids and electrolyte supplements. The oxygenation of his blood had been poor from the start, and he was continued on oxygen by face mask.
At eight in the morning the GU consult saw him and felt that he had peritonitis of the right abdomen, or infection of the saclike membrane which surrounds the abdominal contents. Evidence included tenderness and muscle spasm on the right side, and tenderness when his liver was tapped. Bowel sounds were decreased, suggestive of intra-abdominal infection. There was tenderness to rectal examination, also suggestive of such infection.
At nine, Dr. Minna examined the patient again and agreed that the tenderness was impressive, particularly after a heavy dose of morphine. An X-ray study of the gallbladder was planned. At eleven, he was seen by the surgeons, who agreed that gall bladder infection was possible, even though bilirubin and amylase tests were normal. They advised waiting on surgery, however.
At noon, the gastrointestinal consult reviewed the barium enema, which was normal. They concluded that "we remain in the dark regarding diagnosis but would agree that bacterial sepsis secondary to a right abdominal lesion is the best bet." They suggested, however, that perforated small bowel, duodenal lesion, pancreatitis, and a number of other possibilities remained, and advised an upper GI series of X rays.
At approximately the same time, the attending physician on the wards, Dr. Kurt Block, noted that Mr. O'Connor presented "a very puzzling problem," with some findings suggestive of right-upper abdomen pathology, but no clear indication of what it might be.
Later in the day the surgeons again saw Mr. O'Connor, but disagreed with earlier interpretations. They felt his abdomen had no peritoneal signs, and no localizing signs.
At eight in the evening, the neuromedical consult again evaluated Mr. O'Connor, and concluded that his condition still gave no hint of central nervous system disease. They felt that findings pointed to an abdominal problem.
That same evening, more abnormal results of tests came back from the labs. They had been taken the day of admission, and included an elevated uric acid of 17.1 and an elevated alkaline phosphatase of 37.6. The alkaline phosphatase was repeated, and was found to be still higher, at 61.0. Two other enzymes were also slightly high: the serum glutamic oxalocetic transaminase, or SGOT, was 123, and the lactic dehydrogenase, or LDH, was 540. Blood samples were immediately drawn for repeat determinations.
These two enzymes, SGOT and LDH, are measured as indexes of cell destruction. Cells normally contain them; if the cells die, they rupture and release their enzymes to the bloodstream. A rise in enzyme levels is thought to correspond moderately well with the degree of cellular damage, particularly when followed over several days. However, these enzymes are found in many kinds of cells, and thus an enzyme rise does not pinpoint precisely the area of destruction. For example, heart, skeletal muscle, brain, liver, and kidneys all contain SGOT; damage to any of them will produce an SGOT rise. In recent years, there has been a search for enzymes specific to certain tissues. Creatinine phosphokinase, or CPK, is usually considered more specific for heart damage.
At 3:30 A.M., Michael Soper, a medical resident, got back the new set of enzyme values. Everything was further increased: SGOT was now 640, LDH 1250, and CPK very high, at 320. He wrote: "I've never seen a CPK this high and don't know where it is coming from. Doubt it is solely of cardiac origin. Electrocardiogram tonight is unchanged."
At 7 A.M., on morning rounds, Mr. O'Connor's abdomen was again without localizing signs pointing to disease on the right side. All cultures were back from the labs; all were negative. It was decided to continue only penicillin and chloramphenicol, and discontinue all other antibiotics.
Later in the morning the patient was seen by the infectious disease consult, who concluded that the agitation and unresponsiveness were almost certainly secondary to gastrointestinal disorders and metabolic problems. The elevated enzymes could be the consequence of insufficient oxygen and shock, present at admission. However, they noted that the elevated alkaline phosphatase and elevated uric acid were unexplained. They suggested the possibility, previously unconsidered, of staphylococcal food poisoning.
Since no information could be obtained directly from the patient, his wife was closely requestioned about symptoms of thyroid disease, or long-standing diarrhea or other GI problems. The paregoric which the patient had taken on the day of admission was brought into the hospital and checked; it was, indeed, paregoric.
During this period the patient was examined by Dr. Leaf, the chief of medicine, and Dr. Federman, the assistant chief, as well as by a large number of other physicians, in an informal brainstorming session. Every conceivable diagnosis, including mushroom poisoning and cholera, was considered at this time.
The patient's condition remained unchanged.
Continued problems with oxygenating the patient's bloodstream produced a consultation by the respiratory unit, which advised drying the lungs as much as possible, nasotracheal suctioning, encouraging coughing, and close monitoring by arterial blood gases. The patient improved somewhat during the day, becoming less wild. That evening, for the first time, he responded to his name.
The patient was more alert. He was seen again by the surgeons, who felt his abdomen was still soft, without any indications for surgery. His dose of Valium, to contain his agitation, was reduced.
He was seen in the morning by the neurological consult, who felt that he was "still quite obtunded," confused, and disoriented. Nonetheless, his progress since admission was striking. He could answer questions. When asked where he was, he said, "The hospital," though he could not specify which one. When asked his name, he said, "John." He could state his age. He was taken off Valium entirely. His temperature continued to fluctuate in the range of 99° to 101°. Dr. Minna wrote: "He is better in all ways."
Lab values, back from the day before, continued to climb. CPK had now gone to 2900, the highest in the history of the hospital. There was still no explanation for these enzyme changes. The patient continued to improve in responsiveness, though his mental function was far from satisfactory. In answer to questions, he said that one plus one was "one," and two plus two was "five."
He was able to carry out verbal commands such as "squeeze my hand" and "open your eyes." However, for the most part he lay in bed with his eyes closed; he initiated little spontaneous activity, and never spoke except in reply to questions.
His Foley catheter was removed. He was able to urinate in the normal manner. He was more active mentally, and remembered his last name.