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Predicting prognosis in coma
Predicting Prognosis in Coma Can One Improve Medical Decisions?
FRED PLUM, M.D. DAVID
E. LEVY, M.D.
New York, New York
From the Department of Neurology, The New York bspiil-cornell Medical college, New York, New York. Requests for reprints should be addressed to Dr. Fred Plum, Department of Neurology, The New York Hospital-Cornell University Medical Center, 525 East 66th Street, New York, New York 10021. Manuscript accepted May 16, 1976.
224
August 1978
The
Advances in emergency resuscitation and intensive care are intended to give critically ill patients improved chances for recovery. Concurrently, the same advances can create the risk that some patients will be saved to undergo an indefinite survival with hopelessly damaged brains. The paradox has stimulated extensive discussion and debate. Those concerned with maintaining and delivering the resources for health care fear the impact that new and expensive treatments will have on other parts of the community-shared “medical commons” [ 11. By contrast, many physicians see their primary obligation to the patient as requiring that they apply every possible measure of treatment until death or recovery settles the issue. The debate over how much care to initiate and how long to continue it centers on patients in whom coma develops during the course of medical illness. Both the conventional medical wisdom and the experience of intensive care centers teach that the prognosis in patients in coma is poor [2]. Yet all physicians know that some such persons can recover fully and therefore hope conscientiously to induce such a result to their patients. Direct discussion with colleagues suggests that strongly opposing medical opinions about how much care to provide the critically ill patient in coma often reflect a lack of secure knowledge about what to expect rather than any deep divisions in personal philosophy. Many, perhaps most, physicians and laymen believe that active medical efforts that doomthe bodies of physically helpless and badly demented patients to a prolonged survival are inhumane and medically unethical. They similarly agree that it is unconscionable not to treat a patient who possesses the capacity to recover. The main problem in choosing between these alternatives is that until recently little precise information existed about clinical or laboratory indicants that would predict which patients in coma could recover and which could not. Some patients with the potential for recovery received less treatment than they needed. Others with overwhelming and irreversible brain damage received such good supportive care for their hearts and lungs that they lived a prolonged noncognitive existence, cruelly burdening the emotional and financial resources of their families and communities for months or years. Data now are accumulating which may resolve some of the uncertainties about outcome of patients in coma and provide better base lines upon which to judge the potential effect of new treatments. Neurosurgeons and neurologists in ‘several medical centers located in Europe and the United States have been collaborating in collecting
American Journal of Medlclne
Volume 88
PREDICTING PROGNOSIS IN COMA--PLUM,
prospective information on patients in coma. The aim is to discover neurologic signs that could be used early during an illness to predict outcome from coma under circumstances in which optimal treatment was being delivered. The surgical studies were initiated in 1968 by Jennett et al. [3] in Glasgow and dealt with patients unconscious from head injury. The neurologic studies began in 1970, at the New York Hospital on patients unconscious following cardiac arrest and were shortly thereafter extended to include patients with other nontraumatic illnesses. Subsequently, both studies expanded to involve other institutions. Since 1973, the medical and surgical groups have met together frequently to improve their respective methods for clinical evaluation, to arrange computer storage of the data and to analyze the results. Both the trauma and nontrauma studies have depended heavily on obtaining a relatively small number of pretested and familiar clinical variables, then recording these serially at frequent intervals early during the course of illness. This approach was chosen because more complex approaches often fail in the hands of clinicians, and no other method could meet the universal needs of physicians located everywhere in the world, equipped as they are with different educational backgrounds and economic resources. The surgeons found useful an abbreviated clinical scale (Glasgow scale) that gave attention to the presence or absence of eye opening and verbal responses, and the nature of the patients’ motor responses. They already have examined and analyzed over 1,000 patients in four different medical centers in the Netherlands, Scotland and the United States; their emerging results are given elsewhere [3]. Of interest, however, is that correlation between early signs and outcome of coma from head injury was similar among the three participating countries despite the employment of often dissimilar approaches to treatment. To appraise the course of patients with nontraumatic coma, the neurologists adopted a more extensive, but still practical and rapidly applied clinical index of forebrain and brainstem functions [4]; this directed its main attention to whether or not the patient made any verbal responses and to changes in a relatively small number of neuroophthalmologic and skeletal muscle motor responses. Bates et al. [5] give detailed descriptions of these clinical guides and their implications. Both groups of investigators rigidly defined outcomes from coma into five classes including, good recovery, moderate disability, severe disability, vegetative state and no recovery (or death). To exploit clinical descriptions requires precise definitions. For purposes of this study, coma was defined as sleeplike, unarousable unresponsiveness without the subject giving evidence of awareness of self
LEVY
or environment. Such patients did not open their eyes either spontaneously or in response to any verbal stimulus. They expressed no comprehensible words, and they neither obeyed commands nor moved their extremities appropriately to localize or resist noxious stimuli. The study on nontraumatic coma included all patients in the participating centers who were in coma for more than 6 hours. The main causes of coma were cerebral hypoxia-ischemia due to cardiorespiratory failure in about two fifths, focal cerebral vascular disease in a third, and subarachnoid hemorrhage and hepatic disease in about 10 per cent, each. Miscellaneous other disorders contributed the remainder. Patients less than 10 years of age, and those with poisoning from sedative drugs or alcohol were excluded. (No matter how deep their coma, almost all properly treated patients with a drug overdose recover completely with standard medical care; these good results were as true in days before intensive care centers as they are now [4] .) In 1978, the nontraumatic coma study will complete its goal of collecting and analyzing data on early signs and outcome in 500 patients from Newcastle-UponTyne (U.K.), New York and San Francisco. The participants have already reported their results in the first 3 10 patients, followed for one to 12 months [ 51. The findings indicate that although more numbers and time will be needed to determine the precise power of any given finding, the presence of certain neurologic signs can predict specific outcomes nearly 95 per cent of the time. About half of the first 310 patients were from the United States and half from the United Kingdom. The populations were similar in age, sex and the frequency of early signs of severe illness. Despite differences that emerged in medical practice between the two countries, ultimate medical outcomes were remarkably similar. Patients in the United States received a substantially larger number (385) of diagnostic studies and intensive therapeutic procedures than did those in the United Kingdom (90). The medical effect of this difference in management is difficult to judge since the outcome from coma at one month was similar between the two countries. In the United Kingdom, however, 7 1 per cent of those who died within one month did so within the first three days after their admission to the hospital compared to only 46 per cent who died during this time in the United States (p < 0.001). Whether these differences in short-term survival time reflect temporary life extension by early treatment requires further attention. The development of coma in medical illness proved to be a grave prognostic sign. Seventy per cent of such patients either failed to show improvement or remained in a vegetative state by the end of one month, and only
August 1979
The American Journal of Medlclne
Volume 65
225
PREDICTING PROGNOSIS IN COMA-PLUM,
LEVY
16 per cent made a moderate to good recovery during that time. Certain signs or combinations of signs, however, predicted a significantly better or worse outcome. Patients in whom any of the following signs developed within the first 24 hours had at least twice the chance for recovery (>32 per cent) as did the entire group: made any verbal response, followed with their eyes, regained normal oculovestibular responses, gave localized motor responses to a command or stimulus, or regained ,normal skeletal muscle tone. Conversely, patients had less than an 8 per cent chance of making even a moderately good recovery if after 6 hours of coma any of the following were absent: pupillary reactions, oculovestibular responses, corneal responses, motor responses to stimulation, or deep tendon reflexes. These data represent only a beginning and leave many questions still unanswered. Some patients fell between these two extremes and neither favorable nor unfavorable signs could be recognized early in the course of their illness. Others had both favorable and unfavorable signs. The reliability of these signs and the meaning of combinations of several different signs in individual patients will require analysis of additional data.
Also, predictions based on data already collected must be validated against the actual outcome of prospectively studied future patients. Moreover, the influence on outcome of the specific cause of coma has not yet been fully analyzed. The early results, however, do begin to provide a base line against which the possible effects of future therapy can be measured. Furthermore, they indicate how to select groups of patients with similarly severe degrees of neurologic illness when planning future clinical trials. The results suggest that by taking advantage of the computer’s capacity for providing an easily utilized, accurate and large reservoir for storing data, and by subjecting the findings to proper mathematical analysis, one will be able to identify, either individually or by their illnesses, patients who are most likely to benefit from the intensive and expensive ministrations of critical care facilities. The findings should help physicians to make sensitive and difficult decisions in the care of the critically ill. Hopefully, the results may begin to answer questions of whether some critically ill patients are being prematurely denied the care they need, or others are being subjected to the indignity of valiantly resisting death, only to survive with hopelessly damaged brains.
REFERENCES 1.
Hiatt HH: Protecting the medical ccmmons: who is responsible?
N EnglJ Ned 293: 235, 1975. 2. 3.
226
Cullen DJ: Results and costs of intensive care. Anesthesiology 47: 203, 1977. Jennett B, Teasdale J, Galbraith S, et al.: Severe head injury in three countries. J Neural Neurosurg Psychiat 40: 291,
August 1978
The American Journal of Medlclne
1977. 4. PlumF. Posner JB:The Diagnosisof StuporandComa,2nd ed, 5.
Volume 65
Philadelphia, F. A. Davis, 1972. Bates D, Caronna JJ, Cartlidge NEF, et al.: A prospective study of non-traumatic coma: methods and results in 310 patients. Ann Neurol 2: 211. 1977.
FRED PLUM, M.D. DAVID
E. LEVY, M.D.
New York, New York
From the Department of Neurology, The New York bspiil-cornell Medical college, New York, New York. Requests for reprints should be addressed to Dr. Fred Plum, Department of Neurology, The New York Hospital-Cornell University Medical Center, 525 East 66th Street, New York, New York 10021. Manuscript accepted May 16, 1976.
224
August 1978
The
Advances in emergency resuscitation and intensive care are intended to give critically ill patients improved chances for recovery. Concurrently, the same advances can create the risk that some patients will be saved to undergo an indefinite survival with hopelessly damaged brains. The paradox has stimulated extensive discussion and debate. Those concerned with maintaining and delivering the resources for health care fear the impact that new and expensive treatments will have on other parts of the community-shared “medical commons” [ 11. By contrast, many physicians see their primary obligation to the patient as requiring that they apply every possible measure of treatment until death or recovery settles the issue. The debate over how much care to initiate and how long to continue it centers on patients in whom coma develops during the course of medical illness. Both the conventional medical wisdom and the experience of intensive care centers teach that the prognosis in patients in coma is poor [2]. Yet all physicians know that some such persons can recover fully and therefore hope conscientiously to induce such a result to their patients. Direct discussion with colleagues suggests that strongly opposing medical opinions about how much care to provide the critically ill patient in coma often reflect a lack of secure knowledge about what to expect rather than any deep divisions in personal philosophy. Many, perhaps most, physicians and laymen believe that active medical efforts that doomthe bodies of physically helpless and badly demented patients to a prolonged survival are inhumane and medically unethical. They similarly agree that it is unconscionable not to treat a patient who possesses the capacity to recover. The main problem in choosing between these alternatives is that until recently little precise information existed about clinical or laboratory indicants that would predict which patients in coma could recover and which could not. Some patients with the potential for recovery received less treatment than they needed. Others with overwhelming and irreversible brain damage received such good supportive care for their hearts and lungs that they lived a prolonged noncognitive existence, cruelly burdening the emotional and financial resources of their families and communities for months or years. Data now are accumulating which may resolve some of the uncertainties about outcome of patients in coma and provide better base lines upon which to judge the potential effect of new treatments. Neurosurgeons and neurologists in ‘several medical centers located in Europe and the United States have been collaborating in collecting
American Journal of Medlclne
Volume 88
PREDICTING PROGNOSIS IN COMA--PLUM,
prospective information on patients in coma. The aim is to discover neurologic signs that could be used early during an illness to predict outcome from coma under circumstances in which optimal treatment was being delivered. The surgical studies were initiated in 1968 by Jennett et al. [3] in Glasgow and dealt with patients unconscious from head injury. The neurologic studies began in 1970, at the New York Hospital on patients unconscious following cardiac arrest and were shortly thereafter extended to include patients with other nontraumatic illnesses. Subsequently, both studies expanded to involve other institutions. Since 1973, the medical and surgical groups have met together frequently to improve their respective methods for clinical evaluation, to arrange computer storage of the data and to analyze the results. Both the trauma and nontrauma studies have depended heavily on obtaining a relatively small number of pretested and familiar clinical variables, then recording these serially at frequent intervals early during the course of illness. This approach was chosen because more complex approaches often fail in the hands of clinicians, and no other method could meet the universal needs of physicians located everywhere in the world, equipped as they are with different educational backgrounds and economic resources. The surgeons found useful an abbreviated clinical scale (Glasgow scale) that gave attention to the presence or absence of eye opening and verbal responses, and the nature of the patients’ motor responses. They already have examined and analyzed over 1,000 patients in four different medical centers in the Netherlands, Scotland and the United States; their emerging results are given elsewhere [3]. Of interest, however, is that correlation between early signs and outcome of coma from head injury was similar among the three participating countries despite the employment of often dissimilar approaches to treatment. To appraise the course of patients with nontraumatic coma, the neurologists adopted a more extensive, but still practical and rapidly applied clinical index of forebrain and brainstem functions [4]; this directed its main attention to whether or not the patient made any verbal responses and to changes in a relatively small number of neuroophthalmologic and skeletal muscle motor responses. Bates et al. [5] give detailed descriptions of these clinical guides and their implications. Both groups of investigators rigidly defined outcomes from coma into five classes including, good recovery, moderate disability, severe disability, vegetative state and no recovery (or death). To exploit clinical descriptions requires precise definitions. For purposes of this study, coma was defined as sleeplike, unarousable unresponsiveness without the subject giving evidence of awareness of self
LEVY
or environment. Such patients did not open their eyes either spontaneously or in response to any verbal stimulus. They expressed no comprehensible words, and they neither obeyed commands nor moved their extremities appropriately to localize or resist noxious stimuli. The study on nontraumatic coma included all patients in the participating centers who were in coma for more than 6 hours. The main causes of coma were cerebral hypoxia-ischemia due to cardiorespiratory failure in about two fifths, focal cerebral vascular disease in a third, and subarachnoid hemorrhage and hepatic disease in about 10 per cent, each. Miscellaneous other disorders contributed the remainder. Patients less than 10 years of age, and those with poisoning from sedative drugs or alcohol were excluded. (No matter how deep their coma, almost all properly treated patients with a drug overdose recover completely with standard medical care; these good results were as true in days before intensive care centers as they are now [4] .) In 1978, the nontraumatic coma study will complete its goal of collecting and analyzing data on early signs and outcome in 500 patients from Newcastle-UponTyne (U.K.), New York and San Francisco. The participants have already reported their results in the first 3 10 patients, followed for one to 12 months [ 51. The findings indicate that although more numbers and time will be needed to determine the precise power of any given finding, the presence of certain neurologic signs can predict specific outcomes nearly 95 per cent of the time. About half of the first 310 patients were from the United States and half from the United Kingdom. The populations were similar in age, sex and the frequency of early signs of severe illness. Despite differences that emerged in medical practice between the two countries, ultimate medical outcomes were remarkably similar. Patients in the United States received a substantially larger number (385) of diagnostic studies and intensive therapeutic procedures than did those in the United Kingdom (90). The medical effect of this difference in management is difficult to judge since the outcome from coma at one month was similar between the two countries. In the United Kingdom, however, 7 1 per cent of those who died within one month did so within the first three days after their admission to the hospital compared to only 46 per cent who died during this time in the United States (p < 0.001). Whether these differences in short-term survival time reflect temporary life extension by early treatment requires further attention. The development of coma in medical illness proved to be a grave prognostic sign. Seventy per cent of such patients either failed to show improvement or remained in a vegetative state by the end of one month, and only
August 1979
The American Journal of Medlclne
Volume 65
225
PREDICTING PROGNOSIS IN COMA-PLUM,
LEVY
16 per cent made a moderate to good recovery during that time. Certain signs or combinations of signs, however, predicted a significantly better or worse outcome. Patients in whom any of the following signs developed within the first 24 hours had at least twice the chance for recovery (>32 per cent) as did the entire group: made any verbal response, followed with their eyes, regained normal oculovestibular responses, gave localized motor responses to a command or stimulus, or regained ,normal skeletal muscle tone. Conversely, patients had less than an 8 per cent chance of making even a moderately good recovery if after 6 hours of coma any of the following were absent: pupillary reactions, oculovestibular responses, corneal responses, motor responses to stimulation, or deep tendon reflexes. These data represent only a beginning and leave many questions still unanswered. Some patients fell between these two extremes and neither favorable nor unfavorable signs could be recognized early in the course of their illness. Others had both favorable and unfavorable signs. The reliability of these signs and the meaning of combinations of several different signs in individual patients will require analysis of additional data.
Also, predictions based on data already collected must be validated against the actual outcome of prospectively studied future patients. Moreover, the influence on outcome of the specific cause of coma has not yet been fully analyzed. The early results, however, do begin to provide a base line against which the possible effects of future therapy can be measured. Furthermore, they indicate how to select groups of patients with similarly severe degrees of neurologic illness when planning future clinical trials. The results suggest that by taking advantage of the computer’s capacity for providing an easily utilized, accurate and large reservoir for storing data, and by subjecting the findings to proper mathematical analysis, one will be able to identify, either individually or by their illnesses, patients who are most likely to benefit from the intensive and expensive ministrations of critical care facilities. The findings should help physicians to make sensitive and difficult decisions in the care of the critically ill. Hopefully, the results may begin to answer questions of whether some critically ill patients are being prematurely denied the care they need, or others are being subjected to the indignity of valiantly resisting death, only to survive with hopelessly damaged brains.
REFERENCES 1.
Hiatt HH: Protecting the medical ccmmons: who is responsible?
N EnglJ Ned 293: 235, 1975. 2. 3.
226
Cullen DJ: Results and costs of intensive care. Anesthesiology 47: 203, 1977. Jennett B, Teasdale J, Galbraith S, et al.: Severe head injury in three countries. J Neural Neurosurg Psychiat 40: 291,
August 1978
The American Journal of Medlclne
1977. 4. PlumF. Posner JB:The Diagnosisof StuporandComa,2nd ed, 5.
Volume 65
Philadelphia, F. A. Davis, 1972. Bates D, Caronna JJ, Cartlidge NEF, et al.: A prospective study of non-traumatic coma: methods and results in 310 patients. Ann Neurol 2: 211. 1977.