Carbon monoxide poisoning: neurologic and psychiatric sequelae RONALD A. REMICK,* MD; JAMES E. MILES,t MD, FRCP[C]
Poisoning with carbon monoxide is a frequent means of suicide1 and has an estimated mortality of 30% . However, there have been few case reports of neuropsychiatric sequelae in survivors. We report the case of a young woman with parietal lobe signs 6 months after she had attempted suicide with a combination of barbiturate overdose and carbon monoxide poisoning. The purpose of this report is to call attention to these signs, which may be mistaken for signs of a psychiatric disorder, and to discuss the importance of the barbiturate overdose in this case.
Case report A 24-year-old woman with a 2-year history of bipolar manic-depressive psychosis was referred for psychiatric assessment 6 months after attempting suicide by barbiturate overdose and carbon monoxide poisoning. After exposure to the gas in a closed garage for an estimated 90 minutes she was "barely conscious" and agitated. Blood pressure was 95/45 mm Hg and pulse rate was 140 beats/mm, with a regular rhythm. There were no other physical or neurologic abnormalities. Blood gas values at the time of admission were as follows: pH, 7.35; Pco5, 29.2 mm Hg; Po2, 105 mm Hg; and CO2 content, 16.3 mmol/L. Serum barbiturate value was 3.6 mg/dL (normal, less than 1.0 mg/ dL), and the carboxyhemoglobin value, 40%. Electroencephalogram and echoencephalogram were normal.
After 3 months in hospital the patient was transferred for further treatment to a local rehabilitation hospital, where it was noted that she was disoriented to time, looked perplexed and was inconsistent in her performance. The question was raised whether her impairment was organic or psychologic, and she was transferred to a psychiatric hospital for further evaluation. At the psychiatric hospital her perplexed facial expression was again noted. Her psychomotor activity was clumsy: she had difficulty extending the proper hand for a handshake. Inappropriate mild euphoria was apparent. She did not comprehend commands, nor could she perform simple tasks such as raising her right hand or walking to the door and opening it. She was disoriented to time, place and situation. Immediate recall and recent and
remote memory were substantially impaired. Her general fund of information showed a striking deficit. Judgement, concentration and abstract thinking were severely impaired. An electroencephalogram showed diffuse mixed dysrhythmia and an irregular spike-and-wave discharge pattern with posterior predominance. Dysgraphia, severe disability in naming objects, dyspraxia of both extremities, dyscalculia, finger agnosia and moderate leftright disorientation were consistent with postanoxic encephalopathy involving primarily the parietal lobe. The impairment in her sensorium was consistent throughout her hospital stay. She was discharged to a local boarding home with a daily occupational and recreational therapy program and neurologic follow-up. The diagnosis was organic brain syndrome secondary to barbiturate and carbon monoxide poisoning.
Discussion Subtle neuropsychiatric symptoms may be present after carbon monoxide poisoning. Physicians should be aware that signs of cortical dysfunction, particularly of the frontal and parietal lobes, may mimic psychiatric symptoms. Diagnosis may be difficult because intentional poisoning with carbon monoxide is frequent among patients who have had psychiatric symptoms before the poisoning. While there was some evidence in our patient of more widespread cerebral injury (for example, early reports of "shuffling gait", inappropriate euphoria and memory impairment), it was her indifference to her disabilities that made the staff question the possibility of a functional disorder. Such indifference may be part of the neurologic syndrome of unilateral neglect, a disorder of body image that may vary from unconcern about one's illness to the striking syndrome of anosognosia. Weinstein and Kahn4 presented data indicating that this phenomenon is associated with cerebral lesions at various levels. Critchley,5 however, maintained that this symptom is found most frequently with damage to the nondominant parietal lobe. The indifference, apathy and unconcern of these patients can give rise to the false im-
pression of la belle indiffrrence of the hysterical patient. Our patient's past records noted manipulative and hysterical behaviour and deliberately poor performance. Critchley6 noted when describing parietal dysfunction the "van634 CMA JOURNAL/SEPTEMBER 17, 1977/VOL. 117
9Resident, department of psychiatry, University of British Columbia, Vancouver tAssociate professor and head, department of psychiatry, Shaughnessy Hospital, Vancouver Reprint requests to: Dr. Ronald A. Remick, Department of psychiatry, University of British Columbia, Vancouver, BC V6T 1W5
ability in level of performance, especially in the hands of different examiners", and he stated that "the lack of distress may be taken for the fatuous euphoria of the hysteric". The common assumption in the literature2'3'7 seems to have been that with carbon monoxide poisoning there is either death or complete recovery. Hence these patients may be treated only for their psychiatric disability after emergency room stabilization. However, recent articles in the psychiatric literature have noted the subtle neuropsychiatric after effects of carbon monoxide poisoning,8'9 and Smith and Brandon'0 have indicated that the frequency of neuropsychiatric sequelae of carbon monoxide poisoning might be found to be five times higher than previous estimates if cases were assessed carefully. That lesions of the cerebral white matter, particularly in the parietal lobe, may be more frequent after carbon monoxide poisoning than had previously been suspected is suggested by the results of animal experiments. Ginsberg and Myers1' exposed juvenile Rhesus monkeys to different degrees of carbon monoxide intoxication. The most salient brain lesion was a bilaterally symmetric leukoencephalopathy most extensive in the frontal and posterior parietal regions. They noted that the grey matter was unaffected unless there was extensive brain damage. One would expect a combination of barbiturate overdose and carbon monoxide poisoning to be more lethal than either one by itself. However, the observations of Sluijter'2 reveal the opposite. He studied two groups of patients in deep coma with similar initial carboxyhemoglobin values. In the group with both types of poisoning there were fewer deaths than in the group with only carbon monoxide poisoning. Sluijter speculated that the combined poisoning is more lethal but that in the group with combined poisoning there was probably shorter exposure to carbon monoxide. We wonder whether the barbiturates might in some way protect the patient. Alveolar ventilation is a major factor in the formation of carboxyhemoglobin. It is estimated that absorption of carbon monoxide varies in proportion to alveolar ventilation.'3'5 Perhaps the decrease in respiratory rate and volume caused by the barbiturates was impor-
tant in diminishing the toxic effect of carbon monoxide in our patient. The reduction in central oxidative metabolism by barbiturates might also be important. Such protection is an interesting possibility that merits further investigation. References 1. WHITLOCK FA: Suicide in Brisbane, 1956 to 1973; the drug-death epidemic. Med I Aust 1: 737, 1975 2. SHILLITO
FH,
DRINKER
CK,
SHAUOHNESSY
TJ: The problem of nervous and mental
sequelac in carbon monoxide poisoning. JAMA 106: 669, 1936 3. SMITH JS, BRANDON 5: Acute carbon monoxide poisoning - 3 years of experience in a defined population. Postgrad Med J 46: 65, 1970 4. WEir.smi. EA, KAHN RL: Denial of Illness, Springfield IL CC Thomas, 1955, pp 96-100 5. CRITCHLEY' M:' .The Parietal Lobes, London, Edward Arnold, 1953, p 254 6. Ibid, p 388 7. RICHARDSON JC, CHAMBERS RA, HEYWOOD PM: Encephalopathies of anoxia and hypoglycemia. Arch Neurol 1: 178, 1959 8. GINSBERG R, ROMANO J: Carbon monoxide poisoning: need for appropriate treatment. Am I Psychiatry 133: 317, 1976 9. JEFFERSON JW: Subtle neuropsychiatric sequelae of carbon monoxide intoxication: two case reports. Ibid, p 961
10. SMITH JS, BRANDON S: Morbidity from acute carbon monoxide poisoning at three-year follow-up. Br Med J 1: 318, 1973 11. GINSBERG MD, MYERS RE: Experimental carbon monoxide encephalopathy in the primate. Arch Neurol 30: 202, 1974 12. SLUJJTER ME: The treatment of carbon monoxide poisoning by administration of oxygen at high atmospheric pressure, in Progress in Brain Research, vol 24, Boua H, LEDINGHAM IM (eds), Amsterdam, Elsevier, 1967, pp 123-82 13. FORBES WH,
SARGENT F,
ROUGHTON FJW:
The rate of carbon monoxide uptake by normal men. Am J Physiol 143: 594, 1945 14. FORBEs WH: Carbon monoxide uptake via the lungs. Ann NY Acad Sci 174: 72, 1970 15. BRODY JS, COBURN RF: Effects of elevated carboxyhemoglobin on gas exchange in the lung. Ibid, p 255
Two-year follow-up study of patients with known serum concentrations of carcinoembryonic antigen P.R. BAND,* MD, FRCP[C]; I.T. BECK,f MD, PH D, FACP, FRCP[C]; P.J. DINNER,* M Sc; AB. MILLER,* MB, FRCP[C]
Between 1970 and 1972 five university centres in Canada and the United States collaborated in a study of a test for carcinoembryonic antigen (CEA) in the serum, with the Montreal General Hospital's laboratory acting as the reference laboratory, examining duplicate halves of specimens examined in local laboratories. The National Cancer Institute of Canada acted as the coordinating centre. The first report gave results for 503 patients admitted to the study between June 1971 and April 1972, 146 of whom had cancer of the colon or recturn.1 Discrimination between colorectal cancer and "other" conditions was good at a CEA value of 2.5 ng/mL or more, such a result being obtained in 66% of the patients with colorectal cancer in the local laboratories and 62% in the reference laboratory, compared with 39% and 33%, respectively, of patients with "other" conditions. Patients with Dukes' C lesions of the colon or rectum From *University of Alberta, Edmonton; tQueen's University, Kingston; and .epidemiology unit, National Cancer Institute of Canada, University of Toronto Reprint requests to: Dr. AB. Miller, Director, Epidemiology unit, National Cancer Institute of Canada, University of Toronto, 121 St. Joseph St., Toronto, Ont. M5S 2R9
(those with metastases in regional lymph nodes) were more likely to have elevated CEA values than patients with more localized lesions. CEA was also more commonly found in patients with other cancers or with liver disease than in patients with other (benign) conditions. It was concluded that the test for CEA can be reproduced in other laboratories and that it or another simple technique could become an important diagnostic aid for colorectal cancer. It was also suggested that the CEA value might be an important prognostic indicator and that, for the 33% of patients with elevated CEA values but no colorectal cancer, follow-up might show an abnormally high incidence of colorectal cancer in subsequent years. Follow-up of the original 503 cases (and a smaller number reported after April 1972), at 6, 12, 18 and 24 months after admission to the study, was attempted to examine these hypotheses. A lack of resources severely restricted the extent of documentation of followup in the three American centres, but a special effort was made to determine the status of patients in the two Canadian centres at 24 months. Contact with
the patient at any time up to 3 months before or after this date was accepted as the required 24-month follow-up contact. Results Of the 103 patients admitted to the study from Kingston and the 96 from Edmonton, follow-up forms were returned for 102 and 91, respectively; of these, 14 were lost to follow-up at 2 years. CEA values were reported on the basis of the initial results from the Montreal laboratory to avoid differences between laboratories. As CEA values were not available for 14 of the patients followed up, results are presented for only 165 patients. The prognostic value of the initial CEA value in the 36 patients with colorectal cancer is shown in Table I. If values of 2.5 ng/mL or more are taken as positive the difference in terms of disease-free status and survival at 2 years is significant at the 5% level (X2 = 6.47 and 5.73, respectively, with Yates' continuity correction). If values of 5.0 ng/mL or more are taken as positive the difference in disease-free status does not attain statistical signif-
Table I-Status at 2 years of patients with colorectal cancer according to initial serum concentration of carcinoembryonic antigen (CEA) and Dukes' classification2 CEA concentration (ng/mL) and Dukes' classification*
Poisoning with carbon monoxide is a frequent means of suicide1 and has an estimated mortality of 30% . However, there have been few case reports of neuropsychiatric sequelae in survivors. We report the case of a young woman with parietal lobe signs 6 months after she had attempted suicide with a combination of barbiturate overdose and carbon monoxide poisoning. The purpose of this report is to call attention to these signs, which may be mistaken for signs of a psychiatric disorder, and to discuss the importance of the barbiturate overdose in this case.
Case report A 24-year-old woman with a 2-year history of bipolar manic-depressive psychosis was referred for psychiatric assessment 6 months after attempting suicide by barbiturate overdose and carbon monoxide poisoning. After exposure to the gas in a closed garage for an estimated 90 minutes she was "barely conscious" and agitated. Blood pressure was 95/45 mm Hg and pulse rate was 140 beats/mm, with a regular rhythm. There were no other physical or neurologic abnormalities. Blood gas values at the time of admission were as follows: pH, 7.35; Pco5, 29.2 mm Hg; Po2, 105 mm Hg; and CO2 content, 16.3 mmol/L. Serum barbiturate value was 3.6 mg/dL (normal, less than 1.0 mg/ dL), and the carboxyhemoglobin value, 40%. Electroencephalogram and echoencephalogram were normal.
After 3 months in hospital the patient was transferred for further treatment to a local rehabilitation hospital, where it was noted that she was disoriented to time, looked perplexed and was inconsistent in her performance. The question was raised whether her impairment was organic or psychologic, and she was transferred to a psychiatric hospital for further evaluation. At the psychiatric hospital her perplexed facial expression was again noted. Her psychomotor activity was clumsy: she had difficulty extending the proper hand for a handshake. Inappropriate mild euphoria was apparent. She did not comprehend commands, nor could she perform simple tasks such as raising her right hand or walking to the door and opening it. She was disoriented to time, place and situation. Immediate recall and recent and
remote memory were substantially impaired. Her general fund of information showed a striking deficit. Judgement, concentration and abstract thinking were severely impaired. An electroencephalogram showed diffuse mixed dysrhythmia and an irregular spike-and-wave discharge pattern with posterior predominance. Dysgraphia, severe disability in naming objects, dyspraxia of both extremities, dyscalculia, finger agnosia and moderate leftright disorientation were consistent with postanoxic encephalopathy involving primarily the parietal lobe. The impairment in her sensorium was consistent throughout her hospital stay. She was discharged to a local boarding home with a daily occupational and recreational therapy program and neurologic follow-up. The diagnosis was organic brain syndrome secondary to barbiturate and carbon monoxide poisoning.
Discussion Subtle neuropsychiatric symptoms may be present after carbon monoxide poisoning. Physicians should be aware that signs of cortical dysfunction, particularly of the frontal and parietal lobes, may mimic psychiatric symptoms. Diagnosis may be difficult because intentional poisoning with carbon monoxide is frequent among patients who have had psychiatric symptoms before the poisoning. While there was some evidence in our patient of more widespread cerebral injury (for example, early reports of "shuffling gait", inappropriate euphoria and memory impairment), it was her indifference to her disabilities that made the staff question the possibility of a functional disorder. Such indifference may be part of the neurologic syndrome of unilateral neglect, a disorder of body image that may vary from unconcern about one's illness to the striking syndrome of anosognosia. Weinstein and Kahn4 presented data indicating that this phenomenon is associated with cerebral lesions at various levels. Critchley,5 however, maintained that this symptom is found most frequently with damage to the nondominant parietal lobe. The indifference, apathy and unconcern of these patients can give rise to the false im-
pression of la belle indiffrrence of the hysterical patient. Our patient's past records noted manipulative and hysterical behaviour and deliberately poor performance. Critchley6 noted when describing parietal dysfunction the "van634 CMA JOURNAL/SEPTEMBER 17, 1977/VOL. 117
9Resident, department of psychiatry, University of British Columbia, Vancouver tAssociate professor and head, department of psychiatry, Shaughnessy Hospital, Vancouver Reprint requests to: Dr. Ronald A. Remick, Department of psychiatry, University of British Columbia, Vancouver, BC V6T 1W5
ability in level of performance, especially in the hands of different examiners", and he stated that "the lack of distress may be taken for the fatuous euphoria of the hysteric". The common assumption in the literature2'3'7 seems to have been that with carbon monoxide poisoning there is either death or complete recovery. Hence these patients may be treated only for their psychiatric disability after emergency room stabilization. However, recent articles in the psychiatric literature have noted the subtle neuropsychiatric after effects of carbon monoxide poisoning,8'9 and Smith and Brandon'0 have indicated that the frequency of neuropsychiatric sequelae of carbon monoxide poisoning might be found to be five times higher than previous estimates if cases were assessed carefully. That lesions of the cerebral white matter, particularly in the parietal lobe, may be more frequent after carbon monoxide poisoning than had previously been suspected is suggested by the results of animal experiments. Ginsberg and Myers1' exposed juvenile Rhesus monkeys to different degrees of carbon monoxide intoxication. The most salient brain lesion was a bilaterally symmetric leukoencephalopathy most extensive in the frontal and posterior parietal regions. They noted that the grey matter was unaffected unless there was extensive brain damage. One would expect a combination of barbiturate overdose and carbon monoxide poisoning to be more lethal than either one by itself. However, the observations of Sluijter'2 reveal the opposite. He studied two groups of patients in deep coma with similar initial carboxyhemoglobin values. In the group with both types of poisoning there were fewer deaths than in the group with only carbon monoxide poisoning. Sluijter speculated that the combined poisoning is more lethal but that in the group with combined poisoning there was probably shorter exposure to carbon monoxide. We wonder whether the barbiturates might in some way protect the patient. Alveolar ventilation is a major factor in the formation of carboxyhemoglobin. It is estimated that absorption of carbon monoxide varies in proportion to alveolar ventilation.'3'5 Perhaps the decrease in respiratory rate and volume caused by the barbiturates was impor-
tant in diminishing the toxic effect of carbon monoxide in our patient. The reduction in central oxidative metabolism by barbiturates might also be important. Such protection is an interesting possibility that merits further investigation. References 1. WHITLOCK FA: Suicide in Brisbane, 1956 to 1973; the drug-death epidemic. Med I Aust 1: 737, 1975 2. SHILLITO
FH,
DRINKER
CK,
SHAUOHNESSY
TJ: The problem of nervous and mental
sequelac in carbon monoxide poisoning. JAMA 106: 669, 1936 3. SMITH JS, BRANDON 5: Acute carbon monoxide poisoning - 3 years of experience in a defined population. Postgrad Med J 46: 65, 1970 4. WEir.smi. EA, KAHN RL: Denial of Illness, Springfield IL CC Thomas, 1955, pp 96-100 5. CRITCHLEY' M:' .The Parietal Lobes, London, Edward Arnold, 1953, p 254 6. Ibid, p 388 7. RICHARDSON JC, CHAMBERS RA, HEYWOOD PM: Encephalopathies of anoxia and hypoglycemia. Arch Neurol 1: 178, 1959 8. GINSBERG R, ROMANO J: Carbon monoxide poisoning: need for appropriate treatment. Am I Psychiatry 133: 317, 1976 9. JEFFERSON JW: Subtle neuropsychiatric sequelae of carbon monoxide intoxication: two case reports. Ibid, p 961
10. SMITH JS, BRANDON S: Morbidity from acute carbon monoxide poisoning at three-year follow-up. Br Med J 1: 318, 1973 11. GINSBERG MD, MYERS RE: Experimental carbon monoxide encephalopathy in the primate. Arch Neurol 30: 202, 1974 12. SLUJJTER ME: The treatment of carbon monoxide poisoning by administration of oxygen at high atmospheric pressure, in Progress in Brain Research, vol 24, Boua H, LEDINGHAM IM (eds), Amsterdam, Elsevier, 1967, pp 123-82 13. FORBES WH,
SARGENT F,
ROUGHTON FJW:
The rate of carbon monoxide uptake by normal men. Am J Physiol 143: 594, 1945 14. FORBEs WH: Carbon monoxide uptake via the lungs. Ann NY Acad Sci 174: 72, 1970 15. BRODY JS, COBURN RF: Effects of elevated carboxyhemoglobin on gas exchange in the lung. Ibid, p 255
Two-year follow-up study of patients with known serum concentrations of carcinoembryonic antigen P.R. BAND,* MD, FRCP[C]; I.T. BECK,f MD, PH D, FACP, FRCP[C]; P.J. DINNER,* M Sc; AB. MILLER,* MB, FRCP[C]
Between 1970 and 1972 five university centres in Canada and the United States collaborated in a study of a test for carcinoembryonic antigen (CEA) in the serum, with the Montreal General Hospital's laboratory acting as the reference laboratory, examining duplicate halves of specimens examined in local laboratories. The National Cancer Institute of Canada acted as the coordinating centre. The first report gave results for 503 patients admitted to the study between June 1971 and April 1972, 146 of whom had cancer of the colon or recturn.1 Discrimination between colorectal cancer and "other" conditions was good at a CEA value of 2.5 ng/mL or more, such a result being obtained in 66% of the patients with colorectal cancer in the local laboratories and 62% in the reference laboratory, compared with 39% and 33%, respectively, of patients with "other" conditions. Patients with Dukes' C lesions of the colon or rectum From *University of Alberta, Edmonton; tQueen's University, Kingston; and .epidemiology unit, National Cancer Institute of Canada, University of Toronto Reprint requests to: Dr. AB. Miller, Director, Epidemiology unit, National Cancer Institute of Canada, University of Toronto, 121 St. Joseph St., Toronto, Ont. M5S 2R9
(those with metastases in regional lymph nodes) were more likely to have elevated CEA values than patients with more localized lesions. CEA was also more commonly found in patients with other cancers or with liver disease than in patients with other (benign) conditions. It was concluded that the test for CEA can be reproduced in other laboratories and that it or another simple technique could become an important diagnostic aid for colorectal cancer. It was also suggested that the CEA value might be an important prognostic indicator and that, for the 33% of patients with elevated CEA values but no colorectal cancer, follow-up might show an abnormally high incidence of colorectal cancer in subsequent years. Follow-up of the original 503 cases (and a smaller number reported after April 1972), at 6, 12, 18 and 24 months after admission to the study, was attempted to examine these hypotheses. A lack of resources severely restricted the extent of documentation of followup in the three American centres, but a special effort was made to determine the status of patients in the two Canadian centres at 24 months. Contact with
the patient at any time up to 3 months before or after this date was accepted as the required 24-month follow-up contact. Results Of the 103 patients admitted to the study from Kingston and the 96 from Edmonton, follow-up forms were returned for 102 and 91, respectively; of these, 14 were lost to follow-up at 2 years. CEA values were reported on the basis of the initial results from the Montreal laboratory to avoid differences between laboratories. As CEA values were not available for 14 of the patients followed up, results are presented for only 165 patients. The prognostic value of the initial CEA value in the 36 patients with colorectal cancer is shown in Table I. If values of 2.5 ng/mL or more are taken as positive the difference in terms of disease-free status and survival at 2 years is significant at the 5% level (X2 = 6.47 and 5.73, respectively, with Yates' continuity correction). If values of 5.0 ng/mL or more are taken as positive the difference in disease-free status does not attain statistical signif-
Table I-Status at 2 years of patients with colorectal cancer according to initial serum concentration of carcinoembryonic antigen (CEA) and Dukes' classification2 CEA concentration (ng/mL) and Dukes' classification*
