Am
CLINICAL
AND
RESEARCH
BY
Observations RICHARD
During
ABRAMS,
In a recent monitoring
report, for
AND
Spring
patients
in order
such
drug
to
MICHAEL
Lithium ALAN
(1) recommended
receiving
provide
data
combined
and
TAYLOR,
EEG
on
the
EEG
effects
Neuroleptic
Treatment
M.D.
ium
and
neuroleptics
at the
time
promazine.
of
The subjects included all consecutive admissions to an adult, acute-treatment university psychiatric service for 22 months ending May 1976. Twenty-minute scalp-recorded resting EEGs were obtained in all cooperative patients, usually with sleep. The International 10-20 system and unipolar and bipolar montages were used. EEGs were read by an electroencephalographer (R.A.) who was blind to any information that could identify the patient or indicate psychotropic drug status. All records were classified as normal, borderline, or abnormal, according to the criteria of Gibbs and Gibbs (2). Borderline and abnormal records were subsequently combined for anal-
For
purposes
of calculating
differences
in EEG
abnormalities
ysis.
only and the combined-treatment the neuroleptic-only and groups. Finally, there were between serum lithium level normalities for patients in bined-treatment groups or sample.
Results
Conclusions
Oct.
26,
1978;
accepted
provided EEGs. Of this 17 were taking lithium, 33 and 13 were receiving lithNov.
is consistent with cal neurotoxicity
21, 1978.
0002-953X/79/03/0336/02/$00.35
©
of
mean
dosages
between
the
lithium-
groups or between the combined-treatment no significant correlations and presence of EEG abthe lithium-only or comfor the entire lithium
The combination of lithium and haloperidol produced no more EEG abnormalities than either drug given alone or than no drug at all. This finding, which our previous for combined
report of a lack therapy (3),
of clinifails to
support the need for EEG monitoring of such treatment. It is possible that Spring’s patients (1) may have demonstrated anticholinergic delirious states secondary to thioridazine, the most potent anticholinergic
Dr. Abrams is Professor and Vice-Chairman and Dr. Taylor is Professor and Chairman, Department of Psychiatry and Behavioral Sciences, University of Health SciencesiThe Chicago Medical School, Bldg. 50, North Chicago, Ill. 60064.
336
Each
of neuroleptics received , chlorpromazine was converted to haloperidol at a 10 to 1 ratio. The mean lithium dosage for the combined therapy group was 143 1 mg/day (range =900- 1800 mg/day), with a mean serum lithium level of 0.94 mEq/liter (SD=0.32). The mean haloperidol dosages were 39 mg/ day (range=20-.60 mg/day) for the combined-treatment group and 38 mg/day for the neuroleptic-only group. There was no significant difference in the distribution of EEG abnormalities for the four groups or for the 3 drug treatment groups considered alone (see table 1). Comparisons of the groups separately revealed no
Method
Received
of recording.
the 13 patients in the combined-treatment group was receiving haloperidol. Of the 33 neuroleptic-only patients, 30 were receiving haloperidol and 3 chlor-
lithium
treatment.
A total of 13 1 patients group, 68 were drug-free, were taking neuroleptics,
1979
‘
and neuroleptic drug therapy on the basis of EEG findings in three patients who purportedly developed encephalopathy as a result of a combination of lithium and thioridazine. As part of a larger study, we collected EEGs on a sample of patients receiving lithium and/or neuroleptics,
March
findings, including preliminary data from pilot studies, either clinical or studies; 3) case reports that describe a truly new syndrome or cast new reports that indicate a new therapeutic procedure ofpotential value or call or previously unreported complications of therapeutic interventions. Procannot be printed in this section. Criteriaforformat are listed in ‘Inforpapers that do not adhere to these criteria will be returned to the author.
Combined
M.D.,
/36:3,
REPORTS
This section contains 1) new research laboratory; 2) worthwhile replication light on established ones; and 4) case attention to adverse effects of drugs gram descriptions and literature reviews mation for Contributors” in each issue;
EEG
J Psychiatry
1979
American
Psychiatric
Association
Am
J Psychiatry
136:3,
March
1979
CLINICAL
case
TABLE 1 EEG Abnormality
Normal Treatment
None Lithium only Neuroleptics only Lithium plus neuroleptics aX2 =5 (n.s.).
%
N
%
54 10 28 9
79 59 85 69
14 7 5 4
21 41 15 31
BY AND
Delirium
I. Spring
and
Cardiac
DONALD
disorientation
and
M.D.,
of cardiac
disease
and
surgery
technique
with
‘31I-labeled
a year
and
was
on was
partic-
combined changed
combination by the report
to
beof Co-
Neurotoxicity
progresses
Charts
A. FRANK,
blindly syndrome
PH.D.,
as to the or
presence
hallucinosis.
of either
organic
authors
found
The
that the great majority (81%) of patients in their series had some evidence of organic brain syndrome. It was marked in 22%, moderate in 32%, and mild in 27%. A marked brain syndrome was generally associated with cardiac
index
below
2.5 liters
per
minute
per
meter
squared during the early postoperative period. Conversely, higher outputs were associated with less cerebral dysfunction. Forty-six percent of the patients experienced hallucinosis, some without evidence of brain syndrome. The hallucinosis tended to occur later and was suggestively related to periods of rising car-
(1-3).
albumin.
well
Presented
KENNETH
brain
An association between postcardiotomy delirium and postoperative cardiac index (cardiac output/surface area) has also been shown. In 1966, Blachly and Kloster (4) studied 37 cardiotomy patients who had undergone valve replacement. Cardiac output was measured pre- and postoperatively by a radioisotope dilution
GK:
evaluated
to hallucinations and/or delusions. A number of factors have been found to correlate with this delirium, and a multicausal etiology has been postulated. The existence of the lucid interval led to the hypothesis that the delirium was a reaction to the impact of the open-heart surgery recovery room (OHRR) experience in patients made vulnerable by the physical effects
for
by Spring
done
Output
S. KORNFELD,
at times
had
with combined use of lithium and at the 131st annual meeting of the American Psychiatric Association, Atlanta, Ga, May 8-12, 1978 2. Gibbs FA, Gibbs EL: Medical Electroencephalography. Reading, Mass, Addison-Wesley, 1967 3. Krishna NR, Taylor MA, Abrams R: Combined haloperidol and lithium carbonate in treating manic patients. Compr Psychiatry 19:119-120, 1978 4. Cohen WI, Cohen NH: Lithium carbonate, haloperidol, and irreversible brain damage. JAMA 230:1283-1287, 1974
Thirteen years following its initial description, deliriurn after open-heart surgery continues to occur. The phenomenon consists of a lucid interval followed by and/or
haloperidol
thioridazine.
STANLEY S. HELLER, M.D., PAUL F. HOAR, M.D.
illusions
and
described
she
REPORTS
REFERENCES
neuroleptic available. This is suggested by his description of the first and fourth patients, who showed no abnormalities when lithium was combined with other neuroleptics but developed a transient encephalopathy when lithium was combined with thioridazine. The
Postcardiotomy
patient
RESEARCH
the more toxic lithiumlthioridazine cause ofapprehension engendered hen and Cohen (4).
Abno rmal
N
first
unfortunate;
lithium
EEGa
Drug
of the
ularly
Drug Therapy
and
AND
diac
output.
The improvements pulmonary bypass a thermodilution
method
measures actual of the relationship ium.
were
in cardiac surgery and cardiotechniques and the development of (5,
6) that
more
accurately
cardiac output called for a new between cardiac output and
study delir-
Method Received
Oct.
6, 1978; accepted
Nov.
9, 1978.
We studied 48 patients who placement at Columbia-Presbyterian between July and November equally divided between aortic
The authors are with the Columbia University College of Physicians and Surgeons, 630 West 168th St. , New York, N.Y. 10032, where Dr. Heller is Assistant Professor of Clinical Psychiatry, Dr. Kornfeld is Professor of Clinical Psychiatry, Dr. Frank is Assistant Professor ofClinical Psychology, and Dr. Hoar is Assistant Professor of Anesthesiology. The work was supported by Alcohol, Health Administration grant MH-l2756 of Mental Health.
receiving
Drug Abuse, and Mental from the National Institute
0002-953X/79/03/0337/03/$00.40
©
glutaraldehyde-treated
A triple-lumen was introduced termined via 1979
American
had
a single valve reMedical Center 1977. Patients were and mitral valve cases porcine
heterografts.
flow-directed thermodilution catheter and the average cardiac output was dethe thermodilution principle by using a
Psychiatric
Association
337
CLINICAL
AND
RESEARCH
BY
Observations RICHARD
During
ABRAMS,
In a recent monitoring
report, for
AND
Spring
patients
in order
such
drug
to
MICHAEL
Lithium ALAN
(1) recommended
receiving
provide
data
combined
and
TAYLOR,
EEG
on
the
EEG
effects
Neuroleptic
Treatment
M.D.
ium
and
neuroleptics
at the
time
promazine.
of
The subjects included all consecutive admissions to an adult, acute-treatment university psychiatric service for 22 months ending May 1976. Twenty-minute scalp-recorded resting EEGs were obtained in all cooperative patients, usually with sleep. The International 10-20 system and unipolar and bipolar montages were used. EEGs were read by an electroencephalographer (R.A.) who was blind to any information that could identify the patient or indicate psychotropic drug status. All records were classified as normal, borderline, or abnormal, according to the criteria of Gibbs and Gibbs (2). Borderline and abnormal records were subsequently combined for anal-
For
purposes
of calculating
differences
in EEG
abnormalities
ysis.
only and the combined-treatment the neuroleptic-only and groups. Finally, there were between serum lithium level normalities for patients in bined-treatment groups or sample.
Results
Conclusions
Oct.
26,
1978;
accepted
provided EEGs. Of this 17 were taking lithium, 33 and 13 were receiving lithNov.
is consistent with cal neurotoxicity
21, 1978.
0002-953X/79/03/0336/02/$00.35
©
of
mean
dosages
between
the
lithium-
groups or between the combined-treatment no significant correlations and presence of EEG abthe lithium-only or comfor the entire lithium
The combination of lithium and haloperidol produced no more EEG abnormalities than either drug given alone or than no drug at all. This finding, which our previous for combined
report of a lack therapy (3),
of clinifails to
support the need for EEG monitoring of such treatment. It is possible that Spring’s patients (1) may have demonstrated anticholinergic delirious states secondary to thioridazine, the most potent anticholinergic
Dr. Abrams is Professor and Vice-Chairman and Dr. Taylor is Professor and Chairman, Department of Psychiatry and Behavioral Sciences, University of Health SciencesiThe Chicago Medical School, Bldg. 50, North Chicago, Ill. 60064.
336
Each
of neuroleptics received , chlorpromazine was converted to haloperidol at a 10 to 1 ratio. The mean lithium dosage for the combined therapy group was 143 1 mg/day (range =900- 1800 mg/day), with a mean serum lithium level of 0.94 mEq/liter (SD=0.32). The mean haloperidol dosages were 39 mg/ day (range=20-.60 mg/day) for the combined-treatment group and 38 mg/day for the neuroleptic-only group. There was no significant difference in the distribution of EEG abnormalities for the four groups or for the 3 drug treatment groups considered alone (see table 1). Comparisons of the groups separately revealed no
Method
Received
of recording.
the 13 patients in the combined-treatment group was receiving haloperidol. Of the 33 neuroleptic-only patients, 30 were receiving haloperidol and 3 chlor-
lithium
treatment.
A total of 13 1 patients group, 68 were drug-free, were taking neuroleptics,
1979
‘
and neuroleptic drug therapy on the basis of EEG findings in three patients who purportedly developed encephalopathy as a result of a combination of lithium and thioridazine. As part of a larger study, we collected EEGs on a sample of patients receiving lithium and/or neuroleptics,
March
findings, including preliminary data from pilot studies, either clinical or studies; 3) case reports that describe a truly new syndrome or cast new reports that indicate a new therapeutic procedure ofpotential value or call or previously unreported complications of therapeutic interventions. Procannot be printed in this section. Criteriaforformat are listed in ‘Inforpapers that do not adhere to these criteria will be returned to the author.
Combined
M.D.,
/36:3,
REPORTS
This section contains 1) new research laboratory; 2) worthwhile replication light on established ones; and 4) case attention to adverse effects of drugs gram descriptions and literature reviews mation for Contributors” in each issue;
EEG
J Psychiatry
1979
American
Psychiatric
Association
Am
J Psychiatry
136:3,
March
1979
CLINICAL
case
TABLE 1 EEG Abnormality
Normal Treatment
None Lithium only Neuroleptics only Lithium plus neuroleptics aX2 =5 (n.s.).
%
N
%
54 10 28 9
79 59 85 69
14 7 5 4
21 41 15 31
BY AND
Delirium
I. Spring
and
Cardiac
DONALD
disorientation
and
M.D.,
of cardiac
disease
and
surgery
technique
with
‘31I-labeled
a year
and
was
on was
partic-
combined changed
combination by the report
to
beof Co-
Neurotoxicity
progresses
Charts
A. FRANK,
blindly syndrome
PH.D.,
as to the or
presence
hallucinosis.
of either
organic
authors
found
The
that the great majority (81%) of patients in their series had some evidence of organic brain syndrome. It was marked in 22%, moderate in 32%, and mild in 27%. A marked brain syndrome was generally associated with cardiac
index
below
2.5 liters
per
minute
per
meter
squared during the early postoperative period. Conversely, higher outputs were associated with less cerebral dysfunction. Forty-six percent of the patients experienced hallucinosis, some without evidence of brain syndrome. The hallucinosis tended to occur later and was suggestively related to periods of rising car-
(1-3).
albumin.
well
Presented
KENNETH
brain
An association between postcardiotomy delirium and postoperative cardiac index (cardiac output/surface area) has also been shown. In 1966, Blachly and Kloster (4) studied 37 cardiotomy patients who had undergone valve replacement. Cardiac output was measured pre- and postoperatively by a radioisotope dilution
GK:
evaluated
to hallucinations and/or delusions. A number of factors have been found to correlate with this delirium, and a multicausal etiology has been postulated. The existence of the lucid interval led to the hypothesis that the delirium was a reaction to the impact of the open-heart surgery recovery room (OHRR) experience in patients made vulnerable by the physical effects
for
by Spring
done
Output
S. KORNFELD,
at times
had
with combined use of lithium and at the 131st annual meeting of the American Psychiatric Association, Atlanta, Ga, May 8-12, 1978 2. Gibbs FA, Gibbs EL: Medical Electroencephalography. Reading, Mass, Addison-Wesley, 1967 3. Krishna NR, Taylor MA, Abrams R: Combined haloperidol and lithium carbonate in treating manic patients. Compr Psychiatry 19:119-120, 1978 4. Cohen WI, Cohen NH: Lithium carbonate, haloperidol, and irreversible brain damage. JAMA 230:1283-1287, 1974
Thirteen years following its initial description, deliriurn after open-heart surgery continues to occur. The phenomenon consists of a lucid interval followed by and/or
haloperidol
thioridazine.
STANLEY S. HELLER, M.D., PAUL F. HOAR, M.D.
illusions
and
described
she
REPORTS
REFERENCES
neuroleptic available. This is suggested by his description of the first and fourth patients, who showed no abnormalities when lithium was combined with other neuroleptics but developed a transient encephalopathy when lithium was combined with thioridazine. The
Postcardiotomy
patient
RESEARCH
the more toxic lithiumlthioridazine cause ofapprehension engendered hen and Cohen (4).
Abno rmal
N
first
unfortunate;
lithium
EEGa
Drug
of the
ularly
Drug Therapy
and
AND
diac
output.
The improvements pulmonary bypass a thermodilution
method
measures actual of the relationship ium.
were
in cardiac surgery and cardiotechniques and the development of (5,
6) that
more
accurately
cardiac output called for a new between cardiac output and
study delir-
Method Received
Oct.
6, 1978; accepted
Nov.
9, 1978.
We studied 48 patients who placement at Columbia-Presbyterian between July and November equally divided between aortic
The authors are with the Columbia University College of Physicians and Surgeons, 630 West 168th St. , New York, N.Y. 10032, where Dr. Heller is Assistant Professor of Clinical Psychiatry, Dr. Kornfeld is Professor of Clinical Psychiatry, Dr. Frank is Assistant Professor ofClinical Psychology, and Dr. Hoar is Assistant Professor of Anesthesiology. The work was supported by Alcohol, Health Administration grant MH-l2756 of Mental Health.
receiving
Drug Abuse, and Mental from the National Institute
0002-953X/79/03/0337/03/$00.40
©
glutaraldehyde-treated
A triple-lumen was introduced termined via 1979
American
had
a single valve reMedical Center 1977. Patients were and mitral valve cases porcine
heterografts.
flow-directed thermodilution catheter and the average cardiac output was dethe thermodilution principle by using a
Psychiatric
Association
337
