Department of Psychological Medicine, Monash University
Mental Health Research Institute of Victoria
Department of Forensic Medicine, Monash University and Victorian Institute of Forensic Medicine
Department of Psychological Medicine, Monash University, Victoria, Australia
Correspondence: Professor Paul E. Mullen, Victorian Institute of Forensic Mental Health, Thomas Embling Hospital, Locked Bag 10, Fairfield, Victoria 3078, Australia
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ABSTRACT |
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Aims To examine this association in a large number of cases of choking deaths.
Method Cases of individuals who had died because of choking were linked with a case register recording contacts with public mental health services. The actual and expected rates of psychiatric disorder and the presence of psychotropic medication in post-mortem blood samples were compared.
Results The 70 people who had choked to death were over 20 times more likely to have been treated previously for schizophrenia. They were also more likely to have had a prior organic psychiatric syndrome. The risk for those receiving thioridazine or lithium was, respectively, 92 times and 30 times greater than expected. Other antipsychotic and psychotropic drugs were not over-represented.
Conclusions The increased risk of death in people with schizophrenia may be a combination of inherent predispositions and the use of specific antipsychotic drugs. The increased risk of choking in those with organic psychiatric syndromesis consistent with the consequences of compromised neurological competence.
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INTRODUCTION |
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METHOD |
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Prior contact with mental health services was established using the VPCR. Manual linkage was checked with a computer algorithm with better than 95% agreement. From the databases, information could be obtained on the individuals age and gender; whether the individual had attended publicly funded mental health services in Victoria; any diagnosis made; date of death; cause of death; circumstances of death; and the results of post-mortem toxicological analyses. Relative risks were calculated to express the difference between the actual and the expected incidence of deaths in the different mental disorders. Numbers of deaths per 100 000 head of population per year were also calculated.
Drug consumption figures for the Australian population were derived from the defined daily dosage (DDD) figures published in the annual Australian Statistics on Medicines in the years 19901996 (relating to the years 19891995). These statistics were published in Canberra by the now defunct Australian Commonwealth Department of Health and Family Services. For a chronically administered drug, the DDD indicates how many people per 1000 of the population may have received a standard dose of such a listed medication (as defined by the DDD) daily. From the information published for the years 19891995, the size of the population receiving antipsychotics, antidepressants, anxiolytics and hypnotics during these years was estimated.
From this population figure comparisons could be drawn between the expected numbers of deaths in each population, given their frequency in the general population, and the actual number of individuals found by toxicological analysis to have been taking such medication at the time of death.
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RESULTS |
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Mental health
Twenty-five of the 70 individuals had had prior contact with public sector
mental health services: 10 had received a principal diagnosis of
schizophrenia, 8 had an organic psychiatric disorder, and 1 had another
psychiatric illness (Table 2).
For the other 6 individuals no final diagnosis was recorded. The
representation of people who had received treatment in the mental health
services was significantly higher than expected. None of the groups differed
from the general population in age or gender distribution. Of the 25
individuals who had been in contact with mental health services, 16 had died
by the non-aspiration form of choking: 6 had organic disorders, 7 had
schizophrenia, 1 had another psychiatric illness, and 2 had no final
diagnosis. Relative risk calculations for non-aspiration deaths put the
increased risk at 30 times that of the general population for those with
schizophrenia (95% CI 13.567.5), and 43 times that of the general
population for those with an organic disorder (95% CI 18.4102.6).
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Toxicology
Toxicological analysis was available for 21 of the 70 deaths, of which 14
tested positive for psychotropic medication. Antipsychotic agents were found
in 8 of the choking deaths: thioridazine was found in 5 cases and lithium in 3
cases (on one occasion the drugs were found concurrently). Antidepressants and
anxiolytics were found in 3 cases, in 2 of which the person had also taken
hypnotics.
All five individuals in whom thioridazine was detected were recorded on the VPCR. Three were recorded with a diagnosis of schizophrenia, one had an organic disorder, and another had no diagnosis recorded. Thioridazine was the sole medication taken in two cases; in the other cases it was taken with one other drug lithium, the antidepressant dothiepin, and diazepam, respectively. Lithium was taken once each with thioridazine, dothiepin and diazepam. In the five deaths where diazepam, temazepam or dothiepin was found in the bloodstream, two cases also involved thioridazine or lithium.
Table 3 documents the results of relative risk calculations that follow the population estimates provided by the DDD information. Relative risk calculations were made on the assumption that the case population was the total number of cases originally isolated (that is, all 70 deaths due to choking) rather than only those for whom toxicology data were available. The use of thioridazine was associated with an increase in the relative risk of deaths due to choking to over 90 times that of the general population. Lithium was also associated with a statistically significant increase in the risk of choking, with a relative risk more than 30 times that of the general population.
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DISCUSSION |
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Polypharmacy does not appear to be relevant to the increased mortality rates. Of the five deaths associated with thioridazine, in only two was the patient taking another psychotropic drug. This avoids the possible complicating factor of outright toxicity noted by Jusic & Lader (1994). However, regular toxicological analyses search primarily for chlorpromazine, haloperidol and thioridazine. Unrecognised polypharmacy might have occurred with drugs that were not detected, such as fluphenazine.
In Victoria the law mandates the reporting to the coroner of any death that appears to have been unexpected, unnatural or to have resulted, directly or indirectly, from accident or injury. The law also mandates reporting of patients who die while held involuntarily in the care of a mental health service. In general, however, it is likely that the deaths of individuals who die at home are reported less frequently than those dying in care. Sudden death could be attributed to some natural disease process. Choking deaths, if observed, are sudden and dramatic, and their common association with active eating is such that a report of the death is made to the coroner. Calculations reveal that, given the deaths recorded on the coroners database, for the population with schizophrenia not to have a significantly increased risk of choking death, there would have to have been 756 choking deaths. In effect, 686 such deaths would have to have gone unreported. For the population with an organic psychiatric disorder, 973 hypothetical deaths are required, and for the thioridazine risk not to be significant, the figure is 2552 deaths. It seems unlikely that such a high number of choking deaths would go unreported.
Antipsychotic medications have also been implicated in sudden cardiac deaths (Mehtonen et al, 1991; Reilly et al, 2002) and sudden cardiac deaths also obviously occur in the general community. A sudden cardiac death that appears to be due to choking therefore exists as a confounding factor that would increase the number of deaths attributed to choking.
Limitations
The VPCR does not record individuals who have received all their treatment
from private practitioners. However, the vast majority of those with
schizophrenia appear on the register. The VPCR population with a principal
diagnosis of schizophrenia amounts to 0.7% of the total population of
Victoria, equal in magnitude to the expected prevalence of schizophrenia in
the general community.
In matching surveys such as this, any errors in data collection serve to decrease the chance of a match being made. Incompleteness of databases also decreases the likelihood of a match. In our survey, 12 cases were recorded on the VPCR, indicating that the individual concerned had been in contact with public sector mental health services in Victoria at some time. However, because no other information as to the outcome of their visit was available, these individuals were counted as part of the residual population.
The absence of complete toxicological information for all individuals hampers the studys capacity to differentiate between the effects of mental illness and those of the medication used to treat it. It results in a probable underestimation of the relative risk associated with the use of such drugs. An additional limitation is whether findings of choking and/or aspiration were made consistently to include and exclude the same phenomena. For example, in the context of food, choking may be defined to be merely the blockage of the larynx or laryngopharynx, or only appropriate where there is a complete blockage of the trachea and bronchi by an impacted food bolus. Additional studies should seek to closely monitor the definitions used for classification purposes.
Findings
Elevated rates of death due to choking have been found to be associated
with a diagnosis of schizophrenia, organic disorders and the use of
thioridazine. For the eight individuals with a diagnosis of an organic
disorder, toxicological data were available in only one case. For the ten
individuals with a diagnosis of schizophrenia, toxicological data were
available in six cases: thioridazine use was detected in three of these cases,
lithium in two (once used concurrently with thioridazine), temazepam alone in
one case and the last case had a negative screen. For both populations the
evidence is ambiguous about whether the increased rates were associated with
medication, or were the result of swallowing difficulties or eating habits
inherent in the illness itself (Hussar
& Bragg, 1969; Simpson
et al, 1987). In fact, the possible role of tardive
dyskinesia as a source of respiratory difficulty years after the
discontinuance of antipsychotic therapy means that any retrospective study is
limited in its capacity to determine the role of antipsychotics in choking
(Yassa & Lal, 1986).
Thirty-one of the deaths involved asphyxiation following the aspiration of food. A less dramatic aspiration could precipitate pneumonitis and aspiration pneumonia (Von Brauchitsch & May, 1968). In the absence of adequate treatment the alveoli fill with oedematous fluid and inflammatory cells (pneumonitis), and necrosis results. Death may follow after days, weeks or months. As aspiration leading to death may be occult, and may follow a longer illness, it will probably not be reported to the coroner. This is especially the case given the relative infrequency with which people with schizophrenia report illness. Even if a patients death were reported in conformity with the requirements of the governing legislation, the true cause of the pneumonia might easily be overlooked. Thus, the true extent of deaths due to aspiration that did not cause immediate asphyxiation is at this stage unknown.
Clinical implications
Aspiration may be mediated by a breakdown of the reflexes that serve to
prevent oesophageal reflux, deficits in the cricopharyngeal sphincter reflexes
preventing reflux of food into the pharynx, an interference with normal
sweeping ciliary action in the respiratory tract, or a combination of such
deficits (Plachta, 1965; Solomon, 1977). People with
schizophrenia may be predisposed to choking deaths specifically by disorders
of the physiology of swallowing and reflux, or by behaviour that increases the
risk. Such risks are largely independent of the medications employed to treat
the disorder, and in two of the deaths involving people with schizophrenia
toxicological results showed they were not taking antipsychotics. The
association between organic psychosyndromes and choking is not surprising as
members of this group have compromised neurological competence, are often
troubled by coexisting physical disorders and may have periods of reduced
consciousness predisposing them to aspiration.
The strong association between thioridazine and choking deaths is as dramatic as it is unexpected. Suggestions that the risk of choking could be reduced by the co-administration of anticholinergic drugs (Simpson et al, 1987) might have led to the expectation that thioridazine would be among the safest antipsychotics, rather than uniquely associated with such deaths. We note the recent study into sudden cardiac death (Reilly et al, 2002), as well as prior studies (Mehtonen et al, 1991) that showed an increased risk associated with the use of thioridazine.
Clinically, the implications of treatment are less pronounced. Calculations to determine the number of patients that must be treated before a single choking death occurs (Cook & Sackett, 1995) estimate that 591 patients would need to be treated with thioridazine over the 7-year period before a single death occurred. For lithium, the figure is 1723 patients. This figure is based on the rate of choking in the general population. However, this study also shows increased levels of choking deaths in the population with a diagnosis of schizophrenia. If the rate of death due to choking inherent to schizophrenia is higher than that of the general population, the difference between the rates of choking with and without thioridazine would be smaller and the number of treatments needed before a death resulted would be greater.
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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REFERENCES |
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Received for publication December 4, 2002. Revision received May 22, 2003. Accepted for publication June 13, 2003.
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