Relationship between abnormal pupillary reactivity and the outcome of a psychotropic drug overdose
Original Contribution
Relationship between abnormal pupillary reactivity and the outcome of a Psychotropic drug overdose
Youichi Yanagawa PhD, MD?, Masaki Miyazaki MD, Toshihisa Sakamoto MD, PhD
Department of Traumatology and Critical Care Medicine, National Defense Medical College (NDMC), Saitama 359-8513, Japan
Received 21 January 2009; revised 13 March 2009; accepted 14 March 2009
Abstract
Objective: The association between abnormal pupil reactivity (abnormal) and the outcome among patients with psychotropic drug overdose (OD) was retrospectively investigated.
Methods: The study included patients that had experienced an OD between January and December 2007. The subjects were divided into 2 groups, namely, abnormal and Normal groups.
Results: There were 12 subjects in the abnormal and 74 subjects in the normal group. Glasgow Coma Scale in the abnormal was significantly smaller that that in the normal group. An average quantity of ingested tranquilizer per subject in the abnormal was significantly larger that those in the normal group. However, the duration of admission and survival rates between the two groups were not significantly different.
Conclusion: The patients that experienced an OD, who demonstrated abnormal pupil reactivity, tended to have ingested larger amounts of drugs while also demonstrating severe unconsciousness. However, the patients with abnormal pupil reactivity had a favorable outcome.
(C) 2010
Introduction
The weakness or absence of a light reflex following a head injury, stroke, or hypoxic encephalopathy is sign of a poor prognosis [1-3] because it indicates either brain herniation or diffuse brain injury. A patient may demonstrate a light reflex abnormality following a psychotropic drug overdose [4]. Psychotropic drugs have multiple kinds of pharmacologic functions, and there are many ways in which they can affect the brain. Each drug has a specific action on
* Corresponding author. Tel.: +81 4 2995 1888; fax: +81 4 2996 5221.
E-mail address: [email protected] (Y. Yanagawa).
one or more neurotransmitter or neuroreceptor in the brain. The clinical presentation, including a light reflex abnormality after a drug overdose, tends to demonstrate both an inhibition and activation of certain neurotransmitters or neuroreceptors. Accordingly, the association between a pupil abnormality and the outcome among patients following multiple kinds of Drug overdoses (a patient who ingested multiple kinds and large amount of drugs intentionally) is complicated and has not yet been investigated. However, it is important for clinical physicians to elucidate whether a patient with a psychotropic drug overdose, who demonstrates an abnormal pupil reactivity as a result of a balance between the inhibition and activation of certain receptors induced by multiple kinds of drug overdoses, is unfavorable or not. Therefore, this study retrospectively investigated this association.
0735-6757/$ - see front matter (C) 2010 doi:10.1016/j.ajem.2009.03.012
Subject and methods
The study included patients treated for a psychotropic drug overdose between January and December 2007. Patients with out-of-hospital cardiopulmonary arrest, ophthalmic disease which affected pupil size and light reflex, and where the exact name and quantity of drug, which were ingested by patients were unknown, were excluded. A medical chart review of the subjects was performed. The subjects were divided into 2 groups, the abnormal and normal groups. The abnormal group included the patients whose light reflex on arrival was sluggish or absent, and the normal group included the patients whose light reflex was normal. Regarding pupil reactivity, the first clinical observa- tion of the pupillary response was used. We did not use either paralytics or sedatives to treat any patient before observa- tions. Age, sex, Glasgow Coma Scale (GCS), diameter of pupil, systolic blood pressure, pulse rate, Shock Index (SI: pulse rate divided by systolic blood pressure), psychiatric disease, kinds and quantity of overused drug, estimated time from ingestion to arrival, ratio of tracheal intubation, duration of hospitalization, and survival rate were compared between the 2 groups. The psychiatric diseases were categorized into 4 groups, mood/anxiety disorder, schizo- phrenia, personality disorder, and others. The kinds of drug were categorized into 4 groups, consisting of anxiolytics/ hypnotics, antipsychotics, antidepressants, and others.
Transnasal or transoral intubation, gastric lavage with more than 2 L of lukewarm water, the infusion of
Table 1 Clinical parameters
magnesium citrate, and activated charcoal via a nasogas- tric tube were routinely performed for patients who did not show eye opening in response to pain stimulation due to drug intoxication. The blood levels of the drugs were not measured.
The ?2 and Student t test were used for statistical analyses. A P value of less than .05 was considered to be significant.
Results
There were 130 patients who were transported to the emergency department with acute intoxication. Among them, 7 isolated acute alcohol intoxication, 4 gas inhalation,
6 agricultural substance ingestion, 6 industrial chemical substance ingestion, 6 analgesic substance ingestion, and 2 tobacco ingestion cases were excluded from the study. Among the remaining 99 patients with psychotropic drug overdose, 2 cardiopulmonary arrest, 2 pupil abnormality induced by ophthalmic disease, and 9 cases where the type and quantity of the drug were unknown were excluded. The remaining 86 patients were defined as the subjects. There were 12 subjects in the abnormal group and 74 subjects in the normal group.
The background of the 2 groups is shown in Table 1. Table 2 shows the list of names and total amount of each ingested drug. The age, sex, pupil size, systolic blood pressure, frequency of psychiatric disease, kinds of drug, and
|
Age 34.1 +- 2.8 32.2 +- 1.0 NS
Sex (male/female) 5/7 19/55 NS GCS 7.3 +- 1.2 11.7 +- 0.4 P b .001 Diameter of pupil (mm) 3.5 +- 0.4 3.6 +- 0.1 NS Systolic blood pressure (mm Hg) 113.6 +- 5.2 114.8 +- 1.8 NS Heart rate (/min) 107 +- 8.7 88.0 +- 2.3 P b .01 Shock index 0.98 +- 0.10 0.77 +- 0.02 P b .01 Psychiatric disease NS Mood and anxiety disorder 8 (67%) 45 (62%) Schizophrenia 1 (8%) 11 (14%) Personality disorder 2 (17%) 14 (19%) Others 1 (8%) 4 (5%) Presumed total number of ingested drug NS Anxiolytics/hypnotics 10 (83%) 64 (86%) Antipsychotics 9 (75%) 36 (42%) Antidepressant 7 (58%) 28 (38%) Presumed average amount of ingested drug (estimated dose [mg]) Anxiolytics/hypnotics 23.2 +- 14.2 1.6 +- 0.6 P b .001 Antipsychotics 12.8 +- 4.6 1.4 +- 0.3 P b .0001 Antidepressant 1.0 +- 0.3 2.9 +- 0.66 NS Estimated time from ingestion to arrival (min) 211 +- 66 (n = 10) 165 +- 21 (n = 57) NS |
|
Mean +- standard error. NS indicates not significant. |
the estimated time from ingestion to arrival were not significantly different between two groups. The GCS in the abnormal group was significantly smaller that that in the normal group. The pulse rate, SI, and presumed average quantity of ingested minor and major tranquilizers per
subject in the abnormal group were significantly larger than those in the normal group.
The outcomes of the 2 groups are shown in Table 3. The ratio of tracheal intubation in the abnormal group was significantly larger than that in the normal group. However,
|
Abnormal (n = 12) |
Normal (n = 74) |
P |
|
|
No. of intubations |
6 (50%) |
13 (17.5%) |
P b .05 |
|
Duration of admission |
2.5 +- 0.4 |
2.1 +- 0.2 |
NS |
|
Survival rate |
12 (100%) |
74 (100%) |
NS |
|
Mean +- SE. |
|||
the duration of hospitalization and survival rates between the 2 groups were not significantly different.
Discussion
This study demonstrated that patients with psychotropic drug overdose, who demonstrated abnormal pupil reactivity on arrival, tended to have large amount of drug ingestion, severe unconsciousness, tachycardia, large SI, and high tracheal intubation ratio. However, there was no correlation between abnormal pupil reactivity and the final outcome.
The severity of a psychotropic drug overdose tends to depend on the amount of ingested drug [5]. A more severe psychotropic drug overdose leads to either an excessive dilatation of the peripheral vasculature or a maldistribution of the cardiac output, and these phenomena are followed by an increased heart rate and a decreased blood pressure due to the associated Circulatory insufficiency. Shock also reflects the existence of circulatory insufficiency. Accordingly, the patients who are comatose due to a psychotropic drug overdose also show a more severe state of unconsciousness and circulatory insufficiency.
In this study, the patients with pupillary abnormality for light stimulation tended to have greater severity of psychotropic drug overdose than those with a normal response. In the presence of antidepressants, the latency of light reflex response was previously reported to be prolonged [6]. Thiopental induces unconsciousness and dilation of the pupils with a loss of light reflex initially, probably by paralysis of pupilloconstrictor neurons in the midbrain [7]. The Selective serotonin reuptake inhibitor citalopram can induce fixed pupils, by partially blocking norepinephrine reuptake and thus inhibiting the Eddinger-Westphal nucleus via an ?2-adrenergic effect [8]. Phenothiazines, olanzapine, clonidine, or trazodone act as an ?2-adrenergic antagonist [9-12]. They may also reduce the Pupillary light reflex [12]. In a cat study, an intravenous injection of high-dose diazepam (1 mg/kg) depressed the optic tract evoked potential in the short ciliary nerves, thus resulting in a reduction of the light reflex [13]. Accordingly, deep sedation induced by an overdose of a variety of drug may result in abnormal pupil reactivity in this study.
In children, the frequency of miosis was found to increase with the increasing depth of coma, particularly
among patients who have ingested phenothiazine and barbiturates. In contrast, the diameter of the pupils in the abnormal group, which showed a deeper level of uncon- sciousness than the normal group, did not significantly change in comparison to the normal group. Both groups included only adult patients in this study. Regarding the discrepancies between the 2 studies, the difference in age between 2 groups may be one reason because age can have an effect on the diameter of the pupil [14]. In contrast, sedative drugs cause a decrease in the level of arousal accompanied by constriction of the pupil, thus probably reflecting the attenuation of the sympathetic outflow as sedation sets in [15]. However, tricyclic antidepressant has a potential central anticholinergic effect, thus resulting in mydriasis. Selective serotonin reuptake inhibitor citalopram can induce fully dilated pupils [8]. In addition, thiopental initially induces unconsciousness and dilation of the pupil [7]. The subjects in this study all ingested the drug intentionally so that most subjects ingested multiple kinds and a large amount of drugs. Accordingly, the antagonistic or interactive effects on the pupil size induced by many kinds of drugs may affect the diameter of pupil. Because most children ingest drugs erroneously, they tend to ingest either single drugs or a few kinds and only a small amount of the drug. These differences may explain the discrepancy. The duration of admission of the 2 groups in this study showed no difference, although the severity of psychiatric drug overdose in the abnormal group was greater than that in the normal group. This may be based on the management of the subjects in the normal group. The patients with a drug overdose were observed overnight, even the patients whose consciousness were clear. Accordingly, most of subjects in the normal group might not need hospitalization; however, all subjects actually stayed in the hospital for at least 2 days. On the other hand, the clearance of a psychotropic drug may be rapid due to the development of safer drugs. Accordingly, the subjects in abnormal group regained consciousness and were discharged on the second hospital day even though the subject was comatose on arrival. These factors may also explain our results. Most patients presenting with a psychotropic drug overdose generally have a favorable outcome and the state of unconsciousness induced by such an overdose tends to
improve within a few days [16].
Conclusion
A patient with a psychotropic drug overdose, who demonstrates an abnormal pupil reactivity on arrival, tends to have ingested a large amount of drugs while also demonstrating severe unconsciousness, tachycardia, a large SI, and a high tracheal intubation ratio. However, even those patients with abnormal pupil reactivity usually had a favorable outcome.
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