BACKGROUND. Apparent life-threatening events are a relatively common event in children for which there may be a number of causes. Previous reports have suggested that poisonings, either accidental or intentional, may be causes of some events. However, this theory has not been systematically studied.
METHODS. We conducted a prospective, descriptive study of infants aged <2 years presenting to a pediatric emergency department of a large, urban tertiary care children's hospital with signs and symptoms of an apparent life-threatening event. All of the children presenting with an apparent life-threatening event were to undergo a standardized evaluation, which included obtaining a comprehensive urine toxicology screen. A positive toxicology screen result was defined as follows: a clinically insignificant screen result (identification of a medication that would not cause an apparent life-threatening event) or a clinically significant screen result (identification of a medication that could cause apnea or other event consistent with an apparent life-threatening event, even if it was a medication that the child was known to be taking).
RESULTS. During the study period, 596 children presented to the emergency department with an apparent life-threatening event, and 274 (46.0%) had a toxicology screen performed. Of 274 toxicology screen results, 50 were considered truly positive (18.2%), and 23 positive screen results were considered clinically significant (23 of 274 [8.4%]). Thirteen toxicology screen results were positive for an over-the-counter cold preparation (13 of 274 [4.7%]). No parent admitted to having given his or her child an over-the-counter cold preparation.
CONCLUSIONS. A substantial number of children presenting to the emergency department with an apparent life-threatening event had a positive toxicology screen result. In particular, a number of children were found to have been given an over-the-counter cold preparation. We would recommend that toxicology screens be included as part of the routine evaluation of children who present with an apparent life-threatening event.
Apparent life-threatening events (ALTEs) are relatively common occurrences in children for which there may be a number of causes. Previous reports have suggested that poisonings, whether intentional or unintentional, may be a cause of some events.1, 2 However, the role of poisonings as a causative role in ALTEs has not been systematically studied.
We hypothesized that a substantial number of children presenting to our emergency department (ED) with an ALTE would have a positive toxicology screen result. Furthermore, we hypothesized that the positive screen results would result from either intentional or unintentional poisonings, including from the use of over-the-counter (OTC) cold preparations. We sought to prospectively obtain comprehensive urine toxicology screens on all of the children presenting to the ED with an ALTE and to describe their results.
This study was a prospective, descriptive study of consecutive patients presenting to the ED with signs and symptoms consistent with the National Institutes of Health definition of an ALTE.3
Study Setting and Population
Children <24 months of age, presenting to the ED of the Children's Hospital of Pittsburgh between March 1, 1997, and July 31, 2006, with signs and symptoms of an ALTE were enrolled in the study. One investigator was responsible for determining whether a child's event was consistent with an ALTE, as defined by the National Institutes of Health. The ED is part of a large, urban, tertiary care pediatric hospital that evaluates and manages >60000 patients each year. A clinical guideline that describes the evaluation and management of all of the children presenting to the ED with an ALTE was instituted in the ED in 1997.
Study Protocol and Measurements
At the time of study, patients presenting to the ED with an ALTE underwent routine laboratory testing, which included a comprehensive urine toxicology screen, and were admitted to the hospital. After identification of a child with an ALTE, a standardized questionnaire was used for all of the patients to record pertinent historical and physical examination findings, as well as results of laboratory and radiographic studies. This included complete demographic and clinical characteristics of the patient. The form specifically recorded the following characteristics of the event: apnea, episode was frightening to the observer, change in mental status, color changes, change in muscle tone, choking, and whether the patient was stimulated or received cardiopulmonary resuscitation. In addition, the patient's hospital discharge diagnosis was noted. Data were collected at the time of enrollment in the ED and included a review of the medical chart, as well as an interview with the parent or caregiver. Although all of the children who presented to the ED with an ALTE were to undergo standardized testing, the decision to obtain laboratory and radiographic testing was made by the treating physician. The investigators were responsible for collecting and recording data.
Comprehensive Urine Toxicology Screens
A positive comprehensive urine toxicology screen was defined as the identification of any medication on toxicology screen. Comprehensive urine toxicology screens were performed by using gas chromatography/mass spectrometry. Gas chromatography/mass spectrometry is considered the gold standard for drug identification.
A true-positive comprehensive urine toxicology screen was defined as follows: the identification of a medication on toxicology screen not consistent with medications that the child was known to be taking before his or her ED evaluation or administered during their evaluation and that was not considered a contaminant or the identification of a medication that the child was known to be taking. True-positive screen results were further defined as follows: clinically insignificant screen result (identification of a medication that would not cause an ALTE) or clinically significant screen result (identification of a medication that could cause apnea or other event consistent with an ALTE, even if it was a medication that the child was known to be taking). Thus, the identification of ranitidine in a patient currently taking ranitidine would not count as a clinically significant positive toxicology screen result, because it is not thought that ranitidine could cause an ALTE. However, identification of an OTC cold preparation, even if the child was known to be taking it, would count as a clinically significant positive toxicology screen result. Finally, true-positive screen results were also defined as follows: screen results were positive for an OTC cold preparation, and screen results were negative for an OTC cold preparation.
Clinical and demographic characteristics of study patients are reported as mean values or proportions along with appropriate SDs or 95% confidence intervals. Clinical and demographic characteristics of study patients who did and did not have a toxicology screen performed were compared by using analysis of variance, Student's t, Mann-Whitney U, χ2, or Fisher's exact test. The proportion of patients with a true-positive toxicology screen result, as well as the proportions of patients with a clinically significant positive screen result, was reported. Clinical and demographic characteristics of study patients with and without a clinically significant positive screen result and with and without a screen that tested positive for an OTC cold preparation were compared by using analysis of variance, Student's t, Mann-Whitney U, χ2, or Fisher's exact test. Similarly, results of laboratory testing were compared among study patients with and without a clinically significant positive screen result and with and without a screen that tested positive for an OTC cold preparation. For the purposes of analysis, a P value of ≤.05 was considered significant. Statistical tests were conducted using SPSS 13.0 for Windows 95 (SPSS Inc, Chicago, IL). Written, informed consent was obtained for each patient enrolled in the study. The hospital's institutional review board approved this study.
During the study period, 596 children with an ALTE presented to our ED. There were 285 (47.8%) boys; 411 children (69.0%) were white and 130 (21.8%) were black. The mean age of patients was 2.6 months (SD: 3.4 months). Two hundred and seventy-4 patients (46.0%) had a toxicology screen performed. The mean age of patients who had a toxicology screen performed was 2.5 months (SD: 2.8); 127 patients (46.4%) were male and 183 (66.9%) were white. Patients who had a toxicology screen were less likely to have a significant past medical history (38.3% vs 52.5%; P < .001), were less likely to be premature (19.4% vs 30.2%; P = .003), were less likely to have focal findings on physical examination (14.6% vs 21.7%; P = .025), and were more likely to have received cardiopulmonary resuscitation (18.9% vs 12.3%; P = .029).
Fifty of 274 toxicology screen results were considered true-positive (18.2%). Twenty-three screen results (23 of 274 [8.4%]) were considered clinically significant, and 13 (13 of 274 [4.7%]) were positive for a medication found in OTC cold preparations. Table 1 describes the results of toxicology screening. Clinical and demographic characteristics of patients who did and did not have a clinically significant, positive toxicology screen result are shown in Table 2. Patients with a clinically significant, positive toxicology screen result were more likely to have a history of a viral prodrome (52.1% vs 24.7%; P = .005) and to have an event that occurred during sleep (54.5% vs 33.2%; P = .045). In addition, patients with a clinically significant, positive screen result were more likely to be older (3.8 vs 2.4 months; P = .025) and to have a lower mean cell volume (86.7 vs 92.4 fL; P = .019) and venous HCO3 level (21.7 vs 23.6 meq/L; P = .028).
Clinical and demographic characteristics of patients who did and did not have a positive toxicology screen result for an OTC medication are shown in Table 3. Patients with a toxicology screen result that was positive for an OTC medication were more likely to have a family history of an ALTE (25.0% vs 6.2%; P = .05) and were more likely to have a history of a viral prodrome (69.2% vs 24.9%; P = .001). In addition, patients with a toxicology screen result that was positive for an OTC medication were more likely to be older (4.0 vs 2.4 months; P = .049) and to have a lower mean cell volume level (83.9 vs 92.3 fL; P = .007). Of note, no patient was noted to be taking an OTC cold preparation at the time of enrollment, and no parent admitted to having given their child an OTC cold preparation.
An ALTE is not considered a diagnosis but, rather, a description of an event for which there can be any number of underlying causes. Poisonings, either intentional or unintentional, have been described as a cause of events in some children. In our study, 8.4% of children presenting to the ED after an ALTE were found to have a clinically significant, positive comprehensive toxicology screen. The positive screen results were thought to represent a possible cause of the ALTE. Of note, 4.7% of screen results were positive for an OTC cold preparation despite the fact that no child had a history of being on such a medication and no parent admitted to giving their child such a medication.
To our knowledge, our study is the first study to systematically describe the results of comprehensive toxicology screening in infants presenting to an ED after an ALTE. Although previous reports have specifically described poisonings in children with ALTEs, they have tended to be case reports or case series, with only small numbers of patients. Hickson et al1 described 9 infants with an ALTE who were poisoned by a caretaker, whereas Hardoin et al2 described 8 patients who had ALTEs secondary to the use of a colic medication.
Surprisingly, and of particular importance, we found that ∼5% of our patients had toxicology screen results positive for medications found in common OTC cough and cold preparations. The use of these medications is not recommended in young children, and Food and Drug Administration dosing guidelines do not exist for children under the age of 2 years. Dosages at which such medications can cause illness in young children are not known. Cough and cold medications have been reported to cause apnea in very young infants and have been linked to infant deaths.4–6
Recently, the Centers for Disease Control and Prevention, in response to a report that had estimated that 1519 children <2 years of age were treated in US EDs for adverse events related to cough and cold medications in 2004 and 2005, initiated an e-mail inquiry of reports of deaths in infants <12 months of age because of cough and cold medications during 2005.7 The Centers for Disease Control and Prevention identified 3 infants between the ages of 1 and 6 months who were reported to have died because of a cough or cold medication. Medications identified included dextromethorphan and carbinoxamine (an antihistamine). Both of these medications were identified in our study population.
We suspect that a number of infants are given cold preparations, either inadvertently through breastfeeding or overtly in a misguided attempt to treat the symptoms of cough and congestion. It is even possible that caregivers may give these medications in an attempt to harm the infant. It is interesting to note that no parent or caregiver admitted to having given his or her child an OTC cold medication.
There are a number of limitations to our study. First, not all of the infants presenting to our ED had a comprehensive toxicology screen performed. Second, because there is no control group to compare to with regard to the findings of positive toxicology screen results, it is unclear whether our results are specific to children who have had an ALTE or are indicative of what occurs in the general population of children presenting to the ED. However, in light of the findings by the Centers for Disease Control and Prevention and recent declarations by the Food and Drug Administration, it may be that OTC cold medications are more widely used in this age group than suspected. Finally, we can only suspect, not prove, that the medications found on toxicology screens were the cause of some events in the study population. However, it has been shown that some medications in OTC cold preparations can cause apnea, and the identification of either cocaine or barbiturates would be important in possibly revealing otherwise occult child abuse. Of note, it is important to recognize that gas chromatography/mass spectrometry is considered the gold standard in the identification of drugs on urine toxicology screens. Thus, it is unlikely that the drugs identified on our screens could be explained as false-positives or as the result of cross-reactivity.
We believe that comprehensive toxicology screens should be included as part of the routine evaluation of children presenting to an ED with an ALTE.
- Accepted March 11, 2008.
- Address correspondence to Raymond D. Pitetti, MD, MPH, Department of Pediatrics, Children's Hospital of Pittsburgh, 3705 Fifth Ave, Pittsburgh, PA 15213. E-mail:
The authors have indicated they have no financial relationships relevant to this article to disclose.
What's Known on This Subject
There have been no published studies to date that have systematically evaluated the use of routine toxicology screens in children presenting with an ALTE.
What This Study Adds
To our knowledge, this is the first study to report on the use of comprehensive urine toxicology screens in children presenting with an ALTE. A significant proportion of young infants were found to have a positive screen result for an OTC cold preparation.
- ↵Hickson GB, Altemeier WA, Martin ED, Campbell PW. Parental administration of chemical agents: a cause of apparent life-threatening events. Pediatrics. 1989;83 (5):772– 776
- ↵Hardoin RA, Henslee JA, Christenson CP, Christenson PJ, White M. Colic medication and apparent life-threatening events. Clin Pediatr (Phila). 1991;30 (5):281– 285
- ↵US Department of Health and Human Services. Infantile Apnea and Home Monitoring: Report of a Consensus Development Conference. Publication NIH 87-2905. Bethesda, MD: US Department of Health and Human Services; 1986
- ↵Marinetti L, Lehman L, Casto B, Harshbarger K, Kubiczek P, Davis J. Over-the-counter cold medications: postmortem findings in infants and the relationship to cause of death. J Anal Toxicol. 2005;29 (7):738– 743
- Boland DM, Rein J, Lew EO, Hearn WL. Fatal cold medication intoxication in an infant. J Anal Toxicol. 2003;27 (7):523– 526
- Davis JM, Metrakos K, Aranda JV. Apnea and seizures. Arch Dis Child. 1986;61 (8):791– 793
- Copyright © 2008 by the American Academy of Pediatrics