Do All Infants With Apparent Life-Threatening Events Need to Be Admitted?

METHODS

This study was a prospective observational analysis of consecutive patients with ALTEs who presented to the ED between July 2002 and April 2005. This study was approved by the institutional review board. The National Institutes of Health statement included in the introduction was used to define ALTEs for the purposes of this study.

Our hospital is a tertiary-care, freestanding, academic, pediatric facility with a dedicated ED (annual census: 60000). Of all infants with ALTEs who present to our ED, most are admitted to the hospital, although some are not. The purpose of this study was to develop criteria that might predict whether admission was required. In determining which patients with ALTEs required admission, 2 primary questions were addressed, as follows. The first involved predictive criteria. What potential patient characteristics could be used to predict the risk of serious sequelae in infants with ALTEs? These were tested against outcome criteria to determine whether they predicted accurately the need for admission. To stratify risk, we analyzed factors assumed or debated in the literature to increase the risk of SIDS, including (1) family history of SIDS, (2) patient history of moderate prematurity (gestational age between 30 weeks and 37 weeks), (3) previous ALTEs, (4) patient age, (5) presence of upper respiratory infection symptoms, (6) child's color and tone during the ALTE, (7) duration of the ALTE, as estimated by observers, (8) interventions required, (9) appearance of the child in the ED, (10) suspicion of child abuse, and (11) multiple ALTEs within 24 hours.

The second question involved outcome criteria. What outcomes would be considered to mandate admission? We considered any of the following factors to require admission: (1) subsequent events requiring resuscitation during hospitalization, (2) any subsequent ALTEs and an identifiable pathologic condition that was treated during hospitalization, (3) a diagnosis made after admission that would have put the patient at risk with discharge and would normally necessitate admission if identified in the ED (eg, child abuse or serious neonatal bacterial infection), or (4) development of a life-threatening condition (eg, hypoxemia or respiratory failure) during hospitalization.

Infants <12 months of age were included if they had a convincing history of an ALTE, as determined by the attending physician in the ED. Infants were excluded for a history of extreme prematurity (estimated gestational age of <30 weeks was chosen because of the high risk of persistence of apnea of prematurity for infants with estimated gestational ages of 24–28 weeks¹⁷), uncorrected cardiac disease, known seizure disorder, significant developmental delay, or chronic lung disease requiring treatment. Patients under the care of a neonatologist or pulmonologist because of previous ALTEs were also excluded. All charts were also reviewed by the principle investigator to ensure that the child met the definition of an ALTE and did not meet any exclusion criteria. If a child had an episode of apnea attributable to a clearly discernible disease diagnosed by the ED (ie, pertussis), these were not labeled as ALTEs, and the infants were not included. We included both well- and ill-appearing children. Institutional review board-certified personnel were present 7 days per week, 24 hours per day, to collect a consecutive sample of patients. No family refused consent.

Because this study was purely observational, no modifications were made to the patients' treatment or disposition because of the study. In the ED, the treating physician completed a form documenting the patient characteristics described above. Studies were performed and patients were admitted or discharged at the discretion of the attending physician. Discharged patients were contacted by telephone at 24 to 72 hours, and admitted patients were observed for additional episodes, results of testing, and final diagnosis during their hospital stay. Attempts were also made to contact all patients at 1 week, to obtain outcome data. Regardless of whether patients were actually admitted to the hospital, all patients were categorized as either hospitalization required (HR) or hospitalization not required (HNR), on the basis of the outcome criteria discussed above. Briefly, patients who required resuscitation during hospitalization, experienced subsequent events attributable to a condition identified during hospitalization, or were diagnosed as having a condition that would have put the patient at risk of acute deterioration if he or she had been discharged were classified as HR. Admitted patients who were discharged without an imminently life-threatening diagnosis and experienced either no events or minor, self-resolved events during hospitalization were classified as HNR. Patients discharged from the ED were contacted at 24 to 72 hours and, if well and without subsequent events, were also placed in the HNR category.

Odds ratios (ORs) for the need for hospitalization were calculated by using univariate analyses. Multivariate analysis was not performed because of the small number of patients who ultimately required hospitalization in each subset. Significance was tested by using Fisher's exact tests. In addition, we attempted to develop criteria that would predict with nearly 100% negative predictive value that a child would not require hospitalization. The sample size goal was to enroll sufficient patients to provide a negative predictive value with the lower end of the 95% confidence interval (CI) at 90%. The sensitivity, specificity, and predictive values of these pooled criteria were calculated with CIs.

RESULTS

Sixty-four patients were enrolled, and 59 were included in the final analysis. Of the 5 eliminated, 1 did not meet the definition of an ALTE, 2 met exclusion criteria, and 1 was discharged from the ED and subsequently could not be reached; 1 was well without subsequent events when seen 45 hours into the hospital stay, but all subsequent records were lost and the treating physician could not be contacted. Of the 59 patients in the final analysis, 55 were actually admitted to the hospital, and 4 were discharged from the ED.

In our analysis, 8 (14%) of the 59 patients were placed in the HR category. These 8 patients were all admitted. Two required PICU transfer, 3 had multiple significant apneic episodes while hospitalized, 1 developed an oxygen requirement, and 2 required treatment for significant infectious or neurologic conditions. More information on the patients who required hospital admission is listed in Table 1. The remaining 51 patients did not experience an event or receive a diagnosis that would have required hospitalization and thus were placed in the HNR category. Four of the HNR patients were discharged from the ED and subsequently contacted by telephone, and 47 were admitted.

The most common unifying features of the 8 HR patients were a history of multiple ALTEs within 24 hours of admission (7 of 8 patients) and age of ≤1 month (5 of 8 patients). Prematurity (gestational age of <37 weeks) was also common (3 of 8 patients). When the HR and HNR groups were compared, a history of multiple ALTEs and prematurity proved to be significantly different. An intergroup comparison of the symptoms studied is listed in Table 2.

Because a history of multiple ALTEs and age of ≤1 month (defined as 30 days) were the most common features noted among the HR infants, we evaluated the utility of using either of these features as a criterion for admission. Admitting all patients with ALTEs who were <1 month of age and/or had a history of multiple ALTEs would provide a sensitivity and negative predictive value of 100% to identify patients who require admission, according to our aforementioned outcome criteria. Because an adverse outcome was a rare event in our population, the CI for the sensitivity was large; however, the CI of the negative predictive value was 90% to 100%. Tables 3 and 4 contain the data and the sensitivity, specificity, and predictive values for this tool in identifying infants who require admission.

DISCUSSION

Our study shows that only 14% of the patients who presented to our ED with a diagnosis of ALTE had a condition or subsequent event necessitating hospitalization. The high-risk criteria (multiple ALTEs within 24 hours and age of ≤1 month) identified each of those patients with a negative predictive value of 100%, with a CI lower limit of 90%. Therefore, the possibility of being able to discharge safely a subset of well-appearing, low-risk patients with ALTEs exists, if the results of this pilot study are borne out in a larger, multicenter population of patients with ALTEs. In our small group of 59 infants, 26 (44%) who did not meet high-risk criteria could have been discharged safely from the ED.

Several additional patient characteristics were found to be predictive of subsequent events with calculation of ORs, most notably prematurity (OR: 14) and blue discoloration of the face during the ALTE (OR: 4). These were not included in our high-risk criteria, and all premature or cyanotic patients in our study population who required hospitalization also met the high-risk criteria. However, prudence suggests that prematurity should play a role in physician decision-making. Similarly, we did not include ill appearance in our criteria. Five patients looked ill at presentation, and all of those infants met the high-risk criteria regardless of appearance. Nonetheless, our personal practice continues to be that a child should be well-appearing and have follow-up care ensured to be discharged. No child in this study was admitted for social reasons or suspicion of nonaccidental injuries; however, these factors may be considerations for certain infants with apnea.

Previous studies suggested a higher incidence of SIDS for patients with a family history¹¹ and higher rates of subsequent events for children requiring resuscitation or experiencing multiple events at home¹¹ and those with prolonged apnea and normal muscle tone during the event.¹⁸ Our study was not powered specifically to assess this, but we found no association between the degrees of resuscitation perceived necessary by the parents or the muscle tone during the event and the need for hospitalization. Although it was not the focus of this study, because it would not affect an ED physician's decision to admit a patient in the short term, we attempted to obtain long-term follow-up data on the patients included. One third of the patients were contacted successfully at 3 months. Of those, 2 HNR patients experienced subsequent nonfatal ALTEs (one 3 weeks after discharge and one 6 weeks after discharge), and 1 HNR patient developed possible cardiomyopathy 3 months after admission.

Because the vast majority of our patients fared well throughout their admissions, the number requiring hospitalization was low, which yielded a large CI for the sensitivity of our criteria. However, this does support the rarity of subsequent events and life-threatening conditions for otherwise asymptomatic ALTE patients and the use of a negative predictive value to assess the utility of our work. Ideally, a larger validation set could be tested in a future multicenter study, to confirm our findings. Clearly, the specificity is unacceptably low to be useful; however, our goal was to ensure that all high-risk children are admitted, and we are willing to accept a low specificity to maintain adequate sensitivity and negative predictive value. The 1 patient who was lost to follow-up monitoring after being discharged from the ED presents an additional limitation. Although this child's outcome is not known, there is no record of a return visit to our ED or any complaint or legal action initiated within 2 years after the child's discharge.

CONCLUSIONS

Our study showed that only 14% of infants presenting with an ALTE to the ED had a subsequent clinical course that would have required hospitalization for diagnosis or protection from acute deterioration. All of these cases were predicted because the infants had multiple ALTEs before the ED visit and/or they were <30 days of age. We speculate that most infants who do not meet these high-risk criteria can be discharged safely from the ED.