PEM Pearls: An Approach to Infant Apnea

A 2-day-old female born at 41 weeks presents to the Emergency Department (ED) for an episode of apnea. Her parents noticed she stopped breathing, went limp, and turned blue. They are not sure for how long. The infant has had decreased urine output but is otherwise well without any other symptoms. Mom has an unspecified autoimmune condition and is taking hydroxychloroquine. The pregnancy and birth were largely uneventful. Mom was positive for Group B. Strep, had prolonged rupture of membranes, and was appropriately treated with antibiotics.

Vitals: The infant’s vital signs in the ED are within normal limits except for mild tachypnea.

Initial Exam: Her exam is nonfocal.

Background

Apnea among infants occurs when an infant stops breathing for 20 seconds or longer or stops breathing, for any amount of time, with bradycardia, cyanosis, pallor, and/or hypotonia. The overall incidence of apnea is 1 in 1,000 full-term infants. Infants who are premature (<37 weeks) are at increased risk for apnea; the incidence is almost 100% in infants born less than 28 weeks. Apnea is more common in premature infants due to their immature respiratory systems and physiologic stressors often manifest as respiratory depression in infants [1].

For infants that are actively apneic, the approach is similar to any pediatric resuscitation: ABCs (see ED approach below for management). 

For infants who had an apneic episode that has since resolved, one has more time to think about the differential. 

Differential Diagnosis

Apnea can be benign and physiologic, typically lasting between 5-10 seconds and more often occurring between 2 weeks to 6 months of life. Because physiologic stressors can manifest as respiratory depression in infants, the differential for pathologic apnea is broad. The following are broad categories to consider (similar to “the misfits” mnemonic for the crashing neonate).

1. Sepsis: UTI, pneumonia, necrotizing enterocolitis, meningitis/encephalitis 
2. Pulmonary disease: pneumonia, pneumothorax, viral illness  
3. Congenital heart disease 
4. Metabolic disease: glucose, inborn errors of metabolism, electrolytes 
5. Intracranial abnormalities
6. Non-accidental trauma 
7. Toxins: carbon monoxide, botulism, maternal opioid use 

It’s important to note that apnea in infants may qualify as a BRUE (brief, resolved, unexplained event). However, in this case, the infant is less than 60 days old. This is NEVER a low-risk BRUE [2]. 

Approach for the ED Provider

For the emergency provider, considering all of this can be overwhelming. Our job is to collect pertinent data, stabilize the infant, and start empiric treatment in order for the inpatient teams to further investigate the exact cause of the apnea. The following is a simplified ED approach: 

Key history questions:

1. How was the delivery: Was meconium present? Was there prolonged rupture of membranes? 
2. How was the pregnancy: Did mom get prenatal care? Were there any abnormal results with prenatal testing? What are mom’s medical conditions? Did mom get any treatment during her pregnancy (e.g. PCN for syphilis)?
3. How is the infant feeding, stooling, and urinating? Are there any other symptoms? 

Key workup to initiate (in bold are items we wouldn’t typically send for adult workups and may be forgotten by ED providers who do not primarily care for children):

1. VBG, CBC, CMP, ammonia (for metabolic conditions), blood culture, urinalysis, lumbar puncture (if concerned about sepsis)
2. Respiratory viral panel, pertussis (if endemic and/or area with low vaccination rates)
3. ECG, chest X-ray (if hypoxic or abnormal clinical exam)
4. Pre and post-ductal oxygen saturation and four-point blood pressure (for heart disease, primarily coarctation of the Aorta)

Key physical exam findings (undress the patient fully):

1. Are there bruises or other signs of abuse? 
2. What is the fontanelle size? How do the pupils appear?
3. Is there wheezing, rhonchi, or rales on lung auscultation? Are breath sounds equal? Is there increased work of breathing?
4. Is there abdominal distension or guarding?
5. Are there rashes? Is there edema in the extremities?

Management for infants currently apneic: ABCs.

1. Establish access, connect to monitors, and get a full set of vitals (including rectal temperature).
2. Support the airway. Start with oxygenation and ventilation. Utilize noninvasive pressure ventilation with continuous positive airway pressure (CPAP) or High Flow Nasal Canula (HFNC). Consider intubation if there is no improvement, however, do not jump immediately to intubation as an infant’s respiratory status can quickly change with respiratory support. 
3. Start CPR if there is no pulse or the pulse is less than 60 beats per minute.
4. Begin intravenous fluids at 10-20ml/kg (be careful if you have concerns about heart failure). 
5. Obtain a point of care glucose (and if available, venous blood gas). Consider naloxone if opioid ingestion is possible.

Management for the infants who are not currently apneic: 

1. Monitor vital signs and support respiration as needed (e.g. nasal cannula, CPAP).
2. Give empiric antibiotics if there is a concern for sepsis. Remember, avoid ceftriaxone in neonates less than 28 days due to concern for kernicterus. Instead, use ampicillin and gentamicin. Add vancomycin if concerned about MRSA.
3. Nutritional support – remember that infants have low glucose stores. Start maintenance fluids (D10W (if <28 days) or D5NS +/- KCl).
4. The NICU may want you to start caffeine and/or theophylline in the ED for treatment for apnea of prematurity.

Disposition is mainly to the Neonatal Intensive Care Unit (NICU).

Case Resolution

While in the ED, the infant desaturates to the 80s with improvement on HFNC. She has a full sepsis workup and is started on empiric antibiotics (ampicillin/gentamicin) and antivirals (acyclovir). The infant is found to have hypoglycemia and metabolic acidosis. Her neurologic, cardiac, and infectious workups are unremarkable and she doesn’t have any apneic/cyanotic episodes while hospitalized. She is discharged home with suspected hypoglycemia from poor feeding as the cause.

Conclusion

• The workup for apnea in infants is broad and not limited to pulmonary pathology.
• Remember your ABCs, ask key history questions (prenatal, intrapartum, postpartum), send key diagnostics (including ammonia and pertussis), and collect key physical exam findings (including pre and post-ductal saturation and four-point blood pressure).
• Call your NICU team early.
• You will likely not arrive at the cause of the apnea in the ED, but your early workup and empiric treatment (e.g. CPAP, antibiotics) are critical in caring for these infants.

Read more pediatric emergency medicine topics as part of the PEM Pearls Series on ALiEM.

References

1. Kondamudi NP, Khetarpal S. Apnea In Children. [Updated 2022 Jul 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. https://www.ncbi.nlm.nih.gov/books/NBK441894/ .Accessed September 21, 2022.
2. Tieder JS, Bonkowsky JL, Etzel RA, et al. Brief Resolved Unexplained Events (Formerly Apparent Life-Threatening Events) and Evaluation of Lower-Risk Infants [published correction appears in Pediatrics. 2016 Aug;138(2):]. Pediatrics. 2016;137(5):e20160590. PMID 27244835 

Read more pediatric emergency medicine topics as part of the PEM Pearls Series on ALiEM.