Apnea in the Newborn

Rajiv Aggarwal, Ashwini Singhal, Ashok K Deorari, Vinod K Paul Division of Neonatology, Department of Pediatrics All India Institute of Medical Sciences Ansari Nagar, New Delhi –110029

Address for correspondence: Dr Vinod K Paul Additional Professor Department of Pediatrics All India Institute of Medical Sciences Ansari Nagar, New Delhi 110029 Email: vinodkpaul@hotmail.com

. An approach to the management of apnea in neonates has been described. Apnea is a common manifestation of various etiologies in sick neonates. defined as cessation of breathing resulting in pathological changes in heart rate and oxygen saturation.2 Abstract Apnea. Secondary causes of apnea should be excluded before a diagnosis of apnea of prematurity is made. Methylxanthines and Continuous Positive Airway Pressure form the mainstay of treatment of apnea in neonates. Mechanical ventilation is reserved for apnea resistant to above therapy. In preterm children it may be related to the immaturity of the central nervous system. is a common occurrence in sick neonates.

Apnea is a pathological cessation of breathing that results in physiological changes (decrease in central drive. bradycardia. is usually not associated with any physiological changes in the infant and does not merit any treatment. peripheral perfusion. Definition Apnea is defined as cessation of respiration for >20 sec or cessation of respiration of any duration accompanied by bradycardia (HR <100/min) and/or cyanosis. . AOP is related inversely to gestational age with 25% of preterm below 34 weeks needing either pharmacological or ventilatory support for repeated apneic episodes.3 Apnea in the Newborn 1. Periodic breathing is a normal event. 3. Introduction About 30-45% of preterm babies exhibit a periodic breathing pattern characterized by 3 or more respiratory pauses of greater than 3 seconds duration with less than 20 seconds respiration between pauses. 2. It may be secondary to other causes and is a common manifestation of most neonatal diseases. Incidence Apnea in preterms is usually related to immaturity of the central nervous system and is called Apnea of Prematurity (AOP). cyanosis. hypotonia) and merits treatment.

intracranial hemorrhage. intracranial infections. pneumonia.1 Central apnea: (40%) Both the inspiratory effort and airflow cease simultaneously in this type of apnea (Absence of chest wall movement and airflow). pulmonary hemorrhage. This condition usually presents after 1-2 days of life and within the first 7 days. congestive heart failure. 5. perinatal asphyxia. obstructive airway lesion. Secondary causes: Secondary causes of apnea include: (a) Temperature problems: Hypothermia and hyperthermia. Apnea of prematurity: It is probably related to immaturity of the central nervous system. hyponatremia. 4. esophagitis (f) Hematological: Anemia. drugs. (d) Cardiac: Congenital cyanotic heart disease. Apnea presenting within the first 24 hours or after 7 days of age is unlikely to be AOP.1. hypocalcemia. necrotizing enterocolitis (h) Metabolic: Hypoglycemia. anesthetic drugs (c) Pulmonary: Respiratory distress syndrome (RDS). asphyxia. Causes of apnea1 4. 5. patent ductus arteriosus (e) Gastro-intestinal: Gastro esophageal reflux. pneumonia.4 4. hypernatremia and (i) Inborn errors of metabolism Apnea of prematurity is a diagnosis of exclusion and should be considered only after secondary causes of apnea have been excluded. (b) Neurological: Birth trauma. Types of apnea 5. pneumothorax. temperature instability and anemia. chronic lung disease. . polycythemia (g) Infections: Sepsis. Common causes of secondary apnea include sepsis. hypo/hypertension.2.2 Obstructive apnea: (10%) This type is characterized by absence of airflow in the presence of inspiratory efforts (Presence of chest wall movement but no airflow).

Apnea monitors based on chest wall movement are likely to miss obstructive apnea. 6. 7.3 Pulse oximeters: These are commonly used for monitoring of apnea.3 Mixed apnea: (50%) Central apnea is either preceded or followed by airway obstruction. In general. these monitors will fail to diagnose obstructive apnea and may not distinguish body movements from breathing. as respiratory activity. Monitors with facilities for measuring heart rate and oxygen saturation would be useful in the monitoring of significant apnea in preterm infants.5 5. These monitors will also fail to diagnose obstructive apnea. Apnea monitors 7.1 Movement sensors: (Ripple type mattress) These monitors interpret chest/ abdominal movements as respiration. .2 Thoracic impedence based monitors: These monitors translate changes in thoracic impedence that occur with breathing. 7. These monitors detect changes in heart rate and/ or saturation due to apneic episodes. Monitoring All babies less than 34 weeks gestation should be monitored for at least the first week of life or till absence of apneic episodes for at least 7 days. Babies ≥34 weeks gestation should be monitored if they are sick 7. Facility for detecting chest wall movement is absent in these monitors.

Provide oxygen if patient is hypoxic (maintain saturation 92-95%) by head box or nasal cannula. twitching movements. If the newborn continues to remain apneic and does not respond to tactile stimulation. 8.1 Periodic breathing: It consists of breathing for 10-15 seconds. then the infant should be managed with positive pressure ventilation. cyanosis and airway obstruction. ventilation with bag and mask (BMV) using 100% oxygen should be initiated. Differential diagnosis 8. the infant should be evaluated for a possible underlying cause. Evaluation of a child with apnea 9. The neck should be positioned in slight extension. If BMV fails to initiate spontaneous respiration in the newborn. followed by apnea for 5-10 sec without change of heart rate or color. oro-pharynx gently suctioned and tactile stimulation should be given. vacant stare and up rolling of eyes suggests a seizure. Most apneic spells respond to tactile stimulation. Also tachycardia preceding/ accompanying an apneic attack usually suggests seizure activity. 9. It does not occur within the first 2 days of life. Sudden alteration in muscle tone.6 8.2 Clinical examination After stabilization.2 Subtle seizures: Apnea is an uncommon presentation of a neonatal seizure. History should be reviewed for possible causes of secondary apnea including perinatal asphyxia. maternal drugs. 9.1 Emergency treatment The neonate should be checked for bradycardia. features of neonatal sepsis and feeding intolerance. The infant should be .

abdominal x-ray. hypoglycemia. polycythemia. 10. ultrasound head and other investigations depending on the history and physical examination. Onset of apnea within the first 7 days in a premature baby (gestation < 34 weeks) would be suggestive of apnea of prematurity (AOP). respiratory distress syndrome (RDS). anemia. • Treatment of the underlying cause: sepsis. Treatment 10. hypocalcemia. Decrease environmental temperature to lower end of thermo-neutral range. hypotension. pallor. doxapram . Investigations that should be considered include blood glucose. breathing and circulation (ABC) Avoid vigorous suctioning of the oro-pharynx Avoid oral feeds for at least 24 hours. 10. 9.3 Investigations Neonates with apnea should be investigated to exclude common causes of secondary apnea. arterial blood gas.2 Specific measures Specific measures include: • Drugs including aminophylline. electrolytes. blood culture.7 examined for temperature instability. jaundice. Avoid swings in environmental temperature. • Transfuse packed cells if hematocrit <30%. hematocrit. chest x-ray. septic screen. caffeine. cardiac murmur and poor perfusion.1 General measures: • • • • Maintain airway.

11. Post extubation to reduce the incidence of apnea3. The indications for starting drugs are: • • First line of treatment for apnea of prematurity2. Aminophylline should be continued till 34 weeks corrected gestational age and stopped thereafter if no episodes of apnea have occurred in the last 7 days4. Oral: Theophylline 50 mg/5 ml in Theoped syrup .5-2. The drug is available as: Injection: Aminophylline ampoule 250 mg per 10-ml ampoule.0 mg/kg/dose Q6-8H given IV or PO. Serum levels if available should be maintained between 7-12 µg/ml.1 Theophylline and Aminophylline The loading dose of Aminophylline is 5-7 mg/kg administered IV followed by a maintenance dose of 1. caffeine and doxapram have been used in the treatment of apnea. Pharmacotherapy Aminophylline. For apnea of prematurity. There is no role for prophylactic aminophylline against apnea of prematurity6 Adverse effects include tachycardia. Do not discharge the patient until methylxanthines have been stopped. vomiting and hyperglycemia. Aminophylline initiated in order to facilitate extubation may be stopped after 7 days. feed intolerance. irritability.5.8 • • • Continuous positive airway pressure (CPAP) Mechanical ventilation Kinesthetic stimulation: no role 11. jitteriness.

Adverse effects include seizures. The loading dose is preferably avoided.6-32. The adverse effects and duration of therapy are similar to aminophylline.4 Which drug to use? .5 mg/kg/hr. hyperglycemia and abdominal distension.2 Caffeine7 Caffeine also belongs to the methylxanthine group and is considered as an alternative to aminophylline. The loading dose is 10 mg/kg IV or PO (20-mg/kg caffeine citrate) followed by a maintenance dose of 2. 11. The drug is not available in India at present. hyperactivity. It is associated with fewer side effects than aminophylline8. Doxapram infusion is started at 0. The recommended dose of 2-2.4 mg/kg/day of benzyl alcohol. Injection doxapram has 0. there have been case reports of “gasping syndrome” with this lower dose in literature. Doxapram may be tried for a period of 48 hours before weaning the drug.9% benzyl alcohol as a preservative.9 11. Although this dose is below the toxic dose of alcohol (45 mg/kg/day). hypertension. Methylxanthine therapy should be continued during doxapram infusion. Toxic levels are >40-50 µg/ml.3 Doxapram9 Doxapram is associated with serious side effects and hence should be used with caution or preferably avoided10. indications for doxapram include a failure to respond to both methylxanthine and CPAP therapy. The serum levels should be maintained between 5-25 µg/ml. It should be avoided in the initial few days since hypertensive episodes may be associated with an increased risk of intraventricular hemorrhage (IVH). At present. 11.5 mg/kg/hr would deliver 21.5 mg/kg/hour and increased gradually to a maximum of 2-2. 24 hours after loading dose (5 mg/kg of caffeine citrate).5 mg/kg OD IV or PO.

Hence we prefer to use aminophylline as the drug of first choice in the management of apnea of prematurity. We avoid using doxapram and use CPAP as the next step after aminophylline in the algorithm for management of apnea. which is not available in India. The drug of choice would be caffeine. Adverse effects of CPAP include barotrauma. A CPAP of 3-5cm H 2O is usually used. Continuous positive airway pressure Indications for using continuous positive airway pressure (CPAP) in the treatment of apnea include a failure to respond to methylxanthine therapy11. CPAP has no role in prophylaxis against apnea of prematurity. Endotracheal CPAP is not used in the treatment of apneic spells. Hence CPAP is effective in the management of all types of apnea. 12. splints the upper airway during respiration and prevents collapse of the pharynx during expiration. However their clinical use is dependent upon adverse effects. Indications for starting CPAP in a neonate on aminophylline therapy include (a)>1 episode of apnea needing either BMV or oxygen supplementation within 24 hours (b)>12 episodes in 24 hours (or >6 within in 12 hours) needing tactile stimulation and (c)> 1 episode of apnea (spontaneous) every hour for 12-24 hours.10 Present evidence shows that aminophylline. CPAP may be delivered by nasal prongs or nasopharyngeal tube. caffeine and doxapram are equally effective in the treatment of apnea. abdominal distention. feeding intolerance and local nasal irritation . CPAP may also be used to reduce post-extubation apnea in preterm infants12 Continuous positive airway pressure (CPAP) improves oxygenation.

Mechanical Ventilation The infant should be ventilated if both pharmacotherapy and CPAP have been tried and significant apneas continue to occur. Methylxanthine therapy should be continued if apneic episodes continue to occur beyond 34 weeks of corrected gestational age. 15. Kinesthetic stimulation Water bed.40 seconds) and low FiO2 (0. Persistent apnea Apneic episodes may persist beyond 37-40 weeks in some infants.35-0. especially those born before 28 weeks. This method is effective in all forms of apnea. Present evidence does not support any role for this mode of therapy either in the prevention or treatment of apnea13. 16. 14. Home monitoring is not possible in our country and these infants would require NICU care until drugs can be weaned and stopped. oscillating bed mattress. the infant should be ventilated at minimum pressures (peak inspiratory pressure of 13-14 cm of water and positive end expiratory pressure of 4-5 cm of water). small Ti (0. The neonate should be re-evaluated for secondary causes of apnea especially neurological problems and gastroesophageal reflux.5). Sudden Infant Death Syndrome (SIDS) and Apnea There is evidence to suggest that AOP is not an independent risk factor for SIDS. If the lungs are normal.4-0. Only 24% of patients with SIDS have a history of AOP. low rate (20-25 per minute).11 13. .

Methylxanthine treatment for apnea in preterm infants. WB Saunders. Cochrane Database Syst Rev 2000. Hansen T. Henderson-Smart DJ. Cochrane Database Syst Rev 2000. Cochrane Database Syst Rev 2000. J Pediatr 1986. Steer P. Clin Perinatol 1992. Cochrane Database Syst Rev 2000. Ballard RA.(2):CD000432. Bhatia J. Shaffer S. Davis PG. Continuous positive airway pressure versus theophylline for apnea in preterm infants. Philadelphia pp 552-61 6. Steer PA. Clin Pediatr 2000. Prophylactic methylxanthine for prevention of apnea in preterm infants.(2):CD000273 9.3:61-79 8. Henderson-Smart DJ. 7. Subramanian P. Doxapram treatment for apnea in preterm infants. Hall RT. Cochrane Database Syst Rev 2000. Miller MJ.19:789-808 5.(2):CD001072 . Apnea of prematurity. Davis PG. Cater G. Corbet A.(2):CD000140 3.(2):CD000074 11. Taeusch HW.12 References: 1. Steer PA. Prophylactic methylxanthine for extubation in preterm infants. Martin RJ. Comer AM. Caffeine versus theophylline for apnea in preterm infants. Eds.(2):CD000139 4.39:327-36 2. Henderson-Smart DJ. Henderson-Smart DJ. Caffeine citrate: a review of its use in apnea of prematurity. In Avery’s diseases of the newborn 7th edn 1998. Perry CM. Current options in the management of apnea of prematurity. Henderson-Smart DJ.109:563 10. Figgitt DP. Doxapram for apnea of prematurity. Pediatr Drugs 2001. Henderson-Smart DJ. Control of breathing. Cochrane Database Syst Rev 2000. Steer PA.

Osborn DA. Cochrane Database Syst Rev 2000.13 12. Henderson-Smart DJ.(2):CD000143 13.(2):CD000499 . Davis PG. Cochrane Database Syst Rev 2000. Henderson-Smart DJ. Kinesthetic stimulation for treating apnea in preterm infants. Nasal continuous positive airway pressure immediately after extubation for preventing morbidity in preterm infants.

ABG: arterial blood gas. Ca: calcium.PCV.14 Algorithm for management of neonatal apnea Neonate with apnea Emergency treatment Temperature. Na: sodium. AXR Na. circulation. US: ultrasound CPAP: continuous positive airway pressure. K. BS: blood sugar. breathing.ABG Sepsis screen CXR. K: potassium. PCV: packed cell volume. ABC Evaluation to exclude secondary causes of apnea Apnea of prematurity Investigations BS. Ca US Head Start specific Treatment Start aminophylline Apnea responds No response Trial of doxapram Continue till 34 weeks CPAP No response Stop drugs if no apnea for last 7 days Fails Responds Continue x 48 hours IMV Abbreviations: ABC: airway. IMV: intermittent mandatory ventilation .

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