What is the mechanism by which prostins (prostaglandin analogs) cause apnea and fever in neonates or infants?

Mechanism of Prostin-Induced Apnea and Fever in Neonates

Apnea Mechanism

Apnea occurs in approximately 10-12% of neonates treated with prostaglandin E1 (alprostadil), most commonly in infants weighing less than 2 kg at birth, typically appearing within the first hour of infusion due to central nervous system depression. 1

Central Respiratory Depression Pathway

• Prostaglandins directly suppress the central respiratory drive in the medullary respiratory centers of the brainstem, particularly affecting the immature respiratory control mechanisms in neonates 1
• The effect is most pronounced in preterm and low birth weight infants (<2 kg) who already have baseline immaturity of central nervous system respiratory regulation 2
• This central depression mechanism is distinct from the peripheral pulmonary effects of prostacyclins used for pulmonary hypertension treatment 2

Clinical Risk Factors

• Neonates with immature hepatic and renal function have altered ability to metabolize and excrete prostaglandins, resulting in prolonged drug exposure and increased apnea risk 2
• Former preterm infants have an increased baseline risk of postanesthesia apnea, which may be compounded by prostaglandin administration 2
• The apnea risk necessitates that respiratory status be monitored throughout treatment with immediate ventilatory assistance available 1

Fever Mechanism

Prostaglandins, particularly PGE1 and PGE2, directly reset the hypothalamic thermoregulatory set point upward by acting on the preoptic area of the anterior hypothalamus, causing fever as a central pyrogenic effect.

Hypothalamic Temperature Regulation

• Prostaglandins act as endogenous pyrogens by binding to EP3 receptors in the hypothalamic thermoregulatory center
• This binding triggers an increase in the hypothalamic temperature set point, leading the body to generate heat through increased metabolic activity and vasoconstriction
• The fever response is a direct pharmacologic effect rather than an inflammatory or infectious process

Clinical Implications

• Fever from prostaglandin infusion is predictable and dose-related, distinguishing it from infectious causes
• The pyrogenic effect is reversible upon discontinuation of the prostaglandin infusion
• Monitoring for fever is part of standard vital sign surveillance during prostaglandin therapy 1

Critical Management Considerations

Immediate Preparedness Requirements

• Ventilatory assistance must be immediately available before initiating prostaglandin therapy, including equipment for bag-valve-mask ventilation, CPAP, and potential intubation 1
• Personnel must be skilled in airway management and rescue from apnea, including ability to open the airway, suction secretions, and perform cardiopulmonary resuscitation 2
• Continuous pulse oximetry and respiratory monitoring are required throughout the infusion period 2

High-Risk Population Monitoring

• Neonates weighing <2 kg require the most intensive monitoring during the first hour of prostaglandin infusion when apnea risk is highest 1
• Extended postsedation monitoring is necessary for neonates and former preterm infants due to prolonged drug effects from immature metabolism 2
• Consider that apnea may necessitate mechanical ventilation if it is resistant to stimulation and repositioning 3

Distinguishing from Other Causes

• When apnea occurs during prostaglandin therapy, exclude secondary causes such as metabolic disturbances, sepsis, or intracranial pathology before attributing it solely to the medication 3
• Fever during prostaglandin infusion should be distinguished from infectious etiologies through appropriate clinical assessment and laboratory evaluation when indicated
• The temporal relationship to drug initiation (apnea within first hour, fever as ongoing effect) helps confirm prostaglandin as the causative agent 1