Comparative Effects of Aminophylline, Caffeine, and Doxapram in Hypoxic Neonatal Dogs Born by Cesarean Section

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Abstract
Background: Perinatal hypoxia is a leading cause of early mortality in canine neonates and accounts for over 90% of early deaths in canine neonates. Respiratory depression may result from dystocia, prolonged labor, or anesthetic protocols used during cesarean delivery, requiring rapid pharmacological support. This study evaluated the effects of aminophylline, caffeine, and doxapram on clinical and biochemical viability parameters in hypoxic neonatal dogs. Methods: Forty-five puppies born via elective or emergency cesarean section were included, of which 35 exhibiting cardiorespiratory depression (heart rate ≤ 180 bpm, respiratory rate < 15 movements per minute, Apgar score < 7, and reflex score < 3) were randomly allocated into aminophylline group (AG; n = 12), caffeine group (CafG; n = 11), or doxapram group (DG; n = 12). Ten clinically healthy neonates constituted the physiological control group (CG). Apgar score, neonatal reflexes, lactate, blood glucose, oxygen saturation, blood gas parameters, and cardiac troponin I (cTnI) were evaluated immediately after birth (M1) and 10 min following treatment (M10). Results: No significant differences were observed in laboratory parameters among groups (p > 0.05). Although all evaluated drugs improved clinical status by increasing heart rate, respiratory rate, and reflex scores, caffeine produced the greatest enhancement in vitality. The Δ Apgar score showed a significant difference between CafG and DG (p = 0.0095), while no statistical differences were detected between AG and CafG (p = 0.08) or between AG and GD (p = 0.60). Conclusions: Aminophylline, caffeine, and doxapram supported postnatal resuscitation in hypoxic neonatal puppies; however, caffeine demonstrated superior improvement in Apgar recovery, suggesting its potential as a preferred pharmacological adjunct in neonatal canine resuscitation protocols.
Funding Information
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (2023/17018-1)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (305152/2024-6)

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