Magnesium sulfate after transient hypoxia-ischemia fails to prevent delayed cerebral energy failure in the newborn piglet

Severely birth-asphyxiated human infants develop delayed (''secondary'') cerebral energy failure, which carries a poor prognosis, during the first few days of life. This study tested the hypothesis that i.v. magnesium sulfate (MgSO4) after severe transient cerebral hypoxia-ischemia decreases the severity of delayed energy failure in the newborn piglet. Twelve piglets underwent temporary occlusion of the common carotid arteries and hypoxemia. Resuscitation was started when cerebral [phosphocreatine (PCr)]/[inorganic phosphate (P-i)], as determined by phosphorus magnetic resonance spectroscopy, had fallen virtually to zero, and nucleotide triphosphate (NTP) had fallen below a third of baseline. The piglets were randomized to receive, blind, either: I) three i.v. infusions of 12.5% MgSO4 heptahydrate solution: 400 mg . kg(-1) MgSO4 . 7H(2)O starting 1 h after resuscitation, and 200 mg . kg(-1) 12 and 24 h later (n = 6), or 2) three infusions of placebo, 0.9% NaCl (n = 6). Phosphorus and proton spectroscopy were continued until 48 h after resuscitation, and values were compared between the two groups. Mean plasma magnesium levels, 1 h after each of the three doses of MgSO4, were 2.1, 2.0, and 1.9 mmol . L(-1), respectively, The severity of the primary insult, determined by the time-integral of depletion of cerebral [NTP]/[exchangeable phosphate pool (EPP)], was similar in the MgSO4-treated and placebo groups. After resuscitation, there was no difference in the progression or severity of delayed energy failure between the two groups, as judged by cerebral [PCr]/[P-i], [NTP]/[EPP], or lactate/creatine and N-acetylaspartate/creatine peak-area ratios. We conclude that MgSO4 did not decrease the severity of delayed cerebral energy failure.