Induced brain hypothermia in  asphyxiated human newborn infants:  a retrospective chart analysis  of physiological and adverse effects

Simbruner, G; Haberl, C.; Harrison, V. C.; Linley, L L; Willeitner, A.

doi:10.1007/s001340051020

Cited by 75 publications

(26 citation statements)

References 30 publications

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“…Recent human pilot studies examined the efficacy and safety of total body cooling or selective head cooling during neonatal encephalopathy in infants who were not routinely sedated (35)(36)(37)(38).…”

Section: Discussionmentioning

confidence: 99%

Twenty-Four Hours of Mild Hypothermia in Unsedated Newborn Pigs Starting after a Severe Global Hypoxic-Ischemic Insult Is Not Neuroprotective

et al. 2001

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Three to 12 h of mild hypothermia (HT) starting after hypoxiaischemia is neuroprotective in piglets that are anesthetized during HT. Newborn infants suffering from neonatal encephalopathy often ventilate spontaneously and are not necessarily sedated. We aimed to test whether mild posthypoxic HT lasting 24 h was neuroprotective if the animals were not sedated. Thirty-nine piglets (median weight 1.6 kg, range 0.8 -2.2 kg; median age 24 h, range 7-48 h) were anesthetized and ventilated and subjected to a 45-min hypoxic (FiO 2~6 %) global insult (n ϭ 36) or sham hypoxia (n ϭ 3). On reoxygenation, 18 were maintained normothermic (NT, 39.0°C) for 72 h, and 21 were cooled from 39 (NT) to 35°C (HT) for the first 24 h before NT was resumed (18 experimental, three sham hypoxia). Cardiovascular parameters and intermittent EEG were documented throughout. The brain was perfusion fixed for neuropathology and five main areas examined using light microscopy. The insult severity (duration in minutes of EEG amplitude Ͻ 7V) was similar in the NT and HT groups, mean Ϯ SD (28 Ϯ 7.2 versus 27 Ϯ 8.6 min), as was the mean FiO 2 (5.9 Ϯ 0.7 versus 5.8 Ϯ 0.8%) during the insult. Six NT and seven HT piglets developed posthypoxic seizures that lasted 29 and 30% of the time, respectively. The distribution and degree of injury (0.0 -4.0, normal-maximal damage) within the brain (hippocampus, cortex/white matter, cerebellum, basal ganglia, thalamus) were similar in the NT and HT groups (overall score, mean Ϯ SD, 2.3 Ϯ 1.5 versus 2.4 Ϯ 1.3) as was the EEG background amplitude at 3 h (13 Ϯ 3.5 versus 10 Ϯ 3.3 V).The HT animals shivered and were more active. The sham control group (n ϭ 3) shivered but had normal physiology and neuropathology. Plasma cortisol was significantly higher in the HT group during the HT period, 766 Ϯ 277 versus 244 Ϯ 144 M at 24 h. Mild postinsult HT for 24 h was not neuroprotective in unsedated piglets and did not reduce the number of animals that developed posthypoxic seizures. Cortisol reached 3 times the NT value at the end of HT. We speculate that the stress of shivering and feeling cold interfered with the previously shown neuroprotective effect of HT. Many studies on newborn animal models show that mild HT, which starts after an HI insult, is neuroprotective (1-5). The duration of HT in these studies varies from 3 to 72 h, and the reduction in body temperature varies between 3.5 and 6°C. Some studies, however, show only a minor beneficial effect (6), or the neuroprotection is temporary and not maintained (7).

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Section: Discussionmentioning

confidence: 99%

Twenty-Four Hours of Mild Hypothermia in Unsedated Newborn Pigs Starting after a Severe Global Hypoxic-Ischemic Insult Is Not Neuroprotective

et al. 2001

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“…Risk-benefit assessment should take into account relevant data from laboratory models of asphyxial arrest, 8,30 -32 results from trials of adult cardiac arrest, 18,19 and reports on the use of hypothermia in treatment of neonatal asphyxia. [33][34][35][36][37][38] The results of therapeutic hypothermia are generally favorable in laboratory models of hypoxic ischemic injury to immature brains of various species. Preliminary data from clinical trials of perinatal asphyxia indicate that induced hypothermia is feasible and safe, but data on long-term neurological morbidity are not yet available.…”

Section: Use Of Therapeutic Hypothermia In Childrenmentioning

confidence: 99%

“…Preliminary data from clinical trials of perinatal asphyxia indicate that induced hypothermia is feasible and safe, but data on long-term neurological morbidity are not yet available. [33][34][35][36][37][38] It is difficult to extrapolate from these disparate sources of information, and thus there is no consensus yet for use of therapeutic hypothermia among clinicians who care for these critically ill children.…”

Section: Use Of Therapeutic Hypothermia In Childrenmentioning

confidence: 99%

Therapeutic Hypothermia After Cardiac Arrest

Nolan¹,

Morley²,

Hoek³

et al. 2003

Circulation

795

194

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“…In such occasions, hypothermia was used only for short periods of time after failed resuscitation, but details regarding side-effects or clinical long-term outcome of these infants were not provided [51][52][53][54][55]. Since the late '90s, on the basis of the above mentioned animal studies, pilot studies with selective brain hypothermia associated with generalized mild hypothermia or generalized moderate hypothermia between 35.5 and 33.0°C for 48-72 hours, have been performed in infants with HIE demonstrating the feasibility of this treatment in term infants [56][57][58][59][60][61][62]. In the early 2000, the first cases reports showed better neurodevelopmental outcomes in cooled asphyxiated infants: whole-body hypothermia was observed to reduce the damage of thalami, basal ganglia, and white matter, while selective brain hypothermia appeared to be more effective in protecting the cortex [63][64][65].…”

Section: Hypothermia As a Neuroprotective Treatment In Human Neonatesmentioning

confidence: 99%

Safety and efficacy of topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia (NeoNATI)

Filippi¹

2013

http://isrctn.org/>

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Background: Despite progresses in neonatal care, the mortality and the incidence of neuro-motor disability after perinatal asphyxia have failed to show substantial improvements. In countries with a high level of perinatal care, the incidence of asphyxia responsible for moderate or severe encephalopathy is still 2-3 per 1000 term newborns. Recent trials have demonstrated that moderate hypothermia, started within 6 hours after birth and protracted for 72 hours, can significantly improve survival and reduce neurologic impairment in neonates with hypoxic-ischemic encephalopathy. It is not currently known whether neuroprotective drugs can further improve the beneficial effects of hypothermia. Topiramate has been proven to reduce brain injury in animal models of neonatal hypoxic ischemic encephalopathy. However, the association of mild hypothermia and topiramate treatment has never been studied in human newborns. The objective of this research project is to evaluate, through a multicenter randomized controlled trial, whether the efficacy of moderate hypothermia can be increased by concomitant topiramate treatment. Methods/Design: Term newborns (gestational age ≥ 36 weeks and birth weight ≥ 1800 g) with precocious metabolic, clinical and electroencephalographic (EEG) signs of hypoxic-ischemic encephalopathy will be randomized, according to their EEG pattern, to receive topiramate added to standard treatment with moderate hypothermia or standard treatment alone. Topiramate will be administered at 10 mg/kg once a day for the first 3 days of life. Topiramate concentrations will be measured on serial dried blood spots. 64 participants will be recruited in the study. To evaluate the safety of topiramate administration, cardiac and respiratory parameters will be continuously monitored. Blood samplings will be performed to check renal, liver and metabolic balance. To evaluate the efficacy of topiramate, the neurologic outcome of enrolled newborns will be evaluated by serial neurologic and neuroradiologic examinations. Visual function will be evaluated by means of behavioural standardized tests.

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Induced brain hypothermia in asphyxiated human newborn infants: a retrospective chart analysis of physiological and adverse effects

Abstract: Adverse effects of mild hypothermia induced for 3 days in asphyxiated newborns were significantly less than expected from previous reports on neonates with accidental hypothermia.

Cited by 75 publications

References 30 publications

Twenty-Four Hours of Mild Hypothermia in Unsedated Newborn Pigs Starting after a Severe Global Hypoxic-Ischemic Insult Is Not Neuroprotective

Twenty-Four Hours of Mild Hypothermia in Unsedated Newborn Pigs Starting after a Severe Global Hypoxic-Ischemic Insult Is Not Neuroprotective

Therapeutic Hypothermia After Cardiac Arrest

Safety and efficacy of topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia (NeoNATI)

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