Association between hypocapnia and ventilation during the first days of life and brain injury in asphyxiated newborns treated with hypothermia

Laporte, Maria Agustina Lopez; Wang, Hui; Sanon, Priscille-Nice; Vargas, Stephanie Barbosa; Maluorni, Julie; Rampakakis, Emmanouil; Wintermark, Pia

doi:10.1080/14767058.2017.1404980

Cited by 25 publications

(26 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The blood pH was more alkalotic and PaCO 2 lower at 24 h after HI in HT+M and HT+V versus HT. High variability in CO 2 , in particular hypocapnia 56,57 , is associated with NE adverse outcome and this could exacerbate HT+M brain injury. The contribution of phenobarbitone to brain injury is unclear 58,59 .…”

Section: Scientific Reports |mentioning

confidence: 99%

High-Dose Melatonin and Ethanol Excipient Combined with Therapeutic Hypothermia in a Newborn Piglet Asphyxia Model

Robertson

Lingam

Meehan

et al. 2020

Sci Rep

View full text Add to dashboard Cite

With the current practice of therapeutic hypothermia for neonatal encephalopathy, disability rates and the severity spectrum of cerebral palsy are reduced. Nevertheless, safe and effective adjunct therapies are needed to optimize outcomes. This study's objective was to assess if 18 mg/kg melatonin given rapidly over 2 h at 1 h after hypoxia-ischemia with cooling from 1-13 h was safe, achieved therapeutic levels within 3 h and augmented hypothermic neuroprotection. Following hypoxia-ischemia, 20 newborn piglets were randomized to: (i) Cooling 1-13 h (HT; n = 6); (ii) HT+ 2.5% ethanol vehicle (Ht+V; n = 7); (iii) HT + Melatonin (Ht+M; n = 7). Intensive care was maintained for 48 h; aEEG was acquired throughout, brain MRS acquired at 24 and 48 h and cell death (TUNEL) evaluated at 48 h. There were no differences for insult severity. Core temperature was higher in HT group for first hour after Hi. comparing Ht+M to HT, aEEG scores recovered more quickly by 19 h (p < 0.05); comparing HT+V to HT, aEEG recovered from 31 h (p < 0.05). Brain phosphocreatine/inorganic phosphate and NTP/ exchangeable phosphate were higher at 48 h in HT+M versus Ht (p = 0.036, p = 0.049 respectively). Including both 24 h and 48 h measurements, the rise in Lactate/N-acetyl aspartate was reduced in white (p = 0.030) and grey matter (p = 0.038) after HI. Reduced overall TUNEL positive cells were observed in Ht+M (47.1 cells/mm 2 ) compared to HT (123.8 cells/mm 2 ) (p = 0.0003) and HT+V (97.5 cells/mm 2 ) compared to Ht (p = 0.012). Localized protection was seen in white matter for HT+M versus Ht (p = 0.036) and internal capsule for HT+M compared to Ht (p = 0.001) and HT+V versus Ht (p = 0.006). Therapeutic melatonin levels (15-30mg/l) were achieved at 2 h and were neuroprotective following HI, but ethanol vehicle was partially protective.Intrapartum-related neonatal encephalopathy (NE) is a major healthcare problem. Worldwide in 2010, NE accounted for 287,000 deaths and 400,000 survivors with impairment 1 . NE cannot be prevented in most cases and therapies are limited. The incidence of NE in Western Europe is 1-3/1000 term births and in low-and mid-resource settings the incidence is ~10 times higher 1,2 . Over the last 2 decades, in settings with neonatal intensive care facilities, therapeutic hypothermia (HT) is routinely used for moderate-to-severe NE, improving survival and reducing disability 3 . However, although the severity of cerebral palsy has reduced with HT 4 , survivors have significantly lower cognitive scores which are on average 14 IQ points lower than matched peers even in the absence of cerebral palsy at school-age 5 . Further adjustments to HT protocols do not improve outcome 6,7 , therefore adjunct therapies to augment HT protection are urgently needed.Pre-clinical studies suggest that melatonin (N-acetyl-5-methoxytryptamine) in pharmacologic levels is safe and neuroprotective for hypoxic-ischemic injury in the adult 8 and neonatal 9 brain, mediated by anti-oxidant, anti-apoptotic and anti-inflammatory properties 10,11 . Ex...

show abstract

Section: Scientific Reports |mentioning

confidence: 99%

High-Dose Melatonin and Ethanol Excipient Combined with Therapeutic Hypothermia in a Newborn Piglet Asphyxia Model

Robertson

Lingam

Meehan

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Hypocapnia is associated with poor neurodevelopmental outcome [ 9 , 10 ]. While a causative relationship has not been fully proven [ 6 ], several mechanisms have been suggested including cerebral vasoconstriction, reduced cerebral blood flow, increased neuronal excitability facilitating apoptotic cell death and seizures [ 11 – 13 ]. Maintaining normocapnia is important because hypercapnia may also be deleterious [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Volume guarantee ventilation in neonates treated with hypothermia for hypoxic-ischemic encephalopathy during interhospital transport

Lantos

Berenyi²,

Morley

et al. 2020

J Perinatol

View full text Add to dashboard Cite

Objective We investigated if volume guarantee (VG) ventilation in babies with hypoxic-ischemic encephalopathy (HIE) during interhospital transport decreases tidal volumes and prevents hypocapnia. Study design We computationally collected and analyzed ventilator data of babies ventilated with synchronized intermittent mandatory ventilation (SIMV) with VG (n = 28) or without VG (n = 8). Result The expiratory tidal volume of ventilator inflations was lower with SIMV-VG (median [IQR]: 4.9 [4.6-5.3] mL/kg) than with SIMV only (median [IQR]: 7.1 [5.3-8.0] mL/kg, p = 0.01). Babies receiving SIMV-VG had lower peak inflating pressures (median: 10.7 cmH 2 O, versus 17.5 cmH 2 O, p = 0.01). There was no significant difference in minute ventilation or in pCO 2. Babies with strong spontaneous breathing had a mean PIP < 10 cmH 2 O but this did not result in adverse events or worsening of acidosis. Conclusions The use of VG ventilation in babies with HIE reduces tidal volumes and frequently results in very low inflating pressures without affecting pCO 2 .

show abstract

“…6,[18][19][20][21][22][23]26 Five studies reported short-and/or long-term outcomes in infants with mild hypoxic ischemic encephalopathy who received therapeutic hypothermia (Table 3). There was no mortality in infants with mild hypoxic ischemic encephalopathy who were treated with therapeutic hypothermia in any of the 7 studies 6,[18][19][20][21]26,27 that reported the outcome. Preplanned subgroup analyses could not be done because of lack of relevant data.…”

Section: Resultsmentioning

confidence: 95%

“…The literature search yielded 3590 articles that were screened for eligibility. After removing duplicates and full-text review of the potentially eligible studies, 13 studies 6,8,[17][18][19][20][21][22][23][24][25][26][27] were included in the systematic review (Table 1). Figure 1 describes the study selection process.…”

Section: Resultsmentioning

confidence: 99%

“…The 3 included studies in our systematic review that described the brain injury pattern on MRI in infants with mild hypoxic ischemic encephalopathy showed that 38% to 59% of infants with mild hypoxic ischemic encephalopathy and treated with therapeutic hypothermia have abnormal MRI findings. 6,20,27 A recent systematic review by Conway et al identified 4 randomized controlled trials where the objective was to evaluate therapeutic hypothermia in moderate to severe hypoxic ischemic encephalopathy, but some infants with mild hypoxic ischemic encephalopathy were also trial participants. Of the 330 infants who received therapeutic hypothermia in the randomized controlled trials, 45 infants had only mild hypoxic ischemic encephalopathy (13.6%).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Current Practice of Therapeutic Hypothermia for Mild Hypoxic Ischemic Encephalopathy

Saw¹,

Rakshasbhuvankar

Rao

et al. 2019

J Child Neurol

View full text Add to dashboard Cite

Context: Therapeutic hypothermia is the recommended treatment for neonates with moderate or severe hypoxic ischemic encephalopathy (HIE). There is an increasing trend to use therapeutic hypothermia even in infants with mild hypoxic ischemic encephalopathy, even though there is little evidence to support/refute this. Objective: To estimate the incidences of mild hypoxic ischemic encephalopathy among infants who received therapeutic hypothermia, and its short-and long-term outcomes. Data Sources and Study Selection: PubMed, Embase, CINAHL, and Cochrane library were searched to identify observational studies reporting on therapeutic hypothermia in term and near-term infants with mild hypoxic ischemic encephalopathy. The JBI (Joanna Briggs Institute) tools were used to assess the risk of bias in the included studies. Random effects meta-analysis was conducted to find out the percentage of cooled infants who had only mild hypoxic ischemic encephalopathy. Results: A total of 3590 citations were screened, of which 13 were included. Of the 2783 infants who received therapeutic hypothermia, 573 had mild hypoxic ischemic encephalopathy. Meta-analysis found that 22% of the infants who underwent therapeutic hypothermia had only mild hypoxic ischemic encephalopathy (95% confidence interval: 16%-27%; I 2 statistic ¼ 90.5%). Five studies provided information on adverse effects of therapeutic hypothermia in mild hypoxic ischemic encephalopathy. The reported adverse effects were extreme hypothermia, bradycardia, hypoglycemia, sepsis, skin necrosis, pulmonary hypertension, and systemic hypotension. Limitation: The limitations included relatively small sample size and the lack of data for short-and long-term neurodevelopmental outcome. Conclusions: A significant proportion of infants who received therapeutic hypothermia had mild hypoxic ischemic encephalopathy. Randomized trials are urgently needed to evaluate the efficacy and safety of therapeutic hypothermia in infants with mild hypoxic ischemic encephalopathy.

show abstract

Association between hypocapnia and ventilation during the first days of life and brain injury in asphyxiated newborns treated with hypothermia

Abstract: Intubated and ventilated asphyxiated newborns experienced more severe hypocapnia, and had higher incidences of brain injury. Hypocapnia during the first 4 days of life was associated with an increased risk of developing (more severe) brain injury.

Cited by 25 publications

References 25 publications

High-Dose Melatonin and Ethanol Excipient Combined with Therapeutic Hypothermia in a Newborn Piglet Asphyxia Model

High-Dose Melatonin and Ethanol Excipient Combined with Therapeutic Hypothermia in a Newborn Piglet Asphyxia Model

Volume guarantee ventilation in neonates treated with hypothermia for hypoxic-ischemic encephalopathy during interhospital transport

Current Practice of Therapeutic Hypothermia for Mild Hypoxic Ischemic Encephalopathy

Contact Info

Product

Resources

About