Dataset Information

Effect of therapeutic hypothermia on renal and myocardial function in asphyxiated (near) term neonates: A systematic review and meta-analysis.

ABSTRACT:

Background

Therapeutic hypothermia (TH) is a well-established neuroprotective therapy applied in (near) term asphyxiated infants. However, little is known regarding the effects of TH on renal and/or myocardial function.

Objectives

To describe the short- and long-term effects of TH on renal and myocardial function in asphyxiated (near) term neonates.

Methods

An electronic search strategy incorporating MeSH terms and keywords was performed in October 2019 and updated in June 2020 using PubMed and Cochrane databases. Inclusion criteria consisted of a RCT or observational cohort design, intervention with TH in a setting of perinatal asphyxia and available long-term results on renal and myocardial function. We performed a meta-analysis and heterogeneity and sensitivity analyses using a random effects model. Subgroup analysis was performed on the method of cooling.

Results

Of the 107 studies identified on renal function, 9 were included. None of the studies investigated the effects of TH on long-term renal function after perinatal asphyxia. The nine included studies described the effect of TH on the incidence of acute kidney injury (AKI) after perinatal asphyxia. Meta-analysis showed a significant difference between the incidence of AKI in neonates treated with TH compared to the control group (RR = 0.81; 95% CI 0.67-0.98; p = 0.03). No studies were found investigating the long-term effects of TH on myocardial function after neonatal asphyxia. Possible short-term beneficial effects were presented in 4 out of 5 identified studies, as observed by significant reductions in cardiac biomarkers and less findings of myocardial dysfunction on ECG and cardiac ultrasound.

Conclusions

TH in asphyxiated neonates reduces the incidence of AKI, an important risk factor for chronic kidney damage, and thus is potentially renoprotective. No studies were found on the long-term effects of TH on myocardial function. Short-term outcome studies suggest a cardioprotective effect.

SUBMITTER: van Wincoop M

PROVIDER: S-EPMC7906340 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of therapeutic hypothermia on renal and myocardial function in asphyxiated (near) term neonates: A systematic review and meta-analysis.

van Wincoop Maureen M de Bijl-Marcus Karen K Lilien Marc M van den Hoogen Agnes A Groenendaal Floris F

PloS one 20210225 2

<h4>Background</h4>Therapeutic hypothermia (TH) is a well-established neuroprotective therapy applied in (near) term asphyxiated infants. However, little is known regarding the effects of TH on renal and/or myocardial function.<h4>Objectives</h4>To describe the short- and long-term effects of TH on renal and myocardial function in asphyxiated (near) term neonates.<h4>Methods</h4>An electronic search strategy incorporating MeSH terms and keywords was performed in October 2019 and updated in June ...[more]

PMID: 33630895

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Project description:BackgroundHypoxic perinatal brain injury is caused by lack of oxygen to baby's brain and can lead to death or permanent brain damage. However, the effectiveness of therapeutic hypothermia in birth asphyxiated infants with encephalopathy is uncertain. This systematic review and meta-analysis was aimed to estimate the pooled relative risk of mortality among birth asphyxiated neonates with hypoxic-ischemic encephalopathy in a global context.MethodsWe used the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines to search randomized control trials from electronic databases (PubMed, Cochrane library, Google Scholar, MEDLINE, Embase, Scopus, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and meta register of Current Controlled Trials (mCRT)). The authors extracted the author's name, year of publication, country, method of cooling, the severity of encephalopathy, the sample size in the hypothermic, and non-hypothermic groups, and the number of deaths in the intervention and control groups. A weighted inverse variance fixed-effects model was used to estimate the pooled relative risk of mortality. The subgroup analysis was done by economic classification of countries, methods of cooling, and cooling devices. Publication bias was assessed with a funnel plot and Eggers test. A sensitivity analysis was also done.ResultsA total of 28 randomized control trials with a total sample of 35, 92 (1832 hypothermic 1760 non-hypothermic) patients with hypoxic-ischemic encephalopathy were used for the analysis. The pooled relative risk of mortality after implementation of therapeutic hypothermia was found to be 0.74 (95%CI; 0.67, 0.80; I2 = 0.0%; p<0.996). The subgroup analysis revealed that the pooled relative risk of mortality in low, low middle, upper-middle and high income countries was 0.32 (95%CI; -0.95, 1.60; I2 = 0.0%; p<0.813), 0.5 (95%CI; 0.14, 0.86; I2 = 0.0%; p<0.998), 0.62 (95%CI; 0.41-0.83; I2 = 0.0%; p<0.634) and 0.76 (95%CI; 0.69-0.83; I2 = 0.0%; p<0.975) respectively. The relative risk of mortality was the same in selective head cooling and whole-body cooling method which was 0.74. Regarding the cooling device, the pooled relative risk of mortality is the same between the cooling cap and cooling blanket (0.74). However, it is slightly lower (0.73) in a cold gel pack.ConclusionsTherapeutic hypothermia reduces the risk of death in neonates with moderate to severe hypoxic-ischemic encephalopathy. Both selective head cooling and whole-body cooling method are effective in reducing the mortality of infants with this condition. Moreover, low income countries benefit the most from the therapy. Therefore, health professionals should consider offering therapeutic hypothermia as part of routine clinical care to newborns with hypoxic-ischemic encephalopathy especially in low-income countries.

Project description:BackgroundTheophylline, a non-selective adenosine receptor antagonist, improves renal perfusion in the setting of hypoxia-ischemia and may offer therapeutic benefit in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing hypothermia. We evaluated the pharmacokinetics and dose-exposure relationships of theophylline in this population to guide dosing strategies.MethodsA population pharmacokinetic analysis was performed in 22 neonates with HIE undergoing hypothermia who were part of a prospective study or retrospective chart review. Aminophylline (intravenous salt form of theophylline) was given per institutional standard of care for low urine output and/or rising serum creatinine (5 mg/kg intravenous (i.v.) load then 1.8 mg/kg i.v. q6h). The ability of different dosing regimens to achieve target concentrations (4-10 mg/L) associated with clinical response was examined.ResultsBirth weight was a significant predictor of theophylline clearance and volume of distribution (p < 0.05). The median half-life was 39.5 h (range 27.2-50.4). An aminophylline loading dose of 7 mg/kg followed by 1.6 mg/kg q12h was predicted to achieve target concentrations in 84% of simulated neonates.ConclusionsIn neonates with HIE undergoing hypothermia, theophylline clearance was low with a 50% longer half-life compared to full-term normothermic neonates without HIE. Dosing strategies need to consider the unique pharmacokinetic needs of this population.ImpactTheophylline is a potential renal-protective therapy in neonates with HIE undergoing therapeutic hypothermia; however, the pharmacokinetics and dose needs in this population are not known. Theophylline clearance was low in neonates with HIE undergoing therapeutic hypothermia with a 50% longer half-life compared to full-term normothermic neonates without HIE. As theophylline is advanced in clinical development, dosing strategies will need to consider the unique pharmacokinetic needs of neonates with HIE undergoing therapeutic hypothermia.

Project description:BACKGROUND:Identification of early signs of hypoxic ischemic encephalopathy (HIE) with magnetic resonance imaging (MRI) has proven of prognostic significance. Yet, the importance of intracranial hemorrhage (ICH), being present concomitantly had not been investigated yet, despite the known influence of hypothermia on hemostasis. We aimed to determine whether presence of ICH on MRI alongside the signs of HIE have an impact on prognosis in neonates with the clinical diagnosis of HIE. METHODS:A retrospective study of consecutively sampled 108 asphyxiated term infants admitted to a tertiary neonatal intensive care unit (between 2007 and 2016), treated with whole body hypothermia and having brain MRI within 1 week of life was conducted. Presence or absence of HIE signs on MRI (basal ganglia-thalamus, watershed pattern and total brain injury) and on MR spectroscopy (lactate peak with decreased normal metabolites measured by Lac/NAA ratio) and/or of the five major types of ICH were recorded. Neurodevelopmental outcome was measured with Bayley Scales of Infant Development-II (BSID-II) test. Death or abnormal neurodevelopment (BSID-II score?<?85) was defined as poor outcome in Chi-square test. Multivariate logistic regression analysis was performed on survivors. RESULTS:MRI and MR-spectroscopy (MRS) signs of HIE were present in 72% (n?=?78). 36% (n?=?39) of neonates had ICH, being mainly small in size. Chi-square test showed a relationship between neurodevelopmental outcome and initial MRI. Unadjusted logistic regression showed that neonates presenting MRI and MRS signs of HIE have 6.23 times higher odds for delayed mental development (OR?=?6.2292; CI95%?=?[1.2642; 30.6934], p?=?0.0246), than infants without imaging alterations; with no ICH effect on outcome. Adjustment for clinical and imaging parameters did not change the pattern of results, i.e. HIE remained an independent risk factor for delayed neurodevelopment (OR?=?6.2496; CI95%?=?[1.2018; 32.4983], p?=?0.0294), while ICH remained to have no significant effect. CONCLUSION:HIE related MRI abnormalities proved to be important prognostic factors of poor outcome in cooled asphyxiated infants when present, suggesting that early MRI with MRS is beneficial for prognostication. Interestingly, ICHs present in about one third of all cases had no significant effect on neurodevelopmental outcome, despite the known hemostasis altering effects of hypothermia.

Project description:BackgroundHypoxic-ischaemic encephalopathy (HIE) is a serious birth complication affecting term and late preterm newborns. Although therapeutic hypothermia (cooling) has been shown to be an effective therapy for neonatal HIE, many cooled infants have poor long-term neurodevelopmental outcomes. In animal models of neonatal encephalopathy, inhaled xenon combined with cooling has been shown to offer better neuroprotection than cooling alone.ObjectivesTo determine the effects of xenon as an adjuvant to therapeutic hypothermia on mortality and neurodevelopmental morbidity, and to ascertain clinically important side effects of xenon plus therapeutic hypothermia in newborn infants with HIE. To assess early predictors of adverse outcomes and potential side effects of xenon.Search methodsWe used the standard strategy of the Cochrane Neonatal Review Group to search the Cochrane Library (2017, Issue 8), MEDLINE (from 1966), Embase (from 1966), and PubMed (from 1966) for randomised controlled and quasi-randomised trials. We also searched conference proceedings and the reference lists of cited articles. We conducted our most recent search in August 2017.Selection criteriaWe included all trials allocating term or late preterm encephalopathic newborns to cooling plus xenon or cooling alone, irrespective of timing (starting age and duration) and concentrations used for xenon administration.Data collection and analysisTwo review authors independently assessed results of searches against predetermined criteria for inclusion, assessed risk of bias, and extracted data. We performed meta-analyses using risk ratios (RRs), risk differences (RDs), and number needed to treat for an additional beneficial outcome (NNTB) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences (MDs) for continuous data.Main resultsA single randomised controlled trial enrolling 92 participants was eligible for this review. Researchers have not reported long-term neurodevelopmental outcomes, including the primary outcome of this review - death or long-term major neurodevelopmental disability in infancy (18 months to three years of age). Cooling plus xenon was not associated with reduced mortality at latest follow-up, based upon low quality evidence. Investigators noted no substantial differences between groups for other secondary outcomes of this review, such as biomarkers of brain damage assessed with magnetic resonance imaging and occurrence of seizures during primary hospitalisation. Available data do not show an increased adverse event rate in the cooling plus xenon group compared with the cooling alone group.Authors' conclusionsCurrent evidence from one small randomised controlled pilot trial is inadequate to show whether cooling plus xenon is safe or effective in near-term and term newborns with HIE. Further trials reporting long-term neurodevelopmental outcomes are needed.

Dataset Information

Effect of therapeutic hypothermia on renal and myocardial function in asphyxiated (near) term neonates: A systematic review and meta-analysis.

Background

Objectives

Methods

Results

Conclusions

Publications

Effect of therapeutic hypothermia on renal and myocardial function in asphyxiated (near) term neonates: A systematic review and meta-analysis.

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