Therapeutic Hypothermia Research Articles

Slow rewarming after hypothermia does not ameliorate white matter injury after hypoxia-ischemia in near-term fetal sheep.

The optimal rate to rewarm infants after therapeutic hypothermia is unclear. In this study we examined whether slow rewarming after 72 h of hypothermia would attenuate white matter injury. Near-term fetal sheep received sham occlusion (n = 8) or cerebral ischemia for 30 min, followed by normothermia (n = 7) or hypothermia from 3-72 h, with either spontaneous fast rewarming (n = 8) within 1 h, or slow rewarming at ~0.5 °C/h (n = 8) over 10 h. Fetuses were euthanized 7 days later. Ischemia was associated with loss of total and mature oligodendrocytes, reduced expression of myelin proteins and induction of microglia and astrocytes, compared with sham controls (P < 0.05). Both hypothermia protocols were associated with a significant increase in numbers of total and mature oligodendrocytes, area fraction of myelin proteins and reduced numbers of microglia and astrocytes, compared with ischemia-normothermia (P < 0.05). There was no difference in the number of oligodendrocytes, microglia or astrocytes or expression of myelin proteins between fast and slow rewarming after hypothermia. The rate of rewarming after a clinically relevant duration of hypothermia had no apparent effect on white matter protection by hypothermia after cerebral ischemia in near-term fetal sheep. Persistent white matter injury is a major contributor to long-term disability after neonatal encephalopathy despite treatment with therapeutic hypothermia. The optimal rate to rewarm infants after therapeutic hypothermia is unclear; current protocols were developed on a precautionary basis. We now show that slow rewarming at 0.5 °C/h did not improve histological white matter injury compared with rapid spontaneous rewarming after a clinically established duration of hypothermia in near-term fetal sheep.

Risk factors, incidence, and outcomes of neonatal respiratory extracorporeal membrane oxygenation including association with therapeutic hypothermia in California during 2013-2020.

To evaluate the incidence, indications and outcomes with neonatal extracorporeal membrane oxygenation (ECMO) and its association with therapeutic hypothermia (TH) among infants undergoing invasive mechanical ventilation (IMV) in California during 2013-2020. We analyzed data on neonates ≥34 weeks gestation with ≥4 h of IMV over an 8-year period (2013-2020) from the California Perinatal Quality Care Collaborative (CPQCC) database. Between 2013 and 2020, the ranges for utilization of iNO (13.9 to 17.2%), ECMO (2.1 to 2.5%), TH (10.2 to 15.7%) and TH + ECMO (0.4 to 0.8%) were observed. The most common association with neonatal ECMO was TH (148 cases, OR 3.2, 95% CI 2.6-4.3, p < 0.01). The combination of meconium aspiration syndrome (MAS) and hypoxic ischemic encephalopathy (HIE) increased risk of iNO and ECMO use (OR 11.3, 1.5-86.9), p = 0.02). Ventilated infants ≥34 weeks gestational age undergoing TH are at risk for iNO/ECMO use and need close monitoring.

The Effect of Therapeutic Hypothermia on Ischemic Brain Injury in a Rat Model of Cardiac Arrest: An Assessment Using 18F-FDG PET.

Therapeutic hypothermia (TH) is widely acknowledged as one of the interventions for preventing hypoxic ischemic brain injury in comatose patients following cardiac arrest (CA). Despite its recognized efficacy, recent debates have questioned its effectiveness. This preclinical study evaluated the impact of TH on brain glucose metabolism, utilizing fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in a rat model of CA. Asphyxia CA was induced in Sprague-Dawley rats using vecuronium. Brain PET images using 18F-FDG were obtained from 21 CA rats, who were randomized to receive either TH or no intervention. Of these, 9 rats in the TH group received hypothermia under general anesthesia and mechanical ventilation for eight hours, while the remaining 12 rats in the non-TH group were observed without intervention. We conducted regional and voxel-based analyses of standardized uptake values relative to the pons (SUVRpons) to compare the two groups. Survival rates were identical in both the TH and non-TH groups (67%). There was no discernible difference in the SUVRpons across the brain cortical regions between the groups. However, in a subgroup analysis of the rats that did not survive (n = 7), those in the TH group (n = 3) displayed significantly higher SUVRpons values across most cortical regions compared to those in the non-TH group (n = 4), with statistical significance after false-discovery rate correction (p < 0.05). The enhancement in SUVRpons due to TH intervention was only observed in the cortical regions of rats with severe encephalopathy that subsequently died. These findings suggest that the beneficial effects of TH on brain glucose metabolism in this asphyxia CA model may be confined to cases of severe ischemic encephalopathy.

Early automated classification of neonatal hypoxic-ischemic encephalopathy − An aid to the decision to use therapeutic hypothermia

ObjectiveThe study aimed to address the challenge of early assessment of neonatal hypoxic-ischemic encephalopathy (HIE) severity to identify candidates for therapeutic hypothermia (TH). The objective was to develop an automated classification model for neonatal EEGs, enabling accurate HIE severity assessment 24/7. MethodsEEGs recorded within 6 h of life after perinatal anoxia were visually graded into 3 severity groups (HIE French Classification) and quantified using 6 qEEG markers measuring amplitude, continuity and frequency content. Machine learning models were developed on a dataset of 90 EEGs and validated on an independent dataset of 60 EEGs. ResultsThe selected model achieved an overall accuracy of 80.6% in the development phase and 80% in the validation phase. Notably, the model accurately identified 28 out of 30 children for whom TH was indicated after visual EEG analysis, with only 2 cases (moderate EEG abnormalities) not recommended for cooling. ConclusionsThe combination of clinically relevant qEEG markers led to the development of an effective automated EEG classification model, particularly suited for the post-anoxic latency phase. This model successfully discriminated neonates requiring TH. SignificanceThe proposed model has potential as a bedside clinical decision support tool for TH.

Out of hospital cardiac arrest - new insights and a call for a worldwide registry and guidelines

IntroductionOut of hospital cardiac arrest (OHCA) is a major public health problem with substantial mortality rates worldwide. Genetic diseases and primary electrical disorders are the most common etiologies at younger ages, while ischemic heart disease and cardiomyopathies are common causes at older ages. Despite improvement in prevention and treatment in recent years, OHCA is still a major cause of cardiovascular death.MethodWe report prospective data regarding etiology, characteristics, clinical course, and outcomes of patients with OHCA who were admitted to a tertiary care center intensive cardiac care unit (ICCU) between 2020–2023.ResultsA total of 92 patients admitted after OHCA were included in the cohort. Mean age was 63.8 ± 13.8 years and 75 (82%) were males. The most common etiology of OHCA was acute coronary syndrome (ACS) in 54 (59%) patients, of whom 46 (85%) patients had ST elevation myocardial infarction and 8 (15%) had non-ST elevation myocardial infarction. During hospitalization, 42 (46%) patients underwent targeted temperature management and 13 (14%) received mechanical circulatory support. Interestingly, 77 (84%) patients underwent coronary angiography, while only 51 (55%) received percutaneous coronary intervention (PCI). Neurologic status was favorable in 49 (53%) patients with Cerebral Performance Category score of 1–2. Overall, mortality rates were relatively low, with 15 (16%) in-hospital deaths and 24 (26%) deaths at 30-day follow-up.ConclusionAlthough ACS was the most common etiology for OHCA, only 55% of patients underwent PCI. Most OHCA patients admitted to the ICCU survived hospitalization and were discharged. Increased awareness, public education, worldwide registries, and specific evidence-based guidelines for the treatment of OHCA patients may lead to improved outcomes for these patients who often carry poor prognoses.

Advances in Cerebral Palsy Treatment

Background: Cerebral palsy is a complex neurodevelopmental disorder with various etiological factors and treatment options. This narrative review aimed to summarize the causes of cerebral palsy, identify areas needing additional research in treatment approaches, and highlight areas requiring further investigation. In order to provide a thorough overview of management techniques to lessen the effects of the illness and its consequences, this review has drawn data from a number of studies. Introduction: Prematurity increases the risk of brain damage during the developing stage and accounts for a sizable fraction of cerebral palsy cases. In a sizable portion of cases, maternal diabetes and hypertension are listed as the main causes. Damage to the brain tissue results from hypoxic-ischemic injuries sustained during pregnancy that upset the equilibrium of oxidants and antioxidants. To alter the oxidative stress pathway and ease related issues, pharmacological treatments, such as therapeutic hypothermia, free radical inhibition therapy, and mitochondrial therapy, have been proposed. Therapeutic strategies, such as physiotherapy, occupational therapy, speech therapy, and surgical interventions, have added quality to the lives of the children. Some of the most recent developments in this area include the development of biomarkers for muscle activity detection, machine learning to predict the types of cerebral palsy and abnormal movements, disease prediction with eye images, wireless inertia measuring unit for spasticity detection, computerbased video analysis of typical and atypical infants, identification of intellectual disabilities with algorithms, and deep learning methods for predicting cerebral palsy. Methods: This narrative review is based on a careful analysis of numerous researches conducted on cerebral palsy, which have served as the basis for statistical distribution. It reviews the causes of cerebral palsy, available treatments, and ongoing research with the goal of providing physicians and researchers in the field with useful information. The objectives, study questions, inclusion criteria, and search approach have all been outlined in a thorough protocol. To find pertinent research published up to September 2021, a literature search was carried out using electronic databases, including Google Scholar, PubMed, Cochrane Library, Scopus, and Web of Science. A combination of pertinent keywords, such as "cerebral palsy," "management," "technology," "wearable technology," "prematurity," and "artificial intelligence," has been used in the search approach. Results: Recent advances in the field include the discovery of biomarkers for the detection of muscle activity, machine learning algorithms to predict the types of cerebral palsy and abnormal movements, disease prediction using eye images, wireless inertia measuring units for the detection of spasticity, computer-based video analysis for the detection of atypical infants, and algorithms to identify intellectual disabilities. Additionally, employing technologies, like virtual reality systems, electrical stimulators, activity trackers, machine learning, and deep learning approaches, has shown promise in evaluating, diagnosing, and predicting treatment outcomes linked to gait, upper limb, and lower limb function. Conclusion: Future research should examine the clinical application of nanomedicine, stem cell therapy, and cutting-edge therapeutic strategies to prevent hypoxic-ischemic damage in the developing brain. Additionally, research is required to effectively assist children with severe speech difficulties using alternate communication modalities and cutting-edge computational tools. The outcomes for people with cerebral palsy can be improved by combining interdisciplinary efforts with cutting-edge technological interventions.

Costs of Care for Neonates with Hypoxic-Ischemic Encephalopathy Treated with Therapeutic Hypothermia and Validation of the Canadian Neonatal Network Costing Algorithm

Costs of Care for Neonates with Hypoxic-Ischemic Encephalopathy Treated with Therapeutic Hypothermia and Validation of the Canadian Neonatal Network Costing Algorithm

Circulating MicroRNAs as a biomarker signature of perinatal asphyxia

AimThis study aimed to explore whether microRNAs (miRNAs) could serve as biomarkers of perinatal asphyxia and whether they were correlated with severity of brain magnetic resonance imaging. MethodsWe prospectively enrolled 26 full-term newborns, including 10 with perinatal asphyxia and 16 healthy controls. Plasma samples were collected at 0–6 h and 7 days of age. Encephalopathy was classified according to modified Sarnat staging. Magnetic resonance imaging was performed in surviving infants within 30 days of birth, and a score was established. We used next-generation sequencing to explore differentially expressed miRNAs, which were then further validated using quantitative reverse transcription real-time polymerase chain reaction (RT-PCR). ResultsA significantly lower expression of miR-486-5p was found at 0–6 h of age in the asphyxiated newborns compared with the healthy controls (p = 0.005). The area under the receiver operating characteristic curve (AUC) of miR-486-5p at 0–6 h of age to differentiate the perinatal asphyxia group from the healthy control group was 0.831, and the AUC to differentiate newborns eligible for therapeutic hypothermia from others was 0.782. In addition, a lower expression of miR-486-5p at 7 days of age was noted in the asphyxiated newborns with adverse outcomes compared to those with normal outcomes. ConclusionMiR-486-5p may be a biomarker of perinatal asphyxia in newborns, and further research is warranted to clarify its role.

Differential Mitochondrial Bioenergetics in Neurons and Astrocytes Following Ischemia-Reperfusion Injury and Hypothermia.

The close interaction between neurons and astrocytes has been extensively studied. However, the specific behavior of these cells after ischemia-reperfusion injury and hypothermia remains poorly characterized. A growing body of evidence suggests that mitochondria function and putative transference between neurons and astrocytes may play a fundamental role in adaptive and homeostatic responses after systemic insults such as cardiac arrest, which highlights the importance of a better understanding of how neurons and astrocytes behave individually in these settings. Brain injury is one of the most important challenges in post-cardiac arrest syndrome, and therapeutic hypothermia remains the single, gold standard treatment for neuroprotection after cardiac arrest. In our study, we modeled ischemia-reperfusion injury by using in vitro enhanced oxygen-glucose deprivation and reperfusion (eOGD-R) and subsequent hypothermia (HPT) (31.5 °C) to cell lines of neurons (HT-22) and astrocytes (C8-D1A) with/without hypothermia. Using cell lysis (LDH; lactate dehydrogenase) as a measure of membrane integrity and cell viability, we found that neurons were more susceptible to eOGD-R when compared with astrocytes. However, they benefited significantly from HPT, while the HPT effect after eOGD-R on astrocytes was negligible. Similarly, eOGD-R caused a more significant reduction in adenosine triphosphate (ATP) in neurons than astrocytes, and the ATP-enhancing effects from HPT were more prominent in neurons than astrocytes. In both neurons and astrocytes, measurement of reactive oxygen species (ROS) revealed higher ROS output following eOGD-R, with a non-significant trend of differential reduction observed in neurons. HPT after eOGD-R effectively downregulated ROS in both cells; however, the effect was significantly more effective in neurons. Lipid peroxidation was higher after eOGD-R in neurons, while in astrocytes, the increase was not statistically significant. Interestingly, HPT had similar effects on the reduction in lipoperoxidation after eOGD-R with both types of cells. While glutathione (GSH) levels were downregulated after eOGD-R in both cells, HPT enhanced GSH in astrocytes, but worsened GSH in neurons. In conclusion, neuron and astrocyte cultures respond differently to eOGD-R and eOGD-R + HTP treatments. Neurons showed higher sensitivity to ischemia-reperfusion insults than astrocytes; however, they benefited more from HPT therapy. These data suggest that given the differential effects from HPT in neurons and astrocytes, future therapeutic developments could potentially enhance HPT outcomes by means of neuronal and astrocytic targeted therapies.

Role of mitochondria in neonatal hypoxic-ischemic encephalopathy.

Neonatal hypoxic-ischemic encephalopathy, an important cause of death as well as long-term disability in survivors, is caused by oxygen and glucose deprivation, and limited blood flow. Following hypoxic-ischemic injury in the neonatal brain, three main biochemical damages (excitotoxicity, oxidative stress, and exacerbated inflammation) are triggered. Mitochondria are involved in all three cascades. Mitochondria are the nexus of metabolic pathways to offer most of the energy that our body needs. Hypoxic-ischemic injury affects the characteristics of mitochondria, including dynamics, permeability, and ATP production, which also feed back into the process of neonatal hypoxic-ischemic encephalopathy. Mitochondria can be a cellular hub in inflammation, which is another main response of the injured neonatal brain. Some treatments for neonatal hypoxic-ischemic encephalopathy affect the function of mitochondria or target mitochondria, including therapeutic hypothermia and erythropoietin. This review presents the main roles of mitochondria in neonatal hypoxic-ischemic encephalopathy and discusses some potential treatments directed at mitochondria, which may foster the development of new therapeutic strategies for this encephalopathy.

The compliance with TTM protocol may benefit outcomes in cardiac arrest survivors: A retrospective cohort study

BackgroundEstablished protocols for implementing high-quality targeted temperature management (TTM) provide guidance concerning the cooling rate, duration of maintenance, and rewarming speed. However, whether compliant to TTM protocols results in improved survival and better neurological recovery has not been examined. MethodsA retrospective cohort study enrolled 1141 survivors of non-traumatic adult cardiac arrest with a pre-arrest cerebral performance category (CPC) score of 1–2 from 2015 to 2020 at a tertiary medical center. Of the survivors, 330 patients who underwent TTM were further included. Patients with spontaneous hypothermia (<35 °C) (n = 107) and expired during the TTM (n = 21) were excluded. A total of 202 patients were thus enrolled. One hundred and ten patients underwent TTM that completely complied with the protocol (protocol-complaint group), but 92 patients deviated in some manner from the protocol (protocol non-compliant group). ResultsFifty patients (50%) and 46 patients (50%) in the protocol-compliant and non-compliant groups, respectively, did not survive to hospital discharge. In the protocol-compliant group, 42 patients (38.2%) had favorable neurological recovery, compared with 32 patients (34.8%) in the protocol non-compliant group. After adjusting for age, initial shockable rhythm, witnessed collapse, and cardiopulmonary resuscitation duration, protocol non-compliant was associated with the poor neurological outcomes (aOR 2.44, 95% CI = 1.13–5.25), but not with in-hospital mortality (aOR 1.31, 95% CI = 0.70–2.47). The most common reason for noncompliance was a prolonged duration reaching the target temperature (n = 33, 58.7%). The number of phases of non-compliant was not significantly associated with in-hospital mortality or poor neurological recovery. ConclusionAmong cardiac arrest survivors undergoing TTM, those who did not receive TTM that in compliance with the protocol were more likely to experience poor neurological recovery than those whose TTM fully complied with the protocols. The most frequently identified deviation was a prolonged duration to reaching the target temperature.

Checkpoint for Considering Interleukin-6 as a Potential Target to Mitigate Secondary Brain Injury after Cardiac Arrest.

Interleukin-6 (IL-6) was suggested as a potential target for intervention to mitigate brain injury. However, its neuro-protective effect in post-resuscitation care has not been proven. We investigated the time-course of changes in IL-6 and its association with other markers (systemic inflammation and myocardial and neuronal injury), according to the injury severity of the cardiac arrest. This retrospective study analyzed IL-6 and other markers at baseline and 24, 48, and 72 h after the return of spontaneous circulation. The primary outcome was the association of IL-6 with injury severity as assessed using the revised Post-Cardiac Arrest Syndrome for Therapeutic Hypothermia scoring system (low, moderate, and high severity). Of 111 patients, 22 (19.8%), 61 (55.0%), and 28 (25.2%) had low-, moderate-, and high-severity scores, respectively. IL-6 levels were significantly lower in the low-severity group than in the moderate- and high-severity groups at baseline and at 24 h and 72 h (p < 0.005). While IL-6 was not independently associated with neuronal injury markers in the low-severity group, it was demonstrated to be associated with it in the moderate-severity (β [95% CI] = 4.3 [0.1-8.6], R2 = 0.11) and high-severity (β [95% CI] = 7.9 [3.4-12.5], R2 = 0.14) groups. IL-6 exhibits distinct patterns across severity and shows differential associations with systemic inflammation or neuronal injury.

Neuroprotective treatment options for neonatal hypoxic-ischemic encephalopathy: Therapeutic hypothermia and beyond

Hypoxic-ischemic encephalopathy (HIE) is the most common form of neonatal encephalopathy that develops due to perinatal asphyxia or ischemia in term and late-preterm infants. It is an important cause of significant neurological impairment and also mortality in newborns worldwide. The pathophysiology of HIE is multifactorial and involves complex cascades of cellular and biochemical events in the brain including excitotoxicity, oxidative stress, inflammation, and cell death, respectively. Therapeutic hypothermia (TH), is the only standard neuroprotective therapy for HIE and is associated with reduced composite outcome of death or major neurodevelopmental disability. However, although TH is beneficial, neonates with HIE still experience unacceptably high rate of devistating morbidities. Therefore, research for adjunctive therapies continue to further improve outcomes in infants with HIE. In this review, both TH and other promising adjunctive neuroprotective therapies are discussed for developing future treatment strategies.

Selective brain cooling with a novel catheter reduces infarct growth after recanalization in a canine large vessel occlusion model.

Therapeutic hypothermia has shown potential in cardiac intervention for years; however, its adoption into the neurovascular space has been limited. Studies have pointed to slow cooling and limited depth of hypothermia yielding negative outcomes. Here we present an insulated catheter that allows for consistent infusion of chilled saline directly to the brain. Direct delivery of cold saline allows a faster depth of hypothermia, which could have a benefit to the growth of ischemic lesions. Ten canines were randomized to either receive selective brain cooling or no additional therapy. Eight animals were successfully enrolled (n = 4 per group). Each animal underwent a temporary middle cerebral artery occlusion (MCAO) for a total of 45 min. Five minutes prior to flow restoration, chilled saline was injected through the ipsilateral internal carotid artery using an insulated catheter to ensure delivery temperature. The treatment continued for 20 min, after which the animal was transferred to an MRI scanner for imaging. Of the 8 animals that were successfully enrolled in the study, 3 were able to survive to the 30-day endpoint with no differences between the cooled and control animals. There was no difference in the initial mean infarct size between the groups; however, animals that did not receive cooling had infarcts continuing to progress more rapidly after the MCAO was removed (13.8% vs 161.3%, p = 0.016, cooled vs control). Selective hypothermia was able to reduce the post-MCAO infarct progression in a canine model of temporary MCAO.

COMBINED CRITICAL ILLNESS–RELATED CORTICOSTEROID AND THYROID INSUFFICIENCY DURING TARGETED TEMPERATURE MANAGEMENT: A PROSPECTIVE COHORT STUDY

Objective. To study the effect of therapy for adrenal and thyroid dysfunction on the course and outcomes of critical care. Materials and methods. 51 patients requiring targeted temperature management (ТТМ) were included in a single-center prospective cohort study. Results. Group I (with adrenal and thyroid dysfunction) included 39 (76,5%) patients on TTM, group II (without adrenal and thyroid dysfunction ) included 12 (23,5%) patients without endocrinopathies. In patients on TTM, adrenal dysfunction developed on day (D) 0 and manifested only clinically in the form of vascular insufficiency. When evaluating clinical and laboratory data in patients at TTM, thyroid dysfunction was diagnosed at D1, D2, and D3. The manifestation of adrenal and thyroid dysfunction in patients at is primarily due to central nervous system injury rather than sepsis. Treatment of adrenal and thyroid dysfunction was performed with hydrocortisone and levothyroxine. Conclusion. Formation of combination of adrenal and thyroid dysfunction at TTM leads to the development of multiple organ dysfunction not associated with the development of septic complications. Timely diagnosis and adequate correction of adrenal and thyroid dysfunction in patients undergoing critical illness and requiring TTM allows to reliably reduce mortality.

Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP): study protocol for a multicenter, randomized, adaptive allocation clinical trial to identify the optimal duration of induced hypothermia for neuroprotection in comatose, adult survivors of after out-of-hospital cardiac arrest

BackgroundCardiac arrest is a common and devastating emergency of both the heart and brain. More than 380,000 patients suffer out-of-hospital cardiac arrest annually in the USA. Induced cooling of comatose patients markedly improved neurological and functional outcomes in pivotal randomized clinical trials, but the optimal duration of therapeutic hypothermia has not yet been established.MethodsThis study is a multi-center randomized, response-adaptive, duration (dose) finding, comparative effectiveness clinical trial with blinded outcome assessment. We investigate two populations of adult comatose survivors of cardiac arrest to ascertain the shortest duration of cooling that provides the maximum treatment effect. The design is based on a statistical model of response as defined by the primary endpoint, a weighted 90-day mRS (modified Rankin Scale, a measure of neurologic disability), across the treatment arms. Subjects will initially be equally randomized between 12, 24, and 48 h of therapeutic cooling. After the first 200 subjects have been randomized, additional treatment arms between 12 and 48 h will be opened and patients will be allocated, within each initial cardiac rhythm type (shockable or non-shockable), by response adaptive randomization. As the trial continues, shorter and longer duration arms may be opened. A maximum sample size of 1800 subjects is proposed. Secondary objectives are to characterize: the overall safety and adverse events associated with duration of cooling, the effect on neuropsychological outcomes, and the effect on patient-reported quality of life measures.DiscussionIn vitro and in vivo studies have shown the neuroprotective effects of therapeutic hypothermia for cardiac arrest. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having a good outcome. If the treatment effect of cooling is increasing across duration, for at least some set of durations, then this provides evidence of the efficacy of cooling itself versus normothermia, even in the absence of a normothermia control arm, confirming previous RCTs for OHCA survivors of shockable rhythms and provides the first prospective controlled evidence of efficacy in those without initial shockable rhythms.Trial registrationClinicalTrials.gov NCT04217551. Registered on 30 December 2019.

The Association Between Neonatal Intensive Care Unit Arrival Temperatures and Short-Term Outcomes of Neonates with Moderate and Severe Hypoxic-Ischemic Encephalopathy.

Therapeutic hypothermia (TH) is the only treatment method that is known to reduce mortality and neurological sequela rates in newborns with moderate and severe hypoxic-ischemic encephalopathy (HIE). We aimed to evaluate the relationship between rectal temperatures measured upon arrival to our unit and short-term outcomes in newborns with HIE/TH. This was a retrospective study conducted between January 2022 and January 2023. The neonates were divided into three groups according to their rectal temperatures measured upon arrival at our unit as follows: Group 1) <33°C, Group 2) 33-34°C (group arriving at target temperature), and Group 3) >34°C. Short-term outcomes and mortality were compared between the groups. Group 1 consisted of 17 (19.8%) neonates, Group 2 consisted of 34 (39.5%) neonates, and Group 3 consisted of 35 (40.7%) neonates who had HIE and an indication for TH. Rectal temperature on arrival to the unit was not related to the rate of clinical convulsions, rates of abnormal attenuated electroencephalography and magnetic resonance imaging findings, rate of pulmonary hypertension, duration of mechanical ventilation and length of hospital stay. Although the mortality rate was 29% in Group 1, it was 3% and 6% in Groups 2 and 3, respectively (p = 0.016). No relationship was found between the rectal temperature upon arrival to the NICU and the short-term outcomes in HIE/TH neonates. However, the mortality rate in those who were overcooled was significantly higher compared with the other groups.

Clinical Insights and Future Directions in Hypothermia for Severe Traumatic Brain Injury: A Narrative Review.

Fever control is essential in patients with severe traumatic brain injury (TBI). The efficacy of therapeutic hypothermia (TH) in severe TBI has been investigated over the last few decades; however, in contrast to experimental studies showing benefits, no evidence of efficacy has been demonstrated in clinical practice. In this review, the mechanisms and history of hypothermia were briefly outlined, while the results of major randomized controlled trials (RCTs) and meta-analyses investigating TH for adult TBI were introduced and discussed. The retrieved meta-analyses showed conflicting results, with a limited number of studies indicating the benefits of TH. Some studies have shown the benefits of long-term TH compared with short-term TH. Although TH is effective at lowering elevated intracranial pressure (ICP), reduced ICP does not lead to favorable outcomes. Low-quality RCTs overestimated the benefits of TH, while high-quality RCTs showed no difference or worse outcomes with TH. RCTs assessing standardized TH quality demonstrated the benefits of TH. As TBI has heterogeneous and complicated pathologies, applying a uniform treatment may not be ideal. A meta-analysis of young patients who underwent early cooling and hematoma removal showed better TH results. TH should not be abandoned, and its optimal usage should be advocated on an individual basis.

Servo-controlled therapeutic hypothermia during neonatal transport: a before-and-after quality improvement project.

The use of servo-controlled therapeutic hypothermia makes it possible to reach the temperature target, without increasing the age of arrival in the NICU. • CTH is rarely used during transport in France even if passive hypothermia rarely reaches temperature target, inducing overcooling and hyperthermia. • This study shows better temperature control on arrival in the NICU with CTH compared to passive hypothermia, with no increase in arrival time.

Parent-infant closeness and care practices during therapeutic hypothermia in Swedish neonatal intensive care units

ObjectivesThe aim of this study was to investigate care practices among Neonatal Intensive Care Units (NICU) providing Therapeutic hypothermia (TH), and more specific to investigate staff’s experiences of parental participation, presence, and possibilities of being close with their infant during TH. MethodsA descriptive, qualitative, and quantitative study. All Swedish NICUs providing TH (n = 10) participated. Data were collected during January–April 2021 via a questionnaire followed by a semi-structured interview with the registered nurse and the neonatologist responsible for TH at each unit. Descriptive statistics were calculated, and a qualitative content analysis was performed. ResultsAll NICUs allowed parents unlimited stay with their infants and were keen to support parental presence, which was a prerequisite for promoting parent-infant closeness. Standardized routines regarding the infants’ care space and course of action were described as time-efficient and staff-saving, which freed up time to focus on the families. ConclusionStandardized routines regarding the care space setup and the medical and caring approach, as well as the NICU environment and practices around the families, can promote or curb the possibilities of parent-infant closeness. Well-established care practices and good environmental conditions with flexibility regarding the family’s needs are therefore required.