Whole-body Therapeutic Hypothermia Research Articles

Esophageal Versus Rectal Temperature Monitoring During Whole-Body Therapeutic Hypothermia for Hypoxic–Ischemic Encephalopathy: Association with Short- and Long-Term Outcomes

To compare the short- and long-term outcomes of infants with hypoxic-ischemic encephalopathy (HIE) treated with whole-body therapeutic hypothermia (TH), monitored by esophageal vs rectal temperature. We conducted a secondary analysis of the multicenter High-Dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial. All infants had moderate or severe HIE and were treated with whole-body TH. The primary outcome was death or neurodevelopmental impairment (NDI) at 22-36months of age. Secondary outcomes included seizures, evidence of brain injury on magnetic resonance imaging, and complications of hypothermia. Logistic regression was used with adjustment for disease severity and site as clustering variable because cooling modality differed by site. Of the 500 infants who underwent TH, 294 (59%) and 206 (41%) had esophageal and rectal temperature monitoring, respectively. There were no differences in death or NDI, seizures, or evidence of injury on magnetic resonance imaging between the 2 groups. Infants treated with TH and rectal temperature monitoring had lower odds of overcooling (OR 0.52, 95% CI 0.34-0.80) and lower odds of hypotension (OR 0.57, 95% CI 0.39-0.84) compared with those with esophageal temperature monitoring. Although infants undergoing TH with esophageal monitoring were more likely to experience overcooling and hypotension, the rate of death or NDI was similar whether esophageal monitoring or rectal temperature monitoring was used. Further studies are needed to investigate whether esophageal temperature monitoring during TH is associated with an increased risk of overcooling and hypotension.

Analgesia and sedation strategies in neonates undergoing whole-body therapeutic hypothermia: A scoping review

Background Therapeutic hypothermia (TH) is a widely practiced neuroprotective strategy for neonates with hypoxic-ischemic encephalopathy. Induced hypothermia is associated with shivering, cold pain, agitation, and distress. Objective This scoping review determines the breadth of research undertaken for pain and stress management in neonates undergoing hypothermia therapy, the pharmacokinetics of analgesic and sedative medications during hypothermia and the effect of such medication on short- and long-term neurological outcomes. Methods We searched the following online databases namely, (i) MEDLINE, (ii) Web of Science, (iii) Cochrane Library, (iv) Scopus, (v) CINAHL, and (vi) EMBASE to identify published original articles between January 2005 and December 2022. We included only English full-text articles on neonates treated with TH and reported the sedation/analgesia strategy used. We excluded articles that reported TH on transport or extracorporeal membrane oxygenation, did not report the intervention strategies for sedation/analgesia, and reported hypoxic-ischemic encephalopathy in which hypothermia was not applied. Results The eligible publications (n = 97) included cohort studies (n = 72), non-randomized experimental studies (n = 2), pharmacokinetic studies (n = 4), dose escalation feasibility trial (n = 1), cross-sectional surveys (n = 5), and randomized control trials (n = 13). Neonatal Pain, Agitation, and Sedation Scale (NPASS) is the most frequently used pain assessment tool in this cohort. The most frequently used pharmacological agents are opioids (Morphine, Fentanyl), benzodiazepine (Midazolam) and Alpha2 agonists (Dexmedetomidine). The proportion of neonates receiving routine sedation-analgesia during TH is center-specific and varies from 40–100% worldwide. TH alters most drugs’ metabolic rate and clearance, except for Midazolam. Dexmedetomidine has additional benefits of thermal tolerance, neuroprotection, faster recovery, and less likelihood of seizures. There is a wide inter-individual variability in serum drug levels due to the impact of temperature, end-organ dysfunction, postnatal age, and body weight on drug metabolism. Conclusions No multidimensional pain scale has been tested for reliability and construct validity in hypothermic encephalopathic neonates. There is an increasing trend towards using routine sedation/analgesia during TH worldwide. Wide variability in the type of medication used, administration (bolus versus infusion), and dose ranges used emphasizes the urgent need for standardized practice recommendations and guidelines. There is insufficient data on the long-term neurological outcomes of exposure to these medications, adjusted for underlying brain injury and severity of encephalopathy. Future studies will need to develop framework tools to enable precise control of sedation/analgesia drug exposure customized to individual patient needs.

Early clinical outcome and complications associated in neonates with hypoxic ischemic encephalopathy grade II/III who underwent treatment with servo controlled whole-body therapeutic hypothermia: A prospective observational study

Background: There are limited data regarding servo-controlled whole-body therapeutic hypothermia (TH) for neonates with hypoxic-ischemic encephalopathy (HIE) Stage II/III in the Indian setting. The objectives of this study were to determine the early clinical outcome of neonates with HIE Stage II/III treated with TH and to determine the mortality rate and associated complications. Methods: This study was a prospective observational study done at a Level 3A National Neonatology Forum accredited tertiary care neonatal intensive care unit (NICU). Term neonates with HIE Grade II/III admitted to NICU within 6 h of birth were enrolled in the study. Subjects underwent servo-controlled whole-body therapeutic cooling as per the research protocol. Results: Out of 54 subjects, 22 (40.7%) had stage II HIE and 32 (59.3%) had Stage III. The mortality rate was 24% (n = 13), with all having Stage 3. Direct breastfeeds was achieved in 65.9% of successfully cooled babies within 48 h after TH treatment. About 85.4% of babies who were successfully cooled had good early clinical outcomes as evidenced by good activity, normal tone, successful direct breastfeeding, and early discharge within 72 h post treatment with TH. Coagulopathy was observed in 70.4%, raised liver enzymes in 96.3% and thrombocytopenia in 9.3%. Conclusion: There is a significant correlation of grade of encephalopathy and blood gas abnormality at admission with the outcome in babies with HIE treated with TH. Majority of babies with HIE stage 2/3 who successfully completed TH had good early clinical outcomes at the time of discharge.

Oropharyngeal Dysphagia in Breastfeeding Neonates with Hypoxic-Ischemic Encephalopathy on Therapeutic Hypothermia.

Purpose: To identify symptoms of oropharyngeal dysphagia (OPD) in breastfeeding neonates with hypoxic-ischemic encephalopathy (HIE) on therapeutic hypothermia (TH). Early identification of feeding problems in neonates with HIE by speech-language therapists (SLTs) may prevent secondary complications of OPD such as aspiration pneumonia and death. Materials and Methods: Twenty-eight full-term neonates with HIE (mean chronological age = 4.5 days) and 30 healthy term controls were prospectively recruited for this case-control study. Participants with HIE (mild [n = 15], moderate [n = 11], severe [n = 2]), diagnosed by pediatricians, received whole-body TH. Feeding was clinically evaluated by an SLT using the Preterm Infant Breastfeeding Behavior Scale. Results: Twenty-five neonates (89.2%) had at least one symptom of OPD. Falling asleep during feeding, noticeable oral secretions, coughing, and flaring nostrils were symptoms of OPD most frequently identified. The HIE group displayed limited arousal during breastfeeding and had less obvious rooting, shallower latching onto the breast, and more single sucks in comparison to term newborns. The HIE group had significantly more closed eyes and minimal movement during breastfeeding, while controls showed the quiet-alert state ideal for breastfeeding. Conclusions: OPD was identified in the majority of infants with HIE. Underlying the appearance of an inactive neonate with HIE may be OPD that could be overlooked if not investigated. Interprofessional collaboration between SLTs, pediatricians and nurses to determine feeding-readiness is imperative. SLTs may assist in decision-making to improve safety of breastfeeding in this population. This study contributes to the small body of research on early breastfeeding of neonates with HIE.

SUN-LB087 Successful Prevention of Common Complications of Severe Hypercalcemia Secondary to Subcutaneous Fat Necrosis of the Newborn Following Whole Body Therapeutic Hypothermia

Background: Subcutaneous fat necrosis (SCFN) is a rare form of panniculitis mostly seen in neonates with a history of significant perinatal stress and may be associated with life-threatening hypercalcemia. Clinical Case: An infant boy born by emergent C-section at 39 4/7 weeks to a 32 y/o G2P0 mother due to pre-eclampsia, emerged limp, cyanotic and apneic with heart rate<100 bpm and thick meconium-stained amniotic fluid. Following positive pressure ventilation, his heart rate improved, but, his poor respiratory effort and poor muscle tone persisted. Apgar scores were 2, 5, 6 and 8 at 1, 5, 10 and 15 minutes, respectively. The infant was transferred to the NICU on continuous positive airway pressure. Whole body therapeutic hypothermia (WBTH) was initiated based on the presence of neurologic dysfunction and markers of hypoxic-ischemic injury: metabolic acidosis (cord blood pH 6.89, incalculable bicarbonate), elevated lactate (4.1 mmol/L, n 0.5 - 2 mmol/L), abnormal liver function tests (AST 811 IU/L, n 13 - 39; ALT 1175 IU/L, n 4 - 36 IU/L; LDH >4000 IU/L, n 100 - 250 IU/L), abnormal coagulation panel (PT 75.4 sec, n 9.7 - 12.4 sec; PTT 58.7 sec, n 25 - 37 sec; INR 6.85, n 0.9 - 1.2) and thrombocytopenia (platelet count 90 K/uL, n 150 - 450 K/uL). IV fluids, platelet transfusions and antibiotics were given for presumed sepsis. WBTH was completed on day of life (DOL) 3 and infant was re-warmed overnight. SCFN presented on DOL 4 as erythematous, tender, nodular indurations throughout the skin over the dorsum. Supportive therapy was given: repositioning, morphine for pain during feeding and handling and bacitracin ointment to areas of skin desquamation. Labs were consistent with SCFN. On DOL 18, total serum calcium (TSC) increased to 11.8 mg/dL (n 8.8 - 11.2 mg/dL), intact parathyroid hormone (1 pg/mL, n 14 - 72 pg/mL), PTH related peptide (<2.0 pmol/L, n <2.0 pmol/L), 25 hydroxyvitamin D3 (22.8 ng/mL, n 20 - 50 ng/mL) and 1,25 dihydroxyvitamin D3 (80.7 pg/mL, n 19 - 79.3 pg/mL). Mother discontinued all vitamin supplementation and breastmilk was supplemented with low-calcium infant formula. TSC peaked on DOL 28 to 13.2 mg/dL, and oral furosemide (2 mg/kg/dose, BID) was started. On DOL 30, oral prednisolone (2mg/kg/day) and polycitrate for urine alkalization and prevention of nephrocalcinosis were initiated. Furosemide was discontinued on DOL 32. IV fluids and polycitrate were discontinued on DOL 42. Oral prednisolone was continued following a taper schedule. Urine calcium to urine creatinine ratios initially showed a marked elevation with peak of 1.67 (n <0.86) but eventually began to decline throughout the course of therapy. Head and repeat renal ultrasounds were normal. The infant was discharged home on DOL 50 with down-trending TSC levels and completed a slow oral prednisolone taper on DOL 130. Conclusion: Early recognition and treatment of SCFN and associated hypercalcemia is crucial to prevent morbidity and mortality. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Incidence of hypoxic-ischaemic encephalopathy and use of therapeutic hypothermia in Spain

Abstract Introduction There are no data on the incidence of hypoxic-ischaemic encephalopathy (HIE) and the implementation of therapeutic hypothermia (TH) in Spain. Methods This is a cross-sectional, national study, performed using an on-line questionnaire targeting level III neonatal care units in Spain. Participants were requested to provide data of all newborns ≥ 35 weeks of gestational age diagnosed with moderate-severe HIE over a two year-period (2012–2013), and of the implementation of TH up to June 2015. Results All (90) contacted hospitals participated. HIE incidence rate was 0.77/1000 live newborns (95% CI 0.72–0.83). During 2012–2013, 86% of the newborns diagnosed with moderate-severe HIE received TH (active or passive). Active TH was increasingly used, from 78% in 2012 to 85% in 2013 (P = .01). Of the 14% that did not receive TH, it was mainly due to a delay in the diagnosis or inter-hospital transfer, and to the fact that the treatment was not offered. More than half (57%) were born in hospitals where TH was not provided, and passive hypothermia was used for inter-hospital patient transfer, and in 39% of the cases by inappropriately trained personnel. By June 2015, 57 out of 90 centres had implemented TH, of which 54 performed whole-body TH (using servo-controlled devices). The geographical distribution of centres with active TH, and the number of newborn that received TH, was heterogeneous. Conclusions The incidence of moderate-severe HIE is homogeneous across Spanish territory. Significant progress is being made in the implementation of TH, however it is necessary to increase the availability of active TH between Autonomous Communities, to improve early diagnosis, and to guarantee high quality patient transfer to referral centres.

Population-Based Study of the National Implementation of Therapeutic Hypothermia in Infants with Hypoxic-Ischemic Encephalopathy.

Data on the incidence of hypoxic-ischemic encephalopathy (HIE) in the first 6 hours of life together with the implementation of therapeutic hypothermia (TH) are relevant to delineate actions to achieve the lowest rates of neonatal mortality, morbidity, and long-term impact on health associated with HIE. This is population-based national survey study, including newborns ≥35 weeks of gestation with moderate-to-severe HIE from all level III neonatal care units, to provide the incidence of HIE for the period 2012-2013, and the implementation of TH up to June 2015 in Spain. Incidence rate was 0.77 per 1000 live births (95% confidence interval 0.72-0.83). By June 2015, 63% (57/90) of the units had implemented TH; 95% of them performed servo-controlled whole-body TH. For the 2-year period, 86% of the newborns diagnosed with moderate-to-severe HIE received TH. Active TH increased in use from 78% in 2012 to 85% in 2013 (p = 0.01). The main reasons for not cooling were a delay in the diagnosis (31/682) and the fact that the treatment was not offered (20/682). Interhospital patient transfer was performed using passive hypothermia, by appropriately trained personnel in 61% of centers. Eighteen percent of newborns with moderate or severe HIE died, without significant differences between the 2 years. Up-to-date knowledge of the national coverage of neonatal care of infants with HIE in developed countries is a prerequisite to reducing the load of HIE in this area and to facilitating coordinated, eliminate investigation.

Examining potential side effects of therapeutic hypothermia in experimental intracerebral hemorrhage

Studies treating intracerebral hemorrhage (ICH) with therapeutic hypothermia (TH) have shown inconsistent benefits. We hypothesized that TH’s anti-inflammatory effects may be responsible as inflammatory cells are essential for removing degrading erythrocytes. Here, we subjected rats to a collagenase-induced striatal ICH followed by whole-body TH (∼33℃ for 11–72 h) or normothermia. We used X-ray fluorescence imaging to spatially quantify total and peri-hematoma iron three days post-injury. At three and seven days, we measured non-heme iron levels. Finally, hematoma volume was quantified on one, three, and seven days. In the injured hemisphere, total iron levels were elevated (p < 0.001) with iron increasing in the peri-hematoma region (p = 0.007). Non-heme iron increased from three to seven days (p < 0.001). TH had no effect on any measure of iron (p ≥ 0.479). At one and three days, TH did not affect hematoma volume (p ≥ 0.264); however, at seven days there was a four-fold increase in hematoma volume in 40% of treated animals (p = 0.032). Thus, even when TH does not interfere with initial increases in total and non-heme iron or its containment, TH can cause re-bleeding post-treatment. This serious complication could partly account for the intermittent protection previously observed. This also raises serious concerns for clinical usage of TH for ICH.

The temporal characteristics of seizures in neonatal hypoxic ischemic encephalopathy treated with hypothermia

PurposeThe characteristics of electrographic seizures in newborns with hypoxic-ischaemic encephalopathy (HIE) treated with therapeutic hypothermia (TH) are poorly described. This retrospective, observational study provides reference data on the characteristics of seizures and their evolution over time in newborns with HIE receiving whole-body TH. MethodThe cohort under analysis included 23 infants with HIE and seizures defined by multi-channel EEG recordings. Clinical presentation, details of TH and antiepileptic drugs used were recorded. Time from first to last-recorded electrographic seizure (seizure period) was calculated. Temporal characteristics of seizures – total burden, duration, number, burden in minutes per hour, distribution of burden over time (temporal evolution), time from seizure onset to maximum seizure burden (Tmsb), T1, and time from Tmsb to seizure offset, T2 – were analysed. ResultsThe median age at electrographic seizure onset was 13.1h (IQR: 11.4 to 22.0). Tmsb was reached at a median age of 19.4hours (IQR: 12.2 to 29.7). Median seizure period was 16.5h (IQR: 7.0 to 49.7), median number of seizures per hour was 1.9 (IQR: 1.0 to 3.3). The seizure burden was 4.0min/h (IQR: 2.0 to 7.0). There was no consistent pattern in the temporal evolution of seizures in neonates treated with TH. The skewness was neither positive nor negative (p-value=0.15), there was no difference between the duration of T1 and T2 (p-value=0.09) and no difference in the seizure burden between T1 and T2 (p=0.09).There was an association between Tmsb and Phenobarbital (PB) administration (r=0.76, p-value<0.001). ConclusionThere is no consistent temporal evolution of seizure burden in neonates treated with TH. Seizures are diffuse, and their characteristics are variable.

Less severe cerebral palsy outcomes in infants treated with therapeutic hypothermia.

To describe the incidence, type and severity of cerebral palsy at 24 months in a regional cohort of infants treated with whole-body therapeutic hypothermia for neonatal encephalopathy. Data were collected prospectively in a regional centre providing TH. Antenatal and perinatal clinical variables and severity of encephalopathy were collected. Infants were assessed at 18 months using the Bayley Scales of Infant and Toddler Development-III, and the presence and severity of CP was investigated at 24 months. A total of 125 of 132 infants fulfilled entry criteria for TH trials and completed 72 h of TH. Sixteen (13%) of the 125 infants died, and eight (6%) were not available for follow-up. Eighteen infants (14%; 18% of those assessed) developed CP. Of these, 12 (67%) were classified using the Gross Motor Function Classification System, at level 1, six (33%) at level 5 and none at levels 2, 3 or 4. Our regional clinical cohort had lower mortality and comparable rates of CP compared with historical outcomes in TH trials. In contrast to historical cohorts, only one-third of the 18 children with CP were severely affected and 12 were mildly affected, all of whom were independently ambulant by 24 months.

High blood carbon dioxide variability and adverse outcomes in neonatal hypoxic ischemic encephalopathy

Objective: Hypocarbia during the first 12 h of life is associated with mortality and disability in neonatal hypoxic ischemic encephalopathy (HIE). Notable variation in arterial carbon dioxide tension (PaCO2) during the first 4 d of life is related to severe intraventricular hemorrhages in preterm infants. We examined the association between PaCO2 during 72 h of whole-body therapeutic hypothermia for neonatal HIE and 2-year neurodevelopmental outcomes. Methods: A retrospective review of 23 term neonates treated with whole-body hypothermia documented clinical, demographic and arterial blood gas data. Comparisons were made across good and severe neurodevelopmental outcome groups at 2 years of age. Results: Severe neurodevelopmental outcomes were documented in 8 of 23 toddlers. There were no significant differences between outcome groups with regard to the number of patients with hypocarbic means or measurements. There were also no significant differences with mean PaCO2, PaO2, pH, time-weighted cumulative hypocarbia, and PaCO2 range. The severe neurodevelopmental outcomes group had a significantly higher mean PaCO2 standard deviation (p = 0.04; 95% CI, −5.46 to −0.39). Conclusion: Severe neurodevelopmental outcomes were significantly associated with high PaCO2 variability over 72 h in whole-body-cooled HIE neonates. Mitigating these fluctuations may be a potential management strategy.

The myocardial function during and after whole-body therapeutic hypothermia for hypoxic–ischemic encephalopathy, a cohort study

BackgroundTherapeutic hypothermia has become standard treatment for moderate and severe neonatal hypoxic–ischemic encephalopathy (HIE) to reduce cerebral morbidity and mortality. The effect on the heart is incompletely explored. AimTo assess the myocardial function during and after whole-body therapeutic hypothermia for HIE. Study designObservational cohort study. SubjectsForty-four infants with HIE cooled for 72hours were compared with 48 healthy term infants and 20 normothermic infants with HIE. Outcome measuresTissue Doppler deformation indices of myocardial function (peak systolic strain, peak systolic strain-rate, early diastole strain-rate and strain-rate in atrial systole) during (days 1 and 3) and after (day 4) therapeutic hypothermia. ResultsOn days one and three all indices in both HIE groups were lower than the corresponding indices in the healthy infants. The two HIE groups had similar indices, except peak systolic strain-rate on days 1 and 3 and strain-rate in atrial systole on day 1. All strain-rate indices improved from day 3 to 4 (after rewarming) in the cooled group and achieved similar values to those in healthy infants on day 3. All indices were higher in the cooling-group after rewarming than in the normothermic infants with HIE on day 3, except early diastolic strain-rate. ConclusionsInfants with HIE had similarly impaired myocardial function during days 1–3 whether normothermic or hypothermic. The myocardial function improved significantly at day 4 (after rewarming), approaching the day 3 levels in the healthy neonates.

Preferential Cephalic Redistribution of Left Ventricular Cardiac Output during Therapeutic Hypothermia for Perinatal Hypoxic-Ischemic Encephalopathy

To determine the relationship between left ventricular cardiac output (LVCO), superior vena cava (SVC) flow, and brain injury during whole-body therapeutic hypothermia. Sixteen newborns with moderate or severe hypoxic-ischemic encephalopathy were studied using echocardiography during and immediately after therapeutic hypothermia. Measures were also compared with 12 healthy newborns of similar postnatal age. Newborns undergoing therapeutic hypothermia also had cerebral magnetic resonance imaging as part of routine clinical care on postnatal day 3-4. LVCO was markedly reduced (mean ± SD 126 ± 38 mL/kg/min) during therapeutic hypothermia, whereas SVC flow was maintained within expected normal values (88 ± 27 mL/kg/min) such that SVC flow represented 70% of the LVCO. The reduction in LVCO during therapeutic hypothermia was mainly accounted by a reduction in heart rate (99 ± 13 vs 123 ± 17 beats/min; P < .001) compared with immediately postwarming in the context of myocardial dysfunction. Neonates with brain injury on magnetic resonance imaging had higher SVC flow prerewarming, compared with newborns without brain injury (P = .013). Newborns with perinatal hypoxic-ischemic encephalopathy showed a preferential systemic-to-cerebral redistribution of cardiac blood flow during whole-body therapeutic hypothermia, which may reflect a lack of cerebral vascular adaptation in newborns with more severe brain injury.

Maintenance of whole-body therapeutic hypothermia during patient transport and magnetic resonance imaging

Therapeutic hypothermia has become standard treatment for neonatal hypoxic-ischemic encephalopathy (HIE), with brain MRI commonly performed after the child has been rewarmed. However, early imaging during hypothermia might provide information important in designing clinical trials that refine and personalize therapeutic hypothermia. We tested a protocol to ensure safety and maintenance of hypothermia during in-hospital transport and MRI. MRI during therapeutic hypothermia was performed in 13 newborns on the 2nd-3rd postnatal days. Mean one-way transport time was 20.0 ± 3.3 min. Mean rectal temperatures (°C) leaving the unit, upon arrival at the MR suite, during MRI scan and upon return to the unit were 33.5 ± 0.3 °C, 33.3 ± 0.3 °C, 33.1 ± 0.4 °C and 33.4 ± 0.3 °C, respectively. Using our protocol therapeutic hypothermia was safely and effectively continued during in-hospital transport and MRI without adverse effects.

Effects of whole body therapeutic hypothermia on gastrointestinal morbidity and feeding tolerance in infants with hypoxic ischemic encephalopathy.

Objective. This retrospective cohort study evaluated the effects of whole body therapeutic hypothermia (WBTH) on gastrointestinal (GI) morbidity and feeding tolerance in infants with moderate-to-severe hypoxic ischemic encephalopathy (HIE). Study Design. Infants ≥ 35 weeks gestational age and ≥1800 grams birth weight with moderate-to-severe HIE treated from 2000 to 2012 were compared. 68 patients had documented strictly defined criteria for WBTH: 32 historical control patients did not receive WBTH (non-WBTH) and 36 cohort patients received WBTH. Result. More of the non-WBTH group infants never initiated enteral feeds (28% versus 6%; P = 0.02), never reached full enteral feeds (38% versus 6%, P = 0.002), and never reached full oral feeds (56% versus 19%, P = 0.002). Survival analyses demonstrated that the WBTH group reached full enteral feeds (median time: 11 versus 9 days; P = 0.02) and full oral feeds (median time: 19 versus 10 days; P = 0.01) sooner. The non-WBTH group had higher combined outcomes of death and gastric tube placement (47% versus 11%; P = 0.001) and death and gavage feeds at discharge (44% versus 11%; P = 0.005). Conclusion. WBTH may have beneficial effects on GI morbidity and feeding tolerance for infants with moderate-to-severe HIE.

OFF-LABEL USE OF PAMIDRONATE IN HYPER-CALCEMIC NEWBORN AFFECTED BY SUBCUTANEOUS FAT NECROSIS AFTER THERAPEUTIC HYPOTERMIA

Background: Subcutaneous fat necrosis is a dermatological disorder with characteristic subcutaneous nodules or plaques. It has a benign nature and generally runs a self-limiting course, although can cause significant and dangerous complications, including hypercalcemia. Outbreak of hypercalcemia occurs even several months after hypothermic treatment in asymptomatic or symptomatic way. Irritability, lethargy, hypotonia, emesis, polyuria, polydipsia, constipation and failure to thrive are the most common symptoms of hypercalcemia while seizures, cardiac arrest and acute or chronic renal failure are the most serious manifestations. Chronic hypercalcemia is also associated with nephrocalcinosis and metastatic calcifications of skin, heart, lever and vessels. Low calcium and vitamine D formula preparation milk, diuretics, such as furosemide, and corticosteroids are first-line treatments. In some refractory case pamidronate is used. Pamidronate is a biphosphonate which can modulate bone turnover by leading hydroxyapatite crystals, and it can inhibit osteoclastic bone resorption. Observation: A male full-term infant weighing 2,300 grams was born after an emergency cesarean section due to fetal heart rate decelerations. His initial Apgar scores were 1 at 1 minute, 4 at 5 minutes and 8 at 15 minutes. Due to hypoxicischaemic encephalopathy (stage 1 of Sarnat classification, with abnormal voltage and paroxysmal activities at electroencephalogram),a whole-body therapeutic hypothermia was initiated before sixth hour of life. It was performed to a target rectal temperature of 33,5&deg;C, for about 36 hours. In the third day of life, he developed characteristic subcutaneous fat necrosis skin lesions, such as firm, indurated plaques and red and violaceous nodules, on the upper back area and buttocks. One month after the hypotermic treatment the infant developed a rapid, asymptomatic increase of calcemia. First his milk was changed to a very low calcium and vitamin D formula preparation, without a clinical improvement. Hypercalcemia (total serum calcium 13,8 mg/dL [reference range 9-10.9 mg/dL] and ionized calcium 1,96 mmol/L [reference range 1,12-1,32 mmol/L]) was successfully treated with a 3-days therapy of intravenous pamidronate at dose of 0,5 mg/kg/die. No side effects were detected during the treatment and then serum calcium levels remained stable.

OFF-LABEL USE OF PAMIDRONATE IN HYPER-CALCEMIC NEWBORN AFFECTED BY SUBCUTANEOUS FAT NECROSIS AFTER THERAPEUTIC HYPOTERMIA

Background: Subcutaneous fat necrosis is a dermatological disorder with characteristic subcutaneous nodules or plaques. It has a benign nature and generally runs a self-limiting course, although can cause significant and dangerous complications, including hypercalcemia. Outbreak of hypercalcemia occurs even several months after hypothermic treatment in asymptomatic or symptomatic way. Irritability, lethargy, hypotonia, emesis, polyuria, polydipsia, constipation and failure to thrive are the most common symptoms of hypercalcemia while seizures, cardiac arrest and acute or chronic renal failure are the most serious manifestations. Chronic hypercalcemia is also associated with nephrocalcinosis and metastatic calcifications of skin, heart, lever and vessels. Low calcium and vitamine D formula preparation milk, diuretics, such as furosemide, and corticosteroids are first-line treatments. In some refractory case pamidronate is used. Pamidronate is a biphosphonate which can modulate bone turnover by leading hydroxyapatite crystals, and it can inhibit osteoclastic bone resorption. Observation: A male full-term infant weighing 2,300 grams was born after an emergency cesarean section due to fetal heart rate decelerations. His initial Apgar scores were 1 at 1 minute, 4 at 5 minutes and 8 at 15 minutes. Due to hypoxicischaemic encephalopathy (stage 1 of Sarnat classification, with abnormal voltage and paroxysmal activities at electroencephalogram),a whole-body therapeutic hypothermia was initiated before sixth hour of life. It was performed to a target rectal temperature of 33,5°C, for about 36 hours. In the third day of life, he developed characteristic subcutaneous fat necrosis skin lesions, such as firm, indurated plaques and red and violaceous nodules, on the upper back area and buttocks. One month after the hypotermic treatment the infant developed a rapid, asymptomatic increase of calcemia. First his milk was changed to a very low calcium and vitamin D formula preparation, without a clinical improvement. Hypercalcemia (total serum calcium 13,8 mg/dL [reference range 9-10.9 mg/dL] and ionized calcium 1,96 mmol/L [reference range 1,12-1,32 mmol/L]) was successfully treated with a 3-days therapy of intravenous pamidronate at dose of 0,5 mg/kg/die. No side effects were detected during the treatment and then serum calcium levels remained stable.

Axillary temperature measurement during hypothermia treatment for neonatal hypoxic-ischaemic encephalopathy

ObjectiveTo determine the accuracy of axillary temperature relative to core rectal temperature during whole-body therapeutic hypothermia for moderate-to-severe hypoxic-ischaemic encephalopathy.DesignRetrospective audit.SettingSingle tertiary neonatal intensive care unit at The Royal Women's...

Electrographic Seizures During Therapeutic Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy

Electrographic seizures are common in neonates with hypoxic-ischemic encephalopathy, but detailed data are not available regarding seizure incidence during therapeutic hypothermia. The objective of this prospective study was to determine the incidence and timing of electrographic seizures in term neonates undergoing whole-body therapeutic hypothermia for hypoxic-ischemic encephalopathy as detected by conventional full-array electroencephalography for 72 hours of therapeutic hypothermia and 24 hours of normothermia. Clinical and electroencephalography data were collected from 26 consecutive neonates. Electroencephalograms were reviewed by 2 pediatric neurophysiologists. Electrographic seizures occurred in 17 of 26 (65%) patients. Seizures were entirely nonconvulsive in 8 of 17 (47%), status epilepticus occurred in 4 of 17 (23%), and seizure onset was in the first 48 hours in 13 of 17 (76%) patients. Electrographic seizures were common, were often nonconvulsive, and had onset over a broad range of times in the first days of life.