The effect of temperature on the QTc interval in the newborn infant receiving extracorporeal membrane oxygenation (ECMO)

OBJECTIVE: To explore the changes in the QTc interval during mild hypothermia in neonates receiving extracorporeal membrane oxygenation (ECMO). DESIGN: Twenty seven neonates (median gestation 40 weeks; range 33-41 weeks) enrolled in a pilot study of mild hypothermia were studied during the first five days of ECMO. The first group (N=7) were maintained at 37 degrees C throughout the study period. Subsequent groups (N=5) were cooled to 36 degrees C, 35 degrees C and 34 degrees C respectively for twenty four hours and the final group to 34 degrees C for forty eight hours before being rewarmed to 37 degrees C. Using a 24 h digital monitor, the QT and QTc intervals were recorded continuously during the cooling and rewarming period and validated using standard 12 lead electrocardiograms. Patients were carefully assessed clinically and routine biochemistry (including magnesium and calcium) laboratory tests measured pre ECMO and at timed intervals during cooling and rewarming. RESULTS: The mean difference between the continuous digital and 12 lead ECG values for QTc was -13.3 ms. During the first 24 h of cooling, the mean (95th centile) values for the digitally measured QTc interval at 37 degrees C=431(506) milliseconds (ms); 36 degrees C=459(521) ms; 35 degrees C=445(516) ms; 34 degrees C=465(531) ms; 34 degrees C for 48 h=466(521) ms. During this period overall QTc increased by 3.12 ms (95% confidence intervals 6.17 to 0.84; p=0.04) for each degree fall in body temperature. During rewarming, there was no significant relationship between QTc and temperature change. No serious arrhythmias were during cooling. Using univariate analysis, no relationship was found between QTc and electrolytes, heart rate and blood pressure. CONCLUSIONS: QTc shows significant variability in individuals, and only a small proportion of this can be explained by rectal temperature. Mild hypothermia was not associated with serious cardiac arrhythmias.     

Pilot investigation of hypothermia in neonates receiving extracorporeal membrane oxygenation

BACKGROUND: Infants requiring extracorporeal membrane oxygenation (ECMO) support represent a high risk group in terms of cerebral injury. Mild hypothermia both during and after cerebral hypoxic ischaemia appears to be a promising strategy for offering neuroprotection. OBJECTIVE: To investigate whether mild hypothermia was both feasible and safe in infants receiving ECMO as a prelude to any formal assessment of this approach in a randomised trial. METHODS: Twenty infants (body weight less than 5 kg) with severe cardiopulmonary insufficiency, referred for ECMO support at Glenfield Hospital, Leicester, were enrolled in this study. Twenty consecutive infants (compromising four groups of five) were studied. Baseline data were obtained from a control group who were run throughout their course at 37 degrees C. The patients in the next group were managed with a core temperature of 36 degrees C for the first 12 hours of their ECMO run, before being warmed up to 37 degrees C. After successful completion, the next group of five were cared for at 35 degrees C for the first 12 hours, and, there having been no previous complications, the final group were cared for at 34 degrees C for the first 12 hours. Patients were assessed clinically and biologically. In addition to routine laboratory tests, cytokines (interleukin 6, interleukin 8, tumour necrosis factor alpha, and C reactive protein) were measured and coagulation tests (D-dimer, thrombin-antithrombin III complex, plasmin-alpha(2)-antiplasmin complex) were performed serially for five days. RESULTS: There were no significant differences among the four groups in gestational age, birth weight, age at the time of ECMO, Apgar scores at one and five minutes, pH before cannulation, oxygenation index, duration of ECMO, and survival rate to discharge from hospital. No adverse effects of mild hypothermia were found on patient management during ECMO. Laboratory data for up to five days of ECMO also showed no difference among the four groups. CONCLUSION: Mild hypothermia (34 degrees C) for the initial 12 hours of an ECMO run is feasible.     

Lack of influence of mild hypothermia on amplitude integrated-electroencephalography in neonates receiving extracorporeal membrane oxygenation

OBJECTIVE: To observe amplitude integrated electroencephalography (aEEG) in neonates receiving ECMO and to determine whether mild hypothermia influenced the aEEG recording. METHODS: Twenty-six consecutive neonates enrolled in a pilot study of mild hypothermia during ECMO were studied. The first group (N=6) was maintained at 37 degrees C throughout the study period. Subsequent groups were cooled to 36 degrees C (N=4), 35 degrees C (N=5), and finally 34 degrees C (N=6) respectively for 24 h and the final group (N=5) to 34 degrees C for 48 h before being rewarmed to 37 degrees C. The aEEG was recorded continuously during the first 5 days of ECMO. The aEEG was classified as normal, moderately or severely suppressed and examined for the occurrence of seizures. To assess the effect of temperature, the aEEG was compared over 12 h during the final 6 h of cooling and during the first 6 h once infants were rewarmed. RESULTS: No change in aEEG amplitude was noted over the temperature range studied. Of the 26 traces obtained, 16 (62%) were normal throughout, 6 (23%) were intermittently moderately abnormal and 1 (14%) was severely abnormal. Three (11%) traces had periods of frequent seizure activity and these were not associated with clinical manifestations in two neonates. In one infant who suffered a cerebral haemorrhage, the aEEG became abnormal before cranial ultrasound abnormalities were apparent. CONCLUSIONS: Continuous cerebral monitoring with aEEG is feasible during ECMO and may add information to clinical examination. Mild hypothermia to 34 degrees C for up to 48 h does not influence the aEEG suggesting that cerebral monitoring with aEEG is possible during mild hypothermia.     

选择性头部降温治疗对窒息新生儿心脏功能影响的研究

目的　研究亚低温治疗对窒息新生儿心脏功能的影响。方法　将 50例重度窒息足月新生儿分为治疗组 (2 3例 )和对照组 (2 7例 )。治疗组采用选择性头部降温方法 ,维持鼻咽温度在34 0℃± 0 .5℃ ,持续 72h ;对照组不进行亚低温治疗。超声心动图评估心脏收缩及舒张功能 ,并测定肌钙蛋白T(cardiactroponinT ,cTnT)的含量 ,以判断心肌细胞的损伤程度。 结果　 (1 )亚低温治疗组患儿心率与对照组比较 [分别为 (1 0 3± 1 5)次 /min、(1 2 6± 1 4 )次 /min ,P <0 .0 5]明显降低 ,但无心律失常和低血压。 (2 )亚低温治疗组左室射血分数 (EF)、每搏量 (SV)、每分输出量 (CO)与对照组相比 ,差异无显著意义 (P均 >0 .0 5) ;两组左、右室舒张功能不全例数和肺动脉高压例数 ,差异也无显著意义 (P均 >0 .0 5)。 (3)亚低温治疗组和对照组cTnT水平分别为 (0 .47± 0 .1 5)ng/ml和 (0 .35±0 2 1 )ng/ml,差异无显著意义 (P >0 .0 5)。结论　选择性头部降温 (鼻咽温度 34℃ ,持续 72h)治疗新生儿窒息 ,未加重患儿心脏功能的损伤     

Serum cytokine levels in neonates with congenital diaphragmatic hernia

Cytokines play an important role in immune regulation and fetal lung development. The systemic inflammatory response in newborns with congenital diaphragmatic hernia (CDH) has not been characterized so far. We compared various concentrations of cytokines in serum from newborns with CDH and in healthy term neonates. We analyzed cytokine patterns of CDH newborns under extracorporeal membrane oxygenation (ECMO) and mechanical ventilation (MV).38 newborns with CDH were included: ECMO group (n=13) and non-ECMO group (n=25). Healthy term neonates served as controls (n=13). Serum samples were obtained prospectively after birth and during therapy.Concentrations of IFN-α, IL-3,-6,-7,-8,-10, MIP-1α,-1β and TNF-α in serum of newborns with CDH were higher than in umbilical cord blood of term neonates. Infants with severe CDH requiring ECMO therapy had higher postnatal IL-8,-10, and MIP-1α levels than newborns with milder disease in the non-ECMO treated group. IL-10 progressively decreased during the first 3 days following birth under ECMO. In contrast, the chemokine MIP-1α remained elevated during ECMO therapy compared to mechanically ventilated CDH newborns.The pattern of cytokines in the serum of newborns with CDH showed significant elevations compared to term neonates. Our findings indicate that CDH is associated with systemic inflammatory response immediately after birth. ECMO and MV show a similar increase of IL-1α and IP-10 in CDH newborns assuming a persistent pulmonary inflammatory reaction irrespective of the conducted treatment.     

Study protocol: safety and efficacy of propranolol in newborns with Retinopathy of Prematurity (PROP-ROP): ISRCTN18523491

Background

Existing evidence indicates that once mature neonates with severe cardio-respiratory failure become eligible for Extra Corporeal Membrane Oxygenation (ECMO) their chances of intact survival are doubled if they actually receive ECMO. However, significant numbers survive with disability. NEST is a multi-centre randomised controlled trial designed to test whether, in neonates requiring ECMO, cooling to 34°C for the first 48 to 72 hours of their ECMO course leads to improved later health status. Infants allocated to the control group will receive ECMO at 37°C throughout their course, which is currently standard practice around the world. Health status of both groups will be assessed formally at 2 years corrected age.

Methods/Design

All infants recruited to the study will be cared for in one of the four United Kingdom (UK) ECMO centres. Babies who are thought to be eligible will be assessed by the treating clinician who will confirm eligibility, ensure that consent has been obtained and then randomise the baby using a web based system, based at the National Perinatal Epidemiology Unit (NPEU) Clinical Trials Unit. Trial registration. Babies allocated ECMO without cooling will receive ECMO at 37°C ± 0.2°C. Babies allocated ECMO with cooling will be managed at 34°C ± 0.2°C for up to 72 hours from the start of their ECMO run. The minimum duration of cooling will be 48 hours. Rewarming (to 37°C) will occur at a rate of no more than 0.5°C per hour. All other aspects of ECMO management will be identical. Primary outcome: Cognitive score from the Bayley Scales of Infant and Toddler Development, 3^rd edition (Bayley-III) at age of 2 years (24 - 27 months).

Discussion

For the primary analysis, children will be analysed in the groups to which they are assigned, comparing the outcome of all babies allocated to "ECMO with cooling" with all those allocated to "ECMO" alone, regardless of deviation from the protocol or treatment received. For the primary outcome the analysis will compare the mean scores for each group of surviving babies. The rationale for this choice of primary analysis is to give a fair representation of the average ability of assessable children, accepting the limitation that excluding deaths might impose. The consistency of the effect of cooling on the group of babies recruited to the trial will be explored to see whether cooling is of particular help, or not, to specific subgroups of infants, using the statistical test of interaction. Therefore pre-specified subgroup analyses include: (i) whether the ECMO is veno-arterial or veno-venous; (ii) whether the child's oxygenation index at the time of recruitment is <60 or ≥ 60; (iii) initial aEEG pattern shown on the cerebral function monitor, and (iv) primary diagnostic group.

Trial Registration

Current Controlled Trials ISRCTN72635512.     

体外膜肺氧合技术在持续肺动脉高压新生儿救治中的临床应用北大核心CSCD

目的探讨体外膜肺氧合技术(extracorporeal membrane oxygenation,ECMO)在新生儿持续肺动脉高压(persistent pulmonary hypertension of the newborn,PPHN)救治中的临床应用价值。方法回顾性收集2015年1月至2021年12月在中山市人民医院新生儿重症监护室中应用ECMO支持的11例PPHN新生儿的临床资料,包括患儿的一般资料、临床诊断、实验室检查、ECMO支持时间及过程中各种并发症、住院时间、结局等,进行比较分析。结果11例患儿中有10例撤机成功,撤机成功率91%;存活8例,存活率73%。11例患儿ECMO治疗时间26~185 h,平均治疗时间(81±50)h;呼吸机治疗时间57~392 h,平均治疗时间(198±105)h;住院时间2~49 d,平均住院时间(22±15)d。11例患儿ECMO治疗24 h后氧合指数、血乳酸水平较ECMO治疗前均显著改善(P<0.05);其中10例患儿ECMO治疗24 h后肺动脉压力较ECMO治疗前均显著下降(P<0.05);1例患儿在EMCO治疗期间肺动脉压力呈进行性升高,最终死亡,结合尸检肺组织病理及全外显子测序结果,确诊为肺泡毛细血管发育不良。11例患儿ECMO治疗期间发生颅内出血5例,弥散性血管内凝血1例,胃出血1例,肺出血2例,肾功能不全1例,穿刺处出血3例。结论ECMO技术是一种有效应用于常规治疗无效的PPHN新生儿救治的心肺支持措施。应用ECMO技术的并发症发生率高,需严格掌握适应证、把握时机、提高ECMO管理水平,才能提高患儿的撤机率及存活率。     

A prospective, multicenter, randomized study of high versus low positive end-expiratory pressure during extracorporeal membrane oxygenation.

To test the hypothesis that increased positive end-expiratory pressure (PEEP) could prevent deterioration of pulmonary function and lead to more rapid recovery of lung function, we randomly assigned 74 patients undergoing extracorporeal membrane oxygenation (ECMO) at four centers to receive either high (12 to 14 cm H2O) or low (3 to 5 cm H2O) PEEP. The two groups were similar in terms of weight, gestational age, diagnosis, and pre-ECMO course. All other aspects of care were identical. Dynamic lung compliance was measured at baseline and every 12 hours. Radiographs of the chest were obtained daily. Survival rates were similar in the two groups: 36 of 40 for low PEEP and 34 of 34 for high PEEP. The duration of ECMO therapy was 97.4 +/- 36.3 hours in the high-PEEP group and 131.8 +/- 54.5 hours in the low-PEEP group (p less than 0.01). Dynamic lung compliance throughout the first 72 hours of ECMO was significantly higher in patients receiving high PEEP. Radiographic appearance of the lungs correlated well with lung compliance: patients receiving high PEEP had significant deterioration of the radiographic score less frequently than those receiving low PEEP. High PEEP also was associated with significantly fewer complications. We conclude that PEEP of 12 to 14 cm H2O safely prevents deterioration of pulmonary function during ECMO and results in more rapid lung recovery than traditional lung management with low PEEP.     

Hemolysis during long-term extracorporeal membrane oxygenation

We studied the cause of hemolysis during extracorporeal membrane oxygenation (ECMO) by monitoring hematologic and coagulation profiles in seven consecutive infants treated with this procedure. A constrained vortex pump was used in all patients, and the average duration of ECMO was 224 +/- 111 (SD) hours. In all patients, plasma free hemoglobin was low during the first 48 hours after the initiation of ECMO. Later, when visible clots appeared in the ECMO circuit, plasma hemoglobin progressively rose. A rise in the level of fibrin degradation products and a fall in the fibrinogen level were observed concurrently with a rise in the plasma hemoglobin level. After complete circuit changes in six patients, plasma free hemoglobin, fibrin split products, and fibrinogen all returned to baseline values. Neither circuit component changes nor exchange transfusion was effective in normalizing the levels of plasma free hemoglobin, fibrin split products, and fibrinogen. We conclude that when ECMO is administered for prolonged periods, circuit thrombosis occurs and hemolysis ensues. Additional studies are needed to assess the contribution of the constrained vortex pump to this process.     

Early head cooling in newborn piglets is neuroprotective even in the absence of profound systemic hypothermia

BACKGROUND: Selective head cooling in the newborn infant has been proposed as a neuroprotective treatment with a lower level of systemic adverse effect than that of systemic hypothermia. However, the efficacy is not confirmed as well as that of systemic hypothermia. In order to analyze the safety and efficacy of selective head cooling, 25 newborn piglets were randomly selected for either normothermic or hypothermic treatment. METHODS: Global hypoxic insult was induced by lowering the oxygen concentration to the maximal level to maintain the background electroencephalogram (EEG) voltage under 7 microV for 45 min. The core temperature of normothermic piglets was maintained between 38.5 degrees C and 39 degrees C, while prophylactic cooling was applied to the hypothermic piglets at the same time of the insult. Very mild systemic hypothermia by 1 degrees C was induced in addition to selective head cooling with 10 degrees C coolant temperature. Animals were killed for histopathological examination seven hours after the end of the insult. RESULTS: Two normothermic piglets died while all hypothermic piglets survived. Neuropathological findings were significantly severer in the normothermic group than in the hypothermic group. Intracranial pressure was significantly lower, and EEG recovery was significantly better in the hypothermic piglets. There was no significant difference in the lowest oxygen concentration, degrees of acidosis, blood lactate, and blood pressure between the groups, although heart rate was significantly lower in the hypothermic group. CONCLUSIONS: We have demonstrated that early head cooling was effective in preventing some of the earliest brain damage due to hypoxic insult even in the absence of profound systemic hypothermia.     

Inhaled nitric oxide therapy during the transport of neonates with persistent pulmonary hypertension or severe hypoxic respiratory failure

Our aim was to determine whether starting inhaled nitric oxide (iNO) on critically ill neonates with severe hypoxemic respiratory failure and/or persistent pulmonary hypertension (PPH), at a referring hospital at the start of transport, decreases the need for extracorporeal membrane oxygenation (ECMO), lessens the number of hospital days and improves survival in comparison with those patients who were started on iNO only at the receiving facility. The study was a retrospective review of 94 charts of neonates that had iNO initiated by the transport team at a referring hospital or only at the tertiary neonatal intensive care unit (NICU) of the receiving hospital. Data collected included demographics, mode of transport, total number of hospital days, days on inhaled nitric oxide and ECMO use. Of the 94 patients, 88 were included. Of these, 60 were started on iNO at the referring facility (Field-iNO) and 28 were started at the receiving NICU (CHLA-iNO). All patients survived transport to the receiving NICU. Death rates and ECMO use were similar in both groups. Overall, patients who died were younger and had lower birth weights and Apgar scores. For all surviving patients who did not require ECMO, the length of total hospital stay (median days 22 versus 38, P = 0.018), and the length of the hospital stay at the receiving hospital (median days 18 versus 29, P = 0.006), were significantly shorter for the Field-iNO patients than for the CHLA-iNO patients, respectively. Earlier initiation of iNO may decrease length of hospital stay in surviving neonates with PPH not requiring ECMO.     

Surfactant phosphatidylcholine metabolism in neonates with meconium aspiration syndrome

OBJECTIVE: Because meconium directly inhibits surfactant function, we sought to determine the effect of meconium on endogenous surfactant synthesis and clearance. STUDY DESIGN: We studied surfactant phosphatidylcholine kinetics with the use of stable isotopes in 11 newborn infants with meconium aspiration syndrome (MAS) who required extracorporeal membrane oxygenation (ECMO). For comparison we studied 6 neonates with persistent pulmonary hypertension (PPHN) on ECMO and 10 term neonates ventilated for non-pulmonary indications and not on ECMO. All patients received a 24-hour [U- 13C]glucose infusion as precursor for the palmitic acid in surfactant phosphatidylcholine. RESULTS: In the meconium group, the maximal 13C-incorporation in phosphatidylcholine (PC) was half of that in controls (0.09 +/- 0.01 vs 0.18 +/- 0.03 atom percent excess [APE], P = .027). There was a trend toward lower surfactant synthesis in the MAS group (3.3 +/- 0.7%/day) and PPHN group (2.6 +/- 0.3%/day) compared with controls 8.0 +/- 2.4%/day, P = .058). Significantly lower PC concentrations in tracheal aspirates were found in the MAS group (4.4 +/- 2.6 mg/mL) and PPHN group (3.6 +/- 2.0 mg/mL) compared with controls (12.8 +/- 2.6 mg/mL, P = .01). Endogenously synthesized surfactant had a similar half-life in all groups, ranging from 63 to 98 hours. CONCLUSION: We conclude that surfactant synthesis is disturbed and that surfactant PC concentrations are low in infants with MAS on ECMO.     

Cytokine imbalance in infants receiving extracorporeal membrane oxygenation for respiratory failure

BACKGROUND: It is likely that the imbalance between the pro- and anti-inflammatory cytokines will determine the outcome in infants with severe respiratory failure receiving extracorporeal membrane oxygenation (ECMO). AIMS: We determined if there was an imbalance between pro- and anti-inflammatory cytokines in serial bronchoalveolar lavage (BAL) fluid obtained from survivors and non-survivors of ECMO. METHODS: We therefore measured the cellular changes and the molar ratios of pro-inflammatory and anti-inflammatory cytokines in serial BAL fluid obtained from survivors and non-survivors of ECMO. Fifteen infants surviving ECMO (median age 1 day, range 1-120) and 7 who did not (28 days, range 1-402) were studied. RESULTS: In the lungs of survivors, the increased proportion of airway neutrophils at presentation decreased with time and was matched by a parallel increase in percent alveolar macrophages as the infants' condition improved. The pro- and anti-inflammatory pulmonary cytokine ratios were static in the survivors. In the non-survivors, the ratio of tumour necrosis factor-alpha (TNF-alpha) against soluble TNF-receptor 1 (sTNF-R1) and soluble TNF receptor 2 (sTNF-R2) was increased at days 2-3 when compared to the survivors, but the molar ratio interleukin-1beta (IL-1beta)/soluble IL-1 receptor antagonist (sIL-1RA) was largely undetectable due to undetectable IL-1beta. CONCLUSIONS: These data suggest that the infants who survive ECMO resolve their pulmonary inflammation and that in non-survivors the ratio of TNF-alpha against its receptor antagonists is increased and is associated with a poor outcome. Furthermore, this group of infants were unable to produce significant concentrations of IL-1beta.     

Long-term outcome following extracorporeal membrane oxygenation for congenital diaphragmatic hernia: the UK experience

OBJECTIVE: We evaluated the long-term outcome of neonates receiving extracorporeal membrane oxygenation (ECMO) for congenital diaphragmatic hernia (CDH).Study design A retrospective review of all 73 neonates with CDH supported with ECMO in the United Kingdom between 1991 and 2000, with follow-up to January 2003. Information was from hospital charts and from communication with family doctors and pediatricians. Median follow-up period for survivors was 67 months. RESULTS: 46 infants (63%) were weaned from ECMO, 42 (58%) survived to hospital discharge, and 27 (37%) survived to age 1 year or more. A higher birth weight, higher 5-minute Apgar score, and postnatal diagnosis were "pre-ECMO" predictors of long-term survival. Comorbidity was common in long-term survivors: 13 (48%) had respiratory symptoms, 16(59%) had gastrointestinal problems, and 6 (19%) had severe neurodevelopmental problems. Only 7 children were free of significant neurodevelopmental deficit and required no further medical or surgical intervention. CONCLUSION: Using the current referral criteria, ECMO can be used to support the sickest neonates with CDH. However, there is significant mortality in the first year of life, and long-term physical and neurodevelopmental morbidity remains in the majority of survivors.     

Postnatal hypothermia and cold stress among newborn infants in Nepal monitored by continuous ambulatory recording.

AIMS: To describe the pattern of hypothermia and cold stress after delivery among a normal neonatal population in Nepal; to provide practical advice for improving thermal care in a resource limited maternity hospital. METHODS: The principal government funded maternity hospital in Kathmandu, Nepal, with an annual delivery rate of 15,000 (constituting 40% of all Kathmandu Valley deliveries), severe resource limitations (annual budget Pounds 250,000), and a cold winter climate provided the setting. Thirty five healthy term neonates not requiring special care were enrolled for study within 90 minutes of birth. Continuous ambulatory temperature monitoring, using microthermistor skin probes for forehead and axilla, a flexible rectal probe, and a black ball probe placed next to the infant for ambient temperature, was carried out. All probes were connected to a compact battery powered Squirrel Memory Logger, giving a temperature reading to 0.2 degree C at five minute intervals for 24 hours. Severity and duration of hypothermia, using cutoff values of core temperature less than 36 degrees C, 34 degrees C, and 32 degrees C; and cold stress, using cutoff values of skin-core (forehead-axilla) temperature difference greater than 3 degrees C and 4 degrees C were the main outcome measures. RESULTS: Twenty four hour mean ambient temperatures were generally lower than the WHO recommended level of 25 degrees C (median 22.3 degrees C, range 15.1-27.5 degrees C). Postnatal hypothermia was prolonged, with axillary core temperatures only reaching 36 degrees C after a mean of 6.4 hours (range 0-21.1; SD 4.6). There was persistent and increasing cold stress over the first 24 hours with the core-skin (axillary-forehead) temperature gap exceeding 3 degrees C for more than half of the first 24 hours. CONCLUSIONS: Continuous ambulatory recording identifies weak links in the "warm chain" for neonates. The severity and duration of thermal problems was greater than expected even in a hospital setting where some of the WHO recommendations had already been implemented.     

Hypothermia to treat neonatal hypoxic ischemic encephalopathy: systematic review

OBJECTIVES: To systematically review the effectiveness, as determined by survival without moderate to severe neurodevelopmental disability in infancy and childhood, and the safety of hypothermia vs normothermia in neonates with postintrapartum hypoxic-ischemic encephalopathy and to perform subgroup analyses based on severity of encephalopathy (moderate or severe), type of hypothermia (systemic or selective head cooling), and degree of hypothermia (moderate [or=33.6 degrees C]). DATA SOURCES: MEDLINE, EMBASE, CINAHL (Cumulative Index for Nursing and Allied Health Literature), the Cochrane Library, abstracts of annual meetings of the Pediatric Academic Societies, and bibliographies of identified articles. STUDY SELECTION: Randomized and quasi-randomized controlled trials without language restriction were assessed by 2 reviewers independently and discrepancies were resolved by involving a third reviewer. Quality of the trials was assessed on the basis of concealment of allocation, method of randomization, masking of outcome assessment, and completeness of follow-up. INTERVENTION: Systemic or selective head hypothermia compared with normothermia. MAIN OUTCOME MEASURE: Death or moderate to severe neurodevelopmental disability. RESULTS: Eight studies of acceptable quality were included. The combined outcome of death or neurodevelopmental disability in childhood was reduced in infants receiving hypothermia compared with control infants (4 studies including 497 infants; relative risk, 0.76, 95% confidence interval, 0.65-0.88; number needed to treat, 6; 95% confidence interval, 4-14), as were death and moderate to severe neurodevelopmental disability when analyzed separately. Cardiac arrhythmias and thrombocytopenia were more common with hypothermia; however, they were clinically benign. CONCLUSIONS: In neonates with postintrapartum asphyxial hypoxic-ischemic encephalopathy, hypothermia is effective in reducing death and moderate to severe neurodevelopmental disability either in combination or separately and is a safe intervention.     

Changes in laboratory parameters indicating cell necrosis and organ dysfunction in asphyxiated neonates on moderate systemic hypothermia

AIM: Asphyxia is a major cause of morbidity and mortality in term infants. In addition to cerebral injury other organs are also distressed due to hypoxic-ischaemic insult. Systemic hypothermia has a beneficial effect on brain injury. We tested the impact of hypothermia on hypoxic damage of other internal organs. METHODS: Asphyxiated term neonates (n = 21) were randomised to groups treated with hypothermia (n = 12) and normothermia (n = 9). Hypothermia (33-34 degrees C) was initiated within 6 h of life, and maintained for 72 h. We determined serum transaminase, lactate dehydrogenase, creatine kinase, uric acid, creatinine levels and diuresis during 6, 24, 48 and 72 postnatal hours. RESULTS: Area under curve values of aspartate aminotransferase (ASAT), lactate dehydrogenase (LDH), uric acid and creatinine during the investigated period and alanine aminotransferase (ALAT) value at 72 h were lower in neonates on hypothermia than in those on normothermia. Renal failure and liver impairment affected less hypothermic than normothermic neonates (3/12 vs. 7/9, p = 0.03, 3/12 vs. 6/9 p = 0.08, respectively). Four of the 12 hypothermic and 6 of the 9 normothermic neonates developed multiorgan failure. CONCLUSIONS: These results suggest that systemic hypothermia may protect against cell necrosis and tissue dysfunction of internal organs after neonatal asphyxia.     

Benefits of a lower hematocrit during extracorporeal membrane oxygenation?

OBJECTIVE--To determine the possible benefits of maintaining a lower hematocrit than that normally used (0.35 vs 0.45) in neonates treated with extracorporeal membrane oxygenation. DESIGN--Randomized cohort. SETTING--Neonatal and pediatric intensive care units at a university hospital. PARTICIPANTS--Twenty neonates who met criteria for receiving extracorporeal membrane oxygenation from May 1988 to March 1990. INTERVENTIONS--Hematocrits were maintained at 0.35 for neonates in group 1 and 0.45 for neonates in group 2. MEASUREMENTS/MAIN RESULTS--Hematocrits were measured every 4 hours. Visible clots in the major circuit components were recorded. Infants in group 1 received (mean +/- SD) 2.5 +/- 0.6 mL of packed red blood cells per hour of extracorporeal membrane oxygenation while infants in group 2 received 3.8 +/- 0.9 mL of packed red blood cells per hour of extracorporeal membrane oxygenation. In group 1, clots were noted in six of 10 oxygenators and five of 10 bladder reservoirs. In group 2, clots were found in all 10 oxygenators and bladder reservoirs. CONCLUSIONS--Neonates' hematocrits can be maintained safely at 0.35 during extracorporeal membrane oxygenation with significantly less exposure to packed red blood cells and less clotting in the circuit.     

Changing populations being treated with ECMO in the neonatal period – who are the others?

Extracorporeal life support via extracorporeal membrane oxygenation (ECMO) has served the sickest of neonates for almost 50 years. Naturally, the characteristics of neonates receiving ECMO have changed. Advances in care have averted the need for ECMO for some, while complex cases with uncertain outcomes, previously not eligible for ECMO, are now considered. Characterizing the disease states and outcomes for neonates on ECMO is challenging as many infants do not fall into classic categories, i.e. meconium aspiration syndrome (MAS), respiratory distress syndrome (RDS), or congenital diaphragmatic hernia (CDH). Since 2017, over one third of neonatal respiratory ECMO runs reported to the Extracorporeal Life Support Organization Registry are grouped as Other, a catch-all that encompasses those with a diagnosis not included in the classic categories. This review summarizes the historical neonatal ECMO population, reviews advances in therapy and technology impacting neonatal care, and addresses the unknowns in the ever-growing category of Other.     

Continuous renal replacement therapy to reduce inflammation in a piglet hemorrhage-reperfusion extracorporeal membrane oxygenation model

Background:During extracorporeal membrane oxygenation (ECMO), circulation of blood across synthetic surfaces triggers an inflammatory response. Therefore, we evaluated the ability of continuous renal replacement therapy (CRRT) to remove cytokines and reduce the inflammatory response in a piglet hemorrhage-reperfusion ECMO model.Methods:Three groups were studied: (i) uninjured controls (n = 11); (ii) hemorrhage-reperfusion while on venoarterial ECMO (30% hemorrhage with subsequent blood volume replacement within 60?min) (n = 8); (iii) treatment with CRRT after hemorrhage-reperfusion while on ECMO (n = 7). Hemodynamic parameters, oxygen utilization, and plasma and broncho-alveolar lavage (BAL) cytokine levels were recorded and lung tissue samples collected for histologic comparison.Results:Whereas mean arterial pressures decreased among hemorrhage-reperfusion piglets, ECMO with CRRT did not significantly alter mean arterial pressures or systemic vascular resistance and was able to maintain blood flow as well as oxygen delivery after hemorrhage-reperfusion. Plasma interleukin (IL)-6 and IL-10, and BAL tumor necrosis factor (TNF)-α, IL-1β, IL-6, IL-8, and IL-10 increased as a result of hemorrhage-reperfusion while on ECMO. After a 6-h period of CRRT, plasma IL-6 and BAL TNF-α, IL-6, and IL-8 levels decreased.Conclusion:Data suggest CRRT may decrease inflammatory cytokine levels during the initial phase of ECMO therapy following hemorrhage-reperfusion while maintaining cardiac output and oxygen utilization.