Feeding during neonatal therapeutic hypothermia, assessed using routinely collected National Neonatal Research Database data: a retrospective, UK population-based cohort study.

BACKGROUND: Therapeutic hypothermia is standard of care in high-income countries for babies born with signs of hypoxic ischaemic encephalopathy, but optimal feeding during treatment is uncertain and practice is variable. This study aimed to assess the association between feeding during therapeutic hypothermia and clinically important outcomes. METHODS: We did a population-level retrospective cohort study using the UK National Neonatal Research Database. We included all babies admitted to National Health Service neonatal units in England, Scotland, and Wales between Jan 1, 2010, and Dec 31, 2017, who received therapeutic hypothermia for 72 h or died during this period. For analysis, we created matched groups using propensity scores and compared outcomes in babies who were fed versus unfed enterally during therapeutic hypothermia. The primary outcome was severe necrotising enterocolitis, either confirmed at surgery or causing death. Secondary outcomes include pragmatically defined necrotising enterocolitis (a recorded diagnosis of necrotising enterocolitis in babies who received at least 5 consecutive days of antibiotics while also nil by mouth during their neonatal unit stay), late-onset infection (pragmatically defined as 5 consecutive days of antibiotic treatment commencing after day 3), survival to discharge, measures of breastmilk feeding, and length of stay in neonatal unit. FINDINGS: 6030 babies received therapeutic hypothermia, of whom 1873 (31·1%) were fed during treatment. Seven (0·1%) babies were diagnosed with severe necrotising enterocolitis and the number was too small for further analyses. We selected 3236 (53·7%) babies for the matched feeding analysis (1618 pairs), achieving a good balance for all recorded background variables. Pragmatically defined necrotising enterocolitis was rare in both groups (incidence 0·5%, 95% CI 0·2-0·9] in the fed group vs 1·1% [0·7-1·4] in the unfed group). The enterally fed group had fewer pragmatically defined late-onset infections (difference -11·6% [95% CI -14·0 to -9·3]; p<0·0001), higher survival to discharge (5·2% [3·9-6·6]; p<0·0001), higher proportion of breastfeeding at discharge (8·0% [5·1-10·8]; p<0·0001), and shorter neonatal unit stays (-2·2 [-3·0 to -1·2] days; p<0·0001) compared with the unfed group. INTERPRETATION: Necrotising enterocolitis is rare in babies receiving therapeutic hypothermia. Enteral feeding during hypothermia is safe and associated with beneficial outcomes compared with not feeding, although residual confounding could not be completely ruled out. Our findings support starting milk feeds during therapeutic hypothermia. FUNDING: UK National Institute for Health Research Health Technology Assessment programme 16/79/13.

Sex-Specific Outcome after Ascending Aortic Surgery in Moderate Hypothermic Circulatory Arrest.

BACKGROUND: Historically, female patients had worse outcome undergoing heart surgery. No recent data exist on gender-specific outcome after moderate hypothermic circulatory arrest (MHCA). The aim of this large retrospective analysis was to investigate gender disparity in patients undergoing elective surgery of ascending aorta in MHCA at 24°C. METHODS: We conducted a retrospective review of 905 (33.3% female) cases of elective heart surgery in MHCA for ascending aortic aneurysm (90.9%) or severely calcified aorta (12.5%) between 2001 and 2015. Furthermore, 299 female and 299 male patients matched by propensity score were compared. Patients with dissection of the aorta were excluded. RESULTS: Women were older (68.4 ± 9.9 vs. 65.8 ± 11.6 years; p = 0.002), had higher logistic EuroSCORE I (18.4 [11.7; 29.2] vs. 12.3% [7.4; 22.6]; p < 0.001), and significantly shorter cardiopulmonary bypass (CPB) time (132 [105; 175] vs. 150 [118; 192] minutes; p < 0.001), while mean MHCA time was longer (15 [13; 19] vs. 14 [12; 17] minutes; p = 0.003). Surgical procedures were less complex in women and they were treated more frequently by isolated supracoronary ascending aorta replacement (61 vs. 54%; p = 0.046). Postoperatively, men showed a higher incidence of neurologic complications (7.0 vs. 3.3%; p = 0.03). The 30-day mortality (women 4.9% vs. men 3.9%; p = 0.48) did not differ significantly, likewise after statistical matching (4.7 vs. 2.3%; p = 0.120). Age, CPB time, and blood transfusion, but not female gender, were risk factors for mortality in multivariable regression analysis. CONCLUSION: This study supports the hypothesis that female gender is not associated with increased short-term mortality or perioperative adverse events in elective aortic surgery in MHCA.

Theophylline dosing and pharmacokinetics for renal protection in neonates with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia.

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

Therapeutic hypothermia for moderate and severe hypoxic ischaemic encephalopathy in newborns using low-cost devices - ice packs and phase changing material.

Background: Different methods have been used for therapeutic hypothermia for neonates with moderate-to-severe hypoxic ischaemic encephalopathy (HIE). As standard cooling devices are expensive, there is a need to establish the safety and efficacy of low-cost devices such as ice packs (IP) and phase changing material (PCM). Aim: To assess the efficacy and safety of therapeutic hypothermia (TH) and the clinico-laboratory profile of neonates who underwent cooling with IP or PCM. Methods: The study was retrospective. TH for moderate-to-severe HIE was initiated with IP between 2012 and 2014 and with PCM (MiraCradleTM) from September 2014. A standard protocol for inclusion and management during TH was used for all newborns. All data were collected by means of a local cooling registry. Results: Sixty-two cooled newborns (IP 29, PCM 33) were included in the study. Mean gestational age was 38.6 (1.7) weeks and mean birthweight 2920.6 g (450.7); 66.1% were inborn and 91.9% had moderate encephalopathy. Mean (SD) core temperature during cooling was 33.47°C (0.33) for PCM and 33.44°C (0.34) for IP. Adverse events observed during TH were thrombocytopenia (54.8%), coagulopathy (30.6%), shock (30.6%), skin changes (12.9%) and persistent pulmonary hypertension (8.1%). Forty-nine infants were discharged, two died and 11 were discharged against medical advice. TH was prematurely stopped in seven newborns with serious adverse events such as disseminated intravascular coagulation (DIC), gangrene and arrhythmia (IP 5, PCM 2). Conclusion: Low-cost devices are safe and effective alternatives for maintaining TH in low-resource settings with adequate monitoring. Abbreviations: DAMA, discharged against medical advice; DIC, disseminated intravascular coagulation; HELIX, Hypothermia for Encephalopathy in Low- and Middle-Income Countries Trial; HIE, hypoxic ischaemic encephalopathy; IP, ice packs; LMIC, low- and middle-income countries; NICHD, National Institute of Child Health and Human Development; PCM, phase changing; TH, therapeutic hypothermia (TH); TOBY, total body hypothermia for neonatal encephalopathy.

Effects of Mild Hypothermia on Cardiac and Neurological Function in Piglets Under Pathological and Physiological Stress Conditions.

To investigate the different effects of mild hypothermia on pathological and physiological stress conditions in piglets, 30 pigs were randomized into four groups: cardiac arrest and mild hypothermia (CA-MH group), cardiac arrest and normothermia (CA-NH group), non-CA-MH (NCA-MH group), and a sham operation. The same hypothermia intervention was implemented in both CA-MH and NCA-MH groups. The CA-NH group did not undergo therapeutic hypothermia after resuscitation. The hemodynamic parameters were recorded. Cerebral metabolism variables and neurotransmitters in the extracellular fluid were collected through microdialysis tubes. The serum of venous blood was used to detect levels of inflammatory factors. The cerebral function was evaluated. At 24 and 72 hours after resuscitation, the cerebral performance category and neurological deficit score in the CA-NH group had higher values. Heart rate and cardiac output (CO) in the CA-MH group during cooling were lower than that of the CA-NH group, but CO was higher after rewarming. Glucose was higher during cooling, and extracellular lactate and lactate/pyruvate ratio in the CA-MH group were lower than that of the CA-NH group. Noradrenaline and 5-hydroxytryptamine in the CA-MH and NCA-MH groups were lower than that of the CA-NH group and sham group during cooling, respectively. Inflammatory factor levels, including interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, and tumor necrosis factor-α, in the CA-MH group were lower than that of the CA-NH group at cooling for 12 hours. These values in the NCA-MH group were higher than that of the sham group. Under a light and an electron microscope, the worse pathological results of heart and brain were observed in the two cardiac arrest groups. Mild hypothermia can provide limited organ protection in the specific pathological condition caused by ischemia-reperfusion, but it may produce a negative effect in a normal physiological state.

Continuous surface EMG power reflects the metabolic cost of shivering during targeted temperature management after cardiac arrest.

AIM: Shivering may interfere with targeted temperature management (TTM) after cardiac arrest, contributing to secondary brain injury. Early identification of shivering is challenging with existing tools. We hypothesized that shivering detected by continuous surface sEMG monitoring would be validated with calorimetry and detected earlier than by intermittent clinical observation. METHODS: This prospective observational study enrolled a convenience sample of comatose adult cardiac arrest patients treated with TTM at 33 °C. Clinical shivering was monitored hourly using the Bedside Shivering Assessment Scale (BSAS) by bedside nurses who administered intermittent neuromuscular blockade (NMB) when BSAS ≥ 1. The research team monitored independently for shivering with BSAS every 15 min during continuous blinded monitoring of oxygen consumption (VO2) via indirect calorimetry and sEMG power during the maintenance phase of TTM. A sustained 20% increase in the 5-min rolling average of VO2 above baseline identified the Gold Standard shivering threshold (VO2-20). RESULTS: Among 18 patients, clinical shivering was detected 23 times in 14 patients. Hierarchical models to predict a shiver event determined by the VO2-20 for sEMG power and BSAS revealed an AUC for sEMG power of 0.92 (95%CI = 0.88-0.95), and 0.90 (CI = 0.87-0.94) for BSAS. The optimal threshold of sEMG to predict VO2-20 was 32 decibels (dB), and this was exceeded 38 (29-56) min before nurse-detected shivering. CONCLUSIONS: Shivering was detected by sEMG power earlier than by clinical assessment with BSAS, with similar accuracy compared to the indirect calorimetry gold standard. Continuous sEMG monitoring appears useful for clinical assessment and research for shivering during TTM.

Esophageal Cooling Device Versus Other Temperature Modulation Devices for Therapeutic Normothermia in Subarachnoid and Intracranial Hemorrhage.

Achieving and maintaining normothermia (NT) after subarachnoid hemorrhage (SAH) or intracerebral hemorrhage (ICH) often require temperature modulating devices (TMD). Shivering is a common adverse effect of TMDs that can lead to further costs and complications. We evaluated an esophageal TMD, the EnsoETM (Attune Medical, Chicago, IL), to compare NT performance, shiver burden, and cost of shivering interventions with existing TMDs. Patients with SAH or ICH and refractory fever were treated with the EnsoETM. Patient demographics, temperature data, shiver severity, and amounts and costs of medications used for shiver management were prospectively collected. Controls who received other TMDs were matched for age, gender, and body surface area to EnsoETM recipients, and similar retrospective data were collected. All patients were mechanically ventilated. Fever burden was calculated as areas of curves of time spent above 37.5°C or 38°C. Demographics, temperature data, and costs of EnsoETM recipients were compared with recipients of other TMDs. Eight EnsoETM recipients and 24 controls between October 2015 and November 2016 were analyzed. There were no differences between the two groups in demographics or patient characteristics. No difference was found in temperature at initiation (38.7°C vs. 38.5°C, p = 0.4) and fever burden above 38°C (-0.44°C × hours vs. -0.53°C × hours, p = 0.47). EnsoETM recipients showed a nonsignificant trend in taking longer to achieve NT than other TMDs (5.4 hours vs. 2.9 hours, p = 0.07). EnsoETM recipients required fewer shiver interventions than controls (14 vs. 30, p = 0.02). EnsoETM recipients incurred fewer daily costs than controls ($124.27 vs. $232.76, p = 0.001). The EnsoETM achieved and maintained NT in SAH and ICH patients and was associated with less shivering and lower pharmaceutical costs than other TMDs. Further studies in larger populations are needed to determine the EnsoETM's efficacy in comparison to other TMDs.

Hypothermia for encephalopathy in low and middle-income countries (HELIX): study protocol for a randomised controlled trial.

BACKGROUND: Therapeutic hypothermia reduces death and disability after moderate or severe neonatal encephalopathy in high-income countries and is used as standard therapy in these settings. However, the safety and efficacy of cooling therapy in low- and middle-income countries (LMICs), where 99% of the disease burden occurs, remains unclear. We will examine whether whole body cooling reduces death or neurodisability at 18-22 months after neonatal encephalopathy, in LMICs. METHODS: We will randomly allocate 408 term or near-term babies (aged ≤ 6 h) with moderate or severe neonatal encephalopathy admitted to public sector neonatal units in LMIC countries (India, Bangladesh or Sri Lanka), to either usual care alone or whole-body cooling with usual care. Babies allocated to the cooling arm will have core body temperature maintained at 33.5 °C using a servo-controlled cooling device for 72 h, followed by re-warming at 0.5 °C per hour. All babies will have detailed infection screening at the time of recruitment and 3 Telsa cerebral magnetic resonance imaging and spectroscopy at 1-2 weeks after birth. Our primary endpoint is death or moderate or severe disability at the age of 18 months. DISCUSSION: Upon completion, HELIX will be the largest cooling trial in neonatal encephalopathy and will provide a definitive answer regarding the safety and efficacy of cooling therapy for neonatal encephalopathy in LMICs. The trial will also provide important data about the influence of co-existent perinatal infection on the efficacy of hypothermic neuroprotection. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02387385 . Registered on 27 February 2015.

Prophylactic antibiotics are associated with a lower incidence of pneumonia in cardiac arrest survivors treated with targeted temperature management.

INTRODUCTION: Prophylactic antibiotics (PRO) reduce the incidence of early-onset pneumonia in comatose patients with structural brain injury, but have not been examined in cardiac arrest survivors undergoing targeted temperature management (TTM). We investigated the effect of PRO on the development of pneumonia in that population. METHODS: We conducted a retrospective cohort study comparing patients treated with PRO to those not receiving PRO (no-PRO) using Northern Hypothermia Network registry data. Cardiac arrest survivors ≥ 18 years of age with a GCS<8 at hospital admission and treated with TTM at 32-34 °C were enrolled in the registry. Differences were analyzed in univariate analyses and with logistic regression models to evaluate independent associations of clinical factors with incidence of pneumonia and good functional outcome. RESULTS: 416 of 1240 patients (33.5%) received PRO. Groups were similar in age, gender, arrest location, initial rhythm, and time from collapse to return of spontaneous circulation. PRO patients had less pneumonia (12.6% vs. 54.9%, p < 0.001) and less sepsis (1.2 vs. 5.7%, p < 0.001) compared to no-PRO patients. ICU length of stay (98 vs. 100 h, p = 0.2) and incidence of a good functional outcome (41.1 vs. 36.6%, p = 0.19) were similar between groups. Backwards stepwise logistic regression demonstrated PRO were independently associated with a lower incidence of pneumonia (OR 0.09, 95% 0.06-0.14, p < 0.001) and a similar incidence of good functional outcome. CONCLUSIONS: Prophylactic antibiotics were associated with a reduced incidence of pneumonia but a similar rate of good functional outcome.

Hypothermia and operative mortality during on-pump coronary artery bypass grafting.

OBJECTIVE: Controversy surrounds the effect of hypothermia on operative mortality during cardiac surgery. The present study accessed a large clinical database of coronary artery bypass graft operations to address the issue. METHODS: A retrospective review of the Society of Thoracic Surgeons Adult Cardiac Surgery Database identified patients treated with isolated, nonemergency, on-pump coronary artery bypass grafting from July 2011 to December 2012. The patients were divided into 3 groups according to their lowest core temperature during the procedure: moderate hypothermia (≤ 34 °C), mild hypothermia (>34 °C but ≤ 36 °C), and normothermia (>36 °C). The primary endpoint of the study was operative mortality, defined according to the Database criteria. RESULTS: During the study period, 142,541 patients were available for analysis; 94,777 (66.5%) received moderate hypothermia, 42,750 (30.3%) mild hypothermia, and 5014 (3.5%) normothermia. Operative mortality occurred in 1394 patients (1.5%) in the moderate hypothermia, 534 (1.3%) in the mild hypothermia, and 105 (2.1%) in the normothermia group. Multivariate analysis identified hypothermia (both mild [odds ratio, 0.66; 95% confidence interval, 0.54-0.81; P < .0001] and moderate [odds ratio, 0.73; 95% confidence interval, 0.60-0.89; P = .0015]) was protective against operative mortality compared with normothermia. No incremental benefit was noted between the different hypothermia grades (P = .0827). CONCLUSIONS: Most patients receive hypothermia during on-pump coronary artery bypass grafting. Hypothermia is protective against operative mortality compared with normothermia in such patients. Moderate hypothermia does not provide additional survival benefit.

Feasibility of cognitive functional assessment in cardiac arrest survivors using an abbreviated laptop-based neurocognitive battery.

Cardiac arrest survivors exhibit varying degrees of neurological recovery even in the setting of targeted temperature management (TTM) use, ranging from severe impairments to making a seemingly full return to neurologic baseline function. We sought to explore the feasibility of utilizing a laptop-based neurocognitive battery to identify more subtle cognitive deficits in this population. In a convenience sample of cardiac arrest survivors discharged with a cerebral performance category (CPC) of 1, we evaluated the use of a computerized neurocognitive battery (CNB) in this group compared to a healthy control normative population. The CNB was designed to test 11 specific neurocognitive domains, including such areas as working memory and spatial processing. Testing was scored for both accuracy and speed. In a feasibility convenience sample of 29 cardiac arrest survivors, the mean age was 52.9±16.7 years; 12 patients received postarrest TTM and 17 did not receive TTM. Patients tolerated the battery well and performed at normative levels for both accuracy and speed on most of the 11 domains, but showed reduced accuracy of working memory and speed of spatial memory with large magnitudes (>1 SD), even among those receiving TTM. Across all domains, including those using speed and accuracy, 7 of the 29 subjects (24%) achieved statistically significant scores lower from the normative population in two or more domains. In this population of CPC 1 cardiac arrest survivors, a sensitive neurocognitive battery was feasible and suggests that specific cognitive deficits can be detected compared to a normative population, despite CPC 1 designation. Such testing might allow improved measurement of outcomes following TTM interventions in future trials.

Quantitative assessment of the effects of therapeutic hypothermia on early repolarization in idiopathic ventricular fibrillation survivors: a 7-year cohort study.

BACKGROUND: The early repolarization (ER) pattern on ECG is associated with an increased risk of idiopathic ventricular fibrillation (ID-VF). Hypothermia is known to result in similar electrocardiographic changes. In this retrospective cohort study, we examine the impact of therapeutic hypothermia on ER in survivors of cardiac arrest attributed to ID-VF and draw comparisons with a control group who experienced coronary artery disease-related VF (CAD-VF). METHODS AND RESULTS: All patients who had cardiac arrest and were treated with therapeutic hypothermia over a 7-year period were considered for inclusion in the study. Forty-three patients were identified with ID-VF or CAD-VF arrest. ECGs were obtained during cooling and again after rewarming. ECGs were digitized and assessed for the presence of ER by 2 independent observers. Cooling significantly increased the prevalence (74% during cooling versus 51% at baseline temperature; P=0.044) and mean amplitude (0.78±0.10 mV during cooling versus 0.56±0.09 mV at baseline temperature; P=0.038) of ER in the overall cohort. During cooling, ER was more common among survivors of ID-VF than of CAD-VF (100% versus 67%; P=0.043). ER magnitude was significantly greater among ID-VF survivors than CAD-VF survivors both during cooling (1.16±0.18 versus 0.70±0.11 mV; P=0.044) and at baseline temperature (1.02±0.21 versus 0.42±0.09 mV; P=0.005). CONCLUSIONS: Hypothermia increases both the prevalence and magnitude of ER in cardiac arrest survivors. Despite the association of ER with ID-VF, therapeutic hypothermia only increases ER amplitude in CAD-VF survivors.

Assessment of adverse events and predictors of neurological recovery after therapeutic hypothermia.

BACKGROUND: Therapeutic hypothermia improves neurological recovery after witnessed cardiac arrest from ventricular fibrillation or tachycardia. Its application is expanding despite associated adverse events. OBJECTIVE: To assess the occurrence of adverse events and predictors of good versus poor neurological recovery after therapeutic hypothermia. METHODS: A single-center, retrospective review of medical records of 91 patients who received therapeutic hypothermia for ≥6 hours. Adverse events included laboratory abnormalities, shivering, acute kidney injury, or infection. Cerebral performance categories (CPC) scores delineated good (CPC of 1-3) or poor (CPC of 4 or 5) neurological outcomes. Groups were compared and parameters evaluated for effect on neurological recovery using backward logistic regression analysis. RESULTS: Therapeutic hypothermia was used for several indications, and 42 patients (46.2%) had good neurological recovery. Demographic parameters were similar between groups. Common adverse events were hypoglycemia (98.9%), shivering (84.6%), bradycardia (58.2%), electrolyte abnormalities (26.4%-91.2%), acute kidney injury (52.8%), infection (48.4%), and coagulopathy (40.7%). Characteristics independently associated with neurological recovery included faster return of spontaneous circulation (ROSC), quicker initiation of cooling, and the occurrence of infections. Pulseless electrical activity, faster achievement of goal cooling temperature, seizure, and the administration of insulin or epinephrine were inversely related to neurological recovery. CONCLUSIONS: Adverse events of therapeutic hypothermia were numerous and frequent, necessitating monitoring. Neurological recovery is primarily driven by the type of arrest, the rapidity of ROSC, the time needed to provide and achieve therapeutic hypothermia, the development of seizures or infection, and the use of insulin or epinephrine.

Translational barriers and opportunities for emergency preservation and resuscitation in severe injuries.

BACKGROUND: Hypothermia is commonly used for organ and tissue preservation in multiple clinical settings, but its role in the management of injured patients remains controversial. There is no doubt that temperature modulation is a powerful tool, and hypothermia has been shown to protect cells during ischaemia and reperfusion, decrease organ damage and improve survival. Yet hypothermia is a double-edged sword: unless carefully managed, its induction can be associated with a number of complications. METHODS: A literature review was performed to include important papers that address the impact of hypothermia on key biological processes, and explore the potential therapeutic role of hypothermia in trauma/haemorrhage models. RESULTS: No clinical studies have been conducted to test the therapeutic benefits of hypothermia in injured patients. However, numerous well designed animal studies support this concept. Despite excellent preclinical data, there are several potential barriers to translating hypothermia into clinical practice. CONCLUSION: Therapeutic hypothermia is a promising life-saving strategy. Appropriate patient selection requires a thorough understanding of how temperature modulation affects various biological mechanisms.

Cardiac and neurological assessment of normothermia/warm blood cardioplegia vs hypothermia/cold crystalloid cardioplegia in pediatric cardiac surgery: insight from a prospective randomized trial.

OBJECTIVE: Although normothermia and warm blood cardioplegia are widely used in adults, cold crystalloids and hypothermia remain routinely used in pediatric cardiac surgery. The superiority of either technique in both brain and myocardial protection remains controversial. We designed a prospective randomized study to compare both approaches in terms of early myocardial protection and late neurodevelopmental status. METHODS: From 2004 to 2005, 47 patients were randomly assigned to either mild hypothermia associated to cold crystalloid cardioplegia (CCC, 22 patients) or normothermia with intermittent warm blood cardioplegia (IWBC, 25 patients). Intramyocyte adenosine triphosphate (ATP) was measured before, during and after cardioplegic arrest and results between groups were compared. In addition to their cardiac status, early and late neurologic assessment was performed by psychometric evaluation tests. RESULTS: Intracellular ATP levels were not significantly different between the two groups. However, intragroup comparison revealed different profiles according to myocardial protection: in the normothermia/warm blood cardioplegia group, ATP concentration increased during cardioplegic arrest and returned to initial values afterward (11 nmol mg(-1) vs 21 nmol mg(-1) vs 10 nmol mg(-1), p < 0.001), such changes did not occur in the cold protocol (17 nmol mg(-1) vs 19 nmol mg(-1) vs 14 nmol mg(-1), p = NS). Early neurological outcome was similar in both groups. At late follow-up (mean = 4 years), no significant difference was observed between the two groups. CONCLUSIONS: This study demonstrates that normothermia/IWBC protocols are not deleterious when compared with more conventional approaches. A more physiologic ATP steady state, reflecting the absence of cellular ischemic insult was observed in the IWBC group. Importantly, no significant difference was found between IWBC and CCC groups in terms of early and late neurodevelopmental status.

Internet-based assessment of postoperative neurocognitive function in cardiac and thoracic aortic surgery patients.

OBJECTIVE: The primary purpose of this study was to determine the practicality of long-term, postoperative neurocognitive assessment via remote Internet-based testing in a cohort of patients who had undergone cardiac or thoracic aortic surgery within the previous 6 years. The secondary aim of this study was to examine the relationships among hypothermic circulatory arrest time, cardiopulmonary bypass time, and selective cerebral perfusion time with long-term postoperative neurocognitive function, as assessed by this novel testing method. METHODS: Three hundred patients who had undergone cardiac and/or proximal aortic surgery with cardiopulmonary bypass (n = 207), thoracic aortic surgery with hypothermic circulatory arrest (n = 67), or thoracic aortic surgery with hypothermic circulatory arrest and selective cerebral perfusion (n = 26) within the previous 6 years underwent Internet-based neurocognitive assessment. RESULTS: The duration of hypothermic circulatory arrest was negatively associated with processing speed scores and memory scores; arrest duration greater than 21 to 24 minutes was negatively associated with response speed scores. These associations were independent of time since surgery, age at testing, and educational level. Neither cardiopulmonary bypass duration nor selective cerebral perfusion duration was associated with test score results. CONCLUSIONS: This study demonstrated the practicality of long-term neurocognitive assessment of patients who have undergone cardiac and thoracic aortic surgery by means of Internet-based computerized testing. Furthermore, there was a negative association between the duration of intraoperative hypothermic circulatory arrest and long-term postoperative neurocognitive function that needs further examination in prospective studies.

State of the art in therapeutic hypothermia.

Historically, hypothermia was induced prior to surgery to enable procedures with prolonged ischemia, such as open heart surgery and organ transplant. Within the past decade, the efficacy of hypothermia to treat emergency cases of ongoing ischemia such as stroke, myocardial infarction, and cardiac arrest has been studied. Although the exact role of ischemia/reperfusion is unclear clinically, hypothermia holds significant promise for improving outcomes for patients suffering from reperfusion after ischemia. Research has elucidated two distinct windows of opportunity for clinical use of hypothermia. In the early intra-ischemia window, hypothermia modulates abnormal cellular free radical production, poor calcium management, and poor pH management. In the more delayed post-reperfusion window, hypothermia modulates the downstream necrotic, apoptotic, and inflammatory pathways that cause delayed cell death. Improved cooling and monitoring technologies are required to realize the full potential of this therapy. Herein we discuss the current state of clinical practice, clinical trials, recommendations for cooling, and ongoing research on therapeutic hypothermia.