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- Electrographic seizures are associated with brain injury in newborns undergoing therapeutic hypothermia. [JOURNAL ARTICLE]
- Arch Dis Child Fetal Neonatal Ed 2014 Jan 17.
Seizures are common among newborns with hypoxic-ischaemic encephalopathy (HIE) but the relationship between seizure burden and severity of brain injury among neonates receiving therapeutic hypothermia (TH) for HIE is unclear. We tested the hypothesis that seizure burden is associated with cerebral tissue injury independent of amplitude-integrated EEG (aEEG) background activity.Term neonates undergoing 72 h of TH at four centres were selected for study if they had continuous aEEG and MRI. The aEEG with corresponding 2-channel raw EEG (aEEG/EEG), was classified by severity of background and seizure burden; MR images were classified by the severity of tissue injury.Of 85 neonates, 52% had seizures on aEEG/EEG. Overall, 35% had high seizure burden, 49% had abnormal aEEG background in the first 24 h and 36% had severe injury on MRI. Seizures were most common on the first day, with significant recurrence during and after rewarming. Factors associated with severe injury on MRI were high seizure burden, poor aEEG background, 10 min Apgar and the need for more than one anticonvulsant. In multivariate logistic regression, high seizure burden was independently associated with greater injury on MRI (OR 5.00, 95% CI 1.47 to 17.05 p=0.01). Neither aEEG background, nor 10 min Apgar score were significant.Electrographic seizure burden is associated with severity of brain injury on MRI in newborns with HIE undergoing TH, independent of degree of abnormality on aEEG background. Seizures are common during cooling, particularly on day 1, with a significant rebound on day 4.
- Dehydration improves cryopreservation of mat rush (Juncus decipiens Nakai) basal stem buds on cryo-plates. [Journal Article, Research Support, Non-U.S. Gov't]
- Cryo Letters 2013 Nov-Dec; 34(6):549-60.
Two cryopreservation procedures using aluminium cryo-plates, termed V-Cryo-plate and D-Cryo-plate, were successfully developed for in vitro mat rush (Juncus decipiens Nakai) basal stem buds. Multiple stems induced in liquid MS medium containing 8.9 μM BA by roller culture were cut into small clumps, plated on solid MS medium and cultured for 1 week at 25 degree C. Clumps that had produced many buds were cold-hardened at 5 degree C for 1-2 months. The buds with basal stems were dissected from small clumps and precultured overnight at 25 degree C on solid MS medium containing 0.3 M sucrose. Precultured buds were placed on aluminium cryo-plates and embedded in calcium alginate gel. Osmoprotection was performed by immersing the cryo-plates for 30 min at 25 degree C in loading solution (2 M glycerol + 1.0 M sucrose). In the D-Cryo-plate procedure, the buds were dehydrated to 27-25% moisture content (fresh weight) by placing the cryo-plates in the air current of a laminar flow cabinet for 2 to 3 h. In the V-Cryo-plate procedure, buds were dehydrated by immersing the cryo-plates in PVS2 vitrification solution for 40 min at 25 degree C. In both procedures, cooling was performed by placing the cryo-plates in uncapped cryotubes, which were immersed in liquid nitrogen. For rewarming, cryo-plates were immersed in medium with 1.0 M sucrose for 20 min at room temperature. Regrowth of cryopreserved buds of line 'Kitakei 2' using D-Cryo-plate and V-Cryo-plate procedures, was 90% and 80%, respectively. The two procedures were applied to 20 additional mat rush lines. Using the V-Cryo-plate procedure resulted in regrowth ranging between 13.3 and 86.7%, with an average of 52.5%. The D-Cryo-plate led to regrowth ranging between 73.3 and 96.7%, with an average of 86.3%. The D-Cryo-plate procedure will facilitate cryostorage of mat rush germplasm.
- The effects of the rate of postresuscitation rewarming following hypothermia on outcomes of cardiopulmonary resuscitation in a rat model. [Journal Article]
- Crit Care Med 2014 Feb; 42(2):e106-13.
To investigate the optimal rewarming rate following therapeutic hypothermia in a rate model of cardiopulmonary resuscitation. Both clinical and laboratory studies have demonstrated that mild therapeutic hypothermia following cardiopulmonary resuscitation improves myocardial and neurologic outcomes of cardiac arrest. However, the optimal rewarming strategy following therapeutic hypothermia remains to be explored.Prospective randomized controlled experimental study.University-affiliated research institution.Twenty-three healthy male Sprague-Dawley rats.Four groups of Sprague-Dawley rats were randomized: 1) normothermia group (control), 2) rewarming rate at 2°C/hr, 3) rewarming rate at 1°C/hr, and 4) rewarming rate at 0.5°C/hr. Ventricular fibrillation was induced and untreated for 8 minutes, and defibrillation was attempted after 8 minutes of cardiopulmonary resuscitation. For the 2, 1, and 0.5°C/hr groups, rapid cooling was started at the beginning of cardiopulmonary resuscitation. On reaching the target cooling temperature of 33°C ± 0.2°C, the temperature was maintained with the aid of a cooling blanket until 4 hours after resuscitation. Rewarming was then initiated at the rate of 2.0, 1.0, or 0.5°C/hr, respectively, until the body temperature reached 37°C ±0.2°C. Blood samples were drawn at baseline and postresuscitation of 4, 6, 8, 10, and 12 hours for the measurements of blood gas and serum biomarkers.Blood temperature significantly decreased in the hypothermic groups from cardiopulmonary resuscitation to postresuscitation 4 hours. Significantly better cardiac output, ejection fraction, myocardial performance index, reduced neurologic deficit scores, and longer duration of survival were observed in the 1 and 0.5°C/hr groups. The increased serum concentration of troponin I, interleukin-6, and tumor necrosis factor-α was partly attenuated in the 1 and 0.5°C/hr groups when compared with the control and 2°C/hr groups.This study demonstrated that the severity of myocardial, cerebral injuries, and inflammatory reaction after cardiopulmonary resuscitation was reduced when mild therapeutic hypothermia was applied. A rewarming rate at 0.5-1°C/hr did not alter the beneficial effects of therapeutic hypothermia. However, a rapid rewarming rate at 2°C/hr abolished the beneficial effects of hypothermia.
- In comatose postcardiac arrest patients treated with therapeutic hypothermia: what is the optimal rate of rewarming? [Comment, Editorial]
- Crit Care Med 2014 Feb; 42(2):483-4.
- Ischemic preconditioning attenuates brain injury induced by ischemia/reperfusion during moderate hypothermia low-flow procedures. [JOURNAL ARTICLE]
- Int J Neurosci 2014 Jan 24.
Objective: We determined the effects of ischemic preconditioning (IP) on apoptosis in a rat model of brain injury induced by cerebral ischemia/reperfusion following a moderate hypothermic low-flow (MHLF) procedure. Methods: A total of 180 rats were randomly divided into three groups. The surgery group was subjected to body temperature reduction and bilateral common carotid artery occlusion for 120 min at 25 ± 0.5°C, followed by artery reopening and rewarming. The sham-surgery group underwent the same procedure, but common carotid arteries were not occluded. The ischemic preconditioning-treated surgery group was pretreated with four cycles of 2 min occlusion of bilateral common carotid arteries and 5 min reperfusion, before 120 min of cerebral ischemia. Regional cerebral blood flow was measured continuously in 10 rats per group using laser Doppler flowmetry. We investigated brain cell apoptosis levels and mitochondrial apoptosis signaling pathway components at various time points following reperfusion. Results: The ischemic preconditioning-treated surgery group displayed decreases in apoptotic cell numbers and apoptotic protein expression levels after the procedure at 6 h, 24 h, 72 h, and 7 d. Ischemic preconditioning inhibited cytochrome c release, caspase-3 activation, and mitochondrial apoptosis signaling pathway activation. Conclusion: The protective effects of ischemic preconditioning were associated with a reduction of DNA fragmentation, and inhibition of mitochondrial cytochrome c release and caspase-3 activation, which alleviated cerebral ischemia/reperfusion injury after moderate hypothermic low flow in rats. These findings highlight the potential of ischemic preconditioning as a neuroprotective therapy for surgery involving MHLF.
- Comparison of heat donation through the head or torso on mild hypothermia rewarming. [Journal Article]
- Wilderness Environ Med 2014 Mar; 25(1):4-13.
The purpose of the study was to compare the effectiveness of head vs torso warming in rewarming mildly hypothermic, vigorously shivering subjects using a similar source of heat donation.Six subjects (1 female) were cooled on 3 occasions in 8ºC water for 60 minutes or to a core temperature of 35ºC. They were then dried, insulated, and rewarmed by 1) shivering only; 2) charcoal heater applied to the head; or 3) charcoal heater applied to the torso. The order of rewarming methods followed a balanced design. Esophageal temperature, skin temperature, heart rate, oxygen consumption, and heat flux were measured.There were no significant differences in rewarming rate among the 3 conditions. Torso warming increased skin temperature and inhibited shivering heat production, thus providing similar net heat gain (268 ± 66 W) as did shivering only (355 ± 105 W). Head warming did not inhibit average shivering heat production (290 ± 72 W); it thus provided a greater net heat gain during 35 to 60 minutes of rewarming than did shivering only.Head warming is as effective as torso warming for rewarming mildly hypothermic victims. Head warming may be the preferred method of rewarming in the field management of hypothermic patients if: 1) extreme conditions in which removal of the insulation and exposure of the torso to the cold is contraindicated; 2) excessive movement is contraindicated (eg, potential spinal injury or severe hypothermia that has a risk of ventricular fibrillation); or 3) if emergency personnel are working on the torso.
- Hemodynamics and vasopressor support in therapeutic hypothermia after cardiac arrest: Prognostic implications. [JOURNAL ARTICLE]
- Resuscitation 2014 Jan 9.
Inducing therapeutic hypothermia (TH) in Out-of-Hospital Cardiac Arrest (OHCA) can be challenging due to its impact on central hemodynamics and vasopressors are frequently used to maintain adequate organ perfusion. The aim of this study was to assess the association between level of vasopressor support and mortality.In a 6-year period, 310 comatose OHCA patients treated with TH were included. Temperature, hemodynamic parameters and level of vasopressors were registered from admission to 24h after rewarming. Level of vasopressor support was assessed by the cardiovascular sub-score of Sequential Organ Failure Assessment (SOFA). The population was stratified by use of dopamine as first line intervention (D-group) or use of dopamine+norepinephrine/epinephrine (DA-group). Primary endpoint was 30-day mortality and secondary endpoint was in-hospital cause of death.Patients in the DA-group carried a 49% all-cause 30-day mortality rate compared to 23% in the D-group, plog-rank<0.0001, corresponding to an adjusted hazard ratio (HR) of 2.0 (95% CI: 1.3-3.0), p=0.001). The DA-group had an increased 30-day mortality due to neurological injury (HR=1.7 (95% CI: 1.1-2.7), p=0.02). Cause of death was anoxic brain injury in 78%, cardiovascular failure in 18% and multi-organ failure in 4%. The hemodynamic changes of TH reversed at normothermia, although the requirement for vasopressor support (cardiovascular SOFA≥3) persisted in 80% of patients.In survivors after OHCA treated with TH the induced hemodynamic changes reversed after normothermia, while the need for vasopressor support persisted. Patients requiring addition of norepinephrine/epinephrine on top of dopamine had an increased 30-day all-cause mortality, as well as death from neurological injury.
- Continuous Electroencephalogram in Comatose Postcardiac Arrest Syndrome Patients Treated With Therapeutic Hypothermia: Outcome Prediction Study. [JOURNAL ARTICLE]
- J Intensive Care Med 2014 Jan 7.
Therapeutic Hypothermia (TH) is the only therapeutic intervention proven to significantly improve survival and neurologic outcome in comatose postcardiac arrest patients and is now considered standard of care. When we discuss prognostication with regard to comatose survivors postcardiac arrest, we should look for tools that are both reliable and accurate and that achieve a false-positive rate (FPR) equal to or very closely approaching zero.We retrospectively reviewed data that were prospectively collected on all cardiac arrest patients admitted to our ICU. Continuous electroencephalogram (cEEG) monitoring was performed as part of our protocol for therapeutic hypothermia in comatose postcardiac arrest patients. The primary outcome measure was the best score on hospital discharge on the 5-point Glasgow-Pittsburgh cerebral performance category (CPC) scores.A total of 58 patients were included in this study. Twenty five (43%) patients had a good neurologic outcome (CPC score of 1-2). Three (5.2%) patients had nonconvulsive status epilepticus, all of whom had poor outcome (CPC = 5). Seventeen (29%) patients had burst suppression (BS); all had poor outcome. Both nonconvuslsive seizures (NCS) and BS had a specificity of 100% (95% confidence interval [CI], 84%-100%), positive predictive values of 100% (95% CI, 31%-100%), and 100% (95% CI, 77%-100%), respectively. Both NCS and BS had FPRs of zero (95% CI, 0.0-0.69, and 0.0-0.23, respectively).In comatose postcardiac arrest patients treated with hypothermia, EEG during the maintenance and rewarming phase of hypothermia can contribute to prediction of neurologic outcome. Pending large multicenter prospective studies evaluating the role of cEEG in prognostication, our study adds to the existing evidence that cEEG can play a potential role in prediction of outcome in postcardiac arrest patients treated with hypothermia.
- Quantitative assessment of the effects of therapeutic hypothermia on early repolarization in idiopathic ventricular fibrillation survivors: a 7-year cohort study. [Journal Article]
- Circ Arrhythm Electrophysiol 2014 Feb 1; 7(1):120-6.
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.
- Urine Output Changes During Postcardiac Arrest Therapeutic Hypothermia. [JOURNAL ARTICLE]
- Ther Hypothermia Temp Manag 2013 Dec 1; 3(4):173-177.
While commonly described, no studies have characterized cold-induced diuresis or rewarm anti-diuresis occurring during the delivery of therapeutic hypothermia (TH). We sought to determine urine output changes during the provision of postcardiac arrest TH. We analyzed clinical data on patients receiving postcardiac arrest TH at an urban tertiary care center. TH measures included cooling by cold intravenous fluid, external ice packs, and a commercial external temperature management system. TH treatment was divided into phases: (1) induction, (2) maintenance, (3) rewarm, and (4) post-rewarm. The primary outcome measure was the mean urine output rate (mL/hour). We compared urine output rates between TH phases using a Generalized Estimating Equations model, defining urine output rate (mL/hour) as the dependent variable and TH phase (induction, maintenance, rewarm, and post-rewarm) as the primary exposure variable. We adjusted for age, sex, initial ECG rhythm, location of arrest, shock, acute kidney injury, rate of intravenous fluid input, and body mass index. Complete urine output data were available on 33 patients. Mean urine output rates during induction, maintenance, rewarm, and post-rewarm phases were 157 mL/hour (95% CI: 104-210), 103 mL/hour (95% CI: 82-125), 70 mL/hour (95% CI: 51-88), and 91 mL/hour (95% CI: 65-117), respectively. Compared with the post-rewarm phase, adjusted urine output was higher during the TH induction phase (output rate difference +51 mL/hour; 95% CI: 3-99). Adjusted urine output during the maintenance and rewarm phases did not differ from the post-rewarm phase. In this preliminary study, we observed modest increases in urine output during TH induction. We did not observe urine output changes during TH maintenance or rewarming.