Target Rectal Temperature Research Articles

The effect of repeated hot water immersion on insulin sensitivity, heat shock protein 70, and inflammation in individuals with type 2 diabetes mellitus.

Repeated hot water immersion (HWI) can improve glycemic control in healthy individuals but data are limited for individuals with type 2 diabetes mellitus (T2DM). The present study investigated whether repeated HWI improves insulin sensitivity and inflammatory status and reduces plasma ([extracellular heat shock protein 70]) [eHSP70] and resting metabolic rate (RMR). Fourteen individuals with T2DM participated in this pre- versus postintervention study, with outcome measures assessed in fasted (≥12 h) and postprandial (2-h post-75 g glucose ingestion) states. HWI consisted of 1 h in 40°C water (target rectal temperature 38.5°C-39°C) repeated 8-10 times within a 14-day period. Outcome measures included insulin sensitivity, plasma [glucose], [insulin], [eHSP70], inflammatory markers, RMR, and substrate utilization. The HWI intervention increased fasted insulin sensitivity (QUICKI; P = 0.03) and lowered fasted plasma [insulin] (P = 0.04), but fasting plasma [glucose] (P = 0.83), [eHSP70] (P = 0.08), [IL-6] (P = 0.55), [IL-10] (P = 0.59), postprandial insulin sensitivity (P = 0.19), plasma [glucose] (P = 0.40), and [insulin] (P = 0.47) were not different. RMR was reduced by 6.63% (P < 0.05), although carbohydrate (P = 0.43) and fat oxidation (P = 0.99) rates were unchanged. This study shows that 8-10 HWIs within a 14-day period improved fasting insulin sensitivity and plasma [insulin] in individuals with T2DM, but not when glucose tolerance is challenged. HWI also improves metabolic efficiency (i.e., reduced RMR). Together these results could be clinically important and have implications for metabolic health outcomes and well-being in individuals with T2DM.NEW & NOTEWORTHY This is the first study to investigate repeated HWI to raise deep body temperature on insulin sensitivity, inflammation, eHSP70, and substrate utilization in individuals with T2DM. The principal novel findings were improvements in fasting insulin sensitivity and fasting plasma [insulin] but no change in fasting plasma [glucose], postprandial insulin sensitivity, plasma [insulin], or [glucose]. There was also no change in eHSP70, inflammatory status, or substrate utilization but there were reductions in RMR and oxygen consumption.

Impact of mild hypothermia therapy on hemodynamics during the induction stage in neonates with moderate to severe hypoxic-ischemic encephalopathy

Objective To study the changes in hemodynamics during the induction stage of systemic mild hypothermia therapy in neonates with moderate to severe hypoxic-ischemic encephalopathy (HIE). Methods A total of 21 neonates with HIE who underwent systemic mild hypothermia therapy in the Department of Neonatology, Dongguan Children's Hospital Affiliated to Guangdong Medical University, from July 2017 to April 2020 were enrolled. The rectal temperature of the neonates was lowered to 34℃ after 1-2 hours of induction and maintained at this level for 72 hours using a hypothermia blanket. The impedance method was used for noninvasive hemodynamic monitoring, and the changes in heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), cardiac output (CO), cardiac index (CI), and total peripheral resistance (TPR) from the start of hypothermia induction to the achievement of target rectal temperature (34℃). Blood lactic acid (LAC) and resistance index (RI) of the middle cerebral artery were recorded simultaneously. Results The 21 neonates with HIE had a mean gestational age of (39.6±1.1) weeks, a mean birth weight of (3 439±517) g, and a mean 5-minute Apgar score of 6.8±2.0. From the start of hypothermia induction to the achievement of target rectal temperature (34℃), there were significant reductions in HR, CO, and CI (P 0.05). There was a significant increase in TPR (P 0.05). Conclusions The systemic mild hypothermia therapy may have a significant impact on hemodynamics in neonates with moderate to severe HIE, and continuous hemodynamic monitoring is required during the treatment.

Heat acclimation does not modify autonomic responses to core cooling and the skin thermal comfort zone.

Exercise heat acclimation (HA) is known to magnify the sweating response by virtue of a lower threshold as well as increased gain and maximal capacity of sweating. However, HA has been shown to potentiate the shivering response in a cold-air environment. We investigated whether HA would alter heat loss and heat production responses during water immersion. Twelve healthy male participants underwent a 10-day HA protocol comprising daily 90-min controlled-hyperthermia (target rectal temperature, Tre 38.5°C) exercise sessions. Preceding and following HA, the participants performed a maximal exercise test in thermoneutral conditions (ambient temperature 23°C, relative humidity 50%) and were, following exercise, immersed in 28°C water for 60min. Thermal comfort zone (TCZ) was also assessed with participants regulating the temperature of a water-perfused suit during heating and cooling. Baseline pre-immersion Tre was similar pre- and post-HA (pre: 38.33±0.33°C vs post: 38.12±0.36°C, p=0.092). The Tre cooling rate was identical pre-to post-HA (-0.03±0.01°C·min-1, p=0.31), as was the vasomotor response reflected in the forearm-fingertip temperature difference. Shivering thresholds (p=0.43) and gains (p=0.61) were not affected by HA. TCZ was established at similar temperatures, with the magnitude in regulated water temperature being 7.6 (16.3) °C pre-HA and 5.1 (24.7) °C post-HA (p=0.65). The present findings suggest that heat production and heat loss responses during whole body cooling as well as the skin thermal comfort zone remained unaltered by a controlled-hyperthermia HA protocol.

No ergogenic effects of a 10-day combined heat and hypoxic acclimation on aerobic performance in normoxic thermoneutral or hot conditions.

Hypoxic acclimation enhances convective oxygen delivery to the muscles. Heat acclimation-elicited thermoregulatory benefits have been suggested not to be negated by adding daily exposure to hypoxia. Whether concomitant acclimation to both heat and hypoxia offers a synergistic enhancement of aerobic performance in thermoneutral or hot conditions remains unresolved. Eight young males ([Formula: see text]: 51.6 ± 4.6mLmin-1kg-1) underwent a 10-day normobaric hypoxic confinement (FiO2 = 0.14) interspersed with daily 90-min normoxic controlled hyperthermia (target rectal temperature: 38.5°C) exercise sessions. Prior to, and following the confinement, the participants conducted a 30-min steady-state exercise followed by incremental exercise to exhaustion on a cycle ergometer in thermoneutral normoxic (NOR), thermoneutral hypoxic (FiO2 = 0.14; HYP) and hot (35°C, 50% relative humidity; HE) conditions in a randomized and counterbalanced order. The steady-state exercise was performed at 40% NOR peak power output (Wpeak) to evaluate thermoregulatory function. Blood samples were obtained from an antecubital vein before, on days 1 and 10, and the first day post-acclimation. [Formula: see text] and ventilatory thresholds were not modified in any environment following acclimation. Wpeak increased by 6.3 ± 3.4% in NOR and 4.0 ± 4.9% in HE, respectively. The magnitude and gain of the forehead sweating response were augmented in HE post-acclimation. EPO increased from baseline (17.8 ± 7.0 mIUmL-1) by 10.7 ± 8.8mIUmL-1 on day 1 but returned to baseline levels by day 10 (15.7 ± 5.9 mIUmL-1). A 10-day combined heat and hypoxic acclimation conferred only minor benefits in aerobic performance and thermoregulation in thermoneutral or hot conditions. Thus, adoption of such a protocol does not seem warranted.

Impact of Education on Hypothermia Delivery during Neonatal Transport

Background: Moderate therapeutic hypothermia (TH) initiated within 6 h of life reduces adverse neurodevelopmental outcomes in infants after perinatal hypoxic ischaemic insult. For infants born in non-tertiary centres, TH may be initiated manually en route to a neonatal intensive care unit (NICU). However, both over- and undercooling is reported with this strategy, precluding some infants from the benefits of TH. Objectives: To evaluate the impact of a region-wide educational programme on the safety and efficacy of manual cooling administered by the Wellington Neonatal Transport Service (NeTS). Methods: Clinical records of infants with hypoxic ischaemic encephalopathy (HIE) retrieved by the Wellington NeTS for TH between January 2012 and June 2017 were reviewed retrospectively. Temperature outcomes of infants retrieved before and after the education programme were compared. Results: A total of 101 infants were cooled manually by Wellington NeTS for TH during the study period. Education and training significantly reduced the rate of overcooling to ≤32.0°C (4/43 [9%] vs. 0/58, p = 0.02). However, there was no difference in the proportion of infants who achieved target rectal temperature within 6 h of life (29/43 [65%] vs. 35/58 [60%], p = 0.57). Conclusions: Introduction of a region-wide educational programme may have improved the safety of manual cooling during neonatal transport but it had a negligible impact on its efficacy. The use of servo-controlled cooling during transport should therefore be considered to improve access to the optimal neuroprotective benefits of TH for outborn infants with HIE.

Heat acclimation does not affect maximal aerobic power in thermoneutral normoxic or hypoxic conditions.

What is the central question of this study? Controlled-hyperthermia heat-acclimation protocols induce an array of thermoregulatory and cardiovascular adaptations that facilitate exercise in hot conditions. We investigated whether this ergogenic potential can be transferred to thermoneutral normoxic or hypoxic exercise conditions. What is the main finding and its importance? We showed that heat acclimation did not affect maximal cardiac output or maximal aerobic power in thermoneutral normoxic or hypoxic conditions. Heat acclimation augmented the sweating response in thermoneutral normoxic conditions. The cross-adaptation theory, according to which heat acclimation could facilitate hypoxic exercise capacity, is not supported by our data. Heat acclimation (HA) mitigates heat-induced decrements in maximal aerobic power ( ) and augments exercise thermoregulatory responses in the heat. Whether this beneficial effect of HA is observed in hypoxic or thermoneutral conditions remains unresolved. We explored the effects of HA on cardiorespiratory and thermoregulatory responses to exercise in normoxic, hypoxic and hot conditions. Twelve men [ 54.7(standard deviation 5.7) mlkg-1 min-1 ] participated in a HA protocol consisting of 10 daily 90-min controlled-hyperthermia (target rectal temperature, Tre =38.5°C) exercise sessions. Before and after HA, we determined in thermoneutral normoxic (NOR), thermoneutral hypoxic (fractional inspired O2 =13.5%; HYP) and hot (35°C, 50% relative humidity; HE) conditions in a randomized and counterbalanced order. Preceding each maximal cycling test, a 30-min steady-state exercise bout at 40% of the NOR peak power output was used to evaluate thermoregulatory responses. Heat acclimation induced the expected adaptations in HE: reduced Tre and submaximal heart rate, enhanced sweating response and expanded plasma volume. However, HA did not affect or maximal cardiac output (P=0.61). The peak power output was increased post-HA in NOR (P<0.001) and HE (P<0.001) by 41±21 and 26±22 W, respectively, but not in HYP (P=0.14). Gross mechanical efficiency was higher (P=0.004), whereas resting Tre and sweating thresholds were lower (P<0.01) post-HA across environments. Nevertheless, the gain of the sweating response decreased (P=0.05) in HYP. In conclusion, our data do not support a beneficial cross-over effect of HA on in normoxic or hypoxic conditions.

Therapeutic hypothermia reduced brain damage on rats after cardiopulmonary resuscitation by activating III-type PI3K pathway to increase autophagy

To investigate the effect of III-type phosphatidylinositide 3 kinase (PI3K) pathway adjusting autophagy on brain damage mechanism after cardiopulmonary resuscitation (CPR) and hypothermia treatment. The asphyxia induce cardiac arrest-CPR model was reproduced on healthy male Sprague-Dawley (SD) rats. Sixty rats after restoration of spontaneous circulation (ROSC) were randomly divided into normothermia group, therapeutic hypothermia group and PI3K inhibitor 3-methyl adenine (3-MA) pretreatment group, differentiated by 24 hours and 48 hours after ROSC. Each group had 10 rats at each time point. The anal temperature in the normothermia group was maintained at (37.0±0.2) centigrade, and the rats in the hypothermia group were given cooling treatment immediately after ROSC, and the target rectal temperature was 32-34 centigrade. In the 3-MA pretreatment group, 10 mmol/L 3-MA 5 μL was injected into the ventricle 20 minutes before asphyxia, and other groups were given the same amount of normal saline. Ten rats without CPR were included in Sham group only received anesthesia and catheterization. The rats were sacrificed at 24 hours and 48 hours after ROSC respectively, and the brain tissues were harvested, the brain water content (BWC) was measured by dry-wet weight method. Western Blot was used to determine the autophagy related proteins Beclin-1 and microtubule-associated protein 1 light chain 3 (LC3), apoptosis related proteins Bcl-2 and caspase-3, and the III-type PI3K pathway proteins Vps34 and Atg14. Ultrastructural changes in brain tissue were observed with transmission electron microscope. Neurological deficit scores (NDS) was obtained in each group at 48 hours after ROSC. Compared with Sham group, the cortex at 24 hours after ROSC in normothermic group showed obvious edema, apoptosis and autophagy began to appear under transmission electron microscope, and the expressions of autophagy, apoptosis and III- type PI3K-related proteins in brain tissue were significantly increased in a time-dependent manner, and the neurological function at 48 hours after ROSC was significantly damaged. After hypothermia intervention, brain edema of rats was significantly reduced, no obvious apoptosis was found, but autophagy was increased, the expressions of autophagy-related proteins Vps34, Atg14 and III-type PI3K-related proteins Beclin-1 and LC3 at 48 hours after ROSC were further higher than those of normothermic group (Vps34/GAPDH: 0.25±0.03 vs. 0.15±0.04, Atg14/GAPDH: 0.12±0.03 vs. 0.05±0.04, Beclin-1/GAPDH: 0.060±0.002 vs. 0.018±0.002, LC3 -II/GAPDH: 0.160±0.010 vs. 0.050±0.010, all P < 0.05), the expressions of apoptosis related proteins Bcl-2 and caspase-3 were significantly lowered (Bcl-2/GAPDH: 0.05±0.03 vs. 0.20±0.04, caspase-3/GAPDH: 0.050±0.002 vs. 0.140±0.015, both P < 0.05), neurological function was significantly improved (NDS: 157±85 vs. 343±198, P < 0.05). Pretreatment with 3-MA inhibited the protective effect of hypothermia on brain tissues. The expressions of Vps34, Atg14, Beclin-1 and LC3 in brain tissues at 48 hours after ROSC in 3-MA pretreatment group was significantly lower than those in the hypothermia group (Vps34/GAPDH: 0.18±0.03 vs. 0.25±0.03, Atg14/GAPDH: 0.07±0.04 vs. 0.12±0.03, Beclin-1/GAPDH: 0.015±0.003 vs. 0.060±0.002, LC3-II/GAPDH: 0.045±0.030 vs. 0.160±0.010, all P < 0.05), the expressions of Bcl-2 and caspase-3 were significantly increased (Bcl-2/GAPDH: 0.15±0.04 vs. 0.05±0.03, caspase-3/GAPDH: 0.120±0.015 vs. 0.050±0.002, both P < 0.05), and NDS score was significantly increased (341±208 vs. 157±85, P < 0.05). Hypothermia treatment reduced brain edema and ameliorated brain function after CPR, which might be related to increase autophagy and inhibit apoptosis adjustment by activating III-type PI3K pathway.

Effects of acute or chronic heat exposure, exercise and dehydration on plasma cortisol, IL-6 and CRP levels in trained males

This study examined the acute and chronic effects of euhydrated and hypohydrated heat exposure, on biomarkers of stress and inflammation. Eight trained males [mean (SD) age: 21 (3) y; mass: 77.30 (4.88) kg; V̇O2max: 56.9 (7.2) mL kg−1 min−1] undertook two heat acclimation programmes (balanced cross-over design), once drinking to maintain euhydration and once with restricted fluid-intake (permissive dehydration). Days 1, 6, and 11 were 60 min euhydrated exercise-heat stress tests (40 °C; 50% RH, 35% peak power output), days 2–5 and 7–10 were 90 min, isothermal-strain (target rectal temperature: 38.5 °C) exercise-heat sessions. Plasma was obtained pre- and post- exercise on day 1, 2, and 11 and analysed for cortisol, interleukin-6 (IL-6), and C-reactive protein (CRP). Cortisol and CRP were also assessed on day 6. IL-6 was elevated following the initial (acute) 90 min isothermal heat strain exercise-heat exposure (day 2) with permissive dehydration ((pre exercise: 1.0 pg mL−1 [0.9], post-exercise: 1.8 pg mL−1 [1.0], P = .032) and when euhydrated (pre-exercise: 1.0 pg mL−1 [1.4], post-exercise: 1.6 pg mL−1 [2.1], P = .048). Plasma cortisol levels were also elevated but only during permissive dehydration (P = .032). Body mass loss was strongly correlated with Δcortisol (r = −0.688, P = .003). Although there was a trend for post-exercise cortisol to be decreased following both heat acclimation programmes (chronic effects), there were no within or between intervention differences in IL-6 or CRP. In conclusion, acute exercise in the heat increased IL-6 and cortisol only when fluid-intake is restricted. There were no chronic effects of either intervention on biomarkers of inflammation as evidenced by IL-6 and CRP returning to basal level at the end of heat acclimation.

Effects of 10 days of separate heat and hypoxic exposure on heat acclimation and temperate exercise performance.

Adaptations to heat and hypoxia are typically studied in isolation but are often encountered in combination. Whether the adaptive response to multiple stressors affords the same response as when examined in isolation is unclear. We examined 1) the influence of overnight moderate normobaric hypoxia on the time course and magnitude of adaptation to daily heat exposure and 2) whether heat acclimation (HA) was ergogenic and whether this was influenced by an additional hypoxic stimulus. Eight males [V̇o2max = 58.5 (8.3) ml·kg-1·min-1] undertook two 11-day HA programs (balanced-crossover design), once with overnight normobaric hypoxia (HAHyp): 8 (1) h per night for 10 nights [[Formula: see text] = 0.156; SpO2 = 91 (2)%] and once without (HACon). Days 1, 6, and 11 were exercise-heat stress tests [HST (40°C, 50% relative humidity, RH)]; days 2-5 and 7-10 were isothermal strain [target rectal temperature (Tre) ~38.5°C], exercise-heat sessions. A graded exercise test and 30-min cycle trial were undertaken pre-, post-, and 14 days after HA in temperate normoxia (22°C, 55% RH; FIO2 = 0.209). HA was evident on day 6 (e.g., reduced Tre, mean skin temperature (T̄sk), heart rate, and sweat [Na+], P < 0.05) with additional adaptations on day 11 (further reduced T̄sk and heart rate). HA increased plasma volume [+5.9 (7.3)%] and erythropoietin concentration [+1.8 (2.4) mIU/ml]; total hemoglobin mass was unchanged. Peak power output [+12 (20) W], lactate threshold [+15 (18) W] and work done [+12 (20) kJ] increased following HA. The additional hypoxic stressor did not affect these adaptations. In conclusion, a separate moderate overnight normobaric hypoxic stimulus does not affect the time course or magnitude of HA. Performance may be improved in temperate normoxia following HA, but this is unaffected by an additional hypoxic stressor.

Neurological Outcome at 30 Months of Age after Mild Hypothermia via Selective Head Cooling in Term Neonates with Perinatal Asphyxia Using Low-Cost CoolCap: A Single-Center Randomized Control Pilot Trial in India

AbstractThe objective of this study was to determine the effectiveness and safety of mild systemic hypothermia by selective head cooling in hospital born neonates with hypoxic-ischemic encephalopathy using low-cost CoolCap. The primary outcome was to determine whether selective head cooling reduces neonatal mortality and neurodevelopmental delay (NDD) at &gt; 30 months of age. The secondary outcome was to determine the serious adverse effects during selective head cooling such as thrombocytopenia requiring platelets transfusion, renal and hepatic dysfunction, bradycardia, hypoglycemia, and dyselectrolytemia (hyperkalemia, hyponatremia, and hypocalcemia). This is a single-center randomized control trial. The risk ratios, risk differences, and numbers needed to treat plus 95% confidence interval (CI) were measured. This study was done at the tertiary care perinatal center. Inborn neonates with ≥ 37 completed weeks of gestation with indicators of perinatal asphyxia and moderate to severe clinical encephalopathy were randomly allocated to hypothermia (n = 30) or standard care (n = 30) groups. The neonates were subjected to mild systemic hypothermia via selective head cooling using ice caps, the target rectal temperature being 34 to 35°C for 72 hours. Therapeutic hypothermia reduced the risk of death and NDD at ≥ 30 months of age: 6 of 30 infants (20%) in the hypothermia group and 18 of 30 infants (60%) in the control group died or had a NDD at ≥ 30 months (risk ratio: 0.33 [95% CI: 0.15–0.72]; p = 0 0.0015). The mortality rate decreased, and the survival rate free of any sensorineural disability increased. The benefits were statistically significant in moderately asphyxiated infants. Adverse effects of hypothermia were minimal. Selective head cooling with mild systemic hypothermia in term asphyxiated neonates is safe and inexpensive in low-resource setting. Hypothermia showed statistically significant reduction in mortality and NDD at ≥ 30 months of age when commenced within 6 hours of birth and was not associated with serious adverse effects. The Institutional Clinical Trial Registry number is CNMC/ETHI/317/P.

Isothermic and fixed‐intensity heat acclimation methods elicit equal increases in Hsp72 mRNA

Thermotolerance, to which heat shock protein-72 (Hsp72) contributes, is an acquired state achieved following heat acclimation (HA), eliciting cellular adaption and protection against thermal stress. Optimal HA methods achieving the greatest heat shock response (HSR) are equivocal; therefore, investigation of methods provoking the greatest sustained HSR is required to optimize cellular adaptation. Twenty-four males performed short-term HA (STHA; five sessions) and long-term HA (LTHA; STHA plus further five sessions) utilizing fixed-intensity (FIXED; workload = 50% V ˙ O 2 p e a k ), continuous isothermic HA [ISOCONT ; target rectal temperature (Trec ) = 38.5 °C], or progressive isothermic HA (ISOPROG ; target Trec = 38.5 °C for STHA then target Trec = 39.0 °C for LTHA). Leukocyte Hsp72 mRNA was measured pre- and post day 1, day 5, and day 10 of HA via reverse transcription quantitative polymerase chain reaction to determine the HSR. Hsp72 mRNA increased (P < 0.05) pre- to post day 1, pre- to post day 5, and pre to post day 10 in FIXED, ISOCONT , and ISOPROG , but no differences were observed between methods (P > 0.05). The equal Hsp72 mRNA increases occurring from consistent, reduced, or increased endogenous strain following STHA and LTHA suggest that transcription occurs following attainment of sufficient endogenous criteria. These data give confidence that all reported HA methods increase Hsp72 mRNA and are capable of eliciting adaptations toward thermotolerance.

Phase Changing Material: An Alternative Method for Cooling Babies with Hypoxic Ischaemic Encephalopathy

Background: Therapeutic hypothermia for hypoxic ischaemic encephalopathy (HIE) has been proved effective. Standard equipment is expensive, while ice packs used in low resource settings are labour intensive and associated with wider temperature fluctuations. Objectives: To assess the feasibility of using phase changing material (PCM) as an alternative method for providing therapeutic hypothermia. Methods: We retrospectively analysed 41 babies with HIE who had been cooled with PCM (OM 32™ or HS 29™) to a target rectal temperature of 33-34°C. Rectal temperature was continuously monitored and recorded every hour. If the rectal temperature was >33.8°C, cool gel packs were applied, and if the temperature was <33.2°C, the baby was covered with sheets and the warmer output turned on till the temperature stabilized at 33.5°C. The unit's standard protocol for cooling was followed for monitoring and treatment. The outcome measures were stability and fluctuation of the rectal temperature and the need for interventions to maintain the target temperature. Results: The mean (±SD) temperature during the cooling phase was 33.45 ± 0.26°C. Throughout the cooling phase, the target temperature range was maintained in 96.2% of the time. There was no temperature reading <32°C. With HS 29, ice packs were not used in any baby, and the warmer was used for a median of 7 h (interquartile range 1.5-14). Conclusions: PCM provides a low cost and effective method to maintain therapeutic hypothermia. However, careful monitoring is required during induction and the rewarming phase to avoid hypothermia outside the therapeutic range.

Isothermic and fixed intensity heat acclimation methods induce similar heat adaptation following short and long-term timescales

Heat acclimation requires the interaction between hot environments and exercise to elicit thermoregulatory adaptations. Optimal synergism between these parameters is unknown. Common practise involves utilising a fixed workload model where exercise prescription is controlled and core temperature is uncontrolled, or an isothermic model where core temperature is controlled and work rate is manipulated to control core temperature.Following a baseline heat stress test; 24 males performed a between groups experimental design performing short term heat acclimation (STHA; five 90min sessions) and long term heat acclimation (LTHA; STHA plus further five 90min sessions) utilising either fixed intensity (50% V̇O2peak), continuous isothermic (target rectal temperature 38.5°C for STHA and LTHA), or progressive isothermic heat acclimation (target rectal temperature 38.5°C for STHA, and 39.0°C for LTHA). Identical heat stress tests followed STHA and LTHA to determine the magnitude of adaptation.All methods induced equal adaptation from baseline however isothermic methods induced adaptation and reduced exercise durations (STHA=−66% and LTHA=−72%) and mean session intensity (STHA=−13% V̇O2peak and LTHA=−9% V̇O2peak) in comparison to fixed (p<0.05). STHA decreased exercising heart rate (−10bmin−1), core (−0.2°C) and skin temperature (−0.51°C), with sweat losses increasing (+0.36Lh−1) (p<0.05). No difference between heat acclimation methods, and no further benefit of LTHA was observed (p>0.05). Only thermal sensation improved from baseline to STHA (−0.2), and then between STHA and LTHA (−0.5) (p<0.05). Both the continuous and progressive isothermic methods elicited exercise duration, mean session intensity, and mean Trec analogous to more efficient administration for maximising adaptation.Short term isothermic methods are therefore optimal for individuals aiming to achieve heat adaptation most economically, i.e. when integrating heat acclimation into a pre-competition taper. Fixed methods may be optimal for military and occupational applications due to lower exercise intensity and simplified administration.

Temperature Control of Infants with/without Asphyxia during Transport

Background: Therapeutic hypothermia (TH) has been shown to improve the outcome following perinatal asphyxia. To obtain the maximum benefit, therapeutic hypothermia should be initiated as soon as possible within 6 hr after birth. In Japan, it is important to develop effective and safe protocols to control the temperature during transport. Objective: To evaluate the efficacy and safety of continuous monitoring of rectal temperatures during transport of infants with/without asphyxia in order to control body temperature properly and to induce passive cooling for infants with mild to severe Hypoxic-ischemic-encephalopathy (HIE) safely. Methods: Skin and rectal temperatures during transport were prospectively collected from transported newborns between August 2012 and August 2014 at three regional cooling centers. In the case of infants without asphyxia, the transport team controlled the temperature of the transport incubator 33 ± 2°C to maintain a target rectal temperature at as close to 36.0-36.5°C as possible. While in the case of infants with asphyxia, the transport team controlled the temperature of the transport incubator between 31 and 32°C to maintain a target rectal temperature at as close to 35.0°C as possible. The rectal and skin temperatures were monitored continuously and recorded by the bedside monitor for later analysis. Results: In the 2 year study period, the skin and rectal temperatures of 52 newborns without asphyxia were monitored continuously. The median gestational age and birth weight of them were 38.1 (36.0-41.3) weeks and 2905 (1904-4408) g. The rectal temperature is correlated significantly with skin temperature (p 35.5°C. One of 4 mild HIE infants had a rectal temperature at arrival between 34.5-35.5°C and three >35.5°C. Only one preterm infant with severe HIE was overcooled. Conclusion: Passive cooling by controlling the transport incubator temperature for infants with HIE was relatively safe and could prevent to be elevated body temperature. However, there may be a risk of unintended excessive cooling, especially in severe HIE infants and preterm infants during longer transfer. We suggest that continuous monitoring of the rectal temperature to control body temperature during transport especially for passive cooling is mandatory. We need further studies to clarify protocols to control body temperature of infants during transport including passive cooling.

PS-149 Initiation Of Therapeutic Hypothermia By Referring Hospitals During Neonatal Transport – Experience In Victoria, Australia

<h3>Background</h3> Hypothermia is an effective treatment for moderate-severe hypoxic-ischaemic encephalopathy (HIE) in term newborns. Non-tertiary units (NTUs) may initiate controlled whole-body hypothermia to a target rectal temperature of 33–34<b>°</b>C in consultation with the Newborn Emergency Transport Service (NETS) by removing external heat sources prior to arrival of the NETS team. We aimed to evaluate temperature outcomes during neonatal transport when hypothermia was initiated by the referring NTU. <h3>Method</h3> We retrospectively audited NETS records of infants with HIE treated with hypothermia from September 2008–August 2012. Infants in whom hypothermia was initiated by the NTU were compared with those in whom the NETS team started cooling. <h3>Results</h3> Demographics of the 123 included infants were comparable between groups. Infants cooled by NTUs began cooling earlier (1.10 vs. 3.25 h after birth, p &lt; 0.01) and reached the target temperature (33–34^°C) sooner (3.35 vs. 4.54 h, p &lt; 0.01) than infants cooled by NETS. There was no difference in time of referral, stabilisation, or arrival at receiving hospital. There was a trend towards more infants cooled by NTUs achieving the target temperature (33–34^°C), OR 2.19 (0.96, 4.96). Infants cooled by NTUs were more likely to have temperatures &lt;33^°C, OR (95% CI) 5.39 (1.64, 22.83), but had fewer temperatures &gt;37^°C, OR (95% CI) 0.25 (0.07, 0.85). <h3>Conclusions</h3> Controlled whole body-hypothermia initiated by regional NTUs, with guidance from NETS, allows earlier initiation of cooling, and attains the target 33–34^oC sooner to optimise neuroprotection in newborns with HIE. Clinical practice should focus on avoiding temperatures &lt;33^°C and preventing hyperthermia.

Therapeutic Hypothermia for Refractory Status Epilepticus in a Child with Malignant Migrating Partial Seizures of Infancy andSCN1AMutation: A Case Report

Status epilepticus (SE) is a common indication for neurocritical care and can be refractory to standard measures. Refractory SE (RSE) is associated with high morbidity and mortality. Unconventional therapies may be utilized in certain cases, including therapeutic hypothermia (TH), bumetanide, and the ketogenic diet. However, the literature describing the use of such therapies in RSE is limited. Details of a case of TH for RSE in an infant with malignant migrating partial seizures of infancy were obtained from the medical record. A 4-month-old child developed SE that was refractory to treatment with concurrent midazolam, phenobarbital, fosphenytoin, topiramate, levetiracetam, folinic acid, and pyridoxal-5-phosphate. This led to progressive implementation of three unconventional therapies: TH, bumetanide, and the ketogentic diet. Electrographic seizures ceased for the entirety of a 43-hour period of TH with a target rectal temperature of 33.0°C–34.0°C. No adverse effects of hypothermia were noted other than a single episode of asymptomatic hypokalemia. Seizures recurred 10 hours after rewarming was begun and did not abate with reinstitution of hypothermia. No effect was seen with administration of bumetanide. Seizures were controlled long-term within 48 hours of institution of the ketogenic diet. TH and the ketogenic diet may be effective for treating RSE in children.

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.

Therapeutic Hypothermia Using Gel Packs for Term Neonates with Hypoxic Ischaemic Encephalopathy in Resource-limited Settings: a Randomized Controlled Trial

To evaluate the efficacy of therapeutic hypothermia (TH) using gel packs in reducing mortality and morbidity in term neonates with HIE and study the associated problems with TH. Hypoxic ischaemic encephalopathy babies were randomized into TH and control group. Babies in TH group were cooled for first 72 h of birth using cloth covered cooling gel packs to maintain target rectal temperature of 33-34°C. Infants were followed up to 6 months and were assessed using Baroda Developmental Screening Test. There were no significant differences in baseline parameters. TH group showed significant reduction in the combined rate of death or developmental delay at 6 months of age by 21% (8.1% in the TH group vs. 29% in the control, RR 0.28, 95% CI: 0.11-0.70; p = 0.003). TH using gel packs reduces the risk of death or developmental delay at 6 months of age in infants with HIE.

Factors Influencing Initiation of Therapeutic Hypothermia and Achieving Target Temperature in Neonatal Encephalopathy

Delay in initiating therapeutic hypothermia (TH) for neonatal encephalopathy (NE) reduces neuroprotection in experimental studies.[1] We aimed to investigate the factors influencing initiation of TH and achieving target rectal temperature (TTrec) in NE infants cooled between 2008 and 2010 at Southmead Hospital, Bristol.Methods: Eligibility criteria from TOBY trial [2]were used to cool NE infants. Data collected on our cohort of 49 babies included weight, sex, gestation, year & place of birth, cardiac compressions, intubation at birth, APGAR scores, cord pH & base deficit, age of initiating TH and reaching TTrec. Age of initiating TH was classified as early (< 1h) or late (>1h). Time required to reach TTrec was calculated as difference between age of initiating TH and reaching TTrec. Logistic regression and multiple linear regression (SPSS v15) were used.Results: The cohort‘s baseline characteristics were mean (SD) weight (3252g (770)), gestation (39.7 weeks (1.79)) and female (41%). Early initiation of TH was associated with cardiac compressions (60% vs 22%, p=0.02), year of birth (2008 (23%), 2009 (29%), 2010 (47%)) and 10min APGAR score (median (IQR) 5(3,6) vs 6(5,7), p=0.05). Cardiac compressions (OR 4.7, 95% CI (1.24, 17.9)) independently predicted early initiation of TH. Each 100g increase in birth weight significantly increased the time required to reach TTrec by 7, 95% CI (2, 13) minutes.Conclusion: Cardiac compressions may increase clinicians‘ awareness of the need for TH and heavier babies require longer periods of cooling to reach target temperature.