Development of a Resting Energy Expenditure Estimation in Patients Undergoing Targeted Temperature Management with a Surface Gel Pad Temperature Modulating Device.

Targeted temperature management (TTM) directly impacts energy expenditure via temperature modulation and shivering associated with temperature modulating devices. We hypothesized that resting energy expenditure (REE) can be accurately estimated utilizing data obtained from a surface gel pad temperature modulating device (TMD) and demographic factors. Baseline demographic data, along with concurrent temperature, sedation, and shivering data, and indirect calorimetry (IDC) were collected from patients undergoing TTM. The data from the IDC and temperature modulation device (TMD) were synchronized and averaged over 60-second intervals to provide simultaneous comparisons. Heat transfer (calories) was calculated from the TMD by an equation that assessed water temperature from the TMD to the patient, water temperature returning to the TMD, water flow rates, and device mode. A linear regression model was used to determine factors associated with REE as measured by IDC. A difference in the mean between REE and estimated REE was used to assess accuracy. There were 48 assessments conducted in 40 subjects [mean (standard deviation)] age: 58 (14) years, 60% female, body surface area (BSA): 2.0 ± 0.3 who underwent simultaneous assessments. Target temperature was 36-37°C in 75%, with a median Bedside Shivering Assessment Score of 0 (range 0-2). Factors associated with REE on multivariable linear regression included older age (p < 0.001), male sex (p = 0.004), higher BSA (p < 0.001), higher patient temperature (p < 0.001), and lower heat transfer (p = 0.003). Adjusted prediction coefficients from this model were then tested against REE by a Bland-Altman analysis. The difference between difference in resting energy estimation (REEdiff) and measured REE by IDC was 6.2 calories/min (REEdiff: 95% confidence interval: -14.1 calories, 26.5 calories, p = 0.5). We believe that the heat transfer data from the TMD coupled with clinical characteristics of patients can be utilized to calculate the REE for every minute of TTM. These data can be utilized to mitigate the consequences of shivering and malnutrition during TTM.

Predictors and clinical implications of shivering during therapeutic normothermia.

BACKGROUND: Shivering during induced normothermia (IN) remains a therapeutic limitation. We investigated potential risk factors and clinical implications of shivering during IN. METHODS: Post hoc analysis was performed on 24 patients enrolled in a clinical trial of an automated surface cooling system to achieve IN. Hyponatremia was defined as serum levels <136 mmol/L and hypomagnesaemia as levels <1.5 mg/dL. Continuous heat energy transfer (kcal/h) was averaged hourly. Glasgow Coma Scale (GCS) scores were recorded every 2 h. Shivering status was documented hourly. Mixed effects modeling was used to determine clinical measures associated with shivering. Generalized estimating equation (GEE) models were used to compare baseline-adjusted repeated-measures GCS scores. RESULTS: About of 24 (39%) patients demonstrated shivering. Shivering was associated with men (67% vs. 21%, P = 0.03), hyponatremia (44% vs. 7%, P = 0.03), and hypomagnesaemia (56% vs. 7%, P = 0.02). The average kcal/h (158 +/- 645 kcal/h vs. 493 +/- 645 kcal/h, P = 0.03) was greater in shivering patients. Shivering was positively associated with increases in heart rate (P < 0.001), respiratory rate (P < 0.001), and kcal/h (P < 0.001). Non-shivering patients showed a greater increase from baseline GCS (GEE, P = 0.02) at 24 h. No differences in sedative doses or fever burden were noted between shiverers and non-shiverers. CONCLUSIONS: Men, hyponatremia, and hypomagnesaemia may predispose febrile patients treated with IN to shivering. Shivering dramatically increases the amount of heat transfer required to maintain normothermia, and may be associated with adverse effects on level of consciousness.

Transcranial Doppler ultrasonographic evaluation of middle cerebral artery hemodynamics during mild hypothermia.

BACKGROUND AND PURPOSE: Induced hypothermia holds promise as an effective neuroprotective strategy following cerebral ischemia. The effect of mild hypothermia on cerebral hemodynamics is not well known. The authors investigated the influence of brain temperature on middle cerebral artery (MCA) mean flow velocity (MCA FV) and pulsatility index (MCA PI) in nonintubated, healthy volunteers undergoing mild induced hypothermia. METHODS: Mild hypothermia (target tympanic membrane temperature [T tym] degrees C) was induced in subjects using the Arctic Sun Temperature Management System (Medivance, Inc, Louisville, CO). MCA FV and MCA PI were recorded bilaterally with a 2 MHz pulsed probe every 30 minutes via the transtemporal window. RESULTS: Eighteen subjects (8 males, 10 females) 32 +/- 8 years of age were studied. Multivariate analysis indicated that MCA FV increased with increasing change in temperature (baseline tympanic temperature-tympanic temperature [DeltaT tym]) (P< .001), heart rate (HR) (P< .001), end-tidal CO 2(P= .025), arterial oxygen saturation (O2%) (P= .001), and with decreasing mean arterial blood pressure (P= .004). Multivariate analysis also indicated that ln(MCA PI) (natural logarithm of MCA PI) decreased with decreasing T tym(P< .001) and increasing HR (P< .001). CONCLUSIONS: Mild induced hypothermia is associated with an increase in MCA FV and a decrease in MCA PI. The increase in MCA FV may be partially due to microcirculatory vasodilation.

Magnesium sulfate increases the rate of hypothermia via surface cooling and improves comfort.

BACKGROUND AND PURPOSE: Therapeutic hypothermia shows promise as a treatment for acute stroke. Surface cooling techniques are being developed but, although noninvasive, they typically achieve slower cooling rates than endovascular methods. We assessed the hypothesis that the addition of intravenous MgSO4 to an antishivering pharmacological regimen increases the cooling rate when using a surface cooling technique. METHODS: Twenty-two healthy volunteers were studied. Hypothermia was induced using a surface technique with a target tympanic temperature (Ttym) of 34.5 degrees C (target range 34 to 35 degrees C). Subjects received 1 of the following pharmacological regimens: (1) meperidine monotherapy (n=5); (2) meperidine plus buspirone, 30 to 60 mg PO administered at the time of initiation of cooling (n=4); (3) meperidine and ondansetron, 8 to 16 mg IV administered as an 8 mg bolus at the time of initiation of cooling with an optional second dose after 4 hours as needed for nausea (n=5); or (4) meperidine, ondansetron, and MgSO4, 4 to 6 g IV bolus followed by 1 to 3 g per hour infusion (n=8). Thermal comfort was evaluated with a 100-mm-long visual analog scale. RESULTS: More subjects who received MgSO4 were vasodilated during hypothermia induction (7 of 8 [88%] versus 4 of 14 [29%]; P=0.024). MgSO4 (coefficient -17.265; P=0.039), weight (1.838, 0.001), and the initial 2-hour meperidine dose (0.726, 0.003) were found to significantly impact the time to achieve Ttym of 35 degrees C. Subjects who received MgSO(4) had significantly higher mean comfort scores than those who did not (48+/-15 versus 38+/-12; P<0.001). CONCLUSIONS: Administration of intravenous MgSO(4) increases the cooling rate and comfort when using a surface cooling technique.

Rectal temperature reflects tympanic temperature during mild induced hypothermia in nonintubated subjects.

INTRODUCTION: Mild induced hypothermia holds promise as an effective neuroprotective strategy following acute stroke and cardiac arrest. Dependable noninvasive measurements of brain temperature are imperative for the investigation and clinical application of therapeutic hypothermia. Although the tympanic membrane temperature correlates best with brain temperature, it is a cumbersome location to record from continuously in the clinical setting. Data are lacking regarding the relationship between rectal and tympanic temperatures in nonintubated humans undergoing induced hypothermia via surface cooling. METHODS: We induced mild hypothermia in healthy volunteers using a novel surface cooling method (Arctic Sun Temperature Management System, Medivance, Inc., Louisville, CO). Core temperatures were recorded at the tympanic membrane (Ttym) and rectum (Trec). The gradient was defined as (Ttym-Trec). Controlled hypothermia was maintained for up to 300 minutes with a target Ttym of 34 degrees C to 35 degrees C; subjects were then actively rewarmed to a target Ttym of 36 degrees C over 1.5 to 3 hours. RESULTS: Twenty-two volunteers (10 males and 12 females) 31 +/- 8 years of age were studied. Subjects showed a triphasic temperature response: induction, maintenance, and rewarming. The mean gradient at baseline was -0.1 +/- 0.3 degrees C and the maximum gradient increased to -0.6 +/- 0.4 degrees C at 105 minutes. During maintenance of hypothermia (from 150 to 300 minutes), the mean gradient was -0.3 +/- 0.5 degrees C (95% confidence limits, -1.2 degrees C to 0.6 degrees C). CONCLUSIONS: : Our data suggest that Ttym and Trec are not related during the induction of hypothermia via surface cooling but correlate during the maintenance phase, with a -0.3 degrees C gradient. These findings support the use of rectal temperature as a measure of tympanic and, therefore, brain temperature during maintenance of induced hypothermia in nonintubated humans.

Induction and maintenance of mild hypothermia by surface cooling in non-intubated subjects.

Mild induced hypothermia holds promise as an effective therapy for acute ischemic stroke. We developed a novel strategy to rapidly induce and maintain mild hypothermia in unanesthetized, non-intubated subjects as a model for the treatment of acute stroke patients. We induced and maintained mild hypothermia (tympanic membrane temperature 34 degrees C-35 degrees C) for over 5 hours in 10 healthy volunteers. All subjects received 1000 mg of acetaminophen orally and meperidine intravenously for comfort and suppression of shivering. In phase 1, subjects (n=5) were cooled using Arctic Sun Energy Transfer Pads (Medivance, Inc., Louisville, CO) with manual temperature control. In phase 2, subjects (n=5) were cooled using the Arctic Sun Energy Transfer Pads connected to the Arctic Sun Model 200 Temperature control module (Medivance, Inc.). Core temperatures were measured at the tympanic membrane and rectum. All subjects reached the target tympanic temperature range. The mean time to reach a tympanic temperature of 35 degrees C was 90+/-53 minutes (1.4 degrees C/hour) in phase 2. The most common side effect was nausea, observed in 30% of subjects. There was no statistically significant change in heart rate, blood oxygenation, or diastolic blood pressure compared with baseline; systolic blood pressure was significantly elevated for the 180 minute time point only (140+/-20 mm Hg v 122+/-13 mm Hg; P = .042). We developed a method to rapidly and comfortably induce and maintain mild hypothermia in unanesthetized, non-intubated humans. Further study to optimize the pharmacologic inhibition of thermoregulation and to assess tolerability over longer durations is warranted.