Table 2.
Studies testing different approaches of target temperature management in healthy subjects.
| Study | Population | Cooling approach | Tympanic TM device | Core TM sites | Other TM sites | Main results | ||
|---|---|---|---|---|---|---|---|---|
| Location | Protocol | Feasibility | Comparability | |||||
| Bagić et al. [32] |
N: 10 Age: [21–47] y Male: 50% |
Head and neck cooling | Cooling session lengths: 30 and 60 min. Cooling device T: 1.5 to 4.5–5 °C. | IRTT, Braun PRO 3000 Thermometer, Braun GmbH, Germany; TTy measured in both ears. | Intestinal pill | Scalp, forearm, abdomen, leg, face, and mouth | In both ears, TTy displayed significant differences between the start and end of cooling (p < 0.001). | A significant difference was observed in scalp T (p < 0.001), but not in intestinal T (p = NS). |
| Kallmünzer et al. [33] |
N: 10 Age: 35 (28–42) y Male: 60% |
Neck cooling |
Cooling session length: 190 min Cooling device T: 4 °C. |
IRTT, Genius 2, Tyco Healthcare Group, USA | Rectal | None | TTy displayed a significant drop after neck cooling (−1.7 °C, p = 0.001). | Rectal T displayed a smaller decrease (−0.65 °C, p = 0.019). |
| Koehn et al. [34] |
N: 11 Age: 42 ± 11 y Male: 45% |
Neck cooling |
Cooling session length: 90 min. Cooling device T: 4 °C. |
Thermocouple thermometer, ELan Med GmbH, Germany | Rectal | Neck skin | TTy showed a slight but significant decrease (from 35.6 ± 0.2 °C to 35.0 ± 0.8 °C, p = 0.026) within 10 min of cooling, reaching minimal values (34.7 ± 0.4 °C, p < 0.001) after 50 min | Neck skin and rectal T decreased respectively by a higher and lower extent than TTy. |
| Koehn et al. [35] |
N: 10 Age: 35 ± 13 y Man: 100% |
Head and neck cooling |
Cooling session length: 120 min Cooling device T: 4 °C. |
Thermocouple thermometer, ELan Med GmbH, Germany | Rectal | Forehead skin | TTy decreased to minimal values (from 36.6 ± 0.7 °C to 31.8 ± 1.2 °C, p < 0.001) after 40 min of cooling, with a slow increase thereafter. | Forehead skin and rectal T achieved the respective lowest values at 20 and 120 min, respectively. |
| Zweifler et al. [36] |
N: 22 Age: 31 ± 8 y Male: 45% |
Chest and thighs cooling |
Active cooling plus hypothermia maintenance: < 5 h. TT: 34–35 °C (tympanic). Shivering suppression by meperidine, buspirone, and MgSO4. |
Thermocouple thermometer, Mon-a-Therm, Mallinckrodt Anesthesia Products, USA; ear canal occluded with cotton and gauze, ear probe taped in place. | Rectal | None | TTy reached the TT=35 °C in a median time of 88 min (mean cooling rate of 1.4 ± 0.5 °C/h). | A time-dependent gradient was observed between TTy and rectal T (from −0.1 ± 0.3 °C at baseline to −0.6 ± 0.4 °C at 105 min, −0.3 ± 0.5 °C at maintenance phase). |
| Zweifler et al. [37] |
Intervention 1: N: 8 Age: 33 ± 8 y Male: 37% Intervention 2: N: 14 Age: 30 ± 9 y Male: 36% |
Chest and thighs cooling |
Active cooling plus hypothermia maintenance: < 5 h. TT: 34–35 °C (tympanic). Shivering suppression by meperidine, buspirone, or ondansetron, with (intervention 1) or without MgSO4 (intervention 2). |
Thermocouple thermometer, Mon-a-Therm, Mallinckrodt Anesthesia Products, USA; ear canal occluded with cotton and gauze, ear probe taped in place. | Rectal | None | Baseline TTy was 36.8±0.2 °C in intervention 1 and 37.0±0.3 °C in intervention 2. TTy depicted the prolongation of cooling time induced by meperidine (delay of 36 min, p = 0.003, for each 50 mg of drug) and the reduction of cooling time by MgSO4 (17 min, p = 0.039). | Baseline rectal T was 37.0±0.2 °C in intervention 1 and 37.0±0.3 °C in intervention 2. |
| Zweifler et al. [38] |
Intervention 1: N: 5 Age: 36 ± 5 y Male: 60% Intervention 2: N: 5 Age: 30 ± 11 y Male: 20% |
Intervention 1: Chest and thighs cooling Intervention 2: Thighs, back, and abdomen cooling |
Intervention 1: Active cooling plus hypothermia maintenance: < 5 h. TT: 34–35 °C (tympanic). Intervention 2: Active cooling plus hypothermia maintenance: < 5 h. TT: 34.5 °C (rectal). In both, shivering suppression by meperidine, or chlorpromazine |
Thermocouple thermometer, Mon-a-Therm, Mallinckrodt Anesthesia Products, Inc, USA. | Rectal | Mean skin-surface T from calf, thigh, chest, and upper arm skin. | TTy reached the TT=35 °C in 77 ± 23 min (mean cooling rate of 1.5 ± 0.6 °C/h) in Intervention 1 and in 90 ± 53 min (mean cooling rate of 1.4 ± 0.4 °C/h) in Intervention 2. | Rectal T displayed higher values than TTy over the cooling procedure in intervention 2. |
| Mahmood et al. [39] |
N: 18 Age: 32 ± 8 y Male: 44% |
Chest and thighs cooling |
Active cooling plus hypothermia maintenance: ≤ 5 h. TT: 34.5 °C (tympanic). Shivering suppression by meperidine and/or ondansetron and/or buspirone. |
NR | Rectal | None | TTy changes correlated with the mean flow velocity of the middle cerebral artery (p < 0.001). | At baseline TTy was 36.9 ± 0.3 °C, while rectal T was 37.0 ± 0.2 °C. |
| Adams and Koster [40] |
N: 10 Age: > 18 y Male: 50% |
Face and neck cooling | Device application at ambient T of 19 °C. | IRTT, Genius 3000A, Sherwood-Davis & Geck, Gosport UK | None | None | TTy showed a difference of 0.433 °C (p < 0.0001) between baseline and end of cooling exposure. | NR |
| Doufas et al. [41] |
N: 10 Age: 24 ± 4 y Male: 100% |
Whole body cooling by lactated Ringer’s solution (~4 °C) | Lactate infusion to decrease TTy by 1–2 °C/h until identification of the shivering threshold. Conditions tested: no drug, dexmedetomidine and/or meperidine. | Thermocouple thermometer, Mon-a-Therm, Mallinckrodt Anesthesiology Products, Inc., Ireland; ear canal occluded with cotton, probe taped in place, bandage over the ear. | None | Mean skin surface T from 15 area-weighted sites. | TTy detected the significant (p < 0.001) reduction of the shivering threshold induced by meperidine (drop of 1.2°C), dexmedetomidine (0.7 ± 0.5 °C), and their combination (2.0 ± 0.5 °C). | NR |
| Jackson et al. [42] |
N: 12 Age: 27 ± 11 y Male: 42% |
Head and neck cooling |
Cooling session length: 90 min. Cooling device settings: (i) maximum cooling; (ii) bypass mode in each participant. |
IRTT, Genius 2, Tyco Healthcare Group, USA | None | Sublingual |
In condition (i), TTy decreased from 37.01 ± 0.34 °C to 36.70 ± 0.38 °C (60 min) and to 36.76 ± 0.33 °C (90 min). In (ii), TTy decreased to a smaller extent, from 36.93 ± 0.30 °C to 36.85 ± 0.29 °C (60 min) and 36.85 ± 0.27 °C (90 min). |
Sublingual T showed a slower response. In (i), it decreased from 36.80 ± 0.14 °C to 36.70 ± 0.10 °C (60 min) and to 36.70 ± 0.12 °C (90 min). In (ii), it decreased from 36.74 ± 0.12 °C to 36.72 ± 0.11 °C (60 min) and 36.71 ± 0.08 °C (90 min). |
| Wadhwa et al. [43] |
N: 9 Age: 27 [18–40] y Male: 100% |
Whole body cooling by lactated Ringer’s solution (~4 °C) |
Lactate infusion via central venous catheter for 2 h to decrease TTy by ≈1.5 °C·h−1. Condition tested: intravenous MgSO4 (bolus of 80 mg·kg−1 plus infusion of 2 g·h−1), or an equal volume of saline solution. |
Thermocouple thermometer, Tyco-Mallinckrodt Anesthesiology Products, Inc, USA; ear canal occluded by cotton and gauze. | None | Skin surface |
TTy detected a significant reduction of the shivering threshold (0.3 ± 0.4 °C, p = 0.040) by MgSO4 infusion. TTy was 36.6 ± 0.2 °C after 30 min of MgSO4 infusion vs. 36.8 ± 0.3 °C after 30 min of saline solution infusion. |
Skin T was 33.2 ± 0.7 °C after 30 min of MgSO4 infusion vs. 33.6 ±1.3 °C after 30 min of saline solution infusion. |
Data are numbers (N), percentages (%), mean ± standard deviation, or [range], as available. HR, heart rate; IRTT, infrared tympanic thermometer; MgSO4, magnesium sulfate; NR, not reported; TTy, tympanic temperature; T, temperature; TM, temperature measurement: TT, target temperature; vs., versus; y, years