Table 2 Studies testing different approaches of target temperature management in healthy subjects.

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; T_Ty measured in both ears.

Intestinal pill

Scalp, forearm, abdomen, leg, face, and mouth

In both ears, T_Ty 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

T_Ty 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

T_Ty 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 T_Ty.

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

T_Ty 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

T_Ty 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 T_Ty 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 T_Ty was 36.8±0.2 °C in intervention 1 and 37.0±0.3 °C in intervention 2. T_Ty 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.

T_Ty 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 T_Ty 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

T_Ty changes correlated with the mean flow velocity of the middle cerebral artery (p < 0.001).

At baseline T_Ty 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

T_Ty 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 T_Ty 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.

T_Ty 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), T_Ty 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), T_Ty 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 T_Ty 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

T_Ty detected a significant reduction of the shivering threshold (0.3 ± 0.4 °C, p = 0.040) by MgSO₄ infusion.

T_Ty 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.