Table 3 Studies performing target temperature management in acute cardiovascular events

Busch et al. [44]

CA

N: 84

Age: 71 (63; 79) y

Male: 76%

Post-ROSC trans-nasal cooling.

TT: 33 °C (tympanic and esophageal).

ED/ ICU

IRTT, ThermoScan Pro 4000, Braun GmbH, Germany

Esophageal, or arterial, or bladder, or rectal

None

T_Ty displayed a cooling rate of 2.3 (1.6; 3.0) °C/h. The cooling time to reach the tympanic TT was 60 (36.5; 117.5) min and was reached in 66% of pts.

The cooling rate of overall core sites (esophageal, arterial, bladder, or rectal) was 1.1 (0.7; 1.5) °C/h, with a faster response for esophageal or arterial (1.4 (0.9; 2.0) °C/h) than for bladder or rectal (0.9 (0.5; 1.2) °C/h; p=0.001). The cooling time to reach the core TT was 180 (120; 285) min and was reached in 19% of patients.

Callaway et al. [45]

OHCA

Intervention:

N: 9

Age: 68 ± 15 y

Male: 100%

Control:

N: 13

Age: 80 ± 10 y

Male: 71%

Intervention:

intra-arrest head and neck cooling.

TT: 34 °C (esophageal).

Control:

standard care.

IRTT, NR.

Esophageal

Naso-pharyngeal

T_Ty displayed unpredictable variations due to ice in the ears.

NR

Castren et al. [46]

OHCA

Intervention:

N: 93

Age: 66 y

Male: 72%

Control:

N: 101

Age: 64 y

Male: 78%

Intervention:

intra-arrest trans-nasal cooling.

TT: 34 °C (tympanic and core).

Control:

standard care.

PH

IRTT, NR

Rectal, or bladder, or intravascular

None

T_Ty at hospital arrival was significantly different (p<0.001) in intervention (34.2±1.5 °C) vs. control (35.5±0.9 °C). The cooling rate was 1.3 °C in 26 min. The cooling time to reach the tympanic TT was significantly shorter (p=0.03) in the intervention (102 (81; 155) min) vs. the control (291(183; 416) min) group.

Core T (rectal, or bladder, or intravascular) at admission was 35.1±1.3 °C in intervention vs. 35.8 °C ± 0.9 °C in control (p<0.01). Cooling time to reach the core TT was 155 (124; 315) min in the intervention vs. 284 (172; 471) in the control group.

Hasper et al. [47]

OHCA

N: 10

Age: 71.5 y^§

Male: 80%

Post-ROSC whole body

cooling by cold saline infusion and water pads.

TT: 33 °C (NR).

ED

IRTT, Braun ThermoScan pro4000; Welch Allyn, Germany

Esophageal, or bladder

None

During TTM T_Ty was 33.40 {33.30; 33.60} °C.

T_Ty displayed a small bias with respect to esophageal T (0.021 °C ± 0.80 °C) and a high significant correlation with esophageal (r=0.95, p<0.0001) and bladder T (r=0.96, p<0.0001).

Hachimi-Idrissi et al. [48]

OHCA

Intervention:

N: 16

Age: 77 [52; 95] y

Male: 56%

Control:

N: 14

Age: 74 [59; 91] y

Male: 64%

Intervention:

head and neck cooling.

TT: 34 °C (bladder).

Control:

standard care.

ED

IRTT, Braun Thermoscan, Braun, Germany

Central venous, arterial, or bladder

Scalp

The cooling time to reach the tympanic TT in intervention was 60 (15; 240) min.

The cooling time to reach the bladder TT was longer, 180 (70; 240) min (p = NR).

Islam et al. [49]

OHCA

Intervention:

N: 37

Age: 64 ± 12 y

Male: 86%

Control:

N: 37

Age: 62 ± 13 y

Male: 74%

Intervention:

post-ROSC intra-nasal cooling.

TT: 34 °C (tympanic and esophageal).

Control: standard surface-cooling.

TT: 34 °C (tympanic and esophageal).

CL by direct admission

NR

Esophageal

None

In the first cooling hour, T_Ty showed a significantly larger drop (1.75 °C) in intervention vs. control (0.935 °C, p<0.01).

The cooling time to reach the tympanic TT was 75.2 min in intervention vs. 107.2 min in control (p=NS).

Esophageal T drop in the first hour was not significantly different in intervention (1.148 °C) vs. control (0.904 °C, p = NS).

The cooling time to reach the esophageal TT was 84.7 min in intervention vs. 114.9 min in control (p=NS).

Krizanac et al. [50]

OHCA

N: 20

Age: 63 (43; 88) y

Male: 80%

Post-ROSC cooling by cooling pads, or intravascular cooling catheters and intravenous cold saline infusion.

TT: 33 °C (esophageal).

ED

Thermistor thermometer, Mon-a-Therm, Tyco Healthcare, UK.

Esophageal, bladder, pulmonary artery, or femoral-iliac artery

None

T_Ty tracked temperature changes induced by cooling but continuously and substantially underestimated the pulmonary artery T during cooling as well as during steady state.

The bias of T_Ty compared to pulmonary artery T were -0.6 {−0.8; −0.3} °C (overall) and −0.6 {−0.8; −0.4}°C (cooling phase). The tympanic TT was reached with an anticipation of −38 {−65; −23.5} min compared to the pulmonary artery.

Shin et al. [51]

OHCA

N: 21

Age: 50 ± 20 y

Male: 71%

Post-ROSC cooling by cold saline infusion and external cooling pads.

TT: 33 °C (bladder).

ED

Thermistor thermometer, Probe 400 Series, DeRoyal, USA; inserted after otoscopic exam, taped in place, covered with bandage.

Rectal, bladder, or pulmonary artery

None

T_Ty tracked the changes induced by cold saline cooling, but it underestimated pulmonary artery T through the whole procedure.

The bias^$ of T_Ty compared to pulmonary artery was: −1.03 ± 1.47 °C (overall), −1.11 ± 1.53 °C (induction phase), −1.12 ± 1.29 °C (maintenance phase), and −0.89 ± 1.62 °C (rewarming phase). The correlation was: 0.860 (overall), 0.815 (induction phase), 0.611 (maintenance phase), and 0.776 (rewarming phase).

Stratil et al. [52]

CA

Winter group (outside T ≤ 10 °C):

N: 61

Age: 60 (50; 75) y

Male: 70%

Summer group:

(outside T ≥ 20 °C):

N: 39

Age: 57 (48; 65) y

Male: 77%

Mild therapeutic hypothermia by surface or invasive cooling in 25 winter and 24 summer patients.

TT: <34 °C (NR).

ED

IRTT, Ototemp LighTouch; Exergen, USA; only at admission.

Bladder, or esophageal

None

T_Ty at hospital admission was significantly lower (p=0.001) in winter (34.9 °C (34; 35.6)) vs. summer group (36 °C (35.3–36.3)).

Core T at admission was 35.3 °C (34.8; 35.9) in winter vs. 36.2 °C (35.5–36.7) in summer group (p = 0.001).

Takeda et al. [53]

CA

(mainly OHCA)

Intervention:

N: 53

Age: 72 (62; 81) y

Male: 47%

Control:

N: 55

Age: 72 (64; 78) y

Male: 67%

Intervention:

pre- or post-ROSC pharyngeal cooling plus whole body cooling.

TT: 32 °C (tympanic).

Control: standard care.

ED

Thermistor thermometer, TM400, Covidien, Japan; T_Ty measured bilaterally, insulation with adhesive wrapping material.

Rectal, or bladder

None

In intervention T_Ty showed a drop of 0.06 °C/min in the first 10 min after arrival, followed by a slower decrease. T_Ty was significantly lower in intervention vs. control at 40 min (33.7 ± 1.4 °C vs. 34.1 ± 1.1 °C, p = 0.02) and 120 min (32.9 ± 1.2 °C vs. 34.1 ± 1.3 °C, p < 0.001).

Core T dropped by 0.02 °C/min at 30 min after arrival. Core T was significantly lower in intervention vs. control at 120 min (34.5 ± 1.1 °C vs. 35.3 ± 1.0 °C, p = 0.02).

Wandaller et al. [54]

CA

Intervention 1:

N: 5

Intervention 2:

N: 6

Control: none.

Demographic data: NR.

Intervention:

post-ROSC head cooling without (1) or with neck cooling (2). Additional endovascular cooling if necessary.

TT: 33 °C (esophageal).

ED

Thermocouple thermometer, Mon-a-term, Mallinckrodt, Inc, USA.

Esophageal and jugular

None

T_Ty showed a drop of 3.4 °C in the first 3 h of cooling.

T drop was 3.7 °C at the jugular site and 2.4 °C at the esophageal site.

With respect to esophageal T, T_Ty displayed a bias of − 1.65 {−2.2; −1.1} °C (p=0.001) in Intervention 1 vs. −3.06 {-4.27; −1.85} °C in Intervention 2 (p=0.001).

Zeiner et al. [55]

N: 27

Age: 58 (52; 64) y

Male: 74%

Post-ROSC surface body cooling

plus head and body cooling by pre-cooled

mattress.

TT: 33 ± 1 °C (pulmonary artery).

ED/ICU

IRTT, Ototemp LighTouch, Exergen, USA; only at admission.

Esophageal,

bladder, or pulmonary artery

None

T_Ty was measured only at admission and showed a value of 35.3 °C (34.9–36.0 °C).

NR

Ko et al. [56]

OHCA

Intervention:

N: 23

Age: 55 ± 15 y

Male: 87%

Control:

N: 35

Age: 63 ± 18 y

Male: 71%

Intervention:

post-ROSC whole body cooling by blanket and cold crystalloid intravenous infusion.

TT: 33 °C (tympanic).

Control:

standard care.

ED/ ICU

Non-contact thermometer, NR.

None

None

T_Ty detected significant differences (p = 0.004) during TTM in intervention (35.16 °C) vs. control (36.5 °C).

NR

Skulec et al. [57]

OHCA

Intervention:

N: 40

Age: 61 ± 18 y

Male: 85%

Control:

N: 40

Age: 61 ± 17 y

Male: 72%

Intervention:

post-ROSC, PH cooling by intravenous cold saline infusion plus in-hospital TTM.

TT: <34 °C (tympanic).

Control:

standard care (in-hospital TTM).

PH/ ED

NR

None

None

In intervention, T_Ty dropped by 1.4 ± 0.8 °C (from 36.2 ± 1.5 to 34.7 ± 1.4 °C; p<0.001) in 42.8 ± 19.6 min. The tympanic TT was reached in 17.5% of patients.

NR

Storm et al. [58]

OHCA

Intervention:

N: 20

Age: 62 (52; 71) y

Male: 65%

Control:

N: 25

Age: 58 (44; 66) y

Male: 84%

Intervention:

post-ROSC head cooling by hypothermia cap.

TT: NR.

Control:

standard care.

PH

NR

None

None

In intervention:

T_Ty dropped from 35.5 °C (34.8; 36.3) to 34.4 °C (33.6; 35.4) after head cooling (p<0.001). In two patients, T_Ty was not affected by cooling.

NR

Erlinge et al. [59]

STEMI

Intervention:

N: 61

Age: 57 (37; 79) y

Male: 79%

Control:

N: 59

Age: 59 (30; 75) y

Male: 86%

Intervention:

pre-reperfusion cooling by cold saline infusion.

TT: ≤35 °C (cooling catheter) before reperfusion.

Control: standard care.

CL

NR

None

Cooling catheter sensor, during endovascular cooling

In the intervention group, T_Ty was measured only at baseline and was 36.0 ± 0.7 °C.

The cooling catheter T at reperfusion was 34.7 ± 0.6 °C (p=NR).

Testori et al. [60]

STEMI

Intervention:

N: 47

Age: 58 ± 10 y

Male: 79%

Control:

N: 54

Age: 55 ± 12 y

Male: 81%

Intervention:

PH cooling by cold saline and surface pads, followed by CL endovascular cooling.

TT: 34 °C (cooling catheter).

Control:

standard care.

PH / CL

IRTT, Ototemp Ligh-Touch, Exergen, USA

None

Cooling catheter sensor, during endovascular cooling

In the intervention group, T_Ty displayed a significant decrease from a baseline of 36.1 ± 0.5 °C to 35.5 ± 0.6 °C after PH cooling (p < 0.01).

The cooling catheter T at reperfusion was 34.4 °C ± 0.6 °C.