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. 2021 Jun 12;9:43. doi: 10.1186/s40560-021-00558-4

Table 3.

Studies performing target temperature management in acute cardiovascular events

Study Pathology Population Cooling approach Setting Tympanic TM device Core TM sites Other TM sites Main results
Feasibility Comparability
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 TTy 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.

PH/ ED IRTT, NR. Esophageal Naso-pharyngeal TTy 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 TTy 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 TTy was 33.40 {33.30; 33.60} °C. TTy 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, TTy 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 TTy 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 TTy 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 TTy tracked the changes induced by cold saline cooling, but it underestimated pulmonary artery T through the whole procedure. The bias$ of TTy 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 TTy 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; TTy measured bilaterally, insulation with adhesive wrapping material. Rectal, or bladder None In intervention TTy showed a drop of 0.06 °C/min in the first 10 min after arrival, followed by a slower decrease. TTy 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 TTy 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, TTy 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] OHCA

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 TTy 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 TTy 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, TTy 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:

TTy 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, TTy 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, TTy 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, TTy 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.

Data are numbers (N), percentages (%), mean, mean ± standard deviation or limits of agreements*, mean {95% confidence interval}, median§, median (interquartile range), median [range], as available. $, bias definition reversed with respect to the original publication. CA, cardiac arrest; CL, catheter lab; ED, emergency department; ICU, intensive care unit; IRTT, infrared tympanic thermometer; NR, not reported; NS, not significant; OHCA, out of hospital cardiac arrest; MI, myocardial infarction; PH, pre-hospital; r, correlation coefficient; ROSC, return of spontaneous circulation; STEMI, ST-elevation myocardial infarction; T, temperature; TM, temperature measurement; TT, target temperature; TTy, tympanic temperature; y, years; vs., versus