Table 4.

Studies performing target temperature management in acute neurologic diseases

Study	Disease	Population	Cooling approach		Setting	Tympanic TM device	Core TM site	Other TM sites	Main results
			Location	Protocol					Feasibility	Comparability
Abou-Chebl et al. [61]	TBI, IS, ICH	N: 15* Age: 50 ± 17 y Male: 40% NIHSS: 26.7 ± 6.7	Naso-pharingeal cooling	Administration rate of 80 L/min for 1 h.	NICU	NR	Bladder, or rectal, or esophageal, or pulmonary artery. Brain	None	TTy decreased by 2.2 ± 2 °C during induction, with a drop of 0.65 ± 0.39 °C within 15 min (two outliers excluded).	During induction, T decreased by 1.4 ± 0.4 °C (by 0.53 ± 0.24 °C at 15 min) at the brain and by 1.1 ± 0.6 °C (by 0.43 ± 0.35 °C at 15 min) at core sites (bladder, rectal esophageal, or pulmonary artery).
Poli et al. [62]	IS, ICH, SAH	Intervention 1: N: 10 Age: 65 ± 7 y Male: 60% Intervention 2: N: 10 Age: 56 ± 12 y Male: 50% Overall NIHSS: 14.5 (6.75-24.75)	Intervention 1: Whole body cooling by cold saline infusion (4 °C). Intervention 2: Naso-pharingeal cooling	Intervention 1: Infusion flow rate of 4 L/h for 33 ± 4 min. Intervention 2: rate of 60 L/min for 1 h.	NICU	NR	Bladder, rectal, and esophageal. ICP/T brain probe (>3 cm below the cortical surface)	None	TTy reacted similarly to relative changes of brain T during cold infusion, albeit with slightly different absolute values.	TTy correlated well with brain T changes induced by cold infusion, but overestimated brain cooling by naso-pharyngeal cooling (p = 0.005). TTy was slightly lower than brain T even at baseline (37.1 ± 0.7 °C vs 37.5 ± 0.7 °C, p < 0.001).
Poli et al. [63]	IS, ICH, SAH	N: 11 Age: 58 ± 15 y Male: 73% NIHSS: 22.9 ± 13.2	Head and neck cooling (4 °C); subsequent whole-body surface cooling if requested.	Device applied if body core T > 37.1 °C. Drugs: If body core T > 37.1 °C after 1 h of cooling or initial body core T > 38.0 °C, administration of acetaminophen or metamizole and whole-body surface cooling.	NICU	Thermistor thermometer, TTS 400, Smiths Medical, USA	Bladder. ICP/T brain probe, (>3 cm below the cortical surface)	None	After 1 h of cooling, TTy was reduced by −1.69 ± 1.19 °C (p < 0.001), with a maximum decrease of −1.79 ± 1.19 °C after 37 ± 16 min.	TTy at baseline and during cooling was significantly lower (p <0.001) than brain T. After 1 h of cooling, brain T was reduced by −0.32 ± 0.2 °C (p <0.001), and bladder T by −0.18 ± 0.15 °C (p = 0.003). The maximal decrease of brain T was −0.36 ± 0.22 °C after 49 ± 17 min, and of bladder T −0.25 ± 0.15 °C after 48 ± 19 min.
Kammersgaard et al. [64]	IS, ICH	Intervention: N: 17 Age: 69 ± 16 y Male: 71% SSS: 25.8 (11.5) Control: N: 56 Age: 70 ± 10 y Male: 77% SSS: 28 (11.5).	Intervention: whole-body cooling by “forced air” method. Control: standard care.	Intervention: device applied for 6 h.	SU	IRTT, Diatek Model 9000, Diatek Inc, USA	Rectal	None	The mean TTy decreased significantly after 1 h of cooling (from 36.8 °C at baseline to 36.4 °C, p = 0.002). The lowest TTy was achieved after 6 h (35.5 °C, p = 0.001 vs baseline).	A strong correlation was observed between rectal T and TTy.
Kollmar et al. [65]	IS	N: 10 (9 receiving rtPA) Age: 67 ± 13 y Male: NR NIHSS: 5.5 [4-12].	Whole body cooling by cold saline infusion (4 °C, 25 mL/kg body weight)	Administration for 123 ± 20 min after symptom onset and 17 ± 11 min after rt-PA treatment start. Drugs: pethidine/ buspirone for preventing shivering.	NR	NR	None	None	TTy decreased from a baseline of 37.1 ± 0.7 °C by a maximum of 1.6 ± 0.3 °C (p < 0.005). The lowest measured TTy (35.4 ± 0.7 °C) was reached 52 ± 16 min after cold infusion start.	NR
Sund-Levander and Wahren 2000 [66]	SAH, CH, TBI	N: 7 Age: 57 ± 11 y Male: 29%	Whole body cooling, or wrists, ankles, or groin cooling.	Body surface sponged with cool water or alcohol; or alcohol-saturated wraps on wrists, ankles, or groin. Additional cooling with a fan.	NICU	IRTT, Genius 3000 A, Sherwood Medical, UK	None	Skin surface at the toe tip	An increased TTy - toe T gradient was significantly associated with the occurrence of shivering (p < 0.01).	The TTy - toe T gradient decreased more during the intervention when the arms and legs were covered (9.1 ± 5.7 °C) than uncovered (11.7 ± 4.2 °C, p < 0.001).

Data are numbers (N), percentages (%), mean ± standard deviation, median (interquartile range) or [range], as available. *Hypothermia was performed for neuroprotection only in 6 patients

CH, cerebral haematoma; IRTT, infrared tympanic thermometer; ICH, intracerebral haemorrage; ICP, intracranial pressure; IS, ischemic stroke; NICU, neurointensive care unit; NIHSS, National Institutes of Health Stroke Scale; NR, not reported; rtPA, recombinant tissue-type plasminogen activator; SAH, subarachnoid hemorrhage; SSS, Scandinavian Stroke Scale (SSS) score; SU, stroke unit; T, temperature; TH, therapeutic hypothermia; TM, temperature measurement; TTM, target temperature management; T_Ty, tympanic temperature; TBI, traumatic brain injury; y, years