Experimental and Clinical Use of Therapeutic Hypothermia for Ischemic Stroke: Opportunities and Limitations

Table 1

Clinical studies with therapeutic hypothermia in acute stroke.

First author, year [ref.]	Number of patients	Sedated or awake; (+ antishivering drugs)	Method of cooling	Time to treatment (h)^1	tPA^2	Target temperature (°C) + place of measurement	Duration of cooling	Rewarming rate	Outcome
Schwab et al., 1998 [69]	25	Sedated with fentanyl and propofol	Cooling blanket, cold infusion, cold washing	4–24; Mean 14	−	33; Bladder	48–72 h	Passive rewarming  in 24 h	SSS^4 and BI^5; (4 weeks and 3 months)
Kammersgaard et al. 2001, [70]	17	Awake (pethidine)	Cooling blanket, cold air	<12; Mean 3	−	35.5; Tympanic and rectal	6 h	In 4 h to 36.5°C	SSS^4 (6 months)
Schwab et al., 2001 [71]	50	Sedated with midazolam or propofol and morphine or fentanyl	Cooling blanket, alcohol, ice bags	4–75; Mean 22	−	33; Bladder	24–72 h	Passive rewarming in 11–24 h	NIHSS^6 (4 weeks); mRS^7 (3 months); BI^5 (3 months)
Georgiadis et al., 2001 [72]	6	Sedated with midazolam andfentanyl	Endovascular cooling	12–58; Mean 28	−	33; Bladder	48–72 h	1°C/8 h; Max 0.2°C/h	NA^3
Krieger et al., 2001 [56]	10	Sedated with propofol	Cooling blanket, ice water	Mean 6	+	32; Bladder	12–72 h	0.21°C/h	mRS^7 (3 months)
De Georgia et al., 2004 [73]	18	Awake (meperidine and buspirone)	Endovascular cooling, warming blanket	<12; Mean 9	−	33; Esophageal	24 h	0.2°C/h	NIHSS^6 and mRS^7; (30 +7 days)
Guluma et al., 2006 [22]	10	Awake (meperidine and buspirone)	Endovascular cooling, warming blanket	<6	+	33; Blood	24 h	0.3°C/h; 12 h	NA^3
Kollmar et al., 2009 [74]	10	Awake (pethidine and buspirone)	Ice-cold saline, warming blanket	<3; Mean 2	+	35.5; Tympanic	NA^3	NA^3	NIHSS^6 (1 day and at discharge (± 4.5 days))
Hemmen et al., 2010 [75]	58	Awake (meperidine and buspirone)	Endovascular cooling, warming blanket	0–3; 3–6	+	33; Blood	24 h	0.3°C/h; 12 h	NIHSS^6 (1, 30 and 90 days); mRS^7 (90 days)

¹Time from the insult to initiation of treatment; ²tPA: tissue plasminogen activator (+: administered; −: not administered); ³NA: not available; ⁴SSS: Scandinavian Stroke Scale; ⁵BI: Barthel Index; ⁶NIHSS: National Institutes of Health Stroke Scale; ⁷mRS: modified Rankin scale.