Application of Mild Therapeutic Hypothermia on Stroke: A Systematic Review and Meta-Analysis

Table 2

Self-controlled clinical trials (quasi experiment) of feasibility and efficacy of hypothermic intervention for stroke.

Reference	Study design	Intervention	Patients	Hypothermia induction	Impact on stroke severity	Mortality
[29]^a	Nonrandomized, open label, self-controlled, single-center (quasi-experiment)	Mild hypothermia induced by external cooling within 4 to 24 hours of symptoms onset. Target temperature (33°C)	25 patients with severe ischemic stroke, median SSS 24, mean GCS 9	Target temperature reached in 3.5 to 6.2 h.; Does not clear report the % of patients reaching target temperature, apparently all of them.	Mean initial ICP 20.9±12.4 mmHg and reduced to 13.4±8.3 mmHg during hypothermia (𝑃<0.05); Surviving patients displayed SSS 29 after 4 weeks and 38 three months after stroke	11/25 patients died
[28]^b	Nonrandomized, open label, self-controlled, single-center (quasi-experiment)	Mild hypothermia induced by external cooling within 6 hours of symptoms onset.; Target temperature (33°C)	20 patients with severe ischemic stroke, median SSS 27, mean GCS 9	All patients reached target temperature in about 5-6 h.	Mean SSS was 31.3±8.3, mean mRS 3 and mean BI 65 four weeks after stroke; ICP decreased with initiation of hypothermia	8/20 patients died
[27]	Nonrandomized, open label, self-controlled, single-center (quasi-experiment)	Mild hypothermia induced by external cooling as soon as possible (no mention of time delay after symptoms onset). Target temperature (33-34°C)	6 patients with severe ischemic stroke	Mean duration of hypothermia 63.5 h Does not clear report the % of patients reaching target temperature, apparently all of them.	Decreased CMRO2, transiently reduced CBF and controlled ICP	2/6 patients died of intractable intracranial hypertension
[25]	Nonrandomized, open label, self-controlled, single-center (quasi-experiment)	Mild hypothermia induced by endovascular device within 3 h of symptoms onset Target temperature (33-34°C)	10 patients with acute ischemic stroke NIHSS 4–12	Temperature dropped from 37.1±0.7°C by a maximum of 1.6±0.3°C (𝑃<0.005) at 52±16 min after hypothermia induction.; Does not clear report the % of patients reaching target temperature, apparently all of them.	NIHSS at discharge (1) improved compared to admission (5.5) (𝑃<0.02)	NR
[26]	Nonrandomized, open label, self-controlled, single-center (quasi-experiment)	Mild hypothermia induced by external (𝑛=10) or intravascular (𝑛=8) cooling methods within 6 h of symptoms onset. Target temperature (33–34.5°C)	18 acute stroke patients NIHSS ≥8	13 patients reached target temperature (mean latency 9h43, mean duration 19h48). 2 patients were not cooled due to catheter or machine failure.	NIHSS 15 to 9 in 24 h; NIHSS 6 at discharge	2/18 patients died

(a) Published in Stroke. (b) Published in Acta Neurochirurgica Supplementum. BI: Barthel index; CBF: cerebral blood flow; CMRO2: cerebral metabolic rate of oxygen; GCS: Glasgow Come Scale; ICP: intracranial pressure; mRS: modified Rankin scale; NIHSS: NIH Stroke Scale; NR: not reported; SSS: Scandinavian Stroke Scale.