Therapeutic hypothermia after recanalisation in patients with acute ischaemic stroke

Hong, Ji M, Jin SL, Hee-Jung S, Hye SJ, Huimahn AC, et al. Therapeutic hypothermia after recanalisation in patients with acute ischaemic stroke. Stroke 2014;45:134-40.

Hypothermia attenuates neuronal damage in the injured brain by affecting varied pathways activated due to ischaemia. These include energy depletion, ion shifts, free radical formation, EAA release and inflammation.[1] Cerebral oxygen consumption is reduced at a rate of approximately 6% per 1°C decrease in temperature, allowing reduced oxidative debt in times of ischaemia. This, in turn, maintains ionic homeostasis and prevents release of ischaemia-induced excitatory amino acids, free radicals and inflammatory responses which can increase recruitment of ischaemic penumbra.

Hong et al., carried out a prospective cohort study at two stroke centres to investigate the clinical and radiological effects of therapeutic hypothermia in acute ischaemic stroke patients after recanalisation. They enrolled patients with acute ischaemic stroke of the anterior circulation with an initial National Institutes of Health Stroke Scale (NIHSS) ≥10 who had successful recanalisation (i.e., thrombolysis in cerebral ischaemia). Patients at one centre underwent a mild hypothermia (34.5°C) protocol, which included mechanical ventilation, and 48-hour hypothermia and 48-hour rewarming while patients at the other centre were treated according to the guidelines without hypothermia. Cerebral oedema, haemorrhagic transformation, good outcome (3-month modified Rankin Scale, ≤2), mortality and safety profiles were compared. All potential variables were analyzed before and after initiating intervention. The hypothermia group (n = 39) had less cerebral oedema (P = 0.001), haemorrhagic transformation (P = 0.016) and better outcome (P = 0.017) compared with the normothermia group (n = 36). Mortality, haemicraniectomy rate and medical complications were comparable in both the groups. The authors concluded that in patients with ischaemic stroke, after successful recanalisation, therapeutic hypothermia may reduces the risk of cerebral oedema and haemorrhagic transformation and may lead to improved clinical outcomes. This study is different for reasons like prolonged use of hypothermia (48 hours), compulsory mechanical ventilation and stress on post-recanalisation ischaemia reperfusion complications.

In 2007, van der Worp et al.,[1] carried out a systemic review and meta-analysis of the evidence for efficacy of hypothermia in animal models of ischaemic stroke in which 101 publications reporting the effect of hypothermia on infarct size or functional outcome, including data from a total of 3353 animals were taken into account. Overall, hypothermia reduced infarct size by 44%. Efficacy was highest with cooling to lower temperatures (≤31 (degreeand started before or at the onset of ischaemia in temporary ischaemia models. However, a substantial reduction in infarct volume was also observed with cooling to 35 degree with initiation of treatment between 90 and 180 min and in permanent ischaemia models. The effects of hypothermia on functional outcome were broadly similar and hence the authors concluded that in animal models of focal cerebral ischaemia, hypothermia improves outcome.

The improvement in cranial imaging and functional outcome after institution of hypothermia has also been corroborated in the Kollmar et al., study.[2] Here 12 patients with supratentorial sICH (spontaneous intracerebral haemorrhage) >25 ml were treated by hypothermia of 35°C for longer duration of 10 days. Evolution of haematoma volume and perifocal oedema was measured by cranial CT and functional outcome was assessed after 90 days. The control group comprised patients (n = 25; inclusion criteria: sICH volume >25 ml with no acute restriction of medical therapy on admission) from the local haemorrhage data bank (n = 312). All hypothermic patients survived until day 90, whereas seven patients died in the control group). Also in the hypothermia group, oedema volume remained stable during 14 days whereas oedema significantly increased in the control group from 40+/- 28 ml (day 1) to 88+/- 47 ml (day 14). The incidence of pneumonia was 100% in the hypothermia group and 76% in control group. The authors concluded that hypothermia prevented an increase of peri-haemorrhagic oedema in patients with large sICH.

At present there is no consensus regarding duration of hypothermia to be instituted for neuroprotection in acute ischaemic stroke. Jiang et al., [3] carried out a comparative study between long versus short duration of hypothermia in severe traumatic brain injury (TBI). Two-hundred and fifteen patients aged 18-45-years old with an admission Glasgow Coma Scale ≤8 within 4 h after injury were randomly divided into two groups: long-term mild hypothermia group (n = 108) for 5+/- 1.3 days and short-term mild hypothermia group (n = 107) for 2+/- 0.6 days of mild hypothermia therapy. They found similar rate of adverse events in both the groups while improved outcome in the hypothermia group.

• REFERENCES

• 1 van der Worp HB, Sena ES, Donnan GA, Howells DW, Macleod MR. Hypothermia in animal models of acute ischaemic stroke: A systematic review and meta-analysis. Brain 2007; 130: 3063-74
• 2 Kollmar R, Staykov D, Dörfler A, Schellinger PD, Schwab S, Bardutzky J. Hypothermia reduces perihemorrhagic edema after intracerebral hemorrhage. Stroke 2010; 41: 1684-9
• 3 Jiang JY, Xu W, Li WP, Gao GY, Bao YH, Liang YM. et al. Effect of long-term mild hypothermia or short-term mild hypothermia on outcome of patients with severe traumatic brain injury. J Cereb Blood Flow Metab 2006; 26: 771-6