Feasibility and Safety of Mild Therapeutic Hypothermia in Poor-Grade Subarachnoid Hemorrhage: Prospective Pilot Study

Abstract

Therapeutic hypothermia (TH) improves the neurological outcome in patients after cardiac arrest and neonatal hypoxic brain injury. We studied the safety and feasibility of mild TH in patients with poor-grade subarachnoid hemorrhage (SAH) after successful treatment. Patients were allocated randomly to either the TH group (34.5°C) or control group after successful clipping or coil embolization. Eleven patients received TH for 48 hours followed by 48 hours of slow rewarming. Vasospasm, delayed cerebral ischemia (DCI), functional outcome, mortality, and safety profiles were compared between groups. We enrolled 22 patients with poor-grade SAH (Hunt & Hess Scale 4, 5 and modified Fisher Scale 3, 4). In the TH group, 10 of 11 (90.9%) patients had a core body temperature of < 36°C for > 95% of the 48-hour treatment period. Fewer patients in the TH than control group (n = 11, each) had symptomatic vasospasms (18.1% vs. 36.4%, respectively) and DCI (36.3% vs. 45.6%, respectively), but these differences were not statistically significant. At 3 months, 54.5% of the TH group had a good-to-moderate functional outcome (0–3 on the modified Rankin Scale [mRS]) compared with 9.0% in the control group (P = 0.089). Mortality at 1 month was 36.3% in the control group compared with 0.0% in the TH group (P = 0.090). Mild TH is feasible and can be safely used in patients with poor-grade SAH. Additionally, it may reduce the risk of vasospasm and DCI, improving the functional outcomes and reducing mortality. A larger randomized controlled trial is warranted.

Feasibility and Safety of Mild Therapeutic Hypothermia in Poor-Grade Subarachnoid Hemorrhage: A Prospective Pilot Study

“…Until recently, induced hypothermia during surgical treatment of aneurysm was not routinely recommended. It may represent a reasonable option in selected cases (class III; level of evidence B) (20). We observed limited effects of TH following SAH, which is in contrast to the findings of ischemic stroke and post cardiac arrest care.…”

“…Nevertheless, we assumed applying TH in poor-grade SAH patient before securing the aneurysm might carry a significant re-bleeding risk. Early securing of the aneurysm minimizes its risk of re-bleeding (20). Therefore, we induced TH in selected patients following proper intervention to secure the ruptured aneurysm and reduce the risk of bleeding.…”

“…All eligible patients received standard neurocritical treatment in our stroke center according to the guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage (20). Aneurysms were occluded by microsurgical clipping or endovascular coil embolization within the first 24 hours of admission.…”

Aneurysmal subarachnoid hemorrhage: intensive care for improving neurological outcome

“…Based on these findings and those from studies with animal SAH models clarifying the neuroprotective effect of targeted temperature management (TTM) [ 37 , 38 ], the benefit of TTM for SAH patients was assessed in several studies. Studies exploring the association between TTM and clinical outcomes are summarized in Table 1 [ 39 – 43 ]. A study of TTM for refractory intracranial pressure elevation was excluded [ 44 ].…”

“… Kuramatsu JB 2015 [ 42 ] Matched controlled analysis from single-center, prospective cohort Poor-grade SAH patients (Hunt and Hess grade > 3 and WFNS scale > 3) (1) Induction within 48 h after the hemorrhage (2) 35 °C for 7 days with an endovascular cooling device (3) Rewarming at the rate of 0.5 °C/24 h N = 12 Intravenous paracetamol N = 24 Patients in TTM groups had a significantly lower incidence of DCI (50.0 vs. 84.5%) and a tendency to have better functional outcome (mRS < 3) at 6 months (66.7 vs. 33.3%). Choi W 2017 [ 43 ] Single-center, randomized control trial Poor-grade SAH patients (Hunt and Hess grade > 3 and modified Fisher scale > 2) (1) Induction as soon as possible after ruptured aneurysmal treatment (2) 34.5 °C for 48 h with an endovascular cooling device or a surface cooling device (3) rewarming at the rate of 1 °C/24 h to 36.5 °C N = 11 No detail described N = 11 There were no significant differences in the incidences of DCI (36.3 vs. 45.6%) and favorable neurological outcome (mRS < 3) at 3 months between two groups (27.3 vs. 9.1%). SAH subarachnoid hemorrhage, TTM targeted temperature management, WFNS World Federation of Neurosurgical Society, DCI delayed cerebral ischemia, mRS modified Ranking scale score, GOS Glasgow outcome scale …”