Clinical Neurology and Neurosurgery 221 (2022) 107369

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Clinical Neurology and Neurosurgery

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Full Length Article

Therapeutic hypothermia in patients with poor-grade aneurysmal

subarachnoid hemorrhage
So Young Won a, Mi Kyung Kim b, Jihye Song a, *, 1, Yong Cheol Lim a, *, 1
a
Department of Neurosurgery, Ajou University School of Medicine, Suwon, South Korea
b
Department of Neurosurgery, Myongji St. Mary’s Hospital, T Seoul, South Korea

A R T I C L E I N F O A B S T R A C T

Keywords: Objective: Therapeutic hypothermia improves the prognosis of patients with poor-grade subarachnoid hemor­
Intracranial aneurysm rhage (SAH). We investigated the clinical and radiological effects of therapeutic hypothermia in patients with
Delayed cerebral ischemia poor-grade SAH.
Subarachnoid hemorrhage
Methods: Clinical and radiological data were compared between patients who underwent mild hypothermic
Therapeutic hypothermia
treatment and those who underwent treatment without hypothermia.
Results: Among 670 patients with SAH, 72 had poor-grade SAH. After early clipping or coiling of the aneurysm,
25 patients underwent mild hypothermia and the remaining 47 patients underwent no hypothermia. The medical
complication occurrence rates were similar between the hypothermia treatment and control groups. Signifi­
cantly, cerebral edema was reduced in patients in the hypothermia group (44 %) compared with those in the no-
hypothermia group (9 %) (p = 0.025). The poor clinical outcome rate (modified Rankin scale score > 4) assessed
at discharge (p = 1.000) and 3 months after admission (p = 0.688) was similar between the two groups.
However, 1 month after admission, the mortality rate of the hypothermia group (20.0 %) was remarkably lower
than that of the control group (46.8 %) (p = 0.025). Multivariate logistic regression showed the therapeutic
hypothermia was the most effective treatment for decreasing the mortality (OR = 4.86, P = 0.023).
Conclusion: Mild hypothermia treatment appears to be feasible and safe for patients with poor-grade SAH. The
study supports mild hypothermia treatment and its neuroprotective effects in patients with poor-grade SAH.

1. Introduction hypothermia is an appropriate treatment for ischemic stroke, and the

Aneurysmal subarachnoid hemorrhage (aSAH) is a fatal cerebro­
vascular disease with a 40–60 % mortality rate. The crude incidence of
SAH is calculated to be 9 per 100,000 person-years, and its incidence in
Korea is 9–23 per 100,000 persons [1,2]. The worldwide incidence of
aSAH is approximately 700,000 person-years, with an overall mortality
rate of approximately 40 % [3]. Poor-grade subarachnoid hemorrhage
(SAH) (World Federation of Neurological Surgeons [WFNS] grades IV
and V) accounts for 20–30 % of all aSAH cases [4], with a mortality rate
of 47.5 % [5]. The reasons for high mortality are refractory vasospasms
and subsequent fatal brain ischemia [6]. There is no appropriate treat­
ment for patients with poor-grade aSAH [7].
Therapeutic hypothermia has demonstrated neuroprotective effects
in post-cardiac arrest patients and neonates with hypoxic brain injury in
experimental studies [8]. Previous studies demonstrated that
effects of hypothermia treatment on the prognosis of ischemic stroke
have been investigated [9]. However, therapeutic hypothermia for
hemorrhagic stroke is not adopted in clinical practice for aSAH because
adverse events occur [7]. In addition, some studies have shown that
hypothermia treatment for patients with poor-grade SAH does not
appear to decrease the occurrence or severity of vasospasm [6,10]. Few
clinical case reports or small case series describing hypothermia to
reduce injury after SAH have been published [11]. In particular, only
few retrospective case reports have shown the effects of mild hypo­
thermia through the critical time of poor-grade SAH (WFNS grades IV
and V) [12]. This study thus aimed to investigate the clinical outcomes
of patients treated with therapeutic hypothermia after microsurgical or
endovascular treatment of poor-grade SAH.

* Correspondence to: Department of Neurosurgery, Ajou University Hospital, Ajou University School of Medicine, Suwon 164, South Korea.
E-mail addresses: nssong@aumc.ac.kr (J. Song), earthlim@aumc.ac.kr (Y.C. Lim).
1
Equally responsible for this work.

https://doi.org/10.1016/j.clineuro.2022.107369
Received 11 March 2022; Received in revised form 4 July 2022; Accepted 12 July 2022
Available online 21 July 2022
0303-8467/© 2022 Elsevier B.V. All rights reserved.
S.Y. Won et al.
2. Materials and methods
2.1. Patient selection
A total of 670 patients with aSAH were admitted to our hospital
between March 2015 and November 2018. Selected patients had WFNS
grade V or Hunt and Hess grade V SAH, defined as having poor-grade
aSAH. Selected patients underwent microsurgical clipping or endovas­
cular coil embolization within 24 h. They were evaluated using CT
angiography or intra-arterial cerebral angiography, to identify the
ruptured intracranial aneurysms. Emergency microsurgical clipping or
endovascular treatment with or without surgical decompression was
performed within 24 h of symptom onset in patients with SAH.
Selected patients met the following criteria: (1) age 18–80 years, (2)
spontaneous SAH caused by a ruptured intracranial saccular aneurysm,
(3) complete occlusion of the aneurysm via microsurgical clipping or
endovascular coil embolization within 24 h of symptom development,
(4) poor-grade SAH classified as Hunt and Hess grade V or WFNS grade V
(Glasgow Coma Scale score < 7), and (5) therapeutic hypothermia
reaching the goal temperature within 1 h of treatment.
Excluded patients met the following criteria: (1) sepsis, (2) life-
threatening hemorrhage in progress, (3) multiple or dissecting aneu­
rysms, and (4) disagreement regarding treatment among patients’
family members.
Details collected from the patient included those on demographic
characteristics (age, sex), lifestyle factors (smoking history, body mass
index [BMI]), medical history (hypertension, cardiovascular disease),
post-cardiac arrest status at admission, type of surgical treatment,
postoperative sedation, and radiologic findings.
2.2. Cooling protocol
The patient’s body temperature was lowered via an endovascular-
cooling catheter (Alsius; Zoll Medical, California, USA) inserted in the
inferior vena cava through a femoral venous sheath or a surface-cooling
machine (Arctic Sun; Medivance, Inc., Louisville, CO, USA). The core
body temperature was reduced to 34.5 ◦ C [13], and cooling was
continued for 48 h. Thereafter, rewarming gradually proceeded until the
target temperature of 36 ◦ C was reached (0.5 ◦ C increased every 12 h)
and was subsequently maintained for 5 days thereafter. Therapeutic
hypothermia required sedation with either midazolam or pentobarbital.
The induction time was the time from the initial cooling until the goal
temperature was achieved. Body temperature was documented at an
hourly basis using thermometers placed in the esophagus.
2.3. Imaging analysis
The following radiological outcomes were assessed on admission and
postoperative day 7: parenchymal hemorrhage, delayed cerebral
ischemia, delayed hydrocephalus, and cerebral edema. Delayed cerebral
ischemia was defined as a specific neurologic deterioration or a decrease
of at least 2 points on the Glasgow Coma Scale and an infarction on CT
that was absent initially or immediately after intervention. Global ce­
rebral edema was confirmed when the following findings were observed:
(1) complete or near-complete effacement of the hemispheric sulci and
basal cisterns and (2) bilateral and considerable disruption of the
hemispheric gray–white matter junction at the level of the centrum
semiovale due to blurring, or to diffused peripheral “fingerlike” exten­
sion of the normal demarcation between the gray and white matter [14].
Specific cerebral edema was identified when focal brain tissue hypo­
densities accompanied by a mass effect were observed.
2.4. Adverse events
All patients underwent echocardiographic monitoring for 24 h.
Blood pressure and body temperature were recorded hourly in the
2
Clinical Neurology and Neurosurgery 221 (2022) 107369
intensive care unit. Bradycardia was diagnosed when the heart rate was
< 50/min [15], tachycardia was diagnosed when the heart rate was >
100/min [16], and hypertension was diagnosed when the blood pres­
sure was > 180/105 mmHg [17]. Hypotension was diagnosed when the
blood pressure was < 80 mmHg and the patient required vasopressor
therapy; gastrointestinal bleeding was monitored by observing the fluid
collected via nasogastric tube drainage [18]. Pneumonia was diagnosed
on auscultation and considering pulmonary infiltrates on chest radiog­
raphy (persistent for 48 h) with leukocytosis (normal range 4000–11,
000/mm3) [19]. Serum sodium, potassium, and magnesium levels were
monitored daily. Coagulation abnormalities were detected using pro­
thrombin time, partial thromboplastin time, D-dimer levels, and fibrin
degradation product levels [20]. Hyperglycemia was managed with
continuous insulin treatment, maintaining blood glucose levels between
100 and 200 mg/dL [21,22].
Cardiac arrhythmia encompassed asymptomatic to critical cases, and
critical dysrhythmia was diagnosed as the cause of hemodynamic
instability requiring antiarrhythmic treatment or resulting in the
cessation of therapeutic hypothermia. Congestive heart failure was
confirmed using chest radiography, echocardiography, or blood tests.
Acute myocardial infarction was identified by ST elevation on electro­
cardiography and increased cardiac biomarkers, including creatinine
kinase myocardial bands or troponin I levels. Hyperkalemia (potassium
< 3.5 mmol/L), hyponatremia (sodium < 135 mEq/L), thrombocyto­
penia (platelet < 100,000/µL), hyperglycemia (glucose > 200 mg/dL),
hypoxemia (PaO2 < 50 mmHg), hypercapnia (PaCO2 > 45 mmHg),
acidosis (arterial blood pH < 7.35), and alkalosis (arterial blood pH >
7.45) were also monitored. Acute renal failure was diagnosed at 1.5
times elevation in serum creatinine level from the baseline value within
7 days (persistent for 24 h). Acute liver injury was diagnosed when the
alanine transaminase or aspartate transaminase levels increased to >
100 U/L.
2.5. Outcome assessment
Clinical outcomes, including modified Rankin scale (mRS) scores,
evaluated at discharge and 3 months after admission, were categorized
as either good (mRS score = 0–2) or poor (mRS score = 4–6). Radio­
logical outcomes and mortality were assessed after 1 month.
2.6. Ethics
This study was approved by the Institutional Review Board of Ajou
University School of Medicine (MED-MDB-21-431), and the requirement
for written informed consent was waived owing to the retrospective
study design.
2.7. statistical analysis
Statistical analyses were performed using R software, version 4.1.0.
Categoric variables are expressed as proportions, and continuous vari­
ables are expressed as means and standard deviations. Wilcoxon rank
sum test was used for continuous variables and Chi-square test or
Fisher’s exact test was used for categorical variables, as appropriate.
Multivariate logistic regression analysis was also conducted. A P-value
less than 0.05 was considered statistically significant.
3. Results
3.1. General demographics
Among 670 patients, 72 (10.7 %, 28 men and 44 women) met the
inclusion criteria for poor-grade aSAH. Patient age ranged from 29 to 86
years, with an average of 57.5 years. Of the 72 patients, 25 (34.7 %)
underwent therapeutic hypothermia, 33 (46 %) were treated with
microsurgical clipping, 39 (50 %) with endovascular coiling, and 21
S.Y. Won et al. Clinical Neurology and Neurosurgery 221 (2022) 107369

(29.2 %) with decompressive craniectomy or lobectomy. groups with regard to other complications (Table 2).
Patient characteristics, such as BMI, smoking history, underlying
diseases, post-cardiac arrest status, ratio of Fisher grade 3 to grade 4, 3.3. Clinical and radiologic outcomes
aneurysmal location, and ratio of clipping to coiling between the groups,
showed no significant differences. The average age of patients in the The proportion of patients with parenchymal hemorrhage, delayed
hypothermia group was 50.5 (range 41–63) years, which was signifi­ cerebral ischemia, ventriculoperitoneal (VP) shunt for delayed hydro­
cantly lower than that of patients in the control group (61.3 years, range cephalus, and global cerebral edema upon admission was equivalent in
29–86 years). This discrepancy occurred because of the age limit set for both the groups. However, the hypothermia group demonstrated a sig­
hypothermia treatment at < 65 years. Although the entire study nificant improvement in cerebral edema 7 days post-surgery.
comprised more women (n = 44) than men (n = 28), the control group Clinical outcomes (mRS scores) were evaluated at discharge and
included more men, while the hypothermia group included more after 3 months. The rate of poor outcomes (percentage of patients with
women, with a significant difference (p = 0.030). All patients in the an mRS score > 4 at discharge and 3 months after admission) was not
hypothermia group were sedated with midazolam or barbiturate, remarkably different between the two groups. However, the mortality
whereas only 19.1 % of control group were sedated (p = 0.000) rate 1 month after treatment in the hypothermia group (20.0 %) was
(Table 1). lower than that in the control group (46.8 %) (p = 0.025), indicating the
clinical effectiveness of hypothermia treatment (Table 3).
3.2. Feasibility of therapeutic hypothermia
3.4. Factors associated with mortality in patients with poor-grade SAH
In general, there were more side effects in the control group (n = 47)
than in the therapeutic group (n = 25). Notably, pneumonia/pulmonary Among the 72 patients with poor-grade SAH, 45 survived and 27
edema occurred in 16 % and 23.4 % of the patients in the hypothermia died during the treatment. Age, sex, BMI, smoking history, underlying
and control groups, respectively. The rates of cardiac complications diseases, post-cardiac arrest status, and the ratio of Fisher grade 4 to
(myocardial infarction, heart failure, and arrhythmia) were 0 % and grade 3 were similar between the survivor and non-survivor groups.
12.8 % in the hypothermia and control groups, respectively. This was However, the ratio of anterior to posterior circulation aneurysms in the
observed because only patients with stable vital signs were included in survivor group (38:7) was notably higher than that in the non-survivor
the hypothermic group. No differences were observed between the two group (17:10) (p = 0.038). This result correlates with previous findings
that aneurysms in the posterior circulation remarkably increased the
Table 1 mortality rate because of proximity to the brainstem, and the concur­
Baseline characteristics of patients with poor-grade SAH. rence of intraventricular hemorrhage in the fourth ventricle [23,24].
Variables Total (n = Hypothermia (n Control (n = p- (Table 4).
72) = 25) 47) Value More patients in the survivor group (40 %) than in the non-survivor
Age (y) 57.5 [29–86] 50.5 [41–63] 61.3 [29–86] 0.000 group (11.1 %) underwent decompressive craniectomy or lobectomy (P
Men: women 28:44 14:11 14:33 0.030 = 0.009). In particular, 44.4 % of patients in the survivor group were
BMI (kg/m2) 22.7 23.4 [17.0–29.3] 22.3 0.131 managed with hypothermia, whereas it was 18.5 % of the non-survivor
[16.6–31.1] [16.6–31.1]
group (p = 0.025). Therefore, decompressive craniectomy, lobectomy,
Smoking history 27 (37.5 %) 10 (40 %) 17 (36.2 %) 0.749
Comorbidity and hypothermia treatment contributed to survival rate. According to
≥ 1 Underlying 10 (13.9 %) 1 (4.0 %) 9 (19.1 %) multivariate logistic regression analyses, hypothermia was more effec­
diseases tive in reducing the mortality than lobectomy or clipping of coil or
Hypertension 19 (26.4 %) 5 (20.0 %) 14 (29.8 %) decompressive craniectomy/lobectomy (OR = 4.86, P = 0.023).
Cardiac problem 4 (5.6 %) 1 (4.0 %) 3 (6.4 %)
Delayed cerebral infarction was more common in the non-survivor
Post-cardiac 11 (15.3 %) 6 (24.0 %) 5 (10.6 %) 0.134
arrest status
Fisher grade 3:4 17:55 3:22 14:33 0.091 Table 2
Aneurysm 0.222 Medical complications in patients treated with or without hypothermia.
location
Anterior 55 (76.4 %) 17 (68.0 %) 38 (80.9 %) Variables Total Hypothermia Control p-
circulation (n = 72) (n = 25) (n = 47) Value
ACA and A-com 23 ≥ 1 Underlying diseases 42 14 (56.0 %) 28 (59.6 0.770
artery (58.3 %)
MCA 18 %)
ICA Pneumonia/pulmonary 15 4 (16.0 %) 11 (23.4 0.461
P-com artery 12 edema (20.8 %)
ICA bifurcation 1 %)
Paraclinoid 1 Sepsis 3 (4.2 1 (4.0 %) 2 (4.3 %) 1.000
Posterior 17 %)
circulation Cardiac problem (MI/HF/ 6 (8.3 0 6 (12.8 %) 0.086
Basilar artery 3 arrhythmia) %)
SCA 2 Electrolyte imbalance 12 5 (20.0 %) 7 (14.9 %) 0.580
PICA 3 (hypernatremia/ (16.7
VA 9 hypokalemia) %)
Treatment Thrombocytopenia 16 5 (20.0 %) 11 (23.4 0.741
Clipping:coiling 33:29 12:13 12:26 0.788 (22.2 %)
Craniectomy/ 21 (29.2 %) 10 (40.0 %) 11 (23.4 %) 0.140 %)
lobectomy Acute kidney injury 12 3 (12.0 %) 9 (19.1 %) 0.438
Postop sedation 34 (47.3 %) 25 (100.0 %) 9 (19.1 %) 0.000 (16.7
Midazolam: 22:12 18:7 4:5 %)
pentobarbital Acute liver injury 3 (4.2 2 (8.0 %) 1 (2.1 %) 0.275
BMI, body mass index; ACA, anterior cerebral artery; A-com, anterior commu­ %)
GI bleeding 1 (1.4 0 1 (2.1 %) 1.000
nicating; MCA, middle cerebral artery; ICA, internal carotid artery; P-com ar­
%)
tery, posterior communicating artery; SCA, superior cerebellar artery; PICA,
posterior inferior cerebellar artery; VA, vertebral artery. MI, Myocardial infarction; HF, Heart failure.

3
S.Y. Won et al. Clinical Neurology and Neurosurgery 221 (2022) 107369

Table 3 leading to increased rebleeding, electrolyte imbalances (hypokalemia

Radiologic and clinical outcomes of patients treated with or without and hypophosphatemia), and insulin resistance [27]. These complica­
hypothermia. tions occur when the body temperature drops to < 33 ◦ C, or when the
Variables Total (n Hypothermia (n Control (n p- treatment duration is too long. Therefore, mild hypothermia treatment
= 72) = 25) = 47) Value (34.5 ◦ C for 48 h) may sufficiently avoid these complications.
Radiologic outcomes This study demonstrated that hypothermia treatment was successful
Parenchymal 8 (11.1 3 (12.0 %) 5 (10.6 %) 0.861 in preventing the occurrence of cerebral edema and mortality in patients
hemorrhage %) with poor-grade SAH. Hypothermia could be a feasible treatment
Delayed cerebral 19 (26.4 8 (32.0 %) 11 (23.4 0.431
because it was not associated with increased medical complications in
ischemia %) %)
VP shunt for delayed 25 (34.7 11 (44.0 %) 14 (29.8 0.228 our study.
hydrocephalus %) %) Hypothermia shows neuroprotective effects by decreasing cerebral
Global cerebral edema 50 (69.4 19 (76.0 %) 31 (66.0 0.733 metabolism, interrupting the apoptotic pathway, reducing the expres­
on admission %) %) sion of some anti-inflammatory cytokines, diminishing vascular
Cerebral edema 20 (27.8 11 (44.0 %) 9 (19.1 %) 0.025
improvement on POD %)
permeability, causing less edema, and suppressing free radical forma­
7 tion [28]. Nakamura et al. measured jugular venous oxygen saturation
Clinical outcomes in patients with poor-grade SAH managed with hypothermia and
mRS score ≥ 4 at 66 (91.7 23 (92.0 %) 43 (91.5 1.000 demonstrated that the treatment helps in oxygenation because it pre­
discharge %) %)
vented the disconnection of cerebral circulation and metabolism [29].
mRS score ≥ 4 at 65 (90.3 22 (88.0 %) 43 (91.5 0.6888
admission %) %) Other studies showed that therapeutic hypothermia lowers intra­
Mortality at 1 month 27 (37.5 5 (20.0 %) 22 (46.8 0.025 cranial pressure (ICP) in traumatic brain injuries. An examination of six
%) %) studies reporting ICP records collected before and after the induction of
VP, Ventriculoperitoneal; POD, postoperative day; mRS, modified Rankin Scale. hypothermia (32–34 ◦ C) in 367 patients with severe traumatic brain
injury showed that ICP reduced by an average of 10 mmHg during
treatment [13]. A prospective study of 75 patients with acute ischemic
group (40.7 %) than in the survivor group (17.8 %) (p = 0.032). The
stroke found that mild hypothermia treatment (34.5 ◦ C hypothermia for
proportion of patients who underwent VP shunt surgery for delayed
48 h, rewarming for 48 h) was effective in reducing the occurrence of
hydrocephalus was higher in the survivor group (51.1 %) than in the
cerebral edema and hemorrhagic transformation [30].
non-survivor group (7.4 %) (p = 0.000).
Only a few studies have been conducted on hypothermia treatment
for patients with poor-grade SAH. In a clinical study conducted in the
4. Discussion
United States in 1999, hypothermia treatment (33.5 ◦ C) was applied to
patients with WFNS grade I–III SAH only during the time of clipping
Only few heterogeneous studies have investigated the impact of
surgery, and the percentage of discharge-to-home patients observed in
hypothermia on SAH [25]. The clinical efficacy of therapeutic hypo­
the hypothermia group was higher than that in the normothermia group
thermia for SAH was uncertain because of the complications observed in
(75 % vs. 57 %) [31]. In 2000, Kawamura et al. performed mild hypo­
patients undergoing the treatment. Thus, extended systemic hypother­
thermia (33–34 ◦ C, 48 h) treatment for six patients with WFNS grade
mia should be considered as the last choice of treatment, for a particu­
IV–V SAH and observed good functional outcomes in three patients [32].
larly selected group of younger patients with SAH and persistent
According to a 2003 study by Nagao et al., among five patients who were
intracranial hypertension or cerebral vasospasm [26]. Patients treated
unresponsive to medical and intravascular treatments for cerebral
with hypothermia are at risk of cardiovascular complications such as
vasospasm, four had favorable outcomes after mild hypothermia treat­
hypotension, bradycardia, arrhythmia, and myocardial infarction. In
ment (32–34 ◦ C, 5–14 days) [33]. In 2014, Seule et al. showed that
addition, hypothermia increases the possibility of infections such as
therapeutic hypothermia results in reduction of arterial flow velocity in
aspiration pneumonia and urinary tract infection, owing to a reduced
patients with severe aSAH. In their study, hypothermia was induced 5
number of white blood cells and impaired T-cell activity. There is an
days after SAH and was maintained for 144 h in 20 patients with
increased risk of coagulopathy due to platelet dysfunction, potentially

Table 4
Factors associated with mortality in patients with poor-grade SAH.
Variables Total (n = 72) Survivors (n = 45) Non-survivors (n = 27) Univariate Multivariate

OR (95 % CI) p-Value OR (95 % CI) p-Value

Age (y) 57.5 [29–86] 57.1 [36–86] 58.2 [29–86] 0.99 0.742
Men: women 28:44 20:25 8:19 0.53 0.215
BMI (kg/m2) 22.7 [16.6–31.1] 22.9 [17.0–29.3] 22.3 [16.6–31.1] 1.06 0.460
Smoking history 27 (37.5 %) 18 (40.0 %) 9 (33.3 %) 1.33 0.572
Post-cardiac arrest status 11 (15.3 %) 6 (13.3 %) 5 (18.5 %) 0.68 0.555
Fisher grade 3:4 17:55 11:34 6:21 0.88 0.830
Aneurysm location (anterior: posterior) 55:17 38:7 17:10 3.19 0.043 3.22 0.096
Treatment
Clipping:coiling 33:39 25:20 8:19 2.97 0.035 1.66 0.411
Decompressive craniectomy/lobectomy 21 (29.2 %) 18 (40.0 %) 3 (11.1 %) 5.33 0.014 2.99 0.150
Hypothermia 25 (34.7 %) 22 (44.4 %) 5 (18.5 %) 3.52 0.025 4.86 0.023
Postop sedation 34 (47.3 %) 23 (51.1 %) 11 (40.7 %) 1.52 0.395
Radiologic outcomes
Parenchymal hemorrhage 8 (11.1 %) 5 (11.1 %) 3 (11.1 %) 1.000
Delayed cerebral ischemia 19 (26.4 %) 8 (17.8 %) 11 (40.7 %) 0.032
VP shunt for delayed hydrocephalus 25 (34.7 %) 23 (51.1 %) 2 (7.4 %) 0.000
Global cerebral edema on admission 50 (69.4 %) 31 (68.9 %) 19 (70.4 %) 0.464
Cerebral edema improvement on POD 7 20 (27.8 %) 20 (44.4 %) 0 0.000

BMI, body mass index; VP, ventriculoperitoneal; POD, postoperative day.

4
S.Y. Won et al.
refractory intracranial hypertension or delayed cerebral ischemia. After
hypothermia induction, the mean flow velocity of the middle cerebral
artery significantly decreased by 19.8 cm/s and the mean ICP decreased
by 5.6 mmHg [34]. According to a 2015 paper published in Germany,
mild hypothermia (35 ◦ C) performed for 12 patients with poor-grade
SAH for 7 days resulted in delayed cerebral infarction and in a reduc­
tion in macrovascular spasm and improved functional outcomes [25].
Moreover, in a prospective cohort study conducted in 2017, hypother­
mia treatment (34.5 ◦ C, 48 h) conducted for 22 patients with poor-grade
SAH improved vasospasm, reduced the occurrence of delayed cerebral
ischemia and mortality, and improved functional outcomes [17]. Our
study is more meaningful because of the larger sample size (72 patients).
Moreover, previous studies applied hypothermia treatment for 7 days on
average and up to a maximum of 16 days depending on the period of ICP
elevation and continuation of vasospasm, resulting in the incidence of
adverse effects [11]. Therefore, we maintained hypothermia treatment
for 48 h, resulting in fewer medical complications. Previous reports
mentioned only clipping or coiling surgery for the treatment of ruptured
aneurysms. We also investigated whether decompressive craniectomy or
lobectomy was performed.
4.1. Limitations
First, the mortality rate in the hypothermia group was lower than
that in the control group, probably because the hypothermia treatment
was limited to patients aged < 65 years. Second, although we followed
the commonly accepted neurocritical care management guidelines, a
missed bias could have existed between the hypothermia and control
groups. Finally, the use of different cooling devices was not considered
in the hypothermia group.
5. Conclusion
Mild hypothermia treatment can be safely performed for patients
with poor-grade SAH. The risk of side effects during treatment was
compatible with the standard care for poor-grade SAH; therefore, hy­
pothermia treatment is a useful treatment. We also showed that it re­
duces the risk of vasospasm and DCI.
CRediT authorship contribution statement
Yong Cheol Lim: Conceptualization, Methodology, Investigation,
Resources, Supervision. Mi Kyung Kim: Software, Validation, Formal
analysis, Investigation, Resources, Visualization, Data curation. Jihye
Song: Writing – review & editing, Visualization, Supervision, Project
administration, Funding acquisition. So Young Won: Writing – original
draft, Visualization.
Declaration of interest
None.
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