Improved Neurological Outcome With Mild Hypothermia
in Surviving Patients With Massive Cerebral
Hemispheric Infarction
Yingying Su, MD; Linlin Fan, MD; Yunzhou Zhang, MD; Yan Zhang, MD; Hong Ye, MD;
Daiquan Gao, MD; Weibi Chen, MD; Gang Liu, MD
Background and Purpose—We conducted this randomized controlled trial to investigate the effects of therapeutic
hypothermia on mortality and neurological outcome in patients with massive cerebral hemispheric infarction.
Methods—Patients within 48 hours of symptom onset were randomized to either a hypothermia group or a control group.
Patients in the hypothermia group were given standard medical treatment plus endovascular hypothermia with a target
temperature of 33 or 34°C. Hypothermia was maintained for a minimum of 24 hours. Patients in the control group were
given standard medical treatment only with a target temperature of normothermia. The primary end points were mortality
and the modified Rankin Scale score at 6 months.
Results—There were 16 patients in the hypothermia group and 17 patients in the control group. At 6 months, 8 patients
had died in the hypothermia group versus 7 patients in the control group (P=0.732). The main cause of death was fatal
herniation caused by a pronounced rise in intracranial pressure. Seven patients (43.8%) had a modified Rankin Scale of
1 to 3 in the hypothermia group versus 4 patients (23.5%) in the control group (P=0.282). Additionally, of the survivors,
patients in the hypothermia group achieved better neurological outcomes compared with those in the control group (7/8,
87.5% versus 4/10, 40.0%; P=0.066; odds ratio=10.5; 95% confidence interval, 0.9–121.4).
Conclusions—Mild hypothermia seems to not reduce mortality in patients with massive cerebral hemispheric infarction
but may improve the neurological outcome in survivors. An adequately powered multicenter randomized controlled trial
seems warranted.
Clinical Trial Registration—URL: http://www.chictr.org.cn. Unique identifier: ChiCTR-TCS-12002680. (Stroke. 2016;47:457-463. DOI: 10.1161/STROKEAHA.115.009789.)
Key Words: hypothermia ◼ infarction ◼ ischemia ◼ neuroprotection ◼ stroke
M
assive cerebral hemispheric infarction (MCHI), which
is primarily caused by an occlusion of either the internal carotid or the proximal middle cerebral artery (MCA), is
the most malignant type of supratentorial ischemic stroke.
This event can cause fatal intracranial hypertension because
of the subsequent space-occupying cerebral edema, leading to herniation. Mortality can be as high as 53% to 78%,
even after receiving the strongest medical treatments available.1–5 Consequently, decompressive craniectomy (DC) was
proposed to directly release the intracranial pressure (ICP).
Several randomized controlled trials (RCTs) have demonstrated that DC can reduce the ICP and reduce mortality to
17% to 36%.2–7
Although DC is a lifesaving treatment, not all patients with
MCHI can receive the surgery quickly enough. Additionally,
patients who routinely take antiplatelet or anticoagulant drugs
are at an increased risk of developing massive bleeding during
or after DC, which limits its application. Moreover, the neurological outcomes of patients who accept DC are not always
satisfactory.2–4
Because of the limitations of medical and surgical treatment, therapeutic hypothermia has been proposed as an alternative. Preclinical trials have demonstrated that therapeutic
hypothermia causes both neuroprotection and ICP reduction.8 Additionally, a systematic review and meta-analysis
of RCTs in patients with cardiopulmonary arrest have also
shown that hypothermia treatment reduces mortality (risk
ratios [RR]=1.35; 95% confidence interval [CI], 1.10–1.65)
and improves neurological outcomes (RR=1.55; 95%
CI, 1.22–1.96) compared with normothermia treatment.9
Consequently, therapeutic hypothermia may be an option for
patients with MCHI.
Continuing medical education (CME) credit is available for this article. Go to http://cme.ahajournals.org to take the quiz.
Received April 21, 2015; final revision received November 8, 2015; accepted November 16, 2015.
From the Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China.
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.
115.009789/-/DC1.
Correspondence to Yingying Su, MD, Department of Neurology, Xuan Wu Hospital, Capital Medical University, No. 45, Changchun Street, Xicheng
District, Beijing, China. E-mail [email protected]
© 2015 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.115.009789
457
458 Stroke February 2016
The feasibility and safety of therapeutic hypothermia in
patients with MCHI have been confirmed in prior studies.9–18
However, its effects on mortality and neurological outcome
remain unclear, especially in patients who cannot receive
DC. Therefore, we conducted a RCT to address this issue.
Our aim was to investigate the effects of therapeutic hypothermia on mortality and neurological outcome in patients
with MCHI.
Methods
General Design
The trial was a prospective, single-center RCT approved by
the Ethics Committee of Xuan Wu Hospital, Capital Medical
University, Beijing. Informed consent was obtained from all
patients or their designated surrogates. The trial was registered
in the Chinese Clinical Trial Registry (registration number:
ChiCTR-TCS-12002680).
Patient Population
All patients with acute ischemic stroke from December 2010 to
August 2013 were screened for eligibility. Patients were eligible if
they met all of the following criteria: (1) aged 18 to 80 years, (2) acute
unilateral ischemic stroke <48 hours ago, (3) infarction involving at
least two thirds of the MCA territory on cranial computed tomography or magnetic resonance imaging, (4) a National Institute of Health
Stroke Scale score ≥15 if the nondominant hemisphere was affected
or ≥20 if the dominant hemisphere was affected, (5) a reduced level
of consciousness indicated by a National Institute of Health Stroke
Scale item 1a score ≥1, and (6) unable to undergo DC because of the
premorbid use of antiplatelet or anticoagulant drugs or because the
patient declined the procedure.
Patients were excluded if they met any of the following criteria:
(1) premorbid modified Rankin Scale (mRS) score >2; (2) secondary hemorrhage involving more than one third of the infarction territory with a space-occupying effect; (3) a Glasgow Coma Scale
without a verbal response item score of <6; (4) rapidly improving
symptoms; (5) both pupils fixed and dilated; (6) simultaneous other
brain lesion, including tumors and contralateral or infratentorial
infarctions; (7) platelet count <75 000/mm3; (8) severe coagulopathy or cardiac, liver, or kidney disease; (9) vasospastic disease,
hematological disease with increased risk of thrombosis, or paramyotonia congenita; (10) sepsis; (11) premorbid treatment with a
monoamine oxidase inhibitor or an allergy to pethidine; (12) inferior vena cava fistula or a filter in its place, a mass near the inferior
vena cava, or a height of <1.5 m; (13) pregnancy; or (14) a life
expectancy <6 months.
Randomization
Enrolled patients were randomly assigned to a hypothermia group
or control group according to a previously generated randomization
scheme. The random number was folded and sealed in an envelope
before the initiation of the study. The allocation ratio was 1:1. The
odd numbers were assigned to the hypothermia group, and the even
numbers were assigned to the control group. These envelopes were
opened only by an investigator who was not involved in patient
screening, treatment, data collection, or analysis.
Standard Medical Treatment
All patients included in the study received standard medical treatment. Patients were admitted into the neurointensive care unit immediately after enrollment. The standard medical treatment was initiated
as soon as possible. The temperature of the patients in the control
group was sustained between 36.5 and 37.5°C to maintain normothermia. The standard medical treatment is shown in Table I in the
online-only Data Supplement.
Endovascular Hypothermia Treatment
Patients randomized to the hypothermia group received additional
endovascular hypothermia treatment. An 8.5F 35-cm catheter central line (ICY, Alsius Corporation, Irvine, CA) was inserted into the
femoral vein and advanced to the inferior vena cava. This line included a lumen ending in 3 balloons, which were perfused with a
sterile normal saline solution via a closed-loop tubing system. It was
connected to a mobile temperature-management device (CoolGard,
Alsius Corporation). A Foley temperature catheter was used to maintain the bladder temperature (Monatherm, Mallinckrodt Medical, St.
Louis, MO) and was also connected to the temperature-management
device. This device adjusted the saline temperature according to the
patient’s temperature and the target temperature.
Hypothermia was initiated as soon as possible after admission. A
maximal cooling rate was applied with a target bladder temperature
of 33 or 34°C. The hypothermia was maintained for a minimum of
24 hours and could be prolonged to 72 hours depending on the physician’s decision. The rewarming process was controlled and slow. The
target temperature was raised 0.5°C every 12 hours, and the rewarming rate was 0.1°C/h. In the event of deterioration because of rebound
ICP, the rewarming was intermitted until the patient regained a stable
status. The time course of rewarming varied between 24 and 72 hours.
Shivering was suppressed with cotton-padded gloves, socks, and
a quilt to keep the patient warm. The patients were also given oral
buspirone (60 mg), intravenous (IV) pethidine (1 mg/kg loading dose
followed by an IV infusion of 25–35 mg/h), IV midazolam (0.1 mg/
kg loading dose followed by an IV infusion of 2–3 mg/h), and an
IV muscle relaxant (atracurium, 0.4 mg/kg loading dose followed by
an IV infusion of 0.3 mg/kg/h; vecuronium, 0.03–0.05 mg/kg loading dose followed by an IV infusion of 0.02–0.03 mg/kg/h). The IV
infusion drugs started from the minimum doses and were adjusted
according to the severity of shivering.
ICP was invasively and continuously monitored with a transducer-tipped pressure–temperature monitoring catheter (Camino, Integra
NeuroScience, Plainsboro, NJ); this procedure was only performed in
patients who agreed to receive ICP monitoring.
Data Collection
The patient characteristics included age; gender; underlying diseases
(such as hypertension, coronary heart disease, atrial fibrillation, hyperlipidemia, valvular dysfunction, diabetes mellitus, and stroke);
radiological data (affected hemisphere and infarcted area); stroke severity at enrollment (Glasgow Coma Scale score, National Institute
of Health Stroke Scale score and Acute Physiology and Chronic
Health Evaluation II score); transtentorial herniation; and the administration of thrombolysis, antiplatelet, anticoagulant, or defibrinogen
treatment.
The bladder temperature was collected every minute and then
downloaded from the temperature-management device using the dedicated software Temp Trend CSV (Alsius Corporation) in the hypothermia group. The axillary temperature was collected every 4 hours in the
control group. Physiological data also included respiratory rate, heart
rate, heart rhythm, blood pressure, pulse oxygen saturation, ICP, pupil
status, and shivering (score 0, no shivering; score 1, shivering localized
to the face or masticatory muscles; score 2, shivering localized to the
thorax or extremities; and score 3, shivering involves gross movement
of the trunk and extremities19). These data were collected every 30 minutes in the hypothermia group and every 4 hours in the control group.
The laboratory data included the erythrocyte count, leukocyte
count, platelet count, hemoglobin, international normalized ratio,
thrombin time, prothrombin time, activated partial thromboplastin
time, fibrinogen, total bilirubin, alanine aminotransferase, aspartate
aminotransferase, creatine kinase, creatinine, urea, glucose, total
protein, albumin, sodium, potassium, magnesium, calcium, phosphonium, amylase, lipase, lactate, and arterial blood gas. The tests were
run every 12 hours in the hypothermia group and every other day in
the control group. Chest radiography, electrocardiogram, and deep
venous ultrasound were also performed every 3 days in both groups.
Complications included hemorrhagic transformation, recurrent
infarction, tachycardia (>100 beats/min), bradycardia (<60 beats/
Su et al Hypothermia Improves Outcome in Patients With MCHI 459
min), arrhythmia, heart failure,20 hypotension (mean blood pressure <80 mm Hg), pulmonary embolism, pneumonia,21 gastrointestinal bleeding, gastric retention (gastric residual >200 mL), acute
pancreatitis,22 hiccup, acute liver injury,23 acute kidney injury,24
electrolyte disorder, stress hyperglycemia (>11.1 mmol/L), hypoproteinemia (<60 g/L), hypoalbuminemia (<35 g/L), coagulation
dysfunction, lower extremity deep vein thrombosis, retroperitoneal
or groin hematoma, catheter-related infection, urinary infection,
and sepsis.
Outcome Measurement
The primary outcomes were all-cause mortality and the mRS score25
at 6 months after symptom onset. An investigator who was not involved in the randomization, treatment, or analysis performed the
follow-up by calling the patients or surrogates at 6 months. mRS 0 to
3 was regarded as a good neurological outcome. Secondary outcomes
included bladder temperature, ICP, and complications.
Statistical Analysis
Based on data from a previous open study of hypothermia in stroke
patients, the sample size was calculated to be 168 assuming that the
difference of the mean mRS of the 2 groups was 1 and that the standard deviation was 2 (α=0.05; β=0.10).
SPSS 17.0 (SPSS Inc., Chicago, IL) was used for statistical analysis. Continuous covariates were presented as the mean± standard deviation or the median (range), as appropriate. Categorical covariates
were presented as counts and proportions. Comparisons between 2
groups were performed via a two-tailed t test or the Mann–Whitney
U test for the continuous covariates and via the Pearson χ2 test or
Fisher’s exact test for the categorical covariates, as appropriate. Odds
ratios and 95% CI were calculated. Adjusted odds ratio was also determined via logistic regression to adjust for possible confounders.
All tests were two-tailed, and the level of significance was set to a P
value <0.05.
Results
Patient Characteristics
Thirty-five patients were eligible for the trial, and for 2 of these
patients, the insertion of the ICY catheter into the femoral vein
was unsuccessful because of severe bleeding at the puncture
point or lumen malfunction. Consequently, 33 patients finished the treatment, completed the follow-up, and were eligible for analysis: 16 patients in the hypothermia group and 17
in the control group (Figure 1). The patient characteristics are
listed in Table 1. The patients in the hypothermia group were
younger and more frequently male.
Feasibility of Endovascular Hypothermia
The time between initiation of hypothermia and stroke onset
was 42.0±14.9 hours. Bladder temperature before hypothermia was 37.7±0.8°C. Shivering was observed in 14 patients
(87.5%): 2 patients with a score of 1, 8 with a score of 2, and
4 with a score of 3. Shivering could be suppressed by increasing the dose of antishivering drugs. The bladder temperature
Figure 1. Flow chart of patient profile. mRS indicates modified Rankin scale.
460 Stroke February 2016
Table 1. Patient Characteristics
Age, y (range)
Gender, male/female
Hypothermia Group (n=16)
Control Group (n=17)
P Value
59.8±8.6 (46–75)
68.5±8.5 (53–79)
0.006
15/1
10/7
0.039
11
13
0.708
Underlying disease
Hypertension
Coronary heart disease
3
5
0.688
Atrial fibrillation
5
7
0.721
Hyperlipidemia
5
2
0.225
Valvular dysfunction
1
2
1.000
Diabetes mellitus
3
6
0.438
Stroke
4
4
1.000
11/5
11/6
Affected hemisphere, left/right
Infarcted area, 2/3 MCA/MCA/>MCA
Mean GCS (range)
5/8/3
4/9/4
1.000
0.868
9.8±2.2 (7–14)
9.2±2.2 (7–14)
0.468
Mean NIHSS (range)
19.7±2.9 (15–25)
20.4±3.8 (15–25)
0.541
Mean APACHE II (range)
13.3±4.0 (8–20)
14.5±4.7 (7–22)
0.433
Transtentorial herniation
1
3
0.601
Prior T/A/A/D
7
8
1.000
APACHE II indicates Acute Physiology and Chronic Health Evaluation II; GCS, Glasgow coma scale; MCA, middle cerebral artery; NIHSS,
National Institute of Health Stroke Scale; and T/A/A/D, thrombolysis, antiplatelet, anticoagulant, or defibrinogen treatment.
curve is shown in Figure 2. The axillary temperature of the
patients in the control group was 37.2±0.6°C.
Effects of Endovascular Hypothermia
Neurological Outcome of Survival
At 6 months, more patients in the hypothermia group had
good neurological outcomes. Of the surviving patients,
those in the hypothermia group achieved significantly better
neurological outcomes than those in the control group (7/8,
87.5% versus 4/10, 40.0%; P=0.066; odds ratio=10.5; 95%
CI, 0.9–121.4; adjusted odds ratio=4.794; 95% CI 0.323–
71.103; Figure 3).
Mortality
At 6 months, 8 patients in the hypothermia group and 7
patients in the control group had died. The mortality was
similar between the 2 groups (P=0.732). In the hypothermia
group, 7 patients died of herniation: 1 developed herniation
before cooling, 1 developed it during the cooling period, 3
developed it during the rewarming period, and 2 developed
it after the rewarming. The median rewarming time of these
patients was 37.8 (range, 15.0–88.0) hours compared with
48.0 (range, 14.0–51.0) hours for patients without herniation
in the hypothermia group (P=0.490). In the control group, 6
patients died of herniation, 3 of whom developed herniation
before treatment.
Intracranial Pressure
In the hypothermia group, 10 patients received ICP monitoring
and 5 developed transtentorial herniation. In the 5 patients who
had no herniation, ICP was 22.0±5.6 mm Hg at the initiation of
cooling and decreased to 10.6±3.3 mm Hg when the target temperature was reached. During the maintenance period, the ICP
was stable at 11.4±3.7 mm Hg. It then increased slightly at the
end of rewarming to 15.0±5.8 mm Hg. All 5 patients were alive
at the time of discharge. In the 5 patients who developed herniation, the ICP was 18.7±5.5 mm Hg at the initiation of cooling
and decreased to 12.4±6.0 mm Hg when the target temperature
was reached. During the maintenance period, the ICP increased
reaching 18.8±7.4 mm Hg at the initiation of rewarming.
Additionally, the ICP increased significantly during the rewarming period, reaching 39.4±9.6 mm Hg at the end of rewarming.
All 5 of these patients died from herniation (Figure 4).
Complications
Among the 33 patients in both groups, only 1 patient in the
control group did not experience complications. The incidence
Figure 2. Mean patient temperature in the hypothermia and control groups. The mean bladder temperature curves of the hypothermia group included 4 phases: induction period, maintenance
period, rewarming period, and normothermia period. The axillary
temperatures of the control group were sustained at normothermia (36.5–37.5°C).
Su et al Hypothermia Improves Outcome in Patients With MCHI 461
Figure 3. Modified Rankin scale (mRS) of the
patients at 6 months after stroke onset. There was
a favorable trend toward the hypothermia group
compared with the control group (hypothermia
group, 7/8; control group, 4/10; P=0.066; odds ratio
[OR]=10.5; 95% confidence interval [CI], 0.9–121.4;
adjusted OR=4.794; 95% CI, 0.323–71.103) in the
surviving patients.
of complications is shown in Table 2. The total incidence of
complications was significantly higher in the hypothermia
group than in the control group (P=0.001). The incidences of
bradycardia, electrolyte disorder, gastrointestinal bleeding,
gastric retention, and stress hyperglycemia were significantly
higher in the hypothermia group. However, the complications
in the hypothermia group were not severe, and none of them
caused patient death.
Discussion
Our results show that, among survivors, patients with MCHI
treated with mild hypothermia had a better neurological outcome than those in the control group. Seven patients of the
8 survivors in the hypothermia group had mRS of 1 to 3,
whereas in the control group, only 4 of the 10 survivors had a
mRS of 3. The mortality of the 2 groups was equal.
Hypothermia treatment thus seems to improve neurological outcome in patients with MCHI. Although the mechanism of neuroprotection in response to hypothermia remains
unclear, hypothermia seems to alleviate brain damage through
several mechanisms: prevention of blood–brain barrier disruption; reduction of cerebral glucose metabolism and oxygen
Figure 4. The course of intracranial pressure (ICP) of 10 patients
in the hypothermia group. The ICP values of herniated (n=5)
and nonherniated (n=5) patients decreased during the induction
period of hypothermia. During the maintenance and rewarming
periods, it remained stable in nonherniated patients but increased
slowly during the maintenance period and rebounded during the
rewarming period in herniated patients.
consumption; reduction of the accumulation of excitotoxic
neurotransmitters, intracellular acidosis, intracellular calcium
influx, and oxygen-free radical production; alteration of the
expression of cold shock proteins; reduction of brain edema;
minimization of the risk of thrombosis; and decreasing the
risk of epileptic activities.26–36
Prior studies have shown that the mortality associated with
this condition is high, even after the strongest medical treatments available. Additionally, although DC could improve the
mortality, the neurological outcome of patients with MCHI
remained unsatisfactory.2–4 Therefore, if hypothermia combined with medical treatment could improve neurological outcomes and avoid the need for DC, this treatment would be the
best option, especially in patients who would be high-risk candidates for surgery. Unfortunately, in our study, we found that
the mortality was equal between the hypothermia and control
groups. Eight patients in the hypothermia group and 7 patients
in the control group died. The main cause of death was herniation because of fatal intracranial hypertension. Although the
ICP of patients who developed herniation in the hypothermia
group was 12.4±6.0 mm Hg at target temperature, it increased
gradually during the maintenance period to 18.8±7.4 mm Hg
and severely rebounded during rewarming reaching 39.4±9.6
mm Hg. This result was consistent with those of Saul and
Ducker37 and Marmarou et al.38 The incidences of herniation
in their studies were 28% and 46%, respectively. Additionally,
there was an increased possibility of herniation and death
when the ICP exceeded 20 mm Hg.
The rewarming rate is associated with increased ICP.
Schwab et al15 found that a shorter rewarming period (<16
hours) was associated with a more pronounced rise in ICP.
Therefore, we controlled the rewarming rate and increased it
by 0.5°C every 12 hours. We even decelerated the rewarming
rate to 0.5°C every 24 hours in patients with a high risk of
herniation. Although the rewarming time was slightly shorter
in the herniated patients, the difference was not significant
(median, 37.8 versus 48.0 hours; P=0.490). It is possible that
an even slower rate should be used to rewarm patients to avoid
ICP rebound.
We also hypothesized that the size of territory of infarction could contribute to an increase in ICP. In our study, the
territories of the infarcted area in herniated patients were
much larger than those in nonherniated patients. Among 7
herniated hypothermia patients, there were 3 with affection
of a combination of MCA and anterior cerebral artery and 3
with affection of the entire MCA, whereas in the remaining
9 nonherniated hypothermia patients there were 5 with complete MCA, but none with combined MCA/ anterior cerebral
462 Stroke February 2016
Table 2. Complications
Complications
Hypothermia Control Group
Group (n=16)
(n=17)
P Value
Recurrent infarction
0
2
0.485
Hemorrhagic transformation
1
2
1.000
Bradycardia
7
2
0.057
Tachycardia
9
10
1.000
Arrhythmia
1
3
0.601
Hypotension
6
3
0.259
Pneumonia
7
8
1.000
Lower extremity deep venous
thrombosis
4
2
0.398
0.003
Electrolyte disorder
16
9
Coagulation dysfunction
14
15
1.000
Gastrointestinal bleeding
8
2
0.026
15
7
0.002
6
1
0.039
Gastric retention
Stress hyperglycemia
Hypoalbuminemia
11
7
0.166
Acute liver injury
2
1
0.601
Acute kidney injury
2
0
0.227
109
74
0.001
All cases
There was no heart failure, pulmonary embolism, hiccup, acute pancreatitis,
catheter-related infection, urinary infection, sepsis, retroperitoneal, or groin
hematoma.
artery affection. We recommend ICP monitoring in patients
with MCHI during hypothermia treatment. If there is a significant increase of ICP before rewarming or ICP rebound during
rewarming (ICP>20~25 mm Hg), more aggressive treatment
should be administered, such as hypertonic saline or DC.
The safety of hypothermia was a concern. However, the
safety of mild hypothermia in patients with MCHI had been
confirmed by many studies.9–18 The complications associated
with hypothermia included pneumonia, hyperglycemia, electrolyte disorders, and arrhythmia, among others.39 However,
no significant differences with normothermia treatment were
recorded.10,15,40 In our study, we also observed complications.
In addition to the complications mentioned above, we found
hypotension, gastric retention, coagulation dysfunction, and
others. The complications in the hypothermia group were
more common than in the control group, but they were not
severe. Instead, they were controllable and did not influence
the patient outcome. We were also concerned regarding the
anesthetic medication used for antishivering. Ovesen et al41
found that neurological assessment was difficult in fully anesthetized patients undergoing hypothermia, and that clinical
deterioration might not be detected in time, even with ICP
monitoring. In our study, we enhanced surface warming to
lower the necessary doses of anesthetic. Additionally, our
results showed that hypothermia treatment did not increase
the mortality compared with the control group. Further investigations should be performed to clarify the safety of use of
anesthetics.
There were some shortcomings of our study. Because
DC is the preferred option for patients with MCHI, our study
only included patients who had contraindications of DC to
conform to ethical standards. Therefore, there might be selection bias, and our results may only be relevant for patients
with DC contraindications. Our study was an open RCT,
and it was impossible to blind the physicians to the treatment assignment. As a result, it is possible that the physicians paid more attention to the patients in the hypothermia
group. Additionally, because of the patients’ relatively late
arrival to our emergency department or the surrogate’s hesitation regarding the hypothermia treatment, the average time
between the initiation of hypothermia and stroke onset was
42.0 hours. This delay may underestimate the effectiveness of
hypothermia. Moreover, the incidence of MCHI is low, making it difficult for a single center to collect large samples.
The projected sample size was not achieved because of slow
recruitment. In the future, a multicenter, large-sample RCT is
needed to confirm the results.
Conclusions
Hypothermia treatment represents a new option for patients
with MCHI. Although we did not observe hypothermia to
lower the mortality, it is a promising treatment that could
improve the neurological outcomes in surviving MCHI
patients.
Acknowledgments
We thank all of the patients and families who participated in this trial.
Sources of Funding
The study was supported by a grant from the National Key Department
of Neurology funded by the National Health and Family Planning
Commission of the People’s Republic of China and the National Key
Department of Critical Care Medicine funded by the National Health
and Family Planning Commission of the People’s Republic of China.
Disclosures
None.
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