A Pilot Study of Normobaric Oxygen Therapy in Acute Ischemic Stroke

Harvard University, Cambridge, Massachusetts, United States
Stroke (Impact Factor: 5.72). 04/2005; 36(4):797-802. DOI: 10.1161/01.STR.0000158914.66827.2e
Source: PubMed


Therapies that transiently prevent ischemic neuronal death can potentially extend therapeutic time windows for stroke thrombolysis. We conducted a pilot study to investigate the effects of high-flow oxygen in acute ischemic stroke.
We randomized patients with acute stroke (<12 hours) and perfusion-diffusion "mismatch" on magnetic resonance imaging (MRI) to high-flow oxygen therapy via facemask for 8 hours (n=9) or room air (controls, n=7). Stroke scale scores and MRI scans were obtained at baseline, 4 hours, 24 hours, 1 week, and 3 months. Clinical deficits and MR abnormalities were compared between groups.
Stroke scale scores were similar at baseline, tended to improve at 4 hours (during therapy) and 1 week, and significantly improved at 24 hours in hyperoxia-treated patients. There was no significant difference at 3 months. Mean (+/-SD) relative diffusion MRI lesion volumes were significantly reduced in hyperoxia-treated patients at 4 hours (87.8+/-22% versus 149.1+/-41%; P=0.004) but not subsequent time points. The percentage of MRI voxels improving from baseline "ischemic" to 4-hour "non-ischemic" values tended to be higher in hyperoxia-treated patients. Cerebral blood volume and blood flow within ischemic regions improved with hyperoxia. These "during-therapy" benefits occurred without arterial recanalization. By 24 hours, MRI showed reperfusion and asymptomatic petechial hemorrhages in 50% of hyperoxia-treated patients versus 17% of controls (P=0.6).
High-flow oxygen therapy is associated with a transient improvement of clinical deficits and MRI abnormalities in select patients with acute ischemic stroke. Further studies are warranted to investigate the safety and efficacy of hyperoxia as a stroke therapy.

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    • "Subgroup analyses within their study suggested that patients with severe strokes were more likely to benefit than those with mild strokes; however the study size was too small to define with certainty patients who are likely to derive benefit. A recent very small study [23] of high-flow oxygen treatment after acute stroke showed that cerebral blood volume and blood flow within ischemic regions improved with hyperoxia. Within 24 hours magnetic resonance imaging of the brain showed reperfusion in 50% of hyperoxia-treated patients versus 17% of controls (p = 0.06) but no long-term clinical benefit at three months [23]. "
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    ABSTRACT: Mild hypoxia is common in stroke patients and may have significant adverse effects on the ischemic brain after stroke. The use of oxygen treatment is rapidly increasing in European stroke units but is not without side effects. It impedes early mobilization, could pose an infection risk, and may encourage the formation of toxic free radicals, leading to further damage to the ischemic brain. In the Stroke Oxygen Pilot Study (2 or 3 L/min for 72 hours) neurological recovery at one week was better in the oxygen group than in controls, and after correction for difference in baseline stroke severity and prognostic factors, there was a trend to better outcome with oxygen at six months. Oxygen was as effective in mild as in severe strokes.Oxygen saturation is lower at night than during the day, and episodes of oxygen desaturation are common during sleep. Nocturnal oxygen supplementation is likely to reduce the burden of hypoxia without interfering with daytime mobilization and rehabilitation.Before wider use of oxygen supplementation becomes established it is important to obtain better evidence on which patients benefit from such treatment. Participants will be randomized to one of three groups: the first will receive continuous oxygen for 72 hours (at a rate of 2 or 3 L/min depending on baseline oxygen saturation), the second group will receive nocturnal oxygen only (at a rate of 2 or 3 L/min depending on baseline oxygen saturation) and the third group will not receive any oxygen (control). A baseline assessment is performed at randomization and a one-week follow-up completed. Outcome data at three, six and twelve months will be obtained via a questionnaire sent to the patient by the trial center. This study will provide evidence on the effectiveness of oxygen supplementation for the treatment of stroke and whether nocturnal oxygen is a potentially beneficial therapy regimen.Trial registration: This trial is registered with the ISRCTN register ID number ISRCTN52416964.
    Full-text · Article · Mar 2014 · Trials
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    • "When normobaric hyperoxia is applied it is aimed at keeping PbtO2 greater than 20 to 25 mmHg (2.7 to 3.3 kPa), which is 50% of the normal brain tissue oxygen levels [34]. Also, the increased oxygen availability with high FiO2 levels may lead to induction of cerebral aerobic metabolism, alleviating ischemic injury [35,36]. "
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    ABSTRACT: The relationship between hyperoxemia and outcome in patients with traumatic brain injury (TBI) is controversial. We sought to investigate the independent relationship between hyperoxemia and long-term mortality in patients with moderate-to-severe traumatic brain injury. The Finnish Intensive Care Consortium database was screened for mechanically ventilated patients with a moderate-to-severe TBI. Patients were categorized, according to the highest measured alveolar-arterial O2 gradient or the lowest measured PaO2 value during the first 24 hours of ICU admission, to hypoxemia (< 10.0 kPa), normoxemia (10.0-13.3 kPa) and hyperoxemia (> 13.3 kPa). We adjusted for markers of illness severity to evaluate the independent relationship between hyperoxemia and 6-month mortality. A total of 1116 patients were included in the study, of which 16% (N= 174) were hypoxemic, 51% (N= 567) normoxemic and 33% (N= 375) hyperoxemic. The total 6-month mortality was 39% (N= 435). A significant association between hyperoxemia and a decreased risk of mortality was found in univariate analysis (P= 0.012). However, after adjusting for markers of illness severity in a multivariate logistic regression model hyperoxemia showed no independent relationship with 6-month mortality (hyperoxemia vs. normoxemia OR 0.88, 95% CI 0. 63--1.22, P= 0.43; hyperoxemia vs. hypoxemia OR 0.97, 95% CI 0.63-1.50, P= 0.90). Hyperoxemia in the first 24 hours of ICU admission after a moderate-to-severe TBI is not predictive of 6-month mortality.
    Full-text · Article · Aug 2013 · Critical care (London, England)
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    • "Different results have also been reported in human stroke studies regarding to NBO’s neuroprotection. Singhal et al. reported that NBO therapy via facemask for 8 hours improves stroke scale scores at 24 hours in NBO-treated patients, but not at 3 months [20]. In addition, mean relative diffusion MRI lesion volumes were also significantly reduced in NBO-treated patients at 4 hours but not subsequent time points. "
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    ABSTRACT: Stroke is a leading cause of death and disability due to disturbance of blood supply to the brain. As brain is highly sensitive to hypoxia, insufficient oxygen supply is a critical event contributing to ischemic brain injury. Normobaric hyperoxia (NBO) that aims to enhance oxygen delivery to hypoxic tissues has long been considered as a logical neuroprotective therapy for ischemic stroke. To date, many possible mechanisms have been reported to elucidate NBO's neuroprotection, such as improving tissue oxygenation, increasing cerebral blood flow, reducing oxidative stress and protecting the blood brain barrier. As ischemic stroke triggers a battery of damaging events, combining NBO with other agents or treatments that target multiple mechanisms of injury may achieve better outcome than individual treatment alone. More importantly, time loss is brain loss in acute cerebral ischemia. NBO can be a rapid therapy to attenuate or slow down the evolution of ischemic tissues towards necrosis and therefore "buy time" for reperfusion therapies. This article summarizes the current literatures on NBO as a simple, widely accessible, and potentially cost-effective therapeutic strategy for treatment of acute ischemic stroke.
    Full-text · Article · Jan 2013
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