Normoxic ventilation during resuscitation and outcome from asphyxial cardiac arrest in rats

The Department of Emergency Medicine, Wayne State University, Detroit Receiving Hospital, MI 48201, USA.
Resuscitation (Impact Factor: 4.17). 12/1999; 42(3):221-9. DOI: 10.1016/S0300-9572(99)00083-0
Source: PubMed


The formation of reactive oxygen species during reperfusion is one trigger for neuronal injury after global cerebral ischemia. Because formation of reactive oxygen species requires delivery of molecular oxygen to ischemic tissue, restricting inspired oxygen during reperfusion may decrease neurological damage. This study examined whether ventilation with room air rather than pure oxygen during resuscitation would improve neurological recovery after cardiac arrest in rats. Adult, male rats were subjected to 8 min of asphyxia resulting in cardiac arrest. During resuscitation, rats were ventilated either with hyperoxia (FiO2 = 1.0) or normoxia (FiO2 = 0.21, room air). Neurobehavioral deficits were scored daily for 72 h after resuscitation, after which brains were collected for histology. Normoxia decreased arterial oxygen content. Other physiological parameters and mortality did not differ between groups. All surviving rats exhibited behavioral and histological signs of brain damage. Neurological deficit scores did not differ between normoxia and hyperoxia conditions at any time point. The number of ischemic neurons in the hippocampus also did not differ between groups. These data indicate neither benefit nor detriment of reducing inspired oxygen concentration during resuscitation from asphyxial cardiac arrest in rats.

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    • "In this regard, several experimental studies have suggested that hyperoxia can increase oxidative stress [14], induce more severe histopathological changes [10] and worsen neurological injury [15]. On the other hand, two studies have failed to confirm such findings [16,17], and two other often-quoted major studies did not actually assess animals after cardiac arrest [10,12]. Nonetheless, despite the lack of human data, the International Liaison Committee on Resuscitation moved to advocate the avoidance of arterial hyperoxia. "
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    ABSTRACT: Hyperoxia has recently been reported as an independent risk factor for mortality in patients resuscitated from cardiac arrest. We examined the independent relationship between hyperoxia and outcomes in such patients. We divided patients resuscitated from nontraumatic cardiac arrest from 125 intensive care units (ICUs) into three groups according to worst PaO2 level or alveolar-arterial O2 gradient in the first 24 hours after admission. We defined 'hyperoxia' as PaO2 of 300 mmHg or greater, 'hypoxia/poor O2 transfer' as either PaO2 < 60 mmHg or ratio of PaO2 to fraction of inspired oxygen (FiO2 ) < 300, 'normoxia' as any value between hypoxia and hyperoxia and 'isolated hypoxemia' as PaO2 < 60 mmHg regardless of FiO2. Mortality at hospital discharge was the main outcome measure. Of 12,108 total patients, 1,285 (10.6%) had hyperoxia, 8,904 (73.5%) had hypoxia/poor O2 transfer, 1,919 (15.9%) had normoxia and 1,168 (9.7%) had isolated hypoxemia (PaO2 < 60 mmHg). The hyperoxia group had higher mortality (754 (59%) of 1,285 patients; 95% confidence interval (95% CI), 56% to 61%) than the normoxia group (911 (47%) of 1,919 patients; 95% CI, 45% to 50%) with a proportional difference of 11% (95% CI, 8% to 15%), but not higher than the hypoxia group (5,303 (60%) of 8,904 patients; 95% CI, 59% to 61%). In a multivariable model controlling for some potential confounders, including illness severity, hyperoxia had an odds ratio for hospital death of 1.2 (95% CI, 1.1 to 1.6). However, once we applied Cox proportional hazards modelling of survival, sensitivity analyses using deciles of hypoxemia, time period matching and hyperoxia defined as PaO2 > 400 mmHg, hyperoxia had no independent association with mortality. Importantly, after adjustment for FiO2 and the relevant covariates, PaO2 was no longer predictive of hospital mortality (P = 0.21). Among patients admitted to the ICU after cardiac arrest, hyperoxia did not have a robust or consistently reproducible association with mortality. We urge caution in implementing policies of deliberate decreases in FiO2 in these patients.
    Full-text · Article · Mar 2011 · Critical care (London, England)
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    • "In our canine experiments using 10-min CA, neurologic impairment measured at 24 hr was significantly worse in animals ventilated on 100% O 2 during and for 1 hr after resuscitation than that exhibited by dogs resuscitated on 21% O 2 and subsequently ventilated on 21–30% O 2 to maintain normal PaO 2 (Rosenthal et al., 2003). The one negative study is the report mentioned earlier where no difference in neurologic impairment was observed 72 hr after asphyxia-induced CA in rats (Lipinski et al., 1999). The only published long-term outcome study focused on mortality and used the gerbil bilateral carotid occlusion model. "
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    ABSTRACT: The mammalian pyruvate dehydrogenase complex (PDHC) is a mitochondrial matrix enzyme complex (greater than 7 million Daltons) that catalyzes the oxidative decarboxylation of pyruvate to form acetyl CoA, nicotinamide adenine dinucleotide (the reduced form, NADH), and CO(2). This reaction constitutes the bridge between anaerobic and aerobic cerebral energy metabolism. PDHC enzyme activity and immunoreactivity are lost in selectively vulnerable neurons after cerebral ischemia and reperfusion. Evidence from experiments carried out in vitro suggests that reperfusion-dependent loss of activity is caused by oxidative protein modifications. Impaired enzyme activity may explain the reduced cerebral glucose and oxygen consumption that occurs after cerebral ischemia. This hypothesis is supported by the hyperoxidation of mitochondrial electron transport chain components and NAD(H) that occurs during reperfusion, indicating that NADH production, rather than utilization, is rate limiting. Additional support comes from the findings that immediate postischemic administration of acetyl-L-carnitine both reduces brain lactate/pyruvate ratios and improves neurologic outcome after cardiac arrest in animals. As acetyl-L-carnitine is converted to acetyl CoA, the product of the PDHC reaction, it follows that impaired production of NADH is due to reduced activity of either PDHC or one or more steps in glycolysis. Impaired cerebral energy metabolism and PDHC activity are associated also with neurodegenerative disorders including Alzheimer's disease and Wernicke-Korsakoff syndrome, suggesting that this enzyme is an important link in the pathophysiology of both acute brain injury and chronic neurodegeneration.
    Preview · Article · Jan 2005 · Journal of Neuroscience Research
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    ABSTRACT: Oxygen (O2) is the most frequently used pharmaceutical in anesthesiology and intensive care medicine: Every patient receives O2 during surgery or during a stay in the intensive care unit. Hypoxia and hypoxemia of various origins are the most typical indications which are mentioned in the prescribing information of O2: the goal of the administration of O2 is either an increase of arterial O2 partial pressure in order to treat hypoxia, or an increase of arterial O2 content in order to treat hypoxemia. Most of the indications for O2 administration were developed in former times and have seldom been questioned from that time on as the short-term side-effects of O2 are usually considered to be of minor importance. As a consequence only a small number of controlled randomized studies exist, which can demonstrate the efficacy of O2 in terms of evidence-based medicine. However, there is an emerging body of evidence that specific side-effects of O2 result in a deterioration of the microcirculation. The administration of O2 induces arteriolar constriction which will initiate a decline of regional O2 delivery and subsequently a decline of tissue oxygenation. The aim of the manuscript presented is to discuss the significance of O2 as a pharmaceutical in the clinical setting.
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