| Summary: | 博士 === 國立臺灣大學 === 臨床醫學研究所 === 106 === According to previous animal and human studies, optimization of cerebral oxygen delivery and energy use may be a promising treatment for post-cardiac arrest syndrome. The candidate physiologic parameters used to achieve this goal include mean arterial pressure (MAP), partial pressure of oxygen/ carbon dioxide, hemoglobin level, and blood glucose (BG) level. We examined these candidate physiologic parameters through three different approaches.
First, in the systematic review and meta-analysis, we searched PubMed and Embase from the inception through October 2013. We defined hyperoxia as a PaO2 higher than 300 mm Hg. In the literature search, 14 studies were identified from 2,982 references. Meta-analysis indicated that hyperoxia appeared to be correlated with increased in-hospital mortality (OR, 1.40; 95% CI, 1.02–1.93; I2, 69.27%; 8 studies) but not worsened neurological outcome (OR, 1.62; 95% CI, 0.87–3.02; I2, 55.61%; 2 studies).
Second, we performed the retrospective cohort study at National Taiwan University Hospital (NTUH). We screened patients who suffered IHCA at NTUH between 2006 and 2014. We included patients who met the following criteria: (1) age 18 years or older, (2) documented absence of pulse with performance of chest compression for at least 2 min, (3) no documentation of a do-not-resuscitate order, and (4) achievement of sustained return of spontaneous circulation (ROSC) (i.e., ROSC ≥ 20 min without resumption of chest compression). The primary outcome was favourable neurological outcome at hospital discharge. Multivariable logistic regression analyses were sued to examine the associations between independent variables and outcomes. We used generalized additive models (GAMs) to identify the optimal ranges for the five main physiologic parameters.
The results were as follows: (1) MAP above 85 mm Hg was found to correlate with a favorable neurological outcome (odds ratio [OR] 4.12, 95% confidence interval [CI] 1.47-14.39). For patients without arterial hypertension, the optimal MAP was between 85 and 115 mm Hg (OR 8.80, 95% CI 3.13–28.55); for patients with arterial hypertension, the threshold MAP for achieving a favorable neurological outcome was above 88 mmHg (OR 4.04, 95% CI 1.41–13.03. (2) PaO2 between 70 and 240 mmHg (OR 1.96, 95% CI 1.08–3.64) and PaCO2 levels (OR 0.98, 95% CI 0.95–0.99) were positively and inversely associated with favorable neurological outcome, respectively. (3) The product of hemoglobin × peripheral hemoglobin oxygen saturation (SpO2) was correlated with a favorable neurological outcome (odds ratio 1.003, 95% confidence interval 1.002-1.004). According to recommended SpO2 by resuscitation guidelines [94% to 98%], we calculated the corresponding range of minimum required hemoglobin concentration to be 8.6 to 9.0 g/dL for a favorable neurological outcome. (4) For diabetic patients, a mean BG level between 183 and 307 mg/dL was significantly associated with favourable neurological outcome (OR 2.71, 95% CI 1.18-6.20); a mean BG level between 147 and 317 mg/dL was significantly associated with survival to hospital discharge (OR: 2.38, 95% CI: 1.26-4.53). For non-diabetic patients, a mean BG level between 143 and 268 mg/dL was significantly associated with survival to hospital discharge (OR 2.93, 95% CI 1.62-5.40).
Finally, we used Wistar rats to establish the animal model of asphyxia-induced cardiac arrest. We used norepinephrine to manipulate MAP and observe the influence of OxyFlo-measured brain flow on clinical outcomes. The result showed that in the control group, the cerebral blood flow peaked at 10-15 mins following ROSC and then decreased to nadir at 20-30 mins following ROSC. In the experimental groups, when MAP was increased by norepinephrine infusion, the cerebral blood flow also increased accordingly, suggesting the dysfunction of cerebral auto-regulation mechanism. Clinically, the neurological outcomes in the experimental group receiving norepinephrine infusion for 4 hours tended to be better than the control group.
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