This study was a posthoc analysis of the Japanese Association for Acute Medicine (JAAM) OHCA registry1 between June 2014 and December 2015. The JAAM-OHCA registry is a nationwide, multicenter prospective registry that included 56 institutions in 2014 and 73 institutions in 2015. The registry data included both pre- and in-hospital data; prehospital data were obtained from the All Japan Utstein Registry of the Fire and Disaster Management Agency11, and in-hospital data were collected via an Internet-based system by physicians or medical staff at each institution. The details of the study protocol were previously described.1 All methods were performed in accordance with the relevant guidelines and regulations. This registry and the study protocol were approved by the ethics committee of Kyoto Prefectural University of Medicine (approval ID: ERB-C-650-1) and each institution. The ethics committee waived the need for individual written informed consent.
Data Collection
Patient characteristics and pre- and in-hospital data were defined as sex, age, initial cardiac rhythm (ventricular fibrillation/pulseless ventricular tachycardia [VF/pVT], pulseless electrical activity[PEA], asystole, and other including after ROSC), witnessed the arrest, presence of bystander performed cardiopulmonary resuscitation (CPR), CPR duration, CGS at hospital arrival, PaCO2 values at three time (immediately after ROSC, upon admission to the intensive care unit [ICU], and 24-h after ROSC), hyperoxia exposure (≥ PaO2 300 mmHg) 12, treatments performed after hospital arrival(including using mechanical circulatory device [extracorporeal membrane oxygen and/or intra-aortic balloon pumping] and targeted temperature management [TTM]), cause of cardiac arrest (respiratory diseases, cerebrovascular diseases, malignant tumor others or unknown), 1-month mortality and 1-month neurological outcome using the Glasgow-Pittsburgh cerebral performance category scale CPC; 1 = good cerebral performance, 2 = moderate cerebral disability and, independent in activities of daily life, 3 = severe cerebral disability and dependent on others for daily support, 4 = vegetative state, 5 = death/brain death). 13
Statistical analysis
We determined whether patients were exposed to hypocapnia and hypercapnia during the first 24-h after ROSC, using ABG data from two (upon admission to the ICU and 24-h after ROSC) of three timepoints. PaCO2 immediately after ROSC was considered difficult to control clinically due to the direct influence of cardiac arrest and CPR and was treated as a separate independent variable. We defined severe hypocapnia as PaCO2 < 25 mmHg, mild hypocapnia as 25 mmHg ≦ PaCO2 < 35 mmHg, normocapnia as 35 mmHg ≦ PaCO2 ≦ 45 mmHg, mild hypercapnia as 45 mmHg < PaCO2 ≦ 55 mmHg, and severe hypercapnia as PaCO2 > 55 mmHg by thresholds based on previous studies about PaCO2.9,10,14−17 Patients were allocated into six groups as follows: severe hypocapnia exposure (one or more severe hypocapnic episode), mild hypocapnia exposure (one or more mild hypocapnic episode), normocapnia exposure (only normocapnia recorded), mild hypercapnia exposure (one or more mild hypercapnic episode), severe hypercapnia exposure (one or more severe hypercapnic episode), and both hypocapnia and hypercapnia exposure. Patients exposed to both mild and severe CO2 abnormalities, as shown by the ABG analysis conducted at two different time points, were included in the more severe group (e.g., a patient showing mild hypocapnia upon admission to the ICU but severe hypocapnia 24-h after ROSC was included in the severe hypocapnia group).
Patient characteristics, pre- and in-hospital data, and outcomes for the categories were compared using the Mann-Whitney U-test for continuous variables and the chi-squared test or Fisher’s exact test for categorical variables.
We calculated adjusted odds ratios for outcomes using a multivariate logistic regression model to estimate the association between each PaCO2 exposure group and patient outcomes, adjusted for sex, age (18–64 years, 65–74 years, ≥ 75 years), witnessed arrest, bystander performed CPR, initial cardiac rhythm, CPR duration > 10 min, GCS at hospital arrival (3 to 14), hyperoxia exposure, using the mechanical circulatory device, TTM, cause of cardiac arrest(acute coronary syndrome, cardiac cause excluding acute coronary syndrome[presumed cardiac cause], respiratory cause, cerebrovascular cause, malignant tumor, others or unknown), PaCO2 immediately after ROSC (severe hypocapnia, mild hypocapnia, normocapnia, mild hypercapnia, severe hypercapnia), and PaCO2 group (severe hypocapnia exposure, mild hypocapnia exposure, normocapnia exposure, mild hypercapnia exposure, severe hypercapnia exposure, both hypocapnia and hypercapnia). We treated missing data for each variable as an “unknown category.” Potential confounding variables were selected and classified according to the models defined in previous studies18–20 and clinically important variables were added.
In addition, PaCO2 level immediately after ROSC is important in assessing patient prognosis, since it is thought to affect PaCO2 level for the next 24-h (especially PaCO2 upon admission to the ICU). Therefore, we also showed the patients' character by PaCO2 levels immediately after ROSC and examined the relationship between PaCO2 immediately after ROSC and PaCO2 upon admission to the ICU.
All tests were two-tailed and a p-value < 0.05 was considered statistically significant. All statistical analyses were performed using JMP 14.0 (SAS Institute, Cary, NC).