Association between base excess level at hospital arrival and neurological outcomes of adult out-of-hospital cardiac arrest: A multicentre cohort study

Association between base excess level at hospital arrival and neurological outcomes of adult out-of-hospital cardiac arrest: A multicentre cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Association between base excess level at hospital arrival and neurological outcomes of adult out-of-hospital cardiac arrest: A multicentre cohort study Ryuta Onodera, Norihiro Nishioka, Tomoki Yamada, Shunichiro Nakao, and 25 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6257805/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Cardiac arrest leads to an abrupt cessation of blood flow, resulting in severe metabolic acidosis. Base excess (BE) is a widely used marker of metabolic acidosis. However, its prognostic value in cardiac arrest patients remains unclear, as previous studies have not adjusted for the time from arrest to blood testing. This study aimed to assess the association between BE levels and neurological outcomes in patients with out-of-hospital cardiac arrest (OHCA) by adjusting the time from the onset of cardiac arrest to blood tests. Methods This study in Osaka, Japan, enrolled consecutive patients with OHCA transported to 16 centres between 2012 and 2021. We included adult patients (age ≥ 18 years) with witnessed OHCA and available BE levels upon hospital arrival. The patients were grouped based on BE quartiles: Q1 (BE ≤ − 21.1 mmol/L), Q2 (− 21.1 < BE ≤ − 15.7 mmol/L), Q3 (− 15.7 − 10.4 mmol/L). The primary outcome was 1-month survival with favourable neurological outcomes, defined as a Cerebral Performance Category scale score of 1 or 2. Results Of the 23,854 patients with OHCA, 7,591 met the inclusion criteria, and 6,066 were eligible for analysis. The 1-month favourable neurological outcomes based on BE quartile were 23.5%, 9.8%, 4.7%, and 3.2% Q4, Q3, Q2, and Q1, respectively (p for trend < 0.001). The adjusted odds ratio for Q1 compared with Q4 was 0.13 (95%CI: 0.090–0.19). Subgroup analysis showed an interaction between prehospital return of spontaneous circulation (ROSC) and outcome (p for interaction < 0.001); neurological outcomes worsened as BE decreased in those with ROSC (p for trend < 0.001), but not in those without ROSC (p for trend = 0.12). Conclusions Lower BE levels upon hospital arrival are associated with worse neurological outcomes and may serve as prognostic indicators, especially in patients with OHCA and prehospital ROSC. Base excess BE blood gas Out-of-hospital cardiac arrest Figures Figure 1 Figure 2 Background Out-of-hospital cardiac arrest (OHCA) is a global public health concern, and survival after OHCA remains low and poor[ 1 ]. However, its treatment is intricate and involves multiple disciplines, demanding substantial time and considerable allocation of medical and human resources. Furthermore, many patients who successfully attain a return of spontaneous circulation (ROSC) after OHCA frequently experience subsequent mortality or transition to a state of unresponsive wakefulness syndrome, even after post-resuscitation care.[ 2 , 3 ] Consequently, the early prediction of outcomes in patients with OHCA can facilitate the implementation of intensive care measures, such as extracorporeal membrane oxygenation (ECMO), targeted temperature management (TTM), and appropriate decisions for resuscitation termination. Cardiac arrest leads to an interruption in blood flow to the tissues. Cessation results in extreme hypercarbic and metabolic acidosis at the tissue level.[ 4 ] Metabolic acidosis causes harmful effects, such as reduced myocardial function,[ 5 ]dilation of blood vessels[ 6 ], and weakening of the body’s inflammatory and immune responses[ 7 ], which can result in multiple organ failure. Metabolic acidosis is often observed in patients who have experienced cardiac arrest and is usually thought to be primarily caused by increased lactate levels.[ 8 , 9 ] However, the causes of metabolic acidosis during cardiac arrest are complex, with lactate levels accounting for only approximately 50% of the pathogenesis[ 10 ] The standard base excess (BE) can help in understanding the underlying causes of this condition.[ 10 ] BE, introduced in 1960 as a metric of metabolic acidosis, is widely used.[ 11 – 14 ] It can be measured easily and quickly using blood gas analysis. BE refers to the quantity of base, measured in millimoles, required to bring the pH of 1 L of fully oxygen-saturated arterial blood to 7.40 at a temperature of 37°C and a partial pressure of carbon dioxide level of 40 Torr. The normal range for BE is between + 2 and − 2 mmol/L[ 15 ]. Standard BE (SBE) is a widely researched prognostic indicator used to assess patients with trauma in acute care settings.[ 16 ] In patients with cardiac arrest, a lower BE is associated with worse outcomes.[ 17 – 19 ] However, these findings are based on small samples without adjustments for the time from cardiac arrest to blood tests, which can significantly influence the association between BE levels and outcomes. This study aimed to assess the association between BE levels at hospital arrival and neurological outcomes in patients with OHCA using large-scale multicentre registry data in Osaka, Japan, where termination of resuscitation was not allowed for emergency medical service personnel, by adjusting the time from the onset of cardiac arrest to blood tests. Methods The study protocol was approved by the Ethics Committee of Kyoto University and each participating institution (R1045). The need for written informed consent was waived. Study design and setting The current study performed a retrospective analysis using data obtained from the Comprehensive Registry of Intensive Cares for OHCA Survival (CRITICAL) study. The CRITICAL study is a prospective multicentre registry that aims to collect and analyse data on treatments provided in pre- and in-hospital settings for OHCA. Prehospitalisation data were obtained from the All-Japan Utstein Registry of the Fire and Disaster Management Agency (FDMA).[ 20 – 23 ] In-hospital data were collected from 15 tertiary critical care medical centres and one community hospital with an emergency department, all situated in Osaka Prefecture, Japan. Osaka Prefecture is an urban area encompassing 1,905 km 2 , with a residential population of approximately 8.8 million in 2020. Approximately 7,500 OHCA cases occur annually in Osaka Prefecture (FDMA of the Ministry of Internal Affairs and Communications website. Available from: https://www.fdma.go.jp/publication/rescue/post7.html ), and approximately one in four patients with OHCA (approximately ≥ 2,000 cases) have been registered annually, from 2012 to 2021. The registry for this study is currently ongoing, without a specified study period. In-hospital data were documented by attending physicians and recorded by physicians or medical administrators using a predetermined online form. To ensure data quality, the working group reviewed and verified the collected data.[ 23 ]Incomplete data were returned to the respective institutions for completion. A comprehensive description of the All-Japan Utstein Registry of the FDMA and the CRITICAL study has been previously published[ 23 ] The emergency medical services system in Osaka The emergency medical services (EMS) system in Japan has been previously described in detail[ 24 , 25 ]. Overall, 119 emergency numbers can be called from anywhere within Japan; following such a call, an emergency dispatch centre immediately dispatches the closest ambulance to the location. Emergency services are available 24 h a day. Each ambulance is staffed by a three-member team trained in life support. The most skilled EMS workers are known as emergency lifesaving technicians. They are authorised to establish an intravenous line with lactated Ringer’s solution, administer adrenaline, secure an adjunctive airway, and use a semiautomated external defibrillator for patients with OHCA. Specially trained emergency lifesaving technicians are allowed to perform tracheal intubation in patients with OHCA. They are not allowed to administer sodium bicarbonate for acidosis correction. In Japan, EMS personnel typically cannot comply with do-not-resuscitate requests, meaning they continue resuscitation attempts at the scene. Consequently, EMS teams transport almost all patients with OHCA to a medical facility, except in cases where the patient displays clear indicators of death, such as decapitation, incineration, decomposition, rigor mortis, or dependent cyanosis. All EMS providers performed cardiopulmonary resuscitation (CPR) according to the Japanese CPR guidelines.[ 26 ] Study population In this study, we enrolled adult patients aged 18 years with witnessed OHCA. Included patients were those who had their BE values measured upon arrival at the hospital within the study period from 1 January 2012 to 31 December 2021. We excluded patients with OHCA due to external causes (e.g., trauma, hanging, drowning, drug overdose, or asphyxia) whose measurement time was unknown and whose ECMO was initiated before the BE measurement. Exposures The main exposure was the BE values determined by blood gas analysis from the initial blood test performed upon arrival at the hospital. We divided the patients into quartiles based on BE values of the initial blood test on arrival at the hospital: Q1 (BE ≤ − 21.1 mmol/L), Q2 (− 21.1 < BE ≤ − 15.7 mmol/L), Q3 (− 15.7 − 10.4 mmol/L). In the current study, there was no set protocol to determine whether to use the SBE or BE blood. Decisions regarding these measurements were left to the individual judgment of each physician or the policies of their respective institutions. Outcomes The primary outcome of this study was 30-day survival with good neurological outcomes, defined as a Cerebral Performance Category (CPC) score of 1 or 2. Neurological status was evaluated by the physician responsible for treating the patient using the CPC scale (category 1, good cerebral performance; category 2, moderate cerebral disability; category 3, severe cerebral disability; category 4, coma or vegetative state; category 5, death/brain death).[ 27 ] The secondary outcome of this study was the 1-month survival. Statistical analyses Data are presented as medians with interquartile ranges for continuous variables and as proportions for categorical variables. We estimated adjusted odds ratios (AORs) with their 95% confidence intervals (CIs) by multivariable logistic regression to evaluate the associations between BE categories based on quartiles and each outcome. Trend analysis across the quartiles of BE values was performed using the Cochran–Armitage trend test. As a primary analysis model, we adjusted for age, sex (male or female), origin of cardiac arrest (cardiac or noncardiac), presence of witness (yes or no), presence of bystander CPR, presence of an automated external defibrillator (AED) shock delivery by a bystander, first documented rhythm (shockable, non-shockable, or unknown) at the scene and in hospital, adrenaline administration and advanced airway management and defibrillation by EMS, no flow time for CPR, time from EMS call to hospital arrival, and time from hospital arrival to blood test, which was selected as the most clinically relevant variables for this study. Interpreting BE values can be challenging in patients with preexisting kidney failure or chronic lung disease.[ 15 ] Therefore, as a sensitivity analysis model, we added arterial carbon dioxide pressure (PCO 2 ) and creatinine levels upon hospital arrival as variables to the primary regression model to examine its robustness. Furthermore, the nonlinear relationship between BE values and the estimated probability of favourable neurological outcomes was described visually using a restricted cubic spline[ 28 ]. A subgroup analysis of BE was performed based on the presence or absence of prehospital ROSC. Moreover, we assessed the interaction between each factor and BE values for favourable neurological and survival outcomes in a multivariate logistic regression model, including a cross-product term. All statistical analyses were performed using the R software (R Foundation for Statistical Computing version 4.2.1) and Stata software (version 17; StataCorp, College Station, TX, USA). We performed a complete case analysis because there was hardly any missing information for any key variables after excluding patients according to the exclusion criteria described above (Additional file 1: Table S1 ). All tests were two-tailed, and p-values < 0.05 were considered statistically significant. Results We screened all 23,854 OHCA cases from the CRITICAL study between 2012 and 2021 (Fig. 1 ). In total, 7,591 patients were in witnessed cardiac arrest due to medical reasons at the time of hospital arrival. After applying our eligibility criteria, 6,066 patients remained. These patients were classified according to the quartiles of their BE values. Of these, 1,528 were classified as Q1 (BE ≤ – 21.1 mmol/L), 1,493 as Q2 (–21.1 < BE≤ − 15.7 mmol/L), 1,515 as Q3 (–15.7 − 10.4 mmol/L). Table 1 shows the patient characteristics, pre- and in-hospital information, and outcomes of eligible patients. Regarding pre- and in-hospital information, the Q1 group was less likely to have a bystander witness, bystander CPR, bystander shock delivery by an AED, first documented shockable rhythm, and TTM. Regarding the primary outcome, the lowest proportion of favourable neurological outcomes was 3.2% (49/1,528) in the Q1 group, followed by 4.7% (70/1,493), 9.8% (148/1,515), and 23.5% (359/1,530) in the Q2, Q3, and Q4 groups, respectively (Table 2 ). The proportion of favourable neurological outcomes decreased as the BE values decreased (p for trend < 0.001, Table 2 ). The restricted cubic spline analysis showed a nonlinear positive association between BE and the predicted probability of a favourable neurological outcome (p for nonlinearity < 0.001) (Additional file 3: Fig. S1 ). Table 1 Characteristics of patients with out-of-hospital cardiac arrest categorised based on base excess values. Variables Total n = 6,066 Base excess (BE), mmol/L Quartile 1 (BE \(\:\le\:\) − 21.1) n = 1,528 Quartile 2 (–21.1 < BE ≤ − 15.7) n = 1,493 Quartile 3 (− 15.7 − 10.4) n = 1,530 Prehospital characteristics Age (years) 73 [63–82] 72 [59–80] 74 [63–82] 74 [64–82] 74 [64–82] Male (%) 3,976 (65.6) 1,050 (68.7) 959 (64.2) 1,002 (66.1) 965 (63.1) Cardiac cause (%) 4,541 (74.9) 1,137 (74.4) 1,111 (74.4) 1,146 (75.6) 1,147 (75.0) Bystander CPR (%) 2,399 (39.6) 539 (35.3) 590 (39.5) 612 (40.4) 658 (43.0) Bystander shock delivery by an AED (%) 200 (3.3) 27 (1.8) 35 (2.3) 47 (3.1) 91 (6.0) First documented rhythm (%) Shockable 1,224 (20.2) 214 (14.0) 276 (18.5) 339 (22.4) 395 (25.8) Non-shockable 4,838 (79.8) 1,312 (86.0) 1,217 (81.5) 1,175 (77.6) 1,134 (74.2) Defibrillation by EMS (%) 1,607 (26.5) 320 (20.9) 374 (25.1) 431 (28.5) 482 (31.5) Adrenaline administration by EMS (%) 1,930 (31.8) 563 (36.9) 586 (39.3) 451 (29.8) 330 (21.6) Advanced airway management by EMS (%) 2,934 (48.4) 793 (51.9) 804 (53.9) 720 (47.5) 617 (40.3) No flow time for CPR (min) 3 [0–9] 3 [0–10] 3 [0–9] 3 [0–9] 3 [0–8] Time from witness to hospital arrival (min) 31 [22–39] 32 [23–41] 32 [23–40] 30 [22–38] 29 [22–37] In-hospital characteristics First documented rhythm (%) Shockable 468 (7.7) 112 (7.3) 129 (8.6) 124 (8.2) 103 (6.7) Non-shockable 4,644 (76.6) 1,323 (86.6) 1,194 (80.0) 1,162 (76.7) 965 (63.1) Presence of pulse 954 (15.7) 93 (6.1) 170 (11.4) 229 (15.1) 462 (30.2) Defibrillation in hospital (%) 943 (15.6) 259 (17.0) 261 (17.5) 248 (16.4) 175 (11.4) Time from hospital arrival to blood test (min) 7 [ 3 – 13 ] 8 [ 4 – 15 ] 7 [ 3 – 12 ] 7 [ 3 – 12 ] 6 [ 3 – 12 ] Coronary angiography (%) 1,094 (18.0) 204 (13.4) 238 (15.9) 258 (17.0) 394 (25.8) Target temperature management (%) 774 (12.8) 120 (7.9) 177 (11.9) 212 (14.0) 265 (17.3) Extracorporeal membrane oxygenation initiated after blood test (%) 516 (8.5) 179 (11.7) 161 (10.8) 109 (7.2) 67 (4.4) Laboratory data Lactate (mmol/L) 11.8 [8.7–15.2] 17.0 [14.6–19.7] 13.0 [11.3–15.0] 10.6 [8.9–12.3] 7.4 [5.8–9.2] HCO 3– (mmol/L) 15.5 [11.6–19.5] 10.3 [7.6–12.8] 14.0 [11.5–16.4] 17.4 [14.5–19.7] 21.4 [18.6–23.9] PaCO 2 (mmHg) 70.2 [50.6–89.9] 73.4 [54.0–97.9] 72.5 [52.9–92.7] 72.1 [52.5–89.6] 64.1 [44.3–80.1] Creatinine (mg/dL) 1.19 [0.92–1.65] 1.41 [1.1–2.2] 1.20 [0.95–1.60] 1.14 [0.90–1.60] 1.03 [0.83–1.31] Data are presented as medians [interquartile range, IQR] for continuous variables and n (%) for categorical variables. Abbreviations: IQR, interquartile range; CPR, cardiopulmonary resuscitation; AED, automated external defibrillator; EMS, emergency medical services Table 2 Outcomes after out-of-hospital cardiac arrest according to base excess values by primary analysis. Base excess (BE), mmol/L Quartile 1 (BE \(\:\le\:\) −21.1) n = 1,528 Quartile 2 (− 21.1 < BE ≤ − 15.7) n = 1,493 Quartile 3 (− 15.7 − 10.4) n = 1,530 p for trend Primary outcome Favourable neurological survival, n (%) 49 (3.2) 70 (4.7) 148 (9.8) 359 (23.5) < 0.001 Crude OR (95% CI) 0.11 (0.079–0.15) 0.16 (0.12–0.21) 0.35 (0.29–0.43) Reference Adjusted OR (95% CI) * 0.13 (0.090–0.19) 0.20 (0.15–0.28) 0.36 (0.28–0.47) Reference Secondary outcome Survival, n (%) 101 (6.6) 170 (11.4) 270 (17.8) 480 (31.4) < 0.001 Crude OR (95% CI) 0.15 (0.12–0.19) 0.28 (0.23–0.34) 0.47 (0.40–0.56) Reference Adjusted OR (95% CI) * 0.18 (0.13–0.25) 0.37 (0.28–0.49) 0.53 (0.41–0.68) Reference Abbreviations: OR, odds ratio; CI, confidence interval; CPR, cardiopulmonary resuscitation; EMS, emergency medical services; AED, automated external defibrillator * Adjusted for age, sex, cause of arrest, bystander CPR, AED shock delivery by bystander, first documented rhythm at the scene and in hospital, adrenaline administration by EMS, advanced airway management by EMS, defibrillation by EMS, no flow time for CPR, time from witness to hospital arrival, and time from hospital arrival to blood test [Insert Tables 1 and 2 here] Regarding secondary outcomes, the Q1 group had the lowest proportion of 1-month survival, and the Q4 group had the highest, which has a similar tendency to that of the primary outcome. In the multivariate logistic regression analysis, the proportion of favourable neurological outcomes in the Q1 group was significantly lower compared with that in the Q4 group (AOR, 0.13; 95% CI, 0.090–0.18; Table 2 ). In the model in which the variables PCO 2 and creatinine levels upon hospital arrival were added to the primary regression model (Additional file 2: Table S2 ), the trends in associations with outcomes were similar to those in the primary analysis of the original cohort. In subgroup analysis, there was an interaction between the presence or absence of prehospital ROSC and neurological outcome (p for interaction < 0.001, Fig. 2 , Table 3 ). The neurological outcome in patients with prehospital ROSC decreased when the BE values decreased (p for trend < 0.001, Table 3 ), but not in patients without prehospital ROSC (p for trend = 0.12, Table 3 ). Similar to the primary outcome, a strong association was observed between BE and survival in patients with prehospital ROSC. Table 3 Outcomes after out-of-hospital cardiac arrest based on base excess and the presence or absence of prehospital ROSC. Base excess (BE), mmol/L Quartile 1 (BE \(\:\le\:\) −21.2) n = 1,528 Quartile 2 (− 21.2 < BE ≦ − 15.7) n = 1,493 Quartile 3 (− 15.7 − 10.4) n = 1,530 p for trend p for interaction Primary outcome With prehospital ROSC (n = 1,393) < 0.001 n/N (%) 21/209 (10.1) 43/281 (15.3) 123/339 (36.3) 327/564 (58.0) < 0.001 Crude OR (95% CI) 0.081 (0.050–0.13) 0.13 (0.091–0.19) 0.41 (0.31–0.54) Reference Without prehospital ROSC (n = 4,673) n/N (%) 28/1,319 (2.1) 27/1,212 (2.2) 25/1,176 (2.1) 32/966 (3.3) 0.12 Crude OR (95% CI) 0.63 (0.38–1.06) 0.67 (0.40–1.12) 0.63 (0.37–1.08) Reference Secondary outcome With prehospital ROSC (n = 1,393) < 0.001 n/N (%) 42/209 (20.1) 88/281 (31.3) 187/339 (55.2) 410/564 (72.7) < 0.001 Crude OR (95% CI) 0.09 (0.06–0.14) 0.17 (0.13–0.23) 0.46 (0.35–0.61) Reference Without prehospital ROSC (n = 4,673) n/N (%) 59/1,319 (4.5) 82/1,212 (6.8) 83/1,176 (7.1) 70/966 (7.3) 0.005 Crude OR (95% CI) 0.60 (0.42–0.86) 0.93 (0.67–1.29) 0.97 (0.70–1.35) Reference Abbreviations: ROSC, return of spontaneous circulation; OR, odds ratio; CI, confidence interval The p-value for interaction was calculated between base excess values and the presence of ROSC before the blood test. [Insert Table 3 here] Discussion Consistent with the results of several prior studies,[ 17 – 19 , 29 ]this large-scale, multicentre, prospective study involving > 6,000 adult patients with OHCAs demonstrated that lower BE values at hospital arrival were associated with worse neurological outcomes among patients with bystander-witnessed OHCA, even after adjusting for the time interval from the onset of cardiac arrest to the blood test. This suggests that the BE value upon hospital arrival can serve as a potential prognostic indicator of neurological outcomes after OHCA. Corral et al. reported that venous blood gases measured at the start of CPR in 1552 patients with OHCA indicated that a lower BE was associated with poor neurological outcomes.[ 17 ] Additionally, Matthieu et al. found that, among 826 patients with OHCA admitted to the intensive care unit (ICU), a base deficit was associated with ICU mortality.[ 19 ] However, neither study accounted for the time interval between the occurrence of cardiac arrest and the BE measurement.[ 17 , 19 ] As a longer CPR duration is associated with lower BE values and a lower likelihood of favourable neurological outcomes,[ 18 , 30 ] CPR duration may have confounded these results. Our study demonstrated an association between BE values at hospital arrival and neurological outcomes in patients with OHCA, even after accounting for CPR duration. Subgroup analysis identified an association between the presence of ROSC before hospital arrival and neurological outcomes. Therefore, cardiac arrest does not uniformly affect all tissues and organs. Highly oxygen-demanding organs, such as the brain and heart, are more prone to early oxygen deprivation, potentially leading to localised metabolic acidosis.[ 31 ] Consequently, in patients with cardiac arrest, peripheral blood may not accurately reflect the overall metabolic abnormalities. In particular, patients who do not achieve ROSC may exhibit greater discrepancies between peripheral blood samples and overall metabolic abnormalities than those who achieve ROSC. This discrepancy could be one reason why no association was observed between BE values and neurological outcomes in patients without ROSC. Thus, the presence or absence of prehospital ROSC has a significant effect on outcomes. The lack of association with neurological outcomes in patients who did not achieve prehospital ROSC may be because BE values at hospital arrival alone provide insufficient information regarding neurological outcomes without ROSC. These findings highlight that BE may serve as a valuable indicator of neurological outcomes, specifically in patients who achieve ROSC. One of the strengths of this study is the use of BE rather than lactate or pH. BE provides a more comprehensive assessment of metabolic acidosis by reflecting the overall buffering capacity and acid-base status of the body. While pH is an essential indicator of acid-base balance, it is influenced by compensatory mechanisms, such as respiratory compensation, which may obscure the true extent of metabolic acidosis[ 15 ]. Conversely, lactate is a well-established marker of anaerobic metabolism and tissue hypoxia but does not fully capture the overall metabolic derangement, as it can be influenced by hepatic clearance, renal function, and intravenous fluid administration[ 10 ]. In contrast, BE accounts for both lactate-driven acidosis and other metabolic components, offering a more robust reflection of systemic metabolic disturbances in critically ill patients. A limitation of this study is that the registry did not provide detailed information on each patient’s history, comorbidities, and medications. Interpreting BE values can be challenging in individuals with kidney failure, long-term lung disease, or complex acid-base imbalances. For instance, in a patient with ongoing respiratory acidosis experiencing an increase in PCO 2 levels by 10 mmHg over several days, the BE measurement would be 4 mmol/L.[ 15 ] However, we observed similar results in the sensitivity analysis adjusted for PCO 2 and creatinine levels upon hospital arrival, which was consistent with the primary analysis (Additional file 2: Table S2 ). Conclusion This observational study of adult patients with OHCA demonstrated that lower BE values upon hospital arrival were associated with worse neurological outcomes. BE values may be an effective prognostic indicator of neurological outcomes, especially in patients with OHCA and prehospital ROSC. Abbreviations BE base excess OHCA out-of-hospital cardiac arrest ROSC return of spontaneous circulation FDMA Fire and Disaster Management Agency CRITICAL Comprehensive Registry of Intensive Cares for OHCA Survival EMS emergency medical services SBE standard base excess CPC Cerebral Performance Category CPR cardiopulmonary resuscitation AED automated external defibrillator PCO 2 arterial carbon dioxide pressure AOR adjusted odds ratio CIs confidence intervals ICU intensive care unit Declarations Ethics approval and consent to participate The study protocol was approved by the Ethics Committee of Kyoto University and each participating institution (R1045). The need for written informed consent was waived. Consent for publication Not applicable. Competing interests YO received the research grant from ZOLL foundation. The other authors state that they have no recognised financial conflicts or personal relationships that might have influenced the work presented in this paper. Funding This study was supported by a scientific research grant from the JSPS KAKENHI of Japan (22H03313 to Iwami, 22K09139 to Kitamura, and 22K2144 to Nishioka). Author Contribution R.O. conducted the conceptualization, data curation, formal analysis, methodology, project administration, software development, visualization, and writing of the original draft. N.N. contributed to the writing – review & editing, conceptualization, methodology, project administration, funding acquisition, supervision, and validation. T.I. contributed to methodology, project administration, funding acquisition, supervision, and writing – review & editing. Y.O. and Y.M. participated in data curation, resources, and writing – review & editing. T.K. contributed to data curation, resources, and funding acquisition. T.Y., S.N., K.Y., C.P., T.N., T.I., K.Y., T.K., M.K., K.N., Y.I., T.S., T.M., H.S., Y.H., A.O., and T.M. were responsible for investigation and resources. S.M., S.Y., S.K., S.K., Y.M., L.Z., and K.K. contributed to data curation and resources. All authors reviewed the manuscript. Acknowledgement We sincerely appreciate the efforts of all EMS personnel in collecting the Utstein data and extend our gratitude to Ms. Ikuko Nakamura and Yumiko Murai for their support in the CRITICAL study. We also thank our colleagues at the Osaka University Centre of Medical Data Science and the Advanced Clinical Epidemiology Investigator’s Research Project for their valuable insights and expertise regarding our study. Availability of data and materials The datasets and/or analyses in this study are not publicly available because the ethics committee did not permit them. References Yan S, Gan Y, Jiang N, Wang R, Chen Y, Luo Z, et al. The global survival rate among adult out-of-hospital cardiac arrest patients who received cardiopulmonary resuscitation: A systematic review and meta-analysis. Crit Care 2020;24:61. https://doi.org/10.1186/s13054-020-2773-2. Pichler G, Fazekas F. Cardiopulmonary arrest is the most frequent cause of the unresponsive wakefulness syndrome: A prospective population-based cohort study in Austria. Resuscitation 2016;103:94-8. https://doi.org/10.1016/j.resuscitation.2016.02.023. Laver S, Farrow C, Turner D, Nolan J. Mode of death after admission to an intensive care unit following cardiac arrest. Intensive Care Med 2004;30:2126-8. https://doi.org/10.1007/s00134-004-2425-z. Johnson BA, Weil MH. Redefining ischemia due to circulatory failure as dual defects of oxygen deficits and of carbon dioxide excesses. Crit Care Med 1991;19:1432-8. https://doi.org/10.1097/00003246-199111000-00021. Wildenthal K, Mierzwiak DS, Myers RW, Mitchell JH. Effects of acute lactic acidosis on left ventricular performance. Am J Physiol 1968;214:1352-9. https://doi.org/10.1152/ajplegacy.1968.214.6.1352. Kellum JA, Song M, Venkataraman R. Effects of Hyperchloremic Acidosis on Arterial Pressure and Circulating Inflammatory Molecules in Experimental Sepsis. Chest 2004;125:243-8. https://doi.org/10.1378/chest.125.1.243. Kellum JA, Song M, Li J. Science review: Extracellular acidosis and the immune response: Clinical and physiologic implications. Crit Care 2004;8:331-6. https://doi.org/10.1186/cc2900. Prause G, Ratzenhofer-Comenda B, Smolle-Jüttner F, Heydar-Fadai J, Wildner G, Spernbauer P, et al. Comparison of lactate or BE during out-of-hospital cardiac arrest to determine metabolic acidosis. Resuscitation 2001;51:297-300. https://doi.org/10.1016/S0300-9572(01)00424-5. Capparelli EV, Chow MSS, Kluger J, Fieldman A. Differences in systemic and myocardial blood acid-base status during cardiopulmonary resuscitation. Crit Care Med 1989;17442-6. https://doi.org/10.1097/00003246-198905000-00013. Makino J, Uchino S, Morimatsu H, Bellomo R. A quantitative analysis of the acidosis of cardiac arrest: a prospective observational study. Crit Care 2005;9:R357-62. Ouellet JF, Roberts DJ, Tiruta C, Kirkpatrick AW, Mercado M, Trottier V, et al. Admission base deficit and lactate levels in Canadian patients with blunt trauma: Are they useful markers of mortality? J Trauma Acute Care Surg 2012;72:1532-5. https://doi.org/10.1097/TA.0b013e318256dd5a. Mofidi M, Hasani A, Kianmehr N. Determining the accuracy of base deficit in diagnosis of intra-abdominal injury in patients with blunt abdominal trauma. Am J Emerg Med 2010;28:933-6. https://doi.org/10.1016/j.ajem.2009.06.002. Andersen OS, Engel K, Jørgensen K, Astrup P. A micro method for determination of ph, carbon dioxide tension, base excess and standard bicarbonate in capillary blood. Scand J Clin Lab Invest 1960;12:172-6. https://doi.org/10.3109/00365516009062419. Lichtveld RA, Panhuizen IF, Smit RBJ, Holtslag HR, Van Der Werken C. Predictors of death in trauma patients who are alive on arrival at hospital. Eur J Trauma Emerg Surg 2007;33:201. https://doi.org/10.1007/s00068-007-6097-6. Berend K. Diagnostic Use of Base Excess in Acid–Base Disorders. N Engl J Med 2018;378:1419-28. https://doi.org/10.1056/nejmra1711860. Ibrahim I, Chor WP, Chue KM, Tan CS, Tan HL, Siddiqui FJ, et al. Is arterial base deficit still a useful prognostic marker in trauma? A systematic review. Am J Emerg Med. 2016;34:626-35. https://doi.org/10.1016/j.ajem.2015.12.012. Corral Torres E, Hernández-Tejedor A, Suárez Bustamante R, De Elías Hernández R, Casado Flórez I, San Juan Linares A. Prognostic value of venous blood analysis at the start of CPR in non-traumatic out-of-hospital cardiac arrest: Association with ROSC and the neurological outcome. Crit Care 2020;24:60. https://doi.org/10.1186/s13054-020-2762-5. Takasu A, Sakamoto T, Okada Y. Arterial base excess after CPR: The relationship to CPR duration and the characteristics related to outcome. Resuscitation 2007;73:394-99. https://doi.org/10.1016/j.resuscitation.2006.10.014. Jamme M, Ben Hadj Salem O, Guillemet L, Dupland P, Bougouin W, Charpentier J, et al. Severe metabolic acidosis after out-of-hospital cardiac arrest: risk factors and association with outcome. Ann Intensive Care 2018;8:62. https://doi.org/10.1186/s13613-018-0409-3. Kitamura T, Iwami T, Kawamura T, Nagao K, Tanaka H, Hiraide A. Nationwide public-access defibrillation in Japan. N Engl J Med 2010;362:994-1004. https://doi.org/10.1056/nejmoa0906644. Kitamura T, Kiyohara K, Sakai T, Matsuyama T, Hatakeyama T, Shimamoto T, et al. Public-Access Defibrillation and Out-of-Hospital Cardiac Arrest in Japan. N Engl J Med 2016;375: 1649-59. https://doi.org/10.1056/nejmsa1600011. Jacobs I, Nadkarni V, Bahr J, Berg RA, Billi JE, Bossaert L, et al. Cardiac arrest and cardiopulmonary resuscitation outcome reports: update and simplification of the utstein templates for resuscitation registries. A statement for healthcare professionals from a task force of the international liaison committee on resuscitation (American Heart Association, European Resuscitation Council, Australian Resuscitation Council, New Zealand Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Southern Africa) Resuscitation 2004;63:233-49. https://doi.org/10.1016/j.resuscitation.2004.09.008. Yamada T, Kitamura T, Hayakawa K, Yoshiya K, Irisawa T, Abe Y, et al. Rationale, design, and profile of Comprehensive Registry of In-Hospital Intensive Care for OHCA Survival (CRITICAL) study in Osaka, Japan. J Intensive Care 2016;4:10. https://doi.org/10.1186/s40560-016-0128-5. Iwami T, Nichol G, Hiraide A, Hayashi Y, Nishiuchi T, Kajino K, et al. Continuous improvements in “chain of survival” increased survival after out-of-hospital cardiac arrests: A large-scale population-based study. Circulation 2009;119:728-34. https://doi.org/10.1161/CIRCULATIONAHA.108.802058. Iwami T, Kawamura T, Hiraide A, Berg RA, Hayashi Y, Nishiuchi T, et al. Effectiveness of bystander-initiated cardiac-only resuscitation for patients with out-of-hospital cardiac arrest. Circulation 2007;116:2900-07. https://doi.org/10.1161/CIRCULATIONAHA.107.723411. Japan Resuscitation Council. JRC guidelines for resuscitation 2020. Tokyo. Igaku Shoin (in Japanese) 2021. Becker LB, Aufderheide TP, Geocadin RG, Callaway CW, Lazar RM, Donnino MW, et al. Primary outcomes for resuscitation science studies: a consensus statement from the American Heart Association. Circulation 2011;124:2158-77. https://doi.org/10.1161/cir.0b013e3182340239. Desquilbet L, Mariotti F. Dose-response analyses using restricted cubic spline functions in public health research. Stat Med 2010;29:1037-57. https://doi.org/10.1002/sim.3841. Jouffroy R, Lamhaut L, Guyard A, Phillipe P, Deluze T, Jaffry M, et al. Base excess and lactate as prognostic indicators for patients treated by extra corporeal life support after out hospital cardiac arrest due to acute coronary syndrome. Resuscitation 2014;85:1764-8. https://doi.org/10.1016/j.resuscitation.2014.10.012. Matsuyama T, Ohta B, Kiyohara K, Kitamura T. Cardiopulmonary resuscitation duration and favorable neurological outcome after out-of-hospital cardiac arrest: a nationwide multicenter observational study in Japan (the JAAM-OHCA registry). Crit Care 2022;26:120. https://doi.org/10.1186/s13054-022-03994-2. Choi J, Shoaib M, Yin T, Nayyar G, Shinozaki K, Stevens JF, et al. Tissue-specific metabolic profiles after prolonged cardiac arrest reveal brain metabolome dysfunction predominantly after resuscitation. J Am Heart Assoc 2019;8:e012809. https://doi.org/10.1161/JAHA.119.012809. Additional Declarations No competing interests reported. Supplementary Files Additionalfile1.docx Additional file 1 Microsoft word file Missing data Table S1 Additionalfile2.docx Additional file 2 Microsoft word file Outcomes after out-of-hospital cardiac arrest according to base excess values by sensitivity analysis Table S2 Additionalfile3.docx Additional file 3 Microsoft word file Non-linear relationship between base excess values and the estimated probability of favourable neurological outcome Fig. S1 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6257805","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":435049801,"identity":"f6151a25-30f7-4c6c-ab6b-29237dfccf84","order_by":0,"name":"Ryuta Onodera","email":"","orcid":"","institution":"Kyoto University School of Public Health","correspondingAuthor":false,"prefix":"","firstName":"Ryuta","middleName":"","lastName":"Onodera","suffix":""},{"id":435049802,"identity":"5b97cc20-7b31-4815-a8ef-e6039b43b3e8","order_by":1,"name":"Norihiro Nishioka","email":"data:image/png;base64,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","orcid":"","institution":"Kyoto University School of Public Health","correspondingAuthor":true,"prefix":"","firstName":"Norihiro","middleName":"","lastName":"Nishioka","suffix":""},{"id":435049803,"identity":"667f4eeb-cb37-468d-af8f-e1a5cfa1d1ab","order_by":2,"name":"Tomoki Yamada","email":"","orcid":"","institution":"Osaka Police Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tomoki","middleName":"","lastName":"Yamada","suffix":""},{"id":435049804,"identity":"e4906c57-b37a-4c22-bb79-e144c8707363","order_by":3,"name":"Shunichiro Nakao","email":"","orcid":"","institution":"Osaka University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Shunichiro","middleName":"","lastName":"Nakao","suffix":""},{"id":435049805,"identity":"a9f51846-684b-4de4-9284-217c07033f94","order_by":4,"name":"Kazuhisa Yoshiya","email":"","orcid":"","institution":"Kansai Medical University, Takii Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kazuhisa","middleName":"","lastName":"Yoshiya","suffix":""},{"id":435049806,"identity":"d15e1b08-149d-4ef4-a38d-6a6e147f53b2","order_by":5,"name":"Changhwi Park","email":"","orcid":"","institution":"Tane General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Changhwi","middleName":"","lastName":"Park","suffix":""},{"id":435049808,"identity":"666a65cf-632c-44ce-ab58-3c2bdefe969c","order_by":6,"name":"Tetsuro Nishimura","email":"","orcid":"","institution":"Osaka Metropolitan University","correspondingAuthor":false,"prefix":"","firstName":"Tetsuro","middleName":"","lastName":"Nishimura","suffix":""},{"id":435049809,"identity":"b38d6aee-fe36-4da8-9eb7-40d9f49c0678","order_by":7,"name":"Takuya Ishibe","email":"","orcid":"","institution":"Kindai University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Takuya","middleName":"","lastName":"Ishibe","suffix":""},{"id":435049811,"identity":"ecc5ba8e-9e55-42c5-8aa8-1af92f34de2a","order_by":8,"name":"Kazuma Yamakawa","email":"","orcid":"","institution":"Osaka Medical and Pharmaceutical University","correspondingAuthor":false,"prefix":"","firstName":"Kazuma","middleName":"","lastName":"Yamakawa","suffix":""},{"id":435049813,"identity":"098f8df0-ba9e-4410-b124-38176b3e5a09","order_by":9,"name":"Takeyuki Kiguchi","email":"","orcid":"","institution":"Osaka General Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Takeyuki","middleName":"","lastName":"Kiguchi","suffix":""},{"id":435049816,"identity":"021cea20-0920-4829-8d9d-b67f318beae4","order_by":10,"name":"Masafumi Kishimoto","email":"","orcid":"","institution":"Osaka Prefectural Nakakawachi Medical Center of Acute Medicine","correspondingAuthor":false,"prefix":"","firstName":"Masafumi","middleName":"","lastName":"Kishimoto","suffix":""},{"id":435049820,"identity":"398fcad9-ad82-4a03-adda-f18687019c4f","order_by":11,"name":"Kohei Ninomiya","email":"","orcid":"","institution":"Senshu Trauma and Critical Care Center","correspondingAuthor":false,"prefix":"","firstName":"Kohei","middleName":"","lastName":"Ninomiya","suffix":""},{"id":435049821,"identity":"9fe386a4-27a9-4c5a-b4db-e0ecd8c023b0","order_by":12,"name":"Yusuke Ito","email":"","orcid":"","institution":"Senri Critical Care Medical Center, Saiseikai Senri Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yusuke","middleName":"","lastName":"Ito","suffix":""},{"id":435049822,"identity":"25e8de7a-c6dc-4078-82ad-ced160b89668","order_by":13,"name":"Taku Sogabe","email":"","orcid":"","institution":"National Hospital Organization Osaka National Hospital","correspondingAuthor":false,"prefix":"","firstName":"Taku","middleName":"","lastName":"Sogabe","suffix":""},{"id":435049824,"identity":"5a60bc34-d48c-4e59-bab4-14b5f6cb6906","order_by":14,"name":"Takaya Morooka","email":"","orcid":"","institution":"Osaka City General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Takaya","middleName":"","lastName":"Morooka","suffix":""},{"id":435049826,"identity":"fa5d5808-47cb-49e7-8be1-96af11a91d8c","order_by":15,"name":"Haruko Sakamoto","email":"","orcid":"","institution":"Osaka Red Cross Hospital","correspondingAuthor":false,"prefix":"","firstName":"Haruko","middleName":"","lastName":"Sakamoto","suffix":""},{"id":435049827,"identity":"91fb0d4b-fd0a-4e70-aa38-dea318c53f48","order_by":16,"name":"Yuki Hironaka","email":"","orcid":"","institution":"Kishiwada Tokushukai Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuki","middleName":"","lastName":"Hironaka","suffix":""},{"id":435049828,"identity":"69f7b22b-6f67-4b5c-90eb-af9777c19a74","order_by":17,"name":"Atsunori Onoe","email":"","orcid":"","institution":"Kansai Medical University","correspondingAuthor":false,"prefix":"","firstName":"Atsunori","middleName":"","lastName":"Onoe","suffix":""},{"id":435049829,"identity":"df475d6a-57be-4d82-9af7-f6a44c7cae29","order_by":18,"name":"Tasuku Matsuyama","email":"","orcid":"","institution":"Kyoto Prefectural University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Tasuku","middleName":"","lastName":"Matsuyama","suffix":""},{"id":435049831,"identity":"7fd4c7e9-81be-49ae-ad92-6b33e79c7306","order_by":19,"name":"Yohei Okada","email":"","orcid":"","institution":"Kyoto University School of Public Health","correspondingAuthor":false,"prefix":"","firstName":"Yohei","middleName":"","lastName":"Okada","suffix":""},{"id":435049833,"identity":"2c76d3c8-5cb9-44cd-84cb-5c857842270b","order_by":20,"name":"Satoshi Matsui","email":"","orcid":"","institution":"Hyogo Prefectural Kobe Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Satoshi","middleName":"","lastName":"Matsui","suffix":""},{"id":435049834,"identity":"6a0f05d6-bc9a-4203-87ee-64c0ab51bbc8","order_by":21,"name":"Satoshi Yoshimura","email":"","orcid":"","institution":"Kyoto University School of Public Health","correspondingAuthor":false,"prefix":"","firstName":"Satoshi","middleName":"","lastName":"Yoshimura","suffix":""},{"id":435049835,"identity":"b226ef33-c8f0-4327-82d7-025e148428c8","order_by":22,"name":"Shunsuke Kimata","email":"","orcid":"","institution":"Kyoto University School of Public Health","correspondingAuthor":false,"prefix":"","firstName":"Shunsuke","middleName":"","lastName":"Kimata","suffix":""},{"id":435049836,"identity":"027bc84e-79ba-41a5-bd20-af4a1de4cddb","order_by":23,"name":"Shunsuke Kawai","email":"","orcid":"","institution":"Kyoto University School of Public Health","correspondingAuthor":false,"prefix":"","firstName":"Shunsuke","middleName":"","lastName":"Kawai","suffix":""},{"id":435049837,"identity":"ef38450d-c132-4335-b0f4-aa23fe5e7c2c","order_by":24,"name":"Yuto Makino","email":"","orcid":"","institution":"Nagoya City University Graduate School of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Yuto","middleName":"","lastName":"Makino","suffix":""},{"id":435049838,"identity":"844399c3-669e-4a56-ab0d-a7066c7730f5","order_by":25,"name":"Ling Zha","email":"","orcid":"","institution":"Osaka University","correspondingAuthor":false,"prefix":"","firstName":"Ling","middleName":"","lastName":"Zha","suffix":""},{"id":435049839,"identity":"c881b68b-0a9d-4f15-b80a-45aff5e70d2e","order_by":26,"name":"Kosuke Kiyohara","email":"","orcid":"","institution":"Otsuma Women's University","correspondingAuthor":false,"prefix":"","firstName":"Kosuke","middleName":"","lastName":"Kiyohara","suffix":""},{"id":435049840,"identity":"e2c087c9-df63-47ae-8ff0-f54cfb6e4bfa","order_by":27,"name":"Tetsuhisa Kitamura","email":"","orcid":"","institution":"Osaka University","correspondingAuthor":false,"prefix":"","firstName":"Tetsuhisa","middleName":"","lastName":"Kitamura","suffix":""},{"id":435049841,"identity":"d09e069f-0a03-403f-9b0f-766a0e14a45e","order_by":28,"name":"Taku Iwami","email":"","orcid":"","institution":"Kyoto University School of Public Health","correspondingAuthor":false,"prefix":"","firstName":"Taku","middleName":"","lastName":"Iwami","suffix":""}],"badges":[],"createdAt":"2025-03-19 04:38:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6257805/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6257805/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":79679197,"identity":"47b6599f-e98d-46dc-ab17-9dcb24396bad","added_by":"auto","created_at":"2025-04-01 12:33:30","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":187339,"visible":true,"origin":"","legend":"\u003cp\u003eStudy flowchart\u003c/p\u003e\n\u003cp\u003eAbbreviation: OHCA, out-of-hospital cardiac arrest.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6257805/v1/32cc58f5ad115d10ebd3b722.jpeg"},{"id":79679202,"identity":"a27a7b57-7f17-457a-bc72-430ed452c427","added_by":"auto","created_at":"2025-04-01 12:33:30","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":320486,"visible":true,"origin":"","legend":"\u003cp\u003eNon-linear relationship between base excess and the estimated probability of neurological outcomes by the subgroups.\u003c/p\u003e\n\u003cp\u003eThe lines indicate estimated probability, and the shaded areas represent the 95% confidence intervals. The solid red line represents patients with prehospital return of spontaneous circulation (ROSC), and the dotted blue line represents those without prehospital ROSC.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6257805/v1/f4b130ae721608e91e0b4949.jpeg"},{"id":81957935,"identity":"3fa656f5-e060-4b84-8e0d-521e1c7b7426","added_by":"auto","created_at":"2025-05-05 10:08:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1714612,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6257805/v1/88081cfb-f2c7-4c50-9e57-8d2bcaf11b49.pdf"},{"id":79679193,"identity":"8ad38b74-899e-4dbf-a3a9-599e468a54bb","added_by":"auto","created_at":"2025-04-01 12:33:30","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":16142,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 1\u003c/p\u003e\n\u003cp\u003eMicrosoft word file\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMissing data\u003c/p\u003e\n\u003cp\u003eTable S1\u003c/p\u003e","description":"","filename":"Additionalfile1.docx","url":"https://assets-eu.researchsquare.com/files/rs-6257805/v1/a4ef933567bcc4124bb67743.docx"},{"id":79679198,"identity":"af7a9ad7-e8fe-470c-93b9-179cc9eabc9c","added_by":"auto","created_at":"2025-04-01 12:33:30","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":16725,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 2\u003c/p\u003e\n\u003cp\u003eMicrosoft word file\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOutcomes after out-of-hospital cardiac arrest according to base excess values by sensitivity analysis\u003c/p\u003e\n\u003cp\u003eTable S2\u003c/p\u003e","description":"","filename":"Additionalfile2.docx","url":"https://assets-eu.researchsquare.com/files/rs-6257805/v1/bdeea4def112a949f180c250.docx"},{"id":79679205,"identity":"5eca0217-d133-463a-ab28-abb22cac9222","added_by":"auto","created_at":"2025-04-01 12:33:30","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":174986,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 3\u003c/p\u003e\n\u003cp\u003eMicrosoft word file\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNon-linear relationship between base excess values and the estimated probability of favourable neurological outcome\u003c/p\u003e\n\u003cp\u003eFig. S1\u003c/p\u003e","description":"","filename":"Additionalfile3.docx","url":"https://assets-eu.researchsquare.com/files/rs-6257805/v1/ace39e603c1c053dd39f81be.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association between base excess level at hospital arrival and neurological outcomes of adult out-of-hospital cardiac arrest: A multicentre cohort study","fulltext":[{"header":"Background","content":"\u003cp\u003eOut-of-hospital cardiac arrest (OHCA) is a global public health concern, and survival after OHCA remains low and poor[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. However, its treatment is intricate and involves multiple disciplines, demanding substantial time and considerable allocation of medical and human resources. Furthermore, many patients who successfully attain a return of spontaneous circulation (ROSC) after OHCA frequently experience subsequent mortality or transition to a state of unresponsive wakefulness syndrome, even after post-resuscitation care.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] Consequently, the early prediction of outcomes in patients with OHCA can facilitate the implementation of intensive care measures, such as extracorporeal membrane oxygenation (ECMO), targeted temperature management (TTM), and appropriate decisions for resuscitation termination.\u003c/p\u003e \u003cp\u003eCardiac arrest leads to an interruption in blood flow to the tissues. Cessation results in extreme hypercarbic and metabolic acidosis at the tissue level.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] Metabolic acidosis causes harmful effects, such as reduced myocardial function,[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]dilation of blood vessels[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], and weakening of the body\u0026rsquo;s inflammatory and immune responses[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], which can result in multiple organ failure.\u003c/p\u003e \u003cp\u003eMetabolic acidosis is often observed in patients who have experienced cardiac arrest and is usually thought to be primarily caused by increased lactate levels.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] However, the causes of metabolic acidosis during cardiac arrest are complex, with lactate levels accounting for only approximately 50% of the pathogenesis[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe standard base excess (BE) can help in understanding the underlying causes of this condition.[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] BE, introduced in 1960 as a metric of metabolic acidosis, is widely used.[\u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] It can be measured easily and quickly using blood gas analysis. BE refers to the quantity of base, measured in millimoles, required to bring the pH of 1 L of fully oxygen-saturated arterial blood to 7.40 at a temperature of 37\u0026deg;C and a partial pressure of carbon dioxide level of 40 Torr. The normal range for BE is between +\u0026thinsp;2 and \u0026minus;\u0026thinsp;2 mmol/L[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Standard BE (SBE) is a widely researched prognostic indicator used to assess patients with trauma in acute care settings.[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] In patients with cardiac arrest, a lower BE is associated with worse outcomes.[\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] However, these findings are based on small samples without adjustments for the time from cardiac arrest to blood tests, which can significantly influence the association between BE levels and outcomes.\u003c/p\u003e \u003cp\u003eThis study aimed to assess the association between BE levels at hospital arrival and neurological outcomes in patients with OHCA using large-scale multicentre registry data in Osaka, Japan, where termination of resuscitation was not allowed for emergency medical service personnel, by adjusting the time from the onset of cardiac arrest to blood tests.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e The study protocol was approved by the Ethics Committee of Kyoto University and each participating institution (R1045). The need for written informed consent was waived.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and setting\u003c/h2\u003e \u003cp\u003eThe current study performed a retrospective analysis using data obtained from the Comprehensive Registry of Intensive Cares for OHCA Survival (CRITICAL) study. The CRITICAL study is a prospective multicentre registry that aims to collect and analyse data on treatments provided in pre- and in-hospital settings for OHCA. Prehospitalisation data were obtained from the All-Japan Utstein Registry of the Fire and Disaster Management Agency (FDMA).[\u003cspan additionalcitationids=\"CR21 CR22\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] In-hospital data were collected from 15 tertiary critical care medical centres and one community hospital with an emergency department, all situated in Osaka Prefecture, Japan. Osaka Prefecture is an urban area encompassing 1,905 km\u003csup\u003e2\u003c/sup\u003e, with a residential population of approximately 8.8\u0026nbsp;million in 2020. Approximately 7,500 OHCA cases occur annually in Osaka Prefecture (FDMA of the Ministry of Internal Affairs and Communications website. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.fdma.go.jp/publication/rescue/post7.html\u003c/span\u003e\u003cspan address=\"https://www.fdma.go.jp/publication/rescue/post7.html\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e), and approximately one in four patients with OHCA (approximately\u0026thinsp;\u0026ge;\u0026thinsp;2,000 cases) have been registered annually, from 2012 to 2021.\u003c/p\u003e \u003cp\u003eThe registry for this study is currently ongoing, without a specified study period. In-hospital data were documented by attending physicians and recorded by physicians or medical administrators using a predetermined online form. To ensure data quality, the working group reviewed and verified the collected data.[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]Incomplete data were returned to the respective institutions for completion. A comprehensive description of the All-Japan Utstein Registry of the FDMA and the CRITICAL study has been previously published[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eThe emergency medical services system in Osaka\u003c/h3\u003e\n\u003cp\u003eThe emergency medical services (EMS) system in Japan has been previously described in detail[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Overall, 119 emergency numbers can be called from anywhere within Japan; following such a call, an emergency dispatch centre immediately dispatches the closest ambulance to the location. Emergency services are available 24 h a day. Each ambulance is staffed by a three-member team trained in life support. The most skilled EMS workers are known as emergency lifesaving technicians. They are authorised to establish an intravenous line with lactated Ringer\u0026rsquo;s solution, administer adrenaline, secure an adjunctive airway, and use a semiautomated external defibrillator for patients with OHCA. Specially trained emergency lifesaving technicians are allowed to perform tracheal intubation in patients with OHCA. They are not allowed to administer sodium bicarbonate for acidosis correction.\u003c/p\u003e \u003cp\u003eIn Japan, EMS personnel typically cannot comply with do-not-resuscitate requests, meaning they continue resuscitation attempts at the scene. Consequently, EMS teams transport almost all patients with OHCA to a medical facility, except in cases where the patient displays clear indicators of death, such as decapitation, incineration, decomposition, rigor mortis, or dependent cyanosis. All EMS providers performed cardiopulmonary resuscitation (CPR) according to the Japanese CPR guidelines.[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e\n\u003ch3\u003eStudy population\u003c/h3\u003e\n\u003cp\u003eIn this study, we enrolled adult patients aged 18 years with witnessed OHCA. Included patients were those who had their BE values measured upon arrival at the hospital within the study period from 1 January 2012 to 31 December 2021. We excluded patients with OHCA due to external causes (e.g., trauma, hanging, drowning, drug overdose, or asphyxia) whose measurement time was unknown and whose ECMO was initiated before the BE measurement.\u003c/p\u003e\n\u003ch3\u003eExposures\u003c/h3\u003e\n\u003cp\u003eThe main exposure was the BE values determined by blood gas analysis from the initial blood test performed upon arrival at the hospital. We divided the patients into quartiles based on BE values of the initial blood test on arrival at the hospital: Q1 (BE\u0026thinsp;\u0026le;\u0026thinsp;\u0026minus;\u0026thinsp;21.1 mmol/L), Q2 (\u0026minus;\u0026thinsp;21.1\u0026thinsp;\u0026lt;\u0026thinsp;BE\u0026thinsp;\u0026le;\u0026thinsp;\u0026minus;\u0026thinsp;15.7 mmol/L), Q3 (\u0026minus;\u0026thinsp;15.7\u0026thinsp;\u0026lt;\u0026thinsp;BE\u0026thinsp;\u0026le;\u0026thinsp;\u0026minus;\u0026thinsp;10.4 mmol/L), and Q4 (BE\u0026thinsp;\u0026gt;\u0026thinsp;\u0026minus;\u0026thinsp;10.4 mmol/L). In the current study, there was no set protocol to determine whether to use the SBE or BE blood. Decisions regarding these measurements were left to the individual judgment of each physician or the policies of their respective institutions.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eThe primary outcome of this study was 30-day survival with good neurological outcomes, defined as a Cerebral Performance Category (CPC) score of 1 or 2. Neurological status was evaluated by the physician responsible for treating the patient using the CPC scale (category 1, good cerebral performance; category 2, moderate cerebral disability; category 3, severe cerebral disability; category 4, coma or vegetative state; category 5, death/brain death).[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] The secondary outcome of this study was the 1-month survival.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analyses\u003c/h2\u003e \u003cp\u003eData are presented as medians with interquartile ranges for continuous variables and as proportions for categorical variables. We estimated adjusted odds ratios (AORs) with their 95% confidence intervals (CIs) by multivariable logistic regression to evaluate the associations between BE categories based on quartiles and each outcome. Trend analysis across the quartiles of BE values was performed using the Cochran\u0026ndash;Armitage trend test. As a primary analysis model, we adjusted for age, sex (male or female), origin of cardiac arrest (cardiac or noncardiac), presence of witness (yes or no), presence of bystander CPR, presence of an automated external defibrillator (AED) shock delivery by a bystander, first documented rhythm (shockable, non-shockable, or unknown) at the scene and in hospital, adrenaline administration and advanced airway management and defibrillation by EMS, no flow time for CPR, time from EMS call to hospital arrival, and time from hospital arrival to blood test, which was selected as the most clinically relevant variables for this study.\u003c/p\u003e \u003cp\u003eInterpreting BE values can be challenging in patients with preexisting kidney failure or chronic lung disease.[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] Therefore, as a sensitivity analysis model, we added arterial carbon dioxide pressure (PCO\u003csub\u003e2\u003c/sub\u003e) and creatinine levels upon hospital arrival as variables to the primary regression model to examine its robustness. Furthermore, the nonlinear relationship between BE values and the estimated probability of favourable neurological outcomes was described visually using a restricted cubic spline[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. A subgroup analysis of BE was performed based on the presence or absence of prehospital ROSC. Moreover, we assessed the interaction between each factor and BE values for favourable neurological and survival outcomes in a multivariate logistic regression model, including a cross-product term. All statistical analyses were performed using the R software (R Foundation for Statistical Computing version 4.2.1) and Stata software (version 17; StataCorp, College Station, TX, USA). We performed a complete case analysis because there was hardly any missing information for any key variables after excluding patients according to the exclusion criteria described above (Additional file 1: Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). All tests were two-tailed, and p-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eWe screened all 23,854 OHCA cases from the CRITICAL study between 2012 and 2021 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In total, 7,591 patients were in witnessed cardiac arrest due to medical reasons at the time of hospital arrival. After applying our eligibility criteria, 6,066 patients remained. These patients were classified according to the quartiles of their BE values. Of these, 1,528 were classified as Q1 (BE \u0026le; \u0026ndash; 21.1 mmol/L), 1,493 as Q2 (\u0026ndash;21.1\u0026thinsp;\u0026lt;\u0026thinsp;BE\u0026le; \u0026minus;\u0026thinsp;15.7 mmol/L), 1,515 as Q3 (\u0026ndash;15.7\u0026thinsp;\u0026lt;\u0026thinsp;BE \u0026le; \u0026minus;\u0026thinsp;10.4 mmol/L), and 1,530 as Q4 (BE\u0026gt; \u0026minus;\u0026thinsp;10.4 mmol/L).\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the patient characteristics, pre- and in-hospital information, and outcomes of eligible patients. Regarding pre- and in-hospital information, the Q1 group was less likely to have a bystander witness, bystander CPR, bystander shock delivery by an AED, first documented shockable rhythm, and TTM. Regarding the primary outcome, the lowest proportion of favourable neurological outcomes was 3.2% (49/1,528) in the Q1 group, followed by 4.7% (70/1,493), 9.8% (148/1,515), and 23.5% (359/1,530) in the Q2, Q3, and Q4 groups, respectively (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The proportion of favourable neurological outcomes decreased as the BE values decreased (p for trend\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The restricted cubic spline analysis showed a nonlinear positive association between BE and the predicted probability of a favourable neurological outcome (p for nonlinearity\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Additional file 3: Fig.\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003eS1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of patients with out-of-hospital cardiac arrest categorised based on base excess values.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;6,066\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e \u003cp\u003eBase excess (BE), mmol/L\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eQuartile 1\u003c/p\u003e \u003cp\u003e(BE \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\le\\:\\)\u003c/span\u003e\u003c/span\u003e \u0026minus;\u0026thinsp;21.1)\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;1,528\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eQuartile 2\u003c/p\u003e \u003cp\u003e(\u0026ndash;21.1\u0026thinsp;\u0026lt;\u0026thinsp;BE\u0026thinsp;\u0026le;\u0026thinsp;\u0026minus;\u0026thinsp;15.7)\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;1,493\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eQuartile 3\u003c/p\u003e \u003cp\u003e(\u0026minus;\u0026thinsp;15.7\u0026thinsp;\u0026lt;\u0026thinsp;BE\u0026thinsp;\u0026le;\u0026thinsp;\u0026minus;\u0026thinsp;10.4)\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;1,515\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eQuartile 4\u003c/p\u003e \u003cp\u003e(BE\u0026thinsp;\u0026gt;\u0026thinsp;\u0026minus;\u0026thinsp;10.4)\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;1,530\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ePrehospital characteristics\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73 [63\u0026ndash;82]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72 [59\u0026ndash;80]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e74 [63\u0026ndash;82]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e74 [64\u0026ndash;82]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e74 [64\u0026ndash;82]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3,976 (65.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,050 (68.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e959 (64.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1,002 (66.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e965 (63.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiac cause (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,541 (74.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,137 (74.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,111 (74.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1,146 (75.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1,147 (75.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBystander CPR (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,399 (39.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e539 (35.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e590 (39.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e612 (40.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e658 (43.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBystander shock delivery by an AED (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e200 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e47 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e91 (6.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFirst documented rhythm (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShockable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,224 (20.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e214 (14.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e276 (18.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e339 (22.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e395 (25.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-shockable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,838 (79.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,312 (86.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,217 (81.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1,175 (77.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1,134 (74.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDefibrillation by EMS (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,607 (26.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e320 (20.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e374 (25.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e431 (28.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e482 (31.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdrenaline administration by EMS (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,930 (31.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e563 (36.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e586 (39.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e451 (29.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e330 (21.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdvanced airway management by EMS (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,934 (48.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e793 (51.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e804 (53.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e720 (47.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e617 (40.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo flow time for CPR (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 [0\u0026ndash;9]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 [0\u0026ndash;10]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 [0\u0026ndash;9]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 [0\u0026ndash;9]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3 [0\u0026ndash;8]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime from witness to hospital arrival (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 [22\u0026ndash;39]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 [23\u0026ndash;41]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32 [23\u0026ndash;40]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30 [22\u0026ndash;38]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e29 [22\u0026ndash;37]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eIn-hospital characteristics\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFirst documented rhythm (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShockable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e468 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e112 (7.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e129 (8.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e124 (8.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e103 (6.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-shockable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,644 (76.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,323 (86.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,194 (80.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1,162 (76.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e965 (63.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of pulse\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e954 (15.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e93 (6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e170 (11.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e229 (15.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e462 (30.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDefibrillation in hospital (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e943 (15.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e259 (17.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e261 (17.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e248 (16.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e175 (11.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime from hospital arrival to blood test (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 [\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7 CR8 CR9 CR10 CR11 CR12\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 [\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 [\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7 CR8 CR9 CR10 CR11\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 [\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7 CR8 CR9 CR10 CR11\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6 [\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7 CR8 CR9 CR10 CR11\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoronary angiography (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,094 (18.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e204 (13.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e238 (15.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e258 (17.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e394 (25.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTarget temperature management (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e774 (12.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e120 (7.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e177 (11.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e212 (14.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e265 (17.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtracorporeal membrane oxygenation initiated after blood test (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e516 (8.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e179 (11.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e161 (10.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e109 (7.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e67 (4.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaboratory data\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLactate (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.8 [8.7\u0026ndash;15.2]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.0 [14.6\u0026ndash;19.7]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.0 [11.3\u0026ndash;15.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.6 [8.9\u0026ndash;12.3]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.4 [5.8\u0026ndash;9.2]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHCO\u003csub\u003e3\u0026ndash;\u003c/sub\u003e (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.5 [11.6\u0026ndash;19.5]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.3 [7.6\u0026ndash;12.8]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.0 [11.5\u0026ndash;16.4]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17.4 [14.5\u0026ndash;19.7]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21.4 [18.6\u0026ndash;23.9]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePaCO\u003csub\u003e2\u003c/sub\u003e (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70.2 [50.6\u0026ndash;89.9]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73.4 [54.0\u0026ndash;97.9]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e72.5 [52.9\u0026ndash;92.7]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e72.1 [52.5\u0026ndash;89.6]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e64.1 [44.3\u0026ndash;80.1]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.19 [0.92\u0026ndash;1.65]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.41 [1.1\u0026ndash;2.2]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.20 [0.95\u0026ndash;1.60]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.14 [0.90\u0026ndash;1.60]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.03 [0.83\u0026ndash;1.31]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eData are presented as medians [interquartile range, IQR] for continuous variables and n (%) for categorical variables.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eAbbreviations: IQR, interquartile range; CPR, cardiopulmonary resuscitation; AED, automated external defibrillator; EMS, emergency medical services\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOutcomes after out-of-hospital cardiac arrest according to base excess values by primary analysis.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003eBase excess (BE), mmol/L\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eQuartile 1\u003c/p\u003e \u003cp\u003e(BE \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\le\\:\\)\u003c/span\u003e\u003c/span\u003e \u0026minus;21.1)\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;1,528\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eQuartile 2\u003c/p\u003e \u003cp\u003e(\u0026minus;\u0026thinsp;21.1\u0026thinsp;\u0026lt;\u0026thinsp;BE\u0026thinsp;\u0026le;\u0026thinsp;\u0026minus;\u0026thinsp;15.7)\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;1,493\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eQuartile 3\u003c/p\u003e \u003cp\u003e(\u0026minus;\u0026thinsp;15.7\u0026thinsp;\u0026lt;\u0026thinsp;BE\u0026thinsp;\u0026le;\u0026thinsp;\u0026minus;\u0026thinsp;10.4)\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;1,515\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eQuartile 4\u003c/p\u003e \u003cp\u003e(BE\u0026thinsp;\u0026gt;\u0026thinsp;\u0026minus;\u0026thinsp;10.4)\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;1,530\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep for trend\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePrimary outcome\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFavourable neurological survival, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e49 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e70 (4.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e148 (9.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e359 (23.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCrude OR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.11 (0.079\u0026ndash;0.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.16 (0.12\u0026ndash;0.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.35 (0.29\u0026ndash;0.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdjusted OR (95% CI)\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.13 (0.090\u0026ndash;0.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.20 (0.15\u0026ndash;0.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.36 (0.28\u0026ndash;0.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSecondary outcome\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurvival, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e101 (6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e170 (11.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e270 (17.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e480 (31.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCrude OR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.15 (0.12\u0026ndash;0.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.28 (0.23\u0026ndash;0.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.47 (0.40\u0026ndash;0.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdjusted OR (95% CI)\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.18 (0.13\u0026ndash;0.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.37 (0.28\u0026ndash;0.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.53 (0.41\u0026ndash;0.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eAbbreviations: OR, odds ratio; CI, confidence interval; CPR, cardiopulmonary resuscitation; EMS, emergency medical services; AED, automated external defibrillator\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003csup\u003e*\u003c/sup\u003eAdjusted for age, sex, cause of arrest, bystander CPR, AED shock delivery by bystander, first documented rhythm at the scene and in hospital, adrenaline administration by EMS, advanced airway management by EMS, defibrillation by EMS, no flow time for CPR, time from witness to hospital arrival, and time from hospital arrival to blood test\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e[Insert Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e here]\u003c/p\u003e \u003cp\u003eRegarding secondary outcomes, the Q1 group had the lowest proportion of 1-month survival, and the Q4 group had the highest, which has a similar tendency to that of the primary outcome.\u003c/p\u003e \u003cp\u003eIn the multivariate logistic regression analysis, the proportion of favourable neurological outcomes in the Q1 group was significantly lower compared with that in the Q4 group (AOR, 0.13; 95% CI, 0.090\u0026ndash;0.18; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn the model in which the variables PCO\u003csub\u003e2\u003c/sub\u003e and creatinine levels upon hospital arrival were added to the primary regression model (Additional file 2: Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e), the trends in associations with outcomes were similar to those in the primary analysis of the original cohort.\u003c/p\u003e \u003cp\u003eIn subgroup analysis, there was an interaction between the presence or absence of prehospital ROSC and neurological outcome (p for interaction\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The neurological outcome in patients with prehospital ROSC decreased when the BE values decreased (p for trend\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), but not in patients without prehospital ROSC (p for trend\u0026thinsp;=\u0026thinsp;0.12, Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Similar to the primary outcome, a strong association was observed between BE and survival in patients with prehospital ROSC.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOutcomes after out-of-hospital cardiac arrest based on base excess and the presence or absence of prehospital ROSC.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eBase excess (BE), mmol/L\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eQuartile 1\u003c/p\u003e \u003cp\u003e(BE \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\le\\:\\)\u003c/span\u003e\u003c/span\u003e \u0026minus;21.2)\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;1,528\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eQuartile 2\u003c/p\u003e \u003cp\u003e(\u0026minus;\u0026thinsp;21.2\u0026thinsp;\u0026lt;\u0026thinsp;BE\u0026thinsp;≦\u0026thinsp;\u0026minus;\u0026thinsp;15.7)\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;1,493\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eQuartile 3\u003c/p\u003e \u003cp\u003e(\u0026minus;\u0026thinsp;15.7\u0026thinsp;\u0026lt;\u0026thinsp;BE\u0026thinsp;≦\u0026thinsp;\u0026minus;\u0026thinsp;10.4)\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;1,515\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eQuartile 4\u003c/p\u003e \u003cp\u003e(BE\u0026thinsp;\u0026gt;\u0026thinsp;\u0026minus;\u0026thinsp;10.4)\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;1,530\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep for trend\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ep for interaction\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePrimary outcome\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eWith prehospital ROSC\u003c/em\u003e\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1,393)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en/N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21/209 (10.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43/281 (15.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e123/339 (36.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e327/564 (58.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCrude OR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.081 (0.050\u0026ndash;0.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.13 (0.091\u0026ndash;0.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.41 (0.31\u0026ndash;0.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eWithout prehospital ROSC\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;4,673)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en/N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28/1,319 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27/1,212 (2.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25/1,176 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32/966 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCrude OR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.63 (0.38\u0026ndash;1.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.67 (0.40\u0026ndash;1.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.63 (0.37\u0026ndash;1.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSecondary outcome\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eWith prehospital ROSC\u003c/em\u003e\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1,393)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en/N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42/209 (20.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e88/281 (31.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e187/339 (55.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e410/564 (72.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCrude OR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.09 (0.06\u0026ndash;0.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.17 (0.13\u0026ndash;0.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.46 (0.35\u0026ndash;0.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eWithout prehospital ROSC\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;4,673)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en/N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59/1,319 (4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e82/1,212 (6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e83/1,176 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e70/966 (7.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCrude OR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.60 (0.42\u0026ndash;0.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.93 (0.67\u0026ndash;1.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.97 (0.70\u0026ndash;1.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eAbbreviations: ROSC, return of spontaneous circulation; OR, odds ratio; CI, confidence interval\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eThe p-value for interaction was calculated between base excess values and the presence of ROSC before the blood test.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e[Insert Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e here]\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eConsistent with the results of several prior studies,[\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]this large-scale, multicentre, prospective study involving\u0026thinsp;\u0026gt;\u0026thinsp;6,000 adult patients with OHCAs demonstrated that lower BE values at hospital arrival were associated with worse neurological outcomes among patients with bystander-witnessed OHCA, even after adjusting for the time interval from the onset of cardiac arrest to the blood test. This suggests that the BE value upon hospital arrival can serve as a potential prognostic indicator of neurological outcomes after OHCA.\u003c/p\u003e \u003cp\u003eCorral et al. reported that venous blood gases measured at the start of CPR in 1552 patients with OHCA indicated that a lower BE was associated with poor neurological outcomes.[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] Additionally, Matthieu et al. found that, among 826 patients with OHCA admitted to the intensive care unit (ICU), a base deficit was associated with ICU mortality.[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] However, neither study accounted for the time interval between the occurrence of cardiac arrest and the BE measurement.[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] As a longer CPR duration is associated with lower BE values and a lower likelihood of favourable neurological outcomes,[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] CPR duration may have confounded these results. Our study demonstrated an association between BE values at hospital arrival and neurological outcomes in patients with OHCA, even after accounting for CPR duration.\u003c/p\u003e \u003cp\u003eSubgroup analysis identified an association between the presence of ROSC before hospital arrival and neurological outcomes. Therefore, cardiac arrest does not uniformly affect all tissues and organs. Highly oxygen-demanding organs, such as the brain and heart, are more prone to early oxygen deprivation, potentially leading to localised metabolic acidosis.[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] Consequently, in patients with cardiac arrest, peripheral blood may not accurately reflect the overall metabolic abnormalities. In particular, patients who do not achieve ROSC may exhibit greater discrepancies between peripheral blood samples and overall metabolic abnormalities than those who achieve ROSC. This discrepancy could be one reason why no association was observed between BE values and neurological outcomes in patients without ROSC. Thus, the presence or absence of prehospital ROSC has a significant effect on outcomes. The lack of association with neurological outcomes in patients who did not achieve prehospital ROSC may be because BE values at hospital arrival alone provide insufficient information regarding neurological outcomes without ROSC. These findings highlight that BE may serve as a valuable indicator of neurological outcomes, specifically in patients who achieve ROSC.\u003c/p\u003e \u003cp\u003eOne of the strengths of this study is the use of BE rather than lactate or pH. BE provides a more comprehensive assessment of metabolic acidosis by reflecting the overall buffering capacity and acid-base status of the body. While pH is an essential indicator of acid-base balance, it is influenced by compensatory mechanisms, such as respiratory compensation, which may obscure the true extent of metabolic acidosis[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Conversely, lactate is a well-established marker of anaerobic metabolism and tissue hypoxia but does not fully capture the overall metabolic derangement, as it can be influenced by hepatic clearance, renal function, and intravenous fluid administration[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In contrast, BE accounts for both lactate-driven acidosis and other metabolic components, offering a more robust reflection of systemic metabolic disturbances in critically ill patients.\u003c/p\u003e \u003cp\u003eA limitation of this study is that the registry did not provide detailed information on each patient\u0026rsquo;s history, comorbidities, and medications. Interpreting BE values can be challenging in individuals with kidney failure, long-term lung disease, or complex acid-base imbalances. For instance, in a patient with ongoing respiratory acidosis experiencing an increase in PCO\u003csub\u003e2\u003c/sub\u003e levels by 10 mmHg over several days, the BE measurement would be 4 mmol/L.[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] However, we observed similar results in the sensitivity analysis adjusted for PCO\u003csub\u003e2\u003c/sub\u003e and creatinine levels upon hospital arrival, which was consistent with the primary analysis (Additional file 2: Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e).\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis observational study of adult patients with OHCA demonstrated that lower BE values upon hospital arrival were associated with worse neurological outcomes. BE values may be an effective prognostic indicator of neurological outcomes, especially in patients with OHCA and prehospital ROSC.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ebase excess\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOHCA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eout-of-hospital cardiac arrest\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eROSC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ereturn of spontaneous circulation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFDMA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eFire and Disaster Management Agency\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCRITICAL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eComprehensive Registry of Intensive Cares for OHCA Survival\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEMS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eemergency medical services\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSBE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003estandard base excess\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCPC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCerebral Performance Category\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCPR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecardiopulmonary resuscitation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAED\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eautomated external defibrillator\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePCO\u003csub\u003e2\u003c/sub\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003earterial carbon dioxide pressure\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eadjusted odds ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCIs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003econfidence intervals\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eintensive care unit\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003eThe study protocol was approved by the Ethics Committee of Kyoto University and each participating institution (R1045). The need for written informed consent was waived.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eYO received the research grant from ZOLL foundation. The other authors state that they have no recognised financial conflicts or personal relationships that might have influenced the work presented in this paper.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis study was supported by a scientific research grant from the JSPS KAKENHI of Japan (22H03313 to Iwami, 22K09139 to Kitamura, and 22K2144 to Nishioka).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eR.O. conducted the conceptualization, data curation, formal analysis, methodology, project administration, software development, visualization, and writing of the original draft. N.N. contributed to the writing \u0026ndash; review \u0026amp; editing, conceptualization, methodology, project administration, funding acquisition, supervision, and validation. T.I. contributed to methodology, project administration, funding acquisition, supervision, and writing \u0026ndash; review \u0026amp; editing. Y.O. and Y.M. participated in data curation, resources, and writing \u0026ndash; review \u0026amp; editing. T.K. contributed to data curation, resources, and funding acquisition. T.Y., S.N., K.Y., C.P., T.N., T.I., K.Y., T.K., M.K., K.N., Y.I., T.S., T.M., H.S., Y.H., A.O., and T.M. were responsible for investigation and resources. S.M., S.Y., S.K., S.K., Y.M., L.Z., and K.K. contributed to data curation and resources. All authors reviewed the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe sincerely appreciate the efforts of all EMS personnel in collecting the Utstein data and extend our gratitude to Ms. Ikuko Nakamura and Yumiko Murai for their support in the CRITICAL study. We also thank our colleagues at the Osaka University Centre of Medical Data Science and the Advanced Clinical Epidemiology Investigator\u0026rsquo;s Research Project for their valuable insights and expertise regarding our study.\u003c/p\u003e\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e \u003cp\u003eThe datasets and/or analyses in this study are not publicly available because the ethics committee did not permit them.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eYan S, Gan Y, Jiang N, Wang R, Chen Y, Luo Z, et al. The global survival rate among adult out-of-hospital cardiac arrest patients who received cardiopulmonary resuscitation: A systematic review and meta-analysis. Crit Care 2020;24:61. https://doi.org/10.1186/s13054-020-2773-2.\u003c/li\u003e\n\u003cli\u003ePichler G, Fazekas F. Cardiopulmonary arrest is the most frequent cause of the unresponsive wakefulness syndrome: A prospective population-based cohort study in Austria. Resuscitation 2016;103:94-8. https://doi.org/10.1016/j.resuscitation.2016.02.023.\u003c/li\u003e\n\u003cli\u003eLaver S, Farrow C, Turner D, Nolan J. Mode of death after admission to an intensive care unit following cardiac arrest. Intensive Care Med 2004;30:2126-8. https://doi.org/10.1007/s00134-004-2425-z.\u003c/li\u003e\n\u003cli\u003eJohnson BA, Weil MH. Redefining ischemia due to circulatory failure as dual defects of oxygen deficits and of carbon dioxide excesses. Crit Care Med 1991;19:1432-8. https://doi.org/10.1097/00003246-199111000-00021.\u003c/li\u003e\n\u003cli\u003eWildenthal K, Mierzwiak DS, Myers RW, Mitchell JH. Effects of acute lactic acidosis on left ventricular performance. Am J Physiol 1968;214:1352-9. https://doi.org/10.1152/ajplegacy.1968.214.6.1352.\u003c/li\u003e\n\u003cli\u003eKellum JA, Song M, Venkataraman R. Effects of Hyperchloremic Acidosis on Arterial Pressure and Circulating Inflammatory Molecules in Experimental Sepsis. Chest 2004;125:243-8. https://doi.org/10.1378/chest.125.1.243.\u003c/li\u003e\n\u003cli\u003eKellum JA, Song M, Li J. Science review: Extracellular acidosis and the immune response: Clinical and physiologic implications. Crit Care 2004;8:331-6. https://doi.org/10.1186/cc2900.\u003c/li\u003e\n\u003cli\u003ePrause G, Ratzenhofer-Comenda B, Smolle-J\u0026uuml;ttner F, Heydar-Fadai J, Wildner G, Spernbauer P, et al. Comparison of lactate or BE during out-of-hospital cardiac arrest to determine metabolic acidosis. Resuscitation 2001;51:297-300. https://doi.org/10.1016/S0300-9572(01)00424-5.\u003c/li\u003e\n\u003cli\u003eCapparelli EV, Chow MSS, Kluger J, Fieldman A. Differences in systemic and myocardial blood acid-base status during cardiopulmonary resuscitation. Crit Care Med 1989;17442-6. https://doi.org/10.1097/00003246-198905000-00013.\u003c/li\u003e\n\u003cli\u003eMakino J, Uchino S, Morimatsu H, Bellomo R. A quantitative analysis of the acidosis of cardiac arrest: a prospective observational study. Crit Care 2005;9:R357-62.\u003c/li\u003e\n\u003cli\u003eOuellet JF, Roberts DJ, Tiruta C, Kirkpatrick AW, Mercado M, Trottier V, et al. Admission base deficit and lactate levels in Canadian patients with blunt trauma: Are they useful markers of mortality? J Trauma Acute Care Surg 2012;72:1532-5. https://doi.org/10.1097/TA.0b013e318256dd5a.\u003c/li\u003e\n\u003cli\u003eMofidi M, Hasani A, Kianmehr N. Determining the accuracy of base deficit in diagnosis of intra-abdominal injury in patients with blunt abdominal trauma. Am J Emerg Med 2010;28:933-6. https://doi.org/10.1016/j.ajem.2009.06.002.\u003c/li\u003e\n\u003cli\u003eAndersen OS, Engel K, J\u0026oslash;rgensen K, Astrup P. A micro method for determination of ph, carbon dioxide tension, base excess and standard bicarbonate in capillary blood. Scand J Clin Lab Invest 1960;12:172-6. https://doi.org/10.3109/00365516009062419.\u003c/li\u003e\n\u003cli\u003eLichtveld RA, Panhuizen IF, Smit RBJ, Holtslag HR, Van Der Werken C. Predictors of death in trauma patients who are alive on arrival at hospital. Eur J Trauma Emerg Surg 2007;33:201. https://doi.org/10.1007/s00068-007-6097-6.\u003c/li\u003e\n\u003cli\u003eBerend K. Diagnostic Use of Base Excess in Acid\u0026ndash;Base Disorders. N Engl J Med 2018;378:1419-28. https://doi.org/10.1056/nejmra1711860.\u003c/li\u003e\n\u003cli\u003eIbrahim I, Chor WP, Chue KM, Tan CS, Tan HL, Siddiqui FJ, et al. Is arterial base deficit still a useful prognostic marker in trauma? A systematic review. Am J Emerg Med. 2016;34:626-35. https://doi.org/10.1016/j.ajem.2015.12.012.\u003c/li\u003e\n\u003cli\u003eCorral Torres E, Hern\u0026aacute;ndez-Tejedor A, Su\u0026aacute;rez Bustamante R, De El\u0026iacute;as Hern\u0026aacute;ndez R, Casado Fl\u0026oacute;rez I, San Juan Linares A. Prognostic value of venous blood analysis at the start of CPR in non-traumatic out-of-hospital cardiac arrest: Association with ROSC and the neurological outcome. Crit Care 2020;24:60. https://doi.org/10.1186/s13054-020-2762-5.\u003c/li\u003e\n\u003cli\u003eTakasu A, Sakamoto T, Okada Y. Arterial base excess after CPR: The relationship to CPR duration and the characteristics related to outcome. Resuscitation 2007;73:394-99. https://doi.org/10.1016/j.resuscitation.2006.10.014.\u003c/li\u003e\n\u003cli\u003eJamme M, Ben Hadj Salem O, Guillemet L, Dupland P, Bougouin W, Charpentier J, et al. Severe metabolic acidosis after out-of-hospital cardiac arrest: risk factors and association with outcome. Ann Intensive Care 2018;8:62. https://doi.org/10.1186/s13613-018-0409-3.\u003c/li\u003e\n\u003cli\u003eKitamura T, Iwami T, Kawamura T, Nagao K, Tanaka H, Hiraide A. Nationwide public-access defibrillation in Japan. N Engl J Med 2010;362:994-1004. https://doi.org/10.1056/nejmoa0906644.\u003c/li\u003e\n\u003cli\u003eKitamura T, Kiyohara K, Sakai T, Matsuyama T, Hatakeyama T, Shimamoto T, et al. Public-Access Defibrillation and Out-of-Hospital Cardiac Arrest in Japan. N Engl J Med 2016;375: 1649-59. https://doi.org/10.1056/nejmsa1600011.\u003c/li\u003e\n\u003cli\u003eJacobs I, Nadkarni V, Bahr J, Berg RA, Billi JE, Bossaert L, et al. Cardiac arrest and cardiopulmonary resuscitation outcome reports: update and simplification of the utstein templates for resuscitation registries. A statement for healthcare professionals from a task force of the international liaison committee on resuscitation (American Heart Association, European Resuscitation Council, Australian Resuscitation Council, New Zealand Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Southern Africa) Resuscitation 2004;63:233-49. https://doi.org/10.1016/j.resuscitation.2004.09.008.\u003c/li\u003e\n\u003cli\u003eYamada T, Kitamura T, Hayakawa K, Yoshiya K, Irisawa T, Abe Y, et al. Rationale, design, and profile of Comprehensive Registry of In-Hospital Intensive Care for OHCA Survival (CRITICAL) study in Osaka, Japan. J Intensive Care 2016;4:10. https://doi.org/10.1186/s40560-016-0128-5.\u003c/li\u003e\n\u003cli\u003eIwami T, Nichol G, Hiraide A, Hayashi Y, Nishiuchi T, Kajino K, et al. Continuous improvements in \u0026ldquo;chain of survival\u0026rdquo; increased survival after out-of-hospital cardiac arrests: A large-scale population-based study. Circulation 2009;119:728-34. https://doi.org/10.1161/CIRCULATIONAHA.108.802058.\u003c/li\u003e\n\u003cli\u003eIwami T, Kawamura T, Hiraide A, Berg RA, Hayashi Y, Nishiuchi T, et al. Effectiveness of bystander-initiated cardiac-only resuscitation for patients with out-of-hospital cardiac arrest. Circulation 2007;116:2900-07. https://doi.org/10.1161/CIRCULATIONAHA.107.723411.\u003c/li\u003e\n\u003cli\u003eJapan Resuscitation Council. JRC guidelines for resuscitation 2020. Tokyo. Igaku Shoin (in Japanese) 2021.\u003c/li\u003e\n\u003cli\u003eBecker LB, Aufderheide TP, Geocadin RG, Callaway CW, Lazar RM, Donnino MW, et al. Primary outcomes for resuscitation science studies: a consensus statement from the American Heart Association. Circulation 2011;124:2158-77. https://doi.org/10.1161/cir.0b013e3182340239.\u003c/li\u003e\n\u003cli\u003eDesquilbet L, Mariotti F. Dose-response analyses using restricted cubic spline functions in public health research. Stat Med 2010;29:1037-57. https://doi.org/10.1002/sim.3841.\u003c/li\u003e\n\u003cli\u003eJouffroy R, Lamhaut L, Guyard A, Phillipe P, Deluze T, Jaffry M, et al. Base excess and lactate as prognostic indicators for patients treated by extra corporeal life support after out hospital cardiac arrest due to acute coronary syndrome. Resuscitation 2014;85:1764-8. https://doi.org/10.1016/j.resuscitation.2014.10.012.\u003c/li\u003e\n\u003cli\u003eMatsuyama T, Ohta B, Kiyohara K, Kitamura T. Cardiopulmonary resuscitation duration and favorable neurological outcome after out-of-hospital cardiac arrest: a nationwide multicenter observational study in Japan (the JAAM-OHCA registry). Crit Care 2022;26:120. https://doi.org/10.1186/s13054-022-03994-2.\u003c/li\u003e\n\u003cli\u003eChoi J, Shoaib M, Yin T, Nayyar G, Shinozaki K, Stevens JF, et al. Tissue-specific metabolic profiles after prolonged cardiac arrest reveal brain metabolome dysfunction predominantly after resuscitation. J Am Heart Assoc 2019;8:e012809. https://doi.org/10.1161/JAHA.119.012809.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Base excess, BE, blood gas, Out-of-hospital cardiac arrest","lastPublishedDoi":"10.21203/rs.3.rs-6257805/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6257805/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eCardiac arrest leads to an abrupt cessation of blood flow, resulting in severe metabolic acidosis. Base excess (BE) is a widely used marker of metabolic acidosis. However, its prognostic value in cardiac arrest patients remains unclear, as previous studies have not adjusted for the time from arrest to blood testing. This study aimed to assess the association between BE levels and neurological outcomes in patients with out-of-hospital cardiac arrest (OHCA) by adjusting the time from the onset of cardiac arrest to blood tests.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis study in Osaka, Japan, enrolled consecutive patients with OHCA transported to 16 centres between 2012 and 2021. We included adult patients (age\u0026thinsp;\u0026ge;\u0026thinsp;18 years) with witnessed OHCA and available BE levels upon hospital arrival. The patients were grouped based on BE quartiles: Q1 (BE\u0026thinsp;\u0026le;\u0026thinsp;\u0026minus;\u0026thinsp;21.1 mmol/L), Q2 (\u0026minus;\u0026thinsp;21.1\u0026thinsp;\u0026lt;\u0026thinsp;BE\u0026thinsp;\u0026le;\u0026thinsp;\u0026minus;\u0026thinsp;15.7 mmol/L), Q3 (\u0026minus;\u0026thinsp;15.7\u0026thinsp;\u0026lt;\u0026thinsp;BE\u0026thinsp;\u0026le;\u0026thinsp;\u0026minus;\u0026thinsp;10.4 mmol/L), and Q4 (BE\u0026thinsp;\u0026gt;\u0026thinsp;\u0026minus;\u0026thinsp;10.4 mmol/L). The primary outcome was 1-month survival with favourable neurological outcomes, defined as a Cerebral Performance Category scale score of 1 or 2.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOf the 23,854 patients with OHCA, 7,591 met the inclusion criteria, and 6,066 were eligible for analysis. The 1-month favourable neurological outcomes based on BE quartile were 23.5%, 9.8%, 4.7%, and 3.2% Q4, Q3, Q2, and Q1, respectively (p for trend\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The adjusted odds ratio for Q1 compared with Q4 was 0.13 (95%CI: 0.090\u0026ndash;0.19). Subgroup analysis showed an interaction between prehospital return of spontaneous circulation (ROSC) and outcome (p for interaction\u0026thinsp;\u0026lt;\u0026thinsp;0.001); neurological outcomes worsened as BE decreased in those with ROSC (p for trend\u0026thinsp;\u0026lt;\u0026thinsp;0.001), but not in those without ROSC (p for trend\u0026thinsp;=\u0026thinsp;0.12).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eLower BE levels upon hospital arrival are associated with worse neurological outcomes and may serve as prognostic indicators, especially in patients with OHCA and prehospital ROSC.\u003c/p\u003e","manuscriptTitle":"Association between base excess level at hospital arrival and neurological outcomes of adult out-of-hospital cardiac arrest: A multicentre cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-01 12:33:25","doi":"10.21203/rs.3.rs-6257805/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e3d8fcc4-a236-4a65-9cc1-d402c7e85007","owner":[],"postedDate":"April 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-05-05T10:08:34+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-01 12:33:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6257805","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6257805","identity":"rs-6257805","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}