Can Heparin Improve Clinical Outcomes in Cardiac Arrest? A Retrospective Cohort Study from the EICU Collaborative Research Database

Can Heparin Improve Clinical Outcomes in Cardiac Arrest? 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A Retrospective Cohort Study from the EICU Collaborative Research Database Fei Gao, Yun Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-740945/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: Studies indicate that heparin can improve survival in patients with out-of-hospital cardiac arrest. Thus, we aimed to investigate the effect of heparin on hospitalized patients with cardiac arrest. Methods: Clinical data of cardiac arrest patients from the eICU Collaborative Research Database V2.0 were retrospectively analyzed. We compared neurological prognosis and primary outcomes in a heparin group that received unfractionated heparin or low molecular weight heparin with a non-heparin group. Additionally, we compared the two heparin sub-groups. Results: After propensity score matching, there were 673 patients in the heparin group and 1346 patients in the non-heparin group. The Glasgow Coma Scale score was significantly better in the heparin group (P0.05). Intensive care unit (ICU) mortality and hospital mortality rates were significantly lower in the heparin group (P<0.05). The duration of mechanical ventilation, length of stay in ICU, and length of stay in hospital were significantly longer in the heparin group (P<0.05). Median survival time was significantly longer in the heparin group (P<0.001). In the comparison of patients who received unfractionated heparin and low molecular weight heparin (267 in each group), there were no significant differences in Glasgow Coma Scale score, ICU mortality, hospital mortality, or median survival time between the two groups (P>0.05). Conclusions: Heparin administration may be beneficial in reducing the mortality rate and prolonging the survival time of in-hospital patients with cardiac arrest. It may also improve the prognosis of neurological function to a certain extent. Outcomes were not significantly different between patients who received unfractionated heparin and those who received low molecular weight heparin. Critical Care & Emergency Medicine Cardiac arrest Heparin Retrospective study Propensity Score Matching Figures Figure 1 Figure 2 Background Cardiac arrest is a common and lethal condition frequently encountered by emergency medicine providers. Achieving improvements in survival rates and good neurological outcomes remains a challenge [ 1 ]. There have many studies on drug therapy for cardiac arrest; however, currently there exists a lack of drugs with definite efficacy for improving the prognosis of neurological function and clinical outcomes in patients with cardiac arrest [ 2 – 5 ]. Animal studies have shown that cardiac arrest is accompanied by extensive microthrombosis in the brain [ 6 ]. Clinical reports suggest that thrombosis is often seen in the heart, pulmonary vessels, and other areas in a cardiac arrest [ 7 – 9 ]. Coronary thrombosis and pulmonary embolism are also common causes of cardiac arrest [ 10 , 11 ]. Furthermore, current guidelines recognize thrombosis as a potential (and reversible) cause of cardiac arrest [ 12 ]. Moreover, hypothermia and hypercoagulability are common pathophysiological processes following cardiac arrest [ 13 , 14 ]. Therefore, treatment of the coagulation state and thrombosis may become one of the effective measures for the treatment of cardiac arrest. Thrombolytic is not overly recommended and routine used in cardiac arrest [ 15 , 16 ], with the difficulty in determining early etiology, inability of thrombolytic therapy in improving survival, and the increased risk of bleeding events being the main reasons [ 9 , 15 ]. However, anticoagulant therapy is considered to be associated with significantly fewer bleeding-related complications than thrombolytic therapy [ 17 ]. Animal experimental studies have shown that heparin anticoagulant therapy can significantly improve the prognosis of cardiopulmonary resuscitation model rats [ 18 ]. Moreover, small retrospective studies have shown that aspirin and heparin (AH) can significantly improve survival in patients with out-of-hospital cardiac arrest [ 19 , 20 ]. Therefore, we aimed to establish whether heparin anticoagulant therapy can improve the prognosis of patients’ neurological function and the patients’ clinical outcomes. This study retrospectively analyzed the relationship between the use of unfractionated heparin (UFH) or low molecular weight heparin (LMWH) in patients with cardiac arrest from a multicenter electronic intensive care unit (ICU) database, and to explore patient prognosis and the prospect of the clinical application of heparin in these patients. Materials And Methods Study design and database We conducted a retrospective cohort study using the eICU-CRD V2.0 database. Because all patient records in this database are anonymous, the Review Committee of this study determined that there was no need to obtain informed consent from individual patients. The eICU-CRD V2.0 database was released on 17 May 2018. The database contains clinical data from 200,859 patients in multiple ICUs in the United States between 2014 and 2015. In this study, the corresponding author completed the training on ‘Protection of Human Subjects’ and obtained permission to use the database (certification number: 36026306). The study was approved by the Research Ethics Committee of Wuxi People's Hospital (KS202112). Study subjects All subjects were derived from the eICU-CRD V2.0 database. The inclusion criteria were: (1) Age ≥ 18 years and (2) a diagnosis of cardiac arrest. The exclusion criteria were: (1) missing information on one of sex, age, height, weight, acute physiology and chronic health evaluation score (APACHE-IV), initial simplified acute physiology score (SAPS-II), or Glasgow Coma Scale (GCS) score; and (2) lack of information on ICU and discharge outcomes. Admission venues included emergency department, floor, operation room, and direct admission. Therefore, both in- and out-of-hospital cardiac arrest events were included. Data extraction All data in this study were extracted from the database using Structured Query Language (SQL) scripts and Navicat for PostgreSQL (11.2.9) software [ 21 ]. The extracted variables included: (1) baseline characteristics: sex, age, height, weight, APACHE IV, SAPS Ⅱ score, GCS score, race, type of ICU; (2) diagnosis, initial rhythm types, witnessed or not, and whether or not 15 min have passed before CPR was started; (3) treatment status, including the application of various vasoactive drugs, mechanical ventilation and length, acute renal failure (ARF), and hemodialysis; (4) neurological outcomes, including the highest GCS score, change in mental status, encephalopathy (post-anoxic), seizures, dementia, persistent vegetative state, ventilation (spontaneous-adequate); and (5) mortality and length of stay (LOS), including the status of ICU discharge, LOS in ICU, the status of hospital discharge, and LOS in hospital. Statistical analysis Continuous variables that were normally distributed were described as mean ± standard deviation (SD), comparison between the two groups was performed using the independent sample t-test, and comparison among multiple groups was performed using an analysis of variance (ANOVA). Counting data and classification variables were described by frequency and percentage, and a chi-square test was used for comparison between these groups. To reduce the confounding influence of the differences in baseline characteristics, propensity score matching (PSM) (1:2 in heparin group and non-heparin group, 1:1 in UFH and LMWH) was performed using ‘nearest neighbor’ matching, with a caliper width of 0.02 across sex, age, BMI, APACHE-Ⅳ, SAPS-Ⅱ, initial heart rhythm, and the presence of witnesses. A Kaplan-Meier survival curve (log rank method) was used to evaluate the difference in survival time between the two groups. A significance level was set at 0.05 (for a two-tailed analysis). All analyses were performed with the use of IBM SPSS Statistics software (version 26.0; IBM Corp., Armonk, NY, USA), and R software (version 2.15.3; The R Foundation for Statistical Computing, Vienna, Austria) was used for PSM. Results Patient characteristics A total of 5995 patients were studied, including 4890 in the non-heparin group and 1105 in the heparin group (755 in the UFH group and 350 in the LMWH group) (Fig. 1 ). ANOVA showed that there were no significant differences in age, sex, GCS score, presence of a witness, CPR time, or mechanical ventilation among the three groups (all P > 0.05). BMI, APACHE-Ⅳ, APS-Ⅱ, race, type of ICU, initial rhythm, vasopressor, and the incidence of ARF and hemodialysis were significantly different (all P < 0.05). In the heparin and non-heparin groups, which were matched 1:2 (673 cases for heparin group and 1346 cases for the non-heparin group), there were no significant differences between the two groups in terms of age, sex, BMI, severity of the disease, initial rhythm, witnesses, vasopressor used, ARF, or rate of hemodialysis (all P > 0.05) (Table 1 ). Table 1 Demographic characteristics and basic characteristic Variables Before PSM After PSM non-Heparin N = 4890 UFH N = 755 LMWH N = 350 P value non-Heparin N = 1346 Heparins N = 673 P value Age(years), mean ± sd 63.44±15.44 63.55±14.81 63.26±14.92 0.88 63.38±14.94 63.42±15.22 0.95 Sex(male), n (%) 2874(58.77) 452(59.87) 198(56.57) 0.63 802(59.58) 397(58.99) 0.79 BMI (kg/m2), mean ± sd 28.67 ± 10.62 30.17 ± 10.01 29.78 ± 11.49 < 0.001 30.35 ± 8.37 30.59 ± 8.86 0.56 Disease severity scores (worst within 24 hours), mean ± sd APACH-IV 97.03 ± 7.67 93.47 ± 36.19 89.21 ± 4.15 < 0.001 92.9 ± 37.27 94.14 ± 35.26 0.48 APS-II 85.73 ± 6.41 81.99 ± 34.86 77.31 ± 3.06 < 0.001 81.29 ± 6.82 82.6 ± 34.68 0.44 GCS 6.22 ± 4.31 6.39 ± 4.34 6.77 ± 4.41 0.12 9.77 ± 4.5 9.83 ± 4.31 0.62 Ethnicity, n (%) < 0.001 < 0.001 African American 652(13.33) 122(16.16) 1(0.29) 177(13.15) 128(19.02) Asian 73(1.49) 16(2.12) 10(2.86) 15(1.11) 7(1.04) Caucasian 3605(73.72) 523(69.27) 232(66.29) 1024(76.08) 463(68.8) Hispanic 164(3.35) 46(6.09) 33(9.43) 36(2.67) 37(5.5) Native American 40(0.82) 3(0.4) 1(0.29) 13(0.97) 4(0.59) Other/Unknown 356(7.28) 45(5.96) 16(4.57) 81(6.02) 34(5.05) Initial rhythm, n (%) 0.003 0.07 Asystole 484(9.9) 92(12.19) 38(10.86) 133(9.88) 58(8.62) PEA 842(17.22) 179(23.71) 74(21.14) 211(15.68) 134(19.91) VF 500(10.22) 140(18.54) 58(16.57) 184(13.67) 133(19.76) VT 256(5.24) 70(9.27) 11(3.14) 138(10.25) 70(10.4) unknown 170(3.48) 28(3.71) 10(2.86) 48(3.57) 24(3.57) Witnessed, n (%) 0.22 0.53 witnessed, 15 min CPR 446(9.12) 84(11.13) 34(9.71) 97(7.21) 64(9.51) un-witnessed 246(5.03) 40(5.3) 19(5.43) 75(5.57) 39(5.79) Vasopressor, n (%) 2035(41.62) 337(44.64) 120(34.29) 0.005 695(51.63) 333(49.48) 0.36 Early Defibrillation, n (%) 129(2.64) 17(2.25) 7(2.00) < 0.001 32(2.38) 12(1.78) 0.389 AMI, n (%) 111(2.27) 31(4.11) 3(0.86) < 0.001 29(2.15) 19(2.82) 0.353 MV, n (%) 3652(74.68) 567(75.1) 264(75.43) 0.93 974(72.36) 543(80.68) < 0.01 ARF, n (%) 988(20.2) 192(25.43) 67(19.14) 0.003 287(21.32) 166(24.67) 0.10 Dialysis, n (%) 526(10.76) 109(14.44) 27(7.71) 0.001 131(9.73) 83(12.33) 0.08 DVT prophylaxis 2380 680 311 < 0.001 980 620 < 0.001 Drug therapy 0 359 175 - 0 368 - Compression devices 2380 256 111 < 0.001 980 252 < 0.001 Dialysis 526 109 27 0.001 131 83 0.08 Abbreviations: UFH = Unfractionated heparin, LMWH = Low molecular weight heparin, PSM = Propensity Score Match, BMI = body mass index, APACHE-IV: acute physiology and chronic health evaluation score, APS-II = simplified acute physiology score, GCS = Glasgow Coma Score, MV = Mechanical ventilation, PEA = pulseless electrical activity, VF = ventricular fibrillation, VT = ventricular tachycardia, CPR = cardiopulmonary resuscitation, AMI = acute myocardial infarction, ARF = acute renal failure, DVT = deep vein thrombosis Clinical outcomes between heparin and non-heparin groups Neurological prognosis The heparin group was significantly better than the non-heparin group for three measures: the maximum GCS score, various GCS scores (motor, verbal, and eyes), and GCS score classification (the degree of consciousness disturbance (13–15 was mild, 9–12 was moderate, and 3–8 was severe) (P < 0.05). The incidence of changed mental status, encephalopathy (post-anoxic), seizures, and the duration of mechanical ventilation were higher in the heparin group than in the non-heparin group (P 0.05) (Table 2 ). Table 2 Clinical outcomes between Heparins and non-Heparins, UFH and LMWH. Clinical outcomes Heparins N = 673 non-Heparins N = 1346 P value UFH N = 267 LMWH N = 267 P value GCS (max), mean ± sd 11.89 ± 4.4 11.29 ± 4.75 0.007 12.06 ± 4.48 11.96 ± 4.16 0.81 GCS (motor), mean ± sd 5.02 ± 1.73 4.75 ± 1.94 0.003 5.02 ± 1.79 5.13 ± 1.6 0.51 GCS (verbal), mean ± sd 3.59 ± 1.81 3.39 ± 1.87 0.025 3.72 ± 1.78 3.53 ± 1.81 0.28 GCS (eyes), mean ± sd 3.43 ± 1.12 3.24 ± 1.24 0.001 3.39 ± 1.15 3.49 ± 1.06 0.38 GCS 13–15, n (%) 422(62.7) 792(58.84) 0.041 147(55.06) 135(50.56) 0.21 GCS 9–12, n (%) 67(9.96) 153(11.37) 18(6.74) 29(10.86) GCS 3–8, n (%) 161(23.92) 395(29.35) 48(17.98) 50(18.73) Mental status changed, n (%) 226(33.58) 327(24.29) < 0.001 65(24.34) 118(44.19) < 0.001 Encephalopathy (post-anoxic), n (%) 86(12.78) 108(8.02) 0.001 19(7.12) 47(17.6) < 0.001 Seizures, n (%) 92(13.67) 71(5.27) < 0.001 23(8.61) 51(19.1) < 0.001 Dementia, n (%) 6(0.89) 11(0.82) 0.86 2(0.75) 4(1.5) 0.41 Persistent vegetative state, n (%) 15(2.22) 20(1.49) 0.23 5(1.87) 6(2.25) 0.76 Ventilation (Spontaneous-adequate), n (%) 392(58.25) 779(57.88) 0.87 166(62.17) 161(60.3) 0.66 Ventilation LOS (days), mean ± sd 6.04 ± 6.05 4.63 ± 4.63 < 0.001 5.26 ± 4.46 6.36 ± 6.39 0.021 ICU mortality, n (%) 209(31.05) 503(37.37) 0.005 78(29.21) 86(32.21) 0.45 ICU LOS (days), mean ± sd 7.07 ± 8.38 4.94 ± 5.8 < 0.001 5.94 ± 5.41 7.29 ± 9.85 0.05 Hospital mortality, n (%) 272(40.42) 622(46.21) 0.013 100(37.45) 115(43.07) 0.19 Hospital LOS (days), mean ± sd 12.25 ± 11.12 9.47 ± 9.74 < 0.001 10.37 ± 9.01 12.36 ± 11.58 0.027 Abbreviations: UFH = Unfractionated heparin, LMWH = Low molecular weight heparin, GCS = Glasgow Coma Score, LOS = Length of stay, ICU = Intensive care unit Mortality and LOS The ICU mortality rate (31.05% vs. 37.37%, P = 0.005) and hospital mortality rate (40.42% vs. 46.21%, P = 0.013) in the heparin group were significantly lower than that in the non-heparin group (P < 0.05). However, the LOS was significantly longer in the heparin group compared to the non-heparin group for mechanical ventilation LOS (4.63 ± 4.63 days vs. 6.04 ± 6.05 days, P < 0.001), ICU LOS (4.94 ± 5.80 days vs. 7.07 ± 8.38 days, P < 0.001), and total hospital LOS (9.47 ± 9.74 days vs. 12.25 ± 11.12 days, P < 0.001) (Table 2 ). Clinical outcomes in UFH and LMWH The UFH group and LMWH group were matched 1:1 according to sex, age, BMI, APACHE-Ⅳ, and SAPS-Ⅱ. Finally, 267 pairs of patients were successfully matched. Neurological prognosis There was no statistical significance in the maximum GCS score, various GCS scores, and GCS classification between the two groups (P > 0.05). The incidence of changed mental status, encephalopathy (post-anoxic), seizures, and the duration of mechanical ventilation were significantly higher in the LMWH group than in the UFH group (P 0.05) (Table 2 ). Mortality and LOS There were no significant differences in ICU mortality (29.21% vs. 32.21%, P = 0.45), ICU LOS (5.94 ± 5.41 days vs. 7.29 ± 9.85 days, P = 0.05), and hospitalization mortality (37.45% vs. 43.07%, P = 0.19) between the UFH and LMWH groups. The LOS for mechanical ventilation (5.26 ± 4.46 days vs. 6.36 ± 6.39 days, P = 0.021) and hospital LOS (10.37 ± 9.01 days vs. 12.36 ± 11.58 days, P = 0.027) were significantly shorter in the UFH group compared to the LMWH group, as shown in Table 2 . Survival time The median survival time of the heparin group (20.75 ± 2.37 days) was longer than that of the non-heparin group (14.63 ± 1.26), and this difference was significant (P < 0.001). There was no statistically significant difference in the median survival time between the UFH group (20.96 ± 5.09 days) and the LMWH group (19.54 ± 3.73 days) (P = 0.89), as shown in Fig. 2 . Discussion In this study, patients in the heparin group had significantly improved neurological outcomes (GCS score), ICU mortality, hospital mortality, and survival time compared with those in the non-heparin group. There was no significant difference in the prognosis of some neurological outcomes (spontaneous-adequate ventilation, dementia, and persistent vegetative status). There was no significant difference between the UFH group and the LMWH group for these clinical outcomes. The study cohort was from a United States database. Data show that approximately 30–40% of hospitalized cardiac arrest patients die in the ICU and 40–50% die in the hospital, which is consistent with previous reports [ 1 , 20 ]. Because the guidelines do not recommend heparin for the treatment of cardiac arrest, only 18.43% (1105 patients) in this cohort received heparin for a variety of reasons, and UFH use was about twice as high as LMWH use. In a retrospective study of 384 patients by Grabmaier and his colleagues, the use of AH in patients with out-of-hospital cardiac arrest improved survival from 34–59.4%. AH was found to be an independent predictor of discharge survival in the regression model (hazard ratio 0.60 [0.44–0.82], P = 0.002) [ 20 ]. In this study, the survival rate of the control group was 44.79%, higher than that of the placebo group in the previous study by Grabmaier, and the final discharge survival rate of the heparin group was 59.58%, which was similar to that of the AH group in the Grabmaier study. Although some studies have suggested that the combination of anticoagulant and antiplatelet is not necessary for most situations, the combination of the two studies suggests that the combination of anticoagulant and antiplatelet may improve patient and clinical outcomes. If the treatment levels in the two studies were similar, aspirin’s contribution to survival would be about 10%, and heparin’s contribution to survival would be about 15%, without taking into consideration any cross-actions. More rigorous prospective, double-blind, crossover studies are needed to further clarify the separate effects of aspirin and heparin and whether there is a synergistic interaction between them. In addition, the current study found that heparin significantly extended the survival time of patients with cardiac arrest, which has not been reported in previous studies; however, heparin patients also had longer hospital stays. Neurological outcome is another important clinical outcome in patients with cardiac arrest. The maximum GCS score during the disease was used to evaluate the patient’s state of consciousness. Both the mean value of the maximum GCS and the mean value of each item (motor, verbal, or eyes) were better in the heparin group. A stratified GCS analysis also showed that the heparin group had a higher ratio of good cerebral performance (GCS score of 13–15) (62.7% vs. 58.84%). Moreover, Grabmaier’s research showed that pre-hospital AH administration was associated with favorable neurological outcomes (odds ratio [OR] 2.25 [1.31–3.87], P = 0.003). Patients with AH were more likely to gain return of the spontaneous circulation (OR 2.22 [1.45–3.42], P < 0.001) [ 19 ]. However, it was also found that the incidence of changed mental status, encephalopathy (post-anoxic), seizures, and the duration of mechanical ventilation was longer in the heparin group. This may be associated with an increase in the survival rate of patients who do not have a good neurological outcome under current treatment but whose prognosis is clearly better than that of death. As common anticoagulants, in addition to large differences in molecular weight, UFH and LMWH also have large differences in terms of mechanism of action, pharmacokinetics, and risk of adverse reactions [ 22 ]. UFH can act on variety of thrombin enzymes and can also act on platelets, which have a shorter half-life, lower bioavailability, and pose a higher risk of bleeding [ 23 ]. To further determine whether there is a difference between the two types of heparin, we investigated their effects on clinical outcomes. The results showed that there was no significant difference in the major clinical and neurological outcomes between the two groups. However, UFH was associated with a tendency towards lower ICU and hospital mortality rates compared to LMWH. The same trend was observed for GCS scores. Whether this trend is related to the antiplatelet effect of ordinary heparin needs further study. Because we did not analyze bleeding-related complications, it is unclear whether the common heparin group had a higher risk of bleeding. However, Grabmaier's study showed that AH did not increase the risk of bleeding in patients with cardiac arrest [ 19 ]. Animal studies have shown that a marked activation of blood coagulation occurs and that microthrombi are found in the cerebral vessels after a cardiac arrest of 5 to 10 min [ 18 ]. Microthrombosis, microcirculation disorder, secondary tissue ischemia and hypoxia, and oxygen metabolism disorder followed by a series of nerve cell injury are some of the important influences on the neurological prognosis of cardiac arrest [ 24 – 26 ], and the formation of systemic microthrombosis is also an important mechanism affecting tissue oxygen metabolism and organ function damage [ 25 ]. Resolving the influence of microthrombosis on various organs of cardiac arrest may be an important mechanism for heparin to improve the prognosis of cardiac arrest patients. In addition, the cause of cardiac arrest in most patients is related to thrombosis of blood vessels in the heart or lungs [ 11 ]. Furthermore, the anticoagulant and antiplatelet effects of heparin have a good effect on the improvement of heart or pulmonary vascular infarction. Cardiac arrest is not a contraindication to the use of heparin in clinical practice; however, the occurrence of bleeding complications is a concern. Interestingly, some studies have shown that heparin does not significantly increase the risk of bleeding in cardiac arrest [ 27 , 28 ]. Our study had some limitations. First, heparin may be used for hemodialysis, thrombosis, hemodynamic monitoring, hypercoagulability, or disseminated intravascular coagulation; as this study was limited by data extraction, we could not analyze the reasons for administration of heparin. Second, when heparin anticoagulants are used for different reasons, the frequency, dose, and cycle of medication vary greatly; hence, the total dose of each sample was difficult to obtain, and the dose-response analysis was limited. Third, due to data limitations, we could not determine which bleeding complications were causally associated with heparin; therefore, no comparison of bleeding-related complications was made. Fourth, lack of heparin administration in some cases may stem from a decision to discontinue care due to poor prognosis. Data on the proportion of cases with limited or discontinued treatment because of poor prognosis was unavailable in the database. Finally, coagulation status, D-dimer, and other indicators may directly affect the use of heparin in some patients. Patients’ thrombosis risk score may also be an important basis for the prevention of deep vein thrombosis. The distribution of these factors among each group, the use of heparin, and the effect on outcomes represents a more complex interaction, and this was not covered in this study. Therefore, further research is needed. Conclusions According to the findings of this retrospective cohort study, heparin (UFH or LMWH) may be a promising option for treating hospitalized patients with cardiac arrest because heparin reduced mortality rates and prolonged survival times of in-hospital patients with cardiac arrest and improved prognosis of neurological function to a certain extent. Furthermore, outcomes were not significantly different between patients who received UFH and those who received LMWH. Prospective, randomized controlled studies with larger sample sizes are needed to clarify the value of heparin in treating patients with cardiac arrest. List Of Abbreviations AH, aspirin and heparin; ANOVA, analysis of variance; APACHE-IV, Acute Physiology and Chronic Health Evaluation Score; ARF, acute renal failure; GCS, Glasgow Coma Scale; ICU, intensive care unit; LMWH, low molecular weight heparin; LOS, length of stay; OR, odds ratio; PSM, Propensity Score Matching; SAPS-II, Simplified Acute Physiology Score; SD, standard deviation; SQL, Structured Query Language; UFH, unfractionated heparin. Declarations Ethics approval and consent to participate The corresponding author (YZ) completed the training on ‘Protection of Human Subjects’ and obtained permission to use the database (certification number: 36026306). The study was approved by the Research Ethics Committee of Wuxi People's Hospital (KS202112). Because all patient records in the database are anonymous, the Review Committee of this study waived the requirement to obtain informed consent from individual patients. Consent for publication Not applicable. Availability of data and material The data used in this research is available from the eICU website: https://eicu-crd.mit.edu/. Competing interests The authors declare that they have no competing interests. Funding This work was funded by the Top Talent Support Program for young and middle-aged people of the Wuxi Health Committee (project number: BJ2020007). Authors’ contributions FG was responsible for data validation and writing of the manuscript, and YZ was responsible for research design, data extraction, and analysis. All authors have read and approved the final manuscript. Acknowledgments The authors would like to thank the Philips eICU Research Institute and Philips Healthcare for contribution of the data and Editage ( www.editage.cn ) for English language editing. 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Oami T, Oshima T, Oku R, Nakanishi K. Successful treatment of pulmonary embolism-induced cardiac arrest by thrombolysis and targeted temperature management during pregnancy. Acute Med Surg. 2018;5(3):292–5. Böttiger BW, Arntz HR, Chamberlain DA, Bluhmki E, Belmans A, Danays T, Carli PA, Adgey JA, Bode C, Wenzel V, et al. Thrombolysis during resuscitation for out-of-hospital cardiac arrest. N Engl J Med. 2008;359(25):2651–62. Wang Y, Wang M, Ni Y, Liang B, Liang Z. Can Systemic Thrombolysis Improve Prognosis of Cardiac Arrest Patients During Cardiopulmonary Resusci tation? A Systematic Review and Meta-Analysis. J Emerg Med. 2019;57(4):478–87. Wahby KA, Jhajhria S, Dalal BD, Soubani AO. Heparin dosing in critically ill patients undergoing therapeutic hypothermia following cardiac arrest. Resuscitation. 2014;85(4):533–7. Liu W, Wang Y, Zhou X, Hai K, Jia D, Ye Q. The Effect of Prophylactic Anticoagulation with Heparin on the Brain Cells of Sprague-Dawley Rats in a Cardiopulmonary-Cerebral Resuscitation Model. Evid Based Complement Alternat Med. 2020;2020:8430746. Grabmaier U, Rizas KD, Massberg S, Weckbach L, Fischer M, German Resuscitation Registry Study G. Association of prehospital acetylsalicylic acid and heparin administration with favorable neurological outcome after out-of-hospital cardiac arrest: a matched cohort analysis of the German Resuscitation Registry. Intensive Care Med. 2020;46(10):1934–6. Grabmaier U, Rizas KD, Berghof J, Huflaender Y, Wiegers C, Wakili R, Kaspar M, Angstwurm M, Massberg S, Weckbach LT, et al. Association between survival and non-selective prehospital aspirin and heparin administration in patients with out-of-hospital cardiac arrest: a propensity score-matched analysis. Intensive Care Med. 2018;44(4):537–9. Pollard TJ, Johnson AEW, Raffa JD, Celi LA, Mark RG, Badawi O. The eICU Collaborative Research Database, a freely available multi-center database for critical care research. Sci Data. 2018;5(11):180178. Macki M, Fakih M, Anand SK, Suryadevara R, Elmenini J, Chang V. A direct comparison of prophylactic low-molecular-weight heparin versus unfractionated heparin in neu rosurgery: A meta-analysis. Surg Neurol Int. 2019;10:202. Tao E, Luo YL, Tao Z, Wan L. A meta-analysis of bridging anticoagulation between low molecular weight heparin and heparin. Medicine. 2020;99(3):e18729. Zhou M, Yu T, Fang X, Ge Q, Song F, Huang Z, Jiang L, Wang P. Short-term dietary restriction ameliorates brain injury after cardiac arrest by modulation of mitocho ndrial biogenesis and energy metabolism in rats. Ann Transl Med. 2021;9(1):8. Coppler PJ, Elmer J. Mitochondrial resuscitation after cardiac arrest. Resuscitation 2021,162(5):433–434. Gill R, Teitcher M, Ruland S. Neurologic complications of cardiac arrest. Handb Clin Neurol. 2021;177:193–209. Gorog DA, Price S, Sibbing D, Baumbach A, Capodanno D, Gigante B, Halvorsen S, Huber K, Lettino M, Leonardi S, et al. Antithrombotic therapy in patients with acute coronary syndrome complicated by cardiogenic shock or o ut-of-hospital cardiac arrest: a Joint Position Paper from the European Society of Cardiology (ESC) Working Group on Thrombosis, in association with the Acute Cardiovascular Care Association (ACCA) an d European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J Cardiovasc Pharmacother. 2021;7(2):125–40. Joffre J, Varenne O, Bougouin W, Rosencher J, Mira JP, Cariou A. Stent thrombosis: an increased adverse event after angioplasty following resuscitated cardiac arrest. Resuscitation. 2014;85(6):769–73. 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-740945","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research","associatedPublications":[],"authors":[{"id":42801602,"identity":"2b596467-a1b5-4a80-8e9b-ed17504b1307","order_by":0,"name":"Fei Gao","email":"","orcid":"","institution":"Nanjing Medical University Affiliated Wuxi People's Hospital: Wuxi People's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fei","middleName":"","lastName":"Gao","suffix":""},{"id":42801603,"identity":"fc84ce6c-4d8c-410c-878f-1aeb73b94be6","order_by":1,"name":"Yun Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5ElEQVRIiWNgGAWjYDACCSjNz8CQAKIZG4jWItlAshaDAxCasBb52c3PHn5tO5xnfLvh6WYeBhvZDQeYnz3Ap4VxzjFzY9m2w8Vmdw6k3eZhSDPecIDN3ACfFmaJBDNpybbDidtuJIC0HE7ccICHTQKfFjaJ9G9gLZtngLX8J6yFRyLHTPIjUMsGCbCWA4S1SEjklEkznEtPnAF02M05BsnGMw+zmeHVIj8jfZvkjzLrxP4ZOWk33lTYyfYdb36GVwsIMPOygd2YAIwdEJeQeiBg/PEHRLEfIELtKBgFo2AUjEQAACzmTAI9DeiKAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-7889-2139","institution":"Wuxi People's Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Yun","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2021-07-22 06:45:59","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-740945/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-740945/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":12031883,"identity":"562e6366-363b-43d5-bb84-1203eef5bfcf","added_by":"auto","created_at":"2021-08-02 14:45:06","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":330826,"visible":true,"origin":"","legend":"Process of selecting the study subjects. eICU=The Philips Electronic ICU, UFH=unfractionated heparin, LMWH=Low molecular weight heparin","description":"","filename":"OnlineFig1.png","url":"https://assets-eu.researchsquare.com/files/rs-740945/v1/8b55eaccc42fd68de28ab4f1.png"},{"id":12032148,"identity":"3165d1e6-1b4c-43cb-8275-e45f20668c59","added_by":"auto","created_at":"2021-08-02 14:48:06","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":547281,"visible":true,"origin":"","legend":"Kaplan-Meier survival curves depict cumulative survival to hospital discharge. A. The median survival time of the heparin group and the non-heparin group are 20.75±2.37 days and 14.63±1.26 days. The survival time of the heparin group is longer than that of the non-heparin group (P\u003c0.001). B. The median survival time of the UFH group and the LMWH group (after matching) are 20.96±5.09 days and 19.54±3.73 days, and this difference is not significant (P=0.89). UFH=unfractionated heparin, LMWH=Low molecular weight heparin","description":"","filename":"OnlineFig2.png","url":"https://assets-eu.researchsquare.com/files/rs-740945/v1/cbef8a5f76f8584f84094634.png"},{"id":13707451,"identity":"4070a361-7575-499d-958a-90c4be263890","added_by":"auto","created_at":"2021-09-17 14:02:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":624990,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-740945/v1/2ebdcabb-f674-4f70-8734-110ff2bf91aa.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eCan Heparin Improve Clinical Outcomes in Cardiac Arrest? A Retrospective Cohort Study from the EICU Collaborative Research Database\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eCardiac arrest is a common and lethal condition frequently encountered by emergency medicine providers. Achieving improvements in survival rates and good neurological outcomes remains a challenge [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. There have many studies on drug therapy for cardiac arrest; however, currently there exists a lack of drugs with definite efficacy for improving the prognosis of neurological function and clinical outcomes in patients with cardiac arrest [\u003cspan additionalcitationids=\"CR3 CR4\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAnimal studies have shown that cardiac arrest is accompanied by extensive microthrombosis in the brain [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Clinical reports suggest that thrombosis is often seen in the heart, pulmonary vessels, and other areas in a cardiac arrest [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Coronary thrombosis and pulmonary embolism are also common causes of cardiac arrest [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Furthermore, current guidelines recognize thrombosis as a potential (and reversible) cause of cardiac arrest [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Moreover, hypothermia and hypercoagulability are common pathophysiological processes following cardiac arrest [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Therefore, treatment of the coagulation state and thrombosis may become one of the effective measures for the treatment of cardiac arrest.\u003c/p\u003e \u003cp\u003eThrombolytic is not overly recommended and routine used in cardiac arrest [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], with the difficulty in determining early etiology, inability of thrombolytic therapy in improving survival, and the increased risk of bleeding events being the main reasons [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. However, anticoagulant therapy is considered to be associated with significantly fewer bleeding-related complications than thrombolytic therapy [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Animal experimental studies have shown that heparin anticoagulant therapy can significantly improve the prognosis of cardiopulmonary resuscitation model rats [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Moreover, small retrospective studies have shown that aspirin and heparin (AH) can significantly improve survival in patients with out-of-hospital cardiac arrest [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Therefore, we aimed to establish whether heparin anticoagulant therapy can improve the prognosis of patients\u0026rsquo; neurological function and the patients\u0026rsquo; clinical outcomes. This study retrospectively analyzed the relationship between the use of unfractionated heparin (UFH) or low molecular weight heparin (LMWH) in patients with cardiac arrest from a multicenter electronic intensive care unit (ICU) database, and to explore patient prognosis and the prospect of the clinical application of heparin in these patients.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and database\u003c/h2\u003e \u003cp\u003eWe conducted a retrospective cohort study using the eICU-CRD V2.0 database. Because all patient records in this database are anonymous, the Review Committee of this study determined that there was no need to obtain informed consent from individual patients. The eICU-CRD V2.0 database was released on 17 May 2018. The database contains clinical data from 200,859 patients in multiple ICUs in the United States between 2014 and 2015. In this study, the corresponding author completed the training on \u0026lsquo;Protection of Human Subjects\u0026rsquo; and obtained permission to use the database (certification number: 36026306). The study was approved by the Research Ethics Committee of Wuxi People's Hospital (KS202112).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy subjects\u003c/h2\u003e \u003cp\u003eAll subjects were derived from the eICU-CRD V2.0 database. The inclusion criteria were: (1) Age\u0026thinsp;\u0026ge;\u0026thinsp;18 years and (2) a diagnosis of cardiac arrest. The exclusion criteria were: (1) missing information on one of sex, age, height, weight, acute physiology and chronic health evaluation score (APACHE-IV), initial simplified acute physiology score (SAPS-II), or Glasgow Coma Scale (GCS) score; and (2) lack of information on ICU and discharge outcomes. Admission venues included emergency department, floor, operation room, and direct admission. Therefore, both in- and out-of-hospital cardiac arrest events were included.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eData extraction\u003c/h2\u003e \u003cp\u003eAll data in this study were extracted from the database using Structured Query Language (SQL) scripts and \u003cem\u003eNavicat for PostgreSQL\u003c/em\u003e (11.2.9) software [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The extracted variables included: (1) baseline characteristics: sex, age, height, weight, APACHE IV, SAPS Ⅱ score, GCS score, race, type of ICU; (2) diagnosis, initial rhythm types, witnessed or not, and whether or not 15 min have passed before CPR was started; (3) treatment status, including the application of various vasoactive drugs, mechanical ventilation and length, acute renal failure (ARF), and hemodialysis; (4) neurological outcomes, including the highest GCS score, change in mental status, encephalopathy (post-anoxic), seizures, dementia, persistent vegetative state, ventilation (spontaneous-adequate); and (5) mortality and length of stay (LOS), including the status of ICU discharge, LOS in ICU, the status of hospital discharge, and LOS in hospital.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eContinuous variables that were normally distributed were described as mean \u0026plusmn; standard deviation (SD), comparison between the two groups was performed using the independent sample t-test, and comparison among multiple groups was performed using an analysis of variance (ANOVA). Counting data and classification variables were described by frequency and percentage, and a chi-square test was used for comparison between these groups. To reduce the confounding influence of the differences in baseline characteristics, propensity score matching (PSM) (1:2 in heparin group and non-heparin group, 1:1 in UFH and LMWH) was performed using \u0026lsquo;nearest neighbor\u0026rsquo; matching, with a caliper width of 0.02 across sex, age, BMI, APACHE-Ⅳ, SAPS-Ⅱ, initial heart rhythm, and the presence of witnesses. A Kaplan-Meier survival curve (log rank method) was used to evaluate the difference in survival time between the two groups. A significance level was set at 0.05 (for a two-tailed analysis). All analyses were performed with the use of IBM SPSS Statistics software (version 26.0; IBM Corp., Armonk, NY, USA), and R software (version 2.15.3; The R Foundation for Statistical Computing, Vienna, Austria) was used for PSM.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePatient characteristics\u003c/h2\u003e \u003cp\u003eA total of 5995 patients were studied, including 4890 in the non-heparin group and 1105 in the heparin group (755 in the UFH group and 350 in the LMWH group) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). ANOVA showed that there were no significant differences in age, sex, GCS score, presence of a witness, CPR time, or mechanical ventilation among the three groups (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). BMI, APACHE-Ⅳ, APS-Ⅱ, race, type of ICU, initial rhythm, vasopressor, and the incidence of ARF and hemodialysis were significantly different (all P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In the heparin and non-heparin groups, which were matched 1:2 (673 cases for heparin group and 1346 cases for the non-heparin group), there were no significant differences between the two groups in terms of age, sex, BMI, severity of the disease, initial rhythm, witnesses, vasopressor used, ARF, or rate of hemodialysis (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\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\u003eDemographic characteristics and basic characteristic\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\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\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eBefore PSM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eAfter PSM\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003enon-Heparin N\u0026thinsp;=\u0026thinsp;4890\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUFH\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;755\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLMWH N\u0026thinsp;=\u0026thinsp;350\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP value\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003enon-Heparin N\u0026thinsp;=\u0026thinsp;1346\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHeparins\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;673\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge(years), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;sd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63.44\u0026plusmn;15.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63.55\u0026plusmn;14.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63.26\u0026plusmn;14.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e63.38\u0026plusmn;14.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e63.42\u0026plusmn;15.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex(male), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2874(58.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e452(59.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e198(56.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e802(59.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e397(58.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.79\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m2), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;sd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.67\u0026thinsp;\u0026plusmn;\u0026thinsp;10.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.17\u0026thinsp;\u0026plusmn;\u0026thinsp;10.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.78\u0026thinsp;\u0026plusmn;\u0026thinsp;11.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e30.35\u0026thinsp;\u0026plusmn;\u0026thinsp;8.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e30.59\u0026thinsp;\u0026plusmn;\u0026thinsp;8.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.56\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eDisease severity scores (worst within 24 hours), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;sd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPACH-IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97.03\u0026thinsp;\u0026plusmn;\u0026thinsp;7.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e93.47\u0026thinsp;\u0026plusmn;\u0026thinsp;36.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e89.21\u0026thinsp;\u0026plusmn;\u0026thinsp;4.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e92.9\u0026thinsp;\u0026plusmn;\u0026thinsp;37.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e94.14\u0026thinsp;\u0026plusmn;\u0026thinsp;35.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPS-II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e85.73\u0026thinsp;\u0026plusmn;\u0026thinsp;6.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81.99\u0026thinsp;\u0026plusmn;\u0026thinsp;34.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e77.31\u0026thinsp;\u0026plusmn;\u0026thinsp;3.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e81.29\u0026thinsp;\u0026plusmn;\u0026thinsp;6.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e82.6\u0026thinsp;\u0026plusmn;\u0026thinsp;34.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.44\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGCS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.22\u0026thinsp;\u0026plusmn;\u0026thinsp;4.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.39\u0026thinsp;\u0026plusmn;\u0026thinsp;4.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.77\u0026thinsp;\u0026plusmn;\u0026thinsp;4.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.77\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9.83\u0026thinsp;\u0026plusmn;\u0026thinsp;4.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.62\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eEthnicity, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\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\u003eAfrican American\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e652(13.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e122(16.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(0.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"5\" rowspan=\"6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e177(13.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e128(19.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"5\" rowspan=\"6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73(1.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16(2.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10(2.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15(1.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7(1.04)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCaucasian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3605(73.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e523(69.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e232(66.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1024(76.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e463(68.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHispanic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e164(3.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46(6.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33(9.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e36(2.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e37(5.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNative American\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40(0.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(0.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13(0.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4(0.59)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther/Unknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e356(7.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45(5.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16(4.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e81(6.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e34(5.05)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eInitial rhythm, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsystole\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e484(9.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92(12.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38(10.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"4\" rowspan=\"5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e133(9.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e58(8.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"4\" rowspan=\"5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePEA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e842(17.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e179(23.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e74(21.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e211(15.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e134(19.91)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e500(10.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e140(18.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58(16.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e184(13.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e133(19.76)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e256(5.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70(9.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11(3.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e138(10.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e70(10.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eunknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e170(3.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28(3.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10(2.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e48(3.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e24(3.57)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eWitnessed, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.53\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ewitnessed, \u0026lt;\u0026thinsp;15 min CPR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1190(24.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e278(36.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e104(29.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e317(23.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e209(31.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"2\" rowspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ewitnessed, \u0026gt;\u0026thinsp;15 min CPR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e446(9.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84(11.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34(9.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e97(7.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e64(9.51)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eun-witnessed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e246(5.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40(5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19(5.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e75(5.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e39(5.79)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVasopressor, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2035(41.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e337(44.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e120(34.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e695(51.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e333(49.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEarly Defibrillation, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e129(2.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17(2.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7(2.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e32(2.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e12(1.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.389\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAMI, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e111(2.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31(4.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(0.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e29(2.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e19(2.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.353\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMV, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3652(74.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e567(75.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e264(75.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e974(72.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e543(80.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eARF, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e988(20.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e192(25.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e67(19.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e287(21.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e166(24.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDialysis, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e526(10.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e109(14.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27(7.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e131(9.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e83(12.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDVT prophylaxis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2380\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e680\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e311\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e980\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e620\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\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\u003eDrug therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e359\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e175\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e368\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCompression devices\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2380\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e256\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e111\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e980\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e252\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\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\u003eDialysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e526\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e109\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e131\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eAbbreviations: UFH\u0026thinsp;=\u0026thinsp;Unfractionated heparin, LMWH\u0026thinsp;=\u0026thinsp;Low molecular weight heparin, PSM\u0026thinsp;=\u0026thinsp;Propensity Score Match, BMI\u0026thinsp;=\u0026thinsp;body mass index, APACHE-IV: acute physiology and chronic health evaluation score, APS-II\u0026thinsp;=\u0026thinsp;simplified acute physiology score, GCS\u0026thinsp;=\u0026thinsp;Glasgow Coma Score, MV\u0026thinsp;=\u0026thinsp;Mechanical ventilation, PEA\u0026thinsp;=\u0026thinsp;pulseless electrical activity, VF\u0026thinsp;=\u0026thinsp;ventricular fibrillation, VT\u0026thinsp;=\u0026thinsp;ventricular tachycardia, CPR\u0026thinsp;=\u0026thinsp;cardiopulmonary resuscitation, AMI\u0026thinsp;=\u0026thinsp;acute myocardial infarction, ARF\u0026thinsp;=\u0026thinsp;acute renal failure, DVT\u0026thinsp;=\u0026thinsp;deep vein thrombosis\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eClinical outcomes between heparin and non-heparin groups\u003c/h2\u003e \u003cp\u003eNeurological prognosis\u003c/p\u003e \u003cp\u003eThe heparin group was significantly better than the non-heparin group for three measures: the maximum GCS score, various GCS scores (motor, verbal, and eyes), and GCS score classification (the degree of consciousness disturbance (13\u0026ndash;15 was mild, 9\u0026ndash;12 was moderate, and 3\u0026ndash;8 was severe) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The incidence of changed mental status, encephalopathy (post-anoxic), seizures, and the duration of mechanical ventilation were higher in the heparin group than in the non-heparin group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). There was no significant difference in the incidence of ventilation (spontaneous-adequate), dementia, or persistent vegetative state (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\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\u003eClinical outcomes between Heparins and non-Heparins, UFH and LMWH.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical outcomes\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHeparins\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;673\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003enon-Heparins\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;1346\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUFH\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;267\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLMWH\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;267\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGCS (max), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;sd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.89\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.29\u0026thinsp;\u0026plusmn;\u0026thinsp;4.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.06\u0026thinsp;\u0026plusmn;\u0026thinsp;4.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.96\u0026thinsp;\u0026plusmn;\u0026thinsp;4.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.81\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGCS (motor), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;sd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.02\u0026thinsp;\u0026plusmn;\u0026thinsp;1.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.75\u0026thinsp;\u0026plusmn;\u0026thinsp;1.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.02\u0026thinsp;\u0026plusmn;\u0026thinsp;1.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.13\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.51\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGCS (verbal), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;sd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.59\u0026thinsp;\u0026plusmn;\u0026thinsp;1.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.39\u0026thinsp;\u0026plusmn;\u0026thinsp;1.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.72\u0026thinsp;\u0026plusmn;\u0026thinsp;1.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.53\u0026thinsp;\u0026plusmn;\u0026thinsp;1.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGCS (eyes), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;sd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.43\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.24\u0026thinsp;\u0026plusmn;\u0026thinsp;1.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.39\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.49\u0026thinsp;\u0026plusmn;\u0026thinsp;1.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGCS 13\u0026ndash;15, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e422(62.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e792(58.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.041\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e147(55.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e135(50.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGCS 9\u0026ndash;12, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67(9.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e153(11.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18(6.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e29(10.86)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGCS 3\u0026ndash;8, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e161(23.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e395(29.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e48(17.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e50(18.73)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMental status changed, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e226(33.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e327(24.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65(24.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e118(44.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" 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\u003eEncephalopathy (post-anoxic), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e86(12.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e108(8.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19(7.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e47(17.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" 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\u003eSeizures, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92(13.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71(5.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23(8.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e51(19.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" 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\u003eDementia, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(0.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11(0.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2(0.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4(1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePersistent vegetative state, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15(2.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20(1.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5(1.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6(2.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.76\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVentilation (Spontaneous-adequate), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e392(58.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e779(57.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e166(62.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e161(60.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.66\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVentilation LOS (days), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;sd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.04\u0026thinsp;\u0026plusmn;\u0026thinsp;6.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.63\u0026thinsp;\u0026plusmn;\u0026thinsp;4.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.26\u0026thinsp;\u0026plusmn;\u0026thinsp;4.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.36\u0026thinsp;\u0026plusmn;\u0026thinsp;6.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU mortality, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e209(31.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e503(37.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e78(29.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e86(32.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.45\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU LOS (days), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;sd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.07\u0026thinsp;\u0026plusmn;\u0026thinsp;8.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.94\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.94\u0026thinsp;\u0026plusmn;\u0026thinsp;5.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.29\u0026thinsp;\u0026plusmn;\u0026thinsp;9.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital mortality, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e272(40.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e622(46.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e100(37.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e115(43.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.19\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital LOS (days), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;sd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.25\u0026thinsp;\u0026plusmn;\u0026thinsp;11.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.47\u0026thinsp;\u0026plusmn;\u0026thinsp;9.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.37\u0026thinsp;\u0026plusmn;\u0026thinsp;9.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12.36\u0026thinsp;\u0026plusmn;\u0026thinsp;11.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eAbbreviations: UFH\u0026thinsp;=\u0026thinsp;Unfractionated heparin, LMWH\u0026thinsp;=\u0026thinsp;Low molecular weight heparin, GCS\u0026thinsp;=\u0026thinsp;Glasgow Coma Score, LOS\u0026thinsp;=\u0026thinsp;Length of stay, ICU\u0026thinsp;=\u0026thinsp;Intensive care unit\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eMortality and LOS\u003c/p\u003e \u003cp\u003eThe ICU mortality rate (31.05% vs. 37.37%, P\u0026thinsp;=\u0026thinsp;0.005) and hospital mortality rate (40.42% vs. 46.21%, P\u0026thinsp;=\u0026thinsp;0.013) in the heparin group were significantly lower than that in the non-heparin group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). However, the LOS was significantly longer in the heparin group compared to the non-heparin group for mechanical ventilation LOS (4.63\u0026thinsp;\u0026plusmn;\u0026thinsp;4.63 days vs. 6.04\u0026thinsp;\u0026plusmn;\u0026thinsp;6.05 days, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), ICU LOS (4.94\u0026thinsp;\u0026plusmn;\u0026thinsp;5.80 days vs. 7.07\u0026thinsp;\u0026plusmn;\u0026thinsp;8.38 days, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and total hospital LOS (9.47\u0026thinsp;\u0026plusmn;\u0026thinsp;9.74 days vs. 12.25\u0026thinsp;\u0026plusmn;\u0026thinsp;11.12 days, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eClinical outcomes in UFH and LMWH\u003c/h2\u003e \u003cp\u003eThe UFH group and LMWH group were matched 1:1 according to sex, age, BMI, APACHE-Ⅳ, and SAPS-Ⅱ. Finally, 267 pairs of patients were successfully matched.\u003c/p\u003e \u003cp\u003eNeurological prognosis\u003c/p\u003e \u003cp\u003eThere was no statistical significance in the maximum GCS score, various GCS scores, and GCS classification between the two groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The incidence of changed mental status, encephalopathy (post-anoxic), seizures, and the duration of mechanical ventilation were significantly higher in the LMWH group than in the UFH group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). There was no significant difference in the incidence of ventilation (spontaneous-adequate), dementia, or persistent vegetative state (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMortality and LOS\u003c/p\u003e \u003cp\u003eThere were no significant differences in ICU mortality (29.21% vs. 32.21%, P\u0026thinsp;=\u0026thinsp;0.45), ICU LOS (5.94\u0026thinsp;\u0026plusmn;\u0026thinsp;5.41 days vs. 7.29\u0026thinsp;\u0026plusmn;\u0026thinsp;9.85 days, P\u0026thinsp;=\u0026thinsp;0.05), and hospitalization mortality (37.45% vs. 43.07%, P\u0026thinsp;=\u0026thinsp;0.19) between the UFH and LMWH groups. The LOS for mechanical ventilation (5.26\u0026thinsp;\u0026plusmn;\u0026thinsp;4.46 days vs. 6.36\u0026thinsp;\u0026plusmn;\u0026thinsp;6.39 days, P\u0026thinsp;=\u0026thinsp;0.021) and hospital LOS (10.37\u0026thinsp;\u0026plusmn;\u0026thinsp;9.01 days vs. 12.36\u0026thinsp;\u0026plusmn;\u0026thinsp;11.58 days, P\u0026thinsp;=\u0026thinsp;0.027) were significantly shorter in the UFH group compared to the LMWH group, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eSurvival time\u003c/h2\u003e \u003cp\u003eThe median survival time of the heparin group (20.75\u0026thinsp;\u0026plusmn;\u0026thinsp;2.37 days) was longer than that of the non-heparin group (14.63\u0026thinsp;\u0026plusmn;\u0026thinsp;1.26), and this difference was significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). There was no statistically significant difference in the median survival time between the UFH group (20.96\u0026thinsp;\u0026plusmn;\u0026thinsp;5.09 days) and the LMWH group (19.54\u0026thinsp;\u0026plusmn;\u0026thinsp;3.73 days) (P\u0026thinsp;=\u0026thinsp;0.89), as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, patients in the heparin group had significantly improved neurological outcomes (GCS score), ICU mortality, hospital mortality, and survival time compared with those in the non-heparin group. There was no significant difference in the prognosis of some neurological outcomes (spontaneous-adequate ventilation, dementia, and persistent vegetative status). There was no significant difference between the UFH group and the LMWH group for these clinical outcomes.\u003c/p\u003e \u003cp\u003eThe study cohort was from a United States database. Data show that approximately 30\u0026ndash;40% of hospitalized cardiac arrest patients die in the ICU and 40\u0026ndash;50% die in the hospital, which is consistent with previous reports [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Because the guidelines do not recommend heparin for the treatment of cardiac arrest, only 18.43% (1105 patients) in this cohort received heparin for a variety of reasons, and UFH use was about twice as high as LMWH use. In a retrospective study of 384 patients by Grabmaier and his colleagues, the use of AH in patients with out-of-hospital cardiac arrest improved survival from 34\u0026ndash;59.4%. AH was found to be an independent predictor of discharge survival in the regression model (hazard ratio 0.60 [0.44\u0026ndash;0.82], P\u0026thinsp;=\u0026thinsp;0.002) [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In this study, the survival rate of the control group was 44.79%, higher than that of the placebo group in the previous study by Grabmaier, and the final discharge survival rate of the heparin group was 59.58%, which was similar to that of the AH group in the Grabmaier study. Although some studies have suggested that the combination of anticoagulant and antiplatelet is not necessary for most situations, the combination of the two studies suggests that the combination of anticoagulant and antiplatelet may improve patient and clinical outcomes. If the treatment levels in the two studies were similar, aspirin\u0026rsquo;s contribution to survival would be about 10%, and heparin\u0026rsquo;s contribution to survival would be about 15%, without taking into consideration any cross-actions. More rigorous prospective, double-blind, crossover studies are needed to further clarify the separate effects of aspirin and heparin and whether there is a synergistic interaction between them. In addition, the current study found that heparin significantly extended the survival time of patients with cardiac arrest, which has not been reported in previous studies; however, heparin patients also had longer hospital stays.\u003c/p\u003e \u003cp\u003eNeurological outcome is another important clinical outcome in patients with cardiac arrest. The maximum GCS score during the disease was used to evaluate the patient\u0026rsquo;s state of consciousness. Both the mean value of the maximum GCS and the mean value of each item (motor, verbal, or eyes) were better in the heparin group. A stratified GCS analysis also showed that the heparin group had a higher ratio of good cerebral performance (GCS score of 13\u0026ndash;15) (62.7% vs. 58.84%). Moreover, Grabmaier\u0026rsquo;s research showed that pre-hospital AH administration was associated with favorable neurological outcomes (odds ratio [OR] 2.25 [1.31\u0026ndash;3.87], P\u0026thinsp;=\u0026thinsp;0.003). Patients with AH were more likely to gain return of the spontaneous circulation (OR 2.22 [1.45\u0026ndash;3.42], P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. However, it was also found that the incidence of changed mental status, encephalopathy (post-anoxic), seizures, and the duration of mechanical ventilation was longer in the heparin group. This may be associated with an increase in the survival rate of patients who do not have a good neurological outcome under current treatment but whose prognosis is clearly better than that of death.\u003c/p\u003e \u003cp\u003eAs common anticoagulants, in addition to large differences in molecular weight, UFH and LMWH also have large differences in terms of mechanism of action, pharmacokinetics, and risk of adverse reactions [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. UFH can act on variety of thrombin enzymes and can also act on platelets, which have a shorter half-life, lower bioavailability, and pose a higher risk of bleeding [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. To further determine whether there is a difference between the two types of heparin, we investigated their effects on clinical outcomes. The results showed that there was no significant difference in the major clinical and neurological outcomes between the two groups. However, UFH was associated with a tendency towards lower ICU and hospital mortality rates compared to LMWH. The same trend was observed for GCS scores. Whether this trend is related to the antiplatelet effect of ordinary heparin needs further study. Because we did not analyze bleeding-related complications, it is unclear whether the common heparin group had a higher risk of bleeding. However, Grabmaier's study showed that AH did not increase the risk of bleeding in patients with cardiac arrest [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAnimal studies have shown that a marked activation of blood coagulation occurs and that microthrombi are found in the cerebral vessels after a cardiac arrest of 5 to 10 min [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Microthrombosis, microcirculation disorder, secondary tissue ischemia and hypoxia, and oxygen metabolism disorder followed by a series of nerve cell injury are some of the important influences on the neurological prognosis of cardiac arrest [\u003cspan additionalcitationids=\"CR25\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], and the formation of systemic microthrombosis is also an important mechanism affecting tissue oxygen metabolism and organ function damage [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Resolving the influence of microthrombosis on various organs of cardiac arrest may be an important mechanism for heparin to improve the prognosis of cardiac arrest patients. In addition, the cause of cardiac arrest in most patients is related to thrombosis of blood vessels in the heart or lungs [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Furthermore, the anticoagulant and antiplatelet effects of heparin have a good effect on the improvement of heart or pulmonary vascular infarction. Cardiac arrest is not a contraindication to the use of heparin in clinical practice; however, the occurrence of bleeding complications is a concern. Interestingly, some studies have shown that heparin does not significantly increase the risk of bleeding in cardiac arrest [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur study had some limitations. First, heparin may be used for hemodialysis, thrombosis, hemodynamic monitoring, hypercoagulability, or disseminated intravascular coagulation; as this study was limited by data extraction, we could not analyze the reasons for administration of heparin. Second, when heparin anticoagulants are used for different reasons, the frequency, dose, and cycle of medication vary greatly; hence, the total dose of each sample was difficult to obtain, and the dose-response analysis was limited. Third, due to data limitations, we could not determine which bleeding complications were causally associated with heparin; therefore, no comparison of bleeding-related complications was made. Fourth, lack of heparin administration in some cases may stem from a decision to discontinue care due to poor prognosis. Data on the proportion of cases with limited or discontinued treatment because of poor prognosis was unavailable in the database. Finally, coagulation status, D-dimer, and other indicators may directly affect the use of heparin in some patients. Patients\u0026rsquo; thrombosis risk score may also be an important basis for the prevention of deep vein thrombosis. The distribution of these factors among each group, the use of heparin, and the effect on outcomes represents a more complex interaction, and this was not covered in this study. Therefore, further research is needed.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eAccording to the findings of this retrospective cohort study, heparin (UFH or LMWH) may be a promising option for treating hospitalized patients with cardiac arrest because heparin reduced mortality rates and prolonged survival times of in-hospital patients with cardiac arrest and improved prognosis of neurological function to a certain extent. Furthermore, outcomes were not significantly different between patients who received UFH and those who received LMWH. Prospective, randomized controlled studies with larger sample sizes are needed to clarify the value of heparin in treating patients with cardiac arrest.\u003c/p\u003e"},{"header":"List Of Abbreviations","content":"\u003cp\u003eAH, aspirin and heparin; ANOVA, analysis of variance; APACHE-IV, Acute Physiology and Chronic Health Evaluation Score; ARF, acute renal failure; GCS, Glasgow Coma Scale; ICU, intensive care unit; LMWH, low molecular weight heparin; LOS, length of stay; OR, odds ratio; PSM, Propensity Score Matching; SAPS-II, Simplified Acute Physiology Score; SD, standard deviation; SQL, Structured Query Language; UFH, unfractionated heparin.\u003c/p\u003e "},{"header":"Declarations","content":"\u003ch2\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/h2\u003e \u003cp\u003eThe corresponding author (YZ) completed the training on \u0026lsquo;Protection of Human Subjects\u0026rsquo; and obtained permission to use the database (certification number: 36026306). The study was approved by the Research Ethics Committee of Wuxi People's Hospital (KS202112). Because all patient records in the database are anonymous, the Review Committee of this study waived the requirement to obtain informed consent from individual patients.\u003c/p\u003e \u003ch2\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e\u003ch2\u003eAvailability of data and material\u003c/h2\u003e\n\u003cp\u003eThe data used in this research is available from the eICU website: https://eicu-crd.mit.edu/.\u003c/p\u003e\n \u003ch2\u003e \u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003e This work was funded by the Top Talent Support Program for young and middle-aged people of the Wuxi Health Committee (project number: BJ2020007).\u003c/p\u003e\u003ch2\u003eAuthors\u0026rsquo; contributions\u003c/h2\u003e \u003cp\u003eFG was responsible for data validation and writing of the manuscript, and YZ was responsible for research design, data extraction, and analysis. All authors have read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgments\u003c/h2\u003e \u003cp\u003eThe authors would like to thank the Philips eICU Research Institute and Philips Healthcare for contribution of the data and Editage (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e\u003ca href=\"https://orcid.org/0000-0002-7889-2139\" target=\"_blank\"\u003ewww.editage.cn\u003c/a\u003e\u003c/span\u003e\u003c/span\u003e) for English language editing.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eJentzer JC, Clements CM, Wright RS, White RD, Jaffe AS. Improving Survival From Cardiac Arrest: A Review of Contemporary Practice and Challenges. Ann Emerg Med. 2016;68(6):678\u0026ndash;89.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim F, Maynard C, Dezfulian C, Sayre M, Kudenchuk P, Rea T, Sampson D, Olsufka M, May S, Nichol G. 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European Resuscitation Council and European Society of Intensive Care Medicine 2015 guidelines for post-resuscitation care. Intensive Care Med. 2015;41(12):2039\u0026ndash;56.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaze R, Le May MR, Froeschl M, Hazra SK, Wells PS, Osborne C, Labinaz M, Hibbert B, So DY, investigators CAPIT: Endovascular cooling catheter related thrombosis in patients undergoing therapeutic hypothermia for out of hospital cardiac arrest. \u003cem\u003eResuscitation\u003c/em\u003e 2014, 85(10):1354\u0026ndash;1358.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOami T, Oshima T, Oku R, Nakanishi K. Successful treatment of pulmonary embolism-induced cardiac arrest by thrombolysis and targeted temperature management during pregnancy. Acute Med Surg. 2018;5(3):292\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eB\u0026ouml;ttiger BW, Arntz HR, Chamberlain DA, Bluhmki E, Belmans A, Danays T, Carli PA, Adgey JA, Bode C, Wenzel V, et al. Thrombolysis during resuscitation for out-of-hospital cardiac arrest. N Engl J Med. 2008;359(25):2651\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang Y, Wang M, Ni Y, Liang B, Liang Z. Can Systemic Thrombolysis Improve Prognosis of Cardiac Arrest Patients During Cardiopulmonary Resusci tation? A Systematic Review and Meta-Analysis. J Emerg Med. 2019;57(4):478\u0026ndash;87.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWahby KA, Jhajhria S, Dalal BD, Soubani AO. Heparin dosing in critically ill patients undergoing therapeutic hypothermia following cardiac arrest. Resuscitation. 2014;85(4):533\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu W, Wang Y, Zhou X, Hai K, Jia D, Ye Q. The Effect of Prophylactic Anticoagulation with Heparin on the Brain Cells of Sprague-Dawley Rats in a Cardiopulmonary-Cerebral Resuscitation Model. Evid Based Complement Alternat Med. 2020;2020:8430746.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrabmaier U, Rizas KD, Massberg S, Weckbach L, Fischer M, German Resuscitation Registry Study G. Association of prehospital acetylsalicylic acid and heparin administration with favorable neurological outcome after out-of-hospital cardiac arrest: a matched cohort analysis of the German Resuscitation Registry. Intensive Care Med. 2020;46(10):1934\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrabmaier U, Rizas KD, Berghof J, Huflaender Y, Wiegers C, Wakili R, Kaspar M, Angstwurm M, Massberg S, Weckbach LT, et al. Association between survival and non-selective prehospital aspirin and heparin administration in patients with out-of-hospital cardiac arrest: a propensity score-matched analysis. Intensive Care Med. 2018;44(4):537\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePollard TJ, Johnson AEW, Raffa JD, Celi LA, Mark RG, Badawi O. The eICU Collaborative Research Database, a freely available multi-center database for critical care research. Sci Data. 2018;5(11):180178.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMacki M, Fakih M, Anand SK, Suryadevara R, Elmenini J, Chang V. A direct comparison of prophylactic low-molecular-weight heparin versus unfractionated heparin in neu rosurgery: A meta-analysis. Surg Neurol Int. 2019;10:202.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTao E, Luo YL, Tao Z, Wan L. A meta-analysis of bridging anticoagulation between low molecular weight heparin and heparin. Medicine. 2020;99(3):e18729.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou M, Yu T, Fang X, Ge Q, Song F, Huang Z, Jiang L, Wang P. Short-term dietary restriction ameliorates brain injury after cardiac arrest by modulation of mitocho ndrial biogenesis and energy metabolism in rats. Ann Transl Med. 2021;9(1):8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCoppler PJ, Elmer J. Mitochondrial resuscitation after cardiac arrest. \u003cem\u003eResuscitation\u003c/em\u003e 2021,162(5):433\u0026ndash;434.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGill R, Teitcher M, Ruland S. Neurologic complications of cardiac arrest. Handb Clin Neurol. 2021;177:193\u0026ndash;209.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGorog DA, Price S, Sibbing D, Baumbach A, Capodanno D, Gigante B, Halvorsen S, Huber K, Lettino M, Leonardi S, et al. Antithrombotic therapy in patients with acute coronary syndrome complicated by cardiogenic shock or o ut-of-hospital cardiac arrest: a Joint Position Paper from the European Society of Cardiology (ESC) Working Group on Thrombosis, in association with the Acute Cardiovascular Care Association (ACCA) an d European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J Cardiovasc Pharmacother. 2021;7(2):125\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJoffre J, Varenne O, Bougouin W, Rosencher J, Mira JP, Cariou A. Stent thrombosis: an increased adverse event after angioplasty following resuscitated cardiac arrest. Resuscitation. 2014;85(6):769\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e\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":"Cardiac arrest, Heparin, Retrospective study, Propensity Score Matching","lastPublishedDoi":"10.21203/rs.3.rs-740945/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-740945/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Studies indicate that heparin can improve survival in patients with out-of-hospital cardiac arrest. Thus, we aimed to investigate the effect of heparin on hospitalized patients with cardiac arrest.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eClinical data of cardiac arrest patients from the eICU Collaborative Research Database V2.0 were retrospectively analyzed. We compared neurological prognosis and primary outcomes in a heparin group that received unfractionated heparin or low molecular weight heparin with a non-heparin group. Additionally, we compared the two heparin sub-groups. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eAfter propensity score matching, there were 673 patients in the heparin group and 1346 patients in the non-heparin group. The Glasgow Coma Scale score was significantly better in the heparin group (P\u0026lt;0.05). There were no significant differences in terms of spontaneous respiratory function recovery, dementia, or vegetative state between the two groups (P\u0026gt;0.05). Intensive care unit (ICU) mortality and hospital mortality rates were significantly lower in the heparin group (P\u0026lt;0.05). The duration of mechanical ventilation, length of stay in ICU, and length of stay in hospital were significantly longer in the heparin group (P\u0026lt;0.05). Median survival time was significantly longer in the heparin group (P\u0026lt;0.001). In the comparison of patients who received unfractionated heparin and low molecular weight heparin (267 in each group), there were no significant differences in Glasgow Coma Scale score, ICU mortality, hospital mortality, or median survival time between the two groups (P\u0026gt;0.05).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Heparin administration may be beneficial in reducing the mortality rate and prolonging the survival time of in-hospital patients with cardiac arrest. It may also improve the prognosis of neurological function to a certain extent. Outcomes were not significantly different between patients who received unfractionated heparin and those who received low molecular weight heparin.\u003c/p\u003e","manuscriptTitle":"Can Heparin Improve Clinical Outcomes in Cardiac Arrest? A Retrospective Cohort Study from the EICU Collaborative Research Database","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-08-02 14:45:04","doi":"10.21203/rs.3.rs-740945/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":"b58464e9-36ab-447e-8f32-f4f3b7b17420","owner":[],"postedDate":"August 2nd, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":6133448,"name":"Critical Care \u0026 Emergency Medicine"}],"tags":[],"updatedAt":"2021-08-02T14:45:06+00:00","versionOfRecord":[],"versionCreatedAt":"2021-08-02 14:45:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-740945","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-740945","identity":"rs-740945","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}