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Acute liver failure involvement of multiple organ systems. ARDS=adult respiratory distress syndrome; SIRS=systemic inflammatory response syndrome.
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Although comprising a minority of the transplant population, acute liver failure (ALF) patients represent some of the most challenging cases in terms of the level and complexity of care required. An ALF patient requires much more than a single skilled intensivist, gastroenterologist, or surgeon. Successful care of the ALF patient begins with early...
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Fulminant hepatic failure (FHF) is a relatively rare manifestation of Hodgkin's lymphoma. Clinical features, laboratory findings, and imaging of the liver are usually inconclusive, and liver biopsy may be required for confirmation. We present a case of an FHF in a woman 1 week after the diagnosis of Hodgkin's lymphoma. Chemotherapy could not be ins...
Citations
... Clinically significant bleeding is uncommon in ALF and is seen in approximately 5-10% of patients [29,30]. Prophylactic correction of platelet levels is not necessary, and routine use of fresh frozen plasma (FFP) and other coagulation factors are not supported by evidence, and in fact may lead to increased death or LT due to increased transfusion reactions, thrombosis, and transfusion-related acute lung injury [2,29,31,32]. When considering the insertion of an intracranial pressure (ICP) probe, any hemostasis abnormalities may need treatment. ...
... The insertion of an ICP monitor is controversial and center-dependent. No changes in outcomes have been reported in patients who had ICP monitors or had more interventions to reduce ICP compared to patients who did not, although randomized clinical studies are lacking [4,31,37]. AASLD guidelines recommend ICP monitor use only in patients who are likely to have LT, while the European Association for the Study of the Liver recommends ICP monitoring in patients at high risk for intracranial hypertension (ICH) [3,38]. ICP monitoring is associated with bleeding and infection risks. ...
... Hyperammonemia has been shown to be associated with cerebral edema and is the key driver of astrocyte swelling due to ammonia metabolism to glutamine within astrocytes [4]. Although ammonia-lowering therapies such as lactulose or rifaximin are used for HE in the setting of ALF, there is no clear evidence of the benefit in the setting of ALF [4,31]. Younger patients (<35 years), those with high serum ammonia (150-200 µmol/L), high-grade HE (grade III, IV), SIRS or infection, and patients requiring vasopressor support or RRT have a higher risk of developing cerebral edema [39]. ...
Acute liver failure (ALF) is a rare and specific form of severe hepatic dysfunction characterized by coagulopathy and hepatic encephalopathy in a patient with no known liver disease. ALF carries a high morbidity and mortality. Careful attention should be given to hemodynamics and metabolic parameters along with the active surveillance of infections. Timely transfer and supportive management are important in an intensive care unit in a liver transplant center. Identifying patients who will and will not improve with medical management and may need emergent liver transplantation is critical. In this review, we provide a comprehensive update on the etiology, diagnosis, and management of ALF.
... Acute liver failure (ALF) is a lethal condition characterized by loss of hepatocyte function and subsequent multi-organ failure. 1,2 The most common reasons for ALF are hepatitis virus infection and drug-induced injury. 3 The recent increase in unexplained acute pediatric hepatitis has appeared globally, which leads to ALF. 4,5 Triggering liver inflammation and an overreaction of the immune system are thought to cause unexplained acute hepatitis. ...
Hepatic macrophages represent a key cellular component of the liver and are essential for the progression of acute liver failure (ALF). We construct artificial apoptotic cells loaded with itaconic acid (AI-Cells), wherein the compositions of the synthetic plasma membrane and surface topology are rationally engineered. AI-Cells are predominantly localized to the liver and further transport to hepatic macrophages. Intravenous administration of AI-Cells modulates macrophage inflammation to protect the liver from acetaminophen-induced ALF. Mechanistically, AI-Cells act on caspase-1 to suppress NLRP3 inflammasome-mediated cleavage of pro-IL-1β into its active form in macrophages. Notably, AI-Cells specifically induce anti-inflammatory memory-like hepatic macrophages in ALF mice, which prevent constitutive overproduction of IL-1β when liver reinjury occurs. In light of AI-Cells' precise delivery and training of memory-like hepatic macrophages, they offer promising therapeutic potential in reversing ALF by finely controlling inflammatory responses and orchestrating liver homeostasis, which potentially affect the treatment of various types of liver failure.
... As the synthetic function of the liver is lost in AHF, this leads to dysfunction of coagulation proteins [17]. Additionally, liver function tests like aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) are expected to be significantly elevated, with AST and ALT in the thousands [18]. The patient presented here had elevated ALP and mildly elevated AST on admission, which all had resolved, excluding AHF as a predisposing factor for PF. ...
Purpura fulminans (PF) is a rarely encountered rapidly evolving der-matological manifestation of ischemia, particularly in critically ill patients. Considered one of the very few dermatological emergencies , it has high mortality rate where patients often succumb to the illness. It can manifest in three forms: neonatal, idiopathic, and the more commonly infectious variety, which can be secondary to mostly bacterial and rarely viral etiology. It is also reported to be highly associated with disseminated intravascular coagulation (DIC), heparin-induced thrombocytopenia (HIT), and acute hepatic failure (AHF). Hereditary or acquired deficiency of protein C and dysregulation of the coagulation cascade, mainly protein C-thrombomodulin, has been implicated in the pathogenesis. We present a 55-year-old male admitted to the intensive care unit for diabetic ketoacidosis (DKA) and septic shock. Along with initiating management protocol for DKA and broad-spectrum antibiotics, he was initially started on norepinephrine for septic shock. Because of persistent refractory septic shock, he was subsequently initiated on phenylephrine and vasopressin to maintain adequate perfusion. The following day, he was found to have sharply demarcated blackish non-blanching discoloration on bilateral knees, lower limbs, and scrotum, sparing the acral regions. This cutaneous manifestation persisted throughout his hospital course, although it improved after discontinuation of vasopressin while continuing with other pressors. Vasopressin has been implicated in a few instances of skin necrosis; however, PF has rarely been documented and never within 1 day like ours. This case demonstrates a unique development of PF likely from vasopressin after ruling out the diagnoses of DIC, HIT, thrombotic thrombocytopenic purpura, and AHF.
... However, its utility in cases of sudden liver failure is debatable. According to one study, receiving lactulose helped patients with ALF live a small increase in survival time [22] . Coagulations disorders should be addressed as well. ...
Dengue fever is caused by dengue virus, which has four different serotypes and is transmitted by the Aedes mosquitos. This disease is endemic to Southeast Asian countries, including Nepal. Liver involvement in dengue is a crucial feature, and the effect ranges from an asymptomatic rise in liver enzymes to the development of acute liver failure. Acute liver failure often results in multiorgan dysfunction including hemodynamic instability, renal failure, cerebral edema, and even death because of shock. Prompt diagnosis and management are necessary to prevent complications. However, there is no proven proper treatment for this condition, and the only treatment modality is to prevent the symptoms. We presented the case of a young female with dengue fever who developed a life-threatening acute liver failure because of dengue shock syndrome.
... An excessive hepatocyte loss results in tissue degeneration leading to acute liver failure (ALF). There are many different causes of ALF, and the most common cause is drug-induced liver injuries (DILI) [19]. An adverse reaction during liver metabolic function in biotransformation of xenobiotics is the main cause of DILI [20]. ...
The physiological importance of the liver is demonstrated by its unique and essential ability to regenerate following extensive injuries affecting its function. By regenerating, the liver reacts to hepatic damage and thus enables homeostasis to be restored. The aim of this review is to add new findings that integrate the regenerative pathway to the current knowledge. An optimal regeneration is achieved through the integration of two main pathways: IL-6/JAK/STAT3, which promotes hepatocyte proliferation, and PI3K/PDK1/Akt, which in turn enhances cell growth. Proliferation and cell growth are events that must be balanced during the three phases of the regenerative process: initiation, proliferation and termination. Achieving the correct liver/body weight ratio is ensured by several pathways as extracellular matrix signalling, apoptosis through caspase-3 activation, and molecules including transforming growth factor-beta, and cyclic adenosine monophosphate. The actors involved in the regenerative process are numerous and many of them are also pivotal players in both the immune and non-immune inflammatory process, that is observed in the early stages of hepatic regeneration. Balance of Th17/Treg is important in liver inflammatory process outcomes. Knowledge of liver regeneration will allow a more detailed characterisation of the molecular mechanisms that are crucial in the interplay between proliferation and inflammation.
... DM status was defined by several criteria: the previous history of diabetes mellitus or current use of hypoglycemic agents, fasting plasma glucose ≥ 7:0 mmol/L (≥126 mg/dL), or hemoglobin A1c ≥ 6:2% [34]. Acute liver failure was defined as encephalopathy of any degree with a prothrombin time prolongation of approximately 4-6 seconds or an international normalized ratio ≥ 1:5 [35]. Hypoxic hepatitis was defined as an elevation of AST and/or ALT to more than 20 times the upper limit of the normal range (≤50 IU/L) in the absence of other causes of hepatocellular necrosis [36]. ...
... Bro-Jeppesen et al. reported that endothelial damage and activation were found within the first 72 h after CA and that endothelial damage was associated with a high baseline systemic inflammatory level [53]. Systemic ischemia-reperfusion injury after CA causes systemic inflammatory response syndrome (SIRS) [35]. Disseminated intravascular coagulation (DIC) is a common complication of SIRS, which occurs after cardiac arrest and resuscitation [54]. ...
Introduction:
In recent years, gamma-glutamyl transpeptidase to platelet ratio (GPR) has been proposed as a new inflammatory marker. We aimed to evaluate the association between GPR and outcomes after cardiac arrest (CA).
Methods:
A total of 354 consecutive patients with CA were included in this retrospective study. Patients were divided into three groups according to tertiles of GPR (low, n = 119; middle, n = 117; and high, n = 118). To determine the relationship between GPR and prognosis, a logistic regression analysis was performed. The ability of GPR to predict the outcomes was evaluated by receiver operating characteristic (ROC) curve analysis. Two prediction models were established, and the likelihood ratio test (LRT) and the Akaike Information Criterion (AIC) were utilized for model comparison.
Results:
Among the 354 patients (age 62 [52, 74], 254/354 male) who were finally included in the analysis, those in the high GPR group had poor outcomes. Multivariate logistic regression analysis revealed that GPR was independently associated with the three outcomes, for ICU mortality (odds ratios (OR) = 1.738, 95% confidence interval (CI): 1.221-2.474, P = 0.002), hospital mortality (OR = 1.676[1.164 - 2.413], P = 0.005), and unfavorable neurologic outcomes (OR = 1.623[1.121 - 2.351], P = 0.010). The area under the ROC curve was 0.611 (95% Cl: 0.558-0.662) for ICU mortality, 0.600 (95% CI: 0.547-0.651) for hospital mortality, and 0.602 (95% CI: 0.549-0.653) for unfavorable neurologic outcomes. Further, the LRT analysis showed that compared with the model without GPR, the GPR-combined model had a higher likelihood ratio χ 2 score and smaller AIC.
Conclusion:
GPR, as an inflammatory indicator, was independently associated with outcomes after CA. GPR is helpful in estimating the clinical outcomes of patients with CA.
... The majority of therapy options come with substantial side effects and other health risks. (2) . Alcohol is primarily processed in the liver. ...
... This is consistent with established, defined criteria of shock liver and ischemic hepatitis (14,21,22). INR greater than 1.5 was used to signify an elevated value and separately evaluated (23). ...
Extracorporeal membrane oxygenator support is a powerful clinical tool that is currently enjoying a resurgence in popularity. Wider use of extracorporeal membrane oxygenator support is limited by its significant risk profile and extreme consumption of resources. This study examines the role of markers of liver dysfunction in predicting outcomes of adult patients requiring extracorporeal membrane oxygenator support.
Design:
Retrospective review.
Setting:
Large extracorporeal membrane oxygenator center, Chicago, IL.
Patients:
This study reports a single institution experience examining all adult patients for whom extracorporeal membrane oxygenator support was used over an 8-year period. Data were collected regarding patient demographics, details of extracorporeal membrane oxygenator support provided, laboratory data, and outcomes. Trends in liver function were examined for their ability to predict survival.
Intervention:
Extracorporeal membrane oxygenator support, critical care.
Measurements and main results:
Mean age was 50 years (range, 19-82 yr). There were 86 male patients (56.6%) and 66 female patients (43.4%). Indications for initiation of extracorporeal membrane oxygenator support included cardiac 76 patients (50.0%), respiratory 48 patients (31.6%), extracorporeal cardiopulmonary resuscitation 21 patients (13.3%), and combined cardiac/respiratory seven patients (4.6%). Mean duration of extracorporeal membrane oxygenator support was 17 days (range 1-223 d) or median 8 days (interquartile range, 4-17 d). Overall, in-hospital mortality was 56% (86/152). Forty-five percent of adult patients (68/152) surpassed at least one of the following established liver dysfunction thresholds: total bilirubin greater than 15 mg/dL, aspartate aminotransferase greater than 20× upper limit of normal, and alanine aminotransferase greater than 20× upper limit of normal. The multivariable logistic analysis yielded three significant findings associated with in-hospital mortality: highest total bilirubin greater than 15 (adjusted odds ratio = 4.40; 95% CI, 1.19-21.87; p = 0.04), age (adjusted odds ratio = 1.03; 95% CI, 1.00-1.05; p = 0.04), and highest lactate (adjusted odds ratio = 1.15; 95% CI, 1.06-1.26; p = 0.002).
Conclusions:
Increases in age, highest total bilirubin, and lactate all correlated with in-hospital mortality in multivariable analysis of patients requiring extracorporeal membrane oxygenator support.
... rFVIIa given at a dose of 20-40 mcg/kg, administered 30 min before the procedure has a rapid onset of action and a low volume of infusion making it another option for use prior to invasive procedures (42). However, administration of rFVIIa requires caution due to high cost and the risk of potentially serious thrombotic events (8,45,46). Treatment goals in PALF should focus on acute bleeding management and prevention of infection, uremia, and GI bleeding, rather than prophylactic correction of laboratory values. ...
Pediatric Acute Liver Failure (PALF) is a rapidly progressive clinical syndrome encountered in the pediatric ICU which may rapidly progress to multi-organ dysfunction, and on occasion to life threatening cerebral edema and hemorrhage. Pediatric Acute Liver Failure is defined as severe acute hepatic dysfunction accompanied by encephalopathy and liver-based coagulopathy defined as prolongation of International Normalized Ratio (INR) >1.5. However, coagulopathy in PALF is complex and warrants a deeper understanding of the hemostatic balance in acute liver failure. Although an INR value of >1.5 is accepted as the evidence of coagulopathy and has historically been viewed as a prognostic factor of PALF, it may not accurately reflect the bleeding risk in PALF since it only measures procoagulant factors. Paradoxically, despite the prolongation of INR, bleeding risk is lower than expected (around 5%). This is due to “rebalanced hemostasis” due to concurrent changes in procoagulant, anticoagulant and fibrinolytic systems. Since the liver is involved in both procoagulant (Factors II, V, IX, XI, and fibrinogen) and anticoagulant (Protein C, Protein S, and antithrombin) protein synthesis, PALF results in “rebalanced hemostasis” or even may shift toward a hypercoagulable state. In addition to rebalanced coagulation there is altered platelet production due to decreased thrombopoietin production by liver, increased von Willebrand factor from low grade endothelial cell activation, and hyperfibrinolysis and dysfibrinogenemia from altered synthetic liver dysfunction. All these alterations contribute to the multifactorial nature of coagulopathy in PALF. Over exuberant use of prophylactic blood products in patients with PALF may contribute to morbidities such as fluid overload, transfusion-associated lung injury, and increased thrombosis risk. It is essential to use caution when using INR values for plasma and factor administration. In this review we will summarize the complexity of coagulation in PALF, explore “rebalanced hemostasis,” and discuss the limitations of current coagulation tests. We will also review strategies to accurately diagnose the coagulopathy of PALF and targeted therapies.
... Diabetes mellitus (DM) was defined as a previous history of diabetes and new hyperglycemia, a fasting serum glucose of ≥7.0 mmol/L (≥126 mg/dL), hemoglobin A1c ≥ 6:2%, or current use of hypoglycemic agents [20]. The definition of acute liver failure (ALF) in this study was based on previously published standards, which included an international normalized ratio ðINRÞ ≥ 1:5 in the presence of encephalopathy [21]. Hypoxic hepatitis (HH) is defined as an increase in serum aspartate transaminase and/or serum alanine transaminase to more than 20-fold the upper normal range without any other cause of hepatic cell necrosis after CA [22]. ...
Introduction. The aim of our study was to explore the associations of the aspartate transaminase/alanine transaminase (De-Ritis) ratio with outcomes after cardiac arrest (CA). Methods. This retrospective study included 374 consecutive adult cardiac arrest patients. Information on the study population was obtained from the Dryad Digital Repository. Patients were divided into tertiles based on their De-Ritis ratio. The logistic regression hazard analysis was used to assess the independent relationship between the De-Ritis ratio and mortality. The Kaplan-Meier method and log-rank test were used to estimate the survival of different groups. Receiver operating characteristic (ROC) curve analysis was utilized to compare the prognostic ability of biomarkers. A model combining the De-Ritis ratio was established, and its performance was evaluated using the Akaike information criterion (AIC). Results. Of the 374 patients who were included in the study, 194 patients (51.9%) died in the intensive care unit (ICU), 213 patients (57.0%) died during hospitalization, and 226 patients (60.4%) had an unfavorable neurologic outcome. Logistic regression analysis including potentially confounding factors showed that the De-Ritis ratio was independently associated with mortality, yielding a more than onefold risk of ICU mortality (OR 1.455; 95% CI 1.088-1.946; ) and hospital mortality (OR 1.378; 95% CI 1.031-1.842; ). Discriminatory performance assessed by ROC curves showed an area under the curve of 0.611 (95% CI 0.553-0.668) for ICU mortality and 0.625 (0.567-0.682) for hospital mortality. Further, the likelihood ratio test (LRT) analysis showed that the model combining the De-Ritis ratio had a smaller AIC and higher likelihood ratio score than the model without the De-Ritis ratio. The Kaplan-Meier curves showed that the CA patients in the De-Ritis ratio tertile 3 group clearly had a significantly higher incidence of ICU mortality (). Conclusion. An elevated De-Ritis ratio on admission was significantly associated with ICU mortality and hospital mortality after CA. Assessment of the De-Ritis ratio might help identify groups at high risk for mortality.
1. Introduction
Cardiac arrest (CA) is a life-threatening emergency situation with an incidence rate of 1 per 1000 patients. Patients presenting after CA have a low survival rate. In patients who achieve return of spontaneous circulation (ROSC), more than half of them die from circulatory shock [1]. There is also a high risk of neurological deficits, leading to high disability and morbidity. CA patients admitted to the intensive care unit (ICU) are usually unconscious. Therefore, the therapeutic management of these patients is challenging work. In spite of advances in cardiopulmonary resuscitation (CPR) and postresuscitation management, the prognosis after CA remains poor. Accurate outcome prediction, especially in the early stages of CA, will help to plan surveillance and treatment strategies [2]. In recent years, the factors influencing the outcome after CA have always been an important part of the research. Clinical outcomes following CA are affected by various parameters [3]. The individualized risk assessment of the patient’s potential risk of death or neurological deficits constitutes a crucial diagnostic approach and may influence therapeutic decisions when providing information to family members of patients. The European Resuscitation Council and the European Society of Intensive Care Medicine recommend using a combination of predictors, which include clinical neurological examination, electrophysiological investigations, serum biomarkers, and neuroimaging. However, current guidelines on how to best prognosticate the outcomes of cardiac arrest provide limited guidance and usually focus only on neurological status [4, 5].
In today’s era of personalized medicine, the concept of biomarkers for diagnosis and prognosis has become even more important. It requires prognostic markers that can be easily assessed to facilitate the identification of at-risk patients. In this aspect, aspartate aminotransferase (AST) and alanine transaminase (ALT) are easy to assess and, more importantly, are routinely available [6, 7]. It is considered that ALT mainly mirrors liver-specific dysfunction, while AST has been shown to increase after the death of ischaemic cells in some other tissues, including myocardium, skeletal muscle, kidney, and brain. Some studies have suggested that hepatic dysfunction is a common concomitant symptom of cardiovascular disease (CVD) [8, 9]. Evaluation of serum transaminases can predict morbidity and mortality in patients with CVD [6, 10, 11]. Recent studies have shown that AST and ALT may be used as predictors of prognosis in patients after acute and chronic cardiac events [6, 10–12]. We speculate that AST/ALT as a marker might mirror ischaemic end-organ damage in CA. As AST/ALT may provide more additional information on the risk assessment of patients after CA, we hypothesized that AST/ALT is associated with in-hospital death and neurological outcomes of cardiac arrest survivors. Hence, the study was aimed at exploring the associations of the De-Ritis (aspartate transaminase/alanine transaminase; proposed by Fernando De Ritis in 1957) ratio with outcome after CA [13].
2. Materials and Methods
2.1. Study Population
The primary data used in the study were acquired from the Dryad Digital Repository. The data are accessible in the Dryad Digital Repository (10.5061/dryad.qv6fp83). All patients were collected from a single centre from January 2007 to December 2015. Full details of the study population have been reported previously [14]. This study was a retrospective observational cohort study of adult CA patients treated at the Department of Intensive Care at Erasme Hospital, Brussels (Belgium). The need for informed consent was waived because of its retrospective nature.
2.2. Inclusion Criteria
The study included comatose patients with Glasgow Coma who had experienced in-hospital CA (IHCA) or out-of-hospital CA (OHCA). Patients were excluded if they had (1) missing data on liver function; (2) died within 24 hours of ICU admission; (3) no information on CA and CPR; or (4) lack of information on the neurological outcome at 3 months after CA. According to recent resuscitation guidelines, all patients with sustained return of spontaneous circulation (ROSC) received post-CA care [5, 15]. CA survivors in a coma were treated with 24-hour targeted temperature management (TTM; target body temperature: 32–34°C). The standardized institutional protocol of postresuscitation management has been described previously [16].
2.3. Data Collection
The following data on the basic characteristics of the patient was collected: demographics, location of arrest, presence of a witness on collapse, and cardiac arrest characteristics. Sequential Organ Failure Assessment (SOFA) score [17] and Acute Physiology and Chronic Health Assessment (APACHE) II score [18] were used to assess the severity of disease within 24 hours of admission. Blood samples were taken on admission as the first available laboratory data obtained after ROSC and processed according to local laboratory standards. Routine laboratory sampling included serum aspartate (AST, normal ranges: <41 IU/L) and serum alanine (ALT, normal ranges: <37 IU/L) transaminases, lactate dehydrogenase (LDH, normal ranges: <200 IU/L), gamma-glutamyl transpeptidase (GGT, normal ranges: 8-38 IU/L), total bilirubin (TBIL, normal ranges: ≤1.2 mg/dL), prothrombin time (PT, normal ranges: >70%), international normalized ratio (INR, normal ranges: ≤1.2), and platelet (PLT, normal ranges:150-/mm [3]). The De-Ritis ratio was calculated as the ratio of AST and ALT. Use of mechanical ventilation, continuous renal replacement therapy (CRRT), intra-aortic balloon pump (IABP), extracorporeal membrane oxygenation (ECMO), vasoactive drugs, and the length of ICU stay was recorded. Comorbidities included chronic heart failure (CHF), hypertension (HTN or HT), coronary artery disease (CAD), diabetes, chronic obstructive pulmonary disease (COPD)/asthma, neurological disease, chronic renal failure (CRF), liver cirrhosis, corticosteroids, and chronic anticoagulation. The use of potentially hepatotoxic drugs/interventions that include paracetamol, amiodarone, β-lactams, quinolones, azoles, isoniazid, trimethoprim/sulfamethoxazole (TMP/SMX), metronidazole, and any chemotherapy drugs was documented.
2.4. Definitions
Hypertension was defined as a systolic blood mmHg, diastolic blood mmHg, and/or the current use of antihypertensive medications [19]. Diabetes mellitus (DM) was defined as a previous history of diabetes and new hyperglycemia, a fasting serum glucose of ≥7.0 mmol/L (≥126 mg/dL), hemoglobin %, or current use of hypoglycemic agents [20]. The definition of acute liver failure (ALF) in this study was based on previously published standards, which included an international normalized in the presence of encephalopathy [21]. Hypoxic hepatitis (HH) is defined as an increase in serum aspartate transaminase and/or serum alanine transaminase to more than 20-fold the upper normal range without any other cause of hepatic cell necrosis after CA [22]. Acute kidney injury (AKI) was diagnosed according to AKIN criteria by the changes of serum creatinine during hospitalization [23]. Shock was defined as a systolic arterial mmHg despite adequate fluid resuscitation or use of vasopressor such as dopamine/dobutamine, adrenaline, and others for more than 6 hours.
2.5. Outcome Measures
The primary outcome was ICU mortality, which was defined as an all-cause mortality during the ICU stay. The secondary outcomes of study endpoint was a composite of hospital mortality and poor neurological function outcome at 3 months after CA, defined as cerebral performance categories score (CPC) 3-5, at/or around 90 days. And favorable neurological outcome was considered a CPC 1–2. The CPC score ranged from 1 to 5, with 1 for good brain function or mild disability, 2 for moderate disability, 3 for severe disability, 4 for coma or vegetative state, and 5 for brain death. The CPC assessment was performed prospectively during follow-up period or by telephone interview with the general practitioner.
2.6. Statistical Analysis
Nonnormally distributed continuous data are shown as medians (25th and 75th percentiles) and compared using the Kruskal-Wallis test. Categorical variables are expressed as counts with percentages and compared using the chi-squared test wherever appropriate. The logistic regression model was used to analyze the influence of De-Ritis ratio on ICU mortality, hospital mortality, and neurological outcome. These variables in the model were selected using a backward and forward stepwise method. The results were presented as an odds ratio (OR) with 95% confidence interval (CI) and an OR per standard deviation (OR per SD) increase. In the multivariate analysis, OR was adjusted for potential confounders, including age, male gender, bystander-witnessed CA, bystander CPR, adrenaline, nonshockable rhythm, chronic heart failure, chronic renal failure, liver cirrhosis, shock, AKI, lowest central venous/mixed venous oxygen saturation (ScvO2/SvO2) during the ICU stay, lactate, ScvO2/SvO2, GGT, total bilirubin, and mean arterial pressure (MAP). Kaplan-Meier curves were constructed to visualize differences in survival, and the log-rank test was utilized to declare significance. Receiver operator characteristic (ROC) curves were applied to determine optimal cutoff values of the De-Ritis ratio for mortality, and the predictive validity of the De-Ritis ratio measurements for mortality was assessed using corresponding results for the area under the curve (AUC). In addition, the likelihood ratio test (LRT) was used to calculate values of the goodness of fit between the different multivariate prediction models. In the calculation of the LRT, larger values and smaller Akaike information criterion (AIC) values indicate a better model fit. A two-tailed value < 0.05 was defined as statistically significant. Statistical analyses were performed with SPSS Statistics 25 (IBM SPSS, Armonk, New York, NY, USA), STATA 11.0 (STATA-Corp, College Station, Texas, TX, USA), and GraphPad Prism 8® (GraphPad Software, Inc., San Diego, California, USA).
3. Results
3.1. Distribution of De-Ritis Ratio and Baseline Characteristics
A total of 435 eligible CA patients were admitted, with 61 being excluded. A total of 374 CA patients (270 males, 104 females) were eventually enrolled (Figure 1). The participants were analysed by dividing the De-Ritis ratio into tertiles (tertile 1 group ≤1.13; tertile 2 group 1.14–1.58; and tertile 3 group ≥1.59) and using the first tertile as a reference. Baseline clinical characteristics of the study population at CA are shown in Table 1. Patients in tertile 3 group were older and had a lower rate of OHCA. Significant differences were found among groups in terms of hematology indices on admission, with the exception of ScvO2/SvO2, proteins, pH, PaCO2, PaO2, and creatinine. No significant differences were found in the characteristics of comorbidities or comorbidities. The De-Ritis ratio showed a correlation with PT values (; ) and INR values (; ) (Table 2).
