OBJECTIVE: To investigate the mechanism of human embryonic stem cell-derived mesenchymal stem cells (hESC-MSC) in alleviating brain injury after resuscitation in swine with cardiac arrest (CA). METHODS: Twenty-nine healthy male large white swine were randomly divided into Sham group (n = 9), cardiopulmonary resuscitation (CPR) group (n = 10) and hESC-MSC group (n = 10). The Sham group only completed animal preparation. In CPR group and hESC-MSC group, the swine model of CA-CPR was established by inducing ventricular fibrillation for 10 minutes with electrical stimulation and CPR for 6 minutes. At 5 minutes after successful resuscitation, hESC-MSC 2.5×10⁶/kg was injected via intravenous micropump within 1 hour in hESC-MSC group. Venous blood samples were collected before resuscitation and at 4, 8, 24, 48 and 72 hours of resuscitation. The levels of neuron specific enolase (NSE) and S100B protein (S100B) were detected by enzyme linked immunosorbent assay (ELISA). At 24, 48 and 72 hours of resuscitation, neurological deficit score (NDS) and cerebral performance category (CPC) were used to evaluate the neurological function of the animals. Three animals from each group were randomly selected and euthanized at 24, 48, and 72 hours of resuscitation, and the hippocampus tissues were quickly obtained. Immunofluorescence staining was used to detect the distribution of hESC-MSC in hippocampus. Immunohistochemical staining was used to detect the activation of astrocytes and microglia and the survival of neurons in the hippocampus. The degree of apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL). RESULTS: The serum NSE and S100B levels of brain injury markers in CPR group and hESC-MSC group were significantly higher than those in Sham group at 24 hours of resuscitation, and then gradually increased. The levels of NSE and S100B in serum at each time of resuscitation in hESC-MSC group were significantly lower than those in CPR group [NSE (μg/L): 20.69±3.62 vs. 28.95±3.48 at 4 hours, 27.04±5.56 vs. 48.59±9.22 at 72 hours; S100B (μg/L): 2.29±0.39 vs. 3.60±0.73 at 4 hours, 2.38±0.15 vs. 3.92±0.50 at 72 hours, all P < 0.05]. In terms of neurological function, compared with the Sham group, the NDS score and CPC score in the CPR group and hESC-MSC group increased significantly at 24 hours of resuscitation, and then gradually decreased. The NDS and CPC scores of hESC-MSC group were significantly lower than those of CPR group at 24 hours of resuscitation (NDS: 111.67±20.21 vs. 170.00±21.79, CPC: 2.33±0.29 vs. 3.00±0.00, both P < 0.05). The expression of hESC-MSC positive markers CD73, CD90 and CD105 in the hippocampus of hESC-MSC group at 24, 48 and 72 hours of resuscitation was observed under fluorescence microscope, indicating that hESC-MSC could homing to the damaged hippocampus. In addition, compared with Sham group, the proportion of astrocytes, microglia and apoptotic index in hippocampus of CPR group were significantly increased, and the proportion of neurons was significantly decreased at 24, 48 and 72 hours of resuscitation. Compared with CPR group, the proportion of astrocytes, microglia and apoptotic index in hippocampus of hESC-MSC group decreased and the proportion of neurons increased significantly at 24 hours of resuscitation [proportion of astrocytes: (14.33±1.00)% vs. (30.78±2.69)%, proportion of microglia: (12.00±0.88)% vs. (27.89±5.68)%, apoptotic index: (12.89±3.86)% vs. (52.33±7.77)%, proportion of neurons: (39.44±3.72)% vs. (28.33±1.53)%, all P < 0.05]. CONCLUSIONS Application of hESC-MSC at the early stage of resuscitation can reduce the brain injury and neurological dysfunction after resuscitation in swine with CA. The mechanism may be related to the inhibition of immune cell activation, reduction of cell apoptosis and promotion of neuronal survival.
Animals ; Heart Arrest/therapy* ; Cardiopulmonary Resuscitation ; Swine ; Humans ; Male ; Human Embryonic Stem Cells/cytology* ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/cytology* ; Phosphopyruvate Hydratase/blood* ; Brain Injuries/therapy* ; S100 Calcium Binding Protein beta Subunit ; Apoptosis ; Disease Models, Animal

OBJECTIVE: To construct a longitudinal trajectory model of arterial oxygen tension (PaO₂) within 24 hours after cardiac arrest (CA). METHODS: A retrospective cohort study was conducted. CA patients admitted to the ICU from 2014 to 2015 were selected from the eICU Collaborative Research Database (eICU-CRD). Data about patients' demographic characteristics, history of comorbidities, laboratory test indicators within 24 hours of intensive care unit (ICU) admission [including all PaO₂ data and arterial carbon dioxide tension (PaCO₂)], vasopressor use, and clinical outcomes were extracted from the database. The primary outcome variable was all-cause in-hospital mortality. Group-based trajectory model (GBTM) were built based on the changes in PaO₂ within 24 hours of ICU admission, and patients were grouped according to their initial static PaO₂ values upon ICU admission. Multivariable adjusted Poisson regression analysis was used to compare the in-hospital mortality risk among patients in different PaO₂ dynamic trajectory groups. Sensitivity analyses were performed using multivariable logistic regression and multivariable adjusted Poisson regression without imputation of missing values. RESULTS: A total of 3 866 CA patients were included. Three GBTM trajectory groups were identified based on PaO₂ changes within 24 hours of ICU admission: Group-1 (low level first increased then decreased, 148 cases), Group-2 (sustained low level, 3 040 cases), and Group-3 (first high level then decreased, 678 cases). Significant differences were found among the three groups in age, body weight, maximum serum potassium, maximum PaCO₂, minimum hemoglobin (Hb), vasopressor use, total hospitalization time, ICU stay, and hospital mortality. After incorporating variables with significant differences into the multivariable adjusted Poisson regression model, results showed that compared to Group-2 patients, patients in Group-1 and Group-3 had an increased risk of all-cause in-hospital mortality [Group-1 adjusted relative risk (aRR) = 1.20, 95% confidence interval (95%CI) was 1.02-1.41; Group-3 aRR = 1.11, 95%CI was 1.01-1.24]. Based on initial static PaO₂ values at ICU admission, patients were divided into four groups: PaO₂ < 100 mmHg (1 mmHg = 0.133 kPa; 1 217 cases), PaO₂ 100-200 mmHg (569 cases), PaO₂ 201-300 mmHg (547 cases), and PaO₂ > 300 mmHg (1 082 cases). Multivariable adjusted Poisson regression analysis indicated a significant upward trend in aRR for the latter three groups compared to the PaO₂ < 100 mmHg group. Sensitivity analyses revealed that compared to Group-2, patients in Group-1 and Group-3 had a significantly increased risk of all-cause in-hospital mortality (both P < 0.05). CONCLUSIONS Within 24 hours after return of spontaneous circulation in CA patients, PaO₂ exhibits different dynamic trajectories, and patients with hyperoxia have an increased risk of in-hospital mortality.
Humans ; Retrospective Studies ; Hospital Mortality ; Heart Arrest/blood* ; Prognosis ; Oxygen/blood* ; Intensive Care Units ; Cardiopulmonary Resuscitation ; Male ; Female ; Middle Aged

OBJECTIVE: To assess the effects of Shenfu Injection (, SFI) on blood lactate, and secondarily its effect on the lactate clearance (LC) in patients with post cardiac arrest syndrome (PCAS). METHODS: The present study is a post hoc study of a randomized, assessor-blinded, controlled trial. Patients experienced in-hospital cardiac arrest between 2012 and 2015 were included in the predefined post hoc analyses. Of 1,022 patients enrolled, a total of 978 patients were allocated to the control group (486 cases) and SFI (492 cases) group, receiving standardized post-resuscitation care bundle (PRCB) treatment or PRCB combined with SFI (100 mL/d), respectively. Patients' serum lactate was measured simultaneously with artery blood gas, lactate clearance (LC) was calculated on days 1, 3, and 7 after admission and compared between groups. Lactate and LC were also compared between the survivors and non-survivors according to the 28-d mortality, as well as the survivors and non-survivors subgroups both in the SFI and control groups. RESULTS: In both groups, compared with pre-treatment levels, mean arterial pressure (MAP) and PaO₂ were significantly improved on 1, 3, 7 d after treatment (P<0.05), while heart rate (HR) and blood glucose levels were significantly decreased on 1, 3 and 7 d after treatment (P<0.05). compared with control group, SFI treatment improved the values of MAP and PaO₂ (P<0.05), and significantly decreased the levels of HR and the blood glucose level on 3 and 7 d after treatment (P<0.05). Compared with the control group, lactate levels decreased faster in the SFI group versus the control group on 3 and 7 d (P<0.05). From initiation of treatment and the following 3 and 7 d, SFI treatment greatly increased the LC compared with that in the control group (P<0.05). Compared with survivors, non-survivors had higher admission lactate levels (7.3 ±1.1 mmol/L vs. 5.5 ±2.3 mmol/L; P<0.01), higher lactate levels on days 1, 3 and 7 (P<0.05), and LC were decreased significantly on 3 and 7 d after treatment (P<0.05). Similar results were also found both in the SFI and control groups between survivors and non-survivors subgroups. CONCLUSION SFI in combination with PRCB treatment is effective at lowering lactate level and resulted in increasing LC in a targeted population of PCAS patients.
Blood Glucose ; Drugs, Chinese Herbal/therapeutic use* ; Heart Arrest/drug therapy* ; Humans ; Lactic Acid ; Post-Cardiac Arrest Syndrome

A 34-year-old male was brought to the hospital with a chest gunshot wound. Pulseless upon arrival, blood pressure was absent for 10 minutes. A thoracotomy resulted in return of spontaneous circulation. On hospital day 5, with brainstem reflexes present, he was unresponsive to call or pain, exhibited generalized hyperreflexia and bilateral Babinskys. Median nerve somatosensory evoked potentials (mSSEPs) and brainstem auditory evoked potentials were obtained. International Federation of Clinical Neurophysiology recommendations for mSSEPs and brainstem auditory evoked potentials were followed. Despite absence of the N20 responses from cortical mSSEPs no withdrawal from care was agreed upon. After awaking on day 7, mSSEPs were repeated and present. The patient survived and was discharged with minor deficits. Bilateral absence of N20 responses from mSSEPs performed beyond 48 hours after resuscitation from cardiac arrest is highly associated with bad neurological outcomes. However, variation due to hypothermia, noisy signals, medications, and brain hypo-perfusion must be taken into account.
Adult ; Blood Pressure ; Brain ; Brain Stem ; Critical Care Outcomes ; Evoked Potentials, Auditory, Brain Stem ; Evoked Potentials, Somatosensory ; Heart Arrest ; Humans ; Hypothermia ; Male ; Median Nerve ; Nervous System Diseases ; Neurophysiology ; Prognosis ; Reflex ; Reflex, Abnormal ; Resuscitation ; Thoracotomy ; Thorax ; Wounds, Gunshot

PURPOSE: Rhabdomyolysis is a metabolic disorder in which the content of damaged muscle cells is released into plasma. Its manifestations include asymptomatic, myalgia, gross hematuria, and complications of acute kidney injury. Because of limited data on rhabdomyolysis in children, we performed this study to determine clinical characteristics of rhabdomyolysis in children. METHODS: We retrospectively reviewed the records of patients with rhabdomyolysis who were treated at the Pusan National University Children's hospital from January 2011 to July 2016. The diagnostic criteria were serum myoglobin level of ≥80 ng/mL, exclusive of acute myocardial injury, cardiac arrest, and brain damage. RESULTS: Forty-five patients were enrolled; mean age, 116±68 months. Of these, 35 were boys and 10 were girls. Twenty-six patients experienced myalgia and 12 patients showed gross hematuria. Among these, seven patients initially had both myalgia and gross hematuria. The most common causes of rhabdomyolysis were infection, physical exertion, prolonged seizures, metabolic abnormalities, and drug addiction. Acute kidney injury (AKI) was the most common complication, followed by disseminated intravascular coagulation. Thirty-seven patients improved with sufficient fluid supply but two patients underwent hemodialysis due to deterioration of kidney function. Gross hematuria, positive occult blood test, and positive urine protein were more common in patients with AKI than in those without AKI. CONCLUSIONS: In children, infection was the most common cause of rhabdomyolysis. Most patients recovered by sufficient fluid therapy. However, in severe cases, especially in patients with underlying kidney disease, hemodialysis may be necessary in the present study.
Acute Kidney Injury ; Brain ; Busan ; Child ; Disseminated Intravascular Coagulation ; Female ; Fluid Therapy ; Heart Arrest ; Hematuria ; Humans ; Influenza, Human ; Kidney ; Kidney Diseases ; Muscle Cells ; Myalgia ; Myoglobin ; Occult Blood ; Physical Exertion ; Plasma ; Renal Dialysis ; Retrospective Studies ; Rhabdomyolysis ; Seizures ; Substance-Related Disorders

Carbon monoxide (CO) is well-known as toxic gas and intrinsic signaling molecule such as neurotransmitter and blood vessel relaxant. Recently, it has been reported that low concentration of CO exerts therapeutic actions under various pathological conditions including liver failure, heart failure, gastric cancer, and cardiac arrest. However, little has been known about the effect of CO in neurodegenerative diseases like Parkinson’s disease (PD). To test whether CO could exert a beneficial action during oxidative cell death in PD, we examined the effects of CO on 6-hydroxydopamine (6-OHDA)-induced cell death in C6 glioma cells. Treatment of CO-releasing molecule-2 (CORM-2) significantly attenuated 6-OHDA-induced apoptotic cell death in a dose-dependent manner. CORM-2 treatment decreased Bax/Bcl2 ratio and caspase-3 activity, which had been increased by 6-OHDA. CORM-2 increased phosphorylation of NF-E2-related factor 2 (Nrf2) which is a transcription factor regulating antioxidant proteins. Subsequently, CORM-2 also increased the expression of heme oxygenase-1 and superoxide dismutases (CuZnSOD and MnSOD), which were antioxidant enzymes regulated by Nrf2. These results suggest that CO released by CORM-2 treatment may have protective effects against oxidative cell death in PD through the potentiation of cellular adaptive survival responses via activation of Nrf2 and upregulation of heme oxygenase-1, leading to increasing antioxidant defense capacity.
Blood Vessels ; Carbon Monoxide* ; Carbon* ; Caspase 3 ; Cell Death* ; Glioma* ; Heart Arrest ; Heart Failure ; Heme Oxygenase-1 ; Liver Failure ; Neurodegenerative Diseases ; Neuroprotection ; Neurotransmitter Agents ; NF-E2-Related Factor 2 ; Oxidopamine ; Phosphorylation ; Stomach Neoplasms ; Superoxides ; Transcription Factors ; Up-Regulation

PURPOSE: Cardiovascular or respiratory complications of acute intoxication are the most common causes of mortality. Advanced cardiac life support (ACLS) or specific antidotes help manage these cardiac or respiratory complications in acute intoxication. On the other hand, some cases do not respond to ACLS or antidotes and they require some special treatment, such as extracorporeal life support (ECLS). ECLS will provide the chance of recovery from acute intoxication. This study examined the optimal timing of ECLS in acute intoxication cases. METHODS: This paper is a brief report of a case series about ECLS in acute poisoning. The cases of ECLS were reviewed and the effects of ECLS on the blood pressure and serum lactate level of the patients were analyzed. RESULTS: A total of four cases were reviewed; three of them were antihypertensive agent-induced shock, and one was respiratory failure after the inhalation of acid. The time range of ECLS application was 4.8-23.5 hours after toxic exposure. The causes of ECLS implementation were one for recurrent cardiac arrest, two for shock that did not respond to ACLS, and one for respiratory failure that did not respond to mechanical ventilator support. Three patients showed an improvement in blood pressure and serum lactate level and were discharged alive. In case 1, ECLS was stared at 23.5 hours post toxic exposure; the patient died due to refractory shock and multiple organ failure. CONCLUSION: The specific management of ECLS should be considered when a patient with acute intoxication does not recovery from shock or respiratory failure despite ACLS, antidote therapies, or mechanical ventilator support. ECLS improved the hemodynamic and ventilator condition in complicated poisoned patients. The early application of ECLS may improve the tissue perfusion state and outcomes of these patients before the toxic damage becomes irreversible.
Advanced Cardiac Life Support ; Antidotes ; Blood Pressure ; Hand ; Heart Arrest ; Hemodynamics ; Humans ; Inhalation ; Lactic Acid ; Mortality ; Multiple Organ Failure ; Perfusion ; Poisoning* ; Respiratory Insufficiency ; Shock ; Ventilators, Mechanical

OBJECTIVE: This study aimed to determine whether simultaneous decreases in the serum levels of cell adhesion molecules (intracellular cell adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], and E-selectin) and S100 proteins within the first 24 hours after the return of spontaneous circulation were associated with good neurological outcomes in cardiac arrest survivors. METHODS: This retrospective observational study was based on prospectively collected data from a single emergency intensive care unit (ICU). Twenty-nine out-of-hospital cardiac arrest survivors who were admitted to the ICU for post-resuscitation care were enrolled. Blood samples were collected at 0 and 24 hours after ICU admission. According to the 6-month cerebral performance category (CPC) scale, the patients were divided into good (CPC 1 and 2, n=12) and poor (CPC 3 to 5, n=17) outcome groups. RESULTS: No difference was observed between the two groups in terms of the serum levels of ICAM-1, VCAM-1, E-selectin, and S100 at 0 and 24 hours. A simultaneous decrease in the serum levels of VCAM-1 and S100 as well as E-selectin and S100 was associated with good neurological outcomes. When other variables were adjusted, a simultaneous decrease in the serum levels of VCAM-1 and S100 was independently associated with good neurological outcomes (odds ratio, 9.285; 95% confidence interval, 1.073 to 80.318; P=0.043). CONCLUSION: A simultaneous decrease in the serum levels of soluble VCAM-1 and S100 within the first 24 hours after the return of spontaneous circulation was associated with a good neurological outcome in out-of-hospital cardiac arrest survivors.
Blood-Brain Barrier ; Cardiopulmonary Resuscitation ; Cell Adhesion ; Cell Adhesion Molecules ; E-Selectin ; Emergencies ; Endothelium ; Heart Arrest* ; Humans ; Intensive Care Units ; Intercellular Adhesion Molecule-1 ; Observational Study ; Out-of-Hospital Cardiac Arrest ; Prospective Studies ; Retrospective Studies ; S100 Proteins ; Survivors* ; Vascular Cell Adhesion Molecule-1*

OBJECTIVE: This study examined the initial partial pressure of carbon dioxide (PCO₂) as a possible indicator of prehospital ventilation and its association with prehospital i-gel in out-of-hospital cardiac arrest (OHCA) patients. METHODS: The demographics and arrest parameters, including i-gel insertion and initial arterial blood gas analysis, of OHCA patients who visited the emergency department were analyzed retrospectively. Linear regression analysis was performed to examine the association between i-gel insertion and the initial PCO₂. RESULTS: A total of 106 patients were investigated. Fifty-six patients had prehospital i-gel insertion and 50 patients did not have a prehospital advanced airway. The initial PCO₂ was higher in the i-gel group than the no advanced airway group (105.2 mmHg [77.5–134.9] vs. 87.5 mmHg [56.8–115.3], P=0.03). Prehospital i-gel insertion was associated with a higher initial PCO₂ level (βcoefficient, 20.3; 95% confidence interval, 2.6–37.9; P=0.03). CONCLUSION: Prehospital insertion of i-gel was associated with higher initial PCO₂ values in OHCA patients compared to no advanced airway.
Airway Management ; Blood Gas Analysis ; Carbon Dioxide ; Cardiopulmonary Resuscitation ; Demography ; Emergency Medical Services ; Emergency Service, Hospital ; Heart Arrest ; Humans ; Linear Models ; Out-of-Hospital Cardiac Arrest* ; Partial Pressure ; Retrospective Studies ; Ventilation

BACKGROUND: Hypoglycemia is uncommon in people without diabetes. There have been only a few reports of cardiac arrest in conjunction with hypoglycemia in non-diabetic patients. CASE REPORT: A 66-year-old man visited the emergency room with dizziness. He was a chronic alcoholic. Laboratory test showed no evidence of diabetes mellitus. Brain magnetic resonance imaging revealed a left cerebellar infarction. Abdomen computed tomography demonstrated liver cirrhosis with minimal ascites. During his hospital stay, he consumed only a small amount of food because of nausea and headache. On hospital day 4, he had a cardiac arrest after two seizure episodes. His blood glucose was 10 mg/dL. The combination of liver cirrhosis, renal failure and poor oral intake was presumed to be the causes of the severe hypoglycemia. CONCLUSION: We report a rare case of cardiac arrest occurring in conjunction with severe hypoglycemia in a non-diabetic patient with cerebral infarction.
Abdomen ; Aged ; Alcoholics ; Ascites ; Blood Glucose ; Brain ; Cerebral Infarction ; Diabetes Mellitus ; Dizziness ; Emergency Service, Hospital ; Headache ; Heart Arrest ; Humans ; Hypoglycemia ; Infarction ; Length of Stay ; Liver Cirrhosis ; Magnetic Resonance Imaging ; Nausea ; Renal Insufficiency ; Seizures