RESUMEN
INTRODUCTION: Severe septic cardiomyopathy (SCM) is one of the main causes of refractory septic shock (RSS), with a high mortality. The application of venoarterial extracorporeal membrane oxygenation (ECMO) to support the impaired cardiac function in patients with septic shock remains controversial. Moreover, no prospective studies have been taken to address whether venoarterial ECMO treatment could improve the outcome of patients with sepsis-induced cardiogenic shock. The objective of this study is to assess whether venoarterial ECMO treatment can improve the 30-day survival rate of patients with sepsis-induced refractory cardiogenic shock. METHODS AND ANALYSIS: ExtraCorporeal Membrane Oxygenation in the therapy for REfractory Septic shock with Cardiac function Under Estimated is a prospective, multicentre, non-randomised, cohort study on the application of ECMO in SCM. At least 64 patients with SCM and RSS will be enrolled in an estimated ratio of 1:1.5. Participants taking venoarterial ECMO during the period of study are referred to as cohort 1, and patients receiving only conventional therapy without ECMO belong to cohort 2. The primary outcome is survival in a 30-day follow-up period. Other end points include survival to intensive care unit (ICU) discharge, hospital survival, 6-month survival, quality of life for long-term survival (EQ-5D score), successful rate of ECMO weaning, long-term survivors' cardiac function, the number of days alive without continuous renal replacement therapy, mechanical ventilation and vasopressor, ICU and hospital length of stay, the rate of complications potentially related to ECMO treatment. ETHICS AND DISSEMINATION: The trial has been approved by the Clinical Research and Application Institutional Review Board of the Second Affiliated Hospital of Guangzhou Medical University (2020-hs-51). Participants will be screened and enrolled from ICU patients with septic shock by clinicians, with no public advertisement for recruitment. Results will be disseminated in research journals and through conference presentations. TRIAL REGISTRATION NUMBER: NCT05184296.
Asunto(s)
Oxigenación por Membrana Extracorpórea , Choque Cardiogénico , Choque Séptico , Adulto , Femenino , Humanos , Masculino , Cardiomiopatías/terapia , Oxigenación por Membrana Extracorpórea/métodos , Unidades de Cuidados Intensivos , Estudios Multicéntricos como Asunto , Estudios Prospectivos , Choque Cardiogénico/terapia , Choque Cardiogénico/mortalidad , Choque Séptico/terapia , Choque Séptico/mortalidad , Choque Séptico/complicaciones , Tasa de SupervivenciaRESUMEN
INTRODUCTION: Acute kidney injury (AKI) is one of the most common organ dysfunction in sepsis, and increases the risk of unfavourable outcomes. Renal replacement therapy (RRT) is the predominant treatment for sepsis-associated AKI (SAKI). However, to date, no prospective randomised study has adequately addressed whether initiating RRT earlier will attenuate renal injury and improve the outcome of sepsis. The objective of the trial is to compare the early strategy with delayed strategy on the outcomes in patients with SAKI in the intensive care unit (ICU). METHODS AND ANALYSIS: This is a large-scale, multicentre, randomised controlled trial about SAKI. In total, 460 patients with sepsis and evidence of AKI stage 2 of Kidney Disease Improving Global Outcomes (KDIGO) will be recruited and equally randomised into the early group and the delay group in a ratio of 1:1. In the early group, continuous RRT (CRRT) will be started immediately after randomisation. In the delay group, CRRT will initiated if at least one of the following criteria was met: stage 3 of KDIGO, severe hyperkalaemia, pulmonary oedema, blood urea nitrogen level higher than 112 mg/dL after randomisation. The primary outcome is overall survival in a 90-day follow-up period (90-day all-cause mortality). Other end points include 28-day, 60-day and 1-year mortality, recovery rate of renal function by day 28 and day 90, ICU and hospital length of stay, the numbers of CRRT-free days, mechanical ventilation-free days and vasopressor-free days, the rate of complications potentially related to CRRT, CRRT-related cost, and concentrations of inflammatory mediators in serum. ETHICS AND DISSEMINATION: The trial has been approved by the Clinical Research and Application Institutional Review Board of the Second Affiliated Hospital of Guangzhou Medical University (2017-31-ks-01). Participants will be screened and enrolled from patients in the ICU with SAKI by clinicians, with no public advertisement for recruitment. Results will be disseminated in research journals and through conference presentations. TRIAL REGISTRATION: NCT03175328.
Asunto(s)
Lesión Renal Aguda , Terapia de Reemplazo Renal Continuo , Sepsis , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Humanos , Unidades de Cuidados Intensivos , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Terapia de Reemplazo Renal , Sepsis/complicaciones , Sepsis/terapiaRESUMEN
OBJECTIVE: To investigate the regulatory effect of microRNA-141 (miR-141) on expression of high mobility group protein B1(HMGB1) in human monocytes THP-1 cell line. METHODS: THP-1 cells were transfected with miR-141 mimic or inhibitor (100 nmol/L) for 48 hours with lipofectamine RNAi MAX. The levels of miR-141 and HMGB1 mRNA in the THP-1 cells were detected by real-time fluorescence quantitation reverse transcription-polymerase chain reaction (RT-PCR), and HMGB1 protein was determined with Western blotting. RESULTS: The levels of miR-141 could be up regulated (35.33±7.24 vs. 1.21±0.20, t=-8.408, P=0.010) or down regulated (0.55±0.12 vs 1.09±0.05, t=7.473, P=0.002) after being transfected with 100 nmol/L miR-141 mimic or inhibitor for 48 hours by lipofectamine RNAi MAX in THP-1, and the level of HMGB1 mRNA and protein decreased (mRNA: 0.43±0.06 vs. 0.97±0.08, t=9.760, P=0.001; protein: 0.63±0.12 vs. 1.00±0.11, t=2.991, P=0.040) or increased (mRNA: 2.13±0.11 vs. 1.16±0.13, t=-9.977, P=0.001; protein: 1.78±0.04 vs. 0.96±0.09, t=-13.778, P=0.000) simultaneously compared with the control group. CONCLUSIONS: miR-141 is involved in regulation of inflammation through HMGB1 gene and protein pathway, suggesting that miR-141 plays an important role in regulating immune cells during the inflammatory response.
Asunto(s)
Proteína HMGB1/metabolismo , MicroARNs/metabolismo , Monocitos/metabolismo , Línea Celular , Humanos , Monocitos/citología , TransfecciónRESUMEN
OBJECTIVE: To determine effects of recruitment maneuver (RM) guided by pressure-volume (P-V) curve on respiratory physiology and lung morphology in canine models of acute respiratory distress syndrome of pulmonary or extrapulmonary origin (ARDSp and ARDSexp). METHODS: Twenty-four healthy dogs were randomly divided into two groups with 12 dogs each: ARDSexp and ARDSp. Each dog in ARDSexp group was injected with oleic acid 0.1 ml/kg through femoral vein, and each dog in ARDSp group received hydrochloric acid 2 ml/kg via trachea. Subsequently, dogs with both models were randomly subdivided into lung protective ventilation strategy (LPVS) group and LPVS+RM group, respectively. Dogs in LPVS group were given LPVS only without RM. RM guided by P-V curve was performed in LPVS+RM group followed by LPVS and pressure controlled ventilation (PCV) mode was selected. Phigh was set at upper inflection point (UIP) of the P-V curve, positive end-expiratory pressure (PEEP) was set at lower inflection point (LIP)+2 cm H(2)O (1 cm H(2)O=0.098 kPa), and the duration of RM was 60 seconds. The duration of mechanical ventilation (MV) in both subgroups was 4 hours. The oxygenation index (PaO(2)/FiO(2)), relative lung mechanical indexes were measured in two ARDS models before establishment of ARDS model, and before and after RM. The UIP and LIP were calculated with P-V curve. The percentage of different volume in ventilation of lung accounting for total lung volume was compared by CT scan. RESULTS: The PaO(2)/FiO(2), UIP and LIP did not showed significant differences among all groups before ARDS and before RM. PaO(2)/FiO(2) and respiratory system compliance (Crs) were significantly elevated in LPVS+RM group of both models 4 hours after RM compared with corresponding LPVS group [PaO(2)/FiO(2) (mm Hg, 1 mm Hg=0.133 kPa) of ARDSexp model: 263.9±69.2 vs. 182.8±42.8, Crs (ml/cm H(2)O) of ARDSexp model: 11.3±4.2 vs. 9.7±3.7; PaO(2)/FiO(2) (mm Hg) of ARDSp model: 193.4±33.5 vs. 176.4±40.2, Crs (ml/cm H(2)O) of ARDSp model: 10.1±3.9 vs. 9.0±3.9, P<0.05 or P<0.01], and the airway pressure was significantly declined compared with corresponding LPVS group [peak inspiratory pressure (PIP), cm H(2)O ] of ARDSexp model: 24.1±7.4 vs. 30.2±8.5, plateau pressure (Pplat, cm H(2)O) of ARDSexp model: 19.1±7.3 vs. 25.6±7.7; PIP (cm H(2)O) of ARDSp model: 26.6±8.4 vs. 29.6±10.3, Pplat (cm H(2)O) of ARDSp model: 21.9±7.3 vs. 25.1±8.4, P<0.05 or P<0.01]. Moreover, PaO(2)/FiO(2), Crs, PIP and Pplat were improved better in ARDSexp model than ARDSp model (P<0.05 orP<0.01). Compared with LPVS maneuver, RM plus LPVS maneuver could significantly decrease the proportion of closure and hypoventilation region, and increase the proportion of normal ventilation region in both models [closure region of ARDSexp model: (9.9±3.1)% vs. (16.3±5.2)%, hypoventilation region of ARDSexp model: (10.2±4.2)% vs. (23.4±6.7)%, normal ventilation region of ARDSexp model: (76.2±12.3)% vs. (57.5±10.1)%; closure region of ARDSp model: (14.3±4.8)% vs. (18.2±5.1)%, hypoventilation region of ARDSp model: (17.4±6.3)% vs. (24.1±5.9)%, normal ventilation region of ARDSp model: (63.2±10.7)% vs. (54.6±11.3)%, P<0.05 or P<0.01]. All of the ventilation regions were better improved with ARDSexp model than ARDSp model (all P<0.05). CONCLUSION: RM guided by P-V curve could help obtain better oxygenation, improve pulmonary compliance and lung ventilation in ARDSexp and ARDSp, and better treatment effects are seen in ARDSexp dogs than ARDSp dogs.
Asunto(s)
Pulmón/patología , Síndrome de Dificultad Respiratoria/patología , Síndrome de Dificultad Respiratoria/fisiopatología , Animales , Modelos Animales de Enfermedad , Perros , Femenino , Masculino , Respiración con Presión Positiva , Presión , Síndrome de Dificultad Respiratoria/terapia , Fenómenos Fisiológicos Respiratorios , Volumen de Ventilación PulmonarRESUMEN
OBJECTIVE: To investigate the expression profile of macrophage migration inhibitory factor (MIF) in serum and lung tissues of mice with sepsis, and to explore the effect of MIF antagonist ISO-1 on sepsis in a murine sepsis model. METHODS: Sepsis was reproduced in 40 mice by cecal ligation and puncture (CLP). Heart blood was obtained from 8 mice each at 12, 24, 36, 48 hours after CLP. The content of MIF in serum was determined by enzyme linked immunosorbent assay (ELISA). MIF mRNA and protein expressions in lung tissues of septic mice were assessed by reverse transcription-polymerase chain reaction (RT-PCR) or Western blotting. Another group of 40 mice were selected to investigate the role and the impact of MIF antagonist ISO-1 in septic mice. RESULTS: The content of MIF in serum was higher in septic mice than that in sham operation group, and it peaked at 36 hours, and decreased at 48 hours, but still higher than that in sham operation group (all P<0.01). The MIF mRNA and protein expression in lung tissues of septic mice were higher than those in sham operation group, beginning at 12 hours, and peaked at 48 hours (P<0.05 or P<0.01). ISO-1, which was the antagonist of MIF, could elevate the surviving rate of animals with sepsis [60% (12/20) vs. 25% (5/20), P<0.05]. CONCLUSION: MIF plays a role as a late mediator in sepsis, with a high expression of MIF in serum and lung tissue. ISO-1 can elevate the surviving rate in murine model of sepsis. It is concluded that MIF could be taken as a potential target of treatment of sepsis.