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1.
Medicine (Baltimore) ; 98(39): e17354, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574878

RESUMO

INTRODUCTION: The incidence, mortality, and treatment costs of sepsis are high and, thus, present a major challenge for critical care medicine. Our previous studies suggest that intestinal metabolite granisetron has a potential therapeutic effect on sepsis. Granisetron is a clinically widely used antiemetic, which is safe, inexpensive, and reliable. However, its value in the treatment of sepsis remains unclear. This study aims to explore the efficacy and safety of granisetron in the treatment of sepsis. METHODS AND ANALYSIS: A single-center, single-blind, randomized, controlled clinical trial will be conducted on 154 patients with sepsis. Patients who meet sepsis 3.0 diagnostic criteria, aged ≥18 and ≤80 years, with PCT ≥ 2 ng/mL will be recruited. Patients will be randomized to receive intravenous granisetron 3 mg every 8 hours (n = 77) or an equal volume of normal saline (n = 77) for a treatment period of 4 days or to ICU discharge. The primary outcome is 28-day all-cause mortality. Secondary outcome measures include requirements for organ function support, changes of organ function, changes in infection biomarkers, changes in inflammatory and immune biomarkers, and the proportion of new organ failure. Adverse events and serious adverse events also will be observed closely. ETHICS AND DISSEMINATION: The study was approved by the Clinical Ethics Committee of Zhujiang Hospital of Southern Medical University (2018-ZZJHZX-009). The trial results will be disseminated at national and international conferences and through peer-reviewed journal. TRIAL REGISTRATION: NCT03924518.URL: www.clinicaltrials.gov. PROTOCOL DATE: 1 May 2019. version 2.1.


Assuntos
Granisetron/administração & dosagem , Sepse/tratamento farmacológico , Antagonistas da Serotonina/administração & dosagem , Choque Séptico/tratamento farmacológico , Administração Intravenosa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Sepse/mortalidade , Choque Séptico/mortalidade , Método Simples-Cego , Resultado do Tratamento , Adulto Jovem
3.
Adv Exp Med Biol ; 1145: 321-341, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31364085

RESUMO

Polymyxin B is an antibiotic that shows strong bactericidal activity against Gram-negative bacteria, by binding to and inactivating endotoxin. Systemic administration of polymyxin B in humans is restricted because of its nephrotoxicity and neurotoxicity, and this compound was therefore considered a strong candidate ligand for the extracorporeal selective adsorption of circulating endotoxin in the blood. Toraymyxin® is a direct hemoperfusion column that uses polymyxin B attached to an insoluble carrier to bind endotoxin in the blood. In 1994, the Japanese National Health Insurance system approved the use of Toraymyxin for the treatment of endotoxemia and septic shock.In this chapter, we will review the development, clinical use, and efficacy of Toraymyxin, examine the structure of the Toraymyxin column, and comment on the current position of Toraymyxin in the treatment of severe sepsis and septic shock. We will also highlight some potential new applications of Toraymyxin for pulmonary diseases.


Assuntos
Antibacterianos/farmacologia , Endotoxinas/isolamento & purificação , Hemoperfusão , Polimixina B/farmacologia , Endotoxemia/tratamento farmacológico , Endotoxinas/sangue , Humanos , Sepse/tratamento farmacológico , Choque Séptico/tratamento farmacológico
5.
Ann Hematol ; 98(10): 2311-2318, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432214

RESUMO

The role of adjunctive corticosteroid in septic shock remains debatable, and its role has not been assessed in neutropenic patients. We evaluated whether hydrocortisone reduces 28-day mortality in neutropenic patients with septic shock. We conducted a retrospective cohort study between January 2012 and May 2017 at a tertiary care center in South Korea. Patients who developed septic shock treated with at least one vasopressor and whose absolute neutrophil count was < 1000 cells/µL were included. Patients were classified into a steroid and a no-steroid group. The primary outcome of the study was 28-day mortality. Propensity score matching was used to adjust baseline characteristics and disease severity between the groups. Of the 287 patients analyzed, 189 were classified in the no-steroid group and 98 in the steroid group. Fifty propensity score-matched pairs were compared for the study outcomes. We found no significant difference in 28-day mortality between patients treated with and without steroid after propensity score matching (38.0% and 42.0%, respectively; p = 0.838). Incidences of pneumonia and gastrointestinal bleeding were more frequent in the steroid group, but it was not statistically significant after matching. In conclusion, adjunctive hydrocortisone was not associated with reduced 28-day mortality in neutropenic patients with septic shock.


Assuntos
Hidrocortisona/administração & dosagem , Neutropenia , Choque Séptico , Adulto , Idoso , Feminino , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/mortalidade , Humanos , Hidrocortisona/efeitos adversos , Incidência , Masculino , Pessoa de Meia-Idade , Mortalidade , Neutropenia/complicações , Neutropenia/tratamento farmacológico , Neutropenia/mortalidade , Pneumonia/etiologia , Pneumonia/mortalidade , Estudos Retrospectivos , Choque Séptico/complicações , Choque Séptico/tratamento farmacológico , Choque Séptico/mortalidade , Fatores de Tempo
6.
BMC Infect Dis ; 19(1): 584, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31349818

RESUMO

BACKGROUND: Community-acquired sepsis is a life-threatening systemic reaction, which starts within ≤72 h of hospital admittance in an infected patient without recent exposure to healthcare risks. Our aim was to evaluate the characteristics and the outcomes concerning community-acquired sepsis among patients admitted to a Hungarian high-influx national medical center. METHODS: A retrospective, observational cohort study of consecutive adult patients hospitalized with community-acquired sepsis during a 1-year period was executed. Clinical and microbiological data were collected, patients with pre-defined healthcare associations were excluded. Sepsis definitions and severity were given according to ACCP/SCCM criteria. The primary outcome was in-hospital all-cause mortality. Secondary outcomes were intensive care unit (ICU) admittance, length-of-stay (LOS), source control and bacteraemia rates. Statistical differences were explored with classical comparison tests, predictors of in-hospital all-cause mortality were modelled by multivariate logistic regression. RESULTS: 214 patients (median age 60.0 ± 33.1 years, 57% female, median Charlson score 4.0 ± 5.0) were included, 32.7% of them (70/214) had severe sepsis, and 28.5% (61/214) had septic shock. Prevalent sources of infections were genitourinary (53/214, 24.8%) and abdominal (52/214, 24.3%). The causative organisms were dominantly E. coli (60/214, 28.0%), S. pneumoniae (18/214, 8.4%) and S. aureus (14/214, 6.5%), and bacteraemia was documented in 50.9% of the cases (109/214). In-hospital mortality was high (30/214, 14.0%), and independently associated with shock, absence of fever, male gender and the need for ICU admittance, but source control and de-escalation of empirical antimicrobial therapy were protective. ICU admittance was 27.1% (58/214), source control was achieved in 18.2% (39/214). Median LOS was 10.0 ± 8.0, ICU LOS was 8.0 ± 10.8 days. CONCLUSIONS: Community-acquired sepsis poses a significant burden of disease with characteristic causative agents and sources. Patients at a higher risk for poor outcomes might be identified earlier by the contributing factors shown above.


Assuntos
Sepse/tratamento farmacológico , Choque Séptico/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Estudos de Coortes , Infecções Comunitárias Adquiridas , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Hungria , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Sepse/microbiologia , Sepse/mortalidade , Choque Séptico/microbiologia , Choque Séptico/mortalidade , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Adulto Jovem
7.
Soins ; 64(837): 12-17, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31345301

RESUMO

In cases of septic shock, high quality blood cultures are essential for identifying the causative agent and adapting the antibiotic treatment. Student nurses are relatively unfamiliar with recent guidelines on collecting blood cultures. Improving how they are taught during initial training, a key moment for the learning of best care practices, should help to optimise the global management of septic shock.


Assuntos
Hemocultura , Educação em Enfermagem , Estudantes de Enfermagem/psicologia , Antibacterianos/uso terapêutico , Humanos , Aprendizagem , Choque Séptico/tratamento farmacológico , Choque Séptico/enfermagem
8.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(4): 501-504, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-31109431

RESUMO

OBJECTIVE: Septic shock is a serious stage of sepsis with a hospital mortality rate of more than 40%. The pathophysiology of septic shock is vasodilation and increased permeability. Fluid resuscitation, vasopressor drugs are usually used to maintain the perfusion pressure of the main organs. However, infectious patients usually have the irresponsive vessel to catecholamines and may lead to obvious side effects using high doses of norepinephrine or dopamine. Recent studies have shown that vasopressin (AVP) improves hemodynamics, increases tissue perfusion, and synergizes with norepinephrine in patients with septic shock, showing extent application prospects in the treatment of septic shock. The practice of AVP in septic shock is reviewed in this article in order to provide a reference for clinicians.


Assuntos
Choque Séptico/tratamento farmacológico , Vasopressinas/uso terapêutico , Humanos , Resultado do Tratamento
9.
BMC Infect Dis ; 19(1): 395, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31068145

RESUMO

BACKGROUND: Leptospirosis or Weil's disease is caused by pathogenic spirochete bacteria called Leptospira. It is considered the most common zoonosis in the world and is usually transmitted by urine of rodents and dogs with an incubation time of 7-14 days. The clinical spectrum ranges from a subclinical infection to a fulminant septic course. CASE PRESENTATION: Here, we report the case of a German patient with acute pancreatitis associated with Leptospira interrogans causing fulminant septic shock. The patient was successfully treated with intravenous antibiotics and left the hospital fully recovered after 18 days. CONCLUSIONS: To our knowledge, this is the first case of leptospirosis with acute pancreatitis as the leading clinical manifestation in Central Europe. Serologic and molecular genetic tests for leptospirosis should be considered, if no other causes for pancreatitis can be identified.


Assuntos
Leptospirose/complicações , Pancreatite/microbiologia , Choque Séptico/microbiologia , Vasoplegia/microbiologia , Idoso , Animais , Antibacterianos/uso terapêutico , Europa (Continente) , Humanos , Leptospira interrogans/patogenicidade , Leptospirose/tratamento farmacológico , Leptospirose/microbiologia , Masculino , Pancreatite/tratamento farmacológico , Pancreatite/etiologia , Choque Séptico/tratamento farmacológico , Choque Séptico/etiologia , Vasoplegia/tratamento farmacológico , Vasoplegia/etiologia , Zoonoses/tratamento farmacológico
10.
Crit Care Resusc ; 21(2): 119-125, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31142242

RESUMO

BACKGROUND: Septic shock is associated with poor outcomes. Vitamin C (ascorbic acid) is a cellular antioxidant and has anti-inflammatory properties. Whether the combination therapy of vitamin C, thiamine and hydrocortisone reduces vasopressor dependency in septic shock is unclear. OBJECTIVES: To describe the protocol and statistical analysis plan of a multicentre, open-label, prospective, phase 2 randomised clinical trial evaluating the effects of vitamin C, thiamine and hydrocortisone when compared with hydrocortisone monotherapy on the duration of vasopressor administration in critically ill patients with septic shock. METHODS: VITAMINS is a multicentre cardiovascular efficacy trial in adult patients with septic shock. Randomisation occurs via a secure website with stratification by site, and allocation concealment is maintained throughout the trial. The primary outcome is the duration of time alive and free of vasopressor administration at Day 7. Secondary outcomes include feasibility endpoints and some patientcentred outcomes. All analyses will be conducted on an intention-to-treat basis. CONCLUSION: The VITAMINS trial will determine whether combination therapy of vitamin C, thiamine and hydrocortisone when compared with hydrocortisone increases vasopressor-free hours in critically ill patients with septic shock. The conduct of this study will provide important information on the feasibility of studying this intervention in a phase 3 trial. TRIAL REGISTRATION: ClinicalTrials.gov, identification No. NCT03333278.


Assuntos
Ácido Ascórbico/administração & dosagem , Mortalidade Hospitalar , Hidrocortisona/administração & dosagem , Choque Séptico/tratamento farmacológico , Tiamina/administração & dosagem , Vitaminas/administração & dosagem , Adulto , Ácido Ascórbico/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Hidrocortisona/uso terapêutico , Unidades de Terapia Intensiva , Masculino , Estudos Prospectivos , Choque Séptico/mortalidade , Tiamina/uso terapêutico , Resultado do Tratamento , Vasoconstritores/uso terapêutico , Vitaminas/uso terapêutico
11.
Zhonghua Yi Xue Za Zhi ; 99(17): 1317-1322, 2019 May 07.
Artigo em Chinês | MEDLINE | ID: mdl-31091579

RESUMO

Objective: To investigate the effect of esmolol in septic shock patients with tachycardia. Methods: A prospective randomized controlled trial was conducted. Screening septic shock patients that admitted to Department of General Intensive Care Unit of the First Affiliated Hospital of Zhengzhou University from June 2016 to August 2017. After 24 h resuscitation therapy, 100 cases of septic shock patients with tachycardia (heart rate>100 bpm) were divided into esmolol group (n=50) and control group (n=50) with random number table. Patients in esmolol group accepted standard treatment plus esmolol injection with an initial dose of 25 mg/h. Heart rate target is 80 to 100 bpm. Patients in esmolol group continued to use esmolol for 7 days or to the day the patient left the ICU when the heart rate didn't achieve the target. Patients in control group were given standard treatment. Primary outcome was 28 d mortality. Secondary outcomes included heart rate, norepinephrine dosages, lactate level, inflammatory markers in per day during the trial; acute physiology and chronic health evaluation (APACHE Ⅱ) and sequential organ failure assessment (SOFA) on day 1, 3, 5, 7; length of hospital stay, length of mechanical ventilation, medication time of vasoactive agent. The data were compared with t test or rank sum test between the two groups. Results: The 28 d mortality of esmolol group and control group was 62%, 68%, respectively(χ(2)=0.529, P=0.529). Logistic regression analysis showed that primary heart rate (increase of 10 bpm, OR=1.568, 95%CI: 1.039-1.238, P=0.027), primary APACHEⅡ (OR=1.134, 95%CI: 1.026-1.239, P=0.005), integral heart rate (per 10 bpm, OR=2.207, 95%CI: 1.400-3.479, P=0.001) were independent risk factors for 28 d mortality. Compared with control group, the esmolol group had a lower heart rate on day 1-7; but over all, there was no statistically significant difference in heart rate between the two groups (P>0.05). There was no significant difference in total does of norepinephrine, lactate level, inflammatory markers, APACHE Ⅱ, SOFA, length of hospital stay between the two groups (all P>0.05). Conclusion: Tachycardia significantly increases the risk of death in patients with septic shock, esmolol may decrease the mortality by controlling heart rate.


Assuntos
Propanolaminas/uso terapêutico , Choque Séptico , Humanos , Estudos Prospectivos , Choque Séptico/tratamento farmacológico , Taquicardia
12.
J Vet Emerg Crit Care (San Antonio) ; 29(3): 326-330, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31044499

RESUMO

OBJECTIVE: To describe the successful management of 2 dogs with septic shock and persistent tachycardia using norepinephrine and esmolol, a short-acting beta receptor antagonist. SERIES SUMMARY: Two cases are reviewed. In the first case, septic shock with ventricular tachycardia was diagnosed in a 4-year-old neutered female Great Dane that underwent jejunoileal resection and anastomosis for a partial mesenteric torsion. The patient's tachyarrhythmias failed to respond to lidocaine, and an esmolol infusion was used for heart rate control. The condition of the dog improved and she was discharged after 4 days of hospitalization. The second case was a 7-year-old neutered female Cavalier King Charles Spaniel with septic peritonitis. Following surgery for intestinal resection and anastomosis, supraventricular tachycardia developed that was not responsive to volume resuscitation and was treated with an esmolol infusion. The condition of the dog improved and she was discharged after 6 days of hospitalization. Both patients were doing well at the time of long-term follow-up. NEW OR UNIQUE INFORMATION PROVIDED: This case series highlights a novel method of managing dogs in septic shock with persistent tachycardia based on recently published data in the human literature. The use of esmolol may be considered in certain veterinary patients with septic shock to improve persistent tachycardia not related to hypovolemia.


Assuntos
Doenças do Cão/tratamento farmacológico , Choque Séptico/veterinária , Taquicardia Supraventricular/veterinária , Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Animais , Procedimentos Cirúrgicos do Sistema Digestório/veterinária , Cães , Quimioterapia Combinada/veterinária , Feminino , Norepinefrina/administração & dosagem , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/veterinária , Propanolaminas/administração & dosagem , Choque Séptico/complicações , Choque Séptico/tratamento farmacológico , Taquicardia Supraventricular/complicações , Taquicardia Supraventricular/tratamento farmacológico , Vasoconstritores/administração & dosagem
13.
BMJ Case Rep ; 12(4)2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30967449

RESUMO

A 51-year-old man with a medical history of coronary artery disease and dyslipidaemia presented with acute myocardial infarction resulting in cardiogenic shock, necessitating intra-aortic balloon pump placement and extracorporeal membrane oxygenation (ECMO). His hospital course was complicated by several infectious complications including ECMO circuit Pseudomonas aeruginosa bloodstream infection and presumed infected right atrial thrombus. He subsequently underwent urgent left ventricular assist device placement and had a prolonged hospital stay. On day 100 of admission, he developed acute hypoxic respiratory distress with new pulmonary infiltrates. Sputum cultures grew Cryptococcus neoformans Blood culture also grew C. neoformans after 96 hours of incubation and cryptococcal serum antigen was elevated at 1:20. Cerebrospinal fluid studies from a lumbar puncture were normal. He was treated with 2 weeks of combination antifungal therapy followed by life-long fluconazole suppression.


Assuntos
Criptococose/microbiologia , Oxigenação por Membrana Extracorpórea/efeitos adversos , Coração Auxiliar/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Choque Séptico/microbiologia , Anfotericina B/administração & dosagem , Antibacterianos , Antifúngicos/administração & dosagem , Ciprofloxacino/administração & dosagem , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Cryptococcus neoformans/isolamento & purificação , Fluconazol/administração & dosagem , Flucitosina/administração & dosagem , Humanos , Imunocompetência , Balão Intra-Aórtico , Masculino , Pessoa de Meia-Idade , Choque Séptico/sangue , Choque Séptico/diagnóstico , Choque Séptico/tratamento farmacológico
14.
Eur J Clin Microbiol Infect Dis ; 38(7): 1255-1260, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30968258

RESUMO

Reduced target attainment of ß-lactam antibiotics is reported in critically ill patients. However, as target attainment of cefotaxime in severely ill pediatric sepsis patients may differ from adults due to age-related variation in pharmacokinetics, we aimed to assess target attainment of cefotaxime in this pilot study using meningococcal septic shock patients as a model for severe sepsis. Secondary analysis of prospectively collected data from a randomized controlled trial. Children with meningococcal septic shock (1 month to 18 years) included in this study received cefotaxime 100-150 mg/kg/day as antibiotic treatment. Left-over plasma samples were analyzed using LC-MS/MS to determine cefotaxime concentrations. MIC values from EUCAST were used to determine target attainment of cefotaxime for Neisseria meningitidis (0.125 mg/l), but also for Streptococcus pneumoniae (0.5 mg/l), Enterobacteriaceae (1 mg/l), and Staphylococcus aureus (4 mg/l). Target attainment was adequate when all samples exceeded MIC or fourfold MIC values. One thirty-six plasma samples of 37 severe septic shock patients were analyzed for cefotaxime concentrations. Median age was 2 years with a median PRISM-score of 24 and mortality of 24.8%. The median unbound cefotaxime concentration was 4.8 mg/l (range 0-48.7). Target attainment ranged from 94.6% for the MIC of N. meningitidis to 16.2% for fourfold the MIC S. aureus. Creatinine levels were significantly correlated with cefotaxime levels. Target attainment of cefotaxime with current dosing guidelines seems to be adequate for N. meningitidis but seems to fail for more frequently encountered pathogens in severely ill children.


Assuntos
Antibacterianos/farmacocinética , Cefotaxima/farmacocinética , Infecções Meningocócicas/tratamento farmacológico , Sepse/tratamento farmacológico , Choque Séptico/tratamento farmacológico , Adolescente , Antibacterianos/sangue , Antibacterianos/uso terapêutico , Cefotaxima/sangue , Cefotaxima/uso terapêutico , Criança , Pré-Escolar , Estado Terminal , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Infecções Meningocócicas/sangue , Infecções Meningocócicas/complicações , Neisseria meningitidis/efeitos dos fármacos , Projetos Piloto , Sepse/microbiologia , Choque Séptico/microbiologia
15.
BMC Infect Dis ; 19(1): 302, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30943907

RESUMO

BACKGROUND: Staphylococcus aureus has emerged as a leading cause of invasive severe diseases with a high rate of morbidity and mortality worldwide. The wide spectrum of clinical manifestations and outcome observed in staphylococcal illness may be a consequence of both microbial factors and variability of the host immune response. CASE PRESENTATION: A 14-years old child developed limb ischemia with gangrene following S. aureus bloodstream infection. Histopathology revealed medium-sized arterial vasculitis. The causing strain belonged to the emerging clone CC1-MSSA and numerous pathogenesis-related genes were identified. Patient's genotyping revealed functional variants associated with severe infections. A combination of virulence and host factors might explain this unique severe form of staphylococcal disease. CONCLUSION: A combination of virulence and genetic host factors might explain this unique severe form of staphylococcal disease.


Assuntos
Infecções Estafilocócicas/diagnóstico , Staphylococcus aureus/genética , Vasculite/diagnóstico , Adolescente , Amputação , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Encéfalo/diagnóstico por imagem , Cefotaxima/farmacologia , Cefotaxima/uso terapêutico , Clindamicina/farmacologia , Clindamicina/uso terapêutico , Humanos , Perna (Membro)/cirurgia , Imagem por Ressonância Magnética , Masculino , Meticilina/farmacologia , Choque Séptico/diagnóstico , Choque Séptico/tratamento farmacológico , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Vasculite/complicações , Vasculite/microbiologia
16.
Chem Biol Interact ; 303: 50-56, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-30822415

RESUMO

Dextromethorphan, a wildly used over-the-counter antitussive drug, is reported to have anti-inflammatory effects. Previously, we and others have demonstrated that dextromethorphan at micromolar doses displays potent hepatoprotective effects and enhances mice survival in a sepsis model. Moreover, we also observed potent anti-inflammatory and neuroprotective effects of subpicomolar concentrations of dextromethorphan in rodent primary neuron-glial cultures. The purpose of this study was to provide a proof of principle that ultralow dose dextromethorphan displays anti-inflammatory and cytoprotective effects in animal studies. Here, we report that subpico- and micromolar doses of dextromethorphan showed comparable efficacy in protecting mice from lipopolysaccharide/d-galactosamine (LPS/GalN)-induced hepatotoxicity and mortality. Mice were given injections of dextromethorphan from 30 min before and 2, 4 h after an injection of LPS/GalN (20 µg/600 mg/kg). Our results showed that dextromethorphan at subpicomolar doses promoted survival rate in LPS/GalN-injected mice. Ultralow dose dextromethorphan also significantly reduced serum alanine aminotransferase activity, TNF-α level and liver cell damage of endotoxemia mice. Mechanistic studies using primary liver Kupffer cell cultures revealed that subpicomolar concentrations of dextromethorphan reduced the NADPH oxidase-generated superoxide free radicals from Kupffer cells, which in turn reduced the elevation of its downstream reactive oxygen species (iROS) to relieve the oxidative stress and decreased TNF-α production in Kupffer cells. Taken together, these findings suggest a novel therapeutic concept of using ultralow doses of dextromethorphan for the intervention of sepsis or septic shock.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/patologia , Dextrometorfano/uso terapêutico , Sepse/tratamento farmacológico , Animais , Células Cultivadas , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Endotoxinas/toxicidade , Galactosamina/farmacologia , Macrófagos do Fígado/efeitos dos fármacos , Macrófagos do Fígado/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Choque Séptico/tratamento farmacológico , Taxa de Sobrevida
17.
Expert Opin Pharmacother ; 20(8): 991-1007, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30879348

RESUMO

INTRODUCTION: The last five years, there have been considerable changes in our perception on the pathogenesis of sepsis. This review aims to summarize the current progress of the last five years in the management and research fields of sepsis in a holistic approach. To achieve this, accumulated evidence over the last five years coming from randomized clinical trials (RCTs) and observational studies in adults for the management of sepsis is provided. AREAS COVERED: In this review, the authors discuss available strategies in sepsis, divided into standard-of-care and adjunctive therapies. Standard-of-care approaches comprise antimicrobials, fluids, vasoactive agents, steroids. Antimicrobials remain the mainstay of treatment. However, key-point of management is early recognition of the patient that guides early start of antimicrobials. Patients with suspected infection and any two of: an altered mental state, more than 22 breaths per minute and systolic blood pressure below 100 mmHg should receive early intervention with broad-spectrum antimicrobials and fluids. EXPERT OPINION: Low dose hydrocortisone replacement and fludrocortisone seem promising for the patient at septic shock. Adjunctive macrolide treatment of severe CAP is also associated with survival benefit. Future studies will help to provide additional insight into the field.


Assuntos
Anti-Infecciosos/uso terapêutico , Sepse/tratamento farmacológico , Choque Séptico/tratamento farmacológico , Adulto , Antibacterianos/uso terapêutico , Humanos , Macrolídeos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Esteroides/uso terapêutico
18.
Biomed Res Int ; 2019: 3080827, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30881985

RESUMO

Background: Urosepsis and septic shock are a critical situation leading to a mortality rate up to 30% in patients with obstructive diseases of the urinary tract. Aim: To analyze the bacterial distribution and drug resistance of pathogenic bacteria in patients with urosepsis and to provide a basis for the rational application of antibacterial drugs in clinical practice. Methods: A retrospective analysis of 94 hospitalized patients with urosepsis for 6 years was performed. The strain composition, resistance characteristics, and the antibiogram of common bacteria from positive blood and midstream urine culture were analyzed. Results: A total of 87 strains were isolated, including 65 strains (74.71%) of Gram-negative bacilli, 14 strains (16.09%) of Gram-positive cocci, and 8 strains (9.20%) of fungi. The Gram-negative bacilli included 42 strains of Escherichia coli (E. coli) (64.62%), among which 34 strains (80.95%) were producing ESBLs, and 14 strains (21.84%) of Klebsiella pneumoniae (K. pneumoniae), among which nine strains (64.29%) were producing ESBLs. The most common pathogenic bacteria, ESBL+ E. coli and K. pneumoniae strains, showed sensitivity towards imipenem, ertapenem, piperacillin/tazobactam, amikacin, and cefotetan, but were highly resistant to quinolones. The cure rate of urosepsis was 88.30%, and the susceptibility rate of septic shock was 45.47%. Significance: Gram-negative bacterial infections are the main cause of urosepsis. The mild patient group showed more E. coli (ESBL-) infections, and the number of ESBL producing E. coli isolated from the mild group showed higher drug resistance rates for aztreonam and levofloxacin compared with isolates from the severe group.


Assuntos
Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Sepse/tratamento farmacológico , Choque Séptico/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico , Ertapenem/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/patogenicidade , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/patologia , Humanos , Imipenem/farmacologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/patogenicidade , Quinolonas/farmacologia , Sepse/microbiologia , Sepse/patologia , Choque Séptico/microbiologia , Choque Séptico/patologia , Infecções Urinárias/microbiologia , Infecções Urinárias/patologia
19.
Clin Drug Investig ; 39(5): 429-440, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30848423

RESUMO

BACKGROUND: Sepsis and septic shock are inflammatory disorders associated with high rates of mortality. Patients with sepsis and septic shock frequently become tachycardic as a result of the utilization of vasopressor therapy and cardiac overcompensation owing to hypotension, predisposing patients to an increased risk of atrial fibrillation. Previously, it was thought that beta-blocker therapy in patients with sepsis would exacerbate hypotension; however, recent studies have shown that may not be the case. OBJECTIVE: This review aims to ascertain whether beta-blocker therapy reduces heart rate in patients with sepsis without a corresponding decrease in blood pressure, and if beta-blockade has a beneficial effect on mortality. METHODS: Several databases including Cochrane, EMBASE, PubMed, SCOPUS, and Web of Science were scoured for trials pertaining to the utilization of beta-blockers in sepsis and septic shock, and trials that were either prospective or controlled were included in this review. RESULTS: In the initial search, 1839 articles were found, and those were subsequently reduced to 14 trials (five randomized controlled trials, nine non-randomized trials) that were deemed appropriate for inclusion in this review. All included trials displayed beneficial effects on heart rate without any detriments to blood pressure. Of the six trials that assessed mortality, four showed substantial benefits. CONCLUSION: The majority of the trials assessed in this review displayed beneficial results for beta-blocker use in patients with sepsis. However, owing to the deficit of large-scale randomized controlled trials addressing this topic, further research is needed to ensure the veracity of these results.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Sepse/tratamento farmacológico , Antagonistas Adrenérgicos beta/farmacologia , Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Humanos , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Sepse/fisiopatologia , Choque Séptico/tratamento farmacológico , Choque Séptico/fisiopatologia
20.
Chin Med J (Engl) ; 132(5): 589-596, 2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30807357

RESUMO

OBJECTIVE: Sepsis is a deadly infection that causes injury to tissues and organs. Infection and anti-infective treatment are the eternal themes of sepsis. The successful control of infection is a key factor of resuscitation for sepsis and septic shock. This review examines evidence for the treatment of sepsis. This evidence is combined with clinical experiments to reveal the rules and a standard flowchart of anti-infection therapy for sepsis. DATA SOURCES: We retrieved information from the PubMed database up to October 2018 using various search terms and their combinations, including sepsis, septic shock, infection, antibiotics, and anti-infection. STUDY SELECTION: We included data from peer-reviewed journals printed in English on the relationships between infections and antibiotics. RESULTS: By combining the literature review and clinical experience, we propose a 6Rs rule for sepsis and septic shock management: right patients, right time, right target, right antibiotics, right dose, and right source control. This rule encompasses rational decisions regarding the timing of treatment, the identification of the correct pathogen, the selection of appropriate antibiotics, the formulation of a scientifically based antibiotic dosage regimen, and the adequate control of infectious foci. CONCLUSIONS: This review highlights how to recognize and treat sepsis and septic shock and provides rules and a standard flowchart for anti-infection therapy for sepsis and septic shock for use in the clinical setting.


Assuntos
Sepse/tratamento farmacológico , Choque Séptico/tratamento farmacológico , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Humanos , PubMed
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