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1.
J Med Case Rep ; 15(1): 394, 2021 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-34364400

RESUMO

BACKGROUND: Herpes virus remains dormant in human cells and could reactivate under immunosuppressed conditions, such as prolonged critical illnesses. The phenomenon of viral replication during intensive care is well known, even in patients without a history of immunosuppression, but it usually does not have a clinical impact. Systemic reactivation leads to viral DNA in blood. It remains unclear whether this replication is a marker of morbimortality or a true pathogenic process. Therefore, it is unclear what medical treatment is most appropriate for simple replication. In organ damage suspected to be induced by herpes virus, there is no consensus on the most appropriate treatment duration. Here, we report a rarely described case of multiorgan failure implicating herpes simplex virus and discuss its treatment. CASE REPORT: A 53-year-old Caucasian immunosuppressed woman was admitted to the intensive care unit for septic shock. She presented pneumonia due to Klebsiella pneumoniae. Two weeks after admission, she showed multiorgan failure with acute respiratory distress syndrome and circulation failure. She had digestive and cutaneous lesions typical of herpes simplex virus 1. Blood and respiratory polymerase chain reaction was strongly herpes simplex virus-1 positive. No other bacteria, fungi, or viruses were found. The evolution was rapidly favorable after the initiation of antiviral treatment. Treatment was stopped after 3 weeks of well-conducted antiviral therapy. Curative-dose treatment was interrupted despite continuous strongly positive blood polymerase chain reaction results. In this context, prophylactic treatment was continued. CONCLUSION: We report an exceptional presentation of multiorgan failure in the intensive care unit due to herpes simplex virus-1. The diagnosis was made based on typical herpes simplex virus-1 visceral lesions and the absence of other responsible microorganisms. Intense viral replication is a key diagnostic element. There is no consensus regarding the most appropriate treatment duration, but such decisions should not be based on blood polymerase chain reaction.


Assuntos
Herpes Simples , Herpesvirus Humano 1 , Pneumonia , Choque Séptico , Antivirais/uso terapêutico , Feminino , Herpes Simples/complicações , Herpes Simples/diagnóstico , Herpes Simples/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Pneumonia/tratamento farmacológico , Choque Séptico/tratamento farmacológico
2.
J Card Surg ; 36(10): 3711-3718, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34310744

RESUMO

BACKGROUND AND AIM OF THE STUDY: Although dopamine and norepinephrine are recommended as first-line agents in the treatment of shock, it is unclear which is the optimal vasoactive inotropic agent (VIA) to manage postcardiotomy circulatory shock. This single-center, randomized clinical trial aimed to investigate the efficacy and safety of dopamine versus norepinephrine in postcardiotomy circulatory shock. METHODS: We randomly assigned the patients with postcardiotomy circulatory shock to receive either dopamine or norepinephrine. When shock persisted despite the dose of 20 µg/kg/min of dopamine or the dose of 0.2 µg/kg/min of norepinephrine, epinephrine or vasopressin could be added. The primary endpoint was new-onset tachyarrhythmic event during drug infusion. Secondary endpoints included requirement of additional VIAs, postoperative complications, and all-cause mortality within 30 days of drug initiation. RESULTS: At the planned interim analysis of 100 patients, the boundary for the benefit of norepinephrine has been crossed, and the study was stopped early. Excluding two patients withdrawing a consent, 48 patients were assigned to dopamine and 50 patients to norepinephrine. New-onset tachyarrhythmic event occurred in 12 (25%) patients in the dopamine and one (2%) patient in the norepinephrine group (p = .009). The requirement for additional VIAs was more common in the dopamine group (p < .001). Other secondary endpoints were similar between groups. CONCLUSIONS: Despite the limited study subjects with early determination, in patients with postcardiotomy circulatory shock, dopamine as a first-line vasopressor was associated with higher tachyarrhythmic events and greater need for additional VIAs compared with norepinephrine.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Choque Séptico , Choque , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Dopamina , Humanos , Norepinefrina , Choque/tratamento farmacológico , Choque/etiologia , Choque Séptico/tratamento farmacológico , Vasoconstritores , Vasopressinas
3.
BMJ Open ; 11(7): e042921, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34233965

RESUMO

INTRODUCTION: Septic shock is the subgroup of patients with sepsis, which presents as vasopressor dependence, an elevated blood lactate concentration and is associated with a mortality of at least 30%. Expression of the triggering receptor expressed on myeloid cells 1 (TREM-1) pathway, measured using a serum biomarker of pathway activation (soluble TREM-1, sTREM-1) has been associated with outcome in septic shock. Preclinical and early phase patient data suggest that therapeutic modulation of this pathway may improve survival. METHODS AND ANALYSIS: Efficacy, Safety and Tolerability of Nangibotide in Patients with Septic Shock is a phase IIb randomised controlled trial that will take place in up to 50 centres in seven countries and recruit 450 patients with septic shock to receive either placebo or one of two doses of nangibotide, a novel regulator of the TREM-1 pathway. The primary outcome will be the impact of nangibotide therapy on the change in Sequential Organ Failure Assessment score from a baseline determined before initiation of study drug therapy. This will be assessed first in the patients with an elevated sTREM-1 level and then in the study population as a whole. In addition to safety, secondary outcomes of the study will include efficacy of nangibotide in relation to sTREM-1 levels in terms of organ function, mortality and long-term morbidity. This study will also facilitate the development of a novel platform for the measurement of sTREM-1 at the point of care. ETHICS AND DISSEMINATION: The study has been approved by the responsible ethics committees/institutional review boards in all study countries: Belgium: Universitair Ziekenhuis Antwerpen, France: CPP Ile de France II, Denmark: Region Hovedstaden, Spain: ethics committee from Valld'Hebron Hospital, Barcelona, Finland: Tukija, Ireland: St. James' Hospital (SJH) / Tallaght University Hospital (TUH) Joint Research Ethics Committee, USA: Lifespan, Providence TRIAL REGISTRATION NUMBERS: EudraCT Number: 2018-004827-36 and NCT04055909.


Assuntos
Choque Séptico , Bélgica , Finlândia , França , Humanos , Irlanda , Ensaios Clínicos Controlados Aleatórios como Assunto , Choque Séptico/tratamento farmacológico , Espanha , Resultado do Tratamento
4.
Ann Palliat Med ; 10(6): 6325-6335, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34118843

RESUMO

BACKGROUND: The weaning of vasopressors is usually an empirical choice made by clinicians. The aim of this study is to assess the predictive value of change in effective arterial elastance (ΔEa%) induced by fluid administration in early initiation of norepinephrine (NE) weaning. METHODS: Included were intensive care unit (ICU) septic shock patients with an indwelling pulmonary artery catheter who experienced initial resuscitation and required a fluid challenge. Reduced norepinephrine dose or maintained steady (ΔNE ≤0 µg/min) at 6 hours after inclusion (T6) was defined as early initiation of norepinephrine weaning. Univariate and multivariate analyses were performed to assess ΔEa% viability and other hemodynamic parameters in predicting the possibility of norepinephrine weaning. A receiver operating characteristic (ROC) analysis was used to confirm model predictions. RESULTS: One hundred and eight patients were assessed. Of 108 patients, 75 (69.4%) constituted the NE weaning group at T6. The multivariate analysis showed that ΔEa% [odds ratios (OR): 0.95; 95% confidence interval (CI): 0.89-0.99; P=0.003] was an independent predictive factor for norepinephrine weaning at T6. ROC analysis confirmed that ΔEa% was associated with norepinephrine weaning [area under ROC curve (AUC) at 0.64; 95% CI: 0.52-0.75; P=0.026]. To predict norepinephrine weaning, the optimum threshold for ΔEa% was 5.1% (sensitivity: 61%, specificity: 67%). Notably, the combination of ΔEa%, change in systemic vascular resistance (ΔSVR%) and change in cardiac output (ΔCO%) strengthened the predictive ability with an AUC at 0.73 (95% CI: 0.64-0.83; P=0.001). Median (interquartile range) duration (in hours) of norepinephrine was significantly shorter in the NE weaning group compared with the NE worsening group {48 [34-89] vs. 72 [54-90] hours, P=0.048}. CONCLUSIONS: Change in effective arterial elastance induced by fluid administration may assist clinicians in detecting patients who is possible to initiate norepinephrine weaning. Early initiation of norepinephrine weaning was associated with shorter duration of norepinephrine exposure.


Assuntos
Norepinefrina , Choque Séptico , Hidratação , Humanos , Norepinefrina/uso terapêutico , Estudos Retrospectivos , Choque Séptico/tratamento farmacológico , Desmame
5.
J Infect Chemother ; 27(10): 1471-1476, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34183236

RESUMO

INTRODUCTION: Liposomal amphotericin B (L-AMB), a broad spectrum anti-fungicidal drug, is often administered to treat invasive fungal infections (IFIs). However, the most suitable time to initiate treatment in septic shock patients with IFI is unknown. METHODS: Patients with septic shock treated with L-AMB were identified from the Japanese Diagnosis Procedure Combination national database and were stratified according to L-AMB treatment initiation either at septic shock onset (early L-AMB group) or after the onset (delayed L-AMB group) to determine their survival rates following septic shock onset and the shock cessation period. RESULTS: We identified 141 patients administered L-AMB on the day of or after septic shock onset: 60 patients received early treatment, whereas 81 patients received delayed treatment. Survival rates after septic shock onset were higher in the early L-AMB group than in the delayed L-AMB group (4 weeks: 68.4% vs 57.9%, P = 0.197; 6 weeks: 62.2% vs 44.5%, P = 0.061; 12 weeks: 43.4% vs 35.0%, P = 0.168, respectively). The septic shock cessation period was shorter in the early L-AMB group than in the delayed L-AMB group (7.0 ± 7.0 days vs 16.5 ± 15.4 days, P < 0.001), with a significant difference confirmed after adjusting for confounding factors with propensity score matching (7.1 ± 7.2 days vs 16.7 ± 14.0 days, P = 0.001). CONCLUSION: Early L-AMB administration at septic shock onset may be associated with early shock cessation.


Assuntos
Choque Séptico , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Humanos , Choque Séptico/tratamento farmacológico
6.
Medicine (Baltimore) ; 100(25): e26403, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160425

RESUMO

INTRODUCTION: Sepsis and septic shock are the most severe forms of infection affecting predominantly elderly people, preterm and term neonates, and young infants. Even in high-income countries sepsis causes about 8% of admissions to pediatric intensive care units (PICUs). Early diagnosis, rapid anti-infective treatment, and prompt hemodynamic stabilization are crucial for patient survival. In this context, it is essential to identify the causative pathogen as soon as possible to optimize antimicrobial treatment. To date, culture-based diagnostic procedures (e.g., blood cultures) represent the standard of care. However, they have 2 major problems: on the one hand, in the case of very small sample volumes (and thus usually in children), they are not sufficiently sensitive. On the other hand, with a time-to-result of 2 to 5 days, blood cultures need a relatively long time for the anti-infective therapy to be calculated. To overcome these problems, culture-independent molecular diagnostic procedures such as unbiased sequence analysis of circulating cell-free DNA (cfDNA) from plasma samples of septic patients by next-generation sequencing (NGS) have been tested successfully in adult septic patients. However, these results still need to be transferred to the pediatric setting. METHODS: The Next GeneSiPS-Trial is a prospective, observational, non-interventional, multicenter study used to assess the diagnostic performance of an NGS-based approach for the identification of causative pathogens in (preterm and term) neonates (d1-d28, n = 50), infants (d29 to <1 yr, n = 50), and toddlers (1 yr to <5 yr, n = 50) with suspected or proven severe sepsis or septic shock (according to the pediatric sepsis definition) by the use of the quantitative sepsis indicating quantifier (SIQ) score in comparison to standard of care (culture-based) microbiological diagnostics. Potential changes in anti-infective treatment regimens based on these NGS results will be estimated retrospectively by a panel of 3 independent clinical specialists. DISCUSSION: Neonates, infants, and young children are significantly affected by sepsis. Fast and more sensitive diagnostic approaches are urgently needed. This prospective, observational, non-interventional, multicenter study seeks to evaluate an NGS-based approach in critically ill children suffering from sepsis. TRIAL REGISTRATION: DRKS-ID: DRKS00015705 (registered October 24, 2018). https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00015705.


Assuntos
Bacteriemia/diagnóstico , Bactérias/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala , Técnicas de Diagnóstico Molecular/métodos , Choque Séptico/diagnóstico , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Bactérias/genética , Hemocultura , Pré-Escolar , DNA Bacteriano/isolamento & purificação , Diagnóstico Precoce , Feminino , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Pediátrica , Masculino , Estudos Multicêntricos como Assunto , Estudos Observacionais como Assunto , Estudos Prospectivos , Estudos Retrospectivos , Índice de Gravidade de Doença , Choque Séptico/sangue , Choque Séptico/tratamento farmacológico , Choque Séptico/microbiologia
7.
Int J Mol Sci ; 22(9)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066510

RESUMO

Neutrophil extracellular trap (NET) formation, an innate immune system response, is associated with thrombogenesis and vascular endothelial injury. Circulatory disorders due to microvascular thrombogenesis are one of the principal causes of organ damage. NET formation in organs contributes to the exacerbation of sepsis, which is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. We have previously reported that recombinant human soluble thrombomodulin (rTM) reduces lipopolysaccharide (LPS)-induced NET formation in vitro. Here, we aimed to show that thrombomodulin (TM)-mediated suppression of NET formation protects against organ damage in sepsis. Mice were injected intraperitoneally (i.p.) with 10 mg/kg LPS. rTM (6 mg/kg/day) or saline was administered i.p. 1 h after LPS injection. In the LPS-induced murine septic shock model, extracellular histones, which are components of NETs, were observed in the liver and lungs. In addition, the serum cytokine (interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), macrophage chemotactic protein-1 (MCP-1), and interleukin-10 (IL-10)) levels were increased. The administration of rTM in this model prevented NET formation in the organs and suppressed the increase in the levels of all cytokines except IL-1ß. Furthermore, the survival rate improved. We provide a novel role of TM in treating inflammation and NETs in organs during sepsis.


Assuntos
Armadilhas Extracelulares/metabolismo , Fígado/patologia , Pulmão/patologia , Choque Séptico/tratamento farmacológico , Trombomodulina/uso terapêutico , Animais , Citocinas/sangue , Modelos Animais de Doenças , Armadilhas Extracelulares/efeitos dos fármacos , Feminino , Humanos , Lipopolissacarídeos , Fígado/ultraestrutura , Camundongos Endogâmicos C57BL , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Choque Séptico/sangue , Choque Séptico/induzido quimicamente , Análise de Sobrevida
8.
Artigo em Alemão | MEDLINE | ID: mdl-34187073

RESUMO

Vasopressors are widely used in anaesthesiology and critical care medicine, to treat harmless (e.g. anaesthesia-induced hypotension) as well as life-threatening conditions (e.g. septic shock). Some clinically used vasopressors resemble endogenous substances - such as norepinephrine - while others have been artificially synthesized (e.g. phenylephrine). Most of the substances used in different clinical scenarios have various effects except for vasoconstriction alone. Therefore, a thorough understanding of the pharmacology and clinical profile of every single substance is of highest importance prior to practical usage. Furthermore, the fundamentals of vascular physiology and vasotonic regulation are mandatory to safely provide vasopressor-based therapies. This article covers the essentials of physiology and pharmacology of vasopressors, and the clinical settings they are used in (e.g. septic shock, vasoplegic shock after cardiac surgery, trauma-induced hypotension).


Assuntos
Choque Séptico , Choque , Humanos , Norepinefrina , Fenilefrina , Choque Séptico/tratamento farmacológico , Vasoconstritores/uso terapêutico
11.
Ugeskr Laeger ; 183(18)2021 05 03.
Artigo em Dinamarquês | MEDLINE | ID: mdl-33998442

RESUMO

Toxic shock syndrome is a potentially deadly toxin-mediated disease in which quick diagnosis is imperative for treatment and prognosis. This is a case report of a 21-year-old woman admitted with high fever, confusion, petechial rash and hypotension. During catherisation a tampon was found, and from a vaginal swab Staphylococcus aureus was grown. The patient was hospitalised for eight days, two of which were at the intensive care unit for norepinephrine infusion for hypotension. She was successfully treated with the antibiotics dicloxacillin and clindamycin.


Assuntos
Choque Séptico , Infecções Estafilocócicas , Adulto , Antibacterianos/uso terapêutico , Clindamicina/uso terapêutico , Feminino , Humanos , Choque Séptico/diagnóstico , Choque Séptico/tratamento farmacológico , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus , Adulto Jovem
12.
Int J Clin Pract ; 75(9): e14376, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34003568

RESUMO

OBJECTIVES: This prospective, comparative and randomised clinical study evaluated the effectiveness of triple therapy regimen (hydrocortisone, thiamine and vitamin C) versus hydrocortisone alone in reducing the mortality rate and preventing progressive organ dysfunction in septic shock patients. METHODS: A total of 94 patients were randomly assigned to one of two groups: the first group received hydrocortisone 50 mg/6-h IV for 7 days or till intensive care unit (ICU) discharge, if sooner, followed by tapering. The second group received hydrocortisone 50 mg/6-h IV for 7 days or ICU discharge followed by tapering, vitamin C 1.5 g/6-h IV for 4 days or till ICU discharge and thiamine 200 mg/12-h IV for 4 days or till ICU discharge. RESULTS: The triple therapy regimen showed a non-significant reduction in 28-day mortality compared to hydrocortisone alone (17 [36.2%] vs. 21 [44.7%]; P = .4005), but it was significantly lower than the control group regarding shock time and the duration of vasopressor use in days (4.000 [3.000-7.000]; 5.000 [4.000-8.000], [P = .0100]). The patients in the control group were likely to get 0.59 more in SCr level than those in the intervention group by a linear regression model which was significant (P < .05). Also, the number of patients who developed a fever after 216 hours was significantly higher in the control group (P value = .0299). CONCLUSION: Vitamin C, thiamine, and hydrocortisone regimen for septic shock management showed non-significant efficacy in decreasing 28-day mortality when compared to hydrocortisone monotherapy. On the other hand, it showed significant efficacy in decreasing the shock time and duration on vasopressors.


Assuntos
Hidrocortisona , Choque Séptico , Quimioterapia Combinada , Humanos , Hidrocortisona/uso terapêutico , Estudos Prospectivos , Choque Séptico/tratamento farmacológico , Vitaminas/uso terapêutico
13.
J Int Med Res ; 49(5): 3000605211013176, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33990145

RESUMO

OBJECTIVE: To investigate the effect of focused ultrasonography on clinical outcomes of septic shock. METHODS: Patients with septic shock were randomized into an integrated cardiopulmonary ultrasonography (ICUS) group and conventional (CON) group. Within 1 hour of admission, the ICUS group underwent ICUS examination for hemodynamic decision-making, while the CON group received standard treatment. The primary endpoint was 28-day mortality after admission. The secondary endpoints were cumulative fluid administration in the first 6, 24, and 72 hours; use of vasoactive drugs; lactate clearance; duration of ventilation; and ICU stay. RESULTS: Ninety-four qualified patients were enrolled (ICUS group, 49; CON group, 45). ICUS showed no significant effect on 28-day mortality. Within the initial 6 hours, the ICUS group tended to have a higher fluid balance and fluid intake than the CON group. The duration of vasopressor support was shorter in the ICUS group. There were no differences in the cumulative fluid infusion within 24 or 72 hours, lactate clearance, ICU stay, or duration of ventilation. CONCLUSIONS: The initially focused ICUS did not affect the clinical outcomes of septic shock, but it tended to be associated with a higher fluid balance within the initial 6 hours and shorter duration of vasopressor support.


Assuntos
Choque Séptico , Hidratação , Hemodinâmica , Humanos , Choque Séptico/diagnóstico por imagem , Choque Séptico/tratamento farmacológico , Ultrassonografia , Vasoconstritores/uso terapêutico
14.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(3): 276-280, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33834967

RESUMO

OBJECTIVE: To analysis the risk factors and safety of administration of norepinephrine (NE) via peripheral vein line (PVL) in patients with septic shock. METHODS: A single-center retrospective study was conducted. According to the Lanzhou University Second Hospital information system (HIS) and nursing adverse events report cards, patients with septic shock administrated with NE via PVL to correct the hypotension from January 1st 2015 to December 31st, 2019 were enrolled. The patients' general information, placement location of peripheral venous catheter and venousneedle type, characteristics of NE usage and patient general condition when extravasation occurred were collected. The univariate analysis and Logistic regression were used to analyze risk factors associated with extravasation. Also, the receiver operator characteristic curve (ROC curve) was drawn, and the predictive value of risk factors for extravasation was analyzed. RESULTS: A total of 1 022 cases with NE were enrolled. After a preliminary screening, a total of 910 cases with NE were used to correct low blood pressure, including 116 cases of peripheral venous infusion. The average age was (52.91±18.69) years old, with majority of female (77 cases, 66.4%). Basic diseases were mainly chronic obstructive pulmonary disease (COPD, 100 cases, 86.2%), followed by hypertension (91 cases, 78.4%), coronary heart disease (87 cases, 75.0%), type 2 diabetes (74 cases, 63.8%) respectively, the primary disease was septic shock in 109 cases (94.0%). A total of 147 peripheral venous catheters were inserted, and the most common site of puncture was the forearm [78.9% (116/147)], followed by the hand [12.2% (18/147)] and the median cubital vein [8.8% (13/147)]. 89.9% of the needles were 20 G in diameter, and 75 cases (64.7%) were converted to central venous catheters (CVC) during subsequent treatment due to continuous infusion of NE. Six patients (5.2%) had extravasation, the median time of extravasation was 29 (23-39) hours, and the median time of NE was 23 (11-53) hours, including 2 patients with an infusion concentration of 60 mg/L and 4 patients with an infusion concentration of 120 mg/L.The infusion speed was 0.5-1.0 µg×kg-1×min-1, and the average speed of infusion was (0.75±0.04) µg×kg-1×min-1 when extravasation. Univariate and binary Logistic regression analysis showed that the risk factors related to the occurrence of extravasation included: (1) patient factors: the presence of basic diseases, hypertension [odds ratio (OR) = 3.11, 95% confidence interval (95%CI) was 3.09-3.12, P = 0.001] and edema (OR = 1.79, 95%CI was 1.32-2.99, P = 0.032). (2) Factors of infusion fluid itself: long-term (> 24 hours) infusion (OR = 2.91, 95%CI was 1.04-5.96, P = 0.040), infusion concentration > 60 mg/L (OR = 1.88, 95%CI was 1.32-3.99, P = 0.024), infusion speed > 0.3 µg×kg-1×min-1 (OR = 2.43, 95%CI was 2.38-2.51, P = 0.029) and diameter of needles < 20 G (OR = 3.11, 95%CI was 3.09-3.22, P = 0.033). (3) Medical personnel factors: lack of observation and assessment (OR = 1.09, 95%CI was 1.03-6.77, P = 0.043). The ROC curve analysis showed that: edema, long-term infusion (> 24 hours), infusion rate > 0.3 µg×kg-1×min-1 and diameter of needles < 20 G had a certain predictive value for extravasation of NE through peripheral venous infusion in patients with septic shock, the area under ROC curve (AUC) was 0.610, 0.762, 0.672, 0.629, 95%CI was 0.508-0.713, 0.675-0.849, 0.571-0.772, 0.525-0.732, and P values were 0.044, 0.000, 0.002, 0.019, respectively. CONCLUSIONS: Hypertension, edema, long-term infusion (> 24 hours), infusion concentration > 60 mg/L, infusion speed > 0.3 µg×kg-1×min-1, diameter of needle < 20 G, and lack of observation and evaluation by medical staff regularly were risk factors affecting the safety of peripheral intravenous NE in patients with septic shock. Peripheral NE should be avoided in the presence of the above risk factors.


Assuntos
Diabetes Mellitus Tipo 2 , Choque Séptico , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Norepinefrina , Prognóstico , Estudos Retrospectivos , Choque Séptico/tratamento farmacológico
15.
West J Emerg Med ; 22(2): 196-203, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33856300

RESUMO

INTRODUCTION: Most experts recommend norepinephrine as the first-line agent in septic shock. Our objective was to determine the effectiveness and safety of norepinephrine in patients with septic shock. METHODS: We searched the Cochrane Central Register of Controlled Trials and Epistemonikos, as well as MEDLINE from 1966 till August 2019. Screening of full texts, evaluation for eligibility, and data extraction were done by four independent reviewers. We estimated risk ratios (RR) and mean differences (MD) using a random-effects model with 95% confidence intervals (CI). The primary outcomes included the number of participants who achieved the target mean arterial pressure (MAP), time to achieve the target MAP, and number of participants with all-cause 28-day mortality. The secondary outcomes included the length of stay in the intensive care unit, length of hospital stay, incidence of arrhythmia and myocardial infarction, vasopressor-free days, and number of participants with all-cause 90-day mortality. RESULTS: We identified 11 randomized controlled trials with a total of 4,803 participants. There was no difference in the number of participants who achieved the target MAP between those patients receiving norepinephrine and other vasopressors (RR 1.44; 95% CI, 0.32 to 6.54; P = 0.640; I2 = 94%; two trials, 116 participants). There was no significant difference in time to achieve the target MAP (MD -0.05; 95%, CI, -0.32 to 0.21; P = 0.690; I2 = 26%; two trials, 1763 participants) and all-cause 28-day mortality (RR 0.95; 95% CI, 0.89 to 1.02; P = 0.160; I2 = 0%; seven trials, 4,139 participants). Regarding the secondary outcome, norepinephrine may significantly reduce the incidence of arrhythmia as compared to other vasopressors (RR 0.64; 95% CI, 0.42 to 0.97; P = 0.030; I2 = 64%; six trials, 3974 participants). There was no difference in the incidence of myocardial infarction (RR 1.28; 95% CI, 0.79 to 2.09), vasopressor-free day (RR 0.46; 95% CI, -1.82 to 2.74) and all-cause 90-day mortality (RR 1.08; 95% CI, 0.96 to 1.21) between norepinephrine and vasopressors. CONCLUSION: In minimizing the occurrence of an arrhythmia, norepinephrine is superior to other vasopressors, making it safe to be used in septic shock. However, there was insufficient evidence concerning mortality and achievement of the target MAP outcomes.


Assuntos
Norepinefrina/uso terapêutico , Choque Séptico/tratamento farmacológico , Vasoconstritores/uso terapêutico , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Choque Séptico/mortalidade
16.
Toxins (Basel) ; 13(5)2021 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-33925199

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) can cause chronic lung infections in patients with Cystic Fibrosis (CF). One option for managing them is the use of linezolid. We hereby report the in-host emergence of linezolid resistance (LR) in MRSA in CF siblings via a population analysis. A collection of 171 MRSA strains from 68 samples were characterized by determining their linezolid Minimal Inhibitory Concentrations (MICs), analyzing the locus of staphylococcal protein A (spa) and whole genome sequencing. Courses of linezolid were retraced. Strains belonged to three spa types (t002, t045, t127) and two sequence types (ST1, ST5). Emergence of LR occurred under treatment, one year apart in both siblings, in the CC5-MRSA-I Geraldine clone harboring the toxic shock syndrome toxin-1-encoding gene. Resistance was related to a G2576T substitution present in a variable number of 23S rRNA gene copies. Susceptible and resistant strains were co-isolated within samples. Single Nucleotide Polymorphism-based analysis revealed complex colonizations by highly diversified, clonally related populations. LR remains rare in MRSA and there are very few longitudinal analyses documenting its emergence. Analyzing a large MRSA collection revealed new aspects of LR emergence: it emerges in specific subclonal lineages resulting from adaptive diversification of MRSA in the CF lung and this heterogeneity of intra-sample resistance may contribute to compromising antibiotic management.


Assuntos
Fibrose Cística/complicações , Linezolida/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Choque Séptico/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Adolescente , Criança , Fibrose Cística/microbiologia , Farmacorresistência Bacteriana , Farmacorresistência Bacteriana Múltipla/genética , Feminino , Técnicas de Genotipagem , Humanos , Linezolida/farmacologia , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Choque Séptico/tratamento farmacológico , Irmãos , Infecções Estafilocócicas/microbiologia , Sequenciamento Completo do Genoma
17.
J Comp Eff Res ; 10(8): 673-683, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33860672

RESUMO

Background: The effect of midodrine on lactate clearance has not been assessed in critically ill patients yet. Objective: The goal of this study was to assess the effect of adjunctive midodrine therapy on lactate clearance in patients with septic shock. Materials & methods: Patients with septic shock were assigned to receive either adjunctive midodrine 10 mg three-times a day for 5 days (midodrine group = 15 patients) or not (control group = 13 patients). Results: The lactate clearance was significantly faster in the midodrine group than the control group (p = 0.049) with a large effect size (ηp2 = 0.141). Conclusion: When midodrine was added to intravenous vasopressors, it significantly accelerated lactate clearance in patients with septic shock. Trial registration number: IRCT20100228003449N25 (Clinicaltrials.gov).


Assuntos
Midodrina , Choque Séptico , Humanos , Ácido Láctico , Midodrina/uso terapêutico , Projetos Piloto , Choque Séptico/tratamento farmacológico , Vasoconstritores/uso terapêutico
18.
Eur Rev Med Pharmacol Sci ; 25(7): 3136-3144, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33877683

RESUMO

OBJECTIVE: Disruption of intracellular Ca2+ homeostasis via excessive and pathological Ca2+ release from the endoplasmic reticulum (ER) and/or sarcoplasmic reticulum (SR) through ryanodine receptor (RyRs) Ca2+ channels play a critical role in the pathology of systemic inflammatory response syndrome (SIRS) and associated multiple organ dysfunction syndrome (MODS) in sepsis or septic shock. Dantrolene, a potent inhibitor of RyRs, is expected to ameliorate SIRS and MODS and decrease mortality in sepsis or septic shock patients. This review summarized the potential mechanisms of therapeutic effects of dantrolene in sepsis or septic shock at molecular, cell, and organ levels and provided suggestions and strategies for future clinical studies.


Assuntos
COVID-19/tratamento farmacológico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Dantroleno/uso terapêutico , Sepse/tratamento farmacológico , COVID-19/metabolismo , Cálcio/metabolismo , Reposicionamento de Medicamentos , Retículo Endoplasmático/metabolismo , Humanos , Mortalidade , Insuficiência de Múltiplos Órgãos , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , SARS-CoV-2 , Retículo Sarcoplasmático/metabolismo , Sepse/metabolismo , Choque Séptico/tratamento farmacológico , Choque Séptico/metabolismo
20.
Curr Opin Crit Care ; 27(3): 269-273, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33852500

RESUMO

PURPOSE OF REVIEW: Current goals of resuscitation in septic shock are mainly a fixed volume of fluids and vasopressors to correct hypotension and improve tissue perfusion indicated by decreasing lactate levels. RECENT FINDINGS: Abnormal peripheral perfusion by objective and subjective parameters are associated with increased mortality in various phases of the treatment of critically ill patients including patients with septic shock. Ongoing resuscitation in septic shock patients with normal peripheral perfusion is not associated with improved outcome, rather with increased mortality. Mitigation of fluid resuscitation by using parameters of peripheral perfusion in septic shock seems to be safe. SUMMARY: Septic shock patients with normal peripheral perfusion represent a different clinical phenotype of patients that might benefit from limited resuscitation efforts. Parameters of peripheral perfusion could be used to guide the individualization of patients with septic shock.


Assuntos
Choque Séptico , Hidratação , Humanos , Perfusão , Ressuscitação , Choque Séptico/tratamento farmacológico , Vasoconstritores/uso terapêutico
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