Effects of a single dose of vitamin D in septic children: a randomized, double-blinded, controlled trial.

OBJECTIVE: To assess the effects of a single dose of vitamin D on 25-hydroxyvitamin D (25OHD) levels and clinical outcomes in children with vitamin D deficiency (VDD) and sepsis. METHODS: In this randomized, controlled trial, eligible children with VDD and sepsis were assigned to receive one dose of 150,000 IU of cholecalciferol or placebo. Serum concentrations of 25OHD, angiotensin-II (Ang-II), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were assessed at baseline and 8 days after treatment. The cardiovascular Sequential Organ Failure Assessment (cv-SOFA) score, septic shock incidence, duration of ventilation, and mortality were also examined. RESULTS: One hundred nine participants fulfilled the study requirements. The two groups had comparable baseline characteristics. Ang-II, IL-6, and TNF-α concentrations were all reduced after vitamin D supplementation. Furthermore, the cv-SOFA score (1.76 ± 0.8 vs. 2.3 ± 1.1) and incidence of septic shock (7% vs. 20%) were lower in the treatment group than in the control group. The duration of ventilation and mortality rates did not differ between two groups. CONCLUSIONS: A single dose of vitamin D improved 25OHD levels and the incidence of septic shock in children with VDD and sepsis.

A prospective study of treatment of carbapenem-resistant Enterobacteriaceae infections and risk factors associated with outcome.

BACKGROUND: To describe the clinical and microbiological data of carbapenem-resistant Enterobacteriaceae (CRE) infections, the treatment used, hospital- and infection-related mortality, and risk factors for death. METHODS: A prospective cohort conducted from March 2011 to December 2012. Clinical, demographic, and microbiological data such as in vitro sensitivity, clonality, carbapenemase gene mortality related to infection, and overall mortality were evaluated. Data were analyzed using Epi Info version 7.0 (CDC, Atlanta, GA, USA) and SPSS (Chicago, IL, USA). RESULTS: One hundred and twenty-seven patients were evaluated. Pneumonia, 52 (42 %), and urinary tract infections (UTI), 51 (40.2 %), were the most frequent sites of infection. The isolates were polyclonal; the Bla KPC gene was found in 75.6 % of isolates, and 27 % of isolates were resistant to colistin. Mortality related to infection was 34.6 %, and was higher among patients with pneumonia (61.4 %). Combination therapy was used in 98 (77.2 %), and monotherapy in 22.8 %; 96.5 % of them were UTI patients. Shock, age, and dialysis were independent risk factors for death. There was no difference in infection-related death comparing colistin-susceptible and colistin-resistant infections (p = 0.46); neither in survival rate comparing the use of combination therapy with two drugs or more than two drugs (p = 0.32). CONCLUSIONS: CRE infection mortality was higher among patients with pneumonia. Infections caused by colistin-resistant isolates did not increase mortality. The use of more than two drugs on combination therapy did not show a protective effect on outcome. The isolates were polyclonal, and the bla KPC gene was the only carbapenemase found. Shock, dialysis, and age over 60 years were independent risk factors for death.

Etiologies of illness among patients meeting integrated management of adolescent and adult illness district clinician manual criteria for severe infections in northern Tanzania: implications for empiric antimicrobial therapy.

We describe the laboratory-confirmed etiologies of illness among participants in a hospital-based febrile illness cohort study in northern Tanzania who retrospectively met Integrated Management of Adolescent and Adult Illness District Clinician Manual (IMAI) criteria for septic shock, severe respiratory distress without shock, and severe pneumonia, and compare these etiologies against commonly used antimicrobials, including IMAI recommendations for emergency antibacterials (ceftriaxone or ampicillin plus gentamicin) and IMAI first-line recommendations for severe pneumonia (ceftriaxone and a macrolide). Among 423 participants hospitalized with febrile illness, there were 25 septic shock, 37 severe respiratory distress without shock, and 109 severe pneumonia cases. Ceftriaxone had the highest potential utility of all antimicrobials assessed, with responsive etiologies in 12 (48%) septic shock, 5 (14%) severe respiratory distress without shock, and 19 (17%) severe pneumonia illnesses. For each syndrome 17-27% of participants had etiologic diagnoses that would be non-responsive to ceftriaxone, but responsive to other available antimicrobial regimens including amphotericin for cryptococcosis and histoplasmosis; anti-tuberculosis therapy for bacteremic disseminated tuberculosis; or tetracycline therapy for rickettsioses and Q fever. We conclude that although empiric ceftriaxone is appropriate in our setting, etiologies not explicitly addressed in IMAI guidance for these syndromes, such as cryptococcosis, histoplasmosis, and tetracycline-responsive bacterial infections, were common.

Clinical pathway intervention compliance and effectiveness when used in the treatment of patients with severe sepsis and septic shock at an Intensive Care Unit in Spain.

The purpose of this quasi-experimental study was to assess levels of compliance with the intervention bundles contained in a clinical pathway used in the treatment of patients with severe sepsis and septic shock, and to analyze the pathway's impact on survival and duration of hospital stays. We used data on 125 patients in an Intensive Care Unit, divided into a control group (N=84) and an intervention group (N=41). Levels of compliance increased from 13.1% to 29.3% in 5 resuscitation bundle interventions and from 14.3% to 22% in 3 monitoring bundle interventions. In-hospital mortality at 28 days decreased by 11.2% and the duration of hospital stay was reduced by 5 days. Although compliance was low, the intervention enhanced adherence to the instructions given in the clinical pathway and we observed a decline in mortality at 28 days and shorter hospital stays.

Clinical pathway intervention compliance and effectiveness when used in the treatment of patients with severe sepsis and septic shock at an Intensive Care Unit in Spain / Observância e efetividade das intervenções de um protocolo clínico utilizado para pacientes com sepse grave e choque séptico de uma Unidade de Cuidados Intensivos da Espanha / Cumplimiento y efectividad de las intervenciones de un protocolo clínico utilizado en pacientes con sepsis grave y shock séptico en una Unidad de Cuidados Intensivos en España

The purpose of this quasi-experimental study was to assess levels of compliance with the intervention bundles contained in a clinical pathway used in the treatment of patients with severe sepsis and septic shock, and to analyze the pathway's impact on survival and duration of hospital stays. We used data on 125 patients in an Intensive Care Unit, divided into a control group (N=84) and an intervention group (N=41). Levels of compliance increased from 13.1% to 29.3% in 5 resuscitation bundle interventions and from 14.3% to 22% in 3 monitoring bundle interventions. In-hospital mortality at 28 days decreased by 11.2% and the duration of hospital stay was reduced by 5 days. Although compliance was low, the intervention enhanced adherence to the instructions given in the clinical pathway and we observed a decline in mortality at 28 days and shorter hospital stays.

O objetivo deste estudo quase-experimental foi avaliar o grau de cumprimento das intervenções de um pacote de medidas, em um protocolo clínico proposto para pacientes com sepse grave e choque séptico, e analisar o seu impacto na sobrevivência e duração das permanências hospitalares. Foram incluídos 125 pacientes, alocados no grupo controle (n=84) e intervenção (n=41) de uma Unidade de Cuidados Intensivos, na Espanha. O nível de adesão aumentou em pelo menos 5 intervenções do pacote de reanimação (de 13,1 para 29,3%) e em pelo menos 3 intervenções do pacote de acompanhamento (de 14,3 para 22%). A mortalidade hospitalar aos 28 dias diminuiu em 11,2% e a duração da permanência hospitalar foi reduzida em 5 dias. Embora o cumprimento tenha sido baixo, a intervenção aumentou a adesão às indicações do protocolo clínico e foram observadas queda da mortalidade aos 28 dias e menor duração da permanência hospitalar.

El objetivo de este estudio cuasiexperimental fue valorar el nivel de cumplimiento de las intervenciones de los paquetes de medidas de un protocolo clínico para pacientes con sepsis grave y shock séptico y analizar su impacto sobre la supervivencia y la duración de estancias hospitalarias. Se incluyeron los datos de 125 pacientes divididos en grupo control (N=84) e intervención (N=41) de una Unidad de Cuidados Intensivos. El nivel de cumplimiento aumentó de 13,1% a 29,3% en 5 intervenciones del paquete de reanimación y de 14,3% a 22% en 3 intervenciones del paquete de seguimiento. La mortalidad hospitalaria a los 28 días disminuyó un 11,2% y la duración de la estancia hospitalaria se redujo en 5 días. Aunque el cumplimiento fue bajo, la intervención aumentó la adhesión a las indicaciones del protocolo clínico y se observó un descenso de la mortalidad a los 28 días y menor duración de estancias hospitalarias.

Animal models of sepsis.

In this review, we start with a general discussion of relevant factors that can determine the validity of a sepsis animal model. We briefly review some of the currently used animal models of sepsis (small animal models and large animal models). We discuss the clinical relevance of animal models in sepsis research today and address potential reasons for the apparent underperformance of animal models in predicting therapeutic success of novel drugs in clinical trials.

Atención de las emergencias y urgencias médico-quirúrgicas en un hospital oncológico / Emergencies and urgent medical-surgical conditions attended at a comprehensive cancer center

La incidencia global de las emergencias y urgencias médicoquirúrgicas en pacientes con cáncer ha sido descrita esporádicamente. El objetivo del estudio fue identificar los principales síntomas y diagnósticos de los pacientes que acudieron al Servicio de Urgencias del Hospital de Oncología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social. El diseño fue observacional y retrospectivo. La información fue obtenida del registro de la consulta diaria del Servicio de Admisión Continua. En un periodo de seis meses fueron atendidos 4,937 pacientes. Los cuadros clínicos evaluados como emergencias correspondieron a 3.7 %, como condiciones médicas urgentes 52.5 % y como condiciones no urgentes, 43.7 %. Los síntomas más frecuentes motivo de las consultas de emergencia o urgencias en los pacientes con cáncer fueron dolor grave en 69.5 % y deshidratación con desequilibrio hidroelectrolítico en 11.4 %. Los principales síntomas fueron provocados por el tumor primario o su diseminación metastásica, en 89 %. Los tumores malignos sólidos más frecuentes fueron los carcinomas mamario, de colon/recto, cervicouterino, broncogénico y gástrico. Las principales emergencias registradas en los pacientes con cáncer en este estudio fueron choque séptico y neutropenia severa (20 %), choque hipovolémico por sangrado en diversos sitios (16.5 %) y disnea agudizada por neumonía o derrame pleural (12 %). En aproximadamente 80 % de quienes son tratados paso a paso de manera racional, el dolor por cáncer pudo ser controlado sólo con analgésicos. La analgesia no efectiva se asoció frecuentemente con prescripción inadecuada o ingesta insuficiente de analgésicos opioides. Los servicios de urgencias establecidos funcionalmente en los hospitales monográficos de cáncer ofrecen la mejor oportunidad de tratamiento a los pacientes con cáncer con condiciones emergentes o urgentes.

The global incidence of emergencies and urgent medical?surgical conditions in cancer patients has not been well described. The aim of the study was to identify the main symptoms and diagnoses in patients seen for consultation at the Urgent Care Service in a Mexican Comprehensive Cancer Center. This was a retrospective observational study. The information was obtained from the Continuous Admission Service daily consultation records at the Oncology Hospital, National Medical Center 21st Century, Institute of Social Security, Mexico City. During a 6-month period, 4937 patients were seen for consultation. True oncologic emergencies were 3.7%, urgencies 52.5% and non-urgent were 43.7%. Most common symptoms for emergency and urgency patient consultations were severe pain (69.5%) and dehydration with electrolyte imbalance (11.4%). Prevalent symptoms were associated with the primary tumor or metastatic dissemination (89% cases). The most frequent baseline diseases were breast, colorectal, cervical, lung and stomach carcinomas. Defined oncologic emergencies in this series were septic shock and severe neutropenia (20%), hypovolemic shock due to severe bleeding (16.5%), and severe dyspnea due to pneumonia or pleural efusion (12%). Data evaluating the use of analgesic drug therapy for cancer pain alone indicate that 80% of patients report adequate analgesia. Analgesia failures were associated with an insufficient prescription or with inadequate consumption of opioid analgesics. The Urgent Care Center at a Comprehensive Cancer Center offers the best opportunity for diagnosis and treatment of emergencies and urgent care conditions in cancer patients.

[Emergencies and urgent medical-surgical conditions attended at a comprehensive cancer center]. / Atencián de las emergencias y urgencias médico-quirúrgicas en un hospital oncológico.

The global incidence of emergencies and urgent medical?surgical conditions in cancer patients has not been well described. The aim of the study was to identify the main symptoms and diagnoses in patients seen for consultation at the Urgent Care Service in a Mexican Comprehensive Cancer Center. This was a retrospective observational study. The information was obtained from the Continuous Admission Service daily consultation records at the Oncology Hospital, National Medical Center "21st Century," Institute of Social Security, Mexico City. During a 6-month period, 4937 patients were seen for consultation. True oncologic emergencies were 3.7%, urgencies 52.5% and non-urgent were 43.7%. Most common symptoms for emergency and urgency patient consultations were severe pain (69.5%) and dehydration with electrolyte imbalance (11.4%). Prevalent symptoms were associated with the primary tumor or metastatic dissemination (89% cases). The most frequent baseline diseases were breast, colorectal, cervical, lung and stomach carcinomas. Defined oncologic emergencies in this series were septic shock and severe neutropenia (20%), hypovolemic shock due to severe bleeding (16.5%), and severe dyspnea due to pneumonia or pleural efusion (12%). Data evaluating the use of analgesic drug therapy for cancer pain alone indicate that 80% of patients report adequate analgesia. Analgesia failures were associated with an insufficient prescription or with inadequate consumption of opioid analgesics. The Urgent Care Center at a Comprehensive Cancer Center offers the best opportunity for diagnosis and treatment of emergencies and urgent care conditions in cancer patients.

Bloodstream infection-associated sepsis and septic shock in critically ill adults: a population-based study.

BACKGROUND: Few studies have investigated the epidemiology of sepsis and septic shock in a large population and none have been from Canada. The objective of this study was to define the epidemiology of bloodstream infection (BSI)-associated sepsis and septic shock among all critically ill patients in a large, fully integrated health region in Canada. PATIENTS AND METHODS: All critically ill adults admitted to multidisciplinary intensive care units (ICU) in the Calgary Health Region during May 1, 1999 to April 30, 2000 were included. Clinical, microbiologic and outcome information was obtained from regional databases. RESULTS: We surveyed 1981 patients having at least one ICU admission. Systemic inflammatory response syndrome (SIRS) was diagnosed in 92%, BSI-associated sepsis (BSI with SIRS) in 6% and BSI-associated septic shock (BSI with SIRS and hypotension) in 3%; respective hospital mortality rates were 36%, 40% and 49%. The most common BSI etiologies were Staphylococcus aureus, Escherichia coli and Streptococcus species; only one isolate (1%) was highly antibiotic resistant. Independent risk factors for death among patients with SIRS included age (>or= 65), hypothermia (< 35 degrees C), and higher APACHE II and TISS scores. A surgical diagnosis was associated with decreased mortality risk. Neither a positive blood culture nor hypotension at presentation independently predicted death. CONCLUSION: Knowledge of the epidemiology of these syndromes is important for assessing the burden of disease and providing background information for investigating new therapies.

Addition of alinidine, a specific bradycardic agent, to dobutamine in a canine model of endotoxic shock.

BACKGROUND AND METHODS: Alinidine is a recently developed antiarrhythmic medication that acts directly on the cardiac pacemaker cells to reduce heart rate (HR). At effective doses, alinidine might have cardiodepressant actions that could be hazardous in the presence of hemodynamic instability. On the other hand, one limitation of the use of catecholamines is tachycardia, and alinidine could be beneficial in situations such as septic shock, where adrenergic agents are commonly required. The present study explored the hemodynamic and gasometric effects of alinidine during dobutamine administration in a canine model of septic shock induced by endotoxin administration. In ten pentobarbital-anesthetized, mechanically ventilated dogs (weight 28 +/- 4 kg), Escherichia coli endotoxin (3 mg/kg) injection was followed 30 mins later by saline infusion to restore and maintain pulmonary artery occlusion pressure at the baseline value. Sixty minutes after the endotoxin administration, a dobutamine infusion was started at a rate of 10 micrograms/kg/min. Thirty minutes later, alinidine was administered as a bolus dosage of 1 mg/kg in five dogs; the other five dogs served as a control group. RESULTS: Alinidine administration resulted in a decrease in HR from 157 +/- 20 to 138 +/- 27 beats/min (p less than .01) and a nonsignificant increase in cardiac output from 5.2 +/- 3.0 to 6.8 +/- 2.8 L/min, as a consequence of increases in stroke volume from 31.9 +/- 15.3 to 49.2 +/- 13.9 mL (p less than .01) and in left ventricular stroke work from 32.1 +/- 20.0 to 57.4 +/- 32.1 g.m (p less than .05). CONCLUSIONS: During experimental septic shock, alinidine administration can reverse dobutamine-induced tachycardia and simultaneously improve ventricular function.