Optimal doses of caspofungin during continuous venovenous hemodiafiltration in critically ill patients

Extravascular Lung Water Does Not Increase in Hypovolemic Patients after a Fluid-Loading Protocol Guided by the Stroke Volume Variation

Introduction. Circulatory failure secondary to hypovolemia is a common situation in critical care patients. Volume replacement is the first option for the treatment of hypovolemia. A possible complication of volume loading is pulmonary edema, quantified at the bedside by the measurement of extravascular lung water index (ELWI). ELWI predicts progression to acute lung injury (ALI) in patients with risk factors for developing it. The aim of this study was to assess whether fluid loading guided by the stroke volume variation (SVV), in patients presumed to be hypovolemic, increased ELWI or not.Methods. Prospective study of 17 consecutive postoperative, fully mechanically ventilated patients dia…

Dosing of caspofungin based on a pharmacokinetic/pharmacodynamic index for the treatment of invasive fungal infections in critically ill patients on continuous venovenous haemodiafiltration.

Abstract Introduction The study objective was to evaluate the efficacy of different dosages of caspofungin in the treatment of invasive candidiasis and aspergillosis, in relation to the probability of pharmacokinetic/pharmacodynamic (PK/PD) target attainment, using modelling and Monte Carlo simulations in critically ill adult patients on continuous haemodiafiltration. Methods Critically ill adult patients on continuous venovenous haemodiafiltration treated with caspofungin were analysed. A population PK model was developed. Four caspofungin dosing regimens were simulated: the licensed regimen, 70 mg/day, 100 mg/day or 200 mg/day. A PK/PD target was defined as the ratio between the area unde…

Hyperosmolar therapy for acute brain injury: study protocol for an umbrella review of meta-analyses and an evidence mapping

Introduction Acute brain injury is a challenging public health problem worldwide. Elevated intracranial pressure is a common complication after acute brain injury. Hyperosmolar therapy is one of the main therapeutic strategies for the management of intracranial hypertension. This study protocol outlines an umbrella review of meta-analyses which will investigate the benefits and harms of hyperosmolar therapy routinely used for the management of acute brain injury in the intensive care. Methods and analysis We will search PubMed/MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews. We will include meta-analyses of primary research studies (eg, randomised controlled trials, observat…

Supplemental Perioperative Oxygen and the Risk of Surgical Wound Infection<SUBTITLE>A Randomized Controlled Trial</SUBTITLE>

ContextSupplemental perioperative oxygen has been variously reported to halve or double the risk of surgical wound infection.ObjectiveTo test the hypothesis that supplemental oxygen reduces infection risk in patients following colorectal surgery.Design, Setting, and PatientsA double-blind, randomized controlled trial of 300 patients aged 18 to 80 years who underwent elective colorectal surgery in 14 Spanish hospitals from March 1, 2003, to October 31, 2004. Wound infections were diagnosed by blinded investigators using Centers for Disease Control and Prevention criteria. Baseline patient characteristics, anesthetic treatment, and potential confounding factors were recorded.InterventionsPati…

Optimizing ceftolozane-tazobactam dosage during continuous renal replacement therapy: some nuances

Need to evaluate the performance of real-time PCR assays for the quantitation of cytomegalovirus DNA load in lower respiratory tract specimens

There is an increasing appreciation for the potential clinical value of the quantitation of cytomegalovirus (CMV) DNA in the lower respiratory tract in critically ill patients lacking canonical immunosuppression, in view of the possible pathogenic role of CMV in these patients [1]. No data have been published on the analytical performance of real-time PCR assays for this purpose. We present our data on the performance of the COBAS® AmpliPrep/COBAS® TaqMan CMV PCR Assay (Roche Diagnostics, Mannheim, Germany) for the quantitation of CMV DNA in tracheal aspirates (TA). This CMV PCR assay has been approved recently by the US Food and Drug Administration for use with plasma specimens [2]. We cho…

Poor timing and failure of source control are risk factors for mortality in critically ill patients with secondary peritonitis

PURPOSE: To describe data on epidemiology, microbiology, clinical characteristics and outcome of adult patients admitted in the intensive care unit (ICU) with secondary peritonitis, with special emphasis on antimicrobial therapy and source control. METHODS: Post hoc analysis of a multicenter observational study (Abdominal Sepsis Study, AbSeS) including 2621 adult ICU patients with intra-abdominal infection in 306 ICUs from 42 countries. Time-till-source control intervention was calculated as from time of diagnosis and classified into 'emergency' ( 6 h). Relationships were assessed by logistic regression analysis and reported as odds ratios (OR) and 95% confidence interval (CI). RESULTS: The…

Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial

Background There is no proven specific pharmacological treatment for patients with the acute respiratory distress syndrome (ARDS). The efficacy of corticosteroids in ARDS remains controversial. We aimed to assess the effects of dexamethasone in ARDS, which might change pulmonary and systemic inflammation and result in a decrease in duration of mechanical ventilation and mortality. Methods We did a multicentre, randomised controlled trial in a network of 17 intensive care units (ICUs) in teaching hospitals across Spain in patients with established moderate-to-severe ARDS (defined by a ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen of 200 mm Hg or less assesse…

Anidulafungin dosing in critically ill patients with continuous venovenous haemodiafiltration

Background Anidulafungin is indicated as a first-line treatment for invasive candidiasis in critically ill patients. In the intensive care unit, sepsis is the main cause of acute renal failure, and treatment with continuous renal replacement therapy (CRRT) has increased in recent years. Antimicrobial pharmacokinetics is affected by CRRT, but few studies have addressed the optimal dosage for anidulafungin during CRRT. Patients and methods We included 12 critically ill patients who received continuous venovenous haemodiafiltration to treat acute renal failure. Anidulafungin was infused on 3 consecutive days, starting with a loading dose (200 mg) on Day 1, and doses of 100 mg on Days 2 and 3. …

Pharmacokinetics of anidulafungin during venovenous extracorporeal membrane oxygenation

Echinocandins are currently considered the first-line treatment for invasive candidiasis (IC) in the intensive care unit (ICU) [1, 2]. However, extracorporeal membrane oxygenation (ECMO), a rescue therapy used in patients with severe acute respiratory distress syndrome (ARDS) [3], could alter the pharmacokinetics of certain drugs [4]. We prescribed anidulafungin for suspected IC in a patient with severe ARDS on ECMO and measured the plasma concentrations of the drug using high-performance liquid chromatography (HPLC).

Intraoperative positive end-expiratory pressure and postoperative pulmonary complications: a patient-level meta-analysis of three randomised clinical trials

BACKGROUND: High intraoperative PEEP with recruitment manoeuvres may improve perioperative outcomes. We re-examined this question by conducting a patient-level meta-analysis of three clinical trials in adult patients at increased risk for postoperative pulmonary complications who underwent non-cardiothoracic and non-neurological surgery. METHODS: The three trials enrolled patients at 128 hospitals in 24 countries from February 2011 to February 2018. All patients received volume-controlled ventilation with low tidal volume. Analyses were performed using one-stage, two-level, mixed modelling (site as a random effect; trial as a fixed effect). The primary outcome was a composite of postoperati…

Pharmacokinetics of anidulafungin during albumin dialysis

In the ICU setting, current guidelines recommend echi-nocandins as the first-line treatment for invasive candi-diasis [1]. Albumin dialysis (AD) has been used in theICU as supportive therapy for hepatic failure, but thistechnique can significantly enhance drug elimination [2].We prescribed anidulafungin for suspected invasivecandidiasis in a patient with severe liver failure treatedwith AD and measured the plasma concentrations of thedrug using high-performance liquid chromatography.This study (GEF-ANI-2010-02) was approved by thelocal ethics committee (INCLIVA, Institute of Research,Valencia, Spain) and written informed consent wasobtained from the patient’s next of kin. An adult patientwa…

The impact of frailty on ICU and 30-day mortality and the level of care in very elderly patients (≥ 80 years)

Purpose: Very old critical ill patients are a rapid expanding group in the ICU. Indications for admission, triage criteria and level of care are frequently discussed for such patients. However, most relevant outcome studies in this group frequently find an increased mortality and a reduced quality of life in survivors. The main objective was to study the impact of frailty compared with other variables with regards to short-term outcome in the very old ICU population. Methods: A transnational prospective cohort study from October 2016 to May 2017 with 30 days follow-up was set up by the European Society of Intensive Care Medicine. In total 311 ICUs from 21 European countries participated. Th…

Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE)

Background: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventila…

Epidemiology of invasive candidiasis in a surgical intensive care unit: an observational study

Background: Invasive candidiasis (IC) is a frequent and life-threatening infection in critically ill patients. The aim of this study was to evaluate the epidemiology of IC and the antifungal susceptibility of etiological agents in patients admitted to our surgical intensive care unit (SICU) in Spain. Methods: We designed a prospective, observational, single center, population-based study in a SICU. We included all consecutive adult patients (≥18 years old) who had documented IC, either on admission or during their stay, between January 2012 and December 2013. Results: There were a total of 22 episodes of IC in the 1149 patients admitted during the 24-month study. The overall IC incidence wa…

Individualised perioperative open-lung approach versus standard protective ventilation in abdominal surgery (iPROVE): a randomised controlled trial

Background The effects of individualised perioperative lung-protective ventilation (based on the open-lung approach [OLA]) on postoperative complications is unknown. We aimed to investigate the effects of intraoperative and postoperative ventilatory management in patients scheduled for abdominal surgery, compared with standard protective ventilation. Methods We did this prospective, multicentre, randomised controlled trial in 21 teaching hospitals in Spain. We enrolled patients who were aged 18 years or older, were scheduled to have abdominal surgery with an expected time of longer than 2 h, had intermediate-to-high-risk of developing postoperative pulmonary complications, and who had a bod…

Tratamiento con equinocandinas en un paciente crítico sometido a técnica continua de reemplazo renal

Resumen Antecedentes Los pacientes criticos con candidiasis invasiva (CI) suelen presentar con frecuencia insuficiencia renal, por lo que en ocasiones requieren tecnicas continuas de reemplazo renal (TCRR). Las equinocandinas son la primera opcion en el tratamiento de la CI en el paciente critico con enfermedad moderada o grave. Debido a su perfil farmacocinetico y farmacodinamico (FC/FD), su eliminacion durante las TCRR debe ser despreciable, sin que sea necesario ajustar sus dosis, como asi lo indican los escasos estudios clinicos que hay al respecto. Caso clinico Varon de 66 anos intervenido por peritonitis secundaria a dehiscencia de sutura intestinal, que ingresa en la unidad de cuidad…

Virological and immunological features of active cytomegalovirus infection in nonimmunosuppressed patients in a surgical and trauma intensive care unit.

Cytomegalovirus (CMV) reactivation occurs frequently in critically ill patients. The natural course of CMV infection and the interaction between CMV and the adaptive immune system in this setting remain poorly defined. Fifty-three CMV-seropositive patients in a surgical and trauma intensive care unit were included in this study. The CMV DNA load in tracheal aspirates (TA) and plasma (PL) was monitored by qPCR. CMV-specific T-cell immunity was assessed by intracellular cytokine staining. Plasma TNF-alpha levels were determined by ELISA. CMV reactivation occurred in 39.7% of patients (23% had CMV DNA detected only in TA). The analysis of TA allowed an earlier diagnosis in 28% of patients. Cle…

Ceftolozane Pharmacokinetics in a Septic Critically Ill Patient under Different Extracorporeal Replacement Therapies

Ceftolozane-tazobactam (C/T), a novel fifth-generation cephalosporin/β-lactamase inhibitor combination active against multidrug-resistant (MDR) Pseudomonas aeruginosa, is currently approved by the U.S. Food and Drug Administration (FDA) to treat complicated intra-abdominal and urinary tract

Early adjustment of empirical antibiotic therapy of bloodstream infections on the basis of direct identification of bacteria by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and Gram staining results

Abstract Introduction To assess the potential added value of rapid MALDI-TOF MS-based identification of bacteria in positive blood cultures to the information provided by Gram staining for adequate empirical antibiotic treatment adjustments in patients with bloodstream infections (BSI). Methods We conducted a retrospective, single-center, pre-post quasi-experimental study. In the pre-MALDI-TOF MS phase of the study antibiotic adjustments were made on the basis of Gram stain results, whereas in the MALDI-TOF MS phase they were based on information provided by Gram staining and MALDI-TOF MS results. No antimicrobial stewardship program for BSI was in place within the study period. Antibiotic …

Immunological insights into the pathogenesis of active CMV infection in non-immunosuppressed critically ill patients.

Dissociation of cytomegalovirus (CMV) DNA loads between the lower respiratory tract and blood, with high levels in the former compartment and low or undetectable levels in the latter, commonly occurs during active CMV infection in critically ill patients despite the presence of high frequencies of CMV-specific IFN-γ-producing CD8+ and CD4+ T cells in blood. Data presented in this case report suggest that inter-compartmental differences in interleukin-10 (IL-10) levels may, in part, explain the pathobiology of this phenomenon. In the absence of ganciclovir treatment, a significant correlation was observed between IL-10 levels and CMV DNA loads in lower respiratory tract specimens (P = 0.016)…

Hipertensión endocraneal asociada a la sedación con sevoflurano mediante el dispositivo AnaConDa®en un paciente con traumatismo craneoencefálico severo

Sedation in neurocritical patients remains a challenge as there is no drug that meets all the requirements. Since the appearance of the AnaConDa® device, and according to the latest recommendations, sevoflurane has become an alternative for patients with brain injury. The use of AnaConDa® produces an increase in the anatomical dead space that leads to a decrease in alveolar ventilation. If the decrease in the alveolar ventilation is not offset by an increase in minute volume, there will be an increase in PaCO2. We report the case of a patient with severe traumatic brain injury who suffered an increase in intracranial pressure as a result of increased PaCO2 after starting sedation with the A…

Supplemental Perioperative Oxygen and the Risk of Surgical Wound Infection: A Randomized Controlled Trial

ABSTRACT Three hundred patients were enrolled in a double-blind, randomized, controlled study designed to investigate the ability of supplemental perioperative oxygen to reduce wound infection. Participants were age 18 to 80 years, had no coexisting serious medical conditions, and were scheduled to undergo elective colorectal surgery at one of 14 participating hospitals in Spain. No patients undergoing minor or laparoscopic surgery were included. Anesthesia and antibiotic prophylaxis were standardized for the study. Patients were randomized by computer-generated codes to receive an oxygen/air mixture of 30% or 80% fraction of inspired oxygen (F102) intraoperatively and postoperatively for 6…

Diagnostic accuracy and potential clinical value of the LightCycler SeptiFast assay in the management of bloodstream infections occurring in neutropenic and critically ill patients

Summary Objectives The objectives of this study were to compare the performance of the LightCycler SeptiFast Test MGRADE and conventional blood culture in the etiological diagnosis of febrile episodes occurring in neutropenic and critically ill patients (in the intensive care unit; ICU), and to assess the potential clinical value of the SeptiFast test in patient management. Methods A total of 86 febrile episodes occurring in 33 neutropenic patients and 53 ICU patients were analyzed. Blood samples for blood culture and SeptiFast testing were obtained at the onset of fever, before the implementation of empirical antimicrobial therapy. Results The overall microorganism-to-isolate agreement bet…

Antimicrobial Lessons From a Large Observational Cohort on Intra-abdominal Infections in Intensive Care Units

Severe intra-abdominal infection commonly requires intensive care. Mortality is high and is mainly determined by disease-specific characteristics, i.e. setting of infection onset, anatomical barrier disruption, and severity of disease expression. Recent observations revealed that antimicrobial resistance appears equally common in community-acquired and late-onset hospital-acquired infection. This challenges basic principles in anti-infective therapy guidelines, including the paradigm that pathogens involved in community-acquired infection are covered by standard empiric antimicrobial regimens, and second, the concept of nosocomial acquisition as the main driver for resistance involvement. I…

Looking for biological factors to predict the risk of active cytomegalovirus infection in non-immunosuppressed critically ill patients

The identification of non-immunosuppressed critically ill patients most at risk for developing cytomegalovirus (CMV) reactivation is potentially of great clinical relevance. The current study was aimed at determining (i) whether single nucleotide polymorphisms in the genes coding for chemokine receptor 5 (CCR5), interleukin-10 IL-10), and monocyte chemoattractant protein-1 (MCP-1) have an impact on the incidence rate of active CMV infection, (ii) whether serum levels of CMV-specific IgGs are associated with the risk of CMV reactivation, and (iii) whether detection of CMV DNA in saliva precedes that in the lower respiratory tract or the blood compartment. A total of 36 out of 78 patients (46…