Revisiting Mars and Venus: Understanding gender differences in critical illness

Understanding the nature and biological basis of gender-determined differences in risk of and outcome from infection might identify new therapeutic targets, allow more individualised treatment, and facilitate better risk prediction and application of healthcare resources. Gender differences in behaviours, comorbidities, access to healthcare and biology may result in differences in acquiring infection, or in response to infection once acquired. Some studies have reported higher male susceptibility to infection, and higher risk of death with sepsis, but others have found the opposite effect. The explanation for this disagreement is probably that different studies have included patients at different stages on the continuum from infectious agent exposure to death or recovery. Studying sufficient patient numbers to explore this entire continuum while accounting for heterogeneity in type of infection and comorbidity is difficult because of the number of patients required. However, if true gender effects can be identified, examination of their biological or psychosocial causes will be warranted. © 2011 BioMed Central Ltd

Sedation and delirium in the intensive care unit

Patients in ICUs often require pain relief and sedation to treat both the underlying medical condition and the unpleasantness associated with being in an ICU. This review provides guidance on the identification and treatment of delirium and sedation. Patients in intensive care units (ICUs) are treated with many interventions (most notably endotracheal intubation and invasive mechanical ventilation) that are observed or perceived to be distressing. Pain is the most common memory patients have of their ICU stay.(1) Agitation can precipitate accidental removal of endotracheal tubes or of intravascular catheters used for monitoring or administration of life-sustaining medications. Consequently, sedatives and analgesics are among the most commonly administered drugs in ICUs. Early intensive care practice evolved from intraoperative anesthetic care at a time when mechanical ventilation was delivered by rudimentary machines that were not capable of synchronizing with patients' ..

Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis

BACKGROUND: After a single-center trial and observational studies suggesting that early, goal-directed therapy (EGDT) reduced mortality from septic shock, three multicenter trials (ProCESS, ARISE, and ProMISe) showed no benefit. This meta-analysis of individual patient data from the three recent trials was designed prospectively to improve statistical power and explore heterogeneity of treatment effect of EGDT. METHODS: We harmonized entry criteria, intervention protocols, outcomes, resource-use measures, and data collection across the trials and specified all analyses before unblinding. After completion of the trials, we pooled data, excluding the protocol-based standard-therapy group from the ProCESS trial, and resolved residual differences. The primary outcome was 90-day mortality. Secondary outcomes included 1-year survival, organ support, and hospitalization costs. We tested for treatment-by-subgroup interactions for 16 patient characteristics and 6 care-delivery characteristics. RESULTS: We studied 3723 patients at 138 hospitals in seven countries. Mortality at 90 days was similar for EGDT (462 of 1852 patients [24.9%]) and usual care (475 of 1871 patients [25.4%]); the adjusted odds ratio was 0.97 (95% confidence interval, 0.82 to 1.14; P=0.68). EGDT was associated with greater mean (±SD) use of intensive care (5.3±7.1 vs. 4.9±7.0 days, P=0.04) and cardiovascular support (1.9±3.7 vs. 1.6±2.9 days, P=0.01) than was usual care; other outcomes did not differ significantly, although average costs were higher with EGDT. Subgroup analyses showed no benefit from EGDT for patients with worse shock (higher serum lactate level, combined hypotension and hyperlactatemia, or higher predicted risk of death) or for hospitals with a lower propensity to use vasopressors or fluids during usual resuscitation. CONCLUSIONS: In this meta-analysis of individual patient data, EGDT did not result in better outcomes than usual care and was associated with higher hospitalization costs across a broad range of patient and hospital characteristics. (Funded by the National Institute of General Medical Sciences and others; PRISM ClinicalTrials.gov number, NCT02030158.

Proteína C-reativa não é um marcador útil de infecção em unidade de terapia intensiva cirúrgica

CONTEXT AND OBJECTIVE: C-reactive protein (CRP) is commonly used as a marker for inflammatory states and for early identification of infection. This study aimed to investigate CRP as a marker for infection in patients with postoperative septic shock. DESIGN AND SETTING: Prospective, single-center study, developed in a surgical intensive care unit at Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo. METHODS: This study evaluated 54 patients in the postoperative period, of whom 29 had septic shock (SS group) and 25 had systemic inflammatory response syndrome (SIRS group). All of the patients were monitored over a seven-day period using the Sequential Organ Failure Assessment (SOFA) score and daily CRP and lactate measurements. RESULTS: The daily CRP measurements did not differ between the groups. There was no correlation between CRP and lactate levels and the SOFA score in the groups. We observed that the plasma CRP concentrations were high in almost all of the patients. The patients presented an inflammatory state postoperatively in response to surgical aggression. This could explain the elevated CRP measurements, regardless of whether the patient was infected or not. CONCLUSIONS: This study did not show any correlation between CRP and infection among patients with SIRS and septic shock during the early postoperative period.CONTEXTO E OBJETIVO: A proteína C reativa (PCR) é muito usada como marcador de estados inflamatórios e na identificação precoce de infecção. Este estudo teve como proposta investigar a PCR como marcadora de infecção em pacientes em choque séptico no período pós-operatório. TIPO DE ESTUDO E LOCAL: Estudo prospectivo, monocêntrico, desenvolvido numa unidade de terapia intensiva pós-operatória do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. MÉTODOS: Foram avaliados 54 pacientes no pós-operatório, sendo 29 deles com choque séptico (grupo SS) e 25 com síndrome da resposta inflamatória sistêmica (grupo SI). Todos os pacientes foram acompanhados durante sete dias pelo escore SOFA (Sequential Organ Failure Assessment) e com dosagens diárias de PCR e lactato. RESULTADOS: As dosagens de PCR não diferiram entre os grupos. Não foi observada correlação entre dosagem de PCR e lactato ou escore SOFA nos grupos estudados. Observamos que as concentrações plasmáticas de PCR estavam elevadas em quase todos os pacientes avaliados. Os pacientes no pós-operatório apresentam estado inflamatório em resposta à agressão cirúrgica, sendo este fato capaz de explicar as dosagens de PCR elevadas, independentemente de o paciente estar ou não infectado. CONCLUSÕES: Este estudo não evidenciou correlação entre PCR e infecção nos pacientes com síndrome da resposta inflamatória sistêmica e choque séptico no período pós-operatório precoce

The Effect of Pulmonary Artery Catheter Use on Costs and Long-Term Outcomes of Acute Lung Injury

Background: The pulmonary artery catheter (PAC) remains widely used in acute lung injury (ALI) despite known complications and little evidence of improved short-term mortality. Concurrent with NHLBI ARDS Clinical Trials Network Fluid and Catheters Treatment Trial (FACTT), we conducted a prospectively-defined comparison of healthcare costs and long-term outcomes for care with a PAC vs. central venous catheter (CVC). We explored if use of the PAC in ALI is justified by a beneficial cost-effectiveness profile. Methods: We obtained detailed bills for the initial hospitalization. We interviewed survivors using the Health Utilities Index Mark 2 questionnaire at 2, 6, 9 and 12 m to determine quality of life (QOL) and post-discharge resource use. Outcomes beyond 12 m were estimated from federal databases. Incremental costs and outcomes were generated using MonteCarlo simulation. Results: Of 1001 subjects enrolled in FACTT, 774 (86%) were eligible for long-term follow-up and 655 (85%) consented. Hospital costs were similar for the PAC and CVC groups ($96.8k vs.$89.2k, p = 0.38). Post-discharge to 12 m costs were higher for PAC subjects ($61.1k vs. 45.4k, p = 0.03). One-year mortality and QOL among survivors were similar in PAC and CVC groups (mortality: 35.6$14.4k and mean loss of 0.3 quality-adjusted life years (QALYs)) and a 94.2% probability of being higher than the $100k/QALY willingness-to-pay threshold. Conclusion: PAC use increased costs with no patient benefit and thus appears unjustified for routine use in ALI. Trial Registration: www.clinicaltrials.gov NCT00234767. © 2011 Clermont et al

The methodology for developing a prospective meta-analysis in the family planning community

<p>Abstract</p> <p>Background</p> <p>Prospective meta-analysis (PMA) is a collaborative research design in which individual sites perform randomized controlled trials (RCTs) and pool the data for meta-analysis. Members of the PMA collaboration agree upon specific research interventions and outcome measures, ideally before initiation but at least prior to any individual trial publishing results. This allows for uniform reporting of primary and secondary outcomes. With this approach, heterogeneity among trials contributing data for the final meta-analysis is minimized while each site maintains the freedom to design a specific trial. This paper describes the process of creating a PMA collaboration to evaluate the impact of misoprostol on ease of intrauterine device (IUD) insertion in nulliparous women.</p> <p>Methods</p> <p>After the principal investigator developed a preliminary PMA protocol, he identified potential collaborating investigators at other sites. One site already had a trial underway and another site was in the planning stages of a trial meeting PMA requirements. Investigators at six sites joined the PMA collaborative. Each site committed to enroll subjects to meet a pre-determined total sample size. A final common research plan and site responsibilities were developed and agreed upon through email and face-to-face meetings. Each site committed to contribute individual patient data to the PMA collaboration, and these data will be analyzed and prepared as a multi-site publication. Individual sites retain the ability to analyze and publish their site's independent findings.</p> <p>Results</p> <p>All six sites have obtained Institutional Review Board approval and each has obtained individual funding to meet the needs of that site's study. Sites have shared resources including study protocols and consents to decrease costs and improve study flow. This PMA protocol is registered with the Cochrane Collaboration and data will be analyzed according to Cochrane standards for meta-analysis.</p> <p>Conclusions</p> <p>PMA is a novel research method that improves meta-analysis by including several study sites, establishing uniform reporting of specific outcomes, and yet allowing some independence on the part of individual sites with respect to the conduct of research. The inclusion of several sites increases statistical power to address important clinical questions. Compared to multi-center trials, PMA methodology encourages collaboration, aids in the development of new investigators, decreases study costs, and decreases time to publication.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00613366">NCT00613366</a>, <a href="http://www.clinicaltrials.gov/ct2/show/NCT00886834">NCT00886834</a>, <a href="http://www.clinicaltrials.gov/ct2/show/NCT01001897">NCT01001897</a>, <a href="http://www.clinicaltrials.gov/ct2/show/NCT01147497">NCT01147497</a> and <a href="http://www.clinicaltrials.gov/ct2/show/NCT01307111">NCT01307111</a></p

Recalibration of the delirium prediction model for ICU patients (PRE-DELIRIC): a multinational observational study

Purpose Recalibration and determining discriminative power, internationally, of the existing delirium prediction model (PRE-DELIRIC) for intensive care patients. Methods A prospective multicenter cohort study was performed in eight intensive care units (ICUs) in six countries. The ten predictors (age, APACHE-II, urgent and admission category, infection, coma, sedation, morphine use, urea level, metabolic acidosis) were collected within 24 h after ICU admission. The confusion assessment method for the intensive care unit (CAM-ICU) was used to identify ICU delirium. CAM-ICU screening compliance and inter-rater reliability measurements were used to secure the quality of the data. Results A total of 2,852 adult ICU patients were screened of which 1,824 (64 %) were eligible for the study. Main reasons for exclusion were length of stay <1 day (19.1 %) and sustained coma (4.1 %). CAM-ICU compliance was mean (SD) 82 ± 16 % and inter-rater reliability 0.87 ± 0.17. The median delirium incidence was 22.5 % (IQR 12.8–36.6 %). Although the incidence of all ten predictors differed significantly between centers, the area under the receiver operating characteristic (AUROC) curve of the eight participating centers remained good: 0.77 (95 % CI 0.74–0.79). The linear predictor and intercept of the prediction rule were adjusted and resulted in improved re-calibration of the PRE-DELIRIC model. Conclusions In this multinational study, we recalibrated the PRE-DELIRIC model. Despite differences in the incidence of predictors between the centers in the different countries, the performance of the PRE-DELIRIC-model remained good. Following validation of the PRE-DELIRIC model, it may facilitate implementation of strategies to prevent delirium and aid improvements in delirium management of ICU patients