Assessment of diaphragmatic dysfunction in the critically ill patient with ultrasound: a systematic review

Purpose

Diaphragmatic dysfunction (DD) has a high incidence in critically ill patients and is an under-recognized cause of respiratory failure and prolonged weaning from mechanical ventilation. Among different methods to assess diaphragmatic function, diaphragm ultrasonography (DU) is noninvasive, rapid, and easy to perform at the bedside. We systematically reviewed the current literature assessing the usefulness and accuracy of DU in intensive care unit (ICU) patients.

Methods

Pubmed, Cochrane Database of Systematic Reviews, Embase, Scopus, and Google Scholar Databases were searched for pertinent studies. We included all original, peer-reviewed studies about the use of DU in ICU patients.

Results

Twenty studies including 875 patients were included in the final analysis. DU was performed with different techniques to measure diaphragmatic inspiratory excursion, thickness of diaphragm (Tdi), and thickening fraction (TF). DU is feasible, highly reproducible, and allows one to detect diaphragmatic dysfunction in critically ill patients. During weaning from mechanical ventilation and spontaneous breathing trials, both diaphragmatic excursion and diaphragmatic thickening measurements have been used to predict extubation success or failure. Optimal cutoffs ranged from 10 to 14 mm for excursion and 30–36 % for thickening fraction. During assisted mechanical ventilation, diaphragmatic thickening has been found to be an accurate index of respiratory muscles workload. Observational studies suggest DU as a reliable method to assess diaphragm atrophy in patients undergoing mechanical ventilation.

Conclusions

Current literature suggests that DU could be a useful and accurate tool to detect diaphragmatic dysfunction in critically ill patients, to predict extubation success or failure, to monitor respiratory workload, and to assess atrophy in patients who are mechanically ventilated.

     

Critically ill patients demonstrate large interpersonal variation in intestinal microbiota dysregulation: a pilot study

Purpose

The intestinal microbiota has emerged as a virtual organ with essential functions in human physiology. Antibiotic-induced disruption of the microbiota in critically ill patients may have a negative influence on key energy resources and immunity. We set out to characterize the fecal microbiota composition in critically ill patients both with and without sepsis and to explore the use of microbiota-derived markers for clinical outcome measurements in this setting.

Methods

In this prospective observational cohort study we analyzed the fecal microbiota of 34 patients admitted to the intensive care unit. Fifteen healthy subjects served as controls. The fecal microbiota was phylogenetically characterized by 16S rRNA gene sequencing, and associations with clinical outcome parameters were evaluated.

Results

A marked shift in fecal bacterial composition was seen in all septic and non-septic critically ill patients compared with controls, with extreme interindividual differences. In 13 of the 34 patients, a single bacterial genus made up >50% of the gut microbiota; in 4 patients this was even >75%. A significant decrease in bacterial diversity was observed in half of the patients. No associations were found between microbiota diversity, Firmicutes/Bacteroidetes ratio, or Gram-positive/Gram-negative ratio and outcome measurements such as complications and survival.

Conclusions

We observed highly heterogeneous patterns of intestinal microbiota in both septic and non-septic critically ill patients. Nevertheless, some general patterns were observed, including disappearance of bacterial genera with important functions in host metabolism. More detailed knowledge of the short- and long-term health consequences of these major shifts in intestinal bacterial communities is needed.

     

Effect of synbiotic therapy on the incidence of ventilator associated pneumonia in critically ill patients: a randomised,double-blind,placebo-controlled trial

Objective

To investigate the effect of enteral Synbiotic 2000 FORTE^® (a mixture of lactic acid bacteria and fibre) on the incidence of ventilator associated pneumonia (VAP) in critically ill patients.

Design

Prospective, randomised, double blind, placebo controlled trial.

Setting

Tertiary referral centre, general Adult Intensive Care Unit (ICU).

Patients and participants

259 enterally fed patients requiring mechanical ventilation for 48 h or more were enrolled.

Intervention

All patients were enterally fed as per a standard protocol and randomly assigned to receive either synbiotic 2000 FORTE^® (twice a day) or a cellulose-based placebo for a maximum of 28 days.

Measurements and results

Treatment group (n = 130) was well matched with placebo group (n = 129) for age (mean 49.5 and 50 years, respectively) and APACHE II score (median 17 for both). Oropharyngeal microbial flora and colonisation rates were unaffected by synbiotics. The overall incidence of VAP was lower than anticipated (11.2%) and no statistical difference was demonstrated between groups receiving synbiotic and placebo in the incidence of VAP (9 and 13%, P = 0.42), VAP rate per 1,000 ventilator days (13 and 14.6, P = 0.91) or hospital mortality (27 and 33%, P = 0.39), respectively.

Conclusions

Enteral administration of Synbiotic 2000 FORTE^® has no statistically significant impact on the incidence of VAP in critically ill patients.

     

Erythropoietin response in critically ill mechanically ventilated patients: a prospective observational study

Introduction

Anemia is a common problem in critically ill patients. The etiology of anemia of critical illness is often determined to be multifactorial in the clinical setting, but the pathophysiology remains to be elucidated. Erythropoietin (EPO) is an endogenous glycoprotein hormone that serves as the primary stimulus for erythropoiesis. Recent evidence has demonstrated a blunted EPO response as a factor contributing to anemia of critical illness in specific subsets of patients. Critically ill patients requiring mechanical ventilation who exhibit anemia have not been the subject of previous studies. Our goal was to evaluate the erythropoietic response to anemia in the critically ill mechanically ventilated patient.

Methods

A prospective observational study was undertaken in the medical intensive care unit of a tertiary care, military hospital. Twenty patients admitted to the medical intensive care unit requiring mechanical ventilation for at least 72 hours were enrolled as study patients. EPO levels and complete blood count were measured 72 hours after admission and initiation of mechanical ventilation. Admission clinical and demographic data were recorded, and patients were followed for the duration of mechanical ventilation. Twenty patients diagnosed with iron deficiency anemia in the outpatient setting were enrolled as a control population. Control patients had baseline complete blood count and iron panel recorded by primary care physicians. EPO levels were measured at the time of enrollment in conjunction with complete blood count.

Results

The mean EPO level for the control population was 60.9 mU/ml. The mean EPO level in the mechanically ventilated patient group was 28.7 mU/ml, which was significantly less than in the control group (P = 0.035). The mean hemoglobin value was not significantly different between groups (10.6 g/dl in mechanically ventilated patients versus 10.2 g/dl in control patients; P > 0.05).

Conclusion

Mechanically ventilated patients demonstrate a blunted EPO response to anemia. Further study of therapies directed at treating anemia of critical illness and evaluating its potential impact on mechanical ventilation outcomes and mortality is warranted.

     

Therapeutic management of peritonitis: a comprehensive guide for intensivists

Purpose

The management of peritonitis in critically ill patients is becoming increasingly complex due to their changing characteristics and the growing prevalence of multidrug-resistant (MDR) bacteria.

Methods

A multidisciplinary panel summarizes the latest advances in the therapeutic management of these critically ill patients.

Results

Appendicitis, cholecystitis and bowel perforation represent the majority of all community-acquired infections, while most cases of healthcare-associated infections occur following suture leaks and/or bowel perforation. The micro-organisms involved include a spectrum of Gram-positive and Gram-negative bacteria, as well as anaerobes and fungi. Healthcare-associated infections are associated with an increased likelihood of MDR pathogens. The key elements for success are early and optimal source control and adequate surgery and appropriate antibiotic therapy. Drainage, debridement, abdominal cleansing, irrigation, and control of the source of contamination are the major steps to ensure source control. In life-threatening situations, a "damage control" approach is the safest way to gain time and achieve stability. The initial empirical antiinfective therapy should be prescribed rapidly and must target all of the micro-organisms likely to be involved, including MDR bacteria and fungi, on the basis of the suspected risk factors. Dosage adjustment needs to be based on pharmacokinetic parameters. Supportive care includes pain management, optimization of ventilation, haemodynamic and fluid monitoring, improvement of renal function, nutrition and anticoagulation.

Conclusions

The majority of patients with peritonitis develop complications, including worsening of pre-existing organ dysfunction, surgical complications and healthcare-associated infections. The probability of postoperative complications must be taken into account in the decision-making process prior to surgery.

     

Contrast-associated acute kidney injury in the critically ill: systematic review and Bayesian meta-analysis

Purpose

Critically ill patients, among whom acute kidney injury is common, are often considered particularly vulnerable to iodinated contrast medium nephrotoxicity. However, the attributable incidence remains uncertain given the paucity of observational studies including a control group. This study assessed acute kidney injury incidence attributable to iodinated contrast media in critically ill patients based on new data accounting for sample and effect size and including a control group.

Methods

Systematic review of studies measuring incidence of acute kidney injury in critically ill patients following contrast medium exposure compared to matched unexposed patients. Patient-level meta-analysis implementing a Bayesian nested mixed effects multiple logistic regression model.

Results

Ten studies were identified; only four took into account the baseline acute kidney injury risk, three by patient matching (560 patients). Objective meta-analysis of these three studies (vague and impartial a priori hypothesis concerning attributable acute kidney injury risk) did not find that iodinated contrast media increased the incidence of acute kidney injury (odds ratio 0.95, 95% highest posterior density interval 0.45–1.62). Bayesian analysis demonstrated that, to conclude in favor of a statistically significant incidence of acute kidney injury attributable to contrast media despite this observed lack of association, one’s a priori belief would have to be very strongly biased, assigning to previous uncontrolled reports 3–12 times the weight of evidence strength provided by the matched studies including a control group.

Conclusions

Meta-analysis of matched cohort studies of iodinated contrast medium exposure does not support a significant incidence of acute kidney injury attributable to iodinated contrast media in critically ill patients.

     

The effect of melatonin on sleep and quality of life in patients with advanced breast cancer

Background

Fatigue and sleep problems are prevalent in cancer patients and can be associated with disruption of circadian rhythmicity. In this prospective phase II trial, we sought to assess the effect of melatonin on circadian biomarkers, sleep, and quality of life in breast cancer patients.

Methods

Thirty-two patients with metastatic breast cancer, receiving hormonal or trastuzumab therapy, took 5 mg of melatonin at bedtime for 2 months. Before starting and after 2 months on melatonin therapy, sleep and circadian rhythmicity were assessed by actigraphy, diurnal patterns of serum cortisol, and the expression of the core clock genes PER2 and BMAL1 in peripheral blood mononuclear cells. The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire was completed for subjective parameters.

Results

Bedtime melatonin was associated with a significant improvement in a marker of objective sleep quality, sleep fragmentation and quantity, subjective sleep, fatigue severity, global quality of life, and social and cognitive functioning scales. Morning clock gene expression was increased following bedtime melatonin intake. Melatonin did not affect actigraphy measure of circadian rhythmicity, or the diurnal cortisol pattern.

Conclusion

These results invite further investigation of melatonin as a potentially useful therapeutic agent for improving sleep and quality of life in cancer patients.

     

Appropriate endpoints for evaluation of new antibiotic therapies for severe infections: a perspective from COMBACTE’s STAT-Net

Purpose

In this era of rising antimicrobial resistance, slowly refilling antibiotic development pipelines, and an aging population, we need to ensure that randomized clinical trials (RCTs) determine the added benefit of new antibiotic agents effectively and in a valid way, especially for severely ill patients. Unfortunately, universally accepted endpoints for the evaluation of new drugs in severe infections are lacking.

Methods

We review and discuss the current practices and challenges regarding endpoints in RCTs in this field and propose novel approaches.

Results

Usual endpoints actually recommended for drug development suffer from important flaws. Mortality requires large sample size and only partly related to the infectious process. Clinical cure rate is highly subjective in critically ill patients where symptoms may be related to other intercurrent events. Currently, composite endpoints, hierarchical nested designs, and competing risks analysis seem to be the most promising new tools for designing and analyzing clinical trials in this area, although they require further validation.

Conclusion

Regulatory authorities, pharmaceutical companies, and clinicians need to agree on the most appropriate clinical endpoints for severe infections to ensure efficient approval of new, effective antibiotic agents.

     

Clusters of ineffective efforts during mechanical ventilation: impact on outcome

Purpose

The aim of this study was to investigate the role of ineffective efforts (IEs), specifically clusters of IEs, during mechanical ventilation on the outcome of critically ill patients.

Methods

In a prospective observational study, 24-h recordings were obtained in 110 patients on the 1st day of assisted ventilation (pressure support or proportional assist), using a prototype monitor validated to identify IEs. Patients remaining on assisted ventilation were studied again on the 3rd day (n = 37) and on the 6th day (n = 13). To describe the clusters of IEs, the concept of an IEs event was developed, defined as a 3-min period of time containing more than 30 IEs. Along with all patient data, to minimize selection bias by time of recording, analysis was performed only on 1st day data of patients with ≥16 h of recording (1st day group).

Results

The analysis included 2931 h of assisted ventilation and 4,456,537 breaths. Neither the IEs index (IEs as a percentage of total breaths) in general nor a value above 10 % was correlated with patient outcome. Overall, IEs events were identified in 38 % of patients. In multivariate analysis, the presence of events in the 1st day group (n = 79) was associated with the risk of being on mechanical ventilation ≥8 days after first recording [odds ratio 6.4, 95 % confidence interval (1.1–38.30)] and hospital mortality [20 (2.3–175)]. Analysis of the data for all patients revealed similarly increased risks for prolonged ventilation [3.4 (1.1–10.7)] and mortality [4.9 (1.3–18)].

Conclusions

Clusters of IEs are often present in mechanically ventilated critically ill patients and are associated with prolonged mechanical ventilation and increased mortality. Studies to find ways of improving patient-ventilator interaction are warranted.

     

Mechanical power of ventilation is associated with mortality in critically ill patients: an analysis of patients in two observational cohorts

Purpose

Mechanical power (MP) may unify variables known to be related to development of ventilator-induced lung injury. The aim of this study is to examine the association between MP and mortality in critically ill patients receiving invasive ventilation for at least 48 h.

Methods

This is an analysis of data stored in the databases of the MIMIC–III and eICU. Critically ill patients receiving invasive ventilation for at least 48 h were included. The exposure of interest was MP. The primary outcome was in-hospital mortality.

Results

Data from 8207 patients were analyzed. Median MP during the second 24 h was 21.4 (16.2–28.1) J/min in MIMIC-III and 16.0 (11.7–22.1) J/min in eICU. MP was independently associated with in-hospital mortality [odds ratio per 5 J/min increase (OR) 1.06 (95% confidence interval (CI) 1.01–1.11); p?=?0.021 in MIMIC-III, and 1.10 (1.02–1.18); p?=?0.010 in eICU]. MP was also associated with ICU mortality, 30-day mortality, and with ventilator-free days, ICU and hospital length of stay. Even at low tidal volume, high MP was associated with in-hospital mortality [OR 1.70 (1.32–2.18); p?<?0.001] and other secondary outcomes. Finally, there is a consistent increase in the risk of death with MP higher than 17.0 J/min.

Conclusion

High MP of ventilation is independently associated with higher in-hospital mortality and several other outcomes in ICU patients receiving invasive ventilation for at least 48 h.

     

Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines

Purpose

To provide evidence-based guidelines for early enteral nutrition (EEN) during critical illness.

Methods

We aimed to compare EEN vs. early parenteral nutrition (PN) and vs. delayed EN. We defined “early” EN as EN started within 48 h independent of type or amount. We listed, a priori, conditions in which EN is often delayed, and performed systematic reviews in 24 such subtopics. If sufficient evidence was available, we performed meta-analyses; if not, we qualitatively summarized the evidence and based our recommendations on expert opinion. We used the GRADE approach for guideline development. The final recommendations were compiled via Delphi rounds.

Results

We formulated 17 recommendations favouring initiation of EEN and seven recommendations favouring delaying EN. We performed five meta-analyses: in unselected critically ill patients, and specifically in traumatic brain injury, severe acute pancreatitis, gastrointestinal (GI) surgery and abdominal trauma. EEN reduced infectious complications in unselected critically ill patients, in patients with severe acute pancreatitis, and after GI surgery. We did not detect any evidence of superiority for early PN or delayed EN over EEN. All recommendations are weak because of the low quality of evidence, with several based only on expert opinion.

Conclusions

We suggest using EEN in the majority of critically ill under certain precautions. In the absence of evidence, we suggest delaying EN in critically ill patients with uncontrolled shock, uncontrolled hypoxaemia and acidosis, uncontrolled upper GI bleeding, gastric aspirate >500 ml/6 h, bowel ischaemia, bowel obstruction, abdominal compartment syndrome, and high-output fistula without distal feeding access.

     

Milrinone for cardiac dysfunction in critically ill adult patients: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis

Introduction

Milrinone is an inotrope widely used for treatment of cardiac failure. Because previous meta-analyses had methodological flaws, we decided to conduct a systematic review of the effect of milrinone in critically ill adult patients with cardiac dysfunction.

Methods

This systematic review was performed according to The Cochrane Handbook for Systematic Reviews of Interventions. Searches were conducted until November 2015. Patients with cardiac dysfunction were included. The primary outcome was serious adverse events (SAE) including mortality at maximum follow-up. The risk of bias was evaluated and trial sequential analyses were conducted. The quality of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation criteria.

Results

A total of 31 randomised clinical trials fulfilled the inclusion criteria, of which 16 provided data for our analyses. All trials were at high risk of bias, and none reported the primary composite outcome SAE. Fourteen trials with 1611 randomised patients reported mortality data at maximum follow-up (RR 0.96; 95% confidence interval 0.76–1.21). Milrinone did not significantly affect other patient-centred outcomes. All analyses displayed statistical and/or clinical heterogeneity of patients, interventions, comparators, outcomes, and/or settings and all featured missing data.

Discussion

The current evidence on the use of milrinone in critically ill adult patients with cardiac dysfunction suffers from considerable risks of both bias and random error and demonstrates no benefits. The use of milrinone for the treatment of critically ill patients with cardiac dysfunction can be neither recommended nor refuted. Future randomised clinical trials need to be sufficiently large and designed to have low risk of bias.

     

Relationship between height and outcomes among critically ill adults: a cohort study

Purpose

Many diagnostic and therapeutic interventions for critically ill adult patients are not performed according to patient size, but are standardized for an idealized 174-cm man (ideal body weight 70 kg). This study aims to determine whether critically ill patients with heights significantly different from a standardized patient have higher hospital mortality or greater resource utilization.

Methods

Retrospective cohort study of consecutive patients admitted to 210 intensive care units (ICUs) in the United Kingdom participating in the Intensive Care National Audit and Research Centre’s Case Mix Programme Database from April 1, 2009, to March 31, 2015. Primary outcome was hospital mortality, adjusted for age, comorbid disease, severity of illness, socioeconomic status and body mass index, using hierarchical modeling to account for clustering by ICU. Data were stratified by sex, and the effect of height was modeled continuously using restricted cubic splines.

Results

The cohort included 233,308 men and 184,070 women, with overall hospital mortality of 22.5% and 20.6%, respectively. After adjustment for potential confounders, hospital mortality decreased with increasing height; predicted mortality (holding all other covariates at their mean value) decreased from 24.1 to 17.1% for women and from 29.2 to 21.0% for men across the range of heights. Similar patterns were observed for ICU mortality and several additional secondary outcomes.

Conclusions

Short stature may be a risk factor for mortality in critically ill patients. Further work is needed to determine which unmeasured patient characteristics and processes of care may contribute to the increased risk observed.

     

Performance of Doppler-based resistive index and semi-quantitative renal perfusion in predicting persistent AKI: results of a prospective multicenter study

Purpose

The Doppler-based resistive index (RI) and semi-quantitative evaluation of renal perfusion using color Doppler (SQP) have shown promising results for predicting persistent acute kidney injury (AKI) in preliminary studies. This study aimed at evaluating the performance of RI and SQP to predict short-term renal prognosis in critically ill patients.

Methods

Prospective multicenter cohort study including unselected critically ill patients. Renal Doppler was performed at admission to the intensive care unit. The diagnostic performance of RI and SQP to predict persistent AKI at day 3 was evaluated.

Results

Overall, 371 patients were included, of whom 351 could be assessed for short-term renal recovery. Two thirds of the included patients had AKI (n?=?233; 66.3%), of whom 136 had persistent AKI (58.4%). Doppler-based RI was higher and SQP lower in AKI patients and according to AKI recovery. Overall performance in predicting persistent AKI was however poor with area under ROC curve of respectively 0.58 (95% CI 0.52–0.64) and 0.59 (95% CI 0.54–0.65) for RI and SQP. Optimal cutoff was respectively 0.71 and 2 for RI and SQP. At optimal cutoff, sensitivity and specificity were 50% (95% CI 41–58%) and 68% (62–74%) for RI and 39% (32–45%) and 75% (66–82%) for SQP.

Conclusion

Although statistically associated with AKI occurrence, RI and SQP perform poorly in predicting persistent AKI at day 3. Further studies are needed to adequately describe factors influencing Doppler-based assessment of renal perfusion and to delineate whether these indicators may be useful at the bedside.

Clinicaltrial.gov

NCT02355314.

     

Étude du Transport INTrA-Hospitalier du MAlade de Réanimation (TINTAHMAR)

Introduction

Intra-hospital transport (IHT) of critically ill patients is a frequent care associated with an important risk of adverse events (AEs). To decrease the occurrence of AEs, recent guidelines have been edited. Their consequences on adverse event incidence and nurse workload have not been assessed.

Aim of study

The primary objective was to assess the time necessary for the achievement of IHT. Secondary objectives were to describe practices related to IHT, to compare workload according to the presence of nurses during the IHT, and to assess the occurrence of AEs.

Patients and methods

This French multicentric observational study conducted by the SRLF was conducted in 18 French-speaking intensive care units. All critically ill adults requiring IHT were included.

Results

Three hundred and ninety-six IHTs (mean age 61 ±19, mean IGS II 46±24) were assessed. The mean duration of IHT was 67±35 minutes. There was a training program of IHT in only 11% of centers, a check-list in 22%, and traceability procedures in 17%. There was a nurse during the IHT in 51% of cases. The presence of a nurse had no consequence on IHT durations. Adverse events occurred in 15% of IHT. In multivariable analysis, nurse presence was not associated with IHT associated AEs.

Conclusion

An IHT requires time. Despite the poor adherence to the guidelines, this care was associated with low incidence of AES. The presence of nurses during the IHT had no consequence on IHT duration and AEs occurrence.

     

Cell-surface signatures of immune dysfunction risk-stratify critically ill patients: INFECT study

Purpose

Cellular immune dysfunctions, which are common in intensive care patients, predict a number of significant complications. In order to effectively target treatments, clinically applicable measures need to be developed to detect dysfunction. The objective was to confirm the ability of cellular markers associated with immune dysfunction to stratify risk of secondary infection in critically ill patients.

Methods

Multi-centre, prospective observational cohort study of critically ill patients in four UK intensive care units. Serial blood samples were taken, and three cell surface markers associated with immune cell dysfunction [neutrophil CD88, monocyte human leucocyte antigen-DR (HLA-DR) and percentage of regulatory T cells (T_regs)] were assayed on-site using standardized flow cytometric measures. Patients were followed up for the development of secondary infections.

Results

A total of 148 patients were recruited, with data available from 138. Reduced neutrophil CD88, reduced monocyte HLA-DR and elevated proportions of T_regs were all associated with subsequent development of infection with odds ratios (95% CI) of 2.18 (1.00–4.74), 3.44 (1.58–7.47) and 2.41 (1.14–5.11), respectively. Burden of immune dysfunction predicted a progressive increase in risk of infection, from 14% for patients with no dysfunction to 59% for patients with dysfunction of all three markers. The tests failed to risk stratify patients shortly after ICU admission but were effective between days 3 and 9.

Conclusions

This study confirms our previous findings that three cell surface markers can predict risk of subsequent secondary infection, demonstrates the feasibility of standardized multisite flow cytometry and presents a tool which can be used to target future immunomodulatory therapies.

Trial registration

The study was registered with clinicaltrials.gov (NCT02186522).

     

Erythromycin versus metoclopramide for post-pyloric spiral nasoenteric tube placement: a randomized non-inferiority trial

Purpose

To determine whether erythromycin is non-inferior to metoclopramide in facilitating post-pyloric placement of self-propelled spiral nasoenteric tubes (NETs) in critically ill patients.

Methods

A prospective, multicenter, open-label, parallel, and non-inferiority randomized controlled trial was conducted comparing erythromycin with metoclopramide in facilitating post-pyloric placement of spiral NETs in critically ill patients admitted to intensive care units (ICUs) of eight tertiary hospitals in China. The primary outcome was procedure success defined as post-pyloric placement (spiral NETs reached the first portion of the duodenum or beyond confirmed by abdominal radiography 24 h after tube insertion).

Results

A total of 5688 patients were admitted to the ICUs. Of these, in 355 patients there was a plan to insert a nasoenteric feeding tube, of whom 332 were randomized, with 167 patients assigned to the erythromycin group and 165 patients assigned to the metoclopramide group. The success rate of post-pyloric placement was 57.5% (96/167) in the erythromycin group, as compared with 50.3% (83/165) in the metoclopramide group (a difference of 7.2%, 95% CI ??3.5% to 17.9%), in the intention-to-treat analysis, not including the prespecified margin of ??10% for non-inferiority. The success rates of post-D1 (reaching the second portion of the duodenum or beyond), post-D2 (reaching the third portion of the duodenum or beyond), post-D3 (reaching the fourth portion of the duodenum or beyond), and proximal jejunum placement and the incidence of any adverse events were not significantly different between the groups.

Conclusions

Erythromycin is non-inferior to metoclopramide in facilitating post-pyloric placement of spiral NETs in critically ill patients. The success rates of post-D1, post-D2, post-D3, and proximal jejunum placement were not significantly different.

     

Explore the influence of BMI in the optimal time of weaning from sequential mechanical ventilation for severity chronic obstructive pulmonary disease

Objective

To study the clinical effect of body mass index (BMI) in the optimal time of weaning from sequential invasive-noninvasive mechanical ventilation (MV) by treating severity chronic obstructive pulmonary disease (COPD) patients.

Methods

94 patients with severity COPD were divided into the control group (BMI<21) and the study group (BMI>21). These two groups were treated by similar symptomatic therapies such as mechanical ventilation, antibacterial, antispasmodic, relieving asthma, antitussive, expectorant, correction of electrolyte imbalance and acid-base balance disorders, strengthen nutritional support, etc.

Results

Compared with the control group, the study group had shorter duration of invasive mechanical ventilation, non-invasive mechanical ventilation time, total mechanical ventilation time, total hospital stay (P<0.01). There are significant differences between these two groups in re-intubation rate, VAP occurred in the number of case, hospital mortality rate in 28 days (P<0.05).

Conclusions

It is difficult to wean successfully from sequential mechanical ventilation for severity COPD patients (BMI<21), so BMI as one of important reference index can be used to estimate the optimal time for weaning from sequential mechanical ventilation for severity COPD patients.

     

Terbutaline lessens protein fluxes across the alveolo-capillary barrier during high-volume ventilation

Objective

To evaluate whether a β₂-adrenergic agonist may reduce acute alveolo-capillary barrier alterations during high-volume ventilation.

Design

Experimental study.

Setting

Animal research laboratory.

Subjects

A total of 48 male Wistar rats.

Interventions

A zone of alveolar flooding was produced by liquid instillation in a distal airway. Proteins in the instilled solution were traced with ^99mTc-albumin. ¹¹¹In, which binds to transferrin, was injected into the systemic circulation. Terbutaline was administered in the instilled solution or intra-peritoneally. Conventional ventilation was applied for 30?min followed by different ventilation strategies for 90?min: conventional ventilation, high-volume ventilation with or without 6?cmH₂O PEEP.

Measurements and main results

Protein fluxes across the alveolar and microvascular barriers were evaluated by scintigraphy. High-volume ventilation resulted in immediate leakage of ^99mTc-albumin from alveolar spaces and increased pulmonary uptake of systemic ¹¹¹In-transferrin. Terbutaline in the instilled solution and PEEP lessened alveolar ^99mTc-albumin leakage and pulmonary ¹¹¹In-transferrin uptake due to high-volume ventilation, whereas terbutaline given intra-peritoneally only lessened ¹¹¹In-transferrin uptake. Terbutaline in the instilled solution also lessened the increase in lung wet-to-dry weight ratio due to high-volume ventilation.

Conclusions

Terbutaline reduces protein fluxes across the alveolar epithelial and pulmonary microvascular barriers during high-volume ventilation in vivo. The route of administration may be important.

     

Short-course antibiotic therapy for critically ill patients treated for postoperative intra-abdominal infection: the DURAPOP randomised clinical trial

Purpose

Shortening the duration of antibiotic therapy (ABT) is a key measure in antimicrobial stewardship. The optimal duration of ABT for treatment of postoperative intra-abdominal infections (PIAI) in critically ill patients is unknown.

Methods

A multicentre prospective randomised trial conducted in 21 French intensive care units (ICU) between May 2011 and February 2015 compared the efficacy and safety of 8-day versus 15-day antibiotic therapy in critically ill patients with PIAI. Among 410 eligible patients (adequate source control and ABT on day 0), 249 patients were randomly assigned on day 8 to either stop ABT immediately (n = 126) or to continue ABT until day 15 (n = 123). The primary endpoint was the number of antibiotic-free days between randomisation (day 8) and day 28. Secondary outcomes were death, ICU and hospital length of stay, emergence of multidrug-resistant (MDR) bacteria and reoperation rate, with 45-day follow-up.

Results

Patients treated for 8 days had a higher median number of antibiotic-free days than those treated for 15 days (15 [6–20] vs 12 [6–13] days, respectively; P < 0.0001) (Wilcoxon rank difference 4.99 days [95% CI 2.99–6.00; P < 0.0001). Equivalence was established in terms of 45-day mortality (rate difference 0.038, 95% CI ? 0.013 to 0.061). Treatments did not differ in terms of ICU and hospital length of stay, emergence of MDR bacteria or reoperation rate, while subsequent drainages between day 8 and day 45 were observed following short-course ABT (P = 0.041).

Conclusion

Short-course antibiotic therapy in critically ill ICU patients with PIAI reduces antibiotic exposure. Continuation of treatment until day 15 is not associated with any clinical benefit.

Clinicaltrials.gov identifier

NCT01311765.