Probiotics' effects on the incidence of nosocomial pneumonia in critically ill patients: a systematic review and meta-analysis

ABSTRACT: INTRODUCTION: To evaluate the efficacy of probiotics in preventing nosocomial pneumonia in critically ill patients. METHODS: We searched PubMed, EMBASE, and the Web of Science for relevant studies. Two reviewers extracted data and reviewed the quality of the studies independently. The primary outcome was the incidence of nosocomial pneumonia. Study-level data were pooled using a random-effects model when I2 was > 50% or a fixed-effects model when I2 was < 50%. RESULTS: Twelve randomized controlled studies with a total of 1,546 patients were considered. Pooled analysis showed a statistically significant reduction in nosocomial pneumonia rates due to probiotics (odd ratio [OR]= 0.75, 95% CI 0.57 to 0.97, P = 0.03, I2 = 46%). However, no statistically significant difference was found between groups regarding in-hospital mortality (OR = 0.93, 95% CI 0.50 to 1.74, P = 0.82, I2 = 51%), intensive care unit mortality (OR = 0.84, 95% CI 0.55 to 1.29, P = 0.43, I2 = 0%), duration of stay in the hospital (mean difference [MD] in days = -0.13, 95% CI -0.93 to 0.67, P = 0.75, I2 = 46%), or duration of stay in the intensive care units (MD = -0.72, 95% CI -1.73 to 0.29, P = 0.16, I2 = 68%). CONCLUSIONS: The use of probiotics was associated with a statistically significant reduction in the incidence of nosocomial pneumonia in critically ill patients. However, large, well-designed, randomized, multi-center trials are needed to confirm any effects of probiotics clinical endpoints such as mortality and length of ICU and hospital stay.     

Probiotics' effects on the incidence of nosocomial pneumonia in critically ill patients: a systematic review and meta-analysis

Introduction

Transpulmonary thermodilution is used to measure cardiac output (CO), global end-diastolic volume (GEDV) and extravascular lung water (EVLW). A system has been introduced (VolumeView/EV1000? system, Edwards Lifesciences, Irvine CA, USA) that employs a novel algorithm for the mathematical analysis of the thermodilution curve. Our aim was to evaluate the agreement of this method with the established PiCCO? method (Pulsion Medical Systems SE, Munich, Germany, clinicaltrials.gov identifier: NCT01405040)

Methods

Seventy-two critically ill patients with clinical indication for advanced hemodynamic monitoring were included in this prospective, multicenter, observational study. During a 72-hour observation period, 443 sets of thermodilution measurements were performed with the new system. These measurements were electronically recorded, converted into an analog resistance signal and then re-analyzed by a PiCCO₂? device (Pulsion Medical Systems SE).

Results

For CO, GEDV, and EVLW, the systems showed a high correlation (r² = 0.981, 0.926 and 0.971, respectively), minimal bias (0.2 L/minute, 29.4 ml and 36.8 ml), and a low percentage error (9.7%, 11.5% and 12.2%). Changes in CO, GEDV and EVLW were tracked with a high concordance between the two systems, with a traditional concordance for CO, GEDV, and EVLW of 98.5%, 95.1%, and 97.7% and a polar plot concordance of 100%, 99.8% and 99.8% for CO, GEDV, and EVLW, respectively. Radial limits of agreement for CO, GEDV and EVLW were 0.31 ml/minute, 81 ml and 40 ml, respectively. The precision of GEDV measurements was significantly better using the VolumeView? algorithm compared to the PiCCO? algorithm (0.033 (0.03) versus 0.040 (0.03; median (interquartile range), P = 0.000049).

Conclusions

For CO, GEDV, and EVLW, the agreement of both the individual measurements as well as measurements of change showed the interchangeability of the two methods. For the VolumeView method, the higher precision may indicate a more robust GEDV algorithm.

Trial registration

clinicaltrials.gov NCT01405040.     

Topical chlorhexidine for prevention of ventilator-associated pneumonia: a meta-analysis

OBJECTIVE: To assess the efficacy of topical chlorhexidine for prevention of ventilator-associated pneumonia (VAP) in a meta-analysis. DATA SOURCE: Computerized PubMed and MEDLINE search supplemented by manual searches for relevant articles. STUDY SELECTION: Randomized controlled trials evaluating efficacy of topical chlorhexidine applied to the oropharynx vs. placebo or standard care for prevention of VAP. DATA EXTRACTION: Data were extracted on patient population, inclusion and exclusion criteria, diagnostic criteria for VAP, form and concentration of topical chlorhexidine used, incidence of VAP, and overall mortality. DATA SYNTHESIS: Data on incidence of VAP and mortality were abstracted as dichotomous variables. Pooled estimates of the relative risk and 95% confidence intervals were obtained using the DerSimonian and Laird random effects model and the Mantel-Haenszel fixed effects model. Heterogeneity was assessed using the Cochran Q statistic and I. Subgroup analyses were used to explore heterogeneity. RESULTS: Seven randomized controlled trials met the inclusion criteria. Topical chlorhexidine resulted in a reduced incidence of VAP (relative risk, 0.74; 95% confidence interval, 0.56-0.96; p=.02) using a fixed effects model. Using the more conservative random effects model, the point estimate was similar (relative risk, 0.70; 95% confidence interval, 0.47-1.04; p=.07), but the results failed to achieve statistical significance. The I test showed moderate heterogeneity. Subgroup analysis showed that the benefit of chlorhexidine was most marked in cardiac surgery patients (relative risk, 0.41; 95% confidence interval, 0.17-0.98; p=.04). There was no mortality benefit with chlorhexidine although the sample size was small. CONCLUSIONS: Our analysis showed that topical chlorhexidine is beneficial in preventing VAP; the benefit is most marked in cardiac surgery patients. A large randomized trial is needed to determine the impact of topical chlorhexidine on mortality.     

Administration of antimicrobials via the respiratory tract for the treatment of patients with nosocomial pneumonia: a meta-analysis

BACKGROUND: Aerosolized antibiotics are a widely recognized treatment for patients with cystic fibrosis (CF). We sought to clarify their role in the treatment of non-CF patients with nosocomial pneumonia by performing a meta-analysis of randomized controlled trials (RCTs) that compared administration of antimicrobials via the respiratory tract (with or without concurrent usage of systemic antibiotics) with control treatment. METHODS: An extensive search of PubMed, Scopus, Cochrane Central Register of Controlled Trials, Current Contents and bibliographies from retrieved publications was made. RESULTS: Five RCTs were included in the meta-analysis. Administration of antimicrobials via respiratory tract (either inhaled or endotracheally instilled) as opposed to control was associated with better treatment success in intention-to-treat [fixed effect model: odds ratio (OR) = 2.39, 95% confidence interval (CI) 1.29-4.44; random effects model: OR = 2.75, 95% CI 1.06-7.17] and in clinically evaluable patients (fixed effect model: OR = 3.14, 95% CI 1.48-6.70; random effects model: OR = 3.07, 95% CI 1.15-8.19). There were no statistically significant differences between therapeutic regimens regarding all-cause mortality (fixed effect model: OR = 0.84, 95% CI 0.43-1.64; random effects model: OR = 0.71, 95% CI 0.27-1.88), microbiological success (fixed effect model: OR = 2.06, 95% CI 0.91-4.68; random effects model: OR = 2.23, 95% CI 0.64-7.71) and toxicity (fixed effect model: OR = 0.34, 95% CI 0.04-2.53; random effects model: OR = 0.36, 95% CI 0.04-3.16). CONCLUSIONS: The limited available evidence seems not to preclude a benefit from the administration of antimicrobial agents via the respiratory tract for treating nosocomial pneumonia.     

阿司匹林可降低急性呼吸窘迫综合征发生率的meta分析

目的 血小板在急性呼吸窘迫综合征（acute respiratory distress syndrome, ARDS）的发病机制中起到重要的作用,前期的基础试验也证实血小板抑制剂阿司匹林在ARDS的发生及进展中起到重要作用,本研究在于通过meta分析研究阿司匹林是否可降低患者ARDS发生率。方法 全面搜索2011-2016年PubMed、EMbase、Cochrane、万方数据库和中国期刊网全文数据库,全面获取关于阿司匹林对ARDS发生率影响文献,按照纳入及排除标准筛选文献,提取资料,使用Stata15.0软件对数据进行meta分析。结果 共纳入4篇文献,其中3篇为观察研究性文献,1篇为多中心随机对照试验,共入选具有ARDS高危因素患者5 555例,其中服用阿司匹林患者有1 537例。结果发现：服用与未服用阿司匹林者相比,阿司匹林可以显著降低ARDS的发生率（OR=0.709, 95%CI=0.562 0.896,P=0.004）。结论 本研究发现服用阿司匹林可明显降低ARDS的发生率,但仍需大量的多中心随机对照试验证实。     

Effectiveness of 0.12% chlorhexidine gluconate oral rinse in reducing prevalence of nosocomial pneumonia in patients undergoing heart surgery.

BACKGROUND: Decreasing the levels of bacteria in the oropharynx should reduce the prevalence of nosocomial pneumonia. OBJECTIVES: To test the effectiveness of 0.12% chlorhexidine gluconate oral rinse in decreasing microbial colonization of the respiratory tract and nosocomial pneumonia in patients undergoing open heart surgery. METHODS: A prospective, randomized, case-controlled clinical trial design was used. Peridex (0.12% chlorhexidine gluconate) was the experimental drug, and Listerine (phenolic mixture) was the control drug. A total of 561 patients undergoing aortocoronary bypass or valve surgery requiring cardiopulmonary bypass were randomized to an experimental (n = 270) or a control (n = 291) group. Nosocomial pneumonia was diagnosed by using the criteria established by the Centers for Disease Control and Prevention. RESULTS: The overall rate of nosocomial pneumonia was reduced by 52% (4/270 vs 9/291; P = .21) in the Peridex-treated patients. Among patients intubated for more than 24 hours who had cultures that showed microbial growth (all pneumonias occurred in this group), the pneumonia rate was reduced by 58% (4/19 vs 9/18; P = .06) in patients treated with Peridex. In patients at highest risk for pneumonia (intubated > 24 hours, with cultures showing the most growth), the rate was 71% lower in the Peridex group than in the Listerine group (2/10 vs 7/10; P = .02). CONCLUSIONS: Although rates of nosocomial pneumonia were lower in patients treated with Peridex than in patients treated with Listerine, the difference was significant only in those patients intubated more than 24 hours who had the highest degree of bacterial colonization.     

Facial mask noninvasive mechanical ventilation reduces the incidence of nosocomial pneumonia

Objective: To evaluate the impact of noninvasive positive pressure mechanical ventilation (NPPV) on ventilator-associated pneumonia (VAP). Design: Prospective observational study. Setting: Medical intensive care unit (ICU) of a university teaching hospital. Patients: Cohort of 320 consecutive patients staying in the ICU more than 2 days and mechanically ventilated for ≥ 1 day. Measurements and results: VAP was diagnosed when, satisfying classical clinical and radiological criteria, fiberoptic bronchoalveolar lavage and/or protected specimen brush grew ≥ 10⁴ and ≥ 10³ CFU/ml, respectively, of at least one microorganism. Patients were classified into four subgroups according to the way in which mechanical ventilation was delivered: NPPV then tracheal intubation (TI) (n = 38), TI then NPPV (n = 23), TI only (n = 199), and NPPV only (n = 60). Occurrence of VAP was estimated by incidence rate and density of incidence. Risk factors for VAP were assessed by logistic regression analysis. Twenty-seven patients had 28 episodes of VAP. The incidence rates for patients with VAP were 18 % in NPPV-TI, 22 % in TI-NPPV, 8 % in TI, and 0 % in NPPV (p < 0.0001). The density of incidence of VAP was 0.85 per 100 days of TI and 0.16 per 100 days of NPPV (p = 0.04). Logistic regression showed that length of ICU stay and ventilatory support were associated with VAP. Conclusions: There is a significantly lower incidence of VAP associated with NPPV compared to tracheal intubation. This is mainly explained by differences in patient severity and risk exposure. Received: 29 January 1997 Accepted: 14 July 1997     

持续监测和控制人工气道气囊压力对机械通气患者呼吸机相关肺炎发生率影响的Meta分析

目的系统评价机械通气患者持续或间断监测和控制人工气道气囊压力对呼吸机相关肺炎（VAP）发生率的影响。 方法计算机检索PubMed、Medline、EMbase、OVID、Cochrane、CNKI中国知网、中国生物医学文献数据库（CBM）、维普中文科技期刊数据库（VIP）、万方数据库中关于持续监测和控制人工气道气囊压力（干预组）及间断监测和控制人工气道气囊压力（常规组）对机械通气患者VAP发生率影响的随机对照研究,检索时间为2006年1月到2015年12月。由2名研究者按照纳入及排除标准独立进行文献筛选、资料提取和质量评估后,采用Revman 5.3软件对数据进行Meta分析。 结果共纳入6篇文献,机械通气患者1 263例,其中进行持续监测和控制人工气道气囊压力的干预组机械通气患者654例,进行间断监测和控制人工气道气囊压力的常规组机械通气患者609例。Meta分析结果显示,干预组患者VAP发生率较常规组明显降低[OR = 0.43,95%CI（0.31,0.60）,Z = 5.53,P< 0.05]。但干预组患者ICU病死率较常规组未明显降低,两组比较差异没有统计学意义[OR = 1.02,95%CI（0.71,1.46）,Z = 0.36,P> 0.05]。 结论对机械通气患者进行持续监测和控制人工气道气囊压力可以降低VAP发生率,但对ICU病死率没有明显影响。     

复方氯己定联合苦丁茶对呼吸机相关性肺炎口腔的护理效果

目的：探讨复方氯己定联合苦丁茶对机械通气患者预防呼吸机相关性肺炎口腔的护理效果。方法选取机械通气患者162例,随机分为A组、B组、C组。 A组患者采用复方氯己定擦洗联合苦丁茶冲洗,B组患者采用复方氯己定擦洗,C组患者采用苦丁茶冲洗。连续7d观察三组患者口腔霉菌、口臭、口腔溃疡、咽部和气管内细菌定植数、VAP的发生率,不良反应、口腔护理效果。结果口咽部细菌定植发生率A组患者明显低于B组（P＜0.05）,A组和B组均明显低于C组（均P＜0.05）;VAP发生率A组患者明显低于B组（ P＜0.05）,A组和B组均明显低于C组（均P＜0.05）;牙齿、舌苔发黄等发生率A组和C组均明显低于B组（均P＜0.05）,A组患者明显低于C组（P＜0.05）。结论采用复方氯己定冲洗、擦洗联合苦丁茶液冲洗对VAP患者进行口腔护理可以起到很好地抗菌消炎作用,降低VAP的发生率。     

Effect of a nurse-implemented sedation protocol on the incidence of ventilator-associated pneumonia

OBJECTIVE: To determine whether the use of a nurse-implemented sedation protocol could reduce the incidence of ventilator-associated pneumonia in critically ill patients. DESIGN: Two-phase (before-after), prospective, controlled study. SETTING: University-affiliated, 11-bed medical intensive care unit. PATIENTS: Patients requiring mechanical ventilation for >or=48 hrs and sedative infusion with midazolam or propofol alone.INTERVENTIONS: During the control phase, sedatives were adjusted according to the physician's decision. During the protocol phase, sedatives were adjusted according to a protocol developed by a multidisciplinary team including nurses and physicians. The protocol was based on the Cambridge scale, and sedation level was adjusted every 3 hrs by the nurses. Standard practices, including weaning from the ventilator and diagnosis of VAP, were the same during both study phases. MEASUREMENTS AND MAIN RESULTS: A total of 423 patients were enrolled (control group, n = 226; protocol group, n = 197). The incidence of VAP was significantly lower in the protocol group compared with the control group (6% and 15%, respectively, p = .005). By univariate analysis (log-rank test), only use of a nurse-implemented protocol was significantly associated with a decrease of incidence of VAP (p < .01). A nurse-implemented protocol was found to be independently associated with a lower incidence of VAP after adjustment on Simplified Acute Physiology Score II in the multivariate Cox proportional hazards model (hazard rate, 0.81; 95% confidence interval, 0.62-0.95; p = .03). The median duration of mechanical ventilation was significantly shorter in the protocol group (4.2 days; interquartile range, 2.1-9.5) compared with the control group (8 days; interquartile range, 2.2-22.0; p = .001), representing a 52% relative reduction. Extubation failure was more frequently observed in the control group compared with the protocol group (13% and 6%, respectively, p = .01). There was no significant difference in in-hospital mortality (38% vs. 45% in the protocol vs. control group, respectively, p = .22). CONCLUSIONS: In patients receiving mechanical ventilation and requiring sedative infusions with midazolam or propofol, the use of a nurse-implemented sedation protocol decreases the rate of VAP and the duration of mechanical ventilation.     

Effect of oropharyngeal decontamination by povidone-iodine on ventilator-associated pneumonia in patients with head trauma

OBJECTIVE: To evaluate the effect of a regular oropharyngeal application of povidone-iodine on the prevalence of ventilator-associated pneumonia in patients with severe head trauma. DESIGN: Prospective randomized study. SETTING: A surgical intensive care unit of a university hospital. INTERVENTIONS: Patients with severe head trauma (Glasgow Coma Score of < or =8) expected to need ventilation for > or =2 days were prospectively randomized into three groups: those receiving nasopharynx and oropharynx rinsing with 20 mL of a 10% povidone-iodine aqueous solution, reconstituted in a 60-mL solution with sterile water (povidone-iodine group); those receiving nasopharynx and oropharynx rinsing with 60 mL of saline solution (saline group); or those undergoing a standard regimen without any instillation but with aspiration of oropharyngeal secretions (control group). MEASUREMENTS AND MAIN RESULTS: The prevalence of ventilator-associated pneumonia was compared among the three groups. A total of 98 patients were analyzed (povidone-iodine group, n = 36; saline group, n = 31; and control group, n = 31). A total of 28 cases of ventilator-associated pneumonia were diagnosed. There was a significant decrease in the rate of ventilator-associated pneumonia in the povidone-iodine group when compared with the saline and control groups (3 of 36 patients [8%] vs. 12 of 31 patients [39%] and 13 of 31 patients [42%], respectively; p = .003 and .001, respectively). The length of stay and mortality in the surgical intensive care unit were not statistically different between the three groups. CONCLUSIONS: The regular administration of povidone-iodine may be an effective strategy for decreasing the prevalence of ventilator-associated pneumonia in patients with severe head trauma.     

Protected specimen brush or bronchoalveolar lavage to diagnose bacterial nosocomial pneumonia in ventilated adults: a meta-analysis

OBJECTIVE: We conducted a meta-analysis by using summary receiver operating characteristic curves to compare the diagnostic value for bacterial nosocomial pneumonia of the following: a) quantitative culture (colony-forming units per milliliter or CFU/mL) of respiratory secretions collected with a bronchoscopic protected specimen brush (PSB); b) quantitative culture of a bronchoscopic bronchoalveolar lavage (BAL); and c) the percentage of infected cells (IC) in BAL. DATA SOURCES: All studies published in the English or the French language, through January 1, 1995, on the evaluation of PSB or BAL for the diagnosis of pneumonia were considered for analysis. The relevant literature was identified through computer and reference searching and by experts in the field. STUDY SELECTION: A study was included if at least two of three independent readers regarded its purpose as the evaluation of CFU-PSB, CFU-BAL, or IC-BAL for the diagnosis in human beings of bacterial nosocomial pneumonia in ventilated adults and if the study was prospective and published in a peer-reviewed journal. DATA EXTRACTION: Three readers reviewed all published articles and decided whether to include each study; consensus was defined as agreement by at least two readers. The authors of each original article included in the meta-analysis were asked to complete a questionnaire in which they were asked to check and to correct the data extracted by one of the independent readers. DATA SYNTHESIS: Summary receiver operating characteristic curves were used to compare the efficacy of three diagnostic tests. Eighteen studies on CFU-PSB (795 patients) were included, as well as 11 studies on CFU-BAL (435 patients) and 11 on IC-BAL (766 patients). The accuracy of these tests was not different. However, it seems that administration of previous antibiotics markedly decreased accuracy of CFU-PSB (p = .0002) but not the accuracy of CFU-BAL and that of IC-BAL. CONCLUSION: Both PSB and BAL are reliable to diagnose bacterial nosocomial pneumonia. Because CFU-BAL and IC-BAL seemed more resistant to the effects of antibiotics, we recommend BAL rather than PSB if the patient is already receiving antibiotics.     

Kinetic bed therapy to prevent nosocomial pneumonia in mechanically ventilated patients: a systematic review and meta-analysis

Introduction  

Nosocomial pneumonia is the most important infectious complication in patients admitted to intensive care units. Kinetic bed therapy may reduce the incidence of nosocomial pneumonia in mechanically ventilated patients. The objective of this study was to investigate whether kinetic bed therapy reduces the incidence of nosocomial pneumonia and improves outcomes in critically ill mechanically ventilated patients.