Platelet Transfusion before CVC Placement in Patients with Thrombocytopenia.

BACKGROUND: Transfusion guidelines regarding platelet-count thresholds before the placement of a central venous catheter (CVC) offer conflicting recommendations because of a lack of good-quality evidence. The routine use of ultrasound guidance has decreased CVC-related bleeding complications. METHODS: In a multicenter, randomized, controlled, noninferiority trial, we randomly assigned patients with severe thrombocytopenia (platelet count, 10,000 to 50,000 per cubic millimeter) who were being treated on the hematology ward or in the intensive care unit to receive either one unit of prophylactic platelet transfusion or no platelet transfusion before ultrasound-guided CVC placement. The primary outcome was catheter-related bleeding of grade 2 to 4; a key secondary outcome was grade 3 or 4 bleeding. The noninferiority margin was an upper boundary of the 90% confidence interval of 3.5 for the relative risk. RESULTS: We included 373 episodes of CVC placement involving 338 patients in the per-protocol primary analysis. Catheter-related bleeding of grade 2 to 4 occurred in 9 of 188 patients (4.8%) in the transfusion group and in 22 of 185 patients (11.9%) in the no-transfusion group (relative risk, 2.45; 90% confidence interval [CI], 1.27 to 4.70). Catheter-related bleeding of grade 3 or 4 occurred in 4 of 188 patients (2.1%) in the transfusion group and in 9 of 185 patients (4.9%) in the no-transfusion group (relative risk, 2.43; 95% CI, 0.75 to 7.93). A total of 15 adverse events were observed; of these events, 13 (all grade 3 catheter-related bleeding [4 in the transfusion group and 9 in the no-transfusion group]) were categorized as serious. The net savings of withholding prophylactic platelet transfusion before CVC placement was $410 per catheter placement. CONCLUSIONS: The withholding of prophylactic platelet transfusion before CVC placement in patients with a platelet count of 10,000 to 50,000 per cubic millimeter did not meet the predefined margin for noninferiority and resulted in more CVC-related bleeding events than prophylactic platelet transfusion. (Funded by ZonMw; PACER Dutch Trial Register number, NL5534.).

Effects of decontamination of the oropharynx and intestinal tract on antibiotic resistance in ICUs: a randomized clinical trial.

IMPORTANCE: Selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) are prophylactic antibiotic regimens used in intensive care units (ICUs) and associated with improved patient outcome. Controversy exists regarding the relative effects of both measures on patient outcome and antibiotic resistance. OBJECTIVE: To compare the effects of SDD and SOD, applied as unit-wide interventions, on antibiotic resistance and patient outcome. DESIGN, SETTING, AND PARTICIPANTS: Pragmatic, cluster randomized crossover trial comparing 12 months of SOD with 12 months of SDD in 16 Dutch ICUs between August 1, 2009, and February 1, 2013. Patients with an expected length of ICU stay longer than 48 hours were eligible to receive the regimens, and 5881 and 6116 patients were included in the clinical outcome analysis for SOD and SDD, respectively. INTERVENTIONS: Intensive care units were randomized to administer either SDD or SOD. MAIN OUTCOMES AND MEASURES: Unit-wide prevalence of antibiotic-resistant gram-negative bacteria. Secondary outcomes were day-28 mortality, ICU-acquired bacteremia, and length of ICU stay. RESULTS: In point-prevalence surveys, prevalences of antibiotic-resistant gram-negative bacteria in perianal swabs were significantly lower during SDD compared with SOD; for aminoglycoside resistance, average prevalence was 5.6% (95% CI, 4.6%-6.7%) during SDD and 11.8% (95% CI, 10.3%-13.2%) during SOD (P < .001). During both interventions the prevalence of rectal carriage of aminoglycoside-resistant gram-negative bacteria increased 7% per month (95% CI, 1%-13%) during SDD (P = .02) and 4% per month (95% CI, 0%-8%) during SOD (P = .046; P = .40 for difference). Day 28-mortality was 25.4% and 24.1% during SOD and SDD, respectively (adjusted odds ratio, 0.96 [95% CI, 0.88-1.06]; P = .42), and there were no statistically significant differences in other outcome parameters or between surgical and nonsurgical patients. Intensive care unit-acquired bacteremia occurred in 5.9% and 4.6% of the patients during SOD and SDD, respectively (odds ratio, 0.77 [95% CI, 0.65-0.91]; P = .002; number needed to treat, 77). CONCLUSIONS AND RELEVANCE: Unit-wide application of SDD and SOD was associated with low levels of antibiotic resistance and no differences in day-28 mortality. Compared with SOD, SDD was associated with lower rectal carriage of antibiotic-resistant gram-negative bacteria and ICU-acquired bacteremia but a more pronounced gradual increase in aminoglycoside-resistant gram-negative bacteria. TRIAL REGISTRATION: trialregister.nlIdentifier: NTR1780.

Attributable mortality of ventilator-associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies.

BACKGROUND: Estimating attributable mortality of ventilator-associated pneumonia has been hampered by confounding factors, small sample sizes, and the difficulty of doing relevant subgroup analyses. We estimated the attributable mortality using the individual original patient data of published randomised trials of ventilator-associated pneumonia prevention. METHODS: We identified relevant studies through systematic review. We analysed individual patient data in a one-stage meta-analytical approach (in which we defined attributable mortality as the ratio between the relative risk reductions [RRR] of mortality and ventilator-associated pneumonia) and in competing risk analyses. Predefined subgroups included surgical, trauma, and medical patients, and patients with different categories of severity of illness scores. FINDINGS: Individual patient data were available for 6284 patients from 24 trials. The overall attributable mortality was 13%, with higher mortality rates in surgical patients and patients with mid-range severity scores at admission (ie, acute physiology and chronic health evaluation score [APACHE] 20-29 and simplified acute physiology score [SAPS 2] 35-58). Attributable mortality was close to zero in trauma, medical patients, and patients with low or high severity of illness scores. Competing risk analyses could be done for 5162 patients from 19 studies, and the overall daily hazard for intensive care unit (ICU) mortality after ventilator-associated pneumonia was 1·13 (95% CI 0·98-1·31). The overall daily risk of discharge after ventilator-associated pneumonia was 0·74 (0·68-0·80), leading to an overall cumulative risk for dying in the ICU of 2·20 (1·91-2·54). Highest cumulative risks for dying from ventilator-associated pneumonia were noted for surgical patients (2·97, 95% CI 2·24-3·94) and patients with mid-range severity scores at admission (ie, cumulative risks of 2·49 [1·81-3·44] for patients with APACHE scores of 20-29 and 2·72 [1·95-3·78] for those with SAPS 2 scores of 35-58). INTERPRETATION: The overall attributable mortality of ventilator-associated pneumonia is 13%, with higher rates for surgical patients and patients with a mid-range severity score at admission. Attributable mortality is mainly caused by prolonged exposure to the risk of dying due to increased length of ICU stay. FUNDING: None.

Estimating the attributable mortality of ventilator-associated pneumonia from randomized prevention studies.

OBJECTIVE: To assess the attributable mortality of ventilator-associated pneumonia using results from randomized controlled trials on ventilator-associated pneumonia prevention. DATA SOURCES: A systematic search was performed in PubMed, Embase, Web of Science, and Cochrane Library from their inception until July 2010. In addition, a reference and related article search was performed. STUDY SELECTION: Randomized ventilator-associated pneumonia prevention studies in which all patients were mechanically ventilated and from which ventilator-associated pneumonia and mortality rates of intervention and control group could be extracted were included. DATA EXTRACTION/SYNTHESIS: Fifty-three papers were identified describing 58 comparisons. Statistical significant reductions in ventilator-associated pneumonia incidences were reported in 20 of the 58 comparisons, whereas none of these trials reported a significant reduction of mortality. Pooled estimates of the relative risk reductions of both ventilator-associated pneumonia and mortality were calculated and the attributable mortality was estimated as the ratio between the relative risk reductions of mortality and ventilator-associated pneumonia. Effects of study quality, diagnostic methods used, and effectiveness of preventing ventilator-associated pneumonia on the mortality rate of ventilator-associated pneumonia were assessed in subgroup analyses. The overall attributable mortality of ventilator-associated pneumonia was estimated as 9%. In subgroup analyses, the attributable mortality varied between 3% and 17%. CONCLUSION: Based on the results of 58 randomized studies on ventilator-associated pneumonia prevention, the attributable mortality rate of ventilator-associated pneumonia was estimated to be 9% and ranged between 3% and 17% in subgroup analyses. Together with the results of other recent studies, there is cumulative evidence that the attributable mortality resulting from ventilator-associated pneumonia is approximately 10%.

Oral decontamination with chlorhexidine reduces the incidence of ventilator-associated pneumonia.

RATIONALE: Ventilator-associated pneumonia (VAP) is the most frequently occurring nosocomial infection associated with increased morbidity and mortality. Although oral decontamination with antibiotics reduces incidences of VAP, it is not recommended because of potential selection of antibiotic-resistant pathogens. We hypothesized that oral decontamination with either chlorhexidine (CHX, 2%) or CHX/colistin (CHX/COL, 2%/2%) would reduce and postpone development of VAP, and oral and endotracheal colonization. OBJECTIVES: To determine the effect of oral decontamination with CHX or CHX/COL on VAP incidence and time to development of VAP. METHODS: Consecutive patients needing mechanical ventilation for 48 h or more were enrolled in a randomized, double-blind, placebo-controlled trial with three arms: CHX, CHX/COL, and placebo (PLAC). Trial medication was applied every 6 h into the buccal cavity. Oropharyngeal swabs were obtained daily and quantitatively analyzed for gram-positive and gram-negative microorganisms. Endotracheal colonization was monitored twice weekly. RESULTS: Of 385 patients included, 130 received PLAC, 127 CHX and 128 CHX/COL. Baseline characteristics were comparable. The daily risk of VAP was reduced in both treatment groups compared with PLAC: 65% (hazard ratio [HR]=0.352; 95% confidence interval [CI], 0.160, 0. 791; p=0.012) for CHX and 55% (HR=0.454; 95% CI, 0.224, 0. 925; p=0.030) for CHX/COL. CHX/COL provided significant reduction in oropharyngeal colonization with both gram-negative and gram-positive microorganisms, whereas CHX mostly affected gram-positive microorganisms. Endotracheal colonization was reduced for CHX/COL patients and to a lesser extent for CHX patients. No differences in duration of mechanical ventilation, intensive care unit stay, or intensive care unit survival could be demonstrated. CONCLUSIONS: Topical oral decontamination with CHX or CHX/COL reduces the incidence of VAP.

When can empiric therapy for intensive care unit-acquired pneumonia be withheld or withdrawn?

Diagnosing ventilator-associated pneumonia (VAP) is difficult, creating important clinical dilemmas for intensive care physicians. Adequate empiric antimicrobial therapy is crucial because VAP is associated with increased morbidity and mortality, especially when initial treatment is inappropriate. Because VAP is the most frequent occurring nosocomial infection, it is, to a large extent, responsible for the high antibiotic consumption in ICUs, which is an important cause for selection and induction of antibiotic resistance. In addition, antibiotics may have adverse effects and their costs should be considered. Therefore, a balance should be found between the obvious necessary therapeutic benefits and the negative effects (selection of resistant pathogens, costs, and adverse effects) of antibiotics in the treatment of VAP. Although guidelines for initial antimicrobial therapy have been established, no such recommendations exist for withholding or withdrawing antimicrobial treatment, and little is known about the optimal duration of therapy.