Small Chest Tubes May Be Sufficient for Empyema Tx

Transcription

1 Small Chest Tubes May Be Sufficient for Empyema Tx The Relationship Between Chest Tube Size and Clinical Outcome in Pleural Infection. Rahman NM, Maskell NA, et al: Chest 2010; 137 (March): In this study, smaller chest tubes were associated with less pain and equivalent outcomes in comparison to large-bore tubes. Background: Generations of intensivists have been trained to place large-bore chest tubes via blunt dissection for empyemas. Image guidance and Seldinger techniques have allowed placement of smaller chest tubes; these techniques, while presumptively less painful to the patient, are usually reserved for non-viscous pleural processes. Objective: To determine if small-bore tube thoracostomy can be used to drain an empyema. Design: Analysis of a previously published trial (MIST1) of intrapleural streptokinase in the management of empyema. This trial showed no benefit to streptokinase. Participants: 454 patients treated for an empyema (across 52 centers in the United Kingdom); 405 with a recorded tube size were examined. Methods: Chest tube size and method of placement were chosen per the discretion of the treating physician. Use of imaging guidance during placement was not recorded. Small chest tubes were flushed 3 times daily with 30 ml saline; all tubes were placed at 20 cm H 2 O suction. Primary outcome was death or need for thoracic surgery by 12 months; secondary outcomes included pain (using a validated scoring system) during chest tube placement/maintenance/removal, length of hospital stay, and changes in chest radiography or pulmonary function. Results: Baseline characteristics of patient groups (<10F, 10F to 14F, 15F to 20F, >20F) were largely similar, although patients receiving large chest tubes were incrementally more likely to have purulent, inflammatory pleural fluid and lower serum albumin levels. Tube size had no impact on death or thoracic surgery rates (36% with <10F tubes; 44% with >20F tubes) even when controlling for differences in albumin, a known predictor of death. There were similarly no differences in secondary outcomes. Method of tube placement was not associated with outcome. In subgroup analysis, small-bore chest tubes surprisingly had improved outcomes in patients with purulent fluid (<10F 29%, >20F 45%; P =0.04). Patients with <15F tubes were less likely to report moderate/severe tube pain than were those with larger (>15F) tubes (27% vs 54%; P <0.05). Similarly, the Seldinger technique of placement, highly correlated with small-tube placement, was associated with less pain. Conclusions: Chest tube size does not correlate with outcome in the treatment of empyema, suggesting that smaller, less painful tubes may be used. Reviewer's Comments: Avoiding blunt chest wall dissection and large-tube placement offers obvious improvement in patient comfort. It is important, however, to note that the therapeutic equivalence of small-tube placement observed in this trial may not be due to chest tube size alone. Smaller chest tubes might have been more frequently placed using imaging guidance (eg, by interventional radiology). Therefore, it is possible that smaller tubes have little, or even negative, impact on outcome, but this was balanced by beneficial effects of targeted placement. (Reviewer-Eric P. Schmidt, MD). Keywords: Empyema, Tube Thoracostomy, Pain

2 Delayed Tracheostomy May Ward Off Risky, Unnecessary Steps Early vs Late Tracheotomy for Prevention of Pneumonia in Mechanically Ventilated Adult ICU Patients: A Randomized Controlled Trial. Terragni PP, Antonelli M, et al: JAMA 2010; 303 (April 21): Early tracheostomy offers little benefit in respiratory failure and may subject patients to unnecessary procedures and risks. Background: Tracheostomy is typically reserved for patients who cannot be liberated from ventilator support. Most patients undergoing tracheostomy have, therefore, already spent weeks ventilated through an endotracheal tube, but recent studies have suggested value in earlier placement. These studies, however, have suffered from vague criteria for predicting the risk for chronic ventilator dependence. Objective: To compare early versus delayed tracheostomy in a patient population precisely defined to be at risk for prolonged respiratory failure. Design: Randomized trial across 12 Italian ICUs. Participants: 600 patients were enrolled; after 48 hours of ventilation, 419 patients at high risk for prolonged ventilation (without concurrent pulmonary infection or moribund state) were randomized to early versus late tracheostomy. Methods: High risk for prolonged ventilation was defined at 48 hours by significant hypoxemia (Pao 2 <60.0 mm Hg at Fio 2 >0.5 with PEEP >8.0 cm H 2 O), persistence of underlying pathology that prompted intubation, and a Sequential Organ Failure Assessment score >5. These patients were randomized to tracheostomy at 6 to 8 days or 13 to 15 days after intubation, provided that the clinical state did not improve (oxygenation, improvement in underlying pathology), the patient had not become moribund, and there was no coagulation contraindication to surgery. Bedside tracheostomies were performed; intraoperative and postoperative complications were noted. Primary outcome was 28-day incidence of ventilator-associated pneumonia (VAP; defined by standardized criteria); secondary outcomes included mortality and hospital length of stay. Results: Of 209 patients randomized to early (median, 7 days) tracheostomy, 26% did not ultimately receive a tracheostomy due to either recovery (weaning) or futility (moribund state) during that 7-day period. Of 210 patients randomized to late (median, 14 days) tracheostomy, 40% avoided tracheostomy due to recovery or futility during the 14-day waiting period. There was no difference in VAP rate, survival, or hospital stay between groups. Ventilator-free days were increased with early tracheostomy. There was a 39% risk of tracheostomy complications, typically minor. Conclusions: Tracheostomy should be delayed for >14 days after intubation, avoiding earlier unnecessary (and potential risky) procedures. Reviewer's Comments: This is a large and very well-done study that explicitly defines patients at risk for chronic respiratory failure. Given the absence of clinically relevant benefits of early tracheostomy and the high procedural complication rate, avoiding unnecessary tracheostomies is an important goal. Indeed, waiting 7 days allowed 26% of patients to declare themselves as not needing a tracheostomy, due to either recovery or futility. Waiting another 7 days allowed an additional 14% to avoid an unnecessary intervention. This supports the authors' contention that tracheostomy placement should be delayed for >14 days after intubation. It also underscores that it remains difficult to predict the duration of mechanical ventilation in individuals. (Reviewer- Eric P. Schmidt, MD). Keywords: Tracheostomy, Chronic Respiratory Failure, Acute Respiratory Failure

3 Culturing Only 1 Lumen for CRBSI Frequently Misses Colonized Catheters How Many Lumens Should Be Cultured in the Conservative Diagnosis of Catheter-Related Bloodstream Infections? Guembe M, Rodríguez-Créixems M, et al: Clin Infect Dis 2010; 50 (June 15): More than one third of catheter-related bloodstream infection episodes may be missed if only 1 lumen of a triple-lumen catheter is cultured. Background: Catheter-related bloodstream infection (CRBSI) can be diagnosed using criteria such as differential time to positivity or quantitative culture that compare catheter-drawn blood to peripheral blood for bacterial growth. While these strategies may possibly reduce rates of unnecessary catheter removal, they may also increase the possibility of retaining infected catheters due to missed diagnoses of CRBSI. One important unresolved issue is how many lumens of multi-lumen catheters need to be cultured to allow for sensitive CRBSI diagnosis. Objective: To determine the frequency of missed diagnosis of CRBSI when blood is not cultured from all possible lumens of central venous catheters. Design: Retrospective single-center study. Methods: Cases of CRBSI were identified on the basis of either differential time to positivity (microbial growth detected from catheter-drawn blood 2 hours before growth of same microbe from peripheral blood) or quantitative culture ( 3-fold higher colony count in catheter-drawn blood than in peripheral blood). Only cases in which blood had been cultured from all possible (ie, non-clotted) lumens were considered. The number of CRBSI episodes that would have been missed in double- and triple-lumen catheters if the culture of samples obtained from 1 lumens had been eliminated was calculated by probability analysis. Results: 171 episodes of CRBSI in 154 patients were studied. The most common hospital wards represented were surgery (n=60), oncology (n=28), and ICU (n=24). Of infecting microbes identified, 135 (70%) were Gram-positive bacteria, 36 (18.6%) Gram-negative bacteria, and 22 (11.4%) yeast. Of 112 infections of doublelumen catheters, 61 (54.5%) involved 1 lumen and 51 (45.5%), 2 lumens. Of 59 infections of triple-lumen catheters, 28 (47.5%) involved 1 lumen, 10 (17.0%) 2 lumens, and 21 (35.6%) 3 lumens. Overall, if 1 lumenassociated culture had been eliminated for double- and triple-lumen catheters, 27.2% and 15.8% of CRBSI episodes would have been missed, respectively. If 2 cultures had been eliminated for triple-lumen catheters, 37.3% of episodes would have been missed. Conclusions: A substantial percentage of cases of CRBSI may be missed if all possible lumens of multilumen central venous catheters are not cultured. Reviewer's Comments: The 2009 Infectious Diseases Society of America clinical practice guidelines for CRBSI described an unresolved issue as the optimal number of lumens to be sampled in diagnosing CRBSI. Sampling >1 lumen adds cost, labor, and time, and may contribute to nosocomial anemia. The present study commands our attention as it provides fairly compelling evidence that not sampling all possible lumens may be associated with an intolerably high rate of missed CRBSI diagnoses. Nevertheless, given its retrospective design, single-center status, and fairly narrow patient demographics, further confirmation of this study's results may be warranted. Could multiple lumen specimens be pooled for culture? Should all lumen samples be submitted for quantitative and/or timed culture? These important questions remain unanswered. (Reviewer- Michael B. Fessler, MD). Keywords: Catheter-Related Bloodstream Infection, Cultured Lumens

4 Massive Database Analysis Supports Early Antibiotics in COPD Exacerbations Antibiotic Therapy and Treatment Failure in Patients Hospitalized for Acute Exacerbations of Chronic Obstructive Pulmonary Disease. Rothberg MB, Pekow PS, et al: JAMA 2010; 303 (May 26): U.S. national hospital data indicate that early antibiotic treatment for COPD exacerbation is associated with improvement in a composite measure of treatment failure. Background: Treatment guidelines for COPD exacerbation recommend antibiotic treatment for patients with purulent sputum, increased sputum, and/or increased dyspnea. Evidence supporting these recommendations stems from 11 small randomized trials demonstrating that antibiotics can reduce mortality and treatment failure. However, approximately 50% of COPD exacerbations do not have an identifiable bacterial etiology, and some recent studies have failed to identify a benefit deriving from antibiotics. Objective: To compare outcomes of patients treated with antibiotics in the first 2 hospital days with those treated later or not at all. Design: Retrospective cohort study. Participants: Patients aged 40 years hospitalized from January 2006 to December 2007 for acute COPD exacerbations at 413 acute care facilities throughout the U.S. Patients admitted directly to the ICU were excluded. Methods: Inpatient data were examined for U.S. hospitals participating in the Premier's Perspective database. Acute COPD exacerbation was identified by ICD-9-CM codes. Antibiotic treatment was defined as 2 consecutive days of antibiotics initiated on hospital day 1 or 2. The main outcome measure was a composite measure of treatment failure, defined as initiation of mechanical ventilation after hospital day 2, inpatient mortality, or readmission for acute COPD exacerbation within 30 days of discharge. Results: Of 84,621 patients, 79% received 2 consecutive days of antibiotics. Treated patients were less likely than nontreated patients to receive mechanical ventilation after hospital day 2 (1.07%; 95% CI, 1.06% to 1.08% vs 1.80%; 95% CI, 1.78% to 1.82%), had lower rates of inpatient mortality (1.04%; 95% CI, 1.03% to 1.05% vs 1.59%; 95% CI, 1.57% to 1.61%), and had lower rates of readmission for COPD exacerbation (7.91%; 95% CI, 7.89% to 7.94% vs 8.79%; 95% CI, 8.74% to 8.83%). Patients treated with antibiotics had a higher rate of readmission for Clostridium difficile infection (0.19%; 95% CI, 0.187% to 0.193%) than did those who were not treated (0.09%; 95% CI, 0.086% to 0.094%). After multivariate adjustment, including the propensity for antibiotic treatment, the risk of treatment failure was lower in antibiotic-treated patients (odds ratio, 0.87; 95% CI, 0.82 to 0.92). A grouped treatment approach and hierarchical modeling to account for potential confounding yielded similar results. Analysis stratified by risk of treatment failure found similar magnitudes of benefit across all subgroups. Conclusions: Early antibiotic treatment was associated with an improved outcome among patients hospitalized for acute COPD exacerbation regardless of the risk of treatment failure. Reviewer's Comments: This study reports that antibiotics are associated with a 13% decrease in the risk of a composite measure of treatment failure in COPD exacerbation. The investigators were unable to show that this benefit was restricted to patients with specific clinical presentations. Although this study is limited by its retrospective design and identification of study subjects with administrative data, its conclusions are buttressed by its tremendous size and by its careful propensity analysis. Future prospective confirmatory trials appear warranted. (Reviewer-Michael B. Fessler, MD). Keywords: COPD Exacerbation, Antibiotics

5 Alteplase May Benefit Patients Up to 270 Minutes After Onset of Stroke Symptoms Time to Treatment With Intravenous Alteplase and Outcome in Stroke: An Updated Pooled Analysis of ECASS, ATLANTIS, NINDS, and EPITHET Trials. Lees KR, Bluhmki E, et al: Lancet 2010; 375 (May 15): Odds of favorable outcomes in stroke are inversely proportional to onset of treatment time. Background: Early administration of thrombolytics improves outcomes after ischemic stroke, and guidelines currently recommend IV recombinant tissue plasminogen activator (rt-pa) up to 3 hours after symptom onset. Recent investigations have attempted to assess the safety and efficacy of extending the treatment window beyond 3 hours. Objective: To evaluate outcomes of stroke patients receiving rt-pa up to 6 hours after onset of symptoms for safety and efficacy. Design: Meta-analysis of 8 clinical trials for acute stroke. Participants: Patients with acute stroke randomized to receive rt-pa versus placebo within 360 minutes of symptom onset from 8 previously published clinical trials (NINDS 1 and 2; ECASS I, II, and III; ATLANTIS A and B; and EPITHET). Inclusion and exclusion criteria from the included trials were roughly similar. Methods: Pooled subjects receiving rt-pa (n=1850) and placebo (n=1820) were compared. Primary outcome was favorable outcome at 3 months as defined by modified Rankin Scale score of 0 to 1. Outcomes based on onset of treatment time (OTT, divided into 90-minute intervals from onset of symptoms) were compared through multiple logistic regression. Interventions: Alteplase (rt-pa) at a dose of 0.9 mg/kg (for all trials except ECASS I, 1.1 mg/kg) versus placebo. Results: Baseline characteristics were similar between groups as were numbers of subjects in OTT groups. Odds ratio (OR) of favorable outcomes demonstrated a decreasing statistical significance for OTT at 90 minutes (OR, 2.55; 95% CI, 1.44 to 4.52; P =0.0013) through 270 minutes (OR, 1.34; 95% CI, 1.06 to 1.68; P =0.0202). OTT >271 minutes was not associated with a difference in outcomes (P =0.1628). Mortality was similar between OTT groups, although OTT 271 to 360 minutes approached statistical significance (OR, 1.49; 95% CI, 1.00 to 2.29; P =0.0501) favoring placebo. Large intracranial hemorrhage (ICH) was seen more in rt- PA patients (n=96, 5.2%) than in controls (n=18, 1.0%; P <0.0001), and the OR for ICH was similar between OTT groups. Conclusions: Favorable outcomes are attainable up to 4.5 hours after onset of stroke symptoms, although the greatest benefits are achieved with earlier treatment. Moreover, treatment up to 4.5 hours is safe. Reviewer's Comments: These investigators performed a more inclusive compilation and analysis of large clinical trials using thrombolytic therapy for acute ischemic stroke. Their analysis technique examining the odds of favorable outcomes and safety based on OTT effectively demonstrate utility of thrombolysis up to 4.5 hours. After that point, the risk-benefit ratio precludes lytic use. With the expansion of supporting data, guidelines extending the therapeutic window should be considered. (Reviewer-Jeffrey B. Hoag, MD, MS). Keywords: Stroke

6 Ventilation Modes Have Similar Outcomes Outcomes of Patients Ventilated With Synchronized Intermittent Mandatory Ventilation With Pressure Support: A Comparative Propensity Score Study. Ortiz G, Frutos-Vivar F, et al: Chest 2010; 137 (June): There is no difference in outcome in patients ventilated with synchronized intermittent mandatory ventilation with pressure support compared to assist-control ventilation. Background: Data showing real benefits of one mode of mechanical ventilation over another are sparse. Significant factors driving mode choice are the provider's comfort and familiarity with particular modes and an element of faith. Objective: To compare outcomes in patients mechanically ventilated with either synchronized intermittent mandatory ventilation (SIMV; with pressure support, SMIV-PS) or assist-control (A/C) ventilation. Design: Secondary analysis of observational study. Participants: Mechanically ventilated adults from 349 ICUs in 23 countries. Patients were included if they received exclusively A/C or SIMV-PS ventilation during their ICU stay. Those receiving neuromuscular blockade were excluded. Methods: A propensity score for use of SIMV-PS was developed to account for inability to randomize modes in this observational study. Multivariate analysis was performed to assess factors associated with the likely use of SMIV-PS. Patients were stratified into quintiles by propensity score. Effect on end points was assessed for each quintile based on likelihood of receiving SIMV-PS. The primary outcome was hospital mortality, and secondary outcomes included sedative use, days of mechanical ventilation, ICU length of stay, and ICU mortality. Results: Of 4968 patients, 1228 were mechanically ventilated with A/C exclusively and 350 with SIMV-PS. Those in the SIMV-PS group were more common in the U.S./Canada, had lower Sequential Organ Failure Assessment scores, and were more likely surgical or trauma patients. Those ventilated with A/C tended to have sepsis and cardiovascular failure, and to require mechanical ventilation due to asthma or coma. There was no effect of mode of mechanical ventilation on hospital mortality across propensity score for SIMV-PS use (odds ratio, 1.04; 95% CI, 0.77 to 1.42; P =0.78). Of SIMV-PS patients, 245 (70%) were weaned successfully compared to 638 (52%, P <0.001) in the A/C group. There was no difference in reintubation or tracheostomy rates. Conclusions: SIMV-PS was used more often for less severely ill medical and surgical patients. Also, there was no difference in mortality or duration of mechanical ventilation between modes when accounting for baseline differences in groups. Reviewer's Comments: Although hampered by its observational design, this study suggests no difference in meaningful outcomes related to use of SIMV-PS mode versus A/C. The authors found continued wide use of SIMV-PS in postoperative and trauma patients in particular. Sicker patients were more often ventilated with A/C. Not evaluated in this study was the managing physician's discipline of training, but one could speculate differences in mode use based on medical intensivist training versus anesthesia or surgical training. This study design has numerous opportunities for confounders to color the conclusions. Cohorts differed by diagnoses, by severity of illness, and probably by the type of unit and training of their intensivists. Adjustment or propensity scores still cannot convincingly allow comparison of apples and oranges. It seems that the best mode of ventilation for a given patient population remains unclear. (Reviewer-Jeffrey B. Hoag, MD, MS). Keywords: Synchronized Intermittent Mandatory Ventilation, Pressure Support

7 High Oxygen Levels Associated With Increased Mortality After Cardiac Arrest Association Between Arterial Hyperoxia Following Resuscitation From Cardiac Arrest and In-Hospital Mortality. Kilgannon JH, Jones AE, et al: JAMA 2010; 303 (June 2): Both hyperoxia and hypoxia are associated with increased in-hospital mortality following resuscitation from cardiac arrest, but hyperoxia has a higher incidence. Objective: To investigate whether hyperoxia following resuscitation from cardiac arrest is associated with poor outcomes. Design: Multicenter cohort study. The study used data collected from ICUs at 120 hospitals participating in the Project IMPACT database from 2001 through Participants: Adult participants were included in the analysis if they had been resuscitated from nontraumatic cardiac arrest within 24 hours prior to ICU arrival and had an arterial blood gas performed within 24 hours of ICU admission. If more than 1 arterial blood gas was performed, only the first blood gas values were included. Methods: For the purpose of data analysis, hyperoxia was defined as a partial pressure of oxygen (Pao 2 ) 300 mm Hg. Hypoxia was defined as a Pao 2 60 mm Hg or Pao 2 to Fio 2 ratio <300, and normoxia as all other individuals. Results: Of 6326 individuals included in the analysis, 63% had hypoxia, 19% were normoxia, and 18% had hyperoxia. Mortality was greatest in the hyperoxia group (63%) compared to both the hypoxia group (57%, P <0.001) and the normoxia group (45%, P <0.001). In addition, the percentage of individuals who were independent at hospital discharge was also lower in the hyperoxic group (29% vs 38% for normoxia group; P =0.002). In a multivariate linear regression model, hyperoxia following cardiac arrest was associated with an odds ratio of in-hospital death of 1.80 (95% CI, 1.5% to 2.2%). Hypoxia was also an independent risk factor of death, but the odds ratio was lower than that associated with hyperoxia at 1.3 (95% CI, 1.1 to 1.5). Conclusions: Exposure to hyperoxia after resuscitation from cardiac arrest is common and is an independent risk factor for in-hospital mortality. Reviewer's Comments: While this is a cohort study, the data provide a revelation about potential risks of hyperoxia following cardiac arrest. In many respects, this outcome is counterintuitive. One is tempted to interpret a high Pao 2 after cardiac arrest as being indicative of minimal organ damage. However, the results of this trial indicate a higher mortality in hyperoxia when compared to normoxia or even hypoxia. This was a strong association that included only the first Pao 2 after ICU admission. Whether sustained hyperoxia might have a greater effect is not known. Certainly, potential dangers of hyperoxia have been demonstrated in experimental models, particularly in the setting of ischemia and subsequent reperfusion with generation of reactive oxygen species. The implication of the current study is that avoidable hyperoxia may exacerbate reperfusion injury of multiple organs. However, this association in human studies needs to be better elucidated as this study is a cohort study and can only determine association rather than causation. (Reviewer-Cynthia D. Brown, MD). Keywords: Resuscitation, Arterial Hyperoxia, Cardiac Arrest

8 Lactate-Guided Therapy May Improve Outcomes in Shock Early Lactate-Guided Therapy in ICU Patients: A Multicenter, Open-Label, Randomized Controlled Trial. Jansen TC, van Bommel J, et al: Am J Respir Crit Care Med 2010; May 12 (): epub ahead of print A resuscitation strategy targeted at decreasing serum lactate levels may improve outcomes in shock. Background: Elevated lactate level on ICU admission and failure of lactate to fall in the first day are markers of increased ICU mortality. Objective: To determine if a protocol to decrease elevated serum lactate in the first 8 hours of ICU admission improves ICU mortality. Design: Prospective, randomized, block multicenter trial in 4 closed ICUs with 24-hour intensivist staffing. Participants: Consecutive adult ICU patients with admission lactate 3 meq/l, excluding recent seizure, liver disease, or liver surgery. Methods: Patients were randomized to usual care (UC group) with standard hemodynamic resuscitation end points, or lactate measurements every 2 hours x 4 (LAC group). In the LAC group, mixed venous PO 2 was also monitored continuously, and a resuscitation algorithm targeted both SpO 2 >70% and a 20% fall in lactate every 2 hours. Power analysis required 350 patients, with hospital mortality as the primary outcome. Results: Over the treatment period, 177 patients were randomized to the control group, and 171 to the intervention group. Baseline acuity of illness and median blood lactate levels on admission were 4.5 meq/l in each group. Furthermore, lactate improved equally in both groups over the 8-hour study period. The intervention group received more IV fluids (2.7 ± 2.0 vs 2.2 ± 1.7 L; P =0.011) and more vasodilator therapy (42.5% vs 20.2%; P <0.001). Unadjusted in-hospital mortality was 43.5% in the control group and 33.9% in the intervention group (P =0.067). After adjustment, the hazard ratio for death was 0.61 (95% CI, 0.43 to 0.87). LAC patients also had shorter duration of ventilation, inotropes, and ICU stay. Conclusions: A resuscitation strategy designed to target serum lactate levels may improve outcomes in patients with elevated serum lactate levels on admission. Reviewer's Comments: I find this study interesting as the investigators sought to determine if initial resuscitative therapy based on serum lactate levels affected outcomes in the ICU. The investigators have shown a difference between the LAC and UC groups in adjusted hazard of death. However, this cannot be attributed to differences in lactate between the 2 groups and calls into question use of lactate as a therapeutic end point for monitoring in shock. It is more likely these differences are related to the more rapid and aggressive treatment in the LAC group, perhaps prompted by continuous ScvO 2 monitoring. Use of vasodilator therapy in the intervention group is also interesting and controversial. Additional research would need to be performed on this therapy before its use can be recommended for treatment of shock. Finally, the authors powered the study based on an estimated absolute reduction in mortality of 15%. As the actual difference in mortality between groups was 9.6%, the study is somewhat underpowered to detect a difference between groups without adjustment. (Reviewer-Cynthia D. Brown, MD). Keywords: Resuscitation, Lactate Guidance

9 SSD Reduces Confirmed VAP but Not Mortality Intermittent Subglottic Secretion Drainage and Ventilator-Associated Pneumonia: A Multicenter Trial. Lacherade J-C, De Jonghe B, et al: Am J Respir Crit Care Med 2010; June 3 (): epub ahead of print Subglottic secretion drainage reduces the incidence of microbiologically confirmed ventilator-associated pneumonia. Background: Ventilator-associated pneumonia (VAP) contributes to the morbidity and mortality of patients receiving mechanical ventilation. Aspiration of oropharyngeal and subglottic secretions that pool above the endotracheal tube cuff is thought to be a pathogenetic mechanism of microbial invasion of the lower respiratory tract leading to VAP. Drainage of these secretions could prevent VAP. Objective: To determine if using specially designed endotracheal tubes for subglottic secretion drainage (SSD) could reduce the overall incidence of microbiologically confirmed VAP. Design/Methods: Prospective, randomized, interventional multicenter study involving 4 surgical and medical ICUs. The intervention consisted of suctioning subglottic secretions at an intended frequency of once per hour. All adult patients admitted to one of the participating ICUs were screened to identify patients intubated with a specific endotracheal tube that allows drainage of subglottic secretions and who did not meet exclusion criteria were randomized to receive SSD or not. In patients clinically suspected of VAP, protected telescoping catheter samples or bronchoalveolar lavage fluid was obtained, and microbiologically confirmed VAP was diagnosed based on quantitative cultures. Results: 333 patients were randomized to the SSD (n=169) or control (n=164) groups. Baseline characteristics between groups were similar except for history of cirrhosis, which was more frequent in the SSD group. VAP was clinically suspected at least once in 51 (30.2%) and 60 (36.6%) patients in the SSD and control groups, respectively. Microbiologically confirmed VAP was significantly less frequent in the SSD group (14.8%) compared to the control group (25.6%; P =0.02). Early and late-onset VAP were significantly reduced in patients randomized to receive SSD compared to patients in the control group. Antibiotic usage was similar between groups. There was no significant difference in ICU or in-hospital mortality. Conclusions: Use of an SSD strategy in mechanically ventilated patients decreases the incidence microbiologically confirmed VAP. Reviewer's Comments: This is an interesting study because it illuminates the discrepancy between clinically diagnosed VAP and microbiologically confirmed VAP. There were a similar number of patients clinically suspected of VAP in either group, and 61% of patients suspected of VAP were confirmed to have VAP. Surprisingly, despite having significantly reduced numbers of microbiologically confirmed VAP in the SSD group, there was no difference in clinical outcomes including antibiotic usage, morbidity, or mortality. By implication, clinical suspicion of VAP seems a predominant factor in clinical outcomes, and there seems to be no added benefit to confirming the diagnosis. Until interventions can demonstrate a reduction in clinically suspected VAP, clinicians need to be wary of potential risks of SSD as well as costs of these special endotracheal tubes. To achieve cost savings, SSD may need to be combined with a strict regimen of antibiotic stewardship. (Reviewer-Mahendra Damarla, MD). Keywords: Ventilator-Associated Pneumonia, Subglottic Secretion Drainage

10 Oral Lactobacillus Reduces VAP, C difficile Rates Probiotic Prophylaxis of Ventilator-Associated Pneumonia: A Blinded, Randomized, Controlled Trial. Morrow LE, Kollef MH, Casale TB: Am J Respir Crit Care Med 2010; June 3 (): epub ahead of print Probiotic therapy results in decreased surveillance cultures demonstrating pathogenic strains of bacteria and significant decreases in ventilator-associated pneumonia and Clostridium difficile-associated diarrhea. Background: Ventilator-associated pneumonia (VAP) contributes to morbidity and mortality of patients receiving mechanical ventilation in ICU. Colonization of the aerodigestive tract with pathogenic bacteria and aspiration of contaminated oropharyngeal secretions is thought to be a pathogenetic mechanism in the development of VAP. Probiotic therapy could potentially minimize aerodigestive tract colonization by more virulent species and reduce the incidence of VAP. Objective: To determine the efficacy and safety of probiotic therapy on prevention of VAP in a critically ill population. Design: Prospective, randomized, double-blind, placebo-controlled single-center trial of patients at high risk of developing VAP. Participants: All adult patients admitted at a university-based hospital thought to require mechanical ventilation with an endotracheal tube for at least 72 hours who did not meet exclusion criteria were randomized to receive twice-daily probiotic therapy of Lactobacillus rhamnosus GG or placebo. Patients clinically suspected of VAP had a non-bronchoscopic bronchoalveolar lavage performed, and microbiologically confirmed VAP was diagnosed based on quantitative cultures. Results: 138 patients were randomized to the probiotic (n=68) or placebo (n=70) groups. Baseline characteristics between groups were similar except for more frequent history of chest trauma in the probiotic group. VAP was clinically suspected in 17 (25.0%) and 33 (47.1%) patients in the probiotic and control groups, respectively (P <0.001). Of patients clinically diagnosed with VAP, microbiological confirmation of VAP was also significantly less frequent in the probiotic group (19.1%) compared to the control group (40.0%; P =0.007). Probiotic-treated patients had a significant reduction in rates of Clostridium difficile-associated diarrhea. Mortality and morbidity, defined as duration of mechanical ventilation, ICU stay, and hospital stay, were not significantly different between groups. There were no adverse events associated with probiotic treatment. Conclusions: Probiotic therapy with L rhamnosus GG decreases clinically suspected as well as microbiologically confirmed VAP. Reviewer's Comments: This is an important preliminary study because it illustrates the significance of the host environment in the development of infections. Probiotic therapy resulted in decreased surveillance cultures demonstrating pathogenic strains of bacteria likely contributing to significant decreases in VAP and C difficile-associated diarrhea. Even though this is a single-center study and rates of VAP were somewhat higher than typically reported, significant reductions noted in the incidence of VAP and C difficile-associated diarrhea with probiotic therapy warrant further investigation, especially given the innocuous safety profile of L rhamnosus GG and its low cost. (Reviewer-Mahendra Damarla, MD). Keywords: Ventilator-Associated Pneumonia, Probiotics, Diarrhea

11 C difficile Easily Transferred by Shaking Hands Effectiveness of Alcohol-Based Hand Rubs for Removal of Clostridium difficile Spores From Hands. Jabbar U, Leischner J, et al: Infect Control Hosp Epidemiol 2010; 31 (June): Clostridium difficile is easily transferred by routine contact such as shaking hands. Soap and water handwashing is more effective than alcohol-based rubs to clean hands after known contact with C difficile. Background: The ease and accessibility of alcohol-based hand hygiene products has improved health care personnel's hand hygiene compliance. This is an important way to prevent transmission of pathogens during patient care activities. Some pathogens, including Clostridium difficile, produce spores that are not effectively removed by alcohol-based products. Objective: To compare the effectiveness of soap and water handwashing to alcohol-based rubs for removal of C difficile from hands, and to assess transmission of C difficile during routine contact such as shaking hands. Methods: Hands of 10 volunteers were contaminated with standardized quantities of non-toxigenic C difficile spores. Hand cultures were done after subjects performed hand hygiene with either soap and water washing or 1 of 3 types of alcohol-based hand hygiene rub. Colony-forming units remaining after hand hygiene were quantified to calculate and compare the reduction in spore counts. Plain water rubbing was used as a control group. Volunteers with C difficile-contaminated hands shook hands with uninoculated volunteers to assess the transferability of spores. Results: Compared with plain water washing, soap and water handwashing significantly reduced C difficile spore counts on volunteers' hands. Soap and water washing was significantly more effective than alcoholbased hand rubs at reducing C difficile spore counts, and there was no significant difference in effectiveness among various types of alcohol-based rubs. Of residual C difficile spores, 30% were transferred to recipients' hands during handshaking. Conclusions: Soap and water handwashing is more effective than alcohol-based hand rubs for removal of C difficile spores. C difficile spores are efficiently transferred person-to-person during routine contact such as handshaking. Reviewer's Comments: Hand hygiene is one of the most important means to prevent transmission of infections to patients during health care activities. Despite this, rates of hand hygiene compliance in health care settings remains extremely low. Alcohol-based hand sanitizers have improved the ease and accessibility of hand hygiene for health care providers, especially in older hospitals and facilities without an abundance of accessible sinks for handwashing. This study shows that handwashing with soap and water is more effective than alcohol-based products to remove C difficile spores from hands. Residual spores were easily transferred person-to-person by contact such as shaking hands. It is important to note this efficient transfer of spores during routine contact that reinforces the urgent need for improved hand hygiene compliance by health care providers. Handwashing with soap and water should be done after care for a patient known to have C difficile infection. Either type of hand hygiene is preferable to not cleaning the hands at all, so alcohol-based rubs remain an important way to facilitate and encourage health care providers to clean their hands to prevent transmission of a wide array of other pathogens. (Reviewer-Lisa L. Maragakis, MD, MPH). Keywords:Clostridium difficile, Hand Hygiene, Spores, Infection Control, Alcohol-Based Hand Sanitizer

12 C difficile Is in Air, on Surfaces Surrounding Infected Patients The Potential for Airborne Dispersal of Clostridium difficile From Symptomatic Patients. Best EL, Fawley WN, et al: Clin Infect Dis 2010; 50 (June 1): Clostridium difficile is found in the air and environment surrounding symptomatic infected patients. Contact isolation, private rooms, environmental cleaning, and hand hygiene are important infection control measures to prevent transmission. Background: Clostridium difficile is often transmitted in the health care environment. The recent emergence of particularly virulent strains of C difficile is associated with epidemic spread and severe outcomes including colectomy and death. It is important to understand the organism's mode of transmission to effectively prevent spread. Objective: To measure airborne and environmental C difficile in areas surrounding symptomatic infected patients. Methods: Samples were obtained from the air and environmental surfaces around 63 patients with symptomatic C difficile infection (CDI). Molecular analysis was performed to assess relatedness of environmental and clinical isolates. Results: C difficile was isolated from the air around 12% of patients with CDI during a 1-hour sampling window and from the air around 70% (7 of 10 patients) when a more intensive sampling was used. Airborne C difficile was recovered most often during activity near the patient including food delivery, changing bed linens, and closing curtains. C difficile was found in 10% of all environmental cultures, most commonly from high touch surfaces such as bedrails, tables, and sinks. Molecular analysis showed epidemiological links between patients' clinical CDI isolates and those found in the air and environmental samples. Conclusions: Sporadic aerosolization of C difficile and environmental contamination occur commonly in symptomatic patients with CDI. This may have implications for prevention and control of transmission. Reviewer's Comments: The emergence of a new, virulent epidemic strain of C difficile has led to severe outcomes and death and has intensified concern over how to control health care-associated transmission and outbreaks of disease. The organism is shed in stool from symptomatic patients with CDI, which can easily contaminate surfaces around patient care areas. This study provides evidence of common airborne dispersal of C difficile spores during regular patient care activities of patients with CDI. It also uses molecular techniques to show the relatedness of clinical and environmental isolates. The clinical significance of the demonstrated airborne dispersal is unclear. Airborne particles likely contribute to contamination of nearby environmental surfaces. This and other studies reinforce that hand hygiene, contact isolation, private rooms, and improved environmental cleaning and disinfection are important infection control measures to prevent C difficile transmission. (Reviewer-Lisa L. Maragakis, MD, MPH). Keywords:Clostridium difficile, Airborne Dispersal, Environmental Contamination