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Thursday, 25 October 2018

Beyond Low Tidal Volume Ventilation: Treatment Adjuncts for Severe Respiratory Failure in Acute Respiratory Distress Syndrome

Critical Care Medicine - Most Popular Articles by Fielding-Singh, Vikram; Matthay, Michael A.; Calfee, Carolyn S.  /  7d //  keep unread  //  hide

Objectives: Despite decades of research, the acute respiratory distress syndrome remains associated with significant morbidity and mortality. This Concise Definitive Review provides a practical and evidence-based summary of treatments in addition to low tidal volume ventilation and their role in the management of severe respiratory failure in acute respiratory distress syndrome.
Data Sources: We searched the PubMed database for clinical trials, observational studies, and review articles describing treatment adjuncts in acute respiratory distress syndrome patients, including high positive end-expiratory pressure strategies, recruitment maneuvers, high-frequency oscillatory ventilation, neuromuscular blockade, prone positioning, inhaled pulmonary vasodilators, extracorporeal membrane oxygenation, glucocorticoids, and renal replacement therapy.
Study Selection and Data Extraction: Results were reviewed by the primary author in depth. Disputed findings and conclusions were then reviewed with the other authors until consensus was achieved.
Data Synthesis: Severe respiratory failure in acute respiratory distress syndrome may present with refractory hypoxemia, severe respiratory acidosis, or elevated plateau airway pressures despite lung-protective ventilation according to acute respiratory distress syndrome Network protocol. For severe hypoxemia, first-line treatment adjuncts include high positive end-expiratory pressure strategies, recruitment maneuvers, neuromuscular blockade, and prone positioning. For refractory acidosis, we recommend initial modest liberalization of tidal volumes, followed by neuromuscular blockade and prone positioning. For elevated plateau airway pressures, we suggest first decreasing tidal volumes, followed by neuromuscular blockade, modification of positive end-expiratory pressure, and prone positioning. Therapies such as inhaled pulmonary vasodilators, glucocorticoids, and renal replacement therapy have significantly less evidence in favor of their use and should be considered second line. Extracorporeal membrane oxygenation may be life-saving in selected patients with severe acute respiratory distress syndrome but should be used only when other alternatives have been applied.
Conclusions: Severe respiratory failure in acute respiratory distress syndrome often necessitates the use of treatment adjuncts. Evidence-based application of these therapies in acute respiratory distress syndrome remains a significant challenge. However, a rational stepwise approach with frequent monitoring for improvement or harm can be achieved.

Changes in Temperature Management of Cardiac Arrest Patients Following Publication of the Target Temperature Management Trial*

by Salter, Ryan; Bailey, Michael; Bellomo, Rinaldo; Eastwood, Glenn; Goodwin, Andrew; Nielsen, Niklas; Pilcher, David; Nichol, Alistair; Saxena, Manoj; Shehabi, Yahya; Young, Paul; on behalf of the Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation (ANZICS-CORE)  

Objectives: To evaluate knowledge translation after publication of the target temperature management 33°C versus 36°C after out-of-hospital cardiac arrest trial and associated patient outcomes. Our primary hypothesis was that target temperature management at 36°C was rapidly adopted in Australian and New Zealand ICUs. Secondary hypotheses were that temporal reductions in mortality would be seen and would have accelerated after publication of the target temperature management trial.
Design: Retrospective cohort study (January 2005 to December 2016). Setting: The Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation adult patient database containing greater than 2 million admission episodes from 186 Australian and New Zealand ICUs.
Patients: Sixteen-thousand two-hundred fifty-two adults from 140 hospitals admitted to ICU after out-of-hospital cardiac arrest. Interventions: The primary exposure of interest was admission before versus after publication of the target temperature management trial.
Measurements and Main Results: The primary outcome variable to evaluate changes in temperature management was lowest temperature in the first 24 hours in ICU. The primary clinical outcome variable of interest was inhospital mortality. Secondary outcomes included proportion of patients with fever in the first 24 hours in ICU. Mean ± SD lowest temperature in the first 24 hours in ICU in pre- and posttarget temperature management trial patients was 33.80 ± 1.71°C and 34.70 ± 1.39°C, respectively (absolute difference, 0.98°C [99% CI, 0.89–1.06°C]). Inhospital mortality rate decreased by 1.3 (99% CI, –1.8 to –0.9) percentage points per year from January 2005 until December 2013 and increased by 0.6 (99% CI, –1.4 to 2.6) percentage points per year from January 2014 until December 2016 (change in slope 1.9 percentage points per year [99% CI, –0.6 to 4.4]). Fever occurred in 568 (12.8%) of 4,450 pretarget temperature management trial patients and 853 (16.5%) of 5,184 posttarget temperature management trial patients (odds ratio, 1.35 [99% CI, 1.16–1.57]).
Conclusions: The average lowest temperature of postcardiac arrest patients in the first 24 hours in ICU rose after publication of the target temperature management trial. This change was associated with an increased frequency of fever not seen in the target temperature management trial.

Delirium Monitoring in Neurocritically Ill Patients: A Systematic Review*

by Patel, Mayur B.; Bednarik, Josef; Lee, Patricia; Shehabi, Yahya; Salluh, Jorge I.; Slooter, Arjen J.; Klein, Kate E.; Skrobik, Yoanna; Morandi, Alessandro; Spronk, Peter E.; Naidech, Andrew M.; Pun, Brenda T.; Bozza, Fernando A.; Marra, Annachiara; John, Sayona; Pandharipande, Pratik P.; Ely, E. Wesley  

Objectives: The Society of Critical Care Medicine recommends routine delirium monitoring, based on data in critically ill patients without primary neurologic injury. We sought to answer whether there are valid and reliable tools to monitor delirium in neurocritically ill patients and whether delirium is associated with relevant clinical outcomes (e.g., survival, length of stay, functional independence, cognition) in this population.
Data Sources: We systematically reviewed Cumulative Index to Nursing and Allied Health Literature, Web of Science, and PubMed. Study Selection and Data Extraction: Inclusion criteria allowed any study design investigating delirium monitoring in neurocritically ill patients (e.g., neurotrauma, ischemic, and/or hemorrhagic stroke) of any age. We extracted data relevant to delirium tool sensitivity, specificity, negative predictive value, positive predictive value, interrater reliability, and associated clinical outcomes.
Data Synthesis: Among seven prospective cohort studies and a total of 1,173 patients, delirium was assessed in neurocritically patients using validated delirium tools after considering primary neurologic diagnoses and associated complications, finding a pooled prevalence rate of 12–43%. When able to compare against a common reference standard, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, the test characteristics showed a sensitivity of 62–76%, specificity of 74–98%, positive predictive value of 63–91%, negative predictive value of 70–94%, and reliability kappa of 0.64–0.94. Among four studies reporting multivariable analyses, delirium in neurocritically patients was associated with increased hospital length of stay (n = 3) and ICU length of stay (n = 1), as well as worse functional independence (n = 1) and cognition (n = 2), but not survival.
Conclusions: These data from studies of neurocritically ill patients demonstrate that patients with primary neurologic diagnoses can meet diagnostic criteria for delirium and that delirious features may predict relevant untoward clinical outcomes. There is a need for ongoing investigations regarding delirium in these complicated neurocritically ill patients.

Handovers Among Staff Intensivists: A Study of Information Loss and Clinical Accuracy to Anticipate Events*

by Dutra, Mariana; Monteiro, Mariana V.; Ribeiro, Karina B.; Schettino, Guilherme P.; Kajdacsy-Balla Amaral, Andre Carlos  

Objectives: Handovers are associated with medical errors, and our primary objective is to identify missed diagnosis and goals immediately after a shift handover. Our secondary objective is to assess clinicians’ diagnostic accuracy in anticipating clinical events during the night shift.
Design: Single-center prospective observational cohort study. Setting: Thirty-bed tertiary ICU in Sao Paulo, Brazil.
Patients: Three-hundred fifty-two patient encounters over 44 day-to-night handovers.
Interventions: None.
Measurements and Main Results: We used a multimethods approach to measure transmission of information among staff physicians on diagnoses and goals for the night shift. We surveyed clinicians immediately after a handover and identified clinical events through chart abstractions and interviews with clinicians the next morning. Nighttime clinicians correctly identified 454 of 857 diagnoses (53%; 95% CI 50–56) and 123 of 304 goals (40%; 95% CI, 35–46). Daytime clinicians were more sensitive (65% vs 46%; p < 0.01) but less specific (82% vs 91%; p < 0.01) than nighttime clinicians in anticipating clinical events at night, resulting in similar accuracy (area under the receiver operating characteristic curve, 0.74 [95% CI, 0.68–0.79] vs 0.68 [95% CI 0.63–0.74]; p = 0.09). The positive predictive value of both daytime and nighttime clinicians was low (13% vs 17%; p = 0.2). Gaps in diagnosis and anticipation of events were more pronounced in neurologic diagnoses. Conclusions: Among staff intensivists, diagnoses and goals of treatment are either not conveyed or retained 50–60% of the cases immediately after a handover. Clinicians have limited ability to anticipate events, and the expectation that anticipatory guidance can inform handovers needs to be balanced against information overload. Handovers among staff intensivists showed more gaps in the identification of diagnostic uncertainty and for neurologic diagnoses, which could benefit from communication strategies such as cognitive checklists, prioritizing discussion of neurologic patients, and brief combined clinical examination at handover.

Evaluation of Effect of Probiotics on Cytokine Levels in Critically Ill Children With Severe Sepsis: A Double-Blind, Placebo-Controlled Trial*

 by Angurana, Suresh K.; Bansal, Arun; Singhi, Sunit; Aggarwal, Ritu; Jayashree, Muralidharan; Salaria, Manila; Mangat, Navdeep K.  

Objectives: To evaluate the effect of probiotics on cytokines in children with severe sepsis.
Design: Randomized, double-blind, placebo-controlled trial. Setting: ICU of a tertiary care teaching hospital in North India.
Patients: Children 3 months to 12 years old with severe sepsis. Interventions: Enrolled children were randomized to probiotic (n = 50) and placebo (n = 50) groups. Probiotic group received VSL#3 (Danisco-Dupont USA, Madison, WI) (Lactobacillus paracasei, L. plantarum, L. acidophilus, L. delbrueckii, Bifidobacterium longum, B. infantis, B. breve, Streptococcus salivarius; maltose and silicon dioxide), and placebo group received maltose and silicon dioxide. Dose was 1 sachet twice daily for 7 days. Blood was collected on days 1 and 7 for estimation of interleukin-6, interleukin-12p70, interleukin-17, tumor necrosis factor-α, interleukin-10, and transforming growth factor -β1. “Primary outcome”: Change in cytokine levels in probiotic and placebo groups from day 1 to 7. “Secondary outcomes”: Sequential Organ Failure Assessment score, healthcare-associated infections, ICU stay, and mortality.
Measurements and Main Results: On day 7, probiotic group had significantly lower levels of proinflammatory cytokines (interleukin-6 [80 vs 186 pg/mL, p = 0.001]; interleukin-12p70 [44 vs 79 pg/mL, p = 0.001]; interleukin-17 [217 vs 293 pg/mL, p = 0.01]; and tumor necrosis factor-α [192 vs 348 pg/mL, p = 0.01]) and higher levels of antiinflammatory cytokines (interleukin-10 [320 vs 240 pg/mL, p = 0.02] and transforming growth factor-β1 [311 vs 221 ng/mL, p = 0.01]) than placebo group. From day 1 to 7, probiotic group showed significant decrease in proinflammatory cytokines (interleukin-6 [196–80 pg/mL, p = 0.001]; interleukin-12p70 [71–44 pg/mL, p = 0.01]; interleukin-17 [258–217 pg/mL, p = 0.01]; and tumor necrosis factor-α [347–192 pg/mL, p = 0.001]) and increase in antiinflammatory cytokines (interleukin-10 [198–320 pg/mL, p = 0.001] and transforming growth factor-β1 [216–311 ng/mL, p = 0.001]) as compared to placebo group. Sequential Organ Failure Assessment score on day 7 was significantly less in probiotic group (1 vs 3). There was a nonsignificant trend toward lower incidence of healthcare-associated infections (14% vs 20%) and duration of ICU stay (6.5 vs 9 d) in probiotic group. Mortality was similar in two groups.
Conclusions: Probiotics supplementation for 7 days resulted in significant decrease in proinflammatory and increase in antiinflammatory cytokines in children with severe sepsis.

Survival of Patients With Vancomycin-Resistant Enterococcus faecium Bacteremia Treated With Conventional or High Doses of Daptomycin or Linezolid Is Associated With the Rate of Bacterial Clearance*

 by Chuang, Yu-Chung; Lin, Hsin-Yi; Chen, Pao-Yu; Lin, Chi-Ying; Chen, Yee-Chun; Wang, Jann-Tay; Chang, Shan-Chwen  

Objectives: Vancomycin-resistant enterococci are important pathogens for healthcare-associated infections. Although linezolid is bacteriostatic and daptomycin is rapidly bactericidal against vancomycin-resistant enterococci in vitro, it is not clear whether they differ in their effect on bacterial clearance in patients with vancomycin-resistant enterococci bloodstream infections. 
Design: Prospective observational study.
Setting: Two university hospitals and research laboratory. Patients: Patients with vancomycin-resistant enterococci bloodstream infection proven by blood cultures were prospectively enrolled from January 2010 to July 2015. Interventions: Sequential blood samples were collected. Real-time quantitative polymerase chain reaction was used to monitor bacterial loads.
Measurements and Main Results: One hundred eight patients with vancomycin-resistant enterococci bloodstream infection were enrolled. Quantitative polymerase chain reaction assays were performed on 465 blood isolates. We found this method to be closely correlated with colony-forming units and more sensitive than culture. Sixty-three patients (58.3%) received “conventional dose” daptomycin (6–9 mg/kg), 15 (13.9%) received high-dose daptomycin (≥ 9 mg/kg), and 30 (27.8%) were treated with linezolid (600 mg every 12 hr) as sole agents. The initial mean bacterial load was 1.03 log10 copies/mL and unrelated to survival. Survivors had a more rapid early bacterial clearance than nonsurvivors (Δ log10 copies/mL/d; –0.16 vs 0.31; p = 0.02). Multivariable logistic regression showed that a slower early bacterial clearance independently predicted increased mortality (odds ratio, 3.21; 95% CI, 1.03–10.02; p = 0.045). Conventional dose daptomycin was associated with a significantly slower rate of bacterial clearance than high-dose daptomycin (Δ log10 copies/mL/d; –0.04 vs –0.41; p < 0.001) and linezolid (–0.04 vs –0.56; p = 0.043). Conclusions: We found that survivors of vancomycin-resistant enterococci bloodstream infection had a significantly more rapid early bacterial clearance by quantitative polymerase chain reaction than nonsurvivors. High-dose daptomycin and linezolid were associated with more rapid bacterial clearance than conventional dose daptomycin. These results support recommendations that conventional dose daptomycin not be used for the treatment of patients with vancomycin-resistant enterococci bloodstream infection.

Moderate and Severe Acute Respiratory Distress Syndrome: Hemodynamic and Cardiac Effects of an Open Lung Strategy With Recruitment Maneuver Analyzed Using Echocardiography*

 by Mercado, Pablo; Maizel, Julien; Kontar, Loay; Nalos, Marek; Huang, Stephen; Orde, Sam; McLean, Anthony; Slama, Michel  

Objectives: Open lung ventilation with a recruitment maneuver could be beneficial for acute respiratory distress syndrome patients. However, the increased airway pressures resulting from the recruitment maneuver may induce cardiac dysfunction, limiting the benefit of this maneuver. We analyzed the effect of a recruitment maneuver and decremental positive end-expiratory pressure titration on cardiac function.
Settings: Medical ICU Amiens, France.
Patients: Twenty patients with moderate to severe acute respiratory distress syndrome Interventions: Patients underwent a stepwise recruitment maneuver with respiratory evaluation and echocardiography assessment of cardiac function including longitudinal strain at baseline, peak positive end-expiratory pressure of recruitment maneuver (positive end-expiratory pressure 40 cm H2O), and at “optimal” positive end-expiratory pressure. The patients were divided into two groups based on change on the PaO2/FIO2 ratio (nonresponders < 50%; responders ≥ 50%). 
Measurements and Main Results: At peak positive end-expiratory pressure during the recruitment maneuver, the arterial pressure, cardiac output, left ventricular size decreased and right ventricular size increased. The left ventricular ejection fraction decreased from 60% ± 13% to 48% ± 18% (p = 0.05). Both left and right ventricular global longitudinal strain were impaired (–15.8% ± 4.5% to –11% ± 4.7% and –19% ± 5% to –14% ± 6% [p = 0.05] respectively). Fifty percent of patients were nonresponders and demonstrated a lower hemodynamic tolerance to the recruitment maneuver than responders. Optimal positive end-expiratory pressure was 14 ± 5 cm H2O (vs 11 ± 4 cm H2O at baseline), and PaO2/FIO2 ratio increased from 111 ± 25 to 197 ± 89 mm Hg (p < 0.0001). All hemodynamic variables returned to their baseline value after the recruitment maneuver despite a higher positive end-expiratory pressure.
Conclusions: An open lung strategy with a stepwise recruitment maneuver permitted a higher positive end-expiratory pressure and improved oxygenation without any cardiac impairment. The recruitment maneuver was associated with mild and transient, cardiac dysfunction, with nonresponders demonstrating poorer tolerance.