Characteristics, clinical course, and outcomes of homeless and non-homeless patients admitted to ICU: A retrospective cohort study.

BACKGROUND: Little is known about homeless patients in intensive care units (ICUs). OBJECTIVES: To compare clinical characteristics, treatments, and outcomes of homeless to non-homeless patients admitted to four ICUs in a large inner-city academic hospital. METHODS: 63 randomly-selected homeless compared to 63 age-, sex-, and admitting-ICU-matched non-homeless patients. RESULTS: Compared to matched non-homeless, homeless patients (average age 48±12 years, 90% male, 87% admitted by ambulance, 56% mechanically ventilated, average APACHE II 17) had similar comorbidities and illness severity except for increased alcohol (70% vs 17%,p<0.001) and illicit drug(46% vs 8%,p<0.001) use and less documented hypertension (16% vs 40%,p = 0.005) or prescription medications (48% vs 67%,p<0.05). Intensity of ICU interventions was similar except for higher thiamine (71% vs 21%,p<0.0001) and nicotine (38% vs 14%,p = 0.004) prescriptions. Homeless patients exhibited significantly lower Glasgow Coma Scores and significantly more bacterial respiratory cultures. Longer durations of antibiotics, vasopressors/inotropes, ventilation, ICU and hospital lengths of stay were not statistically different, but homeless patients had higher hospital mortality (29% vs 8%,p = 0.005). Review of all deaths disclosed that withdrawal of life-sustaining therapy occurred in similar clinical circumstances and proportions in both groups, regardless of family involvement. Using multivariable logistic regression, homelessness did not appear to be an independent predictor of hospital mortality. CONCLUSIONS: Homeless patients, admitted to ICU matched to non-homeless patients by age and sex (characteristics most commonly used by clinicians), have higher hospital mortality despite similar comorbidities and illness severity. Trends to longer durations of life supports may have contributed to the higher mortality. Additional research is required to validate this higher mortality and develop strategies to improve outcomes in this vulnerable population.

Reporting Guidelines for Clinical Pharmacokinetic Studies: The ClinPK Statement.

BACKGROUND AND OBJECTIVE: Transparent reporting of all research is essential for assessing the validity of any study. Reporting guidelines are available and endorsed for many types of research but are lacking for clinical pharmacokinetic studies. Such tools promote the consistent reporting of a minimal set of information for end users, and facilitate knowledge translation of research. The objective of this study was to create a guideline to assist in the transparent and complete reporting of clinical pharmacokinetic studies. METHODS: Preliminary content to be considered was identified from a systematic search of the literature and regulatory documents. Stakeholders were identified to participate in a modified Delphi exercise and a virtual meeting to generate consensus for items considered essential in the reporting of clinical pharmacokinetic studies. The proposed checklist was pilot tested on 100 recently published clinical pharmacokinetic studies. Overall and itemized compliance with the proposed guidance was determined for each study. RESULTS: Sixty-eight stakeholders from nine countries consented to participate. Four rounds of a modified Delphi survey and a series of small virtual meetings were required to generate consensus for a 24-item checklist considered to be essential to the reporting of clinical pharmacokinetic studies. When applied to the 100 most recently published clinical pharmacokinetic studies, 45 were determined to be compliant with at least 80 % of the checklist items. Explanatory text was prepared using examples of compliant reporting from these and other relevant studies. CONCLUSIONS: The reader's ability to judge the validity of pharmacokinetic research can be greatly compromised by the incomplete reporting of study information. Using consensus methods, we have developed a tool to guide transparent and accurate reporting of clinical pharmacokinetic studies. Endorsement and implementation of these guidelines by researchers, clinicians and journals would promote more consistent reporting of these studies and allow for better assessment of utility for clinical applications.

Optimal dosing of antibiotics in critically ill patients by using continuous/extended infusions: a systematic review and meta-analysis.

INTRODUCTION: The aim of this study was to determine whether using pharmacodynamic-based dosing of antimicrobials, such as extended/continuous infusions, in critically ill patients is associated with improved outcomes as compared with traditional dosing methods. METHODS: We searched Medline, HealthStar, EMBASE, Cochrane Clinical Trial Registry, and CINAHL from inception to September 2013 without language restrictions for studies comparing the use of extended/continuous infusions with traditional dosing. Two authors independently selected studies, extracted data on methodology and outcomes, and performed quality assessment. Meta-analyses were performed by using random-effects models. RESULTS: Of 1,319 citations, 13 randomized controlled trials (RCTs) (n = 782 patients) and 13 cohort studies (n = 2,117 patients) met the inclusion criteria. Compared with traditional non-pharmacodynamic-based dosing, RCTs of continuous/extended infusions significantly reduced clinical failure rates (relative risk (RR) 0.68; 95% confidence interval (CI) 0.49 to 0.94, P = 0.02) and intensive care unit length of stay (mean difference, -1.5; 95% CI, -2.8 to -0.2 days, P = 0.02), but not mortality (RR, 0.87; 95% CI, 0.64 to 1.19; P = 0.38). No significant between-trial heterogeneity was found for these analyses (I2 = 0). Reduced mortality rates almost achieved statistical significance when the results of all included studies (RCTs and cohort studies) were pooled (RR, 0.83; 95% CI, 0.69 to 1.00; P = 0.054). CONCLUSIONS: Pooled results from small RCTs suggest reduced clinical failure rates and intensive care unit length-of-stay when using continuous/extended infusions of antibiotics in critically ill patients. Reduced mortality rates almost achieved statistical significance when the results of RCTs were combined with cohort studies. These results support the conduct of adequately powered RCTs to define better the utility of continuous/extended infusions in the era of antibiotic resistance.

Corticosteroid use in the intensive care unit: a survey of intensivists.

OBJECTIVE: The efficacy of systemic corticosteroids in many critical illnesses remains uncertain. Our primary objective was to survey intensivists in North America about their perceived use of corticosteroids in clinical practice. DESIGN: Self-administered paper survey. POPULATION: Intensivists in academic hospitals with clinical trial expertise in critical illness. MEASUREMENTS: We generated questionnaire items in focus groups and refined them after assessments of clinical sensibility and test-retest reliability and pilot testing. We administered the survey to experienced intensivists practicing in selected North American centres actively enrolling patients in the multicentre Oscillation for ARDS Treated Early (OSCILLATE) Trial (ISRCTN87124254). Respondents used a four-point scale to grade how frequently they would administer corticosteroids in 14 clinical settings. They also reported their opinions on 16 potential near-absolute indications or contraindications for the use of corticosteroids. MAIN RESULTS: Our response rate was 82% (103/125). Respondents were general internists (50%), respirologists (22%), anesthesiologists (21%), and surgeons (7%) who practiced in mixed medical-surgical units. A majority of respondents reported almost always prescribing corticosteroids in the setting of significant bronchospasm in a mechanically ventilated patient (94%), recent corticosteroid use and low blood pressure (93%), and vasopressor-refractory septic shock (52%). Although more than half of respondents stated they would almost never prescribe corticosteroids in severe community-acquired pneumonia (81%), acute lung injury (ALI, 76%), acute respiratory distress syndrome (ARDS, 65%), and severe ARDS (51%), variability increased with severity of acute lung injury. Near-absolute indications selected by most respondents included known adrenal insufficiency (99%) and suspicion of cryptogenic organizing pneumonia (89%), connective tissue disease (85%), or other potentially corticosteroid-responsive illnesses (85%). CONCLUSIONS: Respondents reported rarely prescribing corticosteroids for ALI, but accepted them for bronchospasm, suspected adrenal insufficiency due to previous corticosteroid use, and vasopressor-refractory septic shock. These competing indications will complicate the design and interpretation of any future large-scale trial of corticosteroids in critical illness.

The occurrence and impact of bacterial organisms complicating critical care illness associated with 2009 influenza A(H1N1) infection.

BACKGROUND: Although secondary infections are recognized as a cause of morbidity and mortality in seasonal influenza, their frequency, characteristics, and associated clinical outcomes in 2009 influenza A(H1N1) (A[H1N1])-related critical illness are unknown. METHODS: In a prospective cohort of adult patients admitted to Canadian ICUs with influenza A(H1N1) infection, the frequency and associated clinical outcomes of prevalent (culture taken within 72 h of ICU admission) and ICU-acquired (culture taken after 72 h from ICU admission) positive bacterial cultures were determined. RESULTS: Among 681 patients, the mean age was 47.9 years (SD, 15.1), APACHE (Acute Physiology and Chronic Health Examination) II score was 21.0 (9.9), and 573 patients (84.0%) were invasively mechanically ventilated. Positive cultures were obtained in 259 patients (38.0%): 77 (29.7%) had prevalent, 115 (44.4%) had ICU-acquired, and 40 (15.4%) had both; culture date was unavailable in 27 (10.4%). The most common bacterial organisms isolated were coagulase-negative staphylococci, Staphylococcus aureus, Pseudomonas species, and Streptococcus pneumoniae. Antibiotics were prescribed in 661 (97.1%), with 3.8 (1.9) prescriptions per patient. Patients with any positive culture had longer days of mechanical ventilation (mean [SD], 15.2 [10.7] vs 10.7 [9.0]; P<.0001), ICU stay (median [interquartile range (IQR)], 18.2 [12.5] days vs 10.8 [9.0] days, P<.0001), and hospitalization (median [IQR], 30.7 [20.7] days vs 19.2 [17.4] days, P<.0001) and a trend toward increased hospital mortality (25.1% vs 19.9%, P=.15). Patients with ICU-acquired positive cultures had worse outcomes compared with those with positive prevalent cultures or who were culture-negative. CONCLUSION: Culture-based evidence of secondary infections commonly complicates A(H1N1)-related critical illness and is associated with worse clinical outcomes despite nearly ubiquitous antibiotic administration.

Nurse- vs nomogram-directed glucose control in a cardiovascular intensive care unit.

BACKGROUND: Paper-based nomograms are reasonably effective for achieving glycemic control but have low adherence and are less adaptive than nurses' judgment. OBJECTIVE: To compare efficacy (glucose control) and safety (hypoglycemia) achieved by use of a paper nomogram versus nurses' judgment. METHODS: Prospective, randomized, open-label, crossover trial in an intensive care unit in postoperative patients with glucose concentrations greater than 8 mmol/L. Consenting nurses with at least 1 year of experience were randomized to use either their judgment or a validated paper-based nomogram for glucose control. After completion of 2 study shifts, the nurses used the alternative method for the next 2 study shifts. Glucose target level and safety and efficacy boundaries were the same for both methods. The primary end point was area under glucose time curve per hour. RESULTS: Thirty-four nurses contributed 95 shifts of data (44 nomogram-directed, 51 nurse-directed). Adherence to the nomogram was higher in the nomogram group than hypothetical adherence in the nurse-directed group for correct adjustments in insulin infusion (70% vs 37%; P < .001) and glucose checks (58% vs 43%; P = .008). The primary end point did not differ between the 2 groups (mean, 9.0 mmol/L; SD, 3.5 vs mean, 8.3 mmol/L; SD, 2.1; P = .08). Glucose variability, amount of time patients were hypoglycemic or hyperglycemic, and number of glucose checks performed were similar in the 2 groups. CONCLUSIONS: In an intensive care unit where nurses generally accepted the need for tight glucose control, nurse-directed control was as effective and as safe as nomogram-based control.