Patient-important upper gastrointestinal bleeding in the ICU: A mixed-methods study of patient and family perspectives.

INTRODUCTION: The objective of this study was to create a definition of patient-important upper gastrointestinal bleeding during critical illness as an outcome for a randomized trial. DESIGN: This was a sequential mixed-methods qualitative-dominant multi-center study with an instrument-building aim. In semi-structured individual interviews or focus groups we elicited views from survivors of critical illness and family members of patients in the intensive care unit (ICU) regarding which features indicate important gastrointestinal bleeding. Quantitative demographic characteristics were collected. We analyzed qualitative data using inductive content analysis to develop a definition for patient-important upper gastrointestinal bleeding. SETTING: Canada and the United States. PARTICIPANTS: 51 ICU survivors and family members of ICU patients. RESULTS: Participants considered gastrointestinal bleeding to be important if it resulted in death, disability, or prolonged hospitalization. The following also signaled patient-important upper gastrointestinal bleeding: blood transfusion, vasopressors, endoscopy, CT-angiography, or surgery. Whether an intervention evinced concern depended on its effectiveness, side-effects, invasiveness and accessibility; contextual influences included participant familiarity and knowledge of interventions and trust in the clinical team. CONCLUSIONS: Survivors of critical illness and family members described patient-important upper gastrointestinal bleeding differently than current definitions of clinically-important upper gastrointestinal bleeding.

The physiological determinants of near-infrared spectroscopy-derived regional cerebral oxygenation in critically ill adults.

BACKGROUND: To maintain adequate oxygen delivery to tissue, resuscitation of critically ill patients is guided by assessing surrogate markers of perfusion. As there is no direct indicator of cerebral perfusion used in routine critical care, identifying an accurate strategy to monitor brain perfusion is paramount. Near-infrared spectroscopy (NIRS) is a non-invasive technique to quantify regional cerebral oxygenation (rSO2) that has been used for decades during cardiac surgery which has led to targeted algorithms to optimize rSO2 being developed. However, these targeted algorithms do not exist during critical care, as the physiological determinants of rSO2 during critical illness remain poorly understood. MATERIALS AND METHODS: This prospective observational study was an exploratory analysis of a nested cohort of patients within the CONFOCAL study ( NCT02344043 ) who received high-fidelity vital sign monitoring. Adult patients (≥ 18 years) admitted < 24 h to a medical/surgical intensive care unit were eligible if they had shock and/or required mechanical ventilation. Patients underwent rSO2 monitoring with the FORESIGHT oximeter for 24 h, vital signs were concurrently recorded, and clinically ordered arterial blood gas samples and hemoglobin concentration were also documented. Simultaneous multiple linear regression was performed using all available predictors, followed by model selection using the corrected Akaike information criterion (AICc). RESULTS: Our simultaneous multivariate model included age, heart rate, arterial oxygen saturation, mean arterial pressure, pH, partial pressure of oxygen, partial pressure of carbon dioxide (PaCO2), and hemoglobin concentration. This model accounted for a significant proportion of variance in rSO2 (R2 = 0.58, p < 0.01) and was significantly associated with PaCO2 (p < 0.05) and hemoglobin concentration (p < 0.01). Our selected regression model using AICc accounted for a significant proportion of variance in rSO2 (R2 = 0.54, p < 0.01) and was significantly related to age (p < 0.05), PaCO2 (p < 0.01), hemoglobin (p < 0.01), and heart rate (p < 0.05). CONCLUSIONS: Known and established physiological determinants of oxygen delivery accounted for a significant proportion of the rSO2 signal, which provides evidence that NIRS is a viable modality to assess cerebral oxygenation in critically ill adults. Further elucidation of the determinants of rSO2 has the potential to develop a NIRS-guided resuscitation algorithm during critical illness. TRIAL REGISTRATION: This trial is registered on clinicaltrials.gov (Identifier: NCT02344043 ), retrospectively registered January 8, 2015.

Dysfunctional cerebral autoregulation is associated with delirium in critically ill adults.

Delirium is common during critical illness and is associated with morbidity and mortality, but its pathophysiology is unknown. We tested whether dysfunctional cerebral autoregulation (CA) contributes to the development of delirium. Adult patients (n = 40) with respiratory failure and/or shock were prospectively enrolled. Continuous recordings of regional cerebral oxygen saturation (rSO2) were obtained by near-infrared spectroscopy (NIRS) during the first 72 h of intensive care unit (ICU) admission. CA function was estimated by the cerebral oximetry index (COx), which is the time-varying correlation between rSO2 and mean arterial pressure (MAP). Delirium was assessed daily. The median ICU stay was seven days (IQR 4-13). Twenty-four patients (60%) screened positive for delirium on at least one day during their stay. Taking positive COx values to reflect periods of CA dysfunction, we found that the cumulative duration of CA dysfunction during the first one to three days in the ICU was significantly associated with the subsequent development of delirium. Additionally, we assessed two alternative methods for estimating optimal MAP targets in individual patients. In summary, early disturbances in CA may contribute to delirium, and NIRS-derived rSO2 may be used to identify individual perfusion targets in critically ill patients.

Low brain tissue oxygenation contributes to the development of delirium in critically ill patients: A prospective observational study.

PURPOSE: To test the hypothesis that poor brain tissue oxygenation (BtO2) during the first 24h of critical illness correlates with the proportion of time spent delirious. We also sought to define the physiological determinants of BtO2. MATERIALS AND METHODS: Adult patients admitted to the ICU within the previous 24h were considered eligible for enrollment if they required mechanical ventilation, and/or vasopressor support. BtO2 was measured using near-infrared spectroscopy, for 24h after enrollment. Hourly vital signs and clinically ordered arterial and central venous blood gases were collected throughout BtO2 monitoring. Patients were screened daily for delirium with the confusion assessment method for the intensive care unit (CAM-ICU). RESULTS: BtO2 and the proportion of time spent delirious did not result in a significant correlation (p=0.168). However, critically ill patients who spent the majority of their ICU stay delirious had significantly lower mean BtO2 compared to non-delirious patients, (p=0.017). BtO2 correlated positively with central venous pO2 (p=0.00003) and hemoglobin concentration (p=0.001). Logistic regression indicated that lower BtO2, higher narcotic doses and a history of alcohol abuse were independent risk factors for delirium. CONCLUSIONS: Poor cerebral oxygenation during the first 24 hours of critical illness contributes to the development of delirium. TRIAL REGISTRATION: This trial is registered on clinicaltrials.gov (Identifier: NCT02344043), retrospectively registered January 8, 2015.

Outcomes of elderly critically ill medical and surgical patients: a multicentre cohort study.

PURPOSE: Very elderly (over 80 yr of age) critically ill patients admitted to medical-surgical intensive care units (ICUs) have a high incidence of mortality, prolonged hospital length of stay, and dependent living conditions should they survive. The primary purpose of this study is to describe the outcomes and differences in outcomes between very elderly medical patients and their surgical counterparts admitted to Canadian ICUs, thereby informing decision-making for clinicians and substitute decision-makers. METHODS: This was a prospective multicentre cohort study of very elderly medical and surgical patients admitted to 22 Canadian academic and non-academic ICUs. Outcome measures included ICU length of stay and mortality, hospital length of stay and mortality, and disposition following hospital discharge. RESULTS: There were 1,671 patients evaluated in this study. Patient demographics included a mean age of 84.5 yr, baseline Acute Physiology and Chronic Health Evaluation (APACHE) II score of 22.4, baseline Sequential Organ Failure Assessment (SOFA) score of 5.3, overall ICU mortality of 21.8%, and overall hospital mortality of 35.0%. Medical patient median ICU length of stay was 4.1 days, hospital length of stay was 16.2 days, ICU mortality was 26.5%, and hospital mortality was 41.5%. Surgical patient median ICU length of stay was 3.8 days, hospital length of stay was 20.1 days, ICU mortality was 18.7%, and hospital mortality was 31.6%. Only 45.0% of medical patients and 41.6% of surgical emergency patients were able to return home to live. CONCLUSIONS: In this large sample of critically ill medical and surgical patients, the admission SOFA score and hospital lengths of stay were not different between the two groups, but medical patients had longer ICU lengths of stay and higher ICU and hospital mortality than surgical patients.

A clinical prediction tool for hospital mortality in critically ill elderly patients.

BACKGROUND: Very elderly (80 years of age and above) critically ill patients admitted to medical intensive care units (ICUs) have a high incidence of mortality, prolonged hospital length of stay, and living in a dependent state should they survive. OBJECTIVE: The objective was to develop a clinical prediction tool for hospital mortality to improve future end-of-life decision making for very elderly patients who are admitted to Canadian ICUs. DESIGN: This was a prospective, multicenter cohort study. SETTING: Data from 1033 very elderly medical patients admitted to 22 Canadian academic and nonacademic ICUs were analyzed. INTERVENTIONS: A univariate analysis of selected predictors to ascertain prognostic power was performed, followed by multivariable logistic regression to derive the final prediction tool. MAIN RESULTS: We included 1033 elderly patients in the analyses. Mean age was 84.6±3.5 years, 55% were male, mean Acute Physiology and Chronic Health Evaluation II score was 23.1±7.9, Sequential Organ Failure Assessment score was 5.3±3.4, median ICU length of stay was 4.1 (interquartile range, 6.2) days, median hospital length of stay was 16.2 (interquartile range, 25.0) days, and ICU mortality and all-cause hospital mortality were 27% and 41%, respectively. Important predictors of hospital mortality at the time of ICU admission include age (85-90 years of age had an odds ratio of hospital mortality of 1.63 [1.04-2.56]; >90 years of age had an odds ratio of hospital mortality of 2.64 [1.27-5.48]), serum creatinine (120-300 had an odds ratio of hospital mortality of 1.57 [1.01-2.44]; >300 had an odds ratio of hospital mortality of 5.29 [2.43-11.51]), Glasgow Coma Scale (13-14 had an odds ratio of hospital mortality of 2.09 [1.09-3.98]; 8-12 had an odds ratio of hospital mortality of 2.31 [1.34-3.97]; 4-7 had an odds ratio of hospital mortality of 5.75 [3.02-10.95]; 3 had an odds ratio of hospital mortality of 8.97 [3.70-21.74]), and serum pH (<7.15 had an odds ratio of hospital mortality of 2.44 [1.07-5.60]). CONCLUSION: We identified high-risk characteristics for hospital mortality in the elderly population and developed a Risk Scale that may be used to inform discussions regarding goals of care in the future. Further study is warranted to validate the Risk Scale in other settings and evaluate its impact on clinical decision making.

The adequacy of timely empiric antibiotic therapy for ventilator-associated pneumonia: an important determinant of outcome.

OBJECTIVE: The individual impact of timeliness vs adequacy of empiric antibiotic therapy for a clinical suspicion of ventilator-associated pneumonia (CSVAP) is unknown. Accordingly, in patients with CSVAP and timely initiation of empiric antibiotic therapy, we determined the impact of inadequate therapy (IT). METHODS: Analysis of a randomized trial of CSVAP treated empirically with meropenem or meropenem plus ciprofloxacin was done. Adequate therapy (AT) was considered present if all pathogens in the index culture were sensitive to the empiric antibiotics; IT was defined as the presence of pathogens resistant to the empiric antibiotics. A priori, for Pseudomonas sp, 2 antibiotics with activity against the organisms were required for AT to be considered present. RESULTS: Of 739 patients with CSVAP, 350 had positive cultures: 313 (89.4%) had AT, and 37 (10.6%), IT. The IT group had higher intensive care unit (35.1% vs 11.8%, P = .0001) and hospital mortalities (48.7% vs 19.5%, P < .0001), increased mechanical ventilation (15.8 vs 6.8 days, P = .0005), intensive care unit stay (13.5 vs 8.4 days, P = .02), and hospital stay (42.2 vs 27.9 days, P = .04). In multivariate analysis and a separate case control analysis, the odds ratio of hospital mortality with IT was 3.05 (95% confidence interval, 1.25-7.45; P = .01) and 3.00 (95% confidence interval, 1.24-7.24; P = .01), respectively. CONCLUSION: In the context of early administration of empiric broad spectrum antibiotics for CSVAP, IT is associated with higher morbidity and mortality.

Mortality, attributable mortality, and clinical events as end points for clinical trials of ventilator-associated pneumonia and hospital-acquired pneumonia.

Appropriate end points are crucial for the successful interpretation of clinical trials. Choosing end points for therapeutic trials of ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP) requires careful consideration, because they are complications of critical illness. It may be difficult to distinguish the consequences of VAP and HAP from manifestations of the underlying illnesses, and it is important to determine their incremental magnitude, to plan for possible treatment effects and, thus, sample size calculations. In this article, we discuss mortality, attributable mortality, and time to clinical events as possible end points for HAP and/or VAP trials. Because of the paucity of evidence on HAP, we focus predominantly on VAP. In a systematic review of applicable trials, VAP appears to have slight intensive care unit and low hospital-attributable mortality. VAP is associated with prolonged durations of intensive care unit stay, hospital stay, and mechanical ventilation. Because of these findings, superiority trials of VAP treatment that use mortality as a primary end point are not possible. Equivalency studies are possible, but there are sample size implications. The use of time to clinical event end points, especially when combined with mortality, may be the best option for trial in the future.

Determinants of outcome in patients with a clinical suspicion of ventilator-associated pneumonia.

INTRODUCTION: In the absence of a reference standard, a probabilistic approach to the diagnosis of ventilator-associated pneumonia (VAP) has been proposed; and clinician judgment augmented by microbiological tests is used to guide therapy for patients having a clinical suspicion of VAP (CSVAP). However, the correlation of both clinician judgment at the time of CSVAP and the probability of VAP with clinical outcomes is unknown. In a cohort of patients with CSVAP, we sought to determine the correlation of clinician judgment and the probability of VAP with clinical outcomes. In addition, we studied the impact of the clinical and microbiological components of CSVAP on the processes of care and outcomes. METHODS: We performed a retrospective analysis of data from a multicenter, randomized trial in 740 patients with CSVAP. Prospective clinician judgment of VAP probability at the time of CSVAP and retrospective adjudication of VAP were compared with clinical outcomes. The following determinants of CSVAP on outcomes were studied: time of CSVAP, index culture results, and the presence of bacteremia. RESULTS: Neither clinician index of suspicion for VAP nor retrospective adjudication of VAP correlated with clinical outcomes. For CSVAP, occurrence >7 days after start of mechanical ventilation and negative index cultures were associated with worse outcomes. Bacteremia was associated with the development of increased organ dysfunction. CONCLUSION: In patients with CSVAP, clinician judgment as to the probability of VAP does not correlate with processes of care and outcomes; and its use to group patients into those with and without VAP is of limited clinical utility.

The impact of ventilator-associated pneumonia on the Canadian health care system.

INTRODUCTION: Ventilator-associated pneumonia (VAP) is a cause of morbidity and mortality in critically ill patients. It is associated with increased health care costs and duration of mechanical ventilation. Using published data and information from public health care providers, we sought to determine the impact of VAP on the Canadian health care system. METHODS: Ventilator-associated pneumonia incidence, attributable mortality, and intensive care unit (ICU) utilization/resource data were obtained through Canadian published and institutional data. Ontario case cost methodology was used for the cost of a critical care bed which is CAN dollars 2396 per day, excluding treatment costs. Antibiotic acquisition costs for Ontario were used. Physician reimbursement rates were obtained from the provincial ministries of health. Ventilator-associated pneumonia data, ICU resource data, and costs were combined to determine the impact of VAP. RESULTS: For the Canadian health care system; ICU utilization is 217 episodes per 100000 population and 1150 days of mechanical ventilation per 100000. The incidence of VAP is 10.6 cases per 1000 ventilator days (95% CI, 5.1-16.1). Ventilator-associated pneumonia increases ICU length of stay 4.3 days (95% CI, 1.5-7.0 days) per episode. The attributable mortality of VAP is 5.8% (95% CI, -2.4 to 14). The number of cases of VAP is estimated to be approximately 4000 cases per year (95% CI, 1900-6100). This results in 230 deaths per year with the lower and upper confidence intervals ranging from 0 to 580. Ventilator-associated pneumonia accounts for approximately 17000 ICU days per year or around 2% of all ICU days in Canada. The cost to the health care system is CAN dollars 46 million (possible range, dollars 10 million to 82 million) per year. CONCLUSION: The impact of VAP on the Canadian health care system is considerable. Eradication of this preventable nosocomial infection would save lives and conserve scarce health care resources.

Venous thromboembolism in critical illness in a community intensive care unit.

BACKGROUND: Venous thromboembolism (VTE) can be a life-threatening complication of critical illness. Venous thromboembolism rates observed depend on the population studied, the screening modality used, and thromboprophylaxis prescribed. Few studies report on the rates of clinically diagnosed VTE in critically ill patients. The purpose of this study was to characterize the incidence of clinically diagnosed VTE, prophylactic strategies used, and diagnostic studies ordered in a critically ill population at a tertiary community intensive care unit (ICU), both during and after their ICU stay. METHODS: We did a retrospective chart review of 600 consecutive critically ill patients admitted to a tertiary community ICU. RESULTS: Fifty (8.3%) patients developed VTE over the course of their ICU and hospital stay (18 [3.0%] patients during their ICU stay and 32 [5.7% of 561 ICU survivors] patients after ICU discharge). By ICU admission diagnosis, most events occurred in neurosurgical patients, although this group comprised only 24.8% of the population. Across all subgroups, most VTE events occurred after ICU discharge. Intensive care unit patients received thromboprophylaxis 87.6% (95% confidence interval, 81.5-93.7) of the time spent in ICU. However, thromboprophylaxis was administered significantly less often after transfer to the ward compared with within the ICU (from 87.6% to 59.8%, P < .001). CONCLUSION: The rates of clinically diagnosed VTE rates in critically ill patients are substantial. Venous thromboembolism occurs before, during, and after ICU discharge. Continued vigilance and thromboprophylaxis are warranted across the continuum of critical illness.