Incorporating Dynamic Assessment of Fluid Responsiveness Into Goal-Directed Therapy: A Systematic Review and Meta-Analysis.

OBJECTIVE: Dynamic tests of fluid responsiveness have been developed and investigated in clinical trials of goal-directed therapy. The impact of this approach on clinically relevant outcomes is unknown. We performed a systematic review and meta-analysis to evaluate whether fluid therapy guided by dynamic assessment of fluid responsiveness compared with standard care improves clinically relevant outcomes in adults admitted to the ICU. DATA SOURCES: Randomized controlled trials from MEDLINE, EMBASE, CENTRAL, clinicaltrials.gov, and the International Clinical Trials Registry Platform from inception to December 2016, conference proceedings, and reference lists of relevant articles. STUDY SELECTION: Two reviewers independently identified randomized controlled trials comparing dynamic assessment of fluid responsiveness with standard care for acute volume resuscitation in adults admitted to the ICU. DATA EXTRACTION: Two reviewers independently abstracted trial-level data including population characteristics, interventions, clinical outcomes, and source of funding. Our primary outcome was mortality at longest duration of follow-up. Our secondary outcomes were ICU and hospital length of stay, duration of mechanical ventilation, and frequency of renal complications. The internal validity of trials was assessed in duplicate using the Cochrane Collaboration's Risk of Bias tool. DATA SYNTHESIS: We included 13 trials enrolling 1,652 patients. Methods used to assess fluid responsiveness included stroke volume variation (nine trials), pulse pressure variation (one trial), and stroke volume change with passive leg raise/fluid challenge (three trials). In 12 trials reporting mortality, the risk ratio for death associated with dynamic assessment of fluid responsiveness was 0.59 (95% CI, 0.42-0.83; I = 0%; n = 1,586). The absolute risk reduction in mortality associated with dynamic assessment of fluid responsiveness was -2.9% (95% CI, -5.6% to -0.2%). Dynamic assessment of fluid responsiveness was associated with reduced duration of ICU length of stay (weighted mean difference, -1.16 d [95% CI, -1.97 to -0.36]; I = 74%; n = 394, six trials) and mechanical ventilation (weighted mean difference, -2.98 hr [95% CI, -5.08 to -0.89]; I = 34%; n = 334, five trials). Three trials were adjudicated at unclear risk of bias; the remaining trials were at high risk of bias. CONCLUSIONS: In adult patients admitted to intensive care who required acute volume resuscitation, goal-directed therapy guided by assessment of fluid responsiveness appears to be associated with reduced mortality, ICU length of stay, and duration of mechanical ventilation. High-quality clinical trials in both medical and surgical ICU populations are warranted to inform routine care.

Extracorporeal membrane oxygenation for blastomycosis-related acute respiratory distress syndrome: a case series.

PURPOSE: Blastomyces dermatitidis is a dimorphic fungus endemic to North America capable of causing fatal respiratory failure. Acute respiratory distress syndrome (ARDS) complicates up to 10% of pulmonary blastomycosis in hospitalized patients and carries a mortality of 50-90%. This report describes the clinical course of four consecutive patients with blastomycosis-related ARDS treated with venovenous extracorporeal membrane oxygenation (ECMO) during 2009-2014. CLINICAL FEATURES: Four adults were referred from northwestern Ontario, Canada with progressive respiratory illnesses. All patients developed diffuse bilateral opacities on chest radiography and required mechanical ventilation within 6-72 hr. Patients satisfied Berlin criteria for severe ARDS with trough PaO2/F i O2 ratios of 44-61 on positive end-expiratory pressure of 12-24 cm H2O. Wet mount microscopy from respiratory samples showed broad-based yeast consistent with B.dermatitidis. Despite lung protective ventilation strategies with maximal F i O2 (patients A-D), neuromuscular blockade (patients A-D), inhaled nitric oxide (patients A and D), and prone positioning (patient D), progressive hypoxemia resulted in initiation of venovenous ECMO by hours 24-90 of mechanical ventilation with subsequent de-escalation of ventilatory support. In all four cases, ECMO decannulation was performed (7-23 days), mechanical ventilation was withdrawn (18-52 days), and the patients survived to hospital discharge (31-87 days). CONCLUSION: This report describes the successful application of ECMO as rescue therapy in aid of four patients with refractory blastomycosis-associated ARDS. In addition to early appropriate antimicrobial therapy, transfer to an institution experienced with ECMO should be considered when caring for patients from endemic areas with rapidly progressive respiratory failure.

The benefits of 24/7 in-house intensivist coverage for prolonged-stay cardiac surgery patients.

OBJECTIVE: The objective of our study was to evaluate the efficacy of 24/7 in-house intensivist care for patients requiring prolonged intensive care unit (ICU) stay following cardiac surgery. METHODS: A propensity-matched retrospective before-and-after observational study comparing 2 models of ICU physician staffing was undertaken. Previously, residents (with intensivist backup) provided care for patients after cardiac surgery (surgical ICU cohort). ICU physician staffing was modified with the implementation of 24/7 in-house board-certified intensivist coverage in a cardiac surgery ICU (cardiac surgery ICU cohort) for postoperative care. Patients with a prolonged ICU stay (ie, >48 hours) were identified and their outcomes analyzed for both models of care. RESULTS: Propensity matching between cohorts was successful for 271 patients (75.7%), with matched patients being used for comparison. There was no difference in ICU or 30-day mortality. There was also no difference in ICU length of stay (LOS); however, the median hospital LOS was significantly shorter in the cardiac surgery ICU cohort (12.3 vs 11.0 days; P < .01). There was a decrease in the proportion of patients receiving transfused red blood cells in the cardiac surgery ICU cohort (80.8% vs 65.7%; P < .001). The cardiac surgery ICU cohort had reduced complications relating to sepsis (4.7% vs 0.7%; P < .01) and renal failure (22.5% vs 12.5%; P < .01); however, the identification of neurologic dysfunction was significantly higher (11.1% vs 20.7%; P < .01). CONCLUSIONS: For patients requiring a prolonged ICU stay, our model of 24/7 in-house intensivist coverage was not associated with changes in ICU LOS, nor ICU and 30-day mortality. However a reduction in blood product use, ICU complications, and total hospital LOS was observed.

Variation in diagnostic testing in ICUs: a comparison of teaching and nonteaching hospitals in a regional system.

OBJECTIVES: To explore variation in the use of diagnostic testing in ICUs, with emphasis on differences between teaching and nonteaching ICUs. DESIGN: Retrospective review of a prospective clinical ICU database. SETTING: Five teaching and four nonteaching ICUs in Winnipeg, Canada, during 2006-2010. PATIENTS: All adults admitted to the nine ICUs during the study period were eligible. After excluding subgroups restricted to teaching ICUs, inter-ICU transfers, prior ICU admission within 90 days, ICU length of stay less than 12 hours, and missing death dates, 10,262 patients were evaluated. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Our primary outcome variable (TotalTesting) was the cumulative number of nine common laboratory tests, three radiologic tests, and electrocardiograms performed in each ICU. We used multivariable median regression to identify factors associated with TotalTesting, including length of stay, demographics, admission details, type and severity of acute illness, and specific medical interventions. We estimated the predictive power of variables as the decline in pseudo-R2 (a goodness-of-fit measure for median regression) when omitting those variables from the model. Median (interquartile range) TotalTesting was 27 (18-49) in teaching ICUs and 20 (13-36) in nonteaching units. With multivariable adjustment, median TotalTesting was 7.1 higher (95% CI, 6.6-7.7) in teaching ICUs. The most influential variable was length of stay, accounting for almost half of the variation. ICU teaching status was the second most important factor, greater than the degree of physiologic derangement and details of medical management. CONCLUSIONS: After adjustment for confounding variables, patients in teaching ICUs had slightly but significantly more diagnostic tests done than those in nonteaching ICUs. In addition to increasing costs, prior studies have shown that excessive testing can cause harm in various ways and does not improve outcomes. Interventions to reduce testing should be directed to all caregivers with responsibility for ordering diagnostic tests, in both teaching and nonteaching institutions.

Impact of 24-hour in-house intensivists on a dedicated cardiac surgery intensive care unit.

BACKGROUND: Intensive care unit (ICU) physician staffing models for cardiac surgery patients vary widely and correlate poorly with outcomes. Clinical outcomes associated with 24-hour, in-house intensivists working in a dedicated post-cardiac surgical unit has not been previously investigated. We sought to examine the safety and efficacy of such a model. METHODS: A retrospective, propensity-matched, cohort study of all patients undergoing a cardiac surgical procedure at a single tertiary center was performed. The control cohort (n = 1,467) consisted of patients admitted to the traditional, mixed surgical intensive care unit (SICU) from January 2005 to January 2007. The intervention cohort (n = 1,089) consisted of patients admitted to a newly created "hybrid" cardiac surgery ICU (CICU) from January 2007 to January 2008, which was staffed by 24-hour in-house consultant intensivists and a daytime, fast track cardiac anesthesiologist. The primary outcomes were blood product utilization, requirement for ventilation, and ICU recidivism. RESULTS: The proportion of patients in the CICU cohort who received transfused red blood cells was decreased compared with the SICU cohort (30.2% versus 42.3%, p < 0.001). Similar reductions in platelets and fresh frozen plasma were also observed. The CICU patients were less likely to arrive to the ICU intubated (43.7% versus 66.5%, p < 0.001). There were no differences in postoperative complications. Overall hospital length of stay was reduced in the CICU cohort by a median of 1 day (6 days [interquartile range, 5 to 8] versus 7 days [5 to 9], p < 0.001). Significant reductions in mortality and ICU recidivism were not observed. CONCLUSIONS: The current Manitoba CICU model of 24-hour intensive care physician/cardiac anesthesiologist staffing in postoperative cardiac surgery care is associated with reduced transfusion of blood components, decreased requirement for mechanical ventilation, and shorter hospital length of stay.

Historical perspectives in critical care medicine: blood transfusion, intravenous fluids, inotropes/vasopressors, and antibiotics.

Significant progress in critical care medicine has been the result of tireless observation, dedicated research, and well-timed serendipity. This article provides a historical perspective for four meaningful therapies in critical care medicine: blood transfusion, fluid resuscitation, vasopressor/inotropic support, and antibiotics. For each therapy, key discoveries and events that have shaped medical history and helped define current practice are discussed. Prominent medical and social pressures that have catalyzed research and innovation in each domain are also addressed, as well as current and future challenges.

Resuscitating patients with early severe sepsis: a Canadian multicentre observational study.

BACKGROUND: Fluid resuscitation is a key factor in restoring hemodynamic stability and tissue perfusion in patients with severe sepsis. We sought to examine associations of the quantity and type of fluid administered in the first six hours after identification of severe sepsis and hospital mortality, intensive care unit (ICU) mortality, and organ failure. METHODS: A retrospective, multicentre cohort study was undertaken at five Canadian tertiary care ICUs. We identified patients with severe sepsis admitted to the ICU between July 1, 2000, and June 30, 2002, using both administrative and clinical databases. Patients were included if they were hypotensive, had an infectious source, and at least two systemic inflammatory response syndrome criteria. We recorded total quantity and type of fluid administered for the first six hours after severe sepsis was identified. The first episode of hypotension defined the starting point for collection of fluid data. Multivariable regression analyses were performed to examine associations between quantity and type of fluid administered and hospital/ICU mortality, and organ failure. RESULTS: Of 2,026 potentially eligible patient charts identified, 496 patients met eligibility criteria. The mean age and Acute Physiology and Chronic Health Evaluation score (APACHE II) were 61.8 +/- 16.5 yr and 29.0 +/- 8.0, respectively. No associations between quantity or type of fluid administered and hospital mortality or ICU mortality were identified, and there were no statistically significant associations between quantity or type of fluid administered and organ failure. However, more fluid resuscitation was associated with an increased risk of cardiovascular failure [odds ratio (OR) and 95% confidence interval (CI)] for 2-4 L 1.67 (1.03-2.70) and > 4 L 2.34 (1.23-4.44) and a reduced risk of renal failure [OR, 95% CI for 2-4 L 0.48 (0.28-0.83) and > 4 L 0.45 (0.22-0.92)] in the first 24 hr of severe sepsis. Administration of colloid and crystalloid fluid as compared to crystalloid fluid alone was associated with a lower risk of renal failure [OR, 95% CI 0.45 (0.26 to 0.76)]. CONCLUSION: An association between hospital mortality and quantity or type of fluid administered in the first six hours after the diagnosis of severe sepsis was not identifiable. These findings should be considered as hypothesis-generating and warrant confirmation or refutation by randomized controlled trials.

Low-dose intrathecal morphine does not delay early extubation after cardiac surgery.

PURPOSE: This study was designed to examine the efficacy of low-dose intrathecal morphine (ITM) on extubation times and pain control after cardiac surgery. METHODS: 43 patients undergoing elective cardiac surgery were enrolled in this prospective, randomized, double-blind placebo controlled trial. Patients were given a pre-induction dose of ITM (6 microg x kg(-1) per ideal body weight in 5 mL normal saline, group ITM) or 5 mL of intrathecal normal saline (group ITS). Anesthesia was induced with thiopental (3 mg x kg(-1)), sufentanil, midazolam and rocuronium. The total allowable doses of sufentanil and midazolam for the entire case were limited to 0.5 microg x kg(-1) and 0.045 mg x kg(-1) respectively. Anesthesia was maintained with isoflurane before and during cardiopulmonary bypass (CPB), and with propofol after CPB. In the postanesthesia care unit, patients received nurse-administered morphine followed by patient-controlled analgesia morphine. Serial visual analogue scale pain scores, morphine use, mini-mental state examinations and pulmonary function tests were measured for 48 hr. Patient satisfaction questionnaires were completed at the time of discharge. RESULTS: Mean times to extubation from the application of dressings were short and did not differ between groups (ITM = 41.4 +/- 33.0 min, ITS = 39.2 +/- 37.1 min). During the first 24 hr postoperatively, the ITM group had improved pain control and a lower iv morphine requirement than the control group, both at rest and during deep breathing. Both forced expiratory volume in one second and forced vital capacity were improved in the ITM group. There were no differences in spinal-related side effects or in the overall complication rates. Patient satisfaction was high in both groups. CONCLUSION: Low-dose ITM for cardiac surgery did not delay early extubation, but it improved postoperative analgesia and pulmonary function.

Management following resuscitation from cardiac arrest: recommendations from the 2003 Rocky Mountain Critical Care Conference.

PURPOSE: To propose a strategy for the management of patients admitted to critical care units after resuscitation from cardiac arrest. SOURCE: Prior to the conference relevant studies were identified via literature searches and brief reviews circulated on the following topics: glucose and blood pressure management; therapeutic hypothermia; prearrest outcome prediction; post-arrest outcome prediction; and management of myocardial ischemia. Two days were devoted to assessing evidence and developing a management strategy at the conference. Consensus opinion of conference participants [intensive care unit (ICU) physicians] was used when high grade evidence was unavailable. Additional literature searches and data grading were performed post-conference. PRINCIPAL FINDINGS: High grade evidence was lacking in most areas. Specific goals of treatment were proposed for: general care; neurologic care; respiratory care; cardiac care; and gastrointestinal care. There was adequate evidence to recommend therapeutic hypothermia for comatose patients who had witnessed ventricular fibrillation or ventricular tachycardia arrests. Conference participants supported extending therapeutic hypothermia to other presenting rhythms in selected circumstances. Additional goals included mean arterial pressure 80 to 100 mmHg, glucose 5 to 8 mmol.L(-1) using insulin infusions, and PaO(2) > 100 mmHg for the first 24 hr. Absent withdrawal to pain 72 hr after resuscitation should prompt consideration of palliative care. The level of evidence for other recommendations was low. CONCLUSIONS: The proposed management strategy represents an approach to manage patients in the ICU following resuscitation from cardiac arrest. Most of the recommendations are based on low grade evidence. Additional research is needed to improve the evidence base. A standard post-arrest management strategy could help facilitate future research.

Variable ventilation improves perioperative lung function in patients undergoing abdominal aortic aneurysmectomy.

BACKGROUND: Optimizing perioperative mechanical ventilation remains a significant clinical challenge. Experimental models indicate that "noisy" or variable ventilation (VV)--return of physiologic variability to respiratory rate and tidal volume--improves lung function compared with monotonous control mode ventilation (CV). VV was compared with CV in patients undergoing abdominal aortic aneurysmectomy, a patient group known to be at risk of deteriorating lung function perioperatively. METHODS: After baseline measurements under general anesthesia (CV with a tidal volume of 10 ml/kg and a respiratory rate of 10 breaths/min), patients were randomized to continue CV or switch to VV (computer control of the ventilator at the same minute ventilation but with 376 combinations of respiratory rate and tidal volume). Lung function was measured hourly for the next 6 h during surgery and recovery. RESULTS: Forty-one patients for aneurysmectomy were studied. The characteristics of the patients in the two groups were similar. Repeated-measures analysis of variance (group x time interaction) revealed greater arterial oxygen partial pressure (P = 0.011), lower arterial carbon dioxide partial pressure (P = 0.012), lower dead space ventilation (P = 0.011), increased compliance (P = 0.049), and lower mean peak inspiratory pressure (P = 0.013) with VV. CONCLUSIONS: The VV mode of ventilation significantly improved lung function over CV in patients undergoing abdominal aortic aneurysmectomy.