Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis.

BACKGROUND: Guidelines currently recommend targeting light sedation with dexmedetomidine or propofol for adults receiving mechanical ventilation. Differences exist between these sedatives in arousability, immunity, and inflammation. Whether they affect outcomes differentially in mechanically ventilated adults with sepsis undergoing light sedation is unknown. METHODS: In a multicenter, double-blind trial, we randomly assigned mechanically ventilated adults with sepsis to receive dexmedetomidine (0.2 to 1.5 µg per kilogram of body weight per hour) or propofol (5 to 50 µg per kilogram per minute), with doses adjusted by bedside nurses to achieve target sedation goals set by clinicians according to the Richmond Agitation-Sedation Scale (RASS, on which scores range from -5 [unresponsive] to +4 [combative]). The primary end point was days alive without delirium or coma during the 14-day intervention period. Secondary end points were ventilator-free days at 28 days, death at 90 days, and age-adjusted total score on the Telephone Interview for Cognitive Status questionnaire (TICS-T; scores range from 0 to 100, with a mean of 50±10 and lower scores indicating worse cognition) at 6 months. RESULTS: Of 432 patients who underwent randomization, 422 were assigned to receive a trial drug and were included in the analyses - 214 patients received dexmedetomidine at a median dose of 0.27 µg per kilogram per hour, and 208 received propofol at a median dose of 10.21 µg per kilogram per minute. The median duration of receipt of the trial drugs was 3.0 days (interquartile range, 2.0 to 6.0), and the median RASS score was -2.0 (interquartile range, -3.0 to -1.0). We found no difference between dexmedetomidine and propofol in the number of days alive without delirium or coma (adjusted median, 10.7 vs. 10.8 days; odds ratio, 0.96; 95% confidence interval [CI], 0.74 to 1.26), ventilator-free days (adjusted median, 23.7 vs. 24.0 days; odds ratio, 0.98; 95% CI, 0.63 to 1.51), death at 90 days (38% vs. 39%; hazard ratio, 1.06; 95% CI, 0.74 to 1.52), or TICS-T score at 6 months (adjusted median score, 40.9 vs. 41.4; odds ratio, 0.94; 95% CI, 0.66 to 1.33). Safety end points were similar in the two groups. CONCLUSIONS: Among mechanically ventilated adults with sepsis who were being treated with recommended light-sedation approaches, outcomes in patients who received dexmedetomidine did not differ from outcomes in those who received propofol. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01739933.).

The Economic and Humanistic Burden of Severe Sepsis.

Sepsis and severe sepsis in particular remain a major health problem worldwide. Their cost to society extends well beyond lives lost, as the impact of survivorship is increasingly felt. A review of the medical literature was completed in MEDLINE using the search phrases "severe sepsis" and "septic shock" and the MeSH terms "epidemiology", "statistics", "mortality", "economics", and "quality of life". Results were limited to human trials that were published in English from 2002 to 2014. Articles were classified by dominant themes to address epidemiology and outcomes, including quality of life of both patient and family caregivers, as well as societal costs. The severity of sepsis is determined by the number of organ failures and the presence of shock. In most developed countries, severe sepsis and septic shock account for disproportionate mortality and resource utilization. Although mortality rates have decreased, overall mortality continues to increase and is projected to accelerate as people live longer with more chronic illness. Among those who do survive, impaired quality of life, increased dependence, and rehospitalization increase healthcare consumption and, along with increased mortality, all contribute to the humanistic burden of severe sepsis. A large part of the economic burden of severe sepsis occurs after discharge. Initial inpatient costs represent only 30 % of the total cost and are related to severity and length of stay, whereas lost productivity and other indirect medical costs following hospitalization account for the majority of the economic burden of sepsis. Timeliness of treatment as well as avoidance of intensive care unit (ICU)-acquired illness/morbidity lead to important differences in both cost and outcome of treatment for severe sepsis and represent areas where improvement in care is possible. The degree of sophistication of a health system from a national perspective results in significant differences in resource use and outcomes for patients with serious infections. Comprehensive understanding of the cost and humanistic burden of severe sepsis provides an initial practical framework for health policy development and resource use.

Establishing goals of volume management in critically ill patients with renal failure.

BACKGROUND: Volume management remains a challenging component of caring for the critically ill. Renal failure complicates fluid management. We sought to identify relationships between delta blood volume and physiology-based targets for both the adequacy of left ventricular filling (stroke volume index [SVI]) and preload dependency (stroke volume variability [SVV]) in patients undergoing dialysis in the intensive care unit. METHODS: Patients undergoing dialysis with an arterial line in place were eligible. Delta blood volume was measured during dialysis along with simultaneous SVI and SVV via an arterial pressure cardiac output monitor. Patients were dichotomized as "negative" fluid strategy if fluid was removed, or "positive" fluid strategy if fluid was added during renal replacement therapy. Delta blood volume's association with SVI and SVV was examined separately by fluid strategy group. RESULTS: A total of 26 patients (11 continuous and 15 intermittent dialysis) were investigated. Compared with that in patients with negative fluid strategy, SVV was significantly higher at baseline in patients with positive fluid strategy, while baseline SVI was significantly lower. Fluid removal was associated with significant increases to SVV in both strategy groups. Fluid removal was associated with significant decreases to SVI, and this effect was similar regardless of fluid strategy. CONCLUSION: Physiologic variables assessing cardiac performance (SVI) and preload responsiveness (SVV) provide simple yet meaningful targets when one is determining the best approach for volume management in critically ill patients undergoing dialysis.

Safe placement of central venous catheters: a measured approach.

INTRODUCTION: To develop a simple method for safely placing central venous catheters (CVCs) outside the heart from the subclavian or internal jugular vein in compliance with Food and Drug Administration (FDA) and manufacturer guidelines. METHODS: Patients requiring CVCs were enrolled into this prospective trial. Central venous catheters were inserted into the subclavian or internal jugular vein from either the right or left side to a depth of 15 cm. Chest radiographs were obtained immediately after insertion of the catheter to check tip placement and to evaluate for mechanical complications. RESULTS: Operators successfully placed 201 of 210 (96%) CVCs outside the heart. Six of these required repositioning. Nine catheter tips were located in an intracardiac position. No cases of pneumothorax, hemothorax, or pericardial tamponade occurred. One case of delayed hydrothorax due to superior vena cava injury occurred. CONCLUSIONS: Using a 15-cm insertion depth via the internal jugular or subclavian vein results in safe catheter tip location in the majority of procedures consistent with FDA and manufacturer guidelines.