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.).

Guidelines for the Acute Treatment of Cerebral Edema in Neurocritical Care Patients.

BACKGROUND: Acute treatment of cerebral edema and elevated intracranial pressure is a common issue in patients with neurological injury. Practical recommendations regarding selection and monitoring of therapies for initial management of cerebral edema for optimal efficacy and safety are generally lacking. This guideline evaluates the role of hyperosmolar agents (mannitol, HTS), corticosteroids, and selected non-pharmacologic therapies in the acute treatment of cerebral edema. Clinicians must be able to select appropriate therapies for initial cerebral edema management based on available evidence while balancing efficacy and safety. METHODS: The Neurocritical Care Society recruited experts in neurocritical care, nursing, and pharmacy to create a panel in 2017. The group generated 16 clinical questions related to initial management of cerebral edema in various neurological insults using the PICO format. A research librarian executed a comprehensive literature search through July 2018. The panel screened the identified articles for inclusion related to each specific PICO question and abstracted necessary information for pertinent publications. The panel used GRADE methodology to categorize the quality of evidence as high, moderate, low, or very low based on their confidence that the findings of each publication approximate the true effect of the therapy. RESULTS: The panel generated recommendations regarding initial management of cerebral edema in neurocritical care patients with subarachnoid hemorrhage, traumatic brain injury, acute ischemic stroke, intracerebral hemorrhage, bacterial meningitis, and hepatic encephalopathy. CONCLUSION: The available evidence suggests hyperosmolar therapy may be helpful in reducing ICP elevations or cerebral edema in patients with SAH, TBI, AIS, ICH, and HE, although neurological outcomes do not appear to be affected. Corticosteroids appear to be helpful in reducing cerebral edema in patients with bacterial meningitis, but not ICH. Differences in therapeutic response and safety may exist between HTS and mannitol. The use of these agents in these critical clinical situations merits close monitoring for adverse effects. There is a dire need for high-quality research to better inform clinicians of the best options for individualized care of patients with cerebral edema.

Ceftriaxone to PRevent pneumOnia and inflammaTion aftEr Cardiac arresT (PROTECT): study protocol for a randomized, placebo-controlled trial.

BACKGROUND: Pneumonia is the most common infection after out-of-hospital cardiac arrest (OHCA) occurring in up to 65% of patients who remain comatose after return of spontaneous circulation. Preventing infection after OHCA may (1) reduce exposure to broad-spectrum antibiotics, (2) prevent hemodynamic derangements due to local and systemic inflammation, and (3) prevent infection-associated morbidity and mortality. METHODS: The ceftriaxone to PRevent pneumOnia and inflammaTion aftEr Cardiac arrest (PROTECT) trial is a randomized, placebo-controlled, single-center, quadruple-blind (patient, treatment team, research team, outcome assessors), non-commercial, superiority trial to be conducted at Maine Medical Center in Portland, Maine, USA. Ceftriaxone 2 g intravenously every 12 h for 3 days will be compared with matching placebo. The primary efficacy outcome is incidence of early-onset pneumonia occurring < 4 days after mechanical ventilation initiation. Concurrently, T cell-mediated inflammation bacterial resistomes will be examined. Safety outcomes include incidence of type-one immediate-type hypersensitivity reactions, gallbladder injury, and Clostridioides difficile-associated diarrhea. The trial will enroll 120 subjects over approximately 3 to 4 years. DISCUSSION: The PROTECT trial is novel in its (1) inclusion of OHCA survivors regardless of initial heart rhythm, (2) use of a low-risk antibiotic available in the USA that has not previously been tested after OHCA, (3) inclusion of anti-inflammatory effects of ceftriaxone as a novel mechanism for improved clinical outcomes, and (4) complete metagenomic assessment of bacterial resistomes pre- and post-ceftriaxone prophylaxis. The long-term goal is to develop a definitive phase III trial powered for mortality or functional outcome. TRIAL REGISTRATION: ClinicalTrials.gov NCT04999592 . Registered on August 10, 2021.

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.

Ventilator autocycling and delayed recognition of brain death.

BACKGROUND: Improvements in technology play an important role in caring for critically ill patients. One example is the advance in ventilator design to facilitate triggering of mechanical breaths. Minimal changes in circuit flow unrelated to respiratory effort can trigger a ventilator breath and may mislead caregivers in recognizing brain death. METHODS: We observed patients with devastating brain injuries in a mixed medical/surgical intensive care unit (ICU) with a high clinical suspicion for brain death including the absence of cranial nerve function with apparent spontaneous breathing during patient-triggered modes of mechanical ventilation. Further clinical observation for spontaneous respirations was assessed upon removal of ventilatory support. RESULTS: Nine patients with brain injury due to multiple etiologies were identified and demonstrated no spontaneous respirations when formally assessed for apnea. Length of time between brain death and its recognition could not be determined. CONCLUSION: When brain-dead patients who are suitable organ donors are mistakenly identified as having cerebral activity, the diagnosis of brain death is delayed. This delay impacts resource utilization, impedes recovery and function of organs for donation, and adversely affects donor families, potential recipients of organs, and patient donors who may have testing and treatment that cannot be beneficial. Patients with catastrophic brain injury and absent cranial nerve function should undergo immediate formal apnea testing.

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.

Resistance training improves strength and functional measures in patients with end-stage renal disease.

BACKGROUND: The current study was designed to examine the effect of 12 weeks of resistance training on strength and functional ability in 10 medically stable hemodialysis patients (age, 42.8 +/- 4.4 years). METHODS: Subjects were tested on four separate occasions, each separated by 6 weeks. The first (T1) and second tests (T2) were controls with no exercise intervention between them. T3 followed 6 weeks of resistance training, and T4 occurred after 12 weeks of training. Variables tested included percentage of body fat, distance covered in the 6-minute walk test, peak torque of quadriceps muscles of the dominant leg, maximal handgrip strength, normal and maximal walking speeds, and time to complete 10 repetitions of the sit-to-stand-to-sit test. Data were analyzed by means of a one-way repeated-measures analysis of variance procedure. RESULTS: Results indicate that after 12 weeks of training, there was a significant (P < 0.05) increase (12.7%) in peak torque at 90 degrees /s (139.1 +/- 19.3 nm) compared with T1 and T2 (mean, 124.1 +/- 18.7 [SEM]; 123.5 +/- 16.9 Nm), respectively. The distance covered during the 6-minute walk was increased ( approximately 5%; P < 0.05) compared with baseline (T1, 522.1 +/- 46.2 m; 521.9 +/- 48.5 m) after 6 weeks of training (548.3 +/- 52.1 m) and remained elevated at week 12 (546.5 +/- 54.2 m). Maximal walking speed was increased (P < 0.05) by week 12 (195.9 +/- 15.4 cm/s) compared with baseline (T1, 182.9 +/- 12.7; 185.5 +/- 13.0 cm/s). Time to complete 10 repetitions of the sit-to-stand-to-sit test decreased at 12 weeks (17.8 +/- 1.9 seconds) versus baseline (T1, 20.3 +/- 1.5 seconds; T2, 20.6 +/- 5.5 seconds). CONCLUSION: Resistance training can be used safely to increase strength and functional capacity in stable hemodialysis patients.

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.

The pulmonary artery catheter in critical care.

Pulmonary artery catheterization has been a routine part of care for critically ill patients over the past 25 years. Primary hemodynamic data regarding cardiac output and pulmonary pressures can be utilized to make diagnoses and guide therapy. Tissue oxygen delivery and utilization allow inferences about the efficiency of the cardiopulmonary system and the impact of disease and medical therapies on tissue metabolism. Goals of high level invasive monitoring of cardiopulmonary function with pulmonary artery catheterization are organ salvage and minimizing complications associated with critical illness. Optimizing renal perfusion and minimizing pulmonary congestion with precise volume titration are common reasons for performing pulmonary artery catheterization in the intensive care unit. Despite being reassuring to clinicians that hemodynamic therapy is optimal, multiple data from well conducted clinical studies have not demonstrated outcome benefits to patients related to pulmonary artery catheterization. Less invasive techniques to obtain data regarding hemodynamic function are now entering the clinical arena and are being actively investigated.