Sedation and Delirium in the Intensive Care Unit-A Practice-Based Approach.

INTRODUCTION: Critically ill patients often require sedation for comfort and to facilitate therapeutic interventions. Sedation practice guidelines provide an evidence-based framework with recommendations that can help improve key sedation-related outcomes. MATERIALS AND METHODS: We conducted a narrative review of current guidelines and recent trials on sedation. RESULTS: From a practice perspective, current guidelines share many limitations including lack of consensus on the definition of light sedation, optimal frequency of sedation assessment, optimal timing for light sedation and consideration of combinations of sedatives. We proposed several strategies to address these limitations and improve outcomes: 1) early light sedation within the first 48 hours with time-weighted monitoring (overall time spent in light sedation in the first 48 hours-sedation intensity-has a dose-dependent relationship with mortality risk, delirium and time to extubation); 2) provision of analgesia with minimal or no sedation where possible; 3) a goal-directed and balanced multimodal approach that combines the benefits of different agents and minimise their side effects; 4) use of dexmedetomidine and atypical antipsychotics as a sedative-sparing strategy to reduce weaning-related agitation, shorten ventilation time and accelerate physical and cognitive rehabilitation; and 5) a bundled approach to sedation that provides a framework to improve relevant clinical outcomes. CONCLUSION: More effort is required to develop a practical, time-weighted sedation scoring system. Emphasis on a balanced, multimodal appraoch that targets light sedation from the early phase of acute critical illness is important to achieve optimal sedation, lower mortality, shorten time on ventilator and reduce delirium.

Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) randomised clinical trial: study protocol.

INTRODUCTION: Bloodstream infections are a leading cause of mortality and morbidity; the duration of treatment for these infections is understudied. METHODS AND ANALYSIS: We will conduct an international, multicentre randomised clinical trial of shorter (7 days) versus longer (14 days) antibiotic treatment among hospitalised patients with bloodstream infections. The trial will include 3626 patients across 60 hospitals and 6 countries. We will include patients with blood cultures confirming a pathogenic bacterium after hospital admission. Exclusion criteria will include patient factors (severe immunosuppression), infection site factors (endocarditis, osteomyelitis, undrained abscesses, infected prosthetic material) and pathogen factors (Staphylococcus aureus, Staphylococcus lugdunensis, Candida and contaminant organisms). We will leave the selection of specific antibiotics, doses and route of delivery to the discretion of treating physicians; no placebo control will be used given the diversity of pathogens and sources of bacteraemia. The intervention will be assignment of treatment duration to be 7 versus 14 days. We will minimise selection bias via central randomisation with variable block sizes, with concealed allocation until day 7 of adequate antibiotic treatment. The primary outcome is 90-day survival; we will test whether 7 days is non-inferior to 14 days of treatment, with a non-inferiority margin of 4% absolute mortality. Secondary outcomes include hospital and intensive care unit (ICU) mortality, relapse rates of bacteraemia, hospital and ICU length of stay, mechanical ventilation and vasopressor duration, antibiotic-free days, Clostridium difficile infection, antibiotic allergy and adverse events and colonisation/infection with antibiotic-resistant organisms. ETHICS AND DISSEMINATION: The study has been approved by the ethics review board at each participating site. Sunnybrook Health Sciences Centre is the central ethics committee. We will disseminate study results via the Canadian Critical Care Trials Group and other collaborating networks to set the global paradigm for antibiotic treatment duration for non-staphylococcal Gram-positive, Gram-negative and anaerobic bacteraemia, among patients admitted to hospital. TRIAL REGISTRATION NUMBER: The BALANCE (Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness) trial was registered at www.clinicaltrials.gov (registration number: NCT03005145).

Use of neostigmine in capecitabine-induced paralytic ileus.

Paralytic ileus is a recognised side effect of the oral agent capecitabine. We present this report on a patient with metastatic colorectal cancer who was treated with capecitabine and presented with persistent paralytic ileus which did not respond to standard conservative measures. Neostigmine was administered safely, resulting in resolution of the paralytic ileus. This approach merits further investigation.