Perioperative use of crystalloids in patients undergoing open radical cystectomy: balanced Ringer's maleate versus a glucose 5%/potassium-based balanced solution: study protocol for a randomized controlled trial

BACKGROUND The optimal crystalloid solution to use perioperatively in patients undergoing open radical cystectomy remains unclear. Many of the fluids used for intravenous hydration contain supraphysiologic concentrations of chloride, which can induce hyperchloremia and metabolic acidosis, resulting in renal vasoconstriction and decreased renal function. In addition, patients receiving less fluid and less sodium show faster recovery of gastrointestinal (GI) function after colonic surgery. METHODS AND DESIGN This is an investigator-initiated, single-center, randomized, controlled, parallel group trial with assessor-blinded outcome assessment, in the Department of Urology, University Hospital Bern, Switzerland. The study will involve 44 patients with bladder cancer scheduled for radical cystectomy and urinary diversion. The primary outcome is the duration between the end of surgery and the return of the GI function (first defecation). Secondary outcomes are fluid balance (body weight difference postoperatively versus preoperatively) and the incidence of kidney function disorders according to the Risk-Injury-Failure-Loss-End Stage Renal Disease (RIFLE classification). An equal number of patients are allocated to receive Ringerfundin® solution or a glucose/potassium-based balanced crystalloid solution as baseline infusion during the entire time that intravenous administration of fluid is necessary during the perioperative period. The randomized crystalloid solution is infused at a rate of 1 ml/kg/h until the bladder has been removed, followed by 3 ml/kg/h until the end of surgery. Postoperative hydration is identical in both groups and consists of 1,500 ml of the randomized crystalloid solution per 24 hours. Postoperative patient care is identical in both groups; patients are allowed to drink clear fluids immediately after surgery, and liquid diet is started on postoperative day 1, as well as active mobilization and the use of chewing gum. Body weight is measured daily in the morning. Time of first flatus and first defecation are recorded. DISCUSSION This trial assesses the benefits and harms of two different balanced crystalloid solutions for perioperative fluid management in patients undergoing open radical cystectomy with urinary diversion, with regard to return of GI function and effects on postoperative renal function. TRIAL REGISTRATION Current Controlled Trials ISRCTN32976792 (registered on November 21 2013).

Corticosteroid treatment for community-acquired pneumonia--the STEP trial: study protocol for a randomized controlled trial

BACKGROUND Community-acquired pneumonia (CAP) is the third-leading infectious cause of death worldwide. The standard treatment of CAP has not changed for the past fifty years and its mortality and morbidity remain high despite adequate antimicrobial treatment. Systemic corticosteroids have anti-inflammatory effects and are therefore discussed as adjunct treatment for CAP. Available studies show controversial results, and the question about benefits and harms of adjunct corticosteroid therapy has not been conclusively resolved, particularly in the non-critical care setting. METHODS/DESIGN This randomized multicenter study compares a treatment with 7 days of prednisone 50 mg with placebo in adult patients hospitalized with CAP independent of severity. Patients are screened and enrolled within the first 36 hours of presentation after written informed consent is obtained. The primary endpoint will be time to clinical stability, which is assessed every 12 hours during hospitalization. Secondary endpoints will be, among others, all-cause mortality within 30 and 180 days, ICU stay, duration of antibiotic treatment, disease activity scores, side effects and complications, value of adrenal function testing and prognostic hormonal and inflammatory biomarkers to predict outcome and treatment response to corticosteroids. Eight hundred included patients will provide an 85% power for the intention-to-treat analysis of the primary endpoint. DISCUSSION This largest to date double-blind placebo-controlled multicenter trial investigates the effect of adjunct glucocorticoids in 800 patients with CAP requiring hospitalization. It aims to give conclusive answers about benefits and risks of corticosteroid treatment in CAP. The inclusion of less severe CAP patients will be expected to lead to a relatively low mortality rate and survival benefit might not be shown. However, our study has adequate power for the clinically relevant endpoint of clinical stability. Due to discontinuing glucocorticoids without tapering after seven days, we limit duration of glucocorticoid exposition, which may reduce possible side effects. TRIAL REGISTRATION 7 September 2009 on ClinicalTrials.gov: NCT00973154.

Safe refeeding management of anorexia nervosa inpatients: an evidence-based protocol.

OBJECTIVE Anorexia nervosa is associated with several serious medical complications related to malnutrition, severe weight loss, and low levels of micronutrients. The refeeding phase of these high-risk patients bears a further threat to health and potentially fatal complications. The objective of this study was to examine complications due to refeeding of patients with anorexia nervosa, as well as their mortality rate after the implementation of guidelines from the European Society of Clinical Nutrition and Metabolism. METHODS We analyzed retrospective, observational data of a consecutive, unselected anorexia nervosa cohort during a 5-y period. The sample consisted of 65 inpatients, 14 were admitted more than once within the study period, resulting in 86 analyzed cases. RESULTS Minor complications associated with refeeding during the first 10 d (replenishing phase) were recorded in nine cases (10.5%), four with transient pretibial edemas and three with organ dysfunction. In two cases, a severe hypokalemia occurred. During the observational phase of 30 d, 16 minor complications occurred in 14 cases (16.3%). Six infectious and 10 non-infectious complications occurred. None of the patients with anorexia nervosa died within a follow-up period of 3 mo. CONCLUSIONS Our data demonstrate that the seriousness and rate of complications during the replenishment phase in this high-risk population can be kept to a minimum. The findings indicate that evidence-based refeeding regimens, such as our guidelines are able to reduce complications and prevent mortality. Despite anorexia nervosa, our sample were affected by serious comorbidities, no case met the full diagnostic criteria for refeeding syndrome.

Solitaire™ with the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) trial: protocol for a randomized, controlled, multicenter study comparing the Solitaire revascularization device with IV tPA with IV tPA alone in acute ischemic stroke.

RATIONALE Early reperfusion in patients experiencing acute ischemic stroke is critical, especially for patients with large vessel occlusion who have poor prognosis without revascularization. Solitaire™ stent retriever devices have been shown to immediately restore vascular perfusion safely, rapidly, and effectively in acute ischemic stroke patients with large vessel occlusions. AIM The aim of the study was to demonstrate that, among patients with large vessel, anterior circulation occlusion who have received intravenous tissue plasminogen activator, treatment with Solitaire revascularization devices reduces degree of disability 3 months post stroke. DESIGN The study is a global multicenter, two-arm, prospective, randomized, open, blinded end-point trial comparing functional outcomes in acute ischemic stroke patients who are treated with either intravenous tissue plasminogen activator alone or intravenous tissue plasminogen activator in combination with the Solitaire device. Up to 833 patients will be enrolled. PROCEDURES Patients who have received intravenous tissue plasminogen activator are randomized to either continue with intravenous tissue plasminogen activator alone or additionally proceed to neurothrombectomy using the Solitaire device within six-hours of symptom onset. STUDY OUTCOMES The primary end-point is 90-day global disability, assessed with the modified Rankin Scale (mRS). Secondary outcomes include mortality at 90 days, functional independence (mRS ≤ 2) at 90 days, change in National Institutes of Health Stroke Scale at 27 h, reperfusion at 27 h, and thrombolysis in cerebral infarction 2b/3 flow at the end of the procedure. ANALYSIS Statistical analysis will be conducted using simultaneous success criteria on the overall distribution of modified Rankin Scale (Rankin shift) and proportions of subjects achieving functional independence (mRS 0-2).

The Prevention of Delirium and Complications Associated with Surgical Treatments (PODCAST) study: protocol for an international multicentre randomised controlled trial

INTRODUCTION Postoperative delirium is one of the most common complications of major surgery, affecting 10-70% of surgical patients 60 years and older. Delirium is an acute change in cognition that manifests as poor attention and illogical thinking and is associated with longer intensive care unit (ICU) and hospital stay, long-lasting cognitive deterioration and increased mortality. Ketamine has been used as an anaesthetic drug for over 50 years and has an established safety record. Recent research suggests that, in addition to preventing acute postoperative pain, a subanaesthetic dose of intraoperative ketamine could decrease the incidence of postoperative delirium as well as other neurological and psychiatric outcomes. However, these proposed benefits of ketamine have not been tested in a large clinical trial. METHODS The Prevention of Delirium and Complications Associated with Surgical Treatments (PODCAST) study is an international, multicentre, randomised controlled trial. 600 cardiac and major non-cardiac surgery patients will be randomised to receive ketamine (0.5 or 1 mg/kg) or placebo following anaesthetic induction and prior to surgical incision. For the primary outcome, blinded observers will assess delirium on the day of surgery (postoperative day 0) and twice daily from postoperative days 1-3 using the Confusion Assessment Method or the Confusion Assessment Method for the ICU. For the secondary outcomes, blinded observers will estimate pain using the Behavioral Pain Scale or the Behavioral Pain Scale for Non-Intubated Patients and patient self-report. ETHICS AND DISSEMINATION The PODCAST trial has been approved by the ethics boards of five participating institutions; approval is ongoing at other sites. Recruitment began in February 2014 and will continue until the end of 2016. Dissemination plans include presentations at scientific conferences, scientific publications, stakeholder engagement and popular media. REGISTRATION DETAILS The study is registered at clinicaltrials.gov, NCT01690988 (last updated March 2014). The PODCAST trial is being conducted under the auspices of the Neurological Outcomes Network for Surgery (NEURONS). TRIAL REGISTRATION NUMBER NCT01690988 (last updated December 2013).