A Systematic Review of Donor Serum Sodium Level and Its Impact on Transplant Recipients.

BACKGROUND: An important aspect of donor management is the optimization of serum sodium levels. OBJECTIVE: To perform a systematic review to determine the effects of donor sodium levels on heart, lung, kidney, and pancreas graft function, recipient mortality, and to identify the optimal donor serum sodium target. METHODS: We searched MEDLINE, Cochrane, Guideline databases, and trial registries from 1946 to May 2019 for studies investigating the effects of donor serum sodium levels on transplant outcomes in all non-hepatic organs. A two-step independent review process was used to identify relevant articles based on inclusion/exclusion criteria. We describe the results narratively, assess the risk of bias, and apply GRADE methodology to evaluate the certainty in the evidence. RESULTS: We included 18 cohort studies in our final analysis (n=28,007). 3 of 4 studies demonstrated an association between donor serum sodium and successful organ transplantation. 5 studies reported no association with graft function, while 6 studies did. 5 studies reported on recipient survival, 3 of which suggested donor sodium is unlikely to be associated with recipient survival. The included studies had serious risk of bias, and the certainty in evidence was deemed to be very low. CONCLUSION: In low risk of bias studies, donor sodium dysregulation is unlikely to affect kidney graft function or mortality of heart and kidney recipients, but the certainty in the evidence is very low due to inconsistency and imprecision. Further research is required to refine the serum sodium target range, quantify the dose-response curve, and identify organs most vulnerable to sodium dysregulation.

Design and rationale of the atrial fibrillation occurring transiently with stress (AFOTS) incidence study.

BACKGROUND: Atrial fibrillation (AF) is often detected for the first time in patients hospitalized for medical illness or non-cardiovascular surgery. AF occurring transiently with stress (AFOTS) describes this manifestation of AF, which may either be the result of a non-cardiac stressor, or existing paroxysmal AF that was not previously detected. Current estimates of AFOTS incidence are imprecise: ranging from 1 to 44%, owing to the marked heterogeneity in patient populations, identification and methods used to detect AFOTS. METHODS: The prospective, two-centre epidemiological AFOTS Incidence study will enroll 250 consecutive participants without a history of AF but with at increased risk of AF (Age ≥ 65 or >50 with one risk factor for AF) admitted to intensive care units (ICUs) for medical illness or non-cardiac surgery. Upon admission, participants will wear an ECG patch monitor that will remain in place for 14 days, or until discharge from hospital. Patients' consent to participation is deferred for up to 72 h after admission. The primary endpoint is the incidence of AF lasting ≥30 s. The study is powered to detect an AF incidence of 17% ±â€¯5%. RESULTS: We conducted a vanguard feasibility study, and 55 participants have completed participation. The median duration of monitoring was seven days. AF was detected by the clinical team in 8 participants (14%; 95% Confidence Interval 7-26%). CONCLUSIONS: The AFOTS Incidence study will employ a systematic and highly sensitive protocol for detecting AFOTS in medical illness and non-cardiac surgery ICU patients. This study is feasible and will provide a reliable estimate of the true incidence of AFOTS in this population.

European Respiratory Society guidelines on long-term home non-invasive ventilation for management of COPD

While the role of acute non-invasive ventilation (NIV) has been shown to improve outcome in acute life-threatening hypercapnic respiratory failure in COPD, the evidence of clinical efficacy of long-term home NIV (LTH-NIV) for management of COPD is less. This document provides evidence-based recommendations for the clinical application of LTH-NIV in chronic hypercapnic COPD patients. The European Respiratory Society task force committee was composed of clinicians, methodologists and experts in the field of LTH-NIV. The committee developed recommendations based on the GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology. The GRADE Evidence to Decision framework was used to formulate recommendations. A number of topics were addressed under a narrative format which provides a useful context for clinicians and patients. The task force committee delivered conditional recommendations for four actionable PICO (target population-intervention-comparator-outcome) questions, 1) suggesting for the use of LTH-NIV in stable hypercapnic COPD; 2) suggesting for the use of LTH-NIV in COPD patients following a COPD exacerbation requiring acute NIV 3) suggesting for the use of NIV settings targeting a reduction in carbon dioxide and 4) suggesting for using fixed pressure support as first choice ventilator mode. Managing hypercapnia may be an important intervention for improving the health outcome of COPD patients with chronic respiratory failure. The task force conditionally supports the application of LTH-NIV to improve health outcome by targeting a reduction in carbon dioxide in COPD patients with persistent hypercapnic respiratory failure. These recommendations should be applied in clinical practice by practitioners that routinely care for chronic hypercapnic COPD patients.

High flow nasal cannula compared with conventional oxygen therapy for acute hypoxemic respiratory failure: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis summarizes the safety and efficacy of high flow nasal cannula (HFNC) in patients with acute hypoxemic respiratory failure. METHODS: We performed a comprehensive search of MEDLINE, EMBASE, and Web of Science. We identified randomized controlled trials that compared HFNC to conventional oxygen therapy. We pooled data and report summary estimates of effect using relative risk for dichotomous outcomes and mean difference or standardized mean difference for continuous outcomes, with 95% confidence intervals. We assessed risk of bias of included studies using the Cochrane tool and certainty in pooled effect estimates using GRADE methods. RESULTS: We included 9 RCTs (n = 2093 patients). We found no difference in mortality in patients treated with HFNC (relative risk [RR] 0.94, 95% confidence interval [CI] 0.67-1.31, moderate certainty) compared to conventional oxygen therapy. We found a decreased risk of requiring intubation (RR 0.85, 95% CI 0.74-0.99) or escalation of oxygen therapy (defined as crossover to HFNC in the control group, or initiation of non-invasive ventilation or invasive mechanical ventilation in either group) favouring HFNC-treated patients (RR 0.71, 95% CI 0.51-0.98), although certainty in both outcomes was low due to imprecision and issues related to risk of bias. HFNC had no effect on intensive care unit length of stay (mean difference [MD] 1.38 days more, 95% CI 0.90 days fewer to 3.66 days more, low certainty), hospital length of stay (MD 0.85 days fewer, 95% CI 2.07 days fewer to 0.37 days more, moderate certainty), patient reported comfort (SMD 0.12 lower, 95% CI 0.61 lower to 0.37 higher, very low certainty) or patient reported dyspnea (standardized mean difference [SMD] 0.16 lower, 95% CI 1.10 lower to 1.42 higher, low certainty). Complications of treatment were variably reported amongst included studies, but little harm was associated with HFNC use. CONCLUSION: In patients with acute hypoxemic respiratory failure, HFNC may decrease the need for tracheal intubation without impacting mortality.

Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017

OBJECTIVE: To update the 2008 consensus statements for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in adult and pediatric patients. PARTICIPANTS: A multispecialty task force of 16 international experts in Critical Care Medicine, endocrinology, and guideline methods, all of them members of the Society of Critical Care Medicine and/or the European Society of Intensive Care Medicine. DESIGN/METHODS: The recommendations were based on the summarized evidence from the 2008 document in addition to more recent findings from an updated systematic review of relevant studies from 2008 to 2017 and were formulated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The strength of each recommendation was classified as strong or conditional, and the quality of evidence was rated from high to very low based on factors including the individual study design, the risk of bias, the consistency of the results, and the directness and precision of the evidence. Recommendation approval required the agreement of at least 80% of the task force members. RESULTS: The task force was unable to reach agreement on a single test that can reliably diagnose CIRCI, although delta cortisol (change in baseline cortisol at 60 min of <9 µg/dl) after cosyntropin (250 µg) administration and a random plasma cortisol of <10 µg/dl may be used by clinicians. We suggest against using plasma free cortisol or salivary cortisol level over plasma total cortisol (conditional, very low quality of evidence). For treatment of specific conditions, we suggest using intravenous (IV) hydrocortisone <400 mg/day for ≥3 days at full dose in patients with septic shock that is not responsive to fluid and moderate- to high-dose vasopressor therapy (conditional, low quality of evidence). We suggest not using corticosteroids in adult patients with sepsis without shock (conditional recommendation, moderate quality of evidence). We suggest the use of IV methylprednisolone 1 mg/kg/day in patients with early moderate to severe acute respiratory distress syndrome (PaO2/FiO2 < 200 and within 14 days of onset) (conditional, moderate quality of evidence). Corticosteroids are not suggested for patients with major trauma (conditional, low quality of evidence). CONCLUSIONS: Evidence-based recommendations for the use of corticosteroids in critically ill patients with sepsis and septic shock, acute respiratory distress syndrome, and major trauma have been developed by a multispecialty task force.

Canadian Guidelines for Controlled Pediatric Donation After Circulatory Determination of Death-Summary Report

OBJECTIVES: Create trustworthy, rigorous, national clinical practice guidelines for the practice of pediatric donation after circulatory determination of death in Canada. METHODS: We followed a process of clinical practice guideline development based on World Health Organization and Canadian Medical Association methods. This included application of Grading of Recommendations Assessment, Development, and Evaluation methodology. Questions requiring recommendations were generated based on 1) 2006 Canadian donation after circulatory determination of death guidelines (not pediatric specific), 2) a multidisciplinary symposium of national and international pediatric donation after circulatory determination of death leaders, and 3) a scoping review of the pediatric donation after circulatory determination of death literature. Input from these sources drove drafting of actionable questions and Good Practice Statements, as defined by the Grading of Recommendations Assessment, Development, and Evaluation group. We performed additional literature reviews for all actionable questions. Evidence was assessed for quality using Grading of Recommendations Assessment, Development, and Evaluation and then formulated into evidence profiles that informed recommendations through the evidence-to-decision framework. Recommendations were revised through consensus among members of seven topic-specific working groups and finalized during meetings of working group leads and the planning committee. External review was provided by pediatric, critical care, and critical care nursing professional societies and patient partners. RESULTS: We generated 63 Good Practice Statements and seven Grading of Recommendations Assessment, Development, and Evaluation recommendations covering 1) ethics, consent, and withdrawal of life-sustaining therapy, 2) eligibility, 3) withdrawal of life-sustaining therapy practices, 4) ante and postmortem interventions, 5) death determination, 6) neonatal pediatric donation after circulatory determination of death, 7) cardiac and innovative pediatric donation after circulatory determination of death, and 8) implementation. For brevity, 48 Good Practice Statement and truncated justification are included in this summary report. The remaining recommendations, detailed methodology, full Grading of Recommendations Assessment, Development, and Evaluation tables, and expanded justifications are available in the full text report. CONCLUSIONS: This process showed that rigorous, transparent clinical practice guideline development is possible in the domain of pediatric deceased donation. Application of these recommendations will increase access to pediatric donation after circulatory determination of death across Canada and may serve as a model for future clinical practice guideline development in deceased donation

Protocol adherence for continuously titrated interventions in randomized trials: an overview of the current methodology and case study.

BACKGROUND: The standard definition for protocol adherence is the proportion of all scheduled doses that are delivered. In clinical research, this definition has several limitations when evaluating protocol adherence in trials that study interventions requiring continuous titration. DISCUSSION: Building upon a specific case study, we analyzed a recent trial of a continuously titrated intervention to assess the impact of different definitions of protocol deviations on the interpretation of protocol adherence. The OVATION pilot trial was an open-label randomized controlled trial of higher (75-80 mmHg) versus lower (60-65 mmHg) mean arterial pressure (MAP) targets for vasopressor therapy in shock. In this trial, potential protocol deviations were defined as MAP values outside the targeted range for >4 consecutive hours during vasopressor therapy without synchronous and consistent adjustments of vasopressor doses. An adjudication committee reviewed each potential deviation to determine if it was clinically-justified or not. There are four reasons for this contextual measurement and reporting of protocol adherence. First, between-arm separation is a robust measure of adherence to complex protocols. Second, adherence assessed by protocol deviations varies in function of the definition of deviations and the frequency of measurements. Third, distinguishing clinically-justified vs. not clinically-justified protocol deviations acknowledges clinically sensible bedside decision-making and offers a clear terminology before the trial begins. Finally, multiple metrics exist to report protocol deviations, which provides different information but complementary information on protocol adherence. CONCLUSIONS: In trials of interventions requiring continuous titration, metrics used for defining protocol deviations have a considerable impact on the interpretation of protocol adherence. Definitions for protocol deviations should be prespecified and correlated with between-arm separation, if it can be measured.

Approaches to interpreting and choosing the best treatments in network meta-analyses.

When randomized trials have addressed multiple interventions for the same health problem, network meta-analyses (NMAs) permit researchers to statistically pool data from individual studies including evidence from both direct and indirect comparisons. Grasping the significance of the results of NMAs may be very challenging. Authors may present the findings from such analyses in several numerical and graphical ways. In this paper, we discuss ranking strategies and visual depictions of rank, including the surface under the cumulative ranking (SUCRA) curve method. We present ranking approaches' merits and limitations and provide an example of how to apply the results of a NMA to clinical practice.

Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy wasdeveloped at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroupsand among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.(AU)

Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient

"OBJECTIVE: To update the 2002 version of ""Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient."" DESIGN: A Task Force comprising 17 members of the Society of Critical Medicine with particular expertise in the use of neuromuscular-blocking agents; a Grading of Recommendations Assessment, Development, and Evaluation expert; and a medical writer met via teleconference and three face-to-face meetings and communicated via e-mail to examine the evidence and develop these practice guidelines. Annually, all members completed conflict of interest statements; no conflicts were identified. This activity was funded by the Society for Critical Care Medicine, and no industry support was provided. METHODS: Using the Grading of Recommendations Assessment, Development, and Evaluation system, the Grading of Recommendations Assessment, Development, and Evaluation expert on the Task Force created profiles for the evidence related to six of the 21 questions and assigned quality-of-evidence scores to these and the additional 15 questions for which insufficient evidence was available to create a profile. Task Force members reviewed this material and all available evidence and provided recommendations, suggestions, or good practice statements for these 21 questions. RESULTS: The Task Force developed a single strong recommendation: we recommend scheduled eye care that includes lubricating drops or gel and eyelid closure for patients receiving continuous infusions of neuromuscular-blocking agents. The Task Force developed 10 weak recommendations. 1) We suggest that a neuromuscular-blocking agent be administered by continuous intravenous infusion early in the course of acute respiratory distress syndrome for patients with a PaO2/FIO2 less than 150. 2) We suggest against the routine administration of an neuromuscular-blocking agents to mechanically ventilated patients with status asthmaticus. 3) We suggest a trial of a neuromuscular-blocking agents in life-threatening situations associated with profound hypoxemia, respiratory acidosis, or hemodynamic compromise. 4) We suggest that neuromuscular-blocking agents may be used to manage overt shivering in therapeutic hypothermia. 5) We suggest that peripheral nerve stimulation with train-of-four monitoring may be a useful tool for monitoring the depth of neuromuscular blockade but only if it is incorporated into a more inclusive assessment of the patient that includes clinical assessment. 6) We suggest against the use of peripheral nerve stimulation with train of four alone for monitoring the depth of neuromuscular blockade in patients receiving continuous infusion of neuromuscular-blocking agents. 7) We suggest that patients receiving a continuous infusion of neuromuscular-blocking agent receive a structured physiotherapy regimen. 8) We suggest that clinicians target a blood glucose level of less than 180 mg/dL in patients receiving neuromuscular-blocking agents. 9) We suggest that clinicians not use actual body weight and instead use a consistent weight (ideal body weight or adjusted body weight) when calculating neuromuscular-blocking agents doses for obese patients. 10) We suggest that neuromuscular-blocking agents be discontinued at the end of life or when life support is withdrawn. In situations in which evidence was lacking or insufficient and the study results were equivocal or optimal clinical practice varies, the Task Force made no recommendations for nine of the topics. 1) We make no recommendation as to whether neuromuscular blockade is beneficial or harmful when used in patients with acute brain injury and raised intracranial pressure. 2) We make no recommendation on the routine use of neuromuscular-blocking agents for patients undergoing therapeutic hypothermia following cardiac arrest. 3) We make no recommendation on the use of peripheral nerve stimulation to monitor degree of block in patients undergoing therapeutic hypothermia. 4) We make no recommendation on the use of neuromuscular blockade to improve the accuracy of intravascular-volume assessment in mechanically ventilated patients. 5) We make no recommendation concerning the use of electroencephalogram-derived parameters as a measure of sedation during continuous administration of neuromuscular-blocking agents. 6) We make no recommendation regarding nutritional requirements specific to patients receiving infusions of neuromuscular-blocking agents. 7) We make no recommendation concerning the use of one measure of consistent weight over another when calculating neuromuscular-blocking agent doses in obese patients. 8) We make no recommendation on the use of neuromuscular-blocking agents in pregnant patients. 9) We make no recommendation on which muscle group should be monitored in patients with myasthenia gravis receiving neuromuscular-blocking agents. Finally, in situations in which evidence was lacking or insufficient but expert consensus was unanimous, the Task Force developed six good practice statements. 1) If peripheral nerve stimulation is used, optimal clinical practice suggests that it should be done in conjunction with assessment of other clinical findings (e.g., triggering of the ventilator and degree of shivering) to assess the degree of neuromuscular blockade in patients undergoing therapeutic hypothermia. 2) Optimal clinical practice suggests that a protocol should include guidance on neuromuscular-blocking agent administration in patients undergoing therapeutic hypothermia. 3) Optimal clinical practice suggests that analgesic and sedative drugs should be used prior to and during neuromuscular blockade, with the goal of achieving deep sedation. 4) Optimal clinical practice suggests that clinicians at the bedside implement measure to attenuate the risk of unintended extubation in patients receiving neuromuscular-blocking agents. 5) Optimal clinical practice suggests that a reduced dose of an neuromuscular-blocking agent be used for patients with myasthenia gravis and that the dose should be based on peripheral nerve stimulation with train-of-four monitoring. 6) Optimal clinical practice suggests that neuromuscular-blocking agents be discontinued prior to the clinical determination of brain death."

National Guidelines for Colorectal Cancer Screening in Saudi Arabia with strength of recommendations and quality of evidence

BACKGROUND: Colorectal cancer is the most common cancer among Saudi men and the third commonest among Saudi women. Given the predominance of colorectal cancer compared with other cancers in Saudi Arabia, context-specific guidelines are needed for screening. METHODS: Experts from the Saudi Society of Colon and Rectal Surgery, Saudi Gastroenterology Association, Saudi Oncology Society, Saudi Chapter of Enterostomal Therapy, Family Medicine and Department of Public Health at the Saudi Arabian Ministry of Health and a patient advocate was assembled by the Saudi Centre for Evidence-Based Healthcare, a subsidiary of the Saudi Arabian Ministry of Health. The panel collaborated with a methodological team from McMaster University, Canada to develop national guidelines for colorectal cancer screening. After identifying key questions, the panel conducted a systematic review of all reports on the utility of screening, the cost of screening for colorectal cancer in Saudi Arabia and on the values and preferences of Saudi patients. Meta- analyses, when appropriate, were performed to generate pooled estimates of effect. Using the GRADE approach, the panel used the evidence-to-decision (EtD) framework to assess all domains important in determining the strength and direction of the recommendations (benefits and harms, values and preferences, resource implications, equity, acceptability, and feasibility). Judgments related to the EtD domains were resolved through consensus or voting, if consensus was not reached. The final recommendations were developed during a two-day meeting held in Riyadh, Saudi Arabia in March 2015. Conflicts of interests among the panel members were handled according to the World Health Organization rules. LIMITATIONS: There is lack of national data on the incidence of adenomatous polyps or the age groups in which the incidence surges. There were no national clinical trials assessing the effectiveness of the different modalities of screening for colorectal cancer and their impact on mortality. CONCLUSION: The panel recommends screening for colorectal cancer in Saudi Arabia in asymptomatic Saudi patients at average risk of colorectal cancer. An infrastructure should be built to achieve that goal.(AU)

Fluid type and the use of renal replacement therapy in sepsis: a systematic review and network meta-analysis.

Fluid resuscitation, along with the early administration of antibiotics, is the cornerstone of treatment for patients with sepsis. However, whether differences in resuscitation fluids impact on the requirements for renal replacement therapy (RRT) remains unclear. To examine this issue, we performed a network meta-analysis (NMA), including direct and indirect comparisons, that addressed the effect of different resuscitation fluids on the use of RRT in patients with sepsis. The data sources MEDLINE, EMBASE, ACPJC, CINAHL and Cochrane Central Register were searched up to March 2014. Eligible studies included randomized trials reported in any language that enrolled adult patients with sepsis or septic shock and addressed the use of RRT associated with alternative resuscitation fluids. The risk of bias for individual studies and the overall certainty of the evidence were assessed. Ten studies (6664 patients) that included a total of nine direct comparisons were assessed. NMA at the four-node level showed that an increased risk of receiving RRT was associated with fluid resuscitation with starch versus crystalloid [odds ratio (OR) 1.39, 95% credibility interval (CrI) 1.17-1.66, high certainty]. The data suggested no difference between fluid resuscitation with albumin and crystalloid (OR 1.04, 95% CrI 0.78-1.38, moderate certainty) or starch (OR 0.74, 95% CrI 0.53-1.04, low certainty). NMA at the six-node level showed a decreased risk of receiving RRT with balanced crystalloid compared to heavy starch (OR 0.50, 95% CrI 0.34-0.74, moderate certainty) or light starch (OR 0.70, 95% CrI 0.49-0.99, high certainty). There was no significant difference between balanced crystalloid and saline (OR 0.85, 95% CrI 0.56-1.30, low certainty) or albumin (OR 0.82, 95% CrI 0.49-1.37, low certainty). Of note, these trials vary in terms of case mix, fluids evaluated, duration of fluid exposure and risk of bias. Imprecise estimates contributed to low confidence in most estimates of effect. Among the patients with sepsis, fluid resuscitation with crystalloids compared to starch resulted in reduced use of RRT; the same may be true for albumin versus starch.