Measurement and prognosis of frail patients undergoing transcatheter aortic valve implantation: a systematic review and meta-analysis.

OBJECTIVES: Our objectives were to review the literature to identify frailty instruments in use for transcatheter aortic valve implantation (TAVI) recipients and synthesise prognostic data from these studies, in order to inform clinical management of frail patients undergoing TAVI. METHODS: We systematically reviewed the literature published in 2006 or later. We included studies of patients with aortic stenosis, diagnosed as frail, who underwent a TAVI procedure that reported mortality or clinical outcomes. We categorised the frailty instruments and reported on the prevalence of frailty in each study. We summarised the frequency of clinical outcomes and pooled outcomes from multiple studies. We explored heterogeneity and performed subgroup analysis, where possible. We also used Grading of Recommendations, Assessment, Development and Evaluation (GRADE) to assess the overall certainty of the estimates. RESULTS: Of 49 included studies, 21 used single-dimension measures to assess frailty, 3 used administrative data-based measures, and 25 used multidimensional measures. Prevalence of frailty ranged from 5.67% to 90.07%. Albumin was the most commonly used single-dimension frailty measure and the Fried or modified Fried phenotype were the most commonly used multidimensional measures. Meta-analyses of studies that used either the Fried or modified Fried phenotype showed a 30-day mortality of 7.86% (95% CI 5.20% to 11.70%) and a 1-year mortality of 26.91% (95% CI 21.50% to 33.11%). The GRADE system suggests very low certainty of the respective estimates. CONCLUSIONS: Frailty instruments varied across studies, leading to a wide range of frailty prevalence estimates for TAVI recipients and substantial heterogeneity. The results provide clinicians, patients and healthcare administrators, with potentially useful information on the prognosis of frail patients undergoing TAVI. This review highlights the need for standardisation of frailty measurement to promote consistency. PROSPERO REGISTRATION NUMBER: CRD42018090597.

Frailty in patients undergoing transcatheter aortic valve implantation: a protocol for a systematic review.

INTRODUCTION: Aortic stenosis is a significant cause of morbidity and mortality in older patients. The advent of transcatheter aortic valve implantation (TAVI) offers an alternative to surgical aortic valve replacement for patients with severe symptomatic aortic stenosis who are at high or intermediate risk of adverse events. Existing evidence highlights the importance of frailty as a predictor of poor outcomes post-TAVI. The objective of this study is to review the operationalisation of frailty instruments for TAVI recipients and determine clinical outcomes and the change in quality of life in frail patients undergoing TAVI. METHODS AND ANALYSIS: Methods are reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 checklist. We will search relevant databases to identify published, completed but unpublished and ongoing studies. We will include studies of patients with aortic stenosis, diagnosed as frail and who underwent a TAVI procedure that report mortality, clinical outcomes or health-related quality of life. Retrospective or prospective cohort studies, randomised controlled trials and non-randomised controlled trials will be eligible for inclusion. Two researchers will independently screen articles for inclusion, with disagreements resolved by a third reviewer. One researcher will extract data with audit by a second researcher. The risk of bias in studies will be evaluated using the Quality in Prognosis Studies tool. Meta-analysis of mortality, survival curve and the change in quality of life will be performed if appropriate. Subgroup analysis, sensitivity analysis and meta-regression will be performed if necessary. ETHICS AND DISSEMINATION: Due to the nature of this study, no ethical issues are foreseen. We will disseminate the results of our systematic review through a peer-reviewed journal. TRIAL REGISTRATION NUMBER: CRD42018090597.

Dexmedetomidine for craniotomy under general anesthesia: A systematic review and meta-analysis of randomized clinical trials.

STUDY OBJECTIVE: To assess the efficacy and safety of dexmedetomidine as an adjunct to general anesthesia for craniotomy. DESIGN: A meta-analysis after systematically searching PubMed, Medline, EMBASE, and Cochrane library for randomized trials (RCTs). Relative risk (RR) and weighted mean difference (WMD) were calculated using random-effects meta-analysis. SETTING: Perioperative setting. PATIENTS: Twenty-two RCTs (1348 patients) with craniotomy under general anesthesia were included. INTERVENTIONS: Dexmedetomidine as an adjunct to general anesthesia versus placebo or other anesthetics. MEASUREMENTS: Primary outcomes included procedure success and postoperative pain; Secondary outcomes included cardiac adverse events, postoperative nausea and vomiting (PONV) and other clinically important outcomes. MAIN RESULTS: Dexmedetomidine vs. Placebo: High to moderate quality evidence suggested that dexmedetomidine reduced postoperative pain (WMD -0.25 cm, 95%CI -0.43 to -0.07 cm on a 10 cm visual analogue scale), postoperative nausea and vomiting (PONV, RR 0.57, 95%CI 0.39 to 0.84), hypertension (RR 0.37, 95%CI 0.22 to 0.61) and tachycardia (RR 0.32, 95%CI 0.12 to 0.85) with no significant increase of hypotension and bradycardia. Moderate quality evidence suggested no significant difference in procedural success. Dexmedetomidine vs. Active Comparators (including remifentanil, fentanyl, or propofol): Moderate quality evidence showed no difference in procedural success and postoperative pain. CONCLUSIONS: Dexmedetomidine as an adjunct to general anesthesia shows small benefits in reduction of pain, PONV, and maintains more stable hemodynamics with comparable effects on procedural success versus placebo. Very limited evidence explored comparative effects between dexmedetomidine and active controls. Further evidence is required to evaluate patient-important outcomes and optimal dosing strategies, particularly versus active comparators.

Fibrinogen Concentrate in Cardiovascular Surgery: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Postoperative bleeding remains a frequent complication after cardiovascular surgery and may contribute to serious morbidity and mortality. Observational studies have suggested a relationship between low endogenous plasma fibrinogen concentration and increased risk of postoperative blood loss in cardiac surgery. Although the transfusion of fibrinogen concentrate has been increasing, potential benefits and risks associated with perioperative fibrinogen supplementation in cardiovascular surgery are not fully understood. METHODS: PubMed, Cochrane Library, Ovid MEDLINE, Embase, Web of Science, and China National Knowledge Infrastructure were searched on January 15, 2017, with automated updates searched until February 15, 2018, to identify all randomized controlled trials (RCTs) of fibrinogen concentrate, whether for prophylaxis or treatment of bleeding, in adults undergoing cardiovascular surgery. All RCTs comparing fibrinogen infusion versus any other comparator (placebo/standard of care or another active comparator) in adult cardiovascular surgery and reporting at least 1 predefined clinical outcome were included. The random-effects model was used to calculate risk ratios and weighted mean differences (95% confidence interval [CI]) for dichotomous and continuous variables, respectively. Subgroup analyses by fibrinogen dose and by baseline risk for bleeding were preplanned. RESULTS: A total of 8 RCTs of fibrinogen concentrate in adults (n = 597) of mixed risk or high risk undergoing cardiovascular surgery were included. Compared to placebo or inactive control, perioperative fibrinogen concentrate did not significantly impact risk of all-cause mortality (risk ratio, 0.41; 95% CI, 0.12-1.38; I = 10%; P = .15). Fibrinogen significantly reduced incidence of allogeneic red blood cell transfusion (risk ratio, 0.64; 95% CI, 0.49-0.83; I = 0%; P = .001). No significant differences were found for other clinical outcomes. Subgroup analyses were unremarkable when analyzed according to fibrinogen dose, time of infusion initiation, mean cardiopulmonary bypass time, and rotational thromboelastometry/fibrinogen temogram use (all P values for subgroup interaction were nonsignificant). CONCLUSIONS: Current evidence remains insufficient to support or refute routine perioperative administration of fibrinogen concentrate in patients undergoing cardiovascular surgery. Fibrinogen concentrate may reduce the need for additional allogeneic blood product transfusion in cardiovascular surgery patients at high risk or with evidence of bleeding. However, no definitive advantage was found for reduction in risk of mortality or other clinically relevant outcomes. The small number of clinical events within existing randomized trials suggests that further well-designed studies of adequate power and duration to measure all-cause mortality, stroke, myocardial infarction, reoperation, and thromboembolic events should be conducted. Future studies should also address cost-effectiveness relative to standard of care.

Remifentanil as an alternative to epidural analgesia for vaginal delivery: A meta-analysis of randomized trials.

OBJECTIVES: Although epidural analgesia is considered the gold standard for labor pain management, its use may be restricted in some conditions due to clinical contraindications or availability, and suitable alternatives may be required. The objective of this meta-analysis was to determine whether evidence from randomized trials suggests remifentanil PCA (R-PCA) results in significant differences in maternal satisfaction, analgesic efficacy, and safety compared with conventional epidural analgesia (EA). DESIGN: We conducted a meta-analysis after systematically searching MEDLINE, EMBASE and Cochrane Library for all randomized controlled trials (RCTs) allocating parturients to R-PCA or EA and reporting at least one outcome of interest. PATIENTS: Eight randomized trials of R-PCA vs EA with 2351 patients were included. MEASUREMENTS: The primary outcome of interest was maternal satisfaction. Secondary outcomes included visual analog pain score (VAS at 1, 2, 3h postoperatively), nausea, vomiting, pruritus, hypoxemia, acute respiratory depression or death (maternal or neonatal), need for Cesarean section, and neonatal Apgar score. MAIN RESULTS: Meta-analysis of the randomized trials showed no significant differences between the R-PCA and EA groups for maternal satisfaction, VAS at 2 or 3h, nausea, vomiting, need for cesarean section, respiratory depression, umbilical pH, and neonatal Apgar score at 1min and 5min. However, incidence of hypoxemia was higher [OR 7.48, 95%CI 3.42-16.36] and VAS at 1h was slightly higher [WMD 1.33, 95%CI 0.30-2.36] with R-PCA versus EA. Pruritus was less frequent in the R-PCA group [OR 0.54, 95%CI 0.32-0.89]. Acute respiratory failure and death were not reported in any of the studies. CONCLUSIONS: While no significant differences were detected for maternal satisfaction or for most clinical outcomes, this meta-analysis remains underpowered to rule out clinically-important differences due to the few existing randomized trials. For obstetric patients who are not candidates for EA, R-PCA may provide an alternative for analgesia in the peri-partum period, but caution is warranted particularly regarding hypoxemia, and suggests the need for increased surveillance and monitoring for R-PCA. Further adequately powered randomized trials with a focus on clinically-relevant maternal and neonatal outcomes are required to more accurately characterize the relative benefits and risks of R-PCA versus EA in this population.

Does preoperative rehabilitation for patients planning to undergo joint replacement surgery improve outcomes? A systematic review and meta-analysis of randomised controlled trials.

OBJECTIVES: The clinical impact of preoperative physiotherapy on recovery after joint replacement remains controversial. This systematic review aimed to assess the clinical impact of prehabilitation before joint replacement. DESIGN: We searched PubMed, Embase and Cochrane CENTRAL up to November 2015 for randomised controlled trials comparing prehabilitation versus no prehabilitation before joint replacement surgery. Postoperative pain and function scores were converted to Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function subscales (0-100, high scores indicate worse outcome). Random effects meta-analysis was performed to calculate weighted mean differences (WMD, 95% CI), subgrouped by hip and knee surgery. PRIMARY AND SECONDARY OUTCOMES: Postoperative pain and function scores, time to resume activities of daily living, quality of life, length of hospital stay, total cost, patient satisfaction, postoperative complications, any adverse events and discontinuations. RESULTS: Of 22 studies (1492 patients), 18 had high risk of bias. Prehabilitation slightly reduced pain scores within 4 weeks postoperatively (WMD -6.1 points, 95% CI -10.6 to -1.6 points, on a scale of 0-100), but differences did not remain beyond 4 weeks. Prehabilitation slightly improved WOMAC function score at 6-8 and 12 weeks (WMD -4.0, 95% CI -7.5 to -0.5), and time to climbing stairs (WMD -1.4 days, 95% CI -1.9 to -0.8 days), toilet use (-0.9 days, 95% CI -1.3 to -0.5 days) and chair use (WMD -1.2 days, 95% CI -1.7 to -0.8 days). Effects were similar for knee and hip surgery. Differences were not found for SF-36 scores, length of stay and total cost. Other outcomes of interest were inadequately reported. CONCLUSIONS: Existing evidence suggests that prehabilitation may slightly improve early postoperative pain and function among patients undergoing joint replacement; however, effects remain too small and short-term to be considered clinically-important, and did not affect key outcomes of interest (ie, length of stay, quality of life, costs).