Point-of-care viscoelastic hemostatic testing in cardiac surgery patients: a systematic review and meta-analysis.

PURPOSE: Thromboelastography and rotational thromboelastometry are point-of-care (POC) viscoelastic tests used to help guide blood product administration. It is unclear whether these tests improve clinical or transfusion-related outcomes. The objective of this study was to appraise data from randomized trials evaluating the benefit of POC testing in cardiac surgery patients. Primary outcomes were the proportion of patients transfused with blood products and all-cause mortality. SOURCE: Medline (Ovid), EMBASE (Ovid), CENTRAL (the Cochrane Library-Wiley), Web of Science, Biosis, Scopus, and CINAHL databases, as well as clinical trial registries and conference proceedings were queried from inception to February 2018. PRINCIPAL FINDINGS: We identified 1,917 records, 11 of which were included in our analysis (8,294 patients). Point-of-care testing was not associated with a difference in the proportion of patients transfused with any blood product (risk ratio [RR], 0.90; 95% confidence interval [CI], 0.79 to 1.02; I2 = 51%; four trials, 7,623 patients), or all-cause mortality (RR, 0.73; 95% CI, 0.47 to 1.13; I2 = 5%; six trials, 7,931 patients). Nevertheless, POC testing was weakly associated with a decrease in the proportion of patients receiving red blood cells (RBC) (RR, 0.91; 95% CI, 0.85 to 0.96; I2 = 0%; seven trials, 8,029 patients), and heterogeneous reductions in frozen plasma (FP) (RR, 0.58; 95% CI, 0.34 to 0.99; I2 = 87%; six trials, 7,989 patients) and platelets (RR, 0.66; 95% CI, 0.49 to 0.90; I2 = 65%; seven trials, 8,029 patients). Meta-analysis of the number of units of RBCs and FP was not possible due to heterogeneity in reporting, however POC testing significantly reduced the units of platelets transfused (standard mean difference, -0.09; 95% CI, -0.18 to 0.00; four trials, 7,643 patients). CONCLUSION: Our review indicates that in cardiac surgery patients, POC viscoelastic hemostatic testing is not associated with a reduction in the proportion of patients receiving any blood product or all-cause mortality. However, viscoelastic testing is weakly associated with a reduction in proportion of patients transfused with specific blood products. Presently, the benefits associated with viscoelastic testing in cardiac surgery patients are insufficiently robust to recommend routine implementation of this technology. TRIAL REGISTRATION: PROSPERO (CRD4201706577). Registered 11 May 2017.

The impact of hyperoxia on outcomes after cardiac surgery: a systematic review and narrative synthesis.

PURPOSE: Historically, cardiac surgery patients have often been managed with supraphysiologic intraoperative oxygen levels to protect against the risks of cellular hypoxia inherent in the un-physiologic nature of surgery and cardiopulmonary bypass. This may result in excessive reactive oxygen species generation and exacerbation of ischemia-reperfusion injury. In this review, we synthesize all available data from randomized controlled trials (RCTs) to investigate the impact that hyperoxia has on postoperative organ dysfunction, length of stay, and mortality during adult cardiac surgery. SOURCE: We searched Medline, Embase, Scopus, and Cochrane Central Register of Controlled Trials databases using a high-sensitivity strategy for RCTs that compared oxygenation strategies for adult cardiac surgery. Our primary outcome was postoperative organ dysfunction defined by postoperative increases in myocardial enzymes, acute kidney injury, and neurologic dysfunction. Secondary outcomes were mortality, ventilator days, and length of stay in the hospital and intensive care unit. PRINCIPAL FINDINGS: We identified 12 RCTs that met our inclusion criteria. Risk of bias was unclear to high in all but one trial. Significant heterogeneity in timing of the treatment period and the oxygenation levels targeted was evident and precluded meta-analysis. The large majority of trials found no difference between hyperoxia and normoxia for any outcome. Two trials reported reduced postoperative myocardial enzymes and one trial reported reduced mechanical ventilation time in the normoxia group. CONCLUSIONS: Hyperoxia had minimal impact on organ dysfunction, length of stay, and mortality in adult cardiac surgery. The current evidence base is small, heterogeneous, and at risk of bias. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) (CRD42017074712). Registered 17 August 2017.

A systematic review and meta-analysis of new interventions for peripheral intravenous cannulation of children.

OBJECTIVE: Establishing intravenous access in children is often challenging for health professionals. Multiple attempts at peripheral intravenous cannulation (PIVC) cause increased pain and delayed delivery of therapy. Our objective was to synthesize and evaluate the best evidence for novel interventions designed to improve pediatric PIVC. METHODS: We searched for published and unpublished studies using MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, Web of Science, ClinicalTrials.gov, and Google.ca. We included studies for meta-analysis if they were randomized, evaluated an intervention other than ultrasound, and reported on 1 of 3 primary outcome measures: success or failure of PIVC, number of attempts to successful cannulation, and procedure time. Two blinded reviewers assessed studies for eligibility and applied a data extraction form to those included. Study quality was assessed using the Cochrane Risk of Bias Tool. RESULTS: Seven studies met the inclusion criteria. Randomized controlled trials (RCTs) of 3 different interventions were identified. A meta-analysis of 3 RCTs found that use of a transilluminator was associated with a decreased risk of first-attempt PIVC failure (risk ratio, 0.66; confidence interval, 0.41-1.06). Meta-analysis of 3 other RCTs found that near-infrared light devices do not impact the risk of first-attempt PIVC failure (risk ratio, 0.99; confidence interval, 0.74-1.33). CONCLUSIONS: Near-infrared light devices might be efficacious in selected subpopulations, but the available evidence does not support an overall benefit in the pediatric population. Transilluminators modestly improve pediatric PIVC, but the clinical significance of this benefit is questionable. Nitroglycerin ointments may increase the risk of PIVC failure and are associated with adverse effects.

Ultrasonographically guided peripheral intravenous cannulation of children and adults: a systematic review and meta-analysis.

STUDY OBJECTIVE: Peripheral intravenous cannulation is procedurally challenging and painful. We perform a systematic review to evaluate ultrasonographic guidance as an aid to peripheral intravenous cannulation. METHODS: We searched MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, ClinicalTrials.gov, and Google.ca. We included randomized trials evaluating ultrasonographically guided peripheral intravenous cannulation and reporting risk of peripheral intravenous cannulation failure, number of attempts, procedure time, or time from randomization to peripheral intravenous cannulation. We separately analyzed pediatric and adult data and emergency department (ED), ICU, and operating room data. Quality assessment used the Cochrane Risk of Bias Tool. RESULTS: We identified 4,664 citations, assessed 403 full texts for eligibility, and included 9 trials. Five had low risk, 1 high risk, and 3 unclear risk of bias. A pediatric ED trial found that ultrasonography decreased mean difference (MD) in the number of attempts (MD -2.00; 95% confidence interval [CI] -2.73 to -1.27) and procedure time (MD -8.10 minutes; 95% CI -12.48 to -3.72 minutes). In an operating room pediatric trial, ultrasonography decreased risk of first-attempt failure (risk ratio 0.23; 95% CI 0.08 to 0.69), number of attempts (MD -1.50; 95% CI -2.52 to -0.48), and procedure time (MD -5.95; 95% CI -10.21 to -1.69). Meta-analysis of adult ED trials suggests that ultrasonography decreases the number of attempts (MD -0.43; 95% CI -0.81 to -0.05). Ultrasonography decreased risk of failure (risk ratio 0.47; 95% CI 0.26 to 0.87) in an adult ICU trial. CONCLUSION: Ultrasonography may decrease peripheral intravenous cannulation attempts and procedure time in children in ED and operating room settings. Few outcomes reached statistical significance. Larger well-controlled trials are needed.

Suppressor mutations identify amino acids in PAA-1/PR65 that facilitate regulatory RSA-1/B″ subunit targeting of PP2A to centrosomes in C. elegans.

Protein phosphorylation and dephosphorylation is a key mechanism for the spatial and temporal regulation of many essential developmental processes and is especially prominent during mitosis. The multi-subunit protein phosphatase 2A (PP2A) enzyme plays an important, yet poorly characterized role in dephosphorylating proteins during mitosis. PP2As are heterotrimeric complexes comprising a catalytic, structural, and regulatory subunit. Regulatory subunits are mutually exclusive and determine subcellular localization and substrate specificity of PP2A. At least 3 different classes of regulatory subunits exist (termed B, B', B″) but there is no obvious similarity in primary sequence between these classes. Therefore, it is not known how these diverse regulatory subunits interact with the same holoenzyme to facilitate specific PP2A functions in vivo. The B″ family of regulatory subunits is the least understood because these proteins lack conserved structural domains. RSA-1 (regulator of spindle assembly) is a regulatory B″ subunit required for mitotic spindle assembly in Caenorhabditis elegans. In order to address how B″ subunits interact with the PP2A core enzyme, we focused on a conditional allele, rsa-1(or598ts), and determined that this mutation specifically disrupts the protein interaction between RSA-1 and the PP2A structural subunit, PAA-1. Through genetic screening, we identified a putative interface on the PAA-1 structural subunit that interacts with a defined region of RSA-1/B″. In the context of previously published results, these data propose a mechanism of how different PP2A B-regulatory subunit families can bind the same holoenzyme in a mutually exclusive manner, to perform specific tasks in vivo.