Vasopressin in Cardiac Surgery: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To summarize the results of randomized controlled trials on the use of vasopressin as a vasopressor agent in cardiac surgery. DESIGN: Meta-analysis. PARTICIPANTS: Six-hundred-twenty-five adult patients undergoing elective or emergency cardiac surgery. INTERVENTIONS: Arginine vasopressin infusion (n = 313) or control/standard therapy (n = 312). MEASUREMENTS AND MAIN RESULTS: The rates of perioperative complications and postoperative mortality were used as primary and secondary endpoints, respectively. Fixed and/or random effects models were used to compare pooled odds ratios. Arginine vasopressin reduced the pooled odds ratio (OR) of perioperative complications (OR, 0.33; 95% confidence interval [CI], 0.2-0.54; p < 0.0001). A sensitivity analysis excluding the largest trial showed an unchanged reduction in perioperative complications (OR, 0.35; 95% CI, 0.18-0.69; p = 0.002). When analyzing each perioperative complication separately, vasopressin reduced the pooled OR of vasodilatory shock (OR, 0.4; 95% CI, 0.16-0.97; p = 0.04) and new-onset atrial fibrillation (OR, 0.42; 95% CI, 0.21-0.82; p = 0.01). The pooled OR of postoperative death was not different between patients treated with arginine vasopressin and those receiving standard therapy or placebo (OR, 0.83; 95% CI, 0.45-1.53; p = 0.55). The funnel plot for the primary endpoint suggested a relevant publication bias. All included trials suffered from a high risk of bias. CONCLUSION: Our meta-analysis suggests that arginine vasopressin may reduce the rate of perioperative complications in patients undergoing elective or emergency cardiac surgery. No difference in postoperative mortality was observed. An adequately powered multicenter trial is required for reliable estimation of the effects of arginine vasopressin on perioperative complication rates and mortality in cardiac surgical patients.

What is the impact of the fluid challenge technique on diagnosis of fluid responsiveness? A systematic review and meta-analysis.

BACKGROUND: The fluid challenge is considered the gold standard for diagnosis of fluid responsiveness. The objective of this study was to describe the fluid challenge techniques reported in fluid responsiveness studies and to assess the difference in the proportion of 'responders,' (PR) depending on the type of fluid, volume, duration of infusion and timing of assessment. METHODS: Searches of MEDLINE and Embase were performed for studies using the fluid challenge as a test of cardiac preload with a description of the technique, a reported definition of fluid responsiveness and PR. The primary outcome was the mean PR, depending on volume of fluid, type of fluids, rate of infusion and time of assessment. RESULTS: A total of 85 studies (3601 patients) were included in the analysis. The PR were 54.4% (95% CI 46.9-62.7) where <500 ml was administered, 57.2% (95% CI 52.9-61.0) where 500 ml was administered and 60.5% (95% CI 35.9-79.2) where >500 ml was administered (p = 0.71). The PR was not affected by type of fluid. The PR was similar among patients administered a fluid challenge for <15 minutes (59.2%, 95% CI 54.2-64.1) and for 15-30 minutes (57.7%, 95% CI 52.4-62.4, p = 1). Where the infusion time was ≥30 minutes, there was a lower PR of 49.9% (95% CI 45.6-54, p = 0.04). Response was assessed at the end of fluid challenge, between 1 and 10 minutes, and >10 minutes after the fluid challenge. The proportions of responders were 53.9%, 57.7% and 52.3%, respectively (p = 0.47). CONCLUSIONS: The PR decreases with a long infusion time. A standard technique for fluid challenge is desirable.

Genomic characteristics and clinical effect of the emergent SARS-CoV-2 B.1.1.7 lineage in London, UK: a whole-genome sequencing and hospital-based cohort study.

BACKGROUND: Emergence of variants with specific mutations in key epitopes in the spike protein of SARS-CoV-2 raises concerns pertinent to mass vaccination campaigns and use of monoclonal antibodies. We aimed to describe the emergence of the B.1.1.7 variant of concern (VOC), including virological characteristics and clinical severity in contemporaneous patients with and without the variant. METHODS: In this cohort study, samples positive for SARS-CoV-2 on PCR that were collected from Nov 9, 2020, for patients acutely admitted to one of two hospitals on or before Dec 20, 2020, in London, UK, were sequenced and analysed for the presence of VOC-defining mutations. We fitted Poisson regression models to investigate the association between B.1.1.7 infection and severe disease (defined as point 6 or higher on the WHO ordinal scale within 14 days of symptoms or positive test) and death within 28 days of a positive test and did supplementary genomic analyses in a cohort of chronically shedding patients and in a cohort of remdesivir-treated patients. Viral load was compared by proxy, using PCR cycle threshold values and sequencing read depths. FINDINGS: Of 496 patients with samples positive for SARS-CoV-2 on PCR and who met inclusion criteria, 341 had samples that could be sequenced. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. We found no evidence of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38]). We detected no B.1.1.7 VOC-defining mutations in 123 chronically shedding immunocompromised patients or in 32 remdesivir-treated patients. Viral load by proxy was higher in B.1.1.7 samples than in non-B.1.1.7 samples, as measured by cycle threshold value (mean 28·8 [SD 4·7] vs 32·0 [4·8]; p=0·0085) and genomic read depth (1280 [1004] vs 831 [682]; p=0·0011). INTERPRETATION: Emerging evidence exists of increased transmissibility of B.1.1.7, and we found increased virus load by proxy for B.1.1.7 in our data. We did not identify an association of the variant with severe disease in this hospitalised cohort. FUNDING: University College London Hospitals NHS Trust, University College London/University College London Hospitals NIHR Biomedical Research Centre, Engineering and Physical Sciences Research Council.

Causes and risk factors for acute dialysis initiation among patients with end-stage kidney disease-a large retrospective observational cohort study.

BACKGROUND: Patients who require acute initiation of dialysis have higher mortality rates when compared with patients with planned starts. Our primary objective was to explore the reasons and risk factors for acute initiation of renal replacement therapy (RRT) among patients with end-stage kidney disease (ESKD). Our secondary objective was to determine the difference in glomerular filtration rate (GFR) change in the year preceding RRT between elective and acute dialysis starts. METHODS: We conducted a single-centre retrospective observational study. ESKD patients either started dialysis electively (planned starters) or acutely and were known to renal services for >90 (unplanned starters) or <90 days (urgent starters). RESULTS: In all, 825 consecutive patients initiated dialysis between January 2013 and December 2015. Of these, 410 (49.7%) patients had a planned start. A total of 415 (50.3%) patients had an acute start on dialysis: 244 (58.8%) unplanned and 171 (41.2%) urgent. The reasons for acute dialysis initiation included acute illness (58%) and unexplained decline to ESKD (33%). Cardiovascular disease [n = 30 (22%)] and sepsis [n = 65 (48%)] accounted for the majority of acute systemic illness. Age and premorbid cardiovascular disease were independent risk factors for acute systemic illness among unplanned starts, whereas autoimmune disease accounted for the majority of urgent starts. The rate of decline in GFR was greater in the month preceding RRT among acute dialysis starters compared with planned starters (P < 0.001). CONCLUSIONS: Cardiovascular disease and advancing age were independent risk factors for emergency dialysis initiation among patients known to renal services for >3 months. The rapid and often unpredictable loss of renal function in the context of acute systemic illness poses a challenge to averting emergency dialysis start.