Comparison of sedation and general anaesthesia for transcatheter aortic valve implantation on cerebral oxygen saturation and neurocognitive outcome

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a treatment strategy for patients with severe aortic stenosis. Although general anaesthesia (TAVI-GA) and sedation (TAVI-S) have previously been described for TAVI, the difference in safety and efficacy of both methods has not been studied in a randomized trial. METHODS: The INSERT trial was a single centre, controlled parallel-group trial with balanced randomization. Sixty-six patients (68-94 yr) with acquired aortic stenosis undergoing transfemoral CoreValve were assigned to TAVI-GA or TAVI-S. Comparable operative risk was determined from risk-scores (EUROscore, STS-Score). Monitoring and anaesthetic drugs were standardized. Near-Infrared-Spectroscopy was used to monitor cerebral-oxymetry blinded. Primary outcome was the perioperative cumulative cerebral desaturation. As secondary outcomes, changes in neurocognitive function and respiratory and haemodynamic adverse events were evaluated. RESULTS: Of 66 included patients, 62 (TAVI-GA: n=31, TAVI-S: n=31) were finally analysed. Baseline characteristics were comparable. In 24 patients (39%) cerebral desaturation was observed. Cumulative cerebral desaturation was comparable (TAVI-GA:(median [IQR]) (0[0/1308] s%) vs. TAVI-S:(0[0/276] s%); P=0.505) between the groups. Neurocognitive function did not change within and between groups. Adverse events were more frequently observed in TAVI-S patients (P<0.001). Bradypnoea (n=16, 52%) and the need for airway manoeuvres (n=11, 36%) or bag-mask-ventilation (n=6, 19%) were the most common respiratory adverse events. CONCLUSIONS: Cerebral desaturation occurred in both patient groups, but there was no significant difference between the two groups. Based on primary outcome, both methods were shown to be comparable. Neurocognitive outcome was similar. The higher incidence of adverse events in the sedation group suggests a potential advantage of general anaesthesia. CLINICAL TRIAL REGISTRATION: NCT 01251328

Comparison of sedation and general anaesthesia for transcatheter aortic valve implantation on cerebral oxygen saturation and neurocognitive outcome

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a treatment strategy for patients with severe aortic stenosis. Although general anaesthesia (TAVI-GA) and sedation (TAVI-S) have previously been described for TAVI, the difference in safety and efficacy of both methods has not been studied in a randomized trial. METHODS: The INSERT trial was a single centre, controlled parallel-group trial with balanced randomization. Sixty-six patients (68-94 yr) with acquired aortic stenosis undergoing transfemoral CoreValve were assigned to TAVI-GA or TAVI-S. Comparable operative risk was determined from risk-scores (EUROscore, STS-Score). Monitoring and anaesthetic drugs were standardized. Near-Infrared-Spectroscopy was used to monitor cerebral-oxymetry blinded. Primary outcome was the perioperative cumulative cerebral desaturation. As secondary outcomes, changes in neurocognitive function and respiratory and haemodynamic adverse events were evaluated. RESULTS: Of 66 included patients, 62 (TAVI-GA: n=31, TAVI-S: n=31) were finally analysed. Baseline characteristics were comparable. In 24 patients (39%) cerebral desaturation was observed. Cumulative cerebral desaturation was comparable (TAVI-GA:(median [IQR]) (0[0/1308] s%) vs. TAVI-S:(0[0/276] s%); P=0.505) between the groups. Neurocognitive function did not change within and between groups. Adverse events were more frequently observed in TAVI-S patients (P<0.001). Bradypnoea (n=16, 52%) and the need for airway manoeuvres (n=11, 36%) or bag-mask-ventilation (n=6, 19%) were the most common respiratory adverse events. CONCLUSIONS: Cerebral desaturation occurred in both patient groups, but there was no significant difference between the two groups. Based on primary outcome, both methods were shown to be comparable. Neurocognitive outcome was similar. The higher incidence of adverse events in the sedation group suggests a potential advantage of general anaesthesia. CLINICAL TRIAL REGISTRATION: NCT 01251328

IL-6 or IL-8 concentrations do not distinguish UTI patients with bacteremia from those without bacteremia.

<p>IL-6 (<b>A</b>) and IL-8 (<b>B</b>) concentrations were determined in the urine of 46 controls (CON), 44 cases with febrile UTI without bacteremia (UTI–B), and 45 cases with febrile UTI with bacteremia (UTI+B). Cytokine concentrations depicted were corrected for urine gravity, for samples below the detection limit the corrected cytokine concentration was set to 0.1. Solid bars represent medians, for statistical analysis a Mann-Whitney test was used.</p

Baseline characteristics of the study population.

<p>Data are presented as n (%) unless otherwise stated. UTI = urinary tract infection, IQR = interquartile range, sd = standard deviation, COPD = chronic obstructive pulmonary disease, BMI = body mass index. ^a Defined as any functional or anatomical abnormality of the urinary tract except urinary catheter and history of nephrolithiasis. ^b Defined as ≥2 UTIs in the last 6 months or ≥3 UTIs in the last 12 months. ^c Eight missing BMI data: 2 in controls, 1 in UTI without bacteremia and 5 in UTI with bacteremia.</p><p>Baseline characteristics of the study population.</p

Genotypes of genetic variations in controls and UTI patients.

<p>* name used in the literature</p><p>Genotypes of genetic variations in controls and UTI patients.</p

Antimicrobial protein concentrations do not distinguish UTI patients with bacteremia from those without bacteremia.

<p>Concentrations of the antimicrobial proteins β-defensin 2 (<b>A</b>) Cathelicidin LL37 (<b>B</b>) and Uromodulin (<b>C</b>) were determined in the urine of 46 controls (CON), 44 febrile UTI cases without bacteremia (UTI–B), and 45 febrile UTI cases with bacteremia (UTI+B). Protein concentrations depicted were corrected for urine gravity, for samples below the detection limit the corrected protein concentration was set to 0.1 (β-defensin 2, Cathelicidin LL37) or 10 (Uromodulin). Solid bars represent medians, for statistical analysis the Mann-Whitney U test was used.</p

Plasma vitamin D concentrations in controls and UTI patients.

<p>Plasma 25(OH) vitamin D concentrations were determined in 46 controls (CON) and 43 UTI patients without bacteremia (UTI-B) and 44 UTI patients with bacteremia (UTI+B) (<b>A</b>). Analysis of plasma 25(OH)D vitamin D concentrations according to season of sampling (<b>B</b>). All controls were recruited in winter. 12 UTI patients were recruited in winter, 16 in spring, 27 in summer and 32 in autumn. Solid bars represent median concentrations; dotted lines represent upper limit of vitamin D deficiency (≤20 ng/ml) and lower limit of vitamin D sufficiency (≥30 ng/ml). The Mann-Whitney U test was used to determine whether groups were statistically different.</p

Primer and probe sequences for the multiplex genotyping assay.

<p>Primer and probe sequences for the multiplex genotyping assay.</p

β-defensin 2 production is associated with a DEFB1 genotype.

<p>Concentration of the antimicrobial protein β-defensin 2 grouped per DEFB1 rs1800972 genotype, the groups are significantly different (p = 0.0002). Protein concentrations were corrected for urine gravity, for samples below the detection limit the corrected cytokine concentration was set to 0.1. Solid bars represent medians, for statistical analysis the Kruskal-Wallis test was used.</p