Adnexectomy by vaginal Natural Orifice Transluminal Endoscopic Surgery versus laparoscopy: results of a first randomised controlled trial (NOTABLE trial).

OBJECTIVE: To compare adnexectomy by vaginal Natural Orifice Transluminal Endoscopic Surgery (vNOTES) versus laparoscopy. DESIGN: Parallel group, 1:1 single-centre single-blinded randomised trial, designed as non-inferiority study with a margin of 15%. SETTING: Belgian teaching hospital. POPULATION: Non-pregnant non-virgin women with an intact uterus and without obliteration of the pouch of Douglas scheduled to undergo removal of an adnexal mass assessed to be benign on ultrasound by IOTA criteria. METHODS: Randomisation to laparoscopy (control group) or vNOTES (experimental group). Stratification according to adnexal size. Blinding of participants and outcome assessors by sham incisions. MAIN OUTCOME MEASURES: The primary outcome measure was adnexectomy by the allocated technique. Secondary outcomes included duration of surgery, pain scores and analgesics used, quality of life and adverse events. RESULTS: We randomly assigned 67 participants (34 to the vNOTES group and 33 to the laparoscopy group). The primary end point was always reached in both groups: there were no conversions. We performed a sensitivity analysis for the primary outcome, assuming one conversion in the vNOTES group and no conversions in the laparoscopy group: the one-sided 95% upper limit for the differences in proportions of conversion was estimated as 13%, which is below the predefined non-inferiority margin of 15%. The secondary outcomes demonstrated a shorter duration of surgery, lower pain scores, lower total dose of analgesics and a trend for more adverse events in the vNOTES group. CONCLUSIONS: vNOTES is non-inferior to laparoscopy for a successful adnexectomy without conversion. vNOTES allowed shorter operating times and less postoperative pain but there was a trend for more adverse events.

Development, behaviour and sensory processing in Marshall-Smith syndrome and Malan syndrome: phenotype comparison in two related syndromes.

BACKGROUND: Ultrarare Marshall-Smith and Malan syndromes, caused by changes of the gene nuclear factor I X (NFIX), are characterised by intellectual disability (ID) and behavioural problems, although questions remain. Here, development and behaviour are studied and compared in a cross-sectional study, and results are presented with genetic findings. METHODS: Behavioural phenotypes are compared of eight individuals with Marshall-Smith syndrome (three male individuals) and seven with Malan syndrome (four male individuals). Long-term follow-up assessment of cognition and adaptive behaviour was possible in three individuals with Marshall-Smith syndrome. RESULTS: Marshall-Smith syndrome individuals have more severe ID, less adaptive behaviour, more impaired speech and less reciprocal interaction compared with individuals with Malan syndrome. Sensory processing difficulties occur in both syndromes. Follow-up measurement of cognition and adaptive behaviour in Marshall-Smith syndrome shows different individual learning curves over time. CONCLUSIONS: Results show significant between and within syndrome variability. Different NFIX variants underlie distinct clinical phenotypes leading to separate entities. Cognitive, adaptive and sensory impairments are common in both syndromes and increase the risk of challenging behaviour. This study highlights the value of considering behaviour within developmental and environmental context. To improve quality of life, adaptations to environment and treatment are suggested to create a better person-environment fit.

Hysterectomy by transvaginal natural orifice transluminal endoscopic surgery versus laparoscopy as a day-care procedure: a randomised controlled trial.

OBJECTIVE: To compare hysterectomy by transvaginal natural orifice transluminal endoscopic surgery (vNOTES) versus total laparoscopic hysterectomy (TLH) as a day-care procedure. DESIGN: Parallel group, 1:1 randomised single-centre single-blinded trial, designed as a non-inferiority study with a margin of 15%. SETTING: Belgian teaching hospital. POPULATION: Women aged 18-70 years scheduled to undergo hysterectomy for benign indications. METHODS: Randomisation to TLH (control group) or vNOTES (experimental group). Stratification according to uterine volume. Blinding of participants and outcome assessors. MAIN OUTCOME MEASURES: The primary outcome was hysterectomy by the allocated technique. We measured the proportion of women leaving within 12 hours after hysterectomy and the length of hospital stay as secondary outcomes. RESULTS: We randomly assigned 70 women to vNOTES (n = 35) or TLH (n = 35). The primary endpoint was always reached in both groups: there were no conversions. We performed a sensitivity analysis for the primary outcome, assuming one conversion in the vNOTES group and no conversions in the TLH group: the one-sided 95% upper limit for the differences in proportions of conversion was estimated as 7.5%, which is below the predefined non-inferiority margin. More women left the hospital within 12 hours after surgery after vNOTES: 77 versus 43%, difference 34% (95% CI 13-56%), P = 0.007. The hospital stay was shorter after vNOTES: 0.8 versus 1.3 days, mean difference -0.5 days, (95% CI -0.98 to -0.02), P = 0.004. CONCLUSIONS: vNOTES is non-inferior to TLH for successfully performing hysterectomy without conversion. Compared with TLH, vNOTES may allow more women to be treated in a day-care setting. TWEETABLE ABSTRACT: RCT: vNOTES is just as good as laparoscopy for successful hysterectomy without conversion but allows more day-care surgery.

Assessment of length-dependent regulation of myocardial function in coronary surgery patients using transmitral flow velocity patterns.

BACKGROUND: In a subset of coronary surgery patients, a transient increase in cardiac load by leg elevation resulted in a decrease in maximal rate of pressure development (dP/dtmax) and a major increase in end-diastolic pressure (EDP). This impairment of left ventricular (LV) function appeared to be related to a deficient length-dependent regulation of myocardial function. The present study investigated whether analysis of transmitral flow patterns with transesophageal echocardiography constituted a noninvasive method to identify these patients. METHODS: High-fidelity LV pressure tracings and transmitral flow signals were obtained in 50 coronary surgery patients during an increase in cardiac load by leg elevation. Using linear regression analysis, changes in transmitral E-wave velocity and deceleration time (DT) were related to changes in dP/dtmax and EDP. RESULTS: Changes in dP/dtmax with leg elevation were closely related to corresponding changes in E-wave velocity (r = 0.81; P < 0. 001) and to changes in DT (r = 0.78; P < 0.001). Similarly, changes in EDP were related to changes in E-wave velocity (r = 0.83; P < 0. 001) and to changes in DT (r = 0.84; P < 0.001). The decrease in dP/dtmax and the major increase in EDP in some patients was associated with an increase in E-wave velocity and a decrease in DT, indicating development of a restrictive LV filling pattern. CONCLUSIONS: Impairment of LV function with leg elevation was associated with the development of a restrictive transmitral filling pattern. Analysis of transmitral flow patterns by means of transesophageal echocardiography therefore allowed noninvasive identification of a subset of coronary surgery patients with impaired length-dependent regulation of LV function.

Role of the nitric oxide-cGMP pathway in the cardiovascular effects of anesthetic agents: a review.

Over the past 10 years, there has been an explosion of new information on the physiological and pathophysiological roles of nitric oxide (NO) within the cardiovascular system. With the increasing knowledge on the importance of NO in the regulation of cardiovascular function, possible involvement of the NO-cyclic guanosine-monmphosphate (cGMP) pathway in myocardial effects of anesthetics has attracted wide attention. This paper reviews the literature on the role of the nitric oxide-cGMP pathway in cardiovascular effects of volatile and intravenous anesthetics.

Sodium nitroprusside enhances in vivo left ventricular function in beta-adrenergically stimulated rabbit hearts.

OBJECTIVE: Sodium nitroprusside (SNP) is an activator of soluble guanylate cyclase, which depresses myocardial contractility. These exclusively negative inotropic effects of SNP were recently challenged by in vitro data.. In isolated rat ventricular myocytes, a moderate increase of cGMP improved the contractile response at baseline and in isoprenaline-stimulated conditions. The present study evaluated in vivo the inotropic effects of SNP at baseline and during administration of low dose dobutamine. METHODS: Anesthetized open-chest rabbits (n = 18) were instrumented with micromanometers, ultrasound crystals and atrial pacing wires. Measurements were obtained during caval occlusion with ventilation suspended at end-expiration. Systolic function was assessed with dP/dtmax and the slope Ees of the end-systolic pressure-volume relation. Diastolic function was assessed with the time constant tau and the stiffness constant Kc of the diastolic pressure-volume relation. SNP (0.02, 0.08, 0.32 microgram x kg-1) was administered at baseline and during low dose dobutamine. RESULTS: At baseline, SNP reduced dP/dtmax from 3750 +/- 88 to 3470+/- 88 mmHg/s (mean +/- s.e.m.) and Ees from 148 +/- 16 to 103 +/- 13 mmHg/ml (P < 0.01) . During dobutamine infusion, SNP increased dP/dtmax from 4340 +/- 125 to 4681 +/- 230 mmHg/s and Ees from 148 +/- 19 to 190 +/- 30 mmHg/ml (P < 0.01). Effects of SNP on dP/dtmax and Ees were different at baseline and during dobutamine (interaction P < 0.01). SNP did not alter Kc at baseline nor during dobutamine. CONCLUSIONS: SNP enhances in vivo systolic function in beta-adrenergically stimulated rabbits.

Effects of calcium on left ventricular function early after cardiopulmonary bypass.

OBJECTIVES: Evaluation of the effects of intravenous CaCl2 on systolic and diastolic function early after separation from cardiopulmonary bypass (CPB) DESIGN: Prospective study SETTING: University hospital PARTICIPANTS: Twenty patients scheduled for elective coronary artery surgery INTERVENTIONS: Left ventricular (LV) pressures were measured with fluid-filled catheters. Data were digitally recorded during pressure elevation induced by tilt-up of the legs. Transgastric short-axis echocardiographic views of the LV were simultaneously recorded on videotape. Measurements were obtained before the start of CPB, 10 minutes after termination of CPB, after intravenous administration of CaCl2, 5 mg/kg, and 10 minutes later. MEASUREMENTS AND MAIN RESULTS: Systolic function was evaluated with the slope (Ees, mmHg/mL) of the systolic pressure-volume relation. Diastolic function was evaluated with the chamber stiffness constant (Kc, mmHg/mL) of the diastolic pressure-volume relation. CaCl2 increased Ees from 2.62 +/- 0.46 to 5.58 +/- 0.61 (mean +/- SD), but induced diastolic dysfunction with an increase in Kc from 0.011 +/- 0.006 to 0.019 +/- 0.007. These changes were transient and had disappeared within 10 minutes after administration of CaCl2. CONCLUSIONS: CaCl2 early after CPB transiently improved systolic function at the expense of an increase in ventricular stiffness, suggesting temporary diastolic dysfunction.

Continuous total intravenous anesthesia, using propofol and fentanyl in an open-thorax rabbit model: evaluation of cardiac contractile function and biochemical assessment.

Effects are reported of an anesthetic protocol involving use of predetermined intravenous (i.v.)-administered drug doses during acute experimental procedures in vagotomized, New Zealand White rabbits with open thorax (n = 20) in a nonsurvival study. After induction of anesthesia by intramuscular (i.m.) administration of ketamine hydrochloride (25 mg/kg of body weight) and xylazine hydrochloride (15 mg/kg), continuous total intravenous anesthesia (TIVA) with propofol (0.6 mg.kg-1.min-1), fentanyl (0.48 micrograms.kg-1.min-1) and the neuromuscular agent vecuronium bromide (0.003 mg.kg-1.min-1) was maintained. Oxygenation conditions, acid-base balance, biochemical and hemodynamic variables, and cardiac contractile function were assessed. Measurements were made and blood analysis was done at the moment of ear vein catheterization (P1); before (P2) and after (P3) sternotomy; after complete instrumentation (P4); and at the beginning (T1), in the middle (T2), and at the end (T3) of the experimental protocol. From T1 to T3, heart rate was kept constant by use of atrial pacing at a rate of 235 +/- 15 beats/min. During surgical preparation and instrumentation, hemoglobin (Hb) concentration decreased from 12.5 +/- 0.9 g/dl (mean +/- SEM) to 7.7 +/- 0.7 g/dl and remained stable thereafter. Blood gas analysis (PO2, PCO2, pH, HCO3-, base excess, measured SaO2) and measurement of plasma lactate concentration revealed constant, adequate oxygenation. Plasma electrolyte values (Na+, Cl-, K+, Ca2+) remained within physiologic ranges throughout. Blood glucose concentration increased from 229 +/- 30 mg/dl at P1 to 382 +/- 34 mg/dl at P3. At T1, glycemia had returned to normal values and remained stable. Heart rate, blood pressure, ventricular elastance (Ees), and diastolic stiffness constant (Kc) remained stable throughout. Other indices of ventricular function (dP/dtmax, thickening, ejection duration, and maximal left ventricular pressure) remained unaltered as well. Left ventricular relaxation (dP/dtmin, tau) did not change. After anesthesia induction by i.m. administration of ketamine and xylazine, TIVA with predetermined drug dosages of propofol and fentanyl provided stable cardiovascular function for open-thorax long-term experimental observations in a nonsurvival setting.

Inotropic effects of sodium nitroprusside: a clinical study on coronary surgery patients.

OBJECTIVE: Sodium nitroprusside (SNP) induces release of nitric oxide and is widely used as a vasoactive drug. Recent research analyzed effects of SNP on cardiac muscle and described variable inotropic effects. The present study evaluated effects of SNP on left ventricular (LV) function in patients undergoing coronary artery surgery. METHODS: The study was performed in 100 patients with a preoperative ejection fraction > 40%. LV pressures were measured with a fluid-filled catheter in the LV cavity. Hearts were placed in AV sequential mode at a rate of 90 beats/min. Measurements were obtained at end-expiration and consisted of a control tracing and a tracing obtained after a 5 min infusion of SNP 0.5 microgram.kg-1.min-1. These measurements were obtained before and after cardiopulmonary bypass (CPB). An average of 5 consecutive beats was obtained for analysis. Ventricular function was assessed with LV pressure and dP/dt. Data were analyzed using two factor analysis of variance for repeated measurements. RESULTS: 1. Baseline patient data (n = 80). Before CPB, a variable inotropic response to SNP was observed. The direction of the inotropic response was related to preoperative beta-blocking medication. LVP and dP/dtmax increased with SNP in patients without preoperative beta-blocking medication. In patients on preoperative beta-blocking medication, SNP did not alter LVP and dP/dtmax. After CPB, a positive inotropic response was not observed in any of the patients. 2. Postoperative patient data under dobutamine (n = 20). Data of these separate observations were similar to baseline data before CPB. After CPB and under dobutamine administration (5 micrograms.kg-1.min-1) all 20 patients developed a positive inotropic response to SNP. CONCLUSIONS: In coronary surgery patients, SNP induced variable inotropic effect. The direction of the inotropic response appeared to be modulated by the beta-adrenergic drive.

Recovery of systolic and diastolic left ventricular function early after cardiopulmonary bypass.

BACKGROUND: Impairment of left ventricular function after cardiopulmonary bypass (CPB) is well recognized, but little is known about the time course of recovery of cardiac function early after separation from CPB. Therefore, recovery of left ventricular function was evaluated early after separation from CPB in patients undergoing coronary artery surgery. The authors tried to determine whether this recovery might be attributed to autoregulation of function by preload. METHODS: Left ventricular pressure was measured with fluid-filled catheters. Data were digitally recorded during increased pressure induced by elevating the legs. Transgastric short-axis echocardiographic views of the left ventricle were simultaneously recorded on videotape. Systolic function was evaluated with the slope (Ees, mmHg/ml) of the systolic pressure-volume relation. Diastolic function was evaluated with the chamber stiffness constant (Kc, ml-1) of the diastolic pressure-volume relation. Cardiac function was assessed before CPB, after termination of CPB, and 5, 10, and 15 min later. Two different separation procedures from CPB were compared: in protocol 1, left ventricular function was documented during the standard procedure (n = 24); in protocol 2, the heart was optimally filled 10 min before separation from CPB (n = 12). RESULTS: In protocol 1, Ees was 2.88 +/- 0.21 mmHg/ml (mean +/- SEM) and Kc was 0.012 +/- 0.001 ml-1 before CPB. Within 10 min after separation from CPB, Ees increased from 1.10 +/- 0.32 to 2.92 +/- 0.34 (P = 0.001) and Kc decreased from 0.022 +/- 0.002 to 0.011 +/- 0.001 (P = 0.001). The parameters remained stable thereafter. In protocol 2, Ees was 2.92 +/- 0.51 mmHg/ ml and Kc was 0.011 +/- 0.002 ml-1 before CPB. Depression of systolic and diastolic function was not observed in these patients. At time 0, Ees was 2.46 +/- 0.16 and Kc was 0.012 +/- 0.002. These values remained stable throughout the entire observation period. CONCLUSIONS: Significant functional recovery was observed early after separation from CPB, which was suggestive of time-dependent changes in both systolic and diastolic left ventricular function induced by preload restoration.