Pressure-Volume Loops for Reviewing Right Ventricular Physiology and Failure in the Context of Left Ventricular Assist Device Implantation.

Right ventricular (RV) function is complex as a number of determinants beyond preload, inotropy and afterload play a fundamental role. In particular, arterial elastance (Ea), ventriculo-arterial coupling (VAC), and (systolic) ventricular interdependence play a vital role for the right ventricle. Understanding and actively visualizing these interactions in the failing RV as well as in the altered hemodynamic and morphological situation of left ventricular assist device (LVAD) implantation may aid clinicians in their understanding of RV dysfunction and failure. While, admittedly, hard data is scarce and invasive pressure-volume loop measurements will not become routine in cardiac surgery, we hope that clinicians will benefit from the comprehensive, simulation-based review of RV pathology. In particular, the aim of this article is to first, address and clarify the pathophysiologic hemodynamic factors that lead to RV dysfunction and then, second, expand upon this basis examining the changes occurring by LVAD implantation. This is illustrated using Harvi software which shows elastance, ventricular arterial coupling, and ventricular interdependence by simultaneously showing pressure volume loops of the right and left ventricle.

Protamine titration to optimize heparin antagonization after cardiopulmonary bypass.

OBJECTIVES: To optimize protamine titration for heparin antagonization after weaning from cardiopulmonary bypass (CPB). DESIGN: A prospective, observational trial. SETTING: Single-center, non-university teaching hospital. PARTICIPANTS: Forty patients presenting for elective on-pump coronary artery bypass grafting with or without single valve surgery. INTERVENTIONS: At the end of CPB, the residual amount of heparin in the patient was estimated using a Bull-curve. The total protamine dose was calculated as 1 unit of protamine for 1 unit of heparin. Protamine was administered as 5 aliquots containing 20% of the total protamine dose each, with 2-min intervals. MEASUREMENTS AND MAIN RESULTS: Activated Clotting Time (ACT) values were measured 2 min after administration of each aliquot. ROTEM(®)-analysis was performed after the full dose of protamine had been administered. After 60% of the total protamine dose had been administered, ACT values were normalized in 86.5% of patients. After the complete dose of protamine had been administered, 61.1% of patients displayed signs of protamine overdose on ROTEM(®)-analysis. CONCLUSIONS: In patients who present for on-pump coronary artery bypass grafting with or without single valve surgery, a 0.6-to-1 ratio of protamine-to-heparin to antagonize heparin may be sufficient and beneficial for patients.

A method to convert neural signals into sound sequences.

We present a method to convert neural signals into sound sequences, with the constraint that the sound sequences precisely reflect the sequences of events in the neural signal. The method consists in quantifying the wave motifs in the signal and using these parameters to generate sound envelopes. We illustrate the procedure for sleep delta waves in the human electro-encephalogram (EEG), which are converted into sound sequences that encode the time structure of the original EEG waves. This procedure can be applied to synthesize personalized sound sequences specific to the EEG of a given subject.

Pituitary surgery as alternative to dopamine agonists treatment for microprolactinomas: a cohort study.

OBJECTIVE: Microprolactinomas are currently treated with dopamine agonists. Outcome information on microprolactinoma patients treated by surgery is limited. This study reports the first large series of consecutive non-invasive microprolactinoma patients treated by pituitary surgery and evaluates the efficiency and safety of this treatment. DESIGN: Follow-up of a cohort of consecutive patients treated by surgery. METHODS: Between January 2008 and October 2020, 114 adult patients with pure microprolactinomas were operated on in a single tertiary expert neurosurgical department, using an endoscopic endonasal transsphenoidal approach. Eligible patients presented with a microprolactinoma with no obvious cavernous invasion on MRI. Prolactin was assayed before and after surgery. Disease-free survival was modeled using Kaplan-Meier representation. A cox regression model was used to predict remission. RESULTS: Median follow-up was 18.2 months (range: 2.8-155). In this cohort, 14/114 (12%) patients were not cured by surgery, including ten early surgical failures and four late relapses occurring 37.4 months (33-41.8) after surgery. From Kaplan-Meier estimates, 1-year and 5-year disease free survival was 90.9% (95% CI: 85.6-96.4%) and 81% (95% CI: 71.2-92.1%) respectively. The preoperative prolactinemia was the only significant preoperative predictive factor for remission (P < 0.05). No severe complication was reported, with no anterior pituitary deficiency after surgery, one diabetes insipidus, and one postoperative cerebrospinal fluid leakage properly treated by muscle plasty. CONCLUSIONS: In well-selected microprolactinoma patients, pituitary surgery performed by an expert neurosurgical team is a valid first-line alternative treatment to dopamine agonists.

Efficacy of endoscopic endonasal transsphenoidal surgery for Cushing's disease in 230 patients with positive and negative MRI.

OBJECT: The primary objective was to assess the remission rate, and the secondary objectives were to evaluate the early complications and recurrence rate and to define the predictive factors for the remission and recurrence rates. PATIENTS AND METHODS: This prospective single-center study included 230 consecutive patients, operated on by a single surgeon for Cushing's disease via a transsphenoidal endoscopic endonasal approach, over a 6-year period (2008-2013). The patients included in this series were all adults (>18 years of age), who presented with clinical and biological characteristics of Cushing's disease confirmed based on dedicated MRI pituitary imaging. Biochemical remission was defined as a postoperative serum cortisol level <5 µg/dl on the 2nd day following surgery that required glucocorticoid replacement therapy. RESULTS: The remission rate for the global population (n = 230) with a follow-up of 21 ± 19.2 months concerned 182 patients (79.1%) divided into 132 patients (82.5%) with positive MRI and 50 patients (71.4%) with negative MRI with no statistically significant difference (p = 0.077). Complications occurred in 77 patients with no deaths. A total of 22% of patients had transient diabetes insipidus and 6.4% long-term diabetes insipidus, and no postoperatively CSF leakage was observed. The recurrence rate was 9.8% with a mean time of 32.7 ± 15.2 months. The predictive factors for the remission rate were the presence of pituitary microadenoma and a positive histology. No risk factors were involved regarding the recurrence rate. CONCLUSION: Whatever the MRI results, the transsphenoidal endonasal endoscopic approach remains the gold standard treatment for Cushing's disease. It was maximally effective with a remission rate of 79.1% and lower morbidity.

Diaphragmatic and intercostal electromyographic activity during neostigmine, sugammadex and neostigmine-sugammadex-enhanced recovery after neuromuscular blockade: A randomised controlled volunteer study.

BACKGROUND: Electromyographic activity of the diaphragm (EMGdi) during weaning from mechanical ventilation is increased after sugammadex compared with neostigmine. OBJECTIVE: To determine the effect of neostigmine on EMGdi and surface EMG (sEMG) of the intercostal muscles during antagonism of rocuronium block with neostigmine, sugammadex and neostigmine followed by sugammadex. DESIGN: Randomised, controlled, double-blind study. SETTING: Intensive care research unit. PARTICIPANTS: Eighteen male volunteers. INTERVENTIONS: A transoesophageal EMGdi recorder was inserted into three groups of six anaesthetised study participants, and sEMG was recorded on their intercostal muscles. To reverse rocuronium, volunteers received 50 µg kg neostigmine, 2 mg kg sugammadex or 50 µg kg neostigmine, followed 3 min later by 2 mg kg sugammadex. MAIN OUTCOME MEASURES: We examined the EMGdi and sEMG at the intercostal muscles during recovery enhanced by neostigmine or sugammadex or neostigmine-sugammadex as primary outcomes. Secondary objectives were the tidal volume, PaO2 recorded between the onset of spontaneous breathing and extubation of the trachea and SpO2 during and after anaesthesia. RESULTS: During weaning, median peak EMGdi was 0.76 (95% confidence interval: 1.20 to 1.80) µV in the neostigmine group, 1.00 (1.23 to 1.82) µV in the sugammadex group and 0.70 (0.91 to 1.21) µV in the neostigmine-sugammadex group (P < 0.0001 with EMGdi increased after sugammadex vs. neostigmine and neostigmine-sugammadex). The median peak intercostal sEMG for the neostigmine group was 0.39 (0.65 to 0.93) µV vs. 0.77 (1.15 to 1.51) µV in the sugammadex group and 0.82 (1.28 to 2.38) µV in the neostigmine-sugammadex group (P < 0.0001 with sEMG higher after sugammadex and after neostigmine-sugammadex vs. neostigmine). CONCLUSION: EMGdi and sEMG on the intercostal muscles were increased after sugammadex alone compared with neostigmine. Adding sugammadex after neostigmine reduced the EMGdi compared with sugammadex alone. Unlike the diaphragm, intercostal EMG was preserved with neostigmine followed by sugammadex. TRIAL REGISTRATION: EudraCT: 2015-001278-16; ClinicalTrials.gov: NCT02403063.

Glucose Control in the ICU: A Continuing Story.

In the present era of near-continuous glucose monitoring (CGM) and automated therapeutic closed-loop systems, measures of accuracy and of quality of glucose control need to be standardized for licensing authorities and to enable comparisons across studies and devices. Adequately powered, good quality, randomized, controlled studies are needed to assess the impact of different CGM devices on the quality of glucose control, workload, and costs. The additional effects of continuing glucose control on the general floor after the ICU stay also need to be investigated. Current algorithms need to be adapted and validated for CGM, including effects on glucose variability and workload. Improved collaboration within the industry needs to be encouraged because no single company produces all the necessary components for an automated closed-loop system. Combining glucose measurement with measurement of other variables in 1 sensor may help make this approach more financially viable.

Spatially Structured Sparse Morphological Component Separation for voltage-sensitive dye optical imaging.

BACKGROUND: Voltage-sensitive dye optical imaging is a promising technique for studying in vivo neural assemblies dynamics where functional clustering can be visualized in the imaging plane. Its practical potential is however limited by many artifacts. NEW METHOD: We present a novel method, that we call "SMCS" (Spatially Structured Sparse Morphological Component Separation), to separate the relevant biological signal from noise and artifacts. It extends Generalized Linear Models (GLM) by using a set of convex non-smooth regularization priors adapted to the morphology of the sources and artifacts to capture. RESULTS: We make use of first order proximal splitting algorithms to solve the corresponding large scale optimization problem. We also propose an automatic parameters selection procedure based on statistical risk estimation methods. COMPARISON WITH EXISTING METHODS: We compare this method with blank subtraction and GLM methods on both synthetic and real data. It shows encouraging perspectives for the observation of complex cortical dynamics. CONCLUSIONS: This work shows how recent advances in source separation can be integrated into a biophysical model of VSDOI. Going beyond GLM methods is important to capture transient cortical events such as propagating waves.

Electromyographic activity of the diaphragm during neostigmine or sugammadex-enhanced recovery after neuromuscular blockade with rocuronium: a randomised controlled study in healthy volunteers.

BACKGROUND: The use of neuromuscular blocking agents has been associated with severe postoperative respiratory morbidity. Complications can be attributed to inadequate reversal, and reversal agents may themselves have adverse effects. OBJECTIVE: To compare the electromyographic activity of the diaphragm (EMGdi) during recovery from neuromuscular blockade using neostigmine and sugammadex. The hypothesis was that there would be better neuromuscular coupling of the diaphragm when sugammadex was used. DESIGN: A randomised, controlled, parallel-group, single-centre, double-blinded study. SETTING: District general hospital in Belgium. PARTICIPANTS: Twelve healthy male volunteers. INTERVENTIONS: Individuals were anaesthetised with propofol and remifentanil. After rocuronium 0.6 mg kg, a transoesophageal electromyography (EMG) recorder was inserted. For reversal of neuromuscular blockade, volunteers received sugammadex 2 mg kg (n = 6) or neostigmine 70 µg kg (n = 6). MAIN OUTCOME MEASURES: EMGdi, airway pressure and flow were continuously measured during weaning from the ventilator until tracheal extubation. Arterial blood gas samples were obtained for PaO2 and PaCO2 analysis at the first spontaneous breathing attempt and after tracheal extubation. RESULTS: During weaning, 560 breaths were retained for analysis. The median (95% CI) peak EMGdi was 1.1 (0.9 to 1.5) µV in the neostigmine group and 1.6 (1.3 to 1.9) µV in the sugammadex group (P < 0.001). Individuals in the neostigmine group had 125 of 228 (55%) breaths with associated EMGdi at least 1 µV vs. 220 of 332 (66%) breaths in the sugammadex group (P = 0.008). The median (95% CI) tidal volume was 287 (256 to 335) ml after neostigmine and 359 (313 to 398) ml after sugammadex (P = 0.013). The median (95% CI) PaO2 immediately after extubation was 30.5 (22.8 to 37.1) kPa after sugammadex vs. 20.7 (12.9 to 27.5) kPa after neostigmine (P = 0.03). CONCLUSION: EMGdi, tidal volume and PaO2 following tracheal extubation were increased after sugammadex compared with neostigmine, reflecting diaphragm-driven inspiration after sugammadex administration. Sugammadex may free more diaphragmatic acetylcholine receptors than neostigmine, which has an indirect effect. TRIAL REGISTRATION: EudraCT ref: 2013-002078-30.

Accuracy of a feasibility version of an intravenous continuous glucose monitor in volunteers with diabetes and hospitalized patients.

BACKGROUND: A feasibility version of the GlucoClear™ continuous glucose monitoring system (Edwards Lifesciences, Irvine, CA), the intravenous blood glucose (IVBG) system, developed to facilitate glycemic management, was evaluated. MATERIALS AND METHODS: Two pilot studies were conducted. Ten volunteers with diabetes (1,725 matched pairs) and 10 patients scheduled for intensive care unit (ICU) admission following surgery (1,393 matched pairs) were studied. The patients' blood glucose concentrations were monitored by the IVBG system every 5 min for up to 72 h. The accuracy of the IVBG system was calculated and compared with the Yellow Springs Instrument (YSI) (Yellows Springs, OH) and Radiometer (Copenhagen, Denmark) measurements to determine the percentage of matched pairs that met 15/20%, 10/15%, 12/12.5%, and 10/10% assessment criteria. Performance was calculated as the percentage of the total measurements that would have been displayed in an unblinded study. Adverse events were monitored. RESULTS: The accuracy of the IVBG system met the International Organization for Standardization ISO 15197 15/20% criterion (99.07% in volunteers, 99.43% in the ICU, and both vs. YSI) and the stricter 10/15% criterion (96.17% in volunteers, 96.77% in the ICU, and both vs. YSI) over the 72-h period and across a broad range of blood glucose concentrations. Performance was 89.97% in the ICU study. The adverse device effects included induration of the peripheral vein, mild bruising, and mild hematoma. In the volunteers, there were patency problems with six catheters. CONCLUSIONS: The IVBG system is safe, accurate, and reliable. This minimally invasive system was not affected by potentially interfering medications. Real-time measurements, alarms, and trends provided by the IVBG system might support glycemic control protocols and prevent glycemic events in critically ill patients.

Continuous glucose control in the ICU: report of a 2013 round table meeting.

Achieving adequate glucose control in critically ill patients is a complex but important part of optimal patient management. Until relatively recently, intermittent measurements of blood glucose have been the only means of monitoring blood glucose levels. With growing interest in the possible beneficial effects of continuous over intermittent monitoring and the development of several continuous glucose monitoring (CGM) systems, a round table conference was convened to discuss and, where possible, reach consensus on the various aspects related to glucose monitoring and management using these systems. In this report, we discuss the advantages and limitations of the different types of devices available, the potential advantages of continuous over intermittent testing, the relative importance of trend and point accuracy, the standards necessary for reporting results in clinical trials and for recognition by official bodies, and the changes that may be needed in current glucose management protocols as a result of a move towards increased use of CGM. We close with a list of the research priorities in this field, which will be necessary if CGM is to become a routine part of daily practice in the management of critically ill patients.

Silent, but not unseen: multimicrocystic aspect on T2-weighted MRI in silent corticotroph adenomas.

OBJECTIVE: Silent corticotroph adenomas (SCAs) present as nonfunctional pituitary tumours in routine pre-operative evaluation. The objective of this study was to evaluate the diagnostic accuracy of MRI T2-weighted sequences for detecting the corticotroph subtype pre-operatively. DESIGN: The pre-operative T2-weighted MRI sequences were retrospectively evaluated in patients with SCA and two control groups: clinically manifest corticotroph macroadenomas (CSMs) and nonfunctional gonadotroph macroadenomas (NFGMs). All were selected from a registry of 1096 patients in whom transsphenoidal surgery was performed in the same tertiary reference centre. T2-weighted MRI sequences were independently classified by one senior endocrinologist and one senior radiologist who were blinded to the clinical and histological features. PATIENTS: Seventeen patients with SCA, 14 with CSM and 60 with NFGM were included in this study. MEASUREMENTS: Pituitary MRI with T2-weighted sequences. Two aspects were retained: multiple microcysts (MMs) and the absence of microcysts. Hormonal data included plasma prolactin, IGF-1, testosterone or oestradiol, LH, FT4, TSH, morning plasma cortisol and an ACTH-stimulation test, when available. RESULTS: Multiple microcysts were present in 76% (13/17) of SCAs, 21% (3/14) of CSMs and 5% (3/60) of NFGMs. The presence of MMs in clinically nonfunctioning macroadenomas had a sensitivity of 76% and a specificity of 95% for predicting SCA. CONCLUSION: The presence of MMs in T2-weighted MRI is a good diagnostic tool to suggest the corticotroph subtype in an apparently nonfunctional pituitary tumour.

Management of tight intraoperative glycemic control during off-pump coronary artery bypass surgery in diabetic and nondiabetic patients.

OBJECTIVES: To optimize intra- and postoperative insulin management in cardiac surgical patients. DESIGN: A prospective, randomized, open-label, single-center study. SETTING: A large nonuniversity hospital. PARTICIPANTS: Sixty diabetics and 60 nondiabetics undergoing off-pump cardiac bypass surgery. INTERVENTIONS: Intra- and postoperative tight glycemic control were achieved using different approaches with a modified insulin protocol. MEASUREMENTS AND MAIN RESULTS: Nondiabetics were divided randomly: in the ND-ind group (n = 30), insulin was started at induction according to preinduction blood glucose (BG) concentrations. In group ND >110 (n = 30), insulin was started when BG concentrations exceeded 110 mg/dL during surgery. Up to 85% of the ND >110 group started on insulin intraoperatively. Intraoperatively, the ND-ind group had more BG within target (80-110 mg/dL) (p = 0.002), less BG >130 mg/dL (p = 0.015), and more BG between 70 and 79 mg/dL (p = 0.002). In diabetics, BG concentration was checked every 30 (DM-30), n = 30) versus 60 minutes (DM-60, n = 30) to improve the protocol's performance. Intraoperatively, there were more BG concentrations within target (80-110 mg/dL) (p = 0.02) and less >130 mg/dL (p = 0.0002) in the DM-30 group. During surgery, the hyperglycemic index and the glycemic penalty index were lower in the ND-ind group (p < 0.05). Postoperatively, the mean BG concentrations, hyperglycemic index, and glycemic penalty index in diabetics and nondiabetics were comparable between groups (p < 0.05). In the overall 2,641 BG samples, the lowest BG concentration in the operating room was 71 and in the intensive care unit (ICU) it was 61 mg/dL. CONCLUSIONS: In diabetics and nondiabetics undergoing off-pump coronary artery bypass surgery, tight perioperative glycemic control is feasible and efficient, with minimal risks for hypo- and hyperglycemia. In nondiabetics, starting insulin therapy from induction onwards results in more measurements within target, without affecting the mean BG. In diabetics, decreasing the sampling interval from 60 to 30 minutes results in more measurements within target and in a mean blood glucose within target at ICU arrival.

Interhemispheric synchrony in visual cortex and abnormal postnatal visual experience.

The question of whether neural synchrony may be preserved in adult mammalian visual cortex despite abnormal postnatal visual experience was investigated by combining anatomical and computational approaches. Single callosal axons in visual cortex of early monocularly deprived (MD) adult cats were labeled anterogradely with biocytin in vivo and reconstructed in 3D. Spike propagation was then orthodromically simulated within each of these axons with NEURON software. Data were systematically compared to those previously obtained in normally reared (NR) adult cats with comparable approaches. The architecture of the callosal axons in MD animals differed significantly from the NR group, with longer branches and first nodes located deeper below the cortex. But, surprisingly, simulation of spike propagation demonstrated that transmission latencies of most spikes remained inferior to 2 ms, like the NR group. These results indicate that synchrony of neural activity may be preserved in adult visual cortex despite abnormal postnatal visual experience. According to the temporal binding hypothesis, this also indicates that the necessary timing for visual perception is present despite anatomical abnormalities in visual cortex.

Perioperative blood glucose management in patients undergoing tumor hepatectomy.

STUDY OBJECTIVE: To determine whether our institutional insulin management (modified Atlanta) protocol is efficient and safe in controlling blood glucose levels in the perioperative period in surgical patients undergoing tumor hepatectomy. DESIGN: Retrospective study. SETTING: Large community hospital. PATIENTS: 20 consecutive patients undergoing liver resection for hepatocellular carcinoma, liver metastasis, or other hepatobiliary tumors. INTERVENTIONS AND MEASUREMENTS: All patients continuously received intravenous glucose (5% dextrose in water, one mL/kg/hr); insulin was administered according to a strict algorithm, and dose adjustments were based on measurements of whole-blood glucose intraoperatively at one-hour intervals, and in the intensive care unit (ICU). Lower and upper blood glucose limits were set at 85 mg/dL and 110 mg/dL, respectively, in the operating room (OR). In the ICU, lower and upper limits were 90 mg/dL and 140 mg/dL, respectively. MAIN RESULTS: Intraoperatively, 51.3% of measurements were within the target range. In the ICU, 75.2% of measurements showed a blood glucose level of 90 - 140 mg/dL. Two of 78 (2.6%) and two of 363 (0.5%) measurements had a blood glucose level < 70 mg/dL in the OR and ICU, respectively. The lowest blood glucose levels were 65 mg/dL (OR) and 66 mg/dL (ICU). CONCLUSIONS: The modified Atlanta protocol is efficient and safe in controlling blood glucose levels in the perioperative period of hepatic tumor resection. Because of decreased insulin needs in the ICU, the use of a more liberal algorithm successfully reduced the risk of hypoglycemia.

Tight glycaemic control: clinical implementation of protocols.

Implementation of tight glycaemic control in hospitalised patients presents a huge challenge. It concerns many patients, there are many interfering factors and many health-care professionals are involved. The current literature provides little practical guidance. This article offers the clinical anesthesiologist direction for the organisation of inpatient blood glucose control in acute situations, in the perioperative setting and in the intensive care unit. An effective, safe and user-friendly algorithm for intravenous insulin administration is presented that can be executed by regular nurses and used in many situations. Practical advice is offered for the use of subcutaneous basal-bolus insulin, for fasting orders and for transition to discharge care. The main safety considerations are discussed.