Bart F. Geerts

Assessment of venous return curve and mean systemic filling pressure in postoperative cardiac surgery patients

Objective:To measure the relationship between blood flow and central venous pressure (Pcv) and to estimate mean systemic filling pressure (Pmsf), circulatory compliance, and stressed volume in patients in the intensive care unit. Design:Intervention study. Setting:Intensive care unit of a university hospital. Patients:Twelve mechanically ventilated postoperative cardiac surgery patients. Interventions:Inspiratory holds were performed during normovolemia in supine position (baseline), relative hypovolemia by placing the patients in 30 degree head-up position (hypo), and relative hypervolemia by volume loading with 0.5 L colloid (hyper). Measurements and Main Results:We measured the relationship between blood flow and Pcv using 12-second inspiratory-hold maneuvers transiently increasing Pcv to three different steady-state levels and monitored the resultant blood flow via the pulse contour method during the last 3 seconds. The Pcv to blood flow relation was linear for all measurements with a slope unaltered by relative volume status. Pmsf decreased with hypo and increased with hyper (18.8 ± 4.5 mm Hg, to 14.5 ± 3.0 mm Hg, to 29.1 ± 5.2 mm Hg [baseline, hypo, hyper, respectively, p < 0.05]). Baseline total circulatory compliance was 0.98 mL·mm Hg−1·kg−1 and stressed volume was 1677 mL. Conclusions:Pmsf can be determined in intensive care patients with an intact circulation with use of inspiratory pause procedures, making serial measures of circulatory compliance and circulatory stressed volume feasible.

Performance of three minimally invasive cardiac output monitoring systems

We evaluated cardiac output (CO) using three new methods – the auto‐calibrated FloTrac–Vigileo (COed), the non‐calibrated Modelflow (COmf ) pulse contour method and the ultra‐sound HemoSonic system (COhs) – with thermodilution (COtd) as the reference. In 13 postoperative cardiac surgical patients, 104 paired CO values were assessed before, during and after four interventions: (i) an increase of tidal volume by 50%; (ii) a 10 cm H2O increase in positive end‐expiratory pressure; (iii) passive leg raising and (iv) head up position. With the pooled data the difference (bias (2SD)) between COed and COtd, COmf and COtd and COhs and COtd was 0.33 (0.90), 0.30 (0.69) and −0.41 (1.11) l.min−1, respectively. Thus, Modelflow had the lowest mean squared error, suggesting that it had the best performance. COed significantly overestimates changes in cardiac output while COmf and COhs values are not significantly different from those of COtd. Directional changes in cardiac output by thermodilution were detected with a high score by all three methods.

Pulse Contour Analysis to Assess Hemodynamic Response to Passive Leg Raising

OBJECTIVE The authors evaluated the ability of 2 pulse contour cardiac output (CO) techniques to track CO changes during passive leg raising (PLR) to assess fluid loading responsiveness. DESIGN A prospective study. SETTING An intensive care unit in a university hospital. PARTICIPANTS Twenty mechanically ventilated postoperative cardiac surgery patients. INTERVENTIONS Thirty-degree PLR. MEASUREMENTS AND MAIN RESULTS The authors estimated CO by 3 techniques: thermodilution (COtd), arterial pulse power (Coli; LiDCO, London, UK), and pulse contour method (Com; FMS, Amsterdam, The Netherlands) based on uncalibrated Modelflow. The authors measured heart rate (HR), central venous pressure, arterial pulse pressure (PP), systolic pressure (SP), and mean arterial pressure (MAP). Stroke volume (SV), SP, PP, and SV variation (PPV and SVV, respectively) were calculated over 5 breaths. SVV was measured by both LiDCO (SVVli) and Modelflow (SVVm) devices. PLR-induced changes in COtd correlated with COli (p < 0.001) and COm (p < 0.001). Preload dependence was predicted with an area under the ROC curve of 0.968 for ΔCOm, 0.841 for ΔCOli, 0.825 for SVVm, 0.873 for SVVli, 0.808 for PPV, 0.778 for ΔSP, 0.714 for ΔPP, and 0.873 for ΔMAP. CONCLUSIONS Changes in COm, COli, SVV, and PPV track COtd changes during PLR with a high degree of accuracy in sedated, ventilated, postoperative cardiac surgery patients. Changes in pulse contour CO after PLR can be used to predict fluid loading responsiveness.

First proof of pharmacology in humans of a novel glucagon receptor antisense drug

Fasting and postprandial hyperglucagonemia in type 2 diabetes mellitus (T2DM) patients cause excessive hepatic glucose production (HGP), suggesting that attenuation of hepatic glucagon action could be a therapeutic strategy for T2DM. In this study we evaluated the safety, tolerability, PK, and pharmacodynamics in healthy human volunteers of single and multiple doses (50–400 mg) ISIS 325568, a 2′‐O‐MOE antisense (ASO) developed to reduce hepatic glucagon receptor (GCGR) mRNA expression. In the multiple dose cohorts, treatment consisted of eight doses of ISIS 325568 or placebo over 6‐weeks. Drug effects were assessed using serial fasting glucagon measurements and the glycemic response to a glucagon challenge at baseline and at the end of 6‐week treatment. ISIS 325568 was not associated with clinically relevant changes. Dose‐dependent predominantly mild injection site reactions were the most common side‐effect. Active treatment caused a gradual increase in fasting glucagon levels and, compared to placebo, a significantly blunted glucagon‐induced increase in plasma glucose AUC (24%, P < 0.0001) and HGP (13%, P = 0.007) at the 400 mg/week dose. Six weeks treatment with ISIS 325568 in healthy volunteers attenuated glucagon‐stimulated HGP and glucose excursions, supporting further evaluation of the GCGR antisense approach in patients with T2DM.

Hydrolyzed Casein Decreases Postprandial Glucose Concentrations in T2DM Patients Irrespective of Leucine Content

ABSTRACT Lifestyle modifications, including diet, are important in the prevention and management of type 2 diabetes mellitus (T2DM). However, limited information is available on the effects of single doses of meal replacements, particularly with regard to their effect on postprandial glucose. Therefore, a study was performed comparing the effects of a single meal replacement in T2DM patients on postprandial serum glucose, insulin, and glucagon. This randomized, double-blind, partial cross-over study was performed in 36 T2DM patients who continued their oral anti-diabetic medication. Each patient received three out of four treatments separated by 7 days. The treatments were a proprietary casein hydrolysate (insuVida™) alone or with additional leucine, unhydrolyzed casein, or placebo. Blood sampling was done for 4 hr. Treatments were compared using repeated measures ANOVA. Results are given as an estimate of the difference (%) for the 4-hr epoch. Glucose concentrations were lowered by −4.7% by insuVida and insuVida plus added leucine compared to placebo (95% CI: −1.6 to −7.7%), while the effect of unhydrolyzed casein was −1.7% (−4.8 to 1.5%). Addition of leucine to insuVida induced the greatest increase in insulin (i.e., 51.8%; 41.1 to 63.4%). All three treatments increased glucagon concentrations by 14% (8 to 20%) compared to placebo. A single dose of insuVida™ with or without addition of leucine significantly lowered plasma glucose compared to placebo and intact casein in T2DM patients. This is most likely due to an insulinotropic effect of insuVida. The data suggest that this type of intervention may be a viable treatment strategy in T2DM.

Arm occlusion pressure is a useful predictor of an increase in cardiac output after fluid loading following cardiac surgery.

Background and objective In pharmacological research, arm occlusion pressure is used to study haemodynamic effects of drugs. However, arm occlusion pressure might be an indicator of static filling pressure of the arm. We hypothesised that arm occlusion pressure can be used to predict fluid loading responsiveness. Methods Twenty-four patients who underwent cardiac surgery were studied during their first 2 h in the ICU. The lungs were ventilated mechanically and left ventricular function was supported as necessary. Arm occlusion pressure was defined as the radial artery pressure after occluding arterial flow for 35 s by a blood pressure cuff inflated to 50 mmHg above SBP. The cuff was positioned around the arm in which a radial artery catheter had been inserted. Measurements were performed before (baseline) and after fluid loading (500 ml hydroxyethyl starch 6%). Patients whose cardiac output increased by at least 10% were defined as responders. Results In responders (n = 17), arm occlusion pressure, mean arterial pressure and central venous pressure increased and stroke volume variation and pulse pressure variation decreased. In non-responders (n = 7), arm occlusion pressure and central venous pressure increased, and pulse pressure variation decreased. Mean arterial pressure, stroke volume variation and heart rate did not change significantly. The area under the curve to predict fluid loading responsiveness for arm occlusion pressure was 0.786 (95% confidence interval 0.567–1.000), at a cut-off of 21.9 mmHg, with sensitivity of 71% and specificity of 88% in predicting fluid loading responsiveness. Prediction of responders with baseline arm occlusion pressure was as good as baseline stroke volume variation and pulse pressure variation. Conclusion Arm occlusion pressure was a good predictor of fluid loading responsiveness in our group of cardiac surgery patients and offers clinical advantages over stroke volume variation and pulse pressure variation.

Defining Fluid Responsiveness: A Guide to Patient-Tailored Volume Titration

FLUID RESPONSIVENESS is a strategy used to select patients who will respond with a positive reaction in a physiologic parameter upon fluid administration. Curiously, there is no generally accepted definition of fluid responsiveness. A provisional definition of fluid responsiveness would be “the positive reaction of a physiologic parameter of a certain size to a standardized volume of a certain type of fluid administered within a certain amount of time and measured within a certain interval.” It is clear that these issues need to be resolved before a more detailed and precise definition can be proposed. The aim of predicting fluid responsiveness is to achieve this positive reaction while using the least amount of fluids. Accurate prediction of fluid responsiveness to facilitate patient-tailored fluid titration is crucial, as it has been shown that only half of critically ill patients will respond to fluid loading with an increase in cardiac output. Moreover, unnecessary fluid administration has shown to increase morbidity, mortality, and hospital and intensive care stays. Over the last decade, the rise in the number of publications about fluid responsiveness in the intensive care and operating room has shown the increased interest in this topic. In this review, the authors describe the physiology, requirements, and limitations of fluid responsiveness. Subsequently, using available literature, a practical definition on fluid responsiveness is proposed. The reliability of clinical, static, and hemodynamic parameters is evaluated to predict the response to fluid loading in critically ill patients. Finally, the potential, shortcomings, and use of passive leg raising are discussed in this review.

Laser speckle contrast imaging identifies ischemic areas on gastric tube reconstructions following esophagectomy

AbstractGastric tube reconstruction (GTR) is a high-risk surgical procedure with substantial perioperative morbidity. Compromised arterial blood supply and venous congestion are believed to be the main etiologic factors associated with early and late anastomotic complications. Identifying low blood perfusion areas may provide information on the risks of future anastomotic leakage and could be essential for improving surgical techniques. The aim of this study was to generate a method for gastric microvascular perfusion analysis using laser speckle contrast imaging (LSCI) and to test the hypothesis that LSCI is able to identify ischemic regions on GTRs.Patients requiring elective laparoscopy-assisted GTR participated in this single-center observational investigation. A method for intraoperative evaluation of blood perfusion and postoperative analysis was generated and validated for reproducibility. Laser speckle measurements were performed at 3 different time pointes, baseline (devascularized) stomach (T0), after GTR (T1), and GTR at 20° reverse Trendelenburg (T2).Blood perfusion analysis inter-rater reliability was high, with intraclass correlation coefficients for each time point approximating 1 (P < 0.0001). Baseline (T0) and GTR (T1) mean blood perfusion profiles were highest at the base of the stomach and then progressively declined towards significant ischemia at the most cranial point or anastomotic tip (P < 0.01). After GTR, a statistically significant improvement in mean blood perfusion was observed in the cranial gastric regions of interest (P < 0.05). A generalized significant decrease in mean blood perfusion was observed across all GTR regions of interest during 20° reverse Trendelenburg (P < 0.05).It was feasible to implement LSCI intraoperatively to produce blood perfusion assessments on intact and reconstructed whole stomachs. The analytical design presented in this study resulted in good reproducibility of gastric perfusion measurements between different investigators. LSCI provides spatial and temporal information on the location of adequate tissue perfusion and may thus be an important aid in optimizing surgical and anesthesiological procedures for strategically selecting anastomotic site in patients undergoing esophagectomy with GTR.

Effect of goal-directed therapy on outcome after esophageal surgery: A quality improvement study

Background Goal-directed therapy (GDT) can reduce postoperative complications in high-risk surgery patients. It is uncertain whether GDT has the same benefits in patients undergoing esophageal surgery. Goal of this Quality Improvement study was to evaluate the effects of a stroke volume guided GDT on post-operative outcome. Methods and findings We compared the postoperative outcome of patients undergoing esophagectomy before (99 patients) and after (100 patients) implementation of GDT. There was no difference in the proportion of patients with a complication (56% vs. 54%, p = 0.82), hospital stay and mortality. The incidence of prolonged ICU stay (>48 hours) was reduced (28% vs. 12, p = .005) in patients treated with GDT. Secondary analysis of complication rate showed a decrease in pneumonia (29 vs. 15%, p = .02), mediastinal abscesses (12 vs. 3%, p = .02), and gastric tube necrosis (5% vs. 0%, p = .03) in patients treated with GDT. Patients in the GDT group received significantly less fluids but received more colloids. Conclusions The implementation of GDT during esophagectomy was not associated with reductions in overall morbidity, mortality and hospital length of stay. However, we observed a decrease in pneumonia, mediastinal abscesses, gastric tube necrosis, and ICU length of stay.

Anaesthesia during oesophagectomy

In this review, we will provide an overview of the current state of the art of perioperative practices for open and laparoscopic oesophagus surgery from the anaesthetists perspective. Morbidity and mortality after oesophagectomy is still high despite multidisciplinary and enhanced recovery pathways showing promising results. The anaesthetist has an important role in the complex care of the oesophageal cancer patient. Minimizing unnecessary fluid administration, adequate pain management, hypotension, and protective lung ventilation are examples of proven strategies that can improve outcome after this high-risk surgery.