Closed-Loop ventilation using sidestream versus mainstream capnography for automated adjustments of minute ventilation-A randomized clinical trial in cardiac surgery patients.

BACKGROUND: INTELLiVENT-Adaptive Support Ventilation (ASV) is a closed-loop ventilation mode that uses capnography to adjust tidal volume (VT) and respiratory rate according to a user-set end-tidal CO2 (etCO2) target range. We compared sidestream versus mainstream capnography with this ventilation mode with respect to the quality of breathing in patients after cardiac surgery. METHODS: Single-center, single-blinded, non-inferiority, randomized clinical trial in adult patients scheduled for elective cardiac surgery that were expected to receive at least two hours of postoperative ventilation in the ICU. Patients were randomized 1:1 to closed-loop ventilation with sidestream or mainstream capnography. Each breath was classified into a zone based on the measured VT, maximum airway pressure, etCO2 and pulse oximetry. The primary outcome was the proportion of breaths spent in a predefined 'optimal' zone of ventilation during the first three hours of postoperative ventilation, with a non-inferiority margin for the difference in the proportions set at -20%. Secondary endpoints included the proportion of breaths in predefined 'acceptable' and 'critical' zones of ventilation, and the proportion of breaths with hypoxemia. RESULTS: Of 80 randomized subjects, 78 were included in the intention-to-treat analysis. We could not confirm the non-inferiority of closed-loop ventilation using sidestream with respect to the proportion of breaths in the 'optimal' zone (mean ratio 0.87 [0.77 to ∞]; P = 0.116 for non-inferiority). The proportion of breaths with hypoxemia was higher in the sidestream capnography group versus the mainstream capnography group. CONCLUSIONS: We could not confirm that INTELLiVENT-ASV using sidestream capnography is non-inferior to INTELLiVENT-ASV using mainstream capnography with respect to the quality of breathing in subjects receiving postoperative ventilation after cardiac surgery. TRIAL REGISTRATION: NCT04599491 (clinicaltrials.gov).

Endobronchial blocker use for massive, focal pulmonary hemorrhage during pulmonary endarterectomy for CTEPH.

Chronic thromboembolic pulmonary hypertension (CTEPH) has a poor prognosis if left untreated but can be cured by pulmonary endarterectomy (PEA). Massive endobronchial pulmonary hemorrhage is a potentially fatal complication of PEA, occurring in 0.5%of patients. We describe the use of an endobronchial blocker (EBB) as an additional method to successfully treat massive, focal pulmonary hemorrhage during PEA.

Noninvasive follow-up strategy after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension.

Background: The success of pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) is usually evaluated by performing a right heart catheterisation (RHC). Here, we investigate whether residual pulmonary hypertension (PH) can be sufficiently excluded without the need for a RHC, by making use of early post-operative haemodynamics, or N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiopulmonary exercise testing (CPET) and transthoracic echocardiography (TTE) 6 months after PEA. Methods: In an observational analysis, residual PH after PEA measured by RHC was related to haemodynamic data from the post-operative intensive care unit time and data from a 6-month follow-up assessment including NT-proBNP, TTE and CPET. After dichotomisation and univariate analysis, sensitivity, specificity, positive predictive value, negative predictive value (NPV) and likelihood ratios were calculated. Results: Thirty-six out of 92 included patients had residual PH 6 months after PEA (39%). Correlation between early post-operative and 6-month follow-up mean pulmonary artery pressure was moderate (Spearman rho 0.465, p<0.001). Early haemodynamics did not predict late success. NT-proBNP >300 ng·L-1 had insufficient NPV (0.71) to exclude residual PH. Probability for PH on TTE had a moderate NPV (0.74) for residual PH. Peak oxygen consumption (V'O2 ) <80% predicted had the highest sensitivity (0.85) and NPV (0.84) for residual PH. Conclusions: CPET 6 months after PEA, and to a lesser extent TTE, can be used to exclude residual CTEPH, thereby safely reducing the number of patients needing to undergo re-RHC after PEA.

Entrustable professional activities (EPAs) for postgraduate competency based intensive care medicine training in the Netherlands: The next step towards excellence in intensive care medicine training.

INTRODUCTION: The Competency Based Training in Intensive Care Education (CoBaTrICE) programme developed common standards of ICM training by describing competencies of an intensivist. Entrustable Professional Activities (EPAs) of Intensive Care Medicine (ICM) (EPAsICM) are presented as a new workplace-based assessment tool in competency-based training of intensivists. EPAs are activities to be entrusted to a trainee once he (or she) has attained competence. EPAs emphasise the role of trust between trainees and supervisors. EPAs bridge the gap between competencies and competence. METHODS: An expert panel of ICM (vice)programme directors and intensivists in The Netherlands integrated the CoBaTrICE and CanMEDS competencies into EPAsICM. Comment and feedback was sought from other ICM programme directors and educational experts and processed in the final version of EPAsICM before implementation in the Dutch ICM training programme. RESULTS: A list of 15 EPAsICM are considered to reflect the spectrum of clinical practice while incorporating the competencies of CoBaTrICE and CanMEDS. The grading system is designed as a 5-point entrustment scale based on the amount of supervision a trainee needs, aligning with daily judgement of trainees by intensivists. CONCLUSION: EPAsICM is an assessment tool that formalises entrustment decisions and can be a valuable addition in international ICM training.

Feasibility of Exercise Testing in Patients Who Are Critically Ill: A Prospective, Observational Multicenter Study.

OBJECTIVE: To evaluate the feasibility and safety of exercise testing and to describe the physiological response to exercise of patients in the Intensive Care Unit (ICU). DESIGN: A prospective observational multicenter study. SETTING: Two mixed medical-surgical ICUs. PARTICIPANTS: Patients (N=37; with no primary neurological disorders, 59% men; median age 50y; ICU length of stay 14.5d; Acute Physiology and Chronic Health Evaluation IV 73.0) who had been mechanically ventilated for more than 48 hours and were hemodynamically stable enough to perform physical exercise. INTERVENTIONS: A passive or active incremental exercise test, depending on muscle strength, on a bed-based cycle ergometer. MAIN OUTCOME MEASURES: Feasibility and safety were evaluated based on protocol adherence and adverse events. Physiological responses to exercise quantified as changes in respiratory frequency (RF), oxygen uptake (Vo2), carbon dioxide output (Vco2), respiratory exchange ratio (RER), and blood lactate. RESULTS: Thirty-seven patients of whom 18 were mechanically ventilated underwent the exercise test. The active incremental test was performed by 28, and the passive test by 9 participants. Thirty-three (89%) accomplished the test according to the protocol and 1 moderate severe adverse event (bradycardia; heart rate 44) occurred shortly after the test. RF, Vo2, Vco2, and lactate increased significantly, whereas RER did not change during the active incremental exercise test. No changes were observed during the passive exercise test. CONCLUSIONS: It is safe and feasible to perform exercise testing on a bed-based cycle ergometer in patients who are critically ill and a physiological response could be measured. Future research should investigate the clinical value of exercise testing in daily ICU practice and whether exercise capacity and its limiting factors could be determined by incremental exercise testing.

Safety of mechanical chest compression devices AutoPulse and LUCAS in cardiac arrest: a randomized clinical trial for non-inferiority.

AIMS: Mechanical chest compression (CC) during cardiopulmonary resuscitation (CPR) with AutoPulse or LUCAS devices has not improved survival from cardiac arrest. Cohort studies suggest risk of excess damage. We studied safety of mechanical CC and determined possible excess damage compared with manual CC. METHODS AND RESULTS: This is a randomized non-inferiority safety study. Randomization to AutoPulse, LUCAS, or manual CC with corrective depth and rate feedback was performed. We included patients with in-hospital cardiac arrest or with out-of-hospital cardiac arrest arriving with manual CPR at the emergency department. The primary outcome was serious or life-threatening visceral resuscitation-related damage, assessed blind by post-mortem computed tomography scan and/or autopsy or by clinical course until discharge. Non-inferiority hypothesis: mechanical CC compared with manual control does not increase the primary outcome by a risk difference of > 10% [upper 95% confidence interval (CI)]. We included 115 patients treated with AutoPulse, 122 with LUCAS, and 137 patients received manual CC. Safety outcome analysis was possible in 337 of 374 (90.1%) included patients. The primary outcome was observed in 12 of 103 AutoPulse patients (11.6%), 8 of 108 LUCAS patients (7.4%), and 8 of 126 controls (6.4%). Rate difference AutoPulse-control: +5.3% (95% CI - 2.2% to 12.8%), P = 0.15. Rate difference LUCAS-control +1.0% (95% CI - 5.5% to 7.6%), P = 0.75. CONCLUSION: LUCAS does not cause significantly more serious or life-threatening visceral damage than manual CC. For AutoPulse, significantly more serious or life-threatening visceral damage than manual CC cannot be excluded.

Hemodynamic and ventilatory responses during exercise in chronic thromboembolic disease.

BACKGROUND: Patients with chronic thromboembolic disease (CTED) may suffer from exercise intolerance without pulmonary hypertension at rest. Pulmonary endarterectomy (PEA) for symptomatic CTED results in improvement of symptoms and quality of life. Neither the pathophysiology of the exercise limitation nor the underlying mechanisms of the PEA-induced improvement have been studied previously. OBJECTIVES: We studied hemodynamic and ventilatory responses upon exercise in 14 patients with CTED. After 1 year, we studied the underlying physiologic mechanisms of the PEA-induced symptomatic improvement. METHODS: Cardiopulmonary exercise testing (CPET) was performed during right heart catheterization, and noninvasive CPET was performed 1 year postoperatively. RESULTS: During exercise, we observed abnormal pulmonary vascular responses, that is, a steep mean pulmonary artery pressure/cardiac output (2.7 ± 1.2 mm Hg·min·L(-1)), and low pulmonary vascular compliance (2.8 ± 1.1 mL·mm Hg(-1)); mean pulmonary artery pressure/cardiac output slope correlated with dead-space ventilation (r = 0.586; P = .028) and ventilatory equivalents for carbon dioxide slope (r = .580; P = .030). Postoperatively, the improvement observed in exercise capacity was related to improvements in CPET-derived parameters pointing to restoration of right ventricle stroke volume response (oxygen pulse: 11.7 ± 3.1 to 13.3 ± 3.3; P = .027; heart rate response: 80.9 ± 12.4 to 72.0 ± 5.7; P = .003); and, indicating improved ventilatory efficiency, the ventilatory equivalents for carbon dioxide slope decreased from 38.2 ± 3.6 to 32.8 ± 7.0 (P = .014). CONCLUSIONS: Patients with CTED showed an abnormal pulmonary vascular response to exercise and a decreased ventilatory efficiency. Responses after PEA point to restoration of right ventricle stroke volume response and ventilatory efficiency.

Progress testing in intensive care medicine training: useful and feasible?!

So far the in-training assessment of knowledge is perhaps underrepresented in postgraduate assessment frameworks in intensive care medicine (ICM). In most contemporary training programs a predominant emphasis is placed on workplace based learning and workplace based assessment. This article provides a concise general background on the nature and use of progress testing, and touches upon potential strengths, and constraints regarding its potential implementation and use in the postgraduate ICM training programs.

Validation of a novel method for measuring intra-abdominal pressure and gastric residual volume in critically ill patients.

BACKGROUND: Gastric residual volume (GRV) can be measured in a variety of ways in critically ill patients, most often, the nasogastric tube is disconnected and the GRV is aspirated via a 60 mL syringe. Bladder pressure (IBP) measurement is the gold standard for intra-abdominal pressure (IAP) estimation. This study will look at the validation of a novel method combining measurement of GRV and estimation of IAP via intra-gastric pressure (IGP). METHODS: In total 135 paired IAP and 146 paired GRV measurements were performed in 37 mechanically ventilated ICU patients. The IAP was estimated via the bladder (i.e. IBP) using the FoleyManometer and via the stomach (i.e. IGP) with the new device. The GRV was measured with the new device (GRVprototype) and via the classic method (GRVclassic). The devices were provided by Holtech Medical (Charlottenlund, Denmark) and data were retrospectively analysed. RESULTS: The number of paired measurements in each patient was 4 ± 1. The mean IBP was 10.7 ± 4.1 and mean IGP was 11.6 ± 4.1 mm Hg. Correlation between the IBP and IGP was significant, however moderate (R2 = 0.51). Analysis according to Bland and Altman showed a bias and precision of 0.8 and 2.7 mm Hg respectively, however the limits of agreement (LA) were large and ranged from -4.5 to 6.1 mm Hg. Changes in IGP correlated well with changes in IBP. The median GRVprototype was 80 mL (0-1050) and equal to the median GRVclassic of 80 mL (0-1250). Correlation between the 2 methods was excellent (R2 = 0.89). Analysis according to Bland and Altman showed a bias and precision of -0.8 and 52.3 mL respectively and the LA ranged from -103 to 102 mL. Changes in GRVclassic correlated well with changes in GRVprototype. CONCLUSIONS: The results of this multicentre pilot study show that GRV can be measured with the new device. Furthermore this allows simultaneous screening for intra-abdominal hypertension with IAP estimation via IGP.

Nutrition before, during, and after surgery increases the arginine:asymmetric dimethylarginine ratio and relates to improved myocardial glucose metabolism: a randomized controlled trial.

BACKGROUND: Nitric oxide (NO) is essential for the optimal perfusion of the heart and its vasculature. NO may be insufficient in surgical patients because its precursor arginine is decreased, and the inhibitor of NO synthesis asymmetric dimethylarginine (ADMA) is increased. Besides arginine, the presence of other amino acids essential for the proper metabolism of cardiac cells may be decreased too. Supplementation of these amino acids with enteral and parenteral nutrition before, during, and after surgery may augment the myocardial and plasma arginine:ADMA ratio and availability of amino acids. Myocardial glucose metabolism and nutritional conditioning may result in a reduction of cardiac injury and support rapid recovery after major surgery. OBJECTIVE: We investigated the effect of nutrition before, during, and after surgery on amino acids and the myocardial arginine:ADMA ratio and its relation to myocardial glucose metabolism. DESIGN: In this trial, 33 patients who were undergoing off-pump coronary artery bypass grafting (CABG) were randomly assigned between enteral, parenteral, or no nutrition (control) from 2 d before, during, and until 2 d after surgery. Both enteral and parenteral solutions were prepared with commercially available products and included proteins or amino acids, glucose, vitamins, and minerals. Concentrations of amino acids including ADMA were analyzed in myocardial tissue and plasma samples. ¹8F-fluorodeoxyglucose positron emission tomography was performed before and after surgery to assess myocardial glucose metabolism. RESULTS: The myocardial arginine:ADMA ratio increased during surgery and was significantly higher in the enteral and parenteral groups than in the control group [median (IQR): 115.0 (98.0-142.2) (P = 0.012), 116.9 (100.3-135.3) (P = 0.004), and 93.3 (82.7-101.1), respectively]. Furthermore, the change in the preoperative to postoperative plasma arginine:ADMA ratio correlated with the change in myocardial glucose metabolism in positron emission tomography (r = 0.427, P = 0.033). CONCLUSION: Enteral or parenteral nutrition before, during, and after CABG may positively influence myocardial glucose metabolism by increasing the plasma and myocardial arginine:ADMA ratio.

Bosentan as a bridge to pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension.

OBJECTIVES: In proximal chronic thromboembolic pulmonary hypertension, pulmonary endarterectomy is the treatment of first choice. In general, medical treatment before pulmonary endarterectomy is not indicated. However, selected "high-risk" patients might benefit by optimization of pulmonary hemodynamics. Moreover, in patients whose surgery is delayed owing to limited medical resources, pretreatment may prevent clinical deterioration. The primary objective of this study was to determine whether the dual endothelin-1 antagonist bosentan improves pulmonary hemodynamics and functional capacity in patients with proximal chronic thromboembolic pulmonary hypertension waiting for pulmonary endarterectomy. METHODS: We used an investigator-initiated, randomized, controlled single-blind study. Patients were randomized to receive bosentan (n = 13) or no bosentan (n = 12) for 16 weeks, next to "best standard of care." The primary end point was change in total pulmonary resistance. Secondary end points included changes in 6-minute walk distance, mean pulmonary artery pressure, and cardiac index. RESULTS: After 16 weeks, the mean differences in change from baseline between the groups were as follows: total pulmonary resistance 299 dynes x s x cm(-5) (P = .004), 6-minute walk distance 33 m (P = .014), mean pulmonary artery pressure 11 mm Hg (P = .005), and cardiac index 0.3 L x min(-1) x m(-2) (P = .08). Treatment with bosentan was safe. After pulmonary endarterectomy, 4 patients died (no-bosentan group: n = 3); the short-term in-hospital postoperative clinical course was similar in both groups of patients. CONCLUSIONS: Patients with proximal chronic thromboembolic pulmonary hypertension may benefit hemodynamically and clinically from treatment with bosentan before pulmonary endarterectomy. Individual factors predictive of a beneficial response and whether this influences either morbidity or mortality associated with pulmonary endarterectomy remain to be established.

Glycine does not add to the beneficial effects of perioperative oral immune-enhancing nutrition supplements in high-risk cardiac surgery patients.

BACKGROUND: Elderly patients and patients with a poor cardiac function have increased morbidity rates when undergoing cardiac surgery. The aim of this study was to determine whether addition of glycine to a standard preoperative oral immune-enhancing nutrition supplement (OIENS) improves outcome. Glycine-enriched OIENS was compared with 2 formulas: standard OIENS and control. METHODS: In this double-blind, 3-armed study, patients scheduled to undergo cardiac surgery with the use of extracorporeal circulation received either the glycine-enriched OIENS (OIENS + glyc, n = 24), standard OIENS (OIENS, n = 25), or control formula (Control, n = 25) for minimally 5 preoperative days. Patients were included if they were aged 70 years or older, had a compromised left ventricular function, or were planned for mitral valve surgery. Main outcome measures were postoperative infectious morbidity, organ function, and postoperative recovery. RESULTS: Infectious morbidity was significantly lower in both treatment groups compared with the control group (p = .02). An infection was diagnosed in 5 and 4 patients in the OIENS + glyc and OIENS groups, respectively, and in 12 control patients. Less supportive therapy was necessary to stabilize circulation in both treatment groups compared with the control group. Median length of hospital stay was 7.0, 6.5, and 8.0 days in the OIENS + glyc, OIENS, and control groups, respectively. Inflammatory responses, as measured by systemic levels of proinflammatory cytokines and surface markers on polymorphonuclear cells, were comparable for all groups. CONCLUSIONS: Preoperative OIENS reduces postoperative infectious morbidity and results in a more stable circulation; the addition of glycine does not result in any beneficial effect over standard OIENS.

Clinically relevant differences in accuracy of enteral nutrition feeding pump systems.

BACKGROUND: There are clinically relevant discrepancies between prescribed volumes and delivered volumes of enteral nutrition (EN) in intensive care unit (ICU) patients. Next to EN-protocol violations due to insufficient care, we hypothesized technical factors to be responsible for this deficit. The aim of this study was to determine the accuracy of EN feeding pump systems frequently used in the ICU. METHODS: Thirteen commercially available EN feeding pumps with their own delivery systems were tested in 12 sessions with different EN feeding tubes and EN formulas in a laboratory setting. The reproducibility of the measurements was determined for the 8 best performing EN feeding pump systems. RESULTS: There were clinically important differences between prescribed volumes and delivered volumes of EN in the tested EN feeding pump systems. The deficit in volume ranged from +66 mL (surplus of 66 mL) to -271 mL (deficit of 271 mL) per 24 hours (14% of prescribed volume). Viscosity of test fluids (water/EN feeding formulas) and resistance of test tubes had no influence on the delivered volume by the tested EN feeding pump systems, because differences between prescribed volumes and delivered volumes were consistently found for each system while varying these test settings. CONCLUSIONS: Differences between prescribed and delivered EN volumes are caused by the function and construction of EN feeding pump systems. To improve nutrition therapy, the flow rate has to be adjusted or the best-performing EN feeding pump has to be purchased.

Generation of platelet-derived microparticles in patients undergoing cardiac surgery is not affected by complement activation.

OBJECTIVE: The mechanisms causing the presence of platelet-derived microparticles in the circulation are unknown. In vitro platelets release platelet-derived microparticles in response to complement activation. This study evaluates the relationship between complement activation and levels of circulating platelet-derived microparticles in patients undergoing cardiac surgery. METHODS: Prospectively, 71 patients were included who underwent elective coronary artery bypass grafting with cardiopulmonary bypass. The patients were randomly allocated to one of the 3 groups: uncoated oxygenator, UnModified Surface (n = 25) or oxygenator coated with either BioPassive Surface (n = 25) or BioActive Surface (n = 21). Platelet-derived microparticles and terminal complement complexes were determined before bypass and after induction of anesthesia, 15 minutes after the start of cardiopulmonary bypass, at the end of cardiopulmonary bypass, and 30 minutes after administration of protamine sulfate. RESULTS: Demographic and cardiopulmonary bypass data were similar for the 3 groups. At the end of cardiopulmonary bypass, platelet-derived microparticle numbers were decreased in all 3 groups. No significant differences were observed among the groups at any sampling point. At the end of cardiopulmonary bypass, terminal complement complex concentrations were increased in all groups (P <.001), and significant differences among the groups were present (P =.002). CONCLUSIONS: Despite significant complement activation, no increase in numbers of circulating platelet-derived microparticles was found in the systemic blood of patients undergoing cardiac surgery with cardiopulmonary bypass. Thus complement activation in vivo does not necessarily affect generation of platelet-derived microparticles.