Effects of Landiolol on Macrocirculatory Parameters and Left and Right Ventricular Performances Following Cardiac Surgery: A Randomized Controlled Trial.

OBJECTIVES: Postoperative atrial fibrillation (POAF) is a major complication after cardiac surgery, and an early postoperative introduction of beta-blockers is recommended to reduce its incidence. Landiolol, a new intravenous short-acting beta-1 blocker, could present a useful and safe macrohemodynamic profile after cardiac surgery. Detailed metabolic and hemodynamic effects of landiolol on cardiac performance, however, remain poorly documented. The authors aimed to investigate the dose-dependent hemodynamic and metabolic effects of landiolol in that specific setting. DESIGN: A prospective, randomized, double-blind study versus placebo. SETTING: A tertiary university hospital. PARTICIPANTS: Adult patients scheduled for elective cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Incremental doses of intravenous landiolol (0.5, 1, 2, 5, and 10 µg/kg/min) were given within the 2 hours after arrival in the intensive care unit. Macrocirculatory parameters and cardiac performances were derived from transpulmonary thermodilution and transthoracic echocardiography. Metabolic data were obtained from arterial blood tests. MEASUREMENTS AND MAIN RESULTS: From January to November 2019, 58 patients were analyzed and divided into a landiolol group (n = 30) and a control group (n = 28). Heart rate significantly decreased in the landiolol group (p < 0.01), whereas mean arterial pressure and stroke volume remained unchanged. No significant modification was found in both left and right systolic and diastolic performances. Metabolic variables were similar in both groups. New-onset POAF occurred in 9 (32%) versus 5 (17%) patients in the control and landiolol groups, respectively (p = 0.28). CONCLUSIONS: Infusion of landiolol in the range of 0.5-to-10 µg/kg/min during the early postoperative period presents a good macrohemodynamic safety profile in cardiac surgical patients and could be useful to prevent POAF.

Efficacy and safety of extracorporeal membrane oxygenation for high-risk pulmonary embolism: A systematic review and meta-analysis.

High-risk pulmonary embolism (PE) requires hemodynamic and respiratory support along with reperfusion strategies. Recently updated European guidelines assign a low class of recommendation to extracorporeal membrane oxygenation (ECMO) for high-risk PE. This systematic review assessed clinical outcomes after ECMO in high-risk PE. We searched electronic databases including PubMed, Embase and Web of Science from January 2000 to April 2020. Efficacy outcomes included in-hospital survival with good neurological outcome and survival at follow-up. Safety outcomes included lower limb ischemia and hemorrhagic and ischemic stroke. Where possible (absence of high heterogeneity), meta-analyses of outcomes were undertaken using a random-effects model. We included 16 uncontrolled case-series (533 participants). In-hospital survival with good neurological outcome ranged between 50% and 95% while overall survival at follow-up ranged from 35% to 95%, both with a major degree of heterogeneity (I2 > 70%). The prevalence of lower limb ischemia was 8% (95% CI 3% to 15%). The prevalence of stroke (either hemorrhagic or ischemic) was 11% (95% CI 3% to 23%), with notable heterogeneity (I² = 63.35%). Based on currently available literature, it is not possible to draw definite conclusions on the usefulness of ECMO for high-risk PE. Prospective, multicenter, large-scale studies or nationwide registries are needed to best define the role of ECMO for high-risk PE. PROSPERO registration ID: CRD42019136282.

Improving the prognostic value of ∆PCO2 following cardiac surgery: a prospective pilot study.

Conflicting results have been published on prognostic significance of central venous to arterial PCO2 difference (∆PCO2) after cardiac surgery. We compared the prognostic value of ∆PCO2 on intensive care unit (ICU) admission to an original algorithm combining ∆PCO2, ERO2 and lactate to identify different risk profiles. Additionally, we described the evolution of ∆PCO2 and its correlations with ERO2 and lactate during the first postoperative day (POD1). In this monocentre, prospective, and pilot study, 25 patients undergoing conventional cardiac surgery were included. Central venous and arterial blood gases were collected on ICU admission and at 6, 12 and 24 h postoperatively. High ∆PCO2 (≥ 6 mmHg) on ICU admission was found to be very frequent (64% of patients). Correlations between ∆PCO2 and ERO2 or lactate for POD1 values and variations were weak or non-existent. On ICU admission, a high ∆PCO2 did not predict a prolonged ICU length of stay (LOS). Conversely, a significant increase in both ICU and hospital LOS was observed in high-risk patients identified by the algorithm: 3.5 (3.0-6.3) days versus 7.0 (6.0-8.0) days (p = 0.01) and 12.0 (8.0-15.0) versus 8.0 (8.0-9.0) days (p < 0.01), respectively. An algorithm incorporating ICU admission values of ∆PCO2, ERO2 and lactate defined a high-risk profile that predicted prolonged ICU and hospital stays better than ∆PCO2 alone.

Capillary refill time variation induced by passive leg raising predicts capillary refill time response to volume expansion.

BACKGROUND: A peripheral perfusion-targeted resuscitation during early septic shock has shown encouraging results. Capillary refill time, which has a prognostic value, was used. Adding accuracy and predictability on capillary refill time (CRT) measurement, if feasible, would benefit to peripheral perfusion-targeted resuscitation. We assessed whether a reduction of capillary refill time during passive leg raising (ΔCRT-PLR) predicted volume-induced peripheral perfusion improvement defined as a significant decrease of capillary refill time following volume expansion. METHODS: Thirty-four patients with acute circulatory failure were selected. Haemodynamic variables, metabolic variables (PCO2gap), and four capillary refill time measurements were recorded before and during a passive leg raising test and after a 500-mL volume expansion over 20 min. Receiver operating characteristic curves were built, and areas under the curves were calculated (ROCAUC). Confidence intervals (CI) were performed using a bootstrap analysis. We recorded mortality at day 90. RESULTS: The least significant change in the capillary refill time was 25% [95% CI, 18-30]. We defined CRT responders as patients showing a reduction of at least 25% of capillary refill time after volume expansion. A decrease of 27% in ΔCRT-PLR predicted peripheral perfusion improvement with a sensitivity of 87% [95% CI, 73-100] and a specificity of 100% [95% CI, 74-100]. The ROCAUC of ΔCRT-PLR was 0.94 [95% CI, 0.87-1.0]. The ROCAUC of baseline capillary refill time was 0.73 [95% CI, 0.54-0.90] and of baseline PCO2gap was 0.79 [0.61-0.93]. Capillary refill time was significantly longer in non-survivors than in survivors at day 90. CONCLUSION: ΔCRT-PLR predicted peripheral perfusion response following volume expansion. This simple low-cost and non-invasive diagnostic method could be used in peripheral perfusion-targeted resuscitation protocols. TRIAL REGISTRATION: CPP Lyon Sud-Est II ANSM: 2014-A01034-43 Clinicaltrial.gov, NCT02248025 , registered 13th of September 2014.

Landiolol for managing atrial fibrillation in post-cardiac surgery.

Landiolol is an intravenous ultra-short acting beta-blocker which has been used in Japan for many years to prevent and/or to treat post-operative atrial fibrillation following cardiac surgery. The drug is now available in Europe. This article is a systematic review of literature regarding the use of landiolol in that specific surgical setting.

Microvascular effects of intravenous esmolol in patients with normal cardiac function undergoing postoperative atrial fibrillation: a prospective pilot study in cardiothoracic surgery.

BACKGROUND: Postoperative atrial fibrillation (POAF) is commonplace after cardiothoracic surgery. A rate control strategy using short-acting beta blockers is recommended as a first-line therapy in patients without hemodynamic instability. Microcirculatory effects of POAF and esmolol have not yet been investigated. We hypothesized that POAF without hemodynamic instability would induce microvascular dysfunction which could be reversed by intravenous esmolol. METHODS: Twenty-five cardiothoracic surgical patients with POAF were included in the study. Microcirculation was assessed by peripheral near-infrared spectroscopy (NIRS) in association with a vascular occlusion test (VOT) before esmolol infusion, during incremental doses of esmolol (25, 50, 100, and 200 µg/kg/min), and after a return to sinus rhythm. Esmolol was given to control heart rate to between 60 and 90 beats/min. Regional tissue oxygen saturation variables (StO2, StO2 min, StO2 max, and ∆StO2) and desaturation/resaturation speeds during VOT were recorded to evaluate the microcirculation. RESULTS: StO2 and resaturation speed were significantly improved when POAF returned to sinus rhythm (StO2 64% ± 6 versus 67% ± 6, P < 0.01; resaturation speed 0.53%/s (0.42-0.97) versus 0.66%/s (0.51-1.04), P = 0.020). ∆StO2 was significantly decreased after a return to sinus rhythm (7.9% ± 4.8 versus 6.1% ± 4.7, P = 0.026). During esmolol infusion, we found a significant decrease in both heart rate (P < 0.001) and blood pressure (P < 0.001), and a non-significant dose-dependent increase in StO2 (P = 0.081) and resaturation speed (P = 0.087). CONCLUSION: POAF without hemodynamic instability is associated with significant impairment in the microcirculation which could be partially reversed by intravenous esmolol.

The impact of an algorithm on the optimization of beta-blockers after cardiac surgery.

OBJECTIVE: To evaluate the impact of a simple written algorithm of early postoperative beta-blocker administration on daily practices. DESIGN: A prospective, single center observational study. SETTING: A 16-bed cardiac surgical intensive care unit in a university teaching hospital. PATIENTS: One hundred twenty-five consecutive adult patients chronically treated with beta-blockers and scheduled for conventional cardiac surgery. INTERVENTIONS: Two successive 4-month phases: Phase 1 = uncontrolled early postoperative beta-blocker administration (n = 73) and phase 2 = beta-blocker administration by an institutional written algorithm using incremental doses of bisoprolol and/or esmolol (n = 52). MEASUREMENTS AND MAIN RESULTS: The main endpoint was the number of patients receiving beta-blockers on the morning of postoperative day 1. Secondary endpoints were the number of patients receiving beta-blockers on the morning of postoperative day 1 and reaching the targeted therapeutic goal and the incidence of postoperative atrial fibrillation in the intensive care unit. A 79% increase in the number of patients receiving beta-blockers on the morning of postoperative day 1 (42% v 75%, p<0.001) was observed during the second phase of the study. The number of patients receiving beta-blockers on the morning of postoperative day 1 and reaching the targeted therapeutic goal was increased significantly by 127% (33% v 75%, p<0.001). The incidence of atrial fibrillation was similar between both phases of the study: 37% versus 31%, p = 0.567. CONCLUSIONS: A simple written algorithm markedly improved early postoperative continuation of beta-blockers in chronically treated patients undergoing conventional cardiac surgery.

Refilling and preload dependence failed to predict cardiac index decrease during fluid removal with continuous renal replacement therapy.

BACKGROUND: Fluid removal can reduce the burden of fluid overload after initial resuscitation. According to the Frank-Starling model, iatrogenic hypovolemia should induce a decrease in cardiac index. We hypothesized that inadequate refilling detected by haemoconcentration during fluid removal or an increase in cardiac index (CI) during passive leg raising (PLR) could predict CI decrease during mechanical fluid removal with continuous renal replacement therapy (CRRT). METHODS: We conducted a single-centre prospective diagnostic accuracy study. The primary objective was to investigate the diagnostic performance of plasma protein concentration variations in detecting a CI decrease ≥ 12% during mechanical fluid removal. Secondary objective was to assess other predictive factors of CI change. The attending physician prescribed a fluid removal challenge consisting of a mechanical fluid removal challenge of 500 mL for one hour. Plasma protein concentration, haemoglobin level, PLR and transpulmonary thermodilution were done before and after the fluid removal challenge. RESULTS: We included 69 adult patients between December 2016 and April 2020. Sixteen patients had a significant CI decrease (23% [95% CI 14-35]). Haemoconcentration and PLR before fluid removal challenge or CI trending failed to predict CI decrease. CONCLUSION: Haemoconcentration variables, preload dependence status and CI trending failed to predict CI decrease during fluid removal challenge.

Effect of open-lung vs conventional perioperative ventilation strategies on postoperative pulmonary complications after on-pump cardiac surgery: the PROVECS randomized clinical trial.

PURPOSE: To evaluate whether a perioperative open-lung ventilation strategy prevents postoperative pulmonary complications after elective on-pump cardiac surgery. METHODS: In a pragmatic, randomized, multicenter, controlled trial, we assigned patients planned for on-pump cardiac surgery to either a conventional ventilation strategy with no ventilation during cardiopulmonary bypass (CPB) and lower perioperative positive end-expiratory pressure (PEEP) levels (2 cm H2O) or an open-lung ventilation strategy that included maintaining ventilation during CPB along with perioperative recruitment maneuvers and higher PEEP levels (8 cm H2O). All study patients were ventilated with low-tidal volumes before and after CPB (6 to 8 ml/kg of predicted body weight). The primary end point was a composite of pulmonary complications occurring within the first 7 postoperative days. RESULTS: Among 493 randomized patients, 488 completed the study (mean age, 65.7 years; 360 (73.7%) men; 230 (47.1%) underwent isolated valve surgery). Postoperative pulmonary complications occurred in 133 of 243 patients (54.7%) assigned to open-lung ventilation and in 145 of 245 patients (59.2%) assigned to conventional ventilation (p = 0.32). Open-lung ventilation did not significantly reduce the use of high-flow nasal oxygenotherapy (8.6% vs 9.4%; p = 0.77), non-invasive ventilation (13.2% vs 15.5%; p = 0.46) or new invasive mechanical ventilation (0.8% vs 2.4%, p = 0.28). Mean alive ICU-free days at postoperative day 7 was 4.4 ± 1.3 days in the open-lung group vs 4.3 ± 1.3 days in the conventional group (mean difference, 0.1 ± 0.1 day, p = 0.51). Extra-pulmonary complications and adverse events did not significantly differ between groups. CONCLUSIONS: A perioperative open-lung ventilation including ventilation during CPB does not reduce the incidence of postoperative pulmonary complications as compared with usual care. This finding does not support the use of such a strategy in patients undergoing on-pump cardiac surgery. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02866578. https://clinicaltrials.gov/ct2/show/NCT02866578.

A perioperative surgeon-controlled open-lung approach versus conventional protective ventilation with low positive end-expiratory pressure in cardiac surgery with cardiopulmonary bypass (PROVECS): study protocol for a randomized controlled trial.

BACKGROUND: Postoperative pulmonary complications (PPCs) are frequent after on-pump cardiac surgery. Cardiac surgery results in a complex pulmonary insult leading to high susceptibility to perioperative pulmonary atelectasis. For technical reasons, ventilator settings interact with the surgical procedure and traditionally, low levels of positive end-expiratory pressure (PEEP) have been used. The objective is to compare a perioperative, multimodal and surgeon-controlled open-lung approach with conventional protective ventilation with low PEEP to prevent PPCs in patients undergoing cardiac surgery. METHODS/DESIGN: The perioperative open-lung protective ventilation in cardiac surgery (PROVECS) trial is a multicenter, two-arm, randomized controlled trial. In total, 494 patients scheduled for elective cardiac surgery with cardiopulmonary bypass (CPB) and aortic cross-clamp will be randomized into one of the two treatment arms. In the experimental group, systematic recruitment maneuvers and perioperative high PEEP (8 cmH2O) are associated with ultra-protective ventilation during CPB. In this group, the settings of the ventilator are controlled by surgeons in relation to standardized protocol deviations. In the control group, no recruitment maneuvers, low levels of PEEP (2 cmH2O) and continuous positive airway pressure during CPB (2 cmH2O) are used. Low tidal volumes (6-8 mL/kg of predicted body weight) are used before and after CPB in each group. The primary endpoint is a composite of the single PPCs evaluated during the first 7 postoperative days. DISCUSSION: The PROVECS trial will be the first multicenter randomized controlled trial to evaluate the impact of a perioperative and multimodal open-lung ventilatory strategy on the occurrence of PPCs after on-pump cardiac surgery. The trial design includes standardized surgeon-controlled protocol deviations that guarantee a pragmatic approach. The results will help anesthesiologists and surgeons aiming to optimize ventilatory settings during cardiac surgery. TRIAL REGISTRATION: Clinical Trials.gov, NCT 02866578 . Registered on 15 August 2016. Last updated 11 July 2017.