Personalised perioperative dosing of ivabradine in noncardiac surgery: a single-centre, randomised, placebo-controlled, double-blind feasibility pilot trial.

BACKGROUND: Perioperative myocardial injury after noncardiac surgery is associated with postoperative mortality. Heart rate (HR) is an independent risk factor for perioperative myocardial injury. In this pilot trial we tested the feasibility of a randomised, placebo-controlled trial of personalised HR-targeted perioperative ivabradine. METHODS: This was a single-centre, randomised, placebo-controlled, double-blind, parallel group, feasibility pilot trial conducted at Geneva University Hospitals. We included patients ≥75 yr old or ≥45 yr old with cardiovascular risk factors planned for intermediate- or high-risk surgery. Patients were randomised to receive ivabradine (2.5, 5.0, or 7.5 mg) or placebo according to their HR, twice daily, from the morning of surgery until postoperative day 2. Primary outcomes were appropriate dosage and blinding success rates. RESULTS: Between October 2020 and January 2022, we randomised 78 patients (recruitment rate of 1.3 patients week-1). Some 439 of 444 study drug administrations were adequate (99% appropriate dosage rate). The blinding success rate was 100%. There were 137 (31%) administrations of Pill A (placebo in both groups for HR ≤70 beats min-1). Nine (11.5%) patients had a high-sensitive cardiac troponin T elevation ≥14 ng L-1 between any two measurements. The number of bradycardia episodes was eight in the placebo group and nine in the ivabradine group. CONCLUSIONS: This pilot study demonstrates the feasibility of, and provides guidance for, a future trial testing the efficacy of personalised perioperative ivabradine. Future studies should include patients at higher risk of cardiac complications. CLINICAL TRIAL REGISTRATION: NCT04436016.

New Noninvasive Method for the Assessment of Central Venous Oxygen Saturations in Critically Ill Patients.

OBJECTIVES: To compare noninvasive external jugular vein oxygen saturations (SjvO2) and central venous oxygen saturation (ScvO2) from a blood sample in patients admitted to the intensive care unit. DESIGN: A prospective, comparative, monocentric clinical trial design was used. SETTING: The study was performed in the Department of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine, University Hospitals of Geneva (Switzerland). PARTICIPANTS: A total of 79 patients were enrolled; patients with confirmed COVID-19 infection requiring invasive mechanical ventilation (patients with COVID-19, n = 36) and patients after liver transplantation (posttransplant patients, n = 43). INTERVENTIONS: Simultaneous measurement of SjvO2 by near-infrared spectroscopy and ScvO2 from central venous blood samples using a blood gas analyzer in stable hemodynamic conditions. MEASUREMENTS AND MAIN RESULTS: A strong linear correlation was evidenced in both the COVID-19 and posttransplant patient groups between the 2 modalities. The Bland-Altman analysis showed low bias in accordance with low percentage error in both groups (0.57% and 8.09% for patients with COVID-19; 0.00% and 13.72% for posttransplant patients). CONCLUSIONS: Central venous oxygen saturation can be estimated reasonably by the continuous noninvasive measurement of SjvO2 using near-infrared spectroscopy.

Benefit of Flow-Controlled Over Pressure-Regulated Volume Control Mode During One-Lung Ventilation: A Randomized Experimental Crossover Study.

BACKGROUND: Application of a ventilation modality that ensures adequate gas exchange during one-lung ventilation (OLV) without inducing lung injury is of paramount importance. Due to its beneficial effects on respiratory mechanics and gas exchange, flow-controlled ventilation (FCV) may be considered as a protective alternative mode of traditional pressure- or volume-controlled ventilation during OLV. We investigated whether this new modality provides benefits compared with conventional ventilation modality for OLV. METHODS: Ten pigs were anaesthetized and randomly assigned in a crossover design to be ventilated with FCV or pressure-regulated volume control (PRVC) ventilation. Arterial partial pressure of oxygen (Pa o2 ), carbon dioxide (Pa co2 ), ventilation and hemodynamical parameters, and lung aeration measured by electrical impedance tomography were assessed at baseline and 1 hour after the application of each modality during OLV using an endobronchial blocker. RESULTS: Compared to PRVC, FCV resulted in increased Pa o2 (153.7 ± 12.7 vs 169.9 ± 15.0 mm Hg; P = .002) and decreased Pa co2 (53.0 ± 11.0 vs 43.2 ± 6.0 mm Hg; P < .001) during OLV, with lower respiratory elastance (103.7 ± 9.5 vs 77.2 ± 10.5 cm H 2 O/L; P < .001) and peak inspiratory pressure values (27.4 ± 1.9 vs 22.0 ± 2.3 cm H 2 O; P < .001). No differences in lung aeration or hemodynamics could be detected between the 2 ventilation modalities. CONCLUSIONS: The application of FCV in OLV led to improvement in gas exchange and respiratory elastance with lower ventilatory pressures. Our findings suggest that FCV may offer an optimal, protective ventilation modality for OLV.

Three-Minute Diagnostic Assessment for Delirium using the Confusion Assessment Method (3D-CAM): French translation and cultural adaptation.

PURPOSE: The routine use of validated diagnostic instruments is key to identifying delirious patients early and expediting care. The 3-Minute Diagnostic Assessment for Delirium using the Confusion Assessment Method (3D-CAM) instrument is a brief, easy to use, sensitive, and specific delirium assessment tool for hospitalized patients. We aimed to translate the original English version into French, and then adapt it to older high-risk patients. METHODS: Translation and adaptation of the questionnaire were guided by an expert committee and the 3D-CAM instrument developer. During the translation phase, we achieved semantic and conceptual equivalence of the instrument by conducting forward and backward translations. During the adaptation phase, we assessed the face validity, clarity of wording, and ease of use of the translated questionnaire by administering it to 30 patients and their caregivers in peri-interventional and medical intermediate care units. During both phases, we used qualitative (goal and adequacy of the questionnaire) and quantitative (Sperber score, clarity score) criteria. RESULTS: Translation: four items were judged inadequate and were revised until all reached a Sperber score of < 3/7. Face validity: 91% of patients thought the questionnaire was designed to assess memory, thoughts, or reasoning. Clarity: eight items required adjustments until all scored ≥ 9/10 for clarity. Ease of use: all bedside caregivers reported that the questionnaire was easy to complete after receiving brief instructions. CONCLUSIONS: We produced a culturally adapted French version of the 3D-CAM instrument that is well understood and well-received by older high-risk patients and their caregivers.

RéSUMé: OBJECTIF: L'administration systématique d'instruments diagnostiques validés est essentielle pour identifier précocement les patients confus. Le questionnaire 3D-CAM (3 Minute Diagnostic Confusion Assessment Method) est un outil d'évaluation bref, facile à administrer en milieu hospitalier, sensible et spécifique pour l'état confusionnel. Notre objectif était de le traduire en français, puis de l'adapter à une population de patients âgés à haut risque. MéTHODE: La traduction et l'adaptation ont été guidées par un comité d'experts et le développeur de l'instrument. Nous avons atteint une équivalence sémantique et conceptuelle en menant des traductions antérogrades, puis rétrogrades. Nous avons évalué la validité de contenu, la clarté lexicale, et la facilité d'administration du questionnaire en le soumettant à 30 patients et 30 soignants dans des unités de soins intermédiaires médicaux et péri-interventionnels. Durant les phases de traduction et d'adaptation, nous avons utilisé des critères qualitatifs et quantitatifs. RéSULTATS: Traduction : quatre questions ont été jugées inadéquates et ont été révisées pour atteindre un score de Sperber < 3/7. Validité de contenu : 91% des patients pensaient que le questionnaire était conçu pour évaluer la mémoire, les pensées, ou le raisonnement. Clarté : huit questions ont dû être modifiées pour atteindre un score de clarté ≥ 9/10. Facilité d'administration : tous les soignants pensaient que le questionnaire était facile à utiliser après une brève formation. CONCLUSIONS: Nous avons produit une version française du questionnaire 3D-CAM qui est adaptée aux patients âgés à haut risque et aux soignants en milieu de soins aigus.

Invasive and non-invasive assessment of macro- and micro-circulatory effects of vasopressors during sevoflurane anesthesia in a pediatric experimental model: A randomized trial.

BACKGROUND: While non-invasive assessment of macro- and micro-circulation has the promise to optimize anesthesia management, evidence is lacking for the relationship between invasive and non-invasive measurements of cardiac output and microcirculatory indices. AIMS: We aimed to compare the abilities of non-invasive techniques to detect changes in macro- and micro-circulation following deep anesthesia and subsequent restoration of the compromised hemodynamic by routinely used vasopressors in a randomized experimental study. METHODS: A 20%-25% drop in mean arterial pressure was induced by sevoflurane in anesthetized mechanically ventilated just-weaned piglets (n = 12) prior to the administration of vasopressors in random order (dopamine, ephedrine, noradrenaline, and phenylephrine). Simultaneous transpulmonary thermodilution cardiac output assessment with the invasive pulse index continuous contour (PiCCO) method was compared with non-invasive estimates obtained with electrical conductivity (ICON) and echo Doppler (Cardio Q). Changes in microcirculation were characterized by sublingual red blood cell velocity, jugular cerebral venous oxygen saturation, and arterial lactate. MAIN OUTCOME MEASURES: Cardiac output indices obtained by invasive and non-invasive methods. RESULTS: Changes in cardiac output measured invasively and non-invasively correlated significantly after sevoflurane (r = .78, p = .003 and r = .76, p = .006 between PiCCO and ICON or Cardio Q, respectively). Following the administration of vasopressors, invasive and non-invasive cardiac output assessments were unrelated with significant correlations observed only between PiCCO and ICON after dopamine and ephedrine. Sevoflurane-induced hypotension decreased jugular cerebral venous oxygen saturation significantly and was recovered by all vasopressors. Sevoflurane and vasopressors had no effect on red blood cell velocity, which increased only after dopamine. No consistent changes in lactate were observed during the study period. CONCLUSIONS: The results of this study suggest that non-invasive cardiac output measurements may not accurately reflect changes in macrocirculation after hemodynamic optimization by vasopressors. Due to the incoherence between macro- and micro-circulation, monitoring microcirculation is essential to guide patient management.

Distribution of ventilation and oxygenation in surgical obese patients ventilated with high versus low positive end-expiratory pressure: A substudy of a randomised controlled trial.

BACKGROUND: Intra-operative ventilation using low/physiological tidal volume and positive end-expiratory pressure (PEEP) with periodic alveolar recruitment manoeuvres (ARMs) is recommended in obese surgery patients. OBJECTIVES: To investigate the effects of PEEP levels and ARMs on ventilation distribution, oxygenation, haemodynamic parameters and cerebral oximetry. DESIGN: A substudy of a randomised controlled trial. SETTING: Tertiary medical centre in Geneva, Switzerland, between 2015 and 2018. PATIENTS: One hundred and sixty-two patients with a BMI at least 35 kg per square metre undergoing elective open or laparoscopic surgery lasting at least 120 min. INTERVENTION: Patients were randomised to PEEP of 4 cmH 2 O ( n  = 79) or PEEP of 12 cmH 2 O with hourly ARMs ( n  = 83). MAIN OUTCOME MEASURES: The primary endpoint was the fraction of ventilation in the dependent lung as measured by electrical impedance tomography. Secondary endpoints were the oxygen saturation index (SaO 2 /FIO 2 ratio), respiratory and haemodynamic parameters, and cerebral tissue oximetry. RESULTS: Compared with low PEEP, high PEEP was associated with smaller intra-operative decreases in dependent lung ventilation [-11.2%; 95% confidence interval (CI) -8.7 to -13.7 vs. -13.9%; 95% CI -11.7 to -16.5; P  = 0.029], oxygen saturation index (-49.6%; 95% CI -48.0 to -51.3 vs. -51.3%; 95% CI -49.6 to -53.1; P  < 0.001) and a lower driving pressure (-6.3 cmH 2 O; 95% CI -5.7 to -7.0). Haemodynamic parameters did not differ between the groups, except at the end of ARMs when arterial pressure and cardiac index decreased on average by -13.7 mmHg (95% CI -12.5 to -14.9) and by -0.54 l min -1  m -2 (95% CI -0.49 to -0.59) along with increased cerebral tissue oximetry (3.0 and 3.2% on left and right front brain, respectively). CONCLUSION: In obese patients undergoing abdominal surgery, intra-operative PEEP of 12 cmH 2 O with periodic ARMs, compared with intra-operative PEEP of 4 cmH 2 O without ARMs, slightly redistributed ventilation to dependent lung zones with minor improvements in peripheral and cerebral oxygenation. TRIAL REGISTRATION: NCT02148692, https://clinicaltrials.gov/ct2.

Accountability, research transparency and data reporting.

More than one published paper are often derived from analyzing the same cohort of individuals to make full use of the collected information. Preplanned study outcomes are generally mentioned in open databases while exhaustive information on methodological aspects are provided in submitted articles.

Pretreatment with glucose-insulin-potassium improves ventricular performances after coronary artery bypass surgery: a randomized controlled trial.

Heart failure is the main cause of poor outcome following open heart surgery and experimental studies have demonstrated that glucose-insulin-potassium (GIK) infusion exerts cardioprotective effects by reducing myocardial ischemia-reperfusion injuries. This randomized controlled trial was designed to assess the effects of GIK on left ventricular function in moderate-to-high risk patients undergoing on-pump isolated coronary artery bypass surgery (CABGS), or combined with aortic valve replacement. The primary outcomes were the effects of GIK on two- and three-dimensional left ventricular ejection fraction (2D and 3D-LVEF), and on transmitral flow propagation velocity (Vp), that occurred between the pre- and post-CPB periods. GIK administration was associated with favorable interaction effects (p < 0.001) on 2D-LVEF, 3D-LVEF and Vp changes over the study periods. In GIK pretreated patients (N = 54), 2-D and 3D-LVEF and Vp increased slightly during surgery (mean difference [MD] + 3.5%, 95% confidence interval [95% CI] - 0.2 to 7.1%, MD + 4.0%, 95% CI 0.6-7.4%, and MD + 22.2%, 95% CI 16.0-28.4%, respectively). In contrast, in the Placebo group (N = 46), 2D-and 3D-LVEF, as well as Vp all decreased after CPB (MD - 7.5% [- 11.6 to - 3.4%], MD - 12.0% [- 15.2 to - 8.8%] and MD - 21.3% [- 25.7 to - 16.9%], respectively). In conclusion, the administration of GIK resulted in better preservation of systolic and diastolic ventricular function in the early period following weaning from CPB.

Glucose-insulin-potassium improves left ventricular performances after aortic valve replacement: a secondary analysis of a randomized controlled trial.

BACKGROUND: Patients with left ventricular (LV) hypertrophy may suffer ischemia-reperfusion injuries at the time of cardiac surgery with impairment in left ventricular function. Using transesophageal echocardiography (TEE), we evaluated the impact of glucose-insulin potassium (GIK) on LV performances in patients undergoing valve replacement for aortic stenosis. METHODS: In this secondary analysis of a double-blind randomized trial, moderate-to-high risk patients were assigned to receive GIK (20 IU insulin with 10 mEq KCL in 50 ml glucose 40%) or saline over 60 min upon anesthetic induction. The primary outcomes were the early changes in 2-and 3-dimensional left ventricular ejection fraction (2D and 3D-LVEF), peak global longitudinal strain (PGLS) and transmitral flow propagation velocity (Vp). RESULTS: At the end of GIK infusion, LV-FAC and 2D- and 3D-LVEF were unchanged whereas Vp (mean difference [MD + 7.9%, 95% confidence interval [CI] 3.2 to 12.5%; P <  0.001) increased compared with baseline values. After Placebo infusion, there was a decrease in LV-FAC (MD -2.9%, 95%CI - 4.8 to - 1.0%), 2D-LVEF (MD -2.0%, 95%CI - 2.8 to - 1.3%, 3D-LVEF (MD -3.0%, 95%CI - 4.0 to - 2.0%) and Vp (MD - 4.5 cm/s, 95%CI - 5.6 to - 3.3 cm/s). After cardiopulmonary bypass, GIK pretreatment was associated with preserved 2D and 3D-LVEF (+ 0.4%, 95% 95%CI - 0.8 to 1.7% and + 0.4%, 95%CI - 1.3 to 2.0%), and PGLS (- 0.9, 95%CI - 1.6 to - 0.2) as well as higher Vp (+ 5.1 cm/s, 95%CI 2.9 to 7.3), compared with baseline. In contrast, in the Placebo group, 2D-LVEF (- 2.2%, 95%CI - 3.4 to - 1.0), 3D-LVEF (- 6.0%, 95%CI - 7.8 to - 4.2), and Vp (- 7.6 cm/s, 95%CI - 9.4 to - 5.9), all decreased after bypass. CONCLUSIONS: Administration of GIK before aortic cross-clamping resulted in better preservation of systolic and diastolic ventricular function in patients with LV hypertrophy undergoing aortic valve replacement. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00788242 , registered on November 10, 2008.

Myocardial Protection by Glucose-Insulin-Potassium in Moderate- to High-Risk Patients Undergoing Elective On-Pump Cardiac Surgery: A Randomized Controlled Trial.

BACKGROUND: Low cardiac output syndrome is a main cause of death after cardiac surgery. We sought to assess the impact of glucose-insulin-potassium (GIK) to enhance myocardial protection in moderate- to high-risk patients undergoing on-pump heart surgery. METHODS: A randomized controlled trial was performed in adult patients (Bernstein-Parsonnet score >7) scheduled for elective aortic valve replacement and/or coronary artery bypass surgery. Patients were randomized to GIK (20 IU of insulin, 10 mEq of potassium chloride in 50 mL of glucose 40%) or saline infusion given over 60 minutes on anesthetic induction. The primary end point was postcardiotomy ventricular dysfunction (PCVD), defined as new/worsening left ventricular dysfunction requiring inotropic support (≥120 minutes). Secondary end points were the intraoperative changes in left ventricular function as assessed by transoesophageal echocardiography, postoperative troponin levels, cardiovascular and respiratory complications, and intensive care unit and hospital length of stay. RESULTS: From 224 randomized patients, 222 were analyzed (112 and 110 in the placebo and GIK groups, respectively). GIK pretreatment was associated with a reduced occurrence of PCVD (risk ratio [RR], 0.41; 95% confidence interval [CI], 0.25-0.66). In GIK-treated patients, the left systolic ventricular function was better preserved after weaning from bypass, plasma troponin levels were lower on the first postoperative day (2.9 ng·mL(-) [interquartile range {IQR}, 1.5-6.6] vs 4.3 ng·mL(-) [IQR, 2.4-8.2]), and cardiovascular (RR, 0.69; 95% CI, 0.50-0.89) and respiratory complications (RR, 0.5; 95% CI, 0.38-0.74) were reduced, along with a shorter length of stay in intensive care unit (3 days [IQR, 2-4] vs 3.5 days [IQR, 2-7]) and in hospital (14 days [IQR, 11-18.5] vs 16 days [IQR, 12.5-23.5]), compared with placebo-treated patients. CONCLUSIONS: GIK pretreatment was shown to attenuate PCVD and to improve clinical outcome in moderate- to high-risk patients undergoing on-pump cardiac surgery.

Assessment of Haemostasis in patients undergoing emergent neurosurgery by rotational Elastometry and standard coagulation tests: a prospective observational study.

BACKGROUND: Rotational elastometry (ROTEM) has been shown useful to monitor coagulation in trauma patients and in major elective surgery. In this study, we aimed to evaluate the utility of ROTEM to identify hemostatic disturbances and to predict the need for transfusion, compared with standard coagulation tests (SCTs) in patients undergoing emergent neurosurgery. METHODS: Over a four-year period, adult patients who met criteria for emergent neurosurgery lasting more than 90 min were included in the study. Blood was collected preoperatively and analyzed with SCTs (international normalized ratio [INR], fibrinogen concentration, prothrombin time [PT or Quick], partial thromboplastine time [PTT], fibrinogen concentration and platelet count), and ROTEM assays. Correlations between SCTs and ROTEM parameters as well as receiver operating characteristic curves were performed to detect a coagulopathic pattern based on standard criteria and the need for transfusing at least 3 units of packed red blood cells (PRBCs). RESULTS: In a cohort of 92 patients, 39 (42%) required ≥3 PRBCs and a coagulopathic pattern was identified in 32 patients based on SCTs and in 19 based on ROTEM. There was a strong correlation between PTT and INTEM coagulation time (R = 0.76) as well as between fibrinogen concentrations and FIBTEM maximal clot firmess (R = 0.70). The need for transfusion (≥ 3 PRBCs) was best predicted by the maximal clot firmess of EXTEM and FIBTEM (AUC of 0.72 and 0.71, respectively) and by fibrinogen concentration (AUC of 0.70). CONCLUSIONS: In patients undergoing emergent neurosurgery, ROTEM analysis provides valid markers of early coagulopathy and predictors of blood transfusion requirements.

Impact of early haemodynamic goal-directed therapy in patients undergoing emergency surgery: an open prospective, randomised trial.

Haemodynamic goal-directed therapies (GDT) may improve outcome following elective major surgery. So far, few data exist regarding haemodynamic optimization during emergency surgery. In this randomized, controlled trial, 50 surgical patients with hypovolemic or septic conditions were enrolled and we compared two algorithms of GDTs based either on conventional parameters and pressure pulse variation (control group) or on cardiac index, global end-diastolic volume index and stroke volume variation as derived from the PiCCO monitoring system (optimized group). Postoperative outcome was estimated by a composite index including major complications and by the Sequential Organ Failure Assessment (SOFA) Score within the first 3 days after surgery (POD1, POD2 and POD3). Data from 43 patients were analyzed (control group, N = 23; optimized group, N = 20). Similar amounts of fluid were given in the two groups. Intraoperatively, dobutamine was given in 45 % optimized patients but in no control patients. Major complications occurred more frequently in the optimized group [19 (95 %) versus 10 (40 %) in the control group, P < 0.001]. Likewise, SOFA scores were higher in the optimized group on POD1 (10.2 ± 2.5 versus 6.6 ± 2.2 in the control group, P = 0.001), POD2 (8.4 ± 2.6 vs 5.0 ± 2.4 in the control group, P = 0.002) and POD 3 (5.2 ± 3.6 and 2.2 ± 1.3 in the control group, P = 0.01). There was no significant difference in hospital mortality (13 % in the control group and 25 % in the optimized group). Haemodynamic optimization based on volumetric and flow PiCCO-derived parameters was associated with a less favorable postoperative outcome compared with a conventional GDT protocol during emergency surgery.

Variable positive end-expiratory pressure in an experimental model of acute respiratory distress syndrome: an advanced ventilation modality.

Background: Introducing variability in tidal volume, ventilatory frequency, or both is beneficial during mechanical ventilation in acute respiratory distress syndrome (ARDS). We investigated whether applying cycle-by-cycle variability in the positive end-expiratory pressure (PEEP) exerts beneficial effect on lung function in a model of ARDS. Methods: Rabbits with lung injury were randomly allocated to receive mechanical ventilation for 6 h by applying a pressure-controlled mode with constant PEEP of 7 cm H2O (PC group: n=6) or variable PEEP (VEEP) with a coefficient of variation of 21.4%, range 4-10 cm H2O (PC-VEEP group; n=6). Lung oxygenation index (Pao2/FiO2) after 6 h of ventilation (H6) was the primary outcome and respiratory mechanics, lung volume, intrapulmonary shunt, and lung inflammatory markers were secondary outcomes. Results: After lung injury, both groups presented moderate-to-severe ARDS (Pao2/FiO2 <27 kPa). The Pao2/FiO2 was significantly higher in the PC-VEEP group than in the PC group at H6 (12.3 [sd 3.5] vs 19.2 [7.2] kPa, P=0.013) and a lower arterial partial pressure of CO2 at 1-3 h (P<0.02). The ventilation-induced increases in airway resistance and tissue elastance were prevented by PC-VEEP. There was no evidence for a difference in minute volume, driving pressure, end-tidal CO2, lung volumes, intrapulmonary shunt fraction, and cytokines between the ventilation modes. Conclusions: Prolonged mechanical ventilation with cycle-by-cycle VEEP prevents deterioration in gas exchange and respiratory mechanics in a model of ARDS, suggesting the benefit of this novel ventilation strategy to optimise gas exchange without increasing driving pressure and lung overdistension.

Benefits of intratracheal and extrathoracic high-frequency percussive ventilation in a model of capnoperitoneum.

Abdominal inflation with CO2 is used to facilitate laparoscopic surgeries, however, providing adequate mechanical ventilation in this scenario is of major importance during anesthesia management. We characterized high-frequency percussive ventilation (HFPV) in protecting from the gas exchange and respiratory mechanical impairments during capnoperitoneum. In addition, we aimed to assess the difference between conventional pressure-controlled mechanical ventilation (CMV) and HFPV modalities generating the high-frequency signal intratracheally (HFPVi) or extrathoracally (HFPVe). Anesthetized rabbits (n = 16) were mechanically ventilated by random sequences of CMV, HFPVi, and HFPVe. The ventilator superimposed the conventional waveform with two high-frequency signals (5 Hz and 10 Hz) during intratracheal HFPV (HFPVi) and HFPV with extrathoracic application of oscillatory signals through a sealed chest cuirass (HFPVe). Lung oxygenation index ([Formula: see text]/[Formula: see text]), arterial partial pressure of carbon dioxide ([Formula: see text]), intrapulmonary shunt (Qs/Qt), and respiratory mechanics were assessed before abdominal inflation, during capnoperitoneum, and after abdominal deflation. Compared with CMV, HFPVi with additional 5-Hz oscillations during capnoperitoneum resulted in higher [Formula: see text]/[Formula: see text], lower [Formula: see text], and decreased Qs/Qt. These improvements were smaller but remained significant during HFPVi with 10 Hz and HFPVe with either 5 or 10 Hz. The ventilation modes did not protect against capnoperitoneum-induced deteriorations in respiratory tissue mechanics. These findings suggest that high-frequency oscillations combined with conventional pressure-controlled ventilation improved lung oxygenation and CO2 removal in a model of capnoperitoneum. Compared with extrathoracic pressure oscillations, intratracheal generation of oscillatory pressure bursts appeared more effective. These findings may contribute to the optimization of mechanical ventilation during laparoscopic surgery.NEW & NOTEWORTHY The present study examines an alternative and innovative mechanical ventilation modality in improving oxygen delivery, CO2 clearance, and respiratory mechanical abnormalities in a clinically relevant experimental model of capnoperitoneum. Our data reveal that high-frequency oscillations combined with conventional ventilation improve gas exchange, with intratracheal oscillations being more effective than extrathoracic oscillations in this clinically relevant translational model.

Lung recruitment by continuous negative extra-thoracic pressure support following one-lung ventilation: an experimental study.

Lung recruitment maneuvers following one-lung ventilation (OLV) increase the risk for the development of acute lung injury. The application of continuous negative extrathoracic pressure (CNEP) is gaining interest both in intubated and non-intubated patients. However, there is still a lack of knowledge on the ability of CNEP support to recruit whole lung atelectasis following OLV. We investigated the effects of CNEP following OLV on lung expansion, gas exchange, and hemodynamics. Ten pigs were anesthetized and mechanically ventilated with pressure-regulated volume control mode (PRVC; FiO2: 0.5, Fr: 30-35/min, VT: 7 mL/kg, PEEP: 5 cmH2O) for 1 hour, then baseline (BL) data for gas exchange (arterial partial pressure of oxygen, PaO2; and carbon dioxide, PaCO2), ventilation and hemodynamical parameters and lung aeration by electrical impedance tomography were recorded. Subsequently, an endobronchial blocker was inserted, and OLV was applied with a reduced VT of 5 mL/kg. Following a new set of measurements after 1 h of OLV, two-lung ventilation was re-established, combining PRVC (VT: 7 mL/kg) and CNEP (-15 cmH2O) without any hyperinflation maneuver and data collection was then repeated at 5 min and 1 h. Compared to OLV, significant increases in PaO2 (154.1 ± 13.3 vs. 173.8 ± 22.1) and decreases in PaCO2 (52.6 ± 11.7 vs. 40.3 ± 4.5 mmHg, p < 0.05 for both) were observed 5 minutes following initiation of CNEP, and these benefits in gas exchange remained after an hour of CNEP. Gradual improvements in lung aeration in the non-collapsed lung were also detected by electrical impedance tomography (p < 0.05) after 5 and 60 min of CNEP. Hemodynamics and ventilation parameters remained stable under CNEP. Application of CNEP in the presence of whole lung atelectasis proved to be efficient in improving gas exchange via recruiting the lung without excessive airway pressures. These benefits of combined CNEP and positive pressure ventilation may have particular value in relieving atelectasis in the postoperative period of surgical procedures requiring OLV.

Flow-controlled ventilation maintains gas exchange and lung aeration in a pediatric model of healthy and injured lungs: A randomized cross-over experimental study.

Flow-controlled ventilation (FCV) is characterized by a constant flow to generate active inspiration and expiration. While the benefit of FCV on gas exchange has been demonstrated in preclinical and clinical studies with adults, the value of this modality for a pediatric population remains unknown. Thus, we aimed at observing the effects of FCV as compared to pressure-regulated volume control (PRVC) ventilation on lung mechanics, gas exchange and lung aeration before and after surfactant depletion in a pediatric model. Ten anesthetized piglets (10.4 ± 0.2 kg) were randomly assigned to start 1-h ventilation with FCV or PRVC before switching the ventilation modes for another hour. This sequence was repeated after inducing lung injury by bronchoalveolar lavage and injurious ventilation. The primary outcome was respiratory tissue elastance. Secondary outcomes included oxygenation index (PaO2/FiO2), PaCO2, intrapulmonary shunt (Qs/Qt), airway resistance, respiratory tissue damping, end-expiratory lung volume, lung clearance index and lung aeration by chest electrical impedance tomography. Measurements were performed at the end of each protocol stage. Ventilation modality had no effect on any respiratory mechanical parameter. Adequate gas exchange was provided by FCV, similar to PRVC, with sufficient CO2 elimination both in healthy and surfactant-depleted lungs (39.46 ± 7.2 mmHg and 46.2 ± 11.4 mmHg for FCV; 36.0 ± 4.1 and 39.5 ± 4.9 mmHg, for PRVC, respectively). Somewhat lower PaO2/FiO2 and higher Qs/Qt were observed in healthy and surfactant depleted lungs during FCV compared to PRVC (p < 0.05, for all). Compared to PRVC, lung aeration was significantly elevated, particularly in the ventral dependent zones during FCV (p < 0.05), but this difference was not evidenced in injured lungs. Somewhat lower oxygenation and higher shunt ratio was observed during FCV, nevertheless lung aeration improved and adequate gas exchange was ensured. Therefore, in the absence of major differences in respiratory mechanics and lung volumes, FCV may be considered as an alternative in ventilation therapy of pediatric patients with healthy and injured lungs.

Myocardial injury after major noncardiac surgery: A secondary analysis of a randomized controlled trial.

BACKGROUND: Myocardial injury after noncardiac surgery frequently occurs and may influence survival. The aims of this study were to examine the association between myocardial injury after noncardiac surgery and patient and procedural factors as well as its impact on postoperative clinical outcome. METHODS: A retrospective analysis was conducted from data collected in adults enrolled in a randomized trial in elective major open abdominal surgery. Preoperative patient characteristics, intraoperative hemodynamic changes, and postoperative adverse events were analyzed, and Kaplan-Meier curves were built for postoperative survival probability. After adjustment for baseline patient and procedural characteristics, the effect of myocardial injury after noncardiac surgery on postoperative outcomes was analyzed in a propensity score matched cohort. RESULTS: Among 394 patients, myocardial injury after noncardiac surgery was reported in 109 (27.7%) and was associated with a higher cardiovascular risk profile, prolonged surgery (333 ± 111 min vs 295 ± 134 min, P = .010), greater need for transfusions (41.3% vs 19.3%, P < .001), higher incidence of major adverse cardiac events (22.9% vs 6.7%, P < .001), pulmonary complications (31.2% vs 17.9%, P = .004) , acute kidney injury (30.3% vs 18.2%, P = .009), and systemic inflammatory syndrome (28.4% vs 13.0%, P < .001). After propensity score matching, the operative time and the need for blood transfusion remained higher among myocardial injury after noncardiac surgery patients who experienced more frequent major adverse cardiac events and acute kidney injury. In both the entire and matched cohorts, survival up to 30 months after surgery was determined mainly by the presence of cancer. CONCLUSION: The burden of cardiovascular disease and operative stress surgery is predictive of myocardial injury after noncardiac surgery and, in turn, with a higher incidence of cardiac adverse events, whereas the presence of cancer is associated with poor survival in patients undergoing major open abdominal surgery. Further studies are needed to determine whether myocardial injury after noncardiac surgery can be prevented by better control of the patient's cardiovascular condition and implementation of less invasive of surgical procedures.

Effect of body position on the redistribution of regional lung aeration during invasive and non-invasive ventilation of COVID-19 patients.

Severe COVID-19-related acute respiratory distress syndrome (C-ARDS) requires mechanical ventilation. While this intervention is often performed in the prone position to improve oxygenation, the underlying mechanisms responsible for the improvement in respiratory function during invasive ventilation and awake prone positioning in C-ARDS have not yet been elucidated. In this prospective observational trial, we evaluated the respiratory function of C-ARDS patients while in the supine and prone positions during invasive (n = 13) or non-invasive ventilation (n = 15). The primary endpoint was the positional change in lung regional aeration, assessed with electrical impedance tomography. Secondary endpoints included parameters of ventilation and oxygenation, volumetric capnography, respiratory system mechanics and intrapulmonary shunt fraction. In comparison to the supine position, the prone position significantly increased ventilation distribution in dorsal lung zones for patients under invasive ventilation (53.3 ± 18.3% vs. 43.8 ± 12.3%, percentage of dorsal lung aeration ± standard deviation in prone and supine positions, respectively; p = 0.014); whereas, regional aeration in both positions did not change during non-invasive ventilation (36.4 ± 11.4% vs. 33.7 ± 10.1%; p = 0.43). Prone positioning significantly improved the oxygenation both during invasive and non-invasive ventilation. For invasively ventilated patients reduced intrapulmonary shunt fraction, ventilation dead space and respiratory resistance were observed in the prone position. Oxygenation is improved during non-invasive and invasive ventilation with prone positioning in patients with C-ARDS. Different mechanisms may underly this benefit during these two ventilation modalities, driven by improved distribution of lung regional aeration, intrapulmonary shunt fraction and ventilation-perfusion matching. However, the differences in the severity of C-ARDS may have biased the sensitivity of electrical impedance tomography when comparing positional changes between the protocol groups.Trial registration: ClinicalTrials.gov (NCT04359407) and Registered 24 April 2020, https://clinicaltrials.gov/ct2/show/NCT04359407 .

Titrated sedation with propofol for medical thoracoscopy: a feasibility and safety study.

BACKGROUND: Bispectral index (BIS) is a valuable tool for assessing the depth of sedation and guiding the administration of sedative drugs. We previously demonstrated the benefits of BIS-guided propofol sedation in patients undergoing flexible bronchoscopy. OBJECTIVE: To examine the feasibility and safety profile of propofol sedation in patients undergoing medical thoracoscopy (MT). METHODS: Patients undergoing MT for diagnostic evaluation or treatment of pleuropulmonary diseases were enrolled over a 2-year period. Nurses and chest physicians were trained by anesthetists to provide analgosedation, to detect and correct cardiopulmonary disturbances. The level of sedation was optimized individually by titrating the propofol infusion according to the BIS and clinical evaluation. Patients' clinical data, procedure time, medications and any adverse events were recorded. RESULTS: Fifty-three patients (60% male) with a median age of 62 years (range 19-84 years) underwent MT. The operative procedure lasted a median time of 28 min (range 9-112 min). The median doses of anesthetic drugs were 145 mg of propofol (range 20-410 mg) and 84 µg of fentanyl (range 0-225 µg). Hemodynamic disturbances occurred in 39 patients (bradycardia n = 4, tachycardia n = 12, hypotension n = 34) and required drug administration in only 4 cases. Hypoxemic events (n = 4) resolved upon gentle patient stimulation (verbal command, chin lift, oral cannula). All patients could be discharged from the recovery unit within 105 min after the procedure. CONCLUSIONS: BIS-guided propofol sedation is a safe method that might replace midazolam sedation in MT and can be managed by well-trained nonanesthesiologist personnel.

Goal-directed hemodynamic therapy versus restrictive normovolemic therapy in major open abdominal surgery: A randomized controlled trial.

BACKGROUND: The aim of this study was to compare the occurrence of postoperative complications in patients undergoing elective open abdominal surgery and receiving intraoperative goal-directed hemodynamic therapy or restrictive normovolemic therapy. METHODS: A total of 401 patients were randomized in the goal-directed hemodynamic therapy or restrictive normovolemic therapy groups. A cardiac output monitor was used in all goal-directed hemodynamic therapy patients and was left at the discretion of anesthetists in charge of patients in the restrictive normovolemic therapy group. The primary outcome was a composite morbidity endpoint (30-day mortality and complications grade 2-4 according to Dindo-Clavien classification). Secondary outcomes were the hospital duration of stay, the incidence of pulmonary, cardiovascular, and renal complications up to 30 days after surgery, and midterm survival. RESULTS: Intraoperatively, the goal-directed hemodynamic therapy group received higher intravenous fluid volumes (mean of 10.8 mL/kg/h and standard deviation of 4.0) compared with the restrictive normovolemic therapy group (mean of 7.2 mL/kg/h and standard deviation of 2.0; P < .001). On the first postoperative day, similar fluid volumes were infused in the 2 groups. The primary outcome occurred in 57.7% of goal-directed hemodynamic therapy and 53.0% of restrictive normovolemic therapy (relative risk, 1.09 [95% confidence interval, 0.91-1.30]), and there was no significant difference between groups for any secondary outcomes. CONCLUSION: Among patients undergoing major open abdominal surgery, the goal-directed hemodynamic therapy and the restrictive normovolemic therapy were associated with similar incidence of moderate-to-severe postoperative complications and hospital resource use.