Individualised flow-controlled ventilation reduces applied mechanical power and improves ventilation efficiency in a porcine intra-abdominal hypertension model.

BACKGROUND: Aim of this study was to evaluate feasibility and effects of individualised flow-controlled ventilation (FCV), based on compliance guided pressure settings, compared to standard of pressure-controlled ventilation (PCV) in a porcine intra-abdominal hypertension (IAH) model. The primary aim of this study was to investigate oxygenation. Secondary aims were to assess respiratory and metabolic variables and lung tissue aeration. METHODS: Pigs were randomly assigned to FCV (n = 9) and PCV (n = 9). IAH was induced by insufflation of air into the abdomen to induce IAH grades ranging from 0 to 3. At each IAH grade FCV was undertaken using compliance guided pressure settings, or PCV (n = 9) was undertaken with the positive end-expiratory pressure titrated for maximum compliance and the peak pressure set to achieve a tidal volume of 7 ml/kg. Gas exchange, ventilator settings and derived formulas were recorded at two timepoints for each grade of IAH. Lung aeration was assessed by a computed tomography scan at IAH grade 3. RESULTS: All 18 pigs (median weight 54 kg [IQR 51-67]) completed the observation period of 4 h. Oxygenation was comparable at each IAH grade, but a significantly lower minute volume was required to secure normocapnia in FCV at all IAH grades (7.6 vs. 14.4, MD - 6.8 (95% CI - 8.5 to - 5.2) l/min; p < 0.001). There was also a significant reduction of applied mechanical power being most evident at IAH grade 3 (25.9 vs. 57.6, MD - 31.7 (95% CI - 39.7 to - 23.7) J/min; p < 0.001). Analysis of Hounsfield unit distribution of the computed tomography scans revealed a significant reduction in non- (5 vs. 8, MD - 3 (95% CI - 6 to 0) %; p = 0.032) and poorly-aerated lung tissue (7 vs. 15, MD - 6 (95% CI - 13 to - 3) %, p = 0.002) for FCV. Concomitantly, normally-aerated lung tissue was significantly increased (84 vs. 76, MD 8 (95% CI 2 to 15) %; p = 0.011). CONCLUSIONS: Individualised FCV showed similar oxygenation but required a significantly lower minute volume for CO2-removal, which led to a remarkable reduction of applied mechanical power. Additionally, there was a shift from non- and poorly-aerated lung tissue to normally-aerated lung tissue in FCV compared to PCV.

Flow-controlled versus pressure-controlled ventilation in cardiac surgery with cardiopulmonary bypass - A single-center, prospective, randomized, controlled trial.

STUDY OBJECTIVE: Multifactorial comparison of flow-controlled ventilation (FCV) to standard of pressure-controlled ventilation (PCV) in terms of oxygenation in cardiac surgery patients after chest closure. DESIGN: Prospective, non-blinded, randomized, controlled trial. SETTING: Operating theatre at an university hospital, Austria. PATIENTS: Patients scheduled for elective, open, on-pump, cardiac surgery. INTERVENTIONS: Participants were randomized to either individualized FCV (compliance guided end-expiratory and peak pressure setting) or control of PCV (compliance guided end-expiratory pressure setting and tidal volume of 6-8 ml/kg) for the duration of surgery. MEASUREMENTS: The primary outcome measure was oxygenation (PaO2/FiO2) 15 min after intraoperative chest closure. Secondary endpoints included CO2-removal assessed as required minute volume to achieve normocapnia and lung tissue aeration assessed by Hounsfield unit distribution in postoperative computed tomography scans. MAIN RESULTS: Between April 2020 and April 2021 56 patients were enrolled and 50 included in the primary analysis (mean age 70 years, 38 (76%) men). Oxygenation, assessed by PaO2/FiO2, was significantly higher in the FCV group (n = 24) compared to the control group (PCV, n = 26) (356 vs. 309, median difference (MD) 46 (95% CI 3 to 90) mmHg; p = 0.038). Additionally, the minute volume required to obtain normocapnia was significantly lower in the FCV group (4.0 vs. 6.1, MD -2.0 (95% CI -2.5 to -1.5) l/min; p < 0.001) and correlated with a significantly lower exposure to mechanical power (5.1 vs. 9.8, MD -5.1 (95% CI -6.2 to -4.0) J/min; p < 0.001). Evaluation of lung tissue aeration revealed a significantly reduced amount of non-aerated lung tissue in FCV compared to PCV (5 vs. 7, MD -3 (95% CI -4 to -1) %; p < 0.001). CONCLUSIONS: In patients undergoing on-pump, cardiac surgery individualized FCV significantly improved oxygenation and lung tissue aeration compared to PCV. In addition, carbon dioxide removal was accomplished at a lower minute volume leading to reduced applied mechanical power.

Improved ventilation efficiency due to continuous gas flow compared to decelerating gas flow in mechanical ventilation: results of a porcine trial.

In pressure-controlled ventilation (PCV), a decelerating gas flow pattern occurs during inspiration and expiration. In contrast, flow-controlled ventilation (FCV) guarantees a continuous gas flow throughout the entire ventilation cycle where the inspiration and expiration phases are simply performed by a change of gas flow direction. The aim of this trial was to highlight the effects of different flow patterns on respiratory variables and gas exchange. Anesthetized pigs were ventilated with either FCV or PCV for 1 h and thereafter for 30 min each in a crossover comparison. Both ventilation modes were set with a peak pressure of 15 cmH2O, positive end-expiratory pressure of 5 cmH2O, a respiratory rate of 20/min, and a fraction of inspired oxygen at 0.3. All respiratory variables were collected every 15 min. Tidal volume and respiratory minute volume were significantly lower in FCV (n = 5) compared with PCV (n = 5) animals [4.6 vs. 6.6, MD -2.0 (95% CI -2.6 to -1.4) mL/kg; P < 0.001 and 7.3 vs. 9.5, MD -2.2 (95% CI -3.3 to -1.0) L/min; P = 0.006]. Notwithstanding these differences, CO2-removal as well as oxygenation was not inferior in FCV compared with PCV. Mechanical ventilation with identical ventilator settings resulted in lower tidal volumes and consecutive minute volume in FCV compared with PCV. This finding can be explained physically by the continuous gas flow pattern in FCV that necessitates a lower alveolar pressure amplitude. Interestingly, gas exchange was comparable in both groups, which is suggestive of improved ventilation efficiency at a continuous gas flow pattern.NEW & NOTEWORTHY This study examined the effects of a continuous (flow-controlled ventilation, FCV) vs. decelerating (pressure-controlled ventilation, PCV) gas flow pattern during mechanical ventilation. It was shown that FCV necessitates a lower alveolar pressure amplitude leading to reduced applied tidal volumes and consequently minute volume. Notwithstanding these differences, CO2-removal as well as oxygenation was not inferior in FCV compared with PCV, which is suggestive of improved gas exchange efficiency at a continuous gas flow pattern.

Catabolism highly influences ICU-acquired hypernatremia in a mainly trauma and surgical cohort.

PURPOSE: To further analyse causes and effects of ICU-acquired hypernatremia. METHODS: This retrospective, single-centre study, analysed 994 patients regarding ICU-acquired hypernatremia. Non-hypernatremic patients (n = 617) were compared to early-hypernatremic (only before ICU-day 4; n = 87), prolonged-hypernatremic (before and after ICU-day 4; n = 169) and late-hypernatremic patients (only after ICU-day 4; n = 121). Trends in glomerular filtration rate (eGFR), urea-to-creatinine ratio (UCR), fraction of urea in total urine osmolality and urine sodium were compared. Risk factors for i) the development of hypernatremia and ii) mortality were determined. RESULTS: Thirty-eight percent (n = 377) developed ICU-acquired hypernatremia. Specifically in the prolonged- and late-group, decreased eGFRs and urine sodium but increased UCR and fractions of urea in urine osmolality were present. Decreased eGFR was a risk factor for the development of hypernatremia in all groups; disease severity and increased catabolism particularly in the prolonged- and late-hypernatremic group. Increased age, SAPS-III and signs of catabolism but not the development of hypernatremia itself was identified as significant risk factor for mortality. CONCLUSIONS: Late- and prolonged-hypernatremia is highly related to an increased protein metabolism. Besides excessive catabolism, initial disease severity and a decrease in renal function must be considered when confronted with ICU-acquired hypernatremia.

Short time effects of compliance guided flow-controlled ventilation versus standard of care pressure-controlled ventilation: a prospective porcine trial.

BACKGROUND: Flow-controlled ventilation (FCV) represents a novel ventilation method, which guarantees a continuous gas flow during inspiration and expiration. Long term comparison to volume- and pressure-controlled ventilation (PCV) after five- and ten hours have shown improved gas exchange parameters and lung tissue aeration. Aim of this porcine trial was to compare gas exchange parameters and lung tissue aeration in short time application of FCV compared to PCV to determine effects which will most probably pertain in short lasting procedures under general anesthesia. METHODS: After induction of general anesthesia nine pigs were randomly ventilated either with compliance guided FCV settings or standard of PCV with compliance titrated positive end-expiratory pressure and peak pressure set to achieve a tidal volume of 7 mL/kg. Subsequently an arterial blood gas sample was obtained, and a computed tomography scan was performed. Afterwards, each animal was extubated and on the following day the same protocol was performed again with the alternative ventilation method. RESULTS: Primary analysis of 18 datasets from nine animals (with paired comparison) revealed a significantly improved oxygenation with FCV compared to control (paO2 118 vs. 109, 95% CI 2 to 16 mm Hg; P=0.042). The required respiratory minute volume was significantly lower with FCV (7.4 vs. 10.8, 95% CI -4.0 to -2.9 L/min; P<0.001) to achieve similar levels of normocapnia. However, lung tissue aeration did not significantly differ between ventilation methods. CONCLUSIONS: In this short-term ventilation comparison FCV improved gas exchange parameters without differences in lung tissue aeration compared to PCV.

Individualised flow-controlled versus pressure-controlled ventilation in a porcine oleic acid-induced acute respiratory distress syndrome model.

BACKGROUND: A continuous gas flow provided by flow-controlled ventilation (FCV) facilitates accurate dynamic compliance measurement and allows the clinician to individually optimise positive end-expiratory and peak pressure settings accordingly. OBJECTIVE: The aim of this study was to compare the efficiency of gas exchange and impact on haemodynamics between individualised FCV and pressure-controlled ventilation (PCV) in a porcine model of oleic acid-induced acute respiratory distress syndrome (ARDS). DESIGN: Randomised controlled interventional trial conducted on 16 pigs. SETTING: Animal operating facility at the Medical University Innsbruck. INTERVENTIONS: ARDS was induced in lung healthy pigs by intravenous infusion of oleic acid until moderate-to-severe ARDS at a stable Horowitz quotient (PaO 2 FiO 2-1 ) of 80 to 120 over a period of 30 min was obtained. Ventilation was then either performed with individualised FCV ( n  = 8) established by compliance-guided pressure titration or PCV ( n  = 8) with compliance-guided titration of the positive end-expiratory pressure and peak pressure set to achieve a tidal volume of 6 ml kg -1 over a period of 2 h. MAIN OUTCOME MEASURES: Gas exchange parameters were assessed by the PaO 2 FiO 2-1 quotient and CO 2 removal by the PaCO 2 value in relation to required respiratory minute volume. Required catecholamine support for haemodynamic stabilisation was measured. RESULTS: The FCV group showed significantly improved oxygenation [149.2 vs. 110.4, median difference (MD) 38.7 (8.0 to 69.5) PaO 2 FiO 2-1 ; P  = 0.027] and CO 2 removal [PaCO 2 7.25 vs. 9.05, MD -1.8 (-2.87 to -0.72) kPa; P  = 0.006] at a significantly lower respiratory minute volume [8.4 vs. 11.9, MD -3.6 (-5.6 to -1.5) l min -1 ; P  = 0.005] compared with PCV. In addition, in FCV-pigs, haemodynamic stabilisation occurred with a significant reduction of required catecholamine support [norepinephrine 0.26 vs. 0.86, MD -0.61 (-1.12 to -0.09) µg kg -1  min -1 ; P  = 0.037] during 2 ventilation hours. CONCLUSION: In this oleic acid-induced porcine ARDS model, individualised FCV significantly improved gas exchange and haemodynamic stability compared with PCV. TRIAL REGISTRATION: Protocol no.: BMBWF-66.011/0105-V/3b/2019).

Individualised flow-controlled ventilation versus pressure-controlled ventilation in a porcine model of thoracic surgery requiring one-lung ventilation: A laboratory study.

BACKGROUND: Flow-controlled ventilation (FCV) enables precise determination of dynamic compliance due to a continuous flow coupled with direct tracheal pressure measurement. Thus, pressure settings can be adjusted accordingly in an individualised approach. OBJECTIVE: The aim of this study was to compare gas exchange of individualised FCV to pressure-controlled ventilation (PCV) in a porcine model of simulated thoracic surgery requiring one-lung ventilation (OLV). DESIGN: Controlled interventional trial conducted on 16 domestic pigs. SETTING: Animal operating facility at the Medical University of Innsbruck. INTERVENTIONS: Thoracic surgery was simulated with left-sided thoracotomy and subsequent collapse of the lung over a period of three hours. When using FCV, ventilation was performed with compliance-guided pressure settings. When using PCV, end-expiratory pressure was adapted to achieve best compliance with peak pressure adjusted to achieve a tidal volume of 6 ml kg -1 during OLV. MAIN OUTCOME MEASURES: Gas exchange was assessed by the Horowitz index (= P aO 2 /FIO 2 ) and CO 2 removal by the P aCO 2 value in relation to required respiratory minute volume. RESULTS: In the FCV group ( n  = 8) normocapnia could be maintained throughout the OLV trial despite a significantly lower respiratory minute volume compared to the PCV group ( n  = 8) (8.0 vs. 11.6, 95% confidence interval, CI -4.5 to -2.7 l min -1 ; P  < 0.001), whereas permissive hypercapnia had to be accepted in PCV ( P aCO 2 5.68 vs. 6.89, 95% CI -1.7 to -0.7 kPa; P  < 0.001). The Horowitz index was comparable in both groups but calculated mechanical power was significantly lower in FCV (7.5 vs. 22.0, 95% CI -17.2 to -11.8 J min -1 ; P  < 0.001). CONCLUSIONS: In this porcine study FCV maintained normocapnia during OLV, whereas permissive hypercapnia had to be accepted in PCV despite a substantially higher minute volume. Reducing exposure of the lungs to mechanical power applied by the ventilator in FCV offers a possible advantage for this mode of ventilation in terms of lung protection.

Impact of COVID-19 Related Lockdown on the Frequency of Acute and Oncological Surgeries-Lessons Learned From an Austrian University Hospital.

Innsbruck Medical University Hospital, Austria, provides the highest level of care for a region of approximately 1.8 million people. During the early COVID-19 outbreak in spring 2020 surgical activity was drastically reduced with the prime goal of preserving hospital capacities, especially intensive care beds. We conducted a retrospective analysis of surgical activities performed at Innsbruck Medical University Hospital during the lockdown period from March 15 to April 14, 2020 and compared these activities to the same period during the previous 5 years. Total surgical activity was reduced by 65.4% compared to the same period during the previous 5 years (p < 0.001); elective surgeries were reduced by 88.7%, acute surgeries by 35.3% and oncological surgeries by 47.8% compared to the previous 5 years (all p < 0.001). This dramatic decrease in acute and oncological surgeries can most likely be ascribed to the fact that many patients avoided health care facilities because of the strict stay-at-home policy and/or the fear of contracting SARS-CoV-2 in the hospital. In view of future waves, the population should be encouraged to seek medical help for acute symptoms and to attend cancer screening programs.

Adrenaline improves regional cerebral blood flow, cerebral oxygenation and cerebral metabolism during CPR in a porcine cardiac arrest model using low-flow extracorporeal support.

BACKGROUND: The effects of adrenaline on cerebral blood vessels during cardiopulmonary resuscitation (CPR) are not well understood. We developed an extracorporeal CPR model that maintains constant low systemic blood flow while allowing adrenaline-associated effects on cerebral vasculature to be assessed at different mean arterial pressure (MAP) levels independently of the effects on systemic blood flow. METHODS: After eight minutes of cardiac arrest, low-flow extracorporeal life support (ECLS) (30 ml/kg/min) was started in fourteen pigs. After ten minutes, continuous adrenaline administration was started to achieve MAP values of 40 (n = 7) or 60 mmHg (n = 7). Measurements included intracranial pressure (ICP), cerebral perfusion pressure (CePP), laser-Doppler-derived regional cerebral blood flow (CBF), cerebral regional oxygen saturation (rSO2), brain tissue oxygen tension (PbtO2) and extracellular cerebral metabolites assessed by cerebral microdialysis. RESULTS: During ECLS without adrenaline, regional CBF increased by only 5% (25th to 75th percentile: -3 to 14; p = 0.2642) and PbtO2 by 6% (0-15; p = 0.0073) despite a significant increase in MAP to 28 mmHg (25-30; p < 0.0001) and CePP to 10 mmHg (8-13; p < 0.0001). Accordingly, cerebral microdialysis parameters showed a profound hypoxic-ischemic pattern. Adrenaline administration significantly improved regional CBF to 29 ± 14% (p = 0.0098) and 61 ± 25% (p < 0.001) and PbtO2 to 15 ± 11% and 130 ± 82% (both p < 0.001) of baseline in the MAP 40 mmHg and MAP 60 mmHg groups, respectively. Importantly, MAP of 60 mmHg was associated with metabolic improvement. CONCLUSION: This study shows that adrenaline administration during constant low systemic blood flow increases CePP, regional CBF, cerebral oxygenation and cerebral metabolism.

A case report of individualized ventilation in a COVID-19 patient - new possibilities and caveats to consider with flow-controlled ventilation.

BACKGROUND: Flow-controlled ventilation (FCV) is a novel ventilation method increasingly being used clinically, particularly during the current COVID-19 pandemic. However, the continuous flow pattern in FCV during inspiration and expiration has a significant impact on respiratory parameters and ventilatory settings compared to conventional ventilation modes. In addition, the constant flow combined with direct intratracheal pressure measurement allows determination of dynamic compliance and ventilation settings can be adjusted accordingly, reflecting a personalized ventilation approach. CASE PRESENTATION: A 50-year old women with confirmed SARS-CoV-2 infection suffering from acute respiratory distress syndrome (ARDS) was admitted to a tertiary medical center. Initial ventilation occurred with best standard of care pressure-controlled ventilation (PCV) and was then switched to FCV, by adopting PCV ventilator settings. This led to an increase in oxygenation by 30 %. Subsequently, to reduce invasiveness of mechanical ventilation, FCV was individualized by dynamic compliance guided adjustment of both, positive end-expiratory pressure and peak pressure; this intervention reduced driving pressure from 18 to 12 cm H2O. However, after several hours, compliance further deteriorated which resulted in a tidal volume of only 4.7 ml/kg. CONCLUSIONS: An individualized FCV approach increased oxygenation parameters in a patient suffering from severe COVID-19 related ARDS. Direct intratracheal pressure measurements allow for determination of dynamic compliance and thus optimization of ventilator settings, thereby reducing applied and dissipated energy. However, although desirable, this personalized ventilation strategy may reach its limits when lung function is so severely impaired that patient's oxygenation has to be ensured at the expense of lung protective ventilation concepts.

Individualized flow-controlled ventilation compared to best clinical practice pressure-controlled ventilation: a prospective randomized porcine study.

BACKGROUND: Flow-controlled ventilation is a novel ventilation method which allows to individualize ventilation according to dynamic lung mechanic limits based on direct tracheal pressure measurement at a stable constant gas flow during inspiration and expiration. The aim of this porcine study was to compare individualized flow-controlled ventilation (FCV) and current guideline-conform pressure-controlled ventilation (PCV) in long-term ventilation. METHODS: Anesthetized pigs were ventilated with either FCV or PCV over a period of 10 h with a fixed FiO2 of 0.3. FCV settings were individualized by compliance-guided positive end-expiratory pressure (PEEP) and peak pressure (Ppeak) titration. Flow was adjusted to maintain normocapnia and the inspiration to expiration ratio (I:E ratio) was set at 1:1. PCV was performed with a PEEP of 5 cm H2O and Ppeak was set to achieve a tidal volume (VT) of 7 ml/kg. The respiratory rate was adjusted to maintain normocapnia and the I:E ratio was set at 1:1.5. Repeated measurements during observation period were assessed by linear mixed-effects model. RESULTS: In FCV (n = 6), respiratory minute volume was significantly reduced (6.0 vs 12.7, MD - 6.8 (- 8.2 to - 5.4) l/min; p < 0.001) as compared to PCV (n = 6). Oxygenation was improved in the FCV group (paO2 119.8 vs 96.6, MD 23.2 (9.0 to 37.5) Torr; 15.97 vs 12.87, MD 3.10 (1.19 to 5.00) kPa; p = 0.010) and CO2 removal was more efficient (paCO2 40.1 vs 44.9, MD - 4.7 (- 7.4 to - 2.0) Torr; 5.35 vs 5.98, MD - 0.63 (- 0.99 to - 0.27) kPa; p = 0.006). Ppeak and driving pressure were comparable in both groups, whereas PEEP was significantly lower in FCV (p = 0.002). Computed tomography revealed a significant reduction in non-aerated lung tissue in individualized FCV (p = 0.026) and no significant difference in overdistended lung tissue, although a significantly higher VT was applied (8.2 vs 7.6, MD 0.7 (0.2 to 1.2) ml/kg; p = 0.025). CONCLUSION: Our long-term ventilation study demonstrates the applicability of a compliance-guided individualization of FCV settings, which resulted in significantly improved gas exchange and lung tissue aeration without signs of overinflation as compared to best clinical practice PCV.

Effects of different adrenaline doses on cerebral oxygenation and cerebral metabolism during cardiopulmonary resuscitation in pigs.

BACKGROUND: The influence of adrenaline during cardiopulmonary resuscitation (CPR) on the neurological outcome of cardiac arrest survivors is unclear. As little is known about the pathophysiological effects of adrenaline on cerebral oxygen delivery and cerebral metabolism we investigated its effects on parameters of cerebral oxygenation and cerebral metabolism in a pig model of CPR. METHODS: Fourteen pigs were anesthetized, intubated and instrumented. After 5 min of cardiac arrest CPR was started and continued for 15 min. Animals were randomized to receive bolus injections of either 15 or 30 µg/kg adrenaline every 5 min after commencement of CPR. RESULTS: Measurements included mean arterial pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), cerebral regional oxygen saturation (rSO2), brain tissue oxygen tension (PbtO2), arterial and cerebral venous blood gases and cerebral microdialysis parameters, e.g. lactate/pyruvate ratio. Adrenaline induced a significant increase in MAP and CPP in all pigs. However, increases in MAP and CPP were short-lasting and tended to decrease with repetitive bolus administration. There was no statistical difference in any parameter of cerebral oxygenation or metabolism between study groups. CONCLUSIONS: Both adrenaline doses resulted in short-lasting CPP peaks which did not translate into improved cerebral tissue oxygen tension and metabolism. Further studies are needed to determine whether other dosing regimens targeting a sustained increase in CPP, may lead to improved brain oxygenation and metabolism, thereby improving neurological outcome of cardiac arrest patients.