A preliminary cost-effectiveness analysis of lung protective ventilation with extra corporeal carbon dioxide removal (ECCO2R) in the management of acute respiratory distress syndrome (ARDS).

BACKGROUND: Mechanical ventilation (MV) is the cornerstone in the management of the acute respiratory distress syndrome (ARDS). Recent research suggests that decreasing the intensity of MV using lung protective ventilation (LPV) with lower tidal volume (Vt) and driving pressure (∆P) could improve survival. Extra-corporal CO2 removal (ECCO2R) precisely enables LPV by allowing lower Vt, ∆P and mechanical power while maintaining PaCO2 within a physiologic range. This study evaluates the potential cost-effectiveness of ECCO2R-enabled LPV in France. METHODS: We modelled the distribution over time of ventilated ARDS patients across 3 health-states (alive & ventilated, alive & weaned from ventilation, dead). We compared the outcomes of 3 strategies: MV (no ECCO2R), LPV (ECCO2R when PaCO2 > 55 mmHg) and Ultra-LPV (ECCO2R for all). Patients characteristics, ventilation settings, survival and lengths of stay were derived from a large ARDS epidemiology study. Survival benefits associated with lower ∆P were taken from the analysis of more than 3000 patients enrolled in 9 randomized trials. Health outcomes were expressed in quality-adjusted life years (QALYs). Incremental cost-effectiveness ratios (ICERs) were computed with both Day 60 cost and Lifetime cost. RESULTS: Both LPV and ULPV as enabled by ECCO2R provided favorable results at Day 60 as compared to MV. Survival rates were increased with the protective strategies, notably with ULPV that provided even more manifest benefits as compared to MV. LPV and ULPV produced +0.162 and + 0.627 incremental QALYs as compared to MV, respectively. LPV and ULPV costs were augmented because of their survival benefits. Nonetheless, ICERs of LPV and ULPV vs. MV were all well below the €50,000 threshold. ULPV also presented with favorable ICERs as compared to LPV (i.e. less than €25,000/QALY). CONCLUSIONS: ECCO2R-enabled LPV strategies might provide cost-effective survival benefit. Additional data from interventional and observational studies are needed to support this preliminary model-based analysis.

ECCO2R therapy in the ICU: consensus of a European round table meeting.

BACKGROUND: With recent advances in technology, patients with acute respiratory distress syndrome (ARDS) and severe acute exacerbations of chronic obstructive pulmonary disease (ae-COPD) could benefit from extracorporeal CO2 removal (ECCO2R). However, current evidence in these indications is limited. A European ECCO2R Expert Round Table Meeting was convened to further explore the potential for this treatment approach. METHODS: A modified Delphi-based method was used to collate European experts' views to better understand how ECCO2R therapy is applied, identify how patients are selected and how treatment decisions are made, as well as to identify any points of consensus. RESULTS: Fourteen participants were selected based on known clinical expertise in critical care and in providing respiratory support with ECCO2R or extracorporeal membrane oxygenation. ARDS was considered the primary indication for ECCO2R therapy (n = 7), while 3 participants considered ae-COPD the primary indication. The group agreed that the primary treatment goal of ECCO2R therapy in patients with ARDS was to apply ultra-protective lung ventilation via managing CO2 levels. Driving pressure (≥ 14 cmH2O) followed by plateau pressure (Pplat; ≥ 25 cmH2O) was considered the most important criteria for ECCO2R initiation. Key treatment targets for patients with ARDS undergoing ECCO2R included pH (> 7.30), respiratory rate (< 25 or < 20 breaths/min), driving pressure (< 14 cmH2O) and Pplat (< 25 cmH2O). In ae-COPD, there was consensus that, in patients at risk of non-invasive ventilation (NIV) failure, no decrease in PaCO2 and no decrease in respiratory rate were key criteria for initiating ECCO2R therapy. Key treatment targets in ae-COPD were patient comfort, pH (> 7.30-7.35), respiratory rate (< 20-25 breaths/min), decrease of PaCO2 (by 10-20%), weaning from NIV, decrease in HCO3- and maintaining haemodynamic stability. Consensus was reached on weaning protocols for both indications. Anticoagulation with intravenous unfractionated heparin was the strategy preferred by the group. CONCLUSIONS: Insights from this group of experienced physicians suggest that ECCO2R therapy may be an effective supportive treatment for adults with ARDS or ae-COPD. Further evidence from randomised clinical trials and/or high-quality prospective studies is needed to better guide decision making.

In vitro characterization of PrismaLung+: a novel ECCO2R device.

BACKGROUND: Invasive mechanical ventilation is lifesaving in the setting of severe acute respiratory failure but can cause ventilation-induced lung injury. Advances in extracorporeal CO2 removal (ECCO2R) technologies may facilitate more protective lung ventilation in acute respiratory distress syndrome, and enable earlier weaning and/or avoid invasive mechanical ventilation entirely in chronic obstructive pulmonary disease exacerbations. We evaluated the in vitro CO2 removal capacity of the novel PrismaLung+ ECCO2R device compared with two existing gas exchangers. METHODS: The in vitro CO2 removal capacity of the PrismaLung+ (surface area 0.8 m2, Baxter) was compared with the PrismaLung (surface area 0.35 m2, Baxter) and A.L.ONE (surface area 1.35 m2, Eurosets) devices, using a closed-loop bovine blood-perfused extracorporeal circuit. The efficacy of each device was measured at varying pCO2 inlet (pinCO2) levels (45, 60, and 80 mmHg) and blood flow rates (QB) of 200-450 mL/min; the PrismaLung+ and A.L.ONE devices were also tested at a QB of 600 mL/min. The amount of CO2 removed by each device was assessed by measurement of the CO2 infused to maintain circuit equilibrium (CO2 infusion method) and compared with measured CO2 concentrations in the inlet and outlet of the CO2 removal device (blood gas analysis method). RESULTS: The PrismaLung+ device performed similarly to the A.L.ONE device, with both devices demonstrating CO2 removal rates ~ 50% greater than the PrismaLung device. CO2 removal rates were 73 ± 4.0, 44 ± 2.5, and 72 ± 1.9 mL/min, for PrismaLung+, PrismaLung, and A.L.ONE, respectively, at QB 300 mL/min and pinCO2 45 mmHg. A Bland-Altman plot demonstrated that the CO2 infusion method was comparable to the blood gas analysis method for calculating CO2 removal. The resistance to blood flow across the test device, as measured by pressure drop, varied as a function of blood flow rate, and was greatest for PrismaLung and lowest for the A.L.ONE device. CONCLUSIONS: The newly developed PrismaLung+ performed more effectively than PrismaLung, with performance of CO2 removal comparable to A.L.ONE at the flow rates tested, despite the smaller membrane surface area of PrismaLung+ versus A.L.ONE. Clinical testing of PrismaLung+ is warranted to further characterize its performance.

Extracorporeal carbon dioxide removal requirements for ultraprotective mechanical ventilation: Mathematical model predictions.

Extracorporeal carbon dioxide (CO2 ) removal (ECCO2 R) facilitates the use of low tidal volumes during protective or ultraprotective mechanical ventilation when managing patients with acute respiratory distress syndrome (ARDS); however, the rate of ECCO2 R required to avoid hypercapnia remains unclear. We calculated ECCO2 R rate requirements to maintain arterial partial pressure of CO2 (PaCO2 ) at clinically desirable levels in mechanically ventilated ARDS patients using a six-compartment mathematical model of CO2 and oxygen (O2 ) biochemistry and whole-body transport with the inclusion of an ECCO2 R device for extracorporeal veno-venous removal of CO2 . The model assumes steady state conditions. Model compartments were lung capillary blood, arterial blood, venous blood, post-ECCO2 R venous blood, interstitial fluid and tissue cells, with CO2 and O2 distribution within each compartment; biochemistry included equilibrium among bicarbonate and non-bicarbonate buffers and CO2 and O2 binding to hemoglobin to elucidate Bohr and Haldane effects. O2 consumption and CO2 production rates were assumed proportional to predicted body weight (PBW) and adjusted to achieve reported arterial partial pressure of O2 and a PaCO2 level of 46 mmHg at a tidal volume of 7.6 mL/kg PBW in the absence of an ECCO2 R device based on average data from LUNG SAFE. Model calculations showed that ECCO2 R rates required to achieve mild permissive hypercapnia (PaCO2 of 46 mmHg) at a ventilation frequency or respiratory rate of 20.8/min during mechanical ventilation increased when tidal volumes decreased from 7.6 to 3 mL/kg PBW. Higher ECCO2R rates were required to achieve normocapnia (PaCO2 of 40 mmHg). Model calculations also showed that required ECCO2R rates were lower when ventilation frequencies were increased from 20.8/min to 26/min. The current mathematical model predicts that ECCO2R rates resulting in clinically desirable PaCO2 levels at tidal volumes of 5-6 mL/kg PBW can likely be achieved in mechanically ventilated ARDS patients with current technologies; use of ultraprotective tidal volumes (3-4 mL/kg PBW) may be challenging unless high mechanical ventilation frequencies are used.

Sepsis Management with a Blood Purification Membrane: European Experience.

BACKGROUND: Septic shock is a leading cause of acute kidney injury (AKI). Endotoxins and cytokine levels are associated with the occurrence and severity of AKI, and different blood purification devices are available to remove them from circulation. One such device, oXiris, is a hollow-fibre purification filter that clears both endotoxins and cytokines. Due to limited evidence, clinical use of this device is not currently advocated in guidelines. However, clinics do regularly use this device, and there is a critical need for guidance on the application of it in sepsis with and without AKI. METHOD: A modified Delphi-based method was used to collate -European experts' views on the indication(s), initiation and discontinuation criteria and success measures for oXiris. RESULTS: A panel of 14 participants was selected based on known clinical expertise in the areas of critical care and sepsis management, as well as their experience of using the oXiris blood purification device. The participants used different criteria to initiate treatment with oXiris in sepsis patients with and without AKI. Septic shock with AKI was the priority patient population, with oXiris used to rapidly improve haemodynamic parameters. Achieving haemodynamic stability within 72 h was a key factor for determining treatment success. CONCLUSION: In the absence of established guidelines, users of hollow-fibre purification devices such as oXiris may benefit from standardised approaches to selecting patients and initiating and terminating treatment, as well as measuring success. Further evidence in the form of randomised clinical trials is urgently required.

Practice of Extracorporeal Therapies for Septic Acute Kidney Injury Patients in Intensive Care Units in Mainland China.

BACKGROUND: Continuous renal replacement therapy (CRRT) and other extracorporeal therapies for acute kidney injury (AKI) and other organ dysfunction syndromes in critically ill patients are common in the intensive care unit (ICU). Many studies have focused on clinical practice for managing these conditions. However, there are few studies that describe the utilization of extracorporeal therapies, especially CRRT, in patients with sepsis-associated AKI. SUMMARY: Two hundred ICU physicians were included in a survey from February 28, 2017, to March 20, 2017, on the current status of septic AKI and clinical practice in CRRT. According to the responses, 40% of sepsis patients in the ICU had AKI, and 25% required extracorporeal therapies. However, 29% of candidates gave up therapy for medical or nonmedical reasons. Overall survival for sepsis was 60%; among survivors, 80% were dialysis free at discharge. CRRT was the most common modality of extracorporeal therapy in the ICU, and 82% of physicians chose convection as the major clearance mode. The survey showed 30% of physicians saw the removal of inflammatory mediators as the major objective of extracorporeal therapies; however, only 18.5% of physicians considered inflammation as a measure to trigger CRRT. The median treatment duration of CRRT in China was 12 h per day for 5 days. Key Messages: There were some similarities and differences in CRRT practice for septic AKI patients in China and globally. The differences reveal some insights into improving the outcomes of these patients.

Near-Continuous Glucose Monitoring Makes Glycemic Control Safer in ICU Patients.

OBJECTIVES: Tight glycemic control using intermittent blood glucose measurements is associated with a risk of hypoglycemia. Glucose concentrations can now be measured near continuously (every 5-15 min). We assessed the quality and safety of glycemic control guided by a near-continuous glucose monitoring system in ICU patients. DESIGN: Prospective, cluster-randomized, crossover study. SETTING: Thirty-five-bed medico-surgical department of intensive care with four separate ICUs. PATIENTS: Adult patients admitted to the department and expected to stay for at least 3 days were considered for inclusion if they had persistent hyperglycemia (blood glucose > 150 mg/dL) up to 6 hours after admission and/or were receiving insulin therapy. INTERVENTIONS: A peripheral venous catheter was inserted in all patients and connected to a continuous glucose monitoring sensor (GlucoClear; Edwards Lifesciences, Irvine, CA). The four ICUs were randomized in pairs in a crossover design to glycemic control using unblinded or blinded continuous glucose monitoring monitors. The insulin infusion rate was adjusted to keep blood glucose between 90 and 150 mg/dL using the blood glucose values displayed on the continuous glucose monitor (continuous glucose monitoring group-unblinded units) or according to intermittent blood glucose readings (intermittent glucose monitoring group-blinded units). MEASUREMENTS AND MAIN RESULTS: The quality and safety of glycemic control were assessed using the proportion of time in range, the frequency of blood glucose less than 70 mg/dL, and the time spent with blood glucose less than 70 mg/dL (TB70), using blood glucose values measured by the continuous glucose monitoring device. Seventy-seven patients were enrolled: 39 in the continuous glucose monitoring group and 38 in the intermittent glucose monitoring group. A total of 43,107 blood glucose values were recorded. The time in range was similar in the two groups. The incidence of hypoglycemia (8/39 [20.5%] vs 15/38 [39.5%]) and the TB70 (0.4% ± 0.9% vs 1.6% ± 3.4%; p < 0.05) was lower in the continuous glucose monitoring than in the intermittent glucose monitoring group. CONCLUSIONS: Use of a continuous glucose monitoring-based strategy decreased the incidence and severity of hypoglycemia, thus improving the safety of glycemic control.

Comparison of Endoaortic and Transthoracic Aortic Clamping in Less-Invasive Mitral Valve Surgery.

BACKGROUND: Less-invasive mitral valve surgery has become a widespread procedure in recent years, although mode of perfusion and aortic clamping are still debated questions. The aim of this study was to compare the results between transthoracic aortic clamping (TTC) and endoaortic clamping (EAC) in a multicenter, retrospective study. METHODS: Data from 3 centers experienced in both TTC and EAC were retrospectively analyzed. Five hundred consecutive patients undergoing less-invasive mitral valve surgery received either TTC (n = 250) or EAC (n = 250). Age, sex, logistic EuroSCORE, ejection fraction, associated procedures, and mitral valve repair rate were similar. A higher incidence of previous cardiac operations was observed in the EAC group (TTC 8.8% versus EAC 16.8%, p = 0.001). RESULTS: Clamping and cardiopulmonary bypass times were comparable between the 2 groups. Reoperation for bleeding (TTC 11.2% versus EAC 3.2%, p < 0.001), conversion to full sternotomy (6 cases in the TTC group), and hospital length of stay (TTC 9 days versus EAC 8 days, p = 0.01) were higher in the TTC group. No differences were found in respiratory failure, renal failure, major vascular complication, stroke, and in-hospital mortality rate. CONCLUSIONS: Despite recent concerns arising about EAC, this large multicenter study shows equivalence in terms of safety and effectiveness of this technique compared with TTC. Reduction in postoperative bleeding was observed in the EAC group despite the higher rate of complex redo cases.

Evaluation of financial burden following complications after major surgery in France: Potential return after perioperative goal-directed therapy.

OBJECTIVE: Perioperative goal-directed therapy (PGDT) has been demonstrated to improve postoperative outcomes and reduce the length of hospital stays. The objective of our analysis was to evaluate the cost of complications, derived from French hospital payments, and calculate the potential cost savings and length of hospital stay reductions. METHODS: The billing of 2388 patients who underwent scheduled high-risk surgery (i.e. major abdominal, gynaecologic, urological, vascular, and orthopaedic interventions) over three years was retrospectively collected from three French hospitals (one public-teaching, one public, and one private hospital). A relationship between mortality, length of hospital stays, cost/patient, and severity scores, based mainly on postoperative complications but also on preoperative clinical status, were analysed. Statistical analysis was performed using Student's t-tests or Wilcoxon tests. RESULTS: Our analyses determined that a severity score of 3 or 4 was associated with complications in 90% of cases and this represented 36% of patients who, compared with those with a score of 1 or 2, were associated with significantly increased costs (€ 8205±3335 to € 22,081±16,090; P<0.001, delta of € 13,876) and a prolonged length of hospital stay (mean of 10 to 27 days; P<0.001, delta of 17 days). According to estimates for complications avoided by PGDT, there was a projected reduction in average healthcare costs of between € 854 and € 1458 per patient and a reduction in total hospital bed days from 1755 to 4423 over three years. Based on French National data (47,000 high risk surgeries per year), the potential financial savings ranged from € 40M to € 68M, not including the costs of PGDT and its implementation. CONCLUSION: Our analysis demonstrates that patients with complications are significantly more expensive to care for than those without complications. In our model, it was projected that implementing PGDT during high-risk surgery may significantly reduce healthcare costs and the length of hospital stays in France while probably improving patient access to care and reducing waiting times for procedures.

Hot shot induction and reperfusion with a specific blocker of the es-ENT1 nucleoside transporter before and after hypothermic cardioplegia abolishes myocardial stunning in acutely ischemic hearts despite metabolic derangement: hot shot drug delivery before hypothermic cardioplegia.

OBJECTIVE: Simultaneous inhibition of the cardiac equilibrative-p-nitrobenzylthioinosine (NBMPR)-sensitive (es) type of the equilibrative nucleoside transport 1 (ENT1) nucleoside transporter, with NBMPR, and adenosine deaminase, with erythro-9-[2-hydroxy-3-nonyl]adenine (EHNA), prevents release of myocardial purines and attenuates myocardial stunning and fibrillation in canine models of warm ischemia and reperfusion. It is not known whether prolonged administration of hypothermic cardioplegia influences purine release and EHNA/NBMPR-mediated cardioprotection in acutely ischemic hearts. METHODS: Anesthetized dogs (n = 46), which underwent normothermic aortic crossclamping for 20 minutes on-pump, were divided to determine (1) purine release with induction of intermittent antegrade or continuous retrograde hypothermic cardioplegia and reperfusion, (2) the effects of postischemic treatment with 100 µM EHNA and 25 µM NBMPR on purine release and global functional recovery, and (3) whether a hot shot and reperfusion with EHNA/NBMPR inhibits purine release and attenuates ventricular dysfunction of ischemic hearts. Myocardial biopsies and coronary sinus effluents were obtained and analyzed using high-performance liquid chromatography. RESULTS: Warm ischemia depleted myocardial adenosine triphosphate and elevated purines (ie, inosine > adenosine) as markers of ischemia. Induction of intermittent antegrade or continuous retrograde hypothermic (4°C) cardioplegia releases purines until the heart becomes cold (<20°C). During reperfusion, the levels of hypoxanthine and xanthine (free radical substrates) were >90% of purines in coronary sinus effluent. Reperfusion with EHNA/NBMPR abolished ventricular dysfunction in acutely ischemic hearts with and without a hot shot and hypothermic cardioplegic arrest. CONCLUSIONS: Induction of hypothermic cardioplegia releases purines from ischemic hearts until they become cold, whereas reperfusion induces massive purine release and myocardial stunning. Inhibition of cardiac es-ENT1 nucleoside transporter abolishes postischemic reperfusion injury in warm and cold cardiac surgery.

New developments in cardiac surgery.

In cardiac surgery new developments in the current area are mainly directed towards minimally invasive surgery techniques. New anastomotic devices for CABG are clinically available and will facilitate partial and total endoscopic CABG techniques. In valve surgery percutaneous techniques are already available for AVR and PVR. Single percutaneous mitral valve repair is not a too far away procedure. Tissue engineering will offer biocompatible heart valves. New developments for heart failure therapy are booming. The major drawback for the achievements of this amazing progress is the financial cost. An open debate between all the parties concerned in healthcare is urgently needed in order to maintain the quality of surgical care for the decades to come.

Ventricular septal defect closure in tetralogy of Fallot: the aortic rule.

Ventricular septal defect (VSD) closure is an important part of the surgical repair of tetralogy of Fallot and related anomalies. Visual appreciation of the VSD size (either transinfundibular or transatrial) can be misleading. My colleagues and I describe a simple and precise way to predict the size and shape of the VSD patch before extracorporeal circulation: the patch should be circular with a diameter identical to that of the mid ascending aorta.

Acute retrograde aortic dissection during endovascular repair of a thoracic aortic aneurysm.

Endovascular aneurysm exclusion represents a valuable alternative treatment for descending thoracic aortic aneurysms. Although the minimally invasive character of this procedure is obvious, major complications are possible. We report a 77-year-old male who developed acute retrograde dissection of the aortic arch and ascending aorta during endovascular stent-grafting of a descending aortic aneurysm. Emergent open surgical repair provided a successful outcome.

Early results of valved bovine jugular vein conduit versus bicuspid homograft for right ventricular outflow tract reconstruction.

BACKGROUND: Homograft conduits are preferable for right ventricular outflow tract reconstruction in children, but their limited availability remains a major concern. Recently, a valve-containing segment of bovine jugular vein (Contegra, Medtronic Inc, Minneapolis, MN) has been introduced as a potential alternative conduit. METHODS: Early clinical and echocardiographic results of right ventricular outflow tract reconstruction were retrospectively compared between 41 children (mean age, 1.9 years), receiving a Contegra conduit and 36 patients (mean age, 2.7 years) with a size-reduced pulmonary homograft. RESULTS: Clinical outcome was comparable with two early deaths in the homograft group and one in the Contegra group. There were no conduit-related complications in either population. Early echocardiographic assessment showed only trivial to mild regurgitation in 9 homografts versus 17 Contegra conduits. The peak gradient across the right ventricular outflow tract conduit was comparable for both groups, although a larger number of patients, treated with a downsized homograft, had a small gradient at the distal junction with the pulmonary arteries (12 versus 6 patients). None of the patients had a gradient at the valvar level. CONCLUSIONS: The valved bovine jugular vein conduit offers a promising substitute for right ventricular outflow tract reconstruction in infants and children, with an early hemodynamic performance that compares favorably with downsized, bicuspid homografts. Clinical advantages are greater shelf availability and the natural continuity between valve and conduit, which allows proximal infundibular shaping without additional material. However, durability must be determined, even though most of these children will require right ventricular outflow tract reoperation after outgrowing the conduit.