Assessing the role of Chemokine (C-C motif) ligand 14 in AKI: a European consensus meeting.

BACKGROUND: Urinary Chemokine (C-C motif) ligand 14 (CCL14) is a biomarker associated with persistent severe acute kidney injury (AKI). There is limited data to support the implementation of this AKI biomarker to guide therapeutic actions. METHODS: Sixteen AKI experts with clinical CCL14 experience participated in a Delphi-based method to reach consensus on when and how to potentially use CCL14. Consensus was defined as ≥ 80% agreement (participants answered with 'Yes', or three to four points on a five-point Likert Scale). RESULTS: Key consensus areas for CCL14 test implementation were: identifying challenges and mitigations, developing a comprehensive protocol and pairing it with a treatment plan, and defining the target population. The majority agreed that CCL14 results can help to prioritize AKI management decisions. CCL14 levels above the high cutoff (> 13 ng/mL) significantly changed the level of concern for modifying the AKI treatment plan (p < 0.001). The highest level of concern to modify the treatment plan was for discussions on renal replacement therapy (RRT) initiation for CCL14 levels > 13 ng/mL. The level of concern for discussion on RRT initiation between High and Low, and between Medium and Low CCL14 levels, showed significant differences. CONCLUSION: Real world urinary CCL14 use appears to provide improved care options to patients at risk for persistent severe AKI. Experts believe there is a role for CCL14 in AKI management and it may potentially reduce AKI-disease burden. There is, however, an urgent need for evidence on treatment decisions and adjustments based on CCL14 results.

Initial renal replacement therapy (RRT) modality associates with 90-day postdischarge RRT dependence in critically ill AKI survivors.

PURPOSE: Real-world comparison of RRT modality on RRT dependence at 90 days postdischarge among ICU patients discharged alive after RRT for acute kidney injury (AKI). METHODS: Using claims-linked to US hospital discharge data (Premier PINC AI Healthcare Database [PHD]), we compared continuous renal replacement therapy (CRRT) vs. intermittent hemodialysis (IHD) for AKI in adult ICU patients discharged alive from January 1, 2018 to June 30, 2021. RRT dependence at 90 days postdischarge was defined as ≥2 RRT treatments in the last 8 days. Between-group differences were balanced using inverse probability treatment weighting (IPTW). RESULTS: Of 34,804 patients, 3804 patients (from 382 hospitals) had claims coverage for days 83-90 postdischarge. Compared to IHD-treated patients (n = 2740), CRRT-treated patients (n = 1064) were younger; had more admission to large teaching hospitals, surgery, sepsis, shock, mechanical ventilation, but lower prevalence of comorbidities (p < 0.05 for all). Compared to IHD-treated patients, CRRT-treated patients had lower RRT dependence at hospital discharge (26.5% vs. 29.8%, p = 0.04) and lower RRT dependence at 90 days postdischarge (4.9% vs. 7.4% p = 0.006) with weighted adjusted OR (95% CI): 0.68 (0.47-0.97), p = 0.03. Results persisted in sensitivity analyses including patients who died during days 1-90 postdischarge (n = 112) or excluding patients from hospitals with IHD patients only (n = 335), or when excluding patients who switched RRT modalities (n = 451). CONCLUSIONS: Adjusted for potential confounders, the odds of RRT dependence at 90 days postdischarge among survivors of RRT for AKI was 30% lower for those treated first with CRRT vs. IHD, overall and in several sensitivity analyses. SUMMARY: Critically ill patients in intensive care units (ICU) may develop acute kidney injury (AKI) that requires renal replacement therapy (RRT) to temporarily replace the injured kidney function of cleaning the blood. Two main types of RRT in the ICU are called continuous renal replacement therapy (CRRT), which is performed almost continuously, i.e., for >18 h per day, and intermittent hemodialysis (IHD), which is a more rapid RRT that is usually completed in a little bit over 6 h, several times per week. The slower CRRT may be gentler on the kidneys and is more likely to be used in the sickest patients, who may not be able to tolerate IHD. We conducted a data-analysis study to evaluate whether long-term effects on kidney function (assessed by ongoing need for RRT, i.e., RRT dependence) differ depending on use of CRRT vs. IHD. In a very large US linked hospital-discharge/claims database we found that among ICU patients discharge alive after RRT for AKI, fewer CRRT-treated patients had RRT dependence at hospital discharge (26.5% vs. 29.8%, p = 0.04) and at 90 days after discharge (4.9% vs. 7.4% p = 0.006). In adjusted models, RRT dependence at 90 days postdischarge was >30% lower for CRRT than IHD-treated patients. These results from a non-randomized study suggest that among survivors of RRT for AKI, CRRT may result in less RRT dependence 90 days after hospital discharge.

Exploring the Cost-Utility of a Biomarker Predicting Persistent Severe Acute Kidney Injury: The Case of C-C Motif Chemokine Ligand 14 (CCL14).

Background: Approximately 24% of hospitalized stage 2-3 acute kidney injury (AKI) patients will develop persistent severe AKI (PS-AKI), defined as KDIGO stage 3 AKI lasting ≥3 days or with death in ≤3 days or stage 2 or 3 AKI with dialysis in ≤3 days, leading to worse outcomes and higher costs. There is currently no consensus on an intervention that effectively reverts the course of AKI and prevents PS-AKI in the population with stage 2-3 AKI. This study explores the cost-utility of biomarkers predicting PS-AKI, under the assumption that such intervention exists by comparing C-C motif chemokine ligand 14 (CCL14) to hospital standard of care (SOC) alone. Methods: The analysis combined a 90-day decision tree using CCL14 operating characteristics to predict PS-AKI and clinical outcomes in 66-year-old patients, and a Markov cohort estimating lifetime costs and quality-adjusted life years (QALYs). Cost and QALYs from admission, 30-day readmission, intensive care, dialysis, and death were compared. Clinical and cost inputs were informed by a large retrospective cohort of US hospitals in the PINC AI Healthcare Database. Inputs and assumptions were challenged in deterministic and probabilistic sensitivity analyses. Two-way analyses were used to explore the efficacy and costs of an intervention preventing PS-AKI. Results: Depending on selected costs and early intervention efficacy, CCL14-directed care led to lower costs and more QALYs (dominating) or was cost-effective at the $50,000/QALY threshold. Assuming the intervention would avoid 10% of PS-AKI complications in AKI stage 2-3 patients identified as true positive resulted in 0.066 additional QALYs and $486 reduced costs. Results were robust to substantial parameter variation. Conclusion: The analysis suggests that in the presence of an efficacious intervention preventing PS-AKI, identifying people at risk using CCL14 in addition to SOC is likely to represent a cost-effective use of resources.

Predictions of Serum Phosphate Concentration during Continuous Renal Replacement Therapy Using a Steady-State Mass Balance Model.

INTRODUCTION: Hypophosphatemia is common during continuous renal replacement therapy (CRRT), but serum phosphate levels can potentially be maintained during treatment by either intravenous phosphate supplementation or addition of phosphate to renal replacement therapy (RRT) solutions. METHODS: We developed a steady-state phosphate mass balance model to assess the effects of CRRT dose on serum phosphate concentration when using both phosphate-free and phosphate-containing RRT solutions, with emphasis on low CRRT doses. RESULTS: The model predicted that measurements of serum phosphate concentration prior to (initial) and during CRRT (final) together with clinical data on CRRT dose, treatment duration, and phosphate supplementation can determine model patient parameters, that is, both the initial generation rate and clearance of phosphate prior to CRRT. Model parameters were then calculated from average patient data reported in several previous publications with a standard or high CRRT dose. Using representative model parameters for typical patients, predictions were then made of the effect of low CRRT dose on the change in serum phosphate levels after implementation of CRRT. The model predicted that CRRT at a low dose using phosphate-free RRT solutions will limit, but not eliminate, the incidence of hypophosphatemia. Further, the model predicted that CRRT at a low dose will have virtually no influence on the incidence of hyperphosphatemia when using phosphate-containing RRT solutions. CONCLUSIONS: This report identifies the clinical measurements to be used with the proposed model for individualizing the CRRT dose and RRT phosphate concentration to maintain serum phosphate concentrations in a desired range.

Experimental hemodialysis in diet-induced ketosis and the potential use of dialysis as an adjuvant cancer treatment.

Numerous in vivo studies on the ketogenic diet, a diet that can induce metabolic conditions resembling those following extended starvation, demonstrate strong outcomes on cancer survival, particularly when combined with chemo-, radio- or immunological treatments. However, the therapeutic application of ketogenic diets requires strict dietary adherence from well-informed and motivated patients, and it has recently been proposed that hemodialysis might be utilized to boost ketosis and further destabilize the environment for cancer cells. Yet, plasma ketones may be lost in the dialysate-lowering blood ketone levels. Here we performed a single 180-min experimental hemodialysis (HD) session in six anesthetized Sprague-Dawley rats given ketogenic diet for five days. Median blood ketone levels pre-dialysis were 3.5 mmol/L (IQR 2.2 to 5.6) and 3.8 mmol/L (IQR 2.2 to 5.1) after 180 min HD, p = 0.54 (95% CI - 0.6 to 1.2). Plasma glucose levels were reduced by 36% (- 4.5 mmol/L), p < 0.05 (95% CI - 6.7 to - 2.5). Standard base excess was increased from - 3.5 mmol/L (IQR - 4 to - 2) to 0.5 mmol/L (IQR - 1 to 3), p < 0.01 (95% CI 2.0 to 5.0). A theoretical model was applied confirming that intra-dialytic glucose levels decrease, and ketone levels slightly increase since hepatic ketone production far exceeds dialytic removal. Our experimental data and in-silico modeling indicate that elevated blood ketone levels during ketosis are maintained during hemodialysis despite dialytic removal.

Economic Analysis of Renal Replacement Therapy Modality in Acute Kidney Injury Patients With Fluid Overload.

Acute kidney injury (AKI) and fluid overload (FO) are among the top reasons to initiate intermittent hemodialysis (IHD) or continuous renal replacement therapy (CRRT). Prior research suggests CRRT provides more precise volume control, but whether CRRT is cost-effective remains unclear. We assessed the cost-effectiveness of CRRT for volume control compared with IHD from a U.S. healthcare payer perspective. DESIGN: Decision analytical model comparing health outcomes and healthcare costs of CRRT versus IHD initiation for AKI patients with FO. The model had an inpatient phase (over 90-d) followed by post-discharge phase (over lifetime). The 90-day phase had three health states: FO, fluid control, and death. After 90 days, surviving patients entered the lifetime phase with four health states: dialysis independent (DI), dialysis dependent (DD), renal transplantation, and death. Model parameters were informed by current literature. Sensitivity analyses were performed to evaluate results robustness to parametric uncertainty. SETTING: ICU. PATIENTS OR SUBJECTS: AKI patients with FO. INTERVENTIONS: IHD or CRRT. MEASUREMENTS AND MAIN RESULTS: The 90-day horizon revealed better outcomes for patients initiated on CRRT (survival: CRRT 59.2% vs IHD 57.5% and DD rate among survivors: CRRT 5.5% vs IHD 6.9%). Healthcare cost was 2.7% (+$2,836) higher for CRRT. Over lifetime, initial CRRT was associated with +0.313 life years (LYs) and +0.187 quality-adjusted life years (QALYs) compared with initial IHD. Even though important savings were observed for initial CRRT with a lower rate of DD among survivors (-$13,437), it did not fully offset the incremental cost of CRRT (+$1,956) and DI survival (+$12,830). The incremental cost-per-QALY gained with CRRT over IRRT was +$10,429/QALY. Results were robust to sensitivity analyses. CONCLUSIONS: Our analysis provides an economic rationale for CRRT as the initial modality of choice in AKI patients with FO who require renal replacement therapy. Our finding needs to be confirmed in future research.

Early versus delayed initiation of renal replacement therapy in cardiac-surgery associated acute kidney injury: an economic perspective.

BACKGROUND: Timing for renal replacement therapy (RRT) initiation for cardiac-surgery associated acute kidney surgery (CSA-AKI) is subject to debate. Evidence suggests earlier initiation leads to shorter length of stay (LoS). We investigated differences in healthcare costs associated with timing of RRT initiation in CSA-AKI. METHODS: A cost-consequences model compared costs of Early (<24 h) vs. Delayed (>24 h) RRT initiation. Data were from the ELAIN trial in Germany, and the HiDenIC database, a US multi-hospital database. Resource utilization was determined by RRT duration, ICU, and hospital LoS. All resources were costed from a US healthcare perspective. Extensive sensitivity analyses (SA) were conducted, notably regarding the proportion of patients not initiated on RRT with the Delayed strategy. RESULTS: Early RRT initiation exhibited cost savings compared to Delayed RRT initiation. With ELAIN data, savings reached -$122,188 (ranging from -$157,707 to -$74,763 in the SA). Findings were confirmed with HiDenIC data; Early RRT initiation showed savings of -$77,303 (ranging from -$108,971 to -$47,012 in the SA). CONCLUSIONS: Our costing model indicates that Early RRT initiation for CSA-AKI may result in appreciable cost savings. Delaying RRT, in the setting of CSA-AKI, may lead to longer LoS and increased healthcare costs.

Cost-effectiveness of the TherMax blood warmer during continuous renal replacement therapy.

Hypothermia is a common adverse event during continuous renal replacement therapy (CRRT), affecting multiple organ systems and increasing risk of poor health outcomes among patients with acute kidney injury (AKI) undergoing CRRT. TheraMax blood warmers are the next generation of extracorporeal blood warmers which reduce risk of hypothermia during CRRT. The purpose of this study is to elucidate the potential health economic impacts of avoiding CRRT-induced hypothermia by using the novel TherMax blood warming device. This study compares health care costs associated with use of the new TherMax blood warmer unit integrated with the PrisMax system compared to CRRT with a standalone blood warming device to avoid hypothermia in continuous renal replacement therapy (CRRT). An economic model was developed in which relevant health states for each intervention were normothermia, hypothermia, discharge, and death. Clinical inputs and costs were obtained from a combination of retrospective chart review and publicly available summary estimates. The proportion of AKI patients treated with CRRT who became hypothermic (<36°C) during CRRT treatment was 34.5% in the TherMax group compared to 71.9% in the 'standalone warmer' group. Given the 78.7-year average life expectancy in the US and the assumed average patient age at discharge/death of 65.4 years, the total life-years gained by avoiding mortality related to hypothermia was 9.0 in the TherMax group compared to 8.0 in the 'standalone warmer' group. Cost per life-year gained was $8,615 in the TherMax group versus $10,115 in the 'standalone warmer' group for a difference of -$1,501 favoring TherMax. The incremental cost-effectiveness ratio was negative, indicating superior cost-effectiveness for TherMax versus 'standalone warmer'. The TherMax blood warming device used with the PrisMax system is associated with lower risk of hypothermia, which our model indicates leads to lower costs, lower risk of mortality due to hypothermia, and superior cost-effectiveness.

Modeling acid-base balance during continuous kidney replacement therapy.

Clinical studies have suggested that use of bicarbonate-containing substitution and dialysis fluids during continuous kidney replacement therapy may result in excessive increases in the carbon dioxide concentration of blood; however, the technical parameters governing such changes are unclear. The current work used a mathematical model of acid-base chemistry of blood to predict its composition within and exiting the extracorporeal circuit during continuous veno-venous hemofiltration (CVVH) and continuous veno-venous hemodiafiltration (CVVHDF). Model predictions showed that a total substitution fluid infusion rate of 2 L/h (33% predilution) with a bicarbonate concentration of 32 mEq/L during CVVH at a blood flow rate of 200 mL/min resulted in only modest increases in plasma bicarbonate concentration by 2.0 mEq/L and partial pressure of dissolved carbon dioxide by 4.4 mmHg in blood exiting the extracorporeal circuit. The relative increase in bicarbonate concentration (9.7%) was similar to that in partial pressure of dissolved carbon dioxide (8.2%), resulting in no significant change in plasma pH in the blood exiting the CVVH circuit. The changes in plasma acid-base levels were larger with a higher infusion rate of substitution fluid but smaller with a higher blood flow rate or use of substitution fluid with a lower bicarbonate concentration (22 mEq/L). Under comparable flow conditions and substitution fluid composition, model predicted changes in acid-base levels during CVVHDF were similar, but smaller, than those during CVVH. The described mathematical model can predict the effect of operating conditions on acid-base balance within and exiting the extracorporeal circuit during continuous kidney replacement therapy.

Targeting arterial partial pressure of carbon dioxide in acute respiratory distress syndrome patients using extracorporeal carbon dioxide removal.

BACKGROUND: A retrospective analysis of SUPERNOVA trial data showed that reductions in tidal volume to ultraprotective levels without significant increases in arterial partial pressure of carbon dioxide (PaCO2 ) for critically ill, mechanically ventilated patients with acute respiratory distress syndrome (ARDS) depends on the rate of extracorporeal carbon dioxide removal (ECCO2 R). METHODS: We used a whole-body mathematical model of acid-base balance to quantify the effect of altering carbon dioxide (CO2 ) removal rates using different ECCO2 R devices to achieve target PaCO2 levels in ARDS patients. Specifically, we predicted the effect of using a new, larger surface area PrismaLung+ device instead of the original PrismaLung device on the results from two multicenter clinical studies in critically ill, mechanically ventilated ARDS patients. RESULTS: After calibrating model parameters to the clinical study data using the PrismaLung device, model predictions determined optimal extracorporeal blood flow rates for the PrismaLung+ and mechanical ventilation frequencies to obtain target PaCO2 levels of 45 and 50 mm Hg in mild and moderate ARDS patients treated at a tidal volume of 3.98 ml/kg predicted body weight (PW). Comparable model predictions showed that reductions in tidal volumes below 6 ml/kg PBW may be difficult for acidotic highly severe ARDS patients with acute kidney injury and high CO2 production rates using a PrismaLung+ device in-series with a continuous venovenous hemofiltration device. CONCLUSIONS: The described model provides guidance on achieving target PaCO2 levels in mechanically ventilated ARDS patients using protective and ultraprotective tidal volumes when increasing CO2 removal rates from ECCO2 R devices.

Modeling acid-base balance for in-series extracorporeal carbon dioxide removal and continuous venovenous hemofiltration devices.

Patients with acute respiratory distress syndrome and acute kidney injury (AKI) treated by kidney replacement therapy may also require treatment with extracorporeal carbon dioxide removal (ECCO2 R) devices to permit protective or ultraprotective mechanical ventilation. We developed a mathematical model of acid-base balance during extracorporeal therapy using ECCO2 R and continuous venovenous hemofiltration (CVVH) devices applied in series for the treatment of mechanically ventilated AKI patients. Published data from clinical studies of mechanically ventilated AKI patients treated by CVVH at known infusion rates of substitution fluid without ECCO2 R were used to adjust the model parameters to fit plasma levels of arterial partial pressure of carbon dioxide (PaCO2 ), arterial plasma bicarbonate concentration ([HCO3 ]), and plasma pH (as well as certain other unmeasured physiological variables). The effects of applying ECCO2 R at an unchanged and a reduced tidal volume on PaCO2 , [HCO3 ] and plasma pH were then simulated assuming carbon dioxide removal rates from the ECCO2 R device measured in the clinical studies. Agreement of such model predictions with clinical data was good whether the ECCO2 R device was positioned proximal or distal to the CVVH device in the extracorporeal circuit. Although carbon dioxide removal rates from the ECCO2 R device measured in one previous clinical study were higher when it was placed proximal to the CVVH device, suggesting that such in-series positioning was optimal, the current mathematical model demonstrates that proximal positioning of the ECCO2 R device also results in lower bicarbonate (and, therefore, total carbon dioxide) removal from the distal CVVH device. Thus, the removal of total carbon dioxide by such extracorporeal circuits is relatively independent of the position of the in-series devices. It is concluded that the described mathematical model has quantitative accuracy; these results suggest that the overall acid-base balance when using ECCO2 R and CVVH devices in a single extracorporeal circuit will be similar, independent of their in-series position.

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.