Visualizing in deceased COVID-19 patients how SARS-CoV-2 attacks the respiratory and olfactory mucosae but spares the olfactory bulb.

Anosmia, the loss of smell, is a common and often the sole symptom of COVID-19. The onset of the sequence of pathobiological events leading to olfactory dysfunction remains obscure. Here, we have developed a postmortem bedside surgical procedure to harvest endoscopically samples of respiratory and olfactory mucosae and whole olfactory bulbs. Our cohort of 85 cases included COVID-19 patients who died a few days after infection with SARS-CoV-2, enabling us to catch the virus while it was still replicating. We found that sustentacular cells are the major target cell type in the olfactory mucosa. We failed to find evidence for infection of olfactory sensory neurons, and the parenchyma of the olfactory bulb is spared as well. Thus, SARS-CoV-2 does not appear to be a neurotropic virus. We postulate that transient insufficient support from sustentacular cells triggers transient olfactory dysfunction in COVID-19. Olfactory sensory neurons would become affected without getting infected.

In Vitro Model of Prepacked Carbon Dioxide Absorber Use: Development and Testing.

BACKGROUND: Carbon dioxide absorbers allow the use of fresh gas flow below minute ventilation (V˙E). Models are developed and tested in vitro to quantify their performance with variable carbon dioxide load (V˙CO2), fresh gas flow, V˙E, end-tidal carbon dioxide (ETco2) fraction, and the type of workstation used. METHODS: First principles are used to derive a linear relationship between fresh gas flow and fractional canister usage or FCU0.5 (the reciprocal of the time for the inspiratory carbon dioxide fraction to reach 0.5%). This forms the basis for two basic models in which V˙E was measured by spirometry or calculated. These models were extended by multiplying V˙E with an empirical workstation factor. To validate the four models, two hypotheses were tested. To test whether the FCU0.5 intercept varied proportionally with V˙CO2 and was independent of V˙E, FCU was measured for 10 canisters tested with a fixed 0.3 l/min fresh gas flow and a range of V˙CO2 while V˙E was either constant or adjusted to maintain ETco2 fraction. A t test was used to compare the two groups. To confirm whether a change in V˙CO2 accompanied by a change in V˙E to maintain ETco2 fraction would shift the linear fresh gas flow-FCU0.5 relationship in a parallel manner, 19 canisters were tested with different combinations of V˙CO2 and fresh gas flow. These measured FCU values were compared to those predicted by the four models using Varvel's performance criteria. RESULTS: With 0.3 l/min fresh gas flow, FCU0.5 was proportional with V˙CO2 and independent of whether V˙E was adjusted to maintain ETco2 fraction or not (P = 0.962). The hypothesized parallel shift of the fresh gas flow-FCU0.5 relationship was confirmed. Both extended models are good candidate models. CONCLUSIONS: The models predict prepacked canister performance in vitro over the range of V˙E, fresh gas flow, and V˙CO2 likely to be encountered in routine clinical practice. In vivo validation is still needed.

Design of a flow modulation device to facilitate individualized ventilation in a shared ventilator setup.

This study aims to resolve the unmet need for ventilator surge capacity by developing a prototype device that can alter patient-specific flow in a shared ventilator setup. The device is designed to deliver a predictable tidal volume (VT), requiring minimal additional monitoring and workload. The prototyped device was tested in an in vitro bench setup for its performance against the intended use and design criteria. The ventilation parameters: VT and airway pressures, and ventilation profiles: pressure, flow and volume were measured for different ventilator and device settings for a healthy and ARDS simulated lung pathology. We obtained VTs with a linear correlation with valve openings from 10 to 100% across set inspiratory pressures (IPs) of 20 to 30 cmH2O. Airway pressure varied with valve opening and lung elastance but did not exceed set IPs. Performance was consistent in both healthy and ARDS-simulated lung conditions. The ventilation profile diverged from traditional pressure-controlled profiles. We present the design a flow modulator to titrate VTs in a shared ventilator setup. Application of the flow modulator resulted in a characteristic flow profile that differs from pressure- or volume controlled ventilation. The development of the flow modulator enables further validation of the Individualized Shared Ventilation (ISV) technology with individualization of delivered VTs and the development of a clinical protocol facilitating its clinical use during a ventilator surge capacity problem.

The hemodynamic interplay between pulmonary ischemia-reperfusion injury and right ventricular function in lung transplantation: a translational porcine model.

Lung transplantation (LTx) is a challenging procedure. Following the process of ischemia-reperfusion injury, the transplanted pulmonary graft might become severely damaged, resulting in primary graft dysfunction. In addition, during the intraoperative window, the right ventricle (RV) is at risk of acute failure. The interaction of right ventricular function with lung injury is, however, poorly understood. We aimed to address this interaction in a translational porcine model of pulmonary ischemia-reperfusion injury. Advanced pulmonary and hemodynamic assessment was used, including right ventricular pressure-volume loop analysis. The acute model was based on clamping and unclamping of the left lung hilus, respecting the different hemodynamic phases of a clinical lung transplantation. We found that forcing entire right ventricular cardiac output through a lung suffering from ischemia-reperfusion injury increased afterload (pulmonary vascular resistance from baseline to end experiment P < 0.0001) and induced right ventricular failure (RVF) in 5/9 animals. Notably, we identified different compensation patterns in failing versus nonfailing ventricles (arterial elastance P = 0.0008; stroke volume P < 0.0001). Furthermore, increased vascular pressure and flow produced by the right ventricle resulted in higher pulmonary injury, as measured by ex vivo CT density (correlation: pressure r = 0.8; flow r = 0.85). Finally, RV ischemia as measured by troponin-T was negatively correlated with pulmonary injury (r = -0.76); however, troponin-T values did not determine RVF in all animals. In conclusion, we demonstrate a delicate balance between development of pulmonary ischemia-reperfusion injury and right ventricular function during lung transplantation. Furthermore, we provide a physiological basis for potential benefit of extracorporeal life support technology.NEW & NOTEWORTHY In contrast to the abundant literature of mechanical pulmonary artery clamping to increase right ventricular afterload, we developed a model adding a biological factor of pulmonary ischemia-reperfusion injury. We did not only focus on the right ventricular behavior, but also on the interaction with the injured lung. We are the first to describe this interaction while addressing the hemodynamic intraoperative phases of clinical lung transplantation.

Endovascular transatrial stenting of pulmonary vein stenosis after lung transplantation.

Pulmonary vein stenosis (PVS) and pulmonary vein occlusion (PVO) represent rare complications after lung transplantation (LTx), with limited therapeutic options and a high risk of graft loss. We present 2 cases of successful endovascular transatrial stenting following double LTx. A 60-year-old woman with chronic obstructive pulmonary disease who underwent double lobar LTx was diagnosed at postoperative day 72 with a high-grade PVS on the left side. A 22-year-old woman with idiopathic pulmonary arterial hypertension who underwent double LTx was diagnosed 9 days later with PVO of the left upper lobe vein. To avoid surgical reintervention, endovascular transatrial dilatation and stenting were performed successfully in both cases. Transatrial endovascular stenting of PVS or PVO after LTx seems an effective and safe treatment option that should be considered for these life-threatening complications and executed with care.

Lung Transplant Outcome From Selected Older Donors (≥70 Years) Equals Younger Donors (<70 Years): A Propensity-matched Analysis.

OBJECTIVE: To describe our experience with lung transplantation (LTx) from donors ≥70 years and compare short and long-term outcomes to a propensity-matched cohort of donors <70 years. BACKGROUND: Although extended-criteria donors have been widely used to enlarge the donor pool, the experience with LTx from older donors (≥70 years) remains limited. METHODS: All single-center bilateral LTx between 2010 and 2020 were retrospectively analyzed. Matching (1:1) was performed for the donor (type, sex, smoking history, x-ray abnormalities, partial pressure of oxygen/fraction of inspired oxygen ratio, and time on ventilator) and recipient characteristics (age, sex, LTx indication, perioperative extracorporeal life support, and cytomegalovirus mismatch). Primary graft dysfunction grade-3, 5-year patient, and chronic lung allograft dysfunction-free survival were analyzed. RESULTS: Out of 647 bilateral LTx, 69 were performed from donors ≥70 years. The mean age in the older donor cohort was 74 years (range: 70-84 years) versus 49 years (range: 12-69 years) in the matched younger group. No significant differences were observed in the length of ventilatory support, intensive care unit, or hospital stay. Primary graft dysfunction-3 was 26% in the older group versus 29% in younger donor recipients ( P = 0.85). Reintervention rate was comparable (29% vs 16%; P = 0.10). Follow-up bronchoscopy revealed no difference in bronchial anastomotic complications ( P = 1.00). Five-year patient and chronic lung allograft dysfunction-free survivals were 73.6% versus 73.1% ( P = 0.72) and 51.5% versus 59.2% ( P = 0.41), respectively. CONCLUSIONS: LTx from selected donors ≥70 years is feasible and safe, yielding comparable short and long-term outcomes in a propensity-matched analysis with younger donors (<70 years).

Radiologic and Histologic Correlates of Early Interstitial Lung Changes in Explanted Lungs.

Background Interstitial lung abnormalities (ILAs) reflect imaging features on lung CT scans that are compatible with (early) interstitial lung disease. Despite accumulating evidence regarding the incidence, risk factors, and prognosis of ILAs, the histopathologic correlates of ILAs remain elusive. Purpose To determine the correlation between radiologic and histopathologic findings in CT-defined ILAs in human lung explants. Materials and Methods Explanted lungs or lobes from participants with radiologically documented ILAs were prospectively collected from 2010 to 2021. These specimens were air-inflated, frozen, and scanned with CT and micro-CT (spatial resolution of 0.7 mm and 90 µm, respectively). Subsequently, the lungs were cut and sampled with core biopsies. At least five samples per lung underwent micro-CT and subsequent histopathologic assessment with semiquantitative remodeling scorings. Based on area-specific radiologic scoring, the association between radiologic and histopathologic findings was assessed. Results Eight lung explants from six donors (median age at explantation, 71 years [range, 60-83 years]; four men) were included (unused donor lungs, n = 4; pre-emptive lobectomy for oncologic indications, n = 2). Ex vivo CT demonstrated ground-glass opacification, reticulation, and bronchiectasis. Micro-CT and histopathologic examination demonstrated that lung abnormalities were frequently paraseptal and associated with fibrosis and lymphocytic inflammation. The histopathologic results showed varying degrees of fibrosis in areas that appeared normal on CT scans. Regions of reticulation on CT scans generally had greater fibrosis at histopathologic analysis. Vasculopathy and bronchiectasis were also often present at histopathologic examination of lungs with ILAs. Fully developed fibroblastic foci were rarely observed. Conclusion This study demonstrated direct histologic correlates of CT-defined interstitial lung abnormalities. © RSNA, 2022 Supplemental material is available for this article. See also the editorial by Jeudy in this issue.

Aspergillus-Specific IgG Antibodies are Associated With Fungal-Related Complications and Chronic Lung Allograft Dysfunction After Lung Transplantation.

Fungal exposure and sensitization negatively affect outcomes in various respiratory diseases, however, the effect of fungal sensitization in lung transplant (LTx) recipients is still unknown. We performed a retrospective cohort study of prospectively collected data on circulating fungal specific IgG/IgE antibodies, and their correlation with fungal isolation, chronic lung allograft dysfunction (CLAD) and overall survival after LTx. 311 patients transplanted between 2014 and 2019 were included. Patients with elevated Aspergillus fumigatus or Aspergillus flavus IgG (10%) had more mold and Aspergillus species isolation (p = 0.0068 and p = 0.0047). Aspergillus fumigatus IgG was specifically associated with Aspergillus fumigatus isolation in the previous or consecutive year (AUC 0.60, p = 0.004 and AUC 0.63, p = 0.022, respectively). Elevated Aspergillus fumigatus or Aspergillus flavus IgG was associated with CLAD (p = 0.0355), but not with death. Aspergillus fumigatus, Aspergillus flavus or Aspergillus niger IgE was elevated in 19.3% of patients, but not associated with fungal isolation, CLAD or death. Mold isolation and Aspergillus species isolation from respiratory cultures were associated with CLAD occurrence (p = 0.0011 and p = 0.0005, respectively), and Aspergillus species isolation was also associated with impaired survival (p = 0.0424). Fungus-specific IgG could be useful in long-term follow-up post-LTx, as a non-invasive marker for fungal exposure, and thus a diagnostic tool for identifying patients at risk for fungal-related complications and CLAD.

Arterial to end-tidal CO2 gradients during isocapnic hyperventilation.

Isocapnic hyperventilation (ICHV) is occasionally used to maintain the end-expired CO2 partial pressure (PETCO2) when the inspired CO2 (PICO2) rises. Whether maintaining PETCO2 with ICHV during an increase of the PICO2 also maintains arterial PCO2 (PaCO2) remains poorly documented. 12 ASA PS I-II subjects undergoing a robot-assisted radical prostatectomy (RARP) (n = 11) or cystectomy (n = 1) under general endotracheal anesthesia with sevoflurane in O2/air (40% inspired O2) were enrolled. PICO2 was sequentially increased from 0 to 0.5, 1.0, 1.5 and 2% by adding CO2 to the inspiratory limb of the circle system, while increasing ventilation to a target PETCO2 of 4.7-4.9% by adjusting respiratory rate during controlled mechanical ventilation. Pa-ETCO2 gradients were determined after a 15 min equilibration period at each PICO2 level and compared using ANOVA. Mean (standard deviation) age, height, and weight were 66 (6) years, 171 (6) cm, and 75 (8) kg, respectively. Capnograms were normal and hemodynamic parameters remained stable. PETCO2 could be maintained within 4.7-4.9% in all subjects at all times except in 1 subject with 1.5% PICO2 and 5 subjects with 2.0% PICO2; data from the one subject in whom both 1.5 and 2.0% PICO2 resulted in PETCO2 > 5.1% were excluded from analysis. Pa-ETCO2 gradients did not change when PICO2 increased. The effect of a modest rise of PICO2 up to 1.5% on PETCO2 during RARP can be readily overcome by increasing ventilation without altering the Pa-ETCO2 gradients. At higher PICO2, airway pressures may become a limiting factor, which requires further study.

Lung transplantation for acute respiratory distress syndrome: A multicenter experience.

Acute respiratory distress syndrome (ARDS) is a rapidly progressive lung disease with a high mortality rate. Although lung transplantation (LTx) is a well-established treatment for a variety of chronic pulmonary diseases, LTx for acute lung failure (due to ARDS) remains controversial. We reviewed posttransplant outcome of ARDS patients from three high-volume European transplant centers. Demographics and clinical data were collected and analyzed. Viral infection was the main reason for ARDS (n = 7/13, 53.8%). All patients were admitted to ICU and required mechanical ventilation, 11/13 were supported with ECMO at the time of listing. They were granted a median LAS of 76 (IQR 50-85) and waited for a median of 3 days (IQR 1.5-14). Postoperatively, median length of mechanical ventilation was 33 days (IQR 17-52.5), median length of ICU and hospital stay were 39 days (IQR 19.5-58.5) and 54 days (IQR 43.5-127). Prolongation of peripheral postoperative ECMO was required in 7/13 (53.8%) patients with a median duration of 2 days (IQR 2-7). 30-day mortality was 7.7%, 1 and 5-year survival rates were calculated as 71.6% and 54.2%, respectively. Given the lack of alternative treatment options, the herein presented results support the concept of offering live-saving LTx to carefully selected ARDS patients.

Practice and challenges for organ donation after medical assistance in dying: A scoping review including the results of the first international roundtable in 2021.

The procedure combining medical assistance in dying (MAiD) with donations after circulatory determination of death (DCDD) is known as organ donation after euthanasia (ODE). The first international roundtable on ODE was held during the 2021 WONCA family medicine conference as part of a scoping review. It aimed to document practice and related issues to advise patients, professionals, and policymakers, aiding the development of responsible guidelines and helping to navigate the issues. This was achieved through literature searches and national and international stakeholder meetings. Up to 2021, ODE was performed 286 times in Canada, the Netherlands, Spain, and Belgium, including eight cases of ODE from home (ODEH). MAiD was provided 17,217 times (2020) in the eight countries where ODE is permitted. As of 2021, 837 patients (up to 14% of recipients of DCDD donors) had received organs from ODE. ODE raises some important ethical concerns involving patient autonomy, the link between the request for MAiD and the request to donate organs and the increased burden placed on seriously ill MAiD patients.

Impact of anastomosis time during lung transplantation on primary graft dysfunction.

Primary graft dysfunction (PGD) is a major obstacle after lung transplantation (LTx), associated with increased early morbidity and mortality. Studies in liver and kidney transplantation revealed prolonged anastomosis time (AT) as an independent risk factor for impaired short- and long-term outcomes. We investigated if AT during LTx is a risk factor for PGD. In this retrospective single-center cohort study, we included all first double lung transplantations between 2008 and 2016. The association of AT with any PGD grade 3 (PGD3) within the first 72 h post-transplant was analyzed by univariable and multivariable logistic regression analysis. Data on AT and PGD was available for 427 patients of which 130 (30.2%) developed PGD3. AT was independently associated with the development of any PGD3 ≤72 h in uni- (odds ratio [OR] per 10 min 1.293, 95% confidence interval [CI 1.136-1.471], p < .0001) and multivariable (OR 1.205, 95% CI [1.022-1.421], p = .03) logistic regression analysis. There was no evidence that the relation between AT and PGD3 differed between lung recipients from donation after brain death versus donation after circulatory death donors. This study identified AT as an independent risk factor for the development of PGD3 post-LTx. We suggest that the implantation time should be kept short and the lung cooled to decrease PGD-related morbidity and mortality post-LTx.

The role of transesophageal echocardiography in guiding heart donation after circulatory death.

Heart donation after circulatory death (DCD) can significantly expand the heart donor pool, helping to overcome the problem of organ shortage and the increase in waiting list mortality and morbidity. To improve the outcome of DCD heart transplantation, thoraco-abdominal normothermic regional perfusion (TA-NRP) can be performed by selectively restoring circulation followed by in vivo functional heart assessment. Here, we report on the use of periprocedural transoesophageal echocardiography (TOE) as a minimally invasive cardiac assessment tool during different stages of a DCD heart procurement procedure using TA-NRP. We conclude that TOE is a valuable method to assess the donor heart for transplantation eligibility before and after withdrawal of life-sustaining therapy and during subsequent TA-NRP.

ESOT Consensus Platform for Organ Transplantation: Setting the Stage for a Rigorous, Regularly Updated Development Process.

The European Society for Organ Transplantation (ESOT) has created a platform for the development of rigorous and regularly updated evidence based guidelines for clinical practice in the transplantation field. A dedicated Guideline Taskforce, including ESOT-council members, a representative from the Centre for Evidence in Transplantation, editors of the journal Transplant International has developed transparent procedures to guide the development of guidelines, recommendations, and consensus statements. During ESOT's first Consensus Conference in November 2022, leading experts will present in-depth evidence based reviews of nine themes and will propose recommendations aimed at reaching a consensus after public discussion and assessment by an independent jury. All recommendations and consensus statements produced for the nine selected topics will be published including the entire evidence-based consensus-finding process. An extensive literature review of each topic was conducted to provide final evidence and/or expert opinion.

Oxygenated machine perfusion at room temperature as an alternative for static cold storage in porcine donor hearts.

BACKGROUND: There is a continued interest in ex situ heart perfusion as an alternative strategy for donor heart preservation. We hypothesize that oxygenated machine perfusion of donor hearts at a temperature that avoids both normothermia and deep hypothermia offers adequate and safe preservation. METHODS: Cardioplegia-arrested porcine donor hearts were randomly assigned to six hours of preservation using cold storage (CS, n = 5) or machine perfusion using an oxygenated acellular perfusate at 21°C (MP, n = 5). Subsequently, all grafts were evaluated using the Langendorff method for 120 min. Metabolic parameters and histology were analyzed. Systolic function was assessed by contractility and elastance. Diastolic function was assessed by lusitropy and stiffness. RESULTS: For both groups, in vivo baseline and post-Langendorff biopsies were comparable, as were lactate difference and myocardial oxygen consumption. Injury markers gradually increased and were comparable. Significant weight gain was seen in MP (p = 0.008). Diastolic function was not impaired in MP, and lusitropy was superior from 30 min up to 90 min of reperfusion. Contractility was superior in MP during the first hour of evaluation. CONCLUSION: We conclude that the initial functional outcome of MP-preserved hearts was transiently superior compared to CS, with no histological injury post-Langendorff. Our machine perfusion strategy could offer feasible and safe storage of hearts prior to transplantation. Future studies are warranted for further optimization.

Clinical evaluation of a cutaneous zero-heat-flux thermometer during cardiac surgery.

We evaluated the disposable non-invasive SpotOn™ thermometer relying on the zero-heat-flux technology. We tested the hypothesis that this technology may accurately estimate the core temperature. The primary objective was to compare cutaneous temperature measurements from this device with blood temperatures measured with the pulmonary artery catheter. Secondary objective was to compare measurements from the zero-heat-flux thermometer indirectly with other routinely used thermometers (nasopharyngeal, bladder, rectal). We included 40 patients electively scheduled for either off-pump coronary artery bypass surgery or pulmonary thromboendarterectomy. Temperatures were measured using zero-heat-flux (SpotOn™), pulmonary artery catheter, nasopharyngeal, rectal, and bladder thermometers. Agreement was assessed using the Bland and Altman random effects method for repeated measures data, and Lin's concordance correlation coefficient. Accuracy was estimated (defined as <0.5° difference with the gold standard), with a 95% confidence interval considering the multiple pairs of measurements per patient. 17 850 sets of temperature measurements were analyzed from 40 patients. The mean overall difference between zero-heat-flux and pulmonary artery catheter thermometer was -0.06 °C (95% limits of agreement of ± 0.89 °C). In addition, 14 968 sets of temperature measurements were analyzed from 34 patients with all thermometers in situ. Results from the zero-heat-flux thermometer showed better agreement with the pulmonary artery catheter than the other secondary core thermometers assessed. In conclusion, the SpotOn™ thermometer reliably assessed core temperature during cardiac surgery. It could be considered an alternative for other secondary thermometers in the assessment of core temperature during general anesthesia.

Memsorb™, a novel CO2 removal device part II: in vivo performance with the Zeus IE®.

Memsorb™ (DMF Medical, Halifax, Canada) is a novel device based upon membrane oxygenator technology designed to eliminate CO2 from exhaled gas when using a circle anesthesia circuit. Exhaled gases pass through semipermeable hollow fibers and sweep gas flowing through these fibers creates a diffusion gradient for CO2 removal. In vivo Memsorb™ performance was tested during target-controlled closed-circuit anesthesia (TCCCA) with desflurane in O2/air using a Zeus IE® anesthesia workstation (Dräger, Lübeck, Germany). Clinical care protocols for using this novel device were guided by in vitro performance results from a prior study (submitted simultaneously). After IRB approval, written informed consent was obtained from 10 ASA PS I-III patients undergoing robot-assisted radical prostatectomy. TCCCA targets were 39% inspired O2 concentration (FIO2) and 5.0% end-expired desflurane concentration (FETdes). Minute ventilation (MV) was adjusted to maintain 4.5-6.0% FETCO2. The O2/air (40% O2) sweep flow into the Memsorb™ was manually adjusted in an attempt to keep inspired CO2 concentration (FICO2) ≤ 0.8%. The following data were collected: FIO2, FETdes, FICO2, FETCO2, MV, fresh gas flow (FGF, O2 and air), sweep flow, and cumulative desflurane usage (Vdes). Vdes of the Zeus IE®-Memsorb™ combination was compared with historical Vdes observed in a previous study when soda lime (DrägerSorb 800 +) was used. Results are reported as median and inter-quartiles. A combination of manually adjusting sweep flow (26 [21,27] L/min) and MV sufficed to maintain FICO2 ≤ 0.8% and FETCO2 ≤ 6.0%, except in one patient in whom the target Zeus IE® FGF had to be increased to 0.7 L/min for 6 min. FIO2 and FETdes were maintained close to their targets. Zeus IE® FGF after 5 min was 0 [0,0] mL/min. Average Vdes after 50 min was higher with Memsorb™ (20.3 mL) compared to historical soda lime canister data (12.3 mL). During target-controlled closed-circuit anesthesia in patients undergoing robot-assisted radical prostatectomy, the Memsorb™ maintained FICO2 ≤ 0.8% and FETCO2 ≤ 6.0%, and FIO2 remained close to target. Modest amounts of desflurane were lost with the use of the Memsorb™. The need for adjustments of sweep flow, minute ventilation, and occasionally Zeus IE® FGF indicates that the Memsorb™ system should preferentially be integrated into an automated closed-loop system.

Memsorb™, a novel CO2 removal device part I: in vitro performance with the Zeus IE®.

Soda lime-based CO2 absorbents are safe, but not ideal for reasons of ecology, economy, and dust formation. The Memsorb™ is a novel CO2 removal device that uses cardiopulmonary bypass oxygenator technology instead: a sweep gas passes through semipermeable hollow fibers, adding or removing gas from the circle breathing system. We studied the in vitro performance of a prototype Memsorb™ used with a Zeus IE® anesthesia machine when administering sevoflurane and desflurane in O2/air mixtures. The Zeus IE® equipped with Memsorb™ ventilated a 2L breathing bag with a CO2 inflow port in its tip. CO2 kinetics were studied by using different combinations of CO2 inflow (VCO2), Memsorb™ sweep gas flow, and Zeus IE® fresh gas flow (FGF) and ventilator settings. More specifically, it was determined under what circumstances the inspired CO2 concentration (FICO2) could be kept < 0.5%. O2 kinetics were studied by measuring the inspired O2 concentration (FIO2) resulting from different combinations of Memsorb™ sweep gas flow and O2 concentrations, and Zeus IE® FGFs and O2 concentrations. Memsorb™'s sevoflurane and desflurane waste was determined by measuring their injection rates during target-controlled closed-circuit anesthesia (TCCCA), and were compared to historical controls when using a soda lime absorbent (Draegersorb 800+) under identical conditions. With 160 mL/min VCO2 and 5 L/min minute ventilation (MV), lowering the sweep gas flow at any fixed Zeus IE® FGF increased FICO2 in a non-linear manner. Sweep gas flow adjustments kept FICO2 < 0.5% over the entire Zeus IE® FGF range tested with VCO2 up to 280 mL/min; tidal volume and respiratory rate affected the required sweep gas flow. At 10 L/min MV and low FGF (< 1.5 L/min), even a maximum sweep flow of 43 L/min was unable to keep FICO2 ≤ 0.5%. When the O2 concentration in the Zeus IE® FGF and the Memsorb™ sweep gas flow differed, FIO2 drifted towards the sweep gas O2 concentration, and more so as FGF was lowered; this effect was absent once FGF > minute ventilation. During sevoflurane and desflurane TCCCA, the Zeus IE® FGF remained zero while agent usage per % end-expired agent increased with increasing end-expired target agent concentrations and with a higher target FIO2. Agent waste during target-controlled delivery was higher with Memsorb™ than with the soda lime product, with the difference remaining almost constant over the FGF range studied. With a 5 L/min MV, Memsorb™ successfully removes CO2 with inflow rates up to 240 mL/min if an FICO2 of 0.5% is accepted, but at 10 L/min MV and low FGF (< 1.5 L/min), even a maximum sweep flow of 43 L/min was unable to keep FICO2 ≤ 0.5%. To avoid FIO2 deviating substantially from the O2 concentration in the fresh gas, the O2 concentration in the fresh gas and sweep gas should match. Compared to the use of Ca(OH)2 based CO2 absorbent, inhaled agent waste is increased. The device is most likely to find its use integrated in closed loop systems.

Consensus statement on normothermic regional perfusion in donation after circulatory death: Report from the European Society for Organ Transplantation's Transplant Learning Journey.

Normothermic regional perfusion (NRP) in donation after circulatory death (DCD) is a safe alternative to in situ cooling and rapid procurement. An increasing number of countries and centres are performing NRP, a technically and logistically challenging procedure. This consensus document provides evidence-based recommendations on the use of NRP in uncontrolled and controlled DCDs. It also offers minimal ethical, logistical and technical requirements that form the foundation of a safe and effective NRP programme. The present article is based on evidence and opinions formulated by a panel of European experts of Workstream 04 of the Transplantation Learning Journey project, which is part of the European Society for Organ Transplantation.

A systematic review and meta-analyses of regional perfusion in donation after circulatory death solid organ transplantation.

In donation after circulatory death (DCD), (thoraco)abdominal regional perfusion (RP) restores circulation to a region of the body following death declaration. We systematically reviewed outcomes of solid organ transplantation after RP by searching PubMed, Embase, and Cochrane libraries. Eighty-eight articles reporting on outcomes of liver, kidney, pancreas, heart, and lung transplants or donor/organ utilization were identified. Meta-analyses were conducted when possible. Methodological quality was assessed using National Institutes of Health (NIH)-scoring tools. Case reports (13/88), case series (44/88), retrospective cohort studies (35/88), retrospective matched cohort studies (5/88), and case-control studies (2/88) were identified, with overall fair quality. As blood viscosity and rheology change below 20 °C, studies were grouped as hypothermic (HRP, ≤20 °C) or normothermic (NRP, >20 °C) regional perfusion. Data demonstrate that RP is a safe alternative to in situ cold preservation (ISP) in uncontrolled and controlled DCDs. The scarce HRP data are from before 2005. NRP appears to reduce post-transplant complications, especially biliary complications in controlled DCD livers, compared with ISP. Comparisons for kidney and pancreas with ISP are needed but there is no evidence that NRP is detrimental. Additional data on NRP in thoracic organs are needed. Whether RP increases donor or organ utilization needs further research.