Physiologic Effects of ECMO in Patients with Severe Acute Respiratory Distress Syndrome.

RATIONALE: Blood flow rate affects mixed venous oxygenation (SvO2) during venovenous extracorporeal membrane oxygenation (ECMO), with possible effects on the pulmonary circulation and the right heart function. OBJECTIVES: We aimed at describing the physiologic effects of different levels of SvO2 obtained by changing ECMO blood flow, in patients with severe ARDS receiving ECMO and controlled mechanical ventilation. METHODS: Low (SvO2 target 70-75%), intermediate (SvO2 target 75-80%) and high (SvO2 target > 80%) ECMO blood flows were applied for 30 minutes in random order in 20 patients. Mechanical ventilation settings were left unchanged. The hemodynamic and pulmonary effects were assessed with pulmonary artery catheter and electrical impedance tomography (EIT). MEASUREMENTS AND MAIN RESULTS: Cardiac output decreased from low to intermediate and to high blood flow/SvO2 (9.2 [6.2-10.9] vs 8.3 [5.9-9.8] vs 7.9 [6.5-9.1] L/min, p = 0.014), as well as mean pulmonary artery pressure (34 ± 6 vs 31 ± 6 vs 30 ± 5 mmHg, p < 0.001), and right ventricle stroke work index (14.2 ± 4.4 vs 12.2 ± 3.6 vs 11.4 ± 3.2 g*m/beat/m2, p = 0.002). Cardiac output was inversely correlated with mixed venous and arterial PO2 values (R2 = 0.257, p = 0.031 and R2 = 0.324, p = 0.05). Pulmonary artery pressure was correlated with decreasing mixed venous PO2 (R2 = 0.29, p <0.001) and with increasing cardiac output (R2 = 0.378 p < 0.007). Measures of ventilation/perfusion mismatch did not differ between the three steps. CONCLUSIONS: In severe ARDS patients, increased ECMO blood flow rate resulting in higher SvO2 decreases pulmonary artery pressure, cardiac output, and right heart workload. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Anticoagulation and Bleeding during Veno-Venous Extracorporeal Membrane Oxygenation: Insights from the PROTECMO Study.

Rationale: Definitive guidelines for anticoagulation management during veno-venous extracorporeal membrane oxygenation (VV ECMO) are lacking, whereas bleeding complications continue to pose major challenges. Objectives: To describe anticoagulation modalities and bleeding events in adults receiving VV ECMO. Methods: This was an international prospective observational study in 41 centers, from December 2018 to February 2021. Anticoagulation was recorded daily in terms of type, dosage, and monitoring strategy. Bleeding events were reported according to site, severity, and impact on mortality. Measurements and Main Results: The study cohort included 652 patients, and 8,471 days on ECMO were analyzed. Unfractionated heparin was the initial anticoagulant in 77% of patients, and the most frequently used anticoagulant during the ECMO course (6,221 d; 73%). Activated partial thromboplastin time (aPTT) was the most common test for monitoring coagulation (86% of days): the median value was 52 seconds (interquartile range, 39 to 61 s) but dropped by 5.3 seconds after the first bleeding event (95% confidence interval, -7.4 to -3.2; P < 0.01). Bleeding occurred on 1,202 days (16.5%). Overall, 342 patients (52.5%) experienced at least one bleeding event (one episode every 215 h on ECMO), of which 10 (1.6%) were fatal. In a multiple penalized Cox proportional hazard model, higher aPTT was a potentially modifiable risk factor for the first episode of bleeding (for 20-s increase; hazard ratio, 1.07). Conclusions: Anticoagulation during VV ECMO was a dynamic process, with frequent stopping in cases of bleeding and restart according to the clinical picture. Future studies might explore lower aPTT targets to reduce the risk of bleeding.

Perioperative Care for Children With Syndromic Craniofacial Synostosis Undergoing Le Fort III Surgery: A Retrospective Cohort Study.

OBJECTIVE: To present characteristics, surgical variables, complications, and postoperative care in pediatric patients with craniofacial synostosis undergoing Le Fort III osteotomy. BACKGROUND: Craniofacial synostoses are a group of genetic syndromes that result in premature fusion of cranial and facial sutures, leading to craniofacial deformities and associated complications. Midface advancement through Le Fort III osteotomy is the most frequent surgical option for these conditions. METHODS: Retrospective monocentric cohort study including patients with syndromic craniofacial synostosis who underwent Le Fort III osteotomy between 2009 and 2022 in a specialized referral center. Data collection encompassed surgical time, blood loss, intraoperative transfusions, fluid balance, and postoperative parameters such as duration of invasive mechanical ventilation and intensive care unit (ICU) length of stay. RESULTS: Twenty-six children were included in the analysis. The median surgical time was 345 minutes (300-360), with an estimated blood loss of 15 (9.9-24) mL/kg. Patients required a median transfusion of 12.63 (7.1-24.5) mL/kg of packed red blood cells and 19.82 (11.1-33) mL/kg of fresh frozen plasma. Intraoperative fluid balance was + 12.5 (0.8-22.8) mL/kg, with a median infusion of 30.4 (23.9-38.7) mL/kg of crystalloids. All patients were transferred to the ICU after surgery to ensure a safe environment for extubation. The median duration of mechanical ventilation in the ICU was 30 (20.25-45) hours, and postoperative ICU length of stay was 2 (2-4) days, and complications were infrequent, with only one extubation failure recorded. CONCLUSION: Le Fort III osteotomy in craniofacial synostosis patients may be characterized by a complex perioperative course. A multidisciplinary approach in the care of these patients allows for minimizing complications in the perioperative phase. Further research is needed to enhance perioperative management in this unique patient population.

Extracorporeal cardio-pulmonary resuscitation in a patient with missed diagnosis of sodium nitrite intoxication.

INTRODUCTION: Critical poisoning with sodium nitrite (NaNO2) can present challenges in promptly identifying and managing acute methemoglobinemia. CASE REPORT: We report the case of an overt self-intoxication by an initially unknown agent, leading to cardiac arrest. Despite prodromal signs of cyanosis, coma, desaturation, and hypotension, methemoglobinemia went unrecognized during extracorporeal cardiopulmonary resuscitation (ECPR) as the point-of-care test failed to provide methemoglobin levels, leading to untreated methemoglobinemia. The blood flowing through the oxygenator notably maintained the same brown colour. Return of spontaneous circulation was never achieved, and the patient was declared dead after 60 min of unsuccessful resuscitation. Cause of death by means of NaNO2 voluntary ingestion was later clarified and confirmed by postmortem finding of elevated nitrite and nitrate concentration. CONCLUSIONS: This case highlights the risk of failure of ECPR in the context of cardiac arrest due to methemoglobinemia, emphasizing the critical need for prompt recognition of the causative agent and early administration of antidotes.

Determinants of increased nursing workload in the COVID-era: A retrospective analysis of prospectively collected data.

BACKGROUND: COVID-19 is associated with increased nursing workload, therefore a high nurse-to-patient ratio would be required. AIM: To analyse difference in nursing workload, as expressed with the Nursing Activities Score (NAS), between COVID-19 patients versus control patients without COVID-19 disease (NCOVID-19 group) in an Italian Extracorporeal Membrane Oxygenation (ECMO) centre. STUDY DESIGN: Retrospective analysis of prospectively collected data, enrolling consecutive patients admitted to a general Intensive Care Unit, between 1st May 2019 and 28th February 2021. A multivariate analysis was then performed to assess if COVID-19 disease was an independent predictor of higher NAS and to assess which other factors and procedures are independently associated with increased workload. RESULTS: We enrolled 574 patients, of which 135 (24%) were in the COVID-19 group and 439 (76%) in the NCOVID-19 group. The average NAS was higher in the COVID-19 group (79 ± 11 vs. 65 ± 15, T = -10.026; p < 0.001). Prone positioning, continuous renal replacement therapy (CRRT) and ECMO were used more frequently in the COVID-19 group. A higher fraction of patients in the COVID group showed colonization from multidrug resistant bacteria. COVID-19 group had a higher duration of mechanical ventilation and longer ICU stay. The COVID-19 diagnosis was independently associated with a higher NAS. Other independent predictors of higher NAS were the use of prone positioning and continuous renal replacement therapy (CRRT). Colonization from multidrug resistant bacteria and ECMO support were not independently associated with higher NAS. CONCLUSIONS: The higher nursing workload in COVID-19 patients is mainly due to specific procedures required to treat the most hypoxemic patients, such as prone positioning. Colonization with multidrug resistant bacteria and ECMO support were not independently associated with a higher NAS. RELEVANCE TO CLINICAL PRACTICE: Higher workload in COVID-19 patients was due to specific interventions, such as prone positioning and CRRT, with the related nursing activities, as continuous presence at patient's bed, mobilization, positioning and complex hygienic procedures.

Patients' recollections of helmet-CPAP treatment during COVID-19 pandemic: A qualitative study.

BACKGROUND: During the pandemic outbreak, helmet continuous positive airway pressure (CPAP) was widely used as respiratory support for COVID-19 patients, inside and outside of intensive care units. The available literature suggests specific interventions to improve the comfort of patients treated with helmet-CPAP. Few reports are available on the experiences of patients undergoing this treatment. AIM: This qualitative study aimed to explore the views and recollections of COVID-19 patients undergoing helmet-CPAP. STUDY DESIGN: We conducted semi-structured interviews with thematic analysis. Participants were recruited from the follow-up programme for COVID-19 patients discharged from an Italian general intensive care unit. Participants were interviewed by telephone. Data analysis followed the principles of thematic synthesis approach. FINDINGS: We conducted 29 phone calls in patients eligible for the study. Five participants declared that they did not remember the time spent in hospital on helmet-CPAP. Twenty-four patients were then included. Two themes and six subthemes were generated from their interview data: (1) The helmet-CPAP as a life-saving treatment (subthemes: recognition of the usefulness of treatment and resilience); (2) the negative feelings related to helmet-CPAP application (subthemes: communication problems, entrapment, mental confusion, fear of dying). Each patient's experience was unique, but some discomfort elements such as noise, gas flow turbulence, choking sensation and thirst were found to be very common. CONCLUSIONS: The application of helmet-CPAP treatment generated positive and negative memories and feelings in COVID-19 patients during the pandemic. The patients' experience has provided an overview of the main factors of discomfort. This can be a starting point for taking corrective measures to promote greater helmet tolerance and subsequent treatment success. RELEVANCE TO CLINICAL PRACTICE: This study has provided an insight into the patient's recollections about helmet-CPAP treatment during a worldwide pandemic. The findings suggested strict applications of interventions aimed to reduce some issues that participants reported, to improve their compliance to treatment. Results from this study could help nurses in understanding the needs of patients treated with helmet-CPAP and may foster a care focused on patient-centred outcomes.

Timing of Prone Positioning During Venovenous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome.

OBJECTIVES: To assess the association of timing to prone positioning (PP) during venovenous extracorporeal membrane oxygenation (V-V ECMO) with the probability of being discharged alive from the ICU at 90 days (primary endpoint) and the improvement of the respiratory system compliance (Cpl,rs). DESIGN: Pooled individual data analysis from five original observational cohort studies. SETTING: European extracorporeal membrane oxygenation (ECMO) centers. PATIENTS: Acute respiratory distress syndrome (ARDS) patients who underwent PP during ECMO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Time to PP during V-V ECMO was explored both as a continuous and a categorical variable with Cox proportional hazard models. Three hundred patients were included in the analysis. The longer the time to PP during V-V ECMO, the lower the adjusted probability of alive ICU discharge (adjusted hazard ratio [HR] 0.90 for each day increase; 95% CI, 0.87-0.93). Two hundred twenty-three and 77 patients were included in the early PP (≤ 5 d) and late PP (> 5 d) groups, respectively. The cumulative 90-day probability of being discharged alive from the ICU was 61% in the early PP group vs 36% in the late PP group (log-rank test, p <0.001). This benefit was maintained after adjustment for confounders (adjusted HR, 2.52; 95% CI, 1.66-3.81; p <0.001). In the early PP group, PP was associated with a significant improvement of Cpl,rs (4 ± 9 mL/cm H2O vs 0 ± 12 in the late PP group, p=0.038). CONCLUSIONS: In a large cohort of ARDS patients on ECMO, early PP during ECMO was associated with a higher probability of being discharged alive from the ICU at 90 days and a greater improvement of Cpl,rs.

Tracheal stenting on venovenous ECMO with a dual lumen right atrium-to-pulmonary artery cannula in a COVID-19 patient with an inferior vena cava filter.

A 47-year-old man, with no medical history, was diagnosed with severe COVID-19 ARDS and pulmonary embolism. Venovenous extracorporeal membrane oxygenation (ECMO) was required for impossibility to deliver protective ventilation. The patient was weaned from ECMO after clinical improvement. An inferior vena cava filter was then positioned to prevent embolization from a persistent left femoral deep venous thrombosis. Two days after the ECMO removal, a large lesion of the tracheal posterior wall was diagnosed. Tracheal stenting was deemed necessary. ECMO support was then re-established, to safely perform the bronchoscopic procedure. Due to the presence of the inferior vena cava filter, the patient was cannulated via the right internal jugular vein with a double lumen ProtekDuo cannula. The patient was then weaned from ECMO support and invasive ventilation. The tracheal stent was removed after 40 days, showing a full recovery of the tracheal lesion. The patient was discharged home in good condition.

How to avoid rapid carbon dioxide changes at the start of veno-venous extracorporeal membrane oxygenation: Role of end-tidal CO2 monitoring.

Background: Venovenous ECMO is a lifesaving technique for patients with severe respiratory failure. Management of carbon dioxide (CO2) levels at ECMO start is crucial, as recent studies found an association between rapid CO2 shifts and increased incidence of neurological complications.Purpose: To describe the role of end tidal CO2 (etCO2) monitoring at the ECMO start to minimize carbon dioxide shifts.Research design: Retrospective cohort study.Methods: We performed a retrospective analysis of patients who started venovenous ECMO support at our institution between 2011 and 2021. We analysed the minute-by-minute variations of etCO2, ventilatory parameters and arterial blood gas before and after the ECMO start.Results: 36 patients with a complete dataset of parameters were included. After the ECMO start, minute ventilation was progressively reduced from 10.8±;3.3 to 2.9±1.2 L/min (p<0.001). etCO2 did not vary significantly (baseline 37±10 vs 35±9 mmHg 20 minutes after ECMO start, p = 0.36). Despite a stable etCO2 level, a mild drop of arterial CO2 tension (9.5 mmHg, corresponding to a 18% change) was recorded at the first ABG sampled after the ECMO start. No patient developed neurological complications after the ECMO commencement.Conclusion: etCO2 monitoring during ECMO start is feasible and allows to adjust gas flow and ventilator settings to limit changes in arterial CO2 levels.

The role of intensive care unit diaries in the grieving process: A monocentric qualitative study.

BACKGROUND: The growing importance of psychological recovery for patients and their families following intensive care unit (ICU) experiences in recent years cannot be overemphasized. The ICU diary is used to aid patients in reducing the prevalence of post-traumatic stress disorder, anxiety, and depression. The usefulness of maintaining a diary during the grieving process has not yet been thoroughly investigated. AIM: To investigate the role of ICU diaries in the grief process experienced by family members of a person who died in the intensive care unit. STUDY DESIGN: Nine family members of seven deceased ICU patients with an ICU diary were contacted and interviewed by phone using a semi-structured interview. A qualitative data analysis was performed using thematic synthesis. SETTING: Italian general intensive care unit. FINDINGS: Interviewed family members felt that the diary helped them during the grieving process. The return of diaries was desired by family members for support and to remember one's loved one. The diary helped them process their losses in various ways, including signs of evidence of care, emotional involvement, consideration, and coping with grief. Four main themes emerged from the analysis: writing the diary, reading the diary, talking about the diary, and the diary during the grieving process. CONCLUSIONS: The overall perception of the ICU diary was positive. The diary mostly helped relatives to "give back something of what we lost". This study also affirms the positive link between ICU diaries and bereavement in Italian ICU. Further studies are required to confirm the usefulness of this tool in the grieving process. RELEVANCE TO CLINICAL PRACTICE: The ICU diary can help patients' family members understand what happened to their loved one and play an important role in the grieving process. The diary served as a valuable source of information that aided in providing bereavement support to the family by helping them to gain a rational and emotional understanding of the patient's death.

Prone positioning during venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a pooled individual patient data analysis.

BACKGROUND: Prone positioning (PP) reduces mortality of patients with acute respiratory distress syndrome (ARDS). The potential benefit of prone positioning maneuvers during venovenous extracorporeal membrane oxygenation (ECMO) is unknown. The aim of this study was to evaluate the association between the use of prone positioning during extracorporeal support and ICU mortality in a pooled population of patients from previous European cohort studies. METHODS: We performed a pooled individual patient data analysis of European cohort studies which compared patients treated with prone positioning during ECMO (Prone group) to "conventional" ECMO management (Supine group) in patients with severe ARDS. RESULTS: 889 patients from five studies were included. Unadjusted ICU mortality was 52.8% in the Supine Group and 40.8% in the Prone group. At a Cox multiple regression analysis PP during ECMO was not significantly associated with a reduction of ICU mortality (HR 0.67 95% CI: 0.42-1.06). Propensity score matching identified 227 patients in each group. ICU mortality of the matched samples was 48.0% and 39.6% for patients in the Supine and Prone group, respectively (p = 0.072). CONCLUSIONS: In a large population of ARDS patients receiving venovenous extracorporeal support, the use of prone positioning during ECMO was not significantly associated with reduced ICU mortality. The impact of this procedure will have to be definitively assessed by prospective randomized controlled trials.

Extracorporeal membrane oxygenation for COVID-19 and influenza H1N1 associated acute respiratory distress syndrome: a multicenter retrospective cohort study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has become an established rescue therapy for severe acute respiratory distress syndrome (ARDS) in several etiologies including influenza A H1N1 pneumonia. The benefit of receiving ECMO in coronavirus disease 2019 (COVID-19) is still uncertain. The aim of this analysis was to compare the outcome of patients who received veno-venous ECMO for COVID-19 and Influenza A H1N1 associated ARDS. METHODS: This was a multicenter retrospective cohort study including adults with ARDS, receiving ECMO for COVID-19 and influenza A H1N1 pneumonia between 2009 and 2021 in seven Italian ICU. The primary outcome was any-cause mortality at 60 days after ECMO initiation. We used a multivariable Cox model to estimate the difference in mortality accounting for patients' characteristics and treatment factors before ECMO was started. Secondary outcomes were mortality at 90 days, ICU and hospital length of stay and ECMO associated complications. RESULTS: Data from 308 patients with COVID-19 (N = 146) and H1N1 (N = 162) associated ARDS who had received ECMO support were included. The estimated cumulative mortality at 60 days after initiating ECMO was higher in COVID-19 (46%) than H1N1 (27%) patients (hazard ratio 1.76, 95% CI 1.17-2.46). When adjusting for confounders, specifically age and hospital length of stay before ECMO support, the hazard ratio decreased to 1.39, 95% CI 0.78-2.47. ICU and hospital length of stay, duration of ECMO and invasive mechanical ventilation and ECMO-associated hemorrhagic complications were higher in COVID-19 than H1N1 patients. CONCLUSION: In patients with ARDS who received ECMO, the observed unadjusted 60-day mortality was higher in cases of COVID-19 than H1N1 pneumonia. This difference in mortality was not significant after multivariable adjustment; older age and longer hospital length of stay before ECMO emerged as important covariates that could explain the observed difference. TRIAL REGISTRATION NUMBER: NCT05080933 , retrospectively registered.

Terrorist attacks and minority perceived discrimination.

A growing strand of the literature finds a causal negative impact of terrorism on undifferentiated discriminatory attitudes toward Muslims, migrants, and other minorities. In this paper, we argue that jihadist terrorism threatens first and foremost Muslims. To evaluate this claim, we estimate the causal effect of jihadist terrorism on the perceived discrimination among Muslims through a 2×2 quasi-experimental design. Exploiting "natural experiments" driven by exogenous variation in terror threat caused by jihadist attacks that unexpectedly occurred during the fieldwork of a large survey, we compare the perceived ethoracial discrimination of the relevant minority (Muslims) against other minorities (non-Muslims) before and after five different terror attacks in five different European countries. We find that jihadist attacks increase perceived ethnoracial discrimination among Muslims while reducing it among non-Muslims, and that individual-level factors including social status and economic insecurity mitigate public opinion responses to a greater extent than group-level factors do. Hence, while in-group attitudes toward out-groups tend to be undifferentiated, the experience of out-groups in the aftermath of jihadist attacks depends on the specific identity of the respondents.

Role of Complete Duplex Ultrasound to Diagnose Deep Vein Thrombosis in COVID-19 Critical Patients.

An increased risk of deep vein thrombosis (DVT) has been reported in critical COVID-19 patients, despite adequate thromboprophylaxis, and most of DVT are probably asymptomatic. As a screening approach has been advocated, the best examination protocol is unknown. The objective of this study is to assess the role of a Complete Duplex Ultrasound (CDUS) examination in detecting DVT in a large population of COVID-19 patients admitted to intensive care unit (ICU) for respiratory failure. Single-center retrospective study of 145 COVID-19 patients admitted to ICU. DVT was assessed with a CDUS performed by experienced radiologist after ICU admission. DVT was confirmed in 38 patients (26%). Most DVT were distal to the knee (66%), while only 16% were proximal. At the time of the examination, 55% of the patients received full-dose anticoagulation, while 45% received thromboprophylaxis, and there were no differences in anticoagulation regimen between positive and negative patients. Patients with DVT had higher dimers compared with those with negative CDUS (P < .002). The observed frequency of DVT is high despite adequate anticoagulation. A comprehensive and experienced ultrasound examination protocol can allow to recognize a large number of distal DVT otherwise missed, albeit their clinical significance is unknown.

Respiratory Electrodialysis. A Novel, Highly Efficient Extracorporeal CO2 Removal Technique.

RATIONALE: We developed an innovative, minimally invasive, highly efficient extracorporeal CO2 removal (ECCO2R) technique called respiratory electrodialysis (R-ED). OBJECTIVES: To evaluate the efficacy of R-ED in controlling ventilation compared with conventional ECCO2R technology. METHODS: Five mechanically ventilated swine were connected to a custom-made circuit optimized for R-ED, consisting of a hemofilter, a membrane lung, and an electrodialysis cell. Electrodialysis regionally modulates blood electrolyte concentration to convert bicarbonate to CO2 before entering the membrane lung, enhancing membrane lung CO2 extraction. All animals underwent three repeated experimental sequences, consisting of four steps: baseline (1 h), conventional ECCO2R (2 h), R-ED (2 h), and final NO-ECCO2R (1 h). Blood and gas flow were 250 ml/min and 10 L/min, respectively. Tidal volume was set at 8 ml/kg, and respiratory rate was adjusted to maintain arterial Pco2 at 50 mm Hg. MEASUREMENTS AND MAIN RESULTS: During R-ED, chloride and H(+) concentration increased in blood entering the membrane lung, almost doubling CO2 extraction compared with ECCO2R (112 ± 6 vs. 64 ± 5 ml/min, P < 0.001). Compared with baseline, R-ED and ECCO2R reduced minute ventilation by 50% and 27%, respectively. Systemic arterial gas analyses remained stable during the experimental phases. No major complication occurred, but there was an increase in creatinine level. CONCLUSIONS: In this first in vivo application, we proved electrodialysis feasible and effective in increasing membrane lung CO2 extraction. R-ED was more effective than conventional ECCO2R technology in controlling ventilation. Further studies are warranted to assess the safety profile of R-ED, especially regarding kidney function.

Regional blood acidification enhances extracorporeal carbon dioxide removal: a 48-hour animal study.

BACKGROUND: Extracorporeal carbon dioxide removal has been proposed to achieve protective ventilation in patients at risk for ventilator-induced lung injury. In an acute study, the authors previously described an extracorporeal carbon dioxide removal technique enhanced by regional extracorporeal blood acidification. The current study evaluates efficacy and feasibility of such technology applied for 48 h. METHODS: Ten pigs were connected to a low-flow veno-venous extracorporeal circuit (blood flow rate, 0.25 l/min) including a membrane lung. Blood acidification was achieved in eight pigs by continuous infusion of 2.5 mEq/min of lactic acid at the membrane lung inlet. The acid infusion was interrupted for 1 h at the 24 and 48 h. Two control pigs did not receive acidification. At baseline and every 8 h thereafter, the authors measured blood lactate, gases, chemistry, and the amount of carbon dioxide removed by the membrane lung (VCO2ML). The authors also measured erythrocyte metabolites and selected cytokines. Histological and metalloproteinases analyses were performed on selected organs. RESULTS: Blood acidification consistently increased VCO2ML by 62 to 78%, from 79 ± 13 to 128 ± 22 ml/min at baseline, from 60 ± 8 to 101 ± 16 ml/min at 24 h, and from 54 ± 6 to 96 ± 16 ml/min at 48 h. During regional acidification, arterial pH decreased slightly (average reduction, 0.04), whereas arterial lactate remained lower than 4 mEq/l. No sign of organ and erythrocyte damage was recorded. CONCLUSION: Infusion of lactic acid at the membrane lung inlet consistently increased VCO2ML providing a safe removal of carbon dioxide from only 250 ml/min extracorporeal blood flow in amounts equivalent to 50% production of an adult man.