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Background: The use of the prone position (PP) has been widespread during the COVID-19 pandemic. While it has demonstrated benefits, including improved oxygenation and lung aeration, the factors influencing the response in terms of gas exchange to PP remain unclear. In particular, the association between baseline quantitative Computed Tomography (qCT) scan results and gas exchange response to PP in intubated, mechanically ventilated subjects with COVID-19 ARDS is unknown. The present study aimed to compare baseline qCT results between subjects responding to PP in terms of oxygenation or carbon dioxide (CO2) clearance and those who did not.Methods: This was a single-center, retrospective observational study, including critically ill, intubated, mechanically ventilated subjects with COVID-19 related acute respiratory distress syndrome admitted to the ICUs of Niguarda Hospital between March 2020 and November 2021. Blood-gas samples were collected before and after PP. Subjects in whom the PaO2/FiO2 increase was ≥ 20 mmHg after PP were defined as Oxygen responders (Oxy-R). CO2-responders (CO2R) were defined when the ventilatory ratio (VR) decreased during PP. Automated qCT analyses were performed to obtain tissue mass and density of the lungs.Results: One hundred twenty-five subjects were enrolled, of which 116 (93%) were Oxy-R and 51 (41%) CO2R. No difference in qCT characteristics and oxygen were observed between Oxy-R and Oxygen Non Responders (Tissue mass 1532 ±396 vs. 1654 ±304 g, p= .28; density -544±109 vs. -562±58 HU, p= .42). Similar findings were observed when dividing the population according to CO2 response (Tissue mass 1551±412 vs. 1534±377 g, p= .89; density -545±123 vs. -546±94 HU, p= .99).Conclusions: Most COVID-19 related ARDS subjects improve their oxygenation at the first pronation cycle. The study suggests that baseline qCT scan data are not associated with the response to PP in oxygenation or CO2 in mechanically ventilated COVID-19 related ARDS subje

Background: Continuous positive airway pressure (CPAP) is frequently used to treat patients with acute respiratory failure in out-of-hospital settings. Compared to a facemask, the helmet has many advantages for the patient but requires a minimum gas flow of 60 L/min to avoid CO2 rebreathing. The aim of the present bench study was to evaluate the performance of four Venturi devices, connected to a single oxygen cylinder, in delivering helmet-CPAP with clinically relevant gas flow, fraction of inspired oxygen (FiO2), and positive end-expiratory pressure (PEEP) values. Methods: Three double-inlet Venturi systems (EasyVent, Ventuplus, Compact-HAR) were connected to full 5-L oxygen cylinders using a double flowmeter, and their oxygen requirements to reach different setups (flow 60-80 L/min; FiO2 0.4-0.5-0.6, PEEP 7.5-10-12.5 cmH2O) were tested. The fourth Venturi system (O2-MAX) was directly attached to the tank, and the flow and FiO2 delivered at preset FiO2 0.3 and 0.6 were recorded. The runtime of the cylinder was assessed. Results: EasyVent, Ventuplus, and O2-MAX were able to deliver helmet-CPAP with clinically useful setups when connected to a single oxygen cylinder, while Compact-HAR did not. The runtime of the cylinders ranged between 28 and 60 minutes according to the preset flow and FiO2. The delivered gas flow decreased slowly and linearly with the drop in cylinder pressure until its exhaustion. Conclusions: Helmet-CPAP might be provided using portable Venturi systems connected to an oxygen cylinder, but not all of them are able to deliver it. The use of a double flowmeter allows delivery of both high flow and high FiO2 when double-inlet Venturi systems are used. Due to the flow drop observed during the cylinder consumption, a flow >60 L/min should be set when helmet-CPAP is started. Considering the flow drop phenomenon, the estimated duration of the tank runtime can be used with a margin of safety when planning patient transport.

Introduction: Metformin intoxication causes lactic acidosis by inhibiting Krebs' cycle and oxidative phosphorylation. Continuous renal replacement therapy (CRRT) is recommended for metformin removal in critically ill patients. According to current guidelines, regional citrate anticoagulation (RCA) is the first-line strategy. However, since metformin also inhibits citrate metabolism, a risk of citrate accumulation could be hypothesized. In the present study, we monitored the potential citrate accumulation in metformin-associated lactic acidosis (MALA) patients treated with CRRT and RCA using the physical-chemical approach to acid-base interpretation. Methods: We collected a case series of 3 patients with MALA. Patients were treated with continuous venovenous hemofiltration (CVVH), and RCA was performed with diluted citrate solution. Citrate accumulation was monitored through two methods: the ratio between total and ionized plasma calcium concentrations (T/I calcium ratio) above 2.5 and the strong ion gap (SIG) to identify an increased concentration of unmeasured anions. Lastly, a mathematical model was developed to estimate the expected citrate accumulation during CVVH and RCA. Results: All 3 patients showed a resolution of MALA after the treatment with CVVH. The T/I calcium ratio was consistently below 2.5, and SIG decreased, reaching values lower than 6 mEq/L after 48 h of CVVH treatment. According to the mathematical model, the estimated SIG without citrate metabolism should have been around 21 mEq/L due to citrate accumulation. Conclusions: In our clinical management, no signs of citrate accumulation were recorded in MALA patients during treatment with CVVH and RCA. Our data support the safe use of diluted citrate to perform RCA during metformin intoxication.

Background: Changing trunk inclination affects lung function in patients with ARDS. However, its impacts on PEEP titration remain unknown. The primary aim of this study was to assess, in mechanically ventilated patients with COVID-19 ARDS, the effects of trunk inclination on PEEP titration. The secondary aim was to compare respiratory mechanics and gas exchange in the semi-recumbent (40° head-of-the-bed) and supine-flat (0°) positions following PEEP titration. Methods: Twelve patients were positioned both at 40° and 0° trunk inclination (randomized order). The PEEP associated with the best compromise between overdistension and collapse guided by Electrical Impedance Tomography (PEEPEIT) was set. After 30 min of controlled mechanical ventilation, data regarding respiratory mechanics, gas exchange, and EIT parameters were collected. The same procedure was repeated for the other trunk inclination. Results: PEEPEIT was lower in the semi-recumbent than in the supine-flat position (8 ± 2 vs. 13 ± 2 cmH2O, p < 0.001). A semi-recumbent position with optimized PEEP resulted in higher PaO2:FiO2 (141 ± 46 vs. 196 ± 99, p = 0.02) and a lower global inhomogeneity index (46 ± 10 vs. 53 ± 11, p = 0.008). After 30 min of observation, a loss of aeration (measured by EIT) was observed only in the supine-flat position (−153 ± 162 vs. 27 ± 203 mL, p = 0.007). Conclusions: A semi-recumbent position is associated with lower PEEPEIT and results in better oxygenation, less derecruitment, and more homogenous ventilation compared to the supine-flat position.

Objective: To assess the different effect of filters’ application during helmet-CPAP delivered with three different flow generators on the delivered fresh gas flow, FiO2, and the noise level inside and outside the helmet. Methods: In a bench study, three flow generators (air-oxygen blender, turbine ventilator and Venturi system) were used to generate two different gas flows (60 L/min and 80 L/min), with a fixed FiO2 at 0.6, to perform a helmet-CPAP on a manikin. Three different fixed PEEP valves (7.5, 10, and 12.5 cmH2O) were applied at the expiratory port. Gas flow, FiO2 and noise were recorded for each Flow-generator/Flow/PEEP combination, first without filter interposition and then after positioning a heat and moister exchanger filter (HMEF) at the helmet inlet port. Results: The application of the HMEF lead to a significant difference in the flow variation among the three flow generators (p < 0.001). Compared to baseline, the highest flow reduction was observed with the VENTURI (−13.4 ± 1.2 %, p < 0.001), a slight increase with the BLENDER (1.2 ± 0.5 %, p < 0.001), whereas no difference was recorded with the TURBINE (0.1 ± 0.6 %, p = 0.12). After HMEF was interposed, a significant FiO2 variation was observed only with VENTURI (11.3 ± 1.8 %, p < 0.001). As for the noise, the TURBINE was the least noisy system, both with and without the filter interposition. Conclusions: Flow generators used to deliver helmet-CPAP have different characteristics and responses to HMEF interposition. Users should be aware of the effects on FiO2 and flow of the different devices in order to make a precise setup of the circuit.

Rationale: Inhalation of nitric oxide (NO) exerts selective pulmonary vasodilation. Nitric oxide also has an antimicrobial effect on a broad spectrum of pathogenic viruses, bacteria and fungi. Objectives: The aim of this study was to investigate the effect of inhaled NO on bacterial burden and disease outcome in a murine model of Klebsiella pneumonia. Methods: Mice were infected with Klebsiella pneumoniae and inhaled either air alone, air mixed with constant levels of NO (at 80, 160, or 200 parts per million (ppm)) or air intermittently mixed with high dose NO (300 ppm). Forty-eight hours after airway inoculation, the number of viable bacteria in lung, spleen and blood was determined. The extent of infiltration of the lungs by inflammatory cells and the level of myeloperoxidase activity in the lungs were measured. Atomic force microscopy was used to investigate a possible mechanism by which nitric oxide exerts a bactericidal effect. Measurements and main results: Compared to control animals infected with K. pneumoniae and breathed air alone, intermittent breathing of NO (300 ppm) reduced viable bacterial counts in lung and spleen tissue. Inhaled NO reduced infection-induced lung inflammation and improved overall survival of mice. NO destroyed the cell wall of K. pneumoniae and killed multiple-drug resistant K. pneumoniae in-vitro. Conclusions: Intermittent administration of high dose NO may be an effective approach to the treatment of pneumonia caused by K. pneumoniae.

Objectives: To test the feasibility, safety, and efficacy of intratracheal delivery of nitric oxide (NO) generated from air by pulsed electrical discharge via a Scoop catheter. Study design: We studied healthy 3- to 4-month-old lambs weighing 34 ± 4 kg (mean ± SD, n = 6). A transtracheal Scoop catheter was inserted through a cuffed tracheostomy tube. U46619 was infused to increase mean pulmonary arterial pressure (mPAP) from 16 ± 1 to 32 ± 3 mmHg (mean ± SD). Electrically generated NO was delivered via the Scoop catheter to awake lambs. A sampling line, to monitor NO and nitrogen dioxide (NO2) levels, was placed in the distal trachea of the lambs. The effect of varying doses of electrically generated NO, produced continuously, on pulmonary hypertension was assessed. Results: In awake lambs with acute pulmonary hypertension, NO was continuously delivered via the Scoop catheter at 400 ml/min. NO induced pulmonary vasodilation. NO2 levels, measured in the trachea, were below 0.5 ppm at intratracheal NO doses of 10–80 ppm. No changes were detected in the levels of methemoglobin in blood samples before and after 5 min of NO breathing. Conclusions: Continuously delivering electrically generated NO through a Scoop catheter produces vasodilation of the pulmonary vasculature of awake lambs with pulmonary hypertension. Transtracheal NO delivery may provide a long-term treatment for patients with chronic pulmonary hypertension as an outpatient without requiring a mask or tracheal intubation.

Background Acid–base status in full-term pregnant women is characterised by hypocapnic alkalosis. Whether this respiratory alkalosis is primary or consequent to changes in CSF electrolytes is not clear. Methods We enrolled third-trimester pregnant women (pregnant group) and healthy, non-pregnant women of childbearing age (controls) undergoing spinal anaesthesia for Caesarean delivery and elective surgery, respectively. Electrolytes, strong ion difference (SID), partial pressure of carbon dioxide (), and pH were measured in simultaneously collected CSF and arterial blood samples. Results All pregnant women (20) were hypocapnic, whilst only four (30%) of the controls (13) had an arterial <4.7 kPa (P<0.001). The incidence of hypocapnic alkalosis was higher in the pregnant group (65% vs 8%; P=0.001). The CSF-to-plasma Pco2 difference was significantly higher in pregnant women (1.5 [0.3] vs 1.0 [0.4] kPa; P<0.001), mainly because of a decrease in arterial Pco2 (3.9 [0.3] vs 4.9 [0.5] kPa; P<0.001). Similarly, the CSF-to-plasma difference in SID was less negative in pregnant women (–7.8 [1.4] vs –11.4 [2.3] mM; P<0.001), mainly because of a decreased arterial SID (31.5 [1.2] vs 36.1 [1.9] mM; P<0.001). The major determinant of the reduced plasma SID of pregnant women was a relative increase in plasma chloride compared with sodium. Conclusions Primary hypocapnic alkalosis characterises third-trimester pregnant women leading to chronic acid–base adaptations of CSF and plasma. The compensatory SID reduction, mainly sustained by an increase in chloride concentration, is more pronounced in plasma than in CSF, as the decrease in Pco2 is more marked in this compartment.

BACKGROUND: When helmet CPAP is performed using a Venturi system, filters are frequently interposed in the respiratory circuit to reduce noise within the helmet. The effect of the interposition of these filters on delivered fresh gas flow and the resulting FIO2 is currently unknown. METHODS: In a bench study, 2 different Venturi systems (WhisperFlow and Harol) were used to generate 3 different gas flow/FIO2 combinations (80 L/min-FIO2 0.6, 100 L/min-FIO2 0.5, 120 L/min-FIO2 0.4). Different combinations of filters were applied at the flow generator input line and/or at the helmet inlet port. Two types of filters were used for this purpose: a heat and moisture exchanger filter and an electrostatic filter. The setup without filters was used as baseline. Gas flow and FIO2 were measured for each setup. RESULTS: Compared to baseline, the interposition of filters reduced the gas flow between 1–13% (P < .001). The application of a filter at the Venturi system or at the helmet generated a comparable flow reduction (-3 ± 2% vs-4 ± 2%, P = .12), whereas a greater flow reduction (-7 ± 4%) was observed when filters were applied at both sites (P < .001). An increase in FIO2 up to 5% was observed with filters applied. A strong inverse linear relationship (P < .001) was observed between the resulting gas flow and FIO2. CONCLUSIONS: The use of filters during helmet CPAP reduced the flow delivered to the helmet and, consequently, modified FIO2. If filters are applied, an adequate gas flow should be administered to guarantee a constant CPAP during the entire respiratory cycle and avoid rebreathing. Moreover, it might be important to measure the effective FIO2 delivered to the patient to guarantee a precise assessment of oxygenation.

Background: Hyperventilation resulting in hypocapnic alkalosis (HA) is frequently encountered in spontaneously breathing patients with acute cerebrovascular conditions. The underlying mechanisms of this respiratory response have not been fully elucidated. The present study describes, applying the physical–chemical approach, the acid-base characteristics of cerebrospinal fluid (CSF) and arterial plasma of spontaneously breathing patients with aneurismal subarachnoid hemorrhage (SAH) and compares these results with those of control patients. Moreover, it investigates the pathophysiologic mechanisms leading to HA in SAH. Methods: Patients with SAH admitted to the neurological intensive care unit and patients (American Society of Anesthesiologists physical status of 1 and 2) undergoing elective surgery under spinal anesthesia were enrolled. CSF and arterial samples were collected simultaneously. Electrolytes, strong ion difference (SID), partial pressure of carbon dioxide (PCO2), weak noncarbonic acids (ATOT), and pH were measured in CSF and arterial blood samples. Results: Twenty spontaneously breathing patients with SAH and 25 controls were enrolled. The CSF of patients with SAH, as compared with controls, was characterized by a lower SID (23.1 ± 2.3 vs. 26.5 ± 1.4 mmol/L, p < 0.001) and PCO2 (40 ± 4 vs. 46 ± 3 mm Hg, p < 0.001), whereas no differences in ATOT (1.2 ± 0.5 vs. 1.2 ± 0.2 mmol/L, p = 0.95) and pH (7.34 ± 0.06 vs. 7.35 ± 0.02, p = 0.69) were observed. The reduced CSF SID was mainly caused by a higher lactate concentration (3.3 ± 1.3 vs. 1.4 ± 0.2 mmol/L, p < 0.001). A linear association (r = 0.71, p < 0.001) was found between CSF SID and arterial PCO2. A higher proportion of patients with SAH were characterized by arterial HA, as compared with controls (40 vs. 4%, p = 0.003). A reduced CSF-to-plasma difference in PCO2 was observed in nonhyperventilating patients with SAH (0.4 ± 3.8 vs. 7.8 ± 3.7 mm Hg, p < 0.001). Conclusions: Patients with

Background and objectives: Carbon monoxide (CO) inhalation is the leading cause of poison-related deaths in the United States. CO binds to hemoglobin (Hb), displaces oxygen, and reduces oxygen delivery to tissues. The optimal treatment for CO poisoning in patients with normal lung function is the administration of hyperbaric oxygen (HBO). However, hyperbaric chambers are only available in medical centers with specialized equipment, resulting in delayed therapy. Visible light dissociates CO from Hb with minimal effect on oxygen binding. In a previous study, we combined a membrane oxygenator with phototherapy at 623 nm to produce a “mini” photo-ECMO (extracorporeal membrane oxygenation) device, which improved CO elimination and survival in CO-poisoned rats. The objective of this study was to develop a larger photo-ECMO device (“maxi” photo-ECMO) and to test its ability to remove CO from a porcine model of CO poisoning. Study design/materials and methods: The “maxi” photo-ECMO device and the photo-ECMO system (six maxi photo-ECMO devices assembled in parallel), were tested in an in vitro circuit of CO poisoning. To assess the ability of the photo-ECMO device and the photo-ECMO system to remove CO from CO-poisoned blood in vitro, the half-life of COHb (COHb-t1/2), as well as the percent COHb reduction in a single blood pass through the device, were assessed. In the in vivo studies, we assessed the COHb-t1/2 in a CO-poisoned pig under three conditions: (1) While the pig breathed 100% oxygen through the endotracheal tube; (2) while the pig was connected to the photo-ECMO system with no light exposure; and (3) while the pig was connected to the photo-ECMO system, which was exposed to red light. Results: The photo-ECMO device was able to fully oxygenate the blood after a single pass through the device. Compared to ventilation with 100% oxygen alone, illumination with red light together with 100% oxygen was twice as efficient in removing CO from blood. Changes in gas flow ra

Background: Advances in regional anesthesia and pain management led to the advent of ultrasound-guided fascial plane blocks, which represent a new and promising route for the administration of local anesthetics. Both practical and theoretical knowledge of locoregional anesthesia are therefore becoming fundamental, requiring specific training programs for residents. Simulation-based medical education and training (SBET) has been recently applied to ultrasound-guided regional anesthesia (UGRA) with remarkable results. With this in mind, the anesthesia and intensive care residency program of the University of Milano-Bicocca organized a 4-h regional anesthesia training workshop with the BlockSim® (Accurate Srl, Cesena) simulator. Our study aimed to measure the residents' improvement in terms of reduction in time required to achieve an erector spinae plane (ESP) block. Methods: Fifty-two first-year anesthesia residents were exposed to a 4-h training workshop focused on peripheral blocks. The course included an introductory theoretical session held by a locoregional anesthetist expert, a practical training on human models and mannequins using Onvision® (B. Braun, Milano) technologies, and two test performances on the BlockSim simulator. Residents were asked to perform two ESP blocks on the BlockSim: the first without previous practice on the simulator, the second at the end of the course. Trainees were also also asked to complete a self-assessment questionnaire. Results: The time needed to achieve the block during the second attempt was significantly shorter (131 [83, 198] vs. 68 [27, 91] s, p < 0.001). We also observed a reduction in the number of needle insertions from 3 [2, 7] to 2 [1, 4] (p = 0.002), and an improvement aiming correctly at the ESP from 30 (58%) to 46 (88%) (p < 0.001). Forty-nine (94%) of the residents reported to have improved their regional anesthesia knowledge, 38 (73%) perceived an improvement in their technical skills and 46 (88%) of the tra

Introduction Postoperative acute kidney injury (AKI) is a common complication in cardiac surgery. Levels of intravascular haemolysis are strongly associated with postoperative AKI and with prolonged (>90 min) use of cardiopulmonary bypass (CPB). Ferrous plasma haemoglobin released into the circulation acts as a scavenger of nitric oxide (NO) produced by endothelial cells. Consequently, the vascular bioavailability of NO is reduced, leading to vasoconstriction and impaired renal function. In patients with cardiovascular risk factors, the endothelium is dysfunctional and cannot replenish the NO deficit. A previous clinical study in young cardiac surgical patients with rheumatic fever, without evidence of endothelial dysfunction, showed that supplementation of NO gas decreases AKI by converting ferrous plasma haemoglobin to ferric methaemoglobin, thus preserving vascular NO. In this current trial, we hypothesised that 24 hours administration of NO gas will reduce AKI following CPB in patients with endothelial dysfunction. Methods This is a single-centre, randomised (1:1) controlled, parallel-arm superiority trial that includes patients with endothelial dysfunction, stable kidney function and who are undergoing cardiac surgery procedures with an expected CPB duration >90 min. After randomisation, 80 parts per million (ppm) NO (intervention group) or 80 ppm nitrogen (N 2, control group) are added to the gas mixture. Test gases (N 2 or NO) are delivered during CPB and for 24 hours after surgery. The primary study outcome is the occurrence of AKI among study groups. Key secondary outcomes include AKI severity, occurrence of renal replacement therapy, major adverse kidney events at 6 weeks after surgery and mortality. We are recruiting 250 patients, allowing detection of a 35% AKI relative risk reduction, assuming a two-sided error of 0.05. Ethics and dissemination The Partners Human Research Committee approved this trial. Recruitment began in February 2017. Dissemina

Background: The effect of nitric oxide (NO) on renal function is controversial in critical illness. We performed a systematic meta-analysis and trial sequential analysis to determine the effect of NO gas on renal function and other clinical outcomes in patients requiring cardiopulmonary bypass (CPB). The primary outcome was the relative risk (RR) of acute kidney injury (AKI), irrespective of the AKI stage. The secondary outcome was the mean difference (MD) in the length of ICU and hospital stay, the RR of postoperative hemorrhage, and the MD in levels of methemoglobin. Trial sequential analysis (TSA) was performed for the primary outcome. Results: 54 trials were assessed for eligibility and 5 studies (579 patients) were eligible for meta-analysis. NO was associated with reduced risk of AKI (RR 0.76, 95% confidential interval [CI], 0.62 to 0.93, I2 = 0%). In the subgroup analysis by NO initiation timing, NO did not decrease the risk of AKI when started at the end of CPB (RR 1.20, 95% CI 0.52–2.78, I2 = 0%). However, NO did significantly reduce the risk of AKI when started from the beginning of CPB (RR 0.71, 95% CI 0.54–0.94, I2 = 10%). We conducted TSA based on three trials (400 patients) using KDIGO criteria and with low risk of bias. TSA indicated a CI of 0.50–1.02 and an optimal information size of 589 patients, suggesting a lack of definitive conclusion. Furthermore, NO does not affect the length of ICU and hospital stay or the risk of postoperative hemorrhage. NO slightly increased the level of methemoglobin at the end of CPB (MD 0.52%, 95% CI 0.27–0.78%, I2 = 90%), but it was clinically negligible. Conclusions: NO appeared to reduce the risk of postoperative AKI in patients undergoing CPB. Additional studies are required to ascertain the finding and further determine the dosage, timing and duration of NO administration.

OBJECTIVE: To investigate whether individualized optimization of mechanical ventilation through the implementation of a lung rescue team could reduce the need for venovenous extracorporeal membrane oxygenation in patients with obesity and acute respiratory distress syndrome and decrease ICU and hospital length of stay and mortality. DESIGN: Single-center, retrospective study at the Massachusetts General Hospital from June 2015 to June 2019. PATIENTS: All patients with obesity and acute respiratory distress syndrome who were referred for venovenous extracorporeal membrane oxygenation evaluation due to hypoxemic respiratory failure. INTERVENTION: Evaluation and individualized optimization of mechanical ventilation by the lung rescue team before the decision to proceed with venovenous extracorporeal membrane oxygenation. The control group was those patients managed according to hospital standard of care without lung rescue team evaluation. MEASUREMENT AND MAIN RESULTS: All 20 patients (100%) allocated in the control group received venovenous extracorporeal membrane oxygenation, whereas 10 of 13 patients (77%) evaluated by the lung rescue team did not receive venovenous extracorporeal membrane oxygenation. Patients who underwent lung rescue team evaluation had a shorter duration of mechanical ventilation (p = 0.03) and shorter ICU length of stay (p = 0.03). There were no differences between groups in in-hospital, 30-day, or 1-year mortality. CONCLUSIONS: In this hypothesis-generating study, individualized optimization of mechanical ventilation of patients with acute respiratory distress syndrome and obesity by a lung rescue team was associated with a decrease in the utilization of venovenous extracorporeal membrane oxygenation, duration of mechanical ventilation, and ICU length of stay. Mortality was not modified by the lung rescue team intervention.

Patients with sepsis have typically reduced concentrations of hemoglobin and albumin, the major components of noncarbonic buffer power (b ). This could expose patients to high pH variations during acid-base disorders. The objective of this study is to compare, in vitro, noncarbonic b of patients with sepsis with that of healthy volunteers, and evaluate its distinct components. Whole blood and isolated plasma of 18 patients with sepsis and 18 controls were equilibrated with different CO2 mixtures. Blood gases, pH, and electrolytes were measured. Noncarbonic b and noncarbonic b due to variations in strong ion difference (b SID) were calculated for whole blood. Noncarbonic b and noncarbonic b normalized for albumin concentrations (b NORM) were calculated for isolated plasma. Representative values at pH = 7.40 were compared. Albumin proteoforms were evaluated via two-dimensional electrophoresis. Hemoglobin and albumin concentrations were significantly lower in patients with sepsis. Patients with sepsis had lower noncarbonic b both of whole blood (22.0 ± 1.9 vs. 31.6 ± 2.1 mmol/L, P < 0.01) and plasma (0.5 ± 1.0 vs. 3.7 ± 0.8 mmol/L, P < 0.01). Noncarbonic b SID was lower in patients (16.8 ± 1.9 vs. 24.4 ± 1.9 mmol/L, P < 0.01) and strongly correlated with hemoglobin concentration (r = 0.94, P < 0.01). Noncarbonic b NORM was lower in patients [0.01 (-0.01 to 0.04) vs. 0.08 (0.06–0.09) mmol/g, P < 0.01]. Patients with sepsis and controls showed different amounts of albumin proteoforms. Patients with sepsis are exposed to higher pH variations for any given change in CO2 due to lower concentrations of noncarbonic buffers and, possibly, an altered buffering function of albumin. In both patients with sepsis and healthy controls, electrolyte shifts are the major buffering mechanism during respiratory acid-base disorders. NEW & NOTEWORTHY Patients with sepsis are poorly protected against acute respiratory acid-base derangements due to a lower noncarbonic buff

Rationale: Acidemia is a severe condition among critically ill patients. Despite lack of evidence, sodium bicarbonate is frequently used to correct pH; however, its administration is burdened by several side effects. We hypothesized that the reduction of plasma chloride concentration could be an alternative strategy to correct acidemia.Objectives: To evaluate feasibility, safety, and effectiveness of a novel strategy to correct acidemia through extracorporeal chloride removal by electrodialysis.Methods: Ten swine (six treated and four control animals) were sedated, mechanically ventilated and connected to an extracorporeal electrodialysis device capable of selectively removing chloride. In random order, an arterial pH of 7.15 was induced either through reduction of ventilation (respiratory acidosis) or through lactic acid infusion (metabolic acidosis). Acidosis was subsequently sustained for 12-14 hours. In treatment pigs, soon after reaching target acidemia, electrodialysis was started to restore pH.Measurements and Main Results: During respiratory acidosis, electrodialysis reduced plasma chloride concentration by 26 ± 5 mEq/L within 6 hours (final pH = 7.36 ± 0.04). Control animals exhibited incomplete and slower compensatory response to respiratory acidosis (final pH = 7.29 ± 0.03; P < 0.001). During metabolic acidosis, electrodialysis reduced plasma chloride concentration by 15 ± 3 mEq/L within 4 hours (final pH = 7.34 ± 0.07). No effective compensatory response occurred in control animals (final pH = 7.11 ± 0.08; P < 0.001). No complications occurred.Conclusions: We described the first in vivo application of an extracorporeal system targeted to correct severe acidemia by lowering plasma chloride concentration. Extracorporeal chloride removal by electrodialysis proved to be feasible, safe, and effective. Further studies are warranted to assess its performance in the presence of impaired respiratory and renal functions.