Combining the Physical-Chemical Approach with Standard Base Excess to Understand the Compensation of Respiratory Acid-Base Derangements: An Individual Participant Meta-analysis Approach to Data from Multiple Canine and Human Experiments.

BACKGROUND: Several studies explored the interdependence between Paco2 and bicarbonate during respiratory acid-base derangements. The authors aimed to reframe the bicarbonate adaptation to respiratory disorders according to the physical-chemical approach, hypothesizing that (1) bicarbonate concentration during respiratory derangements is associated with strong ion difference; and (2) during acute respiratory disorders, strong ion difference changes are not associated with standard base excess. METHODS: This is an individual participant data meta-analysis from multiple canine and human experiments published up to April 29, 2021. Studies testing the effect of acute or chronic respiratory derangements and reporting the variations of Paco2, bicarbonate, and electrolytes were analyzed. Strong ion difference and standard base excess were calculated. RESULTS: Eleven studies were included. Paco2 ranged between 21 and 142 mmHg, while bicarbonate and strong ion difference ranged between 12.3 and 43.8 mM, and 32.6 and 60.0 mEq/l, respectively. Bicarbonate changes were linearly associated with the strong ion difference variation in acute and chronic respiratory derangement (ß-coefficient, 1.2; 95% CI, 1.2 to 1.3; P < 0.001). In the acute setting, sodium variations justified approximately 80% of strong ion difference change, while a similar percentage of chloride variation was responsible for chronic adaptations. In the acute setting, strong ion difference variation was not associated with standard base excess changes (ß-coefficient, -0.02; 95% CI, -0.11 to 0.07; P = 0.719), while a positive linear association was present in chronic studies (ß-coefficient, 1.04; 95% CI, 0.84 to 1.24; P < 0.001). CONCLUSIONS: The bicarbonate adaptation that follows primary respiratory alterations is associated with variations of strong ion difference. In the acute phase, the variation in strong ion difference is mainly due to sodium variations and is not paralleled by modifications of standard base excess. In the chronic setting, strong ion difference changes are due to chloride variations and are mirrored by standard base excess.

Calcium-Citrate Anticoagulation during Continuous Renal Replacement Therapy in Patients with Metformin Intoxication: A Case Series, Mathematical Estimation of Citrate Accumulation, and Literature Review.

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.

Cerebrospinal fluid and arterial acid-base equilibria in spontaneously breathing third-trimester pregnant women.

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 ( [Formula: see text] ), 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 [Formula: see text] <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. CLINICAL TRIAL REGISTRATION: NCT03496311.

Veno-venous extracorporeal blood phototherapy increases the rate of carbon monoxide (CO) elimination in CO-poisoned pigs.

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 rates did not alter CO elimination in one pass through the device. Increases in irradiance up to 214 mW/cm2 were associated with an increased rate of CO elimination. The photo-ECMO device was effective over a range of blood flow rates and with higher blood flow rates, more CO was eliminated. A photo-ECMO system composed of six photo-ECMO devices removed CO faster from CO-poisoned blood than a single photo-ECMO device. In a CO-poisoned pig, the photo-ECMO system increased the rate of CO elimination without significantly increasing the animal's body temperature or causing hemodynamic instability. CONCLUSION: In this study, we developed a photo-ECMO system and demonstrated its ability to remove CO from CO-poisoned 45-kg pigs. Technical modifications of the photo-ECMO system, including the development of a compact, portable device, will permit treatment of patients with CO poisoning at the scene of their poisoning, during transit to a local emergency room, and in hospitals that lack HBO facilities.

Cerebrospinal Fluid and Arterial Acid-Base Equilibrium of Spontaneously Breathing Patients with Aneurismal Subarachnoid Hemorrhage.

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 SAH have a reduction of CSF SID due to an increased lactate concentration. The resulting localized acidifying effect is compensated by CSF hypocapnia, yielding normal CSF pH values and resulting in a higher incidence of arterial HA.

Free Hemoglobin Ratio as a Novel Biomarker of Acute Kidney Injury After On-Pump Cardiac Surgery: Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with a high risk of postoperative acute kidney injury (AKI). Due to limitations of current diagnostic strategies, we sought to determine whether free hemoglobin (fHb) ratio (ie, levels of fHb at the end of CPB divided by baseline fHb) could predict AKI after on-pump cardiac surgery. METHODS: This is a secondary analysis of a randomized controlled trial comparing the effect of nitric oxide (intervention) versus nitrogen (control) on AKI after cardiac surgery (NCT01802619). A total of 110 adult patients in the control arm were included. First, we determined whether fHb ratio was associated with AKI via multivariable analysis. Second, we verified whether fHb ratio could predict AKI and incorporation of fHb ratio could improve predictive performance at an early stage, compared with prediction using urinary biomarkers alone. We conducted restricted cubic spline in logistic regression for model development. We determined the predictive performance, including area under the receiver-operating-characteristics curve (AUC) and calibration (calibration plot and accuracy, ie, number of correct predictions divided by total number of predictions). We also used AUC test, likelihood ratio test, and net reclassification index (NRI) to compare the predictive performance between competing models (ie, fHb ratio versus neutrophil gelatinase-associated lipocalin [NGAL], N-acetyl-ß-d-glucosaminidase [NAG], and kidney injury molecule-1 [KIM-1], respectively, and incorporation of fHb ratio with NGAL, NAG, and KIM-1 versus urinary biomarkers alone), if applicable. RESULTS: Data stratified by median fHb ratio showed that subjects with an fHb ratio >2.23 presented higher incidence of AKI (80.0% vs 49.1%; P = .001), more need of renal replacement therapy (10.9% vs 0%; P = .036), and higher in-hospital mortality (10.9% vs 0%; P = .036) than subjects with an fHb ratio ≤2.23. fHb ratio was associated with AKI after adjustment for preestablished factors. fHb ratio outperformed urinary biomarkers with the highest AUC of 0.704 (95% confidence interval [CI], 0.592-0.804) and accuracy of 0.714 (95% CI, 0.579-0.804). Incorporation of fHb ratio achieved better discrimination (AUC test, P = .012), calibration (likelihood ratio test, P < .001; accuracy, 0.740 [95% CI, 0.617-0.832] vs 0.632 [95% CI, 0.477-0.748]), and significant prediction increment (NRI, 0.638; 95% CI, 0.269-1.008; P < .001) at an early stage, compared with prediction using urinary biomarkers alone. CONCLUSIONS: Results from this exploratory, hypothesis-generating retrospective, observational study shows that fHb ratio at the end of CPB might be used as a novel, widely applicable biomarker for AKI. The use of fHb ratio might help for an early detection of AKI, compared with prediction based only on urinary biomarkers.

Extracorporeal Chloride Removal by Electrodialysis. A Novel Approach to Correct Acidemia.

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.

Intratracheal injection of nitric oxide, generated from air by pulsed electrical discharge, for the treatment of pulmonary hypertension in awake ambulatory lambs.

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.

Quantitative Computed Tomography and Response to Pronation in COVID-19 ARDS.

BACKGROUND: The use of prone position (PP) has been widespread during the COVID-19 pandemic. Whereas 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 (CT) scan results and gas exchange response to PP in invasively ventilated subjects with COVID-19 ARDS is unknown. The present study aimed to compare baseline quantitative CT results between subjects responding to PP in terms of oxygenation or CO2 clearance and those who did not. METHODS: This was a single-center, retrospective observational study including critically ill, invasively ventilated subjects with COVID-19-related ARDS admitted to the ICUs of Niguarda Hospital between March 2020-November 2021. Blood gas samples were collected before and after PP. Subjects in whom the PaO2 /FIO2 increase was ≥ 20 mm Hg after PP were defined as oxygen responders. CO2 responders were defined when the ventilatory ratio (VR) decreased during PP. Automated quantitative CT 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 O2 responders and 51 (41%) CO2 responders. No difference in quantitative CT characteristics and oxygen were observed between responders and non-responders (tissue mass 1,532 ± 396 g vs 1,654 ± 304 g, P = .28; density -544 ± 109 HU vs -562 ± 58 HU P = .42). Similar findings were observed when dividing the population according to CO2 response (tissue mass 1,551 ± 412 g vs 1,534 ± 377 g, P = .89; density -545 ± 123 HU vs -546 ± 94 HU, P = .99). CONCLUSIONS: Most subjects with COVID-19-related ARDS improved their oxygenation at the first pronation cycle. The study suggests that baseline quantitative CT scan data were not associated with the response to PP in oxygenation or CO2 in mechanically ventilated subjects with COVID-19-related ARDS.

Quantifying pH-induced changes in plasma strong ion difference during experimental acidosis: clinical implications for base excess interpretation.

It is commonly assumed that changes in plasma strong ion difference (SID) result in equal changes in whole blood base excess (BE). However, at varying pH, albumin ionic-binding and transerythrocyte shifts alter the SID of plasma without affecting that of whole blood (SIDwb), i.e., the BE. We hypothesize that, during acidosis, 1) an expected plasma SID (SIDexp) reflecting electrolytes redistribution can be predicted from albumin and hemoglobin's charges, and 2) only deviations in SID from SIDexp reflect changes in SIDwb, and therefore, BE. We equilibrated whole blood of 18 healthy subjects (albumin = 4.8 ± 0.2 g/dL, hemoglobin = 14.2 ± 0.9 g/dL), 18 septic patients with hypoalbuminemia and anemia (albumin = 3.1 ± 0.5 g/dL, hemoglobin = 10.4 ± 0.8 g/dL), and 10 healthy subjects after in vitro-induced isolated anemia (albumin = 5.0 ± 0.2 g/dL, hemoglobin = 7.0 ± 0.9 g/dL) with varying CO2 concentrations (2-20%). Plasma SID increased by 12.7 ± 2.1, 9.3 ± 1.7, and 7.8 ± 1.6 mEq/L, respectively (P < 0.01) and its agreement (bias[limits of agreement]) with SIDexp was strong: 0.5[-1.9; 2.8], 0.9[-0.9; 2.6], and 0.3[-1.4; 2.1] mEq/L, respectively. Separately, we added 7.5 or 15 mEq/L of lactic or hydrochloric acid to whole blood of 10 healthy subjects obtaining BE of -6.6 ± 1.7, -13.4 ± 2.2, -6.8 ± 1.8, and -13.6 ± 2.1 mEq/L, respectively. The agreement between ΔBE and ΔSID was weak (2.6[-1.1; 6.3] mEq/L), worsening with varying CO2 (2-20%): 6.3[-2.7; 15.2] mEq/L. Conversely, ΔSIDwb (the deviation of SID from SIDexp) agreed strongly with ΔBE at both constant and varying CO2: -0.1[-2.0; 1.7], and -0.5[-2.4; 1.5] mEq/L, respectively. We conclude that BE reflects only changes in plasma SID that are not expected from electrolytes redistribution, the latter being predictable from albumin and hemoglobin's charges.NEW & NOTEWORTHY This paper challenges the assumed equivalence between changes in plasma strong ion difference (SID) and whole blood base excess (BE) during in vitro acidosis. We highlight that redistribution of strong ions, in the form of albumin ionic-binding and transerythrocyte shifts, alters SID without affecting BE. We demonstrate that these expected SID alterations are predictable from albumin and hemoglobin's charges, or from the noncarbonic whole blood buffer value, allowing a better interpretation of SID and BE during in vitro acidosis.

Flow generators for helmet CPAP: Which to prefer? A bench study.

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.

PEEP Titration Is Markedly Affected by Trunk Inclination in Mechanically Ventilated Patients with COVID-19 ARDS: A Physiologic, Cross-Over Study.

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.

Non-carbonic buffer power of whole blood is increased in experimental metabolic acidosis: An in-vitro study.

Non-carbonic buffer power (ßNC) of blood is a pivotal concept in acid-base physiology as it is employed in several acid-base evaluation techniques, including the Davenport nomogram and the Van Slyke equation used for Base excess estimation in blood. So far, ßNC has been assumed to be independent of metabolic acid-base status of blood, despite theoretical rationale for the contrary. In the current study, we used CO2 tonometry to assess ßNC in blood samples from 10 healthy volunteers, simultaneously analyzing the electrolyte shifts across the red blood cell membrane as these shifts translate the action of intracellular non-carbonic buffers to plasma. The ßNC of the blood was re-evaluated after experimental induction of metabolic acidosis obtained by adding a moderate or high amount of either hydrochloric or lactic acid to the samples. Moreover, the impact of ßNC and pCO2 on the Base excess of blood was examined. In the control samples, ßNC was 28.0 ± 2.5 mmol/L. In contrast to the traditional assumptions, our data showed that ßNC rose by 0.36 mmol/L for each 1 mEq/l reduction in plasma strong ion difference (p < 0.0001) and was independent of the acid used. This could serve as a protective mechanism that increases the resilience of blood to the combination of metabolic and respiratory acidosis. Sodium and chloride were the only electrolytes whose plasma concentration changed relevantly during CO2 titration. Although no significant difference was found between the electrolyte shifts in the two types of acidosis, we observed a slightly higher rate of chloride change in hyperchloremic acidosis, while the variation of sodium was more pronounced in lactic acidosis. Lastly, we found that the rise of ßNC in metabolic acidosis did not induce a clinically relevant bias in the calculation of Base excess of blood and confirmed that the Base excess of blood was little affected by a wide range of pCO2.

Simulation-Based Medical Education and Training Enhance Anesthesia Residents' Proficiency in Erector Spinae Plane Block.

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 trainees declared to be "satisfied/very satisfied" with the course. Conclusions: A 4-h hands-on course based on SBET may enhance first-year residents' UGRA ability, decrease the number of punctures and time needed to perform the ESP block, and improve the correct aim of the fascia.

The Effect of Filters on CPAP Delivery by Helmet.

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.

Antimicrobial effects of nitric oxide in murine models of Klebsiella pneumonia.

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.