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Roberto Chalela,1–3 Lluis Gallart,4,5 Sergi Pascual-Guardia,1–3 Antonio Sancho-Muñoz,1,2 Joaquim Gea,1–3 Mauricio Orozco-Levi1–3 1Respiratory Medicine Department, Hospital del Mar-IMIM, Barcelona, Spain; 2Department CEXS, Universitat Pompeu Fabra, Barcelona, Spain; 3CIBERES, ISCIII, Barcelona, Spain; 4Department of Anesthesia, Hospital del Mar-IMIM, Barcelona, Spain; 5Universitat Autònoma de Barcelona, Barcelona, Spain Background: Hypercapnic encephalopathy is relatively frequent in severe exacerbations of COPD (ECOPDs), with its intensity usually being evaluated through clinical scales. Bispectral index (BIS) is a relatively new technique, based on the analysis of the electroencephalographic signal, which provides a good approximation to the level of consciousness, having already been validated in anesthesia. Objective: The objective of the study was to evaluate the utility of BIS in the assessment of the intensity of hypercapnic encephalopathy in ECOPD patients. Patients and methods: A total of ten ECOPD patients were included, and the level of brain activity was assessed using BIS and different scales: Glasgow Coma Scale, Ramsay Sedation Scale (RSS), and Richmond Agitation–Sedation Scale. The evaluation was performed both in the acute phase and 3 months after discharge. Results: BIS was recorded for a total of about 600 minutes. During ECOPD, BIS values ranged from 58.8 (95% CI: 48.6–69) for RSS score of 4 to 92.2 (95% CI: 90.1–94.3) for RSS score of 2. A significant correlation was observed between values obtained with BIS and those from the three scales, although the best fit was for RSS, followed by Glasgow and Richmond (r=-0.757, r=0.701, and r=0.615, respectively; P

Background: The best use of perioperative cardiac biomarkers assessment is still under discussion. Massive postoperative troponin surveillance can result in untenably high workloads and costs for health care systems and potentially harmful interventions for patients. In a cohort of patients at risk for major adverse cardiovascular and cerebrovascular events (MACCEs), we aimed to (1) determine whether preoperative biomarkers can identify patients at major risk for acute myocardial injury in noncardiac surgery, (2) develop a risk model for acute myocardial injury prediction, and (3) propose an algorithm to optimize postoperative troponin surveillance., Methods: Prospective, single-center cohort study enrolling consecutive adult patients (≥45 years) at risk for MACCE scheduled for intermediate-to-high-risk noncardiac surgery. Baseline high-sensitivity troponin T (hsTnT) and N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP), as well as hsTnT on the first 3 postoperative days were obtained. The main outcome was the occurrence of acute myocardial injury. Candidate predictors of acute myocardial injury were baseline concentrations of hsTnT ≥14 ng/L and NT-proBNP ≥300 pg/mL and preoperative and intraoperative variables. A multivariable risk model and a decision curve were constructed., Results: Of 732 patients, 42.1% had elevated hsTnT and 37.3% had elevated NT-proBNP levels at baseline. Acute myocardial injury occurred in 161 patients (22%). Elevated baseline hsTnT, found in 84% of patients with acute myocardial injury, was strongly associated with this outcome: odds ratio (OR), 12.08 (95% confidence interval [CI], 7.78-19.42). Logistic regression identified 6 other independent predictors for acute myocardial injury: age, sex, estimated glomerular filtration rate (eGFR) <45 mL·min -1 ·1.73 m -2 , functional capacity <4 METs or unknown, NT-proBNP ≥300 pg/mL, and estimated intraoperative blood loss. The c -statistic for the risk model was 77% (95% CI, 0.73-0.81). The net benefit of the model began at a risk threshold of 7%., Conclusions: Baseline determination of cardiac biomarkers in patients at risk for MACCE shortly before intermediate- or high-risk noncardiac surgery helps identify those with the highest risk for acute myocardial injury. A baseline hsTnT ≥14 ng/L indicates the need for postoperative troponin surveillance. In patients with baseline hsTnT <14 ng/L, our 6-predictor model will identify additional patients at risk for acute myocardial injury who may also benefit from postoperative surveillance., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 International Anesthesia Research Society.)

Background: The safety of anaesthesia has improved as a result of better control of anaesthetic depth. However, conventional monitoring does not inform on the nature of nociceptive processes during unconsciousness. A means of inferring the quality of potentially painful experiences could derive from analysis of brain activity using neuroimaging. We have evaluated the dose effects of remifentanil on brain response to noxious stimuli during deep sedation and spontaneous breathing., Methods: Optimal data were obtained in 26 healthy subjects. Pressure stimulation that proved to be moderately painful before the experiment was applied to the thumbnail. Functional MRI was acquired in 4-min periods at low (0.5 ng ml -1 ), medium (1 ng ml -1 ), and high (1.5 ng ml -1 ) target plasma concentrations of remifentanil at a stable background infusion of propofol adjusted to induce a state of light unconsciousness., Results: At low remifentanil doses, we observed partial activation in brain areas processing sensory-discriminative and emotional-affective aspects of pain. At medium doses, relevant changes were identified in structures highly sensitive to general brain arousal, including the brainstem, cerebellum, thalamus, auditory and visual cortices, and the frontal lobe. At high doses, no significant activation was observed., Conclusions: The response to moderately intense focal pressure in pain-related brain networks is effectively eliminated with safe remifentanil doses. However, the safety margin in deep sedation-analgesia would be narrowed in minimising not only nociceptive responses, but also arousal-related biological stress., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Understanding the brain changes occurring during aging can provide new insights for developing treatments that alleviate or reverse cognitive decline. Neurostimulation techniques have emerged as potential treatments for brain disorders and to improve cognitive functions. Nevertheless, given the ethical restrictions of neurostimulation approaches, in silico perturbation protocols based on causal whole-brain models are fundamental to gaining a mechanistic understanding of brain dynamics. Furthermore, this strategy could serve to identify neurophysiological biomarkers differentiating between age groups through an exhaustive exploration of the global effect of all possible local perturbations. Here, we used a resting-state fMRI dataset divided into middle-aged (N =310, <65 years) and older adults (N =310, $\geq $65) to characterize brain states in each group as a probabilistic metastable substate (PMS) space. We showed that the older group exhibited a reduced capability to access a metastable substate that overlaps with the rich club. Then, we fitted the PMS to a whole-brain model and applied in silico stimulations in each node to force transitions from the brain states of the older- to the middle-aged group. We found that the precuneus was the best stimulation target. Overall, these findings could have important implications for designing neurostimulation interventions for reversing the effects of aging on whole-brain dynamics., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

After falling asleep, the brain needs to detach from waking activity and reorganize into a functionally distinct state. A functional MRI (fMRI) study has recently revealed that the transition to unconsciousness induced by propofol involves a global decline of brain activity followed by a transient reduction in cortico-subcortical coupling. We have analyzed the relationships between transitional brain activity and breathing changes as one example of a vital function that needs the brain to readapt. Thirty healthy participants were originally examined. The analysis involved the correlation between breathing and fMRI signal upon loss of consciousness. We proposed that a decrease in ventilation would be coupled to the initial decline in fMRI signal in brain areas relevant for modulating breathing in the awake state, and that the subsequent recovery would be coupled to fMRI signal in structures relevant for controlling breathing during the unconscious state. Results showed that a slight reduction in breathing from wakefulness to unconsciousness was distinctively associated with decreased activity in brain systems underlying different aspects of consciousness including the prefrontal cortex, the default mode network and somatosensory areas. Breathing recovery was distinctively coupled to activity in deep brain structures controlling basic behaviors such as the hypothalamus and amygdala. Activity in the brainstem, cerebellum and hippocampus was associated with breathing variations in both states. Therefore, our brain maps illustrate potential drives to breathe, unique to wakefulness, in the form of brain systems underlying cognitive awareness, self-awareness and sensory awareness, and to unconsciousness involving structures controlling instinctive and homeostatic behaviors., Competing Interests: Declaration of Competing Interest The authors report no financial interests or potential conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Normal aging causes disruptions in the brain that can lead to cognitive decline. Resting-state functional magnetic resonance imaging studies have found significant age-related alterations in functional connectivity across various networks. Nevertheless, most of the studies have focused mainly on static functional connectivity. Studying the dynamics of resting-state brain activity across the whole-brain functional network can provide a better characterization of age-related changes. Here, we employed two data-driven whole-brain approaches based on the phase synchronization of blood-oxygen-level-dependent signals to analyze resting-state fMRI data from 620 subjects divided into two groups (middle-age group (n = 310); age range, 50-64 years versus older group (n = 310); age range, 65-91 years). Applying the intrinsic-ignition framework to assess the effect of spontaneous local activation events on local-global integration, we found that the older group showed higher intrinsic ignition across the whole-brain functional network, but lower metastability. Using Leading Eigenvector Dynamics Analysis, we found that the older group showed reduced ability to access a metastable substate that closely overlaps with the so-called rich club. These findings suggest that functional whole-brain dynamics are altered in aging, probably due to a deficiency in a metastable substate that is key for efficient global communication in the brain., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Choosing perioperative suitable treatments requires reliable and valid outcome measurements. The International Pain Outcome (IPO) questionnaire has been widely used for quality improvement and research purposes within the PAIN-OUT network that has collected more than 550,000 data sets of postoperative patients in 200 hospitals worldwide. Our aim is to confirm psychometric properties of the Spanish version of the IPO questionnaire and its invariance by pain predictors., Method: Sample included 4014 participants within a large age range, who underwent different surgical procedures. Confirmatory factor analysis (CFA) assessed internal structure, considering invariance by sex, age, procedure, smoking, obesity, affective disorder, and chronic pain. Incremental predictive validity of factor scores on question would have liked more pain treatment and opioid requirement was also estimated with logistic binary regression., Results: Confirmatory factor analysis verified original structure in 3 factors measuring pain intensity and interference (F1), adverse effects (F2), and perceptions of care (F3), with good internal consistency. Multigroup CFA analysis confirmed invariance by assessed pain predictors. Good incremental predictive capacity to identify would have liked more pain treatment was achieved., Conclusion: Our study confirms the factor structure, supports reliability, and adds some evidence of convergent validity of the Spanish adaptation of the IPO questionnaire. The sum of scores in its main factors serves a global outcome analysis tool. Low scores in F1 and F2 with high scores in F3 would indicate optimal quality of care., Competing Interests: The authors have no conflicts of interest to declare.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)

Background: Cough pressure, an expression of expiratory muscle strength, is usually measured with esophageal or gastric balloons, but these invasive catheters can be uncomfortable for the patient or their placement impractical. Because pressure in the thorax and abdomen are expected to be similar during a cough, we hypothesized that measurement at other thoracic or abdominal locations might also be similar as well as useful in clinical scenarios. This study aimed to compare cough pressures measured at thoracic and abdominal sites that could serve as alternatives to esophageal pressures (P es )., Methods: Nine patients scheduled for laparotomy were asked to cough as forcefully as possible from total lung capacity in supine position. Three cough maneuvers were performed while P es (the gold standard) as well as gastric, central venous, bladder and rectal pressures (P ga , P cv , P bl , and P rec , respectively) were measured simultaneously. The intraclass correlation coefficient (ICC) was used to evaluate the repeatability of the measurements in each patient at each site and evaluate agreement between alternative sites (P ga , P cv , P bl , and P rec ) and P es . Bland-Altman plots were used to compare P es and the measurements at the other sites., Results: Median (first quartile, third quartile) maximum pressures were as follows: P es 112 (89,148), P ga 105 (92,156), P cv 102 (91,149), P bl 118 (93,157), and P rec 103 (88,150) cmH 2 O. The ICCs showed excellent within-site repeatability of the measurements (p < 0.001) and excellent agreement between alternative sites and P es (p < 0.004). The Bland-Altman plots showed minimal differences between P es , P ga , P cv , and P rec . However, P bl was higher than the other pressures in most patients, and the difference between P es and P bl was slightly larger., Conclusions: Cough pressure can be measured in the esophagus, stomach, superior vena cava or rectum, since their values are similar. It can also be measured in the bladder, although the value will be slightly higher. These results potentially facilitate the assessment of dynamic expiratory muscle strength with fewer invasive catheter placements in most hospitalized patients, thus providing an option that will be particularly useful in those undergoing thoracic or abdominal surgery., Trial Registration: NCT02957045 registered at November 7, 2016. Retrospectively registered.

Background: No externally validated risk score for postoperative pulmonary complications (PPCs) is currently available. The authors tested the generalizability of the Assess Respiratory Risk in Surgical Patients in Catalonia risk score for PPCs in a large European cohort (Prospective Evaluation of a RIsk Score for postoperative pulmonary COmPlications in Europe)., Methods: Sixty-three centers recruited 5,859 surgical patients receiving general, neuraxial, or plexus block anesthesia. The Assess Respiratory Risk in Surgical Patients in Catalonia factors (age, preoperative arterial oxygen saturation in air, acute respiratory infection during the previous month, preoperative anemia, upper abdominal or intrathoracic surgery, surgical duration, and emergency surgery) were recorded, along with PPC occurrence (respiratory infection or failure, bronchospasm, atelectasis, pleural effusion, pneumothorax, or aspiration pneumonitis). Discrimination, calibration, and diagnostic accuracy measures of the Assess Respiratory Risk in Surgical Patients in Catalonia score's performance were calculated for the Prospective Evaluation of a RIsk Score for postoperative pulmonary COmPlications in Europe cohort and three subsamples: Spain, Western Europe, and Eastern Europe., Results: The full Prospective Evaluation of a RIsk Score for postoperative pulmonary COmPlications in Europe data set included 5,099 patients; 725 PPCs were recorded for 404 patients (7.9%). The score's discrimination was good: c-statistic (95% CI), 0.80 (0.78 to 0.82). Predicted versus observed PPC rates for low, intermediate, and high risk were 0.87 and 3.39% (score <26), 7.82 and 12.98% (≥ 26 and <45), and 38.13 and 38.01% (≥ 45), respectively; the positive likelihood ratio for a score of 45 or greater was 7.12 (5.93 to 8.56). The score performed best in the Western Europe subsample-c-statistic, 0.87 (0.83 to 0.90) and positive likelihood ratio, 11.56 (8.63 to 15.47)-and worst in the Eastern Europe subsample. The predicted (5.5%) and observed (5.7%) PPC rates were most similar in the Spain subsample., Conclusions: The Assess Respiratory Risk in Surgical Patients in Catalonia score predicts three levels of PPC risk in hospitals outside the development setting. Performance differs between geographic areas.

Background and Aims: This was a safety and efficacy pharmacogenetic study of a previously performed randomized trial which compared the effectiveness of treatment of hepatitis C virus infection with pegylated interferon alpha (pegIFNα) 2a vs. 2b, both with ribavirin, for 48 weeks, in HCV-HIV coinfected patients., Methods: The study groups were made of 99 patients (efficacy pharmacogenetic substudy) and of 114 patients (safety pharmacogenetic substudy). Polymorphisms in the following candidate genes IL28B, IL6, IL10, TNFα, IFNγ, CCL5, MxA, OAS1, SOCS3, CTLA4 and ITPA were assessed. Genotyping was carried out using Sequenom iPLEX-Gold, a single-base extension polymerase chain reaction. Efficacy end-points assessed were: rapid, early and sustained virological response (RVR, EVR and SVR, respectively). Safety end-points assessed were: anemia, neutropenia, thrombocytopenia, flu-like syndrome, gastrointestinal disturbances and depression. Chi square test, Student's T test, Mann-Whitney U test and logistic regression were used for statistic analyses., Results: As efficacy is concerned, IL28B and CTLA4 gene polymorphisms were associated with RVR (p<0.05 for both comparisons). Nevertheless, only polymorphism in the IL28B gene was associated with SVR (p = 0.004). In the multivariate analysis, the only gene independently associated with SVR was IL28B (OR 2.61, 95%CI 1.2-5.6, p = 0.01). With respect to safety, there were no significant associations between flu-like syndrome or depression and the genetic variants studied. Gastrointestinal disturbances were associated with ITPA gene polymorphism (p = 0.04). Anemia was associated with OAS1 and CTLA4 gene polymorphisms (p = 0.049 and p = 0.045, respectively), neutropenia and thromobocytopenia were associated with SOCS3 gene polymorphism (p = 0.02 and p = 0.002, respectively). In the multivariate analysis, the associations of the SOCS3 gene polymorphism with neutropenia (OR 0.26, 95%CI 0.09-0.75, p = 0.01) and thrombocytopenia (OR 0.07, 95%CI 0.008-0.57, p = 0.01) remained significant., Conclusions: In HCV-HIV coinfected patients treated with PegIFNα and ribavirin, SVR is associated with IL28B rs8099917 polymorphism. HCV treatment-induced neutropenia and thrombocytopenia are associated with SOCS3 rs4969170 polymorphism.

Background: Current knowledge of the risk for postoperative pulmonary complications (PPCs) rests on studies that narrowly selected patients and procedures. Hypothesizing that PPC occurrence could be predicted from a reduced set of perioperative variables, we aimed to develop a predictive index for a broad surgical population., Methods: Patients undergoing surgical procedures given general, neuraxial, or regional anesthesia in 59 hospitals were randomly selected for this prospective, multicenter study. The main outcome was the development of at least one of the following: respiratory infection, respiratory failure, bronchospasm, atelectasis, pleural effusion, pneumothorax, or aspiration pneumonitis. The cohort was randomly divided into a development subsample to construct a logistic regression model and a validation subsample. A PPC predictive index was constructed., Results: Of 2,464 patients studied, 252 events were observed in 123 (5%). Thirty-day mortality was higher in patients with a PPC (19.5%; 95% [CI], 12.5-26.5%) than in those without a PPC (0.5%; 95% CI, 0.2-0.8%). Regression modeling identified seven independent risk factors: low preoperative arterial oxygen saturation, acute respiratory infection during the previous month, age, preoperative anemia, upper abdominal or intrathoracic surgery, surgical duration of at least 2 h, and emergency surgery. The area under the receiver operating characteristic curve was 90% (95% CI, 85-94%) for the development subsample and 88% (95% CI, 84-93%) for the validation subsample., Conclusion: The risk index based on seven objective, easily assessed factors has excellent discriminative ability. The index can be used to assess individual risk of PPC and focus further research on measures to improve patient care.

The aim of the study was to evaluate human plasma circulating levels of adipocyte fatty acid-binding protein (A-FABP) and its relationship with proinflammatory adipocytokines and insulin resistance in a severely obese cohort, before and 1 year after a surgical gastric bypass. Plasmatic levels of A-FABP were measured in 77 morbid-obese women before and 1 year after bariatric surgery. Anthropometrical parameters and body composition by bioelectrical impedance analysis were determined. Circulating levels of soluble tumor necrosis factor receptor 2 (sTNFR2), Interleukin 18 (IL-18), adiponectin, and high-sensitive C-reactive protein (hsCRP) were also analyzed. Insulin resistance by homeostasis model assessment of insulin resistance (HOMA-IR) index was calculated. After massive weight loss, A-FABP plasmatic levels decreased significantly [7.6 (8.9) vs. 4.3 (5.1); P<0,001] but no association with circulating adipokines or proinflammatory cytokines, both at the beginning and at the end of follow-up, was observed. A decrease in sTNFR2, IL-18, hsCRP, and an increase in adiponectin levels (P<0.001 in all cases) were observed after the gastric bypass. HOMA-IR index improved 1 year after surgery and after multiple regression analysis remained associated with A-FABP after controlling for confounding variables (beta=0.322, P=0.014; R2 for the model 0.281). In morbid-obese women, plasma A-FABP concentrations were dramatically reduced after gastric bypass surgery. After weight loss this protein contributed to HOMA-IR index independently of proinflammatory/antinflammatory cytokine profile. Further studies are warranted to elucidate the role of A-FABP in the pathogenesis of insulin resistance in morbid obesity.

Chronic low-grade activation of the immune system may play a role in the pathogenesis of type-2 diabetes mellitus (T2DM). Interleukin-6 (IL6), a powerful inducer of hepatic acute phase response, has been implicated in the etiology of insulin resistance and T2DM. Recently, an IL6 promoter polymorphism (G/C) at position -174 was found to be associated with measures of insulin sensitivity. Because we have previously found an association between high IL6 levels and insulin resistance in both Pima Indians - a population with high rates of insulin resistance and T2DM - and Caucasians, we aimed to assess whether the IL6 promoter polymorphism is associated with T2DM in these populations. We genotyped the IL6 (-174) G/C polymorphism using pyrosequencing in 463 Native Americans and by PCR-RFLP in 329 Spanish Caucasians. Among the Spanish Caucasian subjects, there was a significant difference in genotypic distribution between diabetic and non-diabetic subjects (P=0.028); the GG genotype was more common in diabetic (0.40) than in non-diabetic (0.29) subjects. The G allele was much more frequent in the Native American sample, and among a sample of 143 cases and 145 controls, the GG genotype was significantly more common in diabetic subjects (P=0.019). When this sample population was stratified according to ethnic heritage, all 211 subjects who were of full Pima Indian heritage had the GG genotype, whereas in the 77 American Indian subjects with non-Pima admixture, T2DM was associated with IL6 genotype (P=0.001). These findings are consistent with a role for genetic determinants of inflammation in the development of T2DM in both Native Americans and Caucasians.

Inhaled nitric oxide (iNO), a selective pulmonary vasodilator and intravenously administered almitrine, a selective pulmonary vasoconstrictor, have been shown to increase PaO2 in patients with acute respiratory distress syndrome (ARDS). This prospective study was undertaken to assess the cardiopulmonary effects of combining both drugs. In 48 consecutive patients with early ARDS, cardiorespiratory parameters were measured at control, after iNO 5 ppm, after almitrine 4 micrograms. kg-1. min-1, and after the combination of both drugs. In 30 patients, dose response to 2, 4, and 16 micrograms. kg-1. min-1 of almitrine with and without NO was determined. Almitrine and lactate plasma concentrations were measured in 17 patients. Using pure O2, PaO2 increased by 75 +/- 8 mm Hg after iNO, by 101 +/- 12 mm Hg after almitrine 4 micrograms. kg-1. min-1, and by 175 +/- 18 mm Hg after almitrine combined with iNO (p < 0.001). In 63% of the patients, PaO2 increased by more than 100% with the combination of both drugs. Mean pulmonary artery pressure (Ppa) increased by 1.4 +/- 0.2 mm Hg with almitrine 4 micrograms/kg/ min (p < 0.001) and decreased by 3.4 +/- 0.4 mm Hg with iNO and by 1.5 +/- 0.3 mm Hg with the combination (p < 0.001). The maximum increase in PaO2 was obtained at almitrine concentrations <= 4 micrograms. kg-1. min-1, whereas almitrine increased Ppa dose-dependently. Almitrine plasma concentrations also increased dose-dependently and returned to values close to zero after 12 h. In many patients with early ARDS, the combination of iNO 5 ppm and almitrine 4 micrograms. kg-1. min-1 dramatically increases PaO2 without apparent deleterious effect allowing a rapid reduction in inspired fraction of O2. The long-term consequences of this immediate beneficial effect remain to be determined.

The autosomal dominant multiple endocrine neoplasia type 1 (MEN1) syndrome is characterized by neoplasia of parathyroids, anterior pituitary, and gastrointestinal and pancreatic neuroendocrine tissues. Recently the gene responsible for the MEN1 syndrome has been identified on chromosome region 11q13. Most of the described mutations are nucleotide substitutions and small deletions affecting exons 2 and 3, causing protein truncation. Only one mutation in exon 5 has been found, and this corresponds to a MEN1 sporadic case. Small insertions are also rare. We studied a MENI family composed of five members, two of whom were clinically affected. We found a new germline 1 basepair insertional mutation affecting the exon 5 of the MEN1 gene in the two members affected in this MEN1 family.

Background: Inhaled nitric oxide (NO) improves arterial oxygenation in patients with acute lung injury (ALI) by selectively dilating pulmonary vessels perfusing ventilated lung areas. It can be hypothesized that NO uptake from the lung decreases with increasing ventilation perfusion mismatch. This study was undertaken to determine the factors influencing the fluctuation of tracheal NO concentration over the respiratory cycle as an index of NO pulmonary uptake in patients with ALI., Methods: By using a prototype system (Opti-NO) delivering a constant flow of NO only during the inspiratory phase, 3 and 6 ppm of NO were administered during controlled mechanical ventilation into a lung model and to 11 patients with ALI. All patients had a thoracic computed tomography (CT) scan. Based on an analysis of tomographic densities, lungs were divided into three zones: normally aerated (-1.000 to -500 Hounsfield units [HU]), poorly aerated (-500 to -100 HU), and nonaerated (-100 to +100 HU), and the volume of each zone was computed. Concentrations of NO in the inspiratory limb and trachea were continuously measured by a fast-response chemiluminescence apparatus., Results: In the lung model, tracheal NO concentration was stable with minor fluctuation. In contrast, in patients, tracheal NO concentration fluctuated widely during the respiratory cycle (55 +/- 10%). Because uptake of NO from the lungs was absent in the lung model but present in the patients, this fluctuation was considered as an index of pulmonary uptake of NO. This was further substantiated by (1) the coincidence of the peak and minimum tracheal NO concentration with the end-inspiratory and end-expiratory phases, respectively, and (2) continued decrease of tracheal NO concentration during prolonged expiratory phase. In patients with ALI, the fluctuation of tracheal NO concentration expressed as the difference between inspiratory and expiratory NO concentrations divided by inspiratory NO concentration was greater at 6 ppm than at 3 ppm (P < 0.01), was linearly correlated with normally aerated lung volume, inversely correlated with alveolar dead space and with poorly aerated lung volume., Conclusion: In patients with ALI, fluctuation of tracheal NO concentration over the respiratory cycle can be considered as an index of NO uptake from the lungs that depends on aerated lung volume and perfusion of ventilated lung areas. At bedside, it may be used to follow the evolution of ventilation-perfusion mismatch.

Background: Permissive hypercapnia is a ventilatory strategy aimed at avoiding lung volutrauma in patients with severe acute respiratory distress syndrome (ARDS). Expiratory washout (EWO) is a modality of tracheal gas insufflation that enhances carbon dioxide removal during mechanical ventilation by reducing dead space. The goal of this prospective study was to determine the efficacy of EWO in reducing the partial pressure of carbon dioxide (PaCO2) in patients with severe ARDS treated using permissive hypercapnia., Methods: Seven critically ill patients with severe ARDS (lung injury severity score, 3.1 +/- 0.3) and no contraindications for permissive hypercapnia were studied. On the first day, hemodynamic and respiratory parameters were measured and the extent of lung hyperdensities was assessed using computed tomography. A positive end-expiratory pressure equal to the opening pressure identified on the pressure-volume curve was applied. Tidal volume was reduced until a plateau airway pressure of 25 cm H2O was reached. On the second day, after implementation of permissive hypercapnia, EWO was instituted at a flow of 15 l/min administered during the entire expiratory phase into the trachea through the proximal channel of an endotracheal tube using a ventilator equipped with a special flow generator. Cardiorespiratory parameters were studied under three conditions: permissive hypercapnia, permissive hypercapnia with EWO, and permissive hypercapnia., Results: During permissive hypercapnia, EWO decreased PaCO2 from 76 +/- 4 mmHg to 53 +/- 3 mmHg (-30%; P < 0.0001), increased pH from 7.20 +/- 0.03 to 7.34 +/- 0.04 (P < 0.0001), and increased PaO2 from 205 +/- 28 to 296 +/- 38 mmHg (P < 0.05). The reduction in PaCO2 was accompanied by an increase in end-inspiratory plateau pressure from 26 +/- 1 to 32 +/- 2 cm H2O (P = 0.001). Expiratory washout also decreased cardiac index from 4.6 +/- 0.4 to 3.7 +/- 0.3 l.min-1.m-2 (P < 0.01), mean pulmonary arterial pressure from 28 +/- 2 to 25 +/- 2 mmHg (P < 0.01), and true pulmonary shunt from 47 +/- 2 to 36 +/- 3% (P < 0.01)., Conclusions: Expiratory washout is an effective and easy-to-use ventilatory modality to reduce PaCO2 and increase pH during permissive hypercapnia. However, it significantly increases airway pressures and lung volume through expiratory flow limitation, reexposing some patients to a risk of lung volutrauma if the extrinsic positive end-expiratory pressure is not substantially reduced.

BACKGROUND: The aim of this prospective study was to assess whether the presence of septic shock could influence the dose response to inhaled nitric oxide (NO) in NO-responding patients with adult respiratory distress syndrome (ARDS). RESULTS: Eight patients with ARDS and without septic shock (PaO2 = 95 +/- 16 mmHg, PEEP = 0, FiO2 = 1.0), and eight patients with ARDS and septic shock (PaO2 = 88 +/- 11 mmHg, PEEP = 0, FiO2 = 1.0) receiving exclusively norepinephrine were studied. All responded to 15 ppm inhaled NO with an increase in PaO2 of at least 40 mmHg, at FiO2 1.0 and PEEP 10 cmH2O. Inspiratory intratracheal NO concentrations were recorded continuously using a fast response time chemiluminescence apparatus. Seven inspiratory NO concentrations were randomly administered: 0.15, 0.45, 1.5, 4.5, 15, 45 and 150 ppm. In both groups, NO induced a dose-dependent decrease in mean pulmonary artery pressure (MPAP), pulmonary vascular resistance index (PVRI), and venous admixture (QVA/QT), and a dose-dependent increase in PaO2/FiO2 (P

Background: Several reports suggest that interpleural local anesthetics may have deleterious effects on respiratory function. The current study investigated the effects of interpleural bupivacaine on human respiratory muscles and lung function., Methods: Thirteen patients (55 +/- 4 yr old) with normal respiratory function and scheduled for cholecystectomy entered the study before surgery. Respiratory parameters were compared before and after the interpleural administration of 20 ml 0.5% bupivacaine plus 1:200,000 epinephrine while patients were supine; we evaluated breathing pattern, dynamic and static lung volumes, airway conductance, maximal inspiratory pressures (at the mouth; at the esophagus [Pessniff]; at the abdomen [Pgasniff]; and transdiaphragmatic [Pdisniff]), functional reserve (tension-time index) of the diaphragm, and maximal expiratory pressures (at the mouth; at the esophagus [Pescough]; and at the abdomen [Pgacough]). Hemoglobin oxygen saturation by pulse oximetry, heart rate, and mean arterial pressure were continuously monitored., Results: Respiratory rate (15 +/- 1 to 19 +/- 1 breaths/min; P < 0.01) and heart rate (78 +/- 3 to 83 +/- 3 beats/min; P < 0.01) were slightly increased. Dynamic and static lung volumes, airway conductance, hemoglobin saturation, and the remaining breathing pattern parameters were unchanged. Regarding respiratory muscles, maximal inspiratory pressure at the mouth, Pessniff, and tension-time index of the diaphragm did not change. Pdisniff decreased slightly (102 +/- 10 to 92 +/- 10 cmH2O; P < 0.05) because of a change in Pgasniff (24.2 +/- 7.4 to 18.4 +/- 6.8 cmH2O; P < 0.05). Maximal expiratory pressure at the mouth remained unaltered, but Pgacough decreased (108 +/- 10 to 92 +/- 8 cmH2O; P < 0.01), and Pescough showed a trend to decrease (92 +/- 13 to 78 +/- 10 cmH2O; P = 0.074)., Conclusions: In our experimental conditions, interpleural bupivacaine did not significantly change lung function or inspiratory muscle strength but induced a slight decrease in abdominal muscle strength. Although this effect was minimal, its clinical relevance needs to be evaluated further in patients with impaired respiratory function.