Clinical validation of a capnodynamic method for measuring end-expiratory lung volume in critically ill patients.

RATIONALE: End-expiratory lung volume (EELV) is reduced in mechanically ventilated patients, especially in pathologic conditions. The resulting heterogeneous distribution of ventilation increases the risk for ventilation induced lung injury. Clinical measurement of EELV however, remains difficult. OBJECTIVE: Validation of a novel continuous capnodynamic method based on expired carbon dioxide (CO2) kinetics for measuring EELV in mechanically ventilated critically-ill patients. METHODS: Prospective study of mechanically ventilated patients scheduled for a diagnostic computed tomography exploration. Comparisons were made between absolute and corrected EELVCO2 values, the latter accounting for the amount of CO2 dissolved in lung tissue, with the reference EELV measured by computed tomography (EELVCT). Uncorrected and corrected EELVCO2 was compared with total CT volume (density compartments between - 1000 and 0 Hounsfield units (HU) and functional CT volume, including density compartments of - 1000 to - 200HU eliminating regions of increased shunt. We used comparative statistics including correlations and measurement of accuracy and precision by the Bland Altman method. MEASUREMENTS AND MAIN RESULTS: Of the 46 patients included in the final analysis, 25 had a diagnosis of ARDS (24 of which COVID-19). Both EELVCT and EELVCO2 were significantly reduced (39 and 40% respectively) when compared with theoretical values of functional residual capacity (p < 0.0001). Uncorrected EELVCO2 tended to overestimate EELVCT with a correlation r2 0.58; Bias - 285 and limits of agreement (LoA) (+ 513 to - 1083; 95% CI) ml. Agreement improved for the corrected EELVCO2 to a Bias of - 23 and LoA of (+ 763 to - 716; 95% CI) ml. The best agreement of the method was obtained by comparison of corrected EELVCO2 with functional EELVCT with a r2 of 0.59; Bias - 2.75 (+ 755 to - 761; 95% CI) ml. We did not observe major differences in the performance of the method between ARDS (most of them COVID related) and non-ARDS patients. CONCLUSION: In this first validation in critically ill patients, the capnodynamic method provided good estimates of both total and functional EELV. Bias improved after correcting EELVCO2 for extra-alveolar CO2 content when compared with CT estimated volume. If confirmed in further validations EELVCO2 may become an attractive monitoring option for continuously monitor EELV in critically ill mechanically ventilated patients. TRIAL REGISTRATION: clinicaltrials.gov (NCT04045262).

Capnodynamic monitoring of lung volume and pulmonary blood flow during alveolar recruitment: a prospective observational study in postoperative cardiac patients.

Alveolar recruitment manoeuvres may mitigate ventilation and perfusion mismatch after cardiac surgery. Monitoring the efficacy of recruitment manoeuvres should provide concurrent information on pulmonary and cardiac changes. This study in postoperative cardiac patients applied capnodynamic monitoring of changes in end-expiratory lung volume and effective pulmonary blood flow. Alveolar recruitment was performed by incremental increases in positive end-expiratory pressure (PEEP) to a maximum of 15 cmH2O from a baseline of 5 cmH2O over 30 min. The change in systemic oxygen delivery index after the recruitment manoeuvre was used to identify responders (> 10% increase) with all other changes (≤ 10%) denoting non-responders. Mixed factor ANOVA using Bonferroni correction for multiple comparisons was used to denote significant changes (p < 0.05) reported as mean differences and 95% CI. Changes in end-expiratory lung volume and effective pulmonary blood flow were correlated using Pearson's regression. Twenty-seven (42%) of 64 patients were responders increasing oxygen delivery index by 172 (95% CI 61-2984) mL min-1 m-2 (p < 0.001). End-expiratory lung volume increased by 549 (95% CI 220-1116) mL (p = 0.042) in responders associated with an increase in effective pulmonary blood flow of 1140 (95% CI 435-2146) mL min-1 (p = 0.012) compared to non-responders. A positive correlation (r = 0.79, 95% CI 0.5-0.90, p < 0.001) between increased end-expiratory lung volume and effective pulmonary blood flow was only observed in responders. Changes in oxygen delivery index after lung recruitment were correlated to changes in end-expiratory lung volume (r = 0.39, 95% CI 0.16-0.59, p = 0.002) and effective pulmonary blood flow (r = 0.60, 95% CI 0.41-0.74, p < 0.001). Capnodynamic monitoring of end-expiratory lung volume and effective pulmonary blood flow early in postoperative cardiac patients identified a characteristic parallel increase in both lung volume and perfusion after the recruitment manoeuvre in patients with a significant increase in oxygen delivery.Trial registration This study was registered on ClinicalTrials.gov (NCT05082168, 18th of October 2021).

Autumn destabilization of deep porewater CO2 store in a northern peatland driven by turbulent diffusion.

The deep porewater of northern peatlands stores large amounts of carbon dioxide (CO2). This store is viewed as a stable feature in the peatland CO2 cycle. Here, we report large and rapid fluctuations in deep porewater CO2 concentration recurring every autumn over four consecutive years in a boreal peatland. Estimates of the vertical diffusion of heat indicate that CO2 diffusion occurs at the turbulent rather than molecular rate. The weakening of porewater thermal stratification in autumn likely increases turbulent diffusion, thus fostering a rapid diffusion of deeper porewater CO2 towards the surface where net losses occur. This phenomenon periodically decreases the peat porewater CO2 store by between 29 and 90 g C m-2 throughout autumn, which is comparable to the peatland's annual C-sink. Our results establish the need to consider the role of turbulent diffusion in regularly destabilizing the CO2 store in peat porewater.

Current forest carbon fixation fuels stream CO2 emissions.

Stream CO2 emissions contribute significantly to atmospheric climate forcing. While there are strong indications that groundwater inputs sustain these emissions, the specific biogeochemical pathways and timescales involved in this lateral CO2 export are still obscure. Here, via an extensive radiocarbon (14C) characterisation of CO2 and DOC in stream water and its groundwater sources in an old-growth boreal forest, we demonstrate that the 14C-CO2 is consistently in tune with the current atmospheric 14C-CO2 level and shows little association with the 14C-DOC in the same waters. Our findings thus indicate that stream CO2 emissions act as a shortcut that returns CO2 recently fixed by the forest vegetation to the atmosphere. Our results expose a positive feedback mechanism within the C budget of forested catchments, where stream CO2 emissions will be highly sensitive to changes in forest C allocation patterns associated with climate and land-use changes.

Capnodynamic determination of cardiac output in hypoxia-induced pulmonary hypertension in pigs.

BACKGROUND: Effective pulmonary blood flow (COEPBF) has recently been validated for its ability to measure cardiac output (CO) in children and animals. This study compared COEPBF with the Fick method (COFick) and CO measurements using an invasive pulmonary artery flow probe (COTS). The aim of the study was to validate COEPBF against these reference methods in a porcine model of hypoxia-induced selective pulmonary hypertension. METHODS: Ten anaesthetised mechanically ventilated piglets (median weight 23.9 kg) were exposed to a hypoxic gas mixture inducing selective pulmonary hypertension. Pulmonary hypertension was subsequently reversed with inhaled nitric oxide. Simultaneous recordings of COEPBF, COFick, and COTS were performed throughout the protocol and examined for agreement and trending ability. RESULTS: Overall bias (Bland-Altman) between COEPBF and COTS was 0.2 L min-1 (limits of agreement -0.5 and +0.9 L min-1) with a mean percentage error of 25%. Overall bias between COEPBF and COFick was -0.1 L min-1 (limits of agreement -0.9 and +0.6 L min-1) and a mean percentage error of 25%. The concordance rate was 86% for COEPBF when compared with COTS using a 10% exclusion zone. CONCLUSIONS: Estimation of CO with COEPBF results in values very close to the gold standard reference methods COFick and COTS. COEPBF appears to be an accurate tool for monitoring absolute values and changes in CO during hypoxia-induced pulmonary hypertension and inhaled nitric oxide treatment.

Absence of Disproportionately Enlarged Subarachnoid Space Hydrocephalus, a Sharp Callosal Angle, or Other Morphologic MRI Markers Should Not Be Used to Exclude Patients with Idiopathic Normal Pressure Hydrocephalus from Shunt Surgery.

BACKGROUND AND PURPOSE: Several studies have evaluated the use of MR imaging markers for the prediction of outcome after shunt surgery in idiopathic normal pressure hydrocephalus with conflicting results. Our aim was to investigate the predictive value of a number of earlier proposed morphologic MR imaging markers in a large group of patients with idiopathic normal pressure hydrocephalus. MATERIALS AND METHODS: One hundred sixty-eight patients (mean age, 70 ± 9.3 years) with idiopathic normal pressure hydrocephalus, subjected to standardized quantification of clinical symptoms before and after shunt surgery, were included in the study. Outcome was calculated using a composite score. Preoperative T1, FLAIR, and flow-sensitive images were analyzed regarding the presence of 13 different morphologic MR imaging markers. RESULTS: The median Evans index was 0.41 (interquartile range, 0.37-0.44). All patients had an aqueductal flow void sign present and white matter hyperintensities. The median callosal angle was 68.8° (interquartile range, 57.7°-80.8°). Dilated Sylvian fissures were found in 69%; focally dilated sulci, in 25%; and widening of the interhemispheric fissure, in 55%. Obliteration of the sulci at the convexity was found in 36%, and 36% of patients were characterized as having disproportionately enlarged subarachnoid space hydrocephalus. Sixty-eight percent of patients improved after surgery. None of the investigated MR imaging markers were significant predictors of improvement after shunt surgery. CONCLUSIONS: Disproportionately enlarged subarachnoid space hydrocephalus, a small callosal angle, and the other MR imaging markers evaluated in this study should not be used to exclude patients from shunt surgery. These markers, though they may be indicative of idiopathic normal pressure hydrocephalus, do not seem to be a part of the mechanisms connected to the reversibility of the syndrome.

Validation of capnodynamic determination of cardiac output by measuring effective pulmonary blood flow: a study in anaesthetised children and piglets.

BACKGROUND: Effective pulmonary blood flow (COEPBF) has recently been validated as a technique for determining cardiac output (CO) in animals of varying sizes. The primary aim of our study was to investigate this new technique in paediatric surgical patients, compared with suprasternal two-dimensional Doppler (COSSD). METHODS: A total of 15 children undergoing cleft lip/palate surgery were investigated. Before the start of surgery, manoeuvres that were anticipated to reduce (increase in PEEP from 3 to 10 cm H2O) and increase (atropine) CO were undertaken. A study in mechanically ventilated piglets was also undertaken under general anaesthesia, measuring COEPBF and pulmonary artery (COTS) flow by ultrasonic probe as the comparator. Bias (Bland-Altman plots) and limits of agreement were assessed for effective pulmonary blood flow and COSSD or COTS. RESULTS: In paediatric patients (median age 8.5 months), overall bias was -8.1 (limits of agreement -82 to +66) ml kg-1 min-1, with a mean percentage error of 48% and a concordance rate of 64%. In the piglet model, overall bias was -1 (-36 to +38) ml kg-1 min-1, with a mean percentage error of 31% and a concordance rate of 95%. CONCLUSIONS: Under controlled experimental conditions, COEPBF is associated with excellent agreement and good trending ability when compared with the gold standard COTS. In the paediatric clinical setting, COEPBF performs well; by contrast, COSSD, an operator- and anatomy-dependent technology, appears less reliable than COEPBF.

The Gulf War era multiple sclerosis cohort: 3. Early clinical features.

OBJECTIVES: To present clinical features at diagnosis for a large nationwide incident cohort of multiple sclerosis (MS) among those serving in the US military during the Gulf War era (GWE). MATERIALS & METHODS: Medical records and databases from the Department of Veterans Affairs (VA) for cases of MS with onset in or after 1990, active duty between 1990 and 2007 and service connection by the VA, were reviewed for diagnosis and demographic variables. Neurological involvement was summarized by the Kurtzke Disability Status Scale (DSS) and the Multiple Sclerosis Severity Score (MSSS). RESULTS: Among 1919 cases of clinically definite MS, 94% had a relapsing-remitting course and 6% were primary progressive at diagnosis. More males of all races and blacks of both sexes were progressive. At diagnosis, functional system involvement was pyramidal 69%, cerebellar 58%, sensory 55%, brainstem 45%, bowel/bladder 23%, cerebral 23%, visual 18%, and other 5%. Mean DSS scores were: white males, females 2.9, 2.7; black males, females 3.3, 2.8; and other-race males, females 3.2, 2.6. Mean and median MSSS were marginally greater in black males and other males compared to the other sex-race groups. CONCLUSIONS: In this incident cohort, males and blacks had significantly higher proportions of primary progressive MS. DSS at diagnosis was significantly more severe in blacks and significantly less so in whites and in women vs men, but MSSS was only marginally greater in black males and other-race males. This morbidity assessment early in the course of MS provides population-based data for diagnosis, management, and prognosis.

A novel continuous capnodynamic method for cardiac output assessment in a porcine model of lung lavage.

BACKGROUND: We have evaluated a new method for continuous monitoring of effective pulmonary blood flow (COEPBF ), i.e. cardiac output (CO) minus intra-pulmonary shunt, during mechanical ventilation. The method has shown good trending ability during severe hemodynamic challenges in a porcine model with intact lungs. In this study, we further evaluate the COEPBF method in a model of lung lavage. METHODS: COEPBF was compared to a reference method for CO during hemodynamic and PEEP alterations, 5 and 12 cmH2 O, before and after repeated lung lavages in 10 anaesthetised pigs. Bland-Altman, four-quadrant and polar plot methodologies were used to determine agreement and trending ability. RESULTS: After lung lavage at PEEP 5 cmH2 O, the ratio of arterial oxygen partial pressure related to inspired fraction of oxygen significantly decreased. The mean difference (limits of agreement) between methods changed from 0.2 (-1.1 to 1.5) to -0.9 (-3.6 to 1.9) l/min and percentage error increased from 34% to 70%. Trending ability remained good according to the four-quadrant plot (concordance rate 94%), whereas mean angular bias increased from 4° to -16° when using the polar plot methodology. CONCLUSION: Both agreement and precision of COEPBF were impaired in relation to CO when the shunt fraction was increased after lavage at PEEP 5 cmH2 O. However, trending ability remained good as assessed by the four-quadrant plot, whereas the mean polar angle, calculated by the polar plot, was wide.

Serum proteomic analysis of a pre-symptomatic multiple sclerosis cohort.

BACKGROUND AND PURPOSE: Susceptibility to multiple sclerosis (MS) is determined by environmental and genetic factors, but the cause remains unknown. Changes to the proteome prior to first symptom onset may reflect the underlying pathophysiology of the disease. METHODS: This preliminary study utilized pre-symptomatic and post-symptomatic serum from a sample of 100 incident population-based US military veterans with MS along with 100 matched healthy controls. All samples were obtained from the Department of Defense Serum Repository. Multidimensional protein identification technology tandem mass spectrometry analysis was performed on tryptic peptides of lectin-captured glycosylated serum proteins following albumin/immunoglobulin G depletion. Identified proteins were analyzed with the Ingenuity Pathway Analysis program. RESULTS: The mean intervals between first symptom onset and the collection of pre-symptomatic and post-symptomatic sera were -6.0 and +1.1 years, respectively. Pre-symptomatic proteins from the MS group were differentially regulated compared with both control groups indicating that proteomic changes are detected prior to symptom onset. Pathway analysis showed that proteins involved in the complement and coagulation pathways and lipid transport are significantly altered in the serum of subjects with MS compared with healthy donors. CONCLUSIONS: Compared with healthy controls, differential proteomic changes were noted in the serum of patients with MS that preceded the onset of symptomatic disease. Further work is in progress to confirm or refute these findings.

Novel continuous capnodynamic method for cardiac output assessment during mechanical ventilation.

BACKGROUND: It is important to be able to accurately monitor cardiac output (CO) during high-risk surgery and in critically ill patients. The invasiveness of the pulmonary artery catheter (PAC) limits its use, and therefore, new minimally invasive methods for CO monitoring are needed. A potential method is estimation of CO from endogenous carbon dioxide measurements, using a differentiated Fick's principle to determine effective pulmonary blood flow (EPBF). In this study, we aimed to validate a novel capnodynamic method (COEPBF) in a wide range of clinically relevant haemodynamic conditions. METHODS: COEPBF was studied in 10 pigs during changes in preload, afterload, CO increase, and bleeding. An ultrasonic flow probe around the pulmonary artery was used as reference method of CO determination. CO was also measured using a PAC thermodilution technique (COPAC). CO and other haemodynamic data were recorded before and during each intervention. Accuracy and precision and also the ability to track changes in CO were determined using Bland-Altman, four-quadrant plot and polar plot analysis. RESULTS: COEPBF and COPAC showed equally good agreement, with a tendency to overestimate CO (bias 0.2 and 0.3 litre min(-1), respectively). The overall percentage error was 47% for COEPBF and 49% for COPAC. The concordance for tracking CO changes was 97 and 95% for COEPBF and COPAC, respectively, with an exclusion zone of 15% and radial limits of ±30°. CONCLUSIONS: COEPBF showed reliable trending abilities, equivalent to COPAC. COEPBF and COPAC also showed low bias but high percentage errors. Further studies in animal models of lung injury and in high-risk surgery patients are warranted.

Antimicrobial resistance in colonizing group B Streptococci before the implementation of a Swedish intrapartum antibiotic prophylaxis program.

The prevalence of antibiotic resistance and their genetic determinants in colonizing group B streptococci (GBS) sampled in a Swedish nationwide survey was examined. In five GBS isolates (1.3%), kanamycin/amikacin resistance and the presence of the aphA-3 gene was identified. Three of these isolates carried the aad-6 gene and were streptomycin-resistant. Screening with kanamycin and streptomycin 1,000-µg disks enabled a rapid and easy detection of these isolates. In all, 312/396 (79%) GBS were tetracycline-resistant and 95% of the examined isolates harbored the tetM gene. Among the 22 (5.5%) GBS resistant to erythromycin and/or clindamycin, the ermB gene was detected in nine isolates (41%) and erm(A/TR) in ten isolates (45%). A high level of erythromycin and clindamycin resistance with minimum inhibitory concentrations (MICs) >256 mg/L was found in four serotype V isolates that harbored ermB. The erythromycin/clindamycin resistance was distributed among all of the common serotypes Ia, Ib, II, III, IV, and V, but was not present in any of the 44 serotype III isolates associated to clonal complex 17. Screening for penicillin resistance with 1-µg oxacillin disks showed a homogenous population with a mean inhibition zone of 20 mm. A change in the present oxacillin breakpoints for GBS is suggested.

Apgar score and perinatal death after one previous caesarean delivery.

OBJECTIVE: To assess the impact of the indication for a previous caesarean section on the outcome of a subsequent delivery. DESIGN: Population-based cohort study. SETTING: Sweden. POPULATION: Women with two deliveries between 1987 and 2007 identified using the Swedish Medical Birth Registry. METHODS: The outcome of 69 133 pregnancies after one caesarean section was compared with the outcome of 487 610 pregnancies following one vaginal delivery. The indication for the first caesarean section was estimated using a new hierarchical system based on information from birth records. MAIN OUTCOME MEASURES: Perinatal death, low Apgar score (less than seven at 5 minutes). RESULTS: Infants of women with one previous caesarean section were at increased risk of low Apgar score compared with infants of women with one previous vaginal delivery (OR, 2.0; 95% CI, 1.9-2.1). The risk estimate was reduced when adjustment for maternal and fetal/infant characteristics was made (OR, 1.6; 95% CI, 1.5-1.8). The corresponding crude and adjusted odds ratios for perinatal death were 1.6 (95% CI, 1.4-1.7) and 1.1 (95% CI, 1.0-1.2), respectively. The infant outcome of the delivery after one caesarean section was mainly dependent on the indication for the first-delivery caesarean section and, when no medical indication was present, no increase in risk was detected. CONCLUSIONS: Infants of women with one previous caesarean section were at increased risk of low Apgar score and/or perinatal death compared with infants of women with one previous vaginal delivery. The results suggest that medical conditions, not the previous caesarean section per se, contributed to the increase in risk.

Multiple sclerosis in the Faroe Islands. 8. Notifiable diseases.

OBJECTIVE: To seek evidence for a possible infectious origin of the type 1 epidemic of multiple sclerosis (MS) in the Faroe Islands. This began in 1943 coincident with their British military occupation throughout World War II. MATERIALS AND METHODS: Data obtained from the Danish National Health Service were assessed for all notifiable diseases in the Faroe Islands reported from 1900 to 1977. RESULTS: Among 38 disorders, selective increases were found for acute infectious gastroenteritis (AIGE) and paradysentery, with outbreaks in late 1940 and in 1943 shortly after the introduction and later marked influx, respectively, of British troops. Five other infections showed elevated numbers in 1941 and 1942. CONCLUSIONS: There is a temporal association of AIGE and paradysentery in the Faroe Islands with the first arrival and later marked augmentation of British forces stationed there during the war. Rises in the incidence of other diseases in 1941-1942 seem more likely a consequence of increased foreign commercial travel by Faroese at that time.

Sympathetic nerves do not affect experimental ischemia-reperfusion injury of rat liver.

BACKGROUND: We investigated whether sympathetic, noradrenergic nerves participate in experimental acute ischemia-reperfusion injury of the rat liver. METHODS: Female Wistar rats (200-250 g body weight) were anesthetized with pentobarbital. After tracheotomy, we cannulated a carotid artery and jugular vein. The rats were divided in 2 groups (n = 8 per group). The control group received NaCl IV and the test group received the sympatholytic agent, guanethidine (3 mg/kg, IV). After 30 minutes of drug equilibration, laparotomy was performed to arrange the liver for temporary occlusion (by a ligature) of its vascular supply, corresponding with 70% reduction in hepatic blood flow. The rats were then allowed 60 minutes of equilibration. Thereafter, regional ischemia was induced for 30 minutes. The animals were then monitored for 2 hours of reperfusion. Blood samples for alanine aminotransferase (ALT) estimation (as a measure of injury to the parenchyma) were drawn immediately before ischemia, as well as 60 and 120 minutes after reperfusion. Readings of mean arterial pressure were taken during these times. RESULTS: After 2 hours of reperfusion, there were no significant differences between the groups with regard to ALT or mean arterial pressure. CONCLUSION: Sympathetic, noradrenergic nerves did not affect experimental ischemia-reperfusion injury of rat liver in the current model.