Arterial Blood Concentrations Research Articles

Automated Quantitative Image-Derived Input Function for the Estimation of Cerebral Blood Flow Using Oxygen-15-Labelled Water on a Long-Axial Field-of-View PET/CT Scanner.

The accurate estimation of the tracer arterial blood concentration is crucial for reliable quantitative kinetic analysis in PET. In the current work, we demonstrate the automatic extraction of an image-derived input function (IDIF) from a CT AI-based aorta segmentation subsequently resliced to a dynamic PET series acquired on a Siemens Vision Quadra long-axial field of view scanner in 10 human subjects scanned with [15O]H2O. We demonstrate that the extracted IDIF is quantitative and in excellent agreement with a delay- and dispersion-corrected sampled arterial input function (AIF). Perfusion maps in the brain are calculated and compared from the IDIF and AIF, respectively, showed a high degree of correlation. The results demonstrate the possibility of defining a quantitatively correct IDIF compared with AIFs from the new-generation high-sensitivity and high-time-resolution long-axial field-of-view PET/CT scanners.

Determination of remifentanil in neonatal dried blood spots by liquid chromatography-tandem mass spectrometry.

Remifentanil is an ultra-short-acting synthetic opioid-class analgesic which might be increasingly used "off-label" as pain management during labour. Side effects in parturients during labour, and in the infant at birth are of particular concern, especially respiratory depression which is concentration-dependent, and can occur at levels as low as 3-5 ng mL-1. The safety of such use, particularly in newborns due to remifentanil placental transfer, has not been fully demonstrated yet, partly due to the lack of a suitable non-invasive analytical method. The aim of our work was to develop a sensitive method to monitor the levels of remifentanil in neonates by a non-invasive sampling of umbi lical cord blood to support efficacy and safety trials. The presented LC-MS method is sensitive enough to reliably quantify remifentanil in just 20 µL of blood at only 0.3 ng mL-1. The dried blood spot sample preparation included solvent extraction with subsequent solid-phase extraction. The method was validated in terms of accuracy, precision, recovery, matrix effect, and stability, and was successfully applied to a small pilot study. The estimated arterial blood concentrations at the time of delivery ranged from 0.2 to 0.3, and up to 0.9 ng mL-1 in neonatal, and maternal samples, respectively.

Pharmacokinetics of desflurane uptake and disposition in piglets.

Many respiratory but few arterial blood pharmacokinetics of desflurane uptake and disposition have been investigated. We explored the pharmacokinetic parameters in piglets by comparing inspiratory, end-tidal, arterial blood, and mixed venous blood concentrations of desflurane. Seven piglets were administered inspiratory 6% desflurane by inhalation over 2h, followed by a 2-h disposition phase. Inspiratory and end-tidal concentrations were detected using an infrared analyzer. Femoral arterial blood and pulmonary artery mixed venous blood were sampled to determine desflurane concentrations by gas chromatography at 1, 3, 5, 10, 20, 30, 40, 50, 60, 80, 100, and 120min during each uptake and disposition phase. Respiratory and hemodynamic parameters were measured simultaneously. Body uptake and disposition rates were calculated by multiplying the difference between the arterial and pulmonary artery blood concentrations by the cardiac output. The rates of desflurane body uptake increased considerably in the initial 5min (79.8ml.min-1) and then declined slowly until 120min (27.0ml.min-1). Similar characteristics of washout were noted during the subsequent disposition phase. Concentration-time curves of end-tidal, arterial, and pulmonary artery blood concentrations fitted well to zero-order input and first-order disposition kinetics. Arterial and pulmonary artery blood concentrations were best fitted using a two-compartment model. After 2h, only 21.9% of the desflurane administered had been eliminated from the body. Under a fixed inspiratory concentration, desflurane body uptake in piglets corresponded to constant zero-order infusion, and the 2-h disposition pattern followed first-order kinetics and best fitted to a two-compartment model.

Abstract WP267: The Impact of Anesthetic Agents on Regional Cerebral Blood Flow During Carotid Artery Clamping in Patients With Debranching Thoracic Endovascular Aortic Repair and Carotid Endarterectomy

Background: Carotid endarterectomy (CEA) and debranching thoracic endovascular aortic repair (debranching TEVAR) would lead to the reduction of cerebral blood flow (CBF) during carotid artery clamping. Intravenous anesthetics decrease CBF more than volatile anesthetics and may exacerbate cerebral hypoperfusion during carotid artery clamping. We have developed an innovative quantitative measure of regional cerebral blood flow (rCBF) that can be performed at the bedside using near-infrared spectroscopy (NIRS). Using this technique, we measured rCBF during CEA and TEVAR to determine the optimal anesthetic for carotid artery clamping. Methods: Patients undergoing debranching TEVAR and CEA were enrolled. We used NIRS and intravenous injection of Indocyanine green (ICG) to measure rCBF before carotid artery clamping, 10 minutes after clamping, and after de-clamping. The rCBF was calculated by Fick’s principle, using the maximum gradient model that combines the peak values and change in arterial blood concentration of ICG in the brain tissue. We evaluated the effects of each anesthetic (intravenous and volatile) on the rCBF of the cross-clamp side of the carotid artery. Results: The results of the intermediate analysis are shown below. Thirty-two patients who underwent debranching TEVAR and twenty-six who underwent CEA were enrolled. In patients who underwent debranching TEVAR, the rCBF increased from 48.4 to 53.5 ml/min/100g in patients anesthetized with volatile anesthetics and decreased from 55.1 to 32.8 ml/min/100g in patients anesthetized with intravenous anesthetics, as shown in the Figure. There was a significant difference between both anesthetics (p=0.034) but no significant difference between both anesthetics with CEA (p=0.93). Conclusion: In patients undergoing debranching TEVAR, volatile anesthetics may be preferable to intravenous anesthetics during carotid clamping.

Arginine concentration in arterial vs venous blood in a bleomycin-induced lung inflammation model in mice.

Pneumonia, always a major malady, became the main public health and economic disaster of historical proportions with the COVID-19 pandemic. This study was based on a premise that pathology of lung metabolism in inflammation may have features invariant to the nature of the underlying cause. Amino acid uptake by the lungs was measured from plasma samples collected pre-terminally from a carotid artery and vena cava in mice with bleomycin-induced lung inflammation (N = 10) and compared to controls treated with saline instillation (N = 6). In the control group, the difference in concentrations between the arterial and venous blood of the 19 amino acids measured reached the level of statistical significance only for arginine (-10.7%, p = 0.0372) and phenylalanine (+5.5%, p = 0.0266). In the bleomycin group, 11 amino acids had significantly lower concentrations in the arterial blood. Arginine concentration was decreased by 21.1% (p<0.0001) and only that of citrulline was significantly increased (by 20.1%, p = 0.0002). Global Arginine Bioavailability Ratio was decreased in arterial blood by 19.5% (p = 0.0305) in the saline group and by 30.4% (p<0.0001) in the bleomycin group. Production of nitric oxide (NO) and citrulline from arginine by the inducible nitric oxide synthase (iNOS) is greatly increased in the immune system's response to lung injury. Deprived of arginine, the endothelial cells downstream may fail to provide enough NO to prevent the activation of thrombocytes. Thrombotic-related vascular dysfunction is a defining characteristic of pneumonia, including COVID-19. This experiment lends further support to arginine replacement as adjuvant therapy in pneumonia.

Maternal and umbilical cord blood lactate for predicting perinatal death: a secondary analysis of data from a randomized controlled trial

BackgroundIn high resource settings, lactate and pH levels measured from fetal scalp and umbilical cord blood are widely used as predictors of perinatal mortality. However, the same is not true in low resource settings, where much of perinatal mortality occurs. The scalability of this practice has been hindered by difficulty in collecting fetal scalp and umbilical blood sample. Little is known about the use of alternatives such as maternal blood, which is easier and safer to obtain. Therefore, we aimed to compare maternal and umbilical cord blood lactate levels for predicting perinatal deaths.MethodsThis was secondary analysis of data from a randomized controlled trial assessing the effect of sodium bicarbonate on maternal and perinatal outcomes among women with obstructed labour at Mbale regional referral hospital in Eastern Uganda. Lactate concentration in maternal capillary, myometrial, umbilical venous and arterial blood was measured at the bedside using a lactate Pro 2 device (Akray, Japan Shiga) upon diagnosis of obstructed labour. We constructed Receiver Operating Characteristic curves to compare the predictive ability of maternal and umbilical cord lactate and the optimal cutoffs calculated basing on the maximal Youden and Liu indices.ResultsPerinatal mortality risk was: 102.2 deaths per 1,000 live births: 95% CI (78.1–130.6). The areas under the ROC curves were 0.86 for umbilical arterial lactate, 0.71 for umbilical venous lactate, and 0.65 for myometrial lactate, 0.59 for maternal lactate baseline, and 0.65 at1hr after administration of bicarbonate. The optimal cutoffs for predicting perinatal death were 15 0.85 mmol/L for umbilical arterial lactate, 10.15mmol/L for umbilical venous lactate, 8.75mmol/L for myometrial lactate, and 3.95mmol/L for maternal lactate at recruitment and 7.35mmol/L after 1 h.ConclusionMaternal lactate was a poor predictor of perinatal death, but umbilical artery lactate has a high predictive value. There is need for future studies on the utility of amniotic fluid in predicting intrapartum perinatal deaths.

Metabolic Acidosis in Children: A Literature Review

Metabolic acidosis is characterised by a primary decrease in the serum bicarbonate concentration, a secondary decrease in the arterial partial pressure of CO­2, and a reduction in blood pH. Metabolic acidosis, acute or chronic, may have deleterious effects on cellular function and cause increased morbidity and mortality. A systematic review of the available literature was performed to identify data on the prevalence, manifestations, cause, outcomes, and treatment of metabolic acidosis in children. Online databases (Ovid Medline, Embase, and PubMed), commercial search engines (including Google), and chapters on metabolic acidosis in the standard textbooks of paediatrics and medicine were reviewed. Systematic approach to acute metabolic acidosis starts with proper history taking and examination. This is followed by assessment of acid-base parameters, including pH, partial pressure of CO2, and bicarbonate concentration in arterial blood. Blood gas is needed to differentiate primary metabolic acidosis from compensated respiratory alkalosis. Once the diagnosis of a metabolic acidosis has been confirmed, serum electrolyte values are used to determine the serum anion gap. The various causes of increased and normal anion gap metabolic acidosis have been discussed in the article. The main aim of treatment in metabolic acidosis is to reverse the primary pathophysiology. In acute metabolic acidosis, sodium bicarbonate therapy is not beneficial due to potential complications and is reserved for specific situations. Base therapy is used in chronic metabolic acidosis where it ameliorates many of its untoward effects. Other modalities of treatment of metabolic acidosis include peritoneal or haemodialysis and tris-hydroxymethyl aminomethane.

Changes in ionised calcium in cases of ethylene glycol poisoning

Ethylene glycol is a toxic alcohol that occurs in a variety of chemical preparations. In patients poisoned with ethylene glycol, diagnosis is usually based on clinical suspicion and non-specific tests. Hypocalcaemia is often present and results from production of calcium oxalate crystals from oxalic acid. &#x0D; Assess whether reduction in ionized calcium concentration is a common finding in ethylene glycol poisoning, whether it can be appropriate additional marker for the prognosis of outcome.&#x0D; Retrospective clinical records review of patients with a diagnosis of ethylene glycol poisoning at the Riga East University Hospital from 1 January 2012 to 31 December 2020. Ethylene glycol exposure was confirmed retrospectively, qualitatively in all patients. Results of blood gas samples and serum creatinine were analysed and abnormalities were compared amongst various groups.&#x0D; Ionized calcium concentration in arterial blood was below the normal range in 59% of cases at the time of presentation and more commonly associated with a blood pH &lt; 7.3 in 79% of cases. The number of patients with low ionized calcium concentration increased over time. However, the number of patients with blood pH ≥7.3 fell during the same time period. Linear regression analysis did not show a significant correlation between low ionized calcium and blood pH. However, analysis of results from the time of presentation revealed a moderate negative correlation between low ionized calcium concentration and blood pH and lactate concentration. There was also a moderate correlation between low ionized calcium concentration and serum creatinine.&#x0D; A low ionised calcium concentration was a common finding in cases of ethylene glycol poisoning and was more commonly associated with patients exhibiting metabolic acidosis or developing acute kidney injury. Ionised calcium concentration and pH value may be additional markers for the diagnosis and risk stratification of severity from ethylene glycol poisoning.

Dependency of R2 and R2* relaxation on Gd‐DTPA concentration in arterial blood: Influence of hematocrit and magnetic field strength

Dynamic susceptibility contrast (DSC) MRI is clinically used to measure brain perfusion by monitoring the dynamic passage of a bolus of contrast agent through the brain. For quantitative analysis of the DSC images, the arterial input function is required. It is known that the original assumption of a linear relation between the R2 (*) relaxation and the arterial contrast agent concentration is invalid, although the exact relation is as of yet unknown. Studying this relation in vitro is time‐consuming, because of the widespread variations in field strengths, MRI sequences, contrast agents, and physiological conditions. This study aims to simulate the R2 (*) versus contrast concentration relation under varying physiological and technical conditions using an adapted version of an open‐source simulation tool. The approach was validated with previously acquired data in human whole blood at 1.5 T by means of a gradient‐echo sequence (proof‐of‐concept). Subsequently, the impact of hematocrit, field strength, and oxygen saturation on this relation was studied for both gradient‐echo and spin‐echo sequences. The results show that for both gradient‐echo and spin‐echo sequences, the relaxivity increases with hematocrit and field strength, while the hematocrit dependency was nonlinear for both types of MRI sequences. By contrast, oxygen saturation has only a minor effect. In conclusion, the simulation setup has proven to be an efficient method to rapidly calibrate and estimate the relation between R2 (*) and gadolinium concentration in whole blood. This knowledge will be useful in future clinical work to more accurately retrieve quantitative information on brain perfusion.

Pharmacokinetics of hydrogen after ingesting a hydrogen-rich solution: A study in pigs

Drinking hydrogen (H2)-rich water is a common way to consume H2. Although many studies have shown efficacy of drinking H2-rich water in neuropsychiatric and endocrine metabolic disorders, their authenticity has been questioned because none examined the associated pharmacokinetics of H2. Therefore, we performed the first study to investigate the pharmacokinetics of H2 in pigs given an H2-rich glucose solution with the aim to extrapolate the findings to humans. We inserted blood collection catheters into the jejunal and portal veins, suprahepatic inferior vena cava, and carotid artery of 4 female pigs aged 8 weeks. Then, within 2 min we infused 500 ml of either H2-rich or H2-free glucose solution into the jejunum via a percutaneous gastrostomy tube and measured changes in H2 concentration in venous and arterial blood over 120 min. After infusion of the H2-rich glucose solution, H2 concentration in the portal vein peaked at 0.05 mg/L and remained at more than 0.016 mg/L (H2 saturation level, 1%) after 1 h; it also increased after infusion of H2-free glucose solution but remained below 0.001 mg/L (H2 saturation level, 0.06%). We assume that H2 was subsequently metabolized in the liver or eliminated via the lungs because it was not detected in the carotid artery. In conclusion, drinking highly concentrated H2-rich solution within a short time is a good way to increase H2 concentration in portal blood and supply H2 to the liver.

Validation and optimisation of an automatic blood sampler for preclinical positron emission tomography research in domestic pigs.

In preclinical positron emission tomography animal studies, continuous blood sampling is used to measure the time course of the activity concentration in arterial blood. However, pigs have hypercoagulable blood that tends to clot inside plastic tubes. We tested several tube materials and lengths and the use of three-way connectors. We validated set-ups for automated blood sampling with and without blood recirculation that could run for 90 minutes without problematic clots and without any evidence of emboli formation during necropsy.

Formation of initial changes in hemodynamics and fluid compartments in high surgical risk patients under the influence of acute abdominal pathology

Among the main factors of pathological changes that accompany acute abdominal pathology are the inflammatory process of the peritoneum and fluid deficiency due to its pathological losses. The aim of our study was to analyze the initial state of fluid compartments of the body and hemodynamics in high surgical risk patients with acute surgical abdominal pathology. There were examined 157 patients with acute abdominal pathology who underwent emergency laparotomy. The presence and severity of fluid deficiency were determined clinically by tissue hydrophilicity test by P.I. Shelestiuk, biochemically – by assessing the levels of hematocrit, hemoglobin, erythrocytes, blood electrolytes, vasopressin (ADH) and brain natriuretic propeptide (proBNP), as well as the mean erythrocyte volume and plasma osmolarity. Variables of fluid compartments of the body and central hemodynamics were studied using the non-invasive bioimpedancemetry. Based on the values of oxygen concentration in arterial and venous blood, total oxygen consumption (VO2) and delivery of oxygen (DO2), oxygen extraction ratio (O2ER) were calculated. The detected changes indicate intravascular fluid deficiency and concomitant hemoconcentration with normal electrolytes levels and plasma osmolarity. In patients with high surgical risk and moderate dehydration according to P.I. Shelestiuk, urgent surgical pathology of the abdominal cavity reduces extracellular fluid volume by 19.1% (p=0.019) of the reference by reducing the volume of the interstitium and intravascular fluid respectively by 20.7% (p=0.002) and 16.3% (p=0.001) of regional values, which forms in patients a state of "volume depletion" of moderate severity. This is accompanied by an increase in the ADH concentration by 16.7% (p=0.041) above reference and normal proBNP levels. Stroke volume decreases by 28.8% (p=0.021) against tachycardia (increase in heart rate by 39.7% (p=0.001) above normal) and vascular spasm (increase in systemic vascular resistance by 86.9% (p=0.001) above reference), which supports the normodynamic type of blood circulation (cardiac index – 3.2 (0.4) l/min/m2) with the decrease in stroke index and peripheral perfusion index by 41.3% (p=0.002) and 55.2% (p=0.002) from reference, respectively. DO2 decreases by 11.1% (p=0.011) from reference with VO2 increased by 16.3% (p=0.004) above reference, which leads to a decrease in oxygen utilization by 7.2% (p=0.041) from reference.

Machine Learning Prediction of Liver Allograft Utilization From Deceased Organ Donors Using the National Donor Management Goals Registry.

Several machine learning classifiers were trained to predict transplantation of a liver graft. We utilized 127 variables available in the DMG dataset. We included data from potential deceased organ donors between April 2012 and January 2019. The outcome was defined as liver recovery for transplantation in the operating room. The prediction was made based on data available 12-18 h after the time of authorization for transplantation. The data were randomly separated into training (60%), validation (20%), and test sets (20%). We compared the performance of our models to the Liver Discard Risk Index. Of 13 629 donors in the dataset, 9255 (68%) livers were recovered and transplanted, 1519 recovered but used for research or discarded, 2855 were not recovered. The optimized gradient boosting machine classifier achieved an area under the curve of the receiver operator characteristic of 0.84 on the test set, outperforming all other classifiers. This model predicts successful liver recovery for transplantation in the operating room, using data available early during donor management. It performs favorably when compared to existing models. It may provide real-time decision support during organ donor management and transplant logistics.

Perioperative GABA Blood Concentrations in Infants with Cyanotic and Non-Cyanotic Congenital Heart Diseases.

Perioperative stress detection in children with congenital heart disease (CHD), particularly in the brain, is still limited. Among biomarkers, γ-amino-aminobutyric acid (GABA) assessment in biological fluids appears to be promising for its regulatory action on the cardiovascular and cerebral systems. We aimed to investigate cyanotic (C) or non-cyanotic (N) CHD children for GABA blood level changes in the perioperative period. We conducted an observational study in 68 CHD infants (C: n = 33; N: n = 35) who underwent perioperative clinical, standard laboratory and monitoring parameter recordings and GABA assessment. Blood samples were drawn at five predetermined time-points before, during and after surgery. No significant perioperative differences were observed between groups in clinical and laboratory parameters. In C, perioperative GABA levels were significantly lower than N. Arterial oxygen saturation and blood concentration significantly differed between C and N children and correlated at cardiopulmonary by-pass (CPB) time-point with GABA levels. The present data showing higher hypoxia/hyperoxia-mediated GABA concentrations in C children suggest that they are more prone to perioperative cardiovascular and brain stress/damage. The findings suggest the usefulness of further investigations to detect the “optimal” oxygen concentration target in order to avoid the side effects associated with re-oxygenation during CPB.

Use of Magneto Plethysmogram Sensor for Real-Time Estimation of Hemoglobin Concentration

A novel magnetoplethysmogram (MPG) system is designed and developed for the real time, noninvasive monitoring of hemoglobin concentration in arterial blood. The basic principle of modulated magnetic signature of blood (MMSB), is validated with clinical trial. The MPG probe consists of a permanent magnet and a Giant Magneto Resistance (GMR) sensor. A strap and stand design enable reliable capture of continuous cycles of MPG with relative ease. Clinical validation with data from 64 patients carried out at the institute hospital of IIT Madras, using the proposed system gave a worst-case error of 6.5% in the measurement of hemoglobin concentration in arterial blood. Linear regression analysis using least square method, exhibited a standard deviation of 0.64 g/dL. Results from the clinical validation establish the practicability of the proffered MPG system.

Impact of stressors in the aviation environment on xenobiotic dosimetry in humans: physiologically based prediction of the effect of +Gz-forces

ABSTRACT The application of physiologically based modeling approaches in evaluating health risks in diverse environments is limited by scarcity of comprehensive reviews detailing how physiological parameters are altered due to stressors. A modern high-performance aviation environment in particular has the potential for simultaneous exposure to chemical and non-chemical stressors which may interact via non-chemical stressor-mediated pharmacokinetic alterations. To support physiologically based pharmacokinetic (PBPK) modeling of in-flight disposition inhaled chemicals, literature review, and synthesis was conducted to determine the impact of gravitational (+Gz) forces on PBPK modeling inputs. Specifically, changes in cardiac output and related parameters heart rate and stroke volume, breathing frequency, tidal volume, and pulmonary and alveolar ventilation rate in vivo were extracted from 36 publications and related mathematically to +Gz intensity. A scenario was simulated where a pilot performing test flights might inhale organic chemicals at the occupational exposure guideline level while experiencing sustained, elevated +Gz. Peak arterial blood concentrations of 1,2,4-trimethylbenzene during a 1 h-flight at +4 Gz were predicted to increase 2-fold relative to would occur on the ground under baseline conditions. This case study demonstrates the potential value of scenario-specific physiological information in assessing changes in risk-relevant internal dosimetry, providing better information for potential risk management actions.

Impact of stressors in the aviation environment on xenobiotic dosimetry in humans: physiologically based prediction of the effect of barometric pressure or altitude

ABSTRACT Standard health risks from volatile organic compounds (VOCs) are generally interpreted at ambient environmental conditions. The aim of this study was to develop a strategy for using physiologically based pharmacokinetic (PBPK) modeling to compare known risks in the general population to calculated risks in pilots experiencing pressure-based stressors. PBPK models facilitate these comparisons by prediction of how target-tissue specific doses are altered when a stressor, such as high altitude, produces changes in physiological parameters. Cardiac output, regional blood flow, and alveolar ventilation rate following acute exposure to altitude ranging from moderate to extremely high were estimated from published data from 52 groups of human subjects. Scenarios where pilots might inhale toluene, 1,2,4-trimethylbenzene (1,2,4-TMB), or cyclohexane during routine military flight training were simulated. At the recommended Threshold Limit Values (TLV), arterial blood concentrations were predicted to be higher for exposure at 15000 ft (4572 m) than at sea level. The differences were greater for toluene and TMB, which have higher blood: air and fat: blood partition coefficients than less lipophilic cyclohexane. In summary, quantitative approaches to internal dosimetry prediction that take advantage of existing knowledge of physiological changes induced by occupational stressors possess potential as tools in performing a human health risk assessment.

Differences and Effects of Metabolic Fate of Individual Amino Acid Loss in High-Efficiency Hemodialysis and Hemodiafiltration

The objective of the study was to quantify the loss and arterial blood concentration of the three main classes of amino acids (AAs)-nonessential amino acids (NEAAs), essential amino acids (EAAs), and branched-chain amino acids-as resulting from high-efficiency hemodialysis (HED) and hemodiafiltration (HDF). We moreover aimed to identify the different fates and metabolic effects manifested in patients undergoing hemodialysis and the consequences on body composition and influence of nutritional decline into protein energy wasting. Identical dialysis monitors, membranes, and dialysate/infusate were used to ensure consistency. Ten patients were recruited and randomized to receive treatment with on-line modern HED and HDF. Arterial plasma concentrations of individual AAs were compared in healthy volunteers and patients undergoing hemodialysis, and AA levels outflowing from the dialyzer were evaluated. Baseline AA plasma levels of patients undergoing hemodialysis were compared with findings obtained 1year later. A severe loss of AA with HED/HDF was confirmed: a marked loss of total AAs (5g/session) was detected, corresponding to more than 65% of all AAs. With regard to individual AAs, glutamine displayed a consistent increase (+150%), whereas all other AAs decreased after 12months of HD/HDF. Only a few AAs, such as proline, cysteine, and histidine maintained normal levels. The most severe metabolic consequences may result from losses of EAAs such as valine, leucine, and histidine and from NEAAs including proline, cysteine, and glutamic acid eliciting the onset of hypercatabolism threatening muscle mass loss. Dialysis losses, together with the effect of chronic uremia, resulted in a reduction of fundamental EAAs and NEAAs, which progressively led our patients after 12months to a deterioration of lean mass toward sarcopenia. Therefore, the reintroduction of a correctly balanced AA supplementation in patients undergoing HD to prevent or halt decline of hypercatabolism into cachexia is recommended.

Hyperlactatemia during cardiopulmonary bypass: risk factors and impact on surgical results with a focus on the long-term outcome.

Lactate, a product of anaerobic metabolism, is a biomarker and indicator for tissue hypoperfusion and oxygen debt. An elevated blood lactate level has been associated with poor outcome in many clinical conditions, including cardiac surgery. Nevertheless, debate exists regarding which blood lactate concentration is most indicative of poor outcomes. We evaluate the impact of hyperlactatemia, defined as a peak arterial blood concentration ⩾2.0 mmol/L during cardiopulmonary bypass, on surgical results with a focus on long-term outcome. We reviewed 1,099 consecutive adult patients who underwent cardiac surgery on pump. The patients were divided into two groups based on the presence or not of hyperlactatemia. Pre- and intraoperative risk factors for hyperlactatemia were identified, and the postoperative outcome of patients with or without hyperlactatemia was compared. Hyperlactatemia was present in 372 patients (33.8%). Factors independently associated with hyperlactatemia were urgent/emergency procedure, cardiopulmonary bypass duration and aortic cross-clamp time. Patients with hyperlactatemia had significantly higher rate of prolonged mechanical ventilation time, in-hospital stay and requirement of inotropes and intra-aortic balloon pump support (p < 0.001). Operative (30-day) mortality was higher in the group of patients with hyperlactatemia (7.8% vs. 1.1%; p < 0.001). Kaplan-Meier curve showed worse long-term survival (mean follow-up: 4.02 ± 1.58 years) in patients with hyperlactatemia. Hyperlactatemia during cardiopulmonary bypass has a significant association with postoperative morbidity and mortality. Correction of risk factors for hyperlactatemia, together with prompt detection and correction of this condition, may control complications and improve outcome.

Fentanyl concentration in maternal and umbilical cord plasma following intranasal or subcutaneous administration in labour

BackgroundThe effect that the route of maternal fentanyl administration has on placental transfer of drug to the neonate is not well studied. Plasma concentration ratios are an indicator of fetal exposure, relative to the mother. MethodsA cohort study (n=30) was conducted to measure fentanyl concentrations in maternal plasma, and arterial and venous cord blood, among women administered either intranasal or subcutaneous fentanyl for labour pain relief. Maternal and cord blood samples were collected within 30 min of birth to determine the fentanyl plasma concentration and to assess relative neonatal exposure. Neonatal outcomes were assessed by Apgar scores, need for resuscitation and nursery admission. ResultsThirty paired samples were obtained from healthy parturients with uncomplicated term pregnancies. Highest observed umbilical venous and arterial concentrations were 0.71 ng/mL and 0.56 ng/mL, respectively, and fetal to maternal fentanyl plasma concentration ratios ranged between 0.23 and 0.73, indicating low fetal exposure. While the total intranasal fentanyl dose administered was significantly higher than the subcutaneous fentanyl dose, this did not result in a higher fetal to maternal ratio. All neonates in both groups had 5-min Apgar scores >7, two neonates required short-term stimulation and oxygen (unrelated to fentanyl) and no neonate was admitted to the nursery. ConclusionThis study is the first to examine fetal and maternal fentanyl concentrations after subcutaneous administration. This research supports the safe use of fentanyl for labour analgesia for women.