Citrate, a Ubiquitous Key Metabolite with Regulatory Function in the CNS.

Citrate is key constituent of the tricarboxylic acid (TCA) cycle, serves as substrate for fatty acid and sterol biosynthesis, and functions as a key regulator of intermediary energy metabolism. Ursula Sonnewald had initiated studies using for the first time both proton- and 13C-NMR to investigate metabolic processes in cultured neurons and astrocytes resulting in the important observation that citrate was specifically synthesized in and released from astrocytes in large amounts which is in keeping with the high concentration found in the CSF. The aim of this review is to highlight the possible roles of citrate in physiological and pathophysiological processes in the CNS. An interesting feature of citrate is its ability to chelate Ca2+, Mg2+ and Zn2+and thereby playing a pivotal role as an endogenous modulator of glutamate receptors and in particular the NMDA subtypes of these receptors in the CNS. Besides its presence in cerebrospinal fluid (CSF) citrate is also found in high amounts in prostate fluid reaching concentrations as high as 180 mM and here Zn2+ seems also to play an important role, which makes prostate cells interesting for comparison of features of citrate and Zn2+ between these cells and cells in the CNS.

Effects of an 8-weeks erythropoietin treatment on mitochondrial and whole body fat oxidation capacity during exercise in healthy males.

The present investigation was performed to elucidate if the non-erythropoietic ergogenic effect of a recombinant erythropoietin treatment results in an impact on skeletal muscle mitochondrial and whole body fatty acid oxidation capacity during exercise, myoglobin concentration and angiogenesis. Recombinant erythropoietin was administered by subcutaneous injections (5000 IU) in six healthy male volunteers (aged 21 ± 2 years; fat mass 18.5 ± 2.3%) over 8 weeks. The participants performed two graded cycle ergometer exercise tests before and after the intervention where VO2max and maximal fat oxidation were measured. Biopsies of the vastus lateralis muscle were obtained before and after the intervention. Recombinant erythropoietin treatment increased mitochondrial O2 flux during ADP stimulated state 3 respiration in the presence of complex I and II substrates (malate, glutamate, pyruvate, succinate) with additional electron input from ß-oxidation (octanoylcarnitine) (from 60 ± 13 to 87 ± 24 pmol · s(-1) · mg(-1) P < 0.01). ß-hydroxy-acyl-CoA-dehydrogenase activity was higher after treatment (P < 0.05), whereas citrate synthase activity also tended to increase (P = 0.06). Total myoglobin increased by 16.5% (P < 0.05). Capillaries per muscle area tended to increase (P = 0.07), whereas capillaries per fibre as well as the total expression of vascular endothelial growth factor remained unchanged. Whole body maximal fat oxidation was not increased after treatment. Eight weeks of recombinant erythropoietin treatment increases mitochondrial fatty acid oxidation capacity and myoglobin concentration without any effect on whole body maximal fat oxidation.

Procedure for calculation of potency and efficacy for ligands acting on Gs- and Gi-coupled receptors.

Structure activity relationship (SAR) analyses of pharmacological data of compounds constitute an important part of the discovery process in the design of new drug candidates with improved pharmacological properties. In particular G-Protein Coupled Receptors (GPCRs) associated with the cAMP second messenger systems G(s) and G(i) have constituted one of the most widely used basis for pharmacological in vitro assays for assessing functional receptor effects. Such assays are based on Radio Immuno Assay (RIA) analysis to measure the cellular cAMP concentration as readout of receptor activation. It appears, however, to be a common practice to omit the use of cAMP standard curves to transform the measured signals (cpm or cps) into cAMP concentrations on which estimations of potencies (EC(50) values) and efficacies (E(MAX) values) in G(s) and G(i) coupled receptor stimulation are based. Such practice may lead to significant errors as compounds mediating their effects via G(s) coupled receptors may appear more potent and efficacious than they actually are. Contrary, compounds mediating their effects via G(i) coupled receptors may appear less potent and efficacious than they are in reality. Potency rank orders will therefore change considerably, when estimations are based on incorrect calculation of the original experimental results. Thus, the only correct way to calculate effect data on which to base E(MAX) and EC(50) estimations is to use cAMP concentrations derived from transformation of the measured signals (cpm or cps) using cAMP standard curves. The present work outlines the mathematical procedures by which such transformations are to be performed.

Treatment with epinephrine (adrenaline) in suspected anaphylaxis during anesthesia in Denmark.

BACKGROUND: Literature on the use of epinephrine in the treatment of anaphylaxis during anesthesia is very limited. The objective of this study was to investigate how often epinephrine is used in the treatment of suspected anaphylaxis during anesthesia in Denmark and whether timing of treatment is important. METHODS: A retrospective study of 270 patients investigated at the Danish Anaesthesia Allergy Centre after referral due to suspected anaphylaxis during anesthesia was performed. Reactions had been graded by severity: C1, mild reactions; C2, moderate reactions; C3, anaphylactic shock with circulatory instability; C4, cardiac arrest. Use of epinephrine, dosage, route of administration, and time between onset of circulatory instability and epinephrine administration were noted. RESULTS: A total of 122 (45.2%) of referred patients had C3 or C4 reactions; of those, 101 (82.8%) received epinephrine. Route of administration was intravenous in 95 (94%) patients. Median time from onset of reported hypotension to treatment with epinephrine was 10 min (range, 1-70 min). Defining epinephrine treatment less than or equal to 10 min after onset of hypotension as early, and more than 10 min as late, infusion was needed in 12 of 60 patients (20%) treated early versus 12 of 35 patients (34%) treated late (odds ratio, 2.09) (95% confidence interval, 0.81-5.35). CONCLUSION: Anaphylaxis may be difficult to diagnose during anesthesia, and treatment with epinephrine can be delayed as a consequence. Anaphylaxis should be considered and treated in patients with circulatory instability during anesthesia of no apparent cause who do not respond to the usual treatments.

Nurse-administered early warning score system can be used for emergency department triage.

INTRODUCTION: Studies have shown that early warning score systems can identify in-patients at high risk of catastrophic deterioration and this may possibly be used for an emergency department (ED) triage. Bispebjerg Hospital has introduced a multidisciplinary team (MT) in the ED activated by the Bispebjerg Early Warning Score (BEWS). The BEWS is calculated on the basis of respiratory frequency, pulse, systolic blood pressure, temperature and level of consciousness. The aim of this study is to evaluate the ability of the BEWS to identify critically ill patients in the ED and to examine the feasibility of using the BEWS to activate an MT response. MATERIAL AND METHODS: This study is based on an evaluation of retrospective data from a random sample of 300 emergency patients. On the basis of documented vital signs, a BEWS was calculated retrospectively. The primary end points were admission to an intensive care unit (ICU) and death within 48 hours of arrival at the ED. This study was registered at clinicaltrials.gov (NCT01243021). RESULTS: A BEWS ≥ 5 is associated with a significantly increased risk of ICU admission within 48 hours of arrival (relative risk (RR) 4.1; 95% confidence interval (CI) 1.5-10.9) and death within 48 hours of arrival (RR 20.3; 95% CI 6.9-60.1). The sensitivity of the BEWS in identifying patients who were admitted to the ICU or who died within 48 hours of arrival was 63%. The positive predictive value of the BEWS was 16% and the negative predictive value 98% for identification of patients who were admitted to the ICU or who died within 48 hours of arrival. CONCLUSION: The BEWS is a simple scoring system based on readily available vital signs. It is a sensitive tool for detecting critically ill patients and may be used for ED triage and activation of an MT response.

Low compliance with a validated system for emergency department triage.

INTRODUCTION: Bispebjerg Hospital has introduced a triage system at the Emergency Department (ED) based on "primary criteria" and a physiological scoring system named the Bispebjerg Early Warning Score (BEWS). A BEWS is calculated on the basis of five vital signs which are accessible bedside. Patients who have a "primary criterion" or a BEWS ≥ 5 are presumed to be critically ill or severely injured and should be received by a multidisciplinary team, termed the Emergency Call (EC) and Trauma Call (TC), respectively. The aim of this study was to examine compliance with this triage system at Bispebjerg Hospital. MATERIAL AND METHODS: Retrospective evaluation of the triage of a random sample of 300 ED patients. ED medical charts were searched for "primary criteria", documentation of vital signs and a BEWS score. If a BEWS score had not been calculated, this was done retrospectively by the author. An evaluation was made to determine whether ECs or TCs had been correctly activated. RESULTS: In 47 patients, all five vital signs for calculation of a BEWS had been documented. A BEWS had been calculated in 22 patients. Nine patients had a TC activation criterion, and in all these cases a TC was activated. A total of 48 patients had an EC activation criterion, but an EC had only been activated in 24 patients. Among the 24 patients for whom an EC had not been activated, eight had a "primary criterion" and 16 patients had a retrospective BEWS ≥ 5. CONCLUSION: The triage system is not being used systematically and documentation of vital signs is insufficient at Bispebjerg Hospital. As a consequence, many patients who are presumed to be critically ill are not allocated to an EC. Initiatives have been taken to raise compliance with the system.

Effect of general anesthesia and orthopedic surgery on serum tryptase.

BACKGROUND: Mast cell tryptase is used clinically in the evaluation of anaphylaxis during anesthesia, because symptoms and signs of anaphylaxis are often masked by the effect of anesthesia. No larger studies have examined whether surgery and anesthesia affect serum tryptase. The aim of this study was to investigate the effect of anesthesia and surgery on serum tryptase in the absence of anaphylaxis. METHODS: The study included 120 patients (median age, 54 yr; range, 19-94 yr) undergoing elective orthopedic surgery in general anesthesia. Exclusion criteria were allergic reactions during this or previous anesthesia, hematologic disease, or high-dose corticosteroid treatment. Blood samples for tryptase analysis (ImmunoCAP; Phadia, Uppsala, Sweden) were drawn shortly before anesthesia and after anesthesia and surgery. RESULTS: Median duration of anesthesia was 105 min (range, 44-263 min). Median interval between blood samples was 139 min (range, 39-370 min). Mean tryptase before surgery was 5.01 microg/l, with a mean decrease of 0.55 microg/l (P < 0.0001; 95% CI, 0.3-0.8) postoperatively. All patients received intravenous fluid (median value 750 ml; range, 200-2000 ml) perioperatively. There was no significant effect of gender, age, American Society of Anesthesiologist's physical status classification, or self-reported allergy on serum tryptase. CONCLUSIONS: Serum tryptase shows small intraindividual variation in the absence of anaphylaxis. A small decrease was observed postoperatively, likely due to dilution by intravenous fluid. On suspected anaphylaxis during anesthesia, tryptase values, even within the normal reference interval, should, when possible, be compared with the patient's own basal level taken more than 24 h after the reaction.

Preoperative, single, high-dose glucocorticoid administration in abdominal wall reconstruction: A randomized, double-blinded clinical trial.

BACKGROUND: Although preoperative administration of high-dose glucocorticoid may lead to improved recovery after operative procedures, this regimen has not been examined in patients undergoing abdominal wall reconstruction for repair of large ventral hernias. The aim of the current trial was to examine the effects of preoperative, single high-dose glucocorticoid on recovery after abdominal wall reconstruction. METHOD: Forty patients undergoing abdominal wall reconstruction for repair of ventral incisional hernias with a horizontal fascial defect >10 cm were randomized to intravenous administration of either 125 mg methylprednisolone or placebo at the induction of anesthesia. The primary endpoint was pain in the supine position as assessed by a numeric rating scale of 0 to 10 at rest at 8 am on the first postoperative day. Secondary outcomes included postoperative pain during activity, nausea, fatigue, inflammatory response (measured by plasma levels of C-reactive protein), duration of stay, and 30-day complications or readmissions. RESULTS: There was no difference in pain at rest on the first postoperative day (methylprednisolone mean 1.7 vs placebo 2.2, P > .95), whereas patients in the methylprednisolone group reported less pain during activity (mean 3.0 vs 5.0; P = .011) and during coughing (3.4 vs 5.9; P = .010). There were no differences between the 2 groups regarding postoperative fatigue or nausea. Postoperative levels of C-reactive protein were less in the methylprednisolone group (P = .039). CONCLUSION: A single-shot, high-dose methylprednisolone before abdominal wall reconstruction for a large incisional hernia decreased early postoperative pain and attenuated the inflammatory response.

Amitriptyline accumulation in tissues after coated activated charcoal hemoperfusion-a randomized controlled animal poisoning model.

Amitriptyline poisoning (AT) is a common poisoning, and AT possess the ability to promote life-threatening complications by its main action on the central nervous and cardiovascular systems. The pharmacokinetic properties might be altered at toxic levels compared to therapeutic levels. The effect of coated activated charcoal hemoperfusion (CAC-HP) on the accumulation of AT and its active metabolite nortriptyline (NT) in various tissues was studied in a non-blinded randomized controlled animal trial including 14 female Danish Land Race piglets. All piglets were poisoned with amitriptyline 7.5 mg/kg infused in 20 min, followed by orally instilled activated charcoal at 30 min after infusion cessation. The intervention group received 4 h of CAC-HP followed by a 1-h redistribution phase. At study cessation, the piglets were euthanized, and within 20 min, vitreous fluid, liver tissue, ventricle and septum of the heart, diaphragm and lipoic and brain tissues were collected. AT and NT tissue concentrations were quantified by UHPLC-MS/MS. A 4-h treatment with CAC-HP did not affect the tissue accumulation of AT in the selected organs when tested by Mann-Whitney U test (p values between 0.44 and 0.73). For NT concentrations, p values were between 0.13 and 1.00. Although not significant, an interesting finding was that data showed a tendency of increased tissue accumulation of AT and NT in the CAC-HP group compared with the control group. Coated activated charcoal hemoperfusion does not significantly alter the tissue concentration of AT and NT in the AT-poisoned piglet.

Voluntary respiratory control and cerebral blood flow velocity upon ice-water immersion.

INTRODUCTION: In non-habituated subjects, cold-shock response to cold-water immersion causes rapid reduction in cerebral blood flow velocity (approximately 50%) due to hyperventilation, increasing risk of syncope, aspiration, and drowning. Adaptation to the response is possible, but requires several cold immersions. This study examines whether thorough instruction enables non-habituated persons to attenuate the ventilatory component of cold-shock response. METHODS: There were nine volunteers (four women) who were lowered into a 0 degrees C immersion tank for 60 s. Middle cerebral artery mean velocity (CBFV) was measured together with ventilatory parameters and heart rate before, during, and after immersion. RESULTS: Within seconds after immersion in ice-water, heart rate increased significantly from 95 +/- 8 to 126 +/- 7 bpm (mean +/- SEM). Immersion was associated with an elevation in respiratory rate (from 12 +/- 3 to 21 +/- 5 breaths, min(-1)) and tidal volume (1022 +/- 142 to 1992 +/- 253 ml). Though end-tidal carbon dioxide tension decreased from 4.9 +/- 0.13 to 3.9 +/- 0.21 kPa, CBFV was insignificantly reduced by 7 +/- 4% during immersion with a brief nadir of 21 +/- 4%. DISCUSSION: Even without prior cold-water experience, subjects were able to suppress reflex hyperventilation following ice-water immersion, maintaining the cerebral blood flow velocity at a level not associated with impaired consciousness. This study implies that those susceptible to accidental cold-water immersion could benefit from education in cold-shock response and the possibility of reducing the ventilatory response voluntarily.

Advanced Electrocardiogram Analysis in the Amitriptyline-poisoned Pig Treated with Activated Charcoal Haemoperfusion.

Coated activated charcoal haemoperfusion (CAC-HP) does not reduce the plasma concentration in amitriptyline (AT)-poisoned pigs. The aim of this non-blinded, randomized, controlled animal trial was to determine if CAC-HP reduces the pathological ECG changes caused by AT poisoning. Fourteen female Danish Landrace pigs (mean weight 27.7 kg, range 20-35 kg (CAC-HP) and 24.4 kg, range 18-30 kg (control group, CG), n = 7 in each group) were included. After randomization, the pigs were anaesthetized and intravenously poisoned with AT. The intervention group underwent 4 hr of CAC-HP plus standard care (oral activated charcoal). Intervention was compared to standard care alone. From each pig, a 12-lead ECG and haemodynamic variables were obtained at baseline, at full AT loading dose, before and during CAC-HP. Baseline ECG variables (RR, PR, QRS, QTc, QTp, QTe, TpTe and TpTe/QT) for lead II, v2 and v5 were not significantly different (F = 0.035-0.297, p-values 0.421-0.919). Differences within groups over time and between groups were tested by anova repeated measures. For all variables, the time-plus-group level of significance revealed a p-value > 0.05. Severe cardiovascular arrhythmias occurred in both groups with 3 in the CAC-HP group versus 1 incident with premature death in the CG. The attenuating effect of CAC-HP to orally instilled activated charcoal alone on AT-induced ECG alterations did not differ significantly. We conclude that the use of modern CAC-HP as an adjunctive treatment modality in AT-poisoned pigs is inadequate.

Reduced cerebral perfusion on sudden immersion in ice water: a possible cause of drowning.

INTRODUCTION: Near-drowning incidents and drowning deaths after accidental immersion in open waters have been linked to cold shock response. It consists of inspiratory gasps, hyperventilation, tachycardia, and hypertension in the first 2-3 min of cold-water immersion. This study explored the immediate changes in cerebral blood flow velocity (Vmean) during cold-water immersion since cold shock induced hyperventilation may diminish Vmean and lead to syncope and drowning. METHODS: There were 13 male volunteers who were lowered into a 0 degrees C immersion tank for 30 s. Vmean in the middle cerebral artery (MCA) was measured together with ventilatory parameters and heart rate before, during, and after immersion. RESULTS: Within seconds after immersion in ice water, heart rate increased from 74 +/- 16 to 107 +/- 18 bpm (mean +/- SD; p < 0.05). Immersion was associated with a marked elevation in respiratory rate (from 16 +/- 3 to 38 +/- 14 breaths x min(-1)) and tidal volume (883 +/- 360 to 2292 +/- 689 ml). The end-tidal carbon dioxide tension decreased from 38 +/- 4 to 26 +/- 5 mmHg and MCA Vmean dropped by 43 +/- 8%. Signs of imminent syncope (drowsiness, blurred vision, loss of responsiveness) were shown by two subjects (MCA Vmean dropped 62% and 68%, respectively). DISCUSSION: Following ice-water immersion, hyperventilation induced a marked reduction in MCA Vmean to a level which has been associated with disorientation and loss of consciousness.

Effects of low-dose recombinant human erythropoietin treatment on cognitive performance.

INTRODUCTION: High-dose recombinant human erythropoietin (rhEpo) has been shown to improve cognitive performance in both healthy volunteers and in patients suffering from diseases affecting the brain. The aim of this study was to examine whether administration of low-dose and even micro-dose rhEpo improves cognitive performance in healthy volunteers. METHODS: We enrolled 25 healthy volunteers in a double-blind, randomised, placebo-controlled study to receive either low-dose rhEpo (n = 8, 60 IU/kg/week), micro-dose rhEpo (n = 9, 20 IU/kg/week), or saline (n = 8) for four weeks. Two cognitive performance-tests, the Raven Standard Progressive Matrices (Raven) and the Number Finder (NUFI), were performed during the first and last day of the study period. Semi-structured interviews were conducted weekly and were coded according to a scale. RESULTS: Subjects receiving micro-dose rhEpo improved significantly measured by the Raven score (p = 0.04), and subjects receiving low-dose rhEpo treatment improved significantly measured by the NUFI score (p = 0.047), whereas no improvement was found in experienced cognitive performance in any of the groups. We found no significant difference in either Raven, NUFI or self-reported results between the groups. CONCLUSIONS: In this small study, we found no significant effect of low-dose or micro-dose rhEpo on visual attention, cognitive performance in complex cognitive tasks or self-experienced cognitive performance compared with placebo. FUNDING: The Aase and Ejnar Danielsen's Foundation. Danish Ministry of Science, Innovation and Higher Education. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03093506.

Activated Charcoal Haemoperfusion in the Treatment of Experimental Amitriptyline Poisoning in Pigs - The Effect on Amitriptyline Plasma Concentration and Haemodynamic Parameters.

Coated activated charcoal haemoperfusion (CAC-HP) is a well-known treatment modality. Case reports have revealed conflicting results about the efficacy of CAC-HP in the treatment of amitriptyline (AT) poisoning, and no randomized clinical trials have been identified in the literature. This study aimed at quantifying the efficacy of modern CAC-HP as an adjunctive treatment of AT intoxication compared with standard care alone. Fourteen female Danish landrace pigs were randomized to either standard care or standard care plus 4 hr of CAC-HP. The pigs were anaesthetized, and vital parameters were continuously recorded. Amitriptyline infusion (7.5 mg/kg) was completed in 20 min. Thirty minutes after AT infusion, activated charcoal was instilled orally in both groups. In the intervention group, CAC-HP was initiated 60 min. after AT infusion. Blood and urine samples were collected as were vital parameters at specific time intervals. The protocol was approved by the Danish Experimental Animal Expectorate and complied with the NIH guide for care and use of laboratory animals. Data were managed according to the ARRIVE guidelines. No statistical significant differences between intervention and control groups were found when analysing for differences in AT levels in plasma at any time-point. Furthermore, significant differences between the control and intervention groups in regard to vital parameters could not be found either. In our animal model, the addition of CAC-HP did not improve the clearance of AT compared with standard treatment alone. We suggest that the effect of modern CAC-HP as a treatment modality in AT-poisoned human patients may be inadequate.

Long-term quasi-continuous oxygen saturation levels obtained from sternal photoplethysmography on patients with obstructive lung diseases.

Calculation of long-term quasi-continuous oxygen saturation (SpO2) levels is highly relevant for critically ill patients. The purpose of this study is therefore to conduct a preliminary investigation of the clinical reliability of long-term photoplethysmography (PPG) recordings obtained from the sternum of patients admitted to the hospital with obstructive lung diseases. Due to the lack of a gold standard reference that is suitable for long-term monitoring without interfering with the patient's activity level, we extracted reliable segments based on knowledge from the basic pulse oximeter theory as well as knowledge about the inherent physiological regulation of the SpO2 levels. We included 15 admitted patients who were monitored with a prototype of a sternal PPG sensor for approximately 20 hours. On average, we found that clinically reliable SpO2 levels could be calculated for 58% of the recording time. Furthermore, the average and standard deviation of the longest period of time with unreliable data was only 23.6 ± 19.38 minutes. This indicates a high potential for quasi-continuous calculation of SpO2 levels from sternal PPGs in many different clinical applications in the future.

A clinical study of short-term sternal photoplethysmography: Recordings from patients with obstructive airways diseases.

Traditionally, measurements of the oxygen saturation (SpO2) has been confound to the extremities. In this study, we therefore investigated the possibility for reliable estimation of clinically relevant SpO2 levels from photoplethysmography (PPG) obtained on the sternum of patients with obstructive airway diseases. We initiated the study with a calibration of a prototype sternal PPG sensor. In accordance with the ISO 80601-2-61:2011 guidelines, the calibration was conducted as a controlled desaturation study. We obtained a calibration accuracy of 1.75% which is well within the clinically and commercially accepted range. We then compared the SpO2 levels simultaneously obtained from the sternal PPGs and a commercially available finger pulse oximeter on 28 admitted patients with either asthma or Chronic Obstructive Pulmonary Disease (COPD). The Pearson correlation between the SpO2 levels estimated from the two body locations was found to be 0.89 (p<;0.05) and the mean system bias was only 0.052% with upper and lower limits of agreement of 2.5% and -2.4%, respectively. This finding is very promising for the future design of new sternum based patch technologies that might be able to provide continuous estimates of the SpO2 levels on critically or chronically ill patients.

Preoperative steroid in abdominal wall reconstruction: protocol for a randomised trial.

INTRODUCTION: Preoperative administration of high-dose glucocorticoid leads to improved recovery and decreased length of stay after abdominal surgery. Even so, studies on administration of glucocorticoids for patients undergoing abdominal wall reconstruction (AWR) for giant ventral hernia repair are lacking, perhaps due to a fear of impaired wound healing. We hypothesised that patients undergoing AWR would benefit from preoperative glucocorticoids and aimed at examining this in a randomised controlled trial. METHODS: A total of 40 patients scheduled to undergo AWR for ventral hernias with a fascial defect exceeding 10 cm will be randomised for intravenous administration of either 125 mg methylprednisolone or saline at the induction of anaesthesia. The primary endpoint is pain at rest on the first post-operative day. Patients will be followed until 30 days post-operatively, and secondary outcomes include subjective measures, wound complications and analysis of blood and wound fluids. CONCLUSIONS: This is the first trial on the effect of preoperative glucocorticoid administration in patients undergoing AWR. Due to long post-operative stays and a high rate of post-operative complications, this patient group can potentially benefit much from any post-operative optimisation. Furthermore, insight into any impact of glucocorticoids on wound healing in hernia patients may provide important information. FUNDING: none. TRIAL REGISTRATION: This study was registered with Clinicaltrials.gov (NCT02594241) and Eudra-CT (2015-004916-39).

Clinical evaluation of the lateral sagittal infraclavicular block developed by MRI studies.

BACKGROUND AND OBJECTIVES: Lateral sagittal infraclavicular block by single injection has a faster performance time and causes less discomfort than does axillary block by multiple injections. This prospective, descriptive, multicenter study assessed block effectiveness, onset time, and incidence of adverse events and verified the noninvasive measurements from magnetic resonance imaging (MRI). METHODS: One hundred sixty patients were anesthetized by use of the lateral sagittal infraclavicular block and following the MRI recommendations for needle insertion. Each patient received a mixture that contained equal volumes of ropivacaine 7.5 mg/mL and mepivacaine 20 mg/mL with epinephrine 5 mug/mL, in a total amount that corresponded to 0.5 mL/kg (minimum 30 mL, maximum 50 mL). Block effectiveness (analgesia or anesthesia of all 5 nerves below the elbow after 30 minutes), performance and onset times, needle insertion depth and dorsal angle, twitch type, analgesia of the individual nerves, and incidence of adverse events and complications, as well as patient's acceptance, were recorded. RESULTS: One hundred forty-three patients (91%) had successful blocks, 12 patients required supplementary nerve blocks in the axilla, 3 patients had total failures of blocks (no forearm analgesia at all), and 2 patients were excluded from the assessments. Median block performance time was 4 minutes (range, 2-10 minutes) and the onset time 20 minutes (range, 10-50 minutes). Plexus nerves were found at a mean depth of 53 mm +/- 10 mm and the needle dorsal angle was 23 degrees +/- 9 degrees . Four patients experienced painful paresthesias and 3 patients had accidental punctures of axillary vessels. Signs or symptoms of complications (hematoma, local anesthetic toxicity, pneumothorax, or neuropraxias) were not observed. Only 3 patients would prefer general anesthesia in the future. Finger/wrist extension may be an optimal twitch response (P = .14). CONCLUSIONS: Block effectiveness (91%) and onset time (20 minutes) were satisfactory and comparable to the vertical paracoracoid approach. The low rate of axillary vessel punctures (2%) may be the most important advantage of this block. The needle insertion depth measurements confirmed the MRI findings, but the dorsal angle was steeper than predicted.

Estimation of respiratory rates based on photoplethysmographic measurements at the sternum.

The respiratory rate (RR) is a clinically important vital sign and is a frequently used parameter in the general hospital wards. In current clinical practice, the monitoring of the RR is by manual count of the chest movement for one minute. This paper addresses a new approach where the respiratory rate is extracted using photoplethysmography (PPG) on the chest bone (sternum). Sternal PPG signals were acquired from 10 healthy subjects resting in a supine position. As reference signals, finger PPG, electrocardiogram (ECG), and capnography were simultaneously recorded during spontaneous and paced breathing. The sternal PPG signals were then compared with the reference signals in terms of Bland-Altman analysis, the power spectrum analysis and the magnitude squared coherence. The Bland-Altman analysis showed an average bias of 0.21 breaths/min between RR extracted from sternal PPG and capnography. The respiratory power content at the sternum was 78.8 (38) % in terms of the median and (the interquartile range). The cardiac content was 19 (18.4) % within the cardiac region. The results from the magnitude squared coherence analysis was 0.97 (0.09) in the respiratory region (6 to 27 breaths/min) and 0.98 (0.01) in the cardiac pulse region (30-120 beats/min). This preliminary study demonstrates the possibility of monitoring the RR from sternal PPG on a healthy group of subjects during rest.

Sternal pulse rate variability compared with heart rate variability on healthy subjects.

The heart rate variability (HRV) is a commonly used method to quantify the sympathetic and the parasympathetic modulation of the heart rate. HRV is mainly conducted on electrocardiograms (ECG). However, the use of photo-plethysmography (PPG) as a marker of the autonomic tone is emerging. In this study we investigated the feasibility of deriving pulse rate variability (PRV) using PPG signals recorded by a reflectance PPG sensor attached to the chest bone (sternum) and comparing it to HRV. The recordings were conducted on 9 healthy subjects being in a relaxed supine position and under forced respiration, where the subjects were asked to breathe following a visual scale with a rate of 27 breaths/min. HRV parameters such as the mean intervals (meanNN), the standard deviation of intervals (SDNN), the root mean square of difference of successive intervals (RMSSD), and the proportion of intervals differing more than 50 ms (pNN50) were calculated from the R peak-to-R peak (R-R) and pulse-to-pulse (P-P) intervals. In the frequency domain the low and high frequency ratio of the power spectral density (LF/HF) was also computed. The Pearson correlation coefficient showed significant correlation for all the parameters (r > 0.95 with p < 0.001) and the Bland-Altmann analysis showed close agreement between the two methods for all the parameters during resting and forced respiration condition. Thus, PRV analysis using sternal PPG can be an alternative to HRV analysis on healthy subjects at.