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Background: Our group is attempting to construct an artificial pancreas based on intravenous glucose monitoring and intravenous insulin delivery. To do so, the pharmacology of intravenous insulin administration must be studied. We used a pig model to determine the inherent lag time in the insulin/blood glucose system. The goal was to suggest a method that reduces the blood glucose level in a rapid and yet predictable manner.Methods: Six pigs received continuous intravenous insulin infusions at 0.04, 0.08, or 0.4 IU/kg/h for 60 min. Two pigs received short-term intravenous infusions at 0.4 IU/kg/h for 2 min, repeated five times at 60-min intervals. Four animals received five intravenous insulin bolus injections at 60-min intervals, two at 0.01 IU/kg and two 0.02 IU/kg, with a final dose of 0.04 IU/kg. The blood glucose level was measured every 1-5 min.Results: A high rate of intravenous insulin infusion led to rapid declines in blood glucose levels. The same rapid decline was achieved when the infusion was halted after 2 min. Using the latter method and with intravenous insulin boluses, blood glucose levels started to rise again after approximately 15-20 min. Insulin boluses led to a first detectable decrease in blood glucose level after 2-6 min and to a maximum rate of decrease shortly thereafter.Conclusions: We found that intravenous bolus injections of insulin lowered blood glucose levels rapidly and predictably. Repetitive small intravenous insulin boluses together with an accurate and fast-responding intravascular continuous glucose monitor should be studied as a method of closed-loop glycemic control. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tight blood glucose control is used extensively in perioperative and critically ill patients. Several studies, however, have shown contradictory effects on patient outcomes. A major problem of these studies has been inadequate control of the prime variable, blood glucose. This paper describes the validation of a new intravascular continuous blood glucose sensor. METHODS: The glucose sensor was placed in the superior caval vein of seven anesthetized pigs. Sensor readings were compared with arterial blood gas readings. Fluctuations in blood glucose were created using intravenous glucose and insulin. A total of 807 paired sensor and blood gas readings were obtained. RESULTS: The sensor was tested with a range of blood glucose values (0.63-15.75 mM [mean bias, 0.0131 mM]). Analysis using Bland-Altman plots yielded 95% limits of agreement at -0.908 and 0.934 mM. There were 121 paired measurements with a mean value below 2.2 mM, yielding 95% limits of agreement at -0.553 and 0.466 mM. CONCLUSIONS: The performance of the sensor was in agreement with blood gas measurements in a wide range of glucose values. For the clinician, it is noteworthy that performance was equally good in the hypoglycemic area. [ABSTRACT FROM AUTHOR]

Background: The use of machine learning is becoming increasingly popular in many disciplines, but there is still an implementation gap of machine learning models in clinical settings. Lack of trust in models is one of the issues that need to be addressed in an effort to close this gap. No models are perfect, and it is crucial to know in which use cases we can trust a model and for which cases it is less reliable., Methods: Four different algorithms are trained on the eICU Collaborative Research Database using similar features as the APACHE IV severity-of-disease scoring system to predict hospital mortality in the ICU. The training and testing procedure is repeated 100 times on the same dataset to investigate whether predictions for single patients change with small changes in the models. Features are then analysed separately to investigate potential differences between patients consistently classified correctly and incorrectly., Results: A total of 34 056 patients (58.4%) are classified as true negative, 6 527 patients (11.3%) as false positive, 3 984 patients (6.8%) as true positive, and 546 patients (0.9%) as false negatives. The remaining 13 108 patients (22.5%) are inconsistently classified across models and rounds. Histograms and distributions of feature values are compared visually to investigate differences between groups., Conclusions: It is impossible to distinguish the groups using single features alone. Considering a combination of features, the difference between the groups is clearer. Incorrectly classified patients have features more similar to patients with the same prediction rather than the same outcome., (© 2023. The Author(s).)

Introduction: Postoperative delirium is common in older cardiac surgery patients and associated with negative short-term and long-term outcomes. The alpha-2-adrenergic receptor agonist dexmedetomidine shows promise as prophylaxis and treatment for delirium in intensive care units (ICU) and postoperative settings. Clonidine has similar pharmacological properties and can be administered both parenterally and orally. We aim to study whether repurposing of clonidine can represent a novel treatment option for delirium, and the possible effects of dexmedetomidine and clonidine on long-term cognitive trajectories, motor activity patterns and biomarkers of neuronal injury, and whether these effects are associated with frailty status., Methods and Analysis: This five-centre, double-blind randomised controlled trial will include 900 cardiac surgery patients aged 70+ years. Participants will be randomised 1:1:1 to dexmedetomidine or clonidine or placebo. The study drug will be given as a continuous intravenous infusion from the start of cardiopulmonary bypass, at a rate of 0.4 µg/kg/hour. The infusion rate will be decreased to 0.2 µg/kg/hour postoperatively and be continued until discharge from the ICU or 24 hours postoperatively, whichever happens first.Primary end point is the 7-day cumulative incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, fifth edition). Secondary end points include the composite end point of coma, delirium or death, in addition to delirium severity and motor activity patterns, levels of circulating biomarkers of neuronal injury, cognitive function and frailty status 1 and 6 months after surgery., Ethics and Dissemination: This trial is approved by the Regional Committee for Ethics in Medical Research in Norway (South-East Norway) and by the Norwegian Medicines Agency. Dissemination plans include publication in peer-reviewed medical journals and presentation at scientific meetings., Trial Registration Number: NCT05029050., Competing Interests: Competing interests: HZ has served at scientific advisory boards and/or as a consultant for Alector, Eisai, Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics, Nervgen, AZTherapies, CogRx and Red Abbey Labs, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure and Biogen and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Programme (outside submitted work). AJCS is advisor for Prolira, a start-up company that develops an EEG-based delirium monitor. Any (future) profits from EEG-based delirium monitoring will be used for future scientific research only. GS has participated in one advisory meeting for Biogen. HMN has received lecture fees from Vifor Pharma and Orion Pharma. The other authors declare that they have no competing interests., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Machine learning (ML) holds the promise of becoming an essential tool for utilising the increasing amount of clinical data available for analysis and clinical decision support. However, the lack of trust in the models has limited the acceptance of this technology in healthcare. This mistrust is often credited to the shortage of model explainability and interpretability, where the relationship between the input and output of the models is unclear. Improving trust requires the development of more transparent ML methods., Methods: In this paper, we use the publicly available eICU database to construct a number of ML models before examining their internal behaviour with SHapley Additive exPlanations (SHAP) values. Our four models predicted hospital mortality in ICU patients using a selection of the same features used to calculate the APACHE IV score and were based on random forest, logistic regression, naive Bayes, and adaptive boosting algorithms., Results: The results showed the models had similar discriminative abilities and mostly agreed on feature importance while calibration and impact of individual features differed considerably and did in multiple cases not correspond to common medical theory., Conclusions: We already know that ML models treat data differently depending on the underlying algorithm. Our comparative analysis visualises implications of these differences and their importance in a healthcare setting. SHAP value analysis is a promising method for incorporating explainability in model development and usage and might yield better and more trustworthy ML models in the future., (© 2022. The Author(s).)

Background: Circulatory failure after out-of-hospital cardiac arrest (OHCA) as part of the postcardiac arrest syndrome (PCAS) is believed to be caused by an initial myocardial depression that later subsides into a superimposed vasodilatation. However, the relative contribution of myocardial dysfunction and systemic inflammation has not been established. Our objective was to describe the macrocirculatory and microcirculatory failure in PCAS in more detail., Methods: We included 42 comatose patients after OHCA where circulatory variables were invasively monitored from admission until day 5. We measured the development in cardiac power output (CPO), stroke work (SW), aortic elastance, microcirculatory metabolism, inflammatory and cardiac biomarkers and need for vasoactive medications. We used survival analysis and Cox regression to assess time to norepinephrine discontinuation and negative fluid balance, stratified by inflammatory and cardiac biomarkers., Results: CPO, SW and oxygen delivery increased during the first 48 hours. Although the estimated afterload fell, the blood pressure was kept above 65 mmHg with a diminishing need for norepinephrine, indicating a gradually re-established macrocirculatory homoeostasis. Time to norepinephrine discontinuation was longer for patients with higher pro-brain natriuretic peptide concentration (HR 0.45, 95% CI 0.21 to 0.96), while inflammatory biomarkers and other cardiac biomarkers did not predict the duration of vasoactive pressure support. Markers of microcirculatory distress, such as lactate and venous-to-arterial carbon dioxide difference, were normalised within 24 hours., Conclusion: The circulatory failure was initially characterised by reduced CPO and SW, however, microcirculatory and macrocirculatory homoeostasis was restored within 48 hours. We found that biomarkers indicating acute heart failure, and not inflammation, predicted longer circulatory support with norepinephrine. Taken together, this indicates an early and resolving, rather than a late and emerging vasodilatation., Trial Registration: NCT02648061., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Whole body ischemia and reperfusion injury after cardiac arrest leads to the massive inflammation clinically manifested in the post-cardiac arrest syndrome. Previous studies on the inflammatory effect on circulatory failure after cardiac arrest have either investigated a selected patient group or a limited part of the inflammatory mechanisms. We examined the association between cardiac arrest characteristics and inflammatory biomarkers, and between inflammatory biomarkers and circulatory failure after cardiac arrest, in an unselected patient cohort., Methods: This was a prospective study of 50 consecutive patients with out-of-hospital cardiac arrest. Circulation was invasively monitored from admission until day five, whereas inflammatory biomarkers, i.e. complement activation, cytokines and endothelial injury, were measured daily. We identified predictors for an increased inflammatory response, and associations between the inflammatory response and circulatory failure., Results: We found a marked and broad inflammatory response in patients after cardiac arrest, which was associated with clinical outcome. Long time to return of spontaneous circulation and high lactate level at admission were associated with increased complement activation (TCC and C3bc), pro-inflammatory cytokines (IL-6, IL-8) and endothelial injury (syndecan-1) at admission. These biomarkers were in turn significantly associated with lower mean arterial blood pressure, lower cardiac output and lower systemic vascular resistance, and increased need of circulatory support in the initial phase. High levels of TCC and IL-6 at admission were significantly associated with increased 30-days mortality., Conclusion: Inflammatory biomarkers, including complement activation, cytokines and endothelial injury, were associated with increased circulatory failure in the initial period after cardiac arrest., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Circulatory failure frequently occurs after out-of-hospital cardiac arrest (OHCA) and is part of post-cardiac arrest syndrome (PCAS). The aim of this study was to investigate circulatory disturbances in PCAS by assessing the circulatory trajectory during treatment in the intensive care unit (ICU)., Methods: This was a prospective single-center observational cohort study of patients after OHCA. Circulation was continuously and invasively monitored from the time of admission through the following five days. Every hour, patients were classified into one of three predefined circulatory states, yielding a longitudinal sequence of states for each patient. We used sequence analysis to describe the overall circulatory development and to identify clusters of patients with similar circulatory trajectories. We used ordered logistic regression to identify predictors for cluster membership., Results: Among 71 patients admitted to the ICU after OHCA during the study period, 50 were included in the study. The overall circulatory development after OHCA was two-phased. Low cardiac output (CO) and high systemic vascular resistance (SVR) characterized the initial phase, whereas high CO and low SVR characterized the later phase. Most patients were stabilized with respect to circulatory state within 72 h after cardiac arrest. We identified four clusters of circulatory trajectories. Initial shockable cardiac rhythm was associated with a favorable circulatory trajectory, whereas low base excess at admission was associated with an unfavorable circulatory trajectory., Conclusion: Circulatory failure after OHCA exhibits time-dependent characteristics. We identified four distinct circulatory trajectories and their characteristics. These findings may guide clinical support for circulatory failure after OHCA., Trial Registration: ClinicalTrials.gov: NCT02648061., (© 2021. The Author(s).)

Background: The correlation between pulse transit time and blood pressure has been proposed as a route to measure continuous non-invasive blood pressure. We investigated whether pulse transit time trends could model blood pressure trends during episodes of rapid declines in blood pressure., Methods: From the Medical Information Mart for Intensive Care waveform database we identified substantial blood pressure reductions. Pulse transit time was calculated from the R-peak of the electrocardiogram to the peak of the arterial pulse waveform. The time-series were processed with a moving average filter before comparison. Averaged, continuous heart rate was also analysed as a control. The intra-individual association between variables was assessed per subject using linear regression., Results: In the 511 patients included we found a median correlation coefficient between blood pressure and pulse transit time of -0.93 (IQR -0.98 to -0.76) with regression slopes of -1.23 mmHg/ms (IQR -1.73 to -0.81). The median correlation coefficient between blood pressure and heart rate was 0.46 (IQR -0.16 to 0.83). In supplementary analysis, results did not differ substantially when widening inclusion criteria, but the results were not always consistent within subjects across episodes of hypotension., Conclusions: In a large cohort of critically ill patients experiencing episodes of rapid declines in systolic blood pressure, there was a moderate-strong intra-individual correlation between averaged systolic blood pressure and averaged pulse transit time. Our findings encourage further investigation into using the pulse transit time for non-invasive real-time detection of hypotension., Competing Interests: NKS is chief medical officer and shareholder in Moon Labs, a medical-technology company that is prototyping a wearable biosensor; the company is currently not working with continuous blood pressure monitoring. SGS declares that he has no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The circulatory system is oscillatory in its nature. Oscillatory components linked to physiological processes and underlying regulatory mechanisms are identifiable in circulatory signals. Autonomic regulation is essential for the system's ability to deal with external exposure, and the integrity of oscillations may be considered a hallmark of a healthy system. Loss of complexity is seen as a consequence of several diseases and aging. Heart rate variability is known to decrease after cardiac surgery and remain reduced for up to 6 months. Oscillatory components of circulatory signals are linked to the system's overall complexity. We therefore hypothesize that the frequency distributions of circulatory signals show loss of oscillatory components after cardiac surgery and that the observed changes persist. We investigated the development of the circulatory frequency distributions of eight patients undergoing cardiac surgery by extracting three time series from conventional blood pressure and electrocardiography recordings: systolic blood pressure, heart rate, and amplitude of the electrocardiogram's R-wave. Four 30-min selections, representing key events of the perioperative course, were analyzed with the continuous wavelet transform, and average wavelet power spectra illustrated the circulatory frequency distributions. We identified oscillatory components in all patients and variables. Contrary to our hypothesis, they were randomly distributed through frequencies, patients, and situations, thus, not representing any reduction in the overall complexity. One patient showed loss of a 25-s oscillation after surgery. We present a case where noise is misclassified as an oscillation, raising questions about the robustness of such analyses., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

This study assesses positional changes in cardiac power output and stroke work compared with classic hemodynamic variables, measured before and after elective coronary artery bypass graft surgery. The hypothesis was that cardiac power output was altered in relation to cardiac stunning. The study is a retrospective analysis of data from two previous studies performed in a tertiary care university hospital. Thirty-six patients scheduled for elective coronary artery bypass graft surgery, with relatively preserved left ventricular function, were included. A pulmonary artery catheter and a radial artery catheter were placed preoperatively. Cardiac power output and stroke work were calculated through thermodilution both supine and standing prior to induction of anesthesia and again day one postoperatively. Virtually all systemic hemodynamic parameters changed significantly from pre- to postoperatively, and from supine to standing. Cardiac power output was maintained at 0.9-1.0 (±0.3) W both pre- and postoperatively and from supine to standing on both days. Stroke work fell from pre- to postoperatively from 1.1 to 0.8 J (P < 0.001), there was a significant fall in stroke work with positional change preoperatively from 1.1 to 0.9 J (P < 0.001). Postoperatively the stroke work remained at 0.8 J despite positional change. Cardiac power output was the only systemic hemodynamic variable which remained unaltered during all changes. Stroke work appears to be a more sensitive marker for temporary cardiovascular dysfunction than cardiac power output. Further studies should explore the relationship between stroke work and cardiac performance and whether cardiac power output is an autoregulated intrinsic physiological parameter., (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

It is well-known that blood glucose oscillates with a period of approximately 15 min (900 s) and exhibits an overall complex behaviour in intact organisms. This complexity is not thoroughly studied, and thus, we aimed to decipher the frequency bands entailed in blood glucose regulation. We explored high-resolution blood glucose time-series sampled using a novel continuous intravascular sensor in four pigs under general anaesthesia for almost 24 hours. In all time series, we found several interesting oscillatory components, especially in the 5000-10000 s, 500-1000 s, and 50-100 s regions (0.0002-0.0001 Hz, 0.002-0.001 Hz, and 0.02-0.01 Hz). The presence of these oscillations is not permanent, as they come and go. This is the first report of glucose oscillations in the 50-100 s range. The origin of these oscillations and their role in overall blood glucose regulation is unknown. Although the sample size is small, we believe this finding is important for our understanding of glucose regulation and perhaps for our understanding of general homeostatic regulation in intact organisms.

Background: The post cardiac arrest syndrome (PCAS) is responsible for the majority of in-hospital deaths following cardiac arrest (CA). The major elements of PCAS are anoxic brain injury and circulatory failure., Objective: This study aimed to investigate the clinical characteristics of circulatory failure and inflammatory responses after out-of-hospital cardiac arrest (OHCA) and to identify patterns of circulatory and inflammatory responses, which may predict circulatory deterioration in PCAS., Methods: This study is a single-center cohort study of 50 patients who receive intensive care after OHCA. The patients are followed for 5 days where detailed information from circulatory variables, including measurements by pulmonary artery catheters (PACs), is obtained in high resolution. Blood samples for inflammatory and endothelial biomarkers are taken at inclusion and thereafter daily. Every 10 min, the patients will be assessed and categorized in one of three circulatory categories. These categories are based on mean arterial pressure; heart rate; serum lactate concentrations; superior vena cava oxygen saturation; and need for fluid, vasoactive medications, and other interventions. We will analyze predictors of circulatory failure and their relation to inflammatory biomarkers., Results: Patient inclusion started in January 2016., Conclusions: This study will obtain advanced hemodynamic data with high resolution during the acute phase of PCAS and will analyze the details in circulatory state transitions related to circulatory failure. We aim to identify early predictors of circulatory deterioration and favorable outcome after CA., Trial Registration: ClinicalTrials.gov: NCT02648061; https://clinicaltrials.gov/ct2/show/NCT02648061 (Archived by WebCite at http://www.webcitation.org/6wVASuOla)., (©Halvor Langeland, Daniel Bergum, Magnus Løberg, Knut Bjørnstad, Jan Kristian Damås, Tom Eirik Mollnes, Nils-Kristian Skjærvold, Pål Klepstad. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 19.01.2018.)

Background: Accidental hypothermia with cardiac arrest represents a challenge for pre-hospital rescuers as well as in-hospital staff. For pre-hospital personnel, the main focus is to get the patient to the correct destination without unnecessary delay. For in-hospital personnel early information is vital to assess the possibility for resuscitation with extracorporeal re-warming. The challenge is augmented when rescuers must cross national borders to reach and/or deliver the patients. We present a case where three adolescent boys suffered severe hypothermia after a canoeing accident in Sweden., Case Presentation: Three 14-year-old boys were canoeing a mountain lake close to the Norwegian border when their boat capsized and they all fell into the cold water. The rescue operation was hampered by rough weather conditions, and immersion times spanned from 63 to 125 min. Flight times from the scene of accident to the nearest ECMO center in Norway (Trondheim) and Sweden (Umeå) were about 30 and 90 min respectively. Two of the victims showed no vital signs after retrieval from the water and had extremely low body temperatures. They were brought to Trondheim University Hospital where they were resuscitated successfully with extracorporeal re-warming. Unable to be weaned from ECMO in the initial phase, both patients were retrieved by mobile ECMO teams to Karolinska University Hospital, from where they were discharged to their homes with good outcomes, although with some sequelae. A third victim with moderate to severe hypothermia without cardiac arrest was treated at a local hospital, from where he after a short stay was discharged without physical sequelae., Conclusion: These cases are a reminder of the traditional mantra that «no one is dead until warm and dead». Good communication between pre- and in-hospital staff can be vital for optimizing patient treatment when handling victims of severe hypothermia, and especially when there is multiple victims. Communication between neighboring countries, but even neighboring regions within the same country, can be challenging. We encourage regions similar to ours to review protocols regarding hypothermia management, making them more robust before incidents like this take place.

Hemorrhagic shock is clinically observed as changes in macrocirculatory indices, while its main pathological constituent is cellular asphyxia due to microcirculatory alterations. The coherence between macro- and microcirculatory changes in different shock states has been questioned. This also applies to the hemorrhagic shock. Most studies, as well as clinical situations, of hemorrhagic shock include a "second hit" by tissue trauma. It is therefore unclear to what extent the hemorrhage itself contributes to this lack of circulatory coherence. Nine pigs in general anesthesia were exposed to a controlled withdrawal of 50% of their blood volume over 30 min, and then retransfusion over 20 min after 70 min of hypovolemia. We collected macrocirculatory variables, microcirculatory blood flow measurement by the fluorescent microspheres technique, as well as global microcirculatory patency by calculation of Pv-aCO 2 , and tissue metabolism measurement by the use of microdialysis. The hemorrhage led to anticipated changes in macrocirculatory variables with a coherent change in microcirculatory and metabolic variables. In the late hemorrhagic phase, the animals' variables generally improved, probably through recruitment of venous blood reservoirs. After retransfusion, all variables were normalized and remained same throughout the study period. We find in our nontraumatic model consistent coherence between changes in macrocirculatory indices, microcirculatory blood flow, and tissue metabolic response during hemorrhagic shock and retransfusion. This indicates that severe, but brief, hemorrhage with minimal tissue injury is in itself not sufficient to cause lack of coherence between macro- and microcirculation., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Background: The aim of this study was to construct a non-invasive model for acute right ventricular afterload increase by hypoxic pulmonary vasoconstriction. Intact animal models are vital to improving our understanding of the pathophysiology of acute right ventricular failure. Acute right ventricular failure is caused by increased afterload of the right ventricle by chronic or acute pulmonary hypertension combined with regionally or globally reduced right ventricular contractile capacity. Previous models are hampered by their invasiveness; this is unfortunate as the pulmonary circulation is a low-pressure system that needs to be studied in closed chest animals. Hypoxic pulmonary vasoconstriction is a mechanism that causes vasoconstriction in alveolar vessels in response to alveolar hypoxia. In this study we explored the use of hypoxic pulmonary vasoconstriction as a means to increase the pressure load on the right ventricle., Results: Pulmonary hypertension was induced by lowering the FiO 2 to levels below the physiological range in eight anesthetized and mechanically ventilated pigs. The pigs were monitored with blood pressure measurements and blood gases. The mean pulmonary artery pressures (mPAP) of the animals increased from 18.3 (4.2) to 28.4 (4.6) mmHg and the pulmonary vascular resistance (PVR) from 254 (76) dyns/cm 5 to 504 (191) dyns/cm 5 , with a lowering of FiO 2 from 0.30 to 0.15 (0.024). The animals' individual baseline mPAPs varied substantially as did their response to hypoxia. The reduced FiO 2 level yielded an overall lowering in oxygen offer, but the global oxygen consumption was unaltered., Conclusions: We showed in this study that the mPAP and the PVR could be raised by approximately 100% in the study animals by lowering the FiO 2 from 0.30 to 0.15 (0.024). We therefore present a novel method for minimally invasive (closed chest) right ventricular afterload manipulations intended for future studies of acute right ventricular failure. The method should in theory be reversible, although this was not studied in this work.

Introduction: Measuring cardiac output (CO) with the pulmonary artery catheter intermittent bolus thermodilution technique (PAC-IBTD) is less precise with spontaneous breathing compared to controlled ventilation. We aimed to test if precision could be improved in spontaneous breathing by synchronizing the measurement with respiration or using instructed respiration in 18 post-operative cardiac surgery patients., Methods: We performed eight CO measurements with PAC-IBTD using cold saline in three different situations; in random order: 1) random compared to respiration, 2) timed to the start of expiration, and 3) synchronized with a slow exhalation through a PEP-flute. We calculated the standard deviation (SD), coefficient of variation (CV), and precision in the total material and in the three situations using a linear mixed effects model., Results: A total of 408 CO measurements were performed in 17 included patients. There were no differences between the three study situations regarding mean or precision. The overall CO was 6.0 ± 1.4 l/min (mean ± SD), CV 6.2% and precision 12.2% for single measurements. Averaging three measurements increased the precision to 7.0%., Conclusion: We could not improve the precision of PAC-IBTD in spontaneously breathing patients by synchronizing the measurements with respiration., (© 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

The aim of this study was to construct a glucose regulatory algorithm by employing the natural pulsatile pattern of insulin secretion and the oscillatory pattern of resting blood glucose levels and further to regulate the blood glucose level in diabetic pigs by this method. We developed a control algorithm based on repetitive intravenous bolus injections of insulin and combined this with an intravascular blood glucose monitor. Four anesthetized pigs were used in the study. The animals developed a mildly diabetic state from streptozotocin pretreatment. They were steadily brought within the blood glucose target range of 4.5-6.0 mmol/L in 21 to 121 min and kept within that range for 128 to 238 min (hypoglycemic values varied from 2.9 to 51.1 min). The study confirmed our hypotheses regarding the feasibility of this new principle for blood glucose control, and the algorithm was constantly improved during the study to produce the best results in the last animals. The main obstacles were the drift of the IvS-1 sensor and problems with the calibration procedure, which calls for an improvement in the sensor stability before this method can be applied fully in new studies in animals and humans.

One of several unsolved challenges in the construction of an artificial endocrine pancreas (a system for automatically adjusting the blood glucose level) is the positioning of the glucose sensor. We believe the best positioning to be either intraarterial or in a central vein. It is therefore important to know whether the glucose content in these blood locations is the same. We conducted a post hoc analysis of previously collected data from pigs exposed to gross inflammatory and circulatory stress. Paired arterial and mixed venous glucose values were compared with a mixed effects model. We found the blood glucose values from the arterial and mixed venous blood to be the same.

Background & Objectives: Pulsed-field gel electrophoresis (PFGE) has been used for characterisation of group B streptococci, non-typeable by serotyping. We wanted to compare PFGE with serotyping in order to see the how well the method discriminates between epidemiological unrelated strains., Methods: A total of 78 epidemiological unrelated invasive GBS strains were examined by PFGE using SmaI digested chromosomal DNA. Of these, 11 were nontypeable (NT) with regard to capsular polysaccharide (CPS) serotype. PFGE patterns were analyzed and classified in a dendrogram., Results: 75 strains were typeable by PFGE, and a total of 62 restriction profiles were identified. At an 85 per cent similarity level, 53 different PFGE patterns were identified. Within each serotype, PFGE patterns differed considerably, the largest degree of heterogeneity observed among type IV, Ia, and II strains. Serotype Ib, III, and V strains were more homogeneous. Strains with identical macrorestriction profiles belonged to the same CPS type, but varied with regard to serosubtypes. Any strain among the ones investigated showing a greater than 88 per cent similarity to a restriction profile in the database, could correctly be ascribed to a particular CPS type. Of the 11 NT strains 10 restriction profiles were found, two of which were identical to the PFGE profile for a cluster of type V strains, and one profile were identical to the profile showed by a cluster of 5 type Ib strains., Interpretation & Conclusion: PFGE is a useful technique for classifying strains that are non-typeable by conventional serotyping.