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To systematically evaluate the effect of small changes in transducer position on key hemodynamic variables including CO generated by 4th generation FloTrac software. After cardiac surgery, cardiac output, mean arterial pressure, systemic vascular resistance, and stroke volume variation were measured with 4 generation Flotrac software. The transducer position was randomly placed at the midaxillary plane, 4 cm higher than the midaxillary plane or 4 cm lower than the midaxillary plane. Averages of three measurements were used. Data was available from 20 patients. Cardiac output increased from 4.59 L/min (± 0.92) to 4.78 L/min (± 0.99) with the transducer position at the midaxillary plane to 4 cm higher than the midaxillary plane, and cardiac output decreased to 4.43 L/min (± 0.90) with the transducer 4 cm lower than midaxillary plane (P < 0.001). On the relative scale, CO increased 4.1% (95% CI 3.1-5.0) when comparing the higher transducer level with the midaxillary plane position, and CO decreased 3.4% (95% CI 2.4-4.4) when comparing the midaxillary plane position with the lower transducer level, correspondiong to changes in CO of ≈ 1% per 1 cm change in transducer position. Mean arterial pressure and systemic vascular resistance both changed significantly with transducer position (both P < 0.001), whereas no statistically or clinically significant effect was seen on stroke volume variation (P = 0.98). A four-centimeter change in vertical transducer position induced clinically significant changes in cardiac output measurements by 4th generation FloTrac software. Definitions of optimal cardiac output in goal-directed therapy algorithms require meticulous transducer adjustment and can only be used in the reference patient position., (© 2024. The Author(s).)

We present the INSPIRE dataset, a publicly available research dataset in perioperative medicine, which includes approximately 130,000 surgical operations at an academic institution in South Korea over a ten-year period between 2011 and 2020. This comprehensive dataset includes patient characteristics such as age, sex, American Society of Anesthesiologists physical status classification, diagnosis, surgical procedure code, department, and type of anaesthesia. The dataset also includes vital signs in the operating theatre, general wards, and intensive care units (ICUs), laboratory results from six months before admission to six months after discharge, and medication during hospitalisation. Complications include total hospital and ICU length of stay and in-hospital death. We hope this dataset will inspire collaborative research and development in perioperative medicine and serve as a reproducible external validation dataset to improve surgical outcomes., (© 2024. The Author(s).)

The Hypotension Prediction Index (HPI) algorithm is a commercial prediction algorithm developed to predict hypotension, a mean arterial pressure (MAP) below 65 mmHg. Although HPI has been investigated in several studies, recent concerns of have been raised regarding HPI's predictive abilities, which may have been overstated. A selection bias may have forced the HPI algorithm to learn almost exclusively from MAP. This CON position paper describes the selection bias further and summarises the scientific status of HPI's predictive abilities, including the meaning of a recent erratum retracting the primary conclusion of a published HPI validation study. We argue that the HPI algorithm needs re-validation or complete re-development to achieve a clinically relevant 'added value' in comparison with the predictive performance of a simple and costless MAP alarm threshold in the range of 70 to 75 mmHg., (Copyright © 2023 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Pulse pressure variation (PPV) is a well-established method for predicting fluid responsiveness in mechanically ventilated patients. The predictive accuracy is, however, disputed for ventilation with low tidal volume (V T ) or low heart-rate-to-respiratory-rate ratio (HR/RR). We investigated the effects of V T and RR on PPV and on PPV's ability to predict fluid responsiveness. We included patients scheduled for open abdominal surgery. Prior to a 250 ml fluid bolus, we ventilated patients with combinations of V T from 4 to 10 ml kg -1 and RR from 10 to 31 min -1 . For each of 10 RR-V T combinations, PPV was derived using both a classic approach and a generalized additive model (GAM) approach. The stroke volume (SV) response to fluid was evaluated using uncalibrated pulse contour analysis. An SV increase > 10% defined fluid responsiveness. Fifty of 52 included patients received a fluid bolus. Ten were fluid responders. For all ventilator settings, fluid responsiveness prediction with PPV was inconclusive with point estimates for the area under the receiver operating characteristics curve between 0.62 and 0.82. Both PPV measures were nearly proportional to V T . Higher RR was associated with lower PPV. Classically derived PPV was affected more by RR than GAM-derived PPV. Correcting PPV for V T could improve PPV's predictive utility. Low HR/RR has limited effect on GAM-derived PPV, indicating that the low HR/RR limitation is related to how PPV is calculated. We did not demonstrate any benefit of GAM-derived PPV in predicting fluid responsiveness.Trial registration: ClinicalTrials.gov, reg. March 6, 2020, NCT04298931., (© 2023. The Author(s).)

Fatal poisonings where both methadone and quetiapine are detected post-mortem occurs frequently in legal autopsy cases. It is unclear whether quetiapine increases the risk of fatal methadone poisoning or if it is merely detected due to widespread use. We hypothesized that methadone and quetiapine would have additive toxic effects on respiratory rate, blood pressure, and the QTc-interval. To investigate this hypothesis, we used telemetry implants for measurements of respiratory rate, haemodynamic variables, the velocity of blood pressure changes, temperature, and movement in conscious, freely moving male Wistar rats aged 12-13 weeks. The combined effects of three accumulative i.p. doses of methadone (2.5, 10, 15 mg/kg) and quetiapine (3, 10, 30 mg/kg) were compared to rats treated with the same doses of each drug alone, and a vehicle-treated group in a randomized investigator blinded study. No additive effects of quetiapine and methadone on respiratory rate, haemodynamic variables, or movement were observed. However, body temperature was significantly lower by approximately 1.5°C on average in the group treated with both methadone and quetiapine (15 + 30 mg/kg) compared to the other groups. This indicates a synergistic effect of quetiapine and methadone on thermoregulation, which may increase the risk of fatal poisoning. We suggest studying this finding further in human settings., (© 2023 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Common physiological time series and waveforms are composed of repeating cardiac and respiratory cycles. Often, the cardiac effect is the primary interest, but for, e.g., fluid responsiveness prediction, the respiratory effect on arterial blood pressure also convey important information. In either case, it is relevant to disentangle the two effects. Generalized additive models (GAMs) allow estimating the effect of predictors as nonlinear, smooth functions. These smooth functions can represent the cardiac and respiratory cycles' effects on a physiological signal. We demonstrate how GAMs allow a decomposition of physiological signals from mechanically ventilated subjects into separate effects of the cardiac and respiratory cycles. Two examples are presented. The first is a model of the respiratory variation in pulse pressure. The second demonstrates how a central venous pressure waveform can be decomposed into a cardiac effect, a respiratory effect and the interaction between the two cycles. Generalized additive models provide an intuitive and flexible approach to modelling the repeating, smooth, patterns common in medical monitoring data., (© 2022. The Author(s).)

The Hypotension Prediction Index is a proprietary prediction model incorporated into a commercially available intraoperative hemodynamic monitoring system. The Hypotension Prediction Index uses multiple features of the arterial blood pressure waveform to predict hypotension. The index publication introducing the Hypotension Prediction Index describes the selection of training and validation data. Although precise details of the Hypotension Prediction Index algorithm are proprietary, the authors describe a selection process whereby a mean arterial pressure (MAP) less than 75 mmHg will always predict hypotension. We hypothesize that the data selection process introduced a systematic bias that resulted in an overestimation of the current MAP value's ability to predict future hypotension. Since current MAP is a predictive variable contributing to Hypotension Prediction Index, this exaggerated predictive performance likely also applies to the corresponding Hypotension Prediction Index value. Other existing validation studies appear similarly problematic, suggesting that additional validation work and, potentially, updates to the Hypotension Prediction Index model may be necessary., (Copyright © 2022, the American Society of Anesthesiologists. All Rights Reserved.)

Introduction: Short term hypothermia has been suggested to have cardio protective properties in acute myocardial infarction (AMI) by reducing infarct size as assessed by troponins. There are limited data on the kinetics of these biomarkers in comatose out-of-hospital cardiac arrest (OHCA) patients, with and without AMI, undergoing targeted temperature management (TTM) in the ICU., Purpose: The aim of this post hoc analyses was to evaluate and compare the kinetics of two high-sensitivity cardiac troponins in OHCA survivors, with and without acute myocardial infarction (AMI), during TTM of different durations [24 h (standard) vs. 48 h (prolonged)]., Methods: In a sub-cohort (n = 114) of the international, multicentre, randomized controlled study "TTH48" we measured high-sensitive troponin T (hs-cTnT), high-sensitive troponin I (hs-cTnI) and CK-MB at the following time points: Arrival, 24 h, 48 h and 72 h from reaching the target temperature range of 33 ± 1 °C. All patients diagnosed with an AMI at the immediate coronary angiogram (CAG)-18 in the 24-h group and 25 in the 48-h group-underwent PCI with stent implantation. There were no stent thromboses., Results: Both the hs-cTnT and hs-cTnI changes over time were highly influenced by the cause of OHCA (AMI vs. non-AMI). In contrast to non-AMI patients, both troponins remained elevated at 72 h in AMI patients. There was no difference between the two time-differentiated TTM groups in the kinetics for the two troponins., Conclusion: In comatose OHCA survivors with an aetiology of AMI levels of both hs-cTnI and hs-cTnT remained elevated for 72 h, which is in contrast to the well-described kinetic profile of troponins in normotherm AMI patients. There was no difference in kinetic profile between the two high sensitive assays. Different duration of TTM did not influence the kinetics of the troponins., Trial Registration: Clinicaltrials.gov Identifier: NCT01689077, 20/09/2012., (© 2022. The Author(s).)

Prediction of fluid responsiveness is essential in perioperative goal directed therapy, but dynamic tests of fluid responsiveness are not applicable during open-chest surgery. We hypothesised that two methods could predict fluid responsiveness during cardiac surgery based on their ability to alter preload and thereby induce changes in arterial blood pressure characteristics: (1) the change caused by extrasystolic beats and (2) the change caused by a fast infusion of 50 ml crystalloid (micro-fluid challenge). Arterial blood pressure and electrocardiogram waveforms were collected during surgical preparation of the left internal mammary artery in patients undergoing coronary artery bypass surgery. Patients received a fluid challenge (5 ml/kg ideal body weight). The first 50 ml were infused in 10 s and comprised the micro-fluid challenge. Predictor variables were defined as post-ectopic beat changes (compared with sinus beats preceding ectopy) in arterial blood pressure characteristics, such as pulse pressure and systolic pressure, or micro-fluid challenge induced changes in the same blood pressure characteristics. Patients were considered fluid responsive if stroke volume index increased by 15% or more after the full fluid challenge. Diagnostic accuracy was calculated by the area under the receiver operating characteristics curve (AUC). Fifty-six patients were included for statistical analysis. Thirty-one had extrasystoles. The maximal AUC was found for the extrasystolic change in pulse pressure and was 0.70 (CI [0.35 to 1.00]). The micro-fluid challenge method generally produced lower AUC point estimates. Extrasystoles did not predict fluid responsiveness with convincing accuracy in patients undergoing cardiac surgery and changes in arterial waveform indices following a micro-fluid challenge could not predict fluid responsiveness. Given a low number of fluid responders and inherently reduced statistical power, our data does not support firm conclusions about the utility of the extrasystolic method. CLINICAL TRIAL REGISTRATION: Unique identifier: NCT02903316. https://clinicaltrials.gov/ct2/show/NCT02903316?cond=NCT02903316&rank=1 ., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The mini-fluid challenge (MFC) is a clinical concept of predicting fluid responsiveness by rapidly infusing a small amount of intravenous fluids, typically 100 ml, and systematically assessing its haemodynamic effect. The MFC method is meant to predict if a patient will respond to a subsequent, larger fluid challenge, typically another 400 ml, with a significant increase in stroke volume., Methods: We critically evaluated the general methodology of MFC studies, with statistical considerations, secondary analysis of an existing study and simulations., Results: Secondary analysis of an existing study showed that the MFC could predict the total fluid response (MFC + 400 ml) with an area under the receiver operator characteristic curve (AUROC) of 0.92, but that the prediction was worse than random for the response to the remaining 400 ml (AUROC = 0.33). In a null simulation with no response to both the MFC and the subsequent fluid challenge, the commonly used analysis could predict fluid responsiveness with an AUROC of 0.73., Conclusion: Many existing MFC studies are likely overestimating the classification accuracy of the MFC. This should be considered before adopting the MFC into clinical practice. A better study design includes a second, independent measurement of stroke volume after the MFC. This measurement serves as reference for the response to the subsequent fluid challenge., (© 2021 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Study Design: Single-center, investigator-initiated, prospective cohort study., Objective: This study aimed to determine patient-reported reasons for persistent opioid use following elective spine surgery, assess the frequency of withdrawal symptoms, and characterize pain-related care sought after discharge., Summary of Background Data: Patients are often prescribed opioids at discharge from hospital following surgery. Several studies have shown that a large number of patients fail to discontinue opioid treatment and use opioids even months to years after surgery. Spine surgery has proven to be a high-risk procedure in regard to persistent opioid use. There is, however, limited evidence on why patients continue to take opioids., Methods: Three hundred patients, scheduled to undergo spine surgery at Aarhus University Hospital, Denmark, were included. Baseline characteristics and discharge data on opioid consumption were collected. Data on opioid consumption, patient-reported reasons for opioid use, withdrawal symptoms, and pain-related care sought were collected at 3- and 6-month follow-up via a REDCap survey., Results: Before surgery, opioid use was reported in 53% of patients. Three months after surgery, opioid use was reported in 60% of preoperative opioid-users and in 9% of preoperative opioid non-users. Patients reported the following reasons for postoperative opioid use: treatment of surgery-related pain (53%), treatment of surgery-related pain combined with other reasons (37%), and reasons not related to spine surgery (10%). Withdrawal symptoms were experienced by 33% of patients during the first 3 months after surgery and were associated with failure to discontinue opioid treatment (P < 0.001). Half of patients (52%) contacted health care after discharge with pain-related topics the first 3 months., Conclusion: Patients use opioids after spine surgery for reasons other than surgery-related pain. Withdrawal symptoms are frequent even though patients are given tapering plans at discharge. Further studies should address how to facilitate successful and safe opioid tapering in patients undergoing spine surgery.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To examine the impact of ACE inhibitor (ACE-I)/angiotensin receptor blocker (ARB) use on rate of SARS-CoV-2 infection and adverse outcomes., Methods: This nationwide case-control and cohort study included all individuals in Denmark tested for SARS-CoV-2 RNA with PCR from 27 February 2020 to 26 July 2020. We estimated confounder-adjusted ORs for a positive test among all SARS-CoV-2 tested, and inverse probability of treatment weighted 30-day risk and risk ratios (RRs) of hospitalisation, intensive care unit (ICU) admission and mortality comparing current ACE-I/ARB use with calcium channel blocker (CCB) use and with non-use., Results: The study included 13 501 SARS-CoV-2 PCR-positive and 1 088 695 PCR-negative individuals. Users of ACE-I/ARB had a marginally increased rate of a positive PCR when compared with CCB users (aOR 1.17, 95% CI 1.00 to 1.37), but not when compared with non-users (aOR 1.00 95% CI 0.92 to 1.09).Among PCR-positive individuals, 1466 (11%) were ACE-I/ARB users. The weighted risk of hospitalisation was 36.5% in ACE-I/ARB users and 43.3% in CCB users (RR 0.84, 95% CI 0.70 to 1.02). The risk of ICU admission was 6.3% in ACE-I/ARB users and 5.4% in CCB users (RR 1.17, 95% CI 0.64 to 2.16), while the 30-day mortality was 12.3% in ACE-I/ARB users and 13.9% in CCB users (RR 0.89, 95% CI 0.61 to 1.30). The associations were similar when ACE-I/ARB users were compared with non-users., Conclusions: ACE-I/ARB use was associated neither with a consistently increased rate nor with adverse outcomes of SARS-CoV-2 infection. Our findings support the current recommendation of continuing use of ACE-Is/ARBs during the SARS-CoV-2 pandemic., Trial Registration Number: EUPAS34887., Competing Interests: Competing interests: CFC, UH-J, RWT and HTS have not received any personal fees, grants, travel grants or teaching grants from companies, but the Department of Clinical Epidemiology is involved in studies with funding from various companies as research grants to (and administered by) Aarhus University. MR, LCL, AP and JH have participated in industry-funded projects with money paid to their employer, the University of Southern Denmark. MM has received speaker or advisory board fees from AstraZeneca, Bayer, Boston Scientific, Boehringer-Ingelheim, Bristol-Myers Squibb, and Novo Nordisk., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Treatment decisions on critically ill patients with circulatory shock lack consensus. In an international survey, we aimed to evaluate the indications, current practice, and therapeutic goals of inotrope therapy in the treatment of patients with circulatory shock., Methods: From November 2016 to April 2017, an anonymous web-based survey on the use of cardiovascular drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 14 questions focused on the profile of respondents, the triggering factors, first-line choice, dosing, timing, targets, additional treatment strategy, and suggested effect of inotropes. In addition, a group of 42 international ESICM experts was asked to formulate recommendations for the use of inotropes based on 11 questions., Results: A total of 839 physicians from 82 countries responded. Dobutamine was the first-line inotrope in critically ill patients with acute heart failure for 84% of respondents. Two-thirds of respondents (66%) stated to use inotropes when there were persistent clinical signs of hypoperfusion or persistent hyperlactatemia despite a supposed adequate use of fluids and vasopressors, with (44%) or without (22%) the context of low left ventricular ejection fraction. Nearly half (44%) of respondents stated an adequate cardiac output as target for inotropic treatment. The experts agreed on 11 strong recommendations, all of which were based on excellent (> 90%) or good (81-90%) agreement. Recommendations include the indications for inotropes (septic and cardiogenic shock), the choice of drugs (dobutamine, not dopamine), the triggers (low cardiac output and clinical signs of hypoperfusion) and targets (adequate cardiac output) and stopping criteria (adverse effects and clinical improvement)., Conclusion: Inotrope use in critically ill patients is quite heterogeneous as self-reported by individual caregivers. Eleven strong recommendations on the indications, choice, triggers and targets for the use of inotropes are given by international experts. Future studies should focus on consistent indications for inotrope use and implementation into a guideline for circulatory shock that encompasses individualized targets and outcomes.

Background Angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) may worsen the prognosis of coronavirus disease 2019, but any association could be confounded by the cardiometabolic conditions indicating ACE-I/ARB use. We therefore examined the impact of ACE-Is/ARBs on respiratory tract infection outcomes. Methods and Results This cohort study included all adult patients hospitalized with influenza or pneumonia from 2005 to 2018 in Denmark using population-based medical databases. Thirty-day mortality and risk of admission to the intensive care unit in ACE-Is/ARBs users was compared with nonusers and with users of calcium channel blockers. We used propensity scores to handle confounding and computed propensity score-weighted risks, risk differences (RDs), and risk ratios (RRs). Of 568 019 patients hospitalized with influenza or pneumonia, 100 278 were ACE-I/ARB users and 37 961 were users of calcium channel blockers. In propensity score-weighted analyses, ACE-I/ARB users had marginally lower 30-day mortality than users of calcium channel blockers (13.9% versus 14.5%; RD, -0.6%; 95% CI, -1.0 to -0.1; RR, 0.96; 95% CI, 0.93-0.99), and a lower risk of admission to the intensive care unit (8.0% versus 9.6%; RD, -1.6%; 95% CI, -2.0 to -1.2; RR, 0.83; 95% CI, 0.80-0.87). Compared with nonusers, current ACE-I/ARB users had lower mortality (RD, -2.4%; 95% CI, -2.8 to -2.0; RR, 0.85; 95% CI, 0.83-0.87), but similar risk of admission to the intensive care unit (RD, 0.4%; 95% CI, 0.0-0.7; RR, 1.04; 95% CI, 1.00-1.09). Conclusions Among patients with influenza or pneumonia, ACE-I/ARB users had no increased risk of admission to the intensive care unit and slightly reduced mortality after controlling for confounding.

Echocardiographic measurement of cardiac output with automated software analyses of spectral curves in the left ventricular outflow tract has been introduced. This study aimed to assess the precision and accuracy of cardiac output measurements as well as the ability to track cardiac output changes over time comparing the automated echocardiographic method with the continuous pulmonary artery thermodilution cardiac output technique and the manual echocardiographic method in cardiac surgery patients. Cardiac output was measured simultaneously with all three methods in 50 patients on the morning after cardiac surgery. A second comparison was performed 90-180 min later. Precisions for each method were measured. Bias and limits of agreement (LoA) between methods were assessed and concordance- and polar plots were used for evaluating trending of cardiac output. When comparing the automated echocardiographic method with the thermodilution technique, the mean bias was 0.72 L/min with LoA - 1.89; 3.33 L/min corresponding to a percentage error of 46%. The concordance rate was 47%. The mean bias between the automated- and the manual echocardiographic methods was - 0.06 L/min (95% LoA - 2.33; 2.21 L/min, percentage error 42%). The concordance rate was 79%. The automated echocardiographic method did not meet the criteria for interchangeability with the thermodilution technique or the manual echocardiographic method. Trending ability was poor when compared to the continuous thermodilution technique, but moderate when compared to the manual echocardiographic method.Trial registry number: NCT03372863. Retrospectively registered December 14th 2017.

Near infrared spectroscopy (NIRS) has been used to evaluate regional cerebral tissue oxygen saturation (ScO 2 ) during the last decades. Perioperative management algorithms advocate to maintain ScO 2 , by maintaining or increasing cardiac output (CO), e.g. with fluid infusion. We hypothesized that ScO 2 would increase in responders to a standardized fluid challenge (FC) and that the relative changes in CO and ScO 2 would correlate. This study is a retrospective substudy of the FLuid Responsiveness Prediction Using Extra Systoles (FLEX) trial. In the FLEX trial, patients were administered two standardized FCs (5 mL/kg ideal body weight each) during cardiac surgery. NIRS monitoring was used during the intraoperative period and CO was monitored continuously. Patients were considered responders if stroke volume increased more than 10% following FC. Datasets from 29 non-responders and 27 responders to FC were available for analysis. Relative changes of ScO 2 did not change significantly in non-responders (mean difference - 0.3% ± 2.3%, p = 0.534) or in fluid responders (mean difference 1.6% ± 4.6%, p = 0.088). Relative changes in CO and ScO 2 correlated significantly, p = 0.027. Increasing CO by fluid did not change cerebral oxygenation. Despite this, relative changes in CO correlated to relative changes in ScO 2 . However, the clinical impact of the present observations is unclear, and the results must be interpreted with caution.Trial registration:http://ClinicalTrial.gov identifier for main study (FLuid Responsiveness Prediction Using Extra Systoles-FLEX): NCT03002129.

Background: Intraoperative hypotension is associated with worse perioperative outcomes for patients undergoing major noncardiac surgery. The Hypotension Prediction Index is a unitless number that is derived from an arterial pressure waveform trace, and as the number increases, the risk of hypotension occurring in the near future increases. We investigated the diagnostic ability of the Hypotension Prediction Index in predicting impending intraoperative hypotension in comparison to other commonly collected perioperative hemodynamic variables., Methods: This is a 2-center retrospective analysis of patients undergoing major surgery. Data were downloaded and analyzed from the Edwards Lifesciences EV1000 platform. Receiver operating characteristic curves were constructed for the Hypotension Prediction Index and other hemodynamic variables as well as event rates and time to event., Results: Two hundred fifty-five patients undergoing major surgery were included in the analysis yielding 292,025 data points. The Hypotension Prediction Index predicted hypotension with a sensitivity and specificity of 85.8% (95% CI, 85.8%-85.9%) and 85.8% (95% CI, 85.8%-85.9%) 5 minutes before a hypotensive event (area under the curve, 0.926 [95% CI, 0.925-0.926]); 81.7% (95% CI, 81.6%-81.8%) and 81.7% (95% CI, 81.6%-81.8%) 10 minutes before a hypotensive event (area under the curve, 0.895 [95% CI, 0.894-0.895]); and 80.6% (95% CI, 80.5%-80.7%) and 80.6% (95% CI, 80.5%-80.7%) 15 minutes before a hypotensive event (area under the curve, 0.879 [95% CI, 0.879-0.880]). The Hypotension Prediction Index performed superior to all other measured hemodynamic variables including mean arterial pressure and change in mean arterial pressure over a 3-minute window., Conclusions: The Hypotension Prediction Index provides an accurate real time and continuous prediction of impending intraoperative hypotension before its occurrence and has superior predictive ability than the commonly measured perioperative hemodynamic variables.

Fluid responsiveness prediction is difficult during cardiac surgery. The micro-fluid challenge (micro-FC; rapid central infusion of 50 ml) and the extrasystolic method utilising post-extrasystolic preload increases may predict fluid responsiveness. Two study windows during coronary artery bypass graft surgery were defined, 1: After anaesthesia induction until surgical incision, 2: Left internal mammarian artery surgical preparation period. Each window consisted of 10-15 min observation for extrasystoles before a micro-FC was performed, after which a traditional fluid challenge (FC) was performed (5 ml/kg). Extrasystolic and micro-FC induced changes in hemodynamic variables were derived as predictors of fluid responsiveness defined as stroke volume increasing > 10% following FC. 61 patients were studied. Post-ectopic changes in pulse pressure (PP) predicted fluid responsiveness with receiver operating characteristic area (AUC) of 0.69 [CI 0.40;0.97] in the first study window and 0.64 [0.44;0.86] in the second window. Other post-ectopic predictors such as pre-ejection period (PEP) and systolic blood pressure (SBP) had similar or lower AUCs. Heart rate was 52.9 (SD ±8.4) min - 1 and 53.6 (± 8.8) min - 1 in the two study windows. Micro-FC induced changes in PEP had AUC of 0.74 [0.57;0.90] in the first window and 0.60 [0.40;0.76] in the second window. Correcting micro-FC induced changes in PEP for the micro-FC induced changes in heart rate had AUCs of 0.84 [0.70;0.97] in the first window and 0.63 [0.47;0.79] in the second window. The investigated methods revealed insufficient validity during cardiac surgery. RR interval corrected changes during a micro-FC should be investigated further. Trial registration Clinicaltrials.gov: NCT03002129.

Right ventricular dysfunction (RVD) is associated with end-organ dysfunction and mortality, but has been an overlooked condition in the ICU. We hypothesized that analysis of the arterial waveform in the presence of ventricular extrasystoles could differentiate patients with RVD from patients with a normally functioning right ventricle, because the 2nd and 3rd post-ectopic beat could reflect right ventricular state (pulmonary transit time) during the preceding ectopy. We retrospectively identified patients with echocardiographic evidence of moderate-to-severe RVD and patients with a normal functioning right ventricle (control) from the MIMIC database. We identified waveform records where ECG and arterial pressure were available in combination, simultaneously with echocardiographic evaluation. Ventricular extrasystoles were visually confirmed and the median systolic blood pressure (SBP) of the 2nd and 3rd post-ectopic beats compared with the median SBP of the ten sinus beats preceding the extrasystole. We identified 34 patients in the control group and 24 patients in the RVD group with ventricular extrasystoles. The mean SBP reduction at the 2nd and 3rd beat was lower in the RVD group compared with the control group [- 1.7 (SD: 1.9) % vs. - 3.6 (SD: 1.9) %, p < 0.001], and this characteristic differentiated RVD subjects from control subjects with an AUC of 0.76 (CI [0.64; 0.89]), with a specificity of 91% and sensitivity of 50%. In this proof-of-concept study, we found that post-extrasystolic ABP characteristics were associated with RVD.

The impact of positive pressure ventilation extends the effect on lungs and gas exchange because the altered intra-thoracic pressure conditions influence determinants of cardiovascular function. These mechanisms are called heart-lung interactions, which conceptually can be divided into two components (1) The effect of positive airway pressure on the cardiovascular system, which may be more or less pronounced under various pathologic cardiac conditions, and (2) The effect of cyclic airway pressure swing on the cardiovascular system, which can be useful in the interpretation of the individual patient's current haemodynamic state. It is imperative for the anaesthesiologist to understand the fundamental mechanisms of heart-lung interactions, as they are a foundation for the understanding of optimal, personalised cardiovascular treatment of patients undergoing surgery in general anaesthesia. The aim of this review is thus to describe what the anaesthesiologist needs to know about heart-lung interactions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Hemodynamic management is a mainstay of patient care in the operating room and intensive care unit (ICU). In order to optimize patient treatment, researchers investigate monitoring technologies, cardiovascular (patho-) physiology, and hemodynamic treatment strategies. The Journal of Clinical Monitoring and Computing (JCMC) is a well-established and recognized platform for publishing research in this field. In this review, we highlight recent advancements and summarize selected papers published in the JCMC in 2018 related to hemodynamic monitoring and management.

Background: Vasopressors are commonly applied to restore and maintain blood pressure in patients with sepsis. We aimed to evaluate the current practice and therapeutic goals regarding vasopressor use in septic shock as a basis for future studies and to provide some recommendations on their use., Methods: From November 2016 to April 2017, an anonymous web-based survey on the use of vasoactive drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 17 questions focused on the profile of respondents, triggering factors, first choice agent, dosing, timing, targets, additional treatments, and effects of vasopressors. We investigated whether the answers complied with current guidelines. In addition, a group of 34 international ESICM experts was asked to formulate recommendations for the use of vasopressors based on 6 questions with sub-questions (total 14)., Results: A total of 839 physicians from 82 countries (65% main specialty/activity intensive care) responded. The main trigger for vasopressor use was an insufficient mean arterial pressure (MAP) response to initial fluid resuscitation (83%). The first-line vasopressor was norepinephrine (97%), targeting predominantly a MAP > 60-65 mmHg (70%), with higher targets in patients with chronic arterial hypertension (79%). The experts agreed on 10 recommendations, 9 of which were based on unanimous or strong (≥ 80%) agreement. They recommended not to delay vasopressor treatment until fluid resuscitation is completed but rather to start with norepinephrine early to achieve a target MAP of ≥ 65 mmHg., Conclusion: Reported vasopressor use in septic shock is compliant with contemporary guidelines. Future studies should focus on individualized treatment targets including earlier use of vasopressors.

Background: Extrasystoles may be useful for predicting the response to fluid therapy in hemodynamically unstable patients but their prevalence is unknown. The aim of this study was to estimate the availability of extrasystoles in intensive care unit patients diagnosed with sepsis. The study aim was not to validate the fluid responsiveness prediction ability of extrasystoles., Methods: Twenty-four-hour ECG recordings from a convenience sample of 50 patients diagnosed with sepsis were extracted from the MIMIC-II waveform database, and ECGs were visually examined for correct QRS complex detection. Custom-made algorithms identified potential extrasystoles based on RR intervals. Two raters visually confirmed or rejected the potential extrasystoles and then classified them as ventricular, supraventricular, or unknown origin. Extrasystole availability was calculated as extrasystolic coverage for each 24 h ECG recording, that is, the percentage of the 24 h recording where an extrasystole had occurred in the preceding 30 minutes., Results: Mean extrasystolic coverage was 53.3% (confidence interval: [42.8; 63.6]%) and ventricular extrasystolic coverage was 21.4 [13.5; 29.8]%. Interrater reliability was strong for confirming/rejecting extrasystoles., Conclusions: Extrasystoles are available for fluid responsiveness prediction in septic patients in about half of the time. With this extrasystolic availability, we believe the method to be considered for clinical use, provided that future studies validate the method's fluid responsiveness prediction ability.

Background: Fluid responsiveness prediction with continuously available monitoring is an unsettled matter for the vast majority of critically ill patients, and development of new and reliable methods is desired. We hypothesized that the post-ectopic beat, which is associated with increased preload, could be analyzed in relation to preceding sinus beats and that the change in cardiac performance (e.g., systolic blood pressure) at the post-ectopic beat could predict fluid responsiveness., Methods: Critically ill patients were observed when scheduled for a 500-ml volume expansion. The 30-min ECG prior to volume expansion was analyzed for the occurrence of extrasystoles. Classification variables were defined as the change in a variable (e.g., systolic blood pressure or pre-ejection period) from the median of ten preceding sinus beats to extrasystolic post-ectopic beat. A stroke volume increase > 10% following volume expansion defined fluid responsiveness., Results: Twenty-six patients were included. The change in systolic blood pressure predicted fluid responsiveness with receiver operating characteristic (ROC) area 0.79 (CI [0.52:1.00]), specificity 100%, sensitivity 67%, positive predictive value 100%, and negative predictive value 91% (threshold: 5%). The change in pre-ejection period predicted fluid responsiveness with ROC area 0.74 (CI [0.53:0.94]), specificity 78%, sensitivity 67%, positive predictive value 50%, and negative predictive value 88% (threshold 7.5 ms)., Conclusions: Based on standard critical care monitoring, analysis of the extrasystolic post-ectopic beat predicts fluid responsiveness in critical care patients with good accuracy. The presented results are considered preliminary proof-of-concept results, and further validation is needed to confirm these preliminary findings., Competing Interests: The extrasystoles method was previously protected by a patent application owned by Aarhus University (PCT/DK2014/050094; STV as sole inventor). The application did, however, not lead to the granting of a patent at priority expiry date. TWLS is an associate editor of the Journal of Clinical Monitoring and Computing. TWLS received honoraria for consulting from Edwards Lifesciences and Masimo Corp. TWLS is currently the Chair of the Section Cardiovascular Dynamics of the European Society of Intensive Care Medicine as well as the Chair of the Scientific Subcommittee 14 (Monitoring, Ultrasound, and Equipment) of the European Society of Anaesthesiology. Apart from this, all other authors declare that they have no competing interests.This study was exclusively observational and approved as such by the Danish authorities.Not applicableSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Constipation is suspected to occur frequently after acquired brain injury (ABI). In patients with ABI, heart rate variability (HRV) is reduced suggesting autonomic dysfunction. Autonomic dysfunction may be associated with prolonged gastrointestinal transit time (GITT). The primary aim of this study was to investigate if GITT is prolonged in patients with ABI. Secondarily, HRV and its correlation with GITT was investigated., Methods: We included 25 patients with ABI (18 men, median age: 61.3 years, range [30.7-74.5]). GITT was assessed using radio-opaque markers and HRV was calculated from 24-hour electrocardiograms. Medical records were reviewed for important covariates, including primary diagnosis, time since injury, functional independence measure, and use of medication. The GITT assessed in patients was compared to a control group of 25 healthy subjects (18 men, median age: 61.5 years, range [34.0-70.9])., Results: In ABI patients, the mean GITT was significantly longer than in healthy controls (2.68 days, 95% CI [2.16-3.19] versus (1.92 days, 95% CI [1.62-2.22], p  = 0.011)). No correlation was found between HRV and GITT., Conclusion: Patients with mild to moderate ABI have prolonged GITT unrelated to the HRV., Competing Interests: The authors declare there are no competing interests.

Background: Pleural effusion (PLE) may lead to low blood pressure and reduced cardiac output. Low blood pressure and reduced cardiac output are often treated with fluid loading and vasopressors. This study aimed to determine the impact of fluid loading and norepinephrine infusion on physiologic determinants of cardiac function obtained by ultrasonography during PLE., Methods: In this randomised, blinded, controlled laboratory study, 30 piglets (21.9 ± 1.3 kg) had bilateral PLE (75 mL/kg) induced. Subsequently, the piglets were randomised to intervention as follows: fluid loading (80 mL/kg/h for 1.5 h, n = 12), norepinephrine infusion (0.01, 0.03, 0.05, 0.1, 0.2 and 0.3 μg/kg/min (15 min each, n = 12)) or control (n = 6). Main outcome was left ventricular preload measured as left ventricular end-diastolic area. Secondary endpoints included contractility and afterload as well as global measures of circulation. All endpoints were assessed with echocardiography and invasive pressure-flow measurements., Results: PLE decreased left ventricular end-diastolic area, mean arterial pressure and cardiac output (p values < 0.001), but fluid loading (20 mL/kg) and norepinephrine infusion (0.05 μg/kg/min) restored these values (p values > 0.05) to baseline. Left ventricular contractility increased with norepinephrine infusion (p = 0.002), but was not affected by fluid loading (p = 0.903). Afterload increased in both active groups (p values > 0.001). Overall, inferior vena cava distensibility remained unchanged during intervention (p values ≥ 0.085). Evacuation of PLE caused numerical increases in left ventricular end-diastolic area, but only significantly so in controls (p = 0.006)., Conclusions: PLE significantly reduced left ventricular preload. Both fluid and norepinephrine treatment reverted this effect and normalised global haemodynamic parameters. Inferior vena cava distensibility remained unchanged. The haemodynamic significance of PLE may be underestimated during fluid or norepinephrine administration, potentially masking the presence of PLE.

Purpose of Review: Fluid responsiveness prediction is not always possible with well established dynamic approaches such as passive leg raising or pulse pressure variation in the ICU. The purpose of the present review is to summarize emerging alternative techniques for fluid responsiveness prediction in adult critically ill patients and discuss their methodology and applicability. In addition, the future role of fluid responsiveness prediction in the ICU is discussed., Recent Findings: Several new dynamic techniques have been investigated and they all contribute to the applicability of fluid responsiveness techniques. Although increasing the applicability, most of the emerging techniques still rely on ventilator setting changes in patients that are fully or almost fully adapted to the ventilator or require reliable flow monitoring, which prevents broad applicability. Yet, the mini/micro fluid challenges and the use of extrasystolic preload changes have the potential of being more applicable but all reviewed methods need further validation and methodological refinement., Summary: Emerging techniques are encouraging for broader applicability of fluid responsiveness prediction. Still, the clinical impact of correctly predicting fluid responsiveness remains to be investigated in the critically ill and the research community should have a clear aim of moving toward that type of studies.

Fluid responsiveness prediction is an unsettled matter for most critical care patients and new methods relying only on the continuous basic monitoring are desired. It was hypothesized that the post-ectopic beat, which is associated with increased preload, could be analyzed in relation to preceding sinus beats and that the change in cardiac performance (e.g. systolic blood pressure) at the post-ectopic beat could predict fluid responsiveness. Cardiothoracic critical care patients scheduled for a 500 ml volume expansion were observed. In the 30 min prior to volume expansion, the ECG was analyzed for occurrence of extra systoles preceded by at least 10 sinus beats. Classification variables, were defined as the change in a variable (e.g. systolic blood pressure or pre-ejection period) from the median of 10 preceding sinus beats to extra systolic post-ectopic beat. A stroke volume increase >15 % following volume expansion defined fluid responsiveness. Thirty patients were included. The change in systolic blood pressure predicted fluid responsiveness in 24 patients correctly with 83 % specificity and 75 % sensitivity (optimal threshold: 5 % systolic blood pressure increase), receiver operating characteristic (ROC) area: 0.81 (CI [0.64;0.98]). The change in pre-ejection period predicted fluid responsiveness in 22 patients correctly with 67 % specificity and 83 % sensitivity (optimal threshold: 19 ms pre-ejection period decrease), ROC area: 0.81 (CI [0.66;0.96]). Pulse pressure variation had ROC area of 0.57 (CI [0.39;0.75]). Based on standard critical care monitoring, analysis of the extra systolic post-ectopic beat predicts fluid responsiveness in cardiothoracic critical care patients with good accuracy.

Unlabelled: Abstract Introduction: The relation between motor and cognitive function and autonomic nervous system (ANS) function during neurorehabilitation following acquired brain injury (ABI) has only been investigated sporadically. In the present study, it was hypothesized that clinical measures in severely injured patients would relate to heart rate variability (HRV), a measure of autonomic function., Methods: HRV measurements were initially performed on 49 patients (enrolled in a previous study) and follow-up (> 28 days) HRV measurements were performed. Standard deviation of normal-to-normal intervals (SDNN) and low frequency (LF) were extracted and these HRV variables were related to the clinical measures, Early Functional Ability (EFA) and Functional Independence Measure (FIM). Associations between HRV and clinical measures were analysed on admission data (only EFA), at follow-up and for the longitudinal change in measures., Results: Follow-up HRV was extracted from 19 patients. SDNN and LF were significantly correlated (p < 0.05) to the EFA and FIM at follow-up, but not at admission. SDNN and LF changes were significantly correlated to EFA changes, but not FIM changes. Admission SDNN and LF were unable to provide prognostic information for the EFA and FIM at follow-up., Conclusion: HRV and its change during neurorehabilitation were associated to EFA and EFA changes over time. Further studies are required to clarify a number of limitations arising from this observational study.

Monitoring that can predict fluid responsiveness is an unsettled matter for spontaneously breathing patients. Based on the convincing results with dynamic monitoring based on preload variations induced by mechanical ventilation, we hypothesised that the extra systolic post-ectopic beat could constitute a similar intermittent preload shift inducing a brief variation in blood pressure and that the magnitude of this variation could predict the hemodynamic response to volume expansion in sedated pigs. Ten pigs were sedated and hemodynamically monitored and four intravascular volume shifts were made: blood depletion (25% of estimated blood volume; 660 ml), retransfusion (of 500 ml depleted blood), and two sequential volume expansions (500 ml colloid each). Between volume shifts, supraventricular and ventricular extra systoles were induced by a pacemaker. Hemodynamic variables such as pulse pressure (PP) and pre-ejection period (PEP) were determined for each heart beat and the hemodynamic changes in the post-ectopic beats compared to sinus beats was extracted (e.g. ∆PP and ∆PEP) and used to predict fluid responsiveness of subsequent volume expansions which was determined by receiver operating characteristic (ROC) curves. Ventricular extra systoles were generally useful for fluid responsiveness prediction (ROC areas >0.65). ∆PEP variables best predicted fluid responsiveness: ∆PEP derived from arterial pressure curve and ECG had ROC area of 0.84 and sensitivity of 0.77 and specificity of 0.71; ∆PEP derived from plethysmographic curve and ECG had ROC area of 0.79 and sensitivity of 0.71 and specificity of 0.70. However, ∆PP was not a useful variable in this study (ROC area <0.65). Hemodynamic analysis of post ectopic beats may be a feasible method for fluid responsiveness prediction.

Monitoring that can predict fluid responsiveness is an unsettled matter for spontaneously breathing patients. Mechanical ventilation induces cyclic variations in blood pressure, e.g. pulse pressure variation, whose magnitude predicts fluid responsiveness in mechanically ventilated patients. In this study, we hypothesised that a deep breathing manoeuvre with its effect on heart rate variability (HRV) could induce similar cyclic variations in blood pressure in spontaneously breathing healthy subjects and that the magnitude of these variations could predict the hemodynamic response to controlled haemorrhage. 37 blood donors were instructed to perform two simple deep breathing manoeuvres prior to blood donation; one manoeuvre with a respiratory cycle every 10 s (0.1 Hz) and one every 6 s (0.167 Hz). The variation in the pre-ejection period (∆PEP) was captured with the electrocardiographic and plethysmographic curves, while the hemodynamic response to haemorrhage was estimated with the cardiac output change assessed with ultrasonography. Respiratory HRV was estimated with root mean square of successive differences (RMSSD). Deep breathing induced cyclic changes in ∆PEP magnitude was significantly correlated to RMSSD (p < 0.005). ∆PEP indexed to RMSSD increased significantly following haemorrhage at the 0.167 Hz respiratory frequency (p = 0.01). At none of the respiratory manoeuvres was ∆PEP nor ∆PEP/RMSSD prior to haemorrhage correlated to changes in cardiac output following haemorrhage. Deep breathing induces cyclic changes in blood pressure that are strongly dependent on HRV. These blood pressure variations do, however, not predict the cardiac output response to controlled haemorrhage.

Introduction: Acquired brain injury (ABI) cause neural deficits. In addition to motor and cognitive deficits, the autonomic nervous system may be affected. This has been shown for neurorehabilitation patients with traumatic brain injury (TBI) by means of reduced heart rate variability (HRV). It was hypothesized that patient groups with other ABI aetiology (mainly stroke, subarachnoid haemorrhage and anoxia) would also present reduced HRV., Methods: Patients consecutively admitted and severely ABI injured were considered for HRV measurements. HRV was extracted as a mean of four 5-minute ECG recordings at 6 pm, 10 pm, 2 am and 6 am the following day (scheduled resting periods). One 5-minute HRV recording from a sex- and age-matched group of healthy volunteers constituted control data. Standard deviation of normal-to-normal intervals (SDNN) and low frequency (LF) were primary HRV variables., Results: Of 71 admitted patients, HRV was extracted from 49 patients. Patient SDNN and LF were reduced compared to controls (SDNN: 13 ms (CI = [10.8; 15.3]) vs 40.3 ms (CI = [36.6; 44.2]), p < 0.0001; LF: 29.4 ms² (CI = [19.8; 43.7]) vs 518 ms² (CI = [419; 639]), p < 0.0001). HRV appeared identical across ABI aetiology., Conclusion: It was found that HRV was considerably reduced in an heterogenic ABI patient group admitted for neurorehabilitation.

Background: Ultrasonographic evaluation of the inferior vena cava (IVC) provides information on central hemodynamics and predicts fluid responsiveness during positive pressure ventilation. In spontaneously breathing patients, the correlations between IVC dynamics and the hemodynamic response to volume shifts remain to be described., Objectives: We aimed to describe the correlation between IVC dynamics and the changes in cardiac output (CO) caused by controlled hemorrhage., Methods: Healthy donors from the blood bank were eligible for inclusion. Measurements of the IVC and CO were performed before and immediately after blood donation using ultrasound methods. A control group served to evaluate the effect of resting., Results: Thirty-seven participants completed the study. IVC collapsibility index (IVC-CI) and IVC end expiratory diameter (IVCe) both changed significantly after blood donation (p < 0.001). The baseline IVC-CI and IVCe did not correlate with the change in CO (p-values ≥ 0.40). The alterations in IVC-CI and IVCe induced by blood donation also did not correlate with the change in CO (p ≥ 0.71). The sensitivities of IVC-CI or IVCe, defined as an increase in IVC-CI and a decrease in IVCe, for picking up any decrease in CO were 81.3% and 84.4%, respectively. In the control group, no effect was seen between measurements., Conclusion: IVC-CI and IVCe did not correlate with the magnitude of hemodynamic response to early hemorrhage. The sensitivity of serial IVC measurements was approximately 80% for detecting early blood loss., (Copyright © 2013 Elsevier Inc. All rights reserved.)