BACKGROUND:Haemorrhage is a leading cause of morbidity and mortality in trauma, and prehospital transfusion of blood products is often necessary. Whole blood has been proposed to be the best alternative, but it is unclear whether, and how, storage and transport of the blood in a helicopter affects the blood units. We investigated the coagulation capacity and platelet function in whole blood at different time points during helicopter missions. METHODS:Twenty units of low-titre group O RhD negative whole blood were collected from healthy volunteers and analysed before, during and after transport in a helicopter. Coagulation and platelet function, as measured by thromboelastography, and blood samples for pH, electrolytes, glucose and lactate were assessed at baseline and 24, 72 and 168 h after storage in the helicopter. Plasma concentrations of coagulation factors and haemoglobin and blood counts were measured at baseline and after 168 h. RESULTS:Plasma concentrations of coagulation factors and haemoglobin did not change during storage and transport. Platelet counts decreased from a baseline mean of 172 ± 29 × 109/L to a mean of 120 ± 28 × 109/L after 168 h, and platelet function worsened slightly but significantly by 8%-9% during storage and transport. pH and glucose decreased while potassium and lactate levels increased after 168 h compared with baseline. CONCLUSION:Storage and transport of whole-blood units in a rescue helicopter, for up to 168 h, had a slight impact on the blood quality. Storage of whole blood on board of the helicopter holds up to European standard, measured as temperature and haemolysis.

BACKGROUND:Postoperative neurocognitive decline is a frequent complication triggered by unclear signalling mechanisms. This observational case-control study investigated the effects of hip or knee replacement surgery on the composition of circulating extracellular vesicles (EVs), potential periphery-to-brain messengers, and their association with neurocognitive outcomes. METHODS:We mapped the microRNAome and proteome of plasma-derived EVs from 12 patients (six with good and six with poor neurocognitive outcomes at 3 months after surgery) at preoperative and postoperative timepoints (4, 8, 24, and 48 h). Complement C3-EV association was confirmed by flow cytometry in plasma- and cerebrospinal fluid (CSF)-derived EVs, with total plasma and CSF C3 and C3a concentrations determined using enzyme-linked immunosorbent assay. RESULTS:Differential expression analysis found eight dysregulated EV microRNAs (miRNAs) exclusively in the poor neurocognitive outcomes group. Pathway analysis suggested potential downregulation of proliferative pathways and activation of extracellular matrix and inflammatory response pathways in EV target tissues. Proteome analysis revealed a time-dependent increase in immune-related EV proteins, including complement system proteins, notably EV surface-associated C3. Such upward kinetics was detected earlier in the poor neurocognitive outcomes group. Interestingly, CSF-derived EVs from the same group showed a drastic drop of C3 at 48 h with unchanged concentrations in the good neurocognitive outcomes group. Functionally, the complement system was activated in both patient groups in plasma, but only in the poor neurocognitive outcomes group in CSF. CONCLUSIONS:Our findings highlight the impact of surgery on plasma- and CSF-derived EVs, particularly in patients with poor neurocognitive outcomes, indicating a potential role for EVs. The small sample size necessitates verification with a larger patient cohort.

BACKGROUND:Cardiac surgery with cardiopulmonary bypass (CPB) is associated with impaired renal oxygenation and acute kidney injury. The authors investigated whether an amount higher than their standard blood flow during CPB could improve renal blood flow, the oxygen demand-supply relationship, and function and attenuate tubular injury. METHODS:After ethical approval and informed consent, 36 adult patients undergoing cardiac surgery received either high flow (2.9 l · min -1 · m -2 , n = 19) or standard flow (2.4 l · min -1 · m -2 , n = 17) during CPB in this randomized, nonblinded, parallell-arm study. Systemic hemodynamics and renal variables were measured before and during CPB. Glomerular filtration rate was measured by infusion clearance of iohexol and renal blood flow by infusion clearance of para-aminohippuric acid, corrected for renal extraction of para-aminohippuric acid, using a renal vein catheter. Renal oxygen demand-supply relationship was estimated from renal oxygen extraction and tubular injury assessed by urinary N -acetyl-β- d -glucosaminidase. RESULTS:During CPB, high flow led to a larger increase in systemic oxygen delivery (100 [95% CI, 60 to 141] vs. 31 [1.9 to 65] ml · min -1 · m -2 ]; between-group P < 0.001; effect size Cohen's dz , 0.59) and target mean arterial pressure was maintained at a lower norepinephrine dose (0.03 [-0.01 to 0.06] µg · kg -1 · min -1 ] vs. 0.10 [0.02 to 0.19] µg · kg -1 · min -1 ; P = 0.048; Cohen's dz , 0.62) compared with standard flow. There were no differences in renal blood flow or oxygen extraction between groups. Glomerular filtration rate increased during high-flow CPB (6.4 [1.9 to 10.9] ml · min -1 · 1.73 m -2 ), but not in the standard-flow group (-2.3 [-10.9 to 6.2] ml · min -1 · 1.73 m -2 ; between-group P = 0.044; Cohen's dz , 0.66). The peak urinary excretion of N -acetyl-β- d -glucosaminidase was 1.42 (0.87 to 3.6) versus 3.74 (1.5 to 7.7) units/µmol creatinine in the high-flow and standard-flow groups, respectively ( P = 0.049). No perfusion-related adverse events were seen in either group. CONCLUSIONS:A 20% higher-than-standard CPB flow during cardiac surgery improved renal function, whereas no change in renal blood flow or oxygen demand-supply relationship could be detected. Higher CPB flow was associated with a less pronounced tubular injury marker release compared with standard flow.

BACKGROUND:Renal dysfunction is a common complication after heart transplantation (Htx). Glomerular filtration rate (GFR) can be assessed by various estimating equations (eGFR). We evaluated the correlation, agreement, and accuracy between eGFR and mGFR and the ability of eGFR to track changes in mGFR early after Htx. METHODS:A single-center prospective observational study on 55 patients undergoing Htx. Serum creatinine and mGFR (plasma clearance of Cr51-EDTA or iohexol) were measured preoperatively and on the fourth postoperative day. The accuracy of eGFR to predict true mGFR was calculated as the percentage of patients with an eGFR within 30% of mGFR (P30). The agreement between eGFR and mGFR was assessed according to Bland and Altman. A four-quadrant plot was made to evaluate the ability of eGFR to track changes in mGFR. RESULTS:The accuracy of eGFR to assess mGFR was 52%. The bias was 11.2 ± 17.4 mL/min/1.72 m2. The limits of agreement were -23.0 to 45.4 mL/min/1.72 m2 and the error 58%. The concordance rate between eGFR and mGFR was 72%. CONCLUSIONS:eGFR underestimated mGFR and the agreement between eGFR and mGFR was low with an unacceptably large between-group error and low accuracy. Furthermore, the ability of eGFR to assess changes in mGFR, postoperatively, was poor. Thus, the use of estimating equations from serum creatinine will not adequately assess renal function early after major heart surgery. To gain adequate information on renal function early after Htx, GFR needs to be measured, not estimated.

BACKGROUND:This study focuses on biomarkers in infants after open heart surgery, and examines the association of high-sensitive troponin T (hs-cTnT), interleukin-6 (IL-6), and interleukin-8 (IL-8) with postoperative acute kidney injury (AKI), ventilatory support time and need of vasoactive drugs. METHODS:Secondary exploratory study from a double-blinded clinical randomized trial (Mile-1) on 70 infants undergoing open heart surgery with cardiopulmonary bypass (CPB). In this sub-study, the entire study population was examined without considering the study drugs. The biomarkers' peak concentration (highest concentration at 2 or 6 h post-CPB) were used for statistical analyses. RESULTS:Peak IL-8, hs-cTnT, and IL-6 occurred at 2 h post-CPB for 96%, 79%, and 63% of the patients, respectively. The odds ratio of developing AKI2-3 for IL-6 > 293 pg/mL was 23.4 (95% CI 5.3;104.0), for IL-8 > 100 pg/mL it was 11.5 (3.0;44.2), and for hs-cTnT >5597 pg/mL it was 6.1 (1.5; 24.5). In more than two third of the patients with the highest peak concentrations of IL-8, IL-6, and hs-cTnT, there was a need for ventilatory support for >24 h and use of vasoactive drugs at 24 h post-CPB, while in less than one third of the patients with the lowest peak concentrations of IL-8 and hs-cTnT such requirements were observed. CONCLUSIONS:The peak biomarker concentrations and CPB-time strongly predicted AKI2-3, with IL-6 and IL-8 emerging as strongest predictors. Furthermore, our findings suggest that measuring hs-cTnT and IL-8 just 2 h post-CPB-weaning may assist in identifying infants suitable for early extubation and highlight those at risk of prolonged ventilation.

ABSTRACT The hemodynamic definitions of pulmonary hypertension consider resistive loading (pulmonary vascular resistance [PVR]), but there are increasing evidence that pulsatile loading (pulmonary artery compliance [PAC]) has functional and prognostic importance. The aims of the present study on patients with left heart disease, were to evaluate a novel echocardiographic right ventricular (RV) afterload score and to investigate its relation to risk of mortality or implantation of a left ventricular assist device. Patients (n = 220) with left ventricular ejection fraction < 50% consecutively referred for heart transplant or heart failure workup underwent echocardiography and right heart catheterization. Four metrics were included in the afterload score: the systolic pulmonary artery pressure (sPAPDoppler) and three variables related to pressure reflection in the pulmonary circulation. Two points were allocated for sPAPDoppler ≥ 60 mmHg and for each pressure reflection variable indicating PVR > 3 Wood units (WU). One point was allocated for sPAPDoppler 36–59 mmHg and for pressure reflection variables above the upper normal limit. Low afterload was defined as 0‐to‐1 points, intermediate as 2‐to‐4 points, and high as 5‐to‐8 points. There were in‐between the groups significant differences in PAC and PVR. A 5‐point RV dysfunction score showed with stepwise increased RV afterload more severe dysfunction. Unadjusted hazard ratio for endpoint was 3.34 (1.69–6.79) for intermediate score, and 5.11 (2.52–10.40) for patients with high score. In conclusion, in patients with severe heart failure, a novel echocardiographic RV afterload score is related to increased pulsatile and resistant load, more severe RV dysfunction, and increased risk of adverse outcome.

Aims: The aim of the study was to estimate the effect of household relative poverty on the risk of diabetic ketoacidosis at diagnosis of children with type 1 diabetes using an international standard measurement of relative poverty.Methods: A national population-based retrospective study was conducted. The Swedish National Diabetes Register (NDR) was linked with data from Sweden's public statistical agency (Statistics Sweden). Children who were diagnosed with new-onset type 1 diabetes in the period of 2014-2019 were common identifiers. The definition of diabetic ketoacidosis was venous pH <7.30 or a serum bicarbonate level <18 mmol/L. The exposure variable was defined according to the standard definition of the persistent at-risk-of-poverty rate used by the statistical office of the European Union (Eurostat) and several other European public statistical agencies. Univariate and multi-variable analyses were used to calculate the effect of relative poverty on the risk of diabetic ketoacidosis.Results: Children from households with relative poverty had a 41% higher risk of diabetic ketoacidosis (1.41, CI 1.12-1.77, p = 0.004) and more than double the risk of severe diabetic ketoacidosis (pH <7.10) (RR 2.10, CI 1.35-3.25, p = 0.001), as compared to children from households without relative poverty.Conclusions: Relative poverty significantly increases the risk of diabetic ketoacidosis at onset of type 1 diabetes in children, even in a high-income country with publicly reimbursed health care.

AbstractAimsThis study aimed to assess the use of high‐sensitivity troponin T (hsTNT) and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) in screening for cardiac dysfunction [left ventricular (LV) systolic or diastolic dysfunction or right ventricular (RV) dysfunction] in mixed intensive care unit (ICU) patients and establish whether these biomarkers are independently associated with an increased risk of death.MethodsWe performed a secondary analysis of a single‐centre prospective observational study in which consecutive ICU patients were examined with transthoracic echocardiography (TTE) and cardiac biomarkers. Patients with systolic or diastolic LV dysfunction, RV dysfunction or a combination of these were compared with patients with normal cardiac function. Sensitivity and specificity for different cut‐off levels were calculated using receiver operating characteristic curves. Regression models were used to evaluate the associations between cardiac biomarkers, sepsis, renal failure and mortality.ResultsA total of 276 patients were included. Most of the patients had cardiac dysfunction on TTE (64%). Combined cardiac dysfunction was most prevalent (71 patients, 26%), followed by isolated diastolic LV dysfunction (40 patients, 15%). Levels of hsTNT and NT‐proBNP were higher in all types of cardiac dysfunction versus patients with normal cardiac function. The area under the curve (AUC) for hsTNT to detect any cardiac dysfunction was 0.75. An optimal cut‐off at 30.5 ng/L rendered a positive predictive value (PPV) of 80% and a negative predictive value (NPV) of 58%. The AUC for NT‐proBNP to detect any cardiac dysfunction was 0.788. Using an optimal cut‐off at 1145 ng/L rendered a PPV of 86% and an NPV of 58%. Using a clinically relevant 90% sensitivity for detecting cardiac dysfunction put the cut‐offs at 14.1 ng/L for hsTNT and 247 ng/L for NT‐proBNP, resulting in a specificity of 48% and 46%, respectively. Levels of NT‐proBNP were associated with sepsis and renal failure (P < 0.001), while levels of hsTNT were associated with renal failure only (P < 0.001) after adjustment for cardiac dysfunction. Levels of biomarkers were associated with an increased risk of 90 day mortality after adjustments for age, Simplified Acute Physiology Score 3, cardiac dysfunction and factors independently associated with biomarker increase (sepsis and renal failure) (P = 0.048 for hsTNT and P < 0.006 for NT‐proBNP).ConclusionCardiac biomarkers, hsTNT and NT‐proBNP, are strongly correlated to cardiac dysfunction in ICU patients and have a robust association with increased mortality. However, the relatively low NPV and the low specificity at relevant sensitivity levels of the biomarkers make them unsuitable for use in screening for cardiac dysfunction.

BACKGROUND:Estimating equations for the assessment of glomerular filtration rate (GFR) have been poorly investigated in the critical care setting. We evaluated the agreement between the GFR measured with 51CrEDTA/iohexol (mGFR) and four estimating equations based on serum concentrations of creatine and/or cystatin C (eGFR) in two cohorts: critically ill patients and outpatients with normal-to-moderately reduced GFR. METHODS:Forty-three patients in the critical care group and 48 patients in the outpatient group were included. GFR was measured (mGFR) by plasma infusion clearance of 51Cr-EDTA/iohexol (critical care group) and the single injection, one-sample plasma 51Cr-EDTA clearance technique (outpatients). The following estimating equations (eGFR) were used: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for creatinine (CKD-EPICr), cystatin C (CKD-EPICys C), creatinine+cystatin C (CKD-EPICr + Cys C) and the Lund-Malmö creatinine+cystatin C equation (LMCr + Cys C). Agreement between mGFR and eGFR was assessed by the Bland-Altman method and accuracy by calculating P30 and P10. RESULTS:In the critically ill group, the bias between the estimating equations and mGFR was -3.6 to 2.8 mL/min/1.73 m2, while the error was 121%-127% and the accuracy (P30) 33%-40%. In the outpatients, the bias between the estimating equations and mGFR was -13.0 to 7.6 mL/min/1.73 m2, while the error was 31%-41% and the accuracy (P30), 67%-96%. CONCLUSIONS:All four equations performed poorly in assessing GFR in the critically ill cohort with an unacceptably high error and low accuracy in contrast to the outpatient group. To accurately assess GFR in critically ill patients, GFR must be measured not estimated. EDITORIAL COMMENT:For the assessment of glomerular filtration rate (GFR), it can be measured directly, but is frequently estimated using a point measure of serum creatinine concentration. In this study, ICU case GFR estimations, by different adjusted equations, done also for a cohort of outpatients, showed that these serum creatinine-based estimations for ICU cases are not highly precise or reliable.

BACKGROUND:Cardiopulmonary bypass (CPB) ensures tissue oxygenation during cardiac surgery. New technology allows continuous registration of CPB variables during the operation. The aim of the present investigation was to study the association between CPB management and the risk of postoperative acute kidney injury (AKI). METHODS:This observational study based on prospectively registered data included 2661 coronary artery bypass grafting and/or valve patients operated during 2016-2020. Individual patient characteristics and postoperative outcomes collected from the SWEDEHEART registry were merged with CPB variables automatically registered every 20 s during CPB. Associations between CPB variables and AKI were analyzed with multivariable logistic regression models adjusted for patient characteristics. RESULTS:In total, 387 patients (14.5%) developed postoperative AKI. After adjustments, longer time on CPB and aortic cross-clamp, periods of compromised blood flow during aortic cross-clamp time, and lower nadir hematocrit were associated with the risk of AKI, while mean blood flow, bladder temperature, central venous pressure, and mixed venous oxygen saturation were not. Patient characteristics independently associated with AKI were advanced age, higher body mass index, hypertension, diabetes mellitus, atrial fibrillation, lower left ventricular ejection fraction, estimated glomerular filtration rate <60 or >90 mL/min/m2 , and preoperative hemoglobin concentration below or above the normal sex-specific range. CONCLUSIONS:To reduce the risk of AKI after cardiac surgery, aortic clamp time and CPB time should be kept short, and low hematocrit and periods of compromised blood flow during aortic cross-clamp time should be avoided if possible.

INTRODUCTION:Liver resection carries a high risk for extensive bleeding and need for blood transfusions, which is associated with significant negative impact on outcome. In malignant disease, the most common indication for surgery, it also includes increased risk for recurrence of cancer. Argipressin decreases liver and portal blood flow and may have the potential to reduce bleeding during liver surgery, although this has not been explored. METHOD AND ANALYSIS:ARG-01 is a prospective, randomised, placebo-controlled, double-blinded study on 248 patients undergoing liver resection at Sahlgrenska University Hospital, Sweden. Patients will be randomised to one of two parallel groups, infusion of argipressin or normal saline administered peroperatively. The primary endpoint is peroperative blood loss. Secondary outcomes include need for blood transfusion, perioperative variables, length of hospital stay, the inflammatory response, organ damage markers and complications at 30 days. ETHICS AND DISSEMINATION:The study is enrolling patients since March 2022. The trial is approved by the Swedish Ethical Review Authority (Dnr 2021-03557) and the Swedish Medical Product Agency (Dnr 5.1-2021-90115). Results will be announced at scientific meetings and in international peer-reviewed journals. TRIAL REGISTRATION NUMBER:ClinicalTrials.gov, NCT05293041 and EudraCT, 2021-001806-32.

Acute kidney injury (AKI) and renal dysfunction after heart transplantation are common and serious complications. Atrial natriuretic peptide (ANP) has been shown to increase glomerular filtration rate (GFR) and exert renoprotective effects when used for the prevention/treatment of AKI in cardiac surgery. We tested the hypothesis that intraoperative and postoperative administration of ANP could prevent a postoperative decrease in renal function early after heart transplantation.

Background: Systemic haemodynamic effects of intrathecal anaesthesia in an aging and frail population has not been well investigated. We examined the systemic haemodynamics of fractional spinal anaesthesia following intermittent microdosing of a local anaesthetic and an opioid. Methods: We included 15 patients aged over 65 with significant comorbidities, planned for hip fracture repair. Patients received a spinal catheter and cardiac output monitoring using the LiDCOplus system. All measurements were performed prior to start of surgery. Invasive mean arterial pressure (MAP), cardiac index (CI), systemic vascular resistance index (SVRI), heart rate and stroke volume index (SVI) were registered. Two doses of bupivacaine 2.25 mg and fentanyl 15 µg were administered with 25-minute intervals. Hypotension was defined as a fall in MAP by >30% or a MAP <65 mmHg. Results: The incidence of hypotension was 30%. Hypotensive patients (n=5) were treated with low doses of norepinephrine (0.01-0.12 µg/kg/min). MAP showed a maximum reduction of 17% at 10 minutes following the first dose. CI, systemic vascular resistance index and stroke volume index decreased by 10%, 6%, and 7%, respectively, while heart rate was unchanged over time. After the second dose, none of the systemic haemodynamic variables were affected. Conclusions: Fractional spinal anaesthesia administered prior to surgery induced a minor to moderate fall in MAP, mainly caused by a reduction in cardiac output, induced by systemic venodilation, causing a fall in venous return. Our results are contrary to the widely held belief that hypotension is mainly the result of a reduction of systemic vascular resistance.

Introduction: Intravascular fluids administered to patients may influence hemostasis. In patients undergoing cardiac surgery with cardiopulmonary bypass, the heart-lung machine is primed with 1300 ml of fluid. We assessed postoperative coagulation and platelet function in patients randomized to two different priming solu-tions, one colloid-based (dextran 40) and one crystalloid-based.Materials and methods: Eighty-four elective cardiac surgery patients were randomized to either a dextran-based prime or Ringer's acetate with added mannitol. Blood samples were collected before, and 2 and 24 h after cardiopulmonary bypass. Coagulation was assessed by standard coagulation tests and rotational thromboelas-tometry. Platelet function was assessed with impedance aggregometry. Bleeding volumes and transfusion re-quirements were recorded.Results: Comparing the groups 2 h after bypass, the dextran group showed lower hemoglobin concentration, hematocrit, platelet count, and fibrinogen concentration, and higher INR and aPTT, as well as longer clot for-mation time (+41 +/- 21 % vs. +8 +/- 18 %, p < 0.001) and a larger reduction in fibrinogen-dependent clot strength (-37 +/- 12 % vs.-7 +/- 20 %, p < 0.001). Adenosine diphosphate-dependent platelet activation was reduced in the dextran group but not in the crystalloid group 2 h after bypass (-14 +/- 29 % vs.-1 +/- 41 %, p = 0.041). No significant between-group differences in hemostatic variables remained after 24 h, and no significant differences in perioperative bleeding volumes, re-explorations for bleeding, or transfusion rates were observed.Conclusions: Compared to a crystalloid solution, a dextran-based prime had measurable negative impact on he-mostatic variables but no detectable increase in bleeding volume or transfusion requirements in cardiac surgery patients.

PURPOSE:Left ventricular (LV) diastolic dysfunction is important in critically ill patients, but prevalence and impact on mortality is not well studied. We classified intensive care patients with normal left ventricular function according to current diastolic guidelines and explored associations with mortality. MATERIAL AND METHODS:Echocardiography was performed within 24 h of intensive care admission. Patients with reduced LV ejection fraction, regional wall motion abnormality, or a history of cardiac disease were excluded. Patients were classified according to the 2016 EACVI guidelines, Recommendations for the Evaluation of LV Diastolic Function by Echocardiography. RESULTS:Out of 218 patients, 162 (74%) had normal diastolic function, 21 (10%) had diastolic dysfunction, and 35 (17%) had indeterminate diastolic function. Diastolic dysfunction were more common in female patients, older patients and associated with sepsis, respiratory and cardiovascular comorbidity as well as higher SAPS Score. In a risk-adjusted logistic regression model, patients with indeterminate diastolic dysfunction (OR 4.3 [1.6-11.4], p = 0.004) or diastolic dysfunction (OR 5.1 [1.6-16.5], p = 0.006) had an increased risk of death at 90 days compared to patients with normal diastolic function. CONCLUSION:Isolated diastolic dysfunction, assessed by a multi-parameter approach, is common in critically ill patients and is associated with mortality. TRIAL REGISTRATION:Secondary analysis of data from a single-center prospective observational study focused on systolic dysfunction in intensive care unit patients (Clinical Trials ID: NCT03787810.

Left ventricular (LV) dysfunction is estimated to occur in 10%–25% of the general intensive care unit (ICU) population and is frequently seen as regional wall motion abnormalities (RWMAs). Although RWMA is mostly attributed to myocardial ischemia or infarction, some studies have suggested that nonischemic RWMA might also be prevalent. We sought to establish that RWMA can be seen in critically ill patients with normal coronary arteries and to explore reasons for RWMA in this population.

Background: Systemic haemodynamic effects of intrathecal anaesthesia in an aging and frail population has not been well investigated. We examined the systemic haemodynamics of fractional spinal anaesthesia following intermittent microdosing of a local anaesthetic and an opioid. Methods: We included 15 patients aged over 65 with significant comorbidities, planned for hip fracture repair. Patients received a spinal catheter and cardiac output monitoring using the LiDCOplus system. All measurements were performed prior to start of surgery. Invasive mean arterial pressure (MAP), cardiac index (CI), systemic vascular resistance index (SVRI), heart rate and stroke volume index (SVI) were registered. Two doses of bupivacaine 2.25 mg and fentanyl 15 µg were administered with 25-minute intervals. Hypotension was defined as a fall in MAP by >30% or a MAP <65 mmHg. Results: The incidence of hypotension was 30%. Hypotensive patients (n=5) were treated with low doses of norepinephrine (0.01-0.12 µg/kg/min). MAP showed a maximum reduction of 17% at 10 minutes following the first dose. CI, systemic vascular resistance index and stroke volume index decreased by 10%, 6%, and 7%, respectively, while heart rate was unchanged over time. After the second dose, none of the systemic haemodynamic variables were affected. Conclusions: Fractional spinal anaesthesia administered prior to surgery induced a minor to moderate fall in MAP, mainly caused by a reduction in cardiac output, induced by systemic venodilation, causing a fall in venous return. Our results are contrary to the widely held belief that hypotension is mainly the result of a reduction of systemic vascular resistance.

BACKGROUND:Isolated limb perfusion (ILP) is a regional surgical treatment for localized metastatic disease. High doses of chemotherapeutic agents are administered within an extracorporeal circulated isolated extremity, treating the metastasis, while systemic toxicity is avoided. To our knowledge, indexed oxygen supply/demand relationship during ILP has not previously been described. Our aim was to measure and describe oxygen metabolism, specifically oxygen delivery, consumption, and extraction, in an isolated leg/arm during ILP. Also investigate whether invasive oxygenation measurement during ILP correlates and can be used interchangeable with the non-invasive method, near infrared spectroscopy (NIRS).METHODS:Data from 40 patients scheduled for ILP were included. At six time points blood samples were drawn during the procedure. DO2, VO2, and O2ER were calculated according to standard formulas. NIRS and hemodynamics were recorded every 10 min.RESULTS:For all observations, the mean of DO2 was 190±59 ml/min/m2, VO2 was 35±8 ml/min/m2, and O2ER was 21±8%. VO2 was significantly higher in legs compared to arms (38±8 vs. 29±7 ml/min/m2, p=0.02). Repeated measures showed a significant decrease in DO2 in legs (209±65 to 180±66 ml/min/m2, p=<0.01) and in arms (252±72 to 150±57 ml/min/m2, p=<0.01). Significant increase in O2ER in arms was also found (p=0.03). Significant correlation was detected between NIRS and venous extremity oxygen saturation (SveO2) (rrm=0.568, p=<. 001, 95% CI 0.397-0.701). When comparing SveO2 and NIRS using a Bland-Altman analysis, the mean difference (bias) was 8.26±13.03 (p=<. 001) and the limit of agreement was - 17.28-33.09, with an error of 32.5%.CONCLUSION:DO2 above 170 ml/min/m2 during ILP kept O2ER below 30% for all observations. NIRS correlates significant to SveO2; however, the two methods do not agree sufficiently to work interchangeable. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT04460053 and NCT03073304.

The inodilator levosimendan, in clinical use for over two decades, has been the subject of extensive clinical and experimental evaluation in various clinical settings beyond its principal indication in the management of acutely decompensated chronic heart failure. Critical care and emergency medicine applications for levosimendan have included postoperative settings, septic shock, and cardiogenic shock. As the experience in these areas continues to expand, an international task force of experts from 15 countries (Austria, Belgium, China, Croatia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Spain, Sweden, Switzerland, and the USA) reviewed and appraised the latest additions to the database of levosimendan use in critical care, considering all the clinical studies, meta-analyses, and guidelines published from September 2019 to November 2021. Overall, the authors of this opinion paper give levosimendan a “should be considered” recommendation in critical care and emergency medicine settings, with different levels of evidence in postoperative settings, septic shock, weaning from mechanical ventilation, weaning from veno-arterial extracorporeal membrane oxygenation, cardiogenic shock, and Takotsubo syndrome, in all cases when an inodilator is needed to restore acute severely reduced left or right ventricular ejection fraction and overall haemodynamic balance, and also in the presence of renal dysfunction/failure.