Red Blood Cell Transfusion in the Intensive Care Unit.

Importance: Red blood cell (RBC) transfusion is common among patients admitted to the intensive care unit (ICU). Despite multiple randomized clinical trials of hemoglobin (Hb) thresholds for transfusion, little is known about how these thresholds are incorporated into current practice. Objective: To evaluate and describe ICU RBC transfusion practices worldwide. Design, Setting, and Participants: International, prospective, cohort study that involved 3643 adult patients from 233 ICUs in 30 countries on 6 continents from March 2019 to October 2022 with data collection in prespecified weeks. Exposure: ICU stay. Main Outcomes and Measures: The primary outcome was the occurrence of RBC transfusion during ICU stay. Additional outcomes included the indication(s) for RBC transfusion (consisting of clinical reasons and physiological triggers), the stated Hb threshold and actual measured Hb values before and after an RBC transfusion, and the number of units transfused. Results: Among 3908 potentially eligible patients, 3643 were included across 233 ICUs (median of 11 patients per ICU [IQR, 5-20]) in 30 countries on 6 continents. Among the participants, the mean (SD) age was 61 (16) years, 62% were male (2267/3643), and the median Sequential Organ Failure Assessment score was 3.2 (IQR, 1.5-6.0). A total of 894 patients (25%) received 1 or more RBC transfusions during their ICU stay, with a median total of 2 units per patient (IQR, 1-4). The proportion of patients who received a transfusion ranged from 0% to 100% across centers, from 0% to 80% across countries, and from 19% to 45% across continents. Among the patients who received a transfusion, a total of 1727 RBC transfusions were administered, wherein the most common clinical indications were low Hb value (n = 1412 [81.8%]; mean [SD] lowest Hb before transfusion, 7.4 [1.2] g/dL), active bleeding (n = 479; 27.7%), and hemodynamic instability (n = 406 [23.5%]). Among the events with a stated physiological trigger, the most frequently stated triggers were hypotension (n = 728 [42.2%]), tachycardia (n = 474 [27.4%]), and increased lactate levels (n = 308 [17.8%]). The median lowest Hb level on days with an RBC transfusion ranged from 5.2 g/dL to 13.1 g/dL across centers, from 5.3 g/dL to 9.1 g/dL across countries, and from 7.2 g/dL to 8.7 g/dL across continents. Approximately 84% of ICUs administered transfusions to patients at a median Hb level greater than 7 g/dL. Conclusions and Relevance: RBC transfusion was common in patients admitted to ICUs worldwide between 2019 and 2022, with high variability across centers in transfusion practices.

Mesenchymal Stromal Cell Therapy in Novel Porcine Model of Diffuse Liver Damage Induced by Repeated Biliary Obstruction.

In liver surgery, biliary obstruction can lead to secondary biliary cirrhosis, a life-threatening disease with liver transplantation as the only curative treatment option. Mesenchymal stromal cells (MSC) have been shown to improve liver function in both acute and chronic liver disease models. This study evaluated the effect of allogenic MSC transplantation in a large animal model of repeated biliary obstruction followed by partial hepatectomy. MSC transplantation supported the growth of regenerated liver tissue after 14 days (MSC group, n = 10: from 1087 ± 108 (0 h) to 1243 ± 92 mL (14 days); control group, n = 11: from 1080 ± 95 (0 h) to 1100 ± 105 mL (14 days), p = 0.016), with a lower volume fraction of hepatocytes in regenerated liver tissue compared to resected liver tissue (59.5 ± 10.2% vs. 70.2 ± 5.6%, p < 0.05). Volume fraction of connective tissue, blood vessels and bile vessels in regenerated liver tissue, serum levels of liver enzymes (AST, ALT, ALP and GGT) and liver metabolites (albumin, bilirubin, urea and creatinine), as well as plasma levels of IL-6, IL-8, TNF-α and TGF-ß, were not affected by MSC transplantation. In our novel, large animal (pig) model of repeated biliary obstruction followed by partial hepatectomy, MSC transplantation promoted growth of liver tissue without any effect on liver function. This study underscores the importance of translating results between small and large animal models as well as the careful translation of results from animal model into human medicine.

Vagus Nerve Stimulation Attenuates Multiple Organ Dysfunction in Resuscitated Porcine Progressive Sepsis.

OBJECTIVES: To investigate the potential benefits of vagus nerve stimulation in a clinically-relevant large animal model of progressive sepsis. DESIGN: Prospective, controlled, randomized trial. SETTING: University animal research laboratory. SUBJECTS: Twenty-five domestic pigs were divided into three groups: 1) sepsis group (eight pigs), 2) sepsis + vagus nerve stimulation group (nine pigs), and 3) control sham group (eight pigs). INTERVENTIONS: Sepsis was induced by cultivated autologous feces inoculation in anesthetized, mechanically ventilated, and surgically instrumented pigs and followed for 24 hours. Electrical stimulation of the cervical vagus nerve was initiated 6 hours after the induction of peritonitis and maintained throughout the experiment. MEASUREMENTS AND MAIN RESULTS: Measurements of hemodynamics, electrocardiography, biochemistry, blood gases, cytokines, and blood cells were collected at baseline (just before peritonitis induction) and at the end of the in vivo experiment (24 hr after peritonitis induction). Subsequent in vitro analyses addressed cardiac contractility and calcium handling in isolated tissues and myocytes and analyzed mitochondrial function by ultrasensitive oxygraphy. Vagus nerve stimulation partially or completely prevented the development of hyperlactatemia, hyperdynamic circulation, cellular myocardial depression, shift in sympathovagal balance toward sympathetic dominance, and cardiac mitochondrial dysfunction, and reduced the number of activated monocytes. Sequential Organ Failure Assessment scores and vasopressor requirements significantly decreased after vagus nerve stimulation. CONCLUSIONS: In a clinically-relevant large animal model of progressive sepsis, vagus nerve stimulation was associated with a number of beneficial effects that resulted in significantly attenuated multiple organ dysfunction and reduced vasopressor and fluid resuscitation requirements. This suggests that vagus nerve stimulation might provide a significant therapeutic potential that warrants further thorough investigation.

Clinical and Humoral Determinants of Congestion in Heart Failure: Potential Role of Adiponectin.

BACKGROUND: Some patients with heart failure (HF) are more prone to systemic congestion than others. The goal of this study was to identify clinical and humoral factors linked to congestion and its prognostic impact in HF patients. METHODS: A total of 371 advanced HF patients underwent physical examination, echocardiography, right heart catheterization, blood samplings, and Minnesota Living with HF Questionnaire. Subjects were followed-up for adverse events (death, urgent transplantation, or assist device implantation without heart transplantation). RESULTS: Thirty-one percent of patients were classified as prone to congestion. During a median follow-up of 1,093 days, 159 (43%) patients had an adverse event. In the Cox analysis, the congestion-prone (CP) status was associated with a 43% higher event risk. The CP status was strongly (p ˂ 0.001) associated with body weight loss, right ventricular dysfunction (RVD), dilated inferior vena cava (IVC), diuretics, and beta-blockers prescription and the majority of tested hormones in the univariate analysis. In the multivariate analysis, the only independent variables associated with the CP status were adiponectin, albumin, IVC diameter, and RVD. Adiponectin by itself was predictive of adverse events. In a multivariate model, CP status was no longer predictive of adverse events, in contrast to adiponectin. CONCLUSIONS: CP patients experienced more severe symptoms and had shorter survival. Potential role of adiponectin, a new independent predictor of CP status, should be further examined.

Endothelial glycocalyx in acute care surgery - what anaesthesiologists need to know for clinical practice.

The endothelial glycocalyx (EG) is the thin sugar-based lining on the apical surface of endothelial cells. It has been linked to the physiological functioning of the microcirculation and has been found to be damaged in critical illness and after acute care surgery. This review aims to describe the role of EG in severely injured patients undergoing surgery, discuss specific situations (e.G. major trauma, hemorrhagic shock, trauma induced coagulopathy) as well as specific interventions commonly applied in these patients (e.g. fluid therapy, transfusion) and specific drugs related to perioperative medicine with regard to their impact on EG.EG in acute care surgery is exposed to damage due to tissue trauma, inflammation, oxidative stress and inadequate fluid therapy. Even though some interventions (transfusion of plasma, human serum albumin, hydrocortisone, sevoflurane) are described as potentially EG protective there is still no specific treatment for EG protection and recovery in clinical medicine.The most important principle to be adopted in routine clinical practice at present is to acknowledge the fragile structure of the EG and avoid further damage which is potentially related to worsened clinical outcome.

Propofol versus sevoflurane anaesthesia: effect on cognitive decline and event-related potentials.

Postoperative cognitive dysfunction (POCD) is diagnosed in up to 30% patients after anaesthesia. The causative role of anaesthetic toxicity remains unclear. Using clinical tests, no clear-cut differences have been observed between anaesthetics so far. The aim of this trial was to compare the incidence of POCD diagnosed by a battery of neuropsychologic tests after propofol and sevoflurane anaesthesia. Secondary goal was to examine possible relationship between POCD positivity and changes in auditory event-related potentials (ERPs). Sixty patients undergoing lumbar discectomy were prospectively randomized to receive depth-controlled sevoflurane (SEVO) or propofol (PROP) based anaesthesia. The neuropsychological examination and auditory event-related potentials (N1, P3a and P3b components) recording was performed preoperatively and on days 1, 6 and 42 after surgery. POCD was defined as a decline of more than one standard deviation in three or more tests. In 43 patients (20 in PROP and 23 in SEVO group) all selected tests were performed and used for the evaluation. POCD was present in 48%/60%, 18%/20% and 17%/11% (SEVO/PROP) of patients on days 1, 6 and 42 after surgery, with no significant intergroup difference. Among neuropsychologic tests, the most significant decline was observed in Semantic Verbal Fluency and Letter-Number Sequencing Test scores, congruently in both groups on days 1 and 6, with full recovery on the last control. Transient deteriorations in other tests were observed as well. No association of POCD positivity and ERPs changes was found, although long-term modifications of P3a and P3b components were observed, mainly in SEVO group. In our study, sevoflurane and propofol anaesthesia was associated with the similar incidence of POCD. Cognitive decline, mainly affecting executive functions, was temporary in most of the patients. Prolonged ERPs alterations after the anaesthesia seem not to have any relationship with the impairment registered by the neuropsychological examination and may represent subclinical changes.

Diagnosing hypovolemia and hypervolemia: from clinical examination to modern methods.

In acutely ill patients, disturbances of circulating blood volume and water homeostasis are frequently encountered. In order to choose adequate treatment strategy a well based diagnostics of these disturbance sis necessary, because fluid therapy possess the potential not only to help but also to worsen patients state. Currently we have at hand several possibilities to diagnose hypovolemia or hypervolemia: besides standard clinical assessment novel approaches as dedicated laboratory markers or sonography. Tests of fluid responsiveness are other mean how to ensure that the acutely ill patient will receive just the right amount of fluids. In this review article we will present the current view of the circulating blood volume pathophysiology as well as contemporary diagnostic tools.

Targeting the endothelial glycocalyx in acute critical illness as a challenge for clinical and laboratory medicine.

The purpose of this manuscript is to review the role of endothelial glycocalyx (EG) in the field of critical and perioperative medicine and to discuss possible future directions for investigations in this area. Under physiological conditions, EG has several well-defined functions aimed to prevent the disruption of vessel wall integrity. Under pathological conditions, the EG represent one of the earliest sites of injury during inflammation. EG structure and function distortion contribute to organ dysfunction related to sepsis, trauma, or global ischemia of any origin. Discovering new therapeutic approaches (either pharmacological or non-pharmacological) aimed to protect the EG against injury represents a promising direction in clinical medicine. Further, the currently-used common interventions in the acutely ill - fluids, blood products, nutritional support, organ-supporting techniques (e.g. continuous renal replacement therapy, extracorporeal circulation), temperature modulation and many others - should be re-evaluated during acute illness in terms of their EG "friendliness". To assess new therapies that protect the EG, or to evaluate the effect of currently-used interventions on EG integrity, a relevant marker or method to determine EG damage is needed. Such marker or method should be available to clinicians within hours, preferably in the form of a point-of-care test at the bedside. Collaborative research between clinical disciplines and laboratory medicine is warranted, and targeting the EG represents major challenges for both.

Molecular differences in susceptibility of the kidney to sepsis-induced kidney injury.

BACKGROUND: Septic acute kidney injury affects 40-50% of all septic patients. Molecular differences between septic patients with and without acute kidney injury (AKI) are only poorly understood. Here, we investigated gene expression changes that differentiated the subjects who developed septic AKI from those who did not and coupled this approach with traditional parameters of renal physiology. METHODS: In 15 anesthetized, mechanically ventilated and instrumented pigs, progressive sepsis was induced either by peritonitis or by continuous intravenous infusion of Pseudomonas aeruginosa. Animals received standard intensive care including goal-directed hemodynamic management. Analyses were performed on kidneys from sham operated animals, septic pigs without AKI, and pigs with septic AKI. Before, and at 12, 18 and 22 h of progressive sepsis, systemic and renal hemodynamics, cortex microcirculation and plasma IL-6 and TNF-α were measured. At 22 h whole kidney expression of pre-selected genes was analyzed by quantitative Real Time PCR. RESULTS: Animals with septic AKI had systemic hemodynamic phenotype (normo- or hyperdynamic) comparable with non-AKI subjects, but demonstrated higher plasma levels of cytokines, an increase in renal vascular resistance and early fall in cortical microcirculatory blood flow. The genes whose expression discriminated septic AKI from non-AKI included Toll like receptor 4 (up-regulated 2.7-fold, P = 0.04); Cyclooxygenase-2 (up-regulated 14.6-fold, P = 0.01), Angiotensin II Receptor (up-regulated 8.1-fold, P = 0.01), Caspase 3 (up-regulated 5.1-fold, P = 0.02), Peroxisome Proliferator-Activated Receptor Gamma, Coactivator 1 Alpha (down-regulated 2-fold, P = 0.02). CONCLUSIONS: In this preliminary experimental study, kidney gene expression was profoundly different in animals that developed septic AKI as opposed to septic animals that did not. The biological functions of the genes differentially expressed support a role of inflammatory overstimulation coupled with metabolic and apoptotic molecular responses in early septic AKI. Cyclooxygenase-2 and angiotensin type 2 receptor-dependent downstream mechanisms appear fruitful targets for future mechanistic research.

Comparison of the accuracy of hemoglobin point of care testing using HemoCue and GEM Premier 3000 with automated hematology analyzer in emergency room.

The laboratory analysis provides accurate, but time consuming hemoglobin level estimation especially in the emergency setting. The reliability of time-sparing point of care devices (POCT) remains uncertain. We tested two POCT devices accuracy (HemoCue®201+ and Gem®Premier™3000) in routine emergency department workflow. Blood samples taken from patients admitted to the emergency department were analyzed for hemoglobin concentration using a laboratory reference Beckman Coulter LH 750 (HBLAB), the HemoCue (HBHC) and the Gem Premier 3000 (HBGEM). Pairwise comparison for each device and HbLAB was performed using correlation and the Bland-Altman methods. The reliability of transfusion decision was assessed using three-zone error grid. A total of 292 measurements were performed in 99 patients. Mean hemoglobin level were 115 ± 33, 110 ± 28 and 111 ± 30 g/l for HbHC, HbGEM and HbLAB respectively. A significant correlation was observed for both devices: HbHC versus HbLAB (r2 = 0.93, p < 0.001) and HBGEM versus HBLAB (r2 = 0.86, p < 0.001). The Bland-Altman method revealed bias of -3.7 g/l (limits of agreement -20.9 to 13.5) for HBHC and HBLAB and 2.5 g/l (-18.6 to 23.5) for HBGEM and HBLAB, which significantly differed between POCT devices (p < 0.001). Using the error grid methodology: 94 or 91 % of values (HbHC and HbGEM) fell in the zone of acceptable difference (A), whereas 0 and 1 % (HbHC and HbGEM) were unacceptable (zone C). The absolute accuracy of tested POCT devices was low though reaching a high level of correlation with laboratory measurement. The results of the Morey´s error grid were unfavorable for both POCT devices.

The M2 muscarinic receptors are essential for signaling in the heart left ventricle during restraint stress in mice.

We hypothesized that muscarinic receptors (MRs) in the heart have a role in stress responses and thus investigated changes in MR signaling (gene expression, number of receptors, adenylyl cyclase (AC), phospholipase C (PLC), protein kinase A and C (PKA and PKC) and nitric oxide synthase [NOS]) in the left ventricle, together with telemetric measurement of heart rate (HR) in mice (wild type [WT] and M2 knockout [KO]) during and after one (1R) or seven sessions (7R) of restraint stress (seven mice per group). Stress decreased M2 MR mRNA and cell surface MR in the left ventricle in WT mice. In KO mice, 1R, but not 7R, decreased surface MR. Similarly, AC activity was decreased in WT mice after 1R and 7R, whereas in KO mice, there was no change. PLC activity was also decreased after 1R in WT and KO mice. This is in accord with the concept that cAMP is a key player in HR regulation. No change was found with stress in NOS activity. Amount of AC and PKA protein was not changed, but was altered for PKC isoenzymes (PKCα, ß, γ, η and ϵ (increased) in KO mice, and PKCι (increased) in WT mice). KO mice were more susceptible to stress as shown by inability to compensate HR during 120 min following repeated stress. The results imply that not only M2 but also M3 are involved in stress signaling and in allostasis. We conclude that for a normal stress response, the expression of M2 MR to mediate vagal responses is essential.

Fluid management guided by a continuous non-invasive arterial pressure device is associated with decreased postoperative morbidity after total knee and hip replacement.

BACKGROUND: The use of goal directed fluid protocols in intermediate risk patients undergoing hip or knee replacement was studied in few trials using invasive monitoring. For this reason we have implemented two different fluid management protocols, both based on a novel totally non-invasive arterial pressure monitoring device and compared them to the standard (no-protocol) treatment applied before the transition in our academic institution. METHODS: Three treatment groups were compared in this prospective study: the observational (CONTROL, N = 40) group before adoption of fluid protocols and two randomized groups after the transition to protocol fluid management with the use of the continuous non-invasive blood pressure monitoring (CNAP®) device. In the PRESSURE group (N = 40) standard variables were used for restrictive fluid therapy. Goal directed fluid therapy using pulse pressure variation was used in the GDFT arm (N = 40). The influence on the rate of postoperative complications, on the hospital length of stay and other parameters was assessed. RESULTS: Both protocols were associated with decreased fluid administration and maintained hemodynamic stability. Reduced rate of postoperative infection and organ complications (22 (55 %) vs. 33 (83 %) patients; p = 0.016; relative risk 0.67 (0.49-0.91)) was observed in the GDFT group compared to CONTROL. Lower number of patients receiving transfusion (4 (10 %) in GDFT vs. 17 (43 %) in CONTROL; p = 0.005) might contribute to this observation. No significant differences were observed in other end-points. CONCLUSION: In our study, the use of the fluid protocol based on pulse pressure variation assessed using continuous non-invasive arterial pressure measurement seems to be associated with a reduction in postoperative complications and transfusion needs as compared to standard no-protocol treatment. TRIAL REGISTRATION: ACTRN12612001014842.

Continuous non-invasive monitoring improves blood pressure stability in upright position: randomized controlled trial.

Intermittent blood pressure (BP) monitoring is the standard-of-care during low and intermediate risk anaesthesia, yet it could lead to delayed recognition of BP fluctuations. Perioperative hypotension is known to be associated with postoperative complications. Continuous, non-invasive methods for BP monitoring have been developed recently. We have tested a novel non-invasive, continuous monitor (using the volume clamp method) to assist with maintaining BP in safe ranges for patients undergoing surgery in a beach chair position. Forty adult patients undergoing thyroid gland surgery in an upright position were included in this prospective randomised controlled trial. Patients were equally allocated to the group with continuous monitoring of BP using the CNAP® Monitor and to the control group managed using an intermittent oscillometric BP cuff. The absolute and proportional time spent outside the range of ±20% of the target BP along with other hemodynamic and clinical parameters were evaluated. The continuous monitoring decreased the anaesthesia time spent below -20% pressure range [absolute: 12 min (4-20) vs. 27 min (16-34); p=0.001; relative to procedure length: 14% (7-20) vs. 33.5% (17.5-53); p=0.003]. No significant differences were observed in postoperative morbidity or in hospital length of stay. Continuous non-invasive BP monitoring via the CNAP® Monitor allows for better BP management in patients undergoing surgery in a beach chair position. In our randomised trial the time spent in hypotension was significantly shorter using continuous monitoring.

The effects of goal-directed fluid therapy based on dynamic parameters on post-surgical outcome: a meta-analysis of randomized controlled trials.

INTRODUCTION: Dynamic predictors of fluid responsiveness, namely systolic pressure variation, pulse pressure variation, stroke volume variation and pleth variability index have been shown to be useful to identify in advance patients who will respond to a fluid load by a significant increase in stroke volume and cardiac output. As a result, they are increasingly used to guide fluid therapy. Several randomized controlled trials have tested the ability of goal-directed fluid therapy (GDFT) based on dynamic parameters (GDFTdyn) to improve post-surgical outcome. These studies have yielded conflicting results. Therefore, we performed this meta-analysis to investigate whether the use of GDFTdyn is associated with a decrease in post-surgical morbidity. METHODS: A systematic literature review, using MEDLINE, EMBASE, and The Cochrane Library databases through September 2013 was conducted. Data synthesis was obtained by using odds ratio (OR) and weighted mean difference (WMD) with 95% confidence interval (CI) by random-effects model. RESULTS: In total, 14 studies met the inclusion criteria (961 participants). Post-operative morbidity was reduced by GDFTdyn (OR 0.51; CI 0.34 to 0.75; P <0.001). This effect was related to a significant reduction in infectious (OR 0.45; CI 0.27 to 0.74; P = 0.002), cardiovascular (OR 0.55; CI 0.36 to 0.82; P = 0.004) and abdominal (OR 0.56; CI 0.37 to 0.86; P = 0.008) complications. It was associated with a significant decrease in ICU length of stay (WMD -0.75 days; CI -1.37 to -0.12; P = 0.02). CONCLUSIONS: In surgical patients, we found that GDFTdyn decreased post-surgical morbidity and ICU length of stay. Because of the heterogeneity of studies analyzed, large prospective clinical trials would be useful to confirm our findings.

Cost analysis of the stroke volume variation guided perioperative hemodynamic optimization - an economic evaluation of the SVVOPT trial results.

BACKGROUND: Perioperative goal directed therapy (GDT) can substantially improve the outcomes of high risk surgical patients as shown by many clinical studies. However, the approach needs initial investment and can increase the already very high staff workload. These economic imperatives may be at least partly responsible for weak adherence to the GDT concept. A few models are available for the evaluation of GDT cost-effectiveness, but studies of real economic data based on a recent clinical trial are lacking. In order to address this we have performed a retrospective analysis of the data from the "Intraoperative fluid optimization using stroke volume variation in high risk surgical patients" trial (ISRCTN95085011). METHODS: The health-care payers perspective was used in order to evaluate the perioperative hemodynamic optimization costs. Hospital invoices from all patients included in the trial were extracted. A direct comparison between the study (GDT, N = 60) and control (N = 60) groups was performed. A cost tree was constructed and major cost drivers evaluated. RESULTS: The trial showed a significant improvement in clinical outcomes for GDT treated patients. The mean cost per patient were lower in the GDT group 2877 ± 2336€ vs. 3371 ± 3238€ in controls, but without reaching a statistical significance (p = 0.596). The mean cost of all items except for intraoperative monitoring and infusions were lower for GDT than control but due to the high variability they all failed to reach statistical significance. Those costs associated with clinical care (68 ± 177€ vs. 212 ± 593€; p = 0.023) and ward stay costs (213 ± 108€ vs. 349 ± 467€; p = 0.082) were the most important differences in favour of the GDT group. CONCLUSIONS: Intraoperative fluid optimization with the use of stroke volume variation and Vigileo/FloTrac system showed not only a substantial improvement of morbidity, but was associated with an economic benefit. The cost-savings observed in the overall costs of postoperative care trend to offset the investment needed to run the GDT strategy and intraoperative monitoring. TRIAL REGISTRATION: ISRCTN95085011.

Respiratory induced dynamic variations of stroke volume and its surrogates as predictors of fluid responsiveness: applicability in the early stages of specific critical states.

Respiratory induced dynamic variations of stroke volume and its surrogates are very sensitive and specific predictors of fluid responsiveness, but their use as targets for volume management can be limited. In a recent study, limiting factors were present in 53 % of surgical patients with inserted arterial line. In the intensive care unit (ICU) population the frequency is presumably higher, but the real prevalence is unknown. Our goal was to study the feasibility of dynamic variations guided initial volume resuscitation in specific critical states. We have performed a 5 year retrospective evaluation of patients admitted with diagnosis sepsis, polytrauma, after high risk surgery or cardiac arrest. Occurrence of major (sedation, mandatory ventilation and tidal volume, open chest and arrhythmias) and minor limiting factors (PEEP level, use of vasopressors and presence of arterial catheter) was screened within the first 24 h after admission. In the study period 1296 patients were hospitalized in our ICU with severe sepsis (n = 242), polytrauma (n = 561), after high risk surgery (n = 351) or cardiac arrest (n = 141). From these patients 549 (42.4 %) fulfilled all major criteria for applicability of dynamic variations. In our evaluation only limited number of patients admitted for polytrauma (51 %), sepsis (37 %), after cardiac arrest (39 %) or surgical procedure (33 %) fulfil all the major criteria for use of dynamic variations at the ICU admission. The prevalence was similar in patients with shock. Occurrence of minor factors can pose further bias in evaluation of these patients. General use of dynamic variations guided protocols for initial resuscitations seems not universally applicable.

Ineffectiveness of hemoadsorption in large animals with abdominal sepsis: a randomized controlled porcine study.

OBJECTIVES: The use of hemoadsorption (HA) has become popular in the treatment of vasoplegic states associated with massive cytokine release, including septic shock. However, this approach does not seem to be based on robust evidence, and it does not follow international guidelines. To understand the pathophysiological rationale and timing of HA, we conducted a large animal septic shock experiment. DESIGN: Prospective randomized large-animal peritoneal septic shock experiment. SETTING: Laboratory investigation. SUBJECTS: Twenty-six anesthetized, mechanically ventilated, and instrumented pigs randomly assigned into (1) sham-operated group with HA (SHAM, n = 5); (2) sepsis animals without HA (SEPSIS, n = 5); (3) sepsis group with HA at norepinephrine initiation (EARLY, n = 8); and (4) sepsis group with HA initiated at norepinephrine rate reaching 0.5 µg/kg/min (LATE, n = 8). INTERVENTIONS: Peritoneal sepsis was induced by cultivated autologous feces inoculation. A CytoSorb cartridge (200 g) with a blood flow rate of 200 mL/min and heparin anticoagulation was used to perform HA. The animals received sedation and intensive organ support up to 48 h or until they experienced cardiovascular collapse. MEASUREMENTS AND MAIN RESULTS: Systemic hemodynamics, multiple-organ functions, and immune-inflammatory response were measured at predefined periods. The HA treatment was not associated with any measurable benefit in terms of systemic hemodynamics and organ support. The systemic inflammatory markers were unaffected by any of the treatment timings. In contrast, the HA resulted in higher vasopressor load and decreased 36-h survival (5 animals in SHAM (100%), 4 (80%) in SEPSIS, 4 (57%) in EARLY, and 2 (25%) in LATE; p = 0.041). The HA exposure in healthy animals was associated with hemodynamic deterioration, systemic inflammatory response, and cytopenia. CONCLUSIONS: In this large-animal-controlled fulminant sepsis study, the HA was unable to counteract the disease progression in the early or advanced septic shock phase. However, findings from the HA-exposed sham animals suggest potential safety concerns.