Assessment of cerebral circulation in a porcine model of intravenously given E. coli induced fulminant sepsis

Molnár, L.; Németh, Norbert; Berhés, Mariann; Hajdú, Endre; Papp, Lóránd; Molnár, Ábel; Szabó, Judit; Deák, Ádám; Fülesdi, Béla

doi:10.1186/s12871-017-0389-0

Cited by 4 publications

(3 citation statements)

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“…This model has an identical size, endotoxin sensitivity, tissue antigenicity and immune response as that in human beings and is suitable for investigating the effect of extracorporeal blood therapy in animal models [ 19 ]. Unlike other models using a single infusion of specific live bacteria [ 20 , 21 ] or endotoxin [ 22 ] to induce a transient reaction other than a sustained process, we used a peritonitis-induced sepsis model to mimic polymicrobial and progressive characteristics of clinical situations, most importantly, with an appropriate sepsis severity to avoid rapid death within the first 6 to 12 h due to an overly serious condition [ 23 , 24 ] and to guarantee a sufficient survival time for the completion of the study. As reported in some experiments, an observed time that is too short may not be enough to obtain a full view of sepsis at the end of the investigation [ 25 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical improvement of sepsis by extracorporeal centrifugal leukocyte apheresis in a porcine model

et al. 2022

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Background Extracorporeal blood purification therapies targeting removal of the downstream products of the inflammatory cascade in sepsis have failed to improve mortality. As an upstream process of the inflammatory cascade, activated white blood cells should be a potential therapeutic target for sepsis, and the effect of removing such cells by extracorporeal centrifugal leukocytapheresis (LCAP) is worth considering. Methods Fourteen peritonitis-induced septic pigs were randomly assigned to receive a sham operation (control group, n = 7) or one session of LCAP at 12 h after sepsis induction (treatment group, n = 7). Samples from peripheral blood at various time-points and from LCAP collection were tested. All pigs were euthanized at 48 h, and lung, kidney, liver and spleen tissues were obtained for histopathological examination. Results Two pigs died in accidents before the induction of sepsis, and 12 pigs were finally included for the statistical analysis. A significant clinical improvement was present in the treatment group relative to the control group in terms of the mean arterial blood pressure (MAP), oxygen tension (PaO2), lactic acid level, oxygenation index (PaO2/FiO2), and carbon dioxide tension (PaCO2, P < 0.05). Flow cytometry tests showed that a mixture of B cells, dendritic cells, T helper cells, cytotoxic T cells, monocytes and neutrophils were removed from the circulation by LCAP, resulting in sepsis-induced change trends in the control cells; these change trends were all flattened in the treatment group, although nonsignificantly. Conclusions LCAP may exert a wide-spectrum and bidirectional immunomodulatory effect on sepsis, accompanied by improvements in hemodynamics and oxygenation status.

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Section: Discussionmentioning

confidence: 99%

Clinical improvement of sepsis by extracorporeal centrifugal leukocyte apheresis in a porcine model

et al. 2022

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“…It seems that the inflammatory response that is evoked by E. coli infusion is directed toward the cardiac contractile function (both cardiac index and global ejection faction decreased during the process). As a consequence of this hypodynamic circulatory response, an immediate microcirculatory impairment was observed in an early phase of the bacterial injection [12], whereas cerebral autoregulation remained unaffected [13]. It has been also documented that due to this hemodynamic collapse, lactate levels got elevated followed by the increased appearance of nucleated red blood cells, indicating tissue hypoxia [14].…”

Section: Discussionmentioning

confidence: 99%

Hemodynamic consequences of intravenously given E. coli suspension: observations in a fulminant sepsis model in pigs, a descriptive case–control study

et al. 2019

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BackgroundThe aim of the present work was to assess systemic hemodynamic changes using PiCCo monitoring in a porcine model of E. coli-induced fulminant sepsis.MethodsThirty-one healthy female Hungahib pigs were randomly assigned into control (n = 15) or septic groups (n = 16). In the sepsis group Escherichia coli culture was intravenously administrated in a continuously increasing manner according to the following protocol: 2 ml of bacterial culture suspended in physiological saline was injected in the first 30 min, then 4 ml of bacterial culture was administered within 30 min, followed by infusion of 32 ml bacterial culture for 2 h. Control animals received identical amount of saline infusion. Systemic hemodynamic parameters were assessed by PiCCo monitoring in both groups.ResultsResting hemodynamic parameters were identical in the two groups. In control animals, systemic hemodynamic variables were relatively stable during the entire procedure. In septic animals shock developed in 165 (IQR: 60–255) min after starting the injection of E. coli solution. Blood pressure values gradually decreased, whereas pulse rate increased. A decrease in cardiac index, an increased systemic vascular resistance, and a decreased stroke volume variation were observed.ConclusionsThese results may serve as additional pathophysiological information of hemodynamic changes occurring during hypodynamic sepsis and may contribute to a better understanding of the pathomechanism of septic multiple organ failure.

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“…Recent studies in both humans and animals suggest that altered regulation of the cerebral circulation may play a role in SAE. 9,10 In health, cerebral autoregulation maintains constant brain perfusion in the face of fluctuating blood pressure by adjusting the diameter of cerebral blood vessels, a process known as cerebrovascular reactivity. Higher and lower blood pressure limits of functional cerebral autoregulation vary among individuals, with cerebral blood flow passive to changes in arterial pressure outside these limits.…”

Section: Introductionmentioning

confidence: 99%

Cerebral Autoregulation–Guided Optimal Blood Pressure in Sepsis-Associated Encephalopathy: A Case Series

Rosenblatt

Walker

Goodson

et al. 2019

J Intensive Care Med

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Background: Impaired cerebral autoregulation and cerebral hypoperfusion may play a critical role in the high morbidity and mortality in patients with sepsis-associated encephalopathy (SAE). Bedside assessment of cerebral autoregulation may help individualize hemodynamic targets that optimize brain perfusion. We hypothesize that near-infrared spectroscopy (NIRS)–derived cerebral oximetry can identify blood pressure ranges that enhance autoregulation in patients with SAE and that disturbances in autoregulation are associated with severity of encephalopathy. Methods: Adult patients with acute encephalopathy directly attributable to sepsis were followed using NIRS-based multimodal monitoring for 12 consecutive hours. We used the correlation in time between regional cerebral oxygen saturation and mean arterial pressure (MAP) to determine the cerebral oximetry index (COx) as a measure of cerebral autoregulation. Autoregulation curves were constructed for each patient with averaged COx values sorted by MAP in 3 sequential 4-hour periods; the optimal pressure (MAPOPT), defined as the MAP associated with most robust autoregulation (lowest COx), was identified in each period. Severity of encephalopathy was measured with Glasgow coma scale (GCS). Results: Six patients with extracranial sepsis met the stringent criteria specified, including no pharmacological sedation or neurologic premorbidity. Optimal MAP was identified in all patients and ranged from 55 to 115 mmHg. Additionally, MAPOPT varied within individual patients over time during monitoring. Disturbed autoregulation, based on COx, was associated with worse neurologic status (GCS < 13) both with and without controlling for age and severity of sepsis (adjusted odds ratio [OR]: 2.11; 95% confidence interval [CI]: 1.77-2.52; P < .001; OR: 2.97; 95% CI: 1.63-5.43; P < .001). Conclusions: In this high-fidelity group of patients with SAE, continuous, NIRS-based monitoring can identify blood pressure ranges that improve autoregulation. This is important given the association between cerebral autoregulatory function and severity of encephalopathy. Individualizing blood pressure goals using bedside autoregulation monitoring may better preserve cerebral perfusion in SAE than current practice.

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Assessment of cerebral circulation in a porcine model of intravenously given E. coli induced fulminant sepsis

Cited by 4 publications

References 34 publications

Clinical improvement of sepsis by extracorporeal centrifugal leukocyte apheresis in a porcine model

Clinical improvement of sepsis by extracorporeal centrifugal leukocyte apheresis in a porcine model

Hemodynamic consequences of intravenously given E. coli suspension: observations in a fulminant sepsis model in pigs, a descriptive case–control study

Cerebral Autoregulation–Guided Optimal Blood Pressure in Sepsis-Associated Encephalopathy: A Case Series

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