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Respiratory physiology following smoke-induced acute lung injury and during extra-corporeal membrane oxygenation support in sheep

ABSTRACT: Many successful therapies developed for human medicine involve animal experimentation. Animal studies focused solely on their translational potential, may not sufficiently document unexpected outcomes. Such studies often have hastily developed methods, leading to considerable amounts of archived data that could be used to advance veterinary science, or to refine the base animal model. Sheep, for example, are increasingly being used as models of intensive care and therefore, any experimental data arising from them should be interpreted and published. The hypothesis was that there is little information describing physiological data from multifaceted sheep models of intensive care and the author aimed to analyse such data to provide biological information that is not currently available for sheep receiving extracorporeal life support following smoke-induced acute lung injury. Data from 19 mechanically ventilated adult ewes undergoing intensive care in a study evaluating a form of extracorporeal life support (treatment) for acute lung injury were used to gather clinical observations. Eight sheep were injured by acute smoke inhalation prior to treatment (injured/treated), while another eight were not injured but treated (uninjured/treated). Two sheep were injured but not treated (injured/untreated), while one received room air instead of smoke as the injury, and was not treated (placebo/untreated). The data were then analysed for eleven physiological categories and compared between the two treated groups..Compared with the baseline, treatment contributed to and exacerbated the deterioration of pulmonary pathology by reducing lung compliance and PaO2/FiO2 ratio. The oxygen extraction index changes mirrored those of the PaO2/FiO2 ratio. Decreasing coronary perfusion pressure predicted the severity of cardiopulmonary injury. These novel observations could help in understanding similar pathology such as that which occurs in smoke inhalation animal victims of house or bush fires, aspiration pneumonia secondary to tick paralysis and in the management of severe Coronavirus disease 2019 infections in humans.

SUBMITTER: Saul Chemonges

PROVIDER: S-BSST398 | biostudies-other |

REPOSITORIES: biostudies-other

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Project description:Background: Numerous successful therapies developed for human medicine involve animal experimentation. Animal studies that are focused solely on translational potential, may not sufficiently document unexpected outcomes. Considerable amounts of data from such studies could be used to advance veterinary science. For example, sheep are increasingly being used as models of intensive care and therefore, data arising from such models must be published. In this study, the hypothesis is that there is little information describing cardiorespiratory physiological data from sheep models of intensive care and the author aimed to analyse such data to provide biological information that is currently not available for sheep that received extracorporeal life support (ECLS) following acute smoke-induced lung injury. Methods: Nineteen mechanically ventilated adult ewes undergoing intensive care during evaluation of a form of ECLS (treatment) for acute lung injury were used to collate clinical observations. Eight sheep were injured by acute smoke inhalation prior to treatment (injured/treated), while another eight were not injured but treated (uninjured/treated). Two sheep were injured but not treated (injured/untreated), while one received room air instead of smoke as the injury and was not treated (placebo/untreated). The data were then analysed for 11 physiological categories and compared between the two treated groups. Results: Compared with the baseline, treatment contributed to and exacerbated the deterioration of pulmonary pathology by reducing lung compliance and the arterial oxygen partial pressure to fractional inspired oxygen (PaO 2/FiO 2) ratio. The oxygen extraction index changes mirrored those of the PaO 2/FiO 2 ratio. Decreasing coronary perfusion pressure predicted the severity of cardiopulmonary injury. Conclusions: These novel observations could help in understanding similar pathology such as that which occurs in animal victims of smoke inhalation from house or bush fires, aspiration pneumonia secondary to tick paralysis and in the management of the severe coronavirus disease 2019 (COVID-19) in humans.

Project description:BackgroundMethylprednisolone remains a commonly used ancillary therapy for paediatric acute respiratory distress syndrome (PARDS), despite a lack of level 1 evidence to justify its use. When planning prospective trials it is useful to define response to therapy and to identify if there is differential response in certain patients, i.e. existence of 'responders' and 'non responders' to therapy. This retrospective, observational study carried out in 2 tertiary referral paediatric intensive care units aims to characterize the change in Oxygen Saturation Index, following the administration of low dose methylprednisolone in a cohort of patients with PARDS, to identify what proportion of children treated demonstrated response, whether any particular characteristics predict response to therapy, and to determine if a positive response to corticosteroids is associated with reduced Paediatric Intensive Care Unit mortality.MethodsAll patients who received prolonged, low dose, IV methylprednisolone for the specific indication of PARDS over a 5-year period (2011-2016) who met the PALICC criteria for PARDS at the time of commencement of steroid were included (n = 78).OSI was calculated four times per day from admission until discharge from PICU (or death). Patients with ≥20% improvement in their mean daily OSI within 72 hours of commencement of methylprednisolone were classified as 'responders'. Primary outcome measure was survival to PICU discharge.ResultsMean OSI of the cohort increased until the day of steroid commencement then improved thereafter. 59% of patients demonstrated a response to steroids. Baseline characteristics were similar between responders and non-responders. Survival to PICU discharge was significantly higher in 'responders' (74% vs 41% OR 4.14(1.57-10.87) p = 0.004). On multivariable analysis using likely confounders, response to steroid was an independent predictor of survival to PICU discharge (p = 0.002). Non-responders died earlier after steroid administration than responders (p = 0.003).ConclusionsAn improvement in OSI was observed in 60% of patients following initiation of low dose methylprednisolone therapy in this cohort of patients with PARDS. Baseline characteristics fail to demonstrate a difference between responders and non-responders. A 20% improvement in OSI after commencement of methylprednisolone was independently predictive of survival, Prospective trials are needed to establish if there is a benefit from this therapy.

Project description:Objectives: Several mechanical circulatory assist devices are used to treat critically ill patients requiring hemodynamic support during post-myocardial infarction or cardiogenic shock. However, little guidance is available to choose an appropriate device to match a particular patient's needs. An increased understanding of hemodynamic effects of the pump systems and their impact on myocardial pre-/afterload might help to better understand their behavior in different clinical settings. Methods: This was an open-labeled, randomized acute animal experiment. A model of acute univentricular myocardial injury by temporary balloon occlusion was used. The experiment was carried out in 10 juveniles female Piétrain pigs. The animals were randomized to mechanical hemodynamic support either by peripheral veno-arterial (VA-)ECMO or Impella CP. Results: While both devices were able to provide flows above 3 L/min and maintain sufficient end-organ perfusion, support by Impella resulted in a significantly more pronounced immediate effect on myocardial unloading: At the onset of device support, the remaining native cardiac output was reduced by 23.5 ± 15.3% ECMO vs. 66.2 ± 36.2% (Impella, p = 0.021). Native stroke volume was significantly decreased by Impella support compared to ECMO, indicating less mechanical work being conducted by the Impella-supported hearts despite similar total assisted cardiac output. Conclusions: Peripheral VA-ECMO and the transaortic Impella pump resulted in contrasting hemodynamic fingerprints. Both devices provided sufficient hemodynamic support and reduce left ventricular end-diastolic pressure in the acute setting. Treatment with the Impella device resulted in a more effective volume unloading of the left ventricle. A significant reduction in myocardial oxygen consumption equivalent was achieved by both devices: The Impella device resulted in a left-shift of the pressure-volume loop and a decreased pressure-volume-area (PVA), while VA-ECMO increased PVA but decreased heart rate. These data highlight the importance of specifically targeting heart rate in the management of AMI patients on hemodynamic support.

Project description:BackgroundExtracorporeal membrane oxygenation (ECMO) is an important rescue therapy for patients with refractory respiratory or circulatory failure. High cost and associated complications warrant careful case selection. The aim of this study was to investigate the outcomes and factors associated with mortality in acute hypoxemic respiratory failure patients who received ECMO support, and to externally validate preexisting ECMO survival prediction scoring systems.MethodsThis retrospective study enrolled acute hypoxemic respiratory failure patients who received veno-venous (VV) or veno-arterial (VA) ECMO support at Siriraj Hospital (Bangkok, Thailand) from 2010 to 2020. All relevant baseline patient characteristics including ECMO survival prediction scores were recorded. The primary outcome was in-hospital mortality. Multivariate logistic regression analysis was employed to identify independent predictors of in-hospital mortality.ResultsOf a total of 65 patients, 34 (52%) were male, the median (IQR) age was 61 years (49-70 years), the median body mass index (BMI) was 22.6 kg/m2 (20.6-28 kg/m2), and the median Sequential Organ Failure Assessment (SOFA) score was 13 [11-16]. Forty-three patients (66%) received VV-ECMO, and 22 (34%) received VA-ECMO support. In-hospital mortality was 69%. Multivariate analysis identified a SOFA score >14, hospitalized >72 hours before ECMO initiation, PaO2/FiO2 ratio <60, and pH <7.2 as independent predictors of in-hospital mortality. These four parameters were combined to create the SHOP (S: SOFA >14, H: hospitalize >72 hours, O: PF ratio <60, and P: pH <7.2) score. Compared with three different preexisting ECMO survival prediction scoring systems, the SHOP score had the highest area under the curve (AUC) for predicting in-hospital mortality (overall: 0.873, VV-EMCO: 0.866, and VA-EMCO: 0.891).ConclusionsIn-hospital mortality among ECMO-supported patients was high at 69%. SOFA score >14, hospitalized >72 hours, PaO2/FiO2 ratio <60, and pH <7.2 were found to be independent predictors of in-hospital mortality. A SHOP score of 2 or higher significantly predicts in-hospital mortality in EMCO-supported patients.Trial registrationwww.clinicaltrials.gov (reg. No. NCT04031794).

Project description:Acute respiratory distress syndrome (ARDS) is common after traumatic brain injury (TBI) and is associated with worse neurologic outcomes and longer hospitalization. However, the incidence and associated causes of ARDS in isolated TBI have not been well studied.We performed a subgroup analysis of 210 consecutive patients with isolated severe TBI enrolled in a prospective observational cohort at a Level 1 trauma center between 2005 and 2014. Subjects required endotracheal intubation and had isolated severe TBI defined by a head Abbreviated Injury Scale (AIS) score of 3 or greater and AIS score lower than 3 in all other categories. ARDS within the first 8 days of admission was rigorously adjudicated using Berlin criteria. Regression analyses were used to test the association between predictors of interest and ARDS.The incidence of ARDS in the first 8 days after severe isolated TBI was 30%. Patients who developed ARDS were administered more crystalloids (4.3 L vs. 3.5 L, p = 0.005) and blood products in the first 12 hours of admission. Patients with ARDS had significantly worse clinical outcomes measured at 28 days, including longer median intensive care unit and hospital stays (4 days vs. 13 days, p < 0.001, and 7.5 days vs. 14.5 days, p < 0.001, respectively). In unadjusted logistic regression analyses, the odds of developing ARDS were significantly associated with head AIS score (odds ratio [OR], 1.8; p = 0.018), male sex (OR, 2.9; p = 0.012), and early transfusion of platelets (OR, 2.8; p = 0.003). These associations were similar in a multivariate logistic regression model.In the era of balanced hemostatic resuscitation practices, severity of head injury, male sex, early crystalloids, and early transfusion of platelets are associated with a higher risk of ARDS after severe isolated TBI. Early transfusion of platelets after severe TBI may be a modifiable risk factor for ARDS, and these findings invite further investigation into causal mechanisms driving this observed association.Prognostic/epidemiologic study, level III.

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Respiratory physiology following smoke-induced acute lung injury and during extra-corporeal membrane oxygenation support in sheep

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