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BACKGROUND: Traditional fasting rules for children prior to elective operations ("642 rule") often lead to prolonged fasting times with possible adverse events (discomfort, hypoglycemia, metabolic disorders, agitation/delirium). A new liberal fasting policy allowing children to drink clear fluids until being called to the operating room ("640") was established in our university hospital. This article describes our experiences and retrospectively examines the effects. OBJECTIVE: Evaluation of real fasting times before and up to 6 months after the intervention (success and durability of changing fasting policy). Evaluation of impact on outcome parameters, such as patients' resp. parents' satisfaction as well as perioperative agitation, arterial hypotension after induction and postoperative nausea and vomiting (PONV). MATERIAL AND METHODS: Retrospective evaluation of methods and interventions from 1 month before to 6 months after changing the fasting policy (June-December 2020). Statistical analysis using descriptive statistics, odds ratio and χ2-test. RESULTS: Of 216 analyzed patients 44 were in the pre-change group and 172 in the post-change group. We could significantly reduce clear fluids fasting times over the 6 months after the intervention (median fasting time: from 6.1â¯h to 4.5â¯h; pâ¯= 0.034) and achieve our aim (fasting time for clear fluids less than or equal to 2h) in 47% of the patients. Fasting times became longer again reaching pre-change intervals in the 4th and 5th month, so reminder measures turned out to be necessary. By reminding the staff we could reduce fasting times again in the 6th month and restore patients' resp. parents' satisfaction. Satisfaction was improved by shorter fasting times (median school grade from 2.8 to 2.2; pâ¯= 0.004; odds ratio for better satisfaction 5.24, 2.1-13.2), and preoperative agitation was reduced (agitation modified PAED scale 1-2 in only 34.5% instead of 50%, pâ¯= 0.032). In the liberal fasting group, we observed a nonsignificant smaller incidence of hypotension after induction (7% vs. 14%, pâ¯= 0.26) while PONV was too rare in both groups for statistical purposes. CONCLUSION: With multiple interventions we could significantly reduce fasting times for clear fluids and improve patients' resp. parents' satisfaction as well as preoperative agitation. These interventions included regular presence in all staff meetings, a handout for both parents and staff, as well as a remark on the anesthesia protocol. Children who were operated on later in the day, benefited most from the new liberal fasting policy as they were allowed to drink until being called to the operating room. Following our experience, we consider simple and safe fasting rules for the whole staff as most important for change management. Nevertheless, we could not reduce the fasting intervals in all cases and had to remind the staff after 5 months to preserve this success. For enduring success, we suggest regular staff updates during the change process instead of one single kick-off information event.
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Anestesia Geral , Náusea e Vômito Pós-Operatórios , Humanos , Criança , Estudos Retrospectivos , Anestesia Geral/métodos , Cuidados Pré-Operatórios/métodos , JejumRESUMO
PURPOSE: Frailty is a frequent and underdiagnosed multidimensional age-related syndrome, involving decreased physiological performance reserves and marked vulnerability against major stressors. To standardize the preoperative frailty assessment and identify patients at risk of adverse surgical outcomes, commonly used global health assessment tools were evaluated. We aimed to assess three interdisciplinary preoperative screening assessments to investigate the influence of frailty status with in-hospital complications irrespective of surgical complexity and radicality in older women with ovarian cancer (OC). METHODS: Preoperative frailty status was examined by the G8 geriatric screening tool (G8 Score-geriatric screening), Eastern Cooperative Oncology Group performance status (ECOG PS-oncological screening), and American Society of Anesthesiologists Physical Status System (ASA PS-anesthesiologic screening). The main outcome measures were the relationship between perioperative laboratory results, intraoperative surgical parameters and the incidence of immediate postoperative in-hospital complications with the preoperative frailty status. RESULTS: 116 consecutive women 60 years and older (BMI 24.8 ± 5.2 kg/m2) with OC, who underwent elective oncological surgery in University Medical Center Mainz between 2008 and 2019 were preoperatively classified with the selected global health assessment tools as frail or non-frail. The rate of preoperative anemia (hemoglobin ≤ 12 g/dl) and perioperative transfusions were significantly higher in the G8-frail group (65.9% vs. 34.1%; p = 0.006 and 62.7% vs. 41.8%, p = 0.031; respectively). In addition, patients preoperatively classified as G8-frail exhibited significantly more postoperative clinical in-hospital complications (27.8% vs. 12.5%, p = 0.045) independent of chronological age and BMI. In contrast, ECOG PS and ASA PS did not predict the rates of postoperative complications (all p values > 0.05). After propensity score matching, the complication rate in the G8-frail cohort was approximately 1.7 times more common than in the G8-non-frail cohort. CONCLUSION: Preoperative frailty assessment with the G8 Score identified elderly women with OC recording a significantly higher rate of postoperative in-hospital complications. In G8-frail patients, preoperative anemia and perioperative transfusions were significantly more recorded, regardless of chronological age, abnormal BMI and surgical complexity. Standardized preoperative frailty assessment should be added to clinical routine care to enhance risk stratification in older cancer individuals for surgical patient-centered decision-making.
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Fragilidade , Neoplasias Ovarianas , Humanos , Feminino , Idoso , Fragilidade/complicações , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Idoso Fragilizado , Detecção Precoce de Câncer , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/cirurgia , Fatores de RiscoRESUMO
PURPOSE: The aim of this retrospective study was to evaluate the prognostic impact of global health status assessment tools in elderly patients with endometrial cancer (EC) on survival. METHODS: Preoperative frailty status was assessed by the G8 geriatric screening tool (G8 Score), Lee Schonberg prognostic index, Charlson Comorbidity index and American Society of Anesthesiologists Physical Status System in women older than 60 years with EC. Univariable and multivariable Cox-regression analyses, as well as Kaplan-Meier survival analyses were performed to determine the prognostic impact. Statistical analyses were adjusted for cancer entity-specific risk factors such as conventional histopathological tumor characteristics and relevant anamnestic life style parameters. RESULTS: 153 patients with all stages of EC who were operated at the University Medical Center Mainz between 2008 and 2019 were included. In multivariable analyses, only the G8 Score retained independent significance as a prognostic factor for disease-specific survival (DSS) (HR:4.58; 95% CI [1.35-15.51]) and overall survival (OS) (HR:2.89; 95% CI [1.31-6.39]. 92 patients (61.3%) were classified as G8-non-frail with a significantly increased DSS and OS rate compared to the 58 G8-frail patients (DSS:93.8% vs. 60.8%; p < 0.001 and OS:88.2% vs. 49.7%; p < 0.001; respectively). CONCLUSIONS: This is the first study demonstrates the substantial clinical and prognostic impact of the G8 Score on survival in elderly women with EC. Assessing the frailty status to estimate the individual vulnerability of elderly cancer patients could be useful in preoperative decision-making to individualize treatment plans such as the surgical radicality and to improve pre- and postoperative morbidity.
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Neoplasias do Endométrio , Fragilidade , Humanos , Feminino , Idoso , Estudos Retrospectivos , Estudos de Coortes , Detecção Precoce de Câncer , Neoplasias do Endométrio/cirurgia , Avaliação Geriátrica/métodosRESUMO
Introduction: Perioperative red blood cell (RBC) transfusions have been associated with increased morbidity and worse oncological outcome in some solid neoplasms. In order to elucidate whether RBC transfusions themselves, the preoperative anemia of cancer (AOC), or the impaired global health status might explain this impact on patients with endometrial cancer (EC) or ovarian cancer (OC), we performed a retrospective, single-institution cohort study. Materials and methods: Women older than 60 years with EC or OC were included. The influence of RBC transfusions, AOC, and frailty status determined by the G8 geriatric screening tool (G8 score), as well as the clinical-pathological cancer characteristics on progression-free survival (PFS) and overall survival (OS), was determined by using the Kaplan-Meier method and the Cox regression analyses. Results: In total, 263 patients with EC (n = 152) and OC (n = 111) were included in the study. Patients with EC receiving RBC transfusions were faced with a significantly shorter 5-year PFS (79.8% vs. 26.0%; p < 0.001) and 5-year OS (82.6% vs. 25.7%; p < 0.001). In multivariable analyses, besides established clinical-pathological cancer characteristics, the RBC transfusions remained the only significant prognostic parameter for PFS (HR: 1.76; 95%-CI [1.01-3.07]) and OS (HR: 2.38; 95%-CI [1.50-3.78]). In OC, the G8 score stratified the cohort in terms of PFS rates (G8-non-frail 53.4% vs. G8-frail 16.7%; p = 0.010) and AOC stratified the cohort for 5-year OS estimates (non-anemic: 36.7% vs. anemic: 10.6%; p = 0.008). Multivariable Cox regression analyses determined the G8 score and FIGO stage as independent prognostic factors in terms of PFS (HR: 2.23; 95%-CI [1.16-4.32] and HR: 6.52; 95%-CI [1.51-28.07], respectively). For OS, only the TNM tumor stage retained independent significance (HR: 3.75; 95%-CI [1.87-7.53]). Discussion: The results of this trial demonstrate the negative impact of RBC transfusions on the prognosis of patients with EC. Contrastingly, the prognosis of OC is altered by the preoperative global health status rather than AOC or RBC transfusions. In summary, we suggested a cumulatively restrictive transfusion management in G8-non-frail EC patients and postulated a more moderate transfusion management based on the treatment of symptomatic anemia without survival deficits in OC patients.
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Epidural analgesia could influence the postoperative oncologic outcomes in patients with specific types of non-metastatic solid neoplasms. The present study aimed to investigate the impact of anesthetic technique on survival in elderly patients with ovarian cancer (OC). The records of all women with OC older than 60 years of age undergoing tumor debulking surgery at the University Medical Center of the Johannes Gutenberg University Mainz (Mainz, Germany) between January 2008 and December 2019 were obtained. The study cohort was divided into two groups based on the use of perioperative epidural anesthesia or not. First, Kaplan-Meier analysis was performed to analyze the prognostic influence of anesthetic technique on survival. Second, multivariate Cox proportional hazards model was adjusted for multiple conventional prognostic factors concerning three main categories: i) Current clinical-pathological tumor characteristics; ii) anesthesiologic parameters, including mean age, American Society of Anesthesiologists Performance Status and preexisting comorbidities summarized in the Charlson Comorbidity Index; and iii) oncological and surgical parameters such as oncological radicality and Surgical complexity Score. A total of 110 patients were included in the study and 71 (64.5%) of them received epidural analgesia. The median survival time was 26.0 months from primary debulking surgery and no significant differences in progression-free (PFS) and overall survival (OS) were noted between the 'Epidural' and 'non-Epidural' cohorts. After adjustment for the selected risk factors from the three categories, the effects of epidural analgesia on PFS and OS remained non-significant [PFS: hazard ratio (HR), 1.26; 95% CI, 0.66-2.39; and OS: HR, 0.79; 95% CI, 0.45-1.40]. The present results did not support the independent association between epidural-supplemented anesthesia and improved PFS or OS in elderly patients with standardized ovarian cancer debulking surgery.
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Endotracheal intubation is often a basic requirement for translational research in porcine models for various interventions that require a secured airway or high ventilation pressures. Endotracheal intubation is a challenging skill, requiring a minimum number of successful endotracheal intubations to achieve a high success rate under optimal conditions, which is often unachievable for non-anaesthesiology researchers. Due to the specific porcine airway anatomy, a difficult airway can usually be assumed. The impossibility of establishing a secure airway can result in injury, adverse events, or death of the laboratory animal. Using a prospective, randomized, controlled evaluation approach, it has been shown that fiberoptic-assisted endotracheal intubation takes longer but has a higher first-pass success rate than conventional intubation without causing clinically relevant drops in oxygen saturation. This model presents a standardized regimen for endoscopically guided endotracheal intubation, providing a secured airway, especially for researchers who are inexperienced in the technique of endotracheal intubation via direct laryngoscopy. This procedure is expected to minimize animal suffering and unnecessary animal losses.
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Manuseio das Vias Aéreas , Intubação Intratraqueal , Animais , Manuseio das Vias Aéreas/métodos , Endoscópios , Intubação Intratraqueal/métodos , Intubação Intratraqueal/veterinária , Laringoscopia/métodos , Estudos Prospectivos , SuínosRESUMO
Background: Invasive ventilation during cardiopulmonary resuscitation (CPR) is very complex due to unique thoracic pressure conditions. Current guidelines do not provide specific recommendations for ventilation during ongoing chest compressions regarding positive end-expiratory pressure (PEEP). This trial examines the cardiopulmonary effects of PEEP application during CPR. Methods: Forty-two German landrace pigs were anaesthetised, instrumented, and randomised into six intervention groups. Three PEEP levels (0, 8, and 16 mbar) were compared in high standard and ultralow tidal volume ventilation. After the induction of ventricular fibrillation, mechanical chest compressions and ventilation were initiated and maintained for thirty minutes. Blood gases, ventilation/perfusion ratio, and electrical impedance tomography loops were taken repeatedly. Ventilation pressures and haemodynamic parameters were measured continuously. Postmortem lung tissue damage was assessed using the diffuse alveolar damage (DAD) score. Statistical analyses were performed using SPSS, and p values <0.05 were considered significant. Results: The driving pressure (Pdrive) showed significantly lower values when using PEEP 16 mbar than when using PEEP 8 mbar (p = 0.045) or PEEP 0 mbar (p < 0.001) when adjusted for the ventilation mode. Substantially increased overall lung damage was detected in the PEEP 0 mbar group (vs. PEEP 8 mbar, p = 0.038; vs. PEEP 16 mbar, p = 0.009). No significant differences in mean arterial pressure could be detected. Conclusion: The use of PEEP during CPR seems beneficial because it optimises ventilation pressures and reduces lung damage without significantly compromising blood pressure. Further studies are needed to examine long-term effects in resuscitated animals.
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BACKGROUND: We evaluated the prognostic impact of various global health assessment tools in patients older than 60 years with ovarian cancer (OC). METHODS: G-8 geriatric screening tool (G-8 score), Lee Schonberg prognostic index, Eastern Cooperative Oncology Group (ECOG) performance status, and Charlson Comorbidity Index (CCI) were determined retrospectively in a consecutive cohort of elderly patients with OC. Univariate and multivariate Cox regression analyses and Kaplan-Meier method were performed to analyze the impact of the preoperative global health status on survival. RESULTS: 116 patients entered the study. In multivariate analysis adjusted for clinical-pathological factors, only the G-8 score retained significance as a prognostic parameter of progression-free survival (PFS) (hazard ratio [HR]: 1.970; 95% confidence interval [CI] [1.056-3.677]; p = 0.033). Fifty-six patients were classified as G-8-nonfrail with an increased PFS compared to 50 G-8-frail patients (53.4% vs. 16.7%; p = 0.010). A higher CCI was associated with decreased PFS (45.1% vs. 22.2%; p = 0.012), but it did not influence the risk of recurrences or death (p = 0.360; p = 0.111). The Lee Schonberg prognostic index, the ECOG, and age were not associated with survival. CONCLUSIONS: The G-8 score independently predicted PFS in elderly OC patients regardless of maximal surgical effort. Thus, it could be useful to assess surgical treatment based on frailty rather than age alone.
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Detecção Precoce de Câncer , Neoplasias Ovarianas , Idoso , Estudos de Coortes , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Intervalo Livre de Progressão , Estudos RetrospectivosRESUMO
BACKGROUND: Mechanical chest compression devices are accepted alternatives for cardiopulmonary resuscitation (CPR) under specific circumstances. Current devices lack prospective and comparative data on their specific cardiovascular effects and potential for severe thoracic injuries. OBJECTIVES: To compare CPR effectiveness and thoracic injuries of two mechanical chest compression devices in pigs. STUDY DESIGN: Prospective randomised trial. ANIMALS: Eighteen male German landrace pigs. METHODS: Ventricular fibrillation was induced in anaesthetised and instrumented pigs and the animals were randomised into two intervention groups. Mechanical CPR was initiated by means of LUCAS™ 2 (mCCD1) or Corpuls™ cpr (mCCD2) device. Advanced life support was applied for a maximum of 10 cycles and animals achieving ROSC were monitored for 8 h. Ventilation/perfusion measurements were performed and blood gas analyses were taken. Thoracic injuries were assessed via a standardised damage score. RESULTS: Five animals of the mCCD1 group and one animal of the mCCD2 group achieved ROSC (p = 0.048). Only the mCCD1 animals survived until the end of the monitoring period (p < 0.01). MCCD1 animals showed less pulmonary shunt (p = 0.025) and higher normal V/Q (p = 0.017) during CPR. MCCD2 animals showed significantly more severe thoracic injuries (p = 0.046). CONCLUSION: The LUCAS 2 device shows superior resuscitation outcomes and less thoracic injuries compared to Corpuls cpr when used for experimental CPR in juvenile pigs. Researchers should be aware that different mCCDs for experimental studies may significantly influence the respective outcome of resuscitation studies and affect comparability of different trials. Controlled human and animal CPR studies and a standardised post-resuscitation injury evaluation could help to confirm potential hazards. TRIAL REGISTRATION: Trial approval number: G16-1-042-E4.
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Reanimação Cardiopulmonar , Parada Cardíaca , Traumatismos Torácicos , Animais , Humanos , Masculino , Gasometria , Reanimação Cardiopulmonar/efeitos adversos , Reanimação Cardiopulmonar/instrumentação , Parada Cardíaca/terapia , Parada Cardíaca/veterinária , Pressão , Estudos Prospectivos , Suínos , Traumatismos Torácicos/epidemiologia , Traumatismos Torácicos/veterinária , Tórax , Fibrilação VentricularRESUMO
OBJECTIVE: To establish and evaluate a standardized method of targeted, intrabronchial drug delivery in pigs. STUDY DESIGN: Randomized controlled trial. ANIMALS: A total of 16 German Landrace pigs (Sus scrofa), age range 12â16 weeks, and weighing 28â35 kg. METHODS: The animals were anaesthetized, intubated, and instrumented with extended cardiovascular monitoring. Lung injury was induced by administering via a flexible fibre-optic endoscope using 100 mL saline solution containing either 20 mg of Escherichia coli lipopolysaccharide (E. coli LPS) (n = 8) or no additive (sham, n = 8) into the two distal mainstem bronchi. The animals were monitored for 8 hours and arterial oxygenation, inspiratory pressure and arterial blood pressure were measured repeatedly. Post-mortem, lung tissue was prepared for histologic damage scoring and determination of proinflammatory cytokines Interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFα). Statistical analyses were performed using inter-group analysis of variance and Student's t tests. Data are presented as mean ± standard deviation. A p value <0.05 was considered significant. RESULTS: The targeted application of LPS led to significant deterioration of oxygenation consistent with mild-to-moderate acute respiratory distress syndrome (ARDS) and hypotension (Horowitz ratio: sham 2 hour, 300 ± 39; LPS 2 hour, 193.7 ± 52; p < 0.001). Histologic analyses identified increased inflammation and oedema in the tissues of the animals in the LPS group IL-6 sham: 6.4 ± 4.4 × 10-5 pg mL-1; IL-6 LPS: 2.8 ± 2.4 × 10-4 pg mL-1, p = 0.015. CONCLUSIONS: The targeted application of agents via flexible fibre-optic endoscopy is a valid, reliable method of causing controlled lung damage in a porcine model. The data presented suggest the feasibility and possible advantages of controlled application and could expand the array of techniques used to help understand the critical condition of ARDS. In addition, a targeted approach could help reduce animal numbers used for this purpose.
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Lipopolissacarídeos/uso terapêutico , Síndrome do Desconforto Respiratório , Doenças dos Suínos , Animais , Citocinas , Modelos Animais de Doenças , Inflamação/veterinária , Pulmão , Síndrome do Desconforto Respiratório/induzido quimicamente , Síndrome do Desconforto Respiratório/veterinária , SuínosRESUMO
BACKGROUND: Efficient airway management to facilitate tracheal intubation encompasses essential skills in anaesthesiologic and intensive care. The application of flexible fibreoptic intubation in patients with difficult airways has been identified as the recommended method in various international guidelines. However, providing the opportunity to adequately train residents can be challenging. Using large animals for practice during ongoing studies could help to improve this situation, but there is no recent data on fibreoptic intubation in swine available. METHODS: Thirty male German landrace pigs were anesthetized, instrumented and randomized into two groups. The animals were either intubated conventionally using direct laryngoscopy or a single-use flexible video-endoscope. The intervention was carried out by providers with 3 months experience in conventional intubation of pigs and a brief introduction into endoscopy. Intubation attempts were supervised and aborted, when SpO2 dropped below 93%. After three failed attempts, an experienced supervisor intervened and performed the intubation. Intubation times and attempts were recorded and analysed. RESULTS: Flexible fibreoptic intubation showed a significantly higher success rate in first attempt endotracheal tube placement (75% vs. 47%) with less attempts overall (1.3 ± 0.6 vs. 2.1 ± 1.3, P = 0.043). Conventional intubation was faster (42 s ± 6 s vs. 67 s ± 10s, P < 0.001), but showed a higher complication rate and more desaturation episodes during the trial. CONCLUSIONS: Flexible fibreoptic intubation in swine is feasible and appears to be a safer and more accessible method for inexperienced users to learn. This could not only improve resident training options in hospitals with animal research facilities but might also prevent airway complications and needless animal suffering.
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Manuseio das Vias Aéreas/métodos , Tecnologia de Fibra Óptica/métodos , Internato e Residência/métodos , Intubação Intratraqueal/métodos , Maleabilidade , Cirurgia Vídeoassistida/métodos , Bem-Estar do Animal , Animais , Desenho de Equipamento/métodos , Tecnologia de Fibra Óptica/educação , Humanos , Masculino , Projetos Piloto , Estudos Prospectivos , Suínos , Cirurgia Vídeoassistida/educaçãoRESUMO
Visual impairment and blindness are often caused by retinal ischemia-reperfusion (I/R) injury. We aimed to characterize a new model of I/R in pigs, in which the intraocular pathways were not manipulated by invasive methods on the ocular system. After 12 min of ischemia followed by 20 h of reperfusion, reactivity of retinal arterioles was measured in vitro by video microscopy. Dihydroethidium (DHE) staining, qPCR, immunohistochemistry, quantification of neurons in the retinal ganglion cell layer, and histological examination was performed. Retinal arterioles of I/R-treated pigs displayed marked attenuation in response to the endothelium-dependent vasodilator, bradykinin, compared to sham-treated pigs. DHE staining intensity and messenger RNA levels for HIF-1α, VEGF-A, NOX2, and iNOS were elevated in retinal arterioles following I/R. Immunoreactivity to HIF-1α, VEGF-A, NOX2, and iNOS was enhanced in retinal arteriole endothelium after I/R. Moreover, I/R evoked a substantial decrease in Brn3a-positive retinal ganglion cells and noticeable retinal thickening. In conclusion, the results of the present study demonstrate that short-time ocular ischemia impairs endothelial function and integrity of retinal blood vessels and induces structural changes in the retina. HIF-1α, VEGF-A, iNOS, and NOX2-derived reactive oxygen species appear to be involved in the pathophysiology.
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Endotélio Vascular/fisiopatologia , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Artéria Retiniana/patologia , Células Ganglionares da Retina/patologia , Animais , Arteríolas/metabolismo , Arteríolas/patologia , Bradicinina/farmacologia , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Isquemia/metabolismo , Isquemia/fisiopatologia , NADPH Oxidase 2/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo , Retina/patologia , Artéria Retiniana/metabolismo , Células Ganglionares da Retina/metabolismo , Suínos , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Acute respiratory distress syndrome (ARDS) is a clinical syndrome of acute lung failure in critically sick patients, which severely compromises the function of multiple organs, including the brain. Although, the optic nerve and the retina are a part of the central nervous system, the effects of ARDS on these ocular structures are completely unknown. Thus, the major goal of this study was to test the hypothesis that ARDS affects vascular function in the eye. ARDS was induced in anesthetized pigs by intratracheal injection of lipopolysaccharide (LPS). Sham-treated animals served as controls. Pigs were monitored for 8â¯h and then sacrificed. Subsequently, retinal arterioles and short posterior ciliary arteries were isolated and cannulated with micropipettes to measure vascular responses by videomicroscopy. Levels of reactive oxygen species (ROS) were quantified in isolated vessels using dihydroethidium (DHE). Messenger RNA expression of hypoxic, inflammatory, prooxidative, and antioxidative genes was assessed by real-time PCR. When group-dependent differences in mRNA expression levels were found for a particular gene, immunostainings were conducted. Strikingly, responses to the endothelium-dependent vasodilator, bradykinin, were markedly impaired in retinal arterioles of LPS-treated pigs, but no differences were seen between ciliary arteries of LPS- and sham-treated animals. ROS levels were increased in retinal arterioles but not in ciliary arteries of LPS-treated pigs. Messenger RNA levels for HIF-1α, VEGF-A and NOX2 were markedly increased in retinal arterioles of LPS-treated pigs, whereas ciliary arteries had only negligible mRNA level changes. Pronounced immunoreactivity for HIF-1α, VEGF-A and NOX2 was seen in the endothelium of retinal arterioles from LPS-treated pigs. Histologically, massive edema was seen especially in the retinal nerve fiber layer of pigs treated with LPS. Our study provides the first evidence that ARDS induced by intratracheal LPS application evokes endothelial dysfunction in porcine retinal arterioles together with retinal edema, indicative of vascular leakage. In contrast, ciliary arteries appear to be resistant to intratracheal LPS application.
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Artérias Ciliares/fisiologia , Endotélio Vascular/patologia , Síndrome do Desconforto Respiratório/fisiopatologia , Artéria Retiniana/fisiologia , Animais , Arteríolas/fisiologia , Catalase/metabolismo , Modelos Animais de Doenças , Endotélio Vascular/metabolismo , Ensaio de Imunoadsorção Enzimática , Glutationa Peroxidase/metabolismo , Fator 1 Induzível por Hipóxia/metabolismo , Interleucinas/metabolismo , Lipopolissacarídeos/toxicidade , Masculino , Microscopia de Vídeo , Óxido Nítrico Sintase Tipo II/metabolismo , RNA Mensageiro/genética , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Síndrome do Desconforto Respiratório/metabolismo , Suínos , Glutationa Peroxidase GPX1RESUMO
BACKGROUND: The effects of different ventilation strategies during CPR on patient outcomes and lung physiology are still poorly understood. This study compares positive pressure ventilation (IPPV) to passive oxygenation (CPAP) and a novel ultra-low tidal volume ventilation (ULTVV) regimen in an experimental ventricular fibrillation animal model. STUDY DESIGN: Prospective randomized controlled trial. ANIMALS: 30 male German landrace pigs (16-20 weeks). METHODS: Ventricular fibrillation was induced in anesthetized and instrumented pigs and the animals were randomized into three groups. Mechanical CPR was initiated and ventilation was either provided by means of standard IPPV (RR: 10/min, Vt: 8-9 ml/kg, FiO2: 1,0, PEEP: 5 mbar), CPAP (O2-Flow: 10 l/min, PEEP: 5 mbar) or ULTVV (RR: 50/min, Vt: 2-3 ml/kg, FiO2: 1,0, PEEP: 5 mbar). Guideline-based advanced life support was applied for a maximum of 4 cycles and animals achieving ROSC were monitored for 6 h before terminating the experiment. Ventilation/perfusion ratios were performed via multiple inert gas elimination, blood gas analyses were taken hourly and extended cardiovascular measurements were collected constantly. Brain and lung tissue samples were taken and analysed for proinflammatory cytokine expression. RESULTS: ULTVV provided sufficient oxygenation and ventilation during CPR while demanding significantly lower respiratory and intrathoracic pressures. V/Q mismatch was significantly decreased and lung injury was mitigated in surviving animals compared to IPPV and CPAP. Additionally, cerebral cytokine expression was dramatically reduced. CONCLUSION: Ultra-low-volume ventilation during CPR in a porcine model is feasible and may provide lung-protective benefits as well as neurological outcome improvement due to lower inflammation. Our results warrant further studies and might eventually lead to new therapeutic options in the resuscitation setting.