Factors associated with variation in intracranial pressure in a model of intra-abdominal hypertension with acute lung injury

OBJETIVO: Avaliar o efeito de alterações hemodinâmicas, respiratórias e metabólicas sobre a pressão intracraniana em um modelo de lesão pulmonar aguda e síndrome compartimental abdominal. MÉTODOS: Oito porcos Agroceres foram submetidos, após a instrumentação, a cinco cenários clínicos: 1) estado basal com baixa pressão intra-abdominal e pulmão sadio; 2) pneumoperitôneo, com pressão intra-abdominal de 20 mm Hg; 3) lesão pulmonar aguda induzida por lavagem pulmonar e desativação de surfactante; 4) pneumoperitôneo com pressão intra-abdominal de 20 mm Hg na vigência de lesão pulmonar aguda e com PEEP baixo; e 5) PEEP ajustado a 27 cm H2O na vigência de pneumoperitôneo e lesão pulmonar aguda. Variáveis respiratórias e hemodinâmicas foram coletadas. Análise multivariada foi realizada buscando as variáveis associadas com elevação da pressão intracraniana nos cinco cenários estudados. RESULTADOS: Após a análise multivariada, nas situações não associadas com lesão pulmonar aguda apenas a pressão de platô das vias aéreas se correlacionou positivamente com a pressão intracraniana. Nos modelos associados com lesão pulmonar aguda, a pressão de platô de vias aéreas, a pressão arterial de CO2, o CO2 no final da expiração e a pressão venosa central se correlacionaram positivamente com incrementos da pressão intracraniana. CONCLUSÃO: Em um modelo de disfunção orgânica múltipla com situações clínicas associadas com aumento da pressão torácica e abdominal, o incremento da pressão intracraniana desencadeado pela elevação da pressão abdominal parece ser decorrente da piora da complacência do sistema respiratório e da redução do gradiente para drenagem venosa cerebral ocasionado pela elevação da pressão venosa central.OBJECTIVE: To evaluate the effects of hemodynamic, respiratory and metabolic changes on intracranial pressure in a model of acute lung injury and abdominal compartment syndrome. METHODS: Eight Agroceres pigs were submitted to five different clinical scenarios after instrumentation: 1) a baseline condition with low intra-abdominal pressure and healthy lungs; 2) pneumoperitoneum with 20 mmHg intra-abdominal pressure; 3) acute lung injury induced by pulmonary lavage with surfactant deactivation; 4) pneumoperitoneum with 20 mmHg intra-abdominal pressure with lung pulmonary injury and low positive end-expiratory pressure; and 5) 27 cmH2O positive end-expiratory pressure with pneumoperitoneum and acute lung injury. Respiratory and hemodynamic variables were collected. A multivariate analysis was conducted to search for variables associated with increased intracranial pressure in the five scenarios. RESULTS: Only plateau airway pressure showed a positive correlation with intracranial pressure in the multivariate analysis. In the models with acute lung injury, plateau airway pressure, CO2 arterial pressure, end tidal CO2 and central venous pressure were positively correlated with increased intracranial pressure. CONCLUSION: In a model of multiple organ dysfunction with associated clinical conditions causing increased intra-thoracic and abdominal pressure, increased intracranial pressure triggered by elevated intra-abdominal pressure is apparently caused by worsened respiratory system compliance and a reduced brain venous drainage gradient due to increased central venous pressure

Severe hypoxemia during veno-venous extracorporeal membrane oxygenation: exploring the limits of extracorporeal respiratory support

OBJECTIVE: Veno-venous extracorporeal oxygenation for respiratory support has emerged as a rescue alternative for patients with hypoxemia. However, in some patients with more severe lung injury, extracorporeal support fails to restore arterial oxygenation. Based on four clinical vignettes, the aims of this article were to describe the pathophysiology of this concerning problem and to discuss possibilities for hypoxemia resolution. METHODS: Considering the main reasons and rationale for hypoxemia during veno-venous extracorporeal membrane oxygenation, some possible bedside solutions must be considered: 1) optimization of extracorporeal membrane oxygenation blood flow; 2) identification of recirculation and cannula repositioning if necessary; 3) optimization of residual lung function and consideration of blood transfusion; 4) diagnosis of oxygenator dysfunction and consideration of its replacement; and finally 5) optimization of the ratio of extracorporeal membrane oxygenation blood flow to cardiac output, based on the reduction of cardiac output. CONCLUSION: Therefore, based on the pathophysiology of hypoxemia during veno-venous extracorporeal oxygenation support, we propose a stepwise approach to help guide specific interventions

Noninvasive ventilation immediately after extubation improves weaning outcome after acute respiratory failure: a randomized controlled trial

Abstract\ud \ud \ud \ud Introduction\ud \ud Noninvasive ventilation (NIV), as a weaning-facilitating strategy in predominantly chronic obstructive pulmonary disease (COPD) mechanically ventilated patients, is associated with reduced ventilator-associated pneumonia, total duration of mechanical ventilation, length of intensive care unit (ICU) and hospital stay, and mortality. However, this benefit after planned extubation in patients with acute respiratory failure of various etiologies remains to be elucidated. The aim of this study was to determine the efficacy of NIV applied immediately after planned extubation in contrast to oxygen mask (OM) in patients with acute respiratory failure (ARF).\ud \ud \ud \ud Methods\ud \ud A randomized, prospective, controlled, unblinded clinical study in a single center of a 24-bed adult general ICU in a university hospital was carried out in a 12-month period. Included patients met extubation criteria with at least 72 hours of mechanical ventilation due to acute respiratory failure, after following the ICU weaning protocol. Patients were randomized immediately before elective extubation, being randomly allocated to one of the study groups: NIV or OM. We compared both groups regarding gas exchange 15 minutes, 2 hours, and 24 hours after extubation, reintubation rate after 48 hours, duration of mechanical ventilation, ICU length of stay, and hospital mortality.\ud \ud \ud \ud Results\ud \ud Forty patients were randomized to receive NIV (20 patients) or OM (20 patients) after the following extubation criteria were met: pressure support (PSV) of 7 cm H2O, positive end-expiratory pressure (PEEP) of 5 cm H2O, oxygen inspiratory fraction (FiO2) ≤ 40%, arterial oxygen saturation (SaO2) ≥ 90%, and ratio of respiratory rate and tidal volume in liters (f/TV) < 105. Comparing the 20 patients (NIV) with the 18 patients (OM) that finished the study 48 hours after extubation, the rate of reintubation in NIV group was 5% and 39% in OM group (P = 0.016). Relative risk for reintubation was 0.13 (CI = 0.017 to 0.946). Absolute risk reduction for reintubation showed a decrease of 33.9%, and analysis of the number needed to treat was three. No difference was found in the length of ICU stay (P = 0.681). Hospital mortality was zero in NIV group and 22.2% in OM group (P = 0.041).\ud \ud \ud \ud Conclusions\ud \ud In this study population, NIV prevented 48 hours reintubation if applied immediately after elective extubation in patients with more than 3 days of ARF when compared with the OM group.\ud \ud \ud \ud Trial Registration number\ud \ud ISRCTN: 41524441.We thank all the physicians, physiotherapists, and nurses that took care of the patients throughout the protocol, the statisticians for the statistical analyses, and Adriana Pardini for revision of the language. This study was supported by Division of Critical Care, Hospital de Base de São José do Rio Preto, Rio Preto, SP, Brazil, and Division of Pulmonary and Critical Care Hospital das Clínicas of São Paulo Medical School, University of São Paulo, São Paulo, Brazil

First-year experience of a Brazilian tertiary medical center in supporting severely ill patients using extracorporeal membrane oxygenation

OBJECTIVES: The aim of this manuscript is to describe the first year of our experience using extracorporeal membrane oxygenation support. METHODS: Ten patients with severe refractory hypoxemia, two with associated severe cardiovascular failure, were supported using venous-venous extracorporeal membrane oxygenation (eight patients) or veno-arterial extracorporeal membrane oxygenation (two patients). RESULTS: The median age of the patients was 31 yr (range 14-71 yr). Their median simplified acute physiological score three (SAPS3) was 94 (range 84-118), and they had a median expected mortality of 95% (range 87-99%). Community-acquired pneumonia was the most common diagnosis (50%), followed by P. jiroveci pneumonia in two patients with AIDS (20%). Six patients were transferred from other ICUs during extracorporeal membrane oxygenation support, three of whom were transferred between ICUs within the hospital (30%), two by ambulance (20%) and one by helicopter (10%). Only one patient (10%) was anticoagulated with heparin throughout extracorporeal membrane oxygenation support. Eighty percent of patients required continuous venous-venous hemofiltration. Three patients (30%) developed persistent hypoxemia, which was corrected using higher positive end-expiratory pressure, higher inspired oxygen fractions, recruitment maneuvers, and nitric oxide. The median time on extracorporeal membrane oxygenation support was five (range 3-32) days. The median length of the hospital stay was 31 (range 3-97) days. Four patients (40%) survived to 60 days, and they were free from renal replacement therapy and oxygen support. CONCLUSIONS: The use of extracorporeal membrane oxygenation support in severely ill patients is possible in the presence of a structured team. Efforts must be made to recognize the necessity of extracorporeal respiratory support at an early stage and to prompt activation of the extracorporeal membrane oxygenation team

Longer-term effectiveness of a heterologous coronavirus disease 2019 (COVID-19) vaccine booster in healthcare workers in Brazil

Abstract Objective: To compare the long-term vaccine effectiveness between those receiving viral vector [Oxford-AstraZeneca (ChAdOx1)] or inactivated viral (CoronaVac) primary series (2 doses) and those who received an mRNA booster (Pfizer/BioNTech) (the third dose) among healthcare workers (HCWs). Methods: We conducted a retrospective cohort study among HCWs (aged ≥18 years) in Brazil from January 2021 to July 2022. To assess the variation in the effectiveness of booster dose over time, we estimated the effectiveness rate by taking the log risk ratio as a function of time. Results: Of 14,532 HCWs, coronavirus disease 2019 (COVID-19) was confirmed in 56.3% of HCWs receiving 2 doses of CoronaVac vaccine versus 23.2% of HCWs receiving 2 doses of CoronaVac vaccine with mRNA booster (P < .001), and 37.1% of HCWs receiving 2 doses of ChAdOx1 vaccine versus 22.7% among HCWs receiving 2 doses of ChAdOx1 vaccine with mRNA booster (P < .001). The highest vaccine effectiveness with mRNA booster was observed 30 days after vaccination: 91% for the CoronaVac vaccine group and 97% for the ChAdOx1 vaccine group. Vacine effectiveness declined to 55% and 67%, respectively, at 180 days. Of 430 samples screened for mutations, 49.5% were SARS-CoV-2 delta variants and 34.2% were SARS-CoV-2 omicron variants. Conclusions: Heterologous COVID-19 vaccines were effective for up to 180 days in preventing COVID-19 in the SARS-CoV-2 delta and omicron variant eras, which suggests the need for a second booster

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure &lt;= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Novel potential therapies for septic shock

Sepsis is the systemic inflammatory response syndrome secondary to a local infection. Septic shock, the severe complication of sepsis associated with refractory hypotension, is frequently a near-fatal condition requiring prompt diagnosis and management. Although the recent years have been associated with considerable improvements in the knowledge of the pathophysiology of the disease and remarkable advances have been achieved in sepsis treatment, the morbidity and mortality of this disease are still unacceptably high. In this review, we will briefly discuss the ongoing standard treatment of septic shock and describe novel potential therapies, aiming to improve hemodynamic support and/or control inflammatory response in sepsis. These therapies were associated with benefits in experimental studies and have been tested or are currently under testing in randomized controlled studies with septic patients

Evolução de variáveis hemodinâmicas e perfusionais durante o choque séptico experimental tratado com ressuscitação volêmica guiada por metas Hemodynamic and perfusion variables during experimental septic shock treated with goal-directed fluid resuscitation

OBJETIVOS: Apesar da ressuscitação volêmica guiada por saturação venosa central de oxigênio (SvcO2) ser considerada atualmente padrão ouro no tratamento da sepse, poucos estudos caracterizaram o perfil evolutivo de variáveis hemodinâmicas e perfusionais durante esta abordagem terapêutica. Este estudo teve por objetivo descrever evolutivamente estes parâmetros durante o choque séptico experimental sem ressuscitação e após 12 horas de ressuscitação guiada por metas. MÉTODOS: Treze porcos (35-45 kg) anestesiados foram submetidos a peritonite por inoculação fecal (0,75g/kg). Após desenvolverem hipotensão persistente, ambos os grupos receberam antibióticos e foram randomizados em dois grupos: controle (n=7), com suporte hemodinâmico otimizado para pressão venosa central entre 8-12mmHg, diurese acima de 0,5ml/kg/h e pressão arterial média maior que 65mmHg; e SvO2 (n=6), com os objetivos acima e SvO2 acima de 65%. As intervenções incluíram ringer lactato e noradrenalina nos 2 grupos e dobutamina no grupo SvO2. Os animais foram tratados durante doze horas ou óbito. RESULTADOS: A sepse não tratada associou-se a uma significante redução da SvO2, PvO2, débito cardíaco e pressão venosa central e aumento da diferença arterio-venosa da saturação de oxigênio e veno-arterial de CO2. Após ressuscitação, esses parâmetros foram corrigidos em ambos os grupos. A ressuscitação guiada por metas associou-se a um melhor perfil hemodinâmico caracterizado por maiores SvO2, débito cardíaco e pressão venosa central. CONCLUSÕES: A sepse não ressuscitada apresenta um perfil hemodinâmico sugestivo de hipovolemia, com piora perfusional e hemodinâmica revertida após ressuscitação volêmica. A ressuscitação guiada por metas associa-se a uma significante melhora dos parâmetros hemodinâmicos e perfusionais<br>OBJECTIVES: Although fluid resuscitation guided by central venous oxygen saturation (SvcO2) is currently considered the gold standard in sepsis therapy, few studies have described hemodynamic and perfusion parameters during this procedure. This study aims to describe these parameters during septic shock without resuscitation and after 12 hours of goal-directed resuscitation. METHODS: Thirteen anesthetized pigs (35-45 kg) had peritonitis caused by fecal inoculation (0.75 g/kg). After developing persistent hypotension, both groups were given antibiotics and randomized either to the control group (n=7) or the experimental group (n=6). In the control group, hemodynamic control was optimized to maintain a central venous pressure of 8-12 mmHg, a urinary output above 0.5 mL/kg/hour and a mean arterial blood pressure above 65 mmHg. The experimental group received the above target therapy in addition to maintaining a SvO2 above 65%. The interventions included lactated Ringer's solution and norepinephrine for both groups and dobutamine in the SvO2 group. The animals were treated for 12 hours or until death. RESULTS: Untreated sepsis was associated with significant reductions in SvO2, PvO2, cardiac output and central venous pressure in addition to increased arteriovenous oxygen saturation and veno-arterial CO2 differences. Following resuscitation, these parameters were corrected in both groups. Goal-directed resuscitation was associated with a better hemodynamic profile, characterized by higher SvO2, cardiac output and central venous pressure. CONCLUSIONS: Non-resuscitated sepsis showed a hemodynamic profile suggesting hypovolemia, with worsened perfusion and hemodynamics, which is reversed upon fluid resuscitation. Goal-directed resuscitation is associated with significantly improved hemodynamic and perfusion parameter

Influence of ventilatory settings on static and functional haemodynamic parameters during experimental hypovolaemia

Background and objective The influence of ventilatory settings on static and functional haemodynamic parameters during mechanical ventilation is not completely known. The purpose of this study was to evaluate the effect of positive end-expiratory pressure, tidal volume and inspiratory to expiratory time ratio variations on haemodynamic parameters during haemorrhage and after transfusion of shed blood. Methods Ten anaesthetized pigs were instrumented and mechanically ventilated with a tidal volume of 8 ml kg(-1), a positive end-expiratory pressure of 5 cmH(2)O and an inspiratory to expiratory ratio of 1 : 2. Then, they were submitted in a random order to different ventilatory settings (tidal volume 16 ml kg(-1), positive end-expiratory pressure 15 cmH(2)O or inspiratory to expiratory time ratio 2: 1). Functional and static haemodynamic parameters (central venous pressure, pulmonary artery occlusion pressure, right ventricular end-diastolic volume and pulse pressure variation) were evaluated at baseline, during hypovolaemia (withdrawal of 20% of estimated blood volume) and after an infusion of withdrawn blood (posttransfusion). Results During baseline, a positive end-expiratory pressure of 15cmH(2)O significantly increased pulmonary artery occlusion pressure from 14.6 +/- 1.6 mmHg to 17.4 +/- 1.7 mmHg (P<0.001) and pulse pressure variation from 15.8 +/- 8.5% to 25.3 +/- 9.5% (P<0.001). High tidal volume increased pulse pressure variation from 15.8 8.5% to 31.6 +/- 10.4% (P<0.001), and an inspiratory to expiratory time ratio of 2: 1 significantly increased only central venous pressure. During hypovolaemia, high positive end-expiratory pressure influenced all studied variables, and high tidal volume strongly increased pulse pressure variation (40.5 +/- 12.4% pre vs. 84.2 +/- 19.1 % post, P<0.001). The inversion of the inspiratory to expiratory time ratio only slightly increased filling pressures during hypovolaemia, without without affecting pulse pressure variation or right ventricle end-diastolic volume. Conclusion We concluded that pulse pressure variation measurement is influenced by cyclic variations in intrathoracic pressure, such as those caused by augmentations in tidal volume. The increase in mean airway pressure caused by positive end-expiratory pressure affects cardiac filling pressures and also pulse pressure variation, although to a lesser extent. Inversion of the inspiratory to expiratory time ratio does not induce significant changes in static and functional haemodynamic parameters. Eur J Anaesthesiol 26:66-72 (c) 2009 European Society of Anaesthesiology.Research and Education Institute of the Sirio-Libanes Hospita