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2.
Intensive Care Med Exp ; 5(1): 27, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28550659

RESUMO

BACKGROUND: Mechanical ventilation and hyperoxia have the potential to independently promote lung injury and inflammation. Our purpose was to study both time- and dose-dependent effects of supplemental oxygen in an experimental model of mechanically ventilated mice. METHODS: Healthy male C57Bl/6J mice, aged 9-10 weeks, were intraperitoneally anesthetized and randomly assigned to the mechanically ventilated group or the control group. In total, 100 mice were tracheotomized and mechanically ventilated for either 8 or 12 h after allocation to different settings for the applied fractions of inspired oxygen (FiO2, 30, 50, or 90%) and tidal volumes (7.5 or 15 ml/kg). After euthanisation arterial blood, bronchoalveolar lavage fluid (BALf) and tissues were collected for analyses. RESULTS: Mechanical ventilation significantly increased the lung injury score (P < 0.05), mean protein content (P < 0.001), and the mean number of cells (P < 0.01), including neutrophils in BALf (P < 0.001). In mice ventilated for 12 h, a significant increase in TNF-α, IFN-γ, IL-1ß, IL-10, and MCP-1 (P < 0.01) was observed with 90% FiO2, whereas IL-6 showed a decreasing trend (P for trend = 0.03) across FiO2 groups. KC, MIP-2, and sRAGE were similar between FiO2 groups. HMGB-1 was significantly higher in BALf of mechanically ventilated mice compared to controls and showed a gradual increase in expression with increasing FiO2. Cytokine and chemokine levels in BALf did not markedly differ between FiO2 groups after 8 h of ventilation. Differences between the tidal volume groups were small and did not appear to significantly interact with the oxygen levels. CONCLUSIONS: We demonstrated a severe vascular leakage and a pro-inflammatory pulmonary response in mechanically ventilated mice, which was enhanced by severe hyperoxia and longer duration of mechanical ventilation. Prolonged ventilation with high oxygen concentrations induced a time-dependent immune response characterized by elevated levels of neutrophils, cytokines, and chemokines in the pulmonary compartment.

3.
Ann Intensive Care ; 7(1): 20, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28233196

RESUMO

BACKGROUND: Although oxygen is generally administered in a liberal manner in the perioperative setting, the effects of oxygen administration on dynamic cardiovascular parameters, filling status and cerebral perfusion have not been fully unraveled. Our aim was to study the acute hemodynamic and microcirculatory changes before, during and after arterial hyperoxia in mechanically ventilated patients after coronary artery bypass grafting (CABG) surgery. METHODS: This was a single-center physiological study in a tertiary care ICU in the Netherlands. Twenty-two patients scheduled for ICU admission after elective CABG were enrolled in the study between September 2014 and September 2015. In the ICU, patients were exposed to a fraction of inspired oxygen (FiO2) of 90% allowing a 15-min wash-in period. Various hemodynamic parameters were measured using direct pressure signals and continuous arterial waveform analysis at three sequential time points: before, during and after hyperoxia. RESULTS: During a 15-min exposure to a fraction of inspired oxygen (FiO2) of 90%, the partial pressure of arterial oxygen (PaO2) and arterial oxygen saturation (SaO2) were significantly higher. The systemic resistance increased (P < 0.0001), without altering the heart rate. Stroke volume variation and pulse pressure variation decreased slightly. The cardiac output did not significantly decrease (P = 0.08). Mean systemic filling pressure and arterial critical closing pressure increased (P < 0.01whereas the percentage of perfused microcirculatory vessels decreased (P < 0.01). Other microcirculatory parameters and cerebral blood flow velocity showed only slight changes. CONCLUSIONS: We found that short-term hyperoxia affects hemodynamics in ICU patients after CABG. This was translated in several changes in central circulatory variables, but had only slight effects on cardiac output, cerebral blood flow and the microcirculation. Clinical trial registration Netherlands Trial Register: NTR5064.

4.
Crit Care Med ; 45(2): 187-195, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27763912

RESUMO

OBJECTIVE: Emerging evidence has shown the potential risks of arterial hyperoxia, but the lack of a clinical definition and methodologic limitations hamper the interpretation and clinical relevance of previous studies. Our purpose was to evaluate previously used and newly constructed metrics of arterial hyperoxia and systematically assess their association with clinical outcomes in different subgroups in the ICU. DESIGN: Observational cohort study. SETTING: Three large tertiary care ICUs in the Netherlands. PATIENTS: A total of 14,441 eligible ICU patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 295,079 arterial blood gas analyses, including the PaO2, between July 2011 and July 2014 were extracted from the patient data management system database. Data from all admissions with more than one PaO2 measurement were supplemented with anonymous demographic and admission and discharge data from the Dutch National Intensive Care Evaluation registry. Mild hyperoxia was defined as PaO2 between 120 and 200 mm Hg; severe hyperoxia as PaO2 greater than 200 mm Hg. Characteristics of existing and newly constructed metrics for arterial hyperoxia were examined, and the associations with hospital mortality (primary outcome), ICU mortality, and ventilator-free days and alive at day 28 were retrospectively analyzed using regression models in different subgroups of patients. Severe hyperoxia was associated with higher mortality rates and fewer ventilator-free days in comparison to both mild hyperoxia and normoxia for all metrics except for the worst PaO2. Adjusted effect estimates for conditional mortality were larger for severe hyperoxia than for mild hyperoxia. This association was found both within and beyond the first 24 hours of admission and was consistent for large subgroups. The largest point estimates were found for the exposure identified by the average PaO2, closely followed by the median PaO2, and these estimates differed substantially between subsets. Time spent in hyperoxia showed a linear and positive relationship with hospital mortality. CONCLUSIONS: Our results suggest that we should limit the PaO2 levels of critically ill patients within a safe range, as we do with other physiologic variables. Analytical metrics of arterial hyperoxia should be judiciously considered when interpreting and comparing study results and future studies are needed to validate our findings in a randomized fashion design.


Assuntos
Cuidados Críticos/estatística & dados numéricos , Hiperóxia/epidemiologia , Idoso , Artérias , Gasometria , Feminino , Mortalidade Hospitalar , Humanos , Hiperóxia/complicações , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento
5.
Crit Care Med ; 44(10): e1016, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27635515
6.
Crit Care Med ; 44(12): e1226-e1235, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27513359

RESUMO

OBJECTIVES: A growing body of evidence suggests that age affects the main pathophysiologic mechanisms of the acute respiratory distress syndrome. This may imply the need for developing age-tailored therapies for acute respiratory distress syndrome. However, underlying molecular mechanisms governing age-related susceptibility first need to be unraveled. In a rat model of acute lung injury, we investigated whether age affects the balance between the two key enzymes of the pulmonary renin-angiotensin system, angiotensin-converting enzyme, and angiotensin-converting enzyme 2. We hypothesized that aging shifts the balance toward the lung injury-promoting angiotensin-converting enzyme, which may form an explanation for the differences in severity of lung injury between different age groups. DESIGN: Prospective, randomized controlled animal study. SETTING: University medical research laboratory. SUBJECTS: Infant (15 ± 2 d), juvenile (37 ± 2 d), adult (4 ± 0.2 mo), and elderly (19.5 ± 0.5 mo) male RCCHan Wistar rats. INTERVENTIONS: Lung injury was induced by intratracheal administration of lipopolysaccharide (5 mg/kg) and 4 hours of mechanical ventilation (15 mL/kg). MEASUREMENTS AND MAIN RESULTS: In lipopolysaccharide-exposed and mechanical ventilated rats, angiotensin-converting enzyme activity in bronchoalveolar lavage fluid increased 3.2-fold in elderly when compared with infants. No changes in bronchoalveolar lavage fluid angiotensin-converting enzyme 2 activity were found. In addition, membrane-bound angiotensin-converting enzyme activity decreased. Together with the presence of angiotensin-converting enzyme-sheddase ADAM9 (a disintegrin and metalloproteinase domain-containing protein 9) and an age-dependent increase in tumor necrosis factor-α, an activator of ADAM9, these results indicate increased shedding of angiotensin-converting enzyme in the alveolar compartment, thereby shifting the balance toward the injurious pathway. This imbalance was associated with an increased inflammatory mediator response and more lung injury (wet-to-dry ratio and histology) in elderly rats. CONCLUSIONS: Increasing age is associated with an imbalance of the pulmonary renin-angiotensin system, which correlates with aggravated inflammation and more lung injury. These changes might form the ground for new therapeutic strategies in terms of dosing and effectiveness of renin-angiotensin system-modulating agents for treatment of acute respiratory distress syndrome.


Assuntos
Lesão Pulmonar Aguda/fisiopatologia , Sistema Renina-Angiotensina/fisiologia , Lesão Pulmonar Aguda/etiologia , Fatores Etários , Animais , Pulmão/fisiopatologia , Masculino , Ratos , Ratos Wistar , Síndrome do Desconforto Respiratório do Adulto/etiologia , Síndrome do Desconforto Respiratório do Adulto/fisiopatologia
7.
Crit Care Med ; 44(3): 554-63, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26562347

RESUMO

OBJECTIVES: Conservative oxygen therapy is aimed at the prevention of harm by iatrogenic hyperoxia while preserving adequate tissue oxygenation. Our aim was to study the effectiveness and clinical outcomes of a two-step implementation of conservative oxygenation targets in the ICU. DESIGN: This was a before and after stepwise implementation study of conservative oxygenation targets, between July 2011 and July 2014. The primary endpoint was the proportion of PaO2 values within the target range. Secondary outcomes included ventilator-free days at day 28, length of stay, and mortality. SETTING: Three closed-format ICUs in the Netherlands. PATIENTS: We analyzed data on 15,045 eligible admissions. INTERVENTIONS: The first implementation phase consisted of providing training and feedback on new guidelines instructing for explicit targets for arterial oxygen tension (PaO2, 55-86 mm Hg) and oxyhemoglobin saturation (SpO2, 92-95%). In the second phase, bedside clinicians were additionally assisted in guideline adherence by a computerized decision-support system. MEASUREMENTS AND MAIN RESULTS: The proportion of PaO2 in the target range increased from 47% at baseline to 63% in phase 1 and to 68% in phase 2 (p < 0.0001). Episodes of hyperoxia decreased (p < 0.0001), whereas hypoxic episodes remained unchanged (p = 0.06) during the study. Mechanical ventilation time was significantly lower (p < 0.01) during both study phases. After adjustment for potential confounders, ventilator-free days in phase 1 and phase 2 were higher than baseline: adjusted mean difference, 0.55 (95% CI, 0.25-0.84) and 0.48 (95% CI, 0.11-0.86), respectively. Adjusted ICU mortality and ICU-free days did not significantly differ between study phases. Hospital mortality decreased in reference to baseline: adjusted odds ratio, 0.84 (95% CI, 0.74-0.96) for phase 1 and 0.82 (95% CI, 0.69-0.96) for phase 2. CONCLUSIONS: Stepwise implementation of conservative oxygenation targets was feasible, effective, and seemed safe in critically ill patients. The implementation was associated with several changes in clinical outcomes, but the causal impact of conservative oxygenation is still to be determined.


Assuntos
Estado Terminal/terapia , Oxigenoterapia/métodos , Oxigênio/administração & dosagem , Idoso , Gasometria/métodos , Sistemas de Apoio a Decisões Clínicas , Feminino , Fidelidade a Diretrizes , Mortalidade Hospitalar , Humanos , Hiperóxia/etiologia , Hiperóxia/prevenção & controle , Hipóxia/prevenção & controle , Hipóxia/terapia , Unidades de Terapia Intensiva/normas , Masculino , Pessoa de Meia-Idade , Países Baixos , Oxigênio/efeitos adversos , Oxigênio/sangue , Guias de Prática Clínica como Assunto , Respiração , Respiração Artificial/efeitos adversos , Resultado do Tratamento
8.
Crit Care ; 19: 348, 2015 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-26415731

RESUMO

INTRODUCTION: Arterial concentrations of carbon dioxide (PaCO2) and oxygen (PaO2) during admission to the intensive care unit (ICU) may substantially affect organ perfusion and outcome after cardiac arrest. Our aim was to investigate the independent and synergistic effects of both parameters on hospital mortality. METHODS: This was a cohort study using data from mechanically ventilated cardiac arrest patients in the Dutch National Intensive Care Evaluation (NICE) registry between 2007 and 2012. PaCO2 and PaO2 levels from arterial blood gas analyses corresponding to the worst oxygenation in the first 24 h of ICU stay were retrieved for analyses. Logistic regression analyses were performed to assess the relationship between hospital mortality and both categorized groups and a spline-based transformation of the continuous values of PaCO2 and PaO2. RESULTS: In total, 5,258 cardiac arrest patients admitted to 82 ICUs in the Netherlands were included. In the first 24 h of ICU admission, hypocapnia was encountered in 22 %, and hypercapnia in 35 % of included cases. Hypoxia and hyperoxia were observed in 8 % and 3 % of the patients, respectively. Both PaCO2 and PaO2 had an independent U-shaped relationship with hospital mortality and after adjustment for confounders, hypocapnia and hypoxia were significant predictors of hospital mortality: OR 1.37 (95 % CI 1.17-1.61) and OR 1.34 (95 % CI 1.08-1.66). A synergistic effect of concurrent derangements of PaCO2 and PaO2 was not observed (P = 0.75). CONCLUSIONS: The effects of aberrant arterial carbon dioxide and arterial oxygen concentrations were independently but not synergistically associated with hospital mortality after cardiac arrest.


Assuntos
Dióxido de Carbono/sangue , Parada Cardíaca/mortalidade , Oxigênio/sangue , Ressuscitação/mortalidade , Idoso , Feminino , Parada Cardíaca/sangue , Parada Cardíaca/terapia , Mortalidade Hospitalar , Humanos , Hipercapnia/etiologia , Hipercapnia/mortalidade , Hiperóxia/etiologia , Hiperóxia/mortalidade , Hipocapnia/etiologia , Hipocapnia/mortalidade , Hipóxia/etiologia , Hipóxia/mortalidade , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade
10.
Crit Care ; 19: 284, 2015 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-26278383

RESUMO

Oxygen administration is uniformly used in emergency and intensive care medicine and has life-saving potential in critical conditions. However, excessive oxygenation also has deleterious properties in various pathophysiological processes and consequently both clinical and translational studies investigating hyperoxia during critical illness have gained increasing interest. Reactive oxygen species are notorious by-products of hyperoxia and play a pivotal role in cell signaling pathways. The effects are diverse, but when the homeostatic balance is disturbed, reactive oxygen species typically conserve a vicious cycle of tissue injury, characterized by cell damage, cell death, and inflammation. The most prominent symptoms in the abundantly exposed lungs include tracheobronchitis, pulmonary edema, and respiratory failure. In addition, absorptive atelectasis results as a physiological phenomenon with increasing levels of inspiratory oxygen. Hyperoxia-induced vasoconstriction can be beneficial during vasodilatory shock, but hemodynamic changes may also impose risk when organ perfusion is impaired. In this context, oxygen may be recognized as a multifaceted agent, a modifiable risk factor, and a feasible target for intervention. Although most clinical outcomes are still under extensive investigation, careful titration of oxygen supply is warranted in order to secure adequate tissue oxygenation while preventing hyperoxic harm.


Assuntos
Estado Terminal/terapia , Hiperóxia/complicações , Animais , Cuidados Críticos , Humanos , Hiperóxia/etiologia , Hiperóxia/fisiopatologia , Oxigenoterapia/efeitos adversos , Assistência Perioperatória
11.
Crit Care Med ; 43(7): 1508-19, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25855899

RESUMO

OBJECTIVE: Oxygen is vital during critical illness, but hyperoxia may harm patients. Our aim was to systematically evaluate the methodology and findings of cohort studies investigating the effects of hyperoxia in critically ill adults. DATA SOURCE: A meta-analysis and meta-regression analysis of cohort studies published between 2008 and 2015 was conducted. Electronic databases of MEDLINE, EMBASE, and Web of Science were systematically searched for the keywords hyperoxia and mortality or outcome. STUDY SELECTION: Publications assessing the effect of arterial hyperoxia on outcome in critically ill adults (≥ 18 yr) admitted to critical care units were eligible. We excluded studies in patients with chronic obstructive pulmonary disease, extracorporeal life support or hyperbaric oxygen therapy, and animal studies. Due to a lack of data, no studies dedicated to patients with acute lung injury, sepsis, shock, or multiple trauma could be included. DATA EXTRACTION: Studies were included independent of admission diagnosis and definition of hyperoxia. The primary outcome measure was in-hospital mortality, and results were stratified for relevant subgroups (cardiac arrest, traumatic brain injury, stroke, post-cardiac surgery, and any mechanical ventilation). The effects of arterial oxygenation on functional outcome, long-term mortality, and discharge variables were studied as secondary outcomes. DATA SYNTHESIS: Twenty-four studies were included of which five studies were only for a subset of the analyses. Nineteen studies were pooled for meta-analyses and showed that arterial hyperoxia during admission increases hospital mortality: adjusted odds ratio, 1.21 (95% CI, 1.08-1.37) (p = 0.001). Functional outcome measures were diverse and generally showed a more favorable outcome for normoxia. CONCLUSIONS: In various subsets of critically ill patients, arterial hyperoxia was associated with poor hospital outcome. Considering the substantial heterogeneity of included studies and the lack of a clinical definition, more evidence is needed to provide optimal oxygen targets to critical care physicians.


Assuntos
Estado Terminal , Hiperóxia/complicações , Estudos de Coortes , Humanos , Prognóstico
12.
Int J Behav Nutr Phys Act ; 9: 103, 2012 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-22938557

RESUMO

Physical inactivity is one of the four leading risk factors for global mortality. Accurate measurement of physical activity (PA) and in particular by physical activity questionnaires (PAQs) remains a challenge. The aim of this paper is to provide an updated systematic review of the reliability and validity characteristics of existing and more recently developed PAQs and to quantitatively compare the performance between existing and newly developed PAQs.A literature search of electronic databases was performed for studies assessing reliability and validity data of PAQs using an objective criterion measurement of PA between January 1997 and December 2011. Articles meeting the inclusion criteria were screened and data were extracted to provide a systematic overview of measurement properties. Due to differences in reported outcomes and criterion methods a quantitative meta-analysis was not possible.In total, 31 studies testing 34 newly developed PAQs, and 65 studies examining 96 existing PAQs were included. Very few PAQs showed good results on both reliability and validity. Median reliability correlation coefficients were 0.62-0.71 for existing, and 0.74-0.76 for new PAQs. Median validity coefficients ranged from 0.30-0.39 for existing, and from 0.25-0.41 for new PAQs.Although the majority of PAQs appear to have acceptable reliability, the validity is moderate at best. Newly developed PAQs do not appear to perform substantially better than existing PAQs in terms of reliability and validity. Future PAQ studies should include measures of absolute validity and the error structure of the instrument.


Assuntos
Inquéritos Epidemiológicos/normas , Atividade Motora , Inquéritos e Questionários/normas , Atividades Cotidianas , Metabolismo Energético , Exercício , Inquéritos Epidemiológicos/instrumentação , Humanos , Estilo de Vida , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
13.
Diabetes ; 58(8): 1776-9, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19470610

RESUMO

OBJECTIVE: To examine the prospective association between objectively measured time spent sedentary and insulin resistance and whether this association is independent of moderate- and vigorous-intensity physical activity (MVPA) and other relevant confounders. RESEARCH DESIGN AND METHODS: This was a population-based study (Medical Research Council Ely study) in 376 middle-aged adults (166 men; 210 women) over 5.6 years of follow-up. Physical activity and sedentary time were measured objectively by individually calibrated minute-by-minute heart rate monitoring at both baseline and follow-up. Sedentary time was calculated as the heart rate observations (in minutes) below an individually predetermined threshold (flex heart rate) and expressed as a percentage of total monitored time during waking hours over 4 days. The percentage of time spent above 1.75 x resting heart rate represented MVPA. Fasting plasma insulin was used as a surrogate measure of insulin resistance. RESULTS: Time spent sedentary at baseline was significantly and positively associated with log fasting insulin at follow-up (beta = 0.003, 95% CI 0.0006-0.006, P = 0.015) independent of baseline age, sex, fat mass, fasting insulin, smoking status, and follow-up time. After further adjustment for MVPA, this association was somewhat strengthened (beta = 0.004, 95% CI 0.0009-0.006, P = 0.009). CONCLUSIONS: Time spent sedentary predicts higher levels of fasting insulin independent of the amount of time spent at moderate- and vigorous-intensity activity levels. This highlights the importance of reducing sedentary time in order to improve metabolic health, possibly in addition to the benefits associated with a physically active lifestyle.


Assuntos
Resistência à Insulina/fisiologia , Estilo de Vida , Atividade Motora/fisiologia , Descanso/fisiologia , Aerobiose , Glicemia/metabolismo , Composição Corporal , Estudos de Coortes , Metabolismo Energético , Feminino , Seguimentos , Frequência Cardíaca , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Aptidão Física , Estudos Prospectivos
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