Perioperative Hyperoxyphobia: Justified or Not? Benefits and Harms of Hyperoxia during Surgery.
ABSTRACT: The use of an inspiratory oxygen fraction of 0.80 during surgery is a topic of ongoing debate. Opponents claim that increased oxidative stress, atelectasis, and impaired oxygen delivery due to hyperoxic vasoconstriction are detrimental. Proponents point to the beneficial effects on the incidence of surgical site infections and postoperative nausea and vomiting. Also, hyperoxygenation is thought to extend the safety margin in case of acute intraoperative emergencies. This review provides a comprehensive risk-benefit analysis for the use of perioperative hyperoxia in noncritically ill adults based on clinical evidence and supported by physiological deduction where needed. Data from the field of hyperbaric medicine, as a model of extreme hyperoxygenation, are extrapolated to the perioperative setting. We ultimately conclude that current evidence is in favour of hyperoxia in noncritically ill intubated adult surgical patients.
Project description:BACKGROUND:We describe a combinatorial intensive care approach and discuss the critical factors that allowed us to successfully manage a life-threatening case of acute anaerobic septic shock triggered by descending necrotizing mediastinitis. CASE PRESENTATION:We admitted a 38-year-old critically ill Kosovar Albanian man to our intensive care unit because of clinical manifestations of severe sepsis. His condition had worsened in the previous 2 weeks following unsuccessful antibiotic therapy for tonsillitis complicated by retropharyngeal abscesses. Computed tomography and intraoperative observations identified abscesses in the anterior and middle mediastinum regions and the distal part of the neck, directly on the border with the left lobe of the thyroid gland. Cultures indicated infections with α-hemolytic Streptococcus and Clostridium species: High procalcitonin and lactate levels, blood gas analysis, poor peripheral capillary oxygen saturation, and severe hemodynamic instability pointed to a case of acute septic shock. The entire treatment consisted of an aggressive antibiotic regimen, transthoracic and mediastinal surgical evacuation of the abscess, vacuum sealing drainage with a pleural chest tube, continuous venovenous hemodiafiltration using cytokine-adsorbing hemofilters, and extracorporeal blood hyperoxygenation. CONCLUSIONS:Efficient treatment of severe anaerobic sepsis resulting from descending necrotizing mediastinitis should build on a multidisciplinary approach. In support of first-line therapies with targeted antibiotics and surgical debridement, clinicians should consider alternative therapies such as continuous venovenous hemodiafiltration with cytokine-adsorbing hemofilters and hyperoxygenation.
Project description:Worldwide, fishery managers strive to maintain fish stocks at or above levels that produce maximum sustainable yields, and to rebuild overexploited stocks that can no longer support such yields. In the United States, rebuilding overexploited stocks is a contentious issue, where most stocks are mandated to rebuild in as short a time as possible, and in a time period not to exceed 10 years. Opponents of such mandates and related guidance argue that rebuilding requirements are arbitrary, and create discontinuities in the time and fishing effort allowed for stocks to rebuild due to differences in productivity. Proponents, however, highlight how these mandates and guidance were needed to curtail the continued overexploitation of these stocks by setting firm deadlines on rebuilding. Here we evaluate the statements made by opponents and proponents of the 10-year rebuilding mandate and related guidance to determine whether such points are technically accurate using a simple population dynamics model and a database of U.S. fish stocks to parameterize the model. We also offer solutions to many of the issues surrounding this mandate and its implementation by recommending some fishing mortality based frameworks, which meet the intent of the 10-year rebuilding requirement while also providing more flexibility.
Project description:Background:Few data showed the optimal blood pressure (BP) in noncritically ill patients with acute kidney injury (AKI) relative to mortality or severe AKI. We therefore sought to analyze the data that exist for the ideal target range for BP in noncritically ill patients with AKI. Methods:We performed a retrospective cohort study involving 1,612 hospitalized patients who were diagnosed with AKI using the Kidney Disease: Improving Global Outcomes definition based on serum creatinine measurements for a period of 1 year. The average systolic BP (SBP) was categorized into 10-mmHg increments (within 48 hours after the development of AKI). The primary outcome was a composite of severe AKI or 90-day mortality. Results:The composite outcome rate in patients was 18.7% (302/1,612). The relationship between BP and the composite outcome followed a U-shaped curve, with an increased event rate observed at both low and high BP values. The average SBP after AKI predicted the composite outcome after adjusting for baseline variables (reference SBP: 120-129 mmHg; < 100 mmHg: hazard ratio [HR] 1.84, P = 0.015; 100-109 mmHg: HR 1.56, P = 0.038; 110-119 mmHg: HR 1.15, P = 0.483; 130-139 mmHg: HR 1.51, P = 0.045; ≥ 140 mmHg: HR 1.73, P = 0.005). Conclusion:Among noncritically ill patients with AKI, a U-shaped curve association was observed between the average SBP within 48 hours after AKI and the composite primary outcome of this study, with the lowest event rate for SBP ranging from approximately 110 to 129 mmHg.
Project description:<h4>Background and aims</h4>Minimum unit pricing (MUP) for alcohol was introduced in Scotland on 1 May 2018, and is now on the policy agenda in other devolved administrations and at Westminster. Previous research has explored the arguments deployed for and against MUP, but the congruence between actors in the MUP debate has not been sufficiently examined. This study identified and mapped the discourse coalitions that emerged in the UK MUP debate through an analysis of actors' use of arguments in media coverage of the policy debates.<h4>Design</h4>A sample of print media coverage of MUP was obtained from the LexisNexis newspaper database. The resulting sample was imported into discourse network analysis (DNA) software for coding and subsequent visualization of actor networks.<h4>Setting</h4>United Kingdom.<h4>Observations</h4>A total of 348 articles from eight UK-wide and three Scottish newspapers from an 18-month period, ending in November 2012, were analysed.<h4>Measurements</h4>Actors' arguments were coded to generate structured data for conversion into a weighted actor network where ties represent similarities among actors in terms of arguments in support of or opposition to MUP.<h4>Findings</h4>Two polarized discourse coalitions, Opponents and Proponents of MUP, emerged in media coverage. The Proponents coalition consisted mainly of health advocacy groups, charities, political parties and academic institutions. In the Opponents coalition, the networks were formed of key alcohol manufacturers and economic think-tanks. While producer organizations were central to the Opponents coalition, some commercial actors were more favourable to MUP, highlighting divisions within the industry overall.<h4>Conclusions</h4>Media coverage of minimum unit pricing (MUP) in Scotland from June 2011 to November 2012 showed alignment between the policy positions of (1) alcohol producers and think-tanks opposed to MUP; and (2) public health advocates and health charities in favour of the policy. Some alcohol industry actors were supportive of MUP indicating divisions among the industry. Discourse network analysis may be usefully applied to study other highly contested policy issues in health and beyond.
Project description:Postoperative hyperglycemia is common in critically ill patients, even in those without a prior history of diabetes mellitus. It is well known that hyperglycemia induced by surgical stress often results in dysregulation of liver metabolism and immune function, impairing postoperative recovery. Current evidence suggests that maintaining normoglycemia postoperatively improves surgical outcome and reduces the mortality and morbidity of critically ill patients. On the basis of these observations, several large randomized controlled studies were designed to evaluate the benefit of postoperative tight glycemic control with intensive insulin therapy. However, intensive insulin therapy carries the risk of hypoglycemia, which is linked to serious neurological events. Recently, we demonstrated that perioperative tight glycemic control in surgical patients could be achieved safely using a closed-loop glycemic control system and that this decreased both the incidence of infection at the site of the surgical incision, without the appearance of hypoglycemia, and actual hospital costs. Here, we review the benefits and requirements of perioperative intensive insulin therapy using a closed-loop artificial endocrine pancreas system in hepatectomized patients. This novel intensive insulin therapy is safe and effectively improves surgical outcome after hepatic resection.
Project description:The safety of arterial hyperoxia is under increasing scrutiny. We performed a systematic review of the literature to determine whether any association exists between arterial hyperoxia and mortality in critically ill patient subsets.Medline, Thomson Reuters Web of Science and Scopus databases were searched from inception to June 2014. Observational or interventional studies evaluating the relationship between hyperoxia (defined as a supranormal arterial O2 tension) and mortality in adult intensive care unit (ICU) patients were included. Studies primarily involving patients with exacerbations of chronic pulmonary disease, acute lung injury and perioperative administration were excluded. Adjusted odds ratio (OR) of patients exposed versus those not exposed to hyperoxia were extracted, if available. Alternatively, unadjusted outcome data were recorded. Data on patients, study characteristics and the criteria used for defining hyperoxia exposure were also extracted. Random-effects models were used for quantitative synthesis of the data, with a primary outcome of hospital mortality.In total 17 studies (16 observational, 1 prospective before-after) were identified in different patient categories: mechanically ventilated ICU (number of studies (k) = 4, number of participants (n) = 189,143), post-cardiac arrest (k = 6, n = 19,144), stroke (k = 2, n = 5,537), and traumatic brain injury (k = 5, n = 7,488). Different criteria were used to define hyperoxia in terms of PaO2 value (first, highest, worst, mean), time of assessment and predetermined cutoffs. Data from studies on ICU patients were not pooled because of extreme heterogeneity (inconsistency (I(2)) 96.73%). Hyperoxia was associated with increased mortality in post-cardiac arrest patients (OR = 1.42 (1.04 to 1.92) I(2) 67.73%) stroke (OR = 1.23 (1.06 to 1.43) I(2) 0%) and traumatic brain injury (OR = 1.41 (1.03 to 1.94) I(2) 64.54%). However, these results are limited by significant heterogeneity between studies.Hyperoxia may be associated with increased mortality in patients with stroke, traumatic brain injury and those resuscitated from cardiac arrest. However, these results are limited by the high heterogeneity of the included studies.
Project description:OBJECTIVE:To address the significant uncertainty as to whether transfusion thresholds for critical care versus surgical patients should differ. DESIGN:Meta-analysis of randomized controlled trials. SETTING:Medline, EMBASE, and Cochrane Library searches were performed up to 15 June 2016. PATIENTS:Trials had to enroll adult surgical or critically ill patients for inclusion. INTERVENTIONS:Studies had to compare a liberal versus restrictive threshold for the transfusion of allogeneic packed RBCs. MEASUREMENTS AND MAIN RESULTS:The primary outcome was 30-day all-cause mortality, sub-grouped by surgical and critical care patients. Secondary outcomes included myocardial infarction, stroke, renal failure, allogeneic blood exposure, and length of stay. Odds ratios and weighted mean differences were calculated using random effects meta-analysis. To assess whether subgroups were significantly different, tests for subgroup interaction were used. Subgroup analysis by trials enrolling critically ill versus surgical patients was performed. Twenty-seven randomized controlled trials (10,797 patients) were included. In critical care patients, restrictive transfusion resulted in significantly reduced 30-day mortality compared with liberal transfusion (odds ratio, 0.82; 95% CI, 0.70-0.97). In surgical patients, a restrictive transfusion strategy led to the opposite direction of effect for mortality (odds ratio, 1.31; 95% CI, 0.94-1.82). The subgroup interaction test was significant (p = 0.04), suggesting that the effect of restrictive transfusion on mortality is statistically different for critical care (decreased risk) versus surgical patients (potentially increased risk or no difference). Regarding secondary outcomes, for critically ill patients, a restrictive strategy resulted in reduced risk of stroke/transient ischemic attack, packed RBC exposure, transfusion reactions, and hospital length of stay. In surgical patients, restrictive transfusion resulted in reduced packed RBC exposure. CONCLUSIONS:The safety of restrictive transfusion strategies likely differs for critically ill patients versus perioperative patients. Further trials investigating transfusion strategies in the perioperative setting are necessary.
Project description:BACKGROUND:Studies investigating the role of hyperoxia in critically ill patients have reported conflicting results. We did this analysis to reveal the effect of hyperoxia in the patients admitted to the intensive care unit (ICU). METHODS:Electronic databases were searched for all the studies exploring the role of hyperoxia in adult patients admitted to ICU. The primary outcome was mortality. Random-effect model was used for quantitative synthesis of the adjusted odds ratio (aOR). RESULTS:We identified 24 trials in our final analysis. Statistical heterogeneity was found between hyperoxia and normoxia groups in patients with mechanical ventilation (I2 = 92%, P < 0.01), cardiac arrest(I2 = 63%, P = 0.01), traumatic brain injury (I2 = 85%, P < 0.01) and post cardiac surgery (I2 = 80%, P = 0.03). Compared with normoxia, hyperoxia was associated with higher mortality in overall patients (OR 1.22, 95% CI 1.12~1.33), as well as in the subgroups of cardiac arrest (OR 1.30, 95% CI 1.08~1.57) and extracorporeal life support (ELS) (OR 1.44, 95% CI 1.03~2.02). CONCLUSIONS:Hyperoxia would lead to higher mortality in critically ill patients especially in the patients with cardiac arrest and ELS.
Project description:Perioperative factors promoting cancer recurrence and metastasis are under scrutiny. While oxygen toxicity is documented in several acute circumstances, its implication in tumor evolution is poorly understood. We investigated hyperoxia long-term effects on cancer progression and some underlying mechanisms using both in vitro and in vivo models of triple negative breast cancer (TNBC). We hypothesized that high oxygen exposure, even of short duration, may have long-term effects on cancer growth. Considering that hyperoxic exposure results in reactive oxygen species (ROS) formation, increased oxidative stress and increased Brain-Derived Neurotrophic Factor (BDNF) expression, BDNF may mediate hyperoxia effects offering cancer cells a survival advantage by increased angiogenesis and epithelial mesenchymal transition (EMT). Human breast epithelial MCF10A, human MDA-MB-231 and murine 4T1 TNBC were investigated in 2D in vitro system. Cells were exposed to normoxia or hyperoxia (40%, 60%, 80% O2) for 6 h. We evaluated ROS levels, cell viability and the expression of BDNF, HIF-1?, VEGF-R2, Vimentin and E-Cadherin by immunofluorescence. The in vivo model consisted of 4T1 inoculation in Balb/c mice and tumor resection 2 weeks after and 6 h exposure to normoxia or hyperoxia (40%, 80% O2). We measured lung metastases and the same molecular markers, immediately and 4 weeks after surgery. The in vitro study showed that short-term hyperoxia exposure (80% O2) of TNBC cells increases ROS, increases BDNF expression and that promotes EMT and angiogenesis. The in vivo data indicates that perioperative hyperoxia enhances metastatic disease and this effect could be BDNF mediated.
Project description:The normobaric oxygen paradox states that a short exposure to normobaric hyperoxia followed by rapid return to normoxia creates a condition of 'relative hypoxia' which stimulates erythropoietin (EPO) production. Alterations in glutathione and reactive oxygen species (ROS) may be involved in this process. We tested the effects of short-term hyperoxia on EPO levels and the microcirculation in critically ill patients.In this prospective, observational study, 20 hemodynamically stable, mechanically ventilated patients with inspired oxygen concentration (FiO2) ?0.5 and PaO2/FiO2???200 mmHg underwent a 2-hour exposure to hyperoxia (FiO2 1.0). A further 20 patients acted as controls. Serum EPO was measured at baseline, 24 h and 48 h. Serum glutathione (antioxidant) and ROS levels were assessed at baseline (t0), after 2 h of hyperoxia (t1) and 2 h after returning to their baseline FiO2 (t2). The microvascular response to hyperoxia was assessed using sublingual sidestream dark field videomicroscopy and thenar near-infrared spectroscopy with a vascular occlusion test.EPO increased within 48 h in patients exposed to hyperoxia from 16.1 [7.4-20.2] to 22.9 [14.1-37.2] IU/L (p?=?0.022). Serum ROS transiently increased at t1, and glutathione increased at t2. Early reductions in microvascular density and perfusion were seen during hyperoxia (perfused small vessel density: 85% [95% confidence interval 79-90] of baseline). The response after 2 h of hyperoxia exposure was heterogeneous. Microvascular perfusion/density normalized upon returning to baseline FiO2.A two-hour exposure to hyperoxia in critically ill patients was associated with a slight increase in EPO levels within 48 h. Adequately controlled studies are needed to confirm the effect of short-term hyperoxia on erythropoiesis.ClinicalTrials.gov ( www.clinicaltrials.gov ), NCT02481843 , registered 15th June 2015, retrospectively registered.