Effects of intraoperative PEEP optimization on postoperative pulmonary complications and the inflammatory response: study protocol for a randomized controlled trial.

BACKGROUND: Patients undergoing general anesthesia and mechanical ventilation during major abdominal surgery commonly develop pulmonary atelectasis and/or hyperdistention of the lungs. Recent studies show benefits of lung-protective mechanical ventilation with the use of low tidal volumes, a moderate level of positive end-expiratory pressure (PEEP) and regular alveolar recruitment maneuvers during general anesthesia, even in patients with healthy lungs. The purpose of this clinical trial is to evaluate the effects of intraoperative lung-protective mechanical ventilation, using individualized PEEP values, on postoperative pulmonary complications and the inflammatory response. METHODS/DESIGN: A total number of 40 patients with bladder cancer undergoing open radical cystectomy and urinary diversion (ileal conduit or orthotopic bladder substitute) will be enrolled and randomized into a study (SG) and a control group (CG). Standard lung-protective ventilation with a PEEP of 6 cmH2O will be applied in the CG and an optimal PEEP value determined during a static pulmonary compliance (Cstat)-directed PEEP titration procedure will be used in the SG. Low tidal volumes (6 mL/Kg ideal bodyweight) and a fraction of inspired oxygen of 0.5 will be applied in both groups. After surgery both groups will receive standard postoperative management. Primary endpoints are postoperative pulmonary complications and serum procalcitonin kinetics during and after surgery until the third postoperative day. Secondary and tertiary endpoints will be: organ dysfunction as monitored by the Sequential Organ Failure Assessment Score, in-hospital stay, 28-day and in-hospital mortality. DISCUSSION: This trial will assess the possible benefits or disadvantages of an individualized lung-protective mechanical ventilation strategy during open radical cystectomy and urinary diversion regarding postoperative pulmonary complications and the inflammatory response. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02931409 . Registered on 5 October 2016.

Sevoflurane therapy for life-threatening acute severe asthma: a case report.

INTRODUCTION: Acute severe asthma is a life-threatening form of bronchial constriction in which the progressively worsening airway obstruction is unresponsive to the usual appropriate bronchodilator therapy. Pathophysiological changes restrict airflow, which leads to premature closure of the airway on expiration, impaired gas exchange, and dynamic hyperinflation ("air-trapping"). Additionally, patients suffering from asthma for a prolonged period of time usually have serious comorbidities. These conditions constitute a challenge during the treatment of this disease. Therapeutic interventions are designed to reduce airway resistance and improve respiratory status. To achieve therapeutic goals, appropriate bronchodilator treatment is indispensable, and mechanical ventilation under adequate sedation may also be required. The volatile anesthetic agent, sevoflurane, meets both criteria; therefore, its use can be beneficial and should be considered. CASE PRESENTATION: A 67-yr-old Caucasian male presented with acute life-threatening asthma provoked by an assumed upper airway infection and non-steroidal anti-inflammatory drug antipyretics, complicated by chronic atrial fibrillation and hemodynamic instability. Due to frequent premature ventricular contractions, conventional treatment was considered unsafe and discontinued, and sevoflurane inhalation was initiated via the AnaConDa (Anaesthetic Conserving Device). Symptoms of life-threatening bronchospasm resolved, and the patient's respiratory status improved within hours. Adequate sedation was also achieved without any hemodynamic adverse effects. CONCLUSION: The volatile anesthetic agent, sevoflurane, is used widely in anesthesia practice. Its utility for treatment of refractory bronchospasm has been appreciated for years; however, its administration was difficult within the environment of the intensive care unit due to the need for an anesthesia machine and a scavenging system. The introduction of the AnaConDa eliminates these obstacles and makes the use of sevoflurane safe and simple. Our case report reveals the potential of sevoflurane as a "two-in-one" (bronchodilator and sedative) drug to treat a severe acute asthma attack.

Factor analysis of risk variables associated with low-grade inflammation.

BACKGROUND: Chronic subclinical inflammation, manifesting as elevated levels of inflammatory markers such as C-reactive protein (CRP), predicts future atherothrombotic events. The pathophysiology of low-grade inflammation is complex, and multiple intercorrelated conditions have been associated with elevated CRP. METHODS: Principal factor analysis was used to investigate clustering of variables associated with elevated CRP using data from 1435 subjects without known coronary disease. Components of the metabolic syndrome, uric acid, liver enzymes, pulmonary function tests, smoking status, cardiorespiratory fitness (measured by maximal treadmill test), and high-sensitivity C-reactive protein were determined in each subject. RESULTS: Factor analysis identified three factors, which explained 51.0% of the total variance in the dataset (24.4% factor 1, 17.3% factor 2, and 9.3% factor 3). Based on factor loadings of >or=0.5, these factors were interpreted as (1) "metabolic factor" including BMI, fasting glucose, HDL cholesterol, triglycerides, systolic blood pressure, and uric acid; (2) a cardiorespiratory factor that included fitness level, forced expiratory volume in 1s and sex; and (3) "smoking" factor that included cigarette smoking and age. Each of these factors was significantly associated with the presence of high-risk CRP (>or=3mg/L) in the study population. The ability of a multivariate model that included these three factors to predict high-risk CRP was comparable to a model containing the original 10 variables (area under the receiver-operator characteristics curve 0.7 vs. 0.72, respectively). CONCLUSION: Metabolic perturbations, cardiorespiratory fitness, and smoking are separate and largely independent factors in the pathophysiology of chronic, low-grade inflammation.

Inverse association between pulmonary function and C-reactive protein in apparently healthy subjects.

RATIONALE: Increased levels of systemic markers of inflammation have been reported in patients with impaired lung function due to obstructive or restrictive lung disease. OBJECTIVE: We tested the hypothesis that a decline in lung function within the normal range may be associated with a systemic subclinical inflammation. METHODS: Pulmonary function tests, cardiorespiratory fitness, components of the metabolic syndrome, and high-sensitivity C-reactive protein (CRP) were determined in 1,131 subjects without known pulmonary disease. MEASUREMENTS AND MAIN RESULTS: Ninety-six of the study participants (8.5%) had FEV(1) of less than 80% of predicted values. There was a strong inverse association between CRP levels and quartiles of FEV(1). The median CRP levels in nonsmoking participants were 2.5, 1.8, 1.7, and 1.3 mg/L in the first, second, third, and forth FEV(1) quartiles, respectively (p < 0.0001). A similar inverse association was present in smoking subjects (median CRP levels were 3.8, 2.3, 2.0, and 1.9 mg/L in the first, second, third, and fourth FEV(1) quartiles, respectively; p < 0.0001). These associations remained highly significant after adjustment for age, sex, components of the metabolic syndrome, and fitness level (p = 0.0005). CONCLUSIONS: An inverse linear relationship exists between CRP concentrations and measures of pulmonary function in subjects without pulmonary disease and in never-smokers. These results indicate that systemic inflammation may be linked to early perturbations of pulmonary function.

Association between elevated liver enzymes and C-reactive protein: possible hepatic contribution to systemic inflammation in the metabolic syndrome.

OBJECTIVE: The objective of this study was to test whether the frequent association between liver enzyme elevations and various components of the metabolic syndrome is associated with higher C-reactive protein (CRP) levels. METHODS AND RESULTS: Alanine aminotransferase (ALT), alkaline phosphatase (Alk-P), and high-sensitivity CRP were measured in 1740 subjects. Adjusted geometric mean CRP was calculated for subjects with normal and elevated ALT and for subjects with normal and elevated Alk-P, adjusting for age, sex, smoking, physical activity, body mass index, fasting glucose, triglycerides, the presence of hypertension and low HDL cholesterol, and use of aspirin or hormone replacement therapy. Adjusted CRP levels were higher in subjects with elevated ALT (2.21 versus 1.94 mg/L, P=0.028) or elevated Alk-P (2.58 versus 1.66 mg/L, P<0.0001). Logistic regression showed that compared with subjects with normal liver function tests, the adjusted odds for high-risk CRP (>3 mg/L) were significantly higher in subjects with elevated ALT (OR, 1.5; 95% CI, 1.2 to 1.9, P=0.002) or elevated Alk-P (OR, 2.1; 95% CI, 1.7 to 2.6, P<0.0001). CONCLUSIONS: Elevations of liver enzymes are associated with higher CRP concentrations. Hepatic inflammation secondary to liver steatosis is a potential contributor to the low-grade inflammation associated with the metabolic syndrome.

[Fatal pancytopenia and methotrexate-trimethoprim-sulfamethoxazole interaction].

Low dose methotrexate [MTX] is now frequently used for various inflammatory diseases. This is a case study of a fatal outcome in a patient with rheumatoid arthritis [RA] treated for a short period with low dose MTX. The patient developed severe pancytopenia followed by bacterial and monilial sepsis upon the co-administration of trimethoprim-sulphamethoxazole [TMP-SMX] for an intercurrent infection. The differential diagnosis of pancytopenia and the mechanisms underlying the increase in plasma free MTX by MTX-SMX in the patient are discussed. It should be noted that this fatal case highlights the risk of severe drug interactions in patients with multiple risk factors treated with low dose MTX for a short period of time.

The association between cardiorespiratory fitness and C-reactive protein in subjects with the metabolic syndrome.

OBJECTIVES: We sought to study relationship between cardiorespiratory fitness and C-reactive protein (CRP) in subjects with the metabolic syndrome. BACKGROUND: Recent studies have shown an association between the metabolic syndrome and chronic subclinical inflammation, as determined by elevated CRP. Cardiorespiratory fitness is associated with a lower risk of diabetes and improved insulin resistance. METHODS: Physical fitness was assessed in 1,640 subjects using the Bruce treadmill protocol and expressed as maximal metabolic equivalents. The level of CRP was measured using a high-sensitivity assay. RESULTS: Geometric mean CRP was calculated across quartiles of fitness after adjustment for age, gender, smoking, use of medications, and coronary disease. A strong inverse trend toward decreasing CRP levels with increasing fitness quartiles was present in subjects without metabolic abnormalities, subjects with one or two metabolic abnormalities, and subjects with the metabolic syndrome (all p

C-Reactive protein is inversely related to physical fitness in middle-aged subjects.

INTRODUCTION: Physical fitness has a protective effect with regard to the risk of developing coronary disease or diabetes. C-reactive protein (CRP) levels are directly related to increased risk of coronary disease and diabetes. However, data on the association between physical fitness and CRP are sparse. METHODS: Physical fitness was assessed in a population-based cross-sectional study (n = 892; age 50 +/- 9 years) using the Bruce treadmill protocol. CRP was measured using a high-sensitivity assay. RESULTS: Geometric mean CRP levels were calculated across quartiles of physical fitness after adjustment for age, gender, body mass index, smoking habit, presence of diabetes and hypertension, HDL cholesterol and triglyceride levels, and use of hormone replacement therapy, statins, and aspirin. CRP levels decreased with increasing quartiles of fitness (P for trend <0.0001). When used as a continuous variable in a stepwise linear regression model, the geometric mean of CRP decreased by 0.061 mg/L (95% confidence interval (CI) 0.034-0.089 mg/L) for each 1 unit increase in metabolic equivalents (METs). Multivariate logistic regression models showed that compared to subjects in the lowest fitness quintile, subjects in the highest fitness quintile had significantly lower adjusted odds of having a high-risk (>3 mg/L) CRP level (OR 0.53; 95% CI 0.39-0.71, P = 0.007). CONCLUSION: CRP concentration decreases continuously with increasing levels of physical fitness. The health-related salutary effects of physical fitness may be mediated, in part, through an antiinflammatory mechanism.