Oxytocin maintains lung histological and functional integrity to confer protection in heat stroke.

Oxytocin (OT) has been reported to have a protective effect in lipopolysaccharide-induced experimental acute lung injury (ALI). However, its role in heat stroke-related ALI has never been investigated. Herein, we aimed to explore the therapeutic effects and potential mechanism of action of OT on heat-induced ALI. Rats were treated with OT 60 min before the start of heat stress (42 °C for 80 min). Twenty minutes after the termination of heat stress, the effects of OT on lung histopathological changes, edema, acute pleurisy and the bronchoalveolar fluid levels of inflammatory cytokines and indicators of ischemia, cellular damage, and oxidative damage were assessed. We also evaluated the influence of OT pretreatment on heat-induced hypotension, hyperthermia, ALI score, and death in a rat model of heat stroke. The results showed that OT significantly reduced heat-induced lung edema, neutrophil infiltration, hemorrhage score, myeloperoxidase activity, ischemia, and the levels of inflammatory and oxidative damage markers in bronchoalveolar lavage fluid. The survival assessment confirmed the pathophysiological and biochemical results. An OT receptor antagonist (L-368,899) was administered 10 min before the OT injection to further demonstrate the role of OT in heat-induced ALI. The results showed that OT could not protect against the aforementioned heat stroke responses in rats treated with L-368,899. Interestingly, OT treatment 80 min after the start of heat shock did not affect survival. In conclusion, our data indicate that OT pretreatment can reduce the ischemic, inflammatory and oxidative responses related to heat-induced ALI in rats.

Calycosin-7-O-ß-D-glucoside reduces myocardial injury in heat stroke rats.

BACKGROUND/PURPOSE: Calycosin-7-O-ß-D-glucoside (CG), a calycosin derivative compound derived from Astragali Radix, has protective effect against ischemia/reperfusion injury as well as bacterial endotoxin-induced vascular cell injury. In the present study, we ascertained whether CG could reduce myocardial injury in heatstroke rats. METHODS: Heat stroke was induced by exposing anaesthetized rats to heat stress (43 °C for 70 min). Rats were given an i.p. dose of CG (26.8 mg/ml/kg) or vehicle solution (ml/kg) 15 min before the start of heat stress and immediately after termination of heat stress. Left ventricular performance, myocardial injury markers in the blood, and myocardial damage scores were assessed in heat stroke rats treated with or without CG. Additionally, cardiac levels of oxidative stress and inflammatory status were estimated simultaneously. RESULTS: At the time point of heat stroke onset, compared with normothermic controls, group rats with vehicle solution had significantly decreased survival rate, increased hyperthermia, decreased left ventricular stress markers, and increased cardiac damage scores. Compared with group rats with vehicle solution, group rats with CG had significantly improved survival rate, decreased hyperthermia, decreased cardiac ischemic, inflammatory, and oxidative damage. CONCLUSION: We thus conclude that myocardial injury can be a pressing need for the design of diagnostic and therapeutic modalities for heat stroke. In particular, our data indicate that CG protects against heat stroke in rats by mitigating myocardial injury.

Severe exacerbation and pneumonia in COPD patients treated with fixed combinations of inhaled corticosteroid and long-acting beta2 agonist.

BACKGROUND: It remains unclear whether severe exacerbation and pneumonia of COPD differs between patients treated with budesonide/formoterol and those treated with fluticasone/salmeterol. Therefore, we conducted a comparative study of those who used budesonide/formoterol and those treated with fluticasone/salmeterol for COPD. METHODS: Subjects in this population-based cohort study comprised patients with COPD who were treated with a fixed combination of budesonide/formoterol or fluticasone/salmeterol. All patients were recruited from the Taiwan National Health Insurance database. The outcomes including severe exacerbations, pneumonia, and pneumonia requiring mechanical ventilation (MV) were measured. RESULTS: During the study period, 11,519 COPD patients receiving fluticasone/salmeterol and 7,437 patients receiving budesonide/formoterol were enrolled in the study. Pairwise matching (1:1) of fluticasone/salmeterol and budesonide/formoterol populations resulted in to two similar subgroups comprising each 7,295 patients. Patients receiving fluticasone/salmeterol had higher annual rate and higher risk of severe exacerbation than patients receiving budesonide/formoterol (1.2219/year vs 1.1237/year, adjusted rate ratio, 1.08; 95% CI, 1.07-1.10). In addition, patients receiving fluticasone/salmeterol had higher incidence rate and higher risk of pneumonia than patients receiving budesonide/formoterol (12.11 per 100 person-years vs 10.65 per 100 person-years, adjusted hazard ratio [aHR], 1.13; 95% CI, 1.08-1.20). Finally, patients receiving fluticasone/salmeterol had higher incidence rate and higher risk of pneumonia requiring MV than patients receiving budesonide/formoterol (3.94 per 100 person-years vs 3.47 per 100 person-years, aHR, 1.14; 95% CI, 1.05-1.24). A similar trend was seen before and after propensity score matching analysis, intention-to-treat, and as-treated analysis with and without competing risk. CONCLUSIONS: Based on this retrospective observational study, long-term treatment with fixed combination budesonide/formoterol was associated with fewer severe exacerbations, pneumonia, and pneumonia requiring MV than fluticasone/salmeterol in COPD patients.

Risk of Recurrence After Surviving Severe Sepsis: A Matched Cohort Study.

OBJECTIVES: To examine the risk of recurrence in adults who survived first-episode severe sepsis for at least 3 months. DESIGN: A matched cohort study. SETTING: Inpatient claims data from Taiwan's National Health Insurance Research Database. SUBJECTS: We analyzed 10,818 adults who survived first-episode severe sepsis without recurrence for at least 3 months in 2000 (SS group; mean age, 62.7 yr; men, 54.7%) and a group of age/sex-matched (1:1) population controls who had no prior history of severe sepsis. All subjects were followed from the study entry to the occurrence of end-point, death, or until December 31, 2008, whichever date came first. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary end-point was severe sepsis that occurred after January 1, 2001 (the study entry). Relative risk of the end-point was assessed using competing risk regression model. During the follow-up period, severe sepsis and death occurred in 35.0% and 26.5% of SS group and in 4.3% and 18.6% of controls, respectively, representing a covariate-adjusted sub-hazard ratio of 8.89 (95% CI, 8.04-9.83) for the risk of recurrence. In stratified analysis by patient characteristics, the sub-hazard ratios ranged from 7.74 in rural area residents to 23.17 in young adults. In subgroup analysis by first-episode infection sites in SS group, the sub-hazard ratios ranged from 4.82 in intra-abdominal infection to 9.99 in urinary tract infection. CONCLUSIONS: Risk of recurrence after surviving severe sepsis is substantial regardless of patient characteristics or infection sites. Further research is necessary to find underlying mechanisms for the high risk of recurrence in these patients.

Attenuating heat-induced acute lung inflammation and injury by dextromethorphan in rats.

Dextromethorphan (DM) has been shown to protect against endotoxic shock in mice. Heatstroke resembles sepsis in many respects. The objective of this study was to examine the heat-induced acute lung inflammation and injury in rats with or without DM, and for comparison with those of the rats with MK-801 (an N-methyl-D-aspartate receptor antagonist), SA4503 (a sigma-1 receptor agonist), or fluoxetine (a serotonin reuptake inhibitor). Heatstroke was induced by exposing the anesthetized rats to heat stress (43°C for 68 min). At 68 minutes after start of heat stress, animals treated with vehicle medium, DM (10-30 mg/kg of body weight, intramuscular), MK-801 (1 mg/kg of body weight, intraperitoneal), SA4503 (1 mg/kg of body weight, intraperitoneal), or fluoxetine (5 mg/kg of body weight, intraperitoneal) were allowed to recover at room temperature (26°C). As compared with vehicle-treated heatstroke rats (25-31 min; n = 8), DM (30 mg/kg)-treated heatstroke rats and MK-801 (1 mg/kg)-treated heatstroke rats had significantly greater survival time (193-209 min [n = 7] and 121-133 min [n = 8], respectively). However, the survival times for the SA4503-treated heatstroke rats (28-34 min; n = 8) or the fluoxetine-treated heatstroke rats (20-26 min; n = 8) were not significantly different from the vehicle-treated heatstroke rats. DM treatment significantly: (1) reduced acute lung injury, including edema, neutrophils infiltration, and hemorrhage scores; (2) decreased acute pleurisy; and (3) decreased bronchoalveolar fluid levels of the proinflammatory cytokines, and ischemia and oxidative damage markers during heatstroke. Our results indicate that DM therapy may improve outcomes of heatstroke in rats by antagonizing the N-methyl-D-aspartate receptors.

Increased risks of acute organ dysfunction and mortality in intensive care unit patients with schizophrenia: a nationwide population-based study.

OBJECTIVE: To investigate the risks of acute organ dysfunction and death in intensive care unit (ICU) patients with schizophrenia. METHODS: Using a retrospective matched cohort design, we compared 203 schizophrenic patients to 2036 demographically matched (1:10) nonschizophrenic patients with first-time ICU admission between 2005 and 2007 using the claims data of a nationally representative cohort from the Taiwan National Health Insurance Research Database. Definitions of schizophrenia and associated diagnoses were based on the codes of the International Classification of Diseases, Ninth Revision, Clinical Modification. Analyses were performed using univariate and multivariate analyses. RESULTS: The median age of schizophrenic patients was 53 years; 61.1% were men. Schizophrenic patients were less likely to be hospitalized in a medical center and had fewer surgical conditions and principal cardiovascular diagnoses, but they had a higher prevalence of infection than nonschizophrenic patients. After controlling for the aforementioned baseline covariates, schizophrenic patients had a higher risk of acute organ dysfunction (adjusted odds ratio = 1.52, 95% confidence interval = 1.09-2.10). When individual organ systems were analyzed, they had a 47% higher risk of respiratory dysfunction, a 194% higher risk of renal dysfunction, and a 122% higher risk of neurological dysfunction than nonschizophrenic patients. Hospital mortality was also higher in schizophrenic patients than in nonschizophrenic patients (24.1% versus 14.4%, p < .001; adjusted odds ratio = 1.56, 95% confidence interval = 1.08-2.24). CONCLUSIONS: Among ICU patients, schizophrenic patients were sicker, having a higher risk of acute organ dysfunction and death.

Women receive more trials of noninvasive ventilation for acute respiratory failure than men: a nationwide population-based study.

INTRODUCTION: Previous studies in western countries have observed that women are less likely than men to receive intensive care and mechanical ventilation (MV). We aimed to investigate whether the gender difference also exists in Asian populations and in the provision of different types of MV including invasive (INV) and noninvasive ventilation (NIV). METHODS: We analyzed all adult hospital patients between 2005 and 2007 in the claims data from 1,000,000 randomly selected people in the Taiwan National Health Insurance Research Database. NIV-only was defined as patients receiving NIV as the only ventilator treatment during hospitalization. Gender difference was assessed using multivariable analyses with/without considering a hospital cluster effect by generalized estimating equations models. Subgroup analyses for gender difference in NIV use were performed using propensity score matching method. RESULTS: Of the 128,327 patients enrolled, 53.8% were men, 9.2% received intensive care and 5.2% used MV. After adjusting for potential confounders, women were less likely than men to receive intensive care (adjusted odds ratio [aOR] 0.77, 95% confidence interval [CI] 0.73-0.82) and MV (aOR 0.84, 95% CI 0.78-0.91). Among MV patients, 6.8% received NIV-only; the proportion of which was higher in women than in men (8.6% vs. 5.7%, P < 0.001). After controlling for confounders and a cluster effect, women remained more likely to receive NIV-only (aOR 1.61, 95% CI 1.32-1.96). Subgroup analyses showed that patients with underlying congestive heart failure (CHF) had the highest difference in the provision of NIV-only (female-to-male aOR 2.76, 95% CI 1.38-5.53). A hospital cluster effect on the gender difference in NIV use was found in patients with diseases other than chronic obstructive pulmonary disease and CHF. CONCLUSIONS: Gender differences existed not only in the provision but also in the types of MV. Further studies are needed to understand why gender differences occur.

Epidemiologic trend of severe sepsis in Taiwan from 1997 through 2006.

BACKGROUND: The epidemiologic data of severe sepsis are limited in developing countries. Among patients, the contribution of subsequent severe sepsis episodes to the disease burden is unclear. METHODS: We analyzed the hospitalization claims data of a nationally representative sample of 200,000 people, approximately 1% of the population, enrolled in the Taiwan National Health Insurance program. We identified first and subsequent episodes of severe sepsis hospital admissions from 1997 to 2006 based on International Classification of Diseases, 9th ed., Clinical Modification codes for infections and acute organ dysfunction. RESULTS: During the 10-year period, we identified 5,258 patients having 7,531 hospitalizations for severe sepsis in the study cohort. The age-standardized annual incidence rates of first episodes increased by 1.6-fold from 135 per 100,000 in 1997 to 217 per 100,000 in 2006, with an annual percent change of 3.9% (95% CI, 2.3%-5.5%). Although the proportion of patients with multiorgan (>or= 2) dysfunctions increased from 11.7% in 1997 to 27.6% in 2006, the hospital mortality changed little, averaging 30.8%. Among survivors, 34.4% developed at least one subsequent severe sepsis episode, which contributed 30.2% to the disease burden in 10 years. CONCLUSIONS: The incidence and disease severity of severe sepsis in Taiwan are increasing. One-third of the survivors developed at least one subsequent episode, which contributed substantially to the disease burden over time.

Attenuation of acute lung inflammation and injury by whole body cooling in a rat heatstroke model.

Whole body cooling is the current therapy of choice for heatstroke because the therapeutic agents are not available. In this study, we assessed the effects of whole body cooling on several indices of acute lung inflammation and injury which might occur during heatstroke. Anesthetized rats were randomized into the following groups and given (a) no treatment or (b) whole body cooling immediately after onset of heatstroke. As compared with the normothermic controls, the untreated heatstroke rats had higher levels of pleural exudates volume and polymorphonuclear cell numbers, lung myloperoxidase activity and inducible nitric oxide synthase expression, histologic lung injury score, and bronchoalveolar proinflammatory cytokines and glutamate, and PaCO2. In contrast, the values of mean arterial pressure, heart rate, PaO2, pH, and blood HCO3(-) were all significantly lower during heatstroke. The acute lung inflammation and injury and electrolyte imbalance that occurred during heatstroke were significantly reduced by whole body cooling. In conclusion, we identified heat-induced acute lung inflammation and injury and electrolyte imbalance could be ameliorated by whole body cooling.