Increased 90-Day Mortality in Spontaneously Breathing Patients With Paraquat Poisoning: In Addition to Disease Severity, Lung Strain May Play a Role.

OBJECTIVES: 1) To evaluate the prognostic roles of quantitative CT and pulmonary function tests and 2) to assess the association of dynamic strain and ventilation heterogeneity during unassisted spontaneous breathing with 90-day survival in patients with paraquat poisoning. DESIGN: Prospective study. SETTING: A university hospital ICU. PATIENTS: One-hundred spontaneously breathing patients with paraquat poisoning without mechanical ventilation. INTERVENTIONS: A standardized treatment protocol. MEASUREMENTS AND MAIN RESULTS: Blood samples were collected to measure the plasma paraquat concentration upon arrival. CT scans at suspended inspiration and pulmonary function tests were performed at day 5. The weight of the poorly aerated lung compartment as a percentage of total lung weight (%Wpoor) was exponentially transformed, generating a new variable, Exp(%Wpoor/15). The functional residual capacity that was determined by helium dilution was used to calculate the dynamic strain (tidal volume/functional residual capacity by helium dilution method). Respiratory system reactance at 5 Hz was used as a marker of ventilation heterogeneity. Exp(%Wpoor/15) (adjusted hazard ratio, 2.58; 95% CI, 2.021-3.296; p < 0.001) was most strongly associated with mortality, such that neither blood paraquat concentration nor PaO2 provided any additional prognostic information. The ratio of residual volume to total lung capacity as a percentage of the predicted value (adjusted hazard ratio, 1.041; 95% CI, 1.026-1.057; p < 0.001) was the only variable that added prognostic value to Exp(%Wpoor/15). While controlling for Exp(%Wpoor/15) and percentage of predicted residual volume/total lung capacity, increases in dynamic strain (adjusted hazard ratio, 2.041/0.1 U; 95% CI, 1.283-3.248; p = 0.003) and/or decreases in respiratory system reactance at 5 Hz (adjusted hazard ratio, 1.19/0.1 U; 95% CI, 1.03-1.386; p = 0.02) were independently associated with increased 90-day mortality. CONCLUSIONS: In patients with paraquat poisoning, Exp(%Wpoor/15) and percentage of residual volume/total lung capacity are independent prognostic indicators. Higher dynamic strain and increased ventilation heterogeneity during unassisted spontaneous breathing were associated with worsened survival independent of Exp(%Wpoor/15) and percentage of residual volume/total lung capacity.

Pulse Pressure Variation Adjusted by Respiratory Changes in Pleural Pressure, Rather Than by Tidal Volume, Reliably Predicts Fluid Responsiveness in Patients With Acute Respiratory Distress Syndrome.

OBJECTIVES: 1) To evaluate the ability of pulse pressure variation adjusted by respiratory changes in pleural pressure to predict fluid responsiveness compared with pulse pressure variation alone. 2) To identify factors explaining the poor performance of pulse pressure variation in acute respiratory distress syndrome. DESIGN: Prospective study. SETTING: Forty-bed university hospital general ICU. PATIENTS: Ninety-six mechanically ventilated acute respiratory distress syndrome patients requiring fluid challenge. INTERVENTIONS: Fluid challenge, 500 mL saline over 20 minutes. MEASUREMENTS AND MAIN RESULTS: Before fluid challenge, esophageal pressure was measured at the end-inspiratory and end-expiratory occlusions. Change in pleural pressure was calculated as the difference between esophageal pressure measured at end-inspiratory and end-expiratory occlusions. Hemodynamic measurements were obtained before and after the fluid challenge. Patients were ventilated with tidal volume 7.0 ± 0.8 mL/kg predicted body weight. The fluids increased cardiac output by greater than 15% in 52 patients (responders). Adjusting pulse pressure variation for changes in pleural pressure (area under the receiver operating characteristic curve, 0.94 [0.88-0.98]) and the ratio of chest wall elastance to total respiratory system elastance (area under the receiver operating characteristic curve, 0.93 [0.88-0.98]) predicted fluid responsiveness better than pulse pressure variation (area under the receiver operating characteristic curve, 0.78 [0.69-0.86]; all p < 0.01). The gray zone approach identified a range of pulse pressure variation/changes in pleural pressure values (1.94-2.1) in 3.1% of patients for whom fluid responsiveness could not be predicted reliably. On logistic regression analysis, two independent factors affected the correct classification of fluid responsiveness at a 12% pulse pressure variation cutoff: tidal volume (adjusted odds ratio 1.57/50 mL; 95% CI, 1.05-2.34; p = 0.027) and chest wall elastance/respiratory system elastance (adjusted odds ratio, 2.035/0.1 unit; 95% CI, 1.36-3.06; p = 0.001). In patients with chest wall elastance/respiratory system elastance above the median (0.28), pulse pressure variation area under the receiver operating characteristic curve was 0.94 (95% CI, 0.84-0.99) compared with 0.76 (95% CI, 0.61-0.87) otherwise (p = 0.02). CONCLUSIONS: In acute respiratory distress syndrome patients, pulse pressure variation adjusted by changes in pleural pressure is a reliable fluid responsiveness predictor despite the low tidal volume (< 8 mL/kg). The poor predictive ability of pulse pressure variation in acute respiratory distress syndrome patients is more related to low chest wall elastance/respiratory system elastance ratios than to a low tidal volume.

Salvianolic acid B protects against paraquat-induced pulmonary injury by mediating Nrf2/Nox4 redox balance and TGF-ß1/Smad3 signaling.

The present study was aimed at exploring the protective effects of Salvianolic acid B (SalB) against paraquat (PQ)-induced lung injury in mice. Lung fibrotic injuries were induced in mice by a single intragastrical administration of 300mg/kg PQ, then the mice were administrated with 200mg/kg, 400mg/kg SalB, 100mg/kg vitamin C (Vit C) and dexamethasone (DXM) for 14days. PQ-triggered structure distortion, collagen overproduction, excessive inflammatory infiltration, pro-inflammatory cytokine release, and oxidative stress damages in lung tissues and mortality of mice were attenuated by SalB in a dose-dependent manner. Furthermore, SalB was noted to enhance the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and reduce expression of the reactive oxygen species-generating enzyme Nox4 [NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase-4]. SalB also inhibited the increasing expression of transforming growth factor (TGF)-ß1 and the phosphorylation of its downstream target Smad3 which were enhanced by PQ. These results suggest that SalB may exert protective effects against PQ-induced lung injury and pulmonary fibrosis. Its mechanisms involve the mediation of Nrf2/Nox4 redox balance and TGF-ß1/Smad3 signaling.

Dynamic changes of mononuclear phagocytes in circulating, pulmonary alveolar and interstitial compartments in a mouse model of experimental silicosis.

CONTEXT: Silicosis is a devastating, irreversible lung fibrosis condition exposed to crystalline silica. The mononuclear phagocyte system plays an important role in the pathogenesis of silicosis. OBJECTIVE: The present study was aimed to explore the dynamic changes of mononuclear phagocytes in circulating, pulmonary alveolar and interstitial compartments in experimental silicosis model. MATERIALS AND METHODS: A mouse model of lung fibrosis was developed with crystalline silica particles (2 mg/40 µL via oropharyngeal instillation) using male C57BL/6 mice, and were killed on days 1, 3, 7, 14, and 28. The lung inflammation and fibrosis was investigated using hematoxylin-eosin staining and bronchoalveolar lavage fluid (BALF) analysis, Masson's trichrome staining, and immunofluorescence. Circulating monocyte subsets (Ly6C(hi) and Ly6C(lo)), polarization state of BALF-derived alveolar macrophages (AMϕ) and lung interstitial macrophages (IMϕ, derived from enzymatically digested lung tissue) were analyzed by flow cytometry. RESULTS: The percentage of Ly6C(hi) monocytes significantly increased on day 1 after silica exposure, which reached the peak level from day 7 till day 28. Moreover, M2 (alternative activation) AMϕ (PI - CD64 + CD206+) was dramatically and progressively increased from day 1 to day 28. A parallel increase in IMϕ with M2 polarization (PI-CD64 + CD11b + CD206+) was also observed from day 1 to day 28. CONCLUSION: Our data demonstrate a dynamic view of mononuclear phagocyte change in three compartments after silica challenge, which highlights the remodeling of mononuclear phagocyte system as a potential therapeutic target for silicosis.

Continuous plasma perfusion of dual cartridges in series: rationale and early clinical experience.

To improve the efficiency of plasma perfusion on eliminating plasma paraquat (PQ), we designed continuous plasma perfusion of dual cartridges in series (CPPDCS) on Diapact Braun CRRT machine. The goals of this study were to evaluate the effective of CPPDCS on paraquat removal in patients with acute paraquat intoxication. Our results show that the PQ clearance rate of dual cartridges was significantly higher than that of single cartridge at 1st, 2nd, 3rd, and 4th plasma perfusion. Compared with single-cartridge plasma perfusion, CPPDCS significantly reduced the frequency of cartridge replacement, shorten the time of perfusion. These results indicate that CPPDCS is effective than plasma perfusion of single cartridge on PQ clearance rate and may provide an effective treatment for PQ poisoning.

Clinical management of organophosphate poisoning in pregnancy.

BACKGROUND: Acute organophosphorus pesticide poisoning during pregnancy may lead to spontaneous abortion. Now, there is no definite strategy focused on maintaining pregnancy. METHOD: This is a retrospective analysis of 2 cases of organophosphorus poisoning during pregnancy. All patients received penehyclidine hydrochloride injection,until the tracheobronchial tree is cleared of the secretions, and most secretions were dried. In addition, magnesium sulfate was used in one woman for the correction of hyperdynamic uterine activity. RESULTS: Two women all survived, one fetus died of spontaneous abortion, and one fetus died of incoordinate uterine action. The 2 women had no significant complications during postpartum period. CONCLUSION: Penehyclidine hydrochloride and magnesium sulfate may be used to treat organophosphorus during pregnancy. However, futher study and new experimental need to be designed.

Analysis of cerebrospinal fluid flow dynamics and morphology in Chiari I malformation with cine phase-contrast magnetic resonance imaging.

BACKGROUND: To determine cerebrospinal fluid (CSF) dynamics and morphology in Chiari I malformation (CMI) and assess the response to surgery of the posterior cranial fossa, we examined midsagittal imaging along with anterior cervical 2-3 (AC2-3), posterior cervical 2-3 (PC2-3), and aqueduct CSF flow hydrodynamics in axial imaging by using cine phase-contrast magnetic resonance imaging (PCMR). METHOD: We examined 52 patients with CMI, both with and without syringomyelia (SM), pre-/post-surgery, and compared them to 17 healthy volunteers. Statistical analyses included paired t-tests, independent-samples t-tests, binary logistic regression, and crosstab with MedCalc software. RESULTS: Patients with CMI had significantly shorter clivus length and larger tentorial angle than the healthy controls (P = 0.004, P = 0.019, respectively). The AC2-3 cranial/caudal peak velocity (PV), PC2-3 cranial/caudal PV and aqueduct cranial peak PV of patients with CMI were significantly lower than healthy volunteers pre-surgery (P = 0.034 AC2-3 cranial PV, P = 0.000002 AC2-3 caudal PV; P = 0.046 PC2-3 cranial PV, P = 0.015 PC2-3 caudal PV; P = 0.022 aqueduct cranial PV) and increased after surgery (P = 0.024 AC2-3 cranial PV, P = 0.002 AC2-3 caudal PV; P = 0.001 PC2-3 cranial PV, P = 0.032 PC2-3 caudal PV; P = 0.003 aqueduct cranial PV). The aqueduct caudal PV of patients with CMI was higher than that of healthy controls (P = 0.004) and decreased post-surgery (P = 0.012). Patients with pre-surgery PC2-3 cranial PV >2.63 cm/s and aqueduct cranial PV >2.13 cm/s, respectively, experienced primary symptom improvement after surgery. CONCLUSIONS: The innate bony dysontogenesis in patients with CMI contributes to tonsilar ectopia and exacerbates CSF flow obstruction. A pressure gradient that existed between SM and SAS supports the perivascular space theory that is used to explain SM formation. Our findings demonstrate that PCMR maybe a useful tool for predicting patient prognosis.

[The correlation of helper T lymphocyte 1/helper T lymphocyte 2 with clinical and image features in patients with idiopathic pulmonary fibrosis].

OBJECTIVE: To identify whether the helper T lymphocyte 1 (Th1)/helper T lymphocyte 2 (Th2) of patients' serum and bronchoalveolar lavage fluid (BALF) at admission could represent the severity of idiopathic pulmonary fibrosis (IPF) and whether its change at six months could predict the progression of the disease. METHODS: Eighty-three patients with IPF were subjected to pulmonary function tests (PFTs), dyspnea scores, arterial blood gas analysis, six-minute walk test (6MWT) and high-resolution computed tomography (HRCT). The serum and BALF specimen of these patients were obtained as well as 20 control serum and 10 control BALF specimen. A total of 55 patients were followed up, and their BALF and serum levels of interferon γ(IFNγ) and IL-4 were detected by enzyme-linked immunoadsorbent assay (ELISA). The correlation between the IFNγ/IL-4 levels (at admission and the change of that at six months follow-up) and the clinical, physiological and image features in the IPF patients were analyzed. RESULTS: The baseline serum and BALF level of IFNγ/IL-4 (0.8 ± 0.3) in the IPF patients was lower than that in the control group (1.4 ± 0.2), which showed significant correlation with the course of disease, dyspnea scores, FEV1%, FVC%, TLC%, maximum desaturation, 6MWD and CT-fib (all P values<0.05). The serum level of IFNγ/IL-4 showed positive correlation with CT-alv (r = 0.340, P<0.01). During follow-up, no statistic difference was found in the serum levels of IFNγ, IL-4 and IFNγ/IL-4 between the IPF patients with or without glucocorticoids treatment. There were significant aggravation in the dyspnea scores, FEV1%, FVC%, CT-alv, CT-fib, IFNγ and IL-4 at six months follow-up. Significant correlation had been showed between the change of the serum IFNγ/IL-4 level with the changes of the dyspnea scores, FVC%, TLC%, DLCO%, 6MWD and CT-fib in the IPF patients (P < 0.05). CONCLUSIONS: There are disequilibrium of the Th1/Th2 in the serum and the BALF of the IPF patients. The Th1/Th2 level could represent severity of the disease, and the serum level change of Th1/Th2 in the follow-up could predict the progression of the diseases in the IPF patients.

[Screening of potential proteins from patients with idiopathic pulmonary fibrosis by using of surface enhanced laser desorption/ionization time of flight mass spectrum].

OBJECTIVE: To screen potential proteins in bronchoalveolar lavage fluid (BALF) and serum samples obtained from patients with idiopathic pulmonary fibrosis (IPF), for the purpose of discovering candidate biomarkers. METHODS: BALF and serum samples from 34 patients diagnosed IPF (IPF group) and 25 non-smoker healthy controls (control group) were collected. Surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) was used to obtain protein fingerprints from BALF and serum samples. Biomarker Wizard and Biomarker Pattern were introduced in bioinformatics analysis. RESULTS: A total of 247 protein peaks were detected in BALF, and 13 peaks with statistical difference compared with control group. Among 13 detected protein peaks, 7 with mass/charge ratio (M/Z) values of 2240.57, 3459.32, 3501.78, 4146.50, 4516.51, 4615.88, 5651.26 were statistically up-regulated (all P < 0.01); and 6 peaks with M/Z values of 4989.91, 5043.68, 6968.76, 11 687.70, 11 782.10, 14 733.30 were significantly down-regulated (all P < 0.01). In addition, 142 protein peaks were differentially expressed in serum samples, and 9 peaks with statistical differences. Among them, 9 peaks with M/Z values of 3382.59, 3453.39, 4608.28, 5825.48, 8936.76, 9164.27, 11 525.30, 11 689.40 and 11 886.00 were significantly up-regulated (P < 0.05 or P < 0.01), compared with control group. CONCLUSIONS: The present work demonstrated that SELDI-TOF-MS technology be capable of detecting differentially expressed protein peaks in BALF and serum samples from IPF patients. Further investigations were guaranteed to elucidate their potential diagnostic value in clinical practice.

[Effect of atorvastatin on MMP-9 and TIMP-1 levels in bronchoalveolar lavage fluid and serum of rats with bleomycin-induced pulmonary fibrosis].

OBJECTIVE: To investigate the effects of atorvastatin on matrix metalloproteinase-9 (MMP-9) and the tissue inhibitor-1 of matrix metalloproteinase (TIMP-1) levels in bronchoalveolar lavage fluid (BALF) and serum of rats with experimental pulmonary fibrosis. METHODS: Pulmonary fibrosis was induced by intratracheal administration of bleomycin in 30 female rats, which were further divided into two groups: Group M (without treatment) and Group A (treated with atorvastatin 10 mg/kg); control group (n = 5, Group C) was intratracheally administrated with same volume of saline. Five animals were sacrificed at 2 weeks (M2 and A2), 4 weeks (M4 and A4) and 6 weeks (M6 and A6) after model establishment, respectively. Lung tissue samples were harvested and prepared for HE and Masson's trichrome staining. Concentrations of MMP-9 and TIMP-1 in BALF and serum were measured by ELISA. RESULT: The severity of inflammation and pulmonary fibrosis was significantly reduced in Group A than that in Group M, especially at week 6. No significant difference was noted in the serum concentrations of MMP-9 and TIMP-1 among the Group M, A and Group C. The BALF concentrations of MMP-9 in Group M2 and M6 were significantly higher than those in Group C (P < 0.01 and 0.05), whereas those in the atorvastatin groups (A2, A4 and A6) were lower than those in M2, M4 and M6. Although the MMP-9 was still higher in Groups A2 and A4 than in the Group C, there was no significant difference in MMP-9 between Group A6 and Group C. TIMP-1 levels in BALF were significantly higher in M4 and M6 than Group C (P < 0.01 and 0.05), there were no significant differences between Group M2 and Group C. The TIMP-1 levels in BALF of atorvastatin groups were significantly lower than those of model groups and control group (P < 0.01 and 0.05), which resulted in a significantly increased ratio of MMP-9 to TIMP-1 in the atorvastatin groups. CONCLUSION: Atorvastatin inhibits the synthesis and release of MMP-9 and TIMP-1 in the lung tissue of rats with bleomycin-induced pulmonary fibrosis, and has no significant effect on circulating MMP-9 and TIMP-1, which may be associated with the attenuation of experimental pulmonary fibrosis in rats.

[Paraquat (PQ) clearance through continuous plasma perfusion in PQ poisoning patients: a clinical study].

OBJECTIVE: To examine the impact of continuous plasma perfusion on plasma PQ concentration (PPQ) in acute PQ-poisoning patients for the estimation of its PQ clearance effect. METHODS: 21 PQ-poisoned patients admitted to our poisoning center within 24 hours after the ingestion were prospectively enrolled. Continuous plasma perfusion (flow rate 180 ml/min) was performed, with plasma/blood separation at 40 ml/min and routine cartridges change every 3 hours. Urinary PQ (UPQ), urine flow rate (UFR), and PPQ level at inlet/outlet of the cartridge were obtained right before, and 1.5 hours after the start of each perfusion session for calculation of renal and plasma PQ excretion. RESULTS: In all 8 rounds (108 sessions) of plasma perfusion on the 21 patients, PQ elimination rate (ml/min) by plasma perfusion was found always higher than the renal value: [1st (21 cases) 11.14±6.13 vs. 5.33±4.33; 2nd (21 cases) 18.36±11.32 vs. 4.85±3.15; 3rd (21 cases) 16.13±10.05 vs. 0.84±0.80; 4th (17 cases) 12.86 (6.72, 17.47) vs. 0.28 (0.09, 0.60); 5th (11 cases) 14.12 (10.48, 35.20) vs. 0.10 (0.03, 0.73); 6th (7 cases) 16.47 (11.82; 20.69) vs. 0.13 (0.03, 0.40); 7th (5 cases) 13.33 (9.71, 18.75) vs. 0.33 (0.24, 0.47); 8th (5 cases) 11.27 (9.21, 16.02) vs. 0.32 (0.10, 1.22), P< 0.05 or P< 0.01]. In the study, PPQ was found negatively correlated to PQ elimination by plasma perfusion (r = - 0.4799, P< 0.0001), and positively correlated to the renal elimination ( r = 0.5060, P< 0.0001). The survivors (10 cases) showed a higher PPQ reduction rate (mg×L(-1)×h(-1)) than the non-survivors (11 cases, 0.57± 0.03 vs. 0.47±0.06,P< 0.05). CONCLUSION: Continuous plasma perfusion may be a promising therapeutic tool for its significant PPQ reduction effect, and plasma perfusion should be made available early for patients with acute PQ intoxication.

A decision-tree model for predicting extubation outcome in elderly patients after a successful spontaneous breathing trial.

BACKGROUND: The commonly used single tests, based on a 1-time measurement of a physiologic variable, are often poorly predictive of tracheal extubation outcome because they examine only a single aspect of physiological function that affects the extubation outcome. We hypothesized that the construction of a decision-tree model, which includes multiple variables and considers the changes of these variables, may more accurately predict successful extubation. METHODS: This was a prospective observational study. From 2007 to 2008, 113 elderly patients in the medical intensive care unit on ventilation for >48 hours were enrolled. All patients underwent a 60-minute spontaneous breathing trial (SBT) [positive end-expiratory pressure of 5 cm H(2)O; automatic tube compensation, 100%]. Patients tolerating the trial were extubated immediately. The mouth occlusion pressure (P(0.1)), rapid shallow breathing index (RSBI,) and their combination (P(0.1) × RSBI) were recorded at the first, 30th, and 60th minute of the SBT. The changes in RSBI, which were determined at the 30th and 60th minute of the SBT (ΔRSBI30, ΔRSBI60), were assessed as the ratio (of RSBI30 or RSBI60) to RSBI at the first minute of the SBT. RESULTS: Twenty-two patients (19.5%) failed the SBT and were not included in the analysis, and 91 tolerated the trial and were extubated. At 48 hours, 73 (80.2%) remained extubated (successful extubation), and 18 (19.8%) required reintubation (extubation failure). Although theΔRSBI(30) was significantly higher in the extubation failure patients (118% ± 34%) than that in the successful extubation patients (93% ± 35%, P = 0.01), the receiver operating characteristic (ROC) analysis demonstrated that this index, with the threshold of <98%, presented poor performance in predicting successful extubation with area under the ROC curve (AUC) of only 0.76. The classification and regression-tree analysis selected 3 variables (P(0.1) × RSBI(30), RSBI(1), ΔRSBI(30)) and began with P(0.1) × RSBI(30). For patients with P(0.1) × RSBI-(30) >474 cmH(2)O*breaths/min/L, ΔRSBI(30) >98% defined a group including all failure patients but no success patients, whereas ΔRSBI(30) ≤98% included all success patients with no failure patients. For patients with P(0.1) × RSBI(30) ≤474 cm H(2)O*breaths/min/L, the combination of both a P(0.1) × RSBI(30) >328 cm H(2)O*breaths/min/L and RSBI(1) >112 breaths/min/L also defined a group including all success patients but no failure patients. Indeed, the diagnostic accuracy (DA) of the tree model, which was 89.1% with only the P(0.1) × RSBI(30) included, increased to 94.5% when both the P(0.1) × RSBI(30) and ▵RSBI(30) were included. The final tree model with the inclusion of all 3 discriminators could capture the successful extubation with diagnostic accuracy of 96.7%, AUC of 0.94 (95% confidence interval [CI], 0.87 to 0.98). CONCLUSION: If the current tree model is confirmed by a prospective study with a larger sample size, it would be useful in guiding physicians making extubation decisions in elderly medical intensive care unit patients.

[Effect of different levels of pressure support on physiological variables and patient-ventilator synchronicity during noninvasive pressure support ventilation in patients with respiratory failure].

OBJECTIVE: To evaluate the effects of different levels of pressure support (PS) during noninvasive pressure support ventilation (NPPV) on physiological variables, patient-ventilator synchronicity in patients with acute exacerbation chronic obstructive pulmonary disease (AECOPD) and hypercapnic respiratory failure. METHODS: Fifteen hypercapnic respiratory failure AECOPD patients requiring NPPV in respiratory intensive care unit (RICU) were enrolled. Three different PS levels of 5, 10, 15 cm H2O (1 cm H2O=0.098 kPa) were applied randomly in all the 15 patients. At each PS level the patient was ventilated for 30 minutes, whereas physiological variables, ineffective effort (IE) expressed as IE index were recorded within the last 2 minutes. RESULTS: The IE index, tidal volume (VT), minute ventilation (VE), coefficient of variation of VT, ventilator inspiratory time (TI), expiratory time (TE), leak volume at 15 cm H2O PS level were significantly higher than those at 5 cm H2O level [IE index: (33.8+/-9.1)% vs. (8.0+/-6.0)%, VT (ml): 626+/-203 vs. 339+/-115, VE (L/min): 11.1+/-4.7 vs. 7.7+/-2.7, coefficient of variation of VT: (32.6+/-15.5)% vs. (11.3+/-6.9)%, TI (s): 1.14+/-0.31 vs. 0.76+/-0.15, TE (s): 2.49+/-0.44 vs. 1.87+/-0.28, leak volume (L/min): 8.28+/-4.86 vs. 2.22+/-1.58, all P<0.05], while the ventilator respiratory rate [(17+/-3) breaths/min] was lower at 15 cm H2O PS level than that at 5 cm H2O level [(23+/-3) breaths/min, P<0.05]. At 5 cm H2O level, the IE index was positively correlated with TI (r=0.62, P<0.05). Furthermore, the increase in IE index followed by PS level increase was correlated negatively with the change of VT (Delta VT) and positively with that of the TI (Delta TI, R2=0.88, P=0.000). CONCLUSIONS: (1) The IE at low assistance is associated with prolonged TI. (2) High PS level can significantly increase VE and VT, and reduce the ventilator respiratory rate. However, high PS level also lead to higher IE than low level. The factors favoring a higher increase in IE index as PS level increased include a less increase in VT and a higher increase in TI. However, an increase in leak volume is not associated with an elevated incidence of IE. (3) IE is high at high PS level during NPPV, even the Shape-signal is used as a trigger mechanism.

[The preemptive treatment of invasive Candida infection with reference of corrected colonization index in critically ill patients: a multicenter, prospective, randomized controlled clinical study].

OBJECTIVE: To evaluate preemptive treatment for invasive Candida infection (ICI) with reference of corrected colonization index (CCI) in critically ill patients with high risk factors of Candida infection, and to collect the epidemiology data of Candida infection. METHODS: One hundred and ten critically ill patients with acute physiology and chronic health evaluation II (APACHE II) score>10 were selected from intensive care units (ICUs) of 5 grade III class A hospitals in Tianjin from October 1st 2008 to April 30th 2009, and they were randomly divided into two groups: CCI group and control group (55 cases in each group). CCI was monitored in all patients. In control group the responsible intensivists ordered the treatment according to their own experience, and in CCI group, when the patient's CCI> or =0.4 and with evidence of sepsis, the patients were given anti-Candida immediately. When CCI<0.4, anti-Candida treatment was not given. But when the patients' condition became worse or unstable, complementary anti-Candida treatment was given. RESULTS: There were no significant differences in general data, treatment of diseases of the patients, APACHE II scores, incidence of sepsis and length of ICU stay (LOS) between two groups ( all P>0.05 ). There were 50 patients and 48 patients developing sepsis in control group and CCI group, respectively. In CCI group, the time between the onset of sepsis to beginning of anti-Candida treatment was significantly shorter than the control group [(0.94+/-0.67) days vs. (3.75+/-3.62) days, P<0.05]. In the group of CCI> or =0.4 (57 patients) the LOS [(15.34+/-6.63) days] and the incidence of failure in establishing enteral nutrition (64.9%) were significantly higher than that of the group of CCI<0.4 [53 patients, (7.24+/-3.75) days, 43.4%, both P<0.05]. There was no significant difference in APACHE II scores, incidence of mechanical ventilation and blood purification between two groups ( all P>0.05 ). Analysis of 575 strains of Candida colonized in 110 patients, revealed that C. albicans ranked first (59.3%), C. tropicalis ranked second (10.8%), followed by C. glabrata, Cryptococcus and C. krusei. CONCLUSION: Application of CCI may enhance the accuracy of timely preemptive treatment for ICI, and facilitate the collection of epidemiological data of Candida in critically ill patients.

Blood purification in two patients with clinically amyopathic dermatomyositis associated with interstitial lung disease with anti-melanoma differentiation-associated gene-5 antibody (MDA-5).

Patients of clinically amyopathic dermatomyositis associated with rapidly progressive interstitial pneumonia (CADM-RFIP) with positive anti-MDA5 antibody usually presents rapid deterioration and traditional therapy such as cyclophosphamide combined with high-dose prednisone pulse therapy shows no clear benefit at whiles. However, blood purification combined with traditional therapy works according to the literature. We herein report two CADM-RFIP patients administered with DNA immunoadsorption combined with traditional therapy and then reviewed the literature of blood purification in CADM-RFIP patients at home and abroad to date. We emphasize blood purification such as DNA immunoadsorption could apply in the early stage of CADM-RFIP, which can decrease inflammation and allow us more time to control the condition better.

Synergistic protection of matrine and lycopene against lipopolysaccharide­induced acute lung injury in mice.

Acute lung injury (ALI) is a major cause of morbidity and mortality globally, and is characterized by widespread inflammation in the lungs. Increased production of reactive oxygen species is hypothesized to be associated with ALI. Matrine and lycopene are active products present in traditional Chinese medicine. Matrine is an effective inhibitor of inflammation, whereas lycopene decreases lipid peroxidation. Therefore, it was hypothesized that combinatorial treatment with matrine and lycopene may provide synergistic protection against ALI. In the present study, mice were treated with dexamethasone (DEX; 5 mg/kg), matrine (25 mg/kg), lycopene (100 mg/kg), and matrine (25 mg/kg) + lycopene (100 mg/kg) for 7 days prior to injury induction using lipopolysaccharide (LPS; 5 mg/kg) for 6 h. Lung tissues were collected following the sacrifice of the mice and hematoxylin and eosin staining was used for histological analysis. Malondialdehyde (MDA), glutathione (GSH) and myeloperoxidas (MPO) levels were examined by respective kits. The expressions of interleukin­6 (IL­6) and tumor necrosis factor­α (TNF­α) were evaluated by ELISA. The expressions of IκBα and NF­κB p65 were examined by reverse transcription­quantitative polymerase chain reaction, western blotting and immunohistochemistry. The results indicated that the combined treatment exhibited a similar effect to DEX, both of which attenuated lung structural injuries, downregulated the expressions of IL­6, TNF­α, MPO and MDA, and upregulated that of GSH. Furthermore, the combined treatment and DEX inhibited NF­κB p65 activation. The present study revealed that combined treatment with matrine and lycopene exhibited protective effects on an LPS­induced mouse model of ALI, suggesting that they may serve as a potential alternative to glucocorticoid therapy for ALI.

Effect of activated charcoal hemoperfusion on renal function in patients with paraquat poisoning.

The present study retrospectively analyzed 19 patients diagnosed with paraquat (PQ) poisoning with the aim to investigate the effect of activated charcoal hemoperfusion on renal function and PQ elimination. The results indicated that 7 patients died and 12 survived. Non-oliguric renal failure occurred in all of the 7 patients who died. Among the 12 surviving patients, 10 had normal renal function and 2 developed non-oliguric renal failure. There was a linear correlation between plasma and urine paraquat concentration prior to and during activated charcoal hemoperfusion. The equation parameters together with the correlation coefficient on admission were as follows: Y=0.5820+1.7348X (R2=0.678; F=35.768; P<0.0001). The equation parameters together with the correlation coefficient were as follows during activated charcoal hemoperfusion: Y=0.6827+1.2649X (R2=0.626; F=50.308; P<0.0001). Therefore, it was concluded that in patients with normal renal function, the elimination kinetics of PQ by the kidneys were only associated with the plasma PQ concentration. Activated charcoal hemoperfusion had little effect on avoiding acute kidney injury in patients with severe PQ poisoning.

[Physiologic response to external positive end-expiratory pressure in mechanically ventilated chronic obstructive pulmonary disease patients].

OBJECTIVE: To evaluate the effects of external positive end-expiratory pressure (PEEPe) on respiratory system mechanics in passively ventilated chronic obstructive pulmonary disease (COPD) patients. METHODS: Fifteen patients with acute exacerbation of COPD were randomly enrolled into the study. The patients were admitted into respiratory intensive care unit (RICU) from Jan, 2005 to Jun, 2006 for controlled mechanical ventilation. PEEPe was applied stepwise from zero to 120% of intrinsic PEEP (PEEPi) in all the 15 patients. At each PEEPe level, airway resistance, compliance (Crs), plateau pressure (Pplat), and total PEEP (PEEPtot) were measured. According to the changes of Pplat after PEEPe application, the patients were divided into 2 sub-groups, abnormal response group (n=11) and a perplexing response group (n=4). RESULTS: In all of the 15 patients, airway resistance at PEEPe equal to 80% and 100% of PEEPi (18.5+/-2.0) cm H2O.L(-1).s(-1) (1 cm H2O=0.098 kPa), (18.0+/-2.2) cm H2O.L(-1).s(-1) were significantly lower than that at zero PEEPe [(23.0+/-2.9) cm H2O.L(-1).s(-1), t=5.36, 6.27 respectively, all P<0.01]. At PEEPe levels equal to 120% of PEEPi, airway resistance (17.3+/-2.1) cm H2O.L(-1).s(-1) and PEEPtot (12.7+/-2.2) cm H2O were significantly different compared with those at zero PEEPe (23.0+/-2.9) cm H2O. L(-1).s(-1), (10.0+/-1.1) cm H2O (t=6.79, -3.90 respectively, all P<0.01). There were no significant differences in baseline PEEPi levels (10.0+/-1.0) cm H2O, (10.0+/-1.4) cm H2O, resistance (22.8+/- 1.9) cm H2O.L(-1).s(-1), (23.1+/-4.1) cm H2O.L(-1).s(-1), Crs (39+/-6) ml/cm H2O, (42+/-9) ml/cm H2O and Pplat (20+/-4) cm H2O, (21+/-3) cm H2O between the normal response and the perplexing response groups (t=0.03, 0.10, 0.60, 0.15 respectively, all P>0.05). However, the corresponding values of Pplat changes at different PEEPe levels in the normal response group [DeltaPplat40 (-0.020+/-0.970) cm H2O, DeltaPplat80 (1.6+/-1.0) cm H2O, DeltaPplat100 (4.0+/-2.9) cm H2O, DeltaPplat120 (6.4+/-3.3) cm H2O] were found to be significantly different compared with those in the perplexing response group [DeltaPplat40 (-7.500+/-0.920) cm H2O, DeltaPplat80 (-4.4+/-1.4) cm H2O, DeltaPplat100 (-3.8+/-1.9) cm H2O, DeltaPplat120 (-1.6+/-1.2) cm H2O] (t=-9.64, -5.90, -3.80, -3.92 respectively, all P<0.01). CONCLUSION: At least in some passively ventilated COPD patients, the applied PEEPe may offer benefit by decreasing the Pplat.

Synergistic protection of Schizandrin B and Glycyrrhizic acid against bleomycin-induced pulmonary fibrosis by inhibiting TGF-ß1/Smad2 pathways and overexpression of NOX4.

Pulmonary fibrosis, a progressive and lethal lung disease, is a major therapeutic challenge for which new therapeutic strategies are warranted. Schisandrin B (Sch B) and Glycyrrhizic acid (GA) are the principal active ingredients of Schisandra chinensis and Glycyrrhiza glabra respectively, which have been reported to protect against lung injures. The present study was aimed at exploring the combinatorial therapeutic effects on bleomycin-induced pulmonary fibrosis. Lung fibrotic injuries were induced in mice by a single intratracheal instillation of 5mg/kg bleomycin (BLM). Then, these mice were administered with Sch B (100mg/kg) or/and GA (75mg/kg) for 28days. BLM-triggered structure distortion, collagen overproduction, excessive inflammatory infiltration, pro-inflammatory cytokine release, and oxidative stress damages in lung tissues were attenuated to a higher degree by combinatorial treatment than by treatment of the individual agents. The expression of TGF-ß1 and the phosphorylation of its downstream target, Smad2 were enhanced by BLM, but weakened by Sch B or/and GA. Furthermore, the significant overexpression of NADPH oxidase 4 (NOX4) was observed in BLM-induced pulmonary fibrosis, which was inhibited by Sch B or/and GA. Our study reveals that the synergistic protection by Sch B and GA against BLM-induced pulmonary fibrosis is correlated to its anti-inflammatory, anti-oxidative and anti-fibrotic properties, involving inhibition of TGF-ß1/Smad2 signaling pathways and overexpression of NOX4.

[Changes of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in the bronchoalveolar lavage fluid and the serum of patients with idiopathic pulmonary fibrosis].

OBJECTIVE: To detect the levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the bronchoalveolar lavage fluid (BALF) and the serum of patients with idiopathic pulmonary fibrosis (IPF), and to evaluate the significance of the changes in the pathogenesis of IPF. METHODS: Enzyme-linked immunoadsorbent assay (ELISA) was used to detect MMP-9 and TIMP-1 in the BALF and serum of 30 patients with IPF. RESULTS: The levels of MMP-9 in the BALF and serum of the patients showed no significant difference as compared with those of the control group. The levels of TIMP-1 in the BALF [(522 +/- 81) ng/L] and serum [(166 +/- 29) ng/L] of the patients were higher than those [(201 +/- 31), (87 +/- 16) ng/L] of the control group (P < 0.01). The ratios of MMP-9/TIMP-1 in the BALF (0.53 +/- 0.18) and serum (1.5 +/- 0.3) of patients with IPF were lower than those (1.06 +/- 0.38, 2.6 +/- 0.5) of the control group (P < 0.01, < 0.05). TIMP-1 in the BALF of the patients showed a strong positive correlation with chest CT fibrosis and pulmonary function test scores (P < 0.01), while MMP-9/TIMP-1 in the BALF had negative correlation with them (P < 0.01). CONCLUSION: Pulmonary fibrosis may be associated with increased TIMP-1 and decreased MMP-9/TIMP-1, which is able to inhibit the degradation of extracellular matrix.