Efficacy of initial haemopurification strategy for acute paraquat poisoning in adults: study protocol for a randomised controlled trial (HeSAPP).
ABSTRACT: INTRODUCTION:Paraquat (PQ) is a widely used herbicide which is inexpensive and easily accessible for people in rural areas. A small amount of PQ ingestion could be lethal, yet currently, the optimal treatment is still controversial. Extracorporeal therapies (ECTR) have been practised in PQ poisoning management, though limited evidence could be obtained to suggest its superiority over conservative therapy. Haemodialysis (HD) and haemoperfusion (HP) are most commonly used, while some institutions also choose HP-HD concurrent therapy. The object of the present trial is to investigate whether haemopurification therapy can reduce mortality compared with conservative therapy. METHODS AND ANALYSIS:This is a planned single-centre, non-blinded, randomised controlled trial. Acute PQ poisoned adults who have orally ingested PQ within 24?hours would be recruited. A total of 360 patients would be recruited and randomly assigned to four groups, that is, HP, HD, concurrent HP-HD and control, at a 1:1:1:1 ratio. Subjects would be also stratified by their urine dithionite test results. Primary outcome is 28-day all-cause mortality. Secondary outcomes include survival time, all-cause mortality at the 3rd, 7th and 60th day, rate of major complications, Acute Physiologic and Chronic Health Evaluation score and Poisoning Severity Score, etc. ETHICS AND DISSEMINATION: The protocol and informed consent documents have been approved by the Ethics Committee of The First Affiliated Hospital of Zhengzhou University in September 2017 (approval number: 2017-KY-10). The result of this trial would be submitted to peer-reviewed journal. TRIAL REGISTRATION NUMBER:NCT03314909; Pre-results.
Project description:Mortality in patients with paraquat (PQ) poisoning is related to plasma PQ levels. Concentrations lower than 5,000 ng/mL are considered critical but curable. This study assessed the effects of hemoperfusion (HP) and continuous renal replacement therapy (CRRT) on the survival of PQ-poisoned patients with plasma PQ levels below 5,000ng/mL. We analyzed the records of 164 patients with PQ poisoning who were treated at the First Affiliated Hospital of Wenzhou Medical University in China between January 2011 and May 2015. We divided these patients into six sub-groups based on baseline plasma PQ levels and treatment, compared their clinical characteristics, and analyzed their survival rates. Patient sub-groups did not differ in terms of age, sex, time between poisoning and hospital admission, or time to first gavage. Biochemical indicators improved over time in all sub-groups following treatment, and the combined HP and CRRT treatment yielded better results than HP or CRRT alone. Fatality rates in the three treatment sub-groups did not differ among patients with baseline plasma PQ levels of 50-1,000 ng/mL, but in patients with 1,000-5,000 ng/mL levels, the mortality rate was 59.2% (HP treatment group), 48% (CRRT treatment group), and 37.9% (combined treatment group). Mortality rates were higher 10-30 days after hospitalization than in the first 10 days after admission. In the early stages of PQ poisoning, CRRT is effective in reducing patient fatality rates, particularly when combined with HP. Our data could be useful in increasing survival in acute PQ poisoning patients.
Project description:The efficacy of hemoperfusion (HP) in patients with acute paraquat poisoning (PQ) remains controversial. We conducted a multi-center retrospective study to include acute PQ-poisoned patients admitted to two tertiary medical centers between 2005 and 2015. We used the Severity Index of Paraquat Poisoning (SIPP) to stratify the severity of PQ-poisoned patients. The indication to start HP was a positive result for the semiquantitative urine PQ test and presentation to the hospital was within 24 h. Early HP was defined as the first session of HP performed within five hours of PQ ingestion. A total of 213 patients (100 HP group, 113 non-HP group) were eligible for the study. The overall 60-day mortality of poisoned patients was 75.6% (161/213). Multivariate Cox regression analysis showed no statistically significant difference in 60-day survival between HP and non-HP groups (95% confidence interval (CI): 0.84-1.63, <i>p</i> = 0.363). Further subgroup analysis in the HP group showed early HP (95%CI: 0.54-1.69, <i>p</i> = 0.880), and multiple secessions of HP (95%CI: 0.56-1.07, <i>p</i> = 0.124) were not significantly related to better survival. Among acute PQ-poisoned patients, this study found that HP was not associated with increased 60-day survival. Furthermore, neither early HP nor multiple secessions of HP were associated with survival.
Project description:Paraquat (N, N'-dimethyl-4, 4'-bipyridinium dichloride, PQ) intoxication is a common cause of lethal poisoning. This study aimed to identify the risk of using liberal oxygen therapy in patients with PQ poisoning. This was a multi-center retrospective cohort study involving four medical institutions in Taiwan. Data were extracted from the Chang Gung Research Database (CGRD) from January 2004 to December 2016. Patients confirmed to have PQ intoxication with a urine PQ concentration ? 5 ppm were analyzed. Patients who received oxygen therapy before marked hypoxia (SpO2 ? 90%) were defined as receiving liberal oxygen therapy. The association between mortality and patient demographics, blood paraquat concentration (ppm), and liberal oxygen therapy were analyzed. A total of 416 patients were enrolled. The mortality rate was higher in the liberal oxygen therapy group (87.8% vs. 73.7%, P = 0.007), especially in 28-day mortality (adjusted odds ratio [aOR]: 4.71, 95% confidence interval [CI]: 1.533-14.471) and overall mortality (aOR: 5.97, 95% CI: 1.692-21.049) groups. Mortality in patients with PQ poisoning was also associated with age (aOR: 1.04, 95% CI: 1.015-1.073), blood creatinine level (aOR: 1.49, 95% CI: 1.124-1.978), and blood paraquat concentration (ppm) (aOR, 1.51; 95% CI: 1.298-1.766). Unless the evidence of hypoxia (SpO2 < 90%) is clear, oxygen therapy should be avoided because it is associated with increased mortality.
Project description:PURPOSE:To assess whether extracorporeal treatment (ECTR) improves outcome of patients with metformin-associated lactic acidosis (MALA) and to evaluate the clinical applicability of the Extracorporeal Treatments in Poisoning Workgroup (EXTRIP) criteria for starting ECTR in metformin poisoning. METHODS:Patients with metformin serum concentrations above 2 mg/l who were admitted in the Deventer Teaching Hospital between January 2000 and July 2019 and complied with the definition of MALA (pH?<?7.35 and lactate concentration?>?5 mmol/l) were included. Mortality and clinical parameters of patients treated with ECTR or not were compared. In addition, treatment of MALA in clinical practice was verified against the criteria of EXTRIP. RESULTS:Forty-two patients were included. Lactate (13.8 versus 10.5 mmol/l, p?=?0.01), creatinine (575 versus 254 umol/l, p?<?0.01)), metformin (29.4 versus 8.6 mg/l, p?<?0.01) concentrations, and vasopressor requirement (72% versus 23%, p?<?0.01) were significantly higher in the ECTR-group. Blood pH (7.05 versus 7.19, p?=?0.03) and bicarbonate (6 versus 11 mmol/l, p?<?0.01) were significantly lower. Mortality, length of hospital stay, and mechanical ventilation requirement were not statistically different. In 83% of patients, treatment of MALA was in accordance with the EXTRIP criteria. CONCLUSIONS:Although there was no statistical benefit in mortality shown from ECTR, ECTR might be lifesaving in MALA, considering the ECTR-group was significantly sicker than the non-ECTR-group. The majority of patients were treated in line with the EXTRIP criteria. Severity of lactic acidosis and renal impairment were the main indications for initiating ECTR.
Project description:INTRODUCTION:Haemodialysis (HD) is the cornerstone treatment for patients with end-stage renal disease (ESRD). However, highly protein bound or large molecular weight uremic toxins such as phenolic and indolic compounds and homocysteine, which are associated with adverse outcomes such as cardiovascular disease of patients with ESRD, are difficult to remove via HD but can be effectively eliminates by haemoperfusion (HP). The proposed trial (referred to as HD/HP vs HD below) is a randomised, open-label, multicentre trial comparing HD plus HP versus HD alone in adult patients with ESRD. The primary endpoint measure is all-cause mortality. METHODS AND ANALYSIS:We plan to enrol 1364 maintenance HD patients from 11 medical centres in Shanghai. Participants will be randomised to receive HD plus HP or HD alone at a 1:1 ratio after 1-month run-in period. In both arms, patients will receive low-flux HD at a frequency of two times a week and haemodiafiltration at a frequency of once a week. In the intervention group, subjects also received HP once every 2?weeks. Follow-up is scheduled at 3, 6, 12, 18 and 24?months after randomisation, and will consist the following: routine physical examinations, standard lab panels (blood routine, liver/residual?kidney functions, tests of the coagulation system, etc), dialysis adequacy (standard Kt/V), chest X-ray, ECG, echocardiography, heart function rating. Adverse events will be assessed according to the international conference on harmonisation guidelines. The primary outcome is 24-month all-cause mortality. Secondary outcomes will include cardiovascular-related mortality, the occurrence of major cardiovascular events and the quality of life. ETHICS AND DISSEMINATION:The study protocol has been approved by the Ethical Committees of all 11 participating centres. Clinical Research Unit of Xin Hua Hospital will oversee the study. The results will be presented at national and international academic meetings, and submitted to peer-reviewed journals for publications. TRIAL REGISTRATION NUMBER:NCT03227770; Pre-results.
Project description:BACKGROUND:Pulmonary injury is the main cause of death in acute paraquat (PQ) poisoning. However, whether quantitative lung computed tomography (CT) can be useful in predicting the outcome of PQ poisoning remains unknown. We aimed to identify early findings of quantitative lung CT as predictors of outcome in acute PQ poisoning. METHODS:Lung CT scanning (64-slide) and quantitative CT lesions were prospectively measured for patients after PQ intoxication within 5 days. The study outcome was mortality during 90 days follow-up. Survival curves were derived by the Kaplan-Meier method, and mortality risk factors were analyzed by the forward stepwise Cox regression analysis. RESULTS:Of 97 patients, 41 (42.3%) died. Among the eight different types of lung CT findings which appeared in the first 5-day of PQ intoxication, four ones discriminated between survivors and non-survivors including ground glass opacity (GGO), consolidation, pneumomediastinum and "no obvious lesion". With a cutoff value of 10.8%, sensitivity of 85.4% and specificity of 89.3%, GGO volume ratio is better than adopted outcome indicators in predicting mortality, such as estimated amount of PQ ingestion, plasma or urine PQ concentration, acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores. GGO volume ratios above 10.8% were associated with increased mortality (hazard ratio, 5.82; 95% confidence interval, 4.77-7.09; P < 0.001). CONCLUSIONS:The volume ratio of GGO exceeding 10.8% is a novel, reliable and independent predictors of outcome in acute PQ poisoning.
Project description:Sequential organ failure assessment (SOFA) score is commonly used to determine disease severity and predict prognosis in critically ill patients. However, the prognostic value of SOFA after acute paraquat (PQ) poisoning remains unclear. This meta-analysis aimed to study the capability of SOFA to predict mortality in patients with PQ poisoning. Databases that included PubMed, Embase, Web of Science, ScienceDirect, Embase, and Cochrane Library were searched through May 2018. Six studies involving 946 patients were included in the meta-analysis. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and then ORs with 95% CIs were pooled for the estimation of the prognostic role of SOFA in patients with PQ poisoning. Results showed that higher SOFA in patients with PQ poisoning was related to severe mortality (OR = 8.14, 95%CI 4.26-15.58, p<0.001). The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic OR, and area under the curve were 72% (95%CI 0.65-0.79), 75% (95%CI 0.65-0.83), 2.9 (95%CI 2.0-4.1), 0.37 (95%CI 0.28-0.41), 8 (95%CI 4-14), and 0.79 (95%CI 0.76-0.83), respectively. No evidence of publication bias was detected by funnel plot analysis and formal statistical tests. Sensitivity analyses showed no important differences in the estimates of effects. The high SOFA score (8.1-fold) was associated with severe mortality in patients with PQ poisoning.
Project description:Paraquat (PQ) poisoning is a widespread occurrence, especially in underdeveloped areas. The treatment of PQ poisoning has always been difficult, and there is currently no definite effective treatment. Continuous venovenous hemofiltration (CVVH) treatment for PQ poisoning has been widely used in clinical practice; however, its effect remains uncertain. Accordingly, the purpose of this meta-analysis was to evaluate the efficacy of CVVH in the treatment of PQ poisoning.We searched for relevant trials using PubMed, Embase, the Cochrane Library, and 3 Chinese databases, the Chinese BioMedical Literature Database, National Knowledge Infrastructure Database, and Wanfang Database. We included all qualified randomized controlled trials (RCTs) of CVVH treatment for patients with PQ poisoning. The primary outcome was mortality, while the secondary outcomes included the survival time and constituent ratios of death due to respiratory failure and circulatory failure.Three RCTs involving 290 patients were included. The mortality rates of the intervention and control groups were 57.9% and 61.0%, respectively. Pooled analysis demonstrated no significant difference in mortality between the CVVH treatment and control groups (risk ratio [RR] 0.94, 95% confidence interval [CI]: 0.78-1.15, P?=?.56), with a low level of heterogeneity (X?=?1.75, I?=?0%). However, the CVVH group was associated with a longer survival time compared to the control group (weighted mean difference 1.73, 95% CI: 0.56-2.90, P?=?.004). Respiratory failure as the cause of death was more common in the CVVH group, as compared with the control group (RR 1.66, 95% CI: 1.24-2.23, P?=?.0008), whereas patients in the control group were more likely to die from circulatory failure than in the CVVH group (RR 0.56, 95% CI: 0.40-0.81, P?=?.002).Although CVVH treatment might not noticeably reduce mortality for patients with PQ poisoning, it can prolong the survival time of the patients and improve the stability of the circulatory system, thereby enabling further treatment.
Project description:Paraquat (PQ) poisoning can cause multiple organ failure, in which the lung is the primary target organ. There is currently no treatment for PQ poisoning. Mesenchymal stem cells (MSCs), which differentiate into multiple cell types, have generated much enthusiasm regarding their use for the treatment of several diseases. The aim of this study was to systematically review and analyze published preclinical studies describing MSC administration for the treatment of PQ poisoning in animal models to provide a basis for cell therapy.The electronic databases PubMed and CBMdisc were searched in this systematic review and meta-analysis. The MSC treatment characteristics of animal models of PQ poisoning were summarized. After quality assessment was performed, the effects of MSC transplantation were evaluated based on the survival rate, lung wet/dry weight, fibrosis scores, oxidative stress response, and inflammatory response. Publication bias was assessed.Eleven controlled preclinical studies involving MSC transplantation in animal models of PQ poisoning were included in this review. MSC therapy improved the survival rate and reduced the lung wet/dry weight and histopathological fibrosis changes in most studies. MSCs decreased serum or plasma malondialdehyde levels in the acute phase after 7 and 14 d and increased serum or plasma superoxide dismutase and glutathione levels at the same time points. IL-1?, TNF-? and TGF-?1 levels in blood or lung tissues were decreased to different degrees by MSCs. Lung hydroxyproline was decreased by MSCs after 14 d. No obvious evidence of publication bias was found.MSCs showed anti-fibrosis therapeutic effects in animal models of lung injury caused by PQ poisoning, which may be related to reduced oxidative stress and inflammatory cytokine levels. Our review indicates a potential therapeutic role for MSC therapy to treat PQ poisoning and serves to augment the rationale for clinical studies.
Project description:BACKGROUND:Severity index and plasma paraquat (PQ) concentration can predict the prognosis of patients with PQ poisoning. However, the better parameter is yet to be systematically investigated and determined. Thus, we conduct this systematic review and meta-analysis to investigate the prognostic value of severity index and plasma PQ concentration in patients with PQ poisoning. METHODS:We searched PubMed, Embase, Web of Science, ScienceDirect, and Cochrane Library to identify all relevant papers that were published up to March 2019. All diagnostic studies that compared severity index and plasma PQ concentration to predict mortality in patients with PQ poisoning were enrolled in this meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) for individual trials were pooled using a random-effect model. We also aggregated heterogeneity testing, sensitivity analysis, and publication bias analysis. RESULTS:Ultimately, seven studies involving 821 patients were included. The pooled OR with a 95% CI of severity index was 24.12 (95% CI: 9.34-62.34, P?<?.001), with an area under the curve of 0.88 (95% CI: 0.85-0.90), sensitivity of 0.84 (95% CI: 0.74-0.91), and specificity of 0.81 (95% CI: 0.75-0.87). Meanwhile, the pooled OR with 95% CI of plasma PQ concentration was 34.39 (95% CI: 14.69-80.56, P?<?.001), with an area under the curve of 0.94 (95% CI: 0.91-0.96), sensitivity of 0.86 (95% CI: 0.75-0.93), and specificity of 0.89 (95% CI: 0.76-0.95). Sensitivity analysis demonstrated the stability of the results of our meta-analysis. No significant publication bias was observed in this meta-analysis. CONCLUSION:Overall, this study indicated that severity index and plasma PQ concentration have relatively high-prognostic value in patients with PQ poisoning, and that the sensitivity and specificity of plasma PQ concentration are superior to those of severity index.