Paraquat (PQ) is a nonselective contact herbicide that has long been used worldwide, especially in developing agricultural countries, such as China. PQ is highly toxic to humans, and ingestion of >15–30 mL of 20% (w/v) PQ can be fatal in humans [
Many prognostic indicators have been investigated to evaluate the prognosis of PQ poisoning. Plasma PQ concentration is a marker of severity and prognosis with acceptable sensitivity and specificity [
Recently, many studies have indicated that elevated monocyte count is closely associated with poor prognosis in patients with osteoarticular brucellosis [
This retrospective clinical study was conducted in accordance with the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the Ethics Committee of the Cangzhou Central Hospital (No. 2017-090-01). However, informed consent was unavailable because of its retrospective nature. Informed consent regarding the treatment risk following acute PQ poisoning was obtained from all patients upon their initial admission. All data were gathered in the context of standard practice from clinical patient records without the need for informed consent. Then, the data were anonymized and stored in a protected database.
The medical records of patients with PQ poisoning who were already discharged from the hospital or died between May 2012 and December 2018 were collected for this retrospective analysis. The inclusion criteria were as follows: patients diagnosed with acute PQ poisoning by checking their plasma PQ concentrations; patients aged > 14; patients who suffered from PQ poisoning through oral intake; and hospital admissions within 12 h of poisoning. The exclusion criteria were as follows: patients who suffered from other pesticide poisoning, pregnant patients, cases with infection, cases with immunosuppressive therapy, or cases with blood systemic diseases.
All patients were administered 1 g/kg activated carbon tablets plus Fuller's earth added to 250 mL of 20% mannitol via a gastric tube to minimize further absorption following gastric lavage with room warm water (≥5 L) [
At baseline, clinical data, including age, gender, time from ingestion to gastric lavage, alanine aminotransferase (ALT), creatinine, alveolar oxygen partial pressure (PaO2), plasma PQ concentration, and monocytes, were obtained. In consideration of the possible influence of HP and drug therapy on the predictive value of monocytes, blood samples obtained before HP and drug therapy were eligible, and only this single point of monocytes was used to assess the predictive value of monocytes. Elevated monocytes correspond to a level >1.0×109/L (normal range: 0.2–1.0
All analyses were conducted using SPSS software version 13.0 (SPSS Inc., Chicago, IL). The independent sample t-test was used to evaluate measurement data if normal distribution was followed, and data were presented as mean ± standard deviation; otherwise, two-independent sample nonparametric tests were performed, and data were presented as median ± interquartile range. Categorical variables were analyzed using
Among the 121 patients with acute PQ poisoning from May 2012 to December 2018, 109 patients were enrolled in the study for further analysis, 7 patients presented incomplete data, 3 patients were not followed up, and 2 patients were transferred to another hospital. Among the 109 acute PQ poisoning patients, the survival rate was 41.28%. A total of 109 blood samples were obtained from patients to determine the PQ concentration and clinical laboratory examination upon arrival at the emergency room. Table
General characteristics upon arrival between survival and mortality groups.
Non-survival group | Survival group | | |
---|---|---|---|
Age (years) | 42.50 (31.75) | 33.00 (21.00) | 0.060 |
Gender (male/female) | 27/37 | 20/25 | 0.815 |
Time from ingestion to gastric lavage (h) | 1.00 (1.00) | 1.00 (1.25) | 0.627 |
Alanine aminotransferase (ALT, U/L) | 32.65 (16.93) | 26.60 (10.00) | 0.006 |
Creatinine ( | 104.00 (69.50) | 62.00 (21.00) | <0.001 |
Alveolar oxygen partial pressure (Pa | 89.82±10.50 | 93.90±12.85 | 0.050 |
Plasma PQ concentration (ng/mL) | 3.65 (8.53) | 0.30 (0.85) | <0.001 |
Monocyte (×109/L) | 0.72 (0.72) | 0.36 (0.16) | <0.001 |
PQ: paraquat. Note. Continuous variables are presented as means ± SD or median (interquartile range) and categorical variable is presented as number.
General characteristics upon arrival stratified according to monocyte count.
Monocyte ≤1 | Monocyte >1 | | |
---|---|---|---|
(n=90) | (n=19) | ||
Age (years) | 37.00 (27.00) | 43.00 (28.00) | 0.701 |
Gender (male/female) | 40/50 | 7/12 | 0.543 |
Time from ingestion to gastric lavage (h) | 1.00 (1.00) | 1.00 (1.00) | 0.617 |
Alanine aminotransferase (ALT, U/L) | 28.15 (13.38) | 32.50 (16.70) | 0.088 |
Creatinine ( | 72.00 (31.75) | 139.00 (49.00) | <0.001 |
Alveolar oxygen partial pressure (Pa | 92.34 ±9.84 | 87.00 ±10.51 | 0.036 |
Plasma PQ concentration (ng/mL) | 1.45 (2.63) | 7.80 (18.10) | <0.001 |
PQ: paraquat. Note. Continuous variables are presented as means ± SD or median (interquartile range) and categorical variable is presented as number.
Correlation analysis showed that monocyte count positively correlated with plasma PQ concentration (r= 0.413;
In univariate analysis, plasma PQ concentration, creatinine, ALT, and monocyte count were selected from the Cox proportional hazard model for multivariate analysis (Table
Cox regression model.
Univariate COX model | | Multivariate COX model | | |
---|---|---|---|---|
Age (years) | 1.014 (1.000–1.029) | 0.051 | N/A | |
Gender (male/female) | 0.914 (0.557–1.502) | 0.724 | N/A | |
Time from ingestion to gastric lavage | 1.019 (0.859–1.209) | 0.826 | N/A | |
Plasma PQ concentration | 1.067 (1.048–1.087) | <0.001 | 1.026 (1.001–1.050) | 0.038 |
Alanine aminotransferase (ALT) | 1.010 (1.005–1.037) | 0.010 | 1.015 (0.997–1.033) | 0.109 |
Creatinine | 1.019 (1.014–1.024) | <0.001 | 1.013 (1.006–1.019) | <0.001 |
Alveolar oxygen partial pressure (PaO2,) | 0.978 (0.953–1.004) | 0.101 | N/A | |
Monocyte | 4.302 (2.684–6.897) | <0.001 | 1.841 (1.015–3.340) | 0.044 |
N/A: not applicable; PQ: paraquat.
The area under the curve for 90-day survival prediction was 0.962 of plasma PQ concentrations, 0.844 of creatinine, and 0.828 of monocyte count (Table
ROC curve analysis.
Variable | Area under | 95% CI | Cutoff | Sensitivity | Specificity | Youden |
---|---|---|---|---|---|---|
Plasma PQ concentration | 0.962 | 0.930–0.994 | 1.55 | 89.1 | 91.1 | 0.802 |
Creatinine | 0.844 | 0.771–0.917 | 74.5 | 75.0 | 86.7 | 0.617 |
Monocyte | 0.828 | 0.751–0.904 | 0.51 | 73.4 | 86.7 | 0.601 |
PQ: paraquat; ROC: receiver operating characteristic; CI: confidence interval.
Area under the receiver operating characteristic curve analysis. PQ: paraquat.
The Kaplan–Meier survival curve revealed that patients with elevated monocytes exhibited low 90-day survival (log-rank test;
Kaplan–Meier analysis of survival curves for the groups according to monocyte count.
This study is the first to specifically focus on the prognostic value of monocytes in patients with acute PQ poisoning. Our results show that elevated monocyte count upon patient admission is a predictive factor for 90-day survival. Furthermore, correlation analysis shows that monocytes are positively correlated with plasma PQ concentration and negatively correlated with survival time and 90-day survival.
Peripheral blood monocytes are a population of circulating mononuclear phagocytes that harbor potential to differentiate into macrophages and dendritic cells. After birth, monocytes derive from hematological precursors in the bone marrow and enter the blood circulation, from which they are recruited into tissues throughout the body. The monocyte chemoattractant protein-1 is a member of the C-C chemokine family and regulates the migration and infiltration of monocytes/macrophages. After exposure to PQ, bone marrow mesenchymal stem cells rapidly expressed monocyte chemotactic protein-1 in response to circulating toll-like receptor ligands induced by PQ and induced monocyte trafficking into the bloodstream [
As an important step for the onset and progression of PQ-induced lung injury, monocytes are recruited via chemotaxis such as monocyte chemoattractant protein-1, vascular cell adhesion molecule-1, and intracellular adhesion molecule 1, into the interstitial and alveolar spaces [
The primary target of toxicity in the lung is the alveolar epithelium. Exposure to PQ leads to the accumulation of PQ in the lungs, resulting in swelling, vacuolation, and disruption of mitochondria and the endoplasmic reticulum. This initial phase is followed by a proliferative phase where the alveolar space is filled with mononuclear profibroblasts that mature into fibroblasts within days to weeks. Previous studies showed that patients with PQ poisoning may be left with less diffusion dysfunction and restriction ventilation dysfunction at 2 to 3 months, and long-term follow-up suggests that respiratory function impairment usually fully recovers [
The kidney is the main excretory organ of PQ, and PQ is predominantly excreted through the original form by the kidneys using glomerular filtration and active secretion. Thus, the kidneys are among the organs that can contain the highest concentration of PQ, which explains why remarkable acute renal injury occurs in the early stage of PQ intoxication. PQ is toxic to renal proximal tubule cells through the generation of reactive oxygen species, which cause lipid peroxidation of the cell membrane, leading to loss of membrane integrity and cell death. Other factors influencing the development of acute kidney injury include hypoperfusion from hypovolaemia and/or hypotension and direct glomerular injury [
Several limitations must be considered in the interpretation of the current results. First, as a retrospective study, this study has inherent information bias. Second, the sample size is too small because of the limited experimental conditions, hence the need for expansion or multicenter research. Third, monocyte count prior to PQ intoxication was not measured. Therefore, whether the elevated leucocyte levels were entirely due to PQ ingestion remains unconfirmed.
The present study demonstrated that elevated monocyte count is a useful early predictor of the 90-day survival of patients with acute PQ poisoning. When no facility measures PQ concentration, monocytes can be used as a reference for death risk in acute PQ poisoning.
Paraquat
Area under the curve
Receiver operating characteristic.
The data used to support the findings of this study are included within the article.
The authors have no conflicts of interest.
Yong Zhao and Ya Qi Song contributed equally to this work.