This is the first epidemiological study conducted assessing the association between enema and DQ-induced nervous system injury. To control for the confounding variable of age, we employed age group matching. Our investigation revealed that DQ poisoning patients who underwent 2 and ≥ 3 enemas exhibited a 3.084-fold and 4.643-fold elevated risk of nervous system injury, respectively, after adjustments for DQ plasma concentration, NLR, Scr, and Lac. The results underscore that the administration of 2 or more enemas could potentially heighten the risk of nervous system injury caused by DQ poisoning. While diquat is not inherently a neurotoxin, it has the potential to induce elevated oxidative stress within cerebral tissues12. Research on the impact of DQ poisoning on nervous system damage is sparse, with most existing studies being conducted on animal models. These research indicated that DQ exposure in mice causes oxidative stress, resulting in the degeneration of dopamine neurons, reduced dopamine uptake capacity, and neuroinflammation in the hippocampus6,13. Nevertheless, MR imaging analyses of DQ poisoning revealed that dopaminergic nuclei were unaffected, a finding that contradicted outcomes observed in preclinical animal studies14. The exact mechanism by which DQ poisoning leads to nervous system injury remains unknown.
Enema therapy, a prevalent intervention for acute toxicological emergencies, entails the administration of a fluid into the colon to facilitate the expulsion of unabsorbed toxins. Nonetheless, excessive or recurrent enemas may deplete beneficial microbiota from the gastrointestinal tract, while concurrently introducing pathogenic microorganisms, thereby disrupting the gut microbiome. Disruption of the gut microbiome not only impairs gastrointestinal function but also has the potential to affect the central nervous system through the gut-brain axis. The microbiota-brain-gut axis constitutes an intricate neuroendocrine-immune circuit linking the central nervous system to the gastrointestinal tract. This axis encompasses not only neurochemical signaling but also the interplay of endocrine responses and immunological mediators15,16. Disruption of the gut microbiota can impair the synthesis and equilibrium of neuroactive compounds, potentially leading to dysregulation of the neurotransmitter system and consequent exacerbation or onset of neurological disorders. In addition, the dysbiosis of the gut microbiota can compromise intestinal permeability by disrupting the integrity of the intestinal barrier, thereby permitting the translocation of deleterious substances and bacterial endotoxins into the systemic circulation, which can exacerbate neuroinflammatory responses17. However, it remains to be elucidated whether enema influence the nervous system injury after DQ poisoning via the “microbiota-brain-gut axis”, necessitating validation through future clinical and foundational research.
In order to elucidate the correlation between enema and neurotoxicity induced by DQ poisoning, we implemented a stratified population-based case-control study categorized by age groups. Utilizing univariate analysis, we identified significant statistical disparities between the case and control group concerning plasma DQ levels, NLR, Lac, Scr, and the frequency of enema administration (specifically, twice, or three or more times). To further elucidate the association between enema frequency and DQ-induced neurotoxicity, we conducted a multivariate analysis incorporating plasma DQ concentration, NLR, Lac, and Scr as covariates. The conclusive findings demonstrated that undergoing 2 and ≥ 3 enemas increased the risk of DQ-related nervous system injury, with ORs 3.084(95%CI 1.230, 7.734) and 4.693(95%CI 1.408, 15.645) respectively. To further validate our findings, we performed analyses among subgroups of different age ranges further. Subgroup analysis revealed that the administration of enemas exerts a more pronounced effect on geriatric patients relative to their younger counterparts. Within the subgroup of individuals aged 18 to 44, the prevalence of enemas was not associated with an elevated risk of DQ-induced nervous system injury. In the 45–59 age subgroup, following adjustments for multiple statistically significant variables identified through univariate analyses, plasma DQ concentration, NLR, Lac, and Scr, it was found that receiving ≧ 3 enemas singularly increased the risk of nervous system injury caused by DQ poisoning. Conversely, in the subgroup aged 60 and older, the administration of both 2 and ≧ 3 enemas were correlated with an increased risk of DQ-induced brain injury, even after controlling for statistically significant variables determined by univariate analysis. The data indicated that the susceptibility to DQ-induced nervous system injury after enemas escalates with advancing age, particularly among the geriatric demographic. Senescence is correlated with the deterioration of various physiological systems, including cerebrovascular integrity, intestinal mucosal defenses, immunological responses, and central nervous system functionality18. Furthermore, age-associated modifications in the central nervous system, such as atherosclerosis, hypertension, diabetes mellitus, and other metabolic disorders, may exacerbate the prevalence of encephalopathy following enema administration in elderly individuals. Furthermore, Changes in gut microbiota in older patients may also be an important reason. The precise pathobiological processes facilitating this association remain enigmatic and necessitate extensive scientific investigation.
In conclusion, our findings indicated that enema may be associated with an increased risk of nervous system injury in DQ poisoning, particularly in patients aged over 60. Considering that enemas are among the therapeutic interventions for alleviating DQ toxicity, yet they may increase the risk of neurotoxicity caused by DQ, it is crucial to conduct a comprehensive risk-benefit analysis of the therapeutic efficacy against the potential neurotoxic hazards before integrating this approach into clinical guidelines.
Limitations: The principal and perhaps most vital constraint of any retrospective investigation pertains to the likelihood of selection bias. In our research, we grappled with the phenomenon universally termed Berkson’s bias, emerging when the choice of case studies and controls is swayed by their hospital admission status, contrarily to the condition under scrutiny. This bias is notably pervasive in single-center researches where the chosen sample might not be an accurate reflection of the wider demographic. Another limitation inherent to our study design was the small sample size utilized in subgroup analyses. Subgroup analyses can provide valuable insights, especially when exploring specific characteristics that may modify treatment effects or outcomes. However, when the sample sizes for these subgroups are small, the results become less reliable and more susceptible to variability. Potential confounders, including patients’ baseline health conditions, the procedural timing (specifically, the administration of an enema), and the severity of DQ toxicity, could significantly influence the study’s results. In order to substantiate the observed phenomena and elucidate the precise associations between enema and nervous system injury caused by DQ in this context, it is imperative to undertake additional prospective investigations, characterized by rigorously defined parameters and substantially larger, more representative cohorts.
link