Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital, Sydney, NSW, Australia.
St Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia.
Clin Toxicol (Phila). 2022 Jul;60(7):798-807. doi: 10.1080/15563650.2022.2049811. Epub 2022 Mar 24.
Ethylene glycol poisoning manifests as metabolic acidemia, acute kidney injury and death. The diagnosis and treatment depend on history and biochemical tests. Glycolate is a key toxic metabolite that impacts prognosis, but assay results are not widely available in a clinically useful timeframe. We quantitated the impact of serum glycolate concentration for prognostication and evaluated whether more readily available biochemical tests are acceptable surrogates for the glycolate concentration.
The objectives of this study are to 1) assess the prognostic value of the initial glycolate concentration on the occurrence of AKI or mortality in patients with ethylene glycol exposure (); 2) identify surrogate markers that correlate best with glycolate concentrations ).
A systematic review of the literature was performed using Medline/PubMed, EMBASE, Cochrane library, conference proceedings and reference lists. Human studies reporting measured glycolate concentrations were eligible. Glycolate concentrations were related to categorical clinical outcomes (acute kidney injury, mortality), and correlated with continuous surrogate biochemical measurements (anion gap, base excess, bicarbonate concentration and pH). Receiver operating characteristic curves were constructed to calculate the positive predictive values and the negative predictive values of the threshold glycolate concentrations that predict acute kidney injury and mortality. Further, glycolate concentrations corresponding to 100% negative predictive value for mortality and 95% negative predictive value for acute kidney injury were determined.
Of 1,531 articles identified, 655 were potentially eligible and 32 were included, reflecting 137 cases from 133 patients for the prognostic study and 154 cases from 150 patients for the surrogate study. The median glycolate concentration was 11.2 mmol/L (85.1 mg/dL, range 0-38.0 mmol/L, 0-288.8 mg/dL), 93% of patients were treated with antidotes, 80% received extracorporeal treatments, 49% developed acute kidney injury and 13% died. The glycolate concentration best predicting acute kidney injury was 12.9 mmol/L (98.0 mg/dL, sensitivity 78.5%, specificity 88.1%, positive predictive value 86.4%, negative predictive value 80.9%). The glycolate concentration threshold for a 95% negative predictive value for acute kidney injury was 6.6 mmol/L (50.2 mg/dL, sensitivity 96.9%, specificity 62.7%). The glycolate concentration best predicting mortality was 19.6 mmol/L (149.0 mg/dL, sensitivity 61.1%, specificity 81.4%, positive predictive value 33.3%, negative predictive value 93.2%). The glycolate concentration threshold for a 100% negative predictive value for mortality was 8.3 mmol/L (63.1 mg/dL, sensitivity 100.0%, specificity 35.6%). The glycolate concentration correlated best with the anion gap ( = 0.73), followed by bicarbonate ( = 0.57), pH ( = 0.50) and then base excess ( = 0.25), while there was no correlation between the glycolate and ethylene glycol concentration ( = 0.00). These data can assist clinicians in planning treatments such as extracorporeal treatments and prognostication. Potentially, they may also provide some reassurance regarding when extracorporeal treatments can be delayed while awaiting the results of further testing in patients in whom ethylene glycol poisoning is suspected but not yet confirmed.
This systematic review demonstrates that the glycolate concentration predicts mortality (unlikely if <8 mmol/L [61 mg/dL]). The anion gap is a reasonable surrogate measurement for glycolate concentration in the context of ethylene glycol poisoning. The findings are mainly based on published retrospective data which have various limitations. Further prospective validation studies are of interest.
乙二醇中毒表现为代谢性酸中毒、急性肾损伤和死亡。诊断和治疗取决于病史和生化检查。乙醇酸是一种关键的毒性代谢产物，会影响预后，但在临床有用的时间内，其检测结果并不广泛。我们定量评估了血清乙醇酸浓度对预后的影响，并评估了是否有更容易获得的生化检测可以替代乙醇酸浓度。
本研究的目的是：1）评估初始乙醇酸浓度对乙二醇暴露患者发生急性肾损伤或死亡的预后价值；2）确定与乙醇酸浓度相关性最好的替代标志物。
使用 Medline/PubMed、EMBASE、Cochrane 图书馆、会议记录和参考文献列表进行文献系统回顾。符合条件的研究是报告测量的乙醇酸浓度的人体研究。将乙醇酸浓度与分类临床结局（急性肾损伤、死亡率）相关联，并与连续替代生化测量（阴离子间隙、碱剩余、碳酸氢盐浓度和 pH 值）相关联。构建受试者工作特征曲线，以计算预测急性肾损伤和死亡率的阈值乙醇酸浓度的阳性预测值和阴性预测值。此外，还确定了死亡率 100%阴性预测值和急性肾损伤 95%阴性预测值所对应的乙醇酸浓度。
从 1531 篇文章中，有 655 篇可能符合条件，32 篇被纳入，反映了 133 名患者中的 137 例病例用于预后研究，150 名患者中的 154 例用于替代研究。中位数乙醇酸浓度为 11.2mmol/L（85.1mg/dL，范围 0-38.0mmol/L，0-288.8mg/dL），93%的患者接受了解毒剂治疗，80%接受了体外治疗，49%发生了急性肾损伤，13%死亡。预测急性肾损伤的最佳乙醇酸浓度为 12.9mmol/L（98.0mg/dL，敏感性 78.5%，特异性 88.1%，阳性预测值 86.4%，阴性预测值 80.9%）。预测急性肾损伤的 95%阴性预测值的乙醇酸浓度阈值为 6.6mmol/L（50.2mg/dL，敏感性 96.9%，特异性 62.7%）。预测死亡率的最佳乙醇酸浓度为 19.6mmol/L（149.0mg/dL，敏感性 61.1%，特异性 81.4%，阳性预测值 33.3%，阴性预测值 93.2%）。死亡率 100%阴性预测值的乙醇酸浓度阈值为 8.3mmol/L（63.1mg/dL，敏感性 100.0%，特异性 35.6%）。乙醇酸浓度与阴离子间隙相关性最好（ = 0.73），其次是碳酸氢盐（ = 0.57）、pH 值（ = 0.50）和碱剩余（ = 0.25），而乙醇酸与乙二醇浓度之间无相关性（ = 0.00）。这些数据可以帮助临床医生计划治疗，如体外治疗和预后。潜在地，它们还可以在怀疑但尚未确诊乙二醇中毒的患者中，在等待进一步检测结果的同时，为何时可以延迟体外治疗提供一些保证，因为这些检测结果不太可能在 8mmol/L[61mg/dL]以下。
本系统综述表明，乙醇酸浓度可预测死亡率（<8mmol/L[61mg/dL]时不太可能）。阴离子间隙是乙二醇中毒情况下乙醇酸浓度的合理替代测量值。这些发现主要基于已发表的回顾性数据，这些数据存在各种局限性。进一步的前瞻性验证研究很有意义。
