Utility of serum lactate on differential diagnosis of seizure-like activity: A systematic review and meta-analysis

INTRODUCTION: Differentiating epileptic seizures from other causes of Transient Loss of Consciousness (TLOC) remains a challenge in the Emergency Department (ED), where it may lead to erroneous administration of anti-epileptic drugs. Although video electroencephalography (EEG) is the gold standard for diagnosing epileptic seizures, it is not widely available in ED settings. Therefore, simple and quick diagnostic techniques for patients with TLOC in ED are needed. We performed a meta-analysis to review relevant literature and determine the efficacy of serum lactate in differentiating epileptic seizures from other causes of TLOC in the ED setting. METHODS: We performed a literature search of PubMed and Scopus from inception up to April 2022. Randomized trials and observational (prospective or retrospective) studies reporting lactate levels in adults ≤ 3 h after a TLOC episode were included. The primary outcome of interest was the serum lactate level difference between patients with a generalized tonic-clonic seizures (GTCS) and those with other forms of TLOC. Other outcomes were the differences in serum lactate levels among patients with other types of TLOC, such as psychogenic nonepileptic seizures (PNES), syncope, and non-GTCS. Random-effects meta-analysis was performed to compare the mean difference in serum lactate levels among different types of TLOC. The PROSPERO registration is CRD42022316163. RESULTS: We included eight studies (1348 patients) in our analysis. Serum lactate levels from patients who had GTCS were significantly higher than those from patients who had TLOC from any other cause (mean difference 5.27 mmol/L, 95% CI 1.73, 8.81, P = 0.004). Similarly, there was statistically a significant difference in serum lactate between patients with GTCS and non-GTCS (2.96 mmol/L, 95% CI 1.68, 4.24, P = 0.001), and patients with GTCS and syncope (4.29 mmol/L, 95% CI 2.48, 6.10, P = 0.001). However, there was no difference in mean lactate between syncope and PNES, and between syncope and non-GTCS, demonstrating that the serum lactate levels between other forms of TLOC other than GTCS were similar. A serum lactate concentration of 2.4 mmol/L provided a good capability to differentiate between GTCS and non-GTCS, with AUROC ranging from 0.94 - 0.97. CONCLUSION: Serum lactate can be a valuable tool to differentiate GTCS from other forms of TLOC, but it is not valuable in distinguishing non-GTCS types of TLOC from each other. However, lactate level should not be used as an absolute diagnostic tool and should be interpreted along with proper clinical context