Meropenem as an antidote for intentional valproic acid overdose

Thomas, Caitlin; Priano, James; Smith, Tracey L.

doi:10.1016/j.ajem.2019.09.011

Cited by 22 publications

(27 citation statements)

References 2 publications

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“…Here based on a matched comparative study, we showed that L-carnitine administration was unable to accelerate VPA clearance, speed blood lactate level normalization or limit organ dysfunction. Our findings clearly suggest limiting L-carnitine administration to the most severe VPA-poisoned patients (such as patients with brain edema) and considering alternative therapies that more effectively alter VPA kinetics, such as hemodialysis [ 8 ] or meropemen infusion [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

L-carnitine does not improve valproic acid poisoning management: a cohort study with toxicokinetics and concentration/effect relationships

Nguyên

Chevillard

Gouda

et al. 2022

Ann. Intensive Care

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Background Valproic acid (VPA) poisoning is responsible for life-threatening neurological and metabolic impairments. Despite only low-level evidence of effectiveness, L-carnitine has been used for years to prevent or reverse VPA-related toxicity. We aimed to evaluate the effects of L-carnitine used to treat acute VPA poisoning on the time-course of plasma VPA concentrations and VPA-related toxicity. We designed a single-center cohort study including all VPA-poisoned patients admitted to the intensive care unit. We studied VPA toxicokinetics using a nonlinear mixed-effects model-based population approach and modeled individual plasma VPA/blood lactate concentration relationships. Then, we evaluated L-carnitine-attributed effects by comparing VPA elimination half-lives and time-courses of blood lactate levels and organ dysfunction [assessed by the Sequential Organ Failure Assessment (SOFA) score] between matched L-carnitine-treated and non-treated patients using a multivariate analysis including a propensity score. Results Sixty-nine VPA-poisoned patients (40F/29 M; age, 41 years [32–47]) (median [25th–75th percentiles]; SOFA score, 4 [1–6]) were included. The presumed VPA ingested dose was 15 g [10–32]. Plasma VPA concentration on admission was 231 mg/L [147–415]. The most common manifestations were coma (70%), hyperlactatemia (3.9 mmol/L [2.7–4.9]) and hyperammonemia (127 mmol/L [92–159]). VPA toxicokinetics well fitted a one-compartment linear model with a mean elimination half-life of 22.9 h (coefficient of variation, 28.1%). Plasma VPA (C)/blood lactate concentration (E) relationships were well described by an exponential growth equation [$$E={E}_{0}\times {e}^{k\cdot C}$$ E = E 0 × e k · C ; with baseline E0 = 1.3 mmol/L (43.9%) and rate constant of the effect, k = 0.003 L/mg (59.5%)]. Based on a multivariate analysis, peak blood lactate concentration was the only factor independently associated with L-carnitine administration (odds ratio, 1.9, 95% confidence interval, 1.2–2.8; P = 0.004). We found no significant contribution of L-carnitine to enhancing VPA elimination, accelerating blood lactate level normalization and/or preventing organ dysfunction. Conclusions VPA poisoning results in severe toxicity. While L-carnitine does not contribute to enhancing VPA clearance, its impact on accelerating blood lactate level normalization and/or preventing organ dysfunction remains uncertain. Investigating VPA toxicokinetics and concentration/effect relationships may help understanding how to improve VPA-poisoned patient management.

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Section: Discussionmentioning

confidence: 99%

L-carnitine does not improve valproic acid poisoning management: a cohort study with toxicokinetics and concentration/effect relationships

Nguyên

Chevillard

Gouda

et al. 2022

Ann. Intensive Care

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“…Besides the positive effects, there was reported that it has antagonistic effects on the function and development of brain. More so, some of these agents are accompanied liver toxicity, sedation, anxiety, and depression (Auditeau et al., 2019; Elyamany et al., 2020; Thomas, Priano, & Smith, 2020). Antiepileptic drugs are found to cause oxidative damage by increasing free radical production (Obay, Taşdemir, Tümer, Bilgin, & Atmaca, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…sedation, anxiety, and depression (Auditeau et al, 2019;Elyamany et al, 2020;Thomas, Priano, & Smith, 2020). Antiepileptic drugs are found to cause oxidative damage by increasing free radical production (Obay, Taşdemir, Tümer, Bilgin, & Atmaca, 2008).…”

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confidence: 99%

The effects of chard on brain damage in valproic acid‐induced toxicity

2020

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Valproic acid or valproate (VPA; 2-propyl valeric acid)-a branched chain carboxylic acid-is the most commonly used as anticonvulsant medication due to its broad effect on several categories of seizure (Duncan, Sander, Sisodiya, & Walker, 2006). Also, it acts as mood stabilizer, therefore, recommended for borderline personality disorder, schizoaffective disorders, social phobias, bipolar disorders, schizophrenia, and impulse disorders (Haddad, Das, Ashfaq, & Wieck, 2009). Besides the positive effects, there was reported that it has antagonistic effects on the function and development of brain. More so, some of these agents are accompanied liver toxicity,

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“…Toxicity of anticonvulsants and antipsychotics includes central nervous system depression and cardiotoxicity, which are fatal [ 30 , 37 – 41 ]. Some reports stated that meropenem is effective as an antidote for an overdose of sodium valproate [ 42 , 43 ], and an intravenous injection of lipid emulsion is effective in detoxifying cardiotoxicity due to an overdose of quetiapine [ 44 ]. However, neither anticonvulsants nor antipsychotics have a specific antidote, and the treatment is symptomatic.…”

Section: Discussionmentioning

confidence: 99%

Relationship between tracheal intubation and the drugs used by patients with drug overdose due to self-harm

Nagashima

Hosono

Watanabe

2022

J Pharm Health Care Sci

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Background Tracheal intubation may be performed in patients with drug overdose due to self-harm; however, the details of the causative drug are unknown. The purpose of this study was to clarify the relationship between drugs or its blood levels of patients with drug overdose and the need for tracheal intubation based on the actual measurement results. Methods From October 2018 to March 2020, 132 patients with drug overdose due to self-harm who were transported to the emergency department (ED) were studied. Patient drugs were measured using gas chromatography–mass spectrometry (GC-MS) and were analyzed on the basis of the GC/MS Forensic Toxicological Database. Logistic analysis was performed by combining patient information and GC-MS information. Results The Glasgow Coma Scale (GCS) and Japan Coma Scale (JCS) efficiently predicted tracheal intubation in patients with drug overdose during transport triage; GCS (cut-off value: 12, area under the curve (AUC): 0.81, 95% confidence interval (CI): 0.71–0.88, sensitivity: 0.85, specificity: 0.71, P < 0.05) and JCS (cut-off value: 3, AUC: 0.74, 95% CI: 0.60–0.84, sensitivity: 0.60, specificity: 0.84, P < 0.05). The drugs detected in all patients with drug overdose in order were benzodiazepine receptor agonists (BZs; 43.9%), anticonvulsants (38.6%), antipsychotics (25.0%), and antidepressants (9.8%). In univariate logistic analysis, antipsychotics (odds ratio (OR) 2.46, 95% CI 1.19–5.20, P < 0.05), anticonvulsants (OR 2.71, 95% CI 1.26–5.98, P < 0.05), and anticonvulsants above alert blood levels (OR 27.8, 95% CI 2.92–264.1, P < 0.05) were significantly associated with tracheal intubation in patients with drug overdose, but not BZs and antidepressants. Also, in multivariate logistic analysis, antipsychotics (OR 2.27, 95% CI 1.07–4.83, P < 0.05), anticonvulsants (OR 2.50, 95% CI 1.14–5.64, P < 0.05) and in multivariate logistic analysis of blood levels, anticonvulsants above the alert blood levels (OR 24.9, 95% CI 2.56–241.6, P < 0.05) were significantly associated with tracheal intubation in patients with drug overdose respectively. Conclusions Logistic analysis revealed that the use of anticonvulsants and antipsychotics were significantly associated with an increased OR in the tracheal intubation of patients with drug overdose due to self-harm.

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Meropenem as an antidote for intentional valproic acid overdose

Cited by 22 publications

References 2 publications

L-carnitine does not improve valproic acid poisoning management: a cohort study with toxicokinetics and concentration/effect relationships

L-carnitine does not improve valproic acid poisoning management: a cohort study with toxicokinetics and concentration/effect relationships

The effects of chard on brain damage in valproic acid‐induced toxicity

Relationship between tracheal intubation and the drugs used by patients with drug overdose due to self-harm

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