Randomised trial of intravenous thiamine and/or magnesium sulphate administration on erythrocyte transketolase activity, lactate concentrations and alcohol withdrawal scores

Abstract

Alcohol withdrawal syndrome (AWS) occurs in 2% of patients admitted to U.K. hospitals. Routine treatment includes thiamine and benzodiazepines. Laboratory studies indicate that thiamine requires magnesium for optimal activity, however this has not translated into clinical practice. Patients experiencing AWS were randomized to three groups: (group 1) thiamine, (group 2) thiamine plus MgSO4 or (group 3) MgSO4. Pre- and 2-h post-treatment blood samples were taken. AWS severity was recorded using the Glasgow Modified Alcohol Withdrawal Score (GMAWS). The primary outcome measure was 15% change in erythrocyte transketolase activity (ETKA) in group 3. Secondary outcome measures were change in plasma lactate concentrations and time to GMAWS = 0. 127 patients were recruited, 115 patients were included in the intention-to-treat analysis. Pre-treatment, the majority of patients had normal or high erythrocyte thiamine diphosphate (TDP) concentrations (≥ 275–675/> 675 ng/gHb respectively) (99%), low serum magnesium concentrations (< 0.75 mmol/L) (59%), and high plasma lactate concentrations (> 2 mmol/L) (67%). Basal ETKA did not change significantly in groups 1, 2 or 3. Magnesium deficient patients (< 0.75 mmol/L) demonstrated less correlation between pre-treatment basal ETKA and TDP concentrations than normomagnesemic patients (R2 = 0.053 and R2 = 0.236). Median plasma lactate concentrations normalized (≤ 2.0 mmol/L) across all three groups (p < 0.001 for all groups), but not among magnesium deficient patients in group 1 (n = 22). The median time to achieve GMAWS = 0 for groups 1, 2 and 3 was 10, 5.5 and 6 h respectively (p < 0.001). No significant difference was found between groups for the primary endpoint of change in ETKA. Co-administration of thiamine and magnesium resulted in more consistent normalization of plasma lactate concentrations and reduced duration to achieve initial resolution of AWS symptoms.ClinicalTrials.gov: NCT03466528.

Protocol and application of basal erythrocyte transketolase activity to improve assessment of thiamine status

“…This was in contrast to the use of ETKac cut‐offs that showed no discrimination between cases and controls 17 . The cut‐off value of 0.59 has since been used in other studies, 18,23,35 but remains unsubstantiated. Soukaloun et al 17 .…”

“…This was in contrast to the use of ETKac cut-offs that showed no discrimination between cases and controls. 17 The cut-off value of 0.59 has since been used in other studies, 18,23,35 but remains unsubstantiated. Soukaloun et al 17 also reported reference ranges of between 0.47 and 0.57 U/gHb for children and women aged between 4 and 49 years and derived from UK NDNS data.…”

“…Other clinical populations studied include diabetics and alcoholics in Poland 16 and, in the UK, patients with chronic fatigue syndrome 45 and alcohol withdrawal syndrome. 23 Study designs vary and do not always include healthy control groups. Bailey et al studied apparently healthy adolescents in the UK and reported a mean basal ETK activity of 0.90 U/gHb.…”

“…20,22 More recent reports of basal ETK activity typically lack detail on how the basal activity was measured and/or calculated. 16,18,23 This inhibits further advances in the field by impeding replication and initiatives to harmonize methods between laboratories.…”

“…Where methods are better described, assumptions used in the calculations are commonly not shown and descriptions assume a degree of understanding that may limit their reproducibility 20,22 . More recent reports of basal ETK activity typically lack detail on how the basal activity was measured and/or calculated 16,18,23 . This inhibits further advances in the field by impeding replication and initiatives to harmonize methods between laboratories.…”