Thiamine Administration Research Articles

Relationship between lactate and thiamine-responsive disorders in hospitalised infants and children in Lao PDR: secondary analysis of a prospective cohort study

ABSTRACT Background Lactate is a by-product of thiamine-deficient cellular metabolism, and hyperlactataemia can indicate severe illness. However, little is known about the clinical significance of hyperlactataemia in thiamine deficiency disorders. Aim To describe the relationship between whole-blood lactate level and thiamine-responsive disorders (TRDs) in children with signs/symptoms of thiamine deficiency in a high-risk region. Methods This is a secondary analysis of data from the Lao Thiamine study, a prospective cohort study which enrolled hospitalised infants and children (aged 21 days to <18 months) who had at least one sign or symptom suggestive of thiamine deficiency in Lao PDR. Therapeutic thiamine was administered, and clinical evaluations were completed at several time-points over the next 72 h. Three paediatricians reviewed individual case reports to evaluate clinical response to thiamine and assigned TRD status. Data from 402 children were analysed by logistic regression and predictive modelling to examine the relationship between hyperlactataemia and TRDs. Results Baseline hyperlactataemia (lactate >4.0 mmol/L) was associated with an increased odds of clinical improvement after thiamine administration [OR (95% CI) 2.32 (1.28–4.45), p = 0.007]. Baseline hyperlactataemia was a significant predictor of thiamine deficiency (thiamine diphosphate <40 nmol/L) [area under the receiver operating curve (95% CI) 0.76 (0.67–0.84), p < 0.001], and increased odds of mortality [OR (95% CI) 3.51 (1.38–8.94), p = 0.009]. Conclusions In children with signs/symptoms of thiamine deficiency, hyperlactataemia is associated with a favourable clinical response to thiamine, biochemical thiamine deficiency, and increased odds of mortality. Lactate may be useful in identifying children who might benefit from therapeutic thiamine.

Cellular oxygen consumption in patients with diabetic ketoacidosis

BackgroundDiabetic ketoacidosis (DKA) is a potentially life-threatening disorder associated with severe alterations in metabolism and acid–base status. Mitochondrial dysfunction is associated with diabetes and its complications. Thiamine and coenzyme Q10 (CoQ10) are important factors in aerobic metabolism. In this study, we measured cellular oxygen consumption rates (OCRs) and the effects of in vitro administration of thiamine and CoQ10 on OCRs in patients with DKA versus healthy controls.MethodsBlood samples were collected from a prospective cohort of patients with DKA and from controls. Cellular OCRs were measured in peripheral blood mononuclear cells (PBMC) without treatment and after treatment with thiamine, CoQ10, or both. The mitochondrial profile was measured using an XFe96 Extracellular Flux Analyzer and XF Cell Mito Stress Test Kit (Seahorse Bioscience). A linear quantile mixed model was used to compare OCRs and estimate treatment effects.ResultsA total of 62 patients with DKA and 48 controls were included in the study. The median basal and maximal OCRs were lower in the DKA group than in the control group (basal: 4.7 [IQR: 3.3, 7.9] vs. 7.9 [5.0, 9.5], p = 0.036; maximal: 16.4 [9.5, 28.1] vs. 31.5 [20.6, 46.0] pmol/min/µg protein, p < 0.001). In DKA samples, basal and maximal OCRs were significantly increased when treated with thiamine, CoQ10, or both. In controls, basal and maximal OCR were significantly increased only with thiamine treatment.ConclusionMitochondrial metabolic profiles of patients with DKA demonstrated lower cellular oxygen consumption when compared to healthy controls. Oxygen consumption increased significantly in cells of patients with DKA treated with thiamine or CoQ10. These results suggest that thiamine and CoQ10 could potentially have therapeutic benefits in DKA via their metabolic effects on mitochondrial cellular respiration.

Antepartum Wernicke’s Encephalopathy: Common, and Yet Rarely Diagnosed. Discussion on the Disease and Its Treatment

This review article presents a comprehensive discussion on antepartum Wernicke’s encephalopathy (WE), a serious neurological disorder. This disorder stems from thiamine (Vitamin B1) deficiency, which is critical for normal metabolism and neuronal integrity. During pregnancy, women are more susceptible to this condition due to increased nutritional requirement and metabolic changes. In WE, inadequate thiamine (Vitamin B1) causes disruption of metabolism in cells and impedes neurotransmitter synthesis in the brain, ultimately causing adverse neural consequences. Key risk factors contributing to antepartum WE include conditions that hinder thiamine absorption or increase metabolic demand, such as hyperemesis gravidarum (intense antepartum vomiting), malnutrition, alcoholism, and post-bariatric surgery states. WE's classic triad of symptoms, confusion, ataxia (loss of balance and coordination), and ophthalmoplegia (occlumotor incoordination), are not commonly seen in antepartum WE. Therefore, diagnosing the disorder in pregnancy is challenging and the condition is often misdiagnosed. Pregnancy symptoms like nausea, vomiting, and fatigue often overlap with WE's presentation, complicating diagnosis and confounding treatment. While magnetic resonance imaging (MRI) can reveal characteristic lesions in brain areas such as the thalamus and mammillary bodies, these may not always appear in early stages, adding further diagnostic difficulty. Effective management of antepartum WE relies on early recognition and timely administration of high-dose thiamine, particularly parenteral administration for affected pregnant women. Prompt treatment is critical to preventing irreversible sequalae, neurological and otherwise in both the woman and the child. Once acute symptoms are managed, transitioning to oral thiamine supplementation is the norm to prevent recurrence and maintain normal thiamine levels. Balanced diet of macro-nutrients and maintaining fluid and electrolyte balance, also plays an essential role in recovery. In severe or treatment-resistant cases, more intensive, prolonged thiamine therapy and regular monitoring of maternal and fetal health are necessary, usually managed by a multidisciplinary medical team. This coordinated care approach aims to prevent recurrence and minimize risks associated with WE. The article emphasizes following clinical guidelines, which recommend regular thiamine monitoring and preventive measures in high-risk pregnancies, to improve maternal and fetal outcomes. By adhering to established protocols, healthcare providers can reduce the likelihood of severe complications associated with WE, ensuring better care and recovery for affected pregnant women. Categories: Pregnancy, Neurology, Nutrition.

The emergence of additional causes of thiamine deficiency in the modern world: The impact of gastric surgery

We present a case of shoshin beriberi with non-specific hyperamylasemia but on a different background of thiamine deficiency. Due to the fulminant of the clinical presentation and the lack of rapid diagnostic tests, shoshin beriberi remains under-diagnosed, particularly among non-alcoholic patients. The present report of presumed shoshin beriberi aims to highlight the emergence of additional causes of thiamine deficiency in the modern world, especially those resulting from esophagogastric surgery, which carries a substantial risk of malnutrition in the medium to long term. The timely administration of thiamine is generally safe and can result in rapid improvement, making it both a valuable therapeutic and diagnostic tool.

Thiamine deficiency as a differential diagnosis for severe fatigue in terminally ill cancer patients.

Patients with advanced cancer present various symptoms as their disease progresses. Among these, fatigue is a frequent symptom in patients with advanced cancer and is associated with decreased quality of life (QOL). However, there are few reports regarding its association with thiamine deficiency (TD). We report a case in which we found TD in a patient with advanced lung cancer who presented with weight loss, significant fatigue, and appeared to have a worsening general condition, for whom symptoms were dramatically improved within a short period of time by intravenous administration of thiamine. The patient was a 76-year-old woman who had been diagnosed with lung cancer and liver metastases 6 months earlier. Due to interstitial pneumonia, she was not a candidate for chemotherapy and so palliative care was started. At 8 months after initial diagnosis, the patient complained of fatigue during a medical examination, so a blood sample was taken. A week later, she visited the hospital with a cane. She felt extremely fatigued and was unable to stand, but results from the previous blood test revealed that a TD. The fatigue disappeared 15 minutes after intravenous administration of thiamine and she was able to return home without the cane. Fatigue is a frequent symptom in advanced cancer patients, and TD may be the underlying cause. Inclusion of TD in the differential diagnosis may contribute to improving patient QOL.

Clinical evidence of low-calorie and ketogenic nutrological therapy before, during and after bariatric surgery: a systematic review

Introduction: Obesity is a multifactorial disease that causes serious comorbidities. There are more than 2.2 billion overweight and obese people in the world. Obese patients tend to be predisposed to micronutrient deficiency even before bariatric surgery, therefore, it is imperative to supplement nutrients orally, enterally, or parenterally, according to the indications of each patient. Objective: It was highlighted the importance of low-calorie and ketogenic nutritional therapy before, during, and after bariatric surgery through the systematic analysis of clinical studies. Methods: The systematic review rules of the PRISMA Platform were followed. The search was conducted from June to July 2024 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: 119 articles were found. A total of 40 articles were fully evaluated and 34 were included and developed in the present systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 23 studies with a high risk of bias and 27 that did not meet GRADE and AMSTAR-2. Most studies presented homogeneity in their results, with X2=76.5%&gt;50%. It was concluded that nutrological therapy strategies could represent a possible alternative to other methodologies, especially when it is recommended to improve patient adherence to following the prescribed diet before bariatric surgery. Weight loss induced by the ketogenic diet before bariatric surgery has beneficial effects on reducing liver volume, metabolic profile, and intra- and postoperative complications. Knowledge of the type of bariatric surgery performed and an understanding of its anatomy and physiology are useful to provide optimal care to patients, especially in nutritional complications. Nutritional deficiencies and metabolic disorders result from “malabsorption” procedures such as RYGB. Immediate administration of thiamine is essential. Dextrose should be avoided in intravenous hydration until thiamine is adequately replaced. For all bariatric patients, a protein intake of 60-70 g/d and a multivitamin with iron and vitamin B12 supplementation is recommended. Daily calcium and vitamin D supplementation is also encouraged. In addition, serum micronutrient levels should be monitored regularly and additional supplementation should be prescribed as indicated.

Wernicke Encephalopathy Associated with Hyperemesis Gravidarum: A Case Report

Introduction: Wernicke encephalopathy is a clinical diagnosis that requires a high degree of clinical suspicion to recognize. We report a case of a pregnant patient developing Wernicke encephalopathy in the setting of severe hyperemesis gravidarum. Case Report: The patient was a 22-year-old female 13 weeks pregnant presenting to the emergency department (ED) with neurological deficits after several weeks of hyperemesis gravidarum requiring hospitalization. Exam and workup ultimately revealed the diagnosis of Wernicke encephalopathy. Her symptoms improved after administration of thiamine. Conclusion: Wernicke encephalopathy is a consequence of thiamine deficiency, commonly seen in patients with alcohol use disorder but also with other causes of nutritional deficiency, such as hyperemesis gravidarum. Wernicke encephalopathy is a clinical diagnosis that requires a high degree of suspicion and is, therefore, often missed in the ED setting. Treatment is supplemental thiamine and management of the root cause for nutritional deficiency.

Pharmacological Doses of Thiamine Benefit Patients with the Charcot-Marie-Tooth Neuropathy by Changing Thiamine Diphosphate Levels and Affecting Regulation of Thiamine-Dependent Enzymes.

Charcot-Marie-Tooth (CMT) neuropathy is a polygenic disorder of peripheral nerves with no effective cure. Thiamine (vitaminB1) is a neurotropic compound that improves neuropathies. Our pilot study characterizes therapeutic potential of daily oral administration of thiamine (100mg) in CMT neuropathy and its molecular mechanisms. The patient hand grip strength was determined before and after thiamine administration along with the blood levels of the thiamine coenzyme form (thiamine diphosphate, ThDP), activities of endogenous holo-transketolase (without ThDP in the assay medium) and total transketolase (with ThDP in the assay medium), and transketolase activation by ThDP [1-(holo-transketolase/total transketolase),%], corresponding to the fraction of ThDP-free apo-transketolase. Single cases of administration of sulbutiamine (200mg) or benfotiamine (150mg) reveal their effects on the assayed parameters within those of thiamine. Administration of thiamine or its pharmacological forms increased the hand grip strength in the CMT patients. Comparison of the thiamin status in patients with different forms of CMT disease to that of control subjects without diagnosed pathologies revealed no significant differences in the average levels of ThDP, holo-transketolase, or relative content of holo and apo forms of transketolase. However, the regulation of transketolase by thiamine/ThDP differed in the control and CMT groups: in the assay, ThDP activated transketolase from the control individuals, but not from CMT patients. Thiamine administration paradoxically decreased endogenous holo-transketolase in CMT patients; this effect was not observed in the control group. Correlation analysis revealed sex-specific differences in the relationship between the parameters of thiamine status in both the control subjects and patients with the CMT disease. Thus, our findings link physiological benefits of thiamine administration in CMT patients to changes in their thiamine status, in particular, the blood levels of ThDP and transketolase regulation.

Wernicke encephalopathy

Introduction: Wernicke’s encephalopathy is a life-threatening disease caused by thiamine deficiency with the development of damage to brain. Objective: to analyze the etiological factors, clinical, laboratory and instrumental data, as well as clinical outcomes of Wernicke’s encephalopathy.Material and мethods: the study included 36 patients with Wernicke’s encephalopathy. the average age of patients was 54.5 ± 15.9 years, women were 52.8%, men — 47.2%.Results: the most common causes of Wernicke’s encephalopathy were long-term alcohol abuse and diseases of the gastrointestinal tract or liver. A decrease in the level of wakefulness was detected in 63.9% of patients at the onset of the disease and in 72.2% during the entire period of hospitalization. In all patients, MRI of the brain revealed symmetrical areas of increased signal in the T2 FLAIR and DWI modes in the medial parts of both thalami, and in some cases also in the area of the quadrigeminal plate and/or periaqueductal space of the midbrain.Conclusion. Assessment of blood thiamine levels is not mandatory before starting therapy; thiamine administration should be started without laboratory confirmation of deficiency. Preventive administration of thiamine at a dose of 1000 mg per day is justified for any clinical suspicion of Wernicke’s encephalopathy.

Assessment of Erythrocyte Transketolase, Whole Blood Thiamine Diphosphate, and Human Milk Thiamine Concentrations to Identify Infants and Young Children Responding Favorably to Therapeutic Thiamine Administration: Findings from the Lao Thiamine Study, a Prospective Cohort Study

BackgroundThere is limited information on relationships among biomarkers of thiamine status (whole blood thiamine diphosphate [ThDP], erythrocyte transketolase activity coefficient [ETKac], and human milk thiamine [MTh]) and clinical manifestations of thiamine deficiency. ObjectivesThis study aimed to explore correlations among these biomarkers and thiamine responsive disorders (TRDs), a diagnosis based on favorable clinical response to thiamine. MethodsHospitalized infants and young children (aged 21 d to <18 mo) with respiratory, cardiac, and/or neurological symptoms suggestive of thiamine deficiency were treated with parenteral thiamine (100 mg daily) for ≥3 d alongside other treatments and re-examined systematically. Clinical case reports were reviewed by 3 pediatricians, who determined TRD or non-TRD status. Children in a community comparison group were matched by age, sex, and residence. Venous whole blood ThDP and MTh were determined by high-performance liquid chromatography fluorescence detection and ETKac in washed erythrocytes by ultraviolet spectrophotometry. Associations between biomarkers were assessed using Spearman correlations, and biomarker cutoffs predictive of TRD and ETKac >1.25 were explored using area under the receiver operating characteristic curve framework. ResultsThiamine biomarkers were available for 287 hospitalized children and 228 community children (mean age 4.7 mo; 59.4% male). Median (interquartile range [IQR]) ThDP and ETKac were 66.9 nmol/L (IQR: 41.4, 96.9 nmol/L) and 1.25 nmol/L (IQR: 1.11, 1.48 nmol/L), respectively, among hospitalized children, and 64.1 nmol/L (IQR: 50.0, 85.3 nmol/L) and 1.22 nmol/L (IQR: 1.12, 1.37 nmol/L) among 228 community children (P > 0.05 for both). Forty-five percent of breastfeeding mothers of infants <6 mo had MTh <90 μg/L. ThDP and ETKac, but not MTh, were significantly different between 152 children with TRD and 122 without TRD, but overlapping distributions undermined prediction of individual responses to thiamine. ConclusionsAlthough ETKac, ThDP, and MTh are useful biomarkers of population thiamine status, none of the biomarkers reliably identified individual children with TRD. ThDP is more practical for population assessment because preparing washed erythrocytes is not required.This trial was registered at clinicaltrials.gov as NCT03626337.

From wernicke-korsakoff to central pontine myelinolysis: the potentially irreversible risks of alcohol use

Introduction Sustained alcohol intake, when combined with incomplete treatment, can result in chronic structural changes in the Central Nervous System, including generalized cortical and cerebellar atrophy, amnesic syndromes like Korsakoff’s syndrome, and white matter disorders such as Central Pontine Myelinolysis and Marchiafava-Bignami syndrome. It is crucial to prevent these complications due to their potential for irreversible and debilitating consequences. For Wernicke-Korsakoff syndrome, early recognition and thiamine administration for prevention are paramount, as it arises from thiamine deficiency due to malnutrition caused by persistent alcohol use. In the case of Central Pontine Myelinolysis, which is caused by abrupt fluctuations in serum osmolality, controlled sodium correction is essential.ObjectivesThrough a clinical case and a review of published literature, this study aims to reflect on the importance of preventing neurological injuries associated with chronic alcohol consumption, specifically Wernicke-Korsakoff Syndrome and Central Pontine Myelinolysis.Methods A literature review was conducted by searching for articles on PubMed using the terms “Alcohol Use Disorder,” “Wernicke-Korsakoff syndrome,” and “Central pontine myelinolysis.” A clinical case is presented, featuring a 50-year-old patient with alcohol use disorder who developed Wernicke-Korsakoff syndrome and Central Pontine Myelinolysis. Considering this case, we reflect on the primary approaches that could have been beneficial in preventing these complications and propose a straightforward method for doing so.Results A 50-year-old patient presented with poor general condition, characterized by low weight, significant loss of strength in the limbs and arms, and incoherent speech with anterograde amnesia and confabulation. This condition had progressed to a point where the patient could no longer walk, perform basic self-care tasks such as bathing, dressing, and eating independently, underscoring the severity of his condition. The diagnoses of Wernicke-Korsakoff syndrome and Central Pontine Myelinolysis were established based on clinical manifestations and the presence of hyperintense lesions observed in the central pons on T2/FLAIR axial MRI scans. This clinical case highlights the importance of proper and precocious prevention of complications in patients with alcohol use disorder. The foremost step in preventing these complications is to treat alcohol dependence effectively, even when faced with patient resistance. It’s vital to remain vigilant about potential complications and implement suitable prophylactic measures.ConclusionsThe devastating effects of complications arising from Alcohol Use Disorder, such as Wernicke-Korsakoff syndrome and Central Pontine Myelinolysis, underscore the importance of enhanced attention that clinicians should provide when approaching these patients at all clinical interactions.Disclosure of InterestNone Declared

Thiamine administration in septic shock: a post hoc analysis of two randomized trials

BackgroundThis is a post hoc analysis of combined cohorts from two previous Phase II clinical trials to assess the effect of thiamine administration on kidney protection and mortality in patients with septic shock.MethodsPatient-level data from the Thiamine in Septic Shock Trial (NCT01070810) and the Thiamine for Renal Protection in Septic Shock Trial (NCT03550794) were combined in this analysis. The primary outcome for the current study was survival without the receipt of renal replacement therapy (RRT). Analyses were performed on the overall cohort and the thiamine-deficient cohort (thiamine < 8 nmol/L).ResultsTotally, 158 patients were included. Overall, thiamine administration was associated with higher odds of being alive and RRT-free (adjusted odds ratio [aOR]: 2.05 [95% confidence interval (CI) 1.08–3.90]) and not needing RRT (aOR: 2.59 [95% CI 1.01–6.62]). In the thiamine-deficient group, thiamine administration was associated with higher odds of being alive and RRT-free (aOR: 8.17 [95% CI 1.79–37.22]) and surviving to hospital discharge (aOR: 6.84 [95% CI 1.54–30.36]). There was a significant effect modification by baseline thiamine deficiency for alive and RRT-free (interaction, p = 0.016) and surviving to hospital discharge (p = 0.019).ConclusionIn the combined analysis of two previous randomized trials, thiamine administration was associated with higher odds of being alive and RRT-free at hospital discharge in patients with septic shock. This signal was stronger in patients with thiamine deficiency.

Thiamine as adjunctive therapy for diabetic ketoacidosis (DKAT) trial protocol and statistical analysis plan: a prospective, single-centre, double-blind, randomised, placebo-controlled clinical trial in the USA

IntroductionDiabetic ketoacidosis (DKA) is a potentially life-threatening diabetic complication. Despite the high prevalence of DKA and the substantial associated healthcare burden, limited research on strategies to improve outcomes currently exists.Thiamine...

Successful use of intravenous and oral levetiracetam in a goat to control refractory seizures secondary to suspected polioencephalomalacia.

To assess the clinical efficacy and plasma concentrations of levetiracetam in a goat with seizures. A 5-month-old doeling. The goat was referred because of progressive anorexia and lethargy over 3 days. Clinical signs consisted of weakness, obtundation, opisthotonos, anisocoria, and cortical blindness. Initial evaluation was most consistent with polioencephalomalacia. Neurologic improvement occurred within 4 hours of thiamine administration, with appetite returning over 12 hours. On day 3 of hospitalization, the goat suffered acute onset repetitive seizures that were incompletely responsive to standard interventions over 3 hours. Administration of IV levetiracetam (60 mg/kg) produced resolution of seizure activity within 20 minutes. Levetiracetam was continued twice daily IV, then PO after day 6. Plasma concentrations were above or within therapeutic ranges (5 to 45 μg/mL) as previously established for other species, following both IV and PO levetiracetam. Oral administration (60 mg/kg, PO, q 12 h) resulted in plasma levetiracetam concentrations of 48.1 μg/mL 2 hours after a dose and 23.4 μg/mL 2 hours prior to the next dose. Levetiracetam is a newer anticonvulsant commonly used in humans and small animals due to its efficacy, cost, and wide safety margin. Its use has not previously been reported in domestic small ruminants. In this case, levetiracetam showed excellent clinical efficacy in the face of refractory seizures, with no apparent side effects. Plasma concentrations during oral administration were at the high end of the therapeutic range, indicating absorption in a nonmonogastric species. Further studies are warranted to determine optimal dosing in small ruminants.

Traversing Antepartum Wernicke’s Encephalopathy: In-Depth Insights and Strategies

Antepartum Wernicke’s encephalopathy (WE) is a severe neurological disorder caused by a deficiency of thiamine (Vitamin B1), essential for glucose metabolism, and neuronal function. This review aims to provide an in-depth analysis of WE during pregnancy, highlighting its pathophysiology, risk factors, clinical presentation, diagnostic challenges, and management strategies. Thiamine is critical in the Krebs cycle and neurotransmitter production, and its deficiency leads to substantial biochemical disruptions and neuronal damage. Pregnant women are particularly susceptible due to their increased nutritional demands to support fetal growth and maternal metabolic changes, making them prone to thiamine deficiency and its severe neurological consequences. The clinical manifestations of WE include ophthalmoplegia, ataxia, confusion or altered mental state, peripheral neuropathy, and cardiovascular issues. Diagnosing WE during pregnancy is challenging due to its atypical presentation, requiring a high degree of clinical suspicion and awareness of risk factors. Diagnostic limitations include variable clinical symptoms and challenges in interpreting serum thiamine levels and neuroimaging findings. While neuroimaging can show characteristic brain lesions, its utility is limited by variability. Managing WE during pregnancy requires prompt recognition, immediate thiamine supplementation, continued supportive measures, and careful monitoring. Severe or refractory cases may require advanced management strategies. Pharmacological treatments include standardized thiamine administration protocols, guided by clinical guidelines and recommendations. Early detection and management of WE in pregnant women are vital to prevent irreversible neurological damage and improve maternal and fetal outcomes. Adherence to clinical guidelines is crucial to mitigate the impact of this condition.

Effect of adjuvant thiamine and ascorbic acid administration on the neurologic outcomes of out-of-hospital cardiac arrest patients: A before-and-after study

AimThis study aimed to evaluate the impact of early thiamine and ascorbic acid administration on the neurologic outcome in out-of-hospital cardiac arrest (OHCA) patients treated with targeted temperature management (TTM). MethodsThis before-and-after cohort study used data extracted from two hospitals of the Korean Hypothermia Network prospective registry. The treatment group incorporated patients enrolled from December 2019 to May 2021, that received intravenous thiamine (200 mg) and ascorbic acid (3 g) at 12-hour intervals for a total of six doses. The control group incorporated those enrolled from May 2018 to November 2019. The one-month good neurologic outcome, defined as a Cerebral Performance Category score ≤ 2, between the groups was evaluated using inverse probability of treatment weighting (IPTW). ResultsAmong the 234 OHCA survivors with TTM, 102 were included in the treatment group and 132 were included in the control group. The one-month (31.4 % vs. 29.5 %, respectively; P = 0.76) good neurologic outcome rates did not differ between the treatment and control groups. After adjusting using the IPTW, vitamin supplementation was not associated with good neurologic outcome (odds ratio [OR], 1.134; 95 % confidence interval [CI], 0.644–1.999; P = 0.66). In subgroup analysis, vitamin administration was significantly associated with a good neurologic outcome in older (≥65 years) patients (adjusted OR, 5.53; 95 % CI, 1.21–25.23; P = 0.03). ConclusionAdjuvant thiamine and ascorbic acid administration in OHCA survivors with TTM did not improve their neurologic outcome after one month. Further clinical trials are warranted.

An Overview of Type B Lactic Acidosis Due to Thiamine (B1) Deficiency.

Type B lactic acidosis can occur secondary to several factors, including thiamine deficiency, and is not as common as type A. Recognizing thiamine deficiency-associated lactic acidosis is challenging because serum thiamine concentrations are not routinely obtained, and a thorough and specific history is necessary for clinicians to suspect thiamine deficiency as a root cause. Furthermore, the appropriate dose and duration of thiamine treatment are not well defined. Untreated thiamine deficiency-associated lactic acidosis can lead to critical illness requiring lifesaving extracorporeal therapies. Additionally, if thiamine and glucose are not administered in an appropriate sequence, Wernicke encephalopathy or Korsakoff syndrome may occur. This review aims to summarize therapeutic treatment for thiamine deficiency-associated lactic acidosis, based on case reports/series and nutritional guidance. After a literature search of the PubMed database, 63 citations met inclusion criteria, of which 21 involved pediatric patients and are the focus of this review. -Citations describe dosing regimens ranging from 25 to 1000 mg of intravenous (IV) thiamine as a single dose, or multiple daily doses for several days. Specific guidance for critically ill adults recommends a thiamine range of 100 mg IV once daily to 400 mg IV twice daily. Although there are no specific recommendations for the pediatric population, given the relative safety of thiamine administration, its low cost, and our review of the literature, treatment with thiamine 100 to 200 mg IV at least once is supported, with ongoing daily doses based on clinical response of the patient, regardless of age.

Treatment variability and its relationships to outcomes among patients with Wernicke's encephalopathy: A multicenter retrospective study

BackgroundDespite guidelines and recommendations, Wernicke's encephalopathy (WE) treatment lacks evidence, leading to clinical practice variability. AimsGiven the overall lack of information on thiamine use for WE treatment, we analyzed data from a large, well-characterized multicenter sample of patients with WE, examining thiamine dosages; factors associated with the use of different doses, frequencies, and routes; and the influence of differences in thiamine treatment on the outcome. MethodsThis retrospective study was conducted with data from 443 patients from 21 centers obtained from a nationwide registry of the Spanish Society of Internal Medicine (from 2000 to 2012). Discharge codes and Caine criteria were applied for WE diagnosis, and treatment-related (thiamine dosage, frequency, and route of administration) demographic, clinical, and outcome variables were analyzed. ResultsWe found marked variability in WE treatment and a low rate of high-dose intravenous thiamine administration. Seventy-eight patients out of 373 (20.9%) received > 300mg/day of thiamine as initial dose. Patients fulfilling the Caine criteria or presenting with the classic WE triad more frequently received parenteral treatment. Delayed diagnosis (after 24h hospitalization), the fulfillment of more than two Caine criteria at diagnosis, mental status alterations, and folic acid deficiency were associated significantly with the lack of complete recovery. Malnutrition, reduced consciousness, folic acid deficiency, and the lack of timely thiamine treatment were risk factors for mortality. ConclusionsOur results clearly show extreme variability in thiamine dosages and routes used in the management of WE. Measures should be implemented to ensure adherence to current guidelines and to correct potential nutritional deficits in patients with alcohol use disorders or other risk factors for WE.

Thiamine administration may increase survival benefit in critically ill patients with myocardial infarction.

Myocardial infarction (MI) is a common cardiovascular disease (CVD) in critically ill patients, leading to 17% mortality in the intensive care unit (ICU) setting. Patients with CVD frequently suffer from thiamine insufficiency, thereby thiamine supplements may be helpful. Unfortunately, the relationship between thiamine treatment and survival outcomes in ICU patients with MI is still unknown. The purpose of the research is to demonstrate the survival advantage of thiamine application in these patients. The Medical Information Mart of Intensive Care-IV database served as the foundation for this retrospective cohort analysis. Depending on whether patients were given thiamine therapy during the hospital stay, critically ill MI patients were split into the thiamine and non-thiamine groups. The Kaplan-Meier (KM) method and Cox proportional hazard models were used to evaluate the relationship between thiamine use and the risk of in-hospital, 30-day, and 90-day mortality. To validate the results, a 1:2 closest propensity-score matching (PSM) was also carried out. This study included 1782 patients for analysis with 170 and 1,612 individuals in the thiamine and non-thiamine groups, respectively. The KM survival analyses revealed that the risk of in-hospital, 30-day, and 90-day mortality was significantly lower in the thiamine group than the none-thiamine group. After modifying for a variety of confounding factors, the Cox regression models demonstrated substantial positive impacts of thiamine use on in-hospital, 30-d, and 90-d mortality risk among critically ill patients with MI with hazard ratio being 0.605 [95% confidence interval (CI): 0.397-0.921, p = 0.019], 0.618 (95% CI: 0.398-0.960, p = 0.032), and 0.626 (95% CI: 0.411-0.953, p = 0.028), respectively, in the completely modified model. PSM analyses also obtained consistent results. Thiamine supplementation is related to a decreased risk of mortality risk in critically ill patients with MI who are admitted to the ICU. More multicenter, large-sample, and well-designed randomized controlled trials are needed to validate this finding.

THIAMINE AND HIGH DOSE INSULIN TREATMENT FOR SEPSIS

Sepsis is a major health problem and accounts for 20% of deaths worldwide. It is the most expensive condition treated in United States hospitals at $62 billion per year or about $46,000 per patient. Treatment consisting largely of fluid resuscitation and antibiotics has only a marginal impact. Mortality is about 27% for hospitalised patients and about 42% for patients in intensive care. There are two phases of sepsis – a hyperinflammatory phase and a subsequent hypoinflammatory phase. During the hyperinflammatory phase, the metabolic rate increases, and this is associated with an increase in body temperature and a rapid escalation of immune system functioning including increased numbers of leucocytes and their migration to infected and damaged tissues and increased supply and consumption of glucose to fuel this immune system. During the subsequent hypoinflammatory phase, the metabolic rate decreases, and this is associated with a decrease in body temperature and a generalised decrease in the physiological activity of many organs including the immune system akin to hibernation. The activated immune system has priority for the available glucose over most other organs and physiological functions during such potentially life-threatening circumstances. Thus, adenosine triphosphate (ATP) production by mitochondria (the source of energy at the cellular level for the organism as a whole) also has a lower priority for the available glucose relative to the activated immune system. If glucose availability is threatened, then the mitochondrial production of ATP is partially or substantially suppressed in favour of glycolysis because glycolysis can rapidly produce large quantities of ATP that are necessary for immune cell function in infected, anaerobic, ischaemic, or damaged tissues. However, glycolysis is only a temporary fix as it cannot produce the quantities of ATP necessary on an ongoing basis for the normal functioning of the healthy animal. Mitochondrial production of ATP must be recommenced for full recovery. It appears that the partial or substantial suppression of mitochondrial production of ATP by activation of the immune response becomes relatively fixated in some patients, leading to a substantial ATP deficit. This is the fundamental issue of sepsis. This paper reviews the metabolism of glucose and insulin during sepsis and concludes that high dose insulin with mild hyperglycaemia in conjunction with the intravenous administration of thiamine, an inhibitor of the pyruvate dehydrogenase kinase enzymes, to re-establish physiological ATP production by mitochondria, administered early in the hypometabolic (hypoinflammatory) phase of sepsis, may enhance survival relative to thiamine alone.