High-dose Intravenous Thiamine Research Articles

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.

A STUDY OF THIAMINE DEFICIENCY IN PATIENTS WITH ACUTE ONSETENCEPHALOPATHY

Introduction:Vitamin B1, also known as thiamine, and its crucial role in energy metabolism and proper functioning of the nervous and cardiovascular systems. Thiamine is an essential vitamin that must be obtained through diet since the body does not produce it naturally. It is stored in the liver but only lasts for about 18 days. Thiamine is absorbed in the duodenum and transported across the blood-brain barrier. The recommended daily intake varies based on age, health condition, and life stages.Thiamine plays a vital role in various biochemical pathways in the brain, including energy production, lipid metabolism, neurotransmitter synthesis, and synaptic transmission. Thiamine deficiency can have diverse clinical effects, affecting the nervous and cardiovascular systems most severely and potentially leading to death if left untreated.Different thiamine deficiency syndromes are identified, including dry beriberi (peripheral neurologic manifestations), wet beriberi (cardiac effects), gastrointestinal beriberi (digestive symptoms), and Wernickes encephalopathy (neuropsychiatric condition). While alcohol abuse-associated malnutrition is a common cause of Wernickes encephalopathy in developed countries, it can also occur due to other factors such as decreased thiamine absorption, increased body requirements, or thiamine loss in certain medical conditions.Thiamine deficiency is considered a potential public health concern, particularly in communities in South Asia and West Africa, where diets heavily reliant on polished rice or cassava may contribute to the risk. Studies have shown varying prevalence rates of thiamine deficiency in different populations, including healthy adults and pregnant/lactating mothers in South-East Asia and India. While specific population-based studies are lacking in the Kashmiri population, preliminary evidence suggests the presence of thiamine deficiency disorders in infants, peripartum females, and adults with diverse presentations. Objectives: Early detection and treatment of Patients with Encephalopathy related to Thiamine deficiency Study Design/ Methodology:The study was hospital-based and prospective in nature, conducted in the Department of General Medicine, SMHS, GMC - Srinagar from May 2021 to September 2022. The study was done on patients aged more than 18 years of age attending emergency department of Government Medical College, Srinagar with acute onset encephalopathy. Observations And Results:In this study, 96 patients with acute onset encephalopathy were recruited based on CAM score criteria. The patients were divided into two groups: a low thiamine group and a normal thiamine group, based on their whole-blood thiamine levels. Among the patients, 15.6% had normal thiamine levels, while 84.4% had low thiamine levels. The mean thiamine level in the normal thiamine group was 5.46±4.44 ug/dL, and in the low thiamine group, it was 1.35±0.42 ug/dL (p=0.0001). Patients with normal thiamine levels were excluded from further analysis, leaving a group of 84.4% of patients with thiamine deficiency.Within the thiamine deficiency group, patients were further divided into responders and non-responders based on their response to a thiamine challenge. The responders group comprised 17 patients, including 11 males, 6 females (including 3 pregnant females), with a mean age of 36.25±9.44. Non-responders had a mean age of 61.8±15. Among responders, 70.58% had recurrent vomiting compared to 37.5% in non-responders. Confusion was the most common initial presentation in both groups, followed by lethargy. Behavioural changes were seen in a higher percentage of responders compared to non-responders. Ataxia was more prevalent in the responders group.Various laboratory parameters were analyzed between responders and non-responders. There was no significant difference in mean pH, sodium, potassium, total protein, serum albumin, and blood sugar levels between the two groups. However, lactate levels and the drop in lactate following thiamine therapy were higher in responders. Responders had lower levels of serum urea and serum creatinine compared to non-responders.MRI brain findings suggestive of Wernickes encephalopathy were observed in 53% of responders. Polished rice consumption was common among all patients, with 85% of responders and 62% of non-responders consuming polished rice as their main staple diet. Traditional salt tea intake was also prevalent in both groups. Conclusions: Thiamine deficiency can manifest in various clinical scenarios, including recurrent vomiting, hypoxia, electrolyte imbalances (such as hyponatremia and hypernatremia), and systemic diseases like uremia, hepatic encephalopathy, and septic shock. Pregnant women, who experience increased demand and may have thiamine loss due to vomiting, are also at risk of developing thiamine deficiency.The diagnosis of thiamine deficiency is primarily clinical and is confirmed by the response of neurological signs to high-dose intravenous thiamine treatment. MRI is considered the most valuable paraclinical study for diagnosis. Elevated serum lactate levels and the response of lactate to high-dose parenteral thiamine can serve as surrogate markers for thiamine-responsive encephalopathy. It is crucial to administer high doses of parenteral thiamine immediately to patients suspected of having encephalopathy due to thiamine deficiency to prevent complications associated with Wernicke-Korsakoff syndrome.

A Case of Neural Integrator Failure in Vitamin B1 Deficiency. (P1-9.004)

<h3>Objective:</h3> Case Report <h3>Background:</h3> The nucleus prepositus hypoglossi (NPH) and medial vestibular nuclei (MVN) are two closely related neural integrators situated in the brainstem responsible for horizontal conjugate eye movement. Thiamine deficiency, a hallmark of Wernicke’s encephalopathy, affects the MVN to a greater extent. We report a case of impaired horizontal gaze holding post-sleeve gastrectomy secondary to Vitamin B1 deficiency. <h3>Design/Methods:</h3> A 24-year-old female presented with new onset diplopia on lateral gaze, dizziness, and lower limb distal paraesthesia eight weeks post-sleeve gastrectomy. Examination revealed conjugate eye movements and horizontal gaze-holding failure bilaterally, with intact convergence and vertical gaze. Normal discs were observed on fundoscopy with no retinal haemorrhages, and visual acuity preserved. She had a normal mental state with mild sensory ataxia. Reflexes were present and symmetrical. <h3>Results:</h3> Cerebrospinal fluid analysis was normal, and MRI Brain showed no acute infarction, haemorrhage, or brainstem lesions. Folate, Vitamin B6, B12, and HbA1c levels were within normal range, with a negative infective screen. Vitamin B1 level was found to be low at 44.3nmol/L (normal range: 66.5–200nmol/L). She was commenced on high-dose intravenous thiamine for one week with symptomatic improvement in diplopia and subsequently discharged on long-term thiamine supplementation. <h3>Conclusions:</h3> The high metabolic requirements of MVN neurons responsible for high acceleration horizontal vestibulo-ocular reflex (VOR) is postulated to account for the selective vulnerability to thiamine deprivation. This case highlights an unusual presentation of disruption in horizontal gaze-holding mechanisms through failure of neural integrators, particularly the MVN, in the setting of Vitamin B1 deficiency with preservation of vertical gaze. <b>Disclosure:</b> Dr. Chen has nothing to disclose. Dr. Warfield has nothing to disclose. Dr. Nannery has nothing to disclose. Dr. Togher has nothing to disclose. Dr. Yacoob has nothing to disclose.

Acute Dizziness Treated With Thiamine Supplement: A Case of Wernicke Encephalopathy

Wernicke encephalopathy (WE) is an uncommon but severe neurological disorder caused by thiamine (vitamin B1) deficiency. It is characterized by the sudden onset of altered consciousness, ophthalmoplegia, and ataxia. Apart from chronic alcoholism, a lot of other conditions causing malnutrition and decreasing thiamine absorption must be considered as predisposing factors. Due to its low prevalence and clinical heterogeneity, WE is often misdiagnosed, resulting in persistent dysfunctions or death. Therefore, early diagnosis and prompt treatment with intravenous thiamine supplement might prevent encephalopathy and other neurologic or systemic complications of thiamine depletion. We hereby report of our experience of a WE patient who presented with predominantly vestibular symptoms and signs; the patient was successfully diagnosed and treated with high-dose intravenous thiamine repletion.

Psychogenic anorexia and non-alcoholic Wernicke's encephalopathy: Complete clinicoradiological recovery with thiamine

Rationale: Prolonged undernutrition may arise out of depression and lead to Wernicke's encephalopathy if timely diagnosis and intervention are missed. Wernicke's encephalopathy is potentially treatable, and appropriate treatment may revert clinical depression and cognitive dysfunction to some extent.Patient's concern: A 69-year-old female who had been taking escitalopram for one year developed tremor, ophthalmoplegia, ataxia, progressive cognitive decline, and convulsions. Diagnosis: Non-alcoholic Wernicke's encephalopathy and hypomagnesemia due to psychogenic anorexia.Interventions: High dose intravenous thiamine and magnesium were supplemented.Outcomes: The patient showed remarkable improvement in neurological complications and even in depressive features. Lessons: Wernicke's encephalopathy should not be ignored in the treatment of depression.

Design of a randomized placebo controlled trial of high dose intravenous thiamine for the prevention of delirium in allogeneic hematopoietic stem cell transplantation

BackgroundDelirium is a highly prevalent and preventable neuropsychiatric condition with major health consequences. Thiamine deficiency is a well-established cause of delirium in those with chronic, severe alcoholism, but there remains an underappreciation of its significance in non-alcoholic populations, including patients with cancer. Treatment of suspected thiamine-related mental status changes with high dose intravenous (IV) thiamine has preliminary evidence for improving a variety of cognitive symptoms in oncology inpatient settings but has never been studied for the prevention of delirium in any population. ObjectivesThe primary objective of this clinical trial is to determine if high dose IV thiamine can prevent delirium in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) for treatment of cancer. Secondary objectives are to determine if thiamine status is predictive of delirium onset and if high dose IV thiamine can attenuate the deleterious impact of delirium on health-related quality of life (HRQOL), functional status, and long-term neuropsychiatric outcomes. MethodsIn this phase II study, we are recruiting 60 patients undergoing allogeneic HSCT, randomizing them to treatment with high dose IV thiamine (n = 30) versus placebo (n = 30), and systematically evaluating all participants for delirium and related comorbidities. We use the Delirium Rating Scale to measure the severity and duration of delirium during hospitalization for HSCT. We obtain thiamine levels weekly during the transplantation hospitalization. We assess HRQOL, functional status, depression, post-traumatic stress symptoms, and cognitive function prior to and at one, three, and six months after transplantation.

Sustained High-dose Thiamine Supplementation in High-risk Cardiac Patients Undergoing Cardiopulmonary Bypass: A Pilot Feasibility Study (The APPLY trial)

To test the feasibility and investigate possible cardiovascular effects of a sustained high-dose intravenous thiamine protocol in patients undergoing combined valvular and coronary artery bypass graft surgery. Randomized, placebo-controlled, pilot feasibility trial. Cardiac surgery department of a tertiary hospital. Forty patients undergoing combined valvular and coronary artery bypass surgery. Intravenous thiamine (600 mg on the day of surgery, and 400 mg/day on postoperative days 1, 2, and 3) or placebo. The primary feasibility endpoints were recruitment rate and protocol compliance. Secondary endpoints included markers of possible biological and physiological effects. The mean recruitment rate was 8 patients per month and protocol compliance was 97.5%. There were no differences in median peak postoperative lactate (2.7 mmol/L [interquartile range [IQR] 1.4-4.6] for thiamine v 2.5 mmol/L [IQR 1.4-3.6] for placebo; p = 0.53), median peak postoperative creatinine (104 µmol/L [IQR 92.5-129] for thiamine v 99 µmol/L [IQR 86.5-109.5] for placebo; p = 0.53), median nadir postoperative cardiac index (1.8 L/min/m2 [IQR 1.5-2.1] for thiamine v 2.2 L/min/m2 [IQR 1.5-2.5] for placebo; p = 0.25), or the number of patients on vasopressor/inotropic agents (thiamine, 12 [63%]; placebo, 12 [60%]; p = 0.80), or in the total inotrope/vasopressor dose 0.14 µg/kg for thiamine v 0.12 µg/kg for placebo; p = 0.88). A double-blind trial of sustained high-dose intravenous thiamine supplementation in higher-risk cardiac surgery patients was feasible and appeared to be safe. However, such treatment did not demonstrate evidence of biological or physiological effects.

Prevalence and Improvement of Caine-Positive Wernicke-Korsakoff Syndrome in Psychiatric Inpatient Admissions

Wernicke-Korsakoff Syndrome (WKS) resulting from thiamine deficiency is classically defined as including encephalopathy, ataxia, and ophthalmoplegia. Only 16% of autopsy-confirmed patients with WKS exhibit all three signs. Caine-positive WKS criteria include two or more of the following: nutritional deficiency, delirium or mild memory impairment, cerebellar dysfunction/ataxia, and oculomotor abnormalities. We describe Caine-positive WKS prevalence among psychiatric inpatients and compare pretreatment-versus-posttreatment neurocognitive improvement to an unaffected group. This 6-month quality-improvement evaluation included two-stage screening for Caine-positive WKS, administering high-dose intravenous thiamine (day 1: 1200 mg; days 2-4: 200 mg) with reexamination on day 5. We used descriptive statistics and fitted random effects models to examine rate-of-change differences in pre-/posttreatment Montreal Cognitive Assessment (MoCA), delayed 5-item recall, and gait/coordination scores between treated Caine-positive patients with WKS and untreated Caine-negative patients. Of 262 patients, 32 (12%) had Caine-positive WKS; 17 (53%) used alcohol currently. Treated Caine-positive WKS (n= 26) versus Caine-negative comparison (n= 34) before and after treatment observed a mean change (standard deviation) in the MoCA score of 3.6 (2.5) versus 1.8 (2.5) (P < 0.01); 5-item recall: 1.8 (1.4) versus 0.5 (1.4) (P < 0.001); gait/coordination scores:-0.6 (1.2) versus-0.1 (0.6) (P< 0.001). Oculomotor abnormalities were infrequent (n= 4 in Caine-positive WKS, n= 2 in Caine-negative comparison groups). Caine-positive WKS prevalence among psychiatric inpatients was 12%; only half used alcohol. Patients treated with high-dose thiamine demonstrated clinically significant neurocognitive improvement.

Clinical Characteristics and Outcomes Associated With High-Dose Intravenous Thiamine Administration in Patients With Encephalopathy

Wernicke encephalopathy is a common neuropsychiatric syndrome due to thiamine deficiency. There is no consensus regarding thiamine dosing when Wernicke encephalopathy is suspected.A longstanding dosing strategy for Wernicke encephalopathy is 100mg daily, yet updated clinical guidelines suggest using high-dose intravenous (HDIV) thiamine. To describe thiamine prescribing practices at a large, public academic hospital and investigate clinical characteristics and outcomes associated with HDIV thiamine in patients with encephalopathy who received IV thiamine. Electronic medical records of hospitalized patients who received thiamine between 4/4/2014 and 11/1/2015 were reviewed. Chi-square tests, Wilcoxon Rank Sum tests, and logistic regression were used to compare clinical variables in patients with encephalopathy who received HDIV thiamine (≥ 200mg twice daily) vs lower doses of IV thiamine. Among the total of 5236 thiamine orders, 29% (n = 1531) were IV; 10% (n = 150) of IV orders met HDIV criteria. In patients with encephalopathy who received IV thiamine (n = 432), HDIV thiamine was administered to 20% (n = 86) and only 2.1% (n = 9) received dosing consistent with Royal College of Physicians guidelines. In bivariable analyses, HDIV thiamine was associated with surgical services (p = 0.001), psychiatric consultation (p < 0.001), and decreased mortality (p = 0.004). In multivariable models, the association between HDIV thiamine and decreased in-hospital mortality did not meet statistical significance (p = 0.061). In a large, public academic hospital, guideline-concordant thiamine supplementation is rare and HDIV thiamine is infrequently prescribed to patients with encephalopathy. Further studies are needed to confirm the possible benefits of HDIV thiamine for patients with suspected thiamine-deficient encephalopathy.

66-Year-Old Woman With Falls and Confusion

66-Year-Old Woman With Falls and Confusion

Hyperammonemic Encephalopahty Can Result from a Duodenal Switch

A 41-year-old female had inadequate weight loss 2 years after a vertical sleeve gastrectomy. 1 year prior to presentation, she underwent revision to a duodenal switch with formation of a duodeno-ileal anastomosis. At presentation she had evidence for protein-calorie malnutrition. She denied alcohol use; total parenteral nutrition (TPN) was initiated. Upper endoscopy revealed a normal esophagus and post-operative changes of sleeve gastrectomy with duodenal switch; a nasoileal tube was placed to begin enteral nutrition. On day 9, the patient was moved to the intensive care unit after onset of catatonia and unresponsiveness. On exam, she had no signs of chronic liver disease. Her INR was 1.4, platelet count 237 and had minimal elevations of serum ALT and AST. She had no evidence for metabolic acidosis (AGAP-8 and lactic acid-1.1). CT scan of the head was unremarkable. There was no deficiency of vitamin B12, folate, copper, or zinc, but she had hyperammonemia with a blood level of 223 mcg/dl. The differential diagnosis for non-hepatic hyperammonemia includes medications, hyperalimentation, infections with urease producing bacteria, surgical-induced nutritional deficiency, and errors of metabolism. Other potential explanations were excluded for this patient. She was started on a protein restriction of 40 grams/day, lactulose enemas and high dose intravenous thiamine. She had a decrease in her serum ammonia levels with improvement in her mental status. A 24-hour urine collection revealed an elevated orotic acid level (2.9 mmol/mol Cr) supporting Ornithine Transcarbamylase Deficiency. She underwent revision of her ileo-ileostomy, and the common channel was increased in length. On day 30, TPN was discontinued. She was discharged on a protein limited diet and oral lactulose. This exceedingly rare phenomenon with similar presentations has been described previously involving predominantly female patients developing an often fatal hyperammonemic encephalopathy after gastric bypass surgery, which in some patients was up to 28 years post-operatively. The exact mechanism remains unclear, but this disorder is believed to involve unmasking of inborn errors of urea metabolism after bariatic surgery, the most common of which is Ornithine Transcarbamylase Deficiency. This case report demonstrates that this disorder can also occur after duodenal switch. Gastroenterologists need to be aware of this disorder due to the number of patients undergoing bariatric surgery.

Wernicke&amp;'s encephalopathy in hyperemesis gravidorum

Wernicke&'s encephalopathy (WE) is potentially a fatal complication due to the deficiency of vitamin B1 and presents with a neurological triad of nystagmus, encephalopathy, and ataxia. It is most commonly seen in alcoholics and is a rare complication of pregnancy associated with hyperemesis gravidorum (HG). Since it is a rare condition, difficult to diagnose in pregnancy, and can prove to be fatal, a high index of suspicion should be made in case of pregnancy complicated by HG. We hereby report a case of WE caused by HG successfully treated with a high dose intravenous thiamine. This case is the first of its kind from our part of world.

Wernicke-sjúkdómur meðal áfengissjúkra

Wernicke's encephalopathy (WE) is caused by thiamine (vitamin B1) deficiency and most commonly found in individuals with chronic alcoholism and malnutrition. Clinically, its key features are mental status disorders and oculomotor abnormalities as well as stance and gait ataxia. The diagnosis of WE is frequently missed although delay of appropriate treatment can lead to death or Korsakoff's amnestic syndrome. It is therefore crucial in suspected cases of WE, not to await confirmation of diagnosis, but immediately administer high-dose intravenous thiamine and simultaneously treat magnesium deficiency. Alcoholics at risk of WE should on admission receive immediate prophylactic therapy with parenteral thiamine.

Wernicke’s encephalopathy mimicking variant Creutzfeldt-Jakob disease

A 45-year-old man from tropical Australia was admitted with subacute social withdrawal, cognitive deterioration, reduced awareness and eventual mutism. Variant Creutzfeldt-Jakob disease was considered on the basis of WHO case definition criteria including typical clinical features and MRI showing symmetrical hyperintensity in the pulvinar (posterior) nuclei of the thalami. However, tonsillar biopsy was negative. Wernicke’s encephalopathy was established on the basis of low serum thiamine on admission and eventual clinical improvement on high-dose intravenous thiamine replacement, despite initial failure to respond to the standard dose of 100 mg daily intramuscularly.