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Total parenteral nutrition-induced Wernicke’s encephalopathy after oncologic gastrointestinal surgery

  • Piergiorgio Fedeli , Richard Justin Davies , Roberto Cirocchi EMAIL logo , Georgi Popivanov , Paolo Bruzzone and Michela Giustozzi
Published/Copyright: July 20, 2020
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Open Medicine
From the journal Open Medicine Volume 15 Issue 1

Abstract

Carl Wernicke described the disease bearing his name in 1881 and reported three cases characterized by the presence of mental confusion, ataxia, and ophthalmoplegia. Wernicke’s disease is mainly observed in alcoholic patients, due to decreased vitamin intake as a consequence of an unbalanced diet, and a reduction of absorption due to the effects of alcohol. Likewise, inadequate vitamin intake is prevalent in older patients. Wernicke’s encephalopathy due to inappropriate total parenteral nutrition (TPN) occurs infrequently; recently, there is an increase in the literature concerning Wernicke’s encephalopathy in patients after general and bariatric surgeries. We present two cases of Wernicke’s encephalopathy after oncologic gastrointestinal surgery by failure to administer vitamin B1 during TPN; to our knowledge, these are the first two cases of Wernicke’s encephalopathy after colorectal surgery for cancer. In our opinion, timely diagnosis and treatment are mandatory to avoid nonfunctional recovery and consequent malpractice legal actions as well as an increase in the health-care costs correlated with the prolonged hospital stay and with the nonfunctional recovery.

Keywords: Wernicke’s encephalopathy; parenteral nutrition; malpractice

1 Introduction

Carl Wernicke described the disease that bears his name in 1881, reporting three cases characterized by the presence of mental confusion, ataxia, and ophthalmoplegia; one of these patients had pyloric stenosis due to ingestion of caustics, and the other two were alcoholics [1]. Wernicke could not attribute this disease to vitamin deficiency (vitamin B1), because at that time, vitamins were still unknown. In 1912, Casimir Funk isolated elements in raw white rice and called them for the first time “vitamins” because they were considered indispensable for life [2]. In 1926, Jansen and Donath isolated pure thiamine. In 1929, the Nobel Prize for medicine was awarded to Christian Eijkman and Frederick Gowland Hopkins for having identified that beriberi was linked to the nutritional deficiency of vitamins [3].

Numerous efforts were made to study beriberi, leading to the definition of the role of thiamine deficiency in its aetiology and consequently of its fundamental importance as a therapy.

Vitamin B1 is a coenzyme essential for the integrity of membranes and, therefore, for the normal function of the nervous system, muscles, and heart. Due to its average life of approximately 2 weeks in humans, there are no reserves, and therefore, in people who do not take it with food, deficiency symptoms occur after around 3 weeks [4,5].

The clinical manifestations in critically ill patients are nystagmus and ophthalmoplegia, cerebellar dysfunction (ataxia), confusion, and altered mental status.

Wernicke’s disease incidence is higher in alcoholics, both as a consequence of the decrease of vitamin intake from a very unbalanced diet and due to reduced absorption in alcoholic patients. Data suggest that 3–12% of alcoholics admitted in hospital have clinical signs of Wernicke’s encephalopathy [6,7,8]. It may also affect patients with malabsorption syndrome, leading to chronic diarrhoea.

Likewise, inadequate vitamin intake is prevalent in older adults. Some studies have shown a higher risk of deficiencies in senior citizens living alone or in a psychiatric or nursing home environment [9,10,11,12].

Wernicke’s encephalopathy in hospitalized patients can be caused by two factors: insufficient thiamine content within total parenteral nutrition (TPN) preparations [13,14] or an increase in the requirement if perfusions of glucose solutions used, as the metabolism of glucose consumes thiamine [15,16,17].

In both cases, Wernicke’s encephalopathy should be considered an iatrogenic complication [18,19].

We report two cases of Wernicke’s encephalopathy that could have been harbingers of malpractice legal actions.

2 1th Case report

A 49-year-old male without alcohol addiction underwent subtotal gastrectomy with D2 lymphadenectomy for a locally advanced antral cancer (T3N1M0) and was discharged on the seventh postoperative day. The same evening, while at home, the patient developed sudden diffuse abdominal pain. On next morning, he was readmitted to the hospital, and emergency surgery was performed for peritonitis from dehiscence of the duodenal stump. The patient was transferred to the intensive care unit, where TPN was started. During 2 weeks of TPN, vitamin B1 was not administered. On the 20th postoperative day, there was a gradual appearance of neurological symptomatology and a neurologist arranged transfer to the neurological unit. Ophthalmological examination suggested a partial horizontal and vertical ophthalmoplegia with prominent gait ataxia; a brain computed tomography ruled out organic diseases. The patient was later transferred to another hospital with the diagnosis of “Antral gastric cancer (T3N1M0): subtotal gastrectomy. Acute peritonitis by late duodenal perforation. Septic state. Central nervous disorders of likely toxic origin.” In this hospital, in addition to strict surgical control of the patient’s condition, parenteral nutrition (later on replaced by enteral nutrition) with high-dose parenteral thiamine (500 mg intravenously every 8 h) was immediately started; neurological symptoms slowly improved after 5 days; successively, the dose of thiamine was reduced (100 mg intravenously every day). The patient was discharged after 30 days with the diagnosis of “Outcomes of subtotal gastrectomy with post-operative course complicated by duodenal dehiscence. External biliary fistula. Dizzy syndrome.” At discharge, the surgeons recommended a neurological check-up and therapy with thiamine (100 mg/day orally). He was then admitted to an academic neurology department for another clinical evaluation; the final diagnosis was “Wernicke’s vitamin deficient encephalopathy.” One year later, the patient presented with a cerebellar syndrome, which substantially prevented him from performing movements that required good coordination. This clinical picture made many acts of daily life difficult, such as feeding and personal hygiene, with walking severely limited.

3 2nd Case report

A 59-year-old female with previous mixed dyslipidemia and hypothyroidism underwent laparoscopic anterior resection of the upper rectum for cancer. On the third postoperative day, she complained of continuous vomiting, so the surgeons suspected a small bowel obstruction due to postoperative adhesions. The patient underwent non-operative management (NOM); a central venous catheter was placed, and TPN was started, administering Clinimix® (amino acids and glucose solution). Vomiting persisted, and a mild acute pancreatitis was also diagnosed. The patient was then transferred to the Gastroenterology Unit where the Clinimix® was replaced with Nutriplus Lipid® (including lipid infusion), but no vitamins were administered. Subsequently, the patient did not respond to verbal stimuli; the consultant neurologist described her as “vigilant, oriented, collaborative patient, no segmental force deficits to the limbs. Symmetrical osteotendinous reflexes have been observed. Nystagmus is present with coarse shocks in the extreme lateral gaze” and transferred the patient to the Neurology Unit, suspecting myelinolysis. She was given a vitamin complex (Cernevit®) with high-dose parenteral thiamine (500 mg intravenously every 8 h). The duration of high-dose therapy was 3 days; successively, the patient received a standard dose of 100 mg thiamine daily. Enteral nutrition was later started and continued, with a progressive improvement in the mental state, ophthalmoplegia, and the ability to eat normally. Due to neurological disease and prolonged hospital stay, she was transferred to a Rehabilitation Centre for a further 4 months, obtaining only a moderate clinical improvement. One year later, eyelid ptosis, pyramidal hyperreflexia in the four limbs, improved balance, and persisting dysphasia, dysarthria, and dysphagia were observed.

  1. Consent for publication: Written informed consent was obtained from the patients for publication of these two case reports.

4 Discussion

Wernicke’s encephalopathy due to inappropriate TPN occurs infrequently [20,21,22,23]. However, an increasing number of papers have been published [24,25,26,27,28], reporting this disease after general and bariatric surgeries and thereby raising the possibility of malpractice legal actions [24,25,26,27,28,29].

In 2008, Aasheim reported the results of a systematic review of the literature on this topic, including 84 patients with Wernicke’s encephalopathy after bariatric surgery (gastric bypass or a restrictive procedure had been performed in 80 cases [95%]). From 2008 until 2020, 224 new publications described this disease.

Our two cases had postoperative complications and prolonged TPN was needed. In both patients, after more than 3 weeks from the beginning of the TPN, signs and symptoms related to Wernicke’s encephalopathy were observed. The cause was identified as absolute deficiency of vitamin B1.

This diagnosis was delayed in both patients; late high-dose parenteral thiamine administration reversed some of the acute effects of Wernicke’s encephalopathy. These delays reduced the effectiveness of the treatment, limiting it to improvement without returning to normal clinical conditions.

In everyday clinical practice, traditional regimens include 100 mg of parental (intravenous or intramuscular) thiamine administration for 3–7 days (treatment period), followed by oral thiamine indefinitely. In these two cases, the neurological condition of patients was more severe, and therefore, higher doses (up to 1 g of intravenous thiamine daily) were needed to obtain clinical improvement. An accurate selection of patients is very important; the antioxidant effect of vitamin B1 may change in oncological patients receiving cytotoxic drugs [30]. This hypothesis was supported from a recent study performed by Restivo and colleagues. The authors evaluated 45 patients who underwent gastrointestinal surgery due to cancer (2 total gastrectomies, 4 partial gastrectomies, 9 right hemicolectomies, 2 left hemicolectomies, 17 anterior resections of rectum, 3 abdominal perineal resections, and 4 other colonic resections). A diagnosis of Wernicke was reported in 4.4% at discharge. The authors suggested that “cancer patients submitted to gastrointestinal surgery should be considered at risk of Wernicke and should receive thiamine prophylactic treatment” [31].

The accurate study of medical records, with day-to-day control of components used for TPN, allowed us to highlight these effects of the lack of vitamin B1 in the solutions used for intravenous feeding. This complication should have been avoided given that clinical experience of TPN in surgical patients dates back more than 40 years. In the literature, very few cases of Wernicke’s encephalopathy were reported after oncologic gastrointestinal surgery during TPN, the localization of gastrointestinal cancer was the stomach and the pancreas (Table 1) [32,33,34,35,36,37,38,39,40,41,42,43,44].

Table 1

Review of literature: case report of Wernicke’s encephalopathy after oncologic gastrointestinal surgery

Author and yearType of articleLocation of cancerType of surgery
Kim 2019Case reportPancreasPancreaticoduodenectomy
Tozzo 2017Case reportGastricGastrectomy
Tsao 2017Case reportGastricGastrectomy
Kilinc 2015Case reportGastricGastrectomy
Busani 2014Case reportPancreasPancreaticoduodenectomy
Karayiannakis 2011Case reportPancreasPancreaticoduodenectomy
Onieva-González 2011Case reportPancreasPancreaticoduodenectomy
Attard 2006Case reportGastricGastrectomy
Iwase 2002Case reportGastricGastrectomy
Arai 1997Case reportGastricGastrectomy
Batori 1995Case reportGastricGastrectomy
Shimomura 1998Case reportGastricGastrectomy

In a 1979 publication, the authors stated that “the intake of vitamins consists of vitamins C, K, complex B, folic acid.” In those years, the attending physicians or the hospital pharmacy independently provided TPN solutions [45]. Later on several pre-packaged industrial products have been introduced in clinical practice, substantially improving safety and quality. TPN industrial bags contain nutritional macroelements and electrolytes but still require a supplement of vitamins and trace elements before their infusion.

The physician who prescribes the administration of two- or three-compartment industrial TPN bags must indicate the required additive components; vitamins must be added just before use or they should be administered in a different solution.

Physicians who take care of patients needing TPN, as well as involved dieticians and pharmacists, must be aware of this clinical information [46].

Information for the prevention of Wernicke’s encephalopathy in patients undergoing digestive surgery and particularly gastric procedures has been published [47,48,49]. The guidelines of the European Federation of Neurological Societies for diagnosis, treatment, and prevention of Wernicke’s encephalopathy [50] provide guidance for monitoring surgical patients, mainly after the bariatric surgery [51,52,53,54,55].

5 Conclusion

In our two case reports, the following same errors occurred: late diagnosis, made by different clinicians, of Wernicke’s encephalopathy after use of TPN to manage complications of oncologic digestive surgery. Failure to administer vitamin B1 was the cause in these cases of encephalopathy. This complication led to serious implications for the patients and to an increase in healthcare costs due to prolonged hospital stay and incomplete recovery.

  1. Author contributions: All authors contributed to conceptual ideation, drafting, and critically revising the paper and gave final approval of the version to be published.

  2. Disclosure: The authors report no conflicts of interest in this work.

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Received: 2019-12-18
Revised: 2020-03-31
Accepted: 2020-06-10
Published Online: 2020-07-20

© 2020 Piergiorgio Fedeli et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  55. Clinicopathological features of programmed cell death-ligand 1 expression in patients with oral squamous cell carcinoma
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  65. Prognostic role of SIRT6 in gastrointestinal cancers: a meta-analysis
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  106. Bevacizumab for non-small cell lung cancer patients with brain metastasis: A meta-analysis
  107. Risk factors for cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage
  108. Problems and solutions of personal protective equipment doffing in COVID-19
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  116. Clinicopathological analysis of composite lymphoma: A two-case report and literature review
  117. Trastuzumab-induced thrombocytopenia after eight cycles of trastuzumab treatment
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  119. Inhibition of vitamin D analog eldecalcitol on hepatoma in vitro and in vivo
  120. CCTs as new biomarkers for the prognosis of head and neck squamous cancer
  121. Effect of glucagon-like peptide-1 receptor agonists on adipokine level of nonalcoholic fatty liver disease in rats fed high-fat diet
  122. 72 hour Holter monitoring, 7 day Holter monitoring, and 30 day intermittent patient-activated heart rhythm recording in detecting arrhythmias in cryptogenic stroke patients free from arrhythmia in a screening 24 h Holter
  123. FOXK2 downregulation suppresses EMT in hepatocellular carcinoma
  124. Case Report
  125. Total parenteral nutrition-induced Wernicke’s encephalopathy after oncologic gastrointestinal surgery
  126. Research Article
  127. Clinical prediction for outcomes of patients with acute-on-chronic liver failure associated with HBV infection: A new model establishment
  128. Case Report
  129. Combination of chest CT and clinical features for diagnosis of 2019 novel coronavirus pneumonia
  130. Research Article
  131. Clinical significance and potential mechanisms of miR-223-3p and miR-204-5p in squamous cell carcinoma of head and neck: a study based on TCGA and GEO
  132. Review Article
  133. Hemoperitoneum caused by spontaneous rupture of hepatocellular carcinoma in noncirrhotic liver. A case report and systematic review
  134. Research Article
  135. Voltage-dependent anion channels mediated apoptosis in refractory epilepsy
  136. Prognostic factors in stage I gastric cancer: A retrospective analysis
  137. Circulating irisin is linked to bone mineral density in geriatric Chinese men
  138. Case Report
  139. A family study of congenital dysfibrinogenemia caused by a novel mutation in the FGA gene: A case report
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  141. CBCT for estimation of the cemento-enamel junction and crestal bone of anterior teeth
  142. Case Report
  143. Successful de-escalation antibiotic therapy using cephamycins for sepsis caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae bacteremia: A sequential 25-case series
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  145. Influence factors of extra-articular manifestations in rheumatoid arthritis
  146. Assessment of knowledge of use of electronic cigarette and its harmful effects among young adults
  147. Predictive factors of progression to severe COVID-19
  148. Procedural sedation and analgesia for percutaneous trans-hepatic biliary drainage: Randomized clinical trial for comparison of two different concepts
  149. Acute chemoradiotherapy toxicity in cervical cancer patients
  150. IGF-1 regulates the growth of fibroblasts and extracellular matrix deposition in pelvic organ prolapse
  151. NANOG regulates the proliferation of PCSCs via the TGF-β1/SMAD pathway
  152. An immune-relevant signature of nine genes as a prognostic biomarker in patients with gastric carcinoma
  153. Computer-aided diagnosis of skin cancer based on soft computing techniques
  154. MiR-1225-5p acts as tumor suppressor in glioblastoma via targeting FNDC3B
  155. miR-300/FA2H affects gastric cancer cell proliferation and apoptosis
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  160. Long non-coding RNA FOXD2-AS1 promotes cell proliferation, metastasis and EMT in glioma by sponging miR-506-5p
  161. Analysis of expression and prognosis of KLK7 in ovarian cancer
  162. Circular RNA circ_SETD2 represses breast cancer progression via modulating the miR-155-5p/SCUBE2 axis
  163. Glial cell induced neural differentiation of bone marrow stromal cells
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  167. Diagnosis of complication in lung transplantation by TBLB + ROSE + mNGS
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  175. Advances in the role of miRNAs in the occurrence and development of osteosarcoma
  176. Rheumatoid arthritis increases the risk of pleural empyema
  177. Effect of miRNA-200b on the proliferation and apoptosis of cervical cancer cells by targeting RhoA
  178. LncRNA NEAT1 promotes gastric cancer progression via miR-1294/AKT1 axis
  179. Key pathways in prostate cancer with SPOP mutation identified by bioinformatic analysis
  180. Comparison of low-molecular-weight heparins in thromboprophylaxis of major orthopaedic surgery – randomized, prospective pilot study
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  184. Circular RNA hsa_circ_0007121 regulates proliferation, migration, invasion, and epithelial–mesenchymal transition of trophoblast cells by miR-182-5p/PGF axis in preeclampsia
  185. SRPX2 boosts pancreatic cancer chemoresistance by activating PI3K/AKT axis
  186. Case Report
  187. A case report of cervical pregnancy after in vitro fertilization complicated by tuberculosis and a literature review
  188. Review Article
  189. Serrated lesions of the colon and rectum: Emergent epidemiological data and molecular pathways
  190. Research Article
  191. Biological properties and therapeutic effects of plant-derived nanovesicles
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  193. Clinical characterization of chromosome 5q21.1–21.3 microduplication: A case report
  194. Research Article
  195. Serum calcium levels correlates with coronary artery disease outcomes
  196. Rapunzel syndrome with cholangitis and pancreatitis – A rare case report
  197. Review Article
  198. A review of current progress in triple-negative breast cancer therapy
  199. Case Report
  200. Peritoneal-cutaneous fistula successfully treated at home: A case report and literature review
  201. Research Article
  202. Trim24 prompts tumor progression via inducing EMT in renal cell carcinoma
  203. Degradation of connexin 50 protein causes waterclefts in human lens
  204. GABRD promotes progression and predicts poor prognosis in colorectal cancer
  205. The lncRNA UBE2R2-AS1 suppresses cervical cancer cell growth in vitro
  206. LncRNA FOXD3-AS1/miR-135a-5p function in nasopharyngeal carcinoma cells
  207. MicroRNA-182-5p relieves murine allergic rhinitis via TLR4/NF-κB pathway
https://doi.org/10.1515/med-2020-0210
Keywords for this article
Wernicke’s encephalopathy; parenteral nutrition; malpractice
Creative Commons
BY 4.0

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