Wernicke’s Encephalopathy During Parenteral Nutrition

By Francini-Pesenti, Francesco; Brocadello, Filippo; Famengo, Stefania; Nardi, Mariateresa; Caregaro, Lorenza

ABSTRACT. Background: Thiamine deficiency in humans affects the cardiovascular, muscular, nervous, and gastrointestinal systems. Wernicke’s encephalopathy is described in alcoholism, in hyperemesis gravidarum, and in prolonged IV feeding without vitamin supplementation. Methods: We report a case of a 66-year-old man undergoing surgery for acute necrotic-hemorrhagic pancreatitis, who presented a Wernicke’s syndrome during parenteral nutrition (PN). After surgery, he was treated with infusion of industrial 3- compartment bags, without vitamin supplementation. On the seventh postoperative day, nausea and vomiting began, and 5 days later the patient showed diplopia, ataxia, general muscular stiffness, reduction of osteotendinous reflexes, confusional state, and thrombocytopenia. The magnetic resonance scan evidenced pathologic changes in the medial thalamus, in the third and fourth ventricular floor, in the cerebellar vermis, and in the periaqueductal gray substance. Results: All neurologic signs and platelet blood count gradually normalized after IV supplementation of thiamine, 100 mg daily. The magnetic resonance scan repeated 40 days after the first one was normal. Conclusions: Our report points out the risk of incorrect procedures in management of industrial 3-compartment bags. Moreover, we suggest that thrombocytopenia may be related to thiamine deficiency. (Journal of Parenteral and Enterai Nutrition 31:69-71, 2007)

Thiamine deficiency in humans affects the cardiovascular, muscular, nervous, and gastrointestinal systems. Wernicke’s encephalopathy (WE) is described among the neurologic disorders. This entity was classically observed in alcoholism,1 hyperemesis gravidarum, and prolonged intravenous (IV) feeding without vitamin supplementation.3,4 WE is an acute disorder characterized by ophthalmoplegia, ataxia, and mental confusion.5,6 Abnormal eye movements may consist of horizontal and vertical nystagmus, weakness or paralysis of the lateral rectus muscles, and weakness or paralysis of conjugate gaze. In advanced cases, complete ophthalmoplegia may occur. Altered mental status consists of decreased alertness and attentiveness, perceptual disturbance, and poor memory. Sometimes it may progress to coma. If treated in the acute stages, many of the neurologic abnormalities can be reversed.

Patients fed with parenteral nutrition (PN) without proper supplementation of thiamine have also developed WE.3,7,8 PN is widely used to improve the nutrition status of patients with impaired digestive tracts. There are 2 main all-in-one systems: hospital-compounded bags and industrial 3-compartment bags.9 Three- compartment bags contain macronutrients and electrolytes in 3 separate compartments and require vitamin and trace-element supplementation just before their infusion.

We report the case of a patient treated with PN without vitamin supplementation, who developed WE as a consequence of thiamine deficiency.

CASE REPORT

A 66-year-old man underwent surgery for acute necrotic- hemorrhagic pancreatitis related to gallbladder. On admission, the patient was well nourished, and he referred to no alcohol abuse or weight loss. On the first postoperative day, PN was started. A 2-L 3- compartment bag containing 1.040 nonprotein kJ and 7.3 g of nitrogen (Oliclinomel N5-800, Baxter S.p.A., Rome, Italy) was infused daily. The bags were administered without vitamin and trace-element supplementation.

On the seventh postoperative day, nausea and vomiting began. A gastroscopy performed on the ninth postoperative day was negative. Five days later, the patient showed diplopia, ataxia, general muscular stiffness, reduction of osteotendinous reflexes, and then confused state with inattentiveness, indifference, and disorientation. The patient was apyretic. The platelets blood count, which was 270 10^sup 9^/L before surgery, fell gradually to 18 10^sup 9^/L. Red and white blood cell count, hemostasis parameters, electrolytes, and ammonia and transaminases plasma levels were in the normal range. A total body computed axial tomography scan was negative. EEG revealed diffuse and aspecific changes. Electromyographic evaluation of peripheral nerves showed a mild symmetric neuropathy.

At this point, the nutrition team was advised, and WE was diagnosed according to clinical picture. Magnetic resonance scan (MRI) confirmed the clinical diagnosis, showing symmetric hyperintense lesions in the medial thalamus, in the third and fourth ventricular floor, in the cerebellar vermis, and in the periaqueductal gray substance. All neurologic signs and symptoms gradually normalized after IV administration of 100 mg thiamine daily for 4 days. Three days later, the patient started to eat and PN was gradually reduced. It was stopped after 4 days. The platelets blood count was 18 10^sup 9^/L the day before thiamine administration. It started to rise 3 days after vitamin supplementation, and it was 445 10^sup 9^/L 12 days later. Antithrombotic prophylaxis with nadroparin, 3800 Ul/d, was administered subcutaneously from the postoperative day to the first week after the patient discharge. The MRI scan repeated 40 days after the first one was normal.

DISCUSSION

Thiamine pyrophosphate is an important enzyme cofactor involved in the Krebs cycle. Tissue storage of vitamin B1 is limited. Thiamine deficit shifts the pyruvic acid metabolism toward lactate production, with secondary lactic acidosis and increase of anion gap. WE is a rare but potentially devastating complication of thiamine deficiency. Fatigue; rigidity, particularly in crural muscles; pain; and weakness are usually associated. Inadequate treatment results in atrophy of extensor muscles. Diarrhea and vomiting increase the thiamine requirements.10 Inadequate treatment causes diplopia, paresthesia, nystagmus, ataxia, and peripheral neuropathy, which can rapidly become permanent. To differentiate the symptoms of nausea and vomiting from postoperative complications, a gastroscopy can be performed. Although the measurement of serum thiamine or red cell transketolase activity is still the hallmark for WE diagnosis, MRI can be used to confirm the diagnosis and follow the clinical evolution.11,12 Treatment should be started immediately with thiamine supplementation. Patients with WE require IV administration of at least 100 mg thiamine daily for several days.6 The cardiac symptoms quickly improve with vitamin replacement; the neurologic symptoms improve more slowly. Thiamine deficiency is still underdiagnosed in surgical departments, although surgical patients have many risk factors for thiamine deficiency, such as malnutrition, high stress levels, vomiting, and ileus. Thiamine deficiency due to refractory vomiting can develop early.13,14 In our case report, WE was caused by the lack of vitamin supplementation during PN. Hospital-compounded all-in-one bags are provided ready to use by the PN Service of the Hospital Pharmacy Department. The 3-compartment bags are a “ready-to-use” multichamber system for PN that offer the technical and metabolic advantages of all-in-one bags. The 3-compartment bags provide different formulations with amino acids, carbohydrates, and fats, with or without electrolytes. Industrial multivitamin and trace-element formulations have to be added just before PN administration. In the past, we added a multivitamin formulation daily and a trace-element solution twice a week. In this case, the hospital-compounded bags had been recently replaced with the 3-compartment bags. The ward staff erroneously thought that these bags contained the micronutrients and thus omitted their addition.

Thrombocytopenia is an unusual feature of thiamine deficiency. Other nutrition causes, however, seem unlikely in this case as platelet count rose quickly after thiamine supplementation, and before oral refeeding. Vitamin B12 and folate plasma levels were normal during PN. Anticoagulant drugs, such as heparins, can induce thrombocytopenia. Nevertheless, in this case report the platelets blood count rose, although nadroparin treatment was continued. Thrombocytopenia is a typical feature of thiamine-responsive megaloblastic anemia syndrome, an autosomal recessive disorder that includes megaloblastic anemia, mild thrombocytopenia and leukopenia, sensorineural deafness, and diabetes mellitus.15,16 In this disease, the active thiamine uptake into cells is disturbed. Treatment with pharmacologie doses of thiamine improves the megaloblastic anemia and diabetes mellitus.17 Up to now, thrombocytopenia has never been described in acquired thiamine deficiencies.

In conclusion, our report points out the risk of incorrect procedures in clinical management of industrial 3-compartment bags. These bags require appropriate ward staff training before their use. The development of bags with >3 compartments, including micronutrients, may reduce malpractice during PN. Moreover, we suggest that thrombocytopenia may be related to thiamine deficiency.

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Francesco Francini-Pesenti, MD; Filippo Brocadello, MD; Stefania Famengo, MD; Mariateresa Nardi, MD; and Lorenza Caregaro, MD

From the Clinical Nutrition Unit, Department of Clinical and Experimental Medicine, Azienda Ospedaliera, Padua, Italy

Received for publication June 7, 2006.

Accepted for publication September 20, 2006.

Correspondence: Francesco Francini-Pesenti, MD, Department of Clinical and Experimental Medicine, Azienda Ospedaliera, Padua 35100, Italy. Electronic mail may be sent to francescofrancini@yahoo.com.

Copyright American Society for Parenteral and Enteral Nutrition Jan/ Feb 2007

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