Refeeding Syndrome with Severe Electrolyte Imbalance Leading to Quadriparesis: A Case Report

INTRODUCTION

Refeeding syndrome is defined as a set of clinical complications that occur as a result of fluid and electrolyte shifts during aggressive nutritional rehabilitation of malnourished patients. It is associated with dyselectrolytaemia, including hypokalaemia, hypophosphataemia, and hypomagnesaemia. Hypokalaemia is an important differential diagnosis in patients presenting with acute-onset flaccid paralysis. It can arise from various causes, including gastrointestinal fluid losses, excessive diuretic use, renal tubular acidosis, metabolic alkalosis, Bartter/Gitelman syndrome, Liddle syndrome, and endocrine causes such as Conn’s syndrome and Cushing’s syndrome. In addition, certain drugs, including beta-agonists (e.g., salbutamol), insulin, and amphotericin-B are also frequently known to cause hypokalaemia. While multiple pathogenic mechanisms can lead to hypokalaemia, the most significant are increased renal potassium excretion and transcellular potassium shifts. Another critical differential to consider, especially when the exact aetiology of hypokalaemia with paralysis cannot be ascertained despite extensive evaluation, is periodic paralysis. These are rare neuromuscular disorders caused by defects in muscle ion channels. Hypokalaemic and hyperkalaemic periodic paralyses involve mutations in calcium and sodium channels, respectively. They are grouped as channelopathies and also encompass defects in chloride and potassium channels. Although refeeding syndrome is an uncommon cause of hypokalaemia and other electrolyte disturbances, it should always be considered a potential differential diagnosis in the appropriate clinical context.^1-3

CASE REPORT

A 61-year-old South Asian male with no known medical history presented with complaints of an acute onset, progressive weakness in both upper and lower limbs for the past two days, such that he was unable to get up from his bed. This was followed by multiple episodes of watery, non-bloody, non-foul-smelling diarrhoea, not associated with abdominal pain or cramping. There was no history of fever, muscle pain, dysphagia, or recent vaccination. There was no difficulty in passing urine or stools. The patient denied any personal or family history of similar illness. He had been a heavy tobacco chewer for the past 15 years with intake exceeding 400 g/day. He had recently been admitted to a local drug rehabilitation and deaddiction centre at the insistence of his family, despite initial reluctance to seek professional help. The total duration of his stay at the facility was three months. During this time, he received multiple forms of nicotine replacement therapy in the form of chewing gums and transdermal patches. A documented weight loss of 12 kg occurred over this period. While at the facility, he ate a very limited diet consisting of one Chapati (Indian bread) with vegetables for lunch and dinner, often skipping breakfast. In the 11 days preceding symptom onset, he voluntarily reduced his food intake even further, having very little or no food. Two days before the development of weakness, he resumed oral intake, primarily consisting of rice and fish, after which he developed weakness in all four limbs, followed by loose stools. Upon examination, he was conscious and oriented to verbal commands. He was haemodynamically stable. Pallor was noted, with no evidence of cyanosis, icterus, clubbing, or oedema. Neurologic examination showed generalised muscle wasting with hypotonia and areflexia in all limbs. The remainder of the systemic examination was unremarkable. Initial investigations included electrocardiographic (ECG), chest X-ray, complete blood count with peripheral smear, liver and renal function tests. The ECG revealed a prolonged Corrected QT interval (QTc) (574 ms) with prominent U waves [Figure 1]. Serum electrolytes confirmed the clinical suspicion, showing severe hypokalaemia (K⁺ = 1.7 mEq/L). Other electrolyte abnormalities detected were hypomagnesaemia (0.9 mEq/L) and hypophosphataemia (1.2 mEq/L). Liver function tests (LFTs) showed deranged enzymes, with aspartate aminotransferase (AST) (133 IU/L) disproportionately higher than alanine transaminase (ALT) (13 IU/L) and a rising trend over the next 3 days [Table 1]. Given the enzyme pattern (AST > ALT) in the setting of significant hypokalaemia and hypophosphataemia, serum creatine phosphokinase (CPK) was measured and found to be markedly elevated (4950 IU/L; normal: 55–170 IU/L), consistent with rhabdomyolysis. A baseline venous blood gas revealed significant metabolic alkalosis (pH 7.58, pCO₂ 41 mmHg, HCO_3- 38 mEq/L). To rule out renal potassium loss, a urinary potassium-to-creatinine ratio was obtained, which was within normal limits. Management was initiated with intravenous potassium chloride under close monitoring. Concurrent correction of magnesium and phosphate levels was started using intravenous magnesium sulphate and oral phosphate supplementation, respectively.

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Figure 1:

Electrocardiogram showing prolonged QTc interval with prominent U waves.

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Following potassium correction, the patient demonstrated significant improvement in motor strength, with power in all four limbs improving to grade 4/5 over the next three days. This was accompanied by a gradual resolution of metabolic alkalosis, in parallel with potassium normalisation [Table 1]. Enzyme levels (AST and ALT) also showed serial improvement. Oral feeding was initiated with a target of providing up to 50% of daily caloric requirements initially, followed by phased and gradual increments under strict monitoring of serum electrolytes. Thiamine, along with other multivitamins, was administered before the initiation of feeding, and supplementation was continued for the next 10 days. A screening abdominal ultrasound and chest X-ray revealed no abnormalities. Given the significant weight loss of 12 kg, a high-resolution computed tomography (CT) of the thorax, along with contrast-enhanced computed tomography of the abdomen and pelvis, was performed to rule out any underlying occult malignancy or infective pathology.

On follow-up at four weeks, the patient demonstrated complete neurological recovery with normalisation of serum potassium, phosphate, and magnesium levels. Nutritional rehabilitation was continued with a phased high-protein, high-calorie diet along with multivitamins under dietitian supervision. No recurrence of paralysis was reported. A weight gain of 3.5 kg was noted at this visit.

DISCUSSION

Refeeding syndrome is diagnosed clinically, with a thorough patient history as the cornerstone, supplemented by appropriate laboratory findings. During periods of prolonged fasting or severely reduced food intake, the body undergoes significant hormonal and metabolic adaptations. There is a marked decrease in insulin levels, accompanied by a compensatory rise in counter-regulatory hormones such as glucagon and cortisol. Furthermore, there is a severe depletion of the stores of phosphate and other electrolytes during starvation. Subsequently, upon refeeding, particularly with a carbohydrate-rich diet, there is a sudden surge in insulin secretion and suppression of counter-regulatory hormones. This leads to the activation of multiple downstream anabolic pathways leading to glycogen, fat, and protein synthesis, all utilising various phosphorylated intermediates. Insulin also activates multiple transporters on the cell membranes, driving potassium, magnesium, and phosphate into cells. If the resulting electrolyte disturbances are not promptly identified and corrected, they may lead to serious complications. In this case, the paralysis was multifactorial. While hypokalaemia was profound, the coexisting hypophosphataemia likely contributed significantly, as evidenced by markedly elevated CPK and AST levels consistent with rhabdomyolysis. Hypophosphataemia is a well-recognised cause of ascending paralysis, diaphragmatic weakness, haemolysis, and myocardial dysfunction. Similarly, hypomagnesaemia can independently cause neuromuscular dysfunction, flaccid areflexia and QT prolongation, while also impairing potassium repletion by inducing renal potassium wasting.^2-4 Thus, the patient’s paralysis was not solely attributable to hypokalaemia but reflected the combined effect of all three dyselectrolytemia. In addition, hypokalaemia has been shown to independently cause rhabdomyolysis.¹

Differentiating between the various electrolyte-induced paralyses is clinically important, as each has distinct pathophysiological and clinical implications. Hypokalaemic paralysis typically presents with rapid-onset flaccid weakness that is often promptly reversible with potassium correction. In contrast, hypophosphataemic paralysis is frequently associated with rhabdomyolysis, respiratory muscle weakness, and even respiratory failure, reflecting the central role of phosphate in energy metabolism and muscle function. Hypomagnesaemic paralysis presents with areflexia and neuromuscular dysfunction and is associated with ECG changes such as QT prolongation. Taken together, this reflects the necessity of a holistic approach to electrolyte monitoring and correction in refeeding syndrome, rather than focusing on a single abnormality in isolation.

Gastrointestinal symptoms of varying severity may emerge early in refeeding.¹ LFTs are frequently deranged in the initial weeks, most often due to excessive caloric intake leading to hepatic steatosis or due to hepatocyte apoptosis related to prior malnutrition. Diarrhoea is also common during the early stages of refeeding, primarily due to atrophy of the intestinal mucosa and pancreatic exocrine impairment. This generally resolves early as the villous surface is reconstituted. In addition, taking smaller and more frequent meals can help to alleviate symptoms and support gradual nutritional recovery. Metabolic alkalosis due to various aetiologies is a well-known cause of hypokalaemia. Conversely, hypokalaemia itself can independently contribute to the development of significant metabolic alkalosis through the following mechanisms.^2,3

Hypokalaemia induces intracellular acidosis due to the intracellular shift of hydrogen ions, which subsequently stimulates increased hydrogen ion secretion in both the proximal and distal renal tubules.

It also promotes enhanced renal ammoniagenesis, further contributing to alkalosis.

This phenomenon was clearly demonstrated in our case, where the correction of hypokalaemia led to the simultaneous correction of metabolic alkalosis. Patients weighing <70% of their ideal body weight or those who have lost weight rapidly are at the highest risk of developing refeeding syndrome, even if their body mass index following the weight loss is within normal range. Other well-established risk factors include chronic alcoholism, low baseline electrolytes, anorexia nervosa, prolonged usage of antacids, and the presence of chronic illnesses.^3,5 Refeeding syndrome is largely preventable through a carefully structured nutritional replenishment strategy, beginning with a conservative caloric intake of approximately 10 kcal/kg/day, followed by a gradual escalation to meet full nutritional requirements over a period of 4–7 days.² While certain clinical guidelines advocate for correcting electrolyte imbalances concurrently with refeeding, the traditional approach of pre-emptive correction before refeeding initiation is more broadly endorsed. The entire process should be accompanied by regular monitoring of clinical and laboratory parameters to enable early detection of potentially life-threatening complications.^2,5,6

The case that we present is unique in the following ways:

This case demonstrates that refeeding syndrome can lead to electrolyte disturbances severe enough to cause flaccid quadriparesis. It also highlights the association between hypokalaemia and metabolic alkalosis and illustrates the underlying molecular mechanisms, as evidenced by the resolution of alkalosis following correction of hypokalaemia. There is limited literature describing refeeding syndrome with such an atypical clinical presentation.

CONCLUSION

Refeeding syndrome should be considered as a potential differential diagnosis in patients with a history of prolonged starvation or nutritional deprivation, especially when presenting with electrolyte imbalances, fluid overload, gastrointestinal symptoms, or other atypical clinical features, as illustrated by our case. This diagnosis should be considered in all patient populations at risk of prolonged nutritional compromise, including individuals undergoing chemotherapy, prison inmates, patients admitted to psychiatric wards, individuals in drug rehabilitation programmes, elderly residents in assisted living facilities, etc. A multidisciplinary approach, incorporating psychiatrists, dietitians, and other healthcare professionals alongside the primary treating physician, is essential for achieving optimal outcomes.