HYPOMAGNESEMIA AND PROLONGED HOSPITAL STAY: A CASE REPORT AND LITERATURE REVIEW

Hypomagnesemia is a common finding in hospitalized patients mostly overlooked and rarely given as much attention as other electrolyte disturbances. This case report and literature review highlight how hypomagnesemia is common in patients who have a prolonged hospital stay. in addition, we highlight the multiple causes of hypomagnesemia and discuss them further with a literature review.


…………………………………………………………………………………………………….... Introduction:-
The presentation starts with a 46-year-old Sudanese gentleman presenting to the emergency department after being treated by the family physician for throat infection for which he was given antibiotics and gargle medication. On the second day, he was not feeling well, even developing lower abdominal and left hip joint pain. This was not attributed to any recent trauma. With regards to his abdominal pain; no history of nausea, vomiting, fever nor changes in bowel habits. No change in his weight was documented. He had no contact with any sick person. Patient had not noticed any further complains. Past medical and surgical history were unremarkable.
The patient's family history shows he is a child of a consanguineous marriage with four other siblings in good health. No family history of any medical illness. As for his social history, he arrived in Kuwait and has been here for three years as a driver in an area known for farming. He is married to his cousin and has three children; one boy and two girls all healthy.
In the emergency department, Patient was afebrile and vitals within normal limits.
Examination was unremarkable except for Abdominal guarding and tenderness in left lower quadrant. Patient was admitted to surgical ward as a case of abdominal pain for investigation. The patient's initial labs shown in table 1.with regards to his serum Urea, Creatinine, electrolytes, liver enzymes, troponin I, coagulation profile, lipase, amylase, C-reactive protein and procalcitonin were normal. The abdominal x ray is seen in figure 1, a chest x ray and electrocardiogram were normal and a computerized tomography(CT) scan abdomen was done and showed fatty liver with few reactive bilateral inguinal lymph nodes, small hiatal hernia, and a normal appendix. On the same day, Patient had an episode of seizure which was first witnessed in the hospital; claimed to be the first ever for the patient; lasted for less than 10 minutes with up-rolling of the eyes with tonic clonic movements and frothing. No urinary incontinence nor fever was documented yet a CT brain was done which shows no acute ischemic insult nor space occupying lesion and otherwise unremarkable. Patient was kept under observation and serum electrolytes and glucose werenormal. Next day, Patient developed rigidity in lower limbs then progressed to upper limbs associated with lock jaw and became febrile; temperature was 38 degrees Celsius.A preliminary impression of Tetanus was made and human tetanus Immunoglobulin (Ig) was given by the Neurology and infectious disease team. On the third day, he developed shortness of breath and decreased level of consciousness which was associated with generalized tonic -clonic seizure, so he was intubated and shifted to the Intensive care unit (ICU). He was started on inotropes, pulse steroids, broad spectrum antibiotics and broad-spectrum antiepileptics. Lumbar puncture was done and the results in table 2. Creatinine Kinase was increased as expected reaching up to 5600 IU/ L; also, an EEG was abnormal showing low amplitude cerebral activity, delta waves were   During his ICU stay bronchoscopy was done and showed alveolar haemorrhage attributed to negative pressure pulmonary edema due to status epilepticus which prolonged his duration in the ICU. He developed deep vein thrombosis (DVT) in Left lower limb and was started on anticoagulation. At that point a full immunological and infectious disease panel was sent.The full virology panel was sent came back negative except for EBV which may explain his initial sore throat presentation alongside the abdominal pain. Also, HSV-1 was positive which could explain the seizure and disorientationand was treated for two weeks. Work up for HBV, HCV, HIV were negative; in addition, Leptospira, Brucella, and Malaria was negative. Moreover, the Tuberculosis work up was negative.
Since the alveolar haemorrhage developed suddenly an immunology screen showed low complements yet the rest of the work up was negative. Shown in table 3.
During the ICU stay he developed septicemia and an acute kidney injury. These factors prolonged his weaning process, yet he was discharged to the ward with a tracheostomy.He gradually improved and was feeding from nasogastric tube and later feeding per oral. Post ICU discharge Electromyography showed anaxonal motor involvement of lower limbs and ulnar nerves which is due to the prolonged stay in the ICU. The patient has continued to have a low serum magnesium for the duration of stay in the ward post discharge from the ICU. He was also found to have hypokalemia initially but was corrected upon replacement.The Hypomagnesemia has continued despite daily correction. Initially the omeprazole was stopped yet the patient continued to have hypomagnesemia. A daily correction with intravenous magnesium sulphate was given. The patient's urine electrolytes were sent alongside urine routine and microscopy attached table 4. This showed increase urinary magnesium losses in context of post-acute kidney injury. Acute tubular necrosis is mostly likely the cause of his acute kidney injury since he had a high creatinine kinase, high fractional excretion of sodium in urine and granular casts were present. The patient was given a high protein diet yet still no improvement in the magnesium was evident and he continued to be on oral magnesium tablet replacement. With continuous replacement of magnesium, physiotherapy, and supportive management he improved significantly. Later the patient was discharged with a follow up for further genetic testing.
The literature review will discuss the significance of hypomagnesemia; its different causes and factors that are attributed to our case.

Literature Review:-
Magnesium is an important electrolyte a key part of many reactions such as cellular function and nerve conduction. The Normal serum magnesium levels are between 0.74 to 1.10 mmol/L. Hypomagnesemia is an electrolyte disturbance caused when there is a low level of serum magnesium less than 0.74 mmol/L. the strict hemostasis in the body is strictly regulated by uptake in the small intestine and excretion in the kidney. Hypomagnesemia can be attributed to chronic disease, alcohol use disorder, gastrointestinal losses, renal losses, and other conditions. Signs and symptoms of hypomagnesemia range from mild tremor to cardiac arrythmia. [1][2][3][4] Hypomagnesemia gets less attention in medical literature compared to Hyponatremia, hypokalemia and hypocalcemia. This is evident by the amount of research of the aforementioned presentations. This is due to perhaps the lack of symptoms until the plasma levels are severely low; Clinical manifestations of hypomagnesemia that promptly lead to medical attention involve neuromuscular hyperexcitability that may range from tremors, fasciculation, tetany, to convulsions, and neuropsychiatric disturbances including apathy, delirium, and even coma. Hypomagnesemia's more serious complications are more associated with hypocalcemia and hypokalemia. [5][6] As a daily requirement the Institute of Medicine recommends a daily magnesium intake of 310-420 mg per day in adults. The majority reaching up to 80% of dietary magnesium is absorbed in the intestines, where the absorption itself depends on both intake and body magnesium status and occurs via both passive and active pathways. Approximately two thirds of plasma magnesium in ionized or complexed forms is ultra-filterable in the kidneys. Once filtered, a quarter is reabsorbed passively with sodium and water in the proximal tubules; three quarters of the filtered magnesium load is reabsorbed paracellularly in the thick ascending limb of the loop of Henle. Finally, reabsorption at the Distal convoluted tubules DCT subsegment. this segment is essential to magnesium balance because it determines the final urinary Mg 2+ loss. [7][8] Causes of Hypomagnesemia can be attributed to several causes in the discussed case. Dividing them into different categories, gastrointestinal, renal and miscellaneous. First cause can be attributed to Proton pump inhibitors (PPI), usually with hypocalcemia found to be evident with chronic use of omeprazole. Several studies have showed than use of PPI a lower serum magnesium is evident. A study involving ICU patient demonstrated that concurrent use of diuretics also increased the prevalence of hypomagnesemia. [9][10][11][12] In the case discussed above the patient had been on PPI for at least 6 weeks which may have played a role in him developing hypomagnesemia. Prolonged NGT suction like vomiting could be a potential cause of hypomagnesemia this is also evident in patients with diarrhea, inflammatory bowel disease, intestinal and biliary fistulas and pancreatitis. This is similar to the concept in patients with inflammatory bowel disease [13][14][15][16] Renal causes include the urinary loss of magnesium. This is by far the most common category for hypomagnesemia; can be further divided into volume expansion, alcohol, uncontrolled diabetes mellitus, hypercalcemia, or familial renal magnesium wasting. With volume expansion basically there will be a decreased renal water and sodium reabsorption and hence passive magnesium reabsorption. Alcohol, diabetes mellitus and hypercalcemia as a cause of hypomagnesemia are not applicable to the case since the patient had no history of ethanol intake; nor is he having an uncontrolled blood glucose or hypercalcemia.
Familial renal magnesium wasting perhaps not as common as the other causes yet need to be kept as a possibility this includes Gitelman and Bartter syndrome. Gitelman is an autosomal recessive disease which is known to cause low serum magnesium alongside hypocalciuric and Metabolic Alkalosis. However, in the case the patient did not have metabolic alkalosis nor any evidence of hypercalciuria. With regards to barter syndrome a hypokalemia and metabolic alkalosis is expected to be seen, yet it was not clearly evident in the case discussed above yet cannot rule out a role out since a proper genetic testing is to be done to properly diagnose.
Other genetic disorders that cause renal loss of magnesium include familial hypomagnesemia with hypercalciuria and nephrocalcinosis, autosomal dominant isolated hypomagnesemia, autosomal recessive isolated hypomagnesemia, renal malformations and early onset diabetes mellitus. The patients' relative has been tested and showed a normal serum magnesium level. In the case the urinary calcium was normal and there was no history of renal stones nor any family history pointing towards a familial disorder. Genetic testing is needed to rule out genetic causes of hypomagnesemia.
Acute Kidney Injury is a common medical condition that happens in almost 5.7% of all hospitalized patients and reaching up to 15% in ICU patients [17]. In a study Published by Catalina Et Al., the Prevalence of Hypomagnesemia is found to be high in patients who develop acute kidney injury reaching up to 69% [18]. Low serum Magnesium is mostly observed in the recovery phase of AKI and being symptomatic in more than 70% of patients who had hypomagnesemia post AKI, and symptoms improved with correction of magnesium, which makes it important to monitor magnesium levels post AKI [17].
Medication such as Loop and thiazide diuretics are known to cause hypomagnesemia since it inhibits magnesium reabsorption. Usually the degree of hypomagnesemia is mild since the volume will be contracted promoting the kidney to reabsorb water, sodium and to a certain degree magnesium. In our case the patient had no received any form of diuresis, yet it has to be mentioned as among the most common medication to cause hypomagnesemia. Other medication are found to cause hypomagnesemia. Medication that's is known to cause hypomagnesemia includes thiazide and loop diuretics, Aminoglycosides, cisplatin, Calcineurin inhibitors, mycophenolate and Anti-EGF receptors.
Levetiracetam is among the medication in which have been demonstrated to cause hypomagnesemia. Levetiracetam is generally preferred since it has a few side effects. A case report which has shown a patient which was controlled Sodium Valproate later developed hypokalemia and hypomagnesemia after starting the levetiracetam; however, this has not been widely seen. In the case the patient was started on levetiracetam which may had a role in the development of hypomagnesemia. [19] Other medication that may cause hypomagnesemia and reported to cause a barter-like syndrome is colistin, which was given to our patient as he developed Ventilator acquired Pneumonia (VAP) [20].
Finally, it is important to understand that hypomagnesemia is common finding inpatients and usually multifactorial starting from medication induced to renal causes. It was evident multiple factors were attributed our case as the cause of the hypomagnesemia.The factors were medications such as omeprazole, levetiracetam, and colistin; moreover, acute kidney injury in the form of acute tubular necrosis(ATN), NGT suction, dietary deficiency and possibly any other genetic renal cause since there is strong family history of consanguinity.