Mental Change, Cardiovascular Depression and QT Prolongation Caused by Severe Hypermagnesemia

대한중환자의학회지：제 23 권 제 2 호 ■ 증례■ Vol. 23, No. 2, December, 2008

󰠏 A Case Report 󰠏 Hyung Oh Choi, M.D., Seung Geun Lee, M.D., Pil Hyung Lee, M.D., Sung Nam Lim, M.D., Byeong Seok Sohn, M.D., Yun Hee Chung, M.D. and Gi-Byoung Nam, M.D.

Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

A 50-year-old woman was referred to our hospital for evaluation of mental change and general weakness accompanied by an irregular and weak pulse. She had previously been diagnosed with Bartter’s syndrome and had taken potassium-sparing diuretics. She had developed constipation that had led to abdominal pain and had taken excessive magnesium oxide over a long time. On admission, she was lethargic. Her blood pressure (BP) was 130/74 mmHg, with a heart rate varying from 30 to 78 beats/min. An electrocardiogram (ECG) revealed several abnormalities, including first degree AV block, QT prolongation, sinus pause with a junctional rhythm, and paroxysmal tachycardia alternating with sinus pause. Her serum concentration of magnesium was markedly elevated to 16.19 mg/dl. Hemodialysis and a calcium gluconate infusion was attempted to reduce magnesium levels and to counteract the cardiovascular effect of magnesium. As magnesium levels declined, her general medical condition improved and her ECG changes were normalized. Severe hypermagnesemia should be suspected as the cause of mental change, cardiovascular dysfunction, and variable ECG changes.

Key Words: hypermagnesemia, magnesium oxide.

Hypermagnesemia is fairly rare and is usually considered ECG changes. iatrogenic. The kidney is the principal organ involved in magnesium regulation.1) As magnesium loads increase, the kidney CASE REPORT increases magnesium excretion. A healthy adult can excrete more than 6 g of magnesium daily,2) and symptomatic hyper- A 50-year-old woman was referred to the emergency depart- magnesemia develops almost exclusively in the presence of re- ment for drowsy mentality and bradyarrhythmia. Since being nal insufficiency. Recent reports suggest that hypermagnesemia diagnosed with Bartter’s syndrome 18 years previously, she can occur without severe renal insufficiency, for example when had taken potassium-sparing diuretics. She had been admitted the patient has a bowel disease.3-7) Increased plasma magne- previously for major depression with borderline personality sium concentrations can lead to neuromuscular suppression and disorder. She had severe constipation and abused magnesium- cardioinhibitory action with hypocalcemia.2,8-10) Cardioinhibitory containing cathartics (magnesium oxide), taking 6 g a day for actions include prolongation of PR interval, increase in QT in- 10 years. Four days prior to admission, her general weakness terval, conduction delay, and complete heart block.2,3,10) We de- became aggravated and she began to feel chest discomfort. On scribe a patient with severe hypermagnesemia who presented the day of admission, she was found to be lethargic and she with mental change, cardiopulmonary depression, and variable did not respond well to verbal stimuli. She was then transferred to the emergency department for evaluation of mental Received on July 30, 2008, Accepted on October 29, 2008 change, azotemia, ileus, and bradyarrhythmia. Correspondence to: Gi-Byoung Nam, Department of Internal Medicine, University of Ulsan College of Medicine, 388-1, Poongnap- On admission to the emergency department, she responded dong, Songpa-gu, Seoul 138-736, Korea very slowly but appropriately. Her blood pressure was 130/74 Tel: 82-2-3010-3159, Fax: 82-2-486-5918 mm Hg, her pulse rate fluctuated from 30 to 78 beats/min, E-mail: [email protected] 102 Hyung Oh Choi, et al：Mental Change, Cardiovascular Depression and QT Prolongation Caused by Severe Hypermagnesemia 103 and her body temperature was 34.7oC. Laboratory data showed drowsy mental state showed no acute brain lesion. Calcium mild leukocytosis, azotemia, and hypokalemia. Abnormal labo- gluconate was given to antagonize the cardiovascular effects of ratory values were WBC 11700/mm3 (neutrophils, 87.3%), he- magnesium. moglobin 10.6 g/dl; BUN 71 mg/dl, serum creatinine 1.7 On hospital day 2, she was transferred to the intensive care mg/dl, sodium 132 mEq/dl, potassium 2.9 mEq/dl, chloride 84 unit for close monitoring and hemodialysis. Her pulse rate mEq/dl, calcium 7.6 mg/dl, phosphorus 5.2 mg/dl, and lactate fluctuated greatly from 35 to 125 beats/min and her BP drop- dehydrogenase 492 IU/L. Arterial blood gas analysis in room ped to 52/43 mm Hg during hemodialysis. She also showed air showed a pH of 7.450, pO2 82 mm Hg, pCO2 67.0 mm respiratory depression with a rate of 9 breaths/min. Inotropics

Hg, HCO3 47.0 mEq/L, base excess 19.4 mEq/L, and O2 satu- were infused for hypotension. ECG showed nonsustained nar- ration 96%. The results were interpreted as indicative of mixed row QRS tachycardia alternating with slow junctional rhythm metabolic alkalosis and respiratory acidosis associated with (Fig. 1B). After hemodialysis, her serum magnesium concen- Bartter’s syndrome and respiratory depression. Considering her tration had decreased to 9.7 mg/dl. drug history, her serum magnesium concentration was measured On hospital day 3, she became fully conscious. Her magne- and found to be markedly elevated, to 16.19 mg/dl (reference, sium concentration decreased to 6.74 mg/dl, and an ECG 1.8−3.0 mg/dl). Initial ECG showed atrial bigeminy, frequent showed a sinus rhythm with QT prolongation and T wave APC, T wave inversion (II, III, aVF, and V4-6 lead), pro- inversion. Neither significant arrhythmias nor blood pressure longed QT interval (corrected QT: 545 msec), and first degree fluctuations were observed. On hospital day 12, her magnesium atrioventricular block (PR interval 218 msec) (Fig. 1A). Abdominal radiographs showed severe paralytic ileus. Computed tomography of the abdomen to rule out a hidden abnormality showed no evidence of any obstruction. Magnetic resonance imaging of the brain to evaluate her dysarthria and

Fig. 2. On hospital day 12, the patient’s serum magnesium concentration had decreased to 2.04 mg/dl. Electrocardiography showed near-normal findings.

Fig. 1. Electrocardiography results. (A) On admission, various abnormal findings, such as prolonged PR interval, prolonged QTc interval, and frequent APC, were observed, associated with a magnesium concentration of 16.19 mg/dl. (B) On hospital day 2, serial rhythm strips of electrocardiography show atrial tachyarrhythmia alternating with prolonged sinus pause and slow junctional escape rhythm, associated with a magnesium Fig. 3. Schematic presentation of changes in electrolytes and prolonged concentration of 10.17 mg/dl. QTc. 104 대한중환자의학회지：제 23 권 제 2 호 2008 concentration had decreased to 2.04 mg/dl, her QT prolonga- QT interval.2,3,10) Our patient initially showed a prolonged PR tion and T wave inversion had returned to normal (Fig. 2), interval, prolonged QTc interval, and T wave inversion. Close and her serum creatinine concentration had normalized. Trans- monitoring revealed a rapidly changing arrhythmia of brady- thoracic echocardiography and thallium myocardial perfusion cardia, atrial tachyarrhythmia, and junctional rhythm (Fig. 1B). scan results were within normal limits. Fig. 3 shows that the markedly prolonged QT interval in our patient seemed to be caused mainly by hypermagnesemia, al- DISCUSSION though initially low potassium and calcium concentrations could have contributed to the QT prolongation. Torsades de Magnesium homeostasis is mainly dependent on gastro- pointes is uncommon in hypermagnesemia-induced QT pro- intestinal absorption and renal excretion, with the kidneys play- longation. This condition may be associated with the calcium ing a major role in magnesium regulation.1) Sixty to seventy blocking effect of hypermagnesemia per se. percent of filtered magnesium is reabsorbed mainly in the In conclusion, we describe a patient with severe, sympto- thick ascending limb of Henle.1,10) Because the kidneys can ex- matic, hypermagnesemia, arising after abuse of cathartics. This crete more than 6 g magnesium/day, severe hypermagnesemia finding suggests that hypermagnesemia could develop without usually develops in the presence of renal insufficiency.2) Our renal failure in patients with gastrointestinal disease. Hyper- patient had been diagnosed with Bartter’s syndrome. Because magnesemia should be suspected as a cause of mental change, this defect may be present in the thick ascending limb of cardiovascular dysfunction, and variable ECG changes. Henle's loop, renal magnesium wasting may occur in Bartter’s syndrome, in addition to hypokalemia, hypochloremic metabolic REFERENCES alkalosis, and decreased ability to concentrate and dilute urine.11) Her serum concentration of creatinine and BUN were ele- 1) Weisinger JR, Bellorin-Font E: Magnesium and phosphorus. vated at initial presentation but returned to normal ranges on Lancet 1998; 352: 391-6. hospital day 4, suggesting that the abnormality may have aris- 2)Gibbs MA, Tayal VS: Electrolyte disturbance. In: Rosen's en because of prerenal azotemia caused by hypotension and, emergency medicine: concepts and clinical practice. 6th ed. dehydration. Symptomatic hypermagnesemia has been reported Edited by John A, Marx M: Missouri, Mosby. 2006. Available form http://www.mdconsult.com/das/book/body/114504139-2/ in patients without renal failure, but with decreased gastro- 0/1365/382.html intestinal motility.3-7) This may occur after the ingestion of an- 3) Clark BA, Brown RS: Unsuspected morbid hypermagnesemia ticholinergics or narcotics or in patients with hypomotility dis- in elderly patients. Am J Nephrol 1992; 12: 336-43. orders such as chronic constipation, colitis, bowel obstruction, 4) Fassler CA, Rodriguez RM, Badesch DB, Stone WJ, Marini or gastric dilation.2) The symptomatic hypermagnesemia ob- JJ: Magnesium toxicity as a cause of hypotension and served in our patient may have been caused by gastrointestinal hypoventilation. Occurrence in patients with normal renal function. Arch Intern Med 1985; 145: 1604-6. hypomotility and excessive cathartic ingestion. Hypermagnesem- 5) Kontani M, Hara A, Ohta S, Ikeda T: Hypermagnesemia ia itself can cause bowel hypomotility, enhancing the absorp- induced by massive cathartic ingestion in an elderly woman tion of magnesium and creating a vicious cycle leading to a without pre-existing renal dysfunction. Intern Med 2005; 44: magnesium concentration exceeding renal excretion capacity.12) 448-52. Our patient showed severe symptomatic hypermagnesemia 6) Kutsal E, Aydemir C, Eldes N, Demirel F, Polat R, Taspnar with hypotension, respiratory depression, depressed mental state, O, et al: Severe hypermagnesemia as a result of excessive cathartic ingestion in a child without renal failure. Pediatr and a variety of ECG changes. Magnesium, used for torsade Emerg Care 2007; 23: 570-2. de pointes, acts as an effective calcium channel blocker both 7) Qureshi T, Melonakos TK: Acute hypermagnesemia after extracellularly and intracellularly, and blocks several cardiac laxative use. Ann Emerg Med 1996; 28: 552-5. potassium channels.13) Hypermagnesemia can depress the con- 8) Kleinschmidt KC, Delaney KA: Fluid and electrolytes. In: duction system of the heart. Symptoms and signs of hyper- Clinical toxicology. 1st ed. Edited by Marsha D, Ford MD: magnesemia are usually predictable. Bradycardia and hypo- Philadelphia, WB Saunders. 2001. Available from http://www. mdconsult.com/das/book/body/114504139-2/0/1013/61.html tension are the earliest manifestations. Several ECG changes 9) Pollak MR, Yu ASL, Taylor EN: Disorders of calcium, are observed at higher levels, such as prolongation of the PR magnesium, and phosphate balance. In: Barry M, Brenner M, interval, an increase in QRS duration, and an increase in the editors. Brenner and Rector's the kidney. 8th ed. Philadelphia, Hyung Oh Choi, et al：Mental Change, Cardiovascular Depression and QT Prolongation Caused by Severe Hypermagnesemia 105

WB Saunders. 2007. pp 596-601. 12) Mordes JP, Wacker WE: Excess magnesium. Pharmacol Rev 10) Topf JM, Murray PT: Hypomagnesemia and hypermagne- 1977; 29: 273-300. semia. Rev Endocr Metab Disord 2003; 4: 195-206. 13) Agus ZS, Morad M: Modulation of cardiac ion channels by 11) Sutton RA, Domrongkitchaiporn S: Abnormal renal magne- magnesium. Annu Rev Physiol 1991; 53: 299-307. sium handling. Miner Electrolyte Metab 1993; 19: 232-40.