Intraperitoneal route of magnesium sulphate supplementation in a patient with severe renal magnesium wasting

Bahar Bastani and Gopalakrishna Pandurangan

Division of Nephrology, Department of Internal Medicine, Saint Louis University School of Medicine, St Louis, MO, USA

Keywords: intraperitoneal administration; magnesium deficiency; magnesium sulphate



   Introduction
 Top
 Introduction
 Case
 Discussion
 References
 
Hypomagnesaemia is a common electrolyte abnormality which is observed in approximately 11% of hospitalized [1] and >=20% of the intensive care unit patients [2]. Although gastrointestinal diseases/ malabsorption syndromes are the leading cause of hypomagnesaemia [3], renal magnesium wasting due to diseases such as uncontrolled diabetes mellitus or chronic alcoholism, or use of certain therapeutic agents (e.g. aminoglycosides, amphotericin B, pentamidine, polymixin B, cis-platinum, cyclosporin, capreomycin, viomycin) is also common [4]. About 30% of patients with Bartter's syndrome and all patients with Gitelman's syndrome have hypomagnesaemia, however, both diseases are associated with hypokalaemic metabolic alkalosis [5,6]. Patients with Bartter's syndrome also have hypercalciuria, nephrocalcinosis, and impaired urine-concentration ability. However, patients with Gitelman's syndrome are hypocalciuric. Hypomagnesaemia secondary to isolated renal magnesium loss is a rare hereditary disorder for which both autosomal dominant and recessive modes of inheritance have been reported. The autosomal dominant form is associated with a low urinary calcium excretion rate, whereas in the recessive form urinary calcium excretion rate is normal [79]. A rare autosomal recessive disease (mutation in paracellin-1, a renal tight junction protein required for paracellular Mg2+ reabsorption) characterized by profound renal magnesium wasting, hypercalciuria, nephrocalcinosis and renal failure has been described also [10]. Moreover, in two unrelated families with autosomal dominant isolated renal magnesium loss and hypocalciuria, a mutation has been identified in the {gamma}-subunit of the Na+, K+-ATPase pump, which inhibits the routing of the protein to the plasma membranes [11]. The hereditary renal magnesium loss disorders should be differentiated from the more commonly occurring hypomagnesaemia caused by hereditary intestinal absorption failure, inherited as an autosomal recessive trait [12,13].

Magnesium is the fourth most abundant cation in the body and is a key cofactor in a variety of enzymatic functions, e.g. hydrolysis of high-energy phosphate groups, protein synthesis, synthesis and degradation of DNA, and the actions of the adenylate cyclase system [14]. Magnesium also plays an important role in electrical characteristics of cell membrane and function of membrane ion channels [15]. There have been a number of clinical conditions associated with magnesium depletion such as refractory hypocalcaemia and/or hypokalaemia responsive only to magnesium therapy, increased susceptibility to digoxin-related arrhythmias, arrhythmias, hypertension, coronary artery spasm, sudden death, tremor, myoclonic jerks, Chvostek's sign, generalized muscular weakness, paraesthesia, depression, delirium, and seizures [6]. The renal reabsorption of magnesium occurs predominately by paracellular flux in the thick ascending limb of the loop of Henle (TALH), a process driven by a favourable electrochemical gradient. The conductance of this paracellular shunt pathway is highly regulated, with renal magnesium excretion varying from 0.5 to 80% of the filtered load depending on serum magnesium concentration [10]. Although milder forms of hypomagnesaemia may respond well to oral magnesium supplementation, the more severe cases need parenteral administration of magnesium sulphate. Because the level of serum magnesium determines the rate of magnesium reabsorption across the TALH, and because there is a relatively slow rate of magnesium uptake into the cells, serum magnesium concentration transiently rising during its infusion depresses magnesium reabsorption in the TALH, and hence, approximately half of the infused magnesium is usually excreted in the urine. Magnesium sulphate can be administrated intramuscularly as well, however, because the injections can be very painful this route is not recommended. Intraperitoneal route for magnesium administration has not been reported before. In this communication we would like to report our experience with this route of parenteral administration.



   Case
 Top
 Introduction
 Case
 Discussion
 References
 
A 43-year-old Caucasian female was diagnosed to have hypomagnesaemia in the range of 0.8–0.9 mg/dl, secondary to renal magnesium wasting, in January 1997. Her past medical history was significant for a neuroendocrine benign pancreatic tumour diagnosed in November 1996 after history of flushing, sweating and anxiety attacks, for which she underwent Whipple's procedure (partial pancreatectomy with Rou-enY surgery). Subsequently, she was found to have severe hypomagnesaemia, mild degree of hypokalaemia, borderline hypocalcaemia, and serum bicarbonate levels in the range of 20–25 mEq/l. Her past medical history was also significant for acute myocardial infarction x2 with negative coronary angiography, attributed to coronary vasospasm; left-sided hemiparesis secondary to right parietal stroke in 1997; hypothyroidism secondary to Hashimoto's thyroiditis; mild degree of hypertension; iron deficiency anaemia; uterine fibroid; liver haemangioma; mild non-insulin dependent diabetes for 2 years; and recurring sinusitis. The patient denied any history suggestive of malabsorption syndrome, inflammatory bowel diseases, diuretic use or other drugs known to cause renal magnesium wasting, or alcohol abuse in the past. She was documented to become very symptomatic with severe lethargy, left-sided numbness and hemiparesis, palpitation and severe agitation in association with low serum magnesium levels.

Her family history was significant for hypomagnesaemia in her mother (diagnosed in 1997, age 76, serum Mg2+ level 1.2 mg/dl; associated with nausea, vomiting, numbness in extremities, lethargy, palpitation, s/p cardiac pacemaker), sister (diagnosed in April 1997, age 47, serum Mg2+ level 1.0 mg/dl; associated with tunnel vision, nausea, lethargy, left-sided hemiparesis and numbness, palpitation, chest pain, muscle cramps), a daughter (diagnosed in 1997, age 20, serum Mg2+ level 0.9–1.0 mg/dl; associated with lethargy, slow motion to inability to move, muscle cramps, headache, left-sided hemiparesis, nausea and vomiting, palpitation, numbness and tingling in extremities), and a grandson (age 9 months, serum Mg2+ level 1.2 mg/dl). She also has a brother (57-years-old), and a son (24-years-old) who has two daughters, all of whom are asymptomatic but their serum Mg2+ levels have not been tested yet. This suggested an autosomal dominant mode of inheritance. The patient's parents had no blood relationship to each other, however, her maternal grandparents were first degree cousins. The patient's husband also has no blood relationship with her.

The work-up of her hypomagnesaemia revealed severe renal tubular magnesium wasting. She had required 10 g of magnesium sulphate infusion over 8–10 h intravenous drip on a daily basis, with serum magnesium nadirs at 0.8–0.9 mg/dl. Her 24-h urine collection on two different occasions revealed: urine volume 1150 and 1360 ml total urine creatinine 1159 and 1482 mg, Na+ 120 and 188 mEq, Ca2+ 165 and 163 mg, and Mg2+ 202 and 118 mg. Her creatinine clearances measured on two different occasions were 80 and 105 ml/min, and her intact parathyroid hormone level was 10 pg/ml with a concomitant serum Ca2+ level of 10.1 mg/dl.

When first seen in our clinic in October 1998, she was taking KCl, 20 mEq po tid; magnesium oxide 400 mg, 4 tablets po tid; calcium carbonate 650 mg, 3 tablets po qid; thyroxine, 0.1 mg po qd; spironolactone, 25 mg po qd; and omeprazole, 20 mg po qd. Her drug regimen was modified from magnesium oxide to Mg-Tab SR® (Niche Pharmaceuticals, Inc., Roanoke, TX, USA; magnesium L-lactate dihydrate, 7 mEq Mg2+ per tablet) 2 tablets po tid; spironolactone was changed to amiloride 10 mg po bid; KCl was replaced by potassium citrate for several months and was subsequently discontinued; calderol was started at 50 µg po once per week; calcium carbonate tablets were discontinued; and she was later started on a sustained release theophylline preparation at 200 mg po qd. Her serum magnesium level improved to a range of 1.3–1.9 mg/dl despite gradually decreasing intravenous magnesium sulphate dose to 4 g, infused over 8 h/day. Since she developed frequent infections at the sites of her chronic venous access ports, and since the duration of infusion prohibited her from going back to work, the decision was made to administer her parenteral magnesium supplementation via the intraperitoneal infusion route. Two weeks after insertion of a peritoneal dialysis catheter she received 4 g of magnesium sulphate, diluted in 500 cc of DW 5% (calculated osmolality=411 mosmol/1), over a 20 min period. The infusion was immediately complicated with severe excruciating lower abdominal pain which was not associated with nausea, vomiting, diarrhoea, fever or skin rash. The pain lasted for a few hours, during which her vital signs remained stable. Her serum magnesium concentration before intraperitoneal infusion of magnesium sulphate, ~=6 h after she had taken 4 tablets of Mg-Tab SR, was 1.6 mg/dl. It subsequently peaked at 2.4 mg/dl 4 h after intraperitoneal infusion with a gradual decline to 1.8 mg/dl after 14 h, and 1.0 mg/dl at 20 h after intraperitoneal infusion (Figure 1Go). Second dose of intraperitoneal magnesium sulphate, 4 g infused over 0.5 h, administered next day was similarly complicated with excruciating lower abdominal pain so severe that she equated its severity to ‘labour pain’. The pain started immediately with the initiation of intraperitoneal infusion and lasted for a few hours. It was not complicated with nausea, vomiting, diarrhoea, flushing or skin rash. Her serum magnesium this time peaked at 2.9 mg/dl 2 h after intraperitoneal infusion and was down to 1.6 mg/dl 23 h later (Figure 1Go). To rule out the possibility that peritoneal scarring from previous abdominal surgeries might have resulted in loculation of the intraperitoneal infusion leading to abdominal pain, 500 ml of DW 5% without addition of magnesium sulphate was infused intraperitoneally over a 20-min period. This was not associated with any discomfort or abdominal pain, indicating that the volume of intraperitoneal infusion was not responsible for the development of abdominal pain. Subsequently, the dose of magnesium sulphate was reduced to 2 g mixed in 500 cc DW 5% (calculated osmolality=344 mosmol/1) infused over 20 min intraperitoneally. This was again complicated with moderate to severe lower abdominal pain. However, it was more tolerable than the previous 4 g dose. She was sent home with the instructions to continue all of her oral medications and to infuse 2 g magnesium sulphate intraperitoneally on a daily basis, as a substitute for intravenous infusion, with the instruction to use Percocet (acetaminophen 325 mg with oxycodone 5 mg) as needed for pain. After one week of daily intraperitoneal infusions of 2 g of magnesium sulphate, due to the pain that accompanied each intraperitoneal administration, the dose was reduced to 1 g magnesium sulphate mixed in 500 cc of DW 5% (calculated osmolality=311 mosmol/1) administered intraperitoneally on a twice daily basis. The new regimen significantly reduced the pain associated with the intraperitoneal administration. On a scale of 10, the patient scored severity of the pain as 10 with 4 g intraperitoneal infusions, 8 with 2 g infusions, and only 1 with 1 g infusions. Her serum magnesium remains at 1.4–1.5 mg/dl range with the current regimen. Her serum creatinine concentrations have been stable and in the range of 0.9–1.1 mg/dl in the past 3 years.



View larger version (13K):
[in this window]
[in a new window]
 
Fig. 1. Serum magnesium concentrations at different time points after 4 g magnesium sulphate was infused intraperitoneally (time 0). *Serum level 4 h after the patient had taken four tablets of Mg-Tab SR® orally.

 



   Discussion
 Top
 Introduction
 Case
 Discussion
 References
 
Herein we report the first experience with intraperitoneal administration of magnesium sulphate. Our experience revealed that intraperitoneal administration of magnesium sulphate at doses of 2 or 4 g was extremely painful and was described by our patient as severe as having a ‘labour pain’. We do not think that the osmolality of the solutions (344 or 411 mosmol/1 with 2 or 4 g magnesium sulphate in DW 5%, respectively) was responsible for all abdominal pain, as the routinely used peritoneal dialysis solutions (Dianeal® solution; BaxterHealthCare Corporation, IL, USA) with dextrose concentrations of 1.5%, 2.5%, and 4.25% and osmolalities of 344, 396, and 483 mosmol/l, respectively, are not associated with abdominal pain. However, a 1 g dose of magnesium sulphate was well tolerated with minimal discomfort. We have also shown that magnesium absorption from the peritoneal cavity is a slow, steady process, and occurs over approximately 18–24 h. Our case suggests that patients who require parenteral magnesium sulphate infusion and who cannot afford being connected to an intravenous set for several hours every day may benefit from doses up to 1 g administered intraperitoneally a couple of times per day. This will provide a gradual slow absorption of magnesium without causing peritoneal irritation. It also provides the patient freedom from long hours of intravenous magnesium infusion.



   Acknowledgments
 
The authors appreciate the secretarial help of Ms Tracy Line.



   Notes
 
Correspondence and offprint requests to: Bahar Bastani MD, Professor of Medicine, Division of Nephrology, Saint Louis University School of Medicine, St Louis, MO 63110, USA. Email: bastanib{at}slu.edu Back



   References
 Top
 Introduction
 Case
 Discussion
 References
 

  1. Wong ET, Rude RK, Singer FR et al. A high prevalence of hypomagnesemia and hypermagnesemia in hospitalized patients. Am J Clin Pathol1983; 79: 348–352[ISI][Medline]
  2. Reinhart RA, Desbeins NA. Hypomagnesemia in patients entering the ICU. Crit Care Med1985; 13: 506–507[ISI][Medline]
  3. Wacker WEC, Parisi AF. Magnesium metabolism. Part II. N Engl J Med1968; 278: 712–717[ISI][Medline]
  4. Shah GM, Kirschenbaum MA. Renal magnesium wasting associated with therapeutic agents. Miner Electrolyte Metab1991; 17: 58–64[ISI][Medline]
  5. Cushner HM, Peller TP, Fried T, Delea CS. Does magnesium play a role in the hypokalemia of Bartter's syndrome? Am J Kid Dis1990; 79: 221–223
  6. Stein JH. The pathogenetic spectrum of Bartter's syndrome. Kidney Int1985; 28: 85–95[ISI][Medline]
  7. Meji IC, Saar K, van den Heuvel L et al. Hereditary isolated renal magnesium loss maps to chromosome 11q23. Am J Hum Genet1999; 64: 180–188[ISI][Medline]
  8. Geven WB, Monnens LAH, Willems JL, Buijs W, Hamel CJ. Isolated autosomal recessive renal magnesium loss in two sisters. Clin Genet1987; 32: 398–402[ISI][Medline]
  9. Geven WB, Monnens LAH, Willems JL, Buijs WC, ter Haar BG. Renal magnesium wasting in two families with autosomal dominant inheritance. Kidney Int1987; 31: 1140–1144[ISI][Medline]
  10. Simon DB, Lu Y, Choate KA et al. Paracellin-1, a renal tight junction protein required for paracellular Mg2+ resorption. Science1999; 285: 103–106[Abstract/Free Full Text]
  11. Meji I, Koenderink JB, van Bokhoven H et al. Dominant isolated renal magnesium loss is caused by misrouting of the Na+, K+-ATPase {gamma}-subunit. Nature Genet2000; 26: 266
  12. Chery M, Biancalana V, Philippe C et al. Hypomagnesemia with secondary hypocalcemia in a female with balanced X;9 translocation: mapping of the Xp22 chromosome breakpoint. Hum Genet1994; 93: 587–591[ISI][Medline]
  13. Walder RY, Shalev H, Brennan TM et al. Familial hypomagnesemia maps to chromosome 9q, not to the X chromosome: genetic linkage mapping and analysis of a balanced translocation breakpoint. Hum Mol Genet1997; 6: 1491–1498[Abstract/Free Full Text]
  14. Elin RJ. Magnesium metabolism metabolism in health and disease. Dis Mon1998; 34: 161–218
  15. Hoffman BF, Suckling EE. Effect of several cations on transmembrane potentials of cardiac muscle. Am J Physiol1956; 186: 317–324[Abstract/Free Full Text]
  16. Goldfarb S. Clinical disorders of magnesium metabolism. Part I. Hospital Physician1999; 2: 1–11
Received for publication: 2. 1.01
Revision received 25. 4.01.



This Article
Extract
FREE Full Text (PDF)
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Disclaimer
Request Permissions
Google Scholar
Articles by Bastani, B.
Articles by Pandurangan, G.
PubMed
PubMed Citation
Articles by Bastani, B.
Articles by Pandurangan, G.