Milk-Alkali Syndrome Medication
- Author: R Hal Scofield, MD; Chief Editor: George T Griffing, MD more...
The primary therapy for hypercalcemia in milk-alkali syndrome is intravenous volume replacement with isotonic sodium chloride solution. When ingestion of calcium carbonate has stopped, the pathophysiologic stimulus for hypercalcemia is no longer present. Hypercalcemia in this setting usually is rapidly corrected. Loss of calcium from urine can be increased with the use of a loop diuretic, but this therapy cannot be started until intravascular volume has been replenished. Renal dialysis has been used in a few patients, as has intravenous infusion of pamidronate.
Diuretics induce calciuresis. In patients with severe hypercalcemia, the individual typically is volume depleted, which means that volume should be replaced with saline prior to institution of diuretic therapy.
Furosemide inhibits the resorption of sodium and chloride in the loop of Henle and the proximal and distal tubules of the kidney. Its onset of action is rapid after an intravenous dose.
Calcium Metabolism Modifiers
These agents decrease the movement of calcium from bone to serum. Bisphosphonates are analogues of inorganic pyrophosphate and act by binding to hydroxyapatite in bone matrix, thereby inhibiting the dissolution of crystals. They prevent osteoclast attachment to the bone matrix and osteoclast recruitment and viability.
The newer bisphosphonates are not completely free of the risk of causing a mineralization defect, but their safe therapeutic window is much wider. They clearly are more potent than etidronate in reducing disease activity and normalizing alkaline phosphatase levels. Severe dental disease may be a contraindication for these agents.
Pamidronate's main action is to inhibit the resorption of bone. The mechanism by which this inhibition occurs is not fully known. The drug is adsorbed onto calcium pyrophosphate crystals and may block the dissolution of these crystals, also known as hydroxyapatite, which are an important mineral component of bone. There is also evidence that pamidronate directly inhibits osteoclasts.
Zoledronate inhibits bone resorption. It inhibits osteoclastic activity and induces osteoclastic apoptosis
Kleinig TJ, Torpy DJ. Milk-Alkali syndrome: broadening the spectrum of causes to allow early recognition. Intern Med J. 2004 Jun. 34(6):366-7. [Medline].
Irtiza-Ali A, Waldek S, Lamerton E, Pennell A, Kalra PA. Milk alkali syndrome associated with excessive ingestion of Rennie: case reports. J Ren Care. 2008 Jun. 34(2):64-7. [Medline].
Jousten E, Guffens P. Milk-alkali syndrome caused by ingestion of antacid tablets. Acta Clin Belg. 2008 Mar-Apr. 63(2):103-6. [Medline].
Addington S, Larson N, Scofield RH. Milk-alkali syndrome in pre-eclamptic pregnancy: report of a patient and evaluation of albumin-corrected calcium in pre-eclamptic pregnancies. J Okla State Med Assoc. 2006 Sep. 99(9):480-4. [Medline].
Beall DP, Scofield RH. Milk-alkali syndrome associated with calcium carbonate consumption. Report of 7 patients with parathyroid hormone levels and an estimate of prevalence among patients hospitalized with hypercalcemia. Medicine (Baltimore). 1995. 74(2):89-96. [Medline].
Picolos MK, Lavis VR, Orlander PR. Milk-alkali syndrome is a major cause of hypercalcaemia among non-end-stage renal disease (non-ESRD) inpatients. Clin Endocrinol (Oxf). 2005 Nov. 63(5):566-76. [Medline].
Wu KD, Chuang RB, Wu FL, Hsu WA, Jan IS, Tsai KS. The milk-alkali syndrome caused by betelnuts in oyster shell paste. J Toxicol Clin Toxicol. 1996. 34(6):741-5. [Medline].
Nakanishi T, Uyama O, Yamada T, Sugita M. Sustained metabolic alkalosis associated with development of the milk-alkali syndrome. Nephron. 1992. 60(2):251. [Medline].
Brandwein SL, Sigman KM. Case report: milk-alkali syndrome and pancreatitis. Am J Med Sci. 1994 Sep. 308(3):173-6. [Medline].
Campbell SB, Macfarlane DJ, Fleming SJ, Khafagi FA. Increased skeletal uptake of Tc-99m methylene diphosphonate in milk-alkali syndrome. Clin Nucl Med. 1994 Mar. 19(3):207-11. [Medline].
Duthie JS, Solanki HP, Krishnamurthy M, Chertow BS. Milk-alkali syndrome with metastatic calcification. Am J Med. 1995 Jul. 99(1):102-3. [Medline].
Spital A, Freedman Z. Severe hypercalcemia in a woman with renal failure. Am J Kidney Dis. 1995 Oct. 26(4):674-7. [Medline].
Lin SH, Lin YF, Shieh SD. Milk-alkali syndrome in an aged patient with osteoporosis and fractures. Nephron. 1996. 73(3):496-7. [Medline].
Muldowney WP, Mazbar SA. Rolaids-yogurt syndrome: a 1990s version of milk-alkali syndrome. Am J Kidney Dis. 1996 Feb. 27(2):270-2. [Medline].
Vanpee D, Delgrange E, Gillet JB, Donckier J. Ingestion of antacid tablets (Rennie) and acute confusion. J Emerg Med. 2000 Aug. 19(2):169-71. [Medline].
Liu SW, Kumar AM, Nadel ES, Brown DF. A young woman with altered mental status. J Emerg Med. 2002 May. 22(4):405-8. [Medline].
Robertson WC Jr. Calcium carbonate consumption during pregnancy: an unusual cause of neonatal hypocalcemia. J Child Neurol. 2002 Nov. 17(11):853-5. [Medline].
Morton A. Milk-alkali syndrome in pregnancy, associated with elevated levels of parathyroid hormone-related protein. Intern Med J. 2002 Sep-Oct. 32(9-10):492-3. [Medline].
Gordon MV, McMahon LP, Hamblin PS. Life-threatening milk-alkali syndrome resulting from antacid ingestion during pregnancy. Med J Aust. 2005 Apr 4. 182(7):350-1. [Medline].
Verburg FA, van Zanten RA, Brouwer RM, Woittiez AJ, Veneman TF. [A man with a classic serious milk-alkali syndrome and a carcinoma of the stomach]. Ned Tijdschr Geneeskd. 2006 Jul 22. 150(29):1624-7. [Medline].
Ennen CS, Magann EF. Milk-alkali syndrome presenting as acute renal insufficiency during pregnancy. Obstet Gynecol. 2006 Sep. 108(3 Pt 2):785-6. [Medline].
Dinnerstein E, McDonald BC, Cleavinger HB, Thadani VM, Jobst BC. Mesial temporal sclerosis after status epilepticus due to milk alkali syndrome. Seizure. 2008 Apr. 17(3):292-5. [Medline].
Shah BK, Gowda S, Prabhu H, Vieira J, Mahaseth HC. Modern milk alkali syndrome--a preventable serious condition. N Z Med J. 2007 Sep 21. 120(1262):U2734. [Medline].
Miller PD. Vitamin D, calcium, and cardiovascular mortality: a perspective from a plenary lecture given at the annual meeting of the American Association of Clinical Endocrinologists. Endocr Pract. 2011 Sep 1. 17(5):798-806. [Medline].
Papworth K, Grankvist K, Ljungberg B, Rasmuson T. Parathyroid hormone-related protein and serum calcium in patients with renal cell carcinoma. Tumour Biol. 2005 Jul-Aug. 26(4):201-6. [Medline].
LeGrand SB, Leskuski D, Zama I. Narrative review: furosemide for hypercalcemia: an unproven yet common practice. Ann Intern Med. 2008 Aug 19. 149(4):259-63. [Medline].
Patel AM, Goldfarb S. Got calcium? Welcome to the calcium-alkali syndrome. J Am Soc Nephrol. 2010 Sep. 21(9):1440-3. [Medline].
Swanson CM, Mackey PA, Westphal SA, Argueta R. Nicotine-substitute gum-induced milk alkali syndrome: a look at unexpected sources of calcium. Endocr Pract. 2013 Nov-Dec. 19(6):142-4. [Medline].
Chhabra L, Spodick DH. Milk Alkali syndrome: an electrocardiographic masquerader for non-hypothermic Osborn phenomenon. Heart. 2013 Sep. 99(17):1302-3. [Medline].
Neupane S. Incidence of milk alkali syndrome in the Women's Health Initiative clinical trial and cohort study. Osteoporos Int. 2014 Mar. 25(3):1193. [Medline].
Soyfoo MS, Brenner K, Paesmans M, Body JJ. Non-malignant causes of hypercalcemia in cancer patients: a frequent and neglected occurrence. Support Care Cancer. 2013 May. 21(5):1415-9. [Medline].
|Mean Age||51 Years (Range, 24-95 y)|
|Sex||35 men and 43 women|
|Calcium source||Calcium carbonate in all but 1|
|Ingestion of bicarbonate||In 7 patients|
|Ingestion of milk||In 20 patients (plus one who ate yogurt)|
|Mean serum calcium||15.1mg/dL (3.75mmol/L) (range, 11.1-27.5mg/dL)|
|High serum phosphorus||In 12 patients|
|Permanent renal insufficiency||In 20 of 57 patients eligible for evaluation|
|Parathyroid exploration||In 3 patients|
|Hypocalcemia with treatment||In 16 patients|
|*These data are derived from the 7 patients reported, plus the 28 reviewed in Beall and Scofield, 1995, as well as additional patients reported by Gibbs and Lee, 1992; Nakanishi et al, 1992 ; Brandwein and Sigman, 1994 ; Campbell et al, 1994 ; Duthie et al, 1995 ; Spital and Freedman, 1995 ; Fiorino, 1996 ; Lin et al, 1996 ; Muldowney and Mazbar, 1996 ; Sulkin and Krentz, 1999 ;
Camidge and Peaston, 2000 ; George and Clark, 2000 ; Vanpee et al, 2000 ; Liu et al, 2002 ; Robertson, 2002 ; Morton, 2002 ; Kleinig and Torpy, 2004 ; Picolos et al, 2005 ; Gordon et al, 2005 ; Addington et al, 2006 ; Verburg et al, 2006 ; Ennen and Magann, 2006 ; Caruso et al, 2007 ; Dinnerstein et al, 2007 ; Javid et al, 2007; Kaklamanos and Perros, 2007 ; Shah et al, 2007 ; Irtiza-Ali et al, 2008 ; and Jousten and Guffens, 2008.
Two of the patients were pregnant.