Potassium
and Magnesium
References:
J Intensive Care Med. 2005 Jan-Feb;20(1):3-17.
Magnesium deficiency in critical illness.
Tong GM, Rude RK.
University of Southern California,
School of Medicine, Los Angeles, CA 90089-9317, USA.
Magnesium (Mg) deficiency commonly occurs in critical illness
and correlates with a higher mortality and worse clinical
outcome in the intensive care unit (ICU). Magnesium
has been directly implicated in hypokalemia, hypocalcemia, tetany,
and dysrhythmia. Moreover, Mg may play a role in acute
coronary syndromes, acute cerebral ischemia, and asthma. Magnesium
regulates hundreds of enzyme systems. By regulating enzymes
controlling intracellular calcium, Mg affects smooth muscle
vasoconstriction, important to the underlying pathophysiology
of several critical illnesses. The principle causes
of Mg deficiency are gastrointestinal and renal losses;
however, the diagnosis is difficult to make because of
the limitations of serum Mg levels, the most common assessment
of Mg status. Magnesium tolerance testing and ionized Mg2+
are alternative laboratory assessments; however, each has
its own difficulties in the ICU setting. The use of Mg
therapy is supported by clinical trials in the treatment
of symptomatic hypomagnesemia and preeclampsia and is recommended
for torsade de pointes. Magnesium therapy is not supported
in the treatment of acute myocardial infarction and is
presently undergoing evaluation for the treatment of severe
asthma exacerbation, for the prevention of post-coronary
bypass grafting dysrhythmias, and as a neuroprotective
agent in acute cerebral ischemia ↑ Back To Top
Intern Med. 2004 May;43(5):410-4.
Depressive state and
paresthesia dramatically improved by intravenous MgSO4
in Gitelman's syndrome.
Enya M, Kanoh Y, Mune
T, Ishizawa M, Sarui
H, Yamamoto M, Takeda
N, Yasuda K, Yasujima
M, Tsutaya S, Takeda
J.
Third Department of Internal
Medicine, Gifu University School of Medicine, 40 Tsukasa-machi,
Gifu 500-8705.
A 69-year-old woman was referred to our department for
evaluation of hypokalemia, which had been treated by oral
potassium for more than ten years. She complained of headache,
knee joint pain, sleeplessness and paresthesia in extremities
and, most prominently, depression. Laboratory data suggested Gitelman's
syndrome, which is caused by mutations in the gene
encoding the thiazide-sensitive Na-Cl cotransporter. Direct
sequencing of the gene in this patient revealed homozygous
mutation R964Q in exon 25. Intravenous
supplement of MgSO4 dramatically improved both the depression
and the paresthesia, suggesting that hypomagnesemia
played a role in the clinical manifestations. ↑ Back To Top
Am J Ther. 2006 Mar-Apr;13(2):101-8.
Prevention of thiazide-induced
hypokalemia without magnesium depletion by potassium-magnesium-citrate.
Odvina CV, Mason RP, Pak
CY.
Center for Mineral Metabolism
and Clinical Research, University of Texas Southwestern
Medical Center, Dallas, TX 75390-8885, USA.
Thiazide can cause magnesium depletion, which may exaggerate
renal potassium wasting and hypokalemia. The purpose of
this double-blind, randomized trial was to compare the
metabolic effects of potassium-magnesium-citrate (K-Mg-citrate)
and potassium chloride (KCl) during long-term treatment
with thiazide. Twenty-two normal volunteers received hydrochlorothiazide
50 mg/d. Ten subjects concurrently took K-Mg-citrate (42
mEq K/d and 21 mEq Mg/d), and 12 subjects were given KCl
42 mEq/d. Serum potassium concentration remained unchanged
during K-Mg-citrate supplementation, with a change from
baseline of 21.7% over 6 months, compared with 26.4% with
KCl supplementation. Serum electrolytes were normal and
not significantly different between K-Mg-citrate and KCl.
During K-Mg-citrate treatment, serum magnesium increased
significantly by about 10%, associated with an adequate
increase in urinary magnesium and a nonsignificant increase
in monocyte and free muscle magnesium. Serum magnesium
was unchanged, and monocyte and free muscle magnesium showed
a nonsignificant decline during KCl supplementation. K-Mg-citrate
provided an alkali load, increasing urinary pH,
and reducing urinary undissociated uric acid. It also increased
urinary citrate and tended to lower the saturation of calcium
oxalate. KCl supplementation lacked these actions. K-Mg-citrate
prevents thiazide-induced hypokalemia without provoking
metabolic alkalosis. It seems to prevent magnesium depletion.
By providing an alkali load, it retards the propensity
for the crystallization of uric acid and probably of calcium
oxalate. Though not conclusive, KCl
supplementation may be less effective than K-Mg-citrate
in maintaining normokalemia because of a subtle
magnesium wasting. Moreover, KCl is devoid of protective
action toward crystallization of stone-forming salts. ↑ Back To Top
Acta Med Scand Suppl. 1986;707:33-6.
Intracellular electrolytes
in cardiac failure.
Wester PO, Dyckner T.
In congestive heart failure (CHF) there are several compensatory
mechanisms operating which may influence electrolyte metabolism.
The activation of the renin-angiotensin-aldosterone system
causes retention of sodium (Na) and losses of potassium
(K) and magnesium (Mg). The secondary hyperaldosteronism
may give rise to high intracellular Na and low intracellular
K through a direct permeability effect on the cell membrane. The
Mg deficiency may lead to a further increase of intracellular
Na and decrease of intracellular K since Mg is a necessary
ion for the function of the Na-K pump. In 297 patients
with diuretic treated CHF we found that 42% had hypokalemia,
37% hypomagnesemia and 12% hyponatremia. We
also found that 57% had excess muscle Na, 52% had depletion
of muscle K and 43% had low muscle Mg. We have also shown
that the low muscle K cannot be corrected by K supplementation
when there is a concomitant Mg deficiency and that
Mg infusions may change the disturbed relation between
extra- and intracellular electrolytes towards normal. ↑ Back To Top
Arch Intern Med. 1988 Aug;148(8):1801-5.
The effect of intravenous
magnesium therapy on serum and urine levels of potassium,
calcium, and sodium in patients with ischemic heart disease,
with and without acute myocardial infarction.
Rasmussen HS, Cintin C, Aurup
P, Breum L, McNair P.
Medical Department P/Chest Clinic, Bispebjerg Hospital.
Serum concentrations of magnesium, potassium, calcium,
and sodium were determined on admission of 224 patients
to the hospital and after 2, 4, and 6 days in hospital;
all were admitted to the hospital with suspected acute
myocardial infarction (AMI). On admission, the patients
were randomly allocated to 48 hours of treatment with magnesium
intravenously or placebo. One hundred twenty-three patients
had AMI (of whom 53 [43%] were treated with magnesium)
and 101 had their suspected AMI disproven (of whom 51 [50%]
were treated with magnesium). In a supplementary study,
serum and urine levels of magnesium, potassium, calcium,
and sodium, together with serum levels of parathyroid hormone,
were determined before and after intravenous magnesium
treatment in six patients with AMI and six patients with
ischemic heart disease but without AMI. In both studies,
magnesium therapy was associated with significant alterations
in extracellular ion homeostasis. Serum
concentrations of potassium decreased during the
initial days of hospitalization in the patients treated
with placebo, but increased
slightly in the patients treated with magnesium infusions. These
increments in the serum concentrations of magnesium and
potassium correlated significantly. The increase in the
serum concentration of potassium after magnesium infusions
was due
to a reduced renal potassium excretion level (from
71.3 to 49.4 mmol/24 h), indicating the existence of a
divalent-monovalent cation exchange mechanism in the nephron.
This hypothesis was supported by the observation that renal
sodium excretion likewise decreased after magnesium infusions (from
83.2 to 59.2 mmol/24 h). Serum
concentration of calcium decreased significantly after
magnesium treatment (from 2.35 mmol/L on admission
to 2.15 mmol/L after 24 hours in the hospital) in the AMI
group, in contrast to the placebo-treated patients, where
no significant fluctuations in serum concentration of calcium
were detected during the initial six days. This decrease
in serum concentration of calcium was due
to a marked increase in renal calcium excretion (from
3.43 mmol/24 h before to 6.59 mmol/24 h after magnesium
infusion). A correlation between increments in serum magnesium
concentration and decrements in serum calcium concentration
was detected. No change in serum levels of parathyroid
hormone was found before and after magnesium infusions.
Both serum and urine levels of magnesium significantly
increased after magnesium treatment to levels above the
upper normal limits (serum magnesium concentration increased
from 0.81 to 1.21 mmol/L, urine magnesium excretion levels
from 3.57 to 16.57 mmol/24 h for both serum and urine changes. ↑ Back To Top
Kardiol Pol. 2003 Nov;59(11):402-7.
Acute coronary syndrome: potassium, magnesium and
cardiac arrhythmia. [Article in English, Polish]
Maciejewski P, Bednarz B, Chamiec
T, Gorecki A, Lukaszewicz
R, Ceremuzynski L.
Department of Cardiology, Postgraduate
Medical School, Grochowski Hospital, Warsaw, Poland.
BACKGROUND: Cardiac arrhythmia is often present in patients
with acute coronary syndrome (ACS) and may be due to the
electrolyte imbalance. AIM: To assess the prevalence and
clinical significance of electrolyte imbalance in ACS.
METHODS: Serum potassium and magnesium levels were measured
within the first few hours in 204 consecutive patients
with ACS admitted to our department over a period of 23
months. Cardiac arrhythmia was documented using continuous
ECG monitoring, telemetry or standard ECG. RESULTS: Hypokalemia
was observed in 34% of patients, and was significantly
associated with the occurrence of life-threatening ventricular
arrhythmias (26% of patients with potassium level <4
mmol/l vs 11.9% of patients with normokalemia, p<0.001).
No relationship was found between potassium level and supraventricular
arrhythmias or in-hospital mortality. Decreased magnesium
serum concentration was found in 22% of patients but was
not significantly associated with cardiac arrhythmias or
mortality. CONCLUSIONS:
Hypokalemia and hypomagnesemia are often present in patients
with ACS. The former is associated with dangerous ventricular
arrhythmias. Early assessment of electrolyte serum concentration
is needed in order to implement proper supplementation. ↑ Back To Top
Crit Care Med. 2003 Apr;31(4):1082-7.
Development of ionized
hypomagnesemia is associated with higher mortality rates.
Soliman HM, Mercan D, Lobo
SS, Melot C, Vincent
JL.
Department of Intensive Care, Erasme University Hospital,
Free University of Brussels, Belgium.
OBJECTIVE: Previous studies have shown a wide variation
in the prevalence of total serum hypomagnesemia in intensive
are unit (ICU) patients and in associated mortality rates.
As the ionized part of magnesium is the active portion,
we sought to define the prevalence of ionized hypomagnesemia
in critically ill patients and to evaluate its relationship
with organ dysfunction, length of stay, and mortality.
DESIGN: Prospective observational study. SETTING: A 31-bed,
medical-surgical, university hospital ICU. PATIENTS: A
total of 446 consecutive patients admitted to the ICU over
a 3-month period. INTERVENTIONS: None. MEASUREMENTS AND
MAIN RESULTS: The ionized magnesium level (normal value,
0.42-0.59 mmol/L) was measured at admission and then every
day until discharge from the ICU. At admission, 18% of
patients had ionized hypomagnesemia, 68% had normal ionized
magnesium levels, and 14% had ionized hypermagnesemia.
There was no significant difference in the length of stay
or in the mortality rate between these three groups of
patients. Hypomagnesemic
patients more frequently had total and ionized hypocalcemia,
hypokalemia, and hypoproteinemia. A total of 23
patients developed ionized hypomagnesemia during their
ICU stay; these patients had higher Acute Physiology And
Chronic Health Evaluation II (14.9 +/- 5.4 vs. 11.0 +/-
6.2) and Sequential Organ Failure Assessment (SOFA; 7.1
+/- 5.4 vs. 3.9 +/- 2.8) scores at admission (p <.01
for both), a higher maximum SOFA score during their ICU
stay (10.0 +/- 5.6 vs. 4.4 +/- 3.2, p <.01), a higher
prevalence of severe sepsis and septic shock (57 vs. 11%,
p <.01), a longer ICU stay (15.4 +/- 15.5 vs. 2.8 +/-
4.7 days, p <.01), and a higher mortality rate (35%
vs. 12%, p <.01) than the other patients. The major
risk factors for developing hypomagnesemia during the ICU
stay were a prolonged ICU stay, treatment with diuretics,
and sepsis. CONCLUSION: Development of ionized hypomagnesemia
during an ICU stay is associated with a worse prognosis.
It is often associated with the use of diuretics and the
development of sepsis. Monitoring of ionized magnesium
levels may have prognostic, and perhaps therapeutic, implications ↑ Back To Top
J Am Coll Nutr. 1990 Apr;9(2):114-9.
Effect of intravenous epinephrine on serum magnesium
and free intracellular red blood cell magnesium concentrations
measured by nuclear magnetic resonance.
Ryzen E, Servis KL, Rude
RK.
Department of Internal Medicine, University of Southern
California, Los Angeles.
Hypomagnesemia
is a common clinical finding in hospitalized patients and
can cause hypocalcemia, cardiac arrhythmias, muscular weakness,
and hypokalemia. Hypomagnesemia usually implies
cellular magnesium (Mg) depletion, but stress and some
clinical conditions which raise serum catecholamine concentrations
may lower serum Mg (sMg) concentrations. To help investigate
the mechanism and degree of the effect of catecholamines
on sMg concentration, we gave intravenous epinephrine (0.1
microgram/kg/min) to 12 normal volunteers for 2 hours.
The sMg concentration fell from 1.86 +/- 0.04 mg/dl to
1.63 +/- 0.05 mg/dl (mean +/- SEM, p less than 0.01). Pre-infusion
intracellular free Mg (Mg++) in red blood cells (RBC) as
measured by nuclear magnetic resonance spectrophotometry
(NMR) was 171 +/- 7.6 microM and did not differ significantly
from post-infusion RBC Mg++, 186 +/- 12.6 microM. Total
blood mononuclear cell Mg content and urine Mg excretion
also did not change. These data suggest that epinephrine
has a small but significant effect on the lowering of sMg
concentrations. Endogenous catecholamine release during
stress or acute illness may therefore contribute to the
hypomagnesemia seen in acutely ill patients. Our data also
suggest that hypomagnesemia seen under conditions of acute
stress may not always imply depleted tissue Mg stores.
As no absolute change in cellular Mg or in urinary Mg excretion
was demonstrated, acute intracellular shifts of Mg into
blood cells and/or urinary Mg losses may not account for
the hypomagnesemia. The prevalence and clinical consequences
of stress hypomagnesemia require further investigation. ↑ Back To Top
Crit Care Med. 1996 Jan;24(1):38-45.
Magnesium repletion and its effect on potassium
homeostasis in critically ill adults: results of a double-blind,
randomized, controlled trial.
Hamill-Ruth RJ, McGory R.
Department of Anesthesiology, University of Virginia Health
Sciences Center, Charlottesville 22908, USA.
OBJECTIVES: The aims of this study were to evaluate the
safety and efficacy of magnesium replacement therapy and
to determine its effect on potassium retention in hypokalemic,
critically ill patients. DESIGN: A prospective, double-blind,
randomized, placebo-controlled trial. SETTING: A surgical
intensive care unit (ICU). PATIENTS: A
total of 32 adult surgical ICU patients were admitted to
the study on the basis of documented hypokalemia (potassium
of < 3.5 mmol/L) within the 24-hr period before entering
the study. Patients were randomized to receive either
placebo (n = 15) or magnesium sulfate (n = 17). One patient
from each group was excluded from the study due to failure
to complete the full series of doses. INTERVENTIONS: Patients
received a "test dose" of either magnesium sulfate
(2 g, 8 mmol) or placebo (5% dextrose in water) infused
over 30 mins every 6 hrs for eight doses. The next schedule
test dose was held if hypermagnesemia (magnesium of > 2.8
mg/dL [> 1.15 mmol/L]) was documented at any time during
the study. Routine replacements of potassium and magnesium
continued during the duration of the study, when clinically
indicated, for serum potassium concentrations of 3.5 mmol/L
or serum magnesium concentrations of < 1.8 mg/dL (< 0.74
mmol/L). MEASUREMENTS AND MAIN RESULTS: Age, weight, and
Acute Physiology and Chronic Health Evaluation II scores
were recorded on entry into the study. Just before administration
of each test dose, blood was drawn for magnesium and potassium,
bicarbonate, pH, and glucose determinations, and an aliquot
of the preceding 6 hrs urine collection was sent for magnesium
and potassium determinations. Serum calcium, phosphate,
urea nitrogen, and creatinine concentrations were measured
daily. The amounts of magnesium and potassium administered
via parenteral nutrition, tube feeding, and replacement
infusions were calculated for each 6-hr interval. The amounts
of magnesium and potassium excreted in the urine were similarly
assessed. The groups showed no differences with regard
to age, weight, Acute Physiology and Chronic Health Evaluation
II scores, or initial serum magnesium concentration. Initial
potassium, bicarbonate, pH, calcium, phosphate, glucose,
blood urea nitrogen, and creatinine values were not different
between groups. Patients
receiving magnesium sulfate showed a statistically significant
increase in serum magnesium concentration at 6 hrs when
compared with placebo, as well as with itself at
time 0 (p < .0001), a difference maintained throughout
the study. Compared
with the placebo group, the total amount of elemental magnesium
administered was significantly greater in the treatment
group (1603 +/- 124 vs. 752 +/- 215 mg [65.7 +/-
5.8 vs. 30.8 +/- 8.8 mmol], p < .0001), as was urine
magnesium excretion (1000 +/- 156 vs. 541 +/- 68 mg [41.0
+/- 6.4 vs. 22.2 +/- 2.8 mmol] p < .0001). However,
the net magnesium balance (total magnesium in - total urine
magnesium) was significantly more positive in the treatment
group (612 +/- 180 vs. 216 +/- 217 mg [25.1 +/- 7.4 vs.
8.9 +/- 8.9 mmol], p < .005). The treatment and control
groups had the same serum potassium concentrations and
did not receive different amounts of potassium (245 +/-
39 vs. 344 +/- 45 mmol, respectively, p = .06), although
the treatment group required less potassium replacement/6
hrs by 30 hrs compared with itself at time 0 (p < .05). Despite
the same serum potassium values, the net potassium balance
for 48 hrs was positive in the treatment group (+ 72 +/-
32 mmol) and negative in the control group (-74
+/- 95 mmol, p < .05). There were no complications associated
with the magnesium sulfate administration. CONCLUSIONS:
Magnesium sulfate administered according to the above regimen
safety and significantly increases the circulating magnesium
concentration. Despite greater urine magnesium losses in
the treatment group, this group exhibited significantly
better magnesium retention. ↑ Back To Top
Magnesium. 1984;3(4-6):324-38.
Influence of intravenous Mg++ solutions on renal
excretion of potassium, sodium, calcium, chloride, intraleukocytic
potassium and peripheral vascular resistance: a metabolic
and hemodynamic study in normal volunteers.
Glanzer K, Schlebusch H, Sorger
M, Pannenbecker D, Kruck
F.
In an open randomized crossover trial 8 healthy male volunteers
received an intravenous infusion of potassium chloride,
potassium/magnesium chloride, potassium-(D,L)-aspartate,
and potassium/magnesium-(D,L)-aspartate. Equimolar amounts
of potassium (27.75 mmol) and magnesium (13.9 mmol) were
given in a 500-ml volume during 24 h. During two 9-day
periods subjects were maintained on a constant diet with
a daily intake of 80 mmol potassium and 60 mmol magnesium.
Infusions were administered on day 5 and 7 of each period.
Serum and urine electrolyte concentrations as well as intraleukocyte
potassium were measured before, during, and after the tests;
cardiac output and systemic vascular resistance were determined
by impedance cardiography. Potassium and magnesium containing
solutions did not influence renal elimination of potassium,
and also the circadian rhythm of potassium excretion did
not show any change. The
elimination of sodium, calcium, potassium, and chloride
rose significantly over the corresponding control values
during magnesium infusions, but not when potassium salts
were given. The
increase of calcium excretion after Mg++ is most probably
due to suppression of parathyroid hormone. Intraleukocyte
potassium was not affected significantly by the various
infusions, indicating that intracellular compartments are
completely filled. There was no evidence that the anion
(D,L-aspartate or chloride) had a significant effect on
all measured variables. Mean arterial blood pressure and
peripheral vascular resistance were not altered significantly
during the infusions. ↑ Back To Top
Arch Intern Med. 1988 Nov;148(11):2415-20.
Magnesium metabolism. A review with special reference
to the relationship between intracellular content and serum
levels.
Reinhart RA.
Marshfield Clinic, WI 54449.
Magnesium (Mg++) is a ubiquitous element in nature, playing
a role in photosynthesis and many metabolic functions in
humans. All enzymatic reactions that involve adenosine
triphosphate have an absolute requirement for Mg++.
Levels of Mg++ are controlled by the kidneys and gastrointestinal
tract and appear closely linked to calcium, potassium,
and sodium metabolism. The clinical manifestations
and causes of abnormal Mg++ status are protean. Testing
for altered Mg++ homeostasis is problematic. Serum levels,
which are those generally measured, reflect only a small
part of the total body content of Mg++. The intracellular
content can be low, despite normal serum levels in a person
with clinical Mg++ deficiency. Future directions in research
related to intracellular content of Mg++ are discussed.
Treatment of altered Mg++ status depends on the clinical
setting and may include the addition of a potassium/Mg++-sparing
drug to an existing diuretic regimen. Guidelines for therapy
are given. ↑ Back To Top
Alcohol Clin Exp Res. 1992 Oct;16(5):986-90.
Oral magnesium supplementation improves metabolic
variables and muscle strength in alcoholics.
Gullestad L, Dolva LO, Soyland
E, Manger AT, Falch D, Kjekshus
J.
Department of Internal Medicine, Baerum Hospital, Sandvika,
Norway.
Magnesium deficiency is common among chronic alcoholics,
but the knowledge of oral magnesium supplementation to
this group is limited. We, therefore, randomized 49 chronic
alcoholics, moderate to heavy drinkers for at least 10
years to receive oral magnesium or placebo treatment for
6 weeks according to a double-blind protocol. Effects on
metabolic variables and muscle strength were analyzed. Significant
reduction of aspartate-aminotransferase (ASAT), alanine-aminotransferase
(ALAT) and gamma-glutamyl-transpeptidase (GGT) were seen
after magnesium, whereas no change was observed
with placebo. Bilirubin
decreased in both groups. Serum Na, Ca, and P increased
significantly during magnesium therapy compared
with no statistically significant change in the placebo
group. Serum
K and Mg increased slightly after magnesium supplementation
and decreased in the placebo group, resulting in a significant
difference between the two groups at the end of the study.
Muscle strength increased significantly during magnesium
treatment, contrasting to no change with placebo. Blood
pressure, heart rate, hematological variables, serum lipids
(cholesterol, HDL, TG), glucose tolerance, and creatinine
were unchanged in the two groups after treatment. Alcohol
consumption was similar before and during the trial and
does not explain the differences between the two groups
The results shows that short-term oral magnesium therapy
may improve liver cell function, electrolyte status, and
muscle strength in chronic alcoholics. ↑ Back To Top
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