- Email: [email protected]
K+ and Mg2+ Dyshomeostasis in Acute Hyperadrenergic Stressor States
SPECIAL FEATURE
Pathophysiology in Medicine Karl T. Weber, MD Feature Editor
Kþ and Mg2þ Dyshomeostasis in Acute Hyperadrenergic Stressor States Mannu Nayyar, MD, Jawwad Yusuf, MD, M. Usman Khan, MD and Karl T. Weber, MD ABSTRACT Acute stressor states are linked to neurohormonal activation that includes the adrenergic nervous system. Elevations in circulating epinephrine and norepinephrine unmask an interdependency that exists between Kþ and Mg2þ based on their regulation of a large number of Mg2þ-dependent Naþ/Kþ-ATPase pumps present in skeletal muscle. The hyperadrenergic state accounts for a sudden translocation of cations into muscle with the rapid appearance of hypokalemia and hypomagnesemia. The resultant hypokalemia and hypomagnesemia will cause a delay in myocardial repolarization and electrocardiographic QTc prolongation raising the propensity for supraventricular and ventricular arrhythmias. In this review, we focus on the interdependency between Kþ and Mg2þ, which is clinically relevant to acute hyperadrenergic stressor states found in patients admitted to intensive care units. Key Indexing Terms: Potassium; Magnesium; Catecholamines; Arrhythmias. [Am J Med Sci 2017;](]):]]]–]]].]
INTRODUCTION þ
and Mg2þ are essential in preserving an internal equilibrium necessary for cell function and survival. These cations have important individual actions, and they also have intersecting and even interdependent interactions integral to preserving their physiological concentrations.1,2 Kþ and Mg2þ equilibrium is threatened by acute stressor states and is promoted by their inextricable association with neurohormonal activation, where effector hormones of the hypothalamic-pituitary-adrenal axis and the adrenergic nervous system in particular are elaborated in concert.3-5 The resultant hormonal onslaught, a homeostatic stressor response, provokes iterations in Kþ and Mg2þ concentrations.6 This includes translocation of these cations from the vascular space into the intracellular compartment of soft tissues (e.g., muscle) to culminate in the concordant appearance of hypokalemia and hypomagnesemia. The extent to which these cation concentrations decrease correlates with the severity of injury and, in turn, the degree of neurohormonal activation.7 Decreased serum concentrations of these cations, therefore, predict prognosis.8 In this brief review, we consider the appearance of hypokalemia and hypomagnesemia, which were found in patients having an acute hyperadrenergic stressor state that prompted their admission to intensive care units.
K
HYPOKALEMIA AND HYPOMAGNESEMIA IN ACUTE HYPERADRENERGIC STRESSOR STATES A hyperadrenergic state with elevated serum catecholamine concentrations accompanies acute bodily injury. This includes thermal or electrical burn injury, trauma with or without hemorrhagic shock, subarachnoid hemorrhage, acute myocardial infarction and major
surgery. Illnesses that are akin to bodily injury and invoke neurohormonal activation include sepsis, pneumonia, pancreatitis and diabetic ketoacidosis. These stressorinduced iterations in Kþ and Mg2þ can be contemporaneous in time and concordant in direction. The reference range of serum Kþ and Mg2þ concentrations given by clinical pathology laboratories has been derived for the cation analyzer and its operator assaying randomly obtained blood samples. These values should be placed in this context and not taken as normal biologic values. Trauma Unit In an institutional review board–approved retrospective study conducted in 301 consecutive admissions (age 41 ⫾ 1 years; 70% men) to the Trauma Unit at Regional One Health Center (previously the MED), serum Kþ and Mg2þ were obtained on admission. The Kþ and Mg2þ results are shown in the left and right panels of Figure 1, respectively. Hypokalemia o4.0 mmol/L was present in 79% of these patients and hypomagnesemia (o2.0 mg/dL) in 48%. Hypokalemia was further graded as mild (3.93.5 mmol/L), moderate (3.4-3.0 mmol/L) or severe (o3.0 mmol/L); hypomagnesemia (o2.0 mg/dL) was likewise graded as mild (1.9-1.8 mg/dL), moderate (1.7-1.6 mg/dL) and severe (o1.6 mg/dL). For the entire population, serum Kþ concentration on admission was 3.50 ⫾ 0.02 mmol/L with 78% of patients having hypokalemia, which included 46% with mild, 33% with moderate and 7% of severe degree. In patients treated with a thiazide diuretic before their traumatic episode, the body's pool of Kþ may be compromised and could account for severe hypokalemia on admission. Hypomagnesemia on admission was 1.94 ⫾ 0.01mg/dL and present in 52% of patients where it was of mild,
Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved. www.amjmedsci.com www.ssciweb.org
1
Nayyar et al
FIGURE 1. Acute stressor states and cation dyshomeostasis. Serum Kþ and Mg2þ concentration on hospital day #1 in 301 consecutive admissions to a trauma unit.
moderate or marked severity in 23%, 19% and 10%, respectively. Hence, hypokalemia and hypomagnesemia of mild to moderately severe degree will accompany acute bodily injury. These findings raise awareness as to potential adverse consequences of such cation dyshomeostasis on the appearance of supraventricular and ventricular arrhythmias in these patients.9 Medical Intensive Care Unit An institutional review board–approved retrospective study was conducted of 200 patients (age 58 ⫾ 1 years; 106 women) admitted to the medical intensive care unit at Methodist University Hospital during April to August 2010. Admitting diagnoses included sepsis, pulmonary embolus, acute lymphocytic leukemia, intracranial hemorrhage, subdural hematoma and diabetic ketoacidosis. Exclusion criteria included previously documented arrhythmia or chronic renal failure (serum creatinine 41.4 mg/dL). Individual serum Kþ and Mg2þ values on admission are given in the left and right panels of Figure 2, respectively. Hypokalemia (o4.0 mmol/L) was present in 85% of these patients, where it was o3.5 mmol/L in 65%. Hypomagnesemia was also present on admission in 70% and was of moderate severity (o1.8 mg/dL) in 42%.
Prolongation of the QTc interval (4440 milliseconds) was found in 76% when either Kþ o 4.0 mmol/L or Mg2þ o 2.0 mg/dL were present and was associated with newonset arrhythmias in 50%, including 45% having supraventricular arrhythmias with atrial fibrillation, premature atrial contractions or both; 36% with ventricular arrhythmias, including isolated premature ventricular contractions and nonsustained ventricular tachycardia; and both supraventricular and ventricular arrhythmias in 19%. Thus, hypokalemia and hypomagnesemia are commonly present on admission in patients admitted to the medical intensive care unit, and where they are associated with prolonged QTc interval and increased propensity for supraventricular and ventricular arrhythmias.
PATHOPHYSIOLOGY OF Kþ AND MG2þ DYSHOMEOSTASIS Naþ/Kþ-ATPase, a membrane-bound, energydependent pump whose activity contributes to the regulation of intracellular Kþ has an obligatory dependence on Mg2þ. A large number of these pumps are present in skeletal muscle, where they are regulated by catecholamines.10 Increments in plasma epinephrine and norepinephrine that accompany acute stressor states activate these pumps leading to marked Kþ
FIGURE 2. Acute stressor states and cation dyshomeostasis. Serum Kþ and Mg2þ concentration on hospital day #1 in 200 consecutive admissions to a medical intensive care unit.
2
THE AMERICAN JOURNAL
OF THE
MEDICAL SCIENCES
VOLUME ] NUMBER Suppl 1
] 2017
Kþ and Mg2þ in Stressor States
uptake by muscle and the rapid appearance of hypokalemia. Reductions in myocardial Kþ are accompanied by delayed repolarization and prolongation of the QTc interval of the electrocardiogram—a pathophysiologic scenario that favors an increased propensity for supraventricular and ventricular arrhythmias. Hence, catecholamines are responsible for acute hypokalemia that appears with acute stressor states. Elevations in plasma catecholamines also are accompanied by hypomagnesemia.11,12 This is related to a cyclic AMP-mediated rise in intracellular Mg2þ, together with increased lipolysis and Mg2þ binding to free fatty acids with its sequestration in adipocytes. Increased urinary Mg2þ losses are also contributory. Hypomagnesemia is common in both critically ill children and adults. Predisposing risk factors include hypokalemia, hypocalcemia, thiazide and loop diuretic use and sepsis.13 The hypomagnesemia that is already present at the time of admission in these patients may become more severe during a prolonged hospital stay because of ongoing excretory losses and reduced Mg2þ intake.5 Atrial and ventricular arrhythmias appear when hypomagnesemia is of moderate-to-marked severity (o1.70 mg/dL). Mg2þ-dependent Naþ/Kþ-ATPase activity is reduced with hypomagnesemia, and it further prolongs the QTc interval enhancing the propensity for arrhythmias. Digoxin, a Naþ/Kþ-ATPase inhibitor, accentuates the dyshomeostasis of intracellular Kþ and Mg2þ predisposing to QTc prolongation and arrhythmias. The correction of impaired Kþ balance and hypokalemia will prove difficult unless Mg2þ is first replaced. The QTc interval and its abnormal prolongation (4440 milliseconds) identifies a deficiency of myocardial Kþ and Mg2þ. Daily monitoring of the QTc interval and its normalization during Mg2þ and Kþ supplementation can be used to gauge the adequacy of their intracellular replacement. The attainment of normal QTc with these supplements may require several days more than needed for the more rapid correction of hypokalemia and hypomagnesemia. Less than 1% of Mg2þ is extracellular, and hence serum Mg2þ is not an accurate indicator of intracellular Mg2þ stores and why the QTc interval is a valuable surrogate. Concurrent hypokalemia and hypomagnesemia are common in critically ill patients in whom the interactions between Kþ and Mg2þ are diverse and complex, including the importance of Mg2þ deficiency that interferes with Kþ retention while raising urinary Kþ excretion.1,2 Mg2þ deficiency contemporaneously begets Kþ deficiency. The effective clinical resolution of hypokalemia mandates the simultaneous reversal of hypomagnesemia.14
interval of the electrocardiogram, will increase susceptibility to both supraventricular and ventricular arrhythmias. Ongoing surveillance and prompt correction of hypokalemia and hypomagnesemia are warranted. Maintenance of serum Kþ and Mg2þ at physiologically relevant concentrations of 44.0 mg/DL and 42.0 mg/dL (the 4 and 2 rule) is suggested and must not rely on the hospital laboratory's reference range. Daily monitoring of QTc interval and its normalization provides an indirect measure of intracellular Kþ and Mg2þ and valuable adjunct to the surveillance of serum levels.
ACKNOWLEDGMENTS The authors gratefully acknowledge Dr. Louis J. Magnotti for generously sharing his Trauma Unit data with us and Richard A. Parkinson, M.Ed for editorial assistance and scientific illustrations.
REFERENCES 1. Sheehan JP, Seelig MS. Interactions of magnesium and potassium in the pathogenesis of cardiovascular disease. Magnesium 1984;3:301–14. 2. Solomon R. The relationship between disorders of Kþ and Mgþ homeostasis. Semin Nephrol 1987;7:253–62. 3. Reid JL, Whyte KF, Struthers AD. Epinephrine-induced hypokalemia: the role of beta adrenoceptors. Am J Cardiol 1986;57:23F–7F. 4. Darbar D, Smith M, Morike K, et al. Epinephrine-induced changes in serum potassium and cardiac repolarization and effects of pretreatment with propranolol and diltiazem. Am J Cardiol 1996;77:1351–5. 5. Ryzen E. Magnesium homeostasis in critically ill patients. Magnesium 1989;8:201–12. 6. Khan MU, Komolafe BO, Weber KT. Cation interdependency in acute stressor states. Am J Med Sci 2013;345:401–4. 7. Carlstedt F, Lind L, Wide L, et al. Serum levels of parathyroid hormone are related to the mortality and severity of illness in patients in the emergency department. Eur J Clin Invest 1997;27:977–81. 8. Carlstedt F, Lind L, Rastad J, et al. Parathyroid hormone and ionized calcium levels are related to the severity of illness and survival in critically ill patients. Eur J Clin Invest 1998;28:898–903. 9. Whitted AD, Stanifer JW, Dube P, et al. A dyshomeostasis of electrolytes and trace elements in acute stressor states: impact on the heart. Am J Med Sci 2010;340:48–53. 10. Kjeldsen K. Hypokalemia and sudden cardiac death. Exp Clin Cardiol 2010;15:e96–9. 11. Escuela MP, Guerra M, Añon JM, et al. Total and ionized serum magnesium in critically ill patients. Intensive Care Med 2005;31:151–6. 12. Soliman HM, Mercan D, Lobo SS, et al. Development of ionized hypomagnesemia is associated with higher mortality rates. Crit Care Med 2003;31:1082–7. 13. Weglicki WB. Hypomagnesemia and inflammation: clinical and basic aspects. Annu Rev Nutr 2012;32:55–71. 14. Leier CV, Dei Cas L, Metra M. Clinical relevance and management of the major electrolyte abnormalities in congestive heart failure: hyponatremia, hypokalemia and hypomagnesemia. Am Heart J 1994;128: 564–74.
From the Division of Cardiovascular Diseases (MN, JY, MUK, KTW), University of Tennessee Health Sciences Center, Memphis, Tennessee.
SUMMARY AND CONCLUSIONS
Submitted December 6, 2016; accepted January 5, 2017.
A dyshomeostasis of serum Kþ and Mg2þ is commonplace in acute hyperadrenergic stressor states and can be of mild, moderate and marked severity. Their appearance, together with prolongation of the QTc
The authors have no financial or other conflicts of interest to disclose. Correspondence: Karl T. Weber, MD, Division of Cardiovascular Diseases, University of Tennessee Health Science Center, 956 Court Avenue, Suite A312, Memphis, TN 38163 (E-mail: [email protected]).
Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved. www.amjmedsci.com www.ssciweb.org
3
Pathophysiology in Medicine Karl T. Weber, MD Feature Editor
Kþ and Mg2þ Dyshomeostasis in Acute Hyperadrenergic Stressor States Mannu Nayyar, MD, Jawwad Yusuf, MD, M. Usman Khan, MD and Karl T. Weber, MD ABSTRACT Acute stressor states are linked to neurohormonal activation that includes the adrenergic nervous system. Elevations in circulating epinephrine and norepinephrine unmask an interdependency that exists between Kþ and Mg2þ based on their regulation of a large number of Mg2þ-dependent Naþ/Kþ-ATPase pumps present in skeletal muscle. The hyperadrenergic state accounts for a sudden translocation of cations into muscle with the rapid appearance of hypokalemia and hypomagnesemia. The resultant hypokalemia and hypomagnesemia will cause a delay in myocardial repolarization and electrocardiographic QTc prolongation raising the propensity for supraventricular and ventricular arrhythmias. In this review, we focus on the interdependency between Kþ and Mg2þ, which is clinically relevant to acute hyperadrenergic stressor states found in patients admitted to intensive care units. Key Indexing Terms: Potassium; Magnesium; Catecholamines; Arrhythmias. [Am J Med Sci 2017;](]):]]]–]]].]
INTRODUCTION þ
and Mg2þ are essential in preserving an internal equilibrium necessary for cell function and survival. These cations have important individual actions, and they also have intersecting and even interdependent interactions integral to preserving their physiological concentrations.1,2 Kþ and Mg2þ equilibrium is threatened by acute stressor states and is promoted by their inextricable association with neurohormonal activation, where effector hormones of the hypothalamic-pituitary-adrenal axis and the adrenergic nervous system in particular are elaborated in concert.3-5 The resultant hormonal onslaught, a homeostatic stressor response, provokes iterations in Kþ and Mg2þ concentrations.6 This includes translocation of these cations from the vascular space into the intracellular compartment of soft tissues (e.g., muscle) to culminate in the concordant appearance of hypokalemia and hypomagnesemia. The extent to which these cation concentrations decrease correlates with the severity of injury and, in turn, the degree of neurohormonal activation.7 Decreased serum concentrations of these cations, therefore, predict prognosis.8 In this brief review, we consider the appearance of hypokalemia and hypomagnesemia, which were found in patients having an acute hyperadrenergic stressor state that prompted their admission to intensive care units.
K
HYPOKALEMIA AND HYPOMAGNESEMIA IN ACUTE HYPERADRENERGIC STRESSOR STATES A hyperadrenergic state with elevated serum catecholamine concentrations accompanies acute bodily injury. This includes thermal or electrical burn injury, trauma with or without hemorrhagic shock, subarachnoid hemorrhage, acute myocardial infarction and major
surgery. Illnesses that are akin to bodily injury and invoke neurohormonal activation include sepsis, pneumonia, pancreatitis and diabetic ketoacidosis. These stressorinduced iterations in Kþ and Mg2þ can be contemporaneous in time and concordant in direction. The reference range of serum Kþ and Mg2þ concentrations given by clinical pathology laboratories has been derived for the cation analyzer and its operator assaying randomly obtained blood samples. These values should be placed in this context and not taken as normal biologic values. Trauma Unit In an institutional review board–approved retrospective study conducted in 301 consecutive admissions (age 41 ⫾ 1 years; 70% men) to the Trauma Unit at Regional One Health Center (previously the MED), serum Kþ and Mg2þ were obtained on admission. The Kþ and Mg2þ results are shown in the left and right panels of Figure 1, respectively. Hypokalemia o4.0 mmol/L was present in 79% of these patients and hypomagnesemia (o2.0 mg/dL) in 48%. Hypokalemia was further graded as mild (3.93.5 mmol/L), moderate (3.4-3.0 mmol/L) or severe (o3.0 mmol/L); hypomagnesemia (o2.0 mg/dL) was likewise graded as mild (1.9-1.8 mg/dL), moderate (1.7-1.6 mg/dL) and severe (o1.6 mg/dL). For the entire population, serum Kþ concentration on admission was 3.50 ⫾ 0.02 mmol/L with 78% of patients having hypokalemia, which included 46% with mild, 33% with moderate and 7% of severe degree. In patients treated with a thiazide diuretic before their traumatic episode, the body's pool of Kþ may be compromised and could account for severe hypokalemia on admission. Hypomagnesemia on admission was 1.94 ⫾ 0.01mg/dL and present in 52% of patients where it was of mild,
Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved. www.amjmedsci.com www.ssciweb.org
1
Nayyar et al
FIGURE 1. Acute stressor states and cation dyshomeostasis. Serum Kþ and Mg2þ concentration on hospital day #1 in 301 consecutive admissions to a trauma unit.
moderate or marked severity in 23%, 19% and 10%, respectively. Hence, hypokalemia and hypomagnesemia of mild to moderately severe degree will accompany acute bodily injury. These findings raise awareness as to potential adverse consequences of such cation dyshomeostasis on the appearance of supraventricular and ventricular arrhythmias in these patients.9 Medical Intensive Care Unit An institutional review board–approved retrospective study was conducted of 200 patients (age 58 ⫾ 1 years; 106 women) admitted to the medical intensive care unit at Methodist University Hospital during April to August 2010. Admitting diagnoses included sepsis, pulmonary embolus, acute lymphocytic leukemia, intracranial hemorrhage, subdural hematoma and diabetic ketoacidosis. Exclusion criteria included previously documented arrhythmia or chronic renal failure (serum creatinine 41.4 mg/dL). Individual serum Kþ and Mg2þ values on admission are given in the left and right panels of Figure 2, respectively. Hypokalemia (o4.0 mmol/L) was present in 85% of these patients, where it was o3.5 mmol/L in 65%. Hypomagnesemia was also present on admission in 70% and was of moderate severity (o1.8 mg/dL) in 42%.
Prolongation of the QTc interval (4440 milliseconds) was found in 76% when either Kþ o 4.0 mmol/L or Mg2þ o 2.0 mg/dL were present and was associated with newonset arrhythmias in 50%, including 45% having supraventricular arrhythmias with atrial fibrillation, premature atrial contractions or both; 36% with ventricular arrhythmias, including isolated premature ventricular contractions and nonsustained ventricular tachycardia; and both supraventricular and ventricular arrhythmias in 19%. Thus, hypokalemia and hypomagnesemia are commonly present on admission in patients admitted to the medical intensive care unit, and where they are associated with prolonged QTc interval and increased propensity for supraventricular and ventricular arrhythmias.
PATHOPHYSIOLOGY OF Kþ AND MG2þ DYSHOMEOSTASIS Naþ/Kþ-ATPase, a membrane-bound, energydependent pump whose activity contributes to the regulation of intracellular Kþ has an obligatory dependence on Mg2þ. A large number of these pumps are present in skeletal muscle, where they are regulated by catecholamines.10 Increments in plasma epinephrine and norepinephrine that accompany acute stressor states activate these pumps leading to marked Kþ
FIGURE 2. Acute stressor states and cation dyshomeostasis. Serum Kþ and Mg2þ concentration on hospital day #1 in 200 consecutive admissions to a medical intensive care unit.
2
THE AMERICAN JOURNAL
OF THE
MEDICAL SCIENCES
VOLUME ] NUMBER Suppl 1
] 2017
Kþ and Mg2þ in Stressor States
uptake by muscle and the rapid appearance of hypokalemia. Reductions in myocardial Kþ are accompanied by delayed repolarization and prolongation of the QTc interval of the electrocardiogram—a pathophysiologic scenario that favors an increased propensity for supraventricular and ventricular arrhythmias. Hence, catecholamines are responsible for acute hypokalemia that appears with acute stressor states. Elevations in plasma catecholamines also are accompanied by hypomagnesemia.11,12 This is related to a cyclic AMP-mediated rise in intracellular Mg2þ, together with increased lipolysis and Mg2þ binding to free fatty acids with its sequestration in adipocytes. Increased urinary Mg2þ losses are also contributory. Hypomagnesemia is common in both critically ill children and adults. Predisposing risk factors include hypokalemia, hypocalcemia, thiazide and loop diuretic use and sepsis.13 The hypomagnesemia that is already present at the time of admission in these patients may become more severe during a prolonged hospital stay because of ongoing excretory losses and reduced Mg2þ intake.5 Atrial and ventricular arrhythmias appear when hypomagnesemia is of moderate-to-marked severity (o1.70 mg/dL). Mg2þ-dependent Naþ/Kþ-ATPase activity is reduced with hypomagnesemia, and it further prolongs the QTc interval enhancing the propensity for arrhythmias. Digoxin, a Naþ/Kþ-ATPase inhibitor, accentuates the dyshomeostasis of intracellular Kþ and Mg2þ predisposing to QTc prolongation and arrhythmias. The correction of impaired Kþ balance and hypokalemia will prove difficult unless Mg2þ is first replaced. The QTc interval and its abnormal prolongation (4440 milliseconds) identifies a deficiency of myocardial Kþ and Mg2þ. Daily monitoring of the QTc interval and its normalization during Mg2þ and Kþ supplementation can be used to gauge the adequacy of their intracellular replacement. The attainment of normal QTc with these supplements may require several days more than needed for the more rapid correction of hypokalemia and hypomagnesemia. Less than 1% of Mg2þ is extracellular, and hence serum Mg2þ is not an accurate indicator of intracellular Mg2þ stores and why the QTc interval is a valuable surrogate. Concurrent hypokalemia and hypomagnesemia are common in critically ill patients in whom the interactions between Kþ and Mg2þ are diverse and complex, including the importance of Mg2þ deficiency that interferes with Kþ retention while raising urinary Kþ excretion.1,2 Mg2þ deficiency contemporaneously begets Kþ deficiency. The effective clinical resolution of hypokalemia mandates the simultaneous reversal of hypomagnesemia.14
interval of the electrocardiogram, will increase susceptibility to both supraventricular and ventricular arrhythmias. Ongoing surveillance and prompt correction of hypokalemia and hypomagnesemia are warranted. Maintenance of serum Kþ and Mg2þ at physiologically relevant concentrations of 44.0 mg/DL and 42.0 mg/dL (the 4 and 2 rule) is suggested and must not rely on the hospital laboratory's reference range. Daily monitoring of QTc interval and its normalization provides an indirect measure of intracellular Kþ and Mg2þ and valuable adjunct to the surveillance of serum levels.
ACKNOWLEDGMENTS The authors gratefully acknowledge Dr. Louis J. Magnotti for generously sharing his Trauma Unit data with us and Richard A. Parkinson, M.Ed for editorial assistance and scientific illustrations.
REFERENCES 1. Sheehan JP, Seelig MS. Interactions of magnesium and potassium in the pathogenesis of cardiovascular disease. Magnesium 1984;3:301–14. 2. Solomon R. The relationship between disorders of Kþ and Mgþ homeostasis. Semin Nephrol 1987;7:253–62. 3. Reid JL, Whyte KF, Struthers AD. Epinephrine-induced hypokalemia: the role of beta adrenoceptors. Am J Cardiol 1986;57:23F–7F. 4. Darbar D, Smith M, Morike K, et al. Epinephrine-induced changes in serum potassium and cardiac repolarization and effects of pretreatment with propranolol and diltiazem. Am J Cardiol 1996;77:1351–5. 5. Ryzen E. Magnesium homeostasis in critically ill patients. Magnesium 1989;8:201–12. 6. Khan MU, Komolafe BO, Weber KT. Cation interdependency in acute stressor states. Am J Med Sci 2013;345:401–4. 7. Carlstedt F, Lind L, Wide L, et al. Serum levels of parathyroid hormone are related to the mortality and severity of illness in patients in the emergency department. Eur J Clin Invest 1997;27:977–81. 8. Carlstedt F, Lind L, Rastad J, et al. Parathyroid hormone and ionized calcium levels are related to the severity of illness and survival in critically ill patients. Eur J Clin Invest 1998;28:898–903. 9. Whitted AD, Stanifer JW, Dube P, et al. A dyshomeostasis of electrolytes and trace elements in acute stressor states: impact on the heart. Am J Med Sci 2010;340:48–53. 10. Kjeldsen K. Hypokalemia and sudden cardiac death. Exp Clin Cardiol 2010;15:e96–9. 11. Escuela MP, Guerra M, Añon JM, et al. Total and ionized serum magnesium in critically ill patients. Intensive Care Med 2005;31:151–6. 12. Soliman HM, Mercan D, Lobo SS, et al. Development of ionized hypomagnesemia is associated with higher mortality rates. Crit Care Med 2003;31:1082–7. 13. Weglicki WB. Hypomagnesemia and inflammation: clinical and basic aspects. Annu Rev Nutr 2012;32:55–71. 14. Leier CV, Dei Cas L, Metra M. Clinical relevance and management of the major electrolyte abnormalities in congestive heart failure: hyponatremia, hypokalemia and hypomagnesemia. Am Heart J 1994;128: 564–74.
From the Division of Cardiovascular Diseases (MN, JY, MUK, KTW), University of Tennessee Health Sciences Center, Memphis, Tennessee.
SUMMARY AND CONCLUSIONS
Submitted December 6, 2016; accepted January 5, 2017.
A dyshomeostasis of serum Kþ and Mg2þ is commonplace in acute hyperadrenergic stressor states and can be of mild, moderate and marked severity. Their appearance, together with prolongation of the QTc
The authors have no financial or other conflicts of interest to disclose. Correspondence: Karl T. Weber, MD, Division of Cardiovascular Diseases, University of Tennessee Health Science Center, 956 Court Avenue, Suite A312, Memphis, TN 38163 (E-mail: [email protected]).
Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved. www.amjmedsci.com www.ssciweb.org
3