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• W2043818687 abstract "Commentary on Goyal A, Spertus JA, Gosch K, et al. Serum potassium levels and mortality in acute myocardial infarction. JAMA. 2012;307(2):157-164. Commentary on Goyal A, Spertus JA, Gosch K, et al. Serum potassium levels and mortality in acute myocardial infarction. JAMA. 2012;307(2):157-164. The relationship between imbalances in potassium homeostasis and cardiovascular disease events has been well established for many years.1Harrison T.R. Pilcher C. Ewing G. Studies in congestive heart failure: IV The potassium content of skeletal and cardiac muscle.J Clin Invest. 1930; 8: 325-335Crossref PubMed Google Scholar, 2Grumbach L. The initiation of ventricular tachycardia and fibrillation in isolated hearts by potassium chloride.Circ Res. 1956; 4: 293-297Crossref PubMed Scopus (4) Google Scholar, 3Meneely G.R. Battarbee H.D. High sodium-low potassium environment and hypertension.Am J Cardiol. 1976; 38: 768-785Abstract Full Text PDF PubMed Scopus (223) Google Scholar Most total-body potassium is maintained in the intracellular space through the action of the adenosine triphosphatase sodium/potassium pump while extracellular potassium homeostasis is regulated mainly by the kidneys; homeostasis is achieved when kidney excretion matches oral intake. Changes in intra- and extracellular potassium levels modify the electrophysiologic properties of the resting membrane potential in cardiac cells and subsequently influence the generation and conduction of impulses throughout the heart.4El-Sherif N. Turitto G. Electrolyte disorders and arrhythmogenesis.Cardiol J. 2011; 18: 233-245PubMed Google Scholar, 5Macdonald J.E. Struthers A.D. What is the optimal serum potassium level in cardiovascular patients?.J Am Coll Cardiol. 2004; 43: 155-161Abstract Full Text Full Text PDF PubMed Scopus (247) Google Scholar Studies have shown that hypokalemia increases the automaticity and excitability of myocardial cells, leading to the propensity for ventricular arrhythmias.2Grumbach L. The initiation of ventricular tachycardia and fibrillation in isolated hearts by potassium chloride.Circ Res. 1956; 4: 293-297Crossref PubMed Scopus (4) Google Scholar Hypokalemia has been observed in up to approximately one-fifth6Kafka H. Langevin L. Armstrong P.W. Serum magnesium and potassium in acute myocardial infarction: influence on ventricular arrhythmias.Arch Intern Med. 1987; 147: 465-469Crossref PubMed Scopus (110) Google Scholar of patients admitted to the hospital for acute myocardial infarction (AMI) and is associated with increased risk of ventricular arrhythmias in this setting.7Hohnloser S.H. Verrier R.L. Lown B. Raeder E.A. Effect of hypokalemia on susceptibility to ventricular fibrillation in the normal and ischemic canine heart.Am Heart J. 1986; 112: 32-35Abstract Full Text PDF PubMed Scopus (36) Google Scholar Based on several small nonrandomized observational studies,6Kafka H. Langevin L. Armstrong P.W. Serum magnesium and potassium in acute myocardial infarction: influence on ventricular arrhythmias.Arch Intern Med. 1987; 147: 465-469Crossref PubMed Scopus (110) Google Scholar, 8Madias J.E. Shah B. Chintalapally G. Chalavarya G. Madias N.E. Admission serum potassium in patients with acute myocardial infarction: its correlates and value as a determinant of in-hospital outcome.Chest. 2000; 118: 904-913Crossref PubMed Scopus (48) Google Scholar, 9Nordrehaug J.E. Von der Lippe G. Hypokalemia and ventricular fibrillation in acute myocardial infarction.Br Heart J. 1983; 50: 525-529Crossref PubMed Scopus (171) Google Scholar, 10Hulting J. In-hospital ventricular fibrillation and its relation to serum potassium.Acta Med Scand Suppl. 1981; 647: 109-116PubMed Google Scholar, 11Herlitz J. Hjalmarson A. Bengtson A. Occurrence of hypokalemia in suspected acute myocardial infarction and its relation to clinical history and clinical course.Clin Cardiol. 1988; 11: 678-682Crossref PubMed Scopus (15) Google Scholar various professional societies have issued guidelines that recommend maintaining potassium levels at >4 mEq/L12Antman E.M. Anbe D.T. Armstrong P.W. et al.ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). 2004.http://assets.cardiosource.com/STEMI_2004.pdfGoogle Scholar, 13Cohn J.N. Kowey P.R. Whelton P.K. Prisant L.M. New guidelines for potassium replacement in clinical practice: a contemporary review by the National Council on Potassium in Clinical Practice.Arch Intern Med. 2000; 160: 2429-2436Crossref PubMed Scopus (226) Google Scholar or even >4.5 mEq/L5Macdonald J.E. Struthers A.D. What is the optimal serum potassium level in cardiovascular patients?.J Am Coll Cardiol. 2004; 43: 155-161Abstract Full Text Full Text PDF PubMed Scopus (247) Google Scholar after AMI. The strength of evidence supporting these recommendations is relatively weak because previous investigations examined the relationship between potassium levels and surrogate events or markers and were conducted more than 20 years ago in a time when contemporary management of AMI was not routinely used. With increasing emphasis on improving quality of care based on current guidelines (such as the American Heart Association's “Get With The Guidelines” program), many hospitals across the United States have instituted inpatient order algorithms that automatically recommend initiating treatment when serum potassium levels decrease below certain “goal” values. Although relatively inexpensive, potassium replacement therapy is not entirely benign because it can be very painful when given intravenously and can cause significant gastrointestinal side effects, including bowel ulcerations, if given by an oral route.13Cohn J.N. Kowey P.R. Whelton P.K. Prisant L.M. New guidelines for potassium replacement in clinical practice: a contemporary review by the National Council on Potassium in Clinical Practice.Arch Intern Med. 2000; 160: 2429-2436Crossref PubMed Scopus (226) Google Scholar More importantly, the impact of maintaining a serum potassium level >4 mEq/L on reducing mortality or arrhythmic events in the AMI setting has not been validated in a large clinical cohort treated with modern AMI therapies. Given this lack of good evidence, Goyal et al14Goyal A. Spertus J.A. Gosch K. et al.Serum potassium levels and mortality in acute myocardial infarction.JAMA. 2012; 307: 157-164Crossref PubMed Scopus (228) Google Scholar sought to examine the association of serum potassium levels with mortality, ventricular fibrillation, and sudden cardiac arrest in a large AMI population. The authors provide meaningful insights into the association of admission and postadmission serum potassium levels on mortality, ventricular fibrillation, and sudden cardiac arrest in the setting of AMI. The results challenge current guidelines that recommend that serum potassium level be maintained at >4 mEq/L in patients with AMI. Goyal et al14Goyal A. Spertus J.A. Gosch K. et al.Serum potassium levels and mortality in acute myocardial infarction.JAMA. 2012; 307: 157-164Crossref PubMed Scopus (228) Google Scholar retrospectively analyzed hospital data from the Cerner Health Facts national database of 38,689 patients admitted with AMI to 67 mainly urban US hospitals from 2000-2008. Using ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) codes, the authors examined the relationship between mean postadmission serum potassium level with the primary outcome of in-hospital mortality. They also studied the association of postadmission potassium level with composite secondary outcome of in-hospital ventricular fibrillation or sudden cardiac arrest. Finally, they assessed the relationship of the initial admission serum potassium level to both primary and secondary outcomes. Patients were divided into 7 hierarchal groups based on serum potassium levels (Table 1). There were several significant differences in clinical characteristics among groups, particularly at the extremes of hyper- (potassium >5.5 mEq/L) or hypokalemia (potassium <3.0 mEq/L). Logistic regression analysis showed a U-shaped relationship between mean postadmission potassium level and mortality, even after adjusting for multiple potential patient and procedural confounders, including age, sex, comorbid conditions, admission potassium level, peak troponin level, estimated glomerular filtration rate, acute kidney injury, revascularization, complications, and type of medications used during hospitalization.Table 1Relation of Postadmission Potassium Level to In-Hospital Mortality and Arrhythmic EventsData from Goyal et al.14Goyal A. Spertus J.A. Gosch K. et al.Serum potassium levels and mortality in acute myocardial infarction.JAMA. 2012; 307: 157-164Crossref PubMed Scopus (228) Google ScholarMean Postadmission MeasurementMortalityVentricular Fibrillation or Sudden Cardiac ArrestRateaORRateaORPotassium <3.0 mEq/L46.2% (12/26)8.11aStatistically significant OR compared with the reference group.19.2% (5/26)2.31Potassium = 3.0-<3.5 mEq/L11.4% (89/778)1.45aStatistically significant OR compared with the reference group.6.3% (49/778)1.06Potassium = 3.5-<4.0 mEq/L4.8% (539/11,153)1.00bReference group.4.9% (551/11,153)1.00bReference group.Potassium = 4.0-<4.5 mEq/L5.0% (821/16,536)1.25aStatistically significant OR compared with the reference group.4.1% (683/16,536)1.03Potassium = 4.5-<5.0 mEq/L10.0% (442/4,442)1.96aStatistically significant OR compared with the reference group.4.1% (180/4,442)1.15Potassium = 5.0-<5.5 mEq/L24.8% (208/840)3.27aStatistically significant OR compared with the reference group.6.8% (57/840)1.62aStatistically significant OR compared with the reference group.Potassium ≥5.5 mEq/L61.4% (154/251)6.44aStatistically significant OR compared with the reference group.14.7% (37/251)2.65aStatistically significant OR compared with the reference group.Note: ORs adjusted for age, sex, race, diabetes, heart failure, hypertension, cerebrovascular disease, peripheral vascular disease, chronic obstructive pulmonary disease, dementia, dialysis, admission glomerular filtration rate calculated by the Modification of Diet in Renal Disease Study equation, potassium level, glucose level, white blood cell count, hematocrit, peak troponin level, presence of cardiogenic shock, acute respiratory failure on admission, cardiac catheterization, percutaneous coronary intervention, coronary artery bypass graft surgery, acute kidney injury during hospitalization, fibrinolytic therapy, aspirin, clopidogrel, ticlopidine, β-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, calcium channel blockers, nitrates, diuretics, bronchodilators, statins, insulin treatment, oral antihyperglycemic agents, number of serum potassium checks during hospitalization, length of hospital stay, and clustering by hospital site.Abbreviation: aOR, adjusted odds ratio.a Statistically significant OR compared with the reference group.b Reference group. Open table in a new tab Note: ORs adjusted for age, sex, race, diabetes, heart failure, hypertension, cerebrovascular disease, peripheral vascular disease, chronic obstructive pulmonary disease, dementia, dialysis, admission glomerular filtration rate calculated by the Modification of Diet in Renal Disease Study equation, potassium level, glucose level, white blood cell count, hematocrit, peak troponin level, presence of cardiogenic shock, acute respiratory failure on admission, cardiac catheterization, percutaneous coronary intervention, coronary artery bypass graft surgery, acute kidney injury during hospitalization, fibrinolytic therapy, aspirin, clopidogrel, ticlopidine, β-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, calcium channel blockers, nitrates, diuretics, bronchodilators, statins, insulin treatment, oral antihyperglycemic agents, number of serum potassium checks during hospitalization, length of hospital stay, and clustering by hospital site. Abbreviation: aOR, adjusted odds ratio. Of great interest, the lowest in-hospital mortality, 4.8%, occurred in the group of patients with potassium levels of 3.5-<4.0 mEq/L, a range that current guidelines would suggest treatment to increase potassium levels. As postadmission serum potassium levels increased to >4.5 mEq/L or decreased to <3.5 mEq/L, there was a stepwise U-shape increase in mortality compared with the reference group, with the highest mortality occurring in patients with serum potassium levels >5.5 mEq/L and <3.0 mEq/L. The U-shaped relationship was similar regardless of potassium supplementation during hospitalization or admission potassium level. The relation between postadmission potassium levels and increased odds of ventricular fibrillation or sudden cardiac arrest showed a generally similar pattern, although with fewer events and less statistical power to ascertain differences. Increased risk of ventricular fibrillation or sudden cardiac arrest was significantly different from the reference group (3.5-<4.0 mEq/L) only when postadmission hyperkalemia (potassium >5.0 mEq/L) was present or admission potassium level was <3.5 mEq/L. The lowest rates of ventricular fibrillation or sudden cardiac arrest were at slightly higher levels of potassium (4-<4.5 mEq/L) than those for in-hospital mortality. Although analyses were adjusted for multiple potential confounders, it is important to consider residual confounding as possibly influencing the results because the highest and lowest serum potassium groups (highest mortality groups) had the highest rates of cardiogenic shock, acute kidney injury, and acute respiratory failure and were significantly less likely to be treated with contemporary AMI therapies known to decrease in-hospital mortality. The most striking observation in this study was that what has been traditionally considered by guidelines as a “goal” or “normal” potassium level (4.0 or 4.5 mEq/L) was associated with a slight but significantly increased risk of mortality compared with 3.5-4.0 mEq/L. This finding challenges the current viewpoint that recommends maintaining serum potassium levels at >4 mEq/L post-AMI.5Macdonald J.E. Struthers A.D. What is the optimal serum potassium level in cardiovascular patients?.J Am Coll Cardiol. 2004; 43: 155-161Abstract Full Text Full Text PDF PubMed Scopus (247) Google Scholar, 12Antman E.M. Anbe D.T. Armstrong P.W. et al.ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). 2004.http://assets.cardiosource.com/STEMI_2004.pdfGoogle Scholar, 13Cohn J.N. Kowey P.R. Whelton P.K. Prisant L.M. New guidelines for potassium replacement in clinical practice: a contemporary review by the National Council on Potassium in Clinical Practice.Arch Intern Med. 2000; 160: 2429-2436Crossref PubMed Scopus (226) Google Scholar In agreement with multiple previous studies,6Kafka H. Langevin L. Armstrong P.W. Serum magnesium and potassium in acute myocardial infarction: influence on ventricular arrhythmias.Arch Intern Med. 1987; 147: 465-469Crossref PubMed Scopus (110) Google Scholar, 8Madias J.E. Shah B. Chintalapally G. Chalavarya G. Madias N.E. Admission serum potassium in patients with acute myocardial infarction: its correlates and value as a determinant of in-hospital outcome.Chest. 2000; 118: 904-913Crossref PubMed Scopus (48) Google Scholar, 9Nordrehaug J.E. Von der Lippe G. Hypokalemia and ventricular fibrillation in acute myocardial infarction.Br Heart J. 1983; 50: 525-529Crossref PubMed Scopus (171) Google Scholar, 10Hulting J. In-hospital ventricular fibrillation and its relation to serum potassium.Acta Med Scand Suppl. 1981; 647: 109-116PubMed Google Scholar, 11Herlitz J. Hjalmarson A. Bengtson A. Occurrence of hypokalemia in suspected acute myocardial infarction and its relation to clinical history and clinical course.Clin Cardiol. 1988; 11: 678-682Crossref PubMed Scopus (15) Google Scholar admission hypokalemia (potassium <3.5 mEq/L) was associated with an increased likelihood of hospital ventricular fibrillation or sudden cardiac arrest (Table 2). However, in contrast to multiple studies that failed to show an association of admission hypokalemia to either short- or long-term mortality,8Madias J.E. Shah B. Chintalapally G. Chalavarya G. Madias N.E. Admission serum potassium in patients with acute myocardial infarction: its correlates and value as a determinant of in-hospital outcome.Chest. 2000; 118: 904-913Crossref PubMed Scopus (48) Google Scholar, 9Nordrehaug J.E. Von der Lippe G. Hypokalemia and ventricular fibrillation in acute myocardial infarction.Br Heart J. 1983; 50: 525-529Crossref PubMed Scopus (171) Google Scholar, 11Herlitz J. Hjalmarson A. Bengtson A. Occurrence of hypokalemia in suspected acute myocardial infarction and its relation to clinical history and clinical course.Clin Cardiol. 1988; 11: 678-682Crossref PubMed Scopus (15) Google Scholar the study by Goyal et al14Goyal A. Spertus J.A. Gosch K. et al.Serum potassium levels and mortality in acute myocardial infarction.JAMA. 2012; 307: 157-164Crossref PubMed Scopus (228) Google Scholar showed that patients with profound admission hypokalemia (potassium <3.0 mEq/L) had a higher probability of in-hospital mortality. The highest mortality rates were seen in patients with extreme admission or postadmission hyperkalemia (potassium >5.5 mEq/L), a level which has been previously shown to be an independent risk factor for in-hospital mortality.15Einhorn L.M. Zhan M. Hsu V.D. et al.The frequency of hyperkalemia and its significance in chronic kidney disease.Arch Intern Med. 2009; 169: 1156-1162Crossref PubMed Scopus (410) Google Scholar Of interest, in the report by Goyal et al14Goyal A. Spertus J.A. Gosch K. et al.Serum potassium levels and mortality in acute myocardial infarction.JAMA. 2012; 307: 157-164Crossref PubMed Scopus (228) Google Scholar patients with admission potassium levels of 4.5-<5 mEq/L, there was discordance in risk because in-hospital mortality risk was increased whereas arrhythmic risk was not. Potassium repletion did not seem to alter outcomes because the U-shaped relationship between postadmission potassium level and in-hospital mortality persisted regardless of whether or not patients received potassium repletion during hospitalization.Table 2Relation of Admission Potassium Level to In-Hospital Mortality or Arrhythmic EventsData from Goyal et al.14Goyal A. Spertus J.A. Gosch K. et al.Serum potassium levels and mortality in acute myocardial infarction.JAMA. 2012; 307: 157-164Crossref PubMed Scopus (228) Google ScholarMean Admission MeasurementMortalityVentricular Fibrillation or Sudden Cardiac ArrestRateaORRateaORPotassium <3.0 mEq/L17.2% (82/477)1.93aStatistically significant OR compared with the reference group.15.5% (74/477)2.19aStatistically significant OR compared with the reference group.Potassium = 3.0-<3.5 mEq/L6.6% (199/3,015)1.108.2% (246/3,015)1.53aStatistically significant OR compared with the reference group.Potassium = 3.5-<4.0 mEq/L4.5% (516/11,524)1.00bReference group.4.4% (504/11,524)1.00bReference group.Potassium = 4.0-<4.5 mEq/L5.0% (717/14,261)0.933.4% (488/14,261)0.81aStatistically significant OR compared with the reference group.Potassium = 4.5-<5.0 mEq/L9.0% (535/5,949)1.073.8% (223/5,949)0.75aStatistically significant OR compared with the reference group.Potassium = 5.0-<5.5 mEq/L15.0% (314/2,094)1.28aStatistically significant OR compared with the reference group.4.4% (92/2,094)0.75aStatistically significant OR compared with the reference group.Potassium ≥5.5 mEq/L23.1% (316/1,369)1.31aStatistically significant OR compared with the reference group.5.8% (80/1,369)0.70aStatistically significant OR compared with the reference group.Note: ORs adjusted as described in Table 1.Abbreviation: aOR, adjusted odds ratio.a Statistically significant OR compared with the reference group.b Reference group. Open table in a new tab Note: ORs adjusted as described in Table 1. Abbreviation: aOR, adjusted odds ratio. The results shown by Goyal et al14Goyal A. Spertus J.A. Gosch K. et al.Serum potassium levels and mortality in acute myocardial infarction.JAMA. 2012; 307: 157-164Crossref PubMed Scopus (228) Google Scholar reinforce the strong link between admission hypokalemia (potassium <3.5 mEq/L) and subsequent ventricular fibrillation or sudden cardiac arrest. Therefore, based on the best available evidence and the low likelihood that an adequately sized randomized trial of potassium repletion in AMI will ever be performed, it seems sensible to: (1) avoid profound hypokalemia (potassium <3.0 mEq/L), which is associated with an increased risk of in-hospital mortality; (2) not intervene for potassium levels of 3.5-3.9 mEq/L, which are associated with the least risk of mortality and could be considered the ideal “goal”; and (3) avoid overly aggressive repletion of potassium, which may not be advisable in patients with AMI because it does not appear to alter outcomes and, more importantly, could be associated with possible harm when postadmission levels are ≥4 mEq/L, with escalating risk as levels increase further. It is important to note that the analysis of Goyal et al14Goyal A. Spertus J.A. Gosch K. et al.Serum potassium levels and mortality in acute myocardial infarction.JAMA. 2012; 307: 157-164Crossref PubMed Scopus (228) Google Scholar does not take into account the possibility that some forms of potassium repletion and concomitant effects on potassium serum levels may have favorable effects. In the recently published IMMEDIATE (Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency Care) trial,16Selker H.P. Beshansky J.R. Sheehan P.R. et al.Out-of-hospital administration of intravenous glucose-insulin-potassium in patients with suspected acute coronary syndromes: the IMMEDIATE randomized controlled trial.JAMA. 2012; 307-: 1925-1933Crossref PubMed Scopus (164) Google Scholar intravenous administration of glucose, insulin, and potassium solution early in the course of suspected acute coronary syndromes (started by paramedics in the field) was associated with signals of improved outcome, including a decrease in the composite of in-hospital cardiac arrest or mortality. Complete information for serum potassium levels in the participating cohorts was not provided in the initial publication, but the data remind us that the association of serum levels and outcomes is complex and the drivers of serum levels may have an important influence on the association. In conclusion, the analysis by Goyal et al14Goyal A. Spertus J.A. Gosch K. et al.Serum potassium levels and mortality in acute myocardial infarction.JAMA. 2012; 307: 157-164Crossref PubMed Scopus (228) Google Scholar is a good example of the use of large contemporary observational databases to inform a clinical question that heretofore has only been informed by older small studies. This approach lends itself to related questions, such as the ideal potassium level in patients with heart failure or those with chronic kidney disease.15Einhorn L.M. Zhan M. Hsu V.D. et al.The frequency of hyperkalemia and its significance in chronic kidney disease.Arch Intern Med. 2009; 169: 1156-1162Crossref PubMed Scopus (410) Google Scholar, 17Bowling C.B. Pitt B. Ahmed M.I. et al.Hypokalemia and outcomes in patients with chronic heart failure and chronic kidney disease: findings from propensity-matched studies.Circ Heart Fail. 2010; 3: 253-260Crossref PubMed Scopus (110) Google Scholar The level of “goal” serum potassium in AMI should be changed in contemporary guidelines on the basis of the data presented in the study of Goyal et al.14Goyal A. Spertus J.A. Gosch K. et al.Serum potassium levels and mortality in acute myocardial infarction.JAMA. 2012; 307: 157-164Crossref PubMed Scopus (228) Google Scholar Financial Disclosure: The authors declare that they have no relevant financial interests." @default.
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• W2043818687 title "What Is the “Goal” Serum Potassium Level in Acute Myocardial Infarction?" @default.
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