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EVIDENCE BASED CASE REPORT

Admission Potassium Level as a Predictor of Mortality in Acute Coronary


Syndrome Patients

Authors
dr. Hendra Perkasa 1706118904
dr. Ira Camelia Fitri 1706118910
dr. Laurentius Johan Ardian 1706118923
dr. Naldo Sofian 1706118936
dr. Nur Hidayat 1706118942
dr. R. Agung Suryoputro 1706118955
dr. Rosalin Yuaniarti Maruf 1706118961
dr. Rosatya Imanuela 1706118974
dr. Surya Ulhaq 1706118980
dr. Wirdasari 1706118993

Supervisor
Dr. dr. Sukamto Koesnoe, SpPD-KAI

EVIDENCE BASED MEDICINE MODULE


FACULTY OF MEDICINE UNIVERSITAS INDONESIA
APRIL 2018
APPROVAL SHEET

Potassium Level as a Predictor of Mortality in Acute Coronary Syndrome


Patients

This paper has been checked and approved by our supervisor.

Jakarta, April 2018

EBCR Supervisor

Dr. dr. Sukamto Koesnoe, Sp.PD-KAI


ANTIPLAGIARISM FORM

Authors have declared that this Evidence-Based Case Report was free of any
plagiarism during its process, as being stated in Universitas Indonesia decree. If there
is any evidence of plagiarism involved, authors will take full responsibility and are
aware of the punishment given by Universitas Indonesia.

Jakarta, April 2018

dr. Hendra Perkasa (…………………..)


dr. Ira Camelia Fitri (…………………..)
dr. Laurentius Johan Ardian (…………………..)
dr. Naldo Sofian (…………………..)
dr. Nur Hidayat (…………………..)
dr. R. Agung Suryoputro (…………………..)
dr. Rosatya Imanuela (…………………..)
dr. Rosalin Yuaniarti Maruf (…………………..)
dr. Surya Ulhaq (…………………..)
dr. Wirdasari (…………………..)

SK Rektor Universitas Indonesia No. 208/SK/R/UI/2009 tanggal 17 Maret


2009 tentang Pedoman penyelesaian masalah plagiarisme yang dilakukan
oleh sivitas akademika Universitas Indonesia
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dalam tulisannya seolah-olah ide atau tulisan orang lain tersebut adalah ide, pikiran,
dan/atau tulisan sendiri sehingga merugikan orang lain baik material maupun
nonmaterial, dapat berupa pencurian sebuah kata, frasa, kalimat, paragraf, atau bahkan
pencurian bab dari tulisan atau buku seseorang, tanpa menyebutkan sumbernya,
termasuk dalam plagiarisme adalah plagiarisme diri.
Abstract
INTRODUCTION
Acute myocardial infarction related death can be caused by various mechanisms,
classified into arrhythmic and mechanic cause. A post mortem data of post myocardial
infarctions sudden death showed that the major cause of deaths are arrhythmia (51.4%), the
rest are caused by mechanical etiology.1
Acute myocardial infarctions are reported to be linked with potassium level
fluctutation due to metabolic changes. In acute phase, there is a transient decrease of
potassium level that is caused by potassium influx as consequence of beta adrenergic receptor
signal modulation.2 While hyperkalemia can be induced by various medications given in
myocardial infarction such as beta blockers, mineralocorticoid receptor agonist, and RAAS
antagonist. Beside that, procedures like cardiac bypass and percutaneous interventions can
cause hyperkalemia indirectly through contrast induced nephropathy and acute kidney injury.
On the other hand, interstitial hyperkalemia in acute myocardial infarction will contribute to
the injury of myocardial tissue through shortening of the duration of after depolarization in
the ischemic region.3 Both of the condition can cause arrhythmias such as Torsade de pointes,
polymorphic ventricular tachycardia, and ventricular fibrillation which lead to death.
Current guidelines recommended serum potassium level in acute myocardial
infarctions should be maintained greater than 4 mEq/L, yet no upper level was set. However,
despite being treated, it is unclear whether the abnormal potassium levels on admission can
predict mortality of acute myocardial infarction patients. Thus, it is essential to evaluate
serum potassium level and mortality. The aim of this evidence-based case report is to assess
admission serum potassium level as predictor of mortality in acute myocardial infarction
patients.

CLINICAL SCENARIO
A 50-year-old man was admitted to our emergency department due to persisting angina
for an hour. He described the pain as retro-sternal, pressure-like, and non-radiating. The
patient had history hypertension and family history with coronary arterial diseases. He used
to smoke a cigarette one pack daily. On physical examination, cardiac sounds were normal on
auscultation. His blood pressure was 100/70 mm Hg and heart rate was 120 bpm. On
admission, low-density lipoprotein cholesterol 174 mg/dL, total cholesterol 224 mg/dl, serum
troponin-T 7,38 ng/mL (normal range (NR) 0–0.09 ng/mL) and serum potassium 2.54
mEq/L. His ECG showed normal sinus rhythm with ST segment elevation in leads I, aVL,
V2-V5 and reciprocal ST segment depression in leads III. On echocardiography showed
segmental hypokinetic, ejection fraction 50%, and mild diastolic dysfunction in right
ventricle. Patient had underwent a correction of potassium level in emergency ward before he
underwent primary percutaneous coronary intervention and admitted to intensive
cardiovascular care unit in Cipto Mangunkusumo Hospital. Patient’ family asked to the
physician about the outcome whether the patient will die when the patient's potassium levels
are abnormal regardless he had underwent the electrolyte correction.

CLINICAL QUESTION
Thus, we formulated the following clincial question: Does abnormal serum potassium level
affect mortality rate in patient with acute myocardial infarction?
 Patients : Patients with acute myocardial infarction
 Intervention : Abnormal admission potassium level
 Comparison :-
 Outcome : Mortality rate

METHODS
Literature searching and reviewing was done on April 20th, 2018 in these databases:
Medline, Cochrane, EBSCO, Proquest, Scielo, Science direct, Scopus, and CINAHL. Hand
searching was also done by looking for the relevant articles in google scholar and
portalgaruda.org. The keywords for literature searching was based on PICO and their
synonims. These articles were screened by titles and abstracts using inclusion and exclusion
criteria. The inclusion criteria was cohort study or meta-analysis of cohort study, otherwise
the exclusion criteria were review, non-humans trial, animal study, etc. Then, we defined the
selected articles which assessed the full text availability dan removed the duplication articles.
The final number of useful articles were appraised critically. We assessed validity,
importance, and applicability of eligible articles according to Oxford Critical Appraisal Tool
2005. All agreement were made by consensus of two or more reviewers.

RESULTS
We conducted literature searching in several database. Table 1 presents the strategy of
literature searching completely. The total number of articles from the searching were 40,524
articles. After screening the title and abstract and selecting the articles according to inclusion
and exclusion criteria, we obtained 52 articles after removing duplication. After reading the
full texts, only thirteen articles were appropriate and useful to answer our clinical question.
(Figure 1). These articles consisted of 1 meta-analysis and 12 cohort studies. We appraised 1
meta-analysis and 6 cohort studies because six of cohort studies were included in meta-
analysis. Critical appraisal was done using recommended working sheet for each study
design. Table 2 and Table 3 described the result of critical appraisal comprehensively. We
had 6 selected articles after critical appraisal phase. The description of these evidences were
depicted in Table 4.
Table 1. Strategy for Literature Searching
Database Keywords Number of
(Accessed 20th, April 2018) articles
Medline (((((((((((((acute myocardial infarction[Title/Abstract]) OR acute myocardial infacrtion[MeSH Terms]) OR acute coronary 84
syndrome[Title/Abstract]) OR acute coronary syndrome[MeSH Terms]) OR acute coronary infarction[Title/Abstract]) OR acute
coronary infarction[MeSH Terms]) OR STEMI[Title/Abstract]) OR STEMI[MeSH Terms]) OR ST Elevation[Title/Abstract]) OR
ST Elevation[MeSH Terms]) OR NSTEMI[MeSH Terms]) OR NSTEMI[Title/Abstract]) OR Non-ST Elevation[MeSH Terms]) OR
Non-ST Elevation[Title/Abstract]) AND
(((((((hypokalemia[Title/Abstract]) OR hypokalemia[MeSH Terms]) OR hyperkalemia[Title/Abstract]) OR hyperkalemia[MeSH
Terms]) OR potassium level[Title/Abstract]) OR potassium level[MeSH Terms]) OR potassium abnormalities[Title/Abstract]) OR
potassium abnormalities[MeSH Terms]) AND
(((((mortality[Title/Abstract]) OR mortality[MeSH Terms]) OR death[Title/Abstract]) OR death[MeSH Terms]) OR survival[MeSH
Terms]) OR survival[Title/Abstract])
Cochrane [Title, Abstract, Keywords](acute myocardial infarctionOR acute coronary syndromeOR acute coronary infarctionOR STEMIOR ST 7
Library ElevationOR NSTEMI OR Non-ST Elevation) AND
[Title, Abstract, Keywords](hypokalemiaOR hyperkalemiaOR potassium levelOR potassium abnormalities) AND [Title, Abstract,
Keywords] (death OR mortality OR survival)
ProQuest ab(Acute Coronary Syndome OR Acute Coronary Infarction OR Myocard Infarct OR Acute Myocardial Infarct OR STEMI OR 23.459
NSTEMI OR ST Elevation) AND ab(Hypokalemia OR Hyperkalemia OR Potassium OR Potassium Serum OR Potassium Level)
AND ab(Survival OR Death OR Mortality)
CINAHL (Acute Coronary Syndome OR Acute Coronary Infarction OR Myocard Infarct OR Acute Myocardial Infarct OR STEMI OR 1
NSTEMI OR ST Elevation) AND (Hypokalemia OR Hyperkalemia OR Potassium OR Potassium Serum OR Potassium Level) AND
(Survival OR Death OR Mortality)
Scopus [TITLE-ABS] (Acute Coronary Syndome OR Acute Coronary Infarction OR Myocard Infarct OR Acute Myocardial Infarct OR 95
STEMI OR NSTEMI OR ST Elevation) AND[TITLE-ABS] (Hypokalemia OR Hyperkalemia OR Potassium OR Potassium Serum
OR Potassium Level) AND [TITLE-ABS](Survival OR Death OR Mortality)
Science direct (Acute Coronary Syndome OR Acute Coronary Infarction OR Myocard Infarct OR Acute Myocardial Infarct OR STEMI OR 17.901
NSTEMI OR ST Elevation) AND (Hypokalemia OR Hyperkalemia OR Potassium OR Potassium Serum OR Potassium Level) AND
(Survival OR Death OR Mortality)
Scielo (Acute Coronary Syndome OR Acute Coronary Infarction OR Myocard Infarct OR Acute Myocardial Infarct OR STEMI OR 3
NSTEMI OR ST Elevation) AND (Hypokalemia OR Hyperkalemia OR Potassium OR Potassium Serum OR Potassium Level) AND
(Survival OR Death OR Mortality)
EBSCO (Acute Coronary Syndome OR Acute Coronary Infarction OR Myocard Infarct OR Acute Myocardial Infarct OR STEMI OR 85
NSTEMI OR ST Elevation) AND (Hypokalemia OR Hyperkalemia OR Potassium OR Potassium Serum OR Potassium Level) AND
(Survival OR Death OR Mortality)
DYNAMED (Acute Coronary Syndome OR Acute Coronary Infarction OR Myocard Infarct OR Acute Myocardial Infarct OR STEMI OR 10
NSTEMI OR ST Elevation) AND (Hypokalemia OR Hyperkalemia OR Potassium OR Potassium Serum OR Potassium Level) AND
(Survival OR Death OR Mortality)
Hand (Acute Coronary Syndome OR Acute Coronary Infarction OR Myocard Infarct OR Acute Myocardial Infarct OR STEMI OR 217
Searching NSTEMI OR ST Elevation) AND (Hypokalemia OR Hyperkalemia OR Potassium OR Potassium Serum OR Potassium Level) AND
(Survival OR Death OR Mortality)
(acute myocardial infarction OR acute coronary syndrome OR acute coronary infarction OR STEMI OR ST Elevation OR
NSTEMI OR Non-ST Elevation) AND (hypokalemia OR hyperkalemia OR potassium level OR potassium abnormalities)
AND (mortality OR death OR survival)

Cochrane Proquest CINAHL Dynamed Scopus Science Scielo EBSCO Hand


Medline
Direct searching
All articles 84 7 23.459 10 95 17,901 3 85 217
1

40.524 records

Inclusion criteria: 38,524 records excluded:


- Cohort study or - Review (4,617)
SR/ MA of cohort - Non-human trials (26.823)
study 52 full-text articles - Case Report (123)
- Prognostic study - Conference (185)
assessed for eligibility
- Discussion (215)
after duplicate removed
- Animals (3,319)
- Child (347)
- Adolescents (497)
38 records excluded: - Clinical Practice Guidelines (42)
- Insufficient - Editorial (15)
outcome (32) - Others (4,347)
- Full text
availability (6)
14 studies included
(useful articles)

Figure 1. Flow Chart of Conducted Literature Searching


Table 2. Critical Appraisal of the Systematic Review
Questions Colombo, et. al. (2018)
Validity
Focused clinical question YES
Missing relevant studies NO
Assessment of the validity of included YES
studies
Included studies sufficiently valid YES
Similarity of the study result YES
Importance
Outcomes Both pooled results from six studies investigating short-
term mortality and from five studies examining long-
term mortality revealed significantly increased risks in
patients with serum potassium concentrations of< 3.5
mEq/L, 4.5-<5 mEq/L, and >5.0 mEq/L.
Applicability
Patients in research were so different NO
than our patient
Important Clinical Finding YES

Table 3. Critical Appraisal of the Cohort Studies


Author (Year) Validity Importance Applicability
on those with Different
Subgroup Assessment

(“test-set”) of patients

Time-Based Outcome

were so different than


Prognosis Estimation

Patients in research
Representativeness

Length of time and

independent group
Sample Collection

Important Clinical
Blinded Outcome
Completeness of

Validation in an
Follow-Up

our patient
Prognosis

Accuracy

Finding
Criteria

Colombo, et. al. YES YES NO YES ? A A NO YES


(2018)
Grodzinsky, et. al. YES YES NO YES ? B B - -
(2016)
Peng, et. al. (2016) YES YES YES YES YES C C NO YES
Verma, et. al. (2015) NO NO NO NO NO - - - -
Mati, et. al. (2012) NO NO NO NO NO - - - -
Kaczmarek, et. al. YES YES NO YES YES D D NO YES
(2007)
Shlomai, et. al. YES YES NO YES YES E E NO YES
(2016)
A. The median of follow up 6.1 years. The highest mortality of 29.9% (n = 40) was observed in patients with
potassium level of ≥5.0 mEq/l and the lowest (12.6%, n = 134) in patients with serum potassium level of 3.5
to< 4 mEq/L.
B. In the overall cohort, patients with higher max potassium levels experienced higher in-hospital mortality. The
author did not count the hazard ratio of low/ high potassium level.
C. Mean of follow up period 28.02 ± 13.04 months. Patients with admission serum potassium levels greater
than 4.5 mEq/L or less than 3.5 mEq/L exhibited significantly elevated risks of all cause mortality.
D. The length of follow-up was not clearly mentioned. The in-hospital mortality was significantly higher(9,6%
vs. 5,0%; p<0,001) in patients with low potassiumlevels.
E. Cumulative probability of all-cause mortality at 30 days was significantly higher among patients with
potassium level>4.45-5.2.
Table 4. The Summary of Evidence
Reference Study Design Subjects Outcome Level of
Evidence
Colombo, Systematic Not clear Potassium level less than 3.5 mEq/L and 4.5 mEq/L or I
et. al. review/meta- greater in patients with AMI were associated with a
(2018) analysis higher risk of short-term mortality and long-term
compared with potassium level of 3.5 to less than 4.0
mEq/L.
Colombo, Prospective 3347 Hazard ratio of potassium level 4.5 - <5.0mEq/l in 1- II
et. al. Cohort year mortality was HR=1.9695% CI (1.10–3.48)
(2017) p=0.023.
Hazard ratio of potassium level > 5 mEq/l in 10-year
mortality was HR=1.44 95% CI (1.02–2.05) p=0.0218.
Peng, et. Prospective 3714 Both sides of the U-shaped curve for deaths II
al. (2016) Cohort within 30 days had greater slopes than the
corresponding sides of the curve for deaths after 30
days.
Kaczmarek Retrospective 994 The odds ratio for death among hypokalemic patients II
, et Cohort to normokalemic ones was 2,23 [1,34 to 3,82],
al(2007) p<0,005.
Shlomai, Retrospective 1,277 The hazard ratio for death among “normal-very-high II
et. al. Cohort patients to “low-normal” ones was 2.88, 95% CI 1.05–
(2016) 7.87, p=0.039 and 1-year all-cause mortality (adjusted
hazard ratio 1.98, 95% CI 1.05 to 3.75, p=0.034).

DISCUSSION
Potassium is currently stated as an important marker in electrophysiology of any
cardiovascular diseases, especially for acute coronary syndrome and heart failure. It has unique
role through cardiac potentials in all four phases of action potentials to determine regular
contractility of the heart. Thus, it is plausible that potassium may determine an outcome of
cardiovascular disease and practically examined in most emergency department visit.
There are several studies directly stating on potassium serum influence to mortality in
patients with acute myocardial infarction. Through our prospective trials evidences, both hypo-
and hyperkalemia may cause increase risk of mortality among those with acute myocardial
infarction.
We found strong determinants of many potassium serum levels stratification. Normal
limit values of potassium levels was set as a reference. There are two range of normal values of
potassium serum mostly used in our evidence, 3.5 – 4.0 mEq/L and 4.0 – 4.5 mEq/L. The
number of mortality was increased following the higher level of potassium level. On the other
hand, the hazard ratio of mortality also increased in patients with lower level of potassium (< 3
mEq/L). The hazard ratio of mortality due to abnormality of potassium level was made a U-
shape graph. This hazard ratio U-shaped had greater slope in predict mortality after 30 days
compare with 30-day mortality. Thus, the admission potassium level greater than 4.5 mEq/L or
less than 3.5 mEq/L could more strongly predict mortality within 30 days than mortality after
30 days. (Peng) Shlomai, et al found normal range of potassium level also could predict
mortality. The “normal-very high” (4.46 – 5.2 mEq/L) potassium levels increased the risk for
30-day and 1-year all-cause mortality compare with “normal-low” (3.5-3.9 mEq/L).
Not only predict the mortality within hospital admission, several studies also found the
link between admission potassium level and long term mortality. The longest duration of
follow up was found in Choi, et. al. study which found slightly increase of hazard ratio in
potassium lower than <3.5 mEq/L and 10 times increase of 3-year mortality in potassium level
greater than 5 mEq/L.
Limitations are noted in our evidences analysis. Due to limitation access to local
database, we could not get ongoing trials or unpublished articles in which possibly analyze the
same outcome with ours. However, we have try to overcome it through our local search engine
“Portal Garuda” in which local research be registered. Publication bias is not a problem in this
study since reasons as follows (1) getting meta-analysis and systematic review published in
2018, (2) searching thorough every possible databases and hand searching, (3) similar
directions of study results in Colombo, et al with different point estimate only in several studies
(moderate heterogeneity).
Our case of hypokalemia in myocardial infarction should be noted as potential risk
factors on his mortality. Through our appraisal conclusion, this should be our basis on giving
patient’s relation on potential death. Arrhythmia would be the marker of this electrolyte
imbalance impact which should be considered by in-charge clinicians. In conclusion, our
evidences has high strength of determining risk stratified to many potassium serum
classification which could be applied in our clinical practice.

CONCLUSION
Through this critical appraisal to solve the case, we conclude that abnormal serum potassium
level affect mortality rate in patient with acute myocardial infarction. Both hypo- and
hyperkalemia has marked significant mortality risk.

REFERENCES

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