European Review for Medical and Pharmacological Sciences
2012; 16(Suppl 1): 25-29
QT dispersion in carbon monoxide poisoning M. ATESCELIK1, M.N. BOZDEMIR2, M. YILDIZ3, S. GURBUZ3, M. AYRANCI3, M.C. GOKTEKIN3, M.A. KOBAT4, M.N. DAGLI5, C. EKEN6 1
Department of Emergency Medicine, Sivas State Hospital, Sivas (Turkey) Department of Emergency Medicine, School of Medicine, Selcuk University, Konya (Turkey) 3 Department of Emergency Medicine, School of Medicine, Firat University, Elazıg (Turkey) 4 Department of Cardiology Elazıg Numune Education and Research Hospital, Elazig (Turkey) 5 Department of Cardiology, Firat University School of Medicine, Elazig (Turkey) 6 Department of Emergency Medicine, Akdeniz University School of Medicine, Antalya (Turkey) 2
Abstract. – Background: Carbon monoxide (CO) poisoning are serious health problems, and effect of reducing the blood’s oxygen carrying capacity. Deaths due to CO poisoning are mostly related to myocardial injury and central nervous system pathologies. Aim: The objective of this study was to determine the relationship between carbon monoxide intoxication, QT dispersion, and cardiac markers. Materials and Methods: Patients with possible CO intoxication symptoms were evaluated to be eligible for the study. Patients’ demographic data, carboxyhemoglobin levels, cardiac markers and QT interval measurements were recorded to the study form. Results: A total of 127 patients (79 CO intoxicated and 48 controls) were included into the study with a mean age of 38.6±14.1 years and 62.2% of them were female. Average levels of patient’s carboxyhemoglobin were 21.3 ± 9. QT dispersion (39.0 ± 10.8 vs 24.4 ± 6.2; p < 0,001) and corrected QT dispersion (46.2 ± 14.7 vs 25.3 ± 6.2; p < 0.001) were longer than the control group. Both QT dispersion (39.0 ± 10.8 vs 23.6 ± 7.0; p < 0.001) or corrected QT dispersion (46.2 ± 14.7 vs 27.1 ± 8.7; p < 0.001) were also decreased after one week later from the admission. Conclusion: Carbon monoxide intoxication is related to increased QT dispersion. Emergency physicians should measure QT dispersion in CO intoxicated patients in order to predict the electrical instability in myocardium and future adverse events. Key Words: Carbon monoxide poisoning, QT dispersion, Cardiac marker, Emergency Department.
Introduction Carbon monoxide (CO) poisoning is a serious health problem, which is associated with a high incidence of severe morbidity and mortality. It is thought to be responsible for more than half of the deaths due to the poisoning world wide 1. Mortality rates of CO poisoning is reported as high as 31% in large series2-3. Carbon monoxide poisoning is known to cause myocardial toxicity and life threatening arrhythmias3-6. However, the severity and duration of cardiac abnormalities are not well known. Carbon monoxide poisoning reduces the oxygen carrying capacity of the blood. Furthermore, CO binds with cardiac myoglobin which causes a rapid decrease in myocardial oxygen reserves7. The ventricular fibrillation threshold is lowered by CO, and ECG changes such as ST segment depression, ischemia, atrial flutter, atrial fibrillation, premature ventricular tachycardia, and conduction system disturbances may also be seen seen4,8. Twelve-lead electrocardiography is the most common tool used for detecting myocardial damage and ventricular arrhythmias. QT dispersion (QTd) is defined in 1990 by Day et al as the difference between the greatest and the least QT intervals (QTmax-QTmin) in any of the 12leads. Heart rate play a major role in QT interval variation and it also variates individually9. The most common approach for determining a true QT interval is dividing an QT interval by the square root of the preceding RR interval (Bazett correction). QT dispersion may be an indirect measure of ventricular repolarization
Corresponding Author: Mustafa Yildiz, MD; e-mail:
[email protected]
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M. Atescelik, M.N. Bozdemir, M. Yildiz, S. Gurbuz, M. Ayranci, M.C. Goktekin, et al.
heterogeneity that may also contribute to ventricular arrhythmias10-15. The objective of this study was to determine the effects of CO poisoning on QT dispersion.
Materials and Methods Study Setting This prospective clinical trial was performed in a tertiary care Emergency Unit between January 2007 and May 2008. The local Ethics Committee approved the study. Patients Patients presented due to the complaints indicating CO poisoning such as headache, nausea, vomiting, fatigue, vertigo, palpitation, syncope, dyspnea, chest pain, chilling, altered mental status, abdominal pain and visual disorders were evaluated to be eligible for the study. Carbon monoxide levels were studied with Siemens Rapid Lab 1265 and levels above 5% (10% in smokers) were considered significant. Seventy-nine patients were included into the study finally. An age- and sex-matched 48 patients with mild clinical conditions, not related to CO poisoning, composed the control group. Patients with diabetes mellitus, hypertension, cardiac failure, coronary arterial disease or other known heart disease, e.g., valvular diseases or rhythm disorders were excluded from the study. All patients with CO poisoning were administered oxygen therapy. Informed consent was obtained from the study patients or their legal representatives. Cardiac Markers Blood samples were obtained during the admission for B-type natriuretic peptide (BNP), troponin I, creatine kinase (CK), creatine kinaseMB (CK-MB) and myoglobin levels. CK-MB, myoglobin and troponin I levels were determined by using Triage Cardiac panel, BIOSITE Triage meter plus (BIOSITE Inc. San Diego, CA, USA). B-type natriuretic peptide was also determined by using The Triage® BNP Test, BIOSITE Triage meter plus (BIOSITE Inc. San Diego, CA, USA). Baseline levels of serum creatinine, blood urea nitrogen (BUN), sodium, potassium, glucose, calcium, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and CK fraction were also measured. 26
Electrocardiographic Examination and QT Interval Measures Baseline ECG of each patient with a paper speed of 25 mm/s and standardization of 1.0 mV/cm were recorded at the admission and repeated one week after their discharge from the hospital. The QT interval was measured from the beginning of the QRS complex to the end of the T wave, defined as the return T-P baseline. When a U wave was present, the QT interval was measured to the nadir of the curve between T and U wave. If the end of the T wave was not clear, the lead was excluded from analysis. The QT intervals for each lead were measured and corrected for heart rate (cQT) using Bazett’s formula (cQT = QT/RR1/2). The QT dispersion (QTdc) was then calculated between the difference of shortest and longest QTc intervals in among all the leads. Statistical Analysis The study data was analyzed with SPSS 11.0 software (SPSS, Inc., Chicago, IL, USA). Continuous variables were expressed as mean ± standard deviation (SD), ordinal variables as median (min-max) and frequent data as rates. Two group comparisons for independent data were performed with Student-t data and with paired-t test for dependent data. Correlations between variables were evaluated with the Pearson correlation test. All the hypothesis were constructed as two tailed and a p value < 0.05 was accepted as statistically significant.
Results A total of 127 patients (79 CO intoxicated and 48 controls) were included into the study. The mean age of the patients was 38.6 ± 14.1 years and 62.2% of them were female. Headache, nausea and malaise were the most common symptoms in 55.7%, 53.2% and 50.6% of the patients, respectively (Table I). Mean carboxyhemoglobin levels of study patients were 21.3 ± 9.3. Although CO intoxication did not effect on B-type natriuretic peptide (BNP) levels, it caused myocardial damage in some of the study patients (Table II). Both QT maximum (392.6 ± 27.7 vs 360.0 ± 31.2; p < 0.001) and QT minimum (353.2 ± 27.7 vs 336.0 ± 32.7; < 0.01) durations of CO-intoxicated patients were longer than the control group. QTmax levels significantly decreased after one week (392.6 ± 27.7 vs 379.5 ± 26.2; p < 0,001), but QTmin levels did not (353.2 ± 27.7 vs 355.8 ± 26.5; p > 0,05).
QT dispersion in carbon monoxide poisoning Table I. Symptoms of CO-intoxicated patients. Symptoms
%
Headache Nausea Malaise Dizziness Vomiting Palpitations Syncope Respiratory distress Chest pain Tremor titreme Altered mental state Abdominal pain Visual disturbance Loss of consciousness
55.7 53.2 50.6 49.4 24.1 17.7 11.4 11.4 11.4 10.1 8.9 6.3 5.1 2.5
CO: carbon monoxide.
QT dispersion (39.0 ± 10.8 vs 24.4 ± 6.2; p < 0.001) and corrected QT dispersion (46.2 ± 14.7 vs 25.3 ± 6.2; p < 0.001) were longer than the control group. Both QT dispersion (39.0 ± 10.8 vs 23.6 ± 7.0; p < 0.001) or corrected QT dispersion (46.2 ± 14.7 vs 27.1 ± 8.7; p < 0.001) were also decreased after one week later from the admission. Table III displays the QT measurements of CO intoxicated and control group patients during the admission and one week later.
Discussion QT dispersion was originally proposed as an index of the spatial dispersion of ventricular recovery times. In reality, QT dispersion is a crude and approximate measure of a general abnormality of repolarization16. Ventricular repolarization abnormalities are detected by measuring cQT in-
terval in clinical practice. However, QT measurements may vary lead to lead. These interlead differences called QT interval dispersion, which may reflect the disparity in myocardial recovery times. Several studies have shown the difference between maximum and minimum QT intervals on standard 12 leads ECG (QT dispersion) that has been proposed as a non-invasive measure of the degree of homogeneity in myocardial repolarization, a significant predictor of serious arrhythmias and cardiac mortality in humans17-19. A recent literature review reports that the mean QTd varies between 10.5 ± 10 ms and 71 ± 7 ms, with a weighted mean of 33.4 ± 20.3 ms in healthy subjects3,16. This investigation showed that CO intoxication cause increased QT dispersion. Both normal QTd and corrected QTd were longer in CO intoxicated patients than control group and decreased one week later after intoxication. Sarı et al 20 reported increased QT dispersion and QTmax values in chronically exposure to CO and this increase was correlated with CO values. Gürkan et al3 also reported similar findings to Sarı et al21. McMillan et al5 referred a case of 59 years old with a COHb level of 34% and cQTd 109 ms. The cQTd was measured 55 msn after the oxygen therapy with COHb level of 8.5%. Irene et al 21 reported a similar case, 9 years old, with a cQTd of 441 ms before treatment and 51 ms after treatment. Cevik et al22 observed also increased QTmax, QTd, cQTd measurements in CO intoxicated patients than the control group but not for QTmin values. Clinical presentation of CO intoxication is non-specific. The clinical spectrum may vary from nausea vomiting to altered mental status. However, central nervous system and myocardium are most sensitive to hypoxia. Ventricular dysrhythmias and neurological pathologies are the most common causes of death related CO intoxication.
Table II. Cardiac marker analysis of CO-intoxicated patients at initial presentation. Mean values ± SD CK (U/L) CK-MB (ng/ml) BNP (pg/ml) Troponin I (ng/ml) Myoglobin (ng/ml)
117.86 ± 57.3758 2.55 ± 6.01 57.91± 48.44 0.14 ± 0.655 64.81 ± 48.39
Min-Max 42.00-403.00 1.00-53.40 5.00-165.00 0.05-5.80 10.40-210.00
Normal range 24-195 0-4.3 0-100 0-1 0-107
CK; Creatine kinase, CK-MB; Creatine kinase-MB, BNP; B-type natriuretic peptide.
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M. Atescelik, M.N. Bozdemir, M. Yildiz, S. Gurbuz, M. Ayranci, M.C. Goktekin, et al. Table III. QTmax, QTmin, QTd and cQTd intervals at admission and after one week. CO-intoxicated
Control group
p value
392.6 ± 27.7 379.5 ± 26.2 < 0.001
360.0 ± 31.2
< 0.001
353.2 ± 27.7 355.8 ± 26.5 > 0.05
336.0 ± 32.7
< 0.01
39.0 ± 10.8 23.6 ± 7.0 < 0.001
24.4 ± 6.2
< 0.001
46.2 ± 14.7 27.1 ± 8.7 < 0.001
25.3 ± 6.2
< 0.001
QTmax (ms) Admission ECG After one week ECG p value QTmin (ms) Admission ECG After one week ECG p value QTd (ms) Admission ECG After one week ECG p value cQTd (ms) Admission ECG After one week ECG p value
CO intoxication may cause myocardial injury and increased levels of cardiac markers. Measuring of troponin I, myoglobin, CK and CK-MB level in patients with CO poisoning may be helpful to determine the degree of cardiac damage or dysfunction23-24. Some of patients in our study had increased cardiac markers indicating myocardial injury. There are some limitations to this study. Factors effecting QT dispersion measurements should be noted. High interobserver and intraobserver variability in measuring QT intervals, the number of measurable leads which influences the range of QT interval, existence of Q waves and U waves that all may cause variations in measurements of QT intervals.
Conclusion Carbon monoxide intoxication is related to increased QT dispersion. Emergency physicians should measure QT dispersion in CO intoxicated patients in order to predict the electrical instability in myocardium and future adverse events.
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