Abstract
Objectives: Postoperative arrhythmia is an important complication of coronary artery
bypass grafting (CABG) surgeries among patients. It seems that opioid usage
is implicated in the pathogenesis of this condition due to its impacts on
different organ systems, such as the autonomic nervous system. The present
study was performed to investigate the effect of opium use on postoperative
arrhythmia in patients undergoing CABG surgery.
Methods: Study participants were selected via convenience sampling from patients
undergoing CABG surgery in a referral hospital. Study variables, including
use of inotropic drugs, vital signs monitoring parameters and postoperative
arrhythmia were observed and recorded at baseline and at follow-up time
after surgery.
Results: Sixty-five (14.8%) patients had postoperative arrhythmia, and 104
participants were addicted. Prevalence of postoperative arrhythmia was the
same among addict and non-addict patients. According to the regression
analysis model, only serum level of epinephrine in operating room, heart
rate and central venous pressure at baseline and 48 hours after operation
are known as independent predictors of postoperative arrhythmia among study
population.
Conclusion: This study showed that although opium addiction increased postoperative
arrhythmia among patients undergoing CABG surgery, this difference was not
significant, and this association is probably mediated by other study
variables.
Keywords: Coronary Artery Bypass, Arrhythmias, Cardiac, Opium Dependence, Central Venous Pressure, Epinephrine, Postoperative Period.
Carátula del artículo
Effect of Opium Addiction on Postoperative Arrhythmia Among Patients
Undergoing CABG operation on Cardiopulmonary Bypass
Majid Basirat
Islamic Azad University, Iran
Mohsen Ziyaeifard
Iran University of Medical
Sciences, Iran
Farhad Gorjipour
Iran University of Medical
Sciences, Iran
Mohammad Javad Mehrabanian
Tehran University of Medical
Sciences, Iran
Seyed Hassan Attarzadeh
Iran University of Medical
Sciences, Iran
Majid Nekoofard
Iran University of Medical
Sciences, Iran
Meysam Mortazian
AJA University of Medical Sciences, Iran
Brazilian Journal of Cardiovascular Surgery, vol. 34, no. 4, pp. 444-450, 2019
Sociedade Brasileira de Cirurgia Cardiovascular
Received: 28 November 2018
Accepted: 14 December 2018
INTRODUCTION
Prevalence of cardiovascular diseases (CVD) has increased in recent years. Fifty
percent of deaths in developed countries and 25% of deaths in developing countries
are related to CVD[1].
According to the World Health Organization’s (WHO) reports, CVD causes one third of
all annual deaths around the world[2]. Coronary artery bypass grafting (CABG) surgery is
performed in CVD patients to improve their outcomes and to decrease incidence of
mortality. Postoperative arrhythmia is one of the CABG complications, and different
studies have been performed to the management of this complication among patients
undergoing cardiopulmonary surgery[3,4].
Drug addiction is known as one of the major social health problems in the world.
Opium dependence is highly prevalent among Iranian drug abusers[5,6]. As an example, according to a large clinical survey,
around 5.2% of Iranian patients with CVD were opium-dependent[7]. It seems that there is a
misconception among Iranian population that opium usage might decrease adverse
impacts of hypertension, diabetes mellitus and CVD[8].
Although most of the effects of opium are focused on the central and autonomic
nervous system and the intestinal tract, opium usage may have impacts on some other
organ systems, such as respiratory and cardiovascular systems[9]. Effects of opium usage on the
cardiovascular system are known to be mediated by some endogenous ligands as opioid
peptides[10].
Opioid peptides interact with most of the pathophysiological cardiac outcomes, such
as tachycardia/bradycardia, hypotension/hypertension, and vasodilation. According to
our search in the literature, there were few papers available regarding impacts of
opioid usage on postoperative outcomes such as arrhythmia. We assumed that opioid
usage, due to its impacts on different organs, such as autonomic nervous system, is
potentially a risk factor in postoperative arrhythmia among patients undergoing
cardiac surgeries. The present study was performed to evaluate the effect of opium
consumption on postoperative arrhythmia among patients undergoing CABG.
METHODS
Study Design and Patient Selection
Present clinical research was performed on patients undergoing CABG surgery in
Rajaie Cardiovascular Medical and Research Center (Tehran, Iran). Study
population was selected via convenience sampling from patients who were referred
to heart surgery clinic for CVD management and were candidates for elective CABG
surgery. Study inclusion criteria were elective CABG surgery, age between 18 and
85 years, male or female. Patients with prior history of cardiopulmonary bypass,
known cardiac rhythm disturbances, use of pacemakers or advanced heart failure
were excluded from the study. Study protocol was designed according to the
Declaration of Helsinki and was approved by the Ethics Committee of Iran
University of Medical Sciences. Informed consent was obtained from all study
participants before starting the trial.
Data Collection
Data related to patient demographics and history were extracted and recorded in
standard checklists. Then a checklist for each patient was used for data
collection, and data were taken and recorded by a nursing professional. Use of
inotropic drugs such as epinephrine, norepinephrine, dopamine, milrinone and
dobutamine before, during and after surgery was recorded. Vital signs, including
systolic and diastolic blood pressure, heart rate and central venous pressure,
were measured at baseline, after surgery, in the ICU admission, and 6, 24 and 48
hours after surgery. Heart rhythm of the patients was assessed until 72 hours
after operation and occurrence of dysrhythmia was recorded, and their types were
assessed as dependent variables.
Patients were grouped according to the status of opium addiction or the status of
arrhythmias after operation.
Statistical Analysis
Data were analyzed using SPSS V20 software for statistical analysis. Frequencies
of study variables were compared in the two groups with chi-square and
odds ratio. Quantitative variables were presented as mean
± standard deviation, and qualitative variables were presented as
frequencies and frequency percentage. Independent sample Student’s t-test was
used for comparing the mean of continuous study variables between the two
groups. We used logistic regression model to assess the role of study variables
in the incidence of postoperative arrhythmia. We included all variables that had
a P-value <0.2 in their univariate association with
postoperative arrhythmia. All P-values <0.05 were assumed as
significant results.
RESULTS
Finally, 438 patients (222 female) met our inclusion criteria and were included in
the trial. Mean age, body mass index and preoperative left ventricle ejection
fraction were 61.23±9.05 years, 25.26±4.54 kg/m2 and
41.91%±9.26%, respectively. Among trial participants, 306 patients (69.7%)
had comorbidities including diabetes (47.6%), hypertension (56.9%), thyroid
disorders (6.6%), and renal (9.3%) and neurological lesions (4.6%). The mean surgery
time was 265.02±76.61 minutes and the mean cardiopulmonary bypass (CPB) time
was 86.57±32.85. Among comorbidities, only diabetes
(P=0.008) had a significant association. Hypertension
(P=0.34), thyroid (P=0.16), neurological
(P=0.67) and renal disorders (P=0.08) had no
significant association with the incidence of postoperative arrhythmia.
In total, 104 participants (23.8%) were addicted. Mean CPB time (89.16±3.02
vs. 85.89±31.95; P=0.59) and mean
cross-clamping time (49.15±24.01 vs. 45.83±20.40;
P=0.38) among addict patients were not significantly lower than
other patients. The mean surgery time among addict patients was significantly lower
than other patients (248.85±80.02 vs. 269.60±74.94;
P=0.03). Among inotropic drugs, only mean of epinephrine
(P=0.02) and dopamine (P=0.01) in operating
room (OR) were significantly different among patients with postoperative arrhythmia
and other patients. When comparing the use of inotropic drugs among addicts and
other patients, except epinephrine in OR and ICU, other drugs did not present
significant changes (Tables 1 and 2).
Table 1
Inotropic and anticoagulant drug usage between study population with and
without postoperative arrhythmia.
Table 2
Inotropic and anticoagulant drug usage between study population.
To see if there is a difference between addict and non-addict patients, they were
divided into two groups and compared for their demographic information. No
significant differences were found between the two groups according to their
demographics (Table 3).
Table 3
Comparison of demographic variables between addict and non-addict study
population.
In this study, 65 (14.8%) patients had postoperative arrhythmia. Prevalence of
postoperative arrhythmia was similar among addict and non-addict patients (15, 14.4%
vs. 50, 15.1%; OR: 0.96 95% CI: 0.56-1.63;
P=0.87). When accounting for the type of arrhythmia, there were
also no significant differences between patients with and without history of opium
addiction. Mean age (60.01±8.39 vs. 61.29±9.06;
P=0.74) and mean body mass index (26.18±3.46
vs. 26.26±4.56; P=0.96) were similar
between patients with and without postoperative arrhythmia. Premature ventricular
contractions are the most prevalent arrhythmias in both groups, followed by atrial
fibrillation. However, there was no significant difference between the two groups in
terms of type of arrhythmia (Figure 1).
Systolic and diastolic blood pressure and heart rate at baseline, systolic blood
pressure at 6 and 48 hours after surgery and heart rate in the ICU admission were
significantly different among patients with postoperative arrhythmia and other
patients (Table 4).
Fig. 1
Frequency percentage of patients with each type of arrhythmia in
patients with and without drug addiction. There were no statistically
significant differences between the two groups in the arrhythmia type.
AF=atrial fibrillation; PVC=premature ventricular contractions
Table 4
Comparing blood pressure and heart rate among study population in
different study points between patients with and without postoperative
arrhythmia.
Logistic Regression Analysis Findings
After the inclusion of selected variables in the logistic regression model, only
serum levels of epinephrine in OR, heart rate and central venous pressure at
baseline and 48 hours after surgery remained in the regression model and were
known as independent predictors of postoperative arrhythmia among the study
population (Table 5).
Table 5
Regression analysis for determination of independent predictors of
postoperative arrhythmia among study participants.
DISCUSSION
In this study, 65 (14.8%) patients presented postoperative arrhythmia and 104
participants were addicted. Prevalence of postoperative arrhythmia was similar among
addict and non-addict patients. According to the regression analysis model, only
serum levels of epinephrine in OR, heart rate and central venous pressure level at
baseline and 48 hours after surgery were demonstrated to be independent predictors
of postoperative arrhythmia among study population.
There were several studies which reported opium addiction among different
populations[10,11]. As
an example, prevalence of smoking was 38.5% among Iranian patients undergoing
surgery[12]. In one
study, the prevalence of smoking among CABG patients was 37.5%[13]. There are different studies
with conflicting findings on the association of smoking or opium addiction with CABG
postoperative outcomes. Many similar studies reported that higher morbidity and
mortality rates were found among smokers than nonsmokers after cardiac
surgery[12,14]. Although most studies reported
that the risk of CAD increased with opium usage, in one study in 2004, CAD severity
was lower among methadone or opiate users in comparison with other patients. On the
other hand, researchers believed that long-time opium exposure can decline the
severity of CAD and fatal outcome[15].
Our study findings showed similar postoperative arrhythmia among addict and
non-addict participant patients. We discussed cautiously about findings of similar
studies due to lack of some essential information, such as history of smoking, lipid
profile, and lifestyle among addict patients. In other studies, opium usage has been
shown an independent predictor of coronary artery disorders among patients and has
even correlated with the number of diseased vessels[16]. In another study, investigators found that
opium consumption was a major risk factor for acute myocardial
infarction[17].
When comparing the operating time between two groups of addict and non-addict
patients, a significantly shorter surgery time was observed in addicts. This
difference may be due to chance or due to the patients’ tolerance to analgesics and
opioid anesthetics or other analogs. However, regression analysis revealed no
relationship between surgery time and the occurrence of arrhythmias postoperatively
in the present study.
Different studies in the literature compare outcomes of CABG surgery among opium
users and other patients. They reported that postoperative complications and
duration of hospital stay were similar between the two groups, but opium users were
more likely than other patients to be readmitted in the hospital due to cardiac
complications during the six-month follow-up[18]. Some methodological bias is found among these
clinical studies. Most of the studies had case-control or cross-sectional design.
Although a higher prevalence of opium consumption observed among patients with
coronary artery disease than in controls, a causal interpretation is not warranted
due to the gap between occurrence and exposure times.
Another significant observation was the higher consumption of inotropic agents in
patients without postoperative arrhythmia. This observation can be described as a
consequence of hemodynamic instability and lower preoperative blood pressure in
these patients. Consumption of these agents was also higher in addicts in the OR and
in the ICU. This is probably due to the higher doses of opioids required for
analgesia in these patients. Moreover, some of them probably abuse more of these
opioids in the hospital without the physician’s order. Therefore, these patients
will present lower blood pressure and will need epinephrine administration to
stabilize the hemodynamics.
However, interpretation of the findings of the present study must be very
conservative and inferences about the relationship between these variables are
limited to an association rather than to causality. Cohort or longitudinal study for
approving causal association of opium addiction and postoperative outcomes among
patients undergoing cardiac surgery is warranted.
CONCLUSION
Our study demonstrated that despite the increase in the rate of postoperative
arrhythmia among opium-addicted patients undergoing CABG surgery, this difference
was not significant, and this association is mediated by other study variables.
REFERENCES
Gaziano J. Global burden of cardiovascular disease. In: Zipes D,
Libby P, Bonow R, Braunwald E, editors. Braunwald's Heart Disease. Philadelphia:
: Elsevier Saunders;; 2005. p. 423-55.
Firoozabadi MD, Ebadi A, Ebadi M, Ebadi S, Ahvaz I. Prevalence risk
factors in three vessel disease patients candidate for coronary-artery bypass
surgery. Life Sci J. 2014;11(12s):67-70.
Tiryakioglu O, Demirtas S, Ari H, Tiryakioglu SK, Huysal K,
Selimoglu O, et al. Magnesium sulphate and amiodarone prophylaxis for prevention
of postoperative arrhythmia in coronary by-pass operations. J Cardiothorac Surg.
2009;4:8. doi:10.1186/1749-8090-4-8.
Lan YT, Lee JC, Wetzel G. Postoperative arrhythmia. Curr Opin
Cardiol. 2003;18(2):73-8.
Sadeghian S, Darvish S, Davoodi G, Salarifar M, Mahmoodian M, Fallah
N, et al. The association of opium with coronary artery disease. Eur J
Cardiovasc Prev Rehabil. 2007;14(5):715-7.
doi:10.1097/HJR.0b013e328045c4e9.
Ahmadi J, Toobaee S, Kharras M, Radmehr M. Psychiatric disorders in
opioid dependants. Int J Soc Psychiatry. 2003;49(3):185-91.
doi:10.1177/00207640030493004.
Ribeiro Pinto LF, Swann PF. Opium and oesophageal cancer: effect of
morphine and opium on the metabolism of N-nitrosodimethylamine and
N-nitrosodiethylamine in the rat. Carcinogenesis. 1997;18(2):365-9.
doi:10.1093/carcin/18.2.365.
Safaii N, Kazemi B. Effect of opium use on short-term outcome in
patients undergoing coronary artery bypass surgery. Gen Thorac Cardiovasc Surg.
2010;58(2):62-7. doi:10.1007/s11748-009-0529-7.
Kalant H. Opium revisited: a brief review of its nature,
composition, non medical use and relative risks. Addiction. 1997;92(3):267-77.
doi:10.1111/j.1360-0443.1997.tb03197.x.
van den Brink OW, Delbridge LM, Rosenfeldt FL, Penny D, Esmore DS,
Quick D, et al. Endogenous cardiac opioids: enkephalins in adaptation and
protection of the heart. Heart Lung Circ. 2003;12(3):178-87.
doi:10.1046/j.1444-2892.2003.00240.x.
Kasliwal R, Kulshreshtha A, Agrawal S, Bansal M, Trehan N.
Prevalence of cardiovascular risk factors in Indian patients undergoing coronary
artery bypass surgery. J Assoc Physicians India. 2006;54:371-5.
doi:10.1097/00149831-200605001-00058.
Ashraf M, Mortasawi A, Grayson A, Oo A. Effect of smoking status on
mortality and morbidity following coronary artery bypass surgery. Thorac
Cardiovasc Surg. 2004;52(5):268-73. doi:10.1055/s-2004-821103.
Ahmadi J, Benrazavi L. Substance use among Iranian surgical
patients. Int J Drug Policy. 2002;13(6):509-10.
doi:10.1016/S0955-3959(02)00064-6.
Ahmadi J, Benrazavi L. Substance use among Iranian cardiovascular
patients. Eur J Med Res. 2002;7(2):89-92.
Al-Sarraf N, Thalib L, Hughes A, Tolan M, Young V, McGovern E.
Effect of smoking on short-term outcome of patients undergoing coronary artery
bypass surgery. Ann Thorac Surg. 2008;86(2):517-23.
doi:10.1016/j.athoracsur.2008.03.070.
Marmor M, Penn A, Widmer K, Levin RI, Maslansky R. Coronary artery
disease and opioid use. Am J Cardiol. 2004;93(10):1295-7.
doi:10.1016/j.amjcard.2004.01.072.
Sadeghian S, Graili P, Salarifar M, Karimi AA, Darvish S, Abbasi SH.
Opium consumption in men and diabetes mellitus in women are the most important
risk factors of premature coronary artery disease in Iran. Int J Cardiol.
2010;141(1):116-8. doi:10.1016/j.ijcard.2008.11.063.
Safaei N. Outcomes of coronary artery bypass grafting in patients
with a history of opiate use. Pak J Biol Sci. 2008;11(22):2594-8.
doi:10.3923/pjbs.2008.2594.2598.
Notes
Notes
This study was carried out at the Iran University of Medical Sciences, Tehran,
Iran.
No financial support.
Conflict of interest declaration
No conflict of interest.
Author notes
Correspondence Address: Mohsen Ziyaeifard,
https://orcid.org/0000-0002-5631-4813, Rajaie Cardiovascular, Medical and
Research Center, Iran University of Medical Sciences, Tehran, Iran - Zip code:
14467. E-mail: borhanresearch@gmail.com
