Clinical characteristics and mortality of patients in the intensive care unit with and without new-onset arrhythmias

Objective. The aims of this study were to analyze the risk factors for and types of new-onset arrhythmias in ICU (Intensive care unit), and to evaluate their impact on patient outcomes. Methods. We studied 1051 patients who were admitted to the two general ICUs between December 2013 and February 2016. These patients were divided into two groups: patients with new-onset arrhythmias and patients without new-onset arrhythmias. We compared the risk factors, types and prognoses of new-onset arrhythmias between these two groups. Results. New-onset arrhythmias were observed in 20.84% (n=219) of 1051 patients. The main risk factors leading to arrhythmias included age, emergency operation, past cardiovascular disease, patients with multiple systemic diseases, acute respiratory distress syndrome, severe sepsis/septic shock, acute renal dysfunction, cardiovascular disease, electrolyte disturbance, patients on ventilators, patients on vasopressors and higher Acute Physiology and Chronic Health Evaluation II scores (APACHE II score) on ICU admission. Multivariate logistic regression revealed that age, emergency operation, severe sepsis/septic shock, cardiovascular disease, electrolyte disturbance, patients on ventilators and those with higher APACHE II scores on ICU admission, were all significantly associated with new-onset arrhythmias. Arial fibrillation was the most frequent arrhythmia. ICU mortality in patients with newonset arrhythmias was 22.37% (49 out of 219) compared with 3.61% (30 out of 832) in patients without new-onset arrhythmias (p<0.001). Among surviving patients, ICU stay for those with new-onset arrhythmias was longer than those without new-onset arrhythmias (median stay of 10 days versus 5 days, p<0.001). Conclusion. We found a high prevalence of new-onset arrhythmias in ICU patients. Arrhythmia, especially atrial fibrillation, was a common complication in ICU patients and was associated with increasing length of ICU stay and higher mortality.


INTRODUCTION
Arrhythmias are associated with an unfavorable prognosis, increasing the risk of death.Although arrhythmias are traditionally associated with cardiovascular diseases, there is evidence of a high incidence of arrhythmias in patients with noncardiovascular diseases, such as sepsis, chronic obstructive pulmonary disease, acute renal dysfunction.Arrhythmias are frequently observed in critically ill patients, and studies about arrhythmias in intensive care units (ICU) have been reported.(1)(2)(3) All types of arrhythmias can be observed, but atrial arrhythmias are the most common.(4) In recent years, increasing attention has been paid to atrial fibrillation in septic patients.(5-8) However, there are few studies on the various kinds of patients admitted to a general ICU.Epidemiological insights may help to identify strategies for arrhythmia prevention, monitoring, or risk modification.To better define the burden of arrhythmias in ICU, we analyzed the risk factors, types and prognosis of new-onset arrhythmias in the general ICU population.

MATERIALS AND METHODS
This study was carried out in two general ICUs: the Department of Intensive Care Medicine of the First Affiliated Hospital of Dalian Medical University and The Third People's Hospital of Dalian.Patients were recruited between December 2013 and February 2016.Those who were in the final stage of their chronic disease, who were awaiting cardiac surgery, or were discharged from ICU within 24 hours were excluded from further analysis.This study was approved by the Ethics Committees of Dalian Medical University and The Third People's Hospital of Dalian.All procedures were performed in accordance with the Declaration of Helsinki.Informed consent was obtained from either the patient (if competent) or his/her family.

Data collection
During ICU stay, all patients underwent continuous electrocardiographic monitoring and automatic detection of arrhythmias.All episodes of arrhythmia were recorded.The following outcomes were assessed: (a) sustained tachyarrhythmia lasting more than 30 seconds; (b) tachyarrhythmia requiring therapy; (c) bradycardia of less than 40 beats/ min or requiring intervention; (9) (d) in the case of chronic arrhythmias, only new arrhythmias were considered.We recorded the date of ar- rhythmias and the types of arrhythmias.At least three attending doctors retrospectively analyzed new-onset arrhythmias and then determined the most likely causes and inducing factors.

Statistical analysis
Data were analyzed using SPSS version 17.0 statistical software.Baseline data such as age, Acute Physiology and Chronic Health Evaluation II score (APACHE II score) and ICU length of stay was expressed as mean ± standard deviation (SD) and analyzed using student's t test.Qualitative data were presented as frequencies and analyzed using the Pearson chi-square test.Multivariate logistic regression analysis was performed to determine the most significant risk factors.Survival rates were analyzed using the Kaplan-Meier method and were compared using the logrank test.A value of p< 0.05 was considered statistically significant in all analyses.

Risk factors for arrhythmias
Among 1051 patients, during this 26-month study, 20.84% (n=219) experienced new-onset arrhythmias, while 79.16% (n=832) were those without newonset arrhythmias.Univariate analysis was performed on factors impacting new-onset arrhythmias, based on medical records, as shown in Table 1.In the new-onset group there were 142 males (64.84%) and 77 females (35.16%), with an average age of 70.42±14.99years, while in the group without new-onset arrhythmias, there were 538 males (64.66%) and 294 females (35.33%), with an average age of 64.38±14.77years.These data suggest that there was a significant difference in age (p<0.001),but not in gender (p=0.961), between the groups with or without new-onset arrhythmias.Surgical patients, either for emergency operations or elective operations, accounted for 37.68% (n=396) of cases,.As shown in Table 1, there was a statistically significant difference between the two groups when it came to emergency operations (p<0.001).It was obvious that the patients with a history of cardiovascular disease had an increased incidence of new-onset arrhythmias compared to those without a history of cardiovascular disease (p<0.001).Patients with multiple system diseases were more prone to arrhythmias; however, patients with a history of pulmonary disease, endocrine disease and kidney disease did not show any difference between the groups (p>0.05).There were more patients with acute respiratory distress syndrome (ARDS), severe sepsis/ septic shock, acute renal dysfunction and cardiovascular disease in the group of new-onset arrhythmias than that without new-onset arrhythmias.In addition, a higher percentage of patients in the group of new-onset arrhythmias received mechanical ventilation for more than 24 hours and used vasopressors than those without new-onset arrhythmias (p<0.001).A higher percentage of electrolyte disturbance was also observed in the group of new-onset arrhythmias (p= 0.005).During the ICU stay, as shown in Table 1, the patients in the group of newonset arrhythmias had higher APACHE II scores than those without new-onset arrhythmias, 19.86±6.13versus 16.03±5.83(p<0.001).Multivariate logistic regression revealed that age, emergency operation, severe sepsis/septic shock, cardiovascular disease, electrolyte disturbance, patients on ventilators and higher APACHE II scores on ICU admission, were all significantly associated with new-onset arrhythmias (Table 2).

Arrhythmia types in ICU
As shown in Table 3, atrial arrhythmias, ventricular arrhythmias and conduction abnormalities were recorded.There were 266 arrhythmia episodes in 219 patients with new-onset arrhythmias, which included 150 episodes of atrial arrhythmias in 120 patients, 68 episodes of ventricular arrhythmias in 54 patients and 48 episodes of conduction abnormalities in 37 patients.The average episode time for patients with new-onset arrhythmias was 20.33±18.51hours after ICU admission.New-onset arrhythmia is more likely to occur within the first 48 hours of ICU admission.

Patient prognosis
As shown in Table 4, ICU mortality rate in patients with new-onset arrhythmias was 22.37% (49 out of 219), which was statistically significantly higher than in those without new-onset arrhythmias, 3.61% (37 out of832) (p <0.001).The difference in 28-day mortality rate was also statistically significant between these two groups (p <0.001).Kaplan-Meier survival curves are shown in Figure 1, according to the 28-day mortality rate for patients with or without new-onset arrhythmias.Among the surviving patients, the ones with newonset arrhythmias had a longer ICU stay, a median of 10 days compared to 5 days in those without new-onset arrhythmias (11.70±10.11versus7.94±7.75,p <0.001).The median, minimum, maximum and interquartile range (box) are shown in Figure 2.

DISCUSSION
In our study we reported a high prevalence of new-onset arrhythmias (20.84%) in ICU patients, similar to findings in other studies.(10) Arrhythmias in critically ill patients are a specific risk factor for prognosis and an indication of severity of illness.Most of the studies on arrhythmias have revealed that arrhythmias increase the length of stay in hospital and are markers of poor prognosis.(8,11) As expected, in our study the occurrence of new-onset arrhythmias during critical illness was associated with a poor prognosis; patients with new-onset arrhythmias exhibited a trend towards longer ICU stay and higher mortality rates (Figures 1,2).APACHE II scores have been widely adopted to evaluate the severity of illness.In our study, a higher APACHE II score in patients with new-onset arrhythmias suggested there was an association between severity of illness and the occurrence of arrhythmias.A higher percentage of mechanical ventilation for more than 24 hours and vasopressors usage at ICU admission were also found in the new-onset arrhythmia group.It is clear that during critical illness patients with cardiac disease tend to be at risk for arrhythmias and sudden death.In our study, patients with multiple system diseases were more likely to experience arrhythmias.Although most of our patients (87.06%) were admitted for non-cardiac disease, 10.28% of all patients and 16.35% of patients in the arrhythmia group had a cardiovascular history.It was evident that the occurrence of arrhythmias was increased in patients with an underlying disease, especially with heart disease.Thus, these patients deserve more attention.(12) Elderly patients have a higher incidence of arrhythmia; the etiology is multifactorial.Fibrosis and loss of muscle mass in the heart play a major role in the development of arrhythmia.Fuchs et al. analyzed ICU patients above the age of 65 and above the age of 85 and found that there was a very high incidence of cardiac arrhythmias in the group above the age of 85 (24.6 vs. 43.5%).( 13) Therefore, age was associated with long-term mortality, as discussed by others.(14) Sepsis is a systemic, deleterious host response to infection leading to severe sepsis and septic shock.Sepsis affects more than 1 million hospitalized patients yearly in United States.(15) Severe sepsis and septic shock are affecting millions of people around the world each year, killing one in four (and often more), and increasing in incidence.(16) Severe sepsis/ septic shock is also the main cause of arrhythmias in the ICU.(17) It has been reported that atrial fibrillation is often found in septic patients.(18) Patients with new-onset atrial fibrillation during severe sepsis have greater risk for in-hospital strokes and increased longterm risks of heart failure, ischemic stroke, and death.(19) Besides severe sepsis/septic shock, ARDS was another risk factor for arrhythmia, especially in patients with heart disease, because of the acidosis and hyperkalemia caused by acute hypoxia.As shown in Tables 1 and 2, there was a greater association between electrolyte disturbance and arrhythmias.Abnormal electrolyte serum blood levels, such as high serum potassium, hypomagnesium and hypophosphatemia are highly correlated

Table 1 .
Risk factors for arrhythmias on ICU admission

Table 2 .
Multivariate logistic regression analysis of risk factors for mortality *p <0.05 was defined as indicative of statistical significance ICU, intensive care unit; APACHE II score; Acute Physiology and Chronic Health Evaluation II score.ACKNOWLEDGMENTWe appreciate the technical help and support of the clinical work of Prof. Wan xian yao.

Table 3 .
Arrhythmia types in intensive care unit (ICU) patients

Table 4 .
Prognosis for patients with or without arrhythmia *p <0.05 was defined as indicative of statistical significance.ICU, intensive care unit.