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Intensive Care Med (2001) 27: 1466±1473 DOI 10.1007/s001340101043 Peter Reinelt Georg Delle Karth Alexander Geppert Gottfried Heinz Received: 30 August 2000 Final revision received: 18 June 2001 Accepted: 22 June 2001 Published online: 8 August 2001 Springer-Verlag 2001 P. Reinelt ´ G. D. Karth ´ A. Geppert ´ G. Heinz ( ) Department of Cardiology, University of Vienna, Allgemeines Krankenhaus, Währinger Gürtel 18-20, 1090 Vienna, Austria E-mail: [email protected] ) O R I GI N A L Incidence and type of cardiac arrhythmias in critically ill patients: a single center experience in a medical-cardiological ICU Abstract Objective: To determine the frequency and types of significant, sustained arrhythmias in a mixed ICU. Design and setting: Prospective, observational study in a medical-cardiological-postoperative ICU at a university hospital. Patients: 133 consecutive patients with arrhythmias. Measurements and results: All patients had continuous ECG monitoring and automatic arrhythmia detection. We assessed: (a) sustained (> 30 s) tachyarrhythmias; (b) all tachyarrhythmias requiring therapy; (c) bradycardias of fewer than 40 beats/min or requiring intervention. There were 310 arrhythmia episodes: 278 tachyarrhythmias (108 narrow-QRS complex, 168 wideQRS complex; 179 regular, 97 irregular) and 32 bradycardias. Of the 278 tachycardias in 54 patients, 135 (48.6 %) were ventricular. There were 13 episodes of torsade de pointes (4.67 %) in five patients. Of the 278 tachycardiac episodes 83 were atrial fibrillation (29.8 %, Introduction Critically ill patients frequently develop cardiac arrhythmias, and electrocardiography is the sine qua non in the monitoring of such patients [1]. Despite clinical knowledge and this widely held belief, data in support of this view are available only in selected cohorts of patients. Arrhythmias are well defined in patients after 63 patients), 10 atrial flutter (3.6 %, 8 patients), 21 supraventricular tachycardias (7.55 %, 7 patients), and 2 ectopic junctional tachycardia (0.72 %, 1 patient). The number of patients showing significant arrhythmias was comparable over the years (11±12/1996: 4/28 [14.3], 1997: 52/302 [17.2 %], 1998: 55/286 [19.2 %], 22/140 [15.7 %] 1±7/1999). The ICU stay was significantly longer in arrhythmia patients than in 623 patients without arrhythmias (median 4 vs. 14 days), and there was a trend towards higher mortality (40/133, 30.8 %, vs. 132/623, 21.2 %, P = 0.061, log-rank). Conclusion: Only one-fifth of patients in this mixed ICU had significant arrhythmias, taking a contemporary definition of arrhythmias. Ventricular tachycardia and atrial fibrillation were the most frequent arrhythmias. Keywords Arrhythmias ´ Intensive care unit ´ Incidence ´ Atrial fibrillation ´ Ventricular tachycardia myocardial infarction, in patients with underlying heart disease [2, 3, 4, 5] or pulmonary disease [6, 7], and in patients after cardiac transplantation [8, 9]. There are numerous studies on the therapy of arrhythmias in the ICU, particularly on the therapy of postoperative atrial fibrillation (AFIB) [10, 11, 12, 13, 14, 15, 16]. There are also data on the incidence of atrial and ventricular arrhythmias after cardiac surgery [17, 18, 19, 20], of cardi- 1467 ac ªarrhythmiasº during postural drainage and chest percussion [21], and of arrhythmias during pulmonary artery catheter removals [22]. The incidence of sinus node dysfunction has been extensively studied in orthotopic cardiac transplant recipients [8, 23]. As to the incidence of arrhythmias in a mixed ICU there is a single, extensive epidemiological survey available [25]. The weakness of this and other previous studies are their wide inclusion criteria. For example, ventricular extrasystoles, couplets, or triplets are currently not regarded as significant arrhythmias. Likewise, nonsustained and sustained ventricular tachycardia (VT) are approached differently. Contemporary criteria for arrhythmias were not applied in some studies [21, 22], and one study has been criticized since the tachycardia mechanism was not established [24]. Prospective data on the epidemiology of cardiac arrhythmias in a general ICU are lacking. We felt that arrhythmias are not very frequent even in our cardiologically oriented medical ICU when more contemporary criteria of significant arrhythmias are applied. To test this hypothesis the present study prospectively obtained data on arrhythmia incidence and type of arrhythmias in a medical-cardiological ICU that also admits patients after cardiac and thoracic surgery. Methods and materials Between 18 November 1996 and 17 July 1999 all consecutive arrhythmia episodes in a medical-cardiological ICU were prospectively assessed. Included were all episodes of all patients with new-onset, sustained arrhythmias that were either self-terminated or required intervention. An arrhythmia was considered as sustained if it lasted at least 30 s; it was considered as clinically significant if it was sustained, and/or if intervention/termination was required. The following arrhythmias were included: (a) sustained (³30 s) monomorphic or polymorphic wide-QRS tachycardias that were self-terminated; (b) sustained (³30 s) monomorphic or polymorphic wide-QRS tachycardias that required medical or electrical termination, including any (even if lasting < 30 s) wideQRS tachyarrhythmias that required therapy due to degeneration and hemodynamic instability; (c) sustained narrow-QRS tachycardias such as new-onset atrial flutter or fibrillation, atrial tachycardias, and other narrow-QRS tachycardias usually classified as ªsupraventricularº (AV nodal reentry and AV reentry); and (d) newonset bradycardias that required intervention. These included sinus bradycardias of less than 40 beats/min, junctional bradycardias, second- and third-degree AV blocks and iatrogenically induced bradycardias during procedures or tracheal suctioning. Arrhythmias thought to be related to typical procedures performed in the ICU such as tracheal suctioning were explicitly assessed. The design of the study and the ICU setting did not allow definite differentiation of AV nodal reentry and AV reentry tachycardias, which is possible only in an electrophysiology laboratory. Also, differentiation between VT and supraventricular tachycardia could not always be made by our means. This is confined also to the electrophysiological laboratory. Extrasystoles, couplets, and triplets were excluded. Likewise, short runs of wide-QRS tachycardia lasting less than 30 s were not included if intervention was not required within that time. Also, chronic tachycardic AFIB present before admission to our ICU and sinus tachycardia were excluded. All patients had continuous electrocardiographic monitoring, and all arrhythmias were recorded automatically, including electrocardiography, date and time (Arrhythmia Display/Controller ADC, Hewlett and Packard, Andover, Mass., USA). Thus, systematic arrhythmia detection was ensured according to preset detection parameters. If possible, 12-lead electrocardiography was performed to differentiate possible tachycardiac mechanisms. This, however, was not a prerequisite for inclusion of a tachycardia. Differential diagnosis of wide-QRS tachycardias was carried out according to accepted algorithms [26, 27]. Ventricular fibrillation was classified as an episode of tachycardia but not with respect to QRS width and regularity. If appropriate, increasing doses of adenosine (6, 12, and 18 mg intravenously) were administered for differential diagnosis of tachyarrhythmias. This was performed on clinical grounds at the discretion of the treating physician. If available and deemed necessary, epicardial recordings were obtained via temporary electrodes and were used for differential diagnoses of arrhythmias in postoperative patients. A standardized questionnaire was used by two of the authors to characterize and classify arrhythmias; differences were resolved by consensus. Wide-QRS tachycardias that could not be classified with certainty as VT or aberration, and upon which no consensus could be achieved were classified as ªnot determinable.º Recurrent arrhythmias that were self-limited or self-terminated were recorded as distinct, previous arrhythmia episodes. The following arrhythmia characteristics were assessed: bradycardia/tachycardia, wide-/narrow-QRS complex tachycardia, rate of arrhythmia, regularity versus irregularity of arrhythmia, presence of a short-long initiation sequence, duration and outcome of arrhythmia, the use of adenosine for differential diagnosis, medication used for treatment and dosage, use of synchronized or nonsynchronized direct current cardioversion, use of overdrive termination, overpacing protocols to suppress recurrence of arrhythmia, and use of the Zoll pacemaker. The study followed an episode-based design. First, the number of patients showing ªsignificantº arrhythmias each year was related to the total number of patients treated in this ICU annually. Second, the distribution of the various arrhythmias among patients showing significant arrhythmias is given. This was an uncontrolled study. Only ICU stay and survival were evaluated for the complementary ICU population (n = 623) treated during the time of the study. Diagnoses in our overall ICU population are presented in Table 1; these data were not part of the study protocol and were not evaluated by the authors and are shown here merely for background characterization. Figure 1 presents the number of patients treated and screened during the study period (n = 756), and the number of patients with and without arrhythmias, and the number of patients who died in each group. Data are given as means standard deviation if normally distributed. Skewed data are presented as median and range and were compared by the Mann-Whitney U test. Survival estimates were calculated by the Kaplan-Meier method, and mortality was compared by the log rank test, which is more sensitive in assessing early survival differences. Categorical data are given as number and percentage and compared using the c2 statistic. A P value less than 0.05 was considered significant in all analyses. 1468 Table 1 Diagnoses in the overall ICU population; diagnoses are inclusive (not main diagnoses) Diagnosis 1997 1998 1999 Admissions per year Coronary artery disease Cardiogenic shock Cardiopulmonary resuscitation Heart failure Septic shock Acute respiratory failure Acute renal failure Cardiac surgery 302 84 47 56 77 39 73 74 105 286 115 52 70 89 31 58 48 86 268 68 48 52 80 32 61 58 70 Results Study group characteristics A total of 310 arrhythmia episodes were assessed during the study period, in 133 patients (94 men, 39 women; age 64.9 12 years; Acute Physiology and Chronic Health Evaluation II score 16.9 8). There were a mean of 2.91 episodes/patient (range 1±14). Admission diagnoses were cardiac (n = 48), cardiac surgery (n = 45), resuscitation (n = 12), pulmonary (n = 15), sepsis (n = 5), neurological (n = 2), and others (n = 6). Among the 48 primary cardiac diagnoses there were acute coronary syndrome prior to (n = 1) and after angioplasty (n = 1), coronary artery disease after angioplasty (n = 2; one on extracorporeal membrane oxygenation), congestive heart failure and myocarditis (n = 11), cardiogenic shock (n = 7), cardiogenic shock due to acute myocardial infarction (n = 5), myocardial infarction complicated by septal rupture (n = 2), subacute myocardial infarction requiring mechanical ventilation (n = 17), and valvular heart disease (n = 2). One patient had an internal cardioverter-defibrillator. Group means for serum potassium and magnesium were within the normal range (4.1 0.5 and 0.96 0.2 mmol/l, respectively). However, hypokalemia of 3.5 mmol/dl or higher was noted on 32, and hypomagnesemia of 0.8 mmol/l or higher on 36 instances. Patients were sedated during 187 of the 310 episodes and mechanically ventilated during 238 (78/133 and 95/ 133 patients, respectively). Of the 133 patients 102 were on catecholamines during 233 of the 310 episodes. The dose per minute at the time of arrhythmia was 0.25 0.2 mg/kg norepinephrine (131 occasions), 0.26 0.24 mg/kg epinephrine (128 occurrences), and 4.94 2.4 mg/kg dobutamine (55 occurrences). In 32 patients (72/310 arrhythmia episodes) there had been a previous myocardial infarction, and in 46 patients (126/ 310 instances) there was a recent myocardial infarction as possible arrhythmogenic substrate. There were 162 episodes that occurred in 67 postoperative patients. Fig. 1 Flow chart of patients screened, number of patients with arrhythmias, and mortality in each group Five arrhythmias occurred coincidentally with implantation or withdrawal of central venous catheters or pacemaker leads. A pulmonary artery catheter was in place during 111 of the 310 episodes in 52 of the 133 patients. ICU stay and mortality in the study group and in patients without arrhythmias The length of stay in the ICU was significantly longer in patients with arrhythmias (median 14 days, range 1±220) than in those without (4 days; range 1±246; P < 0.001). ICU survival was lower in patients with arrhythmias (93/133, 69.9 %) than in those without (491/ 623, 78.8 %). Figure 2 presents the Kaplan-Meier estimates for the groups with and without arrhythmias (P = 0.061 log-rank test). Annual number of patients with significant arrhythmias The proportion of patients showing significant arrhythmias in terms of the study criteria was fairly constant over the study period: 52 of 302 patients (17.2 %) in 1997, 55 of 286 (19.2 %) in 1998, and 22 of 140 (15.7 %) until 17 July 1999. In November and December 1996 there were 4 of 28 patients (14.3 %) with arrhythmias; the total number of patients treated in our ICU in 1996 was 252. Types of arrhythmias among patients with arrhythmias (episode based) Raw classification of arrhythmias There were 278 tachycardic and 32 bradycardic events. Among the tachyarrhythmias there were 108 narrowQRS complex tachycardias and 168 wide-QRS complex tachycardias (two episodes of primary ventricular fibril- 1469 Fig. 2 Kaplan-Meier survival estimates for patients with (n = 133) and without (n = 623) arrhyhtmias. Plotted is ICU survival. Note the lower ICU survival in patients with arrhythmias. The difference did not reach statistical significance on log-rank test (P = 0.061) lation were classified as tachyarrhythmia but not with regard to QRS width and regularity). Of the 278 tachycardias 179 were regular and 97 irregular. Arrhythmia diagnoses Figure 3 presents the number and proportion of patients and of episodes in each diagnostic category for tachyarrhythmias, and Fig. 4 for bradyarrhythmias. A majority of wide-QRS complex tachyarrhythmia episodes were monomorphic (Fig. 3) and classified as VT according to widely accepted criteria. On 12 occasions the mechanism and origin of a wide-QRS complex tachycardia (VT versus supraventricular with aberration) could not be delineated by 12-lead electrocardiography. Polymorphic tachycardia and torsade de pointes VT made up for only a small percentage of tachycardias. Torsade de point occurred in one woman with Crohn's disease but was otherwise due to proarrhythmia. Taken together, monomorphic and polymorphic VT occurred in 56 of 133 patients (42.1 %), representing 148 of 278 episodes (53.2 %). Primary ventricular fibrillation and ventricular fibrillation degenerating from VT was an infrequent arrhythmia. More patients were seen in AFIB than in VT. However, AFIB comprised a lower percentage of episodes than VT (Fig. 3). Type I atrial flutter and regular nar- row-QRS tachycardia were less frequent. Naturally, narrow-QRS tachycardias could not be further delineated by our means in the ICU setting and were classified as supraventricular tachycardia. An ectopic junctional tachycardia was seen in one woman postoperatively. The mechanism of that tachycardia was confirmed by epicardial recordings and epimyocardial stimulation via the temporary postoperative pacing wires. Electrocardiography was sufficient to make a specific diagnosis in the majority of cases. Adenosine was used to differentiate the mechanism and origin of a tachycardia in ten narrow-QRS and three wide-QRS complex tachycardias. Outcome of patients according to the arrhythmic event (episode based) Among the 40 patients who later died there were 102 arrhythmia episodes. These were asystole (3/9 episodes), AV block (5/12 episodes), atrial flutter (5/10 episodes), AFIB (22/85 episodes), supraventricular tachycardia (11/21 episodes), monomorphic VT (49/135 episodes), and torsade polymorphic VT (2/13 episodes). Only two patients experienced a terminal arrhythmia episode (asystole). Certain arrhythmias occurred solely in ICU survivors: sinus bradycardia (two episodes), junctional bradycardia (two), escape rhythm (one), other brady- 1470 Fig. 3 Number of patients and arrhythmia episodes in various tachyarrhythmia categories. VT Ventricular tachycardia; VF ventricular fibrillation; AFIB atrial fibrillation; SVT supraventricular tachycardia; EJT ectopic junctional tachycardia; height of bar percentage. Values are expressed as percentage of all 133 patients included (full bars) and as percent of all 278 tachyarrhythmia episodes (open bars) cardia (four), ectopic junctional tachycardia (two), and ventricular fibrillation (two). The distribution of arrhythmias between survivors and nonsurvivors did not differ significantly (c2 = 16.5, p = 0.22). Treatment Tachyarrhythmias (n = 278) were treated by electrical means only in 19 instances. Arrhythmia control or termination was achieved by medication only in 139 cases and terminated medically and electrically in 77 episodes. The tachycardia was self-limited in 43 cases. Bradycardias received solely electrical therapy (3/32), were managed electrically and medically (3 cases), or treated solely medically (11 episodes). Fifteen bradycardias were short lived and required no treatment or solely the elimination of the precipitating factor. Electrical therapy There were 83/88 successful cardioversions/defibrillations. On ten instances a temporary pacemaker lead was placed, and four additional situations required electrical therapy via temporary postoperative pacing wires. In nine of ten cases a tachycardia was terminated using overdrive stimulation via postoperative temporary pacing wires. There was one occurrence of tachycardia acceleration during this procedure. Overpacing success- Fig. 4 Number of patients and arrhythmia episodes in various bradycardiac categories. Brady Bradycardia; Rhy rhythm; AFIB atrial fibrillation; height of bar percentage. Values are expressed as percentage of all 133 patients included (full bars) and as percent of all 32 bradyarrhythmia episodes (open bars) fully suppressed recurrences of torsade de pointes on two instances. A temporary transvenous pacing lead was placed in 6 of 32 cases. The Zoll external pacemaker was used successfully three times. Drug therapy Medical therapy required one or several drugs. Figure 5 presents the groups of drugs used to treat arrhythmias in the ICU and the number of administrations in each drug category. Also, the frequency of drug use is given for AFIB and VT. The single most frequently prescribed drug was amiodarone. Flecainide was used only once as ultima ratio therapy in a young woman with incessant polymorphic, tachycardic rhythm during the course of severe cardiomyopathy. Proarrhythmia Proarrhythmia was assumed 11 times. Among the drugs deemed responsible for proarrhythmia were haloperidol (four times), amiodarone (four times), cisapride (twice), and ibutilide (once). 1471 Fig. 5 Frequency of drugs used to treat arrhythmias. Number above bar Number of drug administrations. Data are given for the entire group and for subgroups of ventricular tachycardia and atrial fibrillation, the two most frequent arrhythmias Discussion The present study examined the epidemiology of arrhythmias in the ICU. Data on arrhythmias were obtained prospectively by a structured, standardized questionnaire in an medical ICU focusing on cardiological and medical patients and admitting also cardiothoracic surgery patients. We were unable to allocate previous comprehensive and prospective data on the issue of arrhythmias in the ICU setting. During the past 20 years only one study (including a quite considerable number of patients) on this subject has been published [25]. The present study demonstrates that, if a more contemporary approach to the classification of clinically significant arrhythmias is used, the annual incidence of patients developing arrhythmias in the ICU is lower than previously portrayed and expected. The yearly incidence of 14.3 %, 17.2 %, 19.2 %, and 15.7 % of patients presenting with arrhythmias in our series is remarkably low. In the study of Artucio et al. [25] the incidence of arrhythmias in various diagnostic groups ranged from less than 50 % in trauma patients to 90 % in cardiovascular critically ill patients. There are several possible reasons for this difference between our findings and those of Artucio et al. First, they included extrasystoles in their survey [25], which does not represent the contemporary perception of arrhythmias. The two Cardiac Arrhythmia Suppression Trial (CAST) [28, 29] studies challenged the concept that a treatment of ventricular extrasystoles would translate into improved survival. Both studies were terminated prematurely due to excess mortality in the flecainide and encainide treatment arms. It is clear from these studies that the risk of (class I) antiarrhythmic therapy exceeds that of an underlying insignificant arrhythmia. In the study by Artucio et al. [25] ventricular extrasystoles accounted for 56 % of all recorded arrhythmias; 82 % of patients were included on the basis of a first-degree AV block, and 39 % showed complete right bundle branch block. In the present study extrasystoles, couplets, triplets, and bigeminy of ventricular or supraventricular origin were not assessed. Likewise, tachycardic chronic AFIB was not included. Second, the spectrum of disease entities and severity of illness is not comparable. For example, our ICU does not treat trauma patients, and intoxicated patients contribute only a minority of cases. On the other hand, the emphasis of the ICU under study is on cardiological and cardiothoracic patients, and these patients have the highest incidence of arrhythmias [25]. These differences in the inclusion criteria and ICU design may explain some differences in the incidence obtained. Whether there are other factors responsible for the differences remains unclear. The yearly incidence of arrhythmias in our study was rather constant. This renders ªsampling biasº of arrhythmia episodes unlikely. The relatively high incidence of VTs is surprising. VT in the Artucio et al. [25] series was noted in 424 of 1426 of tachyarrhythmia patients (29.7 %). After cardiac surgery, ventricular arrhythmias are a rare event ranging from 0.68 to 0.71 % [19, 20]. This higher incidence in our series may be due to the high number of cardiological patients in our ICU and to the high number of those with overt coronary artery disease. One third of patients had an arrhythmogenic substrate for malignant arrhyth- 1472 mias in terms of a myocardial infarction scar. One fourth of the patients had a recent myocardial infarction. The total number of patients with coronary artery disease in this study remains obscure but is certainly even higher. In terms of patients, AFIB was more frequent than VT (63 vs. 56 patients) while AFIB accounted for only 30 % of episodes (compared to roughly 53 % of episodes classified as VT). Thus VT and AFIB are the single most frequent arrhythmias in our ICU. This compares to 419 of 2820 patients (14.8 %) having AFIB in the series of Artucio et al. [25]. Considering only 1426 tachyarrhythmia patients in the study of Artucio et al., the incidence is 29.4 % for AFIB [25]. Thus our incidence of AFIB is consistent with the incidence of AFIB in that study. The frequent occurrence of AFIB in our cohort and in the ICU in general is not unexpected. After cardiac surgery the incidence of atrial arrhythmias ranged from 31.9 % after coronary artery bypass grafting to 48.8 % after aortic valve surgery and 63.6 % after mitral valve surgery [17]. The incidence of AFIB after cardiac surgery was found to vary with age from 3.7 % in patients aged under 40 years to 27.7 % in patients aged 70 years or over [18]. The percentage of patients with torsade de pointes is also high compared to the infrequent occurrence of this type of arrhythmia in the general population. In our series this was due mainly to the use of cisapride and haloperidol in the ICU. These substances are both known for their ability to induce proarrhythmia of the torsade type and are widely used in ICU patients. Additional episodes of torsades occurred in a patient with Crohn's disease. The drugs used in this study reflect the findings of the CAST studies [28, 29] and the therapeutic strategies in the treatment of arrhythmias in the post-CAST era. Amiodarone was the single most frequently used drug for control of tachyarrhythmias. An important reason for the selection and the popularity of this drug is the critically ill cohort with reduced inotropic and hemodynamic reserve. Amiodarone has less negative inotropic and proarrhythmic effects than other antiarrhythmic drugs. Flecainide was used only once as ultima ratio therapy. The use of diltiazem reflects the relatively frequent occurrence of AFIB. Both amiodarone and diltiazem are used to treat new-onset, tachycardic AFIB in critically ill patients. Electrical cardioversion of AFIB is frequently ineffective in this setting of critically ill patients requiring catecholamine therapy [30]. Since this study was episode based, it was uncontrolled. Only survival and ICU stay were compared to that of patients without arrhythmias treated during the time of the study. ICU stay was longer and survival lower in the arrhythmia group, but only two patients experienced a terminal arrhythmia episode. This suggests that the finding of longer ICU stay and lower survival in ªarrhythmia patientsº is rather an indicator of more severe critical illness. Our data are in accordance with previous findings. A higher fatality rate has been reported in septic patients with atrial tachycardias or nodal rhythms and in neurological patients with ventricular tachyarrhythmias [25]. Cardiovascular patients and patients with a respiratory critical illness had a higher mortality when experiencing arrhythmias [25]. In conclusion, the present series provides prospective data on the incidence and type of arrhythmias in a mixed ICU. Using a more contemporary view of arrhythmias, only about 20 % of ICU patients were found to have clinically significant arrhythmias. VT and AFIB were the most frequent types of arrhythmias. 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