T he morbidity due to tachycardia seems to be rela-tively higher in critically ill patients than in other

patients, but the relationship between tachycardia and mortality has not been well studied. In contrast, the association between arrhythmia (mostly consisting of atrial fibrillation [Af]) and postoperative [1], critically ill [2-4], and septic patients [5-15] has been investi-gated in many studies. Tachycardia is commonly seen in intensive care unit (ICU) settings, e.g., intensive surgi-

cal, neurological, and medical settings. There have been few investigations regarding whether a higher heart rate (HR) or a prolonged higher HR actually affects patient outcomes. We conducted the present study to evaluate the association between tachycardia and mortality in critically ill patients. The association between tachycardia and mortality was investigated in critically ill patients in a University Hospital ICU (Okayama University Hospital, Okayama, Japan). Our hypothesis was that higher HR and prolonged tachycar-

Acta Med. Okayama, 2019Vol. 73, No. 2, pp. 147-153CopyrightⒸ 2019 by Okayama University Medical School.

http ://escholarship.lib.okayama-u.ac.jp/amo/Original Article

Prolonged Tachycardia with Higher Heart Rate Is Associated with Higher ICU and In-hospital Mortality

Masao Hayashia＊, Arata Taniguchia, Ryuji Kakua, Shusaku Fujimotob, Satoshi Isoyamaa, Sei Manabec, Tsubasa Yoshidad, Satoshi Suzukia, Kazuyoshi Shimizua, Hiroshi Morimatsua, and Ryusuke Momotae

aDepartment of Anesthesiology and Resuscitology, Okayama University Hospital, bOkayama University Medical School, eDepartment of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,

Okayama 700-8558, Japan, cDepartment of Anesthesiology and Intensive Care Medicine, National Cancer Center Hospital, Tokyo 104-0045, Japan, dDepartment of Anesthesiology, Tottori Municipal Hospital, Tottori 680-8501, Japan

Tachycardia is common in intensive care units (ICUs). It is unknown whether tachycardia or prolonged tachy-cardia affects patient outcomes. We investigated the association between tachycardia and mortality in critically ill patients. This retrospective cohort study’s primary outcome was patient mortality in the ICU and the hospi-tal. We stratified the patients (n = 476) by heart rate (HR) as LowHR, MediumHR, and HighHR groups. We also stratified them by their durations of HR > 100 (prolonged HR; tachycardia): MildT, ModerateT, and SevereT groups. We determined the six groups’ mortality. The ICU mortality rates of the LowHR, MediumHR, and HighHR groups were 1.0%, 1.5%, and 7.9%, respectively; significantly higher in the HighHR vs. LowHR group. The in-hospital mortality rates of these groups were 1%, 4.5%, and 14.6%, respectively; significantly higher in the HighHR vs. LowHR group. The ICU mortality rates of the MildT, ModerateT, and SevereT groups were 0.9%, 5.6%, and 57.1%, respectively. The mortality of the HRT = 0 (i.e., all HR ≤ 100) patients was 0%. The in-hospital mortality rates of the MildT, ModerateT, and SevereT groups were 1.8%, 16.7%, and 85.7%, respectively; that of the HRT = 0 patients was 0.5%. Both higher HR and prolonged tachycardia were associated with poor outcomes.

Key words: tachycardia, mortality, ICU, in-hospital

Received November 30, 2018 ; accepted December 5, 2018.＊Corresponding author. Phone : +81-86-235-7778; Fax : +81-86-235-6984E-mail : mao893@aol.com (M. Hayashi)

Conflict of Interest Disclosures: No potential conflict of interest relevant to this article was reported.

dia cause worse patient outcomes.

Patients and Methods

Study design. This study was approved by the Institutional Review Board (IRB) of Okayama University Hospital. The requirement of written informed consent was waived by the IRB due to the retrospective cohort design of the study. This manuscript adheres to the applicable STROBE guidelines. The primary outcome was patient mortality in the ICU and in the hospital. After the IRB’s approval was obtained, we reviewed the records of patients in the ICU and in the hospital from September 1, 2014 to August 31, 2015, and the patients’ HR values were extracted from automatically recorded vital signs.

A total of 1,863 patients were admitted to Okayama University Hospital’s ICU during this period of time. Of these patients, we excluded the cases of the patients who were admitted to the ICU more than twice, or were discharged from the ICU within 48 h of their admission to the ICU, or were under 17 years old (Fig. 1). The remaining 476 patients were eligible and enrolled.

We first stratified the patients into three groups based only on their HR values: LowHR (100 ≤ HR < 110), MediumHR (110 ≤ HR < 120) and HighHR (HR ≥ 120). All patients’ HR values were recorded automat-ically in the ICU every 60 sec. For this stratification, when we describe a patient as having had an HR value ≥ 100, the HR was > 100 continuously for > 10 min in that patient. When HR values that were in-between each group’s thresholds were observed for > 10 min, the

enrolled group was determined. For example, when a patient’s HR values were 105, 106, 108, etc. for > 10 min, the patient was assigned to the 100 ≤ HR < 110 (LowHR) group.

We then created another three patient groups based on the duration of higher HR (tachycardia), according to our hypothesis that a prolonged higher HR is more life-threatening. The duration of higher HR was mea-sured using the patients’ HR records, and when the HR value was over 100, it would have been counted as (HR-100). The concept of prolonged tachycardia is expressed by the following formula: (HR-100) × the time duration (min) during which the HR was > 100. Since the result of this calculation is HR × time, we named this value the “HRT.” As a result, we created the formula HRT = (HR-100) × the time duration (min) during which the patient’s HR was > 100. This expresses a variable equal to the areas under the curve (AUC) over 100 beats per min.

Using this formula and the patients’ data, we strati-fied the 476 patients into the MildT (1 ≤ HRT < 50400), ModerateT (50400 ≤ HRT < 151200), and SevereT (HRT ≥ 151200) tachycardia groups. The label ‘1 ≤ HRT < 50400’ indicates that the HR value 105 was recorded in the patient for 1 week: (105-100) × 60 × 24 × 7.

The statistical analyses were performed with JMP Pro® ver. 12.2.0 (Tokyo), and differences were consid-ered significant when the p-values were < 0.05. The p-values for mortality were calculated with Fisher’s exact test. The p-values for the Kaplan-Meier curves were calculated by log lank test.

Results

The mean age of all patients was 58.4 ± 0.9 years (Table 1). Of the 476 patients, 200 (42%) were female. The severity of illness was validated with the acute physiology and chronic health evaluation II (APACHE II) score, and the average score was 16.6 ± 0.3 (Table 1). β-blockers were administered to 117 (24.6%) patients, and sinus rhythm was preserved in 391 (82.1%) patients (Table 1).

The characteristics of the patients in the LowHR, MediumHR, and HighHR groups (stratification by HR only) are summarized in Table 1. The ICU mortality rates of the LowHR, MediumHR, and HighHR groups were 1.0%, 1.5%, and 7.9%, respectively; the mortal-ity of the HR < 100 group was 0%. The ICU mortality

148 Hayashi et al. Acta Med. Okayama　Vol. 73, No. 2

1,863

1,387

Fig. 1 Exclusion criteria. Of the total of 1,863 patients, 476 patients were eligible and enrolled.

was significantly higher in the HighHR group compared to the LowHR group (Fig. 2A). The in-hospital mortal-ity rates of the LowHR, MediumHR, and HighHR groups were 1.0%, 4.5%, and 14.6%, respectively; that of the HR < 100 group was 0.5%. In-hospital mortality was significantly higher in the HighHR group compared to the LowHR group (Fig. 2A , B).

The odds ratios (ORs) of MediumHR and HighHR against LowHR were calculated. In terms of ICU mor-

tality, the ORs of MediumHR and HighHR were 1.5 (95%CI: 0.1-37.2) and 7.3 (95%CI: 1.2-138.0, p< 0.05), respectively. With respect to in-hospital mortality, the ORs of MediumHR and HighHR were 4.5 (95%CI: 0.6-91.7) and 13.7 (95%CI: 2.5-256.6, p < 0.01), respectively (Table 2).

We next analyzed the three groups stratified by the duration of HR > 100: MildT, ModerateT, and SevereT. The groups’ patient characteristics are shown in Table 3.

April 2019 Tachycardia Is Associated with Mortality 149

Table 1 Stratification of patients by HR

Total LowHR MediumHR HighHR

Variables (n＝476)HR＜100(n＝222)

100≦HR＜1110(n＝98)

110≦HR＜120(n＝67)

120≦HR(n＝89)

Age 58.4±0.9 59.8±1.2 60.9±1.9 55.4±2.3 54.6±2.0The numberof Female (%)

200(42)

92(41.4)

53(54.1)

23(34.3)†

32(36.0)†

APACHEⅡScore 16.6±0.3 15.7±0.4 16.3±0.7 16.9±0.8 18.8±0.7

Use ofβ-blockers (%)

117(24.6)

45(20.3)

23(23.5)

17(25.4)

41(46.1)＊

Sinus rhythm(%)

391(82.1)

195(87.8)

81(82.7)

55(82.1)

60(67.4)†

Int. Med. (%) 38 (8.0) 13 (5.9) 4 (4.1) 4 (10.5) 17 (14.4)GI Surg. 138 (29.0) 61 (27.5) 30 (30.6) 10 (26.3) 37 (31.4)Lung Surg. 26 (5.5) 6 (2.7) 4 (4.1) 4 (10.5) 12 (10.2)Esop h. Surg. 13 (2.7) 7 (3.2) 2 (2.0) 2 (5.3) 2 (1.7)Cardiac surg. 54 (11.3) 23 (10.4) 18 (18.4) 2 (5.3) 11 (9.3)Neuro Surg. 40 (8.4) 24 (10.8) 7 (7.1) 1 (2.6) 8 (6.8)Others 167 (35.1) 88 (39.6) 33 (33.7) 15 (39.5) 31 (26.3)（†: ＜0.05, ＊: ＜0.01）

LowHR

MediumHR

HighHR＊

timeline (days)

A B1.00

0.98

0.96

0.94

0.92

0.90

0.88

0.86

0 20 40 60 80 100 120 140

HR100_110HR110_120HR120<

Mortality in the ICUMortality in the hospital

16.00%14.00%12.00%10.00%8.00%6.00%4.00%2.00%0.00%

HR<100 100≦HR<110 110≦HR<120 120≦HRLowHR MediumHR HighHR

＊

†

Fig. 2 A, The mortality in the ICU and in the hospital. The patients were stratified by HR alone as LowHR (100 ≤HR ＜110), MediumHR (110 ≤HR ＜120), and HighHR (HR ≥120). Both the ICU and in-hospital mortality rates were significantly higher in the HighHR group compared to the LowHR group. †p＜0.05, ＊p＜0.01 by Fisherʼs exact test; B, The Kaplan-Meier curves of the LowHR, MediumHR, and HighHR groups. These results confirmed those illustrated in panel A. †p＜0.05, ＊p＜0.01 by log rank test.

The usage of β-blockers was significantly higher in the ModerateT and SevereT groups compared to the MildT group. For the MildT, ModerateT, and SevereT groups, the ICU mortality rates were 0.9%, 5.6%, and 57.1%, respectively, while that of the HRT = 0 group was 0%, since HR ≤ 100 means HRT = 0. The ICU mortality was significantly higher in the SevereT group than in the MildT group (p < 0.01) (Fig. 2A). The in-hospital mor-tality rates of the MildT, ModerateT, and SevereT groups were 1.8%, 16.7%, and 85.7%, respectively; that of the HRT = 0 group was 0.5%. In-hospital mor-tality was significantly higher in the ModerateT and SevereT groups compared to the MildT group (p < 0.05 and p < 0.01, respectively) (Fig. 3A , B).

We calculated the ORs of ModerateT and SevereT

against MildT. In terms of ICU mortality, the ORs of ModerateT and SevereT were 3.3 (95%CI: 0.2-24.0) and 75.0 (95%CI: 12.9-514.9, p < 0.01), respectively. For in-hospital mortality, the ORs of ModerateT and SevereT were 5.5 (95%CI: 1.1-21.5, p < 0.05) and 165.8 (95%CI: 24.6-3333.7, p < 0.01), respectively (Table 4).

Discussion

Our retrospective analyses revealed three major findings. First, higher HR was associated with poor patient outcomes and tachyarrhythmia. Second, pro-longed tachycardia and higher HR were also profoundly associated with poor patient outcomes. Finally, patients with HR < 100 had substantially lower mortal-

150 Hayashi et al. Acta Med. Okayama　Vol. 73, No. 2

Table 2 Odds Ratio of group MediumHR and HighHR to LowHR

Groups OR of mortality in ICU OR of mortality in hospital

OR 95%CI p value OR 95%CI p value

LowHR 1 - - 1 - -MediumHR 1.5 0.1-37.2 0.79 4.5 0.6-91.7 0.16HighHR 7.3 1.2-138.0 ＜0.05† 13.7 2.5-256.6 ＜0.01＊

（†: ＜0.05, ＊: ＜0.01）

Table 3 Stratification of patients by HRT

Total MildT ModerateT SevereT

Variables

(n＝476)

HR×duration0

(n＝222)

HR×duration1-50,400(n＝229)

HR×Duration50,400-151,200

(n＝18)

HR×Duration151,200-(n＝7)

Age 58.4±0.9 59.8±1.2 60.9±1.9 57.2±5.5 47.3±8.3The numberof Female (%)

200(42)

92(41.4)

97(42.4)

9(50.0)

2(28.6)

APACHEⅡScore 16.6±0.3 15.7±0.4 17.0±0.4 20.1±1.6 22.9±2.5

Use of β-blockers (%)

117(24.6)

45(20.3)

23(23.5)

11(61.1)＊

5(71.4)†

Sinus rhythm (%)

391(82.1)

195(87.8)

81(82.7)

11(61.1)

5(71.4)

Int. Med. (%) 38 (8.0) 13 (5.9) 4 (8.7) 4 (22.2) 1 (7.7)GI Surg. 138 (29.0) 61 (27.5) 30 (29.3) 10 (33.3) 4 (30.8)Lung Surg. 26 (5.5) 6 (2.7) 4 (6.6) 4 (22.2) 1 (7.7)Esop h. Surg. 13 (2.7) 7 (3.2) 2 (2.6) 0 (0) 0 (0)Cardiac surg. 54 (11.3) 23 (10.4) 18 (13.1) 1 (5.6) 0 (0)Neuro Surg. 40 (8.4) 24 (10.8) 7 (7.0) 0 (0) 0 (0)Others 167 (35.1) 88 (39.6) 33 (32.7) 3 (16.7) 7 (53.8)

（†: ＜0.05, ＊: ＜0.01）

ity.Regarding the first finding that higher HR alone

contributed to poor patient outcomes, our results sug-gest that both the ICU mortality and the in-hospital mortality of patients with HR ≥ 120 (the HighHR group) were significantly higher than those of the patients with 100 ≤ HR < 110 (the LowHR group) (Fig. 2A , B). With this patient stratification, the modality of arrhythmia, which is predominantly Af, was significantly higher compared to the LowHR patients with HR < 100, the LowHR group, or the MediumHR group (Table 1). This suggests that higher HR has a significant associa-tion not only with Af or other arrhythmias but also with significantly increased mortality. Although the associa-tion between arrhythmia and mortality was unclear in the present study, there were no cardiac deaths, such as those due to ventricular fibrillation.

Our second major finding was that prolonged tachy-

cardia with higher HR contributed to higher mortality of patients in the ICU and hospital. Interestingly, even though mortality was highest in the SevereT group, the number of patients with arrhythmia in this group was not significantly higher than the other groups’. This result suggests that prolonged tachycardia with higher HR contributes independently to increased mortality.

Finally, the most surprising finding was that criti-cally ill patients with HR <100 had 100% survival in the ICU, and their hospital survival rate was still > 99%. Overall, 12.2% of the 222 patients with HR < 100 had arrhythmias, which suggests that even if a patient has an arrhythmia, maintaining his or her HR at < 100 may be beneficial.

To the best of our knowledge, the association between tachycardia and mortality has been investi-gated very rarely [16], but the relationship between Af and mortality has been investigated several times [4-12 ,

April 2019 Tachycardia Is Associated with Mortality 151

Table 4 Odds Ratio of group SevereT and ModerateT to MildT

Group OR of mortality in ICU OR of mortality in hospital

OR 95%CI p value OR 95%CI p value

MildT 1 - - 1 - -ModerateT 3.3 0.2-24.0 0.35 5.5 1.1-21.5 ＜0.05†SevereT 75.0 12.9-514.9 ＜0.01＊ 165.8 24.6-3333.7 ＜0.01＊

（†: ＜0.05, ＊: ＜0.01）

AMortality in the ICUMortality in the hospital

90%

80%

70%

60%

50%

40%

30%

20%

10%

0%0 1-50400 50400-151200 151200-

MildT ModerateT SevereT

＊

＊

†

B

timeline (days)

MildT

ModerateT＊

SevereT＊

1.0

0.8

0.6

0.4

0.2

0 20 40 60 80 100 120 140

HRT1_50400HRT50400_151200HRT151200＜

Fig. 3 A, The mortality in the ICU and in the hospital. The patients were stratified by (HR-100)×duration of time (min) when HR is ＞100: MildT (1 ≤HRT ＜50400), ModerateT (50400 ≤HRT ＜151200), and SevereT (HRT ≥151200). In terms of both the ICU and in-hospital mortality, the mortality rates of the SevereT group were significantly higher than those of the MildT group. †p＜0.05, ＊p＜0.01 by Fisherʼs exact test; B, The Kaplan-Meier curve of the MildT, ModerateT, and SevereT groups. The survival rates of ModerateT and SevereT groups were significantly higher than those of the MildT group, confirming the results shown in panel A. †p＜0.05, ＊p＜0.01 by log rank test.

15-17]. Several studies have shown an association between Af and sepsis or septic shock [5-9 , 11-17]. Annane concluded that supraventricular arrhythmias did not significantly impact the hospital survival of crit-ically ill patients [3], while other researchers suggested that supraventricular arrhythmia, especially new-onset Af, had quite a large impact on the survival of patients with sepsis [5 , 7-9 , 11 , 12]. Our hospital’s ICU has a mixed-function design, and it functions relatively more like a surgical ICU, but the present HighHR group still had significantly more patients with arrhythmias and had higher mortality rates. Theerwit noted that criti-cally ill patients with HR > 130 had a higher mortality than patients with HR ≤ 130 [6]; our present findings might reflect that result.

Although there have been few reports of the associ-ation between HR and patient outcomes, a few research groups have investigated the effect of the β1-receptor blocker esmolol in patients with septic shock [13 , 15]. They concluded that esmolol could achieve HR reduc-tion to the target level without adverse events [15] and without changing cardiac output, whereas norepineph-rine requirements were reduced [13]. There is only one report of an investigation of the relationships of HR and prolonged tachycardia with patient outcomes [18], and the report’s authors concluded that critically ill patients with high cardiac risk and HR values > 95 for ≥ 12 h in their ICU stay had a significant risk of major cardiac events [19]. Whether HR reduction would have had any survival benefit in critically ill patients remains unknown. Further studies are needed to determine whether HR reduction contributes to better patient out-comes.

Study limitations. This investigation had some limitations. First, since this was a single-center retro-spective, observational, cohort study, the results have limited generalizability. Second, the cohort consisted mainly of postoperative patients, and the baseline char-acteristics of each group were not similar. This could have resulted in some confounding bias to the out-comes. Third, regarding the stratification of the groups, each cut off-level of HR or HRT was arbitrary. These cut-off levels were sensible but not statistically gener-ated, and the numbers of patients categorized to the ModerateT and SevereT groups were very low. Fourth, the HRT might have been relatively shorter if critically ill patients died soon after being admitted to the ICU.

In conclusion, the results of our analyses indicate

that not only higher HR but also prolonged tachycardia are associated with poor patient outcomes.

Acknowledgments.　We thank Mr. Toshihiro Fujinuma and Mr. Koken So, employees of Nippon Koden Co. Ltd., who extracted and provided huge amounts of data.

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April 2019 Tachycardia Is Associated with Mortality 153