Sleep Disorder and Long-Term Mortality Among Sepsis Survivors: A Nationwide Cohort Study in South Korea

Figures & data

Table 1 Baseline Characteristics of Total Sepsis Survivor from 2011 to 2014 (n=45,826)

Variable	N (%)	Mean (SD)
Age, year		62.9 (19.3)
Gender, Male	19,055 (41.6)
Residence at diagnosis of sepsis
Seoul (Capital city)	10,859 (23.7)
Other metropolitan city	8296 (18.1)
Other area	26,671 (58.2)
Income level at diagnosis of sepsis
Q1 (Lowest)	6993 (15.3)
Q2	6793 (14.8)
Q3	9111 (19.9)
Q4 (Highest)	15,408 (33.6)
Unknown	7521 (16.4)
Underlying disability before sepsis	11,843 (25.8)
Charlson comorbidity index before sepsis		4.8 (3.7)
Total treatment duration for sepsis, day
1–7	22,893 (50.0)
8–15	10,655 (23.3)
16–30	8258 (18.0)
> 30	4020 (8.8)
Treatment of sepsis during hospitalization
Mechanical ventilator use	2295 (5.0)
Endotracheal intubation	1771 (3.9)
CRRT use	491 (1.1)
Vaspressor use	3255 (7.1)
ECMO use	12 (0.0)
Follow up after discharge
Follow up in the same hospital	29,438 (64.2)
Referred to other hospital for admission	2039 (4.4)
Outpatient clinic follow up	14,349 (31.3)
Year of diagnosis of sepsis
2011	10,205 (22.3)
2012	10,958 (23.9)
2013	11,436 (25.0)
2014	13,227 (28.9)
Underlying PTSD	72 (0.2)
Underlying depression	10,731 (23.4)
BDZ or Z-drug user	4191 (9.1)
Sleep disorder before and after sepsis
Control group	34.953 (76.3)
Pre-sepsis sleep disorder group	7938 (17.3)
Insomnia	5120 (11.2)
Other sleep disorder	2818 (6.1)
Post-sepsis sleep disorder group	2935 (6.4)
Insomnia	1988 (4.3)
Other sleep disorder	947 (2.1)

Abbreviations: SD, standard deviation; CRRT, continuous renal replacement therapy; ECMO, extracorporeal membrane oxygenation; PTSD, post-traumatic stress disorder; BDZ, benzodiazepine.

Figure 1 Flow chart depicting patient selection.

Table 2 Comparision of Characteristics Between Three Groups Among Sepsis Survivors

Variable	Control Group n=34,953	Pre-Sepsis Sleep Disorder n=7938	Post-Sepsis Sleep Disorder n=2935	P-value
Age, year	60.7 (19.9)	70.2 (14.8)	69.6 (15.7)	<0.001
Gender, Male	12,485 (44.9)	4819 (34.7)	1751 (42.2)	<0.001
Residence at diagnosis of sepsis				<0.001
Seoul (Capital city)	7444 (26.8)	2569 (18.5)	846 (20.4)
Other metropolitan city	4587 (16.5)	2903 (20.9)	806 (19.4)
Other area	15,747 (56.7)	8430 (60.6)	2494 (60.2)
Income level at diagnosis of sepsis				<0.001
Q1 (Lowest)	4268 (15.4)	2060 (14.8)	665 (16.0)
Q2	4524 (16.3)	1680 (12.1)	589 (14.2)
Q3	5958 (21.4)	2398 (17.2)	755 (18.2)
Q4 (Highest)	9090 (32.7)	4963 (35.7)	1355 (32.7)
Unknown	3938 (14.2)	2801 (20.1)	782 (18.9)
Underlying disability before sepsis	5684 (20.5)	4919 (35.4)	1240 (29.9)	<0.001
Charlson comorbidity index before sepsis	4.5 (3.7)	6.0 (3.6)	6.1 (3.9)	<0.001
Treatment of sepsis during hospitalization
Mechanical ventilator use	1518 (4.3)	573 (7.2)	204 (7.0)	<0.001
Endotracheal intubation	1167 (3.3)	456 (5.7)	148 (5.0)	<0.001
CRRT use	344 (1.0)	107 (1.3)	40 (1.4)	0.005
Vaspressor use	2268 (6.5)	764 (9.6)	223 (7.6)	<0.001
ECMO use	6 (0.0)	4 (0.1)	2 (0.1)	0.089
Total treatment duration for sepsis, day				<0.001
1–7	15,952 (57.4)	5393 (38.8)	1548 (37.3)
8–15	5506 (19.8)	4049 (29.1)	1100 (26.5)
16–30	4386 (15.8)	2930 (21.1)	942 (22.7)
> 30	1934 (7.0)	1530 (11.0)	556 (13.4)
Follow up after discharge				<0.001
Follow up in the same hospital	18,724 (67.4)	8394 (60.4)	2320 (56.0)
Referred to other hospital for admission	1102 (4.0)	687 (4.9)	250 (6.0)
Outpatient clinic follow up	7952 (28.6)	4821 (34.7)	1576 (38.0)
Underlying depression or PTSD	6570 (18.8)	3142 (39.6)	1057 (36.0)	<0.001
BDZ or Z-drug user	2135 (6.1)	1529 (19.3)	503 (17.1)	<0.001
Year of diagnosis of sepsis				<0.001
2011	6955 (25.0)	2242 (16.1)	1008 (24.3)
2012	6838 (24.6)	3115 (22.4)	1005 (24.2)
2013	6594 (23.7)	3827 (27.5)	1015 (24.5)
2014	7391 (26.6)	4718 (33.9)	1118 (27.0)
5-year all-cause mortality	7199 (25.9)	6536 (47.0)	1678 (40.5)	<0.001

Note: Presented as number with percentage or mean with standard deviation.

Abbreviations: CRRT, continuous renal replacement therapy; ECMO, extracorporeal membrane oxygenation; PTSD, post-traumatic stress disorder; BDZ, benzodiazepine.

Table 3 Multivariable Cox Model for 5-Year All-Cause Mortality Among Sepsis Survivor

Variable	Multivariable Cox Model	P-value
	HR (95% CI)
Sleep disorder before and after sepsis (model 1)
Control group	1
Pre-sepsis sleep disorder group	1.19 (1.15, 1.24)	<0.001
Post-sepsis sleep disorder group	1.79 (1.70, 1.89)	<0.001
Sleep disorder before and after sepsis (model 2)
Control group	1
Pre-sepsis insomnia group	1.15 (1.10, 1.23)	<0.001
Pre-sepsis other sleep disorder group	1.05 (1.03, 1.06)	0.014
Post-sepsis insomnia group	1.89 (1.85, 1.94)	<0.001
Post-sepsis other sleep disorder group	1.44 (1.39, 1.48)	<0.001
Age, year	1.06 (1.06, 1.06)	<0.001
Gender, Male	1.50 (1.45, 1.55)	<0.001
Residence at diagnosis of sepsis
Seoul (Capital city)	1
Other metropolitan city	1.11 (1.05, 1.17)	<0.001
Other area	1.08 (1.03, 1.12)	0.001
Income level at diagnosis of sepsis
Q1 (Lowest)	1
Q2	0.97 (0.91, 1.03)	0.360
Q3	0.95 (0.90, 1.00)	0.069
Q4 (Highest)	0.93 (0.88, 0.98)	0.003
Unknown	1.18 (1.11, 1.24)	<0.001
Underlying disability before sepsis	1.45 (1.40, 1.07)	<0.001
Charlson comorbidity index before sepsis, point	1.06 (1.06, 1.07)	<0.001
Treatment of sepsis during hospitalization
Mechanical ventilator use	1.35 (1.22, 1.51)	<0.001
Endotracheal intubation	0.94 (0.83, 1.05)	0.277
CRRT use	0.77 (0.66, 0.89)	0.001
Vaspressor use	0.89 (0.83, 0.95)	<0.001
ECMO use	1.72 (0.64, 4.59)	0.283
Total treatment duration for sepsis, day
1–7	1
8–15	1.46 (1.40, 1.52)	<0.001
16–30	1.36 (1.29, 1.42)	<0.001
> 30	1.50 (1.41, 1.59)	<0.001
Follow up after discharge
Follow up in the same hospital	1
Referred to other hospital for admission	0.82 (0.76, 0.88)	<0.001
Outpatient clinic follow up	0.63 (0.60, 0.65)	<0.001
Underlying depression or PTSD	1.00 (0.99, 1.01)	0.190
BDZ or Z-drug user	1.00 (0.99, 1.00)	0.522
Year of diagnosis of sepsis
2011	1
2012	0.88 (0.84, 0.92)	<0.001
2013	0.88 (0.84, 0.92)	<0.001
2014	0.84 (0.80, 0.88)	<0.001

Notes: C-index: 0.82 (0.81, 0.82). Model fitting information: −2 log likeliwood 308843.0, Chi-square: 13529.0, P<0.001.

Abbreviations: HR, hazard ratio; CI, confidence interval; CRRT, continuous renal replacement therapy; ECMO, extracorporeal membrane oxygenation; PTSD, post-traumatic stress disorder; BDZ, benzodiazepine.

Table 4 Sensitivity Analyses of Multivariable Cox Regression Model for 5-Year All-Cause Mortality According to Sleep Disorder with Depression or PTSD and Sleep Disorder with BDZ or Z-Drug Use

Variable	Multivariable Cox Model	P-value
	HR (95% CI)
Sleep disorder before and after sepsis (Model 1)
Control group (n=34,953)	1
Pre-sepsis sleep disorder group without PTSD or depression (n=4796)	1.19 (1.13, 1.25)	<0.001
Pre-sepsis sleep disorder group with PTSD or depression (n=3142)	1.21 (1.13, 1.29)	<0.001
Post-sepsis sleep disorder group without PTSD or depression (n=1878)	1.67 (1.56, 1.79)	<0.001
Post-sepsis sleep disorder group with PTSD or depression (n=1057)	2.01 (1.84, 2.19)	<0.001
Sleep disorder before and after sepsis (Model 2)
Control group (n=34,953)	1
Pre-sepsis sleep disorder group without BDZ or Z-drug use (n=6409)	1.18 (1.13, 1.23)	<0.001
Pre-sepsis sleep disorder group with BDZ or Z-drug use (n=1529)	1.30 (1.18, 1.43)	<0.001
Post-sepsis sleep disorder group without BDZ or Z-drug use (n=2432)	1.76 (1.66, 1.86)	<0.001
Post-sepsis sleep disorder group with BDZ or Z-drug use (n=503)	2.02 (1.77, 2.30)	<0.001

Abbreviations: HR, hazard ratio; CI, confidence interval; PTSD, post-traumatic stress disorder; BDZ, benzodiazepine.