Return to work after hospitalization for sepsis; a nationwide, registry-based cohort study.

doi:10.21203/rs.3.rs-3328613/v1

Download PDF

Research Article

Return to work after hospitalization for sepsis; a nationwide, registry-based cohort study.

https://doi.org/10.21203/rs.3.rs-3328613/v1

This work is licensed under a CC BY 4.0 License

Journal Publication

published 15 Nov, 2023

Read the published version in Critical Care →

You are reading this latest preprint version

Background: Survivors of sepsis hospitalization commonly experience functional impairment, which may limit return to work. We aimed to investigate return to work (RTW) of patients with sepsis and the associations between patient and clinical characteristics with RTW. Methods: Working-age patients (18 to 60 years) admitted to a Norwegian hospital with sepsis between 2010 and end of 2021 were identified using the Norwegian Patient Registry and linked to sick-leave data from the Norwegian National Social Security System Registry. The outcomes were time to RTW, trends in age-standardized proportions of RTW and probability of sustainable RTW (31 days of consecutive work). The trends were calculated for each admission year, reported as annual percentage change with 95% CI. Cox regression analysis, including crude and adjusted hazard risk (HRs), was used to explore the association between sustainable RTW and patient and clinical characteristics (e.g., COVID-19 vs non-COVID-19 sepsis, ward vs intensive care admission) with RTW. Results Among 35.839 hospitalizations for sepsis among patients aged 18 to 60 years during the study period, 12.260 (34.2%) were working prior to hospitalization and included in this study. The mean age was 43.7 years. At 6 months, 1 year, and 2 years post-discharge, 58.6%, 67.5%, and 63.4%, respectively, were working. The overall annual age-standardized RTW proportion at 6 months and 1 year remained stable throughout the study period, while the 2-year age-standardized RTW declined by 1.51% (95% CI, -2.22 to -0.79) per year, from 70.01% (95% CI, 67.21 to 74.80) in 2010 to 57.04% (95% CI, 53.81to 60.28) in 2019. Characteristics associated with sustainable RTW were younger age, fewer comorbidities, and fewer organ dysfunctions. The probability of sustainable RTW was higher in patients with COVID-19-related sepsis (HR 1.31; 95% CI 1.15 to 1.49) than in sepsis patients and lower in ICU-patients (HR 0.56; 95% CI 0.52 to 0.61) compared to ward-patients. Conclusion The decrease in RTW from 1 to 2 years and the temporal trend of declining RTW at 2 years needs attention, and further work facilitation efforts are required, especially in vulnerable groups that may need other interventions than today to achieve sustained RTW.

Sepsis

RTW

ICU

COVID-19

Sepsis is caused by a dysregulated host immune response to infection, resulting in acute organ dysfunction(1), and is a major cause of worldwide morbidity and mortality, with an estimated 50 million cases and 11 million sepsis-related deaths in 2017(2). Sepsis survivors often experience poor long-term outcomes with new or worsened cognitive and functional impairments(3, 4), making normal activities hard to resume. However, the impact of these problems on sepsis survivors’ ability to return to work (RTW) is less clear.

RTW is a recommended measure of the long-term functional level after disease, including trauma (5), acute respiratory distress syndrome (ARDS), and conditions requiring intensive care and organ support(6-10). A previous Danish study (2018) investigating a general Intensive Care Unit (ICU) cohort found that among survivors receiving organ support therapy 60% had returned to work at 1 year and 68% at 2 years after discharge(9). Prior studies suggest that sepsis survivors have worse overall functional outcomes than other intensive care survivors(11, 12). This is supported by a recent administrative based German study (2023) investigating RTW using the Sepsis-1 and Sepsis-2 definition, which found that only 55% and 65 % of ICU treated sepsis patients returned to work 6 months and 1 year after discharge(13). This suggests delayed RTW up to 1 year, thus negatively health impact can persist over years(10), which warrants RTW estimates beyond 1 year based on latest Sepsis-3 definition to monitor prognosis and trends to plan appropriate interventions for sepsis survivors working prior to the admission.

In light of the recent pandemic, the research on reduced functioning after infection with COVID-19 is evolving, suggesting that 30% of survivors are affected(14-17). RTW estimates at 6 months after a COVID-19 admission varies between 57% to 89%(18-21). Currently, limited research is available on RTW for patients with COVID-19-related sepsis, but one study of 120 COVID-19 patients found no differences in self-reported RTW after 110 days between ward and ICU patients(22).

In sum, knowledge about more long-term outcomes is warranted to understand and facilitate the RTW process for sepsis patients and COVID-19-related sepsis(23). The aim of this nationwide registry study was therefore to investigate the proportion and temporal trends for RTW in patients admitted with sepsis, including COVID-19 sepsis, at 6 months, 1 year, and 2 years in the period from 2010 through 2021. In addition, we examined characteristics associated with sustainable RTW, defined as working at least 31 consecutive days after a hospital discharge with an index sepsis episode.

Design and setting

In this Norwegian nationwide registry-based study, we identified hospitalizations for sepsis using ICD-10 codes in the Norwegian Patient Registry (NPR)(24). We included patients from all Norwegian hospitals in the period from 2010 through 2021 with an index admission for sepsis, defined by an ICD-10 code for infection in combination with an ICD-10 code for acute organ dysfunction (implicit) and/or an ICD-10 code for specific sepsis (explicit) (see Supplemental file, Supplementary Table 1)(2, 25). We used this strategy in the primary and up to 20 secondary co-existing ICD-10 discharge codes. To focus on index sepsis hospitalizations, we examined data from 2008 and excluded patients who had previously been hospitalized with sepsis between 2008 and 2010.

Patients with sepsis were linked to individual data from the Registry of the Norwegian National Social Security System. We limited the study cohort to patients of working age (18 to 60 years), which is 2 years before the earliest retirement possibility in Norway. The rationale for the upper age limit was to identify patients who stopped working due to sepsis, as opposed to patients who retired unrelated to sepsis. We also excluded patients with any disability pension prior to the sepsis hospitalization and patients who did not survive hospital discharge.

Details on the Norwegian National Insurance Scheme

In Norway, all workers have a compulsory membership in The Norwegian National Insurance Scheme(26). Individuals who have been working for at least four weeks before illness, with an income higher than ½ of the ‘basic amount’ (NOK 118 620, or USD 11 798 in 2023), and who have lost work income as a result of a medically-certified illness are entitled to sickness benefits of up to 52 weeks. Sickness benefits begin on the day the employer is notified of the illness. Self-employed individuals and freelance workers are also entitled to benefits but must cover the first 16 days of absence themselves. After 52 weeks, it is possible to apply for more long-term medical benefits, work assessment allowance and permanent disability pension. To qualify for a disability pension, individuals must have at least a 50% reduction in workability documented by a doctor`s certificate. A membership of The Norwegian National Insurance Scheme qualifies for a medical benefit application, even though the patient is without sickness benefits rights. All individuals with benefits in Norway are registered by their social security number in the Norwegian National Social Security System Registry, run by The Norwegian Labour and Welfare Administration(27).

Definition of variables in the study

Working was defined by two criteria, and both had to be met. First, patients had to be registered with no sickness benefit or long-term medical benefit (work assessment allowance and permanent disability pension) for at least 90 of 121 days in the 6-2 months prior to sepsis admission in order to exclude those patients on sickness or medical benefits for other medical conditions than to sepsis as a cause of not being able to RTW. Second, patients had to be registered with a sickness benefit 31 days before the hospital admission date or 31 days after the hospital discharge date in order to identify those patients working before to the sepsis admission.

ICD-10 discharge codes for selected comorbidities were based on diagnostic groups(28), the details regarding comorbidities are provided in a previous publication(29). COVID-19-related sepsis was included based on the presence of a discharge code for COVID-19 (U07.1, U07.2) and ≥one organ dysfunction code and/or explicit code. We categorized infection and acute organ dysfunctions by ICD-10 discharge codes, while ICU stay were retrieved from The Norwegian Intensive Registry(30). A readmission after hospitalization with sepsis was defined as an admission within 30 days after discharge, regardless of cause.

Outcome measures

We subsequently evaluated work status at 6 months, 1 year, and 2 years after discharge from index sepsis hospitalization. We categorized work status at each time point as RTW, ever RTW, never RTW, and dead. Patients without any sickness or medical benefit at the measurement point were categorized as RTW. Patients on sickness or medical benefit at all the measurement points were categorized as never RTW. Lastly, patients who had returned to work at an earlier time point but were back on sickness or medical benefits were categorized as ever RTW. We also investigated sustainable RTW, defined as the absence of any sickness or medical benefit for at least 31 consecutive days after discharge from sepsis hospitalization.

Death and death date was retrieved from the Norwegian Cause of Death Registry(31).

Statistical analysis

Descriptive results are presented as frequencies with percent, means with standard deviation, and medians as appropriate.

Clinical characteristics of interest included sex, age group (18-29, 30-39, 40-49, 50-60 years), number and type of comorbidities, site of infection, number and type of acute organ dysfunctions, ICU treatment, COVID-19-infection status, length of stay (LOS) and readmission within 30 days. These descriptive analyses were also repeated in the group of patients that did not work prior to sepsis admission.

The Norwegian National Social Security System Registry contains information about all members` entry and exit dates and degrees of sickness and medical benefits. To calculate the proportion of patients returning to work, we counted sepsis survivors from discharge date that had status as RTW, never RTW or dead at 6 months, and as RTW, never RTW, ever RTW or dead at 1 year, and 2 years, and divided by all patients working prior to admission, subtracting those who died between each measure point. We also completed analyses stratified by treatment in the ICU vs ward only and by COVID-19-related vs non-COVID-19-related sepsis.

To examine temporal trends in RTW, we calculated 6-month, 1-year, and 2-year RTW by calendar year. This was calculated as the proportions with RTW divided by the number of survivors after the index sepsis admission each year. To avoid potential bias of sepsis hospitalizations over time due to changing age distribution, the RTW proportion was standardized according to 10-year age groups (18-29, 30-39, 40-49, 50-60 years) using the age distribution in 2011 as the base for patients admitted to wards, and the age distribution in 2015 as the base for patients admitted to ICU. Temporal trends in age-standardized RTW were estimated from least-squares linear regression across calendar years and weighted by the inverse variance of the RTW proportion(32).

Clinical characteristics potentially associated with the probability of sustainable RTW were investigated using Cox regression to estimate crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CI). Association with age and sex where mutually adjusted, whereas all other associations were adjusted for both sex (male, female) and age (years). Comorbidities, site of infection, and acute organ dysfunctions were analyzed as categorical variables, using the most common category as the reference. The categories were mutually exclusive, and the analyses were conducted on a restricted sample of patients with none or only one infection site, comorbidity, or acute organ dysfunction, respectively. In all Cox regression models, the patients were followed for 2 years after the date of discharge with an index sepsis admission to make sure the follow-up time covered the time-span of possible sick leave and was within the first possible retirement age. The discharge date was restricted to after 1 July, 2010, to validate the sick-leave data and ensure the participants were in the workforce. In the analysis assessing sustainable RTW in ICU patients compared to ward patients, both the ward and ICU patients entered the study after 1 May, 2014, since earlier information for the ICU patients was unavailable(30). A similar analysis was conducted to compare sepsis and COVID-19-related sepsis patients, but with an entry date of 28 February, 2020, corresponding to the first confirmed hospitalized COVID-19 case in Norway. Patients were censored at the date of sustainable RTW, death date, or the last day of follow-up (31 December, 2021). The last date for inclusion was 1 October, 2021, to allow for a valid assessment of sustainable RTW. As many individuals go on and off sickness benefits, we conducted a sensitivity analysis where sustainable RTW was defined as at least 92 consecutive days without any sickness benefit. The proportional hazards assumption of the Cox model was examined by visual inspection of log-log plots.

All analyses were conducted using STATA version 16.1 (Stata Corp).

Ethics

The study was approved by the Regional Committee for Medical and Health Research Ethics (REK) in Eastern Norway (2019/42772) and the Data Access Committee in Nord-Trøndelag Hospital Trust (2021/184). In accordance with the approval from the REK and the Norwegian law on medical research, the project did not require a written patient consent. This work was analyzed on TSD (Service for Sensitive Data) facilities, owned by the University of Oslo, operated, and developed by the TSD service group at the University of Oslo, IT Department (USIT).

Among 35.839 patients aged 18–60 years who were discharged alive from an index sepsis hospitalization during the study period, 12.260 (34.2%) were confirmed to be working prior to sepsis hospitalization and included in this study. 10.533 (29.3%) patients were excluded for disability pension prior to sepsis hospitalization, 4.735 (13.2%) patients were excluded for > 30 days of sickness or long-term medical benefits in the months prior to sepsis hospitalization indicating other illnesses than sepsis affecting RTW, and 8.311 (23.1%) patients were excluded for lack of employment prior to sepsis hospitalization, as inferred by no sickness or medical benefit surrounding sepsis hospitalization. A flow chart of the exclusion and inclusion process is displayed in Fig. 1.

Figure 1Flowchart of the selection process

Patient characteristics

Characteristics of the study cohort are shown in Table 1. The mean age was 43.7 years, and 59.9% were male. The most common comorbidity was heart or vascular disease, present in 19.5%. The most common sites of infection were respiratory (30.2%) and genitourinary (13.1%). The mean length of hospitalization was 13.9 days. 7.8% were admitted to an intensive care unit, and 29.9% were re-hospitalized within 30 days.

Table 1

Characteristics of the 12.260 patients working prior to sepsis hospitalization
Characteristics	N (%) or mean (SD)
Male, n (%)	7 341 (59.9)
Age, years, mean (SD)	43.7 (11.8)
Age-group, n (%)
18–29	2 077 (16.9)
30–39	2 314 (18.9)
40–49	3 121 (25.4)
50–60	4 748 (38.7)
Comorbidities, n (%)
Heart and vascular	2 394 (19.5)
Cancer	1 941 (15.8)
Lung	681 (5.6)
Diabetes	666 (5.4)
Immune	269 (2.2)
Renal	145 (1.2)
Liver	44 (0.4)
Number of comorbidities, n (%)
0	7 290 (58.5)
1	3 933 (32.1)
2	911 (7.4)
≥3	126 (1.0)
Site of infection, n (%)
Respiratory	3 692 (30.2)
Genitourinary	1 602 (13.1)
Skin and soft tissue	558 (4.4)
Gastrointestinal	827 (6.8)
Intra-abdominal	755 (6.2)
Infections following a procedure	625 (5.1)
Endocarditis/myocarditis	190 (1.6)
Other^a	2 056 (16.8)
COVID-19-related sepsis^b	384 (3.1)
Organ system with acute dysfunction, n (%)
Respiratory	3 063 (25.0)
Circulatory	878 (7.2)
Renal	2 627 (21.4)
Hepatic	194 (1.6)
Coagulation	757 (6.2)
Other^c	2 543 (20.7)
Number of acute organ dysfunctions, n (%)
1	6 422 (87.2)
2	736 (10.0)
3	164 (2.2)
≥4	42 (0.6)
ICU treatment^f, n (%)	951 (7.8)
LOS, days, mean (SD)
Ward patients	12.9 (22.2)
ICU patients^g	25.4 (35.4)
30-day Readmission^e n (%)	3 664 (29.9)
Abbreviation: NA = Not Applicable. ICU = Intensive Care Unit, LOS = Length of stay ^a Other infections = Bone, obstetric, upper airway, central nervous system and unknown ^b Variable calculated from 28th February 2020 ^c Other acute organ dysfunction = Acidosis, unspecific gangrene, central nervous system dysfunctions and Systemic Inflammatory Response Syndrome. ^d Number of hospital admissions = Calculated as new sepsis admission if admission with ICD-10 codes defining sepsis, regardless of time frame for the new sepsis admission. ^e Readmission = admission within 30 days after discharge regardless of cause ^f Variable calculated from May 1, 2014

Table 1Characteristics of the 12.260 patients working prior to sepsis hospitalization

Supplementary Table 2 shows characteristics of the 8.311 individuals inferred to be not working prior to sepsis based on lack of sickness or medical benefit. Compared to patients working before sepsis hospitalization, non-working patients were younger (mean age 40.5 (SD = 13.2) vs 43.7 years, SD = 11.8) and consisted of more women (46.2% vs 40.1%).

Return to work

In the total cohort, the proportion with RTW was 58.6% at 6 months, 67.5% at 1 year, and 63.4% at 2 years. Among patients admitted to wards, the RTW proportion was 60.3% at 6 months, 68.6% at 1 year, and 64.2% at 2 years after discharge. Among patients admitted to ICU, the RTW proportion was 38.5% at 6 months, 53.6% at 1 year, and 52.2% at 2 years after discharge. In 2020 and 2021, for patients admitted with COVID-19-related sepsis, the RTW proportion was 66.9% and 77.8% at 6 months and 1 year after hospital discharge (Table 2).

Table 2

The proportion of RTW, never RTW and ever RTW and dead at 6 months, 1 year and 2 years in the period 2010 through 2021.
Patient group and measurement point	n^a	RTW^b (%)	Never RTW^c (%)	Ever RTW ^d (%)	Dead (%)
All sepsis patients
6 months	12 260	58.6	37.9	NA	3.4
1 year	11 751	67.5	21.6	5.6	5.4
2 year	10 845	63.4	15.3	13.7	7.7
Ward patients
6 months	11 309	60.3	36.2	NA	3.4
1 year	10 856	68.6	20.4	5.6	5.4
2 year	10 085	64.2	14.4	13.7	7.6
ICU patients
6 months	951	38.5	58.0	NA	3.5
1 year	895	53.6	36.2	4.8	5.4
2 year	760	52.2	26.7	13.0	8.0
COVID-19-related sepsis^e,f
6 months	384	66.9	32.6	NA	0.5
1 year	135	77.8	15.6	5.2	1.5
Abbrevation: RTW = return to work, NA = Not Applicable ^a Includes all sepsis patients who survived an admission, ^b Without medical benefit or disability pension at measurement point ^c Patients at medical benefit or disability pension since discharge. ^d Patients without a medical benefit in a period after discharge, but back on medical benefit at measurement point ^e Includes the years 2020 and 2021 ^f Includes those who were admitted at wards and ICU

Table 2The proportion of RTW, never RTW and ever RTW and dead at 6 months, 1 year and 2 years in the period 2010 through 2021.

Temporal trends in RTW

Overall, the annual age-standardized RTW proportion at 6 months was stable with a change of 0.14% (95% CI, -0.20 to 0.47), from 57.57% (95% CI, 53.58 to 61.56) in 2010 to 63.10% (95% CI, 58.23 to 67.87) in 2021. The annual age-standardized RTW proportion at 1 year also remained stable throughout the study period with a change of -0.45% (95% CI, -0.94 to 0.53), from 69.52% (95% CI, 65.71 to 73.33) in 2010 to 64.89% (95% CI, 61.56 to 68.22) in 2020. However, the 2-year age-standardized RTW declined by 1.51% (95% CI, -2.22 to -0.79) per year over the study period, from 70.01% (95% CI, 67.21 to 74.80) in 2010 to 57.04% (95% CI, 53.81to 60.28) in 2019.

For patients admitted to the wards, the annual age-standardized RTW proportion at 6 months and 1 year after discharge remained stable throughout the study period. However, the 2-year age-standardized RTW declined by 1.32% (95% CI, -2.14 to -0.49) per year over the study period, from 70.01% (95% CI, 67.21 to 74.80) in 2010 to 56.96% (95% CI, 53.54 to 60.38) in 2019. This decline was driven mainly by the years after 2016. For patients admitted to the ICU, the annual age-standardized RTW proportion at 6 months, 1 year, and 2 years after discharge remained stable from 2014 through 2021, as shown in Fig. 2A and 2B.

Figure 2 Age-standardized proportions RTW by discharge year for sepsis patients admitted A. wards (2010–2021) and B. ICU (2014–2021).

Characteristics associated with sustainable RTW

The median follow-up time for sustainable RTW was 0.2 years (range 0 to 2 years) and ended when a person started working. The results displayed in Table 3 show that patients and clinical characteristics were associated with sustainable RTW. In short, younger age, fewer comorbidities, and fewer organ failures were associated with sustainable RTW. In addition, patients with genitourinary, gastrointestinal, and skin and soft tissue sites of infection had higher rates of sustainable RTW than the other infections sites, and COVID-19-related sepsis had a 1.31 (95% CI; 1.15 to 1.49) higher chance of sustainable RTW compared to all sepsis patients.

Table 3

Associations of patient and clinical characteristics with sustained RTW
Variable	Person year (py) at risk	Events	Rate per py	Crude HR	Adjusted^a HR (95% C)
Age-group
18–29	720	1 779	2.47	1.00	1.00 (Reference)
30–39	824	1 966	2.38	0.90	0.90 (0.84–0.96)
40–49	1 080	2 552	2.36	0.80	0.78 (0.75–0.85)
50–60	1 595	3 592	2.25	0.69	0.69 (0.65–0.73)
Sex
Male	2 579	5 939	2.30	1.00	1.00 (Reference)
Female	1 639	3 950	2.41	1.03	1.01 (0.97–1.05)
Sepsis subgroup^b
Sepsis	362	989	2.73	1.00	1.00 (Reference)
COVID-19-related	95	324	3.41	1.25	1.31 (1.15–1.49)
Site of infection^c
Respiratory	988	2 462	2.49	1.00	1.00 (Reference)
Genitourinary	260	785	3.01	1.40	1.38 (1.27–1.50)
Intra-abdominal	162	391	2.41	1.03	1.03 (0.92–1.14)
Gastrointestinal infections	169	637	3.80	1.69	1.64 (1.51–1.79)
Skin and soft tissue	105	276	2.64	1.26	1.27 (1.12–1.44)
Infections following a procedure	136	244	1.80	0.83	0.84 (0.73–0.96)
Endocarditis/myocarditis	46	74	1.60	0.70	0.70 (0.56–0.88)
Other infections^d	793	1 800	2.27	1.00	0.96 (0.91–1.02)
Comorbidities^c
Heart and vascular	652	1 175	1.80	1.00	1.00 (Reference)
Cancer	749	736	0.98	0.52	0.52 (0.48–0.58)
Lung	139	367	2.65	1.57	1.60 (1.42–1.80)
Diabetes	97	269	2.80	1.58	1.58 (1.39–1.81)
Renal	17	25	1.48	0.99	0.98 (0.66–1.46)
Immune	29	99	3.42	2.07	2.06 (1.67–2.53)
Liver	5	10	2.03	0.60	0.62 (0.33–1.15)
No. of comorbidities
0	2 113	6 598	3.12	1.00	1.00 (Reference)
1	1 687	2 681	1.59	0.45	0.46 (0.44–0.48)
2	377	547	1.45	0.38	0.39 (0.36–0.42)
≥3	41	63	1.55	0.30	0.32 (0.25–0.41)
Type of acute organ dysfunction^c
Respiratory	819	1 858	2.27	1.00	1.00 (Reference)
Renal	563	1 761	3.12	1.45	1.48 (1.39–1.58)
Circulatory	187	353	1.89	0.89	0.91 (0.82–1.03)
Coagulation	332	407	1.23	0.62	0.64 (0.58–0.71)
Hepatic	37	66	1.79	0.83	0.82 (0.64–1.04)
Other acute organ dysfunctions^e	275	735	2.67	1.33	1.30 (1.19–1.41)
No. of acute organ dysfunctions
1	2 214	5 180	2.34	1.00	1.00 (Reference)
2	337	492	1.46	0.60	0.60 (0.55–0.66)
3	82	109	1.33	0.57	0.56 (0.46–0.68)
≥4	18	25	1.42	0.49	0.49 (0.33–0.72)
ICU treatment^f
No	2 335	5 974	2.56	1.00	1.00 (Reference)
Yes	396	660	1.67	0.57	0.56 (0.52–0.61)
Abbrevation: HR = Hazard Ratio, CI = Confidence Interval, ICU = Intensive Care Unit, LOS = Length of hospital stay in days ^a Cox regression with time to death as dependent variable, the listed variable as covariate (one at the time), and sex and age. ^b Enter date = February 27, 2020 ^c Categorical variable where one ICD-10 code excludes other ICD-10 codes in the same diagnosis group ^d Other infections = Bone, obstetric, upper airway, central nervous system and unknown ^e Other acute organ dysfunctions = Acidosis, unspecific gangrene, central nervous system dysfunctions and Systemic Inflammatory Response Syndrome. ^f Enter date= May 1, 2014

Table 3Associations of patient and clinical characteristics with sustained RTW.

Sensitivity analysis

In sensitivity analysis changing the definition of sustainable RTW to working at least 92 consecutive days after discharge date with an index sepsis episode, the adjusted hazard ratio from Cox regression did not differ from the results in Table 3, see Supplemental File, Supplementary Table 3.

Our study is the first to use complete nationwide registries to estimate RTW in sepsis patients, and we demonstrate that RTW is a challenge for many patients, even 2 years after discharge. Our estimates show that a higher proportion of patients with sepsis returned to work at 1 year compared to 6 months and 2 years after discharge. The trends in RTW were stable throughout the study period, except for the RTW at 2 years where we observed a yearly decrease. Further, we found that decreasing age, fewer comorbidities, and fewer acute organ dysfunctions were associated with sustainable RTW in sepsis survivors and that COVID-19-related sepsis patients had a higher probability of achieving sustainable RTW than other sepsis patients.

One previous study have used administrative data covering 30% of the German population to estimate RTW in sepsis patients with a follow-up to 12 months after discharge(13). They found that 69% returned to work at 6 months and 76% returned to work at 12 months. This is a much higher RTW rate in our study. While they extracted explicit sepsis ICD-10 codes, we extracted both implicit and explicit ICD-10 sepsis codes. Notably, an explicit approach is previous found to underestimate sepsis estimates and may be a possible explanation of the diverging results(33).

Previous studies on RTW in sepsis patients have used critical illness populations, where sepsis patients were a small proportion of the cohorts, and RTW was not reported separately(9, 10, 34–36). Thus, direct comparisons of our results with previous studies are not feasible. A systematic review of ICU studies suggests increasing rates of RTW over time(37), but the included studies have a high degree of RTW variability(9, 35, 37–41). While we use a national mandatory registry to calculate RTW, 51 of the 52 included studies in this systematic review used self-reported answers to questions in face-to-face or telephone interviews or mailed questionnaires to collect data. The majority of the included studies had more than 10% lost to follow-up since ICU/hospital discharge(37), while our complete national registries including weekly updates on RTW enabled us to follow-up everybody until death date and thus no loss to follow-up. In previous studies, the self-reported RTW at 1 year varied between 55–78%(37). The only registry study found that 60% of the ICU patients, regardless of diagnosis, returned to work at 1 year(9). For comparison, we found that 53.6% of the ICU patients with sepsis had returned to work at 1 year. Previous studies have found worse overall functioning outcomes in sepsis survivors compared to other intensive care survivors(11, 12), and since we only included sepsis patients, our result in the lower range is expected.

A Danish study of RTW in COVID-19 patients found that 6.6% of the patients hospitalized with COVID-19 did not work at 3 months(42). In contrast, we found that 33.1% of patients with COVID-19-related sepsis were not working at 6 months. Both our and the Danish study (2022) were based on registry data. However, while the Danish study included all hospitalized patients with a positive SARS-CoV-2 polymerase chain reaction (PCR) test, regardless of organ dysfunction, our study focused solely on COVID-19-related sepsis patients with one or more acute organ dysfunctions. This difference in patient selection with more severely sick patients in our study may explain the diverging results.

The literature regarding new episodes of sick leave after initial RTW is limited for sepsis patients(9, 37, 38). Investigating ICU patients, organ support therapy and RTW, Riddersholm et al. (2018) found that 29% were back on medical benefits within 1 year. For comparison, this is higher than our result (4.8%) at one year among sepsis patients admitted to ICU. If we compare the RTW proportion at 2 years, Riddersholm et al. found that 68% of the patients returned to work, which is higher than our age-standardized proportion at 2 years (58.4%). As previously argued, sepsis patients are expected to have worse outcomes than other critically ill patients, thus the dividing result. In addition, there are differences in social infrastructure with earlier transfer to long-term medical benefit in Denmark than in Norway(27, 43). Thus, potential differences may not all be health-related but may also be influenced by social infrastructure.

Interestingly, we found a decreasing trend of 2-year RTW for sepsis patients admitted to the wards from 2010 through 2021. To our knowledge, these trends in RTW in sepsis patients are not previously described. Based on our previous works, we observed decreasing case fatality rates and decreasing 1- and 2-year mortality in ward patients in this population(29, 44), pointing to a higher proportion of very ill ward sepsis patients being discharged. We therefore hypothesize that the decreasing trend in RTW can be explained by this increased survival. The fact that the ICU patients’ proportion of RTW was stable can be explained by stable mortality in patients receiving ICU treatment over time in the cohort(29, 44), i.e., the same proportion of ill ICU sepsis patients survive and are potential candidates for RTW.

Associations between patients and clinical characteristics in sepsis patients are limited. A recent registry-based Danish study (2018) of ICU patients and the need for organ support therapy found mechanical ventilation to be associated with a decreased chance of RTW(9). Another study investigating different severity stages of acute kidney injury (AKI, stages I-III) in ICU patients surviving acute respiratory failure and/or sepsis found that 50% of those with AKI I and 22% of those with AKI II-III returned to work at 3 months follow-up(45). Our study found that acute renal dysfunctions had a higher probability of sustainable RTW compared to acute respiratory dysfunction. However, we did not have the availability of AKI stages to differentiate and compare directly to Riddersholm et al. Another study by Poulsen and colleagues (2009) investigating patients with septic shock found that 43% of patients returned to work at 1 year(46). This is lower than in our study, where approximately 58% of the ICU patients RTW at 1 year. The diverging result may be explained by differences in the severity of sepsis since our study included all patients with sepsis receiving ICU treatment and not only septic shock. To our knowledge, no previous study has investigated characteristics associated with the probability of sustainable RTW in a patient group consisting of only patients admitted with sepsis, including sepsis patients admitted at the wards. Our findings support results from previous studies reporting that increasing age and pre-existing chronic comorbidities are associated with work status(38, 39). However, compared to our study, these studies were small and based on self-reports, thus direct comparisons are difficult.

There are some limitations to our study. First, the sepsis cohort is extracted from NPR using ICD-10 codes. We used the Sepsis-3 definition throughout the study period when extracting ICD-10 codes, albeit the definition first came in 2016(1). Second, implicit sepsis codes are found to overestimate sepsis while explicit sepsis codes often underestimate sepsis, and by using both approaches, we assume to align the chances for over- and underestimation(33). Moreover, we cannot be sure that all acute organ dysfunction codes are associated with the infection, and thus this could generate an overestimation of sepsis. Third, we observed that 40% of the sepsis patients were without sickness benefits in the period around hospitalization, and as these could not be verified to be working, we had to exclude these patients. The excluded patients were younger and likely consisted of more students, i.e., the RTW might have been higher if these had been included. In addition, we did not differentiate between employed and self-employed individuals. The possibility of not being on sick leave is higher for self-employed since they are only entitled to sickness benefits after the 17th day of absence compared to the first day of absence for employees, which may have caused an underestimation of RTW. Fourth, we did not investigate whether patients received graded sickness or medical benefits, meaning that some could have partly returned to work. Notably, the incidence rate and case fatality are in the lower range compared to estimates from a recent meta-analysis from 2020 and the global burden of disease study from 2017(2, 29, 47). The return to work estimates may also be influenced by social infrastructure, and therefore, the interpretation of the analysis is primarily relevant to countries with the same burden and comparable social welfare systems,

One major strength is that our study is based on complete national administrative data(48), thus the selection bias is minimized. We have complete follow-up data, which is generally not possible in other cohorts based on patients’ self-report, where over 10% lost to follow-up since discharge is common(37). We studied characteristics associated with sustainable RTW, while previous studies report only RTW at fixed time points after receiving ICU treatment. Our group of patients is without any form of benefits and has sustained work for at least 31 consecutive days, thus our results account for the fact that they have probably resumed work after the index sepsis episode. This is a strength because estimates of only fixed time points are snapshots of RTW and lack sustainable RTW. Furthermore, another strength is that we studied RTW over 11 years, thus making it possible to detect RTW trends and report RTW results beyond 1 year.

Two thirds of the patients working prior to the sepsis admission returned to work at 1 year, which was higher compared to 6 months and 2 years. While the trends in RTW at 6 months and 1 year were stable, the trend at 2 years RTW after discharge decreased throughout the study period. Vulnerable groups for not achieving sustainable RTW were patients at higher ages, patients with an increasing number of comorbidities and an increasing number of acute organ dysfunctions, which warrants targeted interventions to improve long-term outcomes.

Ethical Approval and consent to participate

Regional Committee for Medical and Health Research Ethics (REK) in Eastern Norway (2019/42772). Data Access Committee in Nord-Trøndelag Hospital Trust (2021/184).In accordance with the approval from the REK and the Norwegian law on medical research, the project did not require a written patient consent.

Consent for publication

Not applicable

Competing interests

None of the authors have any conflicts of interest to declare

Contributorship statement

Study concept and design: N.V.S., K.M., T.I.L.N., L.A., J.K.D., L.T.G.

Acquisition of data: N.V.S., L.T.G.

Analysis and interpretation of data: N.V.S., K.M., T.I.L.N., L.T.G.

Statistical analysis: N.V.S., K.M.

Drafting of the manuscript: N.V.S

Funding acquisition: L.T.G.

Critical revision of the manuscript for important intellectual content: N.V.S., K.M, T.I.L.N., L.A., H.C.P., J.K.D., L.T.G.

Administrative, technical, or material support: N.V.S., L.T.G.

Study supervision: T.I.L.N., J.K.D., L.T.G.

Funding

Our work was supported by the Helse Midt-Norge (2019/38881) and Helse Nord-Trøndelag (2022/1927, 2022/31982).

Role of the Funder:

The funding body had no role in the designs of the study, data collection, analysis, interpretation of data, or in writing the manuscript.

Availability of data and materials

No additional data available. We do not have ethical approval to deposit our datasets in publicly available repositories. Researchers need approval by the Regional Ethical Committee for handling of NPR, NIR and NAV data files. The NPR has precise information on all data exported to different projects and there are no restrictions regarding data export given REK approval.

Acknowledgements

Not applicable

Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801–10.
Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study. Lancet. 2020;395(10219):200–11.
Prescott HC, Iwashyna TJ, Blackwood B, Calandra T, Chlan LL, Choong K, et al. Understanding and Enhancing Sepsis Survivorship. Priorities for Research and Practice. Am J Respir Crit Care Med. 2019;200(8):972–81.
Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term Cognitive Impairment and Functional Disability Among Survivors of Severe Sepsis. JAMA. 2010;304(16):1787–94.
Uleberg O, Pape K, Kristiansen T, Romundstad PR, Klepstad P. Population-based analysis of the impact of trauma on longer-term functional outcomes. Br J Surg. 2019;106(1):65–73.
Ardolino A, Sleat G, Willett K. Outcome measurements in major trauma–results of a consensus meeting. Injury. 2012;43(10):1662–6.
Jones C, Griffiths RD. Mental and physical disability after sepsis. Minerva Anestesiol. 2013;79(11):1306–12.
Rothenhausler HB, Ehrentraut S, Stoll C, Schelling G, Kapfhammer HP. The relationship between cognitive performance and employment and health status in long-term survivors of the acute respiratory distress syndrome: results of an exploratory study. Gen Hosp Psychiatry. 2001;23(2):90–6.
Riddersholm S, Kragholm K, Rasmussen BS, Christensen S, Christiansen CF. Organ failure and return to work after intensive care. Critical Care. 2018;22.
McPeake J, Mikkelsen ME, Quasim T, Hibbert E, Cannon P, Shaw M, et al. Return to Employment after Critical Illness and Its Association with Psychosocial Outcomes. A Systematic Review and Meta-Analysis. Ann Am Thorac Soc. 2019;16(10):1304–11.
Kayambu G, Boots RJ, Paratz JD. Early rehabilitation in sepsis: a prospective randomised controlled trial investigating functional and physiological outcomes The i-PERFORM Trial (Protocol Article). BMC Anesthesiol. 2011;11:21.
Hayes JA, Black NA, Jenkinson C, Young JD, Rowan KM, Daly K, et al. Outcome measures for adult critical care: a systematic review. Health Technol Assess. 2000;4(24):1–111.
Fleischmann-Struzek C, Ditscheid B, Rose N, Spoden M, Wedekind L, Schlattmann P, et al. Return to work after sepsis-a German population-based health claims study. Front Med (Lausanne). 2023;10:1187809.
Soriano JB, Murthy S, Marshall JC, Relan P, Diaz JV. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis. 2022;22(4):e102-e7.
Fernández-de-Las-Peñas C. Long COVID: current definition. Infection. 2022;50(1):285–6.
Akbarialiabad H, Taghrir MH, Abdollahi A, Ghahramani N, Kumar M, Paydar S, et al. Long COVID, a comprehensive systematic scoping review. Infection. 2021;49(6):1163–86.
PASC Daschboard [Available from: https://pascdashboard.aapmr.org/.
Hodgson CL, Higgins AM, Bailey MJ, Mather AM, Beach L, Bellomo R, et al. The impact of COVID-19 critical illness on new disability, functional outcomes and return to work at 6 months: a prospective cohort study. Crit Care. 2021;25(1):382.
Lindahl A, Aro M, Reijula J, Mäkelä MJ, Ollgren J, Puolanne M, et al. Women report more symptoms and impaired quality of life: a survey of Finnish COVID-19 survivors. Infect Dis (Lond). 2022;54(1):53–62.
Carenzo L, Dalla Corte F, Haines RW, Palandri C, Milani A, Aghemo A, et al. Return to Work After Coronavirus Disease 2019 Acute Respiratory Distress Syndrome and Intensive Care Admission: Prospective, Case Series at 6 Months From Hospital Discharge. Crit Care Med. 2021;49(11):e1157-e62.
van Veenendaal N, van der Meulen IC, Onrust M, Paans W, Dieperink W, van der Voort PHJ. Six-Month Outcomes in COVID-19 ICU Patients and Their Family Members: A Prospective Cohort Study. Healthcare (Basel). 2021;9(7).
Garrigues E, Janvier P, Kherabi Y, Le Bot A, Hamon A, Gouze H, et al. Post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19. J Infect. 2020;81(6):e4-e6.
Garzillo EM, Cioffi A, Carta A, Monaco MGL. Returning to Work after the COVID-19 Pandemic Earthquake: A Systematic Review. Int J Environ Res Public Health. 2022;19(8).
Bakken IJ, Ariansen AMS, Knudsen GP, Johansen KI, Vollset SE. The Norwegian Patient Registry and the Norwegian Registry for Primary Health Care: Research potential of two nationwide health-care registries. Scand J Public Health. 2020;48(1):49–55.
Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29(7):1303–10.
NAV. Membership of the National Insurance Scheme 2019 [Available from: https://www.nav.no/en/home/rules-and-regulations/membership-of-the-national-insurance-scheme.
NAV 2023 [Available from: https://www.nav.no/en/home.
Stausberg J, Hagn S. New Morbidity and Comorbidity Scores based on the Structure of the ICD-10. PLoS One. 2015;10(12):e0143365.
Skei NV, Nilsen TIL, Knoop ST, Prescott H, Lydersen S, Mohus RM, et al. Long-term temporal trends in incidence rate and case fatality of sepsis and COVID-19-related sepsis in Norwegian hospitals, 2008–2021: a nationwide registry study. BMJ Open. 2023;13(8):e071846.
Norwegian Intensive Registry [Available from: https://helse-bergen.no/norsk-intensivregister-nir.
The Norwegian Cause of Death Registry 2014 [Available from: https://www.fhi.no/globalassets/dokumenterfiler/helseregistre/dar/dodelighet-og-dodsarsaker-pdf.pdf.
Kim HJ, Fay MP, Feuer EJ, Midthune DN. Permutation tests for joinpoint regression with applications to cancer rates. Stat Med. 2000;19(3):335–51.
Fleischmann-Struzek C, Thomas-Ruddel DO, Schettler A, Schwarzkopf D, Stacke A, Seymour CW, et al. Comparing the validity of different ICD coding abstraction strategies for sepsis case identification in German claims data. PLoS One. 2018;13(7):e0198847.
Bein T, Blecha S, Weber-Carstens S, Apfelbacher C, Brandstetter S, Dodoo-Schittko F, et al. The quality of acute intensive care and the incidence of critical events have an impact on health-related quality of life in survivors of the acute respiratory distress syndrome - a nationwide prospective multicenter observational study. German medical science: GMS e-journal. 2020;18.
von Bahr V, Kalzen H, Hultman J, Frisen KG, Dobrosavljevic T, Holzgraefe B, et al. Long-term pulmonary function and quality of life in adults after extracorporeal membrane oxygenation for respiratory failure. Perfusion (United Kingdom). 2019;34(1):49–57.
C A, S B, S B, F D-S, M B, C K, et al. Influence of quality of intensive care on quality of life/return to work in survivors of the acute respiratory distress syndrome: prospective observational patient cohort study (DACAPO). BMC public health. 2020;20(1):861.
Kamdar BB, Suri R, Suchyta MR, Digrande KF, Sherwood KD, Colantuoni E, et al. Return to work after critical illness: a systematic review and meta-analysis. Thorax. 2020;75(1):17–27.
Kamdar BB, Huang M, Dinglas VD, Colantuoni E, Von Wachter TM, Hopkins RO, et al. Joblessness and lost earnings after acute respiratory distress syndrome in a 1-year national multicenter study. American Journal of Respiratory and Critical Care Medicine. 2017;196(8):1012–20.
Oeyen S, Vandijck D, Benoit D, Decruyenaere J, Annemans L, Hoste E. Long-term outcome after acute kidney injury in critically-ill patients. Acta Clin Belg. 2007;62 Suppl 2:337–40.
Myhren H, Ekeberg Ø, Stokland O. Health-related quality of life and return to work after critical illness in general intensive care unit patients: a 1-year follow-up study. Crit Care Med. 2010;38(7):1554–61.
Eddleston JM, White P, Guthrie E. Survival, morbidity, and quality of life after discharge from intensive care. Crit Care Med. 2000;28(7):2293–9.
Jacobsen PA, Andersen MP, Gislason G, Phelps M, Butt JH, Køber L, et al. Return to work after COVID-19 infection - A Danish nationwide registry study. Public Health. 2022;203:116–22.
Resource flow performance during resource flows: borger.dk; 2023 [Available from: https://www.borger.dk/arbejde-dagpenge-ferie/fleksjob-loentilskud-for-foertidspensionister-revalidering/ressourceforloebsydelse-under-ressourceforloeb.
Skei NV, Nilsen TIL, Mohus RM, Prescott HC, Lydersen S, Solligård E, et al. Trends in mortality after a sepsis hospitalization: a nationwide prospective registry study from 2008 to 2021. Infection. 2023.
Mayer KP, Ortiz-Soriano VM, Kalantar A, Lambert J, Morris PE, Neyra JA. Acute kidney injury contributes to worse physical and quality of life outcomes in survivors of critical illness. BMC Nephrology. 2022;23(1):137.
Poulsen JB, Møller K, Kehlet H, Perner A. Long-term physical outcome in patients with septic shock. Acta Anaesthesiol Scand. 2009;53(6):724–30.
Fleischmann-Struzek C, Mellhammar L, Rose N, Cassini A, Rudd KE, Schlattmann P, et al. Incidence and mortality of hospital- and ICU-treated sepsis: results from an updated and expanded systematic review and meta-analysis. Intensive Care Med. 2020;46(8):1552–62.
Aasdahl L, Fimland MS, Bjørnelv GMW, Gismervik S, Johnsen R, Vasseljen O, et al. Economic Evaluation of Inpatient Multimodal Occupational Rehabilitation vs. Outpatient Acceptance and Commitment Therapy for Sick-Listed Workers with Musculoskeletal- or Common Mental Disorders. J Occup Rehabil. 2023.

No competing interests reported.

Download PDF

Journal Publication

published 15 Nov, 2023

Read the published version in Critical Care →

Editorial decision: Major revision
04 Oct, 2023
Reviews received at journal
12 Sep, 2023
Reviewers agreed at journal
11 Sep, 2023
Reviewers invited by journal
11 Sep, 2023
Submission checks completed at journal
07 Sep, 2023
Editor assigned by journal
07 Sep, 2023
First submitted to journal
05 Sep, 2023

You are reading this latest preprint version

Return to work after hospitalization for sepsis; a nationwide, registry-based cohort study.

Status:

Journal Publication

Version 1

Abstract

Figures

Introduction

Methods

Design and setting

Outcome measures

Statistical analysis

Ethics

Results

Discussion

CONCLUSION

Declarations

References

Additional Declarations

Supplementary Files

Status:

Journal Publication

Version 1