Changes of HRQOL Over Time in Survivors
During the study period, a decrease was found in the physical functioning, role-physical, general health, vitality, and social functioning dimensions. Scores were lower at ICU discharge and hospital discharge in comparison with baseline values (Table 2). These HRQOL aspects improved at 3 and 6 mo after ICU discharge. There was a distinct pattern of a sharp multidimensional decline during ICU stay and gradual improvement in the 6 mo after ICU discharge in all dimensions except for bodily pain and the MCS. Nevertheless, 6 mo after ICU discharge (n = 95), average scores for the physical functioning, role-physical, and general health dimensions were still significantly lower than baseline values (all P < 0.05; Table 2; Fig. 2). Effect size was medium for the role-physical (0.51) dimension and small for the physical functioning (0.37) and general health (0.41) dimensions. Bodily pain did not change at all during the study period. HRQOL decreased significantly over time in all dimensions in severe sepsis survivors except bodily pain (P < 0.05; Table 2). Interestingly, the significant difference of the bodily pain dimension in sepsis survivors was based on a higher mean at 6 mo compared with preadmission (P < 0.002). The PCS (P < 0.001) and MCS (P < 0.05) changed significantly over time (Fig. 3). The MCS showed a small but significant decline from ICU admission and had recovered to pre-ICU admission values at hospital discharge and improved even further by 6 mo after ICU discharge (Table 2). These changes over time were not influenced by age or admission APACHE II score.
Comparison at 6 mo: Severe Sepsis Survivors Versus General Population
Patients who survived severe sepsis up to 6 mo were compared with an age-matched general population. The average SF-36 scores were lower than normal (i.e., worse) in six of the eight dimensions studied (all P < 0.01), the exceptions being the social functioning and bodily pain dimensions (Table 2). Effect size was medium for the physical functioning, role-physical, and general health dimensions (range: 0.50–0.73). Average SF-36 scores of the bodily pain dimension were higher in the severe sepsis survivors, indicating less pain (Fig. 2, Table 2).
Comparison of HRQOL Before ICU Admission with HRQOL in the General Population
The preadmission HRQOL of severe sepsis survivors was compared with HRQOL in the general population. Three of the eight dimension scores (role-physical, mental health, and vitality) were lower (i.e., worse) in the severe sepsis survivors (all P < 0.001). However, effect sizes tended to be small (range: 0.13–0.28) (Table 3).
This is the first long-term study evaluating the time course of changes in HRQOL for sepsis survivors at ICU admission and discharge, after a general ward stay, and at 6 mo after ICU discharge. Severe sepsis was associated with a sharp multidimensional decrease of HRQOL during the ICU stay and gradual improvement in the 6 mo thereafter. These changes over time were not influenced by age or APACHE II score on admission, which was also reported by others.20 Interestingly, the bodily pain dimension did not change at all during our study. A possible explanation for a lack of change may be a phenomenon called “response shift,” i.e., a change in self-evaluation resulting from changes in internal standards or values in patients confronted with a life-threatening disease or chronic incurable disease.21 One could argue that response shift is more likely to occur in those dimensions which are prone to subjective influences such as pain. However, other studies in general ICU patients22 and in ARDS patients23 showed that the bodily pain dimension scores at 3 and 6 mo after discharge were decreased.
The observed temporal decrease in HRQOL during critical illness, with gradual improvement over time, concurs with previous findings.7,24 Graf et al.7 used the SF-36 in medical ICU patients staying for >24 h and found that physical and role-emotional scores had deteriorated 1 mo after ICU discharge, but returned to baseline 9 mo thereafter. In addition, they showed that the Mental Summary Scale did not change during the investigational period. Wehler et al. investigated patients with multiple organ dysfunction syndrome (MODS) and found that 83%–90% of the survivors had regained HRQOL at 6 mo after ICU discharge, although persistent deterioration was especially noted in the physical health domains.23,25 Herridge et al.23 found that patients with ARDS have persistent functional limitation 1 yr after being discharged from the ICU. In line with our findings, the latter studies showed no impact on mental health domains.23,25
Our study showed a temporal decrease in most domains of HRQOL during ICU stay which was followed by recovery starting immediately after ICU discharge. Other investigators have demonstrated persisting disturbance in HRQOL after ICU stay. Using a different scoring method, the EQ-5D, a study in sepsis survivors (not evaluating baseline values) showed that HRQOL of sepsis survivors was fair at 6 mo after ICU discharge. Nevertheless, moderate to severe problems were reported at percentages ranging from 24% to 46% in the five dimensions of the EQ-5D, which was similar to the HRQOL of other critically ill survivors admitted without sepsis.26 Moreover, the significantly lower response rate for the sepsis group could have induced a response bias, whereby survivors from the sepsis group with a lower HRQOL may be under-represented.26 In addition, using the EQ-5D, in predominantly abdominal sepsis, no significant difference in HRQOL was found between sepsis and trauma patients 2 yr after intensive care treatment. HRQOL was reduced to the same level; i.e., 82% of the patients reported a problem (moderate or extreme) in at least one dimension, but most patients (74%) reported no problems in self-care.27 Bosscha et al.28 determined HRQOL after severe bacterial peritonitis at least 1 yr after discharge and found that about 75% of patients regained a good HRQOL, although some patients, especially those who suffered from persistent polyneuropathy and mental disorders, showed persistent limitations in daily life. Another study in abdominal sepsis patients 15 mo after ICU discharge showed that 75% of survivors were independent, ambulatory, and capable of self-care.29 None of the survivors became completely disabled.
However, in addition to the published literature, our study has shown that, in severe sepsis survivors, recovery already starts after discharge from the ICU to the general ward. In the critical care environment, nursing care can have a positive effect on the psychological well-being of patients and relatives.30 In particular, the way doctors and nurses support the patient during critical illness and recovery periods is seen as an important factor in the patients' contentedness and perceived HRQOL after ICU discharge.31
Comparison of General Population with Sepsis Patients at ICU Admission
The preadmission HRQOL in our study of severe sepsis survivors showed that three of the eight dimension scores (role-physical, mental health, and vitality) were already lower in the severe sepsis survivors compared with HRQOL in the general population. This concurs with the finding that HRQOL at admission was reduced in comparison with a matched population of patients with MODS,25 but also in comparison with general ICU patients.7 In contrast to these findings, pre-ICU HRQOL was reported to be unimpaired in 70% of medical-surgical ICU admissions.32 These differences may be explained by differences in the way HRQOL was measured, but also by the geographical setting, with inherent differences in case mix. Nevertheless, the aforementioned data indicate that severe sepsis patients frequently have a lower HRQOL before critical illness occurs.
Comparison of General Population with Sepsis Patients 6 mo After ICU Discharge
Six months after ICU discharge, HRQOL in severe sepsis survivors was still lower compared with a general population. This impairment occurred particularly in the role-physical, general health, and physical functioning dimensions. Heyland et al.4 also found that survivors of sepsis have significantly lower average scores in physical functioning and general health dimensions, but exhibit no differences in the emotional component compared with the general population. A limitation of that study is the small sample of included patients (n = 30), which also puts the study of Perl et al. in a different perspective. Perl et al.33 assessed the HRQOL of 38 patients who survived Gram-negative sepsis and found that septic patients scored poorly on domains within the SF-36 that measure perceived physical function when compared with the general population. Even stronger impairment in HRQOL was reported by Pettila et al.,34 who studied patients with MODS using the SF-36. They compared HRQOL 1 yr after ICU treatment with HRQOL in a general population and reported impaired scores for ICU survivors in all eight domains. On balance, it would seem that severe sepsis survivors have reduced HRQOL, especially pertaining to physical health. Whether this outcome is a result of the severe sepsis or the underlying co-morbid illness is unknown.
Strengths and Limitations
We conducted a long-term, prospective study which measured HRQOL not only before and after hospital discharge, but also at ICU discharge and in a 6-mo period after ICU discharge. It is possible that the follow-up time of 6 mo may be too short to evaluate final improvement in HRQOL in sepsis patients. However, this evaluation period of 6 mo was predefined in view of some earlier studies that indicated that further changes are minimal among ICU patients after this period.7,16
Only patients on their first admission and admitted for more than 48 h to the ICU were included. Therefore, these results are not generalizable to the group of patients with a short ICU stay or with lower disease severity. Another limitation could be that we did not make a distinction between severe sepsis and septic shock.
It is also important to measure HRQOL before and after ICU discharge to examine the impact of the critical illness and ICU admission on HRQOL. On admission to the ICU, the emergency procedures and abnormal levels of consciousness limit the assessment of HRQOL by the patient. We chose to use proxies for preadmission scores, instead of a retrospective assessment at ICU discharge,35 because the critical illness can influence the patients' recollection of their previous health. The approach of using proxies in this setting was validated in an earlier study by our group5 and by other studies.6,35 However, some investigators have raised concerns about proxy estimations of HRQOL in populations with high disease severity.36 The same study suggested that predictions of poor ICU outcome may be exaggerated if proxies underestimate HRQOL.36 However, in contrast to the situation in our previous validation study, where patients and their proxies were interviewed within 72 h of ICU admission, those investigators interviewed patients 3 mo after ICU discharge and their proxies at study entry. This makes it entirely possible that survivors of critical illness may overestimate preadmission HRQOL.
In our study, at the time of ICU and hospital discharge, the patients were specifically asked to score their HRQOL according to their current situation instead of their HRQOL 4 wk before admission. This was necessary to avoid overlap between periods, but complicates the interpretation of the results at ICU discharge and hospital discharge. However, in our opinion, this is a reasonable approach to gain insight into the patients' perceptions of their HRQOL at that time. Still, a direct comparison of different time points is hampered by the different recall periods and the use of both proxies and patients.
In addition, the presence of delirium could have influenced the response, although we made an effort to screen out delirious patients.
Another limitation may be the phenomenon of response shift, mentioned earlier. Social functioning, for instance, could be perceived differently in the clinical setting because of the many visitors in the hospital and postcards received. Although we did not measure response shift in the present study, dimension scores for bodily pain, social functioning, and mental health at ICU and hospital discharge were higher than we expected. Future research should evaluate whether these effects are at least in part caused by response shift.
This study indicates that HRQOL in severe sepsis survivors showed a sharp multidimensional decline during ICU stay and a gradual improvement approaching normal values 6 mo after ICU discharge, with recovery already beginning after discharge from the ICU to the general ward. This implies that intensive care treatment of severe sepsis is worthwhile. However, despite survival, patients report incomplete recovery in the physical functioning, role-physical, and general health dimensions at 6 mo after ICU discharge, compared with the situation before their ICU stay. A follow-up clinic for patients after ICU and hospital discharge could be a way of improving the speed and quality of long-term recovery from severe sepsis.
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