Quality of life in adult survivors of critical illness: A systematic review of the literature

Transcription

1 Intensive Care Med (2005) 31: DOI /s S Y S T E M A T I C R E V I E W David W. Dowdy Mark P. Eid Artyom Sedrakyan Pedro A. Mendez-Tellez Peter J. Pronovost Margaret S. Herridge Dale M. Needham Quality of life in adult survivors of critical illness: A systematic review of the literature Received: 11 November 2004 Acceted: 17 February 2005 Published online: 1 Aril 2005 Sringer-Verlag 2005 D. W. Dowdy Deartment of Eidemiology, Johns Hokins Bloomberg School of Public Health, Baltimore, MD, USA A. Sedrakyan P. J. Pronovost Deartment of Health Policy and Management, Johns Hokins Bloomberg School of Public Health, Baltimore, MD, USA D. W. Dowdy M. P. Eid School of Medicine, Johns Hokins University, Baltimore, MD, USA P. A. Mendez-Tellez P. J. Pronovost Deartment of Anesthesiology & Critical Care Medicine, Johns Hokins University, Baltimore, MD, USA P. J. Pronovost Deartment of Surgery, Johns Hokins University, Baltimore, MD, USA D. M. Needham () ) Division of Pulmonary & Critical Care Medicine, Johns Hokins University, 1830 E. Monument Street, 5th floor, Baltimore, MD, 21205, USA dale.needham@utoronto.ca M. S. Herridge Interdeartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada Abstract Objective: To determine how the quality of life (QOL) of intensive care unit (ICU) survivors comares with the general oulation, changes over time, and is redicted by baseline characteristics. Design: Systematic literature review including MEDLINE, EMBASE, CI- NAHL and Cochrane Library. Eligible studies measured QOL 30 days after ICU discharge using the Medical Outcomes Study 36-item Short Form (SF-36), EuroQol-5D, Sickness Imact Profile, or Nottingham Health Profile in reresentative oulations of adult ICU survivors. Disease-secific studies were excluded. Measurements and results: Of 8,894 citations identified, 21 indeendent studies with 7,320 atients were reviewed. Three of three studies found that ICU survivors had significantly lower QOL rior to admission than did a matched general oulation. During ost-discharge follow-u, ICU survivors had significantly lower QOL scores than the general oulation in each SF-36 domain (excet bodily ain) in at least four of seven studies. Over 112 months of followu, at least two of four studies found clinically meaningful imrovement in each SF-36 domain excet mental health and general health ercetions. A majority of studies found that age and severity of illness redicted hysical functioning. Conclusions: Comared with the general oulation, ICU survivors reort lower QOL rior to ICU admission. After hosital discharge, QOL in ICU survivors imroves but remains lower than general oulation levels. Age and severity of illness are redictors of hysical functioning. This systematic review rovides a general understanding of QOL following critical illness and can serve as a standard of comarison for QOL studies in secific ICU suboulations. Keywords Critical care Critical illness Health status indicators Intensive care units Outcome assessment (health care) Quality of life

2 612 Introduction As more atients survive critical illness, assessing quality of life (QOL) among intensive care unit (ICU) survivors has become a research riority [1, 2]. Desite a raidly growing body of literature, revious reviews of QOL in ICU survivors have been descritive [37] or methodological [8], and have not broadly synthesized research findings. Secifically, there has been no systematic review of how QOL in ICU survivors (1) comares with the general oulation, (2) changes over time, and (3) is redicted by baseline characteristics. Ultimately, it is imortant to understand QOL in secific ICU suboulations (e.g., acute resiratory distress syndrome (ARDS) and severe sesis) in order to assess the imact of secific interventions on these atients [9]. To lace this knowledge in context, however, an understanding of QOL among the general oulation of critically ill atients is needed as a standard against which to comare outcomes in ICU suboulations. Consequently, in this systematic review, we studied QOL in atient oulations reresentative of all adult ICU survivors. Methods Search strategy To identify studies eligible for the systematic review, we searched Medline ( ), EMBASE ( ), CINAHL ( ), re-cinahl, and the Cochrane Library (2004, Issue 3) on August 13, The following search strategy was used, with all terms maed to the aroriate MeSH/EMTREE subject headings and exloded : ( quality of life OR health status indicators ) AND ( intensive care units OR critical care OR critical illness OR sesis OR adult resiratory distress syndrome ). Sesis and ARDS were included in the strategy because one eligible study identified before conducting the search was not catured using the initial search terms. No limits regarding language or ublication tye were alied. We also hand-searched ersonal files and the reference lists of relevant review articles [38]. For all articles included in the systematic review, we reviewed the reference lists and conducted an Exanded Science Citation Index (ISI Web of Knowledge, Thomson Cororation) search of ublications citing the articles. Two authors (D.W.D., M.P.E.) indeendently reviewed citations, abstracts, and full articles to select eligible studies for review. All citations selected by either author for abstract review were included, and subsequent disagreement regarding eligibility was resolved by consensus. Agreement between the two reviewers was calculated by ercentage agreement and the kaa statistic. For all foreign language articles, English translations of abstracts were reviewed. Eligible articles written in German, French, and Sanish were reviewed, in full, by a single author (D.W.D.). One otentially eligible article written in Czech [10] was excluded without full-text review. Studies were selected for review if they met two inclusion criteria: (1) study of a reresentative oulation of adult ICU survivors (defined as a oulation consisting entirely of medical and/ or surgical ICU atients 14 years old and reresenting a majority of all atients with an ICU length of stay >24 h), and (2) measurement of QOL 30 days after ICU discharge, using one of four widely used instruments: Medical Outcomes Study 36-item Short Form General Health Survey (SF-36) [11], EuroQol-5D (EQ-5D) [12], Sickness Imact Profile (SIP) [13], or Nottingham Health Profile (NHP) [14]. In order to minimize heterogeneity, studies focusing on secific diseases (e.g., ARDS), treatments (e.g., arenteral nutrition), or conditions (e.g., length of stay >7 days) were excluded. Descrition of measurement instruments SF-36, EQ-5D, SIP, and NHP are measures of health-related quality of life commonly used in critical care research. Patrick s Perceived Quality of Life (PQOL) questionnaire [15] was excluded because it measures qualitatively different QOL domains (e.g., family, community, leisure, hel, income, and resect) than the four selected instruments, thereby recluding a meaningful synthesis of results. Other instruments, such as the Fernandez questionnaire [16], were excluded because they lacked secific domains or because they were used in 5 critical care studies, including studies of secific suboulations [3]. SF-36 [11] uses 36 items to measure eight QOL domains: hysical functioning, role limitations due to hysical roblems, bodily ain, general health ercetions, energy/vitality, social functioning, role limitations due to emotional roblems, and mental health. SIP [13] uses 136 questions to evaluate twelve QOL domains: work, recreation, emotional behavior, alertness, home management, slee, body care, eating, ambulation, mobility, communication, and social interaction. Both SF-36 and SIP allow calculation of summary scores from their multile domains: hysical and mental comonent scores for SF-36, and hysical and sychosocial summary scores for SIP. SF-36 and SIP have been comrehensively validated in critically ill atients [17,18]. NHP [14] measures QOL with two arts. Part I evaluates subjective functional status with 38 yes/no statements in six domains: hysical mobility, ain, slee, energy, emotional reactions, and social isolation. Part II is no longer recommended for use by its develoers, due to oor measurement roerties, and is therefore excluded from this review. EQ-5D [12] is a brief, two-art instrument. The EQ-5D self-classifier is a five-item questionnaire that elicits one of three resonses ( no, some, or extreme ) for roblems with mobility, self-care, usual activities, ain/discomfort, and anxiety/deression; the EQ-VAS assesses self-rated health status using a single visual analogue scale (VAS) scored from 0 to 100. Although some studies [19,20] have examined limited asects of NHP validity, NHP and EQ-5D have not been comrehensively validated for ICU atients. Study selection Data extraction, synthesis, and study quality For each eligible study, two authors (D.W.D., M.P.E.) indeendently abstracted measures of study quality, baseline variables (age, severity of illness, gender, ICU length of stay, and admission diagnosis), QOL instrument, method of administration, and QOL outcomes in an unmasked manner [21] with differences resolved by consensus. Due to quantitative and qualitative heterogeneity in the reorting of QOL results, a quantitative synthesis was not ossible. We therefore summarized study results as either statistically significant ( <0.05) or nonsignificant. In addition, differences in SF- 36 scores of more than 5 oints were reorted as clinically meaningful [11]; comarable measures of clinical meaning were not available for the other instruments.

3 613 Fig. 1 Flow diagram of literature search results We assessed study quality using four criteria adated from the United States Preventive Services Task Force [22]: (1) no systematic exclusion of >10% of the adult ICU oulation; (2) descrition of atients lost to follow-u and comarison with those remaining in the study; (3) measurement and reorting of secific QOL domains at baseline and follow-u; and (4) adjustment for confounders including age by stratification, statistical adjustment, or comarison with a matched oulation. Each criterion was assessed indeendently without reorting an overall score. Quality criteria were not used in decisions regarding inclusion or exclusion of eligible studies. Results Search results and study characteristics We identified 8,894 citations, of which 352 abstracts and 111 full-text ublications were reviewed (Fig. 1). A total of 26 reorts (25 articles and one dissertation) describing 21 indeendent atient oulations were eligible for the review (Table 1). Reviewer agreement on selection of eligible citations was 97.4% (kaa=0.71), and on selection of ublications for final review was 99.0% (kaa=0.97). Of the 21 indeendent studies reviewed, five were multicenter studies [17, 19, 25, 40,45]; 16 were conducted in Euroe [17, 19, 23,2634,3640, 45,46], three in the United States [25, 43,44], one in Australia [35], and one in Hong Kong [42]. Ten studies used SF-36, four used EQ-5D, five used SIP, and two used NHP (Table 1). Thirteen of 14 (93%) studies using SF-36 or EQ-5D were ublished in 2000 or later, vs one of seven (14%) using SIP or NHP. One study [33] had a mean atient age of 33, while the mean or median age in all other studies ranged from 45 to 65. Three studies (14%) had a mean ICU length of stay >5 days [19, 26,40]. Nineteen studies (90%) had a follow-u eriod ranging from 324 months, while the remaining two studies had extended follow-u eriods of 6 years [24] and 12 years [33]. The median follow-u time was 7 months. QOL was assessed at follow-u by mailed survey in 16 studies, by telehone in three [26, 36,39], and by ersonal interview in two [28,37].

4 614 Table 1 Characteristics of studies measuring quality of life in adult ICU survivors (ICU intensive care unit, LOS intensive care unit length of stay, SF-36 Medical Outcomes Study 36-item Short First author (year) N a Key exclusion criteria Patient age (years) b Form General Health Survey, EQ-5D EuroQol-5D, SIP Sickness Imact Profile, NHP Nottingham Health Profile, CABG coronary artery byass graft) ICU LOS (days) b Follow-u (months) c SF-36 Pettila (2000) [23] 298 None 53 (16) 5 (6) 12, 72 and Kaarlola (2003) [24] Kleinell (2003) [25] 199 <45 years old; LOS <24 h >45 years d 3 (3) 1, 3, 6, 12 Wehler (2003) [26] 171 LOS 24 h 57 (17) 11 (19) 6 Graf (2003) [27] 164 Delirious/comatose; 64 (13) 1, 9 LOS <24 h Eddleston (2000) [28] 136 None 49 (12) 4 (113) 3 Kvale (2003) [29,30] 126 LOS 24 h 52 (16) 3 (mean) 6, 24 Vedio (2000) [31] 115 Overnight stay 65 (5670) 2 (14) 6 Ridley (1997) [32] 95 Preciitous discharge 62 (mean) 1 (11) 6 Flaaten (2001) [33] 51 Cardiac surgery 33 (22) 5 (7) 12 years and Kvale (2002) [34] Chaboyer (2002) [35] 16 No family roxy 61 (18) 3 (4) 6, 12 EQ-5D Badia (2001) [36] 334 Proxy not available; 57 (4465) 5 (316) 12 LOS <12 h Granja (2002) [37] 275 LOS <24 h [37] 57 (median) 2 (median) 6 and Granja (2004) [38] Garcia Lizana (2003) [39] 96 Uncomlicated 60 (4275) 3 (36) 18 elective surgery Sznajder (2001) [40] 64 None 55 (20) 8 (11) 6 SIP Tian (1995) [17] 3,655 LOS <24 h 60 (15) 3 (4) 6 and Miranda (1994) [41] Short (1999) [42] 853 None 45 (3262) 2 (14) 12 Kleinell (1991) [43] 164 <45 years old >45 years e 4 (6) 7 Sage (1986) [44] 140 CABG atients 56 (mean) 4 (mean) 15 Frick (2002) [45] 85 None 65 (median) 2 (median) 6 NHP Hurel (1997) [19] 223 None 52 (18) 9 (10) 6 Bell (1994) [46] 60 Transferred elsewhere 54 (mean) 3 (mean) 3 a Samle size at first follow-u visit after hosital discharge b Data are reorted as median (interquartile range) or mean (standard deviation) if not secified. c Length of time from ICU or hosital discharge until quality of life measurement d 53% of atients were 4564 years old, and 47% were 6586 years old. e 22% were 4564 years old, 46% were 6579, and 32% were 80 years old. Assessment of study quality A majority of the studies met each of the four quality criteria (Table 2). However, re-admission QOL domains were measured in only five studies (24%). Four studies excluded >10% of the eligible adult ICU oulation; these exclusions were based on age <45 years [25,43] and cardiac surgery status [33,44]. Two studies [42,44] reorted only a summary QOL measure, instead of secific domains. Agreement on assessment of study quality was 93.0% (kaa=0.85). Comaring quality of life in ICU survivors versus the general oulation Seven studies [23, 24, 26, 27,3133] comared QOL in ICU survivors versus a matched general oulation (Table 3). All studies used the SF-36 survey. Three of these studies retrosectively examined QOL rior to ICU admission, with each study reorting statistically significant ( <0.05) and clinically meaningful (>5 oints) decrements in all eight QOL domains. QOL was measured at 6 months to 14 years after ICU admission in eight atient oulations (Table 3). For each domain, excet bodily ain, a majority of oulations reorted significant and meaningful decrements in QOL versus the general oulation. For bodily ain, a clinically meaningful decrement was observed in four oulations (50%), but this finding was statistically significant in only one study (14%). Comared with the general oulation, no study reorted a statistically significant or clinically meaningful increase in any QOL domain among its comlete oulation of ICU survivors.

5 615 Table 2 Assessment of study methods and reorting for quality of life in adult ICU survivors (ICU intensive care unit, QOL quality of life, SF-36 Medical Outcomes Study 36- item Short Form General Health Survey, EQ-5D EuroQol-5D, SIP Sickness Imact Profile, NHP Nottingham Health Profile) Source No major exclusion criteria a Losses to follow-u described Secific QOL domains measured Pre-ICU Post-ICU SF-36 Pettila [23] Kleinell [25] Wehler [26] Graf [27] Eddleston [28] Kvale [29] Vedio [31] Ridley [32] Flaaten [33] Chaboyer [35] EQ-5D Badia [36] Granja [37] Garcia Lizana [39] Sznajder [40] SIP Tian [17] Short [42] Kleinell [43] Sage [44] Frick [45] NHP Hurel [19] Bell [46] Total (of 21 studies) Adjusted for age and gender a Defined as systematic exclusion of >10% of the adult ICU oulation with a length of stay >24 h Table 3 Quality of life measurements in adult ICU survivors versus age- and gender-matched general oulation (ICU intensive care unit, QOL quality of life) Source N a Follow-u Physical QOL domains c Mental QOL domains c time b Physical Role Bodily General Vitality Social Role emotional function hysical ain health function Studies of QOL rior to ICU admission d Wehler [26] 318 # * # * # * # * # * # * # * # * Graf [27] 153 # * # * # * # * # * # * # * # * Ridley [32] e 75 # * # * # * # * # * # * # * # * Studies of QOL after ICU stay Wehler [26] months # * # * # * # * # * # * # * Ridley [32] e 75 6 months # * # * # * # * # * # * # * # * Vedio [31] f Elective 66 6 months # * " Emergency 49 6 months # * # * # # * # * # * Graf [27] months # * # * # * # * # * # * # * Pettila [23] months # * # * # # * # * # # * # Kaarlola [24] g years # # # Flaatten [33] years # * # * # # * # # * # * # * Mental health a Samle size at the time of follow-u b Length of time from ICU or hosital discharge until quality of life measurement c #/" clinically meaningful (i.e., >5-oint) decrement/imrovement in quality of life; # * clinically meaningful and statistically significant (<0.05) decrement in quality of life; non-clinically meaningful (i.e., 5-oint) change in quality of life d QOL rior to ICU admission was measured retrosectively from atient or roxy. e Includes only atients <65 years old f Searately analyzed atients with emergency and elective diagnoses on ICU admission g The study oulation in [24] is a subset of that in [23]. No measure of significance was reorted in [24].

6 616 Table 4 Change in quality of life from baseline for adult ICU survivors a ( ICU intensive care unit, QOL quality of life) Domain Follow-u time b 1 month 6 months 9 months 12 months Kleinell [25] Graf [27] Kleinell [25] Wehler [26] Ridley [32] Graf [27] Kleinell [25] Physical domains Physical functioning " * " * " * " * " * Role hysical # * # * " " " * " * Bodily ain " * " " * " * " General health Mental domains Vitality " " * " * " Social functioning # " * " * " * " * Role emotional # * " " * " Mental health " * " * a Baseline measurements were obtained retrosectively by interview with atient [2527, 32] or roxy [25, 26,32]. Follow-u times are from ICU or hosital discharge. b "/#clinically meaningful (i.e., >5-oint) imrovement/decline in quality of life; " * /# * clinically meaningful and statistically significant (<0.05) imrovement/decline in quality of life; non-clinically meaningful (i.e., 5-oint) change in quality of life. All quality of life measurements at follow-u are comared against baseline. Table 5 Predictors of quality of life using SF-36 ( SF-36 Medical Outcomes Study 36-item Short Form General Health Survey, ICU intensive care unit, QOL quality of life, SOFA Sequential Organ Failure Assessment, APACHE Acute Physiology and Chronic Health Evaluation, SAPS Simlified Acute Physiologic Score) and one study [27] excluded such atients. Four studies used the SF-36 survey (Table 4). Social functioning and role erformance due to both hysical and emotional roblems showed clinically meaningful decreases from baseline at 1-month follow-u, but clinically meaningful increases from baseline at 6 months and 12 months. Vi- b b Source Follow- U a Measure Physical QOL domains Physical Role Bodily General Mental QOL domains Vitality Social Role Mental function hysical ain health function emotional health Age Eddleston [28] 3 months >65 vs. 65 years * of age Kleinell [25] 6 months 65 vs. <65 years of age Wehler [26] 6 months 4 strata of age * * * * * * Graf [27] 9 months 66 vs. <66 years * of age Pettila [23] 12 months Age c * * * * * * Severity of Illness Kleinell [25] 6 months APACHE III c * * Wehler [26] 6 months SOFA 6 vs. <6 * * Vedio [31] 6 months Chronic * * * roblem on APACHE II Graf [27] 9 months SAPS II and SOFA c, d Pettila [23] 12 months SOFA 6 vs. <6 * * * * * * * * Kvale [29] 24 months SAPS II c a Length of time from ICU or hosital discharge until quality of life measurement b *Statistically significant ( <0.05) decrease in quality of life with increase in age or severity of illness; No statistically significant change in quality of life ( >0.05) c Measured as a continuous variable d Both measures were indeendently studied, and neither showed a significant association. Changes in quality of life over time Five studies comared QOL at follow-u with re-admission baseline QOL measured retrosectively. Four of these studies [25, 26, 32,36] used roxies to obtain baseline QOL for atients who were unable to resond,

7 617 Table 6 Predictors of quality of life using EuroQol-5D and SIP ( SIP Sickness Imact Profile, NHP Nottingham Health Profile, ICU intensive care unit, Activ. activities, Pain ain/discomfort, Anx. Der. anxiety/deression, VAS visual analogue scale, Phys hysical subscore, Psych sychosocial subscore, APACHE Acute Physiology and Chronic Health Evaluation, SAPS Simlified Acute Physiologic Score) b b Source Measure Follow- U a EuroQol-5D Mobility Self Care Usual Activ. Pain Anx. Der. VAS SIP Phys Psych Total Age Granja [37] Age c 6 months * * * * * Garcia [39] Age c 18 months * Tian [17] 6 strata of age 6 months * * Kleinell [43] 3 strata of age 7 months * * Short [42] 3 strata of age 12 months * Sage [44] 3 strata of age 15 months * Severity of Illness Granja [37] APACHE II c 6 months * * * * Garcia [39] APACHE II c 18 months * * Tian [17] APACHE II c 6 months Kleinell [43] APACHE II c 7 months Short [42] APACHE II 12 months * (4 strata) Sage [44] APACHE II c 15 months a Length of time from ICU or hosital discharge until quality of life measurement b * Statistically significant ( <0.05) decrease in quality of life with increase in age or severity of illness; no statistically significant change in quality of life ( >0.05) c Measured as a continuous variable tality also showed clinically meaningful imrovement between 1 and 6 months, between 1 and 9 months, and between 1 and 12 months follow-u [25,27]. For both hysical functioning and bodily ain, clinically meaningful imrovement from baseline was observed by 1 month and seen throughout follow-u in five of seven measurements. Only one study [26] showed a clinically meaningful change in mental health, and no study showed a meaningful change in general health ercetions. Using EQ-5D to measure change in QOL from baseline to 12 months after ICU discharge, Badia et al. [36] found a significant increase in mobility, significant decreases in self-care and usual activities, and no significant change in ain/discomfort, anxiety/deression, or the visual analogue scale. Predictors of quality of life Seventeen studies investigated associations of atient age, severity of illness, admission tye, gender, or ICU length of stay with QOL in ICU survivors. Regarding age, a majority of studies found significantly lower hysical functioning (SF-36, Table 5), usual activities (EQ-5D, Table 6), and hysical or total QOL (SIP, Table 6) in older versus younger ICU survivors. No study found a significant association between age and mental health (SF-36), anxiety/deression (EQ-5D) or sychosocial QOL (SIP). Of six studies investigating severity of illness and QOL measured by SF-36, four (67%) found a significant association between severity of illness and lower hysical functioning or general health ercetions (Table 5). Similarly, both EQ-5D studies measuring usual activities and the one study measuring EQ-VAS found significant associations in these domains with severity of illness (Table 6). There was no significant association of severity of illness with the total QOL score in three of four studies using SIP (Table 6) and one study using NHP [38]. Five studies [19, 29, 36, 42,46] examined QOL in ICU survivors with medical versus surgical diagnoses. Only one study [19] found a significant difference in more than one QOL domain. In atients surviving trauma, three studies (100%) [36, 37,39] demonstrated significantly worse ain/discomfort on EQ-5D, comared with other ICU survivors, at 618 months after discharge. Six studies [19, 31, 36, 37, 42,44] evaluated survivors of elective versus emergency surgical rocedures. At 6 18 months after ICU discharge, three studies [19, 42,44] found no significant association between surgical status and overall QOL, and two [31,37] found that emergency surgical atients had significantly worse quality of life in a minority of domains. Two studies [31,36] evaluated changes in QOL over time. Badia et al. [36] observed significant imrovements from baseline to 12 months in four of five EQ-5D domains (mobility, usual activities, ain/discomfort, and anxiety/deression) among scheduled, but not unscheduled, surgical atients. Similarly, Vedio et al. [31] found that 76% of elective, vs. 31% of emergency, surgical atients reorted an imroved QOL from baseline after 6-months follow-u.

8 618 Of nine studies investigating associations between QOL and gender, only two studies [26,39] found a significant association of gender with any domain. Of eight studies investigating ICU length of stay, only one [23] found a significant association with any QOL domain. Discussion This systematic review of quality of life in 7,320 adult ICU survivors has three major findings. First, comared with the general oulation, ICU survivors have lower QOL for all domains (excet bodily ain) at baseline and at 6 months to 14 years after discharge. Second, QOL in ICU survivors imroves with over time after discharge, but this imrovement is not uniform across domains. At 612 months, clinically meaningful imrovements from re-admission baseline occur in six SF-36 domains; however, general health ercetions and mental health do not consistently demonstrate any clinically meaningful difference from baseline. Third, regarding redictors of QOL, older age and increased severity of illness may be associated with oorer hysical function and general health ercetions (severity of illness only), but are not consistently associated with decrements in other QOL domains. Lower QOL at baseline may exlain this finding. Wehler et al. [26] found that older atients, comared with younger atients, did not have a significantly worse change in QOL after discharge. Patient gender, ICU length of stay, and medical versus surgical diagnosis do not aear to be imortant redictors of QOL. Survival after trauma is associated with worse ain/discomfort, and elective surgical atients are more likely than emergency atients to imrove their QOL from re-admission values. Similarly, one excluded study of atients with rolonged ICU stay [47] found QOL at 6 months ost-discharge to be lowest in resiratory and trauma atients and highest in atients undergoing cardiac surgery. Our finding of high study quality contrasts with Heyland et al. s revious methodologic assessment [8]. However, we restricted our analysis to four secific QOL instruments and used different quality assessment criteria. In their review, Heyland et al. [8] noted that few QOL instruments have been adequately validated in ICU oulations; this remains true of EQ-5D and NHP, and reresents an imortant focus for future methodologic research. This systematic review has a number of methodologic limitations. First, in order to reduce heterogeneity between studies, we excluded QOL studies that examined only secific subsets of ICU survivors. QOL outcomes in these subsets may differ in imortant ways from general ICU oulations [19]. Thus, this systematic review cannot rovide a comrehensive icture of QOL in all atient grous. However, this review does rovide a general understanding of QOL after critical illness and serves as a foundation for comarison with future reviews of QOL in secific ICU atient subsets. Second, in this review, we evaluated only four QOL instruments commonly used in critical care research. The exclusion of Patrick s PQOL [15] and other instruments reduces the comrehensiveness of this review. However, our selection of QOL instruments allowed for greater comarability and more meaningful synthesis of study findings than would have been ossible under a more comrehensive review. Standardizing the instrument(s) used for QOL assessment in critical care research would enable more effective comarison between studies [1]. Third, scores for some QOL domains reflect a greater number of survey items, and are thus more recise, than other domains. For examle, on SF-36, hysical functioning reflects ten items, whereas social functioning reflects two items. A 5-oint difference on the latter domain may therefore be less meaningful than a 5-oint difference on the former. However, our findings generally addressed the most recise domains (i.e., hysical functioning, mental health, and general health ercetions on SF-36). Thus, we believe that our synthesized findings do not simly reflect recision differences between QOL domains. We caution, however, that distribution-based measures, such as statistical significance and 5-oint change, are roblematic in translating QOL changes into clinically meaningful terms [48]. Validation of instruments with anchor-based methods in ICU oulations is required to assist in making inference regarding clinically meaningful changes [48]. In addition to methodological concerns, our findings are limited by the infrequent collection of baseline data and inconsistent reorting methods among reviewed studies. Only five studies [2527, 32,36] examined QOL rior to ICU admission, and each demonstrated marked imairments in baseline QOL comared with the general oulation. As a result, it is difficult to determine whether QOL decrements at follow-u reflect the imact of critical illness or simly a lower baseline QOL. Baseline QOL measurement is needed to control for reexisting imairment, but is difficult to erform since it must be obtained retrosectively from the ICU survivor (subject to recall bias) or from his/her roxy (subject to measurement error). Prior studies [49,50] have found fair to good agreement between roxy and atient resonses on the SF-36. Further research comaring methods of estimating baseline QOL is needed to assist with future study design. Due to inconsistent reorting methods, we were unable to quantitatively synthesize results. QOL scores, even from the same instrument, were reorted in a heterogeneous fashion (e.g., absolute scores, z -scores, semiquantitative figures). Standardization of reorting methods for QOL scores, secifically reorting the mean score and standard deviation for each domain, would allow imroved comarison and synthesis of study findings.

9 619 In conclusion, our systematic review of 21 studies involving 7,320 atients demonstrates that ICU survivors reort a lower baseline (re-admission) quality of life that imroves over time in most domains, but remains lower than general oulation levels throughout long-term follow-u. In articular, hysical functioning shows raid imrovement and is associated with atient age and severity of illness, whereas mental health shows no imrovement and is indeendent of baseline characteristics. This synthesis rovides a general understanding of quality of life following critical illness and can serve as a standard of comarison for QOL studies in secific ICU suboulations. Acknowledgements This research is suorted by the National Institutes of Health (ALI SCCOR Grant # P050 HL ). Dr. Needham is suorted by Clinician-Scientist Awards from the Canadian Institutes of Health Research and the University of Toronto, and a Detweiler Fellowshi from the Royal College of Physicians and Surgeons of Canada References 1. Angus DC, Carlet J (2003) Surviving intensive care: a reort from the 2002 Brussels Roundtable. Intensive Care Med 29: Rubenfeld GD, Angus DC, Pinsky MR, Curtis JR, Connors AFJ, Bernard GR (1999) Outcomes research in critical care: results of the American Thoracic Society Critical Care Assembly Worksho on Outcomes Research. Am J Resir Crit Care Med 160: Hayes JA, Black NA, Jenkinson C, Young D, Rowan KM, Daly K, Ridley S (2000) Outcome measures for adult critical care: a systematic review. Health Technol Assess 4:24 4. Chaboyer W, Elliott D (2000) Healthrelated quality of life of ICU survivors: review of the literature. Intensive Crit Care Nurs 16: Buckley TA, Cheng AY, Gomersall CD (2001) Quality of life in long-term survivors of intensive care. Ann Acad Med Singaore 30: Niskanen M (1998) Quality of life after intensive care. Schweiz Med Wochenschr 128: Black NA, Jenkinson C, Hayes JA, Young D, Vella K, Rowan KM, Daly K, Ridley S (2001) Review of outcome measures used in adult critical care. Crit Care Med 29: : Heyland DK, Guyatt G, Cook DJ, Meade M, Junier E, Cronin L, Gafni A (1998) Frequency and methodologic rigor of quality-of-life assessments in the critical care literature. Crit Care Med 26: Rubenfeld G (2002) Looking beyond 28-day all-cause mortality. Crit Care 6: Parîzkovµ R, Cern V, Dostµ P, Vasµtko L, Hora P, Herold I, Novµk I, Nalos D (2001) Monitoring quality of life in critically ill atients: A multicenter study. Anesteziol Neodkladna Pece 12: Ware JE, Snow KK, Kosinski M, Gandek B (1993) SF-36 health survey: Manual and interretation guide. The Health Institute, Boston 12. The EuroQol Grou (1990) EuroQol a new facility for the measurement of health-related quality of life. Health Policy 16: Bergner M, Bobbitt RA, Carter WB, Gilson BS (1981) The Sickness Imact Profile: develoment and final revision of a health status measure. Med Care 19: Hunt SM, McKenna SP, McEwen J, Williams J, Ra E (1981) The Nottingham Health Profile: subjective health status and medical consultations. Soc Sci Med 15A: Patrick DL, Danis M, Southerland LI, Hong G (1988) Quality of life following intensive care. J Gen Intern Med 3: Fernandez RR, Cruz JJ, Vazquez Mata G (1996) Validation of a quality of life questionnaire for critically ill atients. Intensive Care Med 22: Tian ZM, Miranda DR (1995) Quality of life after intensive care with the sickness imact rofile. Intensive Care Med 21: Chrisin PS, Scotton H, Rogers J, Lloyd D, Ridley SA (1997) Short Form 36 in the intensive care unit: assessment of accetability, reliability and validity of the questionnaire. Anaesthesia 52: Hurel D, Loirat P, Saulnier F, Nicolas R, Brivet F (1997) Quality of life 6 months after intensive care: results of a rosective multicenter study using a generic health status scale and a satisfaction scale. Intensive Care Med 23: Dixon JJ (1997) Patient and relative satisfaction with intensive care, imortance of duration and quality of life. Clin Intensive Care 8: Berlin JA (1996) Randomized trial comaring masked/unmasked metaanalyses. In: Reort AHCPR Agency for Health Care Policy and Research, Rockville, MD, USA 22. Harris RP, Helfand M, Woolf SH, Lohr KN, Mulrow CD, Teutsch SM, Atkins D for the Methods Work Grou, Third US Preventive Services Task Force (2001) Current methods of the US Preventive Services Task Force: a review of the rocess. Am J Prev Med 20 [Sul 3]: Pettila V, Kaarlola A, Makelainen A (2000) Health-related quality of life of multile organ dysfunction atients one year after intensive care. Intensive Care Med 26: Kaarlola A, Pettila V, Kekki P (2003) Quality of life six years after intensive care. Intensive Care Med 29: Kleinell RM (2003) Exloring outcomes after critical illness in the elderly. Outcomes Manag 7: Wehler M, Geise A, Hadzionerovic D, Aljukic E, Reulbach U, Hahn EG, Strauss R (2003) Health-related qualityof-life of atients with multile organ dysfunction: individual changes and comarison with normative oulation. Crit Care Med 31: Graf J, Koch M, Dujardin R, Kersten A, Janssens U (2003) Health-related quality of life before, 1 month after, and 9 months after intensive care in medical cardiovascular and ulmonary atients. Crit Care Med 31: Eddleston JM, White P, Guthrie E (2000) Survival, morbidity, and quality of life after discharge from intensive care. Crit Care Med 28: Kvale R, Flaatten H (2003) Changes in health-related quality of life from 6 months to 2 years after discharge from intensive care. Health Qual Life Outcomes 1:2 30. Kvale R, Ulvik A, Flaaten H (2003) Follow-u after intensive care: a single center study. Intensive Care Med 29: Vedio AB, Chinn S, Warburton FG, Griffiths MP, Leach RM, Treacher DF (2000) Assessment of survival and quality of life after discharge from a teaching hosital general intensive care unit. Clin Intensive Care 11:3946

10 Ridley SA, Chrisin PS, Scotton H, Rogers J, Lloyd D (1997) Changes in quality of life after intensive care: comarison with normal data. Anaesthesia 52: Flaatten H, Kvale R (2001) Survival and quality of life 12 years after ICU. A comarison with the general Norwegian oulation. Intensive Care Med 27: Kvale R, Flaaten H (2002) Changes in intensive care from 1987 to 1997 has outcome imroved? A single centre study. Intensive Care Med 28: Chaboyer W, Foster M, Creamer J (2002) Health status of ICU survivors: a ilot study. Aust Crit Care 15: Badia X, Diaz-Prieto A, Gorriz MT, Herdman M, Torrado H, Farrero E, Cavanilles JM (2001) Using the Euro- Qol-5D to measure changes in quality of life 12 months after discharge from an intensive care unit. Intensive Care Med 27: Granja C, Teixeira-Pinto A, Costa- Pereira A (2002) Quality of life after intensive care evaluation with the EQ- 5D questionnaire. Intensive Care Med 28: Granja C, Dias C, Costa-Pereira A, Sarmento A (2004) Quality of life of survivors from severe sesis and setic shock may be similar to that of others who survive critical illness. Crit Care 8:R Garcia Lizana F, Peres Bota D, De Cubber M, Vincent JL (2003) Longterm outcome in ICU atients: what about quality of life? Intensive Care Med 29: Sznajder M, Aegerter P, Launois R, Merliere Y, Guidet B, CubRea (2001) A cost-effectiveness analysis of stays in intensive care units. Intensive Care Med 27: Miranda DR (1994) Quality of life after cardioulmonary resuscitation. Chest 106: Short TG, Buckley TA, Rowbottom MY, Wong E, Oh TE (1999) Long-term outcome and functional health status following intensive care in Hong Kong. Crit Care Med 27: Kleinell RM (1991) Quality of life of critically ill elderly atients. PhD thesis, University of Illinois at Chicago 44. Sage WM, Rosenthal MH, Silverman JF (1986) Is intensive care worth it? An assessment of inut and outcome for the critically ill. Crit Care Med 14: Frick S, Uehlinger DE, Zurcher Zenklusen RM (2002) Assessment of former ICU atients quality of life: comarison of different quality-of-life measures. Intensive Care Med 28: Bell D, Turin K (1994) Quality of life at three months following admission to intensive and coronary care units. Clin Intensive Care 5: Niskanen M, Ruokonen E, Takala J, Rissanen P, Kari A (1999) Quality of life after rolonged intensive care. Crit Care Med 27: Crosby RD, Kolotkin RL, Williams GR (2003) Defining clinically meaningful change in health-related quality of life. J Clin Eidemiol 56: Hofhuis J, Hautvast JL, Schrijvers AJ, Bakker J (2003) Quality of life on admission to the intensive care: can we query the relatives? Intensive Care Med 29: Rogers J, Ridley S, Chrisin P, Scotton H, Lloyd D (1997) Reliability of the next of kins estimates of critically ill atients quality of life. Anaesthesia 52: