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Survival, Quality of Life, and Functional Status Following Prolonged ICU Stay in Cardiac Surgical Patients

A Systematic Review

Trivedi, Vatsal, MD1,2,3; Bleeker, Helena, MD2; Kantor, Navot, MD2; Visintini, Sarah, MLIS3; McIsaac, Daniel I., MD, MPH, FRCPC1,2,4,5; McDonald, Bernard, MD, PhD, FRCPC1,2,3

doi: 10.1097/CCM.0000000000003504
Online Review Articles

Objectives: Compared with noncardiac critical illness, critically ill postoperative cardiac surgical patients have different underlying pathophysiologies, are exposed to different processes of care, and thus may experience different outcome trajectories. Our objective was to systematically review the outcomes of cardiac surgical patients requiring prolonged intensive care with respect to survival, residential status, functional recovery, and quality of life in both hospital and long-term follow-up.

Data Sources: MEDLINE, Embase, CINAHL, Web of Science, and Dissertations and Theses Global up to July 21, 2017.

Study Selection: Studies were included if they assessed hospital or long-term survival and/or patient-centered outcomes in adult patients with prolonged ICU stays following major cardiac surgery. After screening 10,159 citations, 114 articles were reviewed in full; a final 34 articles met criteria for data extraction.

Data Extraction: Two reviewers independently extracted data and assessed risk of bias using the National Institutes of Health Quality Assessment Tool for Observational Studies. Extracted data included the used definition of prolonged ICU stay, number and characteristics of prolonged ICU stay patients, and any comparator short stay group, length of follow-up, hospital and long-term survival, residential status, patient-centered outcome measure used, and relevant score.

Data Synthesis: The definition of prolonged ICU stay varied from 2 days to greater than 14 days. Twenty-eight studies observed greater in-hospital mortality among all levels of prolonged ICU stay. Twenty-five studies observed greater long-term mortality among all levels of prolonged ICU stay. Multiple tools were used to assess patient-centered outcomes. Long-term health-related quality of life and function was equivalent or worse with prolonged ICU stay.

Conclusions: We found consistent evidence that patients with increases in ICU length of stay beyond 48 hours have significantly increasing risk of hospital and long-term mortality. The significant heterogeneity in exposure and outcome definitions leave us unable to precisely quantify the risk of prolonged ICU stay on mortality and patient-centered outcomes.

1Department of Anesthesiology and Pain Medicine, University of Ottawa, Ottawa, ON, Canada.

2Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.

3Division of Cardiac Anesthesiology, University of Ottawa Heart Institute, Ottawa, ON, Canada.

4Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.

5School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Supported, in part, by the University of Ottawa Department of Anesthesiology and Pain Medicine for provision of Distiller SR software.

The authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: bmcdonald@ottawaheart.ca

The majority of patients undergoing cardiac surgical procedures recover without significant postoperative morbidity. However, 5–10% of patients experience major morbidity and require prolonged ICU stays (PrLOS) (1 , 2). Although this proportion is similar to noncardiac critical care, critically ill postoperative cardiac surgical patients have different underlying pathophysiologies, are exposed to different processes of care (3), and thus may experience different outcome trajectories. PrLOS and the associated chronic critical illness not only consumes significant healthcare resources but also burden patients and their families; therefore, understanding the outcomes derived from these stays is crucial (2 , 4). In addition to survival, functional outcomes and quality of life have emerged as important patient-centered outcomes for this population (5). To our knowledge, there is no systematic review examining PrLOS and survival in cardiac surgical patients, whereas a recent review (6) examining the association between PrLOS and patient-centered outcomes had significant methodological limitations (e.g., a limited scope and search strategy, combining measures of quality of life with functional status, which are distinct, albeit-related outcomes). The objective of this systematic review was to synthesize the existing literature on the association between prolonged ICU length of stay after cardiac surgery and survival, functional status, and quality of life outcomes.

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METHODS

The protocol for this systematic review was registered with PROSPERO (CRD42017046535) and was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (7). We included all studies in adult patients 18 years old or older which reported prolonged ICU stay and any of the following outcomes: survival, functional outcomes, and health-related quality of life (HRQoL). Studies evaluating these outcomes in pediatric, pregnant, trauma patients requiring cardiac surgery or patients undergoing catheter-based cardiac procedures or extracorporeal membrane oxygenation were excluded.

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Search Strategy

The search was created and peer reviewed using the Peer Review of Electronic Search Strategies (PRESS) process (8). Publications were searched using a combination of key terms and index headings related to cardiac surgery, prolonged stay, and critical care (for full MEDLINE search strategy, see Appendix 1, Supplemental Digital Content 2, http://links.lww.com/CCM/E203). Searches were executed in MEDLINE (Ovid) (Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) 1946 to Present), Embase (Ovid) (1974 to July 21, 2017), CINAHL (Ebsco) (1981–Present), Web of Science (Thomson Reuters) and Dissertations & Theses Global (Proquest) (1957–Present). All publications indexed up to July 21, 2017 were reviewed. Duplicates were eliminated through systematic review software’s duplicate identification feature and manual inspection.

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Screening and Data Collection

Initial review of titles and abstracts was carried out by two authors for inclusion/exclusion (H.B., N.K.). Further evaluation for eligibility of each included study was carried out in duplicate by two of three authors (V.T., H.B., N.K.,). Any title or abstract rated as “include” or “unsure” by at least one reviewer was moved forward for full text review. At the full text and data extraction phase, disagreements were resolved by consensus or by tie break with a third author. Screening and data collection were completed using systematic review management software (DistillerSR by Evidence Partners, Ottawa, ON, Canada).

Data collected included author, year of publication, journal, country of origin, inclusion period definition of prolonged ICU stay, number of patients with prolonged stay and mean or median ICU stay in prolonged group, number of patients in comparator groups and mean or median stay in the comparator group, characteristics of included patients, and length of subsequent follow-up. Outcome data included in-hospital and long-term survival, institutional status, patient-centered outcome measure used, and relevant score, as well as identified risk factors for prolonged stay in the ICU. Risk of bias of individual studies was assessed by the National Institutes of Health (NIH) Quality Assessment Tool for Observational Studies. A narrative review of outcomes was performed as the heterogeneity of prolonged stay definitions, as well as variable outcome measures would preclude a formal meta-analysis.

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Survival

Both in hospital and long-term survival outcomes between PrLOS and non-PrLOS, patients were reviewed. For studies without published measures of association, crude odds ratios were calculated for in-hospital survival using reported data. Analysis of the crude data for survival was undertaken using Review Manager 5.3 (https://community.cochrane.org/help/tools-and-software/revman-5/revman-5-download), using a Mantel-Haenszel analysis and random-effects model. Long-term survival was defined as assessment of survival at any point following discharge from hospital.

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Patient-Centered Outcomes

We included any functional or HRQoL measure, including de novo scales devised by study authors, such as “Functional Survival”. Broadly, these tools were classified as HRQoL tools (e.g., Short Form [SF] 36, SF12, Nottingham Health Profile, Geriatric Depression Scale), self-reported functional tools (e.g., Karnofsky Performance Status, Barthel Index), objective functional tools (e.g., 6 min walk test), and institutional discharge status.

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RESULTS

Study Selection and Characteristics

Following the search, 10 159 studies were identified. Of these, 114 underwent full text review after title and abstract screening. Thirty-four studies met inclusion criteria. Reasons for exclusion are presented in Figure 1 (PRISMA diagram). Table 1 summarizes included studies.

TABLE 1

TABLE 1

Figure 1

Figure 1

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Definitions of Prolonged Length of Stay

Definitions of prolonged length of stay in the ICU were variable, ranging from greater than 2 days to greater than 14 days. The majority of studies defined prolonged length of stay as greater than 5 days (six studies), greater than 7 days (eight studies), or greater than 14 days (seven studies) in the ICU.

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Survival

Hospital survival was reported in 28 studies and ranged from 55% to 90% for those with prolonged ICU stay (1 , 9–18 , 20 , 22 , 24 , 26–31 , 33 , 34 , 37 , 25 , 21 , 36–38 , 40 , 41). Eighteen studies included non-PrLOS comparator groups (cardiac surgical patients undergoing the same surgical procedures with lengths of stay less than the cut-off employed in the study) in which hospital survival ranged between 87% and 99.2% (1 , 9–13 , 16 , 18 , 19 , 21 , 22 , 24–27 , 29 , 30 , 38). In these 18 studies, both adjusted (9 , 11 , 20 , 23 , 26 , 33) and unadjusted (1 , 10 , 13 , 14 , 18 , 22 , 28–31 , 34 , 40) analyses demonstrated that hospital survival was lower in PrLOS patients. There was significant heterogeneity in populations, exposures, and outcome definitions, and so patients were grouped by definitions of PrLOS (Fig. 2).

Figure 2

Figure 2

Twenty-five studies reported long-term survival outcomes at various stages ranging from 30 days to 6 years after discharge from hospital (1 , 9 , 12–20 , 22 , 23 , 28–31 , 21 , 25 , 38–41). Figure 3 displays unadjusted median survival for long-term follow-up. Compared with non-PrLOS, all follow-up periods reported significantly decreased survival in prolonged stay patients regardless of definition of prolonged stay. At the same follow-up intervals, a general trend of decreasing survival was identified with increasing ICU length of stay (Fig. 3). Eleven studies were published in the 10-year period between 1996 and 2006, whereas 14 studies were published in the 10-year period between 2007 and 2017. There was no difference in means of estimated 1-year survival between these two eras.

Figure 3

Figure 3

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HRQoL, Functional Status, and Institutional Status

Follow-up of Quality of Life and Functional Status.

Thirteen studies (13 , 17 , 20 , 22 , 23 , 31 , 37 , 34–37 , 25 , 21) reported follow-up quality of life and/or functional status of survivors leaving hospital. Of those, seven studies (17 , 20 , 22 , 23 , 37 , 35 , 37) had prospectively scheduled follow-up clinical visits; with the exception of the study of Niskanen et al (32) which had a follow-up rate of 78% at 6-month visit, all of these had no loss to follow-up in hospital survivors who remained alive at 1 year. Six studies had a retrospective cross-sectional follow-up design where telephone and/or mail contact was attempted at varying points from the patients’ critical illness events (13 , 31 , 34 , 36 , 25 , 21). For these studies, mean follow-up times ranged from 1.9 years (36) to 5.0 years (21 , 25), whereas response rates among known survivors at the chosen follow-up time-point ranged from 44.1% (25) to 90.8% (34).

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HRQoL.

Multiple tools were used to assess HRQoL following discharge from hospital. These included SF36 (four studies), SF12 (two studies), Nottingham Health Profile (two studies), Geriatric Depression Scale (one study), and the Hospital Anxiety and Depression Scale (one study). Studies using SF12 or SF36 reported equal (25 , 37) or lower scores (31 , 35 , 36) for PrLOS patients where either a contemporary cohort of cardiac surgical patients matched by age, gender, and surgical procedure but not experiencing PrLOS (31 , 35 , 37) or age- and gender-matched general population norms were used as comparator (25 , 36). In these three studies reporting lower SF36 scores (31 , 35 , 36), the difference appeared to lie in the physical component summary scores, whereas the mental component scores between PrLOS patients and the comparison group were equivalent. In two studies employing the Nottingham Health Profile, Hellgren et al (31) reported PrLOS patients experiencing more difficulties with all domains except sleep and emotional scores compared with contemporary matched (age, sex, and cardiac surgical procedure) controls, whereas Niskanen et al (37) reported no difference between PrLOS patients and population norms. Long-term occurrence of depression was higher in patients with PrLOS compared with non-PrLOS (34). Table 2 summarizes major findings of these studies.

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Self-Reported Functional Status.

Eight studies included tools with self-reported functional status measures such as the Karnofsky Performance Status (three studies), Barthel Index (two studies), Duke Activity Status Index (one study), Katz Activities of Daily Living (ADL) (one study), and an independently created “Functional Scale” (one study). Two studies using the Karnofsky Performance Status reported a small minority of patients as having functional impairment requiring significant assistance (13 , 36), whereas Gaudino et al (23) reported that the majority of PrLOS survivors required considerable assistance. In each of the two studies employing the Barthel Index (34 , 37), and in one study using the Katz index (22), severe impairment in ADLs ranged from 6.3% to 11.1% of PrLOS survivors, whereas Wahl et al (17) reported 20.5% occurrence of moderate disability. Finally, in Bashour et al (20), PrLOS patients reported a median Duke Activity Status Index score equivalent to six metabolic equivalents, corresponding to an ability to undertake moderate physical activity such as brisk walking. Table 2 summarizes major findings of these studies.

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Residency Status.

Two studies assessed residency status using administrative databases which captured institutionalized care at 5 years (1 , 40). PrLOS patients were more likely to be living within institutions; however, the majority of patients continued to reside outside of institutionalized care: 92% versus 81% for non-PrLOS and PrLOS, respectively, at 1 year following discharge (40). Two other studies reported the majority of patients continuing to reside at home at 1- and 2-year follow-up periods: 87% and 60%, respectively (22 , 37). Table 2 summarizes major findings of these studies.

TABLE 2

TABLE 2

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Risk of Bias Assessment

The quality of all included studies was evaluated using the NIH Quality Assessment Tool for Observational Studies. Using this tool, 18 of the 34 included studies were rated as “Good”, 10 studies were rated as “Fair”, and six studies were rated as “Poor”. The most common risk of bias among all studies was lack of justification for sample sizes, variance, or effect estimates. Other sources of bias included lack of measure for different levels of exposure (i.e., different levels of PrLOS), as well as if assessors were blinded to exposure status before rating outcomes. Further detailed analysis of risk of bias for individual studies is available in Supplemental Table 1 (Supplemental Digital Content 1, http://links.lww.com/CCM/E120).

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DISCUSSION

This systematic review was undertaken to inform patients, families, and clinicians of likelihood of survival and expected long-term quality of health and functional status when faced with major morbidity requiring prolonged critical care after cardiac surgery. We have demonstrated that patients with PrLOS after cardiac surgery experience decreased hospital and long-term survival. This risk may persist for up to 6 years post discharge. Importantly, this effect was maintained despite variations in study demographics: year of publication, country of study, and types of cardiac surgery. Not surprisingly, there appears to be a dose-response relationship: as the definitions for PrLOS increased in number of days, more studies reported lower hospital survival. However, a formal meta-analysis that could quantify this relationship could not be performed due to the significant heterogeneity in populations and exposure definitions.

Beyond survival, patient-centered outcomes were assessed using HRQoL and functional status measures. Although related, these are two distinct entities. HRQoL measures typically have a physical function component but also capture emotional, physical, and pain-related aspects of well-being, whereas functional measures typically quantify specific aspects of function, such as walking capacity or capacity for self-care and independent living. In this review, both HRQoL and self-reported functional status were reported using multiple tools across varying follow-up times. Patients with PrLOS demonstrated either equivalent or worse HRQoL when compared with patients with non-PrLOS. In general, any differences in long-term HRQoL attributable to PrLOS appear to lie within the physical health but not the mental health domains. However, even in those studies where differences in HRQoL were measured between PrLOS survivors and a comparator group (31 , 35 , 36), the difference in mean scores tended to be small (< 5 points for SF-36) and it is debatable whether score differences in this range are clinically important (40).

When assessing self-reported functional status, the majority of studies indicated that despite impairments when compared with non-PrLOS patients, the majority of those who survive their hospital stay report good functional status when assessing their ability to complete activities. This was largely supportive of a previous smaller review that evaluated functional outcomes in patients with prolonged length of stay following cardiac surgery (6). This generally good functional status appears to be confirmed by the fact that the majority of PrLOS survivors lived outside of institutionalized care

Taken together, these findings suggest that most cardiac surgical patients who survive long-term after PrLOS have acceptable daily functional independence, small decreases in the physical aspects of HRQoL, and the majority are not living within institutionalized care. However, this inference must be tempered by the limitations of this systematic review. First, the observational design of these studies leads to bias including that of competing risks. PrLOS patients who survive their hospitalization but who die prior to any long-term assessment may have had very poor quality of life that has gone unreported. For example, in the study of Langercrantz et al (36) with a cross-sectional design resulting in a mean follow-up time of 1.9 years, approximately 14% of PrLOS patients who survived their hospitalization would have died prior to any assessment. Furthermore, survivors with lower HRQoL and functional disabilities may be less able or inclined to participate in long-term follow-up, for example, Langercrantz et al (36) had a response rate of 73% for HRQoL assessment. The significant heterogeneity in exposure and outcome definitions leave us unable to precisely quantify the risk of PrLOS on mortality and patient-centered outcomes. Although the inclusion of studies from different jurisdiction and healthcare systems supports generalizability, unmeasured heterogeneity around processes of care and decision-making could also bias results.

Although our review identified several tools used to assess survivors’ HRQoL and functional outcomes, there was an absence of disease-specific tools that may be relevant to cardiac surgical patients (41). This is highlighted by the leading cause of death in PrLOS patients who survived their hospitalization as cardiac in origin (23 , 36). The absence of these tools in the current literature suggests that future research should include disease-specific measures in addition to generic HRQoL measures. Although generic measures allow comparison of health states across different medical conditions as well as comparative cost-effectiveness analyses, disease-specific tools may be better suited to identify specific symptoms and their unique impact within a single condition (42). Ultimately, data from both types of instruments are needed to support high-quality decision-making. There was also an absence of studies adjusting for preoperative quality of life, which often serves as an indication for surgical intervention and a metric for success. This underscores a previous report of quality of life in cardiac surgery where preoperative status and relative changes postoperatively were under researched (43). Finally, given the special importance of postoperative stroke and delirium in cardiac surgical patients as drivers of PrLOS and perioperative mortality (44 , 45) and their associations with long-term psychiatric sequelae of anxiety, depression, and posttraumatic stress disorder (PTSD) (46), it is surprising that only two studies employed tools to specifically evaluate these former two domains (31 , 34), whereas no study concerned itself with PTSD.

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CONCLUSIONS

Although there is considerable variation in the definition of PrLOS following cardiac surgery, we found consistent evidence that patients with increases in ICU length of stay beyond 48 hours have significantly increasing risk of hospital and long-term mortality. The significant heterogeneity in exposure and outcome definitions leave us unable to precisely quantify the risk of PrLOS on mortality and patient-centered outcomes.

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ACKNOWLEDGMENTS

We would like to thank Sascha Davis, MLIS (Library, The Ottawa Hospital, Civic Campus), for peer review of our MEDLINE search strategy.

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      Keywords:

      cardiac surgery; chronic critical illness; functional outcomes; mortality; quality of life

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