The long‐term effects of prolonged intensive care stay postcardiac surgery

Short‐term outcomes for those with a prolonged length of stay (LOS) in intensive care (ITU) following cardiac surgery are poor, with higher rates of in‐hospital mortality and morbidity. Consequently, discharge from hospital has been considered the key measure of success. However, there has been a shift towards long‐term outcomes, functional recovery and quality of life (QoL) as measures of surgical quality. The aim of this review is to compare and critique the findings of multiple studies to determine the long‐term effects of prolonged ITU stay postcardiac surgery.

of stay (LOS) in intensive care (ITU). Prolonged ITU stay has been reported as occurring in 4% to 11% of cardiac patients 4 with other sources citing it to be as high as 36%. 5 This poses both clinical and ethical issues as a very small proportion of patients are consuming an extremely high level of both human and financial resources. Care of the critically ill requires a high level of expenditure of time, money and resources; this includes specialist staff, one to one nursing care and sophisticated equipment and treatments. 6 Critical care units across the UK are running at, or near full, capacity whilst also struggling with staffing shortages. 7  It is widely accepted that short-term outcomes for those with a prolonged LOS in ITU are poor, with higher rates of in-hospital mortality (10% vs 0.6%) and morbidity. 10,11 Additionally, both physical and cognitive impairments have been reported in those who have survived admission to an ICU, symptoms of which can persist for years following discharge, with more recent classification under the term 'post-intensive care syndrome' or PICS. 12 Postoperative delirium in intensive care is a common occurrence in cardiac surgery patients (26%-52%) 13 and there is evidence to suggest that those who experience delirium are at higher risk of long-term cognitive dysfunction. 14 This is compounded by the growing number of elderly patients undergoing surgery, with 37% of critically unwell adults over the age of 65 having pre-existing cognitive impairments such as dementia and depression. 14 PICS also encompasses physical impairments; muscle weakness as a result of critical care admission occurs in 40% of adult patients and in a small number of cases persists beyond discharge, resulting in poor functional ability and reduced quality of life. The mental health repercussions of ITU admission are perhaps the most marked, with 30% of patients experiencing depression, 70% anxiety and up to 50% demonstrating symptoms of posttraumatic stress disorder. 14 As a result of worse short-term clinical outcomes for patients with prolonged ITU stay, discharge from hospital was, until recently, considered the key measure of success. However, there has been a shift towards long-term outcomes, functional recovery and quality of life (QoL) as measures of surgical quality. There is now a body of primary research into long-term postoperative outcomes for cardiac patients with a focus on prolonged ICU stay, but it lacks consolidation. It is the aim of this review, therefore, to compare and critique the findings of multiple studies and provide an overview of the best available research on this topic to determine the long-term effects of prolonged ITU stay, and to inform and influence clinical practice in this area. Better understanding of the outcomes of this demographic of patients will also promote informed decision making for those considering cardiac surgery and allow clinicians to make more accurate decisions regarding treatment options, resource allocation and medical priorities. However to do so, greater understanding of prognosis, long-term survival and QoL is required.

| METHODS
A computerized literature search of CINAHL, EMBASE, and Google Scholar was conducted. Published articles for inclusion in the review were identified using the following keywords/search terms: "longterm effects" and "prolonged intensive care stay" or "ITU stay" or "prolonged ICU stay" and "cardiac surgery."

| Inclusion and exclusion
The search was refined by exclusion of any articles not written in English and any studies of pediatric patients. A timeframe of 2006 to 2020 was set to ensure that the reviewed evidence is relevant to current practice. The definition of 'prolonged' ITU stay varies widely in the literature, as such, abstracts were reviewed and only those defining prolonged stay as >2 days and ≤14 days were included to identify an adequate number of studies for review, whilst mitigating the effects of wider variations in this definition. After removal of duplicates and exclusion of papers that are not relevant because the participants were not adults and had not had cardiac surgery, this resulted in 12 papers (see Table 1: Summary of included papers) for inclusion in the review. A PRISMA flow diagram (see Figure 1) illustrates the results of the adopted process.

| Critical appraisal methods
The usage of a good quality critical appraisal tool allows a structured approach to the assessment of the rigor of the studies being reviewed. 23 The choice of an appropriate critical appraisal tool is considered to be an integral aspect of conducting a systematic review and of evidence-based practice. 24 Additionally, it is important to identify that, due to the wide variation in critical appraisal tools that are available, the quality of the evaluation that results from a review when using different tools will also vary, even when applied to the same literature. Design-specific tools are tailored to highlight potential methodological issues or bias that is unique to the study design; therefore The Critical Appraisal Skills Programme (CASP) tools for cohort studies (qualitative and quantitative) were chosen. CASP is a reputable organization whose tools are free and easy to access, making this review easily reproducible and minimizing the potential for varied evaluations of these pieces of literature.  commented that small trials, if well designed, can still produce reliable estimation of treatment effect; however this is in reference to RCTs which are designed to mitigate the effects of external variables and bias through randomization and blinding, which is not achievable in cohort studies.
Cohort studies are either prospective or retrospective in design; the most common approach amongst these pieces of literature was retrospective (employed in seven of the 12 studies). Retrospective cohort studies are less costly and less time consuming than prospective to conduct, but they are also more susceptible to bias. 26 First, with studies with lengthy follow-up periods of months to years, such as these, there is a risk of attrition bias that occurs from loss to follow-up through death, migration, late refusal to participate or losses that occur as a result of the exposure itself. 26  operatively, that is, more than 50% of participants were alive and non-institutionalized. However, although alive, it is not possible to ascertain whether they would have reported an acceptable QoL or whether they were highly dependent and requiring care. Analysis of long-term survival or mortality was found to be significant in all 12 studies; however those utilizing Karnofsky as a measure of QoL either did not include the statistical analysis in the published article 3 or the results were not statistically significant. 18 Lagercrantz et al 18 used the SF-36 in conjunction with Karnofsky as a QoL measure and the SF-36 results were found to be statistically significant. Length of follow-up was adequate for the assessment of long-term outcomes in all of the studies reviewed, ranging from 6 months to 10 years.
Although the way in which cardiac surgery is performed has not changed dramatically in the last decade, improvements to pre, intra and postoperative care continue to be made in a bid to improve outcomes, changes which may have influenced ICU practices and ultimate timing of patient discharge from ICU. In an effort to mitigate this bias, standard operating procedures and local policies were reported to have been followed. 5

| CONCLUSIONS AND IMPLICATIONS FOR CLINICAL PRACTICE
The findings demonstrate that long-term survival is worse for those who have experienced prolonged ICU LOS. 5,9,10,[18][19][20]22 Notably, mortality is highest in the first 6 months to 1 year postdischarge, indicating that more comprehensive follow-up and surveillance is required in this time. 5

| LIMITATIONS
There are limitations of this review that require acknowledgment.

KEY SUMMARY POINTS
• Long-term survival is worse for those who have experienced prolonged ITU stay (defined as LOS of >2 days and ≤14 days) postcardiac surgery.
• Mortality is highest in the first 6 months to 1 year postdischarge, therefore more frequent and comprehensive follow-up of these patients is required.
• The quality of evidence into QoL for patients with prolonged ITU stay postcardiac surgery is weak and further research is required.
• This review has been limited by a wide variation in definitions of prolonged ITU stay and a standardized definition is required in future research into the cardiac surgery population to ensure consistency and comparability of patient outcomes.

AUTHOR CONTRIBUTIONS
UM-S was responsible for designing the research question, for conducting the literature search, for article review, subsequent analysis, and for drafting of the paper. JL assisted throughout the process including the data analysis, drafting of the paper, and critical revisions leading to its final publication.