Advertisement
Browse Subject Areas
?

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here.

  • Loading metrics

Open Access

Study Protocol

Incidence and factors associated with post-intensive care syndrome among caregivers of intensive care unit survivors: Protocol for a cohort study

Abstract

Background

During the last decades, intensive care unit (ICU) mortality rates have significantly decreased but this progress has come with unintended consequences for patients and their caregivers. The adverse health-related effects observed in caregivers during the post-ICU period are referred to as Post-Intensive Care Syndrome-Family (PICS-F). Despite growing awareness of PICS-F, the long-term challenges faced by caregivers of ICU patients are not well characterized with several gaps in knowledge remaining unaddressed. The proposed study aims to determine the incidence of PICS-F impairments and identify associated factors among caregivers of ICU survivors.

Methods

We plan to conduct a longitudinal prospective cohort study involving 175 caregivers of ICU patients admitted to a public hospital in Chile. Data will be collected during ICU admission, after ICU discharge, 3 months and 6 months after hospital discharge. Questionnaires will evaluate caregivers’ psychological, physical and cognitive outcomes and perceived social support, resilience, family satisfaction and caregiver burden. Factors associated with PICS-F impairments will be explored using generalised linear mixed models.

Discussion

The current understanding of PICS-F is limited, particularly regarding the risk and protective factors associated with the syndrome among caregivers of ICU survivors. This study will contribute to addressing this gap by providing novel data about PICS-F and exploring previously unexamined factors linked to PICS-F such as family satisfaction, psychological buffers and caregiver burden.

Trial Registration

Clinicaltrials.gov: NCT05827354. Registered on 25 April 2023.

Citation: Padilla-Fortunatti C, Rojas-Silva N, Cortes-Maripangue S, Palmeiro-Silva Y, Rojas-Jara V, Nilo-Gonzalez V, et al. (2025) Incidence and factors associated with post-intensive care syndrome among caregivers of intensive care unit survivors: Protocol for a cohort study. PLoS One 20(5): e0324013. https://doi.org/10.1371/journal.pone.0324013

Editor: Jean Baptiste Lascarrou, CHU Nantes, FRANCE

Received: February 4, 2025; Accepted: April 16, 2025; Published: May 16, 2025

Copyright: © 2025 Padilla-Fortunatti et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: No datasets were generated or analysed during the current study. All relevant data from this study will be made available upon study completion.

Funding: CPF was supported by the Chilean National Agency for Research and Development (ANID) through the FONDECYT Iniciación Grant N° 11230203. https://anid.cl/proyectos-de-investigacion/fondecyt-iniciacion/ The funders had no role in study design, data collection, analyses, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Introduction

The sickest patients in a hospital setting are often treated in the intensive care unit (ICU). The advances in the care of ICU patients over the last two decades have significantly decreased in-hospital mortality rates [1]. However, ICU survivors often exhibit cognitive, psychological and physical sequelae, leading to significant disability, frailty and increasing dependence on their caregivers [2,3], posing a new challenge for critical care medicine and public health [4]. Admission to an ICU is often a stressful and overwhelming experience for caregivers [5,6] due to the sudden onset of the critical illness, the risk of death of the patient and the adoption of a substitute decision-making role [7,8].

In 2010, the Society of Critical Care Medicine coined the term Post-Intensive Care Syndrome (PICS) to describe any ‘new or worsening impairment in physical, cognitive, or mental health status arising and persisting after hospitalization for critical illness’ to raise awareness regarding the long-term sequelae of critically ill patients [9]. An estimated 50%–70% of ICU survivors are affected by PICS [10]. The Post-Intensive Care Syndrome–Family (PICS-F) is an extension of this concept, referring to the psychological consequences that may arise after an ICU stay among caregivers [11]. However, there is limited evidence regarding the physical or cognitive impairments among caregivers of ICU survivors. PICS and PICS-F are now recognized as a public health burden with substantial associated costs [2,12]. Despite the increased awareness of PICS-F, there is a paucity of studies involving caregivers of Chilean ICU patients. Moreover, most studies have focused on describing the incidence of PICS-F, while the PICS-F-related factors are not well characterized.

Background

PICS-F psychological impairments

Psychological sequelae are the most frequently reported burden within PICS-F [13], with caregivers of ICU patients experiencing significant psychological distress in terms of anxiety (42%–80%), depressive symptoms (16%–90%) and symptoms of post-traumatic stress disorder (PTSD) (57%) during admission and lasting even 12 months after ICU discharge [14]. A systematic review found a wide variability in the reported incidence of anxiety (4%–94%), depressive symptoms (2%–80%) and PTSD symptoms (3%–62%) among caregivers of ICU survivors [15]. A longitudinal study with assessments at 1, 3, 6 and 12 months after ICU admission found an initial high prevalence of PTSD symptoms (36.3%) which decreased over time (24.5%, 21.5%) but increased in the last evaluation (23.6%), respectively [16]. Another longitudinal study found high levels of PTSD symptoms in 54% of caregivers with a trend to reduce during 6 months after ICU discharge [17].

During the COVID-19 pandemic, Azoulay et al. [18] reported a higher prevalence of anxiety (41% vs 34%), depressive (31% vs 18%) and PTSD (35% vs 19%) symptoms among caregivers of COVID-19 patients at 3 months after ICU discharge compared to their non-COVID-19 counterparts. Another multicenter study exploring psychological distress among caregivers of COVID-19 survivors at 3 months after ICU discharge reported anxiety, depressive and PTSD symptoms rates of 31.6%, 28.3% and 29.6%, respectively [19]. Overall, the variability in the prevalence of PICS-F psychological impairments could be attributed to the diversity of questionnaires used, cut-off values for various parameters and the timing of the assessment. Despite this heterogeneity, the prevalence of PICS-F psychological impairments among caregivers of ICU patients remains higher than the general population [15], including the Chilean population during the COVID-19 pandemic [20].

PICS-F physical & cognitive impairments

Although not included in the original conceptualization of PICS-F [11], there are reports of physical impairments among caregivers of ICU patients. For instance, a study found a significant decline in the physical health of caregivers 6 months after hospital discharge [21]. Similarly, clinically significant fatigue was observed in 43%–53% of caregivers 4 months after hospital discharge, including worsening depressive symptoms, health risk behaviours, burden and sleep quality [22]. In the study by Fumis et al. [7], caregivers showed a decline in physical health one month after ICU discharge with a return to baseline levels at 3 months. Other studies have shown mixed results with a small trend of minimal changes in the physical health of caregivers of ICU patients [23,24].

To the best of our knowledge, there is a lack of studies exploring the potential impact of critical illness on caregivers’ cognitive function. Significant cognitive impairment is unlikely to be observed among caregivers during ICU admission since they must assume a surrogate decision-making role and frequently communicate with the ICU team [9]. Moreover, after hospital discharge, caregiving tasks are unlikely to be assumed by caregivers with relevant cognitive impairment. However, chronic exposure to psychological stress is associated with poorer cognitive function and an accelerated cognitive decline [25]. Considering the high prevalence and incidence of psychological impairments among caregivers of ICU patients, some form of cognitive impairment may be present, particularly in older caregivers.

thumbnail
Download:
Fig 1. Modified version of the Caregiving Stress Model for Post Intensive Care Syndrome – Family impairments.

https://doi.org/10.1371/journal.pone.0324013.g001

Factors associated with PICS-F

Most studies have explored variables influencing PICS-F psychological impairment [13] with caregiver-related factors being younger age, female gender, lower educational level, relationship to the patient, lower financial status, history of anxiety and depression, rural residence and ethnicity [11,15]. Besides, being in a decision-making position, poor communication with the ICU healthcare team, lower educational level and having a loved one who was close to death are associated with psychological PICS-F [2]. Patient-related variables associated with PICS-F psychological impairment include severity of illness, prolonged ICU stay, older age, hospital readmission and patient disposition at discharge (e.g., home vs assisted care facility) [15]. Data on risk factors impacting physical or cognitive PICS-F impairments is scarce, with discharge to home (vs care facility) shown to be associated with significant fatigue 4 months after ICU discharge [22].

Theoretical framework

To provide a conceptual organization of the current and potential variables that may influence known (psychological) and potential (physical and cognitive) PICS-F impairments, this study will employ an adapted version of Pearlin’s Caregiver Stress Model (CSM) [26]. In brief, the CSM aims to explain the occurrence of negative outcomes among caregivers (e.g., depression, anxiety and cognitive disturbances) based on the interaction of the background and contextual factors (caregiver and patient-related), primary stressors (objective and subjective indicators) and secondary strains (role and intrapsychic). Besides, the relationships between the CSM elements are influenced by psychosocial resources (coping or social support) [26]. In this study, the modified version of the CSM model for PICS-F impairments is presented in Fig 1.

The negative outcomes will be PICS-F impairments (psychological, physical or cognitive) influenced by contextual factors and primary stressors (psychological, physical and cognitive) experienced by caregivers during ICU stay and after hospital discharge. Secondary stressors can contribute to PICS-F impairments either during the ICU stay (family satisfaction) or after hospital discharge (caregiver burden). In both scenarios, psychosocial resources (social support and resilience) may buffer primary and secondary stressors and outcomes.

Psychosocial resources

Literature pertaining to PICS-F is focused on caregivers’ psychological distress [14,15] which is described as the emotional suffering product of the imbalance between stressors and psychosocial resources [27]. Described as stress buffers or protective factors, psychosocial resources such as perceived social support, resilience or coping styles have been widely studied among caregivers of different populations [28,29] but to a lesser extent among caregivers of ICU survivors [15,30]. Perceived social support (PSS) refers to the perception of the availability of different types of resources (e.g., instrumental, psychological, informational) from the subject’s close social networks such as family or friends [31]. The few studies that have explored PSS among caregivers of ICU patients have yielded heterogeneous results. During the ICU stay, PSS showed a negative association with anxiety [32,33] and depressive symptoms [33]. In another study, PSS showed no buffer effect on perceived stress or fatigue severity [34]. Caregivers with higher PSS were found to have lower depression levels and higher psychological well-being one year after ICU discharge [23]. In the study of Azoulay et al. [18], caregivers with higher social support showed a lower risk of PTSD symptoms 3 months after ICU discharge. Conversely, a study conducted in Australia found no association between PSS and caregiver burden or self-efficacy three months after hospital discharge [35].

Resilient individuals often use different coping strategies (e.g., positive appraisal, benefit finding) to manage negative emotions related to stress [36]. Caregivers of ICU patients with high resilience may have increased mental strength that improves their ability to recover after difficulties such as the patient´s critical illness [37]. In a study of 171 caregivers, resilient caregivers exhibited fewer symptoms of anxiety, depression or PTSD during their ICU stay [38]. Similarly, another study identified resilience as a protective factor against psychological distress at ICU discharge [33]. To date, only one study has explored resilience in the post-ICU period, showing that resilient caregivers experience fewer symptoms of anxiety, depression, PTSD and caregiver burden [39].

Family satisfaction

During a patient’s ICU stay, caregivers have specific needs that impact their experiences of the patient’s critical illness [5]. Family satisfaction (FS) refers to the extent to which healthcare providers meet these needs and expectations [40]. FS encompasses key aspects of the ICU experience such as communication with healthcare providers, emotional support, proximity to the patient, ICU environment, decision-making involvement and nursing care of the patient [41]. FS may influence post-ICU outcomes such as the psychological dimension of the PICS-F. In a small-scale study, FS and communication with ICU staff showed a negative association with depressive and PTSD symptoms 2 months after ICU discharge [42]. Likewise, low levels of FS during ICU stay were associated with higher levels of anxiety, depression and PTSD symptoms 3 months after hospital discharge [43]. Higher FS with care and decision-making involvement were found to be associated with a lower risk of depression 3 months after ICU admission [44]. Although the role of FS in other PICS-F impairments (e.g., physical, cognitive) is unclear, meeting the needs of caregivers during and after their stay in the ICU may decrease the negative impact of PICS-F [45].

Caregiver burden

Up to 80% of the ICU caregivers become informal caregivers after the patient’s hospital discharge [45,46]. Caregiving is often described as a stressful process that can lead to a multidimensional burden. Caregiver burden (CB) comprises the physical, psychological, social and financial problems associated with the care of an impaired person [47]. CB has been extensively studied in caregivers of patients with different conditions [48] but to a lesser extent in caregivers of ICU survivors. During the ICU stay, caregivers often assume a partial caregiving role such as providing emotional support or surrogate decision-making [11]. However, after hospital discharge, frailty and dependency may arise leading to an increase in caregiving tasks [14].

In a study, 16% of caregivers experienced a high CB and the high CB was associated with anxiety and depressive symptoms [49]. In another study, 53% of caregivers experienced high CB with a positive association with symptoms of anxiety, depression and PTSD as well as sleep disturbances and poor quality of life [50]. Comini et al. [51] reported a high proportion of caregivers with critical levels of burden. Remarkably, although survivors’ global condition improved 6 months after discharge, caregiver strain remained high and the percentage of caregivers needing support tended to increase. Another study found a positive association between CB and depressive symptoms 3 months after ICU admission [52]. In addition, a higher CB was shown to be associated with worse mental health and an elevated risk of psychological symptoms 3 months after ICU discharge [53]. Although the association between CB and PICS-F psychological impairment among caregivers of ICU survivors has been reported, the relationship with caregiver-related variables measured during ICU stay (e.g., psychological distress) remains unclear. Furthermore, a study of the potential association between CB and PICS-F physical and cognitive impairments is warranted due to the conceptual overlap between CB and PICS-F.

Materials and methods

Aims, design, and setting

The primary aim of this study is to determine the incidence of PICS-F impairments (psychological, physical and cognitive) among caregivers of ICU survivors of a public hospital in Chile. A secondary aim is to identify factors during ICU stay and after hospital discharge, associated with the PICS-F impairments. To achieve these aims, a prospective analytical cohort study will collect data from ICU caregivers between the 3rd and 10th day of ICU admission (T1), after ICU discharge (T2) and 3 months (T3) and 6 months (T4) after hospital discharge. This study will follow the STROBE guidelines for reporting observational cohort studies [54].

The study will be conducted in a polyvalent 24-bed adult ICU belonging to the second largest high-complexity public hospital in the Southeast area in Santiago, Chile, with around 400 beds available. The ICU’s visiting policy allows for a 1–2-hour daily visit with flexibility in exceptional cases. Concerning ICU personnel composition, the nurse-to-patient ratio is 1:3 while the medical staff is composed of 4 residents a day plus 3 senior ICU physicians. Daily updates regarding the patient´s condition are provided to the responsible family member (caregiver) by residents during visiting hours but in complex cases (e.g., end of life) a senior ICU physician is involved. Regarding other professionals, physiotherapists are available as well as a social worker who performs mostly administrative tasks related to family members.

Inclusion and exclusion criteria

All adult caregivers identified as a patient’s representative and likely to become responsible for providing direct or indirect care after hospital discharge will be eligible for inclusion. In addition, the inclusion criteria for patients will be as follows: age > 18 years; ICU length of stay between 3 and 10 days; and receiving positive pressure respiratory support. Caregivers of ICU patients with an impending death risk or likely to be discharged from the ICU will be excluded. Caregivers will be withdrawn from the study if the patient dies at any point during the study and no further data will be collected.

Sample size and power

Sample size was calculated based on the primary aim of estimating the incidence of PICS-F impairments. We aimed for a precision level (e) of 5% (representing the half-width of the 95% confidence interval) around the expected incidence estimate. Due to the lack of studies utilizing identical questionnaires and cut-off values in a comparable population, we conservatively used an expected incidence (P) of 20% of PTSD symptoms reported by Heesakkers et al. [19]. Using a 95% confidence level (corresponding to Z = 1.96, alpha = 5%), the required sample size was calculated using the formula: n = [Z² * P * (1-P)]/ e², where P is the expected true proportion in the population and e is the desired precision level. Consequently, the initial sample size required was 247 caregivers.

Then, the estimated total population of eligible subjects that could meet our inclusion criteria before the projected recruitment start was approximately 600 caregivers. Then, the initial sample size of 247 represented 41.2% of this estimated finite population, exceeding the commonly used threshold of 5–10%. Consequently, a finite population correction was applied using the formula [55]: Adjusted n = (finite population * initial sample size)/ (finite population + initial sample size). Thus, the adjusted sample size will be 175 caregivers. However, factoring in a potential 40% attrition rate reported in the literature [53,56], 292 caregivers will be targeted for enrolment.

Study timeline and variables

Relevant sociodemographic variables of caregivers plus demographic and clinical data of the patients will be collected at each time point. Also, patients’ demographic and clinical data will be acquired from their medical charts. The schedule presented in Fig 2 describes the timeline of enrolment and assessments.

thumbnail
Download:
Fig 2. SPIRIT schedule: Timeline of recruitment and assessment. t0: Daily screening; t1: Between the 3rd and 10th day of ICU admission; t2: Near after ICU discharge; t3: 3 months after hospital discharge; t4: 6 months after hospital discharge.

Abbreviations: ICU Intensive Care Unit; MHA: Mental Health Antecedents; PHQ-4: Patient Health Questionnaire – 4; IES – 6: Impact of Event Scale – 6; SF – 36 Vt: Short Form Health Survey – 36 Vitality; MEFO: Memory, Fluency, and Orientation; mMOS – SSS: Modified Medical Outcomes Study Social Support Survey; BRCS: Brief Resilient Coping Scale; Family Satisfaction with Care in the Intensive Care Unit – 24; ZBI: Zarit Burden Interview; BI: Barthel Index. * Will be completed by the caregiver at t1 regarding the patient’s functional independence status before ICU admission. At t2, t3, and t4 it will be applied regarding the current patient status.

https://doi.org/10.1371/journal.pone.0324013.g002

Questionnaires

At each time point, a set of different validated screening questionnaires (Table 1) will be used to explore the incidence of each PICS-F impairment and the role of psychosocial resources, family satisfaction and caregiver burden.

thumbnail
Download:
Table 1. Questionnaire description.

https://doi.org/10.1371/journal.pone.0324013.t001

Data collection and management

A dual (patient/caregiver) screening process will be conducted daily by a collaborating ICU nurse to confirm eligibility based on inclusion/exclusion criteria. During visiting hours, a research assistant will assess caregivers´ eligibility and approach them if they appear emotionally stable. If interested, caregivers will sign the consent form and complete the initial survey (T1), either in person or by phone. Subsequent data collection (T2, T3, T4) will be performed via phone calls. Participant caregivers will be financially compensated for their time spent filling out the questionnaires at T2 and T4.

Caregiver and patient-related data will be anonymized to ensure privacy. Each participant will be assigned a unique identifier to prevent the identification of personal or questionnaire response data. All information will be kept safe in a password-protected database, and access will be granted to the study team. Data monitoring and auditing will be performed by the principal investigator and study coordinator.

Outcomes and statistical analyses

Descriptive statistics will include summary statistics and plots to explore and characterize data. Normally distributed continuous variables will be reported as mean ± standard deviation and non-normally distributed variables as median (interquartile range). Categorical variables will be reported as frequency (percentage). For each questionnaire, internal consistency will be assessed by calculating Cronbach’s alpha.

To determine the incidence of each PICS-F impairment, four dichotomous dependent variables will be defined: psychological (PHQ-4 ≥ 6 or IES-6 ≥ 1.75), physical (SF-36 VT < 45) and cognitive (MEFO < 9) impairments at T3 and T4. Subjects scoring above or below the respective cut-off value will be categorized as having PICS-F in their respective impairment at T3 and/or T4. The number of subjects showing a given PICS-F impairment will be divided by the total number of subjects at T3 and T4. Then, bivariate and multivariate analyses will be conducted to identify factors associated with PICS-F impairments. For the multivariate generalised linear mixed models (GLMMs), variable selection will be guided by established theoretical frameworks, prior literature findings, and clinical relevance. To further enhance model robustness, prevent overfitting, and handle potential multicollinearity, we will consider employing penalised regression techniques, such as LASSO (Least Absolute Shrinkage and Selection Operator) or elastic net, within the GLMM framework.

Longitudinal analysis will be performed to identify variables associated with the PICS-F impairments over time. First, graphical methods, such as panel line plots, will be used to visualize the trend and inter-subject and intra-subject variation over time. This analysis will be useful for determining important covariates and the regression models to be included and applied afterwards. Second, the strength of the outcome correlation should be defined to decide the regression methods. In this scenario and considering the nature of the outcome, generalized linear mixed models (GLMM) will be used [73,74]. Contextual factors (caregiver and patient variables) of each participant will be considered fixed effects, but random effects will be included because of the expected variation in the outcome at each time point and for each subject. Given that the outcomes are measured as a dichotomous variable, the family will be binomial and the link function is expected to be logit. Then, model building will consider the main effects and interactions based on theoretical models, which will be evaluated through Akaike Information Criterion or Bayesian Information Criterion. The initial models proposed for this study are presented in Table 2.

thumbnail
Download:
Table 2. Variables and generalized linear mixed models to explore PICS-F impairments.

https://doi.org/10.1371/journal.pone.0324013.t002

Then, if FS or CB is significantly associated with any of PICS-F impairments at T3 and/or T4, GLMM with and without the selected secondary stressor will be fitted to analyse the extent of this association. First, FS measured at T1 will be added to models 1–4 while the FS measured at T2 will be included in models 5–8. Similarly, CB measured at T3 will be included in models 9–20 while the T4 measure of CB will be added to models 17–20. The original model without a secondary stressor will be contrasted with the same model plus the secondary stressor (either FS or CB). Also, 95% confidence intervals will be reported and a p < 0.05 will be considered statistically significant. All statistical analyses will be conducted in R, using the applicable packages [75].

Missing data

Given the longitudinal study design, some missing data is anticipated. Missing data patterns will be examined to determine if they are missing at random or not missing at random. Depending on the result, appropriate models for estimation will be applied (i.e., selection or pattern mixture models or predictive mean matching) and sensitivity analyses will be conducted.

Ethical considerations

This study will comply with the principles of the Helsinki [76] and Singapore Declarations [77]. Ethical approval for this study was obtained from the Health Sciences Ethics and Scientific Committee at the Pontificia Universidad Catolica de Chile (April 2023) and Southeast Metropolitan Health Service (June 2023). All participating caregivers will sign in-person the informed consent form. Ethics Committees have waived informed consent for acquiring patient-related data from medical charts. Changes to the study protocol and/or the informed consent form will be sent to respective ethics committees as protocol amendments (S1-S2 Appendix).

Status of study

Recruitment of participants began on June 30, 2023. As of January 23, 2025, 223 participants had been enrolled, completing baseline measures and planned follow-ups whenever they proceed. Participant recruitment is expected to conclude around June 2025.

Discussion

The decline in ICU mortality rates over recent decades has led to a growing focus on PICS, with researchers highlighting several challenges for healthcare systems and society, particularly for caregivers of critical illness survivors. Nonetheless, the long-term issues faced by caregivers of ICU patients, including PICS-F, remain poorly understood [78]. To the best of our knowledge, this is one of the first longitudinal studies in Chile to formally investigate the incidence and factors related to PICS-F. Furthermore, it will be one of the first to comprehensively explore physical and cognitive impairments in addition to psychological PICS-F impairments, utilizing the CSM framework [26]. Although Cameron et al. [23] employed the CSM, their study did not measure FS as a secondary stressor or resilience as a psychological resource and they did not explore potential cognitive impairments.

Despite growing awareness of PICS-F, physical and cognitive impairments remain understudied. This study will address this gap by investigating the incidence and factors associated with PICS-F physical impairment and exploring caregivers’ cognitive function during and after ICU stay. The scientific novelty of this study is also grounded in the inclusion of CB as a secondary stressor that may impact PICS-F impairments. While evidence of CB in caregivers of ICU survivors is emerging, this study recognizes that the PICS-F impairments may not solely result from the residual effect of a traumatic event such as an ICU admission, but also from the ongoing burden of caring for an ICU survivor.

Limitations

There are some foreseeable limitations of the proposed study. First, the single-centre scope of the study limits the generalizability of our findings to caregivers of ICU survivors with similar features. Future multicentric studies, including bereaved family members, are required to understand the role of the novel PICS-F variables explored in this study. Second, the sole utilization of questionnaires for data collection, which have well-known limitations (e.g., recall bias), should be complemented in future studies with objective measures while available. Third, limited visiting hours available may influence the caregiver´s psychological symptoms. Fourth, the longitudinal design may increase the odds of attrition and/or withdrawal of participants. Similarly, the low recruitment/high loss to follow-up rates observed among similar studies [18,23] may lead to selection bias, particularly in those caregivers who will not be approached because of evident psychological distress.

Conclusion

ICU survivorship imposes a significant burden on the healthcare system, society and in particular, caregivers of those who endure a critical illness. The proposed study of caregivers of ICU survivors at a public hospital in Chile aims to provide comprehensive insights into the incidence and factors associated with PICS-F impairments. By examining PICS-F-related factors during ICU stay and after hospital discharge, this study will inform healthcare stakeholders and researchers, enabling the development of tailored interventions that address the full spectrum of critical illness, from ICU admission to the caregiving period. This will ultimately improve our understanding of PICS-F and help enhance support for caregivers and ICU survivors.

Supporting information

S1 Appendix. Checklist.

SPIRIT 2013 checklist: Recommended items to address in a clinical trial protocol and related documents.

https://doi.org/10.1371/journal.pone.0324013.s001

(DOC)

S2 Appendix. Original protocol sent to ethics committee.

Original protocol sent to ethics committee (in English).

https://doi.org/10.1371/journal.pone.0324013.s002

(PDF)

Acknowledgments

To all caregivers of ICU survivors who generously share their time while providing care to their loved ones during and after their ICU stay. The adult ICU nurses at Hospital Clinico Dra. Eloísa Díaz collaborate in the screening and data collection processes. To the research assistants involved in recruitment and follow-up: Javiera Garcia, Francisca Cortes, Jesus Valderrama, Rocio Cano, Valentina Tapia and Isidora Valenzuela. The authors would like to thank Enago (www.enago.com) for the English language review.

References

  1. 1. Calle GHL, Martin MC, Nin N. Seeking to humanize intensive care. Rev Bras Ter Intensiva. 2017;29(1):9–13. pmid:28444067
  2. 2. Rawal G, Yadav S, Kumar R. Post-intensive Care Syndrome: an Overview. J Transl Int Med. 2017;5(2):90–2. pmid:28721340
  3. 3. Kean S, Smith GD. Editorial: surviving critical illness: intensive care and beyond. J Clin Nurs. 2014;23(5–6):603–4. pmid:24589228
  4. 4. Wang S, Allen D, Kheir YN, Campbell N, Khan B. Aging and Post-Intensive Care Syndrome: A Critical Need for Geriatric Psychiatry. Am J Geriatr Psychiatry. 2018;26(2):212–21. pmid:28716375
  5. 5. Padilla Fortunatti CF. Most important needs of family members of critical patients in light of the critical care family needs inventory. Invest Educ Enferm. 2014;32(2):306–16. pmid:25230040
  6. 6. Petrinec AB, Daly BJ. Post-Traumatic Stress Symptoms in Post-ICU Family Members: Review and Methodological Challenges. West J Nurs Res. 2016;38(1):57–78. pmid:25061017
  7. 7. Fumis RRL, Ferraz AB, de Castro I, Barros de Oliveira HS, Moock M, Junior JMV. Mental health and quality of life outcomes in family members of patients with chronic critical illness admitted to the intensive care units of two Brazilian hospitals serving the extremes of the socioeconomic spectrum. PLoS One. 2019;14(9):e0221218. pmid:31518359
  8. 8. González-Martín S, Becerro-de-Bengoa-Vallejo R, Angulo-Carrere MT, Iglesias ME-L, Martínez-Jiménez EM, Casado-Hernández I, et al. Effects of a visit prior to hospital admission on anxiety, depression and satisfaction of patients in an intensive care unit. Intensive Crit Care Nurs. 2019;54:46–53. pmid:31358482
  9. 9. Davidson JE, Harvey MA. Patient and Family Post-Intensive Care Syndrome. AACN Adv Crit Care. 2016;27(2):184–6. pmid:27153307
  10. 10. Dean EA, Biehl M, Bash K, Weleff J, Pozuelo L. Neuropsychiatric assessment and management of the ICU survivor. Cleve Clin J Med. 2021;88(12):669–79. pmid:34857605
  11. 11. Davidson JE, Jones C, Bienvenu OJ. Family response to critical illness: postintensive care syndrome-family. Crit Care Med. 2012;40(2):618–24. pmid:22080636
  12. 12. Lone NI, Gillies MA, Haddow C, Dobbie R, Rowan KM, Wild SH, et al. Five-Year Mortality and Hospital Costs Associated with Surviving Intensive Care. Am J Respir Crit Care Med. 2016;194(2):198–208. pmid:26815887
  13. 13. Lee M, Kang J, Jeong YJ. Risk factors for post-intensive care syndrome: A systematic review and meta-analysis. Aust Crit Care. 2020;33(3):287–94. pmid:31839375
  14. 14. van Beusekom I, Bakhshi-Raiez F, de Keizer NF, Dongelmans DA, van der Schaaf M. Reported burden on informal caregivers of ICU survivors: a literature review. Crit Care. 2016;20:16. pmid:26792081
  15. 15. Johnson CC, Suchyta MR, Darowski ES, Collar EM, Kiehl AL, Van J, et al. Psychological Sequelae in Family Caregivers of Critically III Intensive Care Unit Patients. A Systematic Review. Ann Am Thorac Soc. 2019;16(7):894–909. pmid:30950647
  16. 16. Alfheim HB, Hofsø K, Småstuen MC, Tøien K, Rosseland LA, Rustøen T. Post-traumatic stress symptoms in family caregivers of intensive care unit patients: A longitudinal study. Intensive Crit Care Nurs. 2019;50:5–10. pmid:29937075
  17. 17. Alfheim HB, Rosseland LA, Hofsø K, Småstuen MC, Rustøen T. Multiple Symptoms in Family Caregivers of Intensive Care Unit Patients. J Pain Symptom Manage. 2018;55(2):387–94. pmid:28864399
  18. 18. Azoulay E, Resche-Rigon M, Megarbane B, Reuter D, Labbé V, Cariou A, et al. Association of COVID-19 Acute Respiratory Distress Syndrome With Symptoms of Posttraumatic Stress Disorder in Family Members After ICU Discharge. JAMA. 2022;327(11):1042–50. pmid:35179564
  19. 19. Heesakkers H, van der Hoeven JG, Corsten S, Janssen I, Ewalds E, Burgers-Bonthuis D, et al. Mental health symptoms in family members of COVID-19 ICU survivors 3 and 12 months after ICU admission: a multicentre prospective cohort study. Intensive Care Med. 2022 Mar 1;48(3):322–31. pmid:35103824.
  20. 20. Duarte F, Jiménez-Molina Á. Psychological distress during the COVID-19 epidemic in Chile: The role of economic uncertainty. PLoS One. 2021;16(11):e0251683. pmid:34731175
  21. 21. Douglas SL, Daly BJ. Caregivers of long-term ventilator patients: physical and psychological outcomes. Chest. 2003;123(4):1073–81. pmid:12684296
  22. 22. Choi J, Tate JA, Hoffman LA, Schulz R, Ren D, Donahoe MP, et al. Fatigue in family caregivers of adult intensive care unit survivors. J Pain Symptom Manage. 2014;48(3):353–63. pmid:24439845
  23. 23. Cameron JI, Chu LM, Matte A, Tomlinson G, Chan L, Thomas C, et al. One-Year Outcomes in Caregivers of Critically Ill Patients. N Engl J Med. 2016;374(19):1831–41. pmid:27168433
  24. 24. Lemiale V, Kentish-Barnes N, Chaize M, Aboab J, Adrie C, Annane D, et al. Health-related quality of life in family members of intensive care unit patients. J Palliat Med. 2010;13(9):1131–7. pmid:20836638
  25. 25. Scott SB, Graham-Engeland JE, Engeland CG, Smyth JM, Almeida DM, Katz MJ, et al. The Effects of Stress on Cognitive Aging, Physiology and Emotion (ESCAPE) Project. BMC Psychiatry. 2015;15:146. pmid:26138700
  26. 26. Pearlin LI, Mullan JT, Semple SJ, Skaff MM. Caregiving and the stress process: an overview of concepts and their measures. Gerontologist. 1990;30(5):583–94. pmid:2276631
  27. 27. Arvidsdotter T, Marklund B, Kylén S, Taft C, Ekman I. Understanding persons with psychological distress in primary health care. Scand J Caring Sci. 2016;30(4):687–94. pmid:26463897
  28. 28. Ergh TC, Rapport LJ, Coleman RD, Hanks RA. Predictors of caregiver and family functioning following traumatic brain injury: social support moderates caregiver distress. J Head Trauma Rehabil. 2002;17(2):155–74. pmid:11909512
  29. 29. Rodakowski J, Skidmore ER, Rogers JC, Schulz R. Role of social support in predicting caregiver burden. Arch Phys Med Rehabil. 2012;93(12):2229–36. pmid:22824248
  30. 30. Rückholdt M, Tofler GH, Randall S, Buckley T. Coping by family members of critically ill hospitalised patients: An integrative review. Int J Nurs Stud. 2019;97:40–54. pmid:31132688
  31. 31. Ioannou M, Kassianos AP, Symeou M. Coping With Depressive Symptoms in Young Adults: Perceived Social Support Protects Against Depressive Symptoms Only Under Moderate Levels of Stress. Front Psychol. 2019;9:2780. pmid:30692958
  32. 32. Mitchell ML, Courtney M. Reducing family members’ anxiety and uncertainty in illness around transfer from intensive care: an intervention study. Intensive Crit Care Nurs. 2004;20(4):223–31. pmid:15288876
  33. 33. Nadig N, Huff NG, Cox CE, Ford DW. Coping as a Multifaceted Construct: Associations With Psychological Outcomes Among Family Members of Mechanical Ventilation Survivors. Crit Care Med. 2016;44(9):1710–7. pmid:27065467
  34. 34. Chang P-Y, Wang H-P, Chang T-H, Yu J-M, Lee S-Y. Stress, stress-related symptoms and social support among Taiwanese primary family caregivers in intensive care units. Intensive Crit Care Nurs. 2018;49:37–43. pmid:29937076
  35. 35. Foster M, Chaboyer W. Family carers of ICU survivors: a survey of the burden they experience. Scand J Caring Sci. 2003;17(3):205–14. pmid:12919454
  36. 36. Haines KJ, Denehy L, Skinner EH, Warrillow S, Berney S. Psychosocial outcomes in informal caregivers of the critically ill: a systematic review. Crit Care Med. 2015;43(5):1112–20. pmid:25654174
  37. 37. Lin Q, Dong F, Xue Y, Yu Q, Ren J, Zeng L. Predictors of posttraumatic growth of the family members of neurosurgical intensive care unit patients: A cross-sectional study. Intensive Crit Care Nurs. 2022;68:103134. pmid:34750040
  38. 38. Sottile PD, Lynch Y, Mealer M, Moss M. Association Between Resilience and Family Member Psychologic Symptoms in Critical Illness. Crit Care Med. 2016;44(8):e721-7. pmid:27097294
  39. 39. Boniatti MM, RESILIENCE-ICU Group. May resilient family members of critically ill patients experience less caregiving burden?. Intensive Care Med. 2021;47(2):244–5. pmid:33388836
  40. 40. Rothen HU, Stricker KH, Heyland DK. Family satisfaction with critical care: measurements and messages. Curr Opin Crit Care. 2010;16(6):623–31. pmid:20736823
  41. 41. Padilla Fortunatti C, De Santis JP, Munro CL. Family Satisfaction in the Adult Intensive Care Unit: A Concept Analysis. ANS Adv Nurs Sci. 2021;44(4):291–305. pmid:33624988
  42. 42. Carlson EB, Spain DA, Muhtadie L, McDade-Montez L, Macia KS. Care and caring in the intensive care unit: Family members’ distress and perceptions about staff skills, communication, and emotional support. J Crit Care. 2015;30(3):557–61. pmid:25682345
  43. 43. Naef R, von Felten S, Ernst J. Factors influencing post-ICU psychological distress in family members of critically ill patients: a linear mixed-effects model. Biopsychosoc Med. 2021;15(1):4. pmid:33588895
  44. 44. Metzger K, Gamp M, Tondorf T, Hochstrasser S, Becker C, Luescher T, et al. Depression and anxiety in relatives of out-of-hospital cardiac arrest patients: Results of a prospective observational study. J Crit Care. 2019;51:57–63. pmid:30745287
  45. 45. Op ’t Hoog SAJJ, Dautzenberg M, Eskes AM, Vermeulen H, Vloet LCM. The experiences and needs of relatives of intensive care unit patients during the transition from the intensive care unit to a general ward: A qualitative study. Aust Crit Care. 2020;33(6):526–32. pmid:32089387
  46. 46. Griffiths J, Hatch RA, Bishop J, Morgan K, Jenkinson C, Cuthbertson BH, et al. An exploration of social and economic outcome and associated health-related quality of life after critical illness in general intensive care unit survivors: a 12-month follow-up study. Crit Care. 2013;17(3):R100. pmid:23714692
  47. 47. Yu H, Wang X, He R, Liang R, Zhou L. Measuring the Caregiver Burden of Caring for Community-Residing People with Alzheimer’s Disease. PLoS One. 2015;10(7):e0132168. pmid:26154626
  48. 48. Adelman RD, Tmanova LL, Delgado D, Dion S, Lachs MS. Caregiver burden: a clinical review. JAMA. 2014;311(10):1052–60. pmid:24618967
  49. 49. Torres J, Carvalho D, Molinos E, Vales C, Ferreira A, Dias CC, et al. The impact of the patient post-intensive care syndrome components upon caregiver burden. Med Intensiva. 2017;41(8):454–60. pmid:28188064
  50. 50. McPeake J, Devine H, MacTavish P, Fleming L, Crawford R, Struthers R, et al. Caregiver strain following critical care discharge: An exploratory evaluation. J Crit Care. 2016;35:180–4. pmid:27481756
  51. 51. Comini L, Rocchi S, Bruletti G, Paneroni M, Bertolotti G, Vitacca M. Impact of Clinical and Quality of Life Outcomes of Long-Stay ICU Survivors Recovering From Rehabilitation on Caregivers’ Burden. Respir Care. 2016;61(4):405–15. pmid:26759421
  52. 52. Comini L, Rocchi S, Bruletti G, Paneroni M, Bertolotti G, Vitacca M. Impact of Clinical and Quality of Life Outcomes of Long-Stay ICU Survivors Recovering From Rehabilitation on Caregivers’ Burden. Respir Care. 2016;61(4):405–15. pmid:26759421
  53. 53. Milton A, Schandl A, Larsson I-M, Wallin E, Savilampi J, Meijers K, et al. Caregiver burden and emotional wellbeing in informal caregivers to ICU survivors-A prospective cohort study. Acta Anaesthesiol Scand. 2022;66(1):94–102. pmid:34582048
  54. 54. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, et al. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. BMJ. 2007;335(7624):806–8. pmid:17947786
  55. 55. Thrusfield M. Veterinary Epidemiology, 2nd Edition, Blackwell Science, Oxford, UK;2005. p. 183.
    • 56. Zante B, Erne K, Grossenbacher J, Camenisch SA, Schefold JC, Jeitziner M-M. Symptoms of post-traumatic stress disorder (PTSD) in next of kin during suspension of ICU visits during the COVID-19 pandemic: a prospective observational study. BMC Psychiatry. 2021;21(1):477. pmid:34587929
    • 57. Kroenke K, Spitzer RL, Williams JBW, Löwe B. An ultra-brief screening scale for anxiety and depression: the PHQ-4. Psychosomatics. 2009;50(6):613–21. pmid:19996233
    • 58. Caamaño W L, Fuentes M D, González B L, Melipillán A R, Sepúlveda C M, Valenzuela G E. Assessment of the impact of event scale revised for post traumatic stress disorder in Chilean subjects. Rev Med Chil. 2011;139(9):1163–8. pmid:22215395
    • 59. Hosey MM, Leoutsakos J-MS, Li X, Dinglas VD, Bienvenu OJ, Parker AM, et al. Screening for posttraumatic stress disorder in ARDS survivors: validation of the Impact of Event Scale-6 (IES-6). Crit Care. 2019;23(1):276. pmid:31391069
    • 60. Poblete F, Glasinovic A, Sapag J, Barticevic N, Arenas A, Padilla O. Social support and cardiovascular health: Adaptation of a social support scale for hypertensive and diabetic patients in primary care, Chile. Aten Primaria. 2015;47(8):523–31. pmid:25795034
    • 61. Moser A, Stuck AE, Silliman RA, Ganz PA, Clough-Gorr KM. The eight-item modified Medical Outcomes Study Social Support Survey: psychometric evaluation showed excellent performance. J Clin Epidemiol. 2012;65(10):1107–16. pmid:22818947
    • 62. Sinclair VG, Wallston KA. The development and psychometric evaluation of the Brief Resilient Coping Scale. Assessment. 2004;11(1):94–101. pmid:14994958
    • 63. Gallardo-Peralta LP, Rodríguez-Blázquez C, Ayala-García A, Forjaz MJ. Validation of the brief resilient coping scale (brcs) in a multiethnic sample of chilean older people. Interciencia. 2020;45(11):524–31.
    • 64. Delgado Derio C, Guerrero Bonnet S, Troncoso Ponce M, Araneda Yañez A, Slachevsky Chonchol A, Behrens Pellegrino MI. Memory, fluency, and orientation: a five-minute screening test for cognitive decline. Neurologia. 2013;28(7):400–7. pmid:23246219
    • 65. Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992;30(6):473–83. pmid:1593914
    • 66. Olivares-Tirado P. Estado de salud de beneficiarios del sistema de salud de chile: 2004 -2005 documento técnico [internet]. Ministerio de Salud, Departamento de Estudios y Desarrollo; enero 2006. [cited 2022 Mar 19]. Available from: https://www.supersalud.gob.cl/documentacion/666/articles-1062_recurso_1.pdf
      • 67. Wall RJ, Engelberg RA, Downey L, Heyland DK, Curtis JR. Refinement, scoring, and validation of the Family Satisfaction in the Intensive Care Unit (FS-ICU) survey. Crit Care Med. 2007;35(1):271–9. pmid:17133189
      • 68. Padilla-Fortunatti C, Rojas-Silva N, Molina-Muñoz Y, Avendaño-Jara S. Cultural adaptation and psychometric properties of the Chilean-Spanish version of the Family Satisfaction in the Intensive Care Unit - 24 questionnaire. Med Intensiva (Engl Ed). 2023;47(3):140–8. pmid:36068147
      • 69. Zarit SH, Reever KE, Bach-Peterson J. Relatives of the impaired elderly: correlates of feelings of burden. Gerontologist. 1980;20(6):649–55. pmid:7203086
      • 70. Breinbauer K H, Vásquez V H, Mayanz S S, Guerra C, Millán K T. Original and abbreviated Zarit caregiver burden scales. Validation in Chile. Rev Med Chil. 2009;137(5):657–65. pmid:19701555
      • 71. Collin C, Wade DT, Davies S, Horne V. The Barthel ADL Index: a reliability study. Int Disabil Stud. 1988;10(2):61–3. pmid:3403500
      • 72. Muñoz Silva CA, Rojas Orellana PA, Marzuca-Nassr GN. Functional geriatric assessment in primary health care. Rev Med Chil. 2015;143(5):612–8. pmid:26203573
      • 73. Agresti A. Categorical Data Analysis, 3rd ed. John Wiley & Sons; 2005.
        • 74. McCullagh P, Nelder JA. Generalized Linear Models, 2nd ed. Chapman & Hall/CRC Press; 1989.
          • 75. R: A language and environment for statistical computating. http://www.R-project.org.
          • 76. World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191–4. pmid:24141714
          • 77. Resnik DB, Shamoo AE. The singapore statement on research integrity. Account Res. 2011;18(2):71–5. pmid:21390871
          • 78. McPeake J, Auriemma CL, Harhay MO. Understanding the Impact of Critical Illness on Families: A Call for Standardization of Outcomes and Longitudinal Research. Ann Am Thorac Soc. 2021;18(11):1783–5. pmid:34723764