The diagnosis of post-intensive care syndrome (PICS) presents a significant challenge in healthcare, primarily due to the complexities in determining the baseline health status of patients prior to their critical illness. The absence of pre-ICU data makes it difficult to definitively diagnose new or worsening impairments experienced by ICU survivors. Consequently, many studies focus on the prevalence of post-ICU impairments rather than the precise incidence. This article delves into the intricacies of PICS diagnosis, exploring the incidence of impairments, subtypes, risk factors, potential mechanisms, and interventions, aiming to provide a comprehensive understanding of this critical area for healthcare professionals and researchers.
The Diagnostic Challenge: Incidence of Post-ICU Impairments and Baseline Assessment
Establishing the true incidence of PICS is inherently linked to the ability to accurately diagnose new impairments following intensive care. A landmark study conducted in the Netherlands, involving 2,345 ICU survivors, addressed this diagnostic hurdle by collecting baseline health status data. This research utilized questionnaires completed by patients or their proxies to retrospectively assess pre-ICU health for patients urgently admitted. For those admitted for elective surgery, baseline questionnaires were administered during pre-operative visits, providing a more prospective baseline assessment.
The findings revealed significant insights into the incidence of new impairments across different admission types. Among patients admitted for medical reasons (28%), urgent surgery (12%), and elective surgery (60%), the study reported that 58%, 64%, and 43%, respectively, developed new physical, cognitive, and/or mental health problems within one year post-ICU discharge (Table 1). Notably, this study highlighted that physical problems were evaluated using a non-validated questionnaire, underscoring the ongoing need for standardized diagnostic tools in PICS.
Further analysis of the Dutch study revealed that urgent surgical patients experienced a higher incidence of frailty, fatigue, muscle weakness, anxiety, depression, and cognitive impairment at the 1-year mark compared to elective surgery patients. This difference may be partly attributed to the shorter ICU stays observed in elective surgery patients. While elective surgery patients showed greater improvements in physical and mental functioning at the 1-year follow-up, it’s important to note that baseline fatigue and anxiety were more prevalent in this group. Overall, this study offered crucial insights into the incidence of new impairments, emphasizing the diagnostic complexities and the variability of PICS across different patient populations.
Table 1: Percentage of patients experiencing new impairments one year after ICU admission, categorized by the reason for their admission. This data highlights the varying incidence rates across medical, urgent surgery, and elective surgery patients, emphasizing the need for tailored diagnostic approaches.
An earlier UK-based study with a smaller cohort (N=293) also contributed to the diagnostic understanding of PICS. Using the EQ-5D subscales, this study found that ICU survivors reported more mobility issues, self-care difficulties, pain, and anxiety/depression compared to their pre-ICU status. However, the study’s reliance on recall for baseline status and the use of simple one-item assessments within the EQ-5D subscales introduces potential limitations related to recall bias and assessment depth.
Another UK study focusing on anxiety and depression in ICU survivors (N=36) attempted to isolate new symptoms by excluding patients with pre-existing psychological conditions. Utilizing the Hospital Anxiety and Depression Scale (HADS), the study found that at 1 month post-discharge, 44% and 47% of participants were classified as “disorder likely” for anxiety and depression, respectively. This study provides valuable insight into the early onset of mental health impairments post-ICU, aiding in the diagnostic timeline for PICS.
These studies collectively underscore the challenges in PICS diagnosis, particularly in establishing pre-ICU baselines and utilizing consistent, validated assessment tools. Future research must prioritize the refinement of diagnostic methods to better understand the true incidence and nature of long-term impairments attributable to critical illness.
Subtypes of PICS: Guiding Diagnosis Through Impairment Patterns
To refine PICS diagnosis, researchers have explored the identification of distinct subtypes based on the patterns of physical, cognitive, and mental health impairments. The ALTOS study, involving 698 ARDS survivors, identified four subtypes at 6- and 12-month follow-ups using weighted network analysis and recursive partitioning:
- Mildly impaired physical and mental health status (22%): This subtype represents a less severe form of PICS, suggesting a better prognosis and potentially requiring less intensive intervention.
- Moderately impaired physical and mental health status (39%): The most prevalent subtype, indicating a significant need for rehabilitation and support across physical and mental health domains.
- Severely impaired physical and moderately impaired mental health status (15%): This subtype highlights the potential for disproportionate physical impairment, necessitating targeted physical rehabilitation strategies.
- Severely impaired physical and mental health status (24%): The most severe subtype, requiring comprehensive and multidisciplinary interventions addressing both physical and mental health needs.
These subtypes emphasize the close association between physical and mental impairments, distinct from cognitive impairment. Interestingly, ICU-related variables and illness severity were not found to be associated with these subtypes, suggesting that patient-specific factors may play a more significant role in determining PICS subtypes. Importantly, all subtypes showed declines from retrospectively-assessed baseline status, reinforcing the diagnostic relevance of pre-ICU health assessment.
Another study focusing on COVID-19 survivors revealed that physical and mental impairments were closely linked but did not consistently co-occur with cognitive impairments. In contrast, a separate COVID-19 study of ICU survivors reported that cognitive and mental impairments always occurred together at the 1-year follow-up. These findings suggest potential variations in PICS subtypes based on the nature of the critical illness (e.g., ARDS vs. COVID-19) and highlight the need for subtype-specific diagnostic approaches.
Understanding these subtypes is crucial for refining PICS diagnosis. By recognizing these distinct patterns of impairment, clinicians can move towards a more nuanced diagnostic approach, tailoring assessments and interventions to the specific needs of each patient based on their subtype profile.
Risk Factors: Identifying Individuals at Higher Diagnostic Probability for PICS
Identifying risk factors for PICS is essential for proactive diagnosis and early intervention. A comprehensive systematic review of 89 publications identified 60 risk factors, categorized roughly equally as patient-related and ICU-related. Significant risk factors associated with physical, mental, and/or cognitive impairments include:
- Patient-related factors: Advanced age, female sex, pre-existing mental illness. These factors are non-modifiable but crucial for risk stratification and heightened diagnostic vigilance.
- ICU-related factors: Severity of illness, negative ICU patient experience (including distressing memories), and delirium. These factors are potentially modifiable and represent targets for preventative strategies that indirectly aid in reducing PICS incidence and improving diagnostic clarity.
Specifically, negative ICU experiences and delirium have a strong association with anxiety, PTSD, and cognitive dysfunction, emphasizing their importance as diagnostic indicators within the ICU stay itself. While patient-related risk factors cannot be changed, they are invaluable for identifying high-risk individuals who warrant closer monitoring and comprehensive PICS assessment post-discharge. Interventions aimed at modifying ICU-related risk factors, such as strategies to reduce delirium, promote early mobilization, optimize pain management, and minimize restraint use, can contribute to improved patient experiences and potentially lower the likelihood of PICS development, thereby simplifying the diagnostic landscape by reducing overall incidence. These patient-centered approaches not only improve care quality but also address modifiable risks that impact PICS diagnosis.
Potential Mechanisms: Inflammatory Subphenotypes and Diagnostic Implications
Exploring the underlying mechanisms of PICS is crucial for developing more targeted diagnostic and therapeutic strategies. Recent research utilizing data from the ALTOS study investigated the relationship between ICU-based hyper- vs. hypo-inflammatory subphenotypes and long-term impairments. While the hyper-inflammatory phenotype was associated with increased 90-day mortality, survival beyond 90 days and physical, cognitive, and mental outcomes at 6- and 12-month follow-ups were similar across both inflammatory subphenotypes. This suggests that the acute inflammatory response during critical illness may not be a direct predictor of long-term PICS outcomes or a useful diagnostic marker for chronic PICS.
Further research examining acute systemic inflammation and coagulation markers early in critical illness found no association with cognitive function at 3 and 12-month follow-ups. Only two markers showed a weak association with disability in activities of daily living over the follow-up period. These findings challenge the notion that early inflammation is a primary mechanistic driver of long-term PICS impairments, suggesting that inflammation measured during acute illness may not be a reliable diagnostic biomarker for predicting PICS.
However, it’s important to note that these studies focused on acute inflammation. The role of prolonged inflammation after hospital discharge in PICS development remains an area requiring further investigation. Future research should explore whether persistent inflammation beyond the acute phase of critical illness is a more relevant mechanistic target and a potential diagnostic marker for PICS. Identifying such prolonged inflammatory markers could provide valuable diagnostic tools and insights into the pathophysiology of chronic PICS.
Interventions: Informing Diagnostic and Management Strategies for PICS
Understanding effective interventions for PICS is not only crucial for patient care but also informs diagnostic and management strategies. A systematic review of 36 studies evaluating non-pharmacological interventions for improving long-term outcomes after critical illness categorized interventions into: early mobilization and physical rehabilitation (56%), post-ICU follow-up (14%), psychosocial programs (8%), ICU diaries (8%), and educational activities (6%).
Table 2: Overview of evaluations of non-pharmacological interventions designed to improve long-term outcomes following critical illness. This table summarizes the diverse range of interventions studied and their potential impact on PICS, guiding the development of comprehensive diagnostic and management protocols.
The review highlighted that only 31% of studies included post-discharge interventions, despite the prolonged nature of PICS impairments. This underscores the need for more research focusing on interventions delivered after hospital discharge to address the chronic aspects of PICS. The existing studies also revealed limitations, including risks of bias from incomplete reporting and loss to follow-up, along with a lack of standardization in outcome measurement instruments. These methodological challenges highlight the need for improved study designs in future intervention research.
While the design and evaluation of non-pharmacological interventions for PICS are still in early stages, the evidence base is growing. The focus on early mobilization and physical rehabilitation, psychosocial support, and post-ICU follow-up programs provides a framework for developing comprehensive PICS management strategies that complement diagnostic efforts. Further research is needed to refine these interventions and to establish standardized outcome measures, which will enhance our ability to diagnose PICS severity and track treatment response effectively. Ultimately, well-designed intervention studies will not only improve patient outcomes but also contribute to a deeper understanding of PICS and its diagnostic markers.
Conclusion: Advancing PICS Diagnosis for Improved Patient Outcomes
Diagnosing post-intensive care syndrome remains a complex undertaking, primarily due to the challenges in establishing pre-illness baselines and the heterogeneous nature of long-term impairments. Current research underscores the importance of considering PICS subtypes, risk factors, and potential mechanisms to refine diagnostic approaches. While acute inflammatory markers may not be reliable diagnostic tools, further investigation into prolonged inflammation and other biomarkers is warranted. Non-pharmacological interventions, particularly those focusing on rehabilitation and psychosocial support, play a crucial role in PICS management and can inform diagnostic strategies by clarifying impairment profiles and treatment responses.
Future progress in PICS diagnosis hinges on:
- Developing and validating standardized diagnostic tools for assessing pre-ICU baseline status and for consistently measuring PICS impairments across physical, cognitive, and mental health domains.
- Conducting longitudinal studies to better understand the natural history of PICS and to identify reliable diagnostic markers for early and accurate detection.
- Prioritizing research on post-discharge interventions to address the chronic nature of PICS and to develop comprehensive management protocols that integrate diagnostic and therapeutic strategies.
- Focusing on subtype-specific diagnostic and treatment approaches to tailor care to the unique needs of different PICS patient populations.
By addressing these key areas, the healthcare community can move towards more effective diagnostic strategies for PICS, ultimately leading to improved long-term outcomes and quality of life for ICU survivors.
