Chronic critical illness and post-intensive care syndrome: from pathophysiology to clinical challenges

Abstract

Background Post‐intensive care syndrome (PICS) encompasses physical, cognition, and mental impairments persisting after intensive care unit (ICU) discharge. Ultimately it significantly impacts the long‐term prognosis, both in functional outcomes and survival. Thus, survivors often develop permanent disabilities, consume a lot of healthcare resources, and may experience prolonged suffering. This review aims to present the multiple facets of the PICS, decipher its underlying mechanisms, and highlight future research directions. Main text This review abridges the translational data underlying the multiple facets of chronic critical illness (CCI) and PICS. We focus first on ICU-acquired weakness, a syndrome characterized by impaired contractility, muscle wasting, and persisting muscle atrophy during the recovery phase, which involves anabolic resistance, impaired capacity of regeneration, mitochondrial dysfunction, and abnormalities in calcium homeostasis. Second, we discuss the clinical relevance of post-ICU cognitive impairment and neuropsychological disability, its association with delirium during the ICU stay, and the putative role of low-grade long-lasting inflammation. Third, we describe the profound and persistent qualitative and quantitative alteration of the innate and adaptive response. Fourth, we discuss the biological mechanisms of the progression from acute to chronic kidney injury, opening the field for renoprotective strategies. Fifth, we report long-lasting pulmonary consequences of ARDS and prolonged mechanical ventilation. Finally, we discuss several specificities in children, including the influence of the child’s pre-ICU condition, development, and maturation. Conclusions Recent understandings of the biological substratum of the PICS’ distinct features highlight the need to rethink our patient trajectories in the long term. A better knowledge of this syndrome and precipitating factors is necessary to develop protocols and strategies to alleviate the CCI and PICS and ultimately improve patient recovery.

Virtual and augmented reality in critical care medicine: the patient’s, clinician’s, and researcher’s perspective

“…Following ICU treatment, many patients suffer from Post Intensive Care Syndrome (PICS), which consists of mental health issues, cognitive dysfunction, and problems with mobility [ 32 ]. It was therefore hypothesised that more information on ICU therapy and subsequent medical procedures might be beneficial.…”

Immunopathology of chronic critical illness in sepsis survivors: Role of abnormal myelopoiesis

“…Thus, catabolism, malnutrition, and persistent inflammation could be a possible explanation for the observed accelerated aging of limb muscles and sarcopenia in ICU survivors (inflamm-aging) (Figure 4). 73,74 The maladaptive immunologic dyscrasia shown in CCI/PICS is caused by multiple cellular and redundant molecular pathways that promote the expansion and persistence of MDSCs. In addition, these patients show suppression of protective immunity via lymphopenia, Tcell exhaustion, increased appearance of Tregs, increased production of soluble PD-L1, and reduced HLA-DR expression, which have been also associated to an increased susceptibility to secondary infections and all-cause mortality.…”

“…Thus, catabolism, malnutrition, and persistent inflammation could be a possible explanation for the observed accelerated aging of limb muscles and sarcopenia in ICU survivors (inflamm‐aging) (Figure 4). 73,74 …”

Post COVID‐19 condition: critical need for a clear definition and detailed pathophysiology

“… 6 Half the patients admitted to the intensive care unit are vulnerable to muscle wasting. 7 This post‐intensive care syndrome or intensive care acquired weakness is a physical, cognitive and mental disorder that occurs during hospitalization or after hospital discharge 8 , 9 and contributes to the very long recovery process after hospital discharge. Symptoms include muscle weakness, exercise intolerance, fatigue and cognitive problems.…”