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There has been a significant increase in patients with chronic critical illness (CCI): patients with prolonged hospitalizations, high resource utilization, and dismal long-term outcomes.
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Persistent inflammation, immunosuppression, and catabolism syndrome (PICS) describes a subgroup of patients with CCI who have experienced recurrent inflammatory insults.
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Prolonged expansion of myeloid-derived suppressor cells (MDSCs) provides a plausible mechanism for the pathobiology and poor outcomes observed
Persistent Inflammation, Immunosuppression and Catabolism Syndrome
Section snippets
Key points
Evolving epidemiology of multiple organ failure and emergence of persistent inflammation, immunosuppression, and catabolism syndrome
MOF emerged in the early 1970s as a result of advances in ICU technology that allowed patients to survive single-organ failure (Fig. 1).1 Early studies provided convincing evidence that MOF occurred as a result of uncontrolled sepsis leading to fulminant organ failure and early death, with the primary source being intra-abdominal infections (IAIs).1 As a result, research efforts in the early 1980s were focused on the prevention/treatment of IAI and were effective in reducing this highly fatal
The new paradigm of persistent inflammation, immunosuppression, and catabolism syndrome
Based on recent laboratory and clinical research data, the following paradigm was proposed (Fig. 2).5 Following an inflammatory insult (either trauma or sepsis), SIRS and CARS occur simultaneously. In some cases, SIRS can become overwhelming leading to an early MOF and fulminant death trajectory. Fortunately, modern ICU care is directed at early detection and prevention of this trajectory’s fatal expression. If the severely insulted patients do not die of early MOF, there are two alternatives.
Pathophysiology of persistent inflammation, immunosuppression, and catabolism syndrome
Although other investigators have described the growing epidemic of CCI, glaringly absent is any unifying mechanistic explanation. The PICS paradigm was described based on observed outcomes of surgical ICU patients who had a major inflammatory event (trauma/surgical sepsis) and who experienced recurrent insults (principally nosocomial infections). The authors propose a mechanism that can explain the persistent low-grade inflammation with the concurrent adaptive immune suppression and associated
Clinical implications
Persistent inflammation, MDSC expansion, and suppression of protective immunity via anergy, lymphopenia, and dysfunctional innate effector cells predispose patients to reactivation of latent viral infections, nosocomial infections, continued protein catabolism, and malnutrition. This reactivation creates a propagating cycle whereby recurrent infections exacerbate inflammation driving aberrant myelopoiesis and continued expansion of MDSCs, which in turn induces suppression of adaptive immunity (
Summary
Management of MOF has evolved significantly over the past four decades as has our understanding of the pathobiology of trauma and sepsis. Advances in the early management and resuscitation of trauma and sepsis have significant reduced early mortality and early MOF. Additionally, there has been a significant reduction in late-stage MOF and steady improvements in hospital survival for both entities. This successful recognition and management of the early inflammatory response has resulted in
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Supported in part by grants P50 GM-111152-03, R01 GM-40586-24 and R01 GM-104481-04, awarded by the National Institute of General Medical Sciences (NIGMS), U.S.P.H.S. J.C. Mira was supported by a postgraduate training grant (T32 GM-08721) in burns, trauma, and perioperative injury by NIGMS.
Disclosure Statement: The authors have nothing to disclose.