Persistent Inflammation, Immunosuppression and Catabolism Syndrome: Another Consideration in Critical Care

By Kimberly Gottesman, DCN, RDN, LDN, CNSC

What is PICS?

Persistent inflammation, immunosuppression and catabolism syndrome (PICS) was first described by Gentile et al in 20121 to help better understand the pathophysiology behind the simultaneous processes of continuous inflammation (known as systemic inflammation response syndrome), adaptive immunosuppression (known as compensatory anti-inflammatory response syndrome) and protein catabolism.1-4 PICS is often observed among patients who survive an initial sepsis/injury insult yet enter chronic critical illness.3,5  Chronic critical illness is defined as low-grade organ dysfunction and intensive care unit length of stay greater than 14 days.2,5-6 Patients more likely to develop chronic critical illness are the elderly and those with poor premorbid health or infections.2,5-6

Patients who develop PICS are susceptible to nosocomial infections, pressure injuries, and loss of lean muscle mass.2-4,6 They experience poor wound healing and decreased functional status.2,4 Despite nutritional intervention, cachexia or malnutrition are possible.2-4,6 Often patients with PICS are transferred to long-term acute care facilities post-discharge where they are at risk of physical and cognitive debility, readmission to the hospital or indolent death.2-3,5

“PICS is a vicious cycle of persistent inflammation, reduced protective immunity, ongoing organ damage, and loss of muscle function and mass.”

Pathophysiology of PICS

The pathophysiology of PICS has been explored. The theory is myeloid-derived suppressor cells (MDSC) and ‘emergency granulopoiesis/myelopoiesis’ are responsible for the concurrent inflammation and immunosuppression observed.4 In response to sepsis or trauma, cytokines, chemokine release and adrenergic stimulation cause granulocytes in bone marrow and secondary lymphoid organs to release and move to the site of the injury/infection; thus leaving space in bone marrow for expansion of hematopoietic stem cells.2-3,5 The new hematopoietic stem cells are preferentially directed to the myeloid pathways towards mature granulocytes, macrophages and dendritic cells.3 During sepsis, immature myeloid cells remain as MDSC instead of maturing into granulocytes, monocytes/macrophages and dendritic cells.3 Myelopoiesis (production of bone marrow) takes place at the expense of lymphopoiesis and erythropoiesis, both which are suppressed, and lymphopenia and anemia occur.3,5  The rapid breakdown and repopulation of bone marrow with innate immune effector cells by hematopoietic stem cells and immature myeloid cells is known as ‘emergency granulopoiesis/myelopoiesis’.3   During the process of  ‘emergency granulopoiesis/myelopoiesis’, the MDSC are not allowed to mature and are released early from the bone marrow.2-4 The number of mature myeloid cells is reduced while the production of MDSC with inflammatory and immunosuppressive tendencies rises.2 PICS is a vicious cycle of persistent inflammation, reduced protective immunity, ongoing organ damage, and loss of muscle function and mass.5

Diagnosing PICS

So how is PICS recognized? There are clinical biomarkers that are used to identify PICS.1-3 These include: 1) length of stay in the intensive care unit greater than 14 days; 2) ongoing inflammation characterized by C-reactive protein greater than 50 μg/dL; 3) ongoing immunosuppression characterized by total lymphocyte count < 0.80 x 109/L and; 4) catabolism reflected by serum albumin < 3.0 g/dL, prealbumin < 10 mg/dL, creatinine height index < 80%, weight loss > 10%, or a body mass index < 18 kg/m2 while hospitalized.2-3

Treating PICS

Treatment for PICS is multimodal and focuses on interruption of the inflammation/immunosuppression cycle.2 A combination of pharmacotherapy, nutrition intervention, early mobilization and physical therapies is proposed for ideal outcomes.3,6

Recommendations for nutritional care are based upon observations from disease states that are physiologically similar to PICS, such as burns or cancer cachexia.4,6 Early enteral nutrition is suggested due to its beneficial effects on the gut.4  As the stomach is recognized as an immunological organ, feeding the gut could potentially lessen the severity of systemic immunosuppression and reduce nosocomial infections.2,4 While the optimal protein intake in PICS is not yet known, 1.2-2.0 gm/kg/day protein is suggested based on protein recommendations for burns, sarcopenia and cancer cachexia.4 Treatment options such as the use of immune enhanced enteral formulas or supplemental leucine (to support anabolism), arginine (to prevent MDSC expansion) or anabolic adjuncts (to reduce protein losses and muscle breakdown) have been proposed in the management of PICS; although, additional research is needed to determine effects of these products on the syndrome and optimal supplementation.2,4

What can registered dietitians (RDs) do if a patient is diagnosed with PICS? RDs can become familiar with the clinical biomarkers of PICS and the pathophysiology of the syndrome. They can continue to explore the research available for best nutritional practices and address nutritional needs in a timely manner. Most importantly, RDs can work as part of the interprofessional team to help to optimize nutritional and medical management of a patient with PICS.

Kim Gottesman Headshot

Kimberly Gottesman is a freelance registered dietitian with a strong background in clinical and food service management. Her clinical and research interests include neonatology, critical care, and weight management. Kimberly is an educator, a published author, and a volunteer ACEND Program Reviewer. In her spare time, Kimberly likes to run, take yoga classes, travel and spend time with her family and friends.

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References:
  1. Gentile LF, Cuenca AG, Efron PA et al.  Persistent inflammation and immunosuppression: a common syndrome and new horizon for surgical intensive care.  J Trauma Acute Care Surg.  2012;72(6):1491-1501.
  2. Mira JC, Brakenridge SC, Moldawer LL, Moore FA. Persistent inflammation, immunosuppression and catabolism syndrome (PICS).  Crit Care Clin.  2017;33(2):245-258.
  3. Mira JC, Gentile LF, Mathias BJ, et al. Sepsis pathophysiology, chronic critical illness and PICS.  Crit Care Med.  2017;45(2):253-262.
  4. Moore FA, Phillips S, McClain C, Patel JJ, Martindale R. Nutrition support for persistent inflammation, immunosuppression and catabolism syndrome.  Nutr Clin Pract.  2017;32(1 Suppl):121S-127S.
  5. Hawkins RB, Raymond SL, Stortz JA et al. Chronic critical illness and the persistent inflammation, immunosuppression, and catabolism syndrome.   Front Immunol. 2018;9:1511. DOI: 10.3389/fimmu.2018.01511.
  6. Rosenthal MD, Moore FA. Persistent inflammatory, immunosuppressed, catabolic syndrome (PICS): a new phenotype of multiple organ failure.  J Adv Nutr Hum Metab.  2015;1(1).   DOI: 10.14800/janhm.784.

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