Chronic Critically Ill Septic Patients Exhibit Persistent Expression of Pro-Inflammatory Lipidomics

Abstract Objectives In order to evaluate the therapeutic potential of resolvins to reduce inflammation in CCI-PICS, we recapitulated Glue Grant leukotriene and resolvin lipidomic scores above to quantify lipidomics in severe sepsis/septic shock survivors. Methods Ongoing University of Florida (UF) Sepsis Critical Illness Research Center (SCIRC) research studies indicate that Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) occurs as a result of a self-perpetuating cycle of low-grade inflammation. However, specialized pro-resolving mediators (SPMs) – metabolically active lipid byproducts of omega-3 fatty acids – can promote inflammatory deceleration and resolution.,1 Post hoc analysis of the Glue Grant Data developed a mathematical lipidomic expression to better understand genes responsible for production and degradation of resolvins and leukotrienes.,2 Leukotriene Score = (ALOX5 * ALX5AP * LTA4H * LTB4R)/(HPGD + PTGR1 + CYP4F3) Resolvin Score = [(ALOX5 * ALOX15) * (FPR2 + GPR32 + CMKLR1)]/(HPGD + PTGR1) When the targeted genes were scored using a weighted scheme accounting for enzyme and receptor activity, patients with uncomplicated recoveries had higher resolvin scores (P < 0.001) and lower leukotriene scores (P < 0.001). Utilizing our PICS patient data, we recapitulated the aforementioned lipidomic scores above to quantify expression in severe sepsis/septic shock survivors. Results Leukotriene and resolvin scores are depicted in Figure 1 at specific time points 0 (healthy controls), 3 hours, 1 and 14 days. The leukotriene score remains elevated consistent with ongoing inflammatory genotypic expression. Interestingly, the resolvin score also remains elevated in the CCI (Glue Grant complicated cohort) patient population when compared to our Rapid Recovery (RAP or uncomplicated) patients *Accompanied by two graphs depicting correlating numerical values for the aforementioned Leukotriene and Resolvin scores. Conclusions In our patient population of sepsis survivors, the leukotriene score is similarly elevated to the complicated Glue Grant patients of polytrauma. The resolvin score, however, remains elevated in the CCI-PICS population compared to RAP; this is contrary to expected scores if resolution of inflammation is predicted. Funding Sources University of Florida.

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Prognostic significance of body temperature in the emergency department vs the ICU in Patients with severe sepsis or septic shock: A nationwide cohort study

PLoS ONE ◽

10.1371/journal.pone.0243990 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0243990

Author(s):

Malin Inghammar ◽

Jonas Sunden-Cullberg

Keyword(s):

Emergency Department ◽

Septic Shock ◽

Severe Sepsis ◽

Quality Of Care ◽

Body Temperature ◽

Prognostic Significance ◽

Low Grade ◽

Nurse Workload ◽

Sepsis Bundle

Background Increased body temperature in the Emergency Department (BT-ED) and the ICU (BT-ICU) is associated with lower mortality in patients with sepsis. Here, we compared how well BT-ED and BT-ICU predict mortality; investigated mortality in various combinations of BT-ED and BT-ICU, and; compared degree of fever in the ED and ICU and associated quality of care. Methods 2385 adults who were admitted to an ICU within 24 hours of ED arrival with severe sepsis or septic shock were included. Results Thirty-day mortality was 23.6%. Median BT-ED and BT-ICU was 38.1 and 37.6°C. Crude mortality decreased more than 5% points per°C increase for both BT-ED and BT-ICU. Adjusted OR for mortality was 0.82/°C increase for BT-ED (0.76–0.88, p < 0.001), and 0.89 for BT-ICU (0.83–0.95, p<0.001). Patients who were at/below median temperature in both the ED and in the ICU had the highest mortality, 32%, and those with over median in the ED and at/below in the ICU had the lowest, 16%, (p<0.001). Women had 0.2°C lower median BT-ED (p = 0.03) and 0.3°C lower BT-ICU (p<0.0001) than men. Older patients had lower BT in the ICU, but not in the ED. Fever was associated with a higher rate of sepsis bundle achievement in the ED, but lower nurse workload in the ICU. Conclusions BT-ED was more useful to prognosticate mortality than BT-ICU. Despite better prognosis in patients with elevated BT, fever was associated with higher quality of care in the ED. Future studies should assess how BT-ED can be used to improve triage of infected patients, assigning higher priority to patients with low-grade/no fever and vice versa. Patients with at/below median BT in both ED and ICU have the highest mortality and should receive special attention. Different BT according to sex and age also needs further study.

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Chronic Critical Illness and PICS Nutritional Strategies

Journal of Clinical Medicine ◽

10.3390/jcm10112294 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2294

Author(s):

Martin D. Rosenthal ◽

Erin L. Vanzant ◽

Frederick A. Moore

Keyword(s):

Critical Illness ◽

Low Grade ◽

Long Term Outcomes ◽

Persistent Inflammation ◽

Chronic Critical Illness ◽

Similar Phenotype ◽

Sepsis Survivors ◽

Low Grade Inflammation ◽

Nutritional Strategies

The nutritional hallmark of chronic critical illness (CCI) after sepsis is persistent inflammation, immunosuppression, and catabolism syndrome (PICS), which results in global resistance to the anabolic effect of nutritional supplements. This ultimately leaves these patients in a downward phenotypic spiral characterized by cachexia with profound weakness, decreased capacity for rehabilitation, and immunosuppression with the propensity for sepsis recidivism. The persistent catabolism is driven by a pathologic low-grade inflammation with the inability to return to homeostasis and by ongoing increased energy expenditure. Better critical care support systems and advances in technology have led to increased intensive care unit (ICU) survival, but CCI due to PICS with poor long-term outcomes has emerged as a frequent phenotype among ICU sepsis survivors. Unfortunately, therapies to mitigate or reverse PICS-CCI are limited, and recent evidence supports that these patients fail to respond to early ICU evidence-based nutrition protocols. A lack of randomized controlled trials has limited strong recommendations for nutrition adjuncts in these patients. However, based on experience in other conditions characterized by a similar phenotype, immunonutrients aimed at counteracting inflammation, immunosuppression, and catabolism may be important for improving outcomes in PICS-CCI patients. This manuscript intends to review several immunonutrients as adjunctive therapies in treating PICS-CCI.

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Effect of fluid bolus triggers and their combination on fluid responsiveness in optimization phase of severe sepsis and septic shock resuscitation

MedPharmRes ◽

10.32895/ump.mpr.2.3.27 ◽

2018 ◽

Vol 2 (3) ◽

pp. 27-32

Author(s):

Bien Le ◽

Dai Huynh ◽

Mai Tuan ◽

Minh Phan ◽

Thao Pham ◽

...

Keyword(s):

Blood Pressure ◽

Septic Shock ◽

Severe Sepsis ◽

Fluid Responsiveness ◽

Statistical Significance ◽

Venous Pressure ◽

Fluid Bolus ◽

Low Blood Pressure ◽

Low Central Venous Pressure ◽

Sepsis And Septic Shock

Objectives: to evaluate the fluid responsiveness according to fluid bolus triggers and their combination in severe sepsis and septic shock. Design: observational study. Patients and Methods: patients with severe sepsis and septic shock who already received fluid after rescue phase of resuscitation. Fluid bolus (FB) was prescribed upon perceived hypovolemic manifestations: low central venous pressure (CVP), low blood pressure, tachycardia, low urine output (UOP), hyperlactatemia. FB was performed by Ringer lactate 500 ml/30 min and responsiveness was defined by increasing in stroke volume (SV) ≥15%. Results: 84 patients were enrolled, among them 30 responded to FB (35.7%). Demographic and hemodynamic profile before fluid bolus were similar between responders and non-responders, except CVP was lower in responders (7.3 ± 3.4 mmHg vs 9.2 ± 3.6 mmHg) (p 0.018). Fluid response in low CVP, low blood pressure, tachycardia, low UOP, hyperlactatemia were 48.6%, 47.4%, 38.5%, 37.0%, 36.8% making the odd ratio (OR) of these triggers were 2.81 (1.09-7.27), 1.60 (0.54-4.78), 1.89 (0.58-6.18), 1.15 (0.41-3.27) and 1.27 (0.46-3.53) respectively. Although CVP < 8 mmHg had a higher response rate, the association was not consistent at lower cut-offs. The combination of these triggers appeared to raise fluid response but did not reach statistical significance: 26.7% (1 trigger), 31.0% (2 triggers), 35.7% (3 triggers), 55.6% (4 triggers), 100% (5 triggers). Conclusions: fluid responsiveness was low in optimization phase of resuscitation. No fluid bolus trigger was superior to the others in term of providing a higher responsiveness, their combination did not improve fluid responsiveness as well.

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