Sepsis Patients in Critical Care Units with Obesity: Is Obesity Protective?

Kalani, Charlene; Venigalla, Tejaswi; Bailey, Janay; Udeani, George; Surani, Salim

doi:10.7759/cureus.6929

Cited by 12 publications

(13 citation statements)

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“…This is because hardly anything is known about differences in the immune response between the two in the course of sepsis as well as on possible causes of the paradox. The elevated adipose tissue mass and associated energy stores were proposed to be the causative factor due to the catabolic nature of sepsis [ 34 ]. On the other hand, as obesity is accompanied by a low-grade inflammation, altered course of systemic inflammation was suggested in obese individuals.…”

Section: Introductionmentioning

confidence: 99%

Scrutinizing Mechanisms of the ‘Obesity Paradox in Sepsis’: Obesity Is Accompanied by Diminished Formation of Neutrophil Extracellular Traps (NETs) Due to Restricted Neutrophil–Platelet Interactions

Cichoń

Ortmann

Santocki

et al. 2021

Cells

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Systemic inflammation is a detrimental condition associated with high mortality. However, obese individuals seem to have higher chances of surviving sepsis. To elucidate what immunological differences exist between obese and lean individuals we studied the course of endotoxemia in mice fed high-fat diet (HFD) and ob/ob animals. Intravital microscopy revealed that neutrophil extracellular trap (NET) formation in liver vasculature is negligible in obese mice in sharp contrast to their lean counterparts (ND). Unlike in lean individuals, neutrophil influx is not driven by leptin or interleukin 33 (IL-33), nor occurs via a chemokine receptor CXCR2. In obese mice less platelets interact with neutrophils forming less aggregates. Platelets transfer from ND to HFD mice partially restores NET formation, and even further so upon P-selectin blockage on them. The study reveals that in obesity the overexaggerated inflammation and NET formation are limited during sepsis due to dysfunctional platelets suggesting their targeting as a therapeutic tool in systemic inflammation.

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Section: Introductionmentioning

confidence: 99%

Scrutinizing Mechanisms of the ‘Obesity Paradox in Sepsis’: Obesity Is Accompanied by Diminished Formation of Neutrophil Extracellular Traps (NETs) Due to Restricted Neutrophil–Platelet Interactions

Cichoń

Ortmann

Santocki

et al. 2021

Cells

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“…Various hypotheses have been postulated by investigators to explain this protective effect of obesity, including the excess adipose tissue fat stores, which might serve as a reservoir of energy to be used during the catabolic state created by sepsis-related inflammation. 32,33 Another possible explanation is related to the immunomodulatory effect of the adipose tissue and possible differential sepsis related systemic inflammatory response among patients with obesity compared to control population leading to dampening of the proinflammatory mediators and contributing to a favourable outcome. 32,34 There could be a selection bias among patients with obesity with severe sepsis being cared for in intensive care units and end up being recipients of more aggressive therapy in anticipation of a difficult clinical course which may partly explaining the obesity paradox.…”

Section: Discussionmentioning

confidence: 99%

“…demonstrated that morbid obesity had a protective effect over inhospital mortality among patients with severe sepsis and septic shock, whereas Kalani et al suggested a U-shaped relationship between BMI and mortality, implying an increased mortality risk observed in patients with underweight and morbid obesity. 28,32 Whether the increased prevalence of visceral adiposity, metabolic syndrome and related cardiovas- 6). We also found that diabetes mellitus and skin infections were commonly associated with the severity of obesity.…”

Section: Discussionmentioning

confidence: 99%

“…This protective effect was consistently significant for patients with septic shock as well (OR 0.46; CI: 0.34–0.62, p < 0.001) (Table 5). Various hypotheses have been postulated by investigators to explain this protective effect of obesity, including the excess adipose tissue fat stores, which might serve as a reservoir of energy to be used during the catabolic state created by sepsis‐related inflammation 32,33 . Another possible explanation is related to the immunomodulatory effect of the adipose tissue and possible differential sepsis related systemic inflammatory response among patients with obesity compared to control population leading to dampening of the proinflammatory mediators and contributing to a favourable outcome 32,34 .…”

Section: Discussionmentioning

confidence: 99%

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Effect of obesity on mortality among hospitalized paediatric patients with severe sepsis

et al. 2021

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Summary Introduction Severe sepsis is one of the leading causes of mortality among children. Studies in adults have suggested a protective effect of obesity on mortality among patients hospitalized with sepsis. Paediatric studies evaluating similar relationship is lacking. Methods We analysed non‐overlapping years of the Kids Inpatient Database (KID) and National Inpatient Sample (NIS) database between 2003 and 2014 of all paediatric patients with severe sepsis (PSS) up to 20 years of age. PSS was defined using specific International Classification of Diseases (ICD) codes and modified Angus criteria. Using ICD‐9 diagnosis codes, patients were divided into three mutually exclusive groups (obesity, morbid obesity and control groups), and these groups were compared for outcomes measures including in‐hospital mortality and healthcare resource utilization using the length of stay and inflation‐adjusted hospitalization charges. Results We analysed 109 026 hospitalizations due to PSS. The prevalence rate of obesity was 1.5% (n = 1643), and morbid obesity was 1.05% (n = 1147). Multivariate regression models showed obesity was associated with 63% (OR 0.37, CI: 0.29–0.47, p < 0.001) and 54% reduction in mortality among PSS patients and patients with septic shock respectively. Contrastingly, morbid obesity was not associated with mortality among PSS patients and but was associated with 1.37 times (CI: 1.06–1.78, p = 0.01) increased risk of mortality among paediatric patients with septic shock. Conclusions Paediatric obesity is associated with reduced mortality among patients with PSS, with the exception of morbid obesity. Further prospective studies are needed to better understand the relationship between obesity and outcomes in PSS.

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“…Adiponectin levels, a protein hormone secreted by adipocytes, are inversely associated with Apo-A-1 catabolism, independent of obesity, insulin resistance, and HDL triglyceride content. Its levels are decreased significantly during sepsis as well as obesity [ 68 , 69 ]. While lower adiponectin levels are correlated with obesity, visceral fat loss has not been shown to significantly raise levels [ 70 ].…”

Section: Alterations Of Lipid Metabolism In Sepsis Contribute To Failed Inflammation Resolutionmentioning

confidence: 99%

Lipid and Lipoprotein Dysregulation in Sepsis: Clinical and Mechanistic Insights into Chronic Critical Illness

Barker

Leeuwenburgh

Brusko

et al. 2021

JCM

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In addition to their well-characterized roles in metabolism, lipids and lipoproteins have pleiotropic effects on the innate immune system. These undergo clinically relevant alterations during sepsis and acute inflammatory responses. High-density lipoprotein (HDL) plays an important role in regulating the immune response by clearing bacterial toxins, supporting corticosteroid release, decreasing platelet aggregation, inhibiting endothelial cell apoptosis, reducing the monocyte inflammatory response, and inhibiting expression of endothelial cell adhesion molecules. It undergoes quantitative as well as qualitative changes which can be measured using the HDL inflammatory index (HII). Pro-inflammatory, or dysfunctional HDL (dysHDL) lacks the ability to perform these functions, and we have also found it to independently predict adverse outcomes and organ failure in sepsis. Another important class of lipids known as specialized pro-resolving mediators (SPMs) positively affect the escalation and resolution of inflammation in a temporal fashion. These undergo phenotypic changes in sepsis and differ significantly between survivors and non-survivors. Certain subsets of sepsis survivors go on to have perilous post-hospitalization courses where this inflammation continues in a low grade fashion. This is associated with immunosuppression in a syndrome of persistent inflammation, immunosuppression, and catabolism syndrome (PICS). The continuous release of tissue damage-related patterns and viral reactivation secondary to immunosuppression feed this chronic cycle of inflammation. Animal data indicate that dysregulation of endogenous lipids and SPMs play important roles in this process. Lipids and their associated pathways have been the target of many clinical trials in recent years which have not shown mortality benefit. These results are limited by patient heterogeneity and poor animal models. Considerations of sepsis phenotypes and novel biomarkers in future trials are important factors to be considered in future research. Further characterization of lipid dysregulation and chronic inflammation during sepsis will aid mortality risk stratification, detection of sepsis, and inform individualized pharmacologic therapies.

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Sepsis Patients in Critical Care Units with Obesity: Is Obesity Protective?

Cited by 12 publications

References 50 publications

Scrutinizing Mechanisms of the ‘Obesity Paradox in Sepsis’: Obesity Is Accompanied by Diminished Formation of Neutrophil Extracellular Traps (NETs) Due to Restricted Neutrophil–Platelet Interactions

Scrutinizing Mechanisms of the ‘Obesity Paradox in Sepsis’: Obesity Is Accompanied by Diminished Formation of Neutrophil Extracellular Traps (NETs) Due to Restricted Neutrophil–Platelet Interactions

Effect of obesity on mortality among hospitalized paediatric patients with severe sepsis

Lipid and Lipoprotein Dysregulation in Sepsis: Clinical and Mechanistic Insights into Chronic Critical Illness

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