Free Fatty Acids’ Level and Nutrition in Critically Ill Patients and Association with Outcomes: A Prospective Sub-Study of PermiT Trial

Abstract

Objectives: The objectives of this study were to evaluate the clinical and nutritional correlates of high free fatty acids (FFAs) level in critically ill patients and the association with outcomes, and to study the effect of short-term caloric restriction (permissive underfeeding) on FFAs level during critical illness. Patients/Method: In this pre-planned sub-study of the PermiT (Permissive Underfeeding vs. Target Enteral Feeding in Adult Critically Ill Patients) trial, we included critically ill patients who were expected to stay for ≥14 days in the intensive care unit. We measured FFAs level on day 1, 3, 5, 7, and 14 of enrollment. Of 70 enrolled patients, 23 (32.8%) patients had high FFAs level (baseline FFAs level >0.45 mmol/L in females and >0.6 mmol/L in males). Results: Patients with high FFAs level were significantly older and more likely to be females and diabetics and they had lower ratio of partial pressure of oxygen to the fraction of inspired oxygen, higher creatinine, and higher total cholesterol levels than those with normal FFAs level. During the study period, patients with high FFAs level had higher blood glucose and required more insulin. On multivariable logistic regression analysis, the predictors of high baseline FFAs level were diabetes (adjusted odds ratio (aOR): 5.36; 95% confidence interval (CI): 1.56, 18.43, p = 0.008) and baseline cholesterol level (aOR, 4.29; 95% CI: 11.64, 11.19, p = 0.003). Serial levels of FFAs did not differ with time between permissive underfeeding and standard feeding groups. FFAs level was not associated with 90-day mortality (aOR: 0.49; 95% CI: 0.09, 2.60, p = 0.40). Conclusion: We conclude that high FFAs level in critically ill patients is associated with features of metabolic syndrome and is not affected by short-term permissive underfeeding.

Development and Clinical Translation of a Perioperative Nomogram Incorporating Free Fatty Acids to Predict Poor Outcome of Aneurysmal Subarachnoid Hemorrhage Following Endovascular Treatment

“…Biologically, FFA mainly originates from the hydrolysis of TG and serves as a preferred energy fuel for tissue (29). Acute critical illnesses, such as trauma or sepsis, could induce elevated FFA levels in serum (30). In cerebral diseases, FFA has been proven to be independently associated with both the poor prognosis and stroke recurrence in patients with ischemic stroke (31,32); however, scarce data reveal the roles of serum FFA in aSAH outcome.…”

The Impact of Glucose-Based or Lipid-Based Total Parenteral Nutrition on the Free Fatty Acids Profile in Critically Ill Patients

“…The physiological reference range for plasma FFA concentrations in our laboratory ranged from 0.100 to 0.600 mmol•L −1 . In the ICU patients, Arabi et al [7] considered a cut-off value to be 0.45 mmol•L-1 in females and 0.6 mmol•L −1 in males, as the upper limits of normal. In accordance with their cut off, 29.1% of the patients had elevated levels of FFAs at the start of the study, which was almost the same as the Arabi study (32.8%).…”

“…The provision of specific types of TPN admixtures for several weeks significantly changed the concentrations of total FFAs in plasma. From a clinical point of view, it has been reported that high concentrations of FFA are present in patients with acute respiratory distress syndrome or sepsis [7,37]. Thus, FFA modulation may be important in positively influencing the inflammatory markers; however, the exact mechanism is unclear.…”

“…Elevated levels of FFAs are frequent in obese subjects and especially in those who are obese and insulin-resistant or in those who are already type 2 diabetics [6]. Recently, Arabi et al, in their study, described a positive relationship between the elevated levels of FFAs and blood glucose with increased insulin requirements in critically ill patients with diabetes and in older patients, thus suggesting a connection between elevated FFA levels and metabolic syndrome [7]. It was previously shown that therapeutic procedures that indirectly influence the levels of FFAs could be important in some clinical states.…”

Should nutrition therapy be modified to account for mitochondrial dysfunction in critical illness?

“…Early critical illness is associated with impaired β‐oxidation and reduced enzyme concentrations and thus an inability to effectively utilize fat 3,19 . This is associated with decreased mitochondrial biogenesis and a compromised bioenergetic status 19,26 …”