Altered Serum Acylcarnitines Profile after a Prolonged Stay in Intensive Care

Abstract

A stay in intensive care unit (ICU) exposes patients to a risk of carnitine deficiency. Moreover, acylated derivates of carnitine (acylcarnitines, AC) are biomarkers for metabolic mitochondrial dysfunction that have been linked to post-ICU disorders. This study aimed to describe the AC profile of survivors of a prolonged ICU stay (≥7 days). Survivors enrolled in our post-ICU clinic between September 2020 and July 2021 were included. Blood analysis was routinely performed during the days after ICU discharge, focusing on metabolic markers and including AC profile. Serum AC concentrations were determined by LC-MS/MS and were compared to the reference ranges (RR) established from serum samples of 50 non-hospitalized Belgian adults aged from 18 to 81 years. A total 162 patients (65.4% males, age 67 (58.7–73) years) survived an ICU stay of 9.7 (7.1–19.3) days and were evaluated 5 (3–8) days after discharge. Their AC profile was significantly different compared to RR, mostly in terms of short chain AC: the sum of C3, C4 and C5 derivates reached 1.36 (0.98–1.99) and 0.86 (0.66–0.99) µmol/L respectively (p < 0.001). Free carnitine (C0) concentration of survivors (46.06 (35.04–56.35) µmol/L) was similar to RR (43.64 (36.43–52.96) µmol/L) (p = 0.55). C0 below percentile 2.5 of RR was observed in 6/162 (3.7%) survivors. Their total AC/C0 ratio was 0.33 (0.22–0.42). A ratio above 0.4 was observed in 45/162 (27.8%) patients. In ICU survivors, carnitine deficiency was rare, but AC profile was altered and AC/C0 ratio was abnormal in more than 25%. The value of AC profile as a marker of post-ICU dysmetabolism needs further investigations.

Serum Acylcarnitines Profile in Critically Ill Survivors According to Illness Severity and ICU Length of Stay: An Observational Study

“…In the present study, LCACs were elevated in both groups compared to the reference population [ 4 ]. LCACs are also considered as markers of mitochondrial dysfunction, as increased levels are associated with the impaired mitochondrial ability of fatty acid oxidation [ 3 ].…”

“…Inflammation is a well-known trigger for mitochondrial dysfunction [ 19 , 20 ]. Residual or persistent inflammation is typically observed early after ICU discharge [ 4 ]. Skeletal muscle, rich in mitochondria, is vulnerable to the various forms of mitochondrial alterations observed early after critical illness, thus explaining at least partly the neuromuscular failure in ICU survivors [ 21 ].…”

“…In a recent study, we showed that the AC profile was altered after a prolonged stay in the ICU compared to a reference adult population [ 4 ]. Short-chain ACs were found in excess, while an increased AC/C0 ratio was observed in more than 25% of the cohort.…”

Carnitine Deficiency in Intensive Care Unit Patients Undergoing Continuous Renal Replacement Therapy: A Single-center Retrospective Study

“…Sepsis, which is considered a risk factor for ICU-AW, is one of the primary diseases for which CRRT is commenced in the ICU (19) ; it accounted for half of the eligible ICU cases in this study. Furthermore, recent reports have found that muscle weakness in ICU patients is due to mitochondrial dysfunction (9) , (20) . Impaired β-oxidation of fatty acids in the mitochondria may induce the accumulation of acyl-CoA and contribute to mitochondrial dysfunction (9) , (21) .…”

“…L-carnitine replacement therapy can reduce the risk of cardiac complications, anemia, muscle weakness, and other complications (6) , (7) , (8) . However, reports on the comprehensive evaluation of carnitine concentrations in critically ill patients are scarce, and carnitine deficiency in intensive care settings has not been adequately assessed (9) . Furthermore, reports of carnitine deficiency in adult patients undergoing continuous renal replacement therapy (CRRT), which is used in intensive care settings, are lacking.…”