Mid-Term Evolution of the Serum Acylcarnitine Profile in Critically Ill Survivors: A Metabolic Insight into Survivorship.

It is unknown if the abnormal acylcarnitine (AC) profile observed early after discharge of a prolonged stay in an intensive care unit (ICU) would persist over time. This prospective observational study aimed to describe the mid-term AC profile evolution in survivors of a prolonged ICU stay (≥7 days). Adults enrolled in our post-ICU follow-up program and who attended the consultation 3 months (M3) after discharge were included. Serum AC concentrations were assessed within 7 days following ICU discharge (T0) and at M3. A total of 64 survivors were analyzed after an ICU stay of 15 (9-24) days. Free carnitine (C0) concentration decreased from 45.89 (35.80-127.5) to 28.73 (20.31-38.93) µmol/L (p < 0.001). C0 deficiency was not observed at T0 but in 7/64 (11%) survivors at M3. The total AC/C0 ratio (normal ≤ 0.4) was 0.33 (0.24-0.39) at T0 and reached 0.39 (0.30-0.56) at M3 (p = 0.001). A ratio >0.4 was observed in 16/64 (25%) at T0 and in 32/64 (50%) at M3 (p = 0.006). The short-chain ACs decreased from 1.310 (0.927-1.829) at T0 to 0.945 (0.709-1.127) µmol/L at M3 (p < 0.001). In parallel, the urea/creatinine ratio and the Sarcopenic Index, respectively, decreased and increased between T0 and M3. This AC profile is suspected to signal a mitochondrial dysfunction and was, especially for short-chain ACs, a marker of protein catabolism.

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

The acylcarnitine (AC) profile has been shown to be altered in survivors of a prolonged stay in intensive care unit (ICU), with higher short-chain derivates compared to reference ranges. The present study aimed at describing the AC profile of patients surviving a short ICU stay versus patients surviving a >7-day multiple organ dysfunction. Patients discharged from ICU after an elective and non-complicated cardiac surgery (CS) were recruited. For each CS, one to two adults, matched for gender and age, were recruited among patients enrolled in our post-ICU follow-up program after an ICU stay ≥7 days (PS). In both groups, the AC profile was determined during the week following ICU discharge. A total of 50 CS patients (SAPS II 23 (18-27)) survived an ICU stay of 2 (2-3) days and were matched to 85 PS patients (SAPS II 36 (28-51), p < 0.001) who survived an ICU stay of 11 (8-15.5) days. No carnitine deficiency was observed in either group. Their total AC/C0 ratio was similar: 0.355 (0.268-0.415) and 0.358 (0.289-0.417), respectively (p = 0.391). A ratio >0.4 representing a disturbed mitochondrial metabolism was observed in 26/85 (30.6%) PS patients and in 15/50 (30%) CS patients (p > 0.999). The long-chain ACs were elevated in both groups, with a greater increase in the CS group. The short-chain ACs were higher in the PS group: 1.520 (1.178-1.974) vs. 1.185 (0.932-1.895) µmol/L (p < 0.001). The role of the AC profile as potential marker of catabolism and/or mitochondrial dysfunction during the critical illness trajectory should be further investigated.

Characteristics of Mid-Term Post-Intensive Care Syndrome in Patients Attending a Follow-Up Clinic: A Prospective Comparison Between COVID-19 and Non-COVID-19 Survivors.

At present, it is not clear if critically ill COVID-19 survivors have different needs in terms of follow-up compared with other critically ill survivors, and thus if duplicated post-ICU trajectories are mandatory. OBJECTIVES: To compare the post-intensive care syndrome (PICS) of COVID-19 acute respiratory distress syndrome and non-COVID-19 (NC) survivors referred to a follow-up clinic at 3 months (M3) after ICU discharge. DESIGN SETTING AND PARTICIPANTS: Adults who survived an ICU stay greater than or equal to 7 days and attended the M3 consultation were included in this observational study performed in a post-ICU follow-up clinic of a single tertiary hospital. MAIN OUTCOMES AND MEASURES: Patients underwent a standardized assessment, addressing health-related quality of life (3-level version of EQ-5D), sleep disorders (Pittsburgh Sleep Quality Index [PSQI]), physical status (Barthel index, handgrip and quadriceps strengths), mental health disorders (Hospital Anxiety and Depression Scale and Impact of Event Scale-Revised [IES-R]), and cognitive impairment (Montreal Cognitive Assessment [MoCA]). RESULTS: A total of 143 survivors (86 COVID and 57 NC) attended the M3 consultation. Their median age and severity scores were similar. NC patients had a shorter ICU stay (10 d [8-17.2 d]) compared with COVID group (18 d [10.8-30 d]) (p = 0.001). M3 outcomes were similar in the two groups, except for a higher PSQI (p = 0.038) in the COVID group (6 [3-9.5]) versus NC group (4 [2-7]), and a slightly lower Barthel index in the NC group (100 [100-100]) than in the COVID group (100 [85-100]) (p = 0.026). However, the proportion of patients with abnormal values at each score was similar in the two groups. Health-related quality of life was similar in the two groups. The three MoCA (≥ 26), IES-R (<33), and Barthel (=100) were normal in 58 of 143 patients (40.6%). In contrast, 68.5% (98/143) had not returned to their baseline level of daily activities. CONCLUSIONS AND RELEVANCE: In our follow-up clinic at 3 months after discharge, the proportion of patients presenting alterations in the main PICS domains was similar whether they survived a COVID-19 or another critical illness, despite longer ICU stay in COVID group. Cognition and sleep were the two most affected PICS domains.

Measured Energy Expenditure Using Indirect Calorimetry in Post-Intensive Care Unit Hospitalized Survivors: A Comparison with Predictive Equations.

Actual energy needs after a stay in intensive care units (ICUs) are unknown. The aims of this observational study were to measure the energy expenditure (mEE) of ICU survivors during their post-ICU hospitalization period, and to compare this to the estimations of predictive equations (eEE). Survivors of an ICU stay ≥ 7 days were enrolled in the general ward during the first 7 days after ICU discharge. EE was measured using the Q-NRG calorimeter in canopy mode. This measure was compared to the estimated EE using the Harris−Benedict (HB) equation multiplied by a 1.3 stress factor, the Penn−State (PS) equation or the 30 kcal weight-based (WB) equation. A total of 55 adults were included (67.3% male, age 60 (52−67) y, body mass index 26.1 (22.2−29.7) kg/m2). Indirect calorimetry was performed 4 (3−6) d after an ICU stay of 12 (7−16) d. The mEE was 1682 (1328−1975) kcal/d, corresponding to 22.9 (19.1−24.2) kcal/kg/day. The eEE values derived using HB and WB equations were significantly higher than mEE: 3048 (1805−3332) and 2220 (1890−2640) kcal/d, respectively (both p < 0.001). There was no significant difference between mEE and eEE using the PS equation: 1589 (1443−1809) kcal/d (p = 0.145). The PS equation tended to underestimate mEE with a bias of −61.88 kcal and a wide 95% limit of agreement (−717.8 to 594 kcal). Using the PS equation, agreement within 15% of the mEE was found in 32/55 (58.2%) of the patients. In the present cohort of patients who survived a prolonged ICU stay, mEE was around 22−23 kcal/kg/day. In this post-ICU hospitalization context, none of the tested equations were accurate in predicting the EE measured by indirect calorimetry.

Adequacy of Nutritional Intakes during the Year after Critical Illness: An Observational Study in a Post-ICU Follow-Up Clinic.

Whether nutritional intakes in critically ill survivors after hospital discharge are adequate is unknown. The aims of this observational study were to describe the energy and protein intakes in ICU survivors attending a follow-up clinic compared to empirical targets and to explore differences in outcomes according to intake adequacy. All adult survivors who attended the follow-up clinic at 1, 3 and 12 months (M1, M3, M12) after a stay in our intensive care unit (ICU) ≥ 7 days were recruited. Average energy and protein intakes over the 7 days before the face-to-face consultation were quantified by a dietician using food anamnesis. Self-reported intakes were compared empirically to targets for healthy people (FAO/WHO/UNU equations), for critically ill patients (25 kcal/kg/day and 1.3 g protein/kg/day). They were also compared to targets that are supposed to fit post-ICU patients (35 kcal/kg/day and 1.5 g protein/kg/day). Blood prealbumin level and handgrip strength were also measured at each timepoint. A total of 206 patients were analyzed (49, 97 and 60 at the M1, M3 and M12, respectively). At M1, M3 and M12, energy intakes were 73.2 [63.3-86.3]%, 79.3 [69.3-89.3]% and 82.7 [70.6-93.7]% of healthy targets (p = 0.074), respectively. Protein intakes were below 0.8 g/kg/day in 18/49 (36.7%), 25/97 (25.8%) and 8/60 (13.3%) of the patients at M1, M3 and M12, respectively (p = 0.018), and the protein intakes were 67.9 [46.5-95.8]%, 68.5 [48.8-99.3]% and 71.7 [44.9-95.1]% of the post-ICU targets (p = 0.138), respectively. Prealbumin concentrations and handgrip strength were similar in patients with either inadequate energy intakes or inadequate protein intakes, respectively. In our post-ICU cohort, up to one year after discharge, energy and protein intakes were below the targets that are supposed to fit ICU survivors in recovery phase.

Exercise Limitation after Critical Versus Mild COVID-19 Infection: A Metabolic Perspective.

Exercise limitation in COVID-19 survivors is poorly explained. In this retrospective study, cardiopulmonary exercise testing (CPET) was coupled with an oxidative stress assessment in COVID-19 critically ill survivors (ICU group). Thirty-one patients were included in this group. At rest, their oxygen uptake (VO2) was elevated (8 [5.6-9.7] mL/min/kg). The maximum effort was reached at low values of workload and VO2 (66 [40.9-79.2]% and 74.5 [62.6-102.8]% of the respective predicted values). The ventilatory equivalent for carbon dioxide remained within normal ranges. Their metabolic efficiency was low: 15.2 [12.9-17.8]%. The 50% decrease in VO2 after maximum effort was delayed, at 130 [120-170] s, with a still-high respiratory exchange ratio (1.13 [1-1.2]). The blood myeloperoxidase was elevated (92 [75.5-106.5] ng/mL), and the OSS was altered. The CPET profile of the ICU group was compared with long COVID patients after mid-disease (MLC group) and obese patients (OB group). The MLC patients (n = 23) reached peak workload and predicted VO2 values, but their resting VO2, metabolic efficiency, and recovery profiles were similar to the ICU group to a lesser extent. In the OB group (n = 15), no hypermetabolism at rest was observed. In conclusion, the exercise limitation after a critical COVID-19 bout resulted from an altered metabolic profile in the context of persistent inflammation and oxidative stress. Altered exercise and metabolic profiles were also observed in the MLC group. The contribution of obesity on the physiopathology of exercise limitation after a critical bout of COVID-19 did not seem relevant.

Post-intensive care screening: French translation and validation of the Healthy Aging Brain Care-Monitor, hybrid version.

BACKGROUND: The Healthy Aging Brain Care-Monitor (HABC-M) questionnaires (self-reported version and caregiver version) have been validated for post-intensive care syndrome (PICS) detection in patients surviving a stay in the intensive care unit (ICU). Their authors have also developed a hybrid version (HABC-M-HV) suited to the daily needs of their post-ICU follow-up clinic. The objectives of the present cross-sectional observational study were to translate the HABC-M-HV questionnaire into French (HABC-M-HV-F) according to international guidelines and to test its measurement properties. METHODS: The HABC-M-HV was translated according to international guidelines. The measurement performances of the questionnaire were tested using internal consistency, test-retest reliability, Standard Error of Measurement (SEM) and Smallest Detectable Change (SDC) calculation, floor and ceiling effect measurement and construct validity. RESULTS: The validation study included 51 ICU survivors (27.5% women, 63 [55-71] years old). The questionnaire was administered by phone. The internal consistency was very good (Cronbach's alpha coefficient 0.79). The intra- and inter-examinator reliabilities were excellent (Intraclass Coefficient Correlation = 0.99 and 0.97, respectively). The SEM was 0.62 and the SDC was 1.72. No floor or ceiling effects were observed. The convergent validity was almost entirely confirmed with 71.4% of our hypothesis confirmed. CONCLUSION: The HABC-M-HV-F has been shown to be a valid and reliable tool for PICS screening and follow-up in French-speaking ICU survivors. A remote administration by phone was feasible. TRIAL REGISTRATION: Not applicable.

Cardiopulmonary Exercise Testing in Critically Ill Coronavirus Disease 2019 Survivors: Evidence of a Sustained Exercise Intolerance and Hypermetabolism.

To investigate exercise capacity at 3 and 6 months after a prolonged ICU stay. DESIGN: Observational monocentric study. SETTING: A post-ICU follow-up clinic in a tertiary university hospital in Liège, Belgium. PATIENTS: Patients surviving an ICU stay greater than or equal to 7 days for a severe coronavirus disease 2019 pneumonia and attending our post-ICU follow-up clinic. MEASUREMENTS AND MAIN RESULTS: Cardiopulmonary and metabolic variables provided by a cardiopulmonary exercise testing on a cycle ergometer were collected at rest, at peak exercise, and during recovery. Fourteen patients (10 males, 59 yr [52-62 yr], all obese with body mass index > 27 kg/m2) were included after a hospital stay of 40 days (35-53 d). At rest, respiratory quotient was abnormally high at both 3 and 6 months (0.9 [0.83-0.96] and 0.94 [0.86-0.97], respectively). Oxygen uptake was also abnormally increased at 3 months (8.24 mL/min/kg [5.38-10.54 mL/min/kg]) but significantly decreased at 6 months (p = 0.013). At 3 months, at the maximum workload (67% [55-89%] of predicted workload), oxygen uptake peaked at 81% (64-104%) of predicted maximum oxygen uptake, with oxygen pulse and heart rate reaching respectively 110% (76-140%) and 71% (64-81%) of predicted maximum values. Ventilatory equivalent for carbon dioxide remains within normal ranges. The 50% decrease in oxygen uptake after maximum effort was delayed, at 130 seconds (115-142 s). Recovery was incomplete with a persistent anaerobic metabolism. At 6 months, no significant improvement was observed, excepting an increase in heart rate reaching 79% (72-95%) (p = 0.008). CONCLUSIONS: Prolonged reduced exercise capacity was observed up to 6 months in critically ill coronavirus disease 2019 survivors. This disability did not result from residual pulmonary or cardiac dysfunction but rather from a metabolic disorder characterized by a sustained hypermetabolism and an impaired oxygen utilization.

Post-intensive care syndrome after a critical COVID-19: cohort study from a Belgian follow-up clinic.

PURPOSE: Many patients with coronavirus disease 2019 (COVID-19) required critical care. Mid-term outcomes of the survivors need to be assessed. The objective of this single-center cohort study was to describe their physical, cognitive, psychological, and biological outcomes at 3 months following intensive care unit (ICU)-discharge (M3). PATIENTS AND METHODS: All COVID-19 adults who survived an ICU stay ≥ 7 days and attended the M3 consultation at our multidisciplinary follow-up clinic were involved. They benefited from a standardized assessment, addressing health-related quality of life (EQ-5D-3L), sleep disorders (PSQI), and the three principal components of post-intensive care syndrome (PICS): physical status (Barthel index, handgrip and quadriceps strength), mental health disorders (HADS and IES-R), and cognitive impairment (MoCA). Biological parameters referred to C-reactive protein and creatinine. RESULTS: Among the 92 patients admitted to our ICU for COVID-19, 42 survived a prolonged ICU stay and 32 (80%) attended the M3 follow-up visit. Their median age was 62 [49-68] years, 72% were male, and nearly half received inpatient rehabilitation following ICU discharge. At M3, 87.5% (28/32) had not regained their baseline level of daily activities. Only 6.2% (2/32) fully recovered, and had normal scores for the three MoCA, IES-R and Barthel scores. The main observed disorders were PSQI > 5 (75%, 24/32), MoCA < 26 (44%, 14/32), Barthel < 100 (31%, 10/32) and IES-R ≥ 33 (28%, 9/32). Combined disorders were observed in 13/32 (40.6%) of the patients. The EQ-5D-3L visual scale was rated at 71 [61-80]. A quarter of patients (8/32) demonstrated a persistent inflammation based on CRP blood level (9.3 [6.8-17.7] mg/L). CONCLUSION: The burden of severe COVID-19 and prolonged ICU stay was considerable in the present cohort after 3 months, affecting both functional status and biological parameters. These data are an argument on the need for closed follow-up for critically ill COVID-19 survivors.