Medical nutrition therapy in long-term adult intensive care patients: effects of protein quantity on muscle mass, biochemical markers, and clinical outcome

Research suggests that degradation of muscle mass and loss of functional proteins due to catabolism are associated with an adverse outcome in critically ill patients. While an adequate protein supply within a medical nutrition concept is suggested to minimize proteolysis, the specificities on appropriate dosage and timing are still unclear. The current study aimed to evaluate the effect of two different quantities of protein as part of a standardized energetically controlled nutrition therapy on the preservation of muscle mass in the late phase of critical illness. A randomized controlled trial was conducted in 42 critically ill patients (age 65 ± 15; 12 female; simplified acute physiology score [SAPS] 45 ± 11; therapeutic intervention scoring system [TISS] 20 ± 7; sequential organ failure assessment [SOFA-] score 7 ± 3). The subjects were randomly assigned to either intervention (1.8 g protein/kg body weight [BW]/d) or standard (1.2 g protein/kg BW/d) group. Nutrient supply via enteral and/or parenteral nutrition was calculated based on the individual energy expenditure measured by indirect calorimetry and target protein content. Quadriceps muscle layer thickness (QMLT) was measured through sonography at inclusion and two times during the follow-up period (two and four weeks after inclusion). The measuring points were fixed on two sides at midpoint and two-thirds between anterior superior iliac spine and top of the patella. The data were analyzed descriptively and group differences were analyzed by chi-squared tests or unpaired two-sample t-tests. Daily changes in muscle mass were estimated using a linear mixed model procedure. Data are shown as the mean ± standard deviation (SD) and the estimation ± standard error (SE), respectively. Actual protein intake reached 1.5 ± 0.5 g and 1.0 ± 0.5 g/kg BW/d in the intervention and standard group, respectively. Mean values of all QMLT measurement points at inclusion (day 13 ± 2 after intensive care unit [ICU] admission) were 13.5 ± 7.4 mm and 13.4 ± 7.1 mm in the intervention and standard group, respectively (P = 0.967). In both the groups, QMLT decreased over time (P < 0.001), while the estimated mean values of daily QMLT changes were -0.15 ± 0.08 mm (intervention) and -0.28 ± 0.08 mm (standard) without significant between-group differences (intervention effect, P = 0.368; time x intervention effect, P = 0.242). Biochemical markers (except for triglycerides and 25-hydroxyvitamin D3), illness scores, and clinical outcome showed no between-group differences at the end of the study period. In this single-center trial the increased amounts of protein (1.5 g vs. 1.0 g/kg BW/d) provided through medical nutrition therapy in the late phase of critical illness did not achieve a statistically significant impact on the loss of muscle mass, selected biochemical markers, illness scores, and clinical outcome in long-term immobilized ICU patients. Larger multi-center trials are needed to evaluate, whether the numerical differences in muscle loss observed between the intervention and standard group could reach statistical significance and will improve clinical outcome.Ernährungstherapie langliegender IntensivpatientInnen: Effekte der quantitativen Proteinzufuhr auf die Muskelmasse, biochemische Parameter und das klinische Outcome Wissenschaftliche Untersuchungen zeigen, dass der Abbau von Muskelmasse und der Verlust von Funktionsproteinen mit einem verschlechterten Outcome von Intensivpatienten einhergehen. Während eine adäquate Proteinzufuhr generell zur Verringerung der Proteolyse empfohlen wird, sind die Spezifikationen zu Dosierung und Zeitpunkt derzeit noch nicht eindeutig definiert. Ziel der vorliegenden Studie war es, den Effekt zweier unterschiedlicher Proteindosierungen als Bestandteil einer standardisierten, Energie-kontrollierten Ernährungstherapie auf den Erhalt von Muskelmasse in der Spätphase einer kritischen Erkankung zu untersuchen. Es wurde eine randomisierte, kontrollierte Interventionsstudie an 42 Intensivpatienten (65 ± 15 Jahre; 12 Frauen; Simplified Acute Physiology Score [SAPS] 45 ± 11; Therapeutic Intervention Scoring System [TISS] 20 ± 7; Sequential Organ Failure Assessment [SOFA-] Score 7 ± 3) durchgeführt. Es erfolgte eine Randomisierung der Patienten in eine Interventionsgruppe (1,8 g Protein/kg Körpergewicht/d) und eine Standardgruppe (1,2 g Protein/kg Körpergewicht/d). Die Nährstoffzufuhr erfolgte mittels enteraler und/oder parenteraler Ernährung und wurde auf Basis des mittels indirekter Kalorimetrie gemessenen individuellen Energieumsatzes und der Ziel-Proteinzufuhr kalkuliert. Die Muskeldicke des Quadrizeps (Quadriceps Muscle Layer Thickness, QMLT) wurde mittels Sonographie bei Einschluss sowie zwei und vier Wochen nach Studienbeginn gemessen. Die Messpunkte wurden beidseitig auf der Mitte und auf zwei Drittel zwischen der Spina iliaca anterior superior und der Oberkante der Patella festgelegt. Die Analyse der Daten erfolgte deskriptiv; Gruppenvergleiche wurden mittels Chi-Quadrat- Tests bzw. ungepaarten zweiseitigen t-Tests vorgenommen. Die tägliche Veränderung des Gehalts an Muskelmasse wurden mittels linear gemischter Modelle geschätzt. Die Daten sind als Mittelwert ± Standardabweichung bzw. Schätzer ± Standardfehler dargestellt. Die tatsächliche Proteinaufnahme lag bei 1,5 ± 0,5 g und 1,0 ± 0,5 g/kg Körpergewicht/d in der Interventions- bzw. Standardgruppe. Der Mittelwert aller QMLT-Messpunkte bei Einschluss (Tag 13 ± 2 nach Aufnahme) betrug 13,5 ± 7,4 mm und 13,4 ± 7,1 mm in der Interventions- bzw. Standardgruppe (P = 0,967). In beiden Gruppen nahm die QMLT über die Zeit ab (P &lt; 0,001); die geschätzten täglichen QMLT-Veränderungen betrugen -0,15 ± 0,08 mm und -0,28 ± 0,08 mm in der Interventions- bzw. Standardgruppe, es bestanden keine signifikanten Unterschiede zwischen den Gruppen (Interventionseffekt, P = 0,368; Zeit x Interventionseffekt, P = 0,242). In den biochemischen Markern (mit Ausnahme von Triglyceriden und 25-Hydroxy-Vitamin D3), den Krankheitsscores sowie dem klinisch Outcome zeigten sich keine Gruppen-Unterschiede. In dieser Monozenterstudie konnte eine erhöhte Proteinzufuhr (1,5 g vs. 1,0 g/kg BW/d) im Rahmen der Ernährungstherapie in der Spätphase einer kritischen Erkrankung keine statistisch signifikante Verbesserung von Muskelmasseverlust, ausgewählten biochemischen Parametern, Krankheitsscores und klinischem Outcome bei Langzeit-Intensivpatienten erzielen. Größere Multizenterstudien sind unabdingbar um zu untersuchen, ob die in dieser Studie beobachteten zahlenmäßigen Unterschiede im Verlust an Muskelmasse zwischen der Interventions- und Standardgruppe statistische Signifikanz erreichen und das klinische Outcome verbessern können

An update of the effects of vitamins D and C in critical illness

Many critically ill patients are vitamin D and vitamin C deficient and the current international guidelines state that hypovitaminoses should be compensated. However, uncertainty about optimal dosage, timing and indication exists in clinical routine, mainly due to the conflicting evidence. This narrative review discusses both micronutrients with regards to pathophysiology, clinical evidence of benefits, potential risks, and guideline recommendations. Evidence generated from the most recent clinical trials are summarized and discussed. In addition, pragmatic tips for the application of these vitamins in the clinical routine are given. The supplementations of vitamin D and C represent cost-effective and simple interventions with excellent safety profiles. Regarding vitamin D, critically ill individuals require a loading dose to improve 25(OH)D levels within a few days, followed by a daily or weekly maintenance dose, usually higher doses than healthy individuals are needed. For vitamin C, dosages of 100–200 mg/d are recommended for patients receiving parenteral nutrition, but needs may be as high as 2–3 g/d in acutely ill patients

History of scurvy and use of vitamin C in critical illness: A narrative review

In 1747, an important milestone in the history of clinical research was set, as the Scottish surgeon James Lind conducted the first randomized controlled trial. Lind was interested in scurvy, a severe vitamin C deficiency which caused the death of thousands of British seamen. He found that a dietary intervention with oranges and lemons, which are rich in vitamin C by nature, was effective to recover from scurvy. Because of its antioxidative properties and involvement in many biochemical processes, the essential micronutrient vitamin C plays a key role in the human biology. Moreover, the use of vitamin C in critical illness—a condition also resulting in death of thousands in the 21st century—has gained increasing interest, as it may restore vascular responsiveness to vasoactive agents, ameliorate microcirculatory blood flow, preserve endothelial barriers, augment bacterial defense, and prevent apoptosis. Because of its redox potential and powerful antioxidant capacity, vitamin C represents an inexpensive and safe antioxidant, with the potential to modify the inflammatory cascade and improve clinical outcomes of critically ill patients. This narrative review aims to update and provide an overview on the role of vitamin C in the human biology and in critically ill patients, and to summarize current evidence on the use of vitamin C in diverse populations of critically ill patients, in specific focusing on patients with sepsis and coronavirus disease 2019

Overview of oxidative stress and the role of micronutrients in critical illness

Inflammation and oxidative stress represent physiological response mechanisms to different types of stimuli and injury during critical illness. Its proper regulation is fundamental to cellular and organismal survival and are paramount to outcomes and recovery from critical illness. A proper maintenance of the delicate balance between inflammation, oxidative stress, and immune response is crucial for resolution from critical illness with important implications for patient outcome. The extent of inflammation and oxidative stress under normal conditions is limited by the antioxidant defense system of the human body, whereas the antioxidant capacity is commonly significantly compromised, and serum levels of micronutrients and vitamins significantly depleted in patients who are critically ill. Hence, the provision of antioxidants and anti-inflammatory nutrients may help to reduce the extent of oxidative stress and therefore improve clinical outcomes in patients who are critically ill. As existing evidence of the beneficial effects of antioxidant supplementation in patients who are critically ill is still unclear, actual findings about the most promising anti-inflammatory and antioxidative candidates selenium, vitamin C, zinc, and vitamin D will be discussed in this narrative review. The existing evidence provided so far demonstrates that several factors need to be considered to determine the efficacy of an antioxidant supplementation strategy in patients who are critically ill and indicates the need for adequately designed multicenter prospective randomized control trials to evaluate the clinical significance of different types and doses of micronutrients and vitamins in selected groups of patients with different types of critical illness