The effect of higher versus lower protein delivery in critically ill patients: a systematic review and meta-analysis of randomized controlled trials

Background: The optimal protein dose in critical illness is unknown. We aim to conduct a systematic review of randomized controlled trials (RCTs) to compare the effect of higher versus lower protein delivery (with similar energy delivery between groups) on clinical and patient-centered outcomes in critically ill patients. Methods: We searched MEDLINE, EMBASE, CENTRAL and CINAHL from database inception through April 1, 2021.We included RCTs of (1) adult (age ≥ 18) critically ill patients that (2) compared higher vs lower protein with (3) similar energy intake between groups, and (4) reported clinical and/or patient-centered outcomes. We excluded studies on immunonutrition. Two authors screened and conducted quality assessment independently and in duplicate. Random-effect meta-analyses were conducted to estimate the pooled risk ratio (dichotomized outcomes) or mean difference (continuous outcomes). Results: Nineteen RCTs were included (n = 1731). Sixteen studies used primarily the enteral route to deliver protein. Intervention was started within 72 h of ICU admission in sixteen studies. The intervention lasted between 3 and 28 days. In 11 studies that reported weight-based nutrition delivery, the pooled mean protein and energy received in higher and lower protein groups were 1.31 ± 0.48 vs 0.90 ± 0.30 g/kg and 19.9 ± 6.9 versus 20.1 ± 7.1 kcal/kg, respectively. Higher vs lower protein did not significantly affect overall mortality [risk ratio 0.91, 95% confidence interval (CI) 0.75-1.10, p = 0.34] or other clinical or patient-centered outcomes. In 5 small studies, higher protein significantly attenuated muscle loss (MD -3.44% per week, 95% CI -4.99 to -1.90; p < 0.0001). Conclusion: In critically ill patients, a higher daily protein delivery was not associated with any improvement in clinical or patient-centered outcomes. Larger, and more definitive RCTs are needed to confirm the effect of muscle loss attenuation associated with higher protein delivery. PROSPERO registration number: CRD42021237530

Tracheobronchial amyloidosis managed with multimodality therapies

Amyloidosis is a systemic disease involving abnormal extracellular deposition of amyloid and autologous fibrillar protein material in β-pleated sheets. Accumulation of this abnormal protein leads to organ dysfunction, although respiratory tract involvement is rare. We present two cases of tracheobronchial amyloidosis successfully treated with surgery and radiation

Editorial: Introduction to the 2018 ESPEN guidelines on clinical nutrition in the intensive care unit: food for thought and valuable directives for clinicians!

Introduction: The recently published 2018 ESPEN Guidelines on Clinical Nutrition in the Intensive Care Unit [1] represents a valuable revision of the 2006 Enteral Nutrition Guidelines [2] and the 2009 Parenteral Nutrition Guidelines [3] published earlier by this European group. The guidelines committee members have done an excellent job in putting thismanuscript together, providing directives that are clear, concise, brief, and most importantly, transparent. They included only studies published since 2000 for use in their meta-analyses, commenting that this time of transition heralded a new era in the literature involving higher quality randomized control trials (RCTs) and methodologic innovations such as trial registry. Not mentioned (but felt by many within the nutrition community) was the sense that this particular time was a tipping point, following the publication of Van den Berghe’s seminal paper on intensive insulin therapy [4]. Studies published in nutrition prior to this date were felt to reflect an older more antiquated style of management that was less effective. These authors utilized the persistent inflammation catabolism syndrome (PICS) system where four parameters (the patient, intervention, controls, and outcomes) are clearly described, which in turn direct the questions that the guideline committee members were to address. Quality of evidence was assessed by GRADE methodology, and a cut-off date of August 2017 for data entry from the literature was clearly identified. Not all of the recommendations were based on RCTs. The authors are to be commended in that they provided recommendations based on Level 4 low-quality evidence, in areas where RCTs were not available, clearly taking advantage of the group of experts on the committee to provide practical guidance for clinicians where there was a paucity of literature to support evidence-based practices

Impact of enteral feeding on vasoactive support in septic shock: A retrospective observational study

Background: Introducing enteral nutrition (EN) during hemodynamic instability may induce the splanchnic steal phenomenon, which may worsen systemic oxygen delivery and increase vasopressor dose. We aimed to determine the change in vasopressor dose in septic shock patients who received concomitant EN. We hypothesize that EN delivery is not associated with worsening hemodynamic instability, as defined by an increase in vasopressor dose ≥50% at 24 hours.Methods: This is a retrospective observational cohort study of adult patients with septic shock who were admitted to the intensive care unit from January 2015 to June 2015 and received EN. Vasopressor and EN parameters were collected at 6-hour intervals for the first 24 hours.Results: Data were available for 28 consecutive patients. The mean age was 60 years (SD = 18), and 54% were females. Norepinephrine (NE) was used in 100%. EN and vasopressor overlap totaled 36 hours (interquartile range [IQR], 27-69). Median NE dose when starting EN was 5.9 μg/min (IQR, 3.88). Median change in dose from 0 to 6 hours was 0.85 μg/min (95% CI, 0.681.06; P = 0.136), corresponding to a median increase of 14.5%. Total NE duration was 60.5 hours (IQR, 47.5-75.5). No serious complications occurred.Conclusion: The median vasopressor dose did not increase by ≥50% during the first 24 hours of EN. This suggests early EN delivered during septic shock is not associated with worsening hemodynamic instability. Limitations include a small sample size and residual confounding. Prospective data are needed

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

An Unusual Suspect Causing Hypoxemic Respiratory Failure

Introduction: Antisynthetase syndrome (ASS) is characterized by the presence of anti-Jo-1 antibodies in conjunction with clinical findings of fever, polymyositis-dermatomyositis, and interstitial lung disease (ILD). Inflammatory myopathies carry a high risk of malignancy, but this association is less well outlined in ASS. We present the case of a patient with ASS who developed non-Hodgkin’s lymphoma with acute hypoxemic respiratory failure. Case Presentation: A 44-year-old female with ASS presented with acute hypoxemic respiratory failure. She was empirically treated with broad-spectrum antibiotics for a health care–associated pneumonia; however, she failed to improve. Chest computed tomography revealed extensive bilateral ground glass opacities as well as extensive mediastinal and axillary lymphadenopathy. Infectious workup was negative. A surgical lung biopsy revealed peripheral T-cell lymphoma (PTCL). The patient was started on chemotherapy with complete resolution of hypoxemic respiratory failure. Conclusions: Malignancy is very rare in the setting of ASS; and our case illustrates the unique presentation of PTCL in ASS. In addition, lung involvement in PTCL is variable (incidence ranging from 8% to 20%); and in this case, bilateral multifocal consolidation was biopsied and proven to be PTCL involving the lungs. This case highlights the rare noninfectious conditions that can present as acute hypoxemic respiratory failure in the setting of ASS