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Critical Care (London, England) Jul 2023Personalization of ICU nutrition is essential to future of critical care. Recommendations from American/European guidelines and practice suggestions incorporating recent... (Review)
Review
Personalization of ICU nutrition is essential to future of critical care. Recommendations from American/European guidelines and practice suggestions incorporating recent literature are presented. Low-dose enteral nutrition (EN) or parenteral nutrition (PN) can be started within 48 h of admission. While EN is preferred route of delivery, new data highlight PN can be given safely without increased risk; thus, when early EN is not feasible, provision of isocaloric PN is effective and results in similar outcomes. Indirect calorimetry (IC) measurement of energy expenditure (EE) is recommended by both European/American guidelines after stabilization post-ICU admission. Below-measured EE (~ 70%) targets should be used during early phase and increased to match EE later in stay. Low-dose protein delivery can be used early (~ D1-2) (< 0.8 g/kg/d) and progressed to ≥ 1.2 g/kg/d as patients stabilize, with consideration of avoiding higher protein in unstable patients and in acute kidney injury not on CRRT. Intermittent-feeding schedules hold promise for further research. Clinicians must be aware of delivered energy/protein and what percentage of targets delivered nutrition represents. Computerized nutrition monitoring systems/platforms have become widely available. In patients at risk of micronutrient/vitamin losses (i.e., CRRT), evaluation of micronutrient levels should be considered post-ICU days 5-7 with repletion of deficiencies where indicated. In future, we hope use of muscle monitors such as ultrasound, CT scan, and/or BIA will be utilized to assess nutrition risk and monitor response to nutrition. Use of specialized anabolic nutrients such as HMB, creatine, and leucine to improve strength/muscle mass is promising in other populations and deserves future study. In post-ICU setting, continued use of IC measurement and other muscle measures should be considered to guide nutrition. Research on using rehabilitation interventions such as cardiopulmonary exercise testing (CPET) to guide post-ICU exercise/rehabilitation prescription and using anabolic agents such as testosterone/oxandrolone to promote post-ICU recovery is needed.
Topics: Humans; Intensive Care Units; Nutritional Support; Critical Care; Nutritional Status; Enteral Nutrition; Critical Illness
PubMed: 37403125
DOI: 10.1186/s13054-023-04539-x -
American Journal of Physiology. Cell... Jul 2021Critical illnesses, including sepsis, cancer cachexia, and burn injury, invoke a milieu of systemic metabolic and inflammatory derangements that ultimately results in... (Review)
Review
Critical illnesses, including sepsis, cancer cachexia, and burn injury, invoke a milieu of systemic metabolic and inflammatory derangements that ultimately results in increased energy expenditure leading to fat and lean mass catabolism. Burn injuries present a unique clinical challenge given the magnitude and duration of the hypermetabolic response compared with other forms of critical illness, which drastically increase the risk of morbidity and mortality. Skeletal muscle metabolism is particularly altered as a consequence of burn-induced hypermetabolism, as it primarily provides a main source of fuel in support of wound healing. Interestingly, muscle catabolism is sustained long after the wound has healed, indicating that additional mechanisms beyond wound healing are involved. In this review, we discuss the distinctive pathophysiological response to burn injury with a focus on skeletal muscle function and metabolism. We first examine the diverse consequences on skeletal muscle dysfunction between thermal, electrical, and chemical burns. We then provide a comprehensive overview of the known mechanisms underlying skeletal muscle dysfunction that may be attributed to hypermetabolism. Finally, we review the most promising current treatment options to mitigate muscle catabolism, and by extension improve morbidity and mortality, and end with future directions that have the potential to significantly improve patient care.
Topics: Burns; Cachexia; Epigenesis, Genetic; Exercise; Human Growth Hormone; Humans; Insulin; Metformin; Muscle Proteins; Muscle, Skeletal; Muscular Atrophy; Oxandrolone; Propranolol; Protein Biosynthesis; Proteolysis; Sepsis; Signal Transduction; Wound Healing
PubMed: 33909503
DOI: 10.1152/ajpcell.00106.2021 -
The Journal of Pharmacy Technology :... Aug 2022Burn injuries remain among the most severe traumatic injuries globally. With the discovery of cortisol, the use of steroids has become an essential therapy for the... (Review)
Review
Burn injuries remain among the most severe traumatic injuries globally. With the discovery of cortisol, the use of steroids has become an essential therapy for the management of inflammatory and metabolic conditions. Several studies have shown the steroid oxandrolone improves burn injuries through stimulating anabolic and reducing catabolic processes. In this review, we examine the efficacy and applications of oxandrolone with regard to burn management and treatment. A literature search was performed using the PubMed database from January 1990 to May 2020 to identify articles on oxandrolone and burn management. A total of 18 studies were included in our review. The keywords used in our search strategy for PubMed included "oxandrolone" and "burns." The main benefit of oxandrolone is the improved long-term lean body, protein, and bone mineral mass of burn patients. In addition, 3 separate meta-analyses showed oxandrolone shortened length of hospital stay, donor-site healing time, reduced weight loss, and net protein loss. However, oxandrolone therapy did not affect mortality, infection, or liver function. Oxandrolone remains an effective therapy for reducing the hypermetabolic response and comorbidities from burn injuries. Future clinical trials are needed using larger sample sizes and long-term follow-up to determine whether oxandrolone in the context of rehabilitation programs can reduce mortality, lower treatment costs, and improve function outcomes among burn patients.
PubMed: 35832568
DOI: 10.1177/87551225221091115 -
Molecules (Basel, Switzerland) Jan 2021Oxandrolone, a synthetic testosterone analog, is used for the treatment of several diseases associated with weight loss. Unfortunately, oxandrolone is abused by many...
Oxandrolone, a synthetic testosterone analog, is used for the treatment of several diseases associated with weight loss. Unfortunately, oxandrolone is abused by many athletes and bodybuilders due to its strong anabolic effect. We have developed and validated a highly sensitive and rapid on-line SPE-UHPLC-MS/MS method for the determination of oxandrolone and simultaneous identification of its major metabolite 17-epi-oxandrolone in urine matrices. Enrichment of the analytes via an integrated solid-phase extraction was achieved using an Acquity UPLC BEH C18 Column. Subsequently, the chromatographic separation of the on-line preconcentrated sample fraction was achieved using an Acquity HSS T3 C18 Column. For the structural identification of these analytes, a high-resolution mass spectrometer Synapt-G2Si coupled to the Acquity M-class nano-LC system with ionKey source was used. A highly sensitive determination of oxandrolone was achieved using a tandem quadrupole mass spectrometer XEVO TQD. The method was successfully validated in the linear range of oxandrolone from 81.63 pg·mL (limit of quantification, LOQ) to 5000 pg·mL in the human urine matrix. It was applied to the analysis of real urine samples obtained from a healthy volunteer after the oral administration of one dose (10 mg) of oxandrolone. Concentration vs. time dependence was tested in the time interval of 4 h-12 days (after oral administration) to demonstrate the ability of the method to detect the renal elimination of oxandrolone from the human body. Favorable performance parameters along with successful application indicate the usefulness of the proposed method for its routine use in antidoping control labs.
Topics: Chromatography, High Pressure Liquid; Humans; Oxandrolone; Solid Phase Extraction; Tandem Mass Spectrometry; Urinalysis
PubMed: 33477515
DOI: 10.3390/molecules26020480 -
Acta Cirurgica Brasileira 2014This study is a systematic literature review and meta-analysis concerning the use of a testosterone synthetic analog, oxandrolone, and its use in severe adult burns. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
This study is a systematic literature review and meta-analysis concerning the use of a testosterone synthetic analog, oxandrolone, and its use in severe adult burns.
METHODS
Randomized prospective clinical studies, in English, Portuguese or Spanish, were sought on the following databases: MEDLINE, COCHRANE, EMBASE and LILACS. There was no restriction in relation to the publication date.
RESULTS
This search produced 24 studies on MEDLINE and twelve articles were presented on the COCHRANE database .Sixteen were excluded due to the title not being related to this search or by including children. Of the eigth residual studies, after adaptation to the inclusion criteria, only four were selected. After analyzing the results, two were discarded since they did not present adequate patient characterization and the facts on these articles were analyzed differently from the others, hindering the meta-analysis.
CONCLUSION
The analysis of the available data demonstrated significant benefits (p<0.05) considering lesser loss of corporal mass, lesser nitrogen loss, and shorter donor area healing time, when Oxandrolone was used, comparatively with the control group (placebo or not).
Topics: Adult; Body Mass Index; Burns; Humans; Length of Stay; Nitrogen; Oxandrolone; Randomized Controlled Trials as Topic; Time Factors; Wound Healing
PubMed: 25351160
DOI: 10.1590/s0102-86502014001700013 -
Current Opinion in Critical Care Aug 2016A complex network of hormones and other effectors characterize the hypermetabolic response in critical illness; these mediators work together to induce numerous... (Review)
Review
PURPOSE OF REVIEW
A complex network of hormones and other effectors characterize the hypermetabolic response in critical illness; these mediators work together to induce numerous pathophysiologic alterations. Increased incidence of infection, multiorgan failure, long-term debilitation, delays in rehabilitation, and death result from an inability to meet the prohibitively elevated protein and energy requirements, which occur during illness and can persist for several years. Pharmacologic interventions have been successfully utilized to attenuate particular aspects of the hypermetabolic response; these modalities are a component of managing critically ill patients - including those patients with severe burns. Here, we review recent advances in pharmacologically attenuating the hypermetabolic and catabolic responses.
RECENT FINDINGS
Propranolol, a nonspecific β-adrenergic receptor antagonist, is one of the most widely used anticatabolic therapies. Oxandrolone, testosterone, and intensive insulin therapy represent anabolic pharmacological strategies. Promising therapies, such as metformin, glucagon-like peptide 1, peroxisome proliferator-activated receptor agonists, are currently being investigated.
SUMMARY
Profound metabolic derangements occur in critically ill patients; this hypermetabolic response is a major contributor to adverse outcomes. Despite the pharmacological therapies currently available to counteract this devastating cascade, future studies are warranted to explore new multimodality agents that will counteract these effects while maintaining glycemic control and preventing unfavorable complications.
Topics: Adrenergic beta-Antagonists; Anabolic Agents; Critical Care; Critical Illness; Humans; Insulin; Oxandrolone; Propranolol
PubMed: 27272101
DOI: 10.1097/MCC.0000000000000330 -
Allergologie Select 2018The aim of treatment of hereditary angioedema (HAE) due to C1 esterase inhibitor deficiency (HAE-C1-INH) is either treating acute attacks or preventing attacks by using... (Review)
Review
The aim of treatment of hereditary angioedema (HAE) due to C1 esterase inhibitor deficiency (HAE-C1-INH) is either treating acute attacks or preventing attacks by using prophylactic treatment. For treating acute attacks, plasma-derived C1 inhibitor (C1-INH) concentrates, a bradykinin B2 receptor antagonist, and a recombinant human C1-INH are available in Europe. In the United States, a plasma-derived C1-INH concentrate, a bradykinin B2 receptor antagonist, and a plasma kallikrein inhibitor were approved for the treatment of acute attacks. Fresh frozen plasma is also available for treating acute attacks. Short-term prophylactic treatment focuses on C1-INH and attenuated androgens. Long-term prophylactic treatments include attenuated androgens such as danazol, stanozolol, and oxandrolone, antifibrinolytics, and a plasma-derived C1-INH concentrate. Plasma-derived C1-INH and a bradykinin B2 receptor antagonist are admitted for self-administration and home therapy. So the number of management options increased considerably within the last few years thus helping to diminish the burden of HAE.
PubMed: 31826031
DOI: 10.5414/ALX1561E -
Bone Research 2015Severe burn injury triggers the body's nonspecific adaptive responses to acute insult, including the systemic inflammatory and stress responses, as well as the... (Review)
Review
Severe burn injury triggers the body's nonspecific adaptive responses to acute insult, including the systemic inflammatory and stress responses, as well as the sympathetic response to immobilization. These responses trigger inflammatory bone resorption followed by glucocorticoid-induced apoptosis of osteoblasts and probably osteocytes. Because these patients are catabolic, they suffer concomitant muscle wasting and negative nitrogen balance. The use of anabolic agents such as recombinant human growth hormone and oxandrolone results in improved bone mineral content and muscle strength after approximately 1 year. Use of bisphosphonates within the first 10 days of a severe burn completely blocks the resorptive bone loss and has the added advantage of appearing to preserve muscle protein from excessive breakdown. The mechanism for the protective effect on muscle is not currently known. However, if the effect of bisphosphonates on muscle can be confirmed, it raises the possibility that bone communicates with muscle.
PubMed: 26273535
DOI: 10.1038/boneres.2015.2 -
Journal of Plastic, Reconstructive &... Aug 2022Major thermal injury induces a complex pathophysiological state characterized by burn shock and hypercatabolism. Steroids are used to modulate these post-injury...
BACKGROUND
Major thermal injury induces a complex pathophysiological state characterized by burn shock and hypercatabolism. Steroids are used to modulate these post-injury responses. However, the effects of steroids on acute post-burn outcomes remain unclear.
METHODS
In this study of 52 thermally injured adult patients (median total burn surface area 42%, 33 males and 19 females), the effects of corticosteroid and oxandrolone on mortality, multi-organ failure (MOF), and sepsis were assessed individually. Clinical data were collected at days 1, 3, 7, and 14 post-injury.
RESULTS
Twenty-two (42%) and 34 (65%) burns patients received corticosteroids and oxandrolone within the same cohort, respectively. Following separate analysis for each steroid, corticosteroid use was associated with increased odds of in-hospital mortality (OR 3.25, 95% CI: 1.32-8•00), MOF (OR 2.36, 95% CI: 1.00-1.55), and sepsis (OR 5.95, 95% CI: 2.53-14.00). Days alive (HR 0.32, 95% CI: 0.18-0.60) and sepsis-free days (HR 0.54, 95% CI: 0.37-0.80) were lower among corticosteroid-treated patients. Oxandrolone use was associated with reduced odds of 28-day mortality (OR 0.11, 95% CI: 0.04-0.30), in-hospital mortality (OR 0.19, 95% CI: 0.08-0.43), and sepsis (OR 0.24, 95% CI: 0.08-0.69). Days alive, at 28 days (HR 6.42, 95% CI: 2.77-14.9) and in-hospital (HR 3.30, 95% CI: 1.93-5.63), were higher among the oxandrolone-treated group. However, oxandrolone was associated with increased MOF odds (OR 7.90, 95% CI: 2.89-21.60) and reduced MOF-free days (HR 0.23, 95% CI: 0.11-0.50).
CONCLUSION
Steroid therapies following major thermal injury may significantly affect patient prognosis. Oxandrolone was associated with better outcomes except for MOF. Adverse effects of corticosteroids and oxandrolone should be considered when managing burn patients.
Topics: Adult; Anabolic Agents; Cohort Studies; Female; Hospital Mortality; Humans; Male; Oxandrolone; Sepsis
PubMed: 35599217
DOI: 10.1016/j.bjps.2022.04.007 -
Burns : Journal of the International... Feb 2020Major thermal injury induces profound metabolic derangements secondary to an inflammatory "stress-induced" hormonal environment. Several pharmacological interventions... (Review)
Review
Major thermal injury induces profound metabolic derangements secondary to an inflammatory "stress-induced" hormonal environment. Several pharmacological interventions have been tested in an effort to halt the hypermetabolic response to severe burns. Insulin, insulin growth factor 1, insulin growth factor binding protein 3, metformin, human growth hormone, thyroid hormones, testosterone, oxandrolone, and propranolol, among others, have been proposed to have anabolic or anticatabolic effects. The aim of this broad analysis of pharmacological interventions was to raise awareness of treatment options and to help establishing directions for future clinical research efforts. A PubMed search was conducted on the anabolic and anticatabolic agents used in burn care. One hundred and thirty-five human studies published between 1999 and 2017 were included in this review. The pharmacological properties, rationale for the treatments, efficacy considerations and side effect profiles are summarized in the article. Many of the drugs tested for investigational purposes in the severely thermally injured are not yet gold-standard therapies in spite of their potential benefit. Propranolol and oxandrolone have shown great promise but further evidence is still needed to clarify their potential use for anabolic and anticatabolic purposes.
Topics: Anabolic Agents; Burns; Clonidine; Growth Hormone-Releasing Hormone; Hormones; Human Growth Hormone; Humans; Hypoglycemic Agents; Inflammation; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Metformin; Oxandrolone; Propranolol; Testosterone; Thyroid Hormones
PubMed: 31852612
DOI: 10.1016/j.burns.2018.03.009