-
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 Surgical Clinics of North America Jun 2023Hypermetabolism is a hallmark of larger burn injuries. The hypermetabolic response is characterized by marked and sustained increases in catecholamines, glucocorticoids,... (Review)
Review
Hypermetabolism is a hallmark of larger burn injuries. The hypermetabolic response is characterized by marked and sustained increases in catecholamines, glucocorticoids, and glucagon. There is an increasing body of literature for nutrition and metabolic treatment and supplementation to counter the hypermetabolic and catabolic response secondary to burn injury. Early and adequate nutrition is key in addition to adjunctive therapies, such as oxandrolone, insulin, metformin, and propranolol. The duration of administration of anabolic agents should be at minimum for the duration of hospitalization, and possibly up to 2 to 3 years postburn.
Topics: Humans; Anabolic Agents; Oxandrolone; Insulin; Nutritional Support; Burns
PubMed: 37149383
DOI: 10.1016/j.suc.2023.01.009 -
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 -
Seminars in Plastic Surgery May 2024Nutrition and modulation of the hypermetabolic response to acute burns are reviewed in this article. Methods to determine caloric requirements are evaluated, including... (Review)
Review
Nutrition and modulation of the hypermetabolic response to acute burns are reviewed in this article. Methods to determine caloric requirements are evaluated, including indirect calorimetry and predictive equations. Individual nutritional components of carbohydrates, fat, protein, vitamins, and trace elements are discussed specifically in relation to acute burn care. Selection of formula and route of administration are outlined, with an enteral high-carbohydrate, low-fat diet being preferable. Awareness and recognition of the signs and symptoms of malnutrition is critical in the management of variable caloric needs throughout hospitalization. Lastly, the catabolic state of acute burns is addressed through early excision and grafting and implementation of various pharmacologic agents, including growth hormone, insulin-like growth factor-1, insulin-like growth factor-binding protein-3, insulin, propranolol, and oxandrolone. Through a multipronged approach to nutrition, pediatric burn patients are provided the substrates for successful recovery and rehabilitation.
PubMed: 38746694
DOI: 10.1055/s-0044-1782648 -
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 -
Drug Testing and Analysis Jan 2022Oxandrolone is an anabolic-androgenic steroid with favourable anabolic to androgenic ratio, making it an effective anabolic agent with less androgenic side effects....
Oxandrolone is an anabolic-androgenic steroid with favourable anabolic to androgenic ratio, making it an effective anabolic agent with less androgenic side effects. Although its metabolism has been studied in humans, its phase I and II metabolism has not been previously reported in the horse. The purpose of this study was to investigate the in vitro metabolism of oxandrolone (using both equine liver microsomes and S9) and in vivo metabolism following oral administration (three daily doses of 50 mg of oxandrolone to a single Thoroughbred horse), using both gas and liquid chromatography-mass spectrometry techniques. The in vitro phase I transformations observed included 16-hydroxylated (two epimers), 17-methyl-hydroxylated and 16-keto metabolites. In addition to parent oxandrolone and these hydroxylated metabolites, the 17-epimer and a 17,17-dimethyl-18-norandrost-13-ene analogue were detected in biological samples following the administration. 16-keto-oxandrolone was only observed in urine. The 16- and 17-methyl-hydroxylated oxandrolone metabolites were predominantly excreted as sulfate conjugates in urine, whereas parent oxandrolone, its epimer and 17,17-dimethyl-18-norandrost-13-ene derivative were found predominantly in the unconjugated urine fraction. The most abundant analyte detected in both plasma and urine was parent oxandrolone. However, the longest detection period using the developed analytical method was provided by 17-hydroxymethyl-oxandrolone in both matrices. The results of this study provided knowledge of how best to detect the use of oxandrolone in regulatory samples.
Topics: Anabolic Agents; Androgens; Animals; Chromatography, Liquid; Doping in Sports; Gas Chromatography-Mass Spectrometry; Horses; Male; Mass Spectrometry; Microsomes, Liver; Oxandrolone; Substance Abuse Detection
PubMed: 34378336
DOI: 10.1002/dta.3139 -
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 -
American Journal of Men's Health 2020During adolescence, androgens are responsible for the development of secondary sexual characteristics, pubertal growth, and the anabolic effects on bone and muscle mass.... (Review)
Review
During adolescence, androgens are responsible for the development of secondary sexual characteristics, pubertal growth, and the anabolic effects on bone and muscle mass. Testosterone is the most abundant testicular androgen, but some effects are mediated by its conversion to the more potent androgen dihydrotestosterone (DHT) or to estradiol. Androgen deficiency, requiring replacement therapy, may occur due to a primary testicular failure or secondary to a hypothalamic-pituitary disorder. A very frequent condition characterized by a late activation of the gonadal axis that may also need androgen treatment is constitutional delay of puberty. Of the several testosterone or DHT formulations commercially available, very few are employed, and none is marketed for its use in adolescents. The most frequently used androgen therapy is based on the intramuscular administration of testosterone enanthate or cypionate every 3 to 4 weeks, with initially low doses. These are progressively increased during several months or years, in order to mimic the physiology of puberty, until adult doses are attained. Scarce experience exists with oral or transdermal formulations. Preparations containing DHT, which are not widely available, are preferred in specific conditions. Oxandrolone, a non-aromatizable drug with higher anabolic than androgenic effects, has been used in adolescents with preserved testosterone production, like Klinefelter syndrome, with positive effects on cardiometabolic health and visual, motor, and psychosocial functions. The usual protocols applied for androgen therapy in boys and adolescents are discussed.
Topics: Adolescent; Androgens; Child; Clinical Protocols; Disorders of Sex Development; Hormone Replacement Therapy; Humans; Klinefelter Syndrome; Male; Outcome Assessment, Health Care; Puberty
PubMed: 32448030
DOI: 10.1177/1557988320922443 -
Current Pharmaceutical Design 2022Oxandrolone is a synthetic testosterone analog that is widely used among bodybuilders and athletes. However, oxandrolone causes male infertility. Recently, it was found...
BACKGROUND
Oxandrolone is a synthetic testosterone analog that is widely used among bodybuilders and athletes. However, oxandrolone causes male infertility. Recently, it was found that metformin reduces the risk of infertility associated with diabetes mellitus.
AIM
This study aimed to investigate the protective effects of metformin against oxandrolone-induced infertility in male rats.
METHODS
Rats continuously received one of four treatments (n=7) over 14 days: control DMSO administration, oxandrolone administration, metformin administration, or co-administration of oxandrolone and metformin. Doses were equivalent to those used for human treatment. Subsequently, testicular and blood samples were collected for morphological, biochemical, and histological examination. In addition, gene expression of the testosterone synthesizing enzyme CYP11A1 was analyzed in the testes using RT-PCR.
RESULTS
Oxandrolone administration induced male infertility by significantly reducing relative weights of testes by 48%, sperm count by 82%, and serum testosterone levels by 96% (ANOVA, P value < 0.05). In addition, histological examination determined that oxandrolone caused spermatogenic arrest, which was associated with 2-fold downregulation of testicular CYP11A1 gene expression. However, co-administration of metformin with oxandrolone significantly ameliorated toxicological alterations induced by oxandrolone exposure (ANOVA, P-value < 0.05).
CONCLUSION
Metformin administration provided protection against oxandrolone-induced infertility in male rats. Further clinical studies are needed to confirm the protective effect of metformin against oxandrolone-induced infertility among athletes.
Topics: Animals; Humans; Infertility, Male; Male; Metformin; Oxandrolone; Rats; Testis; Testosterone
PubMed: 33121403
DOI: 10.2174/1381612826666201029101524