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1.
JAMA ; 325(8): 742-750, 2021 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-33620405

RESUMEN

Importance: Sepsis is a common syndrome with substantial morbidity and mortality. A combination of vitamin C, thiamine, and corticosteroids has been proposed as a potential treatment for patients with sepsis. Objective: To determine whether a combination of vitamin C, thiamine, and hydrocortisone every 6 hours increases ventilator- and vasopressor-free days compared with placebo in patients with sepsis. Design, Setting, and Participants: Multicenter, randomized, double-blind, adaptive-sample-size, placebo-controlled trial conducted in adult patients with sepsis-induced respiratory and/or cardiovascular dysfunction. Participants were enrolled in the emergency departments or intensive care units at 43 hospitals in the United States between August 2018 and July 2019. After enrollment of 501 participants, funding was withheld, leading to an administrative termination of the trial. All study-related follow-up was completed by January 2020. Interventions: Participants were randomized to receive intravenous vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) every 6 hours (n = 252) or matching placebo (n = 249) for 96 hours or until discharge from the intensive care unit or death. Participants could be treated with open-label corticosteroids by the clinical team, with study hydrocortisone or matching placebo withheld if the total daily dose was greater or equal to the equivalent of 200 mg of hydrocortisone. Main Outcomes and Measures: The primary outcome was the number of consecutive ventilator- and vasopressor-free days in the first 30 days following the day of randomization. The key secondary outcome was 30-day mortality. Results: Among 501 participants randomized (median age, 62 [interquartile range {IQR}, 50-70] years; 46% female; 30% Black; median Acute Physiology and Chronic Health Evaluation II score, 27 [IQR, 20.8-33.0]; median Sequential Organ Failure Assessment score, 9 [IQR, 7-12]), all completed the trial. Open-label corticosteroids were prescribed to 33% and 32% of the intervention and control groups, respectively. Ventilator- and vasopressor-free days were a median of 25 days (IQR, 0-29 days) in the intervention group and 26 days (IQR, 0-28 days) in the placebo group, with a median difference of -1 day (95% CI, -4 to 2 days; P = .85). Thirty-day mortality was 22% in the intervention group and 24% in the placebo group. Conclusions and Relevance: Among critically ill patients with sepsis, treatment with vitamin C, thiamine, and hydrocortisone, compared with placebo, did not significantly increase ventilator- and vasopressor-free days within 30 days. However, the trial was terminated early for administrative reasons and may have been underpowered to detect a clinically important difference. Trial Registration: ClinicalTrials.gov Identifier: NCT03509350.


Asunto(s)
Antiinflamatorios/uso terapéutico , Ácido Ascórbico/uso terapéutico , Hidrocortisona/uso terapéutico , Respiración Artificial , Sepsis/tratamiento farmacológico , Tiamina/uso terapéutico , Vitaminas/uso terapéutico , Adulto , Anciano , Enfermedad Crítica , Método Doble Ciego , Quimioterapia Combinada , Terminación Anticipada de los Ensayos Clínicos , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Puntuaciones en la Disfunción de Órganos , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapia , Sepsis/complicaciones , Sepsis/mortalidad , Sepsis/terapia , Resultado del Tratamiento , Vasoconstrictores/uso terapéutico
2.
Artículo en Inglés | MEDLINE | ID: mdl-33542545

RESUMEN

The current Coronavirus disease outbreak requires that physicians work in collaboration with other physicians especially in intensive care and emergency units. To fight against this new disease, whose pathogenesis, effects, and results have not been clearly demonstrated, especially in patients with the pre-existing chronic disease, requires special expertise and perspectives. Due to the need for dynamic glucocorticoid treatment at different stages of the disease in patients with adrenal insufficiency, the existence of reports indicating that "coronavirus disease 2019" also affects the adrenal reserve, and the use of glucocorticoids also in advanced stages in patients with Coronavirus disease require this issue to be emphasized with precision. Herein, treatment of the pre-existing adrenal insufficiency in patients with actual Coronavirus disease and the effects of the this critical disease on the adrenal gland have been reviewed.


Asunto(s)
Insuficiencia Suprarrenal/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Hidrocortisona/uso terapéutico , Glándulas Suprarrenales/metabolismo , Insuficiencia Suprarrenal/complicaciones , Insuficiencia Suprarrenal/metabolismo , Manejo de la Enfermedad , Progresión de la Enfermedad , Terapia de Reemplazo de Hormonas/métodos , Hospitalización , Humanos , Inflamación , Estrés Fisiológico
3.
Eur J Endocrinol ; 184(4): R111-R122, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33449912

RESUMEN

Glucocorticoids are, besides non-steroidal anti-inflammatory drugs, the most widely used anti-inflammatory medications. Prevalence studies indicate substantial use of both systemic and locally acting agents. A recognised adverse effect of glucocorticoid treatment is adrenal insufficiency, which is highly prevalent based on biochemical testing, but its clinical implications are poorly understood. Current evidence, including randomised trials and observational studies, indicates substantial variation among patients in both risk and course of glucocorticoid-induced adrenal insufficiency, but both are currently unpredictable. Oral and intra-articular formulations, as well as long-term and high-dose treatments, carry the highest risk of glucocorticoid-induced adrenal insufficiency defined by biochemical tests. However, no route of administration, treatment duration, or dose can be considered without risk. More research is needed to estimate the risk and temporal pattern of glucocorticoid-induced adrenal insufficiency, to investigate its clinical implications, and to identify predictors of risk and prognosis. Randomized trials are required to evaluate whether hydrocortisone replacement therapy mitigates risk and symptoms of glucocorticoid-induced adrenal insufficiency in patients discontinuing glucocorticoid treatment. This review aims to provide an overview of the available evidence, pointing to knowledge gaps and unmet needs.


Asunto(s)
Insuficiencia Suprarrenal/inducido químicamente , Insuficiencia Suprarrenal/tratamiento farmacológico , Glucocorticoides/efectos adversos , Terapia de Reemplazo de Hormonas , Insuficiencia Suprarrenal/fisiopatología , Antiinflamatorios/efectos adversos , Antiinflamatorios/uso terapéutico , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéutico , Humanos , Hidrocortisona/uso terapéutico , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/fisiopatología , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/fisiopatología
4.
BMJ Case Rep ; 14(1)2021 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-33509872

RESUMEN

We report an interesting case of a 38-year-old woman presenting with reverse Takotsubo syndrome (TTS) secondary to an Addisonian crisis, her second such episode. A few years prior, she had presented with typical TTS in the setting of Addisonian crisis; diagnostic work-up revealing Auto-Immune Polyglandular Syndrome Type II (APS II). We believe this to be the first case report of typical and variant phenotypes of TTS in a patient with APS II. The pathogenic link between these two conditions is explored. In patients presenting with Addisonian crises and refractory shock, the possibility of concurrent TTS should be considered. TTS muddies the diagnostic waters and poses therapeutic challenges as outlined.


Asunto(s)
Enfermedad de Addison/tratamiento farmacológico , Hidrocortisona/uso terapéutico , Cumplimiento de la Medicación , Poliendocrinopatías Autoinmunes/tratamiento farmacológico , Cardiomiopatía de Takotsubo/fisiopatología , Enfermedad de Addison/complicaciones , Adulto , Progresión de la Enfermedad , Ecocardiografía , Femenino , Humanos , Hipotiroidismo/complicaciones , Hipotiroidismo/tratamiento farmacológico , Poliendocrinopatías Autoinmunes/complicaciones , Recurrencia , Infecciones del Sistema Respiratorio/complicaciones , Cardiomiopatía de Takotsubo/diagnóstico , Cardiomiopatía de Takotsubo/etiología , Tiroxina/uso terapéutico
5.
BMJ Case Rep ; 14(1)2021 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-33495195

RESUMEN

Takotsubo cardiomyopathy (TCMP) is an important, though under-recognised, syndrome which mimics acute coronary syndrome (ACS) presenting with similar clinical, biochemical and ECG features. A 68-year-old man was referred as ACS for emergency coronary angiography; however, a history of lethargy, weight loss and electrolyte abnormalities prompted further investigations. Angiography was postponed, adrenal insufficiency confirmed and steroid replacement commenced. Echocardiography demonstrated reduced left ventricular (LV) function (45%) with regional wall motion abnormalities, although angiography confirmed unobstructed arteries. Steroid replacement induced a rapid improvement in symptoms and LV function. Few cases of TCMP associated with adrenal insufficiency have been reported. This appears to be the first case describing TCMP precipitated by new-onset secondary adrenal insufficiency following long-term steroid use in a male patient, and highlights the importance of considering TCMP in patients presenting with suspected ACS. Here, prompt recognition and treatment of a serious underlying disorder prevented a potentially life-threatening Addisonian crisis.


Asunto(s)
Síndrome Coronario Agudo/diagnóstico , Insuficiencia Suprarrenal/diagnóstico , Cardiomiopatía de Takotsubo/diagnóstico , Pruebas de Función de la Corteza Suprarrenal , Insuficiencia Suprarrenal/inducido químicamente , Insuficiencia Suprarrenal/complicaciones , Insuficiencia Suprarrenal/tratamiento farmacológico , Anciano , Asma/tratamiento farmacológico , Proteína C-Reactiva/metabolismo , Diagnóstico Diferencial , Ecocardiografía , Eccema/tratamiento farmacológico , Electrocardiografía , Glucocorticoides/efectos adversos , Terapia de Reemplazo de Hormonas , Humanos , Hidrocortisona/uso terapéutico , Hiperpotasemia/etiología , Hiponatremia/etiología , Masculino , Neumonía/complicaciones , Neumonía/diagnóstico , Cardiomiopatía de Takotsubo/complicaciones
6.
BMJ Case Rep ; 14(1)2021 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-33509877

RESUMEN

An 88-year-old Inuit man from Northern Canada presented with an extensive skin rash associated with numerous violaceous skin nodules on his palms and lower extremities. Biopsy of a skin nodule revealed Kaposi's sarcoma (KS), a human herpesvirus 8 (HHV8)-associated malignancy, whereas biopsy of the erythematous skin showed an atypical infiltrate of CD4-positive T-cells that, together with TCR gene rearrangement and presence of clonal T-cells in peripheral blood by flow cytometry, was consistent with a T-cell lymphoma, mycosis fungoides (MF) subtype. Serology was negative for HIV and HTLV-I/II and no immunodeficiency syndrome was identified. The patient was successfully treated with an oral retinoid for KS, and with topical hydrocortisone and ultraviolet B (UVB) phototherapy for MF. This case highlights the existence of HHV8-related lesions in native persons of Northern Canada, and also that MF-induced immunosuppression combined with immunosenescence may play a role in the development of non-HIV-related KS.


Asunto(s)
Inuits , Micosis Fungoide/patología , Neoplasias Primarias Múltiples/patología , Sarcoma de Kaposi/patología , Neoplasias Cutáneas/patología , Acitretina/uso terapéutico , Administración Cutánea , Anciano de 80 o más Años , Antiinflamatorios/uso terapéutico , Herpesvirus Humano 8 , Humanos , Hidrocortisona/uso terapéutico , Huésped Inmunocomprometido , Inmunosenescencia , Masculino , Micosis Fungoide/inmunología , Micosis Fungoide/terapia , Neoplasias Primarias Múltiples/inmunología , Neoplasias Primarias Múltiples/terapia , Sarcoma de Kaposi/tratamiento farmacológico , Sarcoma de Kaposi/etnología , Sarcoma de Kaposi/inmunología , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/terapia , Terapia Ultravioleta/métodos
7.
Eur J Endocrinol ; 184(4): 553-563, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33460392

RESUMEN

Objective: Despite published guidelines no unified approach to hormone replacement in congenital adrenal hyperplasia (CAH) exists. We aimed to explore geographical and temporal variations in the treatment with glucocorticoids and mineralocorticoids in CAH. Design: This retrospective multi-center study, including 31 centers (16 countries), analyzed data from the International-CAH Registry. Methods: Data were collected from 461 patients aged 0-18 years with classic 21-hydroxylase deficiency (54.9% females) under follow-up between 1982 and 2018. Type, dose and timing of glucocorticoid and mineralocorticoid replacement were analyzed from 4174 patient visits. Results: The most frequently used glucocorticoid was hydrocortisone (87.6%). Overall, there were significant differences between age groups with regards to daily hydrocortisone-equivalent dose for body surface, with the lowest dose (median with interquartile range) of 12.0 (10.0-14.5) mg/m2/day at age 1-8 years and the highest dose of 14.0 (11.6-17.4) mg/m2/day at age 12-18 years. Glucocorticoid doses decreased after 2010 in patients 0-8 years (P < 0.001) and remained unchanged in patients aged 8-18 years. Fludrocortisone was used in 92% of patients, with relative doses decreasing with age. A wide variation was observed among countries with regards to all aspects of steroid hormone replacement. Conclusions: Data from the I-CAH Registry suggests international variations in hormone replacement therapy, with a tendency to treatment with high doses in children.


Asunto(s)
Corticoesteroides/uso terapéutico , Hiperplasia Suprarrenal Congénita/tratamiento farmacológico , Terapia de Reemplazo de Hormonas/métodos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Adolescente , Corticoesteroides/administración & dosificación , Factores de Edad , Niño , Preescolar , Femenino , Fludrocortisona/administración & dosificación , Fludrocortisona/uso terapéutico , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéutico , Terapia de Reemplazo de Hormonas/estadística & datos numéricos , Humanos , Hidrocortisona/administración & dosificación , Hidrocortisona/uso terapéutico , Lactante , Recién Nacido , Masculino , Sistema de Registros , Estudios Retrospectivos
8.
Rev Fac Cien Med Univ Nac Cordoba ; 77(4): 363-366, 2020 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-33351369

RESUMEN

BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) outbreak originated in Wuhan (China) rapidly turned into a pandemic. Due to a national compulsive decree of quarantine, office visits for chronic disease control were delay. Hypopituitarism includes all clinical conditions that result in partial or complete failure of the pituitary gland's ability to secrete hormones. Pituitary insufficiency per se has been associated with an increase in both morbidity and mortality, particularly due to cardiovascular disease, which is an important risk factor for COVID-19 disease severity. OBJECTIVE: To report the first case of SARS-CoV-2 infection in a patient with hypopituitarism, discuss the implications of the treatments the patient was taking and grade up the value of telemedicine in the present scenario. METHODS: Report of the clinical record of a patient with hypopituitarism and infection with SARS-CoV-2. RESULTS: During the span of the infection, the patient remained on the same hormonal therapeutic scheme (thyroid, gonadal and adrenal axis). The dose of hydrocortisone was not changed during the course of the infection as she was asymptomatic. We use telemedicine to control and advise her on the treatment. CONCLUSION: Health care professionals should carefully follow up on the evolution of patients with hypopituitarism to provide them a safer outcome. The use of telemedicine as a methodology for selected patients acquires relevance in the present epidemiological context.


Asunto(s)
/complicaciones , Hipopituitarismo/tratamiento farmacológico , Infecciones Asintomáticas , Femenino , Humanos , Hidrocortisona/uso terapéutico , Hipopituitarismo/complicaciones
9.
BMJ Case Rep ; 13(12)2020 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-33372021

RESUMEN

Bilateral adrenal haemorrhage is a rare and often fatal condition that most commonly occurs under conditions of severe physiological stress. We describe a 33-year-old male patient with ulcerative colitis who presented with acute worsening epigastric pain, vomiting and raised inflammatory markers. Initial differentials included gastritis and peptic ulceration. Gastroscopy revealed no abnormalities. By day 3, he had developed sepsis with a sequential organ failure assessment score of 2 as well as coagulopathy. A subsequent CT scan diagnosed bilateral adrenal haemorrhage. A short Synacthen Test confirmed adrenal insufficiency and he was treated with replacement steroids and antibiotics for a possible urinary tract infection or pyelonephritis and he recovered well. Several days later he developed fever, dyspnoea and a productive cough. Subsequently, he became hypotensive (Blood Pressure (BP) 95/65 mm Hg) and unresponsive with a Glasgow Coma Scale of 7 and was hyponatraemic and hyperkalaemic. He was intubated and transferred to a tertiary hospital for intensive care unit management where investigations confirmed the patient to be influenza A positive.


Asunto(s)
Insuficiencia Suprarrenal/etiología , Infecciones Bacterianas/complicaciones , Trastornos de la Coagulación Sanguínea/complicaciones , Colitis Ulcerosa/complicaciones , Hemorragia/etiología , Gripe Humana/complicaciones , Sepsis/complicaciones , Insuficiencia Suprarrenal/tratamiento farmacológico , Adulto , Antibacterianos/uso terapéutico , Antiinflamatorios/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Coinfección , Diagnóstico Diferencial , Hemorragia/complicaciones , Humanos , Hidrocortisona/uso terapéutico , Virus de la Influenza A , Masculino , Sepsis/tratamiento farmacológico , Tomografía Computarizada por Rayos X
10.
Cochrane Database Syst Rev ; 10: CD013101, 2020 10 12.
Artículo en Inglés | MEDLINE | ID: mdl-33045104

RESUMEN

BACKGROUND: Corticosteroids are routinely given to children undergoing cardiac surgery with cardiopulmonary bypass (CPB) in an attempt to ameliorate the inflammatory response. Their use is still controversial and the decision to administer the intervention can vary by centre and/or by individual doctors within that centre. OBJECTIVES: This review is designed to assess the benefits and harms of prophylactic corticosteroids in children between birth and 18 years of age undergoing cardiac surgery with CPB. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and Conference Proceedings Citation Index-Science in June 2020. We also searched four clinical trials registers and conducted backward and forward citation searching of relevant articles. SELECTION CRITERIA: We included studies of prophylactic administration of corticosteroids, including single and multiple doses, and all types of corticosteroids administered via any route and at any time-point in the perioperative period. We excluded studies if steroids were administered therapeutically. We included individually randomised controlled trials (RCTs), with two or more groups (e.g. multi-drug or dose comparisons with a control group) but not 'head-to-head' trials without a placebo or a group that did not receive corticosteroids. We included studies in children, from birth up to 18 years of age, including preterm infants, undergoing cardiac surgery with the use of CPB. We also excluded studies in patients undergoing heart or lung transplantation, or both; studies in patients already receiving corticosteroids; in patients with abnormalities of the hypothalamic-pituitary-adrenal axis; and in patients given steroids at the time of cardiac surgery for indications other than cardiac surgery. DATA COLLECTION AND ANALYSIS: We used the Covidence systematic review manager to extract and manage data for the review. Two review authors independently assessed studies for inclusion, extracted data, and assessed risks of bias. We resolved disagreements by consensus or by consultation with a third review author. We assessed the certainty of evidence with GRADE. MAIN RESULTS: We found 3748 studies, of which 888 were duplicate records. Two studies had the same clinical trial registration number, but reported different populations and interventions. We therefore included them as separate studies. We screened titles and abstracts of 2868 records and reviewed full text reports for 84 studies to determine eligibility. We extracted data for 13 studies. Pooled analyses are based on eight studies. We reported the remaining five studies narratively due to zero events for both intervention and placebo in the outcomes of interest. Therefore, the final meta-analysis included eight studies with a combined population of 478 participants. There was a low or unclear risk of bias across the domains. There was moderate certainty of evidence that corticosteroids do not change the risk of in-hospital mortality (five RCTs; 313 participants; risk ratio (RR) 0.83, 95% confidence interval (CI) 0.33 to 2.07) for children undergoing cardiac surgery with CPB. There was high certainty of evidence that corticosteroids reduce the duration of mechanical ventilation (six RCTs; 421 participants; mean difference (MD) 11.37 hours lower, 95% CI -20.29 to -2.45) after the surgery. There was high-certainty evidence that the intervention probably made little to no difference to the length of postoperative intensive care unit (ICU) stay (six RCTs; 421 participants; MD 0.28 days lower, 95% CI -0.79 to 0.24) and moderate-certainty evidence that the intervention probably made little to no difference to the length of the postoperative hospital stay (one RCT; 176 participants; mean length of stay 22 days; MD -0.70 days, 95% CI -2.62 to 1.22). There was moderate certainty of evidence for no effect of the intervention on all-cause mortality at the longest follow-up (five RCTs; 313 participants; RR 0.83, 95% CI 0.33 to 2.07) or cardiovascular mortality at the longest follow-up (three RCTs; 109 participants; RR 0.40, 95% CI 0.07 to 2.46). There was low certainty of evidence that corticosteroids probably make little to no difference to children separating from CPB (one RCT; 40 participants; RR 0.20, 95% CI 0.01 to 3.92). We were unable to report information regarding adverse events of the intervention due to the heterogeneity of reporting of outcomes. We downgraded the certainty of evidence for several reasons, including imprecision due to small sample sizes, a single study providing data for an individual outcome, the inclusion of both appreciable benefit and harm in the confidence interval, and publication bias. AUTHORS' CONCLUSIONS: Corticosteroids  probably do not change the risk of mortality for children having heart surgery using CPB at any time point. They probably reduce the duration of postoperative ventilation in this context, but have little or no effect on the total length of postoperative ICU stay or total postoperative hospital stay. There was inconsistency in the adverse event outcomes reported which, consequently, could not be pooled. It is therefore impossible to provide any implications and policy-makers will be unable to make any recommendations for practice without evidence about adverse effects. The review highlighted the need for well-conducted RCTs powered for clinical outcomes to confirm or refute the effect of corticosteroids versus placebo in children having cardiac surgery with CPB. A core outcome set for adverse event reporting in the paediatric major surgery and intensive care setting is required.


Asunto(s)
Corticoesteroides/uso terapéutico , Procedimientos Quirúrgicos Cardíacos/métodos , Puente Cardiopulmonar/efectos adversos , Inflamación/prevención & control , Adolescente , Corticoesteroides/efectos adversos , Sesgo , Procedimientos Quirúrgicos Cardíacos/mortalidad , Puente Cardiopulmonar/mortalidad , Causas de Muerte , Niño , Preescolar , Dexametasona/uso terapéutico , Máquina Corazón-Pulmón/efectos adversos , Mortalidad Hospitalaria , Humanos , Hidrocortisona/uso terapéutico , Lactante , Recién Nacido , Inflamación/etiología , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Tiempo de Internación , Metilprednisolona/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Respiración Artificial/estadística & datos numéricos
11.
Artículo en Inglés | MEDLINE | ID: mdl-33071957

RESUMEN

Introduction: Italy, since the end of February 2020, is experiencing the corona virus disease 2019 (COVID-19) pandemic that may present as an acute respiratory infection. We report on COVID-19 pneumonia in the context of a complex case of Cushing's disease (CD). Case Report: A 67-year-old man with CD, who was admitted to our hospital, presented with signs and symptoms of adrenal insufficiency with persistent hypotension and glycemia toward the lower limits. We progressively withdrew almost all treatments for diabetes and CD (pasireotide and metyrapone), and i.v. hydrocortisone was necessary. A tendency to hyperkalemia was probably associated to enoxaparin. We summarized the many possible interactions between medications of Cushing's syndrome (CS) and COVID-19. Conclusion: Adrenal insufficiency might be a clinical challenge that needs a prompt treatment also in CS patients during COVID-19 infection. We should consider the possibility to titrate or temporary halt medical therapies of CS in the context of COVID-19 infection. Unexpected hyperkalemia in CS patients under treatment with heparin might be the signal of aldosterone suppression.


Asunto(s)
Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Síndrome de Cushing/tratamiento farmacológico , Hidrocortisona/uso terapéutico , Metirapona/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Anciano , Antiinflamatorios/uso terapéutico , Antimetabolitos/uso terapéutico , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/virología , Síndrome de Cushing/complicaciones , Síndrome de Cushing/virología , Manejo de la Enfermedad , Humanos , Masculino , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/virología
16.
Crit Care Resusc ; 22(3): 191-199, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32900325

RESUMEN

OBJECTIVE: To determine whether hydrocortisone is a cost-effective treatment for patients with septic shock. DESIGN: Data linkage-based cost-effectiveness analysis. SETTING: New South Wales and Queensland intensive care units. PARTICIPANTS AND INTERVENTION: Patients with septic shock randomly assigned to treatment with hydrocortisone or placebo in the Adjunctive Glucocorticoid Therapy in Patients with Septic Shock (ADRENAL) trial. MAIN OUTCOME MEASURES: Health-related quality of life at 6 months using the EuroQoL 5-dimension 5-level questionnaire. Data on hospital resource use and costs were obtained by linking the ADRENAL dataset to government administrative health databases. Clinical outcomes included mortality, health-related quality of life, and quality-adjusted life-years gained; economic outcomes included hospital resource use, costs and cost-effectiveness from the health care payer perspective. We also assessed cost-effectiveness by sex. To increase the precision of cost-effectiveness estimates, we conducted unrestricted bootstrapping. RESULTS: Of 3800 patients in the ADRENAL trial, 1772 (46.6%) were eligible and 1513 (85.4% of those eligible) were included. There was no difference between hydrocortisone or placebo groups in regards to mortality (218/742 [29.4%] v 227/759 [29.9%]; HR, 0.93; 95% CI, 0.78-1.12; P = 0.47), mean number of QALYs gained (0.10 ± 0.09 v 0.10 ± 0.09; P = 0.52), or total hospital costs (A$73 515 ± 61 376 v A$69 748 ± 61 793; mean difference, A$3767; 95% CI, -A$2891 to A$10 425; P = 0.27). The incremental cost of hydrocortisone was A$1 254 078 per quality-adjusted life-year gained. In females, hydrocortisone was cost-effective in 46.2% of bootstrapped replications and in males it was cost-effective in 2.7% of bootstrapped replications. CONCLUSIONS: Adjunctive hydrocortisone did not significantly affect longer term mortality, health-related quality of life, health care resource use or costs, and is unlikely to be cost-effective.


Asunto(s)
Antiinflamatorios/economía , Antiinflamatorios/uso terapéutico , Hidrocortisona/economía , Hidrocortisona/uso terapéutico , Choque Séptico/tratamiento farmacológico , Análisis Costo-Beneficio , Femenino , Humanos , Masculino , Nueva Gales del Sur , Calidad de Vida , Años de Vida Ajustados por Calidad de Vida , Choque Séptico/mortalidad
17.
JAMA ; 324(13): 1298-1306, 2020 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-32876689

RESUMEN

Importance: Coronavirus disease 2019 (COVID-19) is associated with severe lung damage. Corticosteroids are a possible therapeutic option. Objective: To determine the effect of hydrocortisone on treatment failure on day 21 in critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute respiratory failure. Design, Setting, and Participants: Multicenter randomized double-blind sequential trial conducted in France, with interim analyses planned every 50 patients. Patients admitted to the intensive care unit (ICU) for COVID-19-related acute respiratory failure were enrolled from March 7 to June 1, 2020, with last follow-up on June 29, 2020. The study intended to enroll 290 patients but was stopped early following the recommendation of the data and safety monitoring board. Interventions: Patients were randomized to receive low-dose hydrocortisone (n = 76) or placebo (n = 73). Main Outcomes and Measures: The primary outcome, treatment failure on day 21, was defined as death or persistent dependency on mechanical ventilation or high-flow oxygen therapy. Prespecified secondary outcomes included the need for tracheal intubation (among patients not intubated at baseline); cumulative incidences (until day 21) of prone position sessions, extracorporeal membrane oxygenation, and inhaled nitric oxide; Pao2:Fio2 ratio measured daily from day 1 to day 7, then on days 14 and 21; and the proportion of patients with secondary infections during their ICU stay. Results: The study was stopped after 149 patients (mean age, 62.2 years; 30.2% women; 81.2% mechanically ventilated) were enrolled. One hundred forty-eight patients (99.3%) completed the study, and there were 69 treatment failure events, including 11 deaths in the hydrocortisone group and 20 deaths in the placebo group. The primary outcome, treatment failure on day 21, occurred in 32 of 76 patients (42.1%) in the hydrocortisone group compared with 37 of 73 (50.7%) in the placebo group (difference of proportions, -8.6% [95.48% CI, -24.9% to 7.7%]; P = .29). Of the 4 prespecified secondary outcomes, none showed a significant difference. No serious adverse events were related to the study treatment. Conclusions and Relevance: In this study of critically ill patients with COVID-19 and acute respiratory failure, low-dose hydrocortisone, compared with placebo, did not significantly reduce treatment failure (defined as death or persistent respiratory support) at day 21. However, the study was stopped early and likely was underpowered to find a statistically and clinically important difference in the primary outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT02517489.


Asunto(s)
Antiinflamatorios/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Hidrocortisona/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Respiración Artificial , Insuficiencia Respiratoria/terapia , Anciano , Antiinflamatorios/administración & dosificación , Betacoronavirus , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/terapia , Enfermedad Crítica , Método Doble Ciego , Terminación Anticipada de los Ensayos Clínicos , Femenino , Humanos , Hidrocortisona/administración & dosificación , Masculino , Persona de Mediana Edad , Terapia por Inhalación de Oxígeno , Pandemias , Neumonía Viral/mortalidad , Neumonía Viral/terapia , Respiración Artificial/estadística & datos numéricos , Insuficiencia Respiratoria/tratamiento farmacológico , Insuficiencia Respiratoria/etiología , Insuficiencia del Tratamiento
18.
JAMA ; 324(13): 1330-1341, 2020 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-32876694

RESUMEN

Importance: Effective therapies for patients with coronavirus disease 2019 (COVID-19) are needed, and clinical trial data have demonstrated that low-dose dexamethasone reduced mortality in hospitalized patients with COVID-19 who required respiratory support. Objective: To estimate the association between administration of corticosteroids compared with usual care or placebo and 28-day all-cause mortality. Design, Setting, and Participants: Prospective meta-analysis that pooled data from 7 randomized clinical trials that evaluated the efficacy of corticosteroids in 1703 critically ill patients with COVID-19. The trials were conducted in 12 countries from February 26, 2020, to June 9, 2020, and the date of final follow-up was July 6, 2020. Pooled data were aggregated from the individual trials, overall, and in predefined subgroups. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance-weighted fixed-effect meta-analysis of overall mortality, with the association between the intervention and mortality quantified using odds ratios (ORs). Random-effects meta-analyses also were conducted (with the Paule-Mandel estimate of heterogeneity and the Hartung-Knapp adjustment) and an inverse variance-weighted fixed-effect analysis using risk ratios. Exposures: Patients had been randomized to receive systemic dexamethasone, hydrocortisone, or methylprednisolone (678 patients) or to receive usual care or placebo (1025 patients). Main Outcomes and Measures: The primary outcome measure was all-cause mortality at 28 days after randomization. A secondary outcome was investigator-defined serious adverse events. Results: A total of 1703 patients (median age, 60 years [interquartile range, 52-68 years]; 488 [29%] women) were included in the analysis. Risk of bias was assessed as "low" for 6 of the 7 mortality results and as "some concerns" in 1 trial because of the randomization method. Five trials reported mortality at 28 days, 1 trial at 21 days, and 1 trial at 30 days. There were 222 deaths among the 678 patients randomized to corticosteroids and 425 deaths among the 1025 patients randomized to usual care or placebo (summary OR, 0.66 [95% CI, 0.53-0.82]; P < .001 based on a fixed-effect meta-analysis). There was little inconsistency between the trial results (I2 = 15.6%; P = .31 for heterogeneity) and the summary OR was 0.70 (95% CI, 0.48-1.01; P = .053) based on the random-effects meta-analysis. The fixed-effect summary OR for the association with mortality was 0.64 (95% CI, 0.50-0.82; P < .001) for dexamethasone compared with usual care or placebo (3 trials, 1282 patients, and 527 deaths), the OR was 0.69 (95% CI, 0.43-1.12; P = .13) for hydrocortisone (3 trials, 374 patients, and 94 deaths), and the OR was 0.91 (95% CI, 0.29-2.87; P = .87) for methylprednisolone (1 trial, 47 patients, and 26 deaths). Among the 6 trials that reported serious adverse events, 64 events occurred among 354 patients randomized to corticosteroids and 80 events occurred among 342 patients randomized to usual care or placebo. Conclusions and Relevance: In this prospective meta-analysis of clinical trials of critically ill patients with COVID-19, administration of systemic corticosteroids, compared with usual care or placebo, was associated with lower 28-day all-cause mortality.


Asunto(s)
Corticoesteroides/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Betacoronavirus , Causas de Muerte , Infecciones por Coronavirus/mortalidad , Enfermedad Crítica , Dexametasona/uso terapéutico , Humanos , Hidrocortisona/uso terapéutico , Metilprednisolona/uso terapéutico , Pandemias , Neumonía Viral/mortalidad , Ensayos Clínicos Controlados Aleatorios como Asunto
19.
Life Sci ; 261: 118366, 2020 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-32871182

RESUMEN

AIMS: Intensive care unit-acquired weakness (ICU-AW) is a complex spectrum of disability that delays recovery of critically ill-immobilized patients with sepsis. Much discrepancy remain on the use of corticosteroids and their impact on muscle regeneration in critical illness management. Therefore, the aim of this study is to investigate whether hydrocortisone (HCT) modulates muscle mass turnover in ICU-AW induced by sepsis with limb immobilization (SI). MAIN METHODS: Sepsis by cecal ligation puncture (CLP) with forelimb-immobilization were performed in rats. The study consisted of four groups: Sham (left forelimb-immobilization), Sham HCT (left forelimb-immobilization + HCT), SI (CLP + left forelimb-immobilization) and SI HCT (CLP + left forelimb-immobilization + HCT). Motor force, blood and muscle sampling were assessed. KEY FINDINGS: HCT prevented body weight loss associated with SI and attenuated systemic and muscular inflammation. Besides, myosin was restituted in SI HCT group in conjunction to muscle mass and strength restoration. Pro-hypertrophic calcineurin (PP2B-Aß) and nuclear factor of activated T-cells C3 (NFATc3) but not protein kinase B (Akt) were re-activated by HCT. Finally, pro-atrophic extracellular signal-regulated kinases (ERK1/2) and p38 mitogen-activated protein kinases (p38) but not nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) were inhibited in SI HCT group. SIGNIFICANCE: This study unravels new molecular events thought to control muscle protein synthesis in ICU-AW induced by sepsis and limb immobilization. HCT has a potential to fine-tune muscle-signaling pathways and to reduce the negative outcomes of ICU-AW.


Asunto(s)
Extremidades/patología , Hidrocortisona/uso terapéutico , Inmovilización , Unidades de Cuidados Intensivos , Debilidad Muscular/tratamiento farmacológico , Atrofia Muscular/tratamiento farmacológico , Sepsis/complicaciones , Transducción de Señal , Animales , Peso Corporal , Modelos Animales de Enfermedad , Hidrocortisona/farmacología , Hipertrofia , Mediadores de Inflamación/sangre , Masculino , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Modelos Biológicos , Debilidad Muscular/sangre , Debilidad Muscular/complicaciones , Atrofia Muscular/sangre , Atrofia Muscular/complicaciones , Miosinas/metabolismo , Factores de Transcripción NFATC/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Ratas Wistar , Sepsis/sangre
20.
Cochrane Database Syst Rev ; 8: CD013202, 2020 08 19.
Artículo en Inglés | MEDLINE | ID: mdl-32813884

RESUMEN

BACKGROUND: Hypoxic-ischaemic encephalopathy (HIE) is a leading cause of mortality and long-term neurological sequelae, affecting thousands of children worldwide. Current therapies to treat HIE are limited to cooling. Stem cell-based therapies offer a potential therapeutic approach to repair or regenerate injured brain tissue. These preclinical findings have now culminated in ongoing human neonatal trials. OBJECTIVES: To determine the efficacy and safety of stem cell-based interventions for the treatment of hypoxic-ischaemic encephalopathy (HIE) in newborn infants. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 5), MEDLINE via PubMed (1966 to 8 June 2020), Embase (1980 to 8 June 2020), and CINAHL (1982 to 8 June 2020). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised controlled trials, quasi-randomised controlled trials and cluster trials comparing 1) stem cell-based interventions (any type) compared to control (placebo or no treatment); 2) use of mesenchymal stem/stromal cells (MSCs) of type (e.g. number of doses or passages) or source (e.g. autologous versus allogeneic, or bone marrow versus cord) versus MSCs of other type or source; 3) use of stem cell-based interventions other than MSCs of type (e.g. mononuclear cells, oligodendrocyte progenitor cells, neural stem cells, hematopoietic stem cells, and inducible pluripotent stem cells) or source (e.g. autologous versus allogeneic, or bone marrow versus cord) versus stem cell-based interventions other than MSCs of other type or source; or 4) MSCs versus stem cell-based interventions other than MSCs. DATA COLLECTION AND ANALYSIS: For each of the included trials, two authors independently planned to extract data (e.g. number of participants, birth weight, gestational age, type and source of MSCs or other stem cell-based interventions) and assess the risk of bias (e.g. adequacy of randomisation, blinding, completeness of follow-up). The primary outcomes considered in this review are all-cause neonatal mortality, major neurodevelopmental disability, death or major neurodevelopmental disability assessed at 18 to 24 months of age. We planned to use the GRADE approach to assess the quality of evidence. MAIN RESULTS: Our search strategy yielded 616 references. Two review authors independently assessed all references for inclusion. We did not find any completed studies for inclusion. Fifteen RCTs are currently registered and ongoing. We describe the three studies we excluded. AUTHORS' CONCLUSIONS: There is currently no evidence from randomised trials that assesses the benefit or harms of stem cell-based interventions for the prevention of morbidity and mortality following hypoxic-ischaemic encephalopathy in newborn infants.


Asunto(s)
Hipoxia-Isquemia Encefálica/terapia , Trasplante de Células Madre , Antiinflamatorios/uso terapéutico , Sangre Fetal/citología , Humanos , Hidrocortisona/uso terapéutico , Hipotermia Inducida , Hipoxia-Isquemia Encefálica/complicaciones , Hipoxia-Isquemia Encefálica/mortalidad , Recién Nacido
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