-
Intensive Care Medicine Aug 2022Severe community-acquired pneumonia (CAP) requiring intensive care unit admission is associated with significant acute and long-term morbidity and mortality. We... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Severe community-acquired pneumonia (CAP) requiring intensive care unit admission is associated with significant acute and long-term morbidity and mortality. We hypothesized that downregulation of systemic and pulmonary inflammation with prolonged low-dose methylprednisolone treatment would accelerate pneumonia resolution and improve clinical outcomes.
METHODS
This double-blind, randomized, placebo-controlled clinical trial recruited adult patients within 72-96 h of hospital presentation. Patients were randomized in 1:1 ratio; an intravenous 40 mg loading bolus was followed by 40 mg/day through day 7 and progressive tapering during the 20-day treatment course. Randomization was stratified by site and need for mechanical ventilation (MV) at the time of randomization. Outcomes included a primary endpoint of 60-day all-cause mortality and secondary endpoints of morbidity and mortality up to 1 year of follow-up.
RESULTS
Between January 2012 and April 2016, 586 patients from 42 Veterans Affairs Medical Centers were randomized, short of the 1420 target sample size because of low recruitment. 584 patients were included in the analysis. There was no significant difference in 60-day mortality between the methylprednisolone and placebo arms (16% vs. 18%; adjusted odds ratio 0.90, 95% CI 0.57-1.40). There were no significant differences in secondary outcomes or complications.
CONCLUSIONS
In patients with severe CAP, prolonged low-dose methylprednisolone treatment did not significantly reduce 60-day mortality. Treatment was not associated with increased complications.
Topics: Adult; Community-Acquired Infections; Critical Illness; Humans; Methylprednisolone; Pneumonia; Respiration, Artificial; Treatment Outcome
PubMed: 35723686
DOI: 10.1007/s00134-022-06684-3 -
The New England Journal of Medicine Dec 2022Although perioperative prophylactic glucocorticoids have been used for decades, whether they improve outcomes in infants after heart surgery with cardiopulmonary bypass... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Although perioperative prophylactic glucocorticoids have been used for decades, whether they improve outcomes in infants after heart surgery with cardiopulmonary bypass is unknown.
METHODS
We conducted a multicenter, prospective, randomized, placebo-controlled, registry-based trial involving infants (<1 year of age) undergoing heart surgery with cardiopulmonary bypass at 24 sites participating in the Society of Thoracic Surgeons Congenital Heart Surgery Database. Registry data were used in the evaluation of outcomes. The infants were randomly assigned to receive prophylactic methylprednisolone (30 mg per kilogram of body weight) or placebo, which was administered into the cardiopulmonary-bypass pump-priming fluid. The primary end point was a ranked composite of death, heart transplantation, or any of 13 major complications. Patients without any of these events were assigned a ranked outcome based on postoperative length of stay. In the primary analysis, the ranked outcomes were compared between the trial groups with the use of odds ratios adjusted for prespecified risk factors. Secondary analyses included an unadjusted odds ratio, a win ratio, and safety outcomes.
RESULTS
A total of 1263 infants underwent randomization, of whom 1200 received either methylprednisolone (599 infants) or placebo (601 infants). The likelihood of a worse outcome did not differ significantly between the methylprednisolone group and the placebo group (adjusted odds ratio, 0.86; 95% confidence interval [CI], 0.71 to 1.05; P = 0.14). Secondary analyses (unadjusted for risk factors) showed an odds ratio for a worse outcome of 0.82 (95% CI, 0.67 to 1.00) and a win ratio of 1.15 (95% CI, 1.00 to 1.32) in the methylprednisolone group as compared with the placebo group, findings suggestive of a benefit with methylprednisolone; however, patients in the methylprednisolone group were more likely than those in the placebo group to receive postoperative insulin for hyperglycemia (19.0% vs. 6.7%, P<0.001).
CONCLUSIONS
Among infants undergoing surgery with cardiopulmonary bypass, prophylactic use of methylprednisolone did not significantly reduce the likelihood of a worse outcome in an adjusted analysis and was associated with postoperative development of hyperglycemia warranting insulin in a higher percentage of infants than placebo. (Funded by the National Center for Advancing Translational Sciences and others; STRESS ClinicalTrials.gov number, NCT03229538.).
Topics: Humans; Methylprednisolone; Prospective Studies; Cardiac Surgical Procedures; Insulin
PubMed: 36342116
DOI: 10.1056/NEJMoa2212667 -
The New England Journal of Medicine May 1990Studies in animals indicate that methylprednisolone and naloxone are both potentially beneficial in acute spinal-cord injury, but whether any treatment is clinically... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study.
Studies in animals indicate that methylprednisolone and naloxone are both potentially beneficial in acute spinal-cord injury, but whether any treatment is clinically effective remains uncertain. We evaluated the efficacy and safety of methylprednisolone and naloxone in a multicenter randomized, double-blind, placebo-controlled trial in patients with acute spinal-cord injury, 95 percent of whom were treated within 14 hours of injury. Methylprednisolone was given to 162 patients as a bolus of 30 mg per kilogram of body weight, followed by infusion at 5.4 mg per kilogram per hour for 23 hours. Naloxone was given to 154 patients as a bolus of 5.4 mg per kilogram, followed by infusion at 4.0 mg per kilogram per hour for 23 hours. Placebos were given to 171 patients by bolus and infusion. Motor and sensory functions were assessed by systematic neurological examination on admission and six weeks and six months after injury. After six months the patients who were treated with methylprednisolone within eight hours of their injury had significant improvement as compared with those given placebo in motor function (neurologic change scores of 16.0 and 11.2, respectively; P = 0.03) and sensation to pinprick (change scores of 11.4 and 6.6; P = 0.02) and touch (change scores, 8.9 and 4.3; P = 0.03). Benefit from methylprednisolone was seen in patients whose injuries were initially evaluated as neurologically complete, as well as in those believed to have incomplete lesions. The patients treated with naloxone, or with methylprednisolone more than eight hours after their injury, did not differ in their neurologic outcomes from those given placebo. Mortality and major morbidity were similar in all three groups. We conclude that in patients with acute spinal-cord injury, treatment with methylprednisolone in the dose used in this study improves neurologic recovery when the medication is given in the first eight hours. We also conclude that treatment with naloxone in the dose used in this study does not improve neurologic recovery after acute spinal-cord injury.
Topics: Acute Disease; Adolescent; Adult; Double-Blind Method; Female; Humans; Infusions, Intravenous; Injections, Intravenous; Male; Methylprednisolone; Middle Aged; Motor Activity; Multicenter Studies as Topic; Naloxone; Randomized Controlled Trials as Topic; Sensation; Spinal Cord Injuries; Time Factors
PubMed: 2278545
DOI: 10.1056/NEJM199005173222001 -
The New England Journal of Medicine Feb 1992The use of corticosteroids to treat optic neuritis is controversial. At 15 clinical centers, we randomly assigned 457 patients with acute optic neuritis to receive oral... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
BACKGROUND AND METHODS
The use of corticosteroids to treat optic neuritis is controversial. At 15 clinical centers, we randomly assigned 457 patients with acute optic neuritis to receive oral prednisone (1 mg per kilogram of body weight per day) for 14 days; intravenous methylprednisolone (1 g per day) for 3 days, followed by oral prednisone (1 mg per kilogram per day) for 11 days; or oral placebo for 14 days. Visual function was assessed over a six-month follow-up period.
RESULTS
Visual function recovered faster in the group receiving intravenous methylprednisolone than in the placebo group; this was particularly true for the reversal of visual-field defects (P = 0.0001). Although the differences between the groups decreased with time, at six months the group that received intravenous methylprednisolone still had slightly better visual fields (P = 0.054), contrast sensitivity (P = 0.026), and color vision (P = 0.033) but not better visual acuity (P = 0.66). The outcome in the oral-prednisone group did not differ from that in the placebo group. In addition, the rate of new episodes of optic neuritis in either eye was higher in the group receiving oral prednisone, but not the group receiving intravenous methylprednisolone, than in the placebo group (relative risk for oral prednisone vs. placebo, 1.79; 95 percent confidence interval, 1.08 to 2.95).
CONCLUSIONS
Intravenous methylprednisolone followed by oral prednisone speeds the recovery of visual loss due to optic neuritis and results in slightly better vision at six months. Oral prednisone alone, as prescribed in this study, is an ineffective treatment and increases the risk of new episodes of optic neuritis.
Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Color Perception; Female; Follow-Up Studies; Humans; Injections, Intravenous; Male; Methylprednisolone; Middle Aged; Multiple Sclerosis; Optic Neuritis; Patient Compliance; Prednisone; Recurrence; Visual Acuity; Visual Fields
PubMed: 1734247
DOI: 10.1056/NEJM199202273260901 -
Steroids Jul 2022The roles of methylprednisolone in treatment of patients with COVID-19 remain unclear. The aim of this study was to evaluate the efficacy and safety of... (Meta-Analysis)
Meta-Analysis Review
The roles of methylprednisolone in treatment of patients with COVID-19 remain unclear. The aim of this study was to evaluate the efficacy and safety of methylprednisolone in treatment of COVID-19 patients. PubMed, Cochrane and Web of Science were searched for studies comparing methylprednisolone and no glucocorticoids treatment in patients with COVID-19. Statistical pooling was reported as risk ratio (RR) or mean difference (MD) with corresponding 95 % confidence interval (CI). Thirty-three studies were eligible, including 5 randomized trials and 28 observational studies. Meta-analysis showed that compared with no glucocorticoids, methylprednisolone in treatment of COVID-19 patients was associated with reduced short-term mortality (RR 0.73; 95% CI 0.60-0.89), less need for ICU admission (RR 0.77; 95% CI 0.66-0.91) and mechanical ventilation (RR 0.69; 95% CI 0.57-0.84), increased 28-day ventilator-free days (MD 2.81; 95% CI 2.64-2.97), without increasing risk of secondary infections (RR 1.04; 95% CI 0.82-1.32), but could prolong duration of viral shedding (MD 1.03; 95% CI 0.25-1.82). Subgroup analyses revealed that low-dose (≤2mg/kg/day) methylprednisolone treatment for ≤ 7 days in severe COVID-19 patients was associated with relatively better clinical outcomes, without increasing duration of viral shedding. Compared with no glucocorticoids, methylprednisolone treatment in COVID-19 patients is associated with reduced short-term mortality and better clinical outcomes, without increasing secondary infections, but could slightly prolong duration of viral shedding. Patients with severe COVID-19 are more likely to benefit from short-term low-dose methylprednisolone treatment (1-2 mg/kg/day for ≤ 7 days).
Topics: Coinfection; Glucocorticoids; Humans; Methylprednisolone; Respiration, Artificial; COVID-19 Drug Treatment
PubMed: 35346661
DOI: 10.1016/j.steroids.2022.109022 -
BMC Infectious Diseases Mar 2022Racial/ethnic minorities are at higher risk for severe COVID-19. This may be related to social determinants that lead to chronic inflammatory states. The aims of the...
BACKGROUND
Racial/ethnic minorities are at higher risk for severe COVID-19. This may be related to social determinants that lead to chronic inflammatory states. The aims of the study were to determine if there are racial/ethnic disparities with inflammatory markers and association of methylprednisolone to in hospital survival.
METHODS
This was a secondary analysis of a retrospective cohort study of patients ≥ 18 years of age and admitted for severe COVID-19 pneumonia between March and June 2020 in 13 Hospitals in New Jersey, United States. Patients who received other formulation of corticosteroids were not included. Area under the receiver operating characteristics curves were performed to test for discriminatory ability of each inflammatory makers. Univariate and multivariate Cox regression assessed the association of variables to in hospital survival.
RESULTS
Propensity matched sample (n = 759) between no methylprednisolone (n = 380) and methylprednisolone (n = 379) had 338 Whites, 102 Blacks, 61 Asian/Indians, and 251 non-Black non-White Hispanics. Compared to CRP, area under receiving operating characteristic curve for d-dimer in Hispanics (0.742) was statistically different (DeLong Test P = 0.0041). Multivariate cox regression showed that different variables in Blacks [age ≥ 60 years (HR = 3.71, P = 0.0281), mechanical ventilation (HR = 5.07, P = 0.0281) and creatinine ≥ 1.5 mg/dL (HR = 3.61, P = 0.0007)], Whites [cancer (HR = 1.68, P = 0.0213), qSOFA score of 1 (HR = 1.81, P = 0.0213), qSOFA score of 2 (HR = 5.16, P < 0.0001), qSOFA score of 3 (HR = 11.81, P < 0.0001) and creatinine ≥ 1.5 mg/dL (HR = 2.16, P = 0.0006)], Hispanics [hypertension (HR = 2.52, P = 0.0007), cancer (HR = 2.99, P = 0.0244 and D-dimer ≥ 2 mcg/mL (HR = 2.22, P = 0.0077)], and Asian/Indians [ chronic kidney disease (HR = 6.36, P = 0.0031) and CRP > 20 mg/L (HR = 5.02, P = 0.0032)] were statistically significant for mortality. Low dose and high dose methylprednisolone were significantly associated with prolonged survival in Whites [low dose (HR = 0.37, P < 0.0001) and high dose (HR = 0.48, P < 0.0183)] and Asian/Indians [low dose (HR = 0.13, P = 0.0101) and high dose (HR = 0.15, P = 0.01)]. However, high dose was not associated with improved survival compared to low dose. Methylprednisolone was not associated with prolonged survival in Blacks and Hispanics.
CONCLUSION
Racial/Ethnic disparities with inflammatory markers preclude the use of one marker as a predictor of survival. Methylprednisolone is associated with prolonged survival in Asian/Indians and Whites.
Topics: Ethnicity; Humans; Inflammation; Methylprednisolone; Middle Aged; Retrospective Studies; United States; COVID-19 Drug Treatment
PubMed: 35287602
DOI: 10.1186/s12879-022-07237-1 -
The Annals of Thoracic Surgery Jun 2022Neurodevelopmental impairment is an important consequence for survivors of surgery for critical congenital heart disease. This study sought to determine whether... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Neurodevelopmental impairment is an important consequence for survivors of surgery for critical congenital heart disease. This study sought to determine whether intraoperative methylprednisolone during neonatal cardiac surgery is associated with neurodevelopmental outcomes at 12 months of age and to identify early prognostic variables associated with neurodevelopmental outcomes.
METHODS
We performed a planned secondary analysis of a 2-center, double-blind, randomized, placebo-controlled trial of intraoperative methylprednisolone in neonates undergoing cardiac surgery. A brain injury biomarker was measured during surgery. Bayley Scales of Infant and Toddler Development-III (BSID-III) were performed at 12 months of age. Two-sample t tests and generalized linear models were used.
RESULTS
There were 129 participants (n = 61 methylprednisolone; n = 68 placebo). There were no significant differences in BSID-III scores and brain injury biomarker levels between treatment groups. Participants who underwent a palliative (versus corrective) procedure had lower mean BSID-III cognitive (101 ± 15 versus 106 ± 14; P = .03) and motor scores (85 ± 18 versus 94 ± 16; P < .01). Longer ventilation time was associated with lower motor scores. Longer cardiac intensive care unit stay was associated with lower cognitive, language, and motor scores. Cardiopulmonary bypass time, aortic cross-clamp time, and deep hypothermic circulatory arrest were not associated with BSID-III scores.
CONCLUSIONS
Neurodevelopmental outcomes were not associated with intraoperative methylprednisolone or intraoperative variables. Participants who underwent a neonatal palliative (versus corrective) procedure had longer cardiac intensive care unit stays and worse neurodevelopmental outcomes at 1 year. This work suggests that interventions focused solely on the operative period may not be associated with a long-term neurodevelopmental benefit.
Topics: Biomarkers; Brain Injuries; Cardiac Surgical Procedures; Humans; Infant; Infant, Newborn; Methylprednisolone; Neurodevelopmental Disorders; Prognosis
PubMed: 33864754
DOI: 10.1016/j.athoracsur.2021.04.006 -
BMC Infectious Diseases May 2023The preferred agent of glucocorticoids in the treatment of patients with severe COVID-19 is still controversial. This study aimed to compare the efficacy and safety of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The preferred agent of glucocorticoids in the treatment of patients with severe COVID-19 is still controversial. This study aimed to compare the efficacy and safety of methylprednisolone and dexamethasone in the treatment of patients with severe COVID-19.
METHODS
By searching the electronic literature database including PubMed, Cochrane Central Register of Controlled Trials, and Web of Science, the clinical studies comparing methylprednisolone and dexamethasone in the treatment of severe COVID-19 were selected according to the inclusion criteria and exclusion criteria. Relevant data were extracted and literature quality was assessed. The primary outcome was short-term mortality. The secondary outcomes were the rates of ICU admission and mechanical ventilation, PaO/FiO ratio, plasma levels of C-reactive protein (CRP), ferritin, and neutrophil/lymphocyte ratio, hospital stay, and the incidence of severe adverse events. Statistical pooling applied the fixed or random effects model and reported as risk ratio (RR) or mean difference (MD) with the corresponding 95% confidence interval (CI). Meta-analysis was performed using Review Manager 5.1.0.
RESULTS
Twelve clinical studies were eligible, including three randomized controlled trials (RCTs) and nine non-RCTs. A total of 2506 patients with COVID-19 were analyzed, of which 1242 (49.6%) received methylprednisolone and 1264 (50.4%) received dexamethasone treatment. In general, the heterogeneity across studies was significant, and the equivalent doses of methylprednisolone were higher than that of dexamethasone. Our meta-analysis showed that methylprednisolone treatment in severe COVID-19 patients was related to significantly reduced plasma ferritin and neutrophil/lymphocyte ratio compared with dexamethasone, and that no significant difference in other clinical outcomes between the two groups was found. However, subgroup analyses of RCTs demonstrated that methylprednisolone treatment was associated with reduced short-term mortality, and decreased CRP level compared with dexamethasone. Moreover, subgroup analyses observed that severe COVID-19 patients treated with a moderate dose (2 mg/kg/day) of methylprednisolone were related to a better prognosis than those treated with dexamethasone.
CONCLUSIONS
This study showed that compared with dexamethasone, methylprednisolone could reduce the systemic inflammatory response in severe COVID-19, and its effect was equivalent to that of dexamethasone on other clinical outcomes. It should be noted that the equivalent dose of methylprednisolone used was higher. Based on the evidence of subgroup analyses of RCTs, methylprednisolone, preferably at a moderate dose, has an advantage over dexamethasone in the treatment of patients with severe COVID-19.
Topics: Humans; Glucocorticoids; Methylprednisolone; COVID-19; COVID-19 Drug Treatment; Dexamethasone
PubMed: 37147596
DOI: 10.1186/s12879-023-08280-2 -
The American Journal of Sports Medicine Jul 2023The chondrotoxic effects of methylprednisolone acetate (MP) and triamcinolone acetonide (TA) have been well described. However, the mechanical effects of these commonly...
BACKGROUND
The chondrotoxic effects of methylprednisolone acetate (MP) and triamcinolone acetonide (TA) have been well described. However, the mechanical effects of these commonly used steroids on native cartilage are largely unknown.
PURPOSE
To investigate the in vitro effects of a single 1-hour MP or TA exposure on the viability, mechanics, and biochemical content of native articular cartilage explants.
STUDY DESIGN
Controlled laboratory study.
METHODS
Articular cartilage explants (n = 6 per group) were harvested from the femoral condyles of bovine stifles. Explants were exposed to chondrogenic medium containing a clinical dose of MP or TA for 1 hour, followed by fresh medium wash and exchange. Explants in the control group underwent the same treatment with chondrogenic medium alone. At 24 hours after treatment, samples were assessed for viability (live/dead), mechanical properties (creep indentation and Instron tensile testing), biochemical (collagen and glycosaminoglycan) content, and pyridinoline crosslinking via mass spectrometry.
RESULTS
Mean cell viability was significantly decreased in native explants exposed to MP (35.5%) compared with the control (49.8%; < .001) and TA (45.7%; = .01) specimens. Significant decreases were seen in the mechanical properties of steroid-treated native explants when compared with controls, with decreases in aggregate modulus (646.3 vs 312.8 kPa [MP] and 257.0 kPa [TA]; < .001), shear modulus (370.1 vs 191.2 kPa [MP] and 157.4 kPa [TA]; < .001), and ultimate tensile strength (9.650 vs 5.648 MPa [MP; = .021] and 6.065 MPa [TA; = .0403]). No significant differences in collagen and glycosaminoglycan content were found in the steroid-treated groups. Pyridinoline crosslinking was significantly decreased in explants exposed to TA compared with controls ( = .027).
CONCLUSION
Exposure of MP to articular cartilage explants was chondrotoxic, and exposure of articular cartilage explants to MP or TA resulted in significant decreases in mechanical properties of articular cartilage explants compared with controls. Clinicians should be judicious regarding use of intra-articular steroids, particularly in patients with intact healthy articular cartilage.
Topics: Humans; Animals; Cattle; Methylprednisolone; Triamcinolone; Cartilage, Articular; Triamcinolone Acetonide; Methylprednisolone Acetate; Glycosaminoglycans
PubMed: 37183987
DOI: 10.1177/03635465231162644 -
Kidney360 Sep 2023The contribution of IV methylprednisolone to glucocorticoid toxicity is often overlooked with limited evidence supporting its use. Markedly reduced cumulative...
KEY POINTS
The contribution of IV methylprednisolone to glucocorticoid toxicity is often overlooked with limited evidence supporting its use. Markedly reduced cumulative glucocorticoid dosing for remission induction therapy in AAV is safe and effective. Reduced IV methylprednisolone and radical steroid avoidance strategies have not been shown to have any significant adverse effect on outcomes.
BACKGROUND
Glucocorticoids (GCs) remain integral to the management of ANCA-associated vasculitis (AAV), but are associated with significant adverse effects. Recent studies have shown reduced oral GC dosing to be safe and effective; however, data guiding the use of intravenous (IV) methylprednisolone (MTP) are limited.
METHOD
A single-center retrospective cohort of patients with AAV were divided into two groups: low-dose GC (patients receiving 250 mg of IV MTP, followed by a tapering course of 30 mg of prednisolone daily) versus high-dose GC (1.5 g of IV MTP, followed by a tapering course of 40–60 mg of prednisolone daily). Primary outcomes included ESKD and mortality, and secondary outcomes included GC-related toxicity, remission, and relapse rates. This study was applied to patients with newly diagnosed AAV, including those with severe or life-threatening disease.
RESULTS
Sixty-five patients were included in the final analysis—34 in the high-dose treatment group and 31 in the low-dose treatment group. At diagnosis, more advanced renal impairment and histological disease were present in the low-dose cohort. The rate of ESKD was similar between the groups at 6 and 12 months ( = 0.22, = 0.60, respectively). More deaths occurred in the high-dose group (26.5% versus 6.5%, = 0.05), although this was not significant on multivariable analysis ( = 0.06). Remission rates were comparable, and there was no significant difference in relapses. Adverse events were seen in both groups, but patients in the high-dose group experienced a higher incidence of severe infections, weight gain, and steroid-induced diabetes.
CONCLUSION
We demonstrate that a markedly reduced dose of IV MTP with a lower overall cumulative dose of GCs is safe and effective in the management of severe AAV disease, with no significant difference in primary outcomes.
Topics: Humans; Methylprednisolone; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Immunosuppressive Agents; Remission Induction
PubMed: 37668468
DOI: 10.34067/KID.0000000000000222