Administration Of High-dose Corticosteroids Research Articles

Effect of high-dose corticosteroids on the incidence of deep vein thrombosis after total hip replacement

Fifty patients receiving uncemented total hip prostheses were examined by venography of the legs on the 2nd postoperative day. The patients were randomly divided into two groups, a non-steroid group (n = 26) and a steroid group (n = 24). Both groups received dextran thrombo-prophylaxis. The patients in the steroid group were treated with high-dose corticosteroids. The incidence of deep vein thrombosis (DVT) was 38% (19/50). No patients had clinical signs or symptoms of DVT. All thrombi were located distally in the leg. DVT was bilateral in nine patients, in the operated leg in three, and in the non-operated leg in seven. The administration of high-dose corticosteroids did not influence the incidence or pattern of DVT. All patients were followed up clinically and plethysmographically up to 12 months after surgery. Distally located asymptomatic DVT were not given specific treatment. The postoperative course was uneventful except for one patient in each group who developed clinically, apparent DVT more than 3 weeks after operation, although the initial venographic studies were normal.

Alterations in gastrointestinal motility during postoperative acute corticosteroid withdrawal

Patients receiving exogenous corticosteroids may develop iatrogenic adrenal insufficiency, with resultant nausea, emesis, and abdominal distension if perioperative “stress steroid” dosages are inadequate. To investigate these gastrointestinal disturbances, motility measurements were obtained using perfused catheters in 10 dogs before steroid treatment (control), during administration of high-dose corticosteroids, and daily during 5 days of abrupt withdrawal. Withdrawal was characterized by a significant disruption in normal antral, duodenal, and jejunal motility with a prolongation of the migrating motor complex (MMC) and phases I and II, but not III (I = quiescence, II = irregular activity, and III = regular activity). Retrograde giant contractions (RGCs), giant migrating contractions (GMCs), and/or “intestinal fibrillation” were also observed during the first two withdrawal days. Adrenal weights and morphology did not change. We conclude: (1) high-dose corticosteroids can induce profound adrenal suppression in dogs without morphologic changes within 3 weeks; (2) high-dose steroid administration enhances gastrointestinal motility; and (3) acute withdrawal causes disappearance or shortening of MMC and the development of RGCs and GMCs with associated emesis.

CORTICOSTEROID INHIBITION OF THE OKT3-INDUCED CYTOKINE-RELATED SYNDROME

The data presented extend to a larger series of 27 consecutive renal allograft recipients treated prophylactically with OKT3 our previous observation that the acute OKT3-induced clinical syndrome is related to massive release in the circulation of some cytokines, among which are tumor necrosis factor and interferon gamma. In addition, a pilot randomized study was set up including 12 consecutive patients receiving high-dose corticosteroid treatment (0.5 g solumedrol) either before or at the same time as the first OKT3 injection. Results confirm that when corticosteroids are given in sufficient amount and, importantly, 1 hr before the first OKT3 injection, they significantly decrease the release of both tumor necrosis factor and interferon gamma. In addition, the pretreatment with corticosteroids may totally abolish the IL-2 release induced by OKT3. Given the key role the massive although transient cytokine release plays in determining the OKT3-induced acute syndrome, these results provide the biological basis supporting a precise kinetics of administration of high-dose corticosteroids to better decrease the severity of the clinical reaction.

ADULT RESPIRATORY DISTRESS SYNDROME: AN UNRECOGNIZED PREMORTEM EVENT IN SYSTEMIC LUPUS ERYTHEMATOSUS

A retrospective study of the medical records of 46 patients, comprising our SLE population over a 6-year period, noted that mortality (7 of 46:15.2%) was directly related to the adult respiratory distress syndrome. In five, a concomitant severe infection was detected. Overall, 17 of our 46 patients presented with infectious episodes. The only statistically significant factor predisposing to both infection and the adult respiratory distress syndrome was high dose corticosteroid administration. Our results suggest that adult respiratory distress syndrome is a clinical condition related to the death of lupus patients and commonly complicates infection.

Early Administration of Corticosteroids in Emergency Room Treatment of Acute Asthma

To determine the effect of early administration of high-dose intravenous corticosteroids on duration of emergency room treatment and hospital admission rate in patients with acute asthma. Randomized, double-blind, placebo-controlled trial. The emergency room of a large, urban hospital with primary and referral care responsibilities. Eighty-one patients from 18 to 45 years of age with acute bronchial asthma and without pneumonitis or other serious underlying illnesses were studied on 91 occasions and were randomly assigned to control or experimental groups. The steroid group received 125 mg of intravenous methylprednisolone whereas the control group received intravenous normal saline 30 minutes after initial treatment. Additional treatment included aerosolized metaproterenol and oral theophylline therapy. Six hours after study entry, remaining patients were treated with 40 mg of intravenous methylprednisolone. Hospitalization was mandatory if total treatment time was greater than 12 hours. Age, sex, peak expiratory flow at entry, and prevalence of recent corticosteroids use were similar in both groups. Duration of emergency room treatment was 6.7 +/- 4.2 (SD) hours in the steroid group and 6.3 +/- 4.1 hours in the control group (P = 0.66). Hospitalization was necessary in 18% (95% CI, 7% to 30%) of the steroid group and in 13% (CI, 3% to 22%) of the control group. Frequency of return visits for acute asthma 2 days after emergency room discharge was 11% (CI, -1% to 22%) in the steroid group and 13% (CI, 2% to 23%) in the control group. These results fail to show any benefit for early administration of corticosteroids in patients with acute asthma. Routine administration of corticosteroids on initial presentation in such patients may not be warranted.

Optic nerve decompression via the lateral facial approach

Two cases of visual loss after lateral orbital wall fracture are presented: one with retrobulbar hematoma and evidence of optic nerve compression who failed to respond to lateral canthotomy and high-dose corticosteroid administration, and the second with immediate, total blindness associated with fracture of the bony optic canal. In both, extradural decompression of the orbit and optic nerve was achieved through the lateral facial approach with partial return of visual acuity and without surgical complications. The role of orbital and optic nerve decompression in the management of patients with blindness following orbital trauma is controversial. Orbital decompression may be of value for cases of post-traumatic visual loss unresponsive to medical management. If optic nerve injury is suspected as the cause, the additional step of decompression of the optic nerve is a logical but unproven procedure. The indications for optic nerve decompression are not established and should be considered only within the context of the specific needs of the individual patient.

Severe cardiovascular adverse effects in association with acute, high-dose corticosteroid administration.

Severe cardiovascular adverse reactions including death have been associated with high-dose intravenous corticosteroid therapy. Some of the patients appeared to have acute hypersensitivity reactions to the corticosteroid, with rashes and bronchospasm; other problems included arrhythmias and myocardial infarctions. Most of the patients had underlying renal disease and/or were undergoing renal transplantation. All of the patients having the cardiovascular reactions associated with the corticosteroid received individual doses of at least 250 mg of methylprednisolone or its equivalent. The doses were usually administered over a 30-minute period or less. A cause-effect relationship between high-dose corticosteroid therapy and severe cardiovascular reactions has not been scientifically proved by a controlled trial, but caution is advised when high-dose corticosteroid therapy is administered.

OKT3 SALVAGE THERAPY IN A QUADRUPLE IMMUNO SUPPRESSIVE PROTOCOL IN CADAVERIC RENAL TRANSPLANTATION

Since the introduction of OKT3 at our center in January 1986, we have performed 246 cadaveric renal transplants (220 primary, 26 nonprimary). All patients received quadruple immunosuppression consisting of prednisone, azathioprine, and the sequential use of Minnesota antilymphoblast globulin (MALG) and cyclosporine. OKT3 (Orthoclone OKT3) therapy was reserved for corticosteroid- and/or ALG-resistant rejection. Of the 246 patients, 138 developed one or more rejection episodes (56.1%). Ninety-seven (70.3%) were successfully reversed with prednisone and/or ALG, whereas 41 (29.7%) required additional treatment with OKT3. Initial graft salvage occurred in 34 (82.9%) patients treated with OKT3, but rejection recurred in 18 (52.9%) and was successfully reversed in only 6 patients. However, the rate of recurrent rejection was much lower in patients given OKT3 early (14%), shortly after it was apparent that high-dose corticosteroid therapy was proving ineffective, than in patients who received OKT3 after a prolonged or second course of corticosteroids (64%) or ALG (60%). Graft survival after a mean follow-up interval of 11 months in all OKT3-treated patients was 54%. One or more infections occurred in 19 (46%) patients treated with OKT3. Patients developing infections following OKT3 therapy received significantly larger total doses of prednisone during graft rejection (46.3 mg/kg vs. 27.9 mg/kg, P less than .05) than OKT3-treated patients who did not develop infectious complications. Our experience shows that use of OKT3 for treatment of corticosteroid- and/or ALG-resistant rejection is associated with a high rate of recurrent rejection, except when given early, as soon as it is clear that high-dose corticosteroid therapy is not reversing the rejection episode. It further suggests that prolonged administration of high-dose corticosteroids and possibly ALG for the treatment of rejection prior to beginning OKT3 greatly increases the rate of infection following OKT3 therapy.

Hepatomegaly following short-term high-dose steroid therapy.

Children treated with large doses of corticosteroids were found to develop hepatomegaly within a few days. No relationship could be established between the condition for which steroids were given and the liver enlargement. Liver biopsy was thought to be indicated, and thus was performed in three children because of diagnostic uncertainty. The light and electron microscopic examinations revealed normal liver architecture, without edema, sinusoid engorgement, or inflammatory changes. The hepatocytes were distended by increased amounts of glycogen. In a pattern reminiscent of some glycogen storage diseases, mitochondria and other cytosol components were displaced toward the cell membrane or around the nucleus, which occasionally contained glycogen. Moderate sinusoidal compression, interhepatocytic free glycogen particles, and mild increase in lipid droplets were also found. It is concluded that the hepatomegaly noted in patients given short-term, high-dosage steroid therapy is due to excessive glycogen accumulation within parenchymal cells. This finding is in accordance with observations in animals, as well as with biochemical studies demonstrating hepatocytic glycogen deposition after steroid therapy. Being benign and reversible, early hepatomegaly following administration of high-dose corticosteroids should not influence the initial therapeutic plan required by the basic disease.

Invasive aspergillosis in renal transplant recipients: correlation with corticosteroid therapy.

During a 31-month period in 1979-1981, nine patients at a renal transplant center in Tennessee developed invasive infections with Aspergillus species. Despite an extensive search, no common environmental source of contamination was found. A matched case-control study of host risk factors showed that leukopenia, prior administration of antibiotics, and treatment with azathioprine and antilymphocyte serum were not significantly related to the development of aspergillosis. In contrast, the administration of high-dose corticosteroids posed a significant risk. An average daily dose of greater than or equal to 1.25 mg of prednisone/kg per day for the entire interval studied was the best predictor of subsequent invasive infection with Aspergillus.

Noncardiogenic Pulmonary Edema and Peripheral Vascular Collapse following Cardiopulmonary Bypass

Four instances of severe anaphylactoid reaction occurring subsequent to cardiopulmonary bypass are described. These catastrophic reactions, from which 2 patients died, took place approximately an hour following administration of protamine and were characterized by marked peripheral vasodilatation, loss of capillary membrane integrity, and fulminant noncardiogenic pulmonary edema. Primary cardiac depression was not evident. We hypothesize that protamine was the causative agent in these unusually severe reactions. Differential diagnosis from other causes of acute cardiorespiratory dysfunction depended on early assessment of pulmonary artery and left ventricular filling pressures, cardiac output, respiratory mechanics, and arterial blood gases. Therapy was difficult; success in 1 of the patients seemed to have been effected in part by prompt administration of high-dose corticosteroids and maintenance of peripheral vascular tone with an alpha-adrenergic agonist.

Noncardiogenic Pulmonary Edema and Peripheral Vascular Collapse Following Cardiopulmonary Bypass: Rare Protamine Reaction?

Four instances of severe anaphylactoid reaction occurring subsequent to cardiopulmonary bypass are described. These catastrophic reactions, from which 2 patients died, took place approximately an hour following administration of protamine and were characterized by marked peripheral vasodilatation, loss of capillary membrane integrity, and fulminant noncardiogenic pulmonary edema. Primary cardiac depression was not evident. We hypothesize that protamine was the causative agent in these unusually severe reactions. Differential diagnosis from other causes of acute cardiorespiratory dysfunction depended on early assessment of pulmonary artery and left ventricular filling pressures, cardiac output, respiratory mechanics, and arterial blood gases. Therapy was difficult; success in 1 of the patients seemed to have been effected in part by prompt administration of high-dose corticosteroids and maintenance of peripheral vascular tone with an alpha-adrenergic agonist.

Hormone Treatment of Breast Cancer

Alteration of the hormonal milieu is still one of the major and most successful methods for treating advanced breast cancer. With the exception of the use of thyroid hormone in conjunction with corticosteroids, we are not aware of any proved advantageous combination of hormonal agents that improves the objective regression rates in advanced breast cancer.

A case of severe repeated immunological reactions to intermittent rifampicin treatment

A case is reported in which a 36-year-old patient twice suffered a rapidly-developing severe reaction to intermittent rifampicin therapy. The symptoms were upper abdominal and back pain, nausea and shivering. Acute renal failure, thrombocytopenia, jaundice and haemolytic anaemia also developed. Aetiologically this was due to an immunopathological effect. This case was unusual in that all the previously observed reactions to rifampicin of an immunological aetiology occurred together, resulting in a marked leucocytosis with the presence of immature cells. It appears that the immediate administration of high-dose corticosteroids can favourably influence this condition. We consider that despite its greater risks daily treatment with rifampicin is to be preferred to discontinuous therapy because of its better tuberculostatic effect.