Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study. The perioperative use of corticosteroids and bupivacaine in the management of lumbar disc disease. 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. High-dose methylprednisolone prevents extensive sick leave after whiplash injury. A prospective, randomized, double-blind study. Early complications of high-dose methylprednisolone sodium succinate treatment in the follow-up of acute cervical spinal cord injury.
To compare the efficacy of methylprednisolone administered for 24 hours with methyprednisolone administered for 48 hours or tirilazad mesylate administered for 48 hours in patients with acute spinal cord injury.
                Double-blind, randomized clinical trial.
                Sixteen acute spinal cord injury centers in North America.
                A total of 499 patients with acute spinal cord injury diagnosed in National Acute Spinal Cord Injury Study (NASCIS) centers within 8 hours of injury.
                All patients received an intravenous bolus of methylprednisolone (30 mg/kg) before randomization. Patients in the 24-hour regimen group (n=166) received a methylprednisolone infusion of 5.4 mg/kg per hour for 24 hours, those in the 48-hour regimen group (n=167) received a methylprednisolone infusion of 5.4 mg/kg per hour for 48 hours, and those in the tirilazad group (n=166) received a 2.5 mg/kg bolus infusion of tirilazad mesylate every 6 hours for 48 hours.
                Motor function change between initial presentation and at 6 weeks and 6 months after injury, and change in Functional Independence Measure (FIM) assessed at 6 weeks and 6 months.
                Compared with patients treated with methylprednisolone for 24 hours, those treated with methylprednisolone for 48 hours showed improved motor recovery at 6 weeks (P=.09) and 6 months (P=.07) after injury. The effect of the 48-hour methylprednisolone regimen was significant at 6 weeks (P=.04) and 6 months (P=.01) among patients whose therapy was initiated 3 to 8 hours after injury. Patients who received the 48-hour regimen and who started treatment at 3 to 8 hours were more likely to improve 1 full neurologic grade (P=.03) at 6 months, to show more improvement in 6-month FIM (P=.08), and to have more severe sepsis and severe pneumonia than patients in the 24-hour methylprednisolone group and the tirilazad group, but other complications and mortality (P=.97) were similar. Patients treated with tirilazad for 48 hours showed motor recovery rates equivalent to patients who received methylprednisolone for 24 hours.
                Patients with acute spinal cord injury who receive methylprednisolone within 3 hours of injury should be maintained on the treatment regimen for 24 hours. When methylprednisolone is initiated 3 to 8 hours after injury, patients should be maintained on steroid therapy for 48 hours. The introduction of microdiscectomy to lumbar spine surgery has resulted in a significant decrease in postoperative pain and length of hospital stay. Intraoperative application of long-acting local anesthetic agents has been used for many general and neurosurgical procedures for the management of postoperative pain. In addition, many surgeons routinely use intraoperative corticosteroids during lumbar discectomy to reduce traumatic nerve root inflammation. However, the efficacy of intraoperative long-acting local anesthetic agents and corticosteroids for reduction of postoperative discomfort has not been reported for lumbar discectomy. This study evaluated 32 patients at a university-based Veterans Administration hospital undergoing lumbar microdiscectomy. All 32 patients presented with radicular symptoms and had radiographic confirmation of a herniated nucleus pulposus. These patients were divided into three groups. Group 1 (12 patients) received 160 mg intramuscular Depo-Medrol (methylprednisolone acetate) and 250 mg intravenous Solu-Medrol (methyl-prednisolone sodium succinate) at the start of the operation. A macerated fat graft soaked in 80 mg Depo-Medrol was placed over the affected nerve root following discectomy. In addition, 30 ml of 0.25% bupivacaine was infiltrated into the paraspinal musculature at skin incision and during closure. Group 2 (10 patients) received 30 ml of 0.25% bupivacaine infiltrated into the paraspinal musculature at skin incision and at closure. In this group of patients, a saline-soaked fat graft was placed over the affected nerve root. Group 3 (10 patients) acted as a control group, undergoing lumbar microdiscectomy without corticosteroids or bupivacaine. Patients receiving bupivacaine and corticosteroids (Group 1) had a statistically significantly shorter hospital stay (1.4 days) compared to the control group (4.0 days) (p = 0.0004, Mann-Whitney U-test). Patients in Group 1 required less postoperative narcotic analgesia than the other groups. Finally, a larger percentage of patients in Group 1 reported complete relief of back and radicular pain on postoperative Day 1 compared to other groups. Postoperative complications and functional outcome were not different between the groups. These results indicate that the combination of long-acting anesthetic agents and corticosteroids can reduce postoperative discomfort and subsequently the length of postoperative hospital stay. 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. A prospective, randomized, double-blind study comparing high-dose methylprednisolone with placebo.
                To evaluate the efficacy of high-dose methylprednisolone when administered within 8 hours after whiplash injury.
                Whiplash injury often results in chronic symptoms. The management of whiplash injuries is controversial, and pharmacologic therapy has received little evaluation. In recent reports, dysfunction of the central nervous system has been indicated in several cases. Methylprednisolone administered within 8 hours after the injury to patients with acute spinal cord injury has been demonstrated to improve the outcome. This procedure was also adopted in a randomized study of cases of whiplash injury in car accidents.
                Forty patients, 22 men and 18 women with a mean age of 35 years (range, 19-65), were included in the study, 20 in each of two groups. They were treated for whiplash injury, which they had sustained in car accidents. The patients were enrolled if their diagnoses were complete and treatment had begun within 8 hours after injury. Disabling symptoms severe enough to prevent the patient from returning to work, number of sick days before and after injury, and sick-leave profile after injury were used as parameters for the evaluation of the effects of the treatment. Baseline demographic data were controlled for when statistical analysis had been performed.
                At the follow-up examination 6 months after initial treatment, there was a significant difference in disabling symptoms between the actively treated patients and the placebo group (P = 0.047), total number of sick days (P = 0.01), and sick-leave profile (P = 0.003).
                The results of this study indicate that acute treatment with high-dose methylprednisolone may be beneficial in preventing extensive sick leave after whiplash injury. However, the number of patients studied was small, and therefore further prospective, controlled studies are needed. A prospective, randomized, and double-blind study comparing high-dose methylprednisolone sodium succinate (MPSS) with placebo, in the treatment of patients with acute cervical spinal cord injury.
                To evaluate the complications of high-dose MPSS in patients with acute cervical spinal cord injury when administered within 8 hours of injury.
                High-dose therapy with MPSS has been demonstrated to improve the recovery of motor function in patients with acute cervical spinal cord injury. However, little is known about the follow-up complications.
                Forty-six patients, 42 men and 4 women (mean age, 60.6 years; range, 18-84), were included in the study: 23 in the MPSS group and 23 in the placebo group. They were treated without surgery for spinal cord injury in the cervical spine, and were enrolled in the trial if a diagnosis had been made and treatment had begun within 8 hours. Complications of high-dose therapy with MPSS were compared with placebo treatment throughout the study period and up to 2 months after injury.
                The MPSS group had 13 patients (56.5%) with complications, whereas the placebo group had 8 (34.8%). The difference between the two groups was not statistically significant (P = 0.139). There were eight instances of pulmonary complication with MPSS (34.8%) and one instance (4.34%) with placebo (P = 0.009). There were four instances of gastrointestinal complication (17.4%) with MPSS and none with placebo (P = 0.036). Pulmonary (complications were more prevalent in patients aged more than 60 years (P = 0.029).
                Aged patients with cervical spinal injury may be more likely to have pulmonary side effects (P = 0.029) after high-dose therapy with MPSS and thus deserve special care.