Ketorolac for sickle cell vaso-occlusive crisis pain in the emergency department: lack of a narcotic-sparing effect. Transcutaneous electrical nerve stimulation treatment of sickle cell pain crises. High-dose intravenous methylprednisolone therapy for pain in children and adolescents with sickle cell disease. Randomised trial of oral morphine for painful episodes of sickle-cell disease in children. Butorphanol versus morphine: equally ineffective when given incorrectly. Effect of ketorolac in pediatric sickle cell vaso-occlusive pain crisis. Enhancement of pain control with ketorolac tromethamine in patients with sickle cell vaso-occlusive crisis.
To determine if a single dose of intramuscular ketorolac given on presentation to the emergency department has a narcotic-sparing effect in adult patients with sickle cell vaso-occlusive crisis pain.
                A prospective, randomized, single-dose, double-blind study.
                ED of a university hospital and an affiliated county hospital.
                Eighteen adult patients who presented to the ED with sickle cell crisis pain a total of 24 times.
                Patients were randomized to receive either ketorolac 60 mg IM or placebo on presentation to the ED. Subjects were administered meperidine on presentation and then received a standardized dose of meperidine every 30 minutes during the four-hour observation period based on the severity of pain.
                The 12 subjects in the ketorolac group received an average of 231 +/- 92 mg meperidine, whereas the 12 subjects in the placebo group received an average meperidine dose of 250 +/- 85 mg (P = .61).
                The use of intramuscular ketorolac did not lead to a clinically significant reduction in the requirement for narcotics during the four-hour ED treatment period. Transcutaneous electrical nerve stimulation (TENS) has been used in a variety of acute and chronic painful conditions, but has not been studied in sickle cell pain crises. We compared TENS versus placebo in a randomized, double-blind, cross-over study involving 60 trials in 4 crisis severity categories. TENS electrodes were applied to the area of severest pain and patients' pain ratings and medication usage were evaluated over a 4-hour period. Pain ratings and analgesic requirements at 1 and 4 h from onset of study were similar in the TENS and placebo groups. Patients assessments of overall treatment efficacy indicated that TENS was more frequently helpful, but there was a substantial placebo effect. Although the value of TENS in this condition was not established in this study, further trials, using varied stimulation parameters, are warranted. The management of episodes of severe pain in patients with sickle cell disease is a difficult clinical problem. We studied 36 children and adolescents with sickle cell disease who had 56 acute episodes of severe pain (44 in 27 patients with sickle cell anemia, 8 in 7 patients with sickle cell-hemoglobin C disease, and 4 in 2 patients with sickle cell-beta (+)-thalassemia). The patients were randomly assigned in double-blind fashion to receive an intravenous infusion of either saline placebo or high-dose methylprednisolone (15 mg per kilogram of body weight, to a maximum of 1000 mg) on their admission to the hospital and again 24 hours later. All the patients received intravenous morphine sulfate until severe pain abated and were then given acetaminophen with codeine.
                For all episodes of pain, the duration of inpatient analgesic therapy (intravenous and oral) was significantly shorter for the patients who received methylprednisolone than for those given placebo (mean, 41.3 vs 71.3 hours; P = 0.030). The difference was still significant (31.0 vs. 62.5 hours; P = 0.010) when we excluded seven episodes that were complicated by the chest syndrome (three in the methylprednisolone group and four in the placebo group). The patients who received methylprednisolone had recurrent episodes of pain shortly after the discontinuation of therapy more often than did the patients receiving placebo. No adverse effects of methylprednisolone were observed.
                A short course of high-dose methylprednisolone decreased the duration of severe pain in children and adolescents with sickle cell disease, but patients who received methylprednisolone had more rebound attacks after therapy was discontinued. On balance, corticosteroids are promising as an adjunct to supportive therapy for painful episodes in children and adolescents with sickle cell disease. Oral controlled-release morphine can provide effective analgesia through a non-invasive route and may facilitate outpatient management of severe episodes of sickle-cell pain. We compared the clinical efficacy and safety of oral morphine with continuous intravenous morphine in children with severe episodes of sickle-cell pain, by a double-blind, randomised, parallel-group design.
                56 children aged 5-17 years received loading doses of intravenous morphine of up to 0.15 mg/kg, followed by randomly assigned oral morphine 1.9 mg/kg every 12 h plus intravenous placebo (saline), or intravenous morphine 0.04 mg kg-1 h-1, plus placebo tablet. Breakthrough pain was treated with oral, immediate-release morphine 0.4 mg/kg every 2-3 h as required. Pain was assessed daily at 0900 h, 1300 h, 1700 h, and 2100 h with a picture face scale, a pictorial scale (Oucher), a behavioural-observational scale (CHEOPS), and by an investigator.
                50 children completed the study (28 boys, 22 girls; mean age 11.2 years [SD 3.5]; mean oral morphine dose 2.99 mg/kg daily [0.75]; mean intravenous morphine dose, 0.81 mg/kg daily [0.30]). Mean overall pain scores were similar for oral and intravenous morphine (CHEOPS, 6.3 [1.5] vs 6.4 [1.4], p = 0.8; Oucher, 31.5 [25.4] vs 39.2 [21.7], p = 0.3; Faces, 2.2 [1.4] vs 2.4 [1.3], p = 0.6; clinical rating, 1.7 [0.7] vs 1.9 [0.5], p = 0.3). Opioid analgesia was required for a mean of 4.2 days (1.7) and 5.4 days (2.6), respectively (p = 0.0591). Pain scores from all scales correlated significantly (r = 0.5865-0.8980, p = 0.0001). Frequency of rescue analgesia did not differ significantly between the oral and intravenous morphine groups (0.7 [0.8] vs 0.9 [0.7] doses daily, p = 0.2). Frequency and severity of adverse events did not differ significantly.
                Oral, controlled-release morphine is a reliable, non-invasive alternative to continuous intravenous morphine for the management of painful episodes of sickle-cell disease in children. nan Ketorolac is a parenteral, nonsteroidal analgesic that does not have a narcotic's risks of respiratory depression, hypotension, or dependence. Its usefulness in providing pain relief in pediatric patients with acute vaso-occlusive crisis of sickle cell disease has not been studied to date.
                Twenty-nine patients with sickle cell disease between the ages of 5 and 18 years who presented to The Children's Hospital of Alabama emergency department (ED) with 41 distinct episodes of acute vaso-occlusive pain crisis were enrolled prospectively and randomized to receive either 0.9 mg/kg intravenous (IV) ketorolac or placebo in a double-blind fashion. All patients also received IV fluids and an initial 0.1 mg/kg of IV morphine. Subsequent standardized doses of morphine were given every 2 hours over a 6-hour observation period based upon severity of pain as scored by a 10-cm linear visual analog scale (VAS). Vital signs and pain severity were recorded initially and assessed hourly. Disposition was made at the end of the observation period.
                Patients receiving ketorolac and those receiving placebo were of similar age, weight, gender, number of prior ED visits, number of prior hospital admissions, duration of pain prior to presentation, and initial pain score. The total dose of morphine received, reduction in severity of pain as measured by VAS, rate of hospital admission, and rate of return to the ED for discharged patients did not differ significantly between the two groups.
                We were unable to demonstrate a synergistic analgesic effect for ketorolac in the treatment of pain from acute vaso-occlusive crisis in pediatric sickle cell disease. Further investigations involving larger samples of sickle cell patients may be needed to further define a role for ketorolac in the acute management of sickle cell vaso-occlusive pain. Twenty one patients with sickle cell disease admitted to the hospital with the pain of vaso-occlusive crisis (VOC) were treated by continuous IV infusion of ketorolac or normal saline for up to 5 days. All patients received supplemental IM injections of meperidine, 100 mg, as necessary, but not more frequently than every 3 hr. Over the 5 days the ketorolac treated patients (KT) required 33% less meperidine than did the placebo treated patients (PL), P = 0.04, and had significantly better pain relief as assessed by categorical, visual analog, and pain relief scales. By the end of 5 days infusions had been discontinued in six KT and one PL. The time to discontinuation of the infusion was significantly shorter in KT, (P = 0.009). The median duration of hospital stay from the start of treatment was 3.3 days for KT and 7.2 days for PL, P = 0.027. Adverse events were mainly related to the digestive system. This study showed that continuous infusion of ketorolac significantly reduced total meperidine requirement and that the analgesia produced by this combination was superior to that produced by meperidine alone. Further evaluation of this drug in the management of sickle cell VOC is warranted.
There were no studies addressing chronic pain in sickle cell disease. There is limited evidence for analgesic interventions in acute pain crises. Studies have been under-powered. There is not enough data for inter-trial comparisons. In one trial, there was no difference in the efficacy of sustained-release oral versus parenteral morphine, which suggests that oral morphine should be considered for acute pain. Parenteral corticosteroids appear to shorten the period over which analgesics are required and hospital length-of-stay, without producing short-term major adverse effects.More research is needed to improve pain management in sickle cell disease.