Tramadol use in pediatric sickle cell disease patients with vaso-occlusive crisis

AIM: To evaluate whether the addition of scheduled oral tramadol to intravenous morphine and intravenous ketorolac reduces morphine requirements.METHODS: This single-centered, Institutional Review Board-approved, retrospective study at Moses Cone Memorial Hospital included pediatric patients who were ≥ 2 years old with vaso-occlusive crisis (VOC) caused by sickle cell disease (SCD), were on morphine patient-controlled analgesia (PCA), and had scheduled oral tramadol added to their standard pain regimen. The study population was admitted between March 2008 and March 2011. The data was collected from electronic records and included age, weight, morphine use, tramadol use, hemoglobin, pain scores, number of days on PCA, length of hospital stay, respiratory rate, and polyethylene glycol use. Thirty patients were analyzed as independent admissions and seven patients as paired admissions.RESULTS: Eighteen pediatric SCD patients with VOC received morphine PCA and intravenous ketorolac and twelve patients received morphine PCA and intravenous ketorolac and scheduled oral tramadol. Baseline characteristics were similar between both groups with the exception of the average weight, which was greater in the tramadol group than in the morphine group. The average morphine requirements in patients with and without the use of tramadol were similar, both for the independent admissions [0.58 mg/kg per day vs 0.65 mg/kg per day (P = 0.31)] and the paired admissions [0.71 mg/kg per day vs 0.77 mg/kg per day (P = 0.5)]. The daily polyethylene glycol requirement was less in the tramadol group for both the independent [0.5 g/kg per day vs 0.6 g/kg per day (P = 0.64)] and paired admissions analyses [and 0.41 g/kg per day vs 0.55 g/kg per day (P = 0.67)].CONCLUSION: The addition of scheduled tramadol in patients receiving concomitant morphine and ketorolac demonstrates a trend toward decreased morphine and polyethylene glycol use.     

Home care of vaso-occlusive crisis in sickle cell disease in Togo]

BACKGROUND: Many people with sickle cell disease manage their pain crises at home. This study aims to describe the home management of sickle cell pain by Togolese patients. PATIENTS AND METHODS: From July 1996 to April 1997, parents of children with sickle cell disease, and some adults with sickle cell disease living in rural and urban regions were interviewed about their home treatment habits during pain crises. RESULTS: A total of 165 patients with sickle cell disease (82 from urban and 83 from rural areas) were selected. The techniques most frequently used for pain management included salicylates (61.8%), paracetamol (37%), non-steroidal anti-inflammatory drugs (15.1%), vasodilators and pentoxifylline (5.4%). Only 4.2% of the patients mentioned adequate hydration. None used other antalgics (weak or strong opium derivatives). No difference was noticed between the treatment habits of rural regions and those of urban regions. CONCLUSION: In order to improve the quality of life of patients with sickle cell disease, information and awareness programs must be organized in order to establish a standard home pain management. Emphasis must be put on the use of salicylates and paracetamol at the correct dosage, the intake of abundant fluids, the easy use of analgesic of the second step of the Word Health Organization, and the systematic treatment of malaria which can induce pain crises.     

Impact of hospitalization for vaso-occlusive crisis on health-related quality of life in children with sickle cell disease

Background

Sickle cell disease (SCD) is characterized by vaso-occlusive crises (VOCs) that impair the health-related quality of life (HRQoL). The aim of this study is to evaluate the impact of hospitalization for VOCs on HRQoL in children with SCD over time.

Methods

In this longitudinal cohort study, children aged 8–18 years diagnosed with SCD at the Amsterdam UMC were included between 2012 and 2021. HRQoL was annually measured as part of standard care using the Pediatric Quality of Life Inventory. The impact of hospitalization for VOC on HRQoL was evaluated using linear mixed models 3, 6, 9, and 12 months after hospitalization. The effect of frequency of hospitalization for VOC on HRQoL was evaluated over the last 12 months.

Results

In total, 94 children with SCD were included with a median age of 11.8 years (interquartile range [IQR]: 9–14). Thirty-seven patients (39%) had been hospitalized for a VOC. Hospitalization for VOC led to a decrease of 3.2–4.8 points in total HRQoL compared to patients without hospitalization, most pronounced 3 months after hospitalization. Recurrent admission for VOC in the last 12 months was associated with a decrease of 2.3 points in total HRQoL (p = .04). The most affected subscale was physical functioning.

Conclusion

The adverse effects of hospitalization for VOC in children with SCD persist up to 12 months after hospitalization. After hospitalization for VOC, extra attention and support for its negative impact on HRQoL are recommended. This study also underlines the importance of systematically measuring HRQoL, allowing clinicians to intervene accordingly.     

Primary hyperparathyroidism mimicking vaso-occlusive crises in sickle cell disease

We report a case of bone pain associated with primary hyperparathyroidism in a patient with sickle cell disease. A 17-year-old girl with sickle cell disease (SS phenotype) was seen for bilateral knee and back pain. She had had recurrent severe vaso-occlusive crises and acute chest syndrome in the course of her disease. In the last 2 years, she had frequent visits to the emergency department for severe bone pain. She complained of long-standing fatigue and lethargy. Her physical examination was normal. Hydroxyurea treatment, as well as and long- and short-acting narcotics were given, with little improvement in symptoms. Poor compliance with medication, family dysfunction, and potential narcotic addiction were felt to be significant contributors to the patient's symptoms. She was incidentally found to have an extremely elevated total calcium level of 3.19 mmol/L (range: 2.25-2.76) with an ionized calcium level of 1.9 mmol/L (range: 1.15-1.35). Phosphorus level was 0.82 mmol/L (range: 0.90-1.50), alkaline phosphatase level was elevated at 519 U/L (range: 10-170), and parathyroid hormone level was extremely high at 1645 pg/mL (range: 10-60). Her renal function was normal. Ultrasonography of the neck and a Sestamibi scan revealed a single left inferior parathyroid adenoma adjacent to the thyroid lobe. There was no evidence of an underlying multiple endocrine neoplasia. The patient was diagnosed with primary hyperparathyroidism. Fluid hydration, hydrocortisone, calcitonin, and bisphosphonates were initiated for acute hypercalcemia management before surgical excision of the left parathyroid adenoma. On review of previous blood work, a borderline calcium level of 2.72 was present 18 months before this admission. Two years postsurgery, she has normal renal function, calcium, and parathyroid hormone levels. The weekly visits to the emergency department for pain episodes decreased to 1 every 2 months within the first few months after her surgery. The decrease in pain episodes, even if it coincided with the treatment of primary hyperparathyroidism, may still reflect the natural evolution of sickle cell disease in this patient. However, the high morbidity associated with primary hyperparathyroidism was successfully prevented in this patient. Primary hyperparathyroidism is rare in childhood. In a recent study, it occurred more commonly in female adolescents and was because of a single adenoma, as in our patient. Significant morbidity, mainly secondary to renal dysfunction, was because of the delay in diagnosis after the onset of symptoms (2.0-4.2 years), emphasizing the need for a rapid diagnosis. Sickle cell disease affects approximately 1 of every 600 blacks in North America. Acute episodes of severe vaso-occlusive crisis account for > 90% of sickle cell-related hospitalizations and are a significant cause of morbidity in patients. There is no known association between sickle cell disease and primary hyperparathyroidism, and this case is most probably a random occurrence. However, as emphasized by this case report, pain may also be a harbinger of other disease processes in sickle cell disease. Because management may vary, we suggest that care providers consider the diagnosis of vaso-occlusive crisis as the diagnosis of exclusion and that other etiologies for pain be envisaged in this patient population, especially in the presence of prolonged pain or unusual clinical, radiologic, or biological findings.     

Intravenous ketorolac in the emergency department management of sickle cell pain and predictors of its effectiveness

OBJECTIVES: To evaluate the effectiveness of intravenous (IV) ketorolac tromethamine in the treatment of children with sickle cell disease with moderate to severe acute vaso-occlusive pain (VOP) and to develop a predictive model that would determine who would need additional IV analgesics. DESIGN: A prospective case series. SETTING: The emergency department of an urban children's hospital in the southeastern United States. PATIENTS: A convenience sample of 51 children aged 6 to 18 years, representing 70 distinct episodes of VOP requiring IV analgesics. INTERVENTION: All patients were given 0.5 to 1 mg/kg IV ketorolac and IV fluids. MAIN OUTCOME MEASURES: Patients, parents, nurses, and physicians assessed pain before and after ketorolac using a standard 100-mm visual analog scale (VAS). RESULTS: Of the 70 episodes of VOP, 37 (53%) adequately resolved with IV ketorolac and IV fluids and required no IV opioids (group A). Thirty-one episodes (47%) required the addition of an IV opioid (group B). Group B had a significantly greater proportion of episodes reporting 4 or more painful sites than group A, 43% (12/28) vs 9% (3/33), respectively (P<.01). Group B also had significantly higher mean initial VAS scores than group A as assessed by the patient (81 vs 60; P<.01), parent (71 vs 54; P<.01), nurse (78 vs 51, P<.01), and physician (69 vs 53; P =.01). Of the patient assessments with an initial VAS score greater than 70, 69% (18/26) required the addition of an opioid. CONCLUSIONS: First-line therapy with IV ketorolac and IV fluids resulted in adequate resolution of pain in 53% of episodes with acute VOP. A reported 4 or more painful sites and an initial VAS score greater than 70 were predictors of the likelihood to need additional IV analgesics.     

Patterns of arginine and nitric oxide in patients with sickle cell disease with vaso-occlusive crisis and acute chest syndrome

PURPOSE: Our objective was to evaluate L-arginine and nitric oxide metabolite (NOx) levels in children with sickle cell disease (SCD) at steady-state and during vaso-occlusive crisis (VOC). Because alterations in nitric oxide production may have an important role in the pathophysiology of SCD, our second aim was to determine if a relationship exists between these levels and vaso-occlusive crisis (VOC). PATIENTS AND METHODS: Plasma L-arginine and serum NOx levels were examined in 36 patients with SCD with 39 episodes of VOC and 10 children with SCD at steady-state. Daily levels were obtained in children requiring hospitalization. RESULTS: Steady-state L-arginine levels were normal in children with SCD. L-arginine levels were low, however, in children with VOC (37.4 +/- 2.7 vs. 53.6 +/- 4.6 micromol/L; P = 0.008) but returned to baseline during hospitalization. In contrast, NOx levels were normal at presentation but decreased during hospitalization for both patients with VOC and patients with acute chest syndrome (ACS) (21.1 +/- 2.0, 17.4 +/- 2.4, and 12.3 +/- 1.6 micromol/L, respectively; P < 0.05). In the patients with VOC who had ACS develop, L-arginine decreased to the lowest levels at the time of the ACS diagnosis, correlating with decreasing NOx levels. CONCLUSION: These data suggest that there may be a relationship between the L-arginine-nitric oxide pathway and vaso-occlusion in SCD. Low arginine levels during VOC could reflect a state of acute substrate depletion that results in a decrease in nitric oxide production.     

Micronutrients and sickle cell disease, effects on growth, infection and vaso-occlusive crisis: a systematic review

Patients with Sickle cell disease (SCD) exhibit signs of poor growth, increased susceptibility to infection and recurrent episodes of painful vaso-occlusive crises. Micronutrient deficiencies may increase susceptibility to these outcomes. We conducted a systematic review to assess the strength of evidence for improved outcomes related to micronutrient interventions. Six randomized-controlled trials of moderate quality met the inclusion criteria. Zinc supplementation was associated with improved growth and decreased incidence of infection and is a promising intervention in the management of SCD patients. Omega-3 fatty acid supplementation was associated with limited reduction in vaso occlusive crises. This review identifies key knowledge gaps, which are important research priorities for nutritional interventions.     

Intravenous narcotic therapy for children with severe sickle cell pain crisis

Few studies have been published about analgesic management practices during sickle cell pain crisis. Therefore, we reviewed the records of all hospitalized children with this complication during a recent five-year period. The 38 patients (98 painful episodes) who received intravenous narcotic therapy were the subjects of this review. In 76 patients, an initial intravenous bolus injection of morphine sulfate or meperidine hydrochloride was followed by a continuous intravenous infusion of one of these two drugs. To achieve adequate pain control, adjustments in infusion rates were made according to a written protocol. In 22 other patients, subsequent narcotic treatment consisted only of intermittent intravenous bolus injections of meperidine. Satisfactory pain relief was achieved in all 98 episodes. Patients given continuous infusions required more narcotic to control their pain and had more side effects than those treated with bolus injections alone, suggesting a dose-response relationship between narcotic dose and several known side effects. Common side effects included nausea and vomiting, lethargy, and abdominal distention. Although clinically evident respiratory depression was quite uncommon, chest syndrome was a frequent complication, and severe respiratory distress occurred in three patients. Narcotic withdrawal or addiction was not observed. With careful monitoring (including special attention directed to avoiding dosing error), continuous intravenous narcotic infusions are safe and provide effective pain relief for severe sickle cell pain crisis.     

Nocturnal enuresis in pediatric sickle cell disease.

To assess the prevalence of nocturnal enuresis in children and adolescents with sickle cell disease (SCD) and associated factors, structured telephone interviews were conducted with primary caregivers of 217 children and adolescents with SCD aged 5 years or older. Prevalence, perceived causes, interventions undertaken, and emotional impact were assessed. Nocturnal enuresis was significantly higher for males (28.2% of males) than for females (11% of females), p = .002, and compared with cited population prevalence rates, nocturnal enuresis was significantly higher for children with SCD, p < .01. SCD was the most common reason given by primary caregivers for enuresis. Primary caregivers used a wide range of interventions for nocturnal enuresis, but few used empirically supported treatments for enuresis or spoke with their health care team about the enuresis. These data suggest that systematic assessment and intervention for nocturnal enuresis must be implemented in the follow-up care of children and adolescents with SCD.