Prospective randomized crossover evaluation of three anesthetic regimens for painful procedures in children with cancer.

OBJECTIVE: To identify the most effective sedation regimen for bone marrow aspiration and lumbar puncture procedures with a prospective trial of 3 combinations of sedation/analgesia. STUDY DESIGN: In this double-blind crossover study, we randomly assigned 162 children with acute lymphoblastic leukemia or lymphoblastic lymphoma to receive fentanyl 1 mcg/kg, fentanyl 0.5 mcg/kg, or placebo, in addition to propofol and topical anesthetic for 355 procedures. RESULTS: We found no significant differences among the 3 regimens in the frequency of pain (pain score > 0) or severe pain (pain score ≥ 5) during recovery, or a >20% increase in hemodynamic/respiratory variables during anesthesia. Treatment with fentanyl 1 mcg/kg was associated with a lower frequency of movement during procedure compared with treatment with fentanyl 0.5 mcg/kg (P = .0476) or treatment with placebo (P = .0545). The placebo group required longer time to recover (median, 18 minutes) compared with the fentanyl 0.5 mcg/kg group (median, 9 minutes) (median difference 2.0, P = .007) and the fentanyl 1 mcg/kg (median 8 minutes), (median difference 2.0, P = .15). The placebo group also required larger total dose of propofol (median 5 mg/kg) compared with that of the fentanyl 1 mcg/kg group (median, 3.5 mg/kg) and the fentanyl 0.5 mcg/kg group (median 3.5 mg/kg) (median differences 1.5, P < .00005, in both comparisons). CONCLUSION: The addition of fentanyl 1 mcg/kg to propofol for brief painful procedures reduces movement, propofol dose, and recovery time.

Neuropathic pain during treatment for childhood acute lymphoblastic leukemia.

BACKGROUND: Improved cure rates for childhood acute lymphoblastic leukemia (ALL) over the past 2 decades have allowed greater attention to patients' quality of life. Neuropathic pain (NP) is an unpleasant side effect of chemotherapeutic agents for leukemia, especially vincristine. PROCEDURE: We retrospectively reviewed the records of 498 patients treated on a single protocol for ALL to investigate the risk factors, the incidence, and the use of therapeutic and prophylactic gabapentin treatment for NP. RESULTS: White non-Hispanic race was the only patient variable predictive of NP. One hundred and seventy-four of 498 patients (34.9%) experienced 207 episodes of NP; 16% (28 of 174) patients experienced at least one recurrence of pain after the initial episode. No statistical significance was found in the relation between the severity (grade) of the NP episode and the cumulative dose of vincristine (P = 0.45) or the vincristine dose that immediately preceded the diagnosis (1.5 mg/m(2) versus 2.0 mg/m(2) [correction made here after initial online publication], P = 0.59). Of 180 episodes with treatment data, 62.2% (112) and 37.8% (68) were treated with gabapentin or opioids, respectively. The selection of treatment with gabapentin or opioids was not influenced by the pain intensity score at the time of diagnosis of NP (P = 0.91). The mean gabapentin dose used for 112 episodes was 15.5 mg/kg/day (SD 7.9). We found no evidence that gabapentin prevented recurrence of NP. CONCLUSIONS: Our results highlight the need for prospective randomized studies to elucidate the value of gabapentin regimen for prevention or treatment of vincristine-related pain during treatment of childhood leukemia.

Treatment of pain in children after limb-sparing surgery: an institution's 26-year experience.

A significant proportion of patients report long-term pain that is ≥5 on a 0-10 intensity scale after limb-sparing surgery for malignancies of the long bones. Patients experience several distinct types of pain after limb-sparing surgery which constitute a complex clinical entity. This retrospective study examined 26 years of experience in a pediatric institution (1981-2007) in pain management as long as 6 months after limb-sparing surgery and reviewed the historical evolution of pain interventions. One hundred fifty patients underwent 151 limb-salvage surgeries for bone cancer of the extremities in this series. Pain treatment increased progressively in complexity. Therapies included opioids, nonsteroidal antiinflammatory drugs, acetaminophen-opioid combinations, postoperative continuous epidural infusion, anticonvulsants and tricyclic antidepressants for neuropathic pain, local anesthetic wound catheters, and continuous peripheral nerve block catheters. Management of pain after limb-sparing surgery has evolved over the 26 years of this review. It currently relies on multiple "layers" of pharmacologic and nonpharmacologic strategies to address the complex mixed nociceptive and neuropathic mechanisms of pain in this patient population.

Safe anesthesia for radiotherapy in pediatric oncology: St. Jude Children's Research Hospital Experience, 2004-2006.

PURPOSE: To determine the incidence of anesthesia-related complications in children undergoing radiotherapy and the associated risk factors. METHODS AND MATERIALS: We retrospectively investigated the incidence and types of anesthesia-related complications and examined their association with age, weight, oncology diagnosis, type of anesthetic (propofol vs. propofol and adjuncts), total propofol dose, anesthetic duration, type of radiotherapy procedure (simulation vs. radiotherapy) and patient position (prone vs. supine). RESULTS: Between July 2004 and June 2006, propofol was used in 3,833 procedures (3,611 radiotherapy sessions and 222 simulations) in 177 patients. Complications occurred during 49 anesthetic sessions (1.3%). On univariate analysis, four factors were significantly associated with the risk of complications: procedure duration (p <0.001), total propofol dose (p <0.001), use of adjunct agents (vs. propofol alone; p = 0.029), and simulation (vs. radiotherapy; p = 0.014). Patient position (prone vs. supine) was not significantly associated with the frequency of complications (odds ratio, 0.71; 95% confidence interval, 0.33-1.53; p = 0.38). On multivariate analysis, the procedure duration (p <0.0001) and total propofol dose (p < or =0.03) were the most significant risk factors after adjustment for age, weight, anesthetic type, and procedure type. We found no evidence of the development of tolerance to propofol. CONCLUSION: The rate of anesthesia-related complications was low (1.3%) in our study. The significant risk factors were procedure duration, total propofol dose, the use of adjunct agents with propofol, and simulation (vs. radiotherapy).

Cognitive deficits in children with sickle cell disease.

We tested a hypothesis that children with sickle cell disease who are completely normal by magnetic resonance imaging can still be cognitively impaired, as predicted by a model of diffuse brain injury. Fifty-four patients with hemoglobin SS (average age 10.9 years +/- 2.9 years SD) were examined with the Wechsler Intelligence Scale for Children-III (WISC-III) and were randomly matched by age, race, and gender with healthy children from the Wechsler normative database. Patients were also imaged at 1.5 Tesla with standard imaging sequences. Among 30 patients who were normal by magnetic resonance imaging, there were substantial deficits in Wechsler Full-Scale IQ, Verbal IQ, and Performance IQ (all P < .01) compared with African-American controls. The patient Wechsler Full-Scale IQ was 12.9 points lower than that of controls and decreased as a function of age (probability = .014). The findings suggest that there is diffuse brain injury in patients and that patient deficits increase with age.

Methadone use in children and young adults at a cancer center: a retrospective study.

OBJECTIVE: To augment the literature on methadone applications in pediatric oncology, the authors reviewed the use of methadone at a pediatric cancer center over a 5-year period. DESIGN AND SETTING: Forty-one patients received methadone for inpatient or outpatient pain management. The authors retrospectively reviewed their demographic characteristics, diagnoses, type of pain (nociceptive, neuropathic, or mixed) and causes of pain, and the indications, dose regimens, adverse effects, and outcomes of methadone treatment. RESULTS: There were four types of clinical uses for methadone in 41 patients (10 patients had two): nociceptive pain unresponsive to other opioids (17 patients, 33.3 percent), neuropathic pain (20 patients, 39.2 percent), facilitation of weaning from opioids (11 patients, 21.6 percent), and end-of-life pain management (3 patients, 5.9 percent). The mean age of the 24 males (58.5 percent) and 17 females (41.5 percent) at the start of treatment was 15.7 years (range, 0.6-23 years). The most common diagnoses were leukemia (n = 10, 24.4 percent), osteosarcoma (n = 7, 17.0 percent), and rhabdomyosarcoma (n = 5, 12.2 percent). The causes of pain were bone marrow transplant (n = 13, 31.7 percent), amputation (n = 6, 14.6 percent), chemotherapy (n = 5, 12.2 percent), tumor (n = 5, 12.2 percent), limb-sparing surgery (n = 4, 9.8 percent), and other (n = 8, 19.5 percent). Efficacy was assessed at the end (or after 6 months) of methadone treatment. For many patients (43.1 percent), methadone showed efficacy in achieving the purpose for which it was prescribed, including reduction of nociceptive or neuropathic pain and prevention of opioid withdrawal. Sedation was the most common side effect (24.4 percent). CONCLUSIONS: Methadone was effective for pediatric patients with neuropathic pain or nociceptive pain unresponsive to other opioids, and it effectively prevented opioid withdrawal.

Brain imaging findings in pediatric patients with sickle cell disease.

PURPOSE: To determine prevalence of imaging abnormalities in the brain of children with sickle cell disease (SCD) and to identify clinical and methodological factors that influence prevalence estimate. MATERIALS AND METHODS: Magnetic resonance (MR) imaging and MR angiographic findings for 185 patients with SCD examined at St Jude Children's Research Hospital since 1993 were reviewed. At least two readers independently reviewed images. Standard MR imaging criteria were used to identify lacunae, loss of white matter volume, encephalomalacia, or leukoencephalopathy. Patients were assigned grades to indicate limited or extensive abnormalities. Standard MR angiographic criteria were used to identify arterial tortuosity (limited vasculopathy) and stenosis or occlusion (extensive vasculopathy). Findings were evaluated as a function of patient clinical status (including stroke) and diagnosis. Recent methods (T1- and T2-weighted MR imaging plus fluid-attenuated inversion recovery [FLAIR] at 3-mm section thickness) were compared with older methods (T1- and T2-weighted MR imaging without FLAIR at 5-mm section thickness). RESULTS: At mean age of 10 years, overall prevalence of infarction, ischemia, or atrophy in patients with SCD was 44% (82 of 185), and prevalence of vasculopathy was 55% (102 of 185), without evidence of a significant referral bias. Twenty-six of 27 patients with clinical stroke had abnormal findings at imaging, but even if patients with stroke were excluded, 35% (56 of 158) had a "silent infarction" (MR imaging-visible injury without clinical stroke), and 49% (78 of 158) had abnormal findings at MR angiography. Patients with clinically severe disease had more abnormalities at MR imaging (P <.001) and MR angiography (P <.004) than did patients with milder disease. Severe vasculopathy was more prevalent in patients with hemoglobin SS than in those with hemoglobin SC (P <.001). Recent imaging methods showed more abnormalities than did older methods (P <.01). With newer methods, 43% (29 of 67) of patients had extensive abnormalities, whereas with older methods, 28% (33 of 116) had extensive abnormalities. CONCLUSION: Prevalence of ischemic brain injury in pediatric patients with SCD is substantially higher than was previously reported, in part because of improvements in imaging methods.

Prospective brain imaging evaluation of children with sickle cell trait: initial observations.

PURPOSE: To determine whether sickle cell trait (hemoglobin AS) is associated with abnormalities in the brain of asymptomatic children. MATERIALS AND METHODS: Magnetic resonance (MR) imaging and MR angiography were performed prospectively in 26 siblings (eight girls, 18 boys; mean age, 10.5 years) of patients with sickle cell disease. Two neuroradiologists, blinded as to whether a child had hemoglobin AS or AA, reviewed images obtained in siblings. With MR imaging, lacunae, loss of white matter volume, encephalomalacia, or leukoencephalopathy was identified. With MR angiography, arterial stenosis, occlusion, or tortuosity was identified. Images with definite or possible abnormalities were mixed with randomly selected images and were referred to a third neuroradiologist for a completely blinded review. In cases in which all neuroradiologists concurred, a score was assigned that indicated the sibling had an abnormality. MR angiographic findings were assigned a score for tortuosity with a new quantitative scale. RESULTS: Among 26 siblings screened, 21 children had sickle cell trait. Among these 21 children, two had mild abnormalities at MR imaging (sample prevalence rate, 10% [95% CI: 1%, 29%]), and four had arterial tortuosity (sample prevalence rate, 19% [95% CI: 5%, 42%]). When children with sickle cell trait were compared with 31 control subjects without the trait, arterial tortuosity was significantly more common in children with sickle cell trait (P =.014). Among children with sickle cell trait, percentage of hemoglobin S was significantly greater in children who had tortuosity than percentage of hemoglobin S in children who had normal blood vessels at MR angiography (P <.03). CONCLUSION: Findings suggest that greater percentage of hemoglobin S is associated with mild vasculopathy. This vasculopathy may explain some of the excess risk of stroke among African Americans.