Angela W. Miser

Transdermal fentanyl for pain control in patients with cancer

&NA; Five cancer patients experienced satisfactory pain relief for periods of 3–156 days using continuous transdermal delivery of the narcotic fentanyl. The patients, aged 16–68 years, had all been experiencing pain and were either unable to take oral analgesic medications or these agents were ineffective in controlling pain. Doses were adjusted to individual patient needs and varied from 75 &mgr;g/h to 350 &mgr;/h (median = 225 &mgr;g/h). Plasma fentanyl levels reflected the administered dose and remained constant throughout the treatment. Transdermal delivery of narcotics provides a new option for the cancer patient unable to achieve satisfactory analgesia with oral medications.

Evaluation of growth hormone release and human growth hormone treatment in children with cranial irradiation-associated short stature

We studied nine children who had received cranial irradiation for various malignancies and subsequently experienced decreased growth velocity. Their response to standard growth hormone stimulation and release tests were compared with that in seven children with classic GH deficiency and in 24 short normal control subjects. With arginine and L-dopa stimulation, six of nine patients who received radiation had a normal GH response (greater than 7 ng/ml), whereas by design none of the GH deficient and all of the normal children had a positive response. Only two of nine patients had a normal response to insulin hypoglycemia, with no significant differences in the mean maximal response of the radiation and the GH-deficient groups. Pulsatile secretion was not significantly different in the radiation and GH-deficient groups, but was different in the radiation and normal groups. All subjects in the GH-deficient and radiation groups were given human growth hormone for 1 year. Growth velocity increased in all, with no significant difference in the response of the two groups when comparing the z scores for growth velocity of each subjects bone age. We recommend a 6-month trial of hGH in children who have had cranial radiation and are in prolonged remission with a decreased growth velocity, as there is no completely reliable combination of GH stimulation or release tests to determine their response.

Pain as a presenting symptom in children and young adults with newly diagnosed malignancy.

&NA; The incidence and nature of pain in 92 children and young adults presenting with newly diagnosed malignancy at the Pediatric Branch of the National Cancer Institute over a 26 month period were assessed. At the time of their initial evaluation, 72 of the total 92 patients were experiencing pain that had been present for a median of 74 days (range 3–821 days) prior to initiation of cancer treatment. In 57 patients, pain had been an initial symptom of cancer; 42 patients had experienced sleep disturbance due to pain. Following the institution of cancer therapy, pain persisted for a median of 10 days. One patient died of malignancy after 5 months without resolution of her pain, and only 4 had persistent pain for greater than 9 months after the start of treatment. Persistent pain is an important symptom of cancer in children and young adults and is often present for long periods before the diagnosis of malignancy is made. Cancer in children usually responds rapidly to modern therapy, and pain usually persists only briefly after the initiation of treatment.

Variation in morphine pharmacokinetics in children with cancer.

Morphine plasma concentrations were determined in 19 children with cancer. A single dose of morphine, 0.09-0.15 mg/kg, was given intravenously over 3-5 min. The plasma concentrations of morphine ranged from 23 to 472 ng/ml at 10 min and from 6.1 to 20.8 ng/ml at 60 min after morphine administration. The morphine plasma concentration exceeded the reported average analgesic concentration of about 20 ng/ml in only 1 patient at 60 min and subsequently declined further except for 4 patients in whom plasma levels exhibited a secondary peak. The pharmacokinetics of morphine was studied in 6 children. The total clearance of morphine ranged from 9.03 to 53.4 ml/min/kg. The apparent volume of the central compartment and the apparent volume of distribution at steady state ranged from 0.17 to 1.10 and from 2.06 to 7.86 l/kg, respectively. The elimination half-life ranged from 0.86 to 7.55 h. These data indicate that an interindividual variation in morphine pharmacokinetics is one factor responsible for varying dosage requirements in children with cancer.

The use of oral methadone to control moderate and severe pain in children and young adults with malignancy

Twenty-two courses of oral methadone were given to control moderate or severe pain in 19 children with cancer. Of these, 21 courses gave adequate pain control for periods of 5 to 267 days (median 24 days). In 16 courses, methadone was continued until death or until the pain resolved; in five remaining courses, a change to parenteral narcotics was ultimately required. Toxicity was minimal. A safe starting dose of methadone appears to be 0.1 mg/kg given every 4 hours, or the equivalent total daily dose given less frequently, with escalation as required to achieve and maintain adequate pain control.

Prospective study of continuous intravenous and subcutaneous morphine infusions for therapy-related or cancer-related pain in children and young adults with cancer

Thirty continuous intravenous (i.v.) morphine infusions administered to 26 patients with cancer resulted in adequate pain control in 27 instances after inadequate control had been achieved with intermittent paren-teral narcotics. Three i.v. infusions were converted to subcutaneous infusions to avoid the use of an i.v. All infusions administered to control tumor-related pain provided adequate pain control; however, dose-limiting toxicity prevented adequate pain control during three (18%) infusions for non-tumor-related pain (mucositis) in spite of lower doses. Adverse reactions (11 episodes) appeared to be related to an interaction between the morphine and concurrent treatment in some cases.

Sweet syndrome in a patient with osteosarcoma

Neutrophilic dermatosis (Sweet syndrome) is a rare condition characterized by painful indurated cutaneous plaques infiltrated with mature neutrophils and may be accompanied by fever, granulocytosis, arthritis, and conjunctivitis. It is associated with various malignant and preneoplastic states, the most common being leukemia and myeloproliferative disorders. Its association with solid tumors is infrequent. The case described here represents, to our knowledge, the first report of Sweet syndrome in a patient with osteogenic sarcoma, a primary tumor of bone arising from mesenchymal cells.

Use of a patient-controlled device for nitrous oxide administration to control procedure-related pain in children and young adults with cancer

A patient-controlled device for administration of 50% nitrous oxide in oxygen (Nitronox®) was used by 28 children and young adults with cancer aged 8–27 years during 40 painful diagnostic procedures. The pain experienced by 26 evaluable patients, as measured by a visual analogue scale (VAS), was significantly reduced compared to the pain experienced by 16 patients during a previous, identical painful procedure without nitrous oxide (p < 0.01 Wilcoxon 1 -sample test). Although patient-related toxicity was minimal, high levels of occupational exposure to nitrous oxide were documented during the five procedures in which room air levels were monitored.

Fatal erythroblastosis fetalis due to anti-Kell isoimmune disease

case descr ibed here, can only be detected by procedures such as the M T T cytochemica l method , which are too expens ive and t ime consuming for rout ine use. However, w h e n e v e r unexpla ined neonata l j aund ice occurs, particularly in e thnic groups such as the Greeks or Chinese in w h o m severe G-6 -PD deficiency is prevalent, identification of G-6-PD deficiency in the neonate may alert family and physic ian to the need for avoidance of potentially hemolyt ic agents during subsequen t pregnancies. The ery throcytes o f such newborn infants should, therefore , be eva lua ted routinely for the presence of G-6-PD deficiency.

Continuous intravenous fentanyl for pain control in children and young adults with cancer

Continuous intravenous infusions of fentanyl citrate were administered to 15 patients during 20 episodes of pain refractory to intermittent narcotic boluses. The infusions were administered for 0.5–33 days (median: 11 days). Adequate pain control was achieved at the median dose of 3.6 μg/kg/h (range: 0.8–243.8 μg/kg/h) during 14 of the 20 infusions. The major toxicities of the fentanyl infusions were dose-limiting respiratory depression (transient during two infusions, persistent during three infusions) and significant central nervous system (CNS) toxicity in three patients when fentanyl was given con-currently with another CNS-toxic drug. One patient developed acute aphonia felt to be related to fentanyl.