Medication Errors in Pediatrics: Proposals to Improve the Quality and Safety of Care Through Clinical Risk Management

Medication errors represent one of the most common causes of adverse events in pediatrics and are widely reported in the literature. Despite the awareness that children are at increased risk for medication errors, little is known about the real incidence of the phenomenon. Most studies have focused on prescription, although medication errors also include transcription, dispensing, dosage, administration, and certification errors. Known risk factors for therapeutic errors include parenteral infusions, oral fluid administration, and tablet splitting, as well as the off-label use of drugs with dosages taken from adult literature. Emergency Departments and Intensive Care Units constitute the care areas mainly affected by the phenomenon in the hospital setting. The present paper aims to identify the risk profiles in pediatric therapy to outline adequate preventive strategies. Precisely, through the analysis of the available evidence, solutions such as standardization of recommended doses for children, electronic prescribing, targeted training of healthcare professionals, and implementation of reporting systems will be indicated for the prevention of medication errors.

A patient with extensive cerebral calcification due to pseudohypoparathyroidism: a case report

Background Pseudohypoparathyroidism(PHP) is a heterogeneous group of disorders due to impaired activation of c AMP dependant pathways following binding of parathyroid hormone (PTH) to its receptor. In PHP end organ resistance to PTH results in hypocalcaemia, hyperphosphataemia and high PTH levels. Case presentation A 59 year old male presented with a history of progressive impairment of speech and unsteadiness of gait for 1 week and acute onset altered behavior for 1 day and one episode of generalized seizure. His muscle power was grade four according to MRC (medical research council) scale in all limbs and Chovstek’s and Trousseau’s signs were positive. Urgent non contrast computed tomography scan of the brain revealed extensive bilateral cerebral and cerebellar calcifications. A markedly low ionized calcium level of 0.5 mmol/l, an elevated phosphate level of 9.5 mg/dl (reference range: 2.7–4.5 mg/dl) and an elevated intact PTH of 76.3 pg/l were noted. His renal functions were normal. His hypocalcemia was accentuated by the presence of hypomagnesaemia. His 25 hydroxy vitamin D level was only marginally low which could not account for severe hypocalcaemia. A diagnosis of pseudohypoparathyroidism without phenotypic defects, was made due to hypocalcaemia and increased parathyroid hormone levels with cerebral calcifications. The patient was treated initially with parenteral calcium which was later converted to oral calcium supplements. His coexisting Vitamin D deficiency was corrected with 1αcholecalciferol escalating doses. His hypomagnesaemia was corrected with magnesium sulphate parenteral infusions initially and later with oral preparations. With treatment there was a significant clinical and biochemical response. Conclusion Pseudohypoparathyroidism can present for the first time in elderly resulting in extensive cerebral calcifications. Identification and early correction of the deficit will result in both symptomatic and biochemical response.

HBED: The Continuing Development of a Potential Alternative to Deferoxamine for Iron-Chelating Therapy

To further examine the potential clinical usefulness of the hexadentate phenolic aminocarboxylate iron chelatorN,N′-bis(2-hydroxybenzyl)ethylenediamine-N,N′-diacetic acid (HBED) for the chronic treatment of transfusional iron overload, we performed a subchronic toxicity study of the HBED monosodium salt in rodents and have evaluated the iron excretion in primates induced by HBED. The HBED-induced iron excretion was determined for the monohydrochloride dihydrate that was first dissolved in a 0.1-mmol/L sodium phosphate buffer at pH 7.6 and administered to the primates either orally (PO) at a dose of 324 μmol/kg (149.3 mg/kg, n = 5), subcutaneously (sc) at a dose of 81 μmol/kg (37.3 mg/kg, n = 5), sc at 324 μmol/kg (n = 5), and sc at 162 μmol/kg (74.7 mg/kg) for 2 consecutive days for a total dose of 324 μmol/kg (n = 3). In addition, the monosodium salt of HBED in saline was administered to the monkeys sc at a single dose of 150 μmol/kg (64.9 mg/kg, n = 5) or at a dose of 75 μmol/kg every other day for three doses, for a total dose of 225 μmol/kg (n = 4). For comparative purposes, we have also administered deferoxamine (DFO) PO and sc in aqueous solution at a dose of 300 μmol/kg (200 mg/kg). In the iron-loadedCebus apella monkey, whereas the PO administration of DFO or HBED even at a dose of 300 to 324 μmol/kg was ineffective, the sc injection of HBED in buffer or its monosodium salt, 75 to 324 μmol/kg, produced a net iron excretion that was nearly three times that observed after similar doses of sc DFO. In patients with transfusional iron overload, sc injections of HBED may provide a much needed alternative to the use of prolonged parenteral infusions of DFO. Note: After the publication of our previous paper (Blood, 91:1446, 1998) and the completion of the studies described here, it was discovered that the HBED obtained from Strem Chemical Co (Newburyport, MA) that was labeled and sold as a dihydrochloride dihydrate was in fact the monohydrochloride dihydrate. Therefore, the actual administered doses were 81, 162, or 324 μmol/kg; not 75, 150, or 300 μmol/kg as was previously reported. The new data have been recalculated accordingly, and the data from our earlier study, corrected where applicable, are shown in parentheses.

HBED: The Continuing Development of a Potential Alternative to Deferoxamine for Iron-Chelating Therapy

To further examine the potential clinical usefulness of the hexadentate phenolic aminocarboxylate iron chelatorN,N′-bis(2-hydroxybenzyl)ethylenediamine-N,N′-diacetic acid (HBED) for the chronic treatment of transfusional iron overload, we performed a subchronic toxicity study of the HBED monosodium salt in rodents and have evaluated the iron excretion in primates induced by HBED. The HBED-induced iron excretion was determined for the monohydrochloride dihydrate that was first dissolved in a 0.1-mmol/L sodium phosphate buffer at pH 7.6 and administered to the primates either orally (PO) at a dose of 324 μmol/kg (149.3 mg/kg, n = 5), subcutaneously (sc) at a dose of 81 μmol/kg (37.3 mg/kg, n = 5), sc at 324 μmol/kg (n = 5), and sc at 162 μmol/kg (74.7 mg/kg) for 2 consecutive days for a total dose of 324 μmol/kg (n = 3). In addition, the monosodium salt of HBED in saline was administered to the monkeys sc at a single dose of 150 μmol/kg (64.9 mg/kg, n = 5) or at a dose of 75 μmol/kg every other day for three doses, for a total dose of 225 μmol/kg (n = 4). For comparative purposes, we have also administered deferoxamine (DFO) PO and sc in aqueous solution at a dose of 300 μmol/kg (200 mg/kg). In the iron-loadedCebus apella monkey, whereas the PO administration of DFO or HBED even at a dose of 300 to 324 μmol/kg was ineffective, the sc injection of HBED in buffer or its monosodium salt, 75 to 324 μmol/kg, produced a net iron excretion that was nearly three times that observed after similar doses of sc DFO. In patients with transfusional iron overload, sc injections of HBED may provide a much needed alternative to the use of prolonged parenteral infusions of DFO. Note: After the publication of our previous paper (Blood, 91:1446, 1998) and the completion of the studies described here, it was discovered that the HBED obtained from Strem Chemical Co (Newburyport, MA) that was labeled and sold as a dihydrochloride dihydrate was in fact the monohydrochloride dihydrate. Therefore, the actual administered doses were 81, 162, or 324 μmol/kg; not 75, 150, or 300 μmol/kg as was previously reported. The new data have been recalculated accordingly, and the data from our earlier study, corrected where applicable, are shown in parentheses.

HBED: A Potential Alternative to Deferoxamine for Iron-Chelating Therapy

To examine the potential clinical usefulness of the hexadentate phenolic aminocarboxylate iron chelatorN,N-bis(2-hydroxybenzyl)ethylenediamine-N,N-diacetic acid (HBED) for the chronic treatment of transfusional iron overload, we compared the iron excretion induced by subcutaneous (SC) injection of HBED and deferoxamine (DFO), the reference chelator, in rodents and primates. In the non–iron-overloaded, bile-duct–cannulated rat, a single SC injection of HBED, 150 μmol/kg, resulted in a net iron excretion that was more than threefold greater than that after the same dose of DFO. In the iron-loaded Cebus apella monkey, a single SC injection of HBED, 150 μmol/kg, produced a net iron excretion that was more than twice that observed after the same dose of SC DFO. In patients with transfusional iron overload, SC injections of HBED may provide a much needed alternative to the use of prolonged parenteral infusions of DFO.

Maintaining muscle protein anabolism after a metabolic stress: role of dextrose vs. amino acid availability

The effect of chronic hypocaloric parenteral infusions of amino acids (AA) vs. dextrose (D) on protein homeostasis after a generalized metabolic stress was examined. Multicatheterized mongrel dogs were metabolically challenged by a 4-day fast and then administered a 4-day intravenous infusion of saline (S, n = 8), D (n = 8), or isocaloric AA (n = 7). Although nitrogen balance (g.kg.1.day-1) was similarly negative with S (-0.37 +/- 0.05), D (-0.28 +/- 0.03), and AA (-0.37 +/- 0.04) during the fasting period, it was less negative (P < or = 0.05) with AA (-0.06 +/- 0.04) than with D (-0.20 +/- 0.03) or S (-0.23 +/- 0.04) during nutrient infusion. AA resulted in net hindlimb uptake and D in net hindlimb release of essential AA (570 +/- 261 vs. -248 +/- 59 nmol.kg-1.min-1). Whereas S and D infusions led to net hindlimb muscle protein loss (-37 +/- 24 and -89 +/- 33 micrograms.kg-1.min-1, respectively, P < or = 0.05 vs. AA), parenteral AA resulted in net deposition (169 +/- 62 micrograms.kg-1.min-1) as measured using L-[ring-2H5]phenylalanine. Thus hypocaloric parenteral D infusion after a metabolic stress does not favor nitrogen conservation, because net whole body nitrogen loss, skeletal muscle protein catabolism, and hindlimb AA release were not blunted compared with S infusion. Conversely, hypocaloric AA infusion preserves whole body and muscle protein stores.