Suxamethonium-induced hyperkalaemia 6 weeks after chemoradiotherapy in a patient with rectal carcinoma.

Suxamethonium causes an efflux of potassium (K+) ions by depolarizing acetylcholine receptors within the neuromuscular junction and produces a transient, small rise in serum K+ concentration in normal individuals that is usually of little clinical importance. Despite the clear efficacy and relative safety of suxamethonium in many patients, anaesthetists are also very aware that acute, severe hyperkalaemia resulting in important cardiovascular sequelae (e.g. malignant ventricular arrhythmias, cardiac arrest) may also occur with administration of suxamethonium in susceptible patients, including those with skeletal muscle injury or thermal trauma. In the current report, we describe a patient with rectal cancer initially treated with chemoradiotherapy who developed hyperkalaemia after suxamethonium and further discuss the potential factors that contributed to this response.

Newborn screening for congenital hypothyroidism, Victoria, Australia, 1977-1997. Part 1: The screening programme, demography, baseline perinatal data and diagnostic classification.

Clinical, demographic and laboratory data from infants with congenital hypothyroidism (CH) born in the Australian state of Victoria from the commencement of neonatal screening in mid-1977 until December 1988 are reported. These provide a baseline for a 12-year prospective longitudinal study on physical and neuro-psychological outcome until mid-1997, the subject of a second paper. Infants with CH were detected using a primary TT4 screening test. Demographic data were collected prospectively using a clinical assessment protocol. Nearly all affected infants underwent 99mTc pertechnetate scanning at the initial assessment to determine the underlying aetiology of their hypothyroidism. 704,723 infants were screened and 199 with permanent primary hypothyroidism (one in 3,541) were identified. The most common aetiologies were thyroid ectopia (46%), thyroid aplasia (33%), and 'dyshormonogenesis' (11%). The clinical abnormalities classically described in CH were more evident in infants with aplasia, and the striking female preponderance in infants with thyroid dysplasia (syn. dysgenesis) was confirmed. Other features included increased frequencies of 'dyshormonogenesis' in infants of parents of Middle-Eastern origin and of labour induction in infants with dysplasia. A closed posterior fontanelle was not found in any infant with thyroid aplasia.

Newborn screening for congenital hypothyroidism, Victoria, Australia, 1977-1997. Part 2: Treatment, progress and outcome.

A controlled longitudinal prospective study is reported of physical and neuropsychological progress up to 12 years in 152 children with congenital hypothyroidism (CH), detected by newborn screening in the Australian state of Victoria and born between the onset of screening in mid-1977 and December 1988. Linear growth of the CH children was normal. Throughout they were slightly heavier and the median head circumference was slightly larger compared with reference data. Those with thyroid aplasia required a marginally larger dose of thyroxine to achieve euthyroidism. Assessment of cognitive outcome in the children with permanent primary CH revealed the mean scores at 2, 5 and 8 years to be from 8.5 (p<0.001) to 10.2 (p<0.001) points lower than in a group of 60 euthyroid controls. However, there was large overlap and, of the affected children, only 10.1% at 2 years, 3.9% at 5 years and 6.8% at 8 years fell more than 2 SD below the means of the euthyroid controls. On univariate analysis, variables shown to have significant correlation with cognitive outcome at 8 years in the CH children were newborn activity, baseline TT4 and FTI, initial T4 dosage, socio-economic classification, maternal age, maternal education and presence of a serious accompanying disorder. On multiple regression analysis, significant variables were baseline bone age, maternal age and education, and presence of a serious accompanying disorder. No single thyroidal or extra-thyroidal variable could be identified to account for the discrepancy between the children with CH and the controls.

Publication rates of abstracts from two pharmacy meetings.

OBJECTIVE: To determine the rate of publication of abstracts presented at the 1994 American Society of Health System Pharmacists (ASHP) Mid-year Clinical Meeting and the 1994 American College of Clinical Pharmacists (ACCP) Annual Meeting. METHODS: Abstracts presented at the 1994 ASHP Midyear Clinical Meeting and the 1994 ACCP Annual Meeting were evaluated for subsequent publication as full articles in journals indexed in MEDLINE, International Pharmaceutical Abstracts, and Current Contents. RESULTS: Five hundred one abstracts presented at the 1994 ASHP Mid-year Clinical Meeting were evaluated; 55 (11%) of these had been published. Two hundred fifteen abstracts presented at the 1994 ACCP Annual Meeting were evaluated; 71 (33%) of these had been published. CONCLUSIONS: The publication rates for abstracts presented at ASHP and ACCP meetings were found to be lower than many of those for other medical groups. The presentation of research abstracts at professional meetings is an integral part of the exchange of scientific information; however, many of the presented abstracts are not subsequently published as full research reports. The failure to publish the results of the studies may limit the ability of a reader to judge the validity, reliability, and generalizability of the research. This could affect the use of the findings in clinical practice and in supporting or refuting other research findings.

Use of gabapentin in pain management.

There have been many proposed uses for gabapentin, including midscapular pain secondary to radiation myelopathy, RSD, neuropathic pain, postherpetic neuralgia, and migraine prophylaxis. However, the published reports consist of a small number of patients and limited data. Limited data provided in published case reports do not allow adequate evaluation of expected adverse effects or efficacy. It is unclear whether gabapentin is more effective for a specific type of pain and how gabapentin may compare with placebo or other therapeutic alternatives. Therefore, randomized, double-blind, placebo-controlled, prospective studies are warranted to further elucidate gabapentin uses beyond what is recommended by the Food and Drug Administration. Gabapentin should only be considered for pain management after well-established therapies have failed to produce desired outcomes.

Oral immunoglobulins for gastroenteritis.

Preliminary literature suggests that oral immunoglobulin therapy may be of value in severe GI infections, but the optimal antibody class, dosage, and duration of treatment still need to be defined in larger, controlled clinical trials. Most of the information currently available comes from case series and small, uncontrolled trials. Additionally, there is no clear indication on how to select the best candidates for this type of therapy, since the limited information in the literature comes from different patient populations. In all probability, the substantial cost of this approach to treatment will not be justifiable in most pediatric patients with gastroenteritis.

Valproic acid: a migraine prophylaxis alternative.

While studies have noted possible benefits of valproate for migraine prophylaxis, most have small study samples (range 22-34 patients). The more recent, larger clinical trial confirms the effectiveness of valproate in the prevention of migraines. The available evidence suggests that valproic acid should provide another alternative to conventional migraine prophylaxis. However, it would still be beneficial to see other large studies conducted to determine valproate's place among the migraine prophylactic therapies currently available. The Food and Drug Administration recently approved divalproex sodium for the prevention of migraine headaches. The usual starting dosage is 250 mg bid, titrating to 1000 mg/d if necessary.

Intravenous antihypertensive agents for patients unable to take oral medications.

The treatment of chronic hypertension in patients unable to take oral medications is challenging. Little information on the comparative safety and efficacy of i.v. alternatives is available. Hydralazine, methyldopate, enalaprilat, and nicardipine appear to be the best options for patients temporarily requiring i.v. medications for controlling chronic hypertension. Therapy should be selected on the basis of the individual patient's needs and diseases, the potential for adverse events, the monitoring required, drug costs, and the expected duration of therapy. The choices may be limited, but understanding the proper use of i.v. antihypertensives should enhance blood pressure control and patient care.

Adjusting dosage intervals of intermittent intravenous ranitidine according to creatinine clearance: a cost-minimization analysis.

To provide effective ranitidine therapy at the lowest possible cost to institutions and patients, the main study objectives were to develop a dosage intervention strategy for intermittent intravenous ranitidine and to document the resultant cost savings through cost-minimization analysis. During a 6-week baseline phase, a pharmacy resident prospectively monitored all patients in the intensive care unit receiving intravenous ranitidine and evaluated appropriateness of dose according to creatinine clearance. Staff pharmacists collected identical data during the 6-week intervention phase but also made recommendations for dosage interval adjustment. In patients with creatinine clearance rates less than 50 mL per minute, the mean number of doses per patient treatment-day was reduced from 2.33 +/- 0.81 during baseline phase to 1.56 +/- 0.70 during intervention phase (P < 0.001). The hospital cost per patient treatment-day was decreased by 33%, from $5.29 +/- 1.83 to $3.54 +/- 1.59 (P < 0.001). Thus a program of prospective monitoring and verbal interventions by pharmacists effectively reduced the number of inappropriate ranitidine doses and hospital cost.

Interferon beta for multiple sclerosis.

OBJECTIVE: To introduce readers to the use of a new agent, interferon beta-1b (IFN beta ser), in the treatment of relapsing-remitting multiple sclerosis (RRMS). Therapeutic and economic issues surrounding IFN beta ser are discussed, as are its pharmacology, clinical efficacy, adverse effects, and dosage guidelines. DATA SOURCES: A MEDLINE search was used to identify pertinent literature, including clinical trials and reviews. STUDY SELECTIONS: All available trials were reviewed. DATA EXTRACTION: Since trials evaluating subcutaneously administered interferon beta are sparse, clinical trials evaluating intrathecal IFN beta ser were included, as was toxicology information from the oncology population. DATA SYNTHESIS: IFN beta ser has recently been approved by the Food and Drug Administration for the treatment of RRMS. Its exact mechanism of action is unknown, but it may downregulate interferon gamma (IFN gamma) production and the IFN gamma-stimulated major histocompatibility complex antigen expression, and/or augment T-suppressor cell function. Primary adverse effects include flu-like symptoms, fever, chills, myalgia, sweating, and injection-site reactions. Clinical efficacy has been investigated in 372 ambulatory patients with RRMS. IFN beta ser treatment resulted in a reduction in the annual exacerbation rate and a greater proportion of exacerbation-free patients. Burden of central nervous system disease was also significantly reduced in treated patients. However, no reductions were detected on the Scripps Neurologic Rating Scale or with confirmed endpoint scores on the Kurtzke Expanded Disability Status Scale. Although many questions remain concerning IFN beta ser's long-term efficacy, its benefits in patients with other types of multiple sclerosis (MS), and its effect on progression of disease and ultimate disability, IFN beta ser is the first treatment modality that has substantially altered the natural course of MS in a controlled clinical trial. CONCLUSIONS: IFN beta ser is not a cure for MS, but it is well tolerated and patients with RRMS have shown significant improvements in exacerbation rates and burden of central nervous system disease. IFN beta ser should be considered a definite improvement in RRMS treatment, although many therapeutic issues remain unanswered. Additional clinical trials are needed.

Vigabatrin.

OBJECTIVE: To introduce the reader to the use of a new agent, vigabatrin, in the treatment of refractory complex partial seizures. Clinical trials and pharmacokinetic data are reviewed, as well as neuropathology, adverse effects, drug interactions, and dosage guidelines. DATA SOURCES: A MEDLINE search through March 1992 was used to identify pertinent English-language literature, including clinical trials, reviews, abstracts, and conference proceedings. Indexing terms included vigabatrin and anticonvulsants. STUDY SELECTIONS: All clinical trials (total of 21) were reviewed, as were all pharmacokinetic studies (total of 8). Selected studies highlighting chemistry, pharmacology, neuropathology, and adverse effects were also reviewed. DATA EXTRACTION: Performed subjectively by the author. Trials were assessed by design, sample size, types of seizures of the subjects, and clinical response. DATA SYNTHESIS: Vigabatrin represents the first of a new class of antiepileptic drugs (AEDs)--the gamma-aminobutyric acid transaminase (GABA-T) inhibitors. Vigabatrin works by selective, irreversible inhibition of GABA-T, thus preventing the breakdown of GABA. It has been shown to produce dose-dependent increases in cerebrospinal fluid GABA concentrations, and decreases in GABA-T activity. Vigabatrin may also cause a decrease in excitation-related amino acids. It is well absorbed, is not protein bound, and is eliminated by glomerular filtration. However, even with a short half-life (5-7 h), vigabatrin may be given once or twice daily because of its mechanism of action. Few drug interactions have been reported with this agent, although decreases in phenytoin concentration may reach clinical significance. Concern over neuropathologic findings (microvacuolization of white matter) in animals caused trials of vigabatrin to be halted in 1983, but trials have now resumed as there is no evidence of toxicity in humans. Clinical efficacy of vigabatrin has been evaluated in controlled trials and appears to be most effective in complex partial seizures, producing a 50 percent or greater reduction in seizure frequency in approximately 50 percent of the adult patients studied. Efficacy in children with partial seizures also appears promising, and one uncontrolled study suggests that further study of vigabatrin in infantile spasms may be warranted. CONCLUSIONS: Vigabatrin appears to be effective in treating refractory complex partial seizures in adults and refractory partial seizures in children. Its relatively benign adverse-effect profile and few known drug interactions may given this agent an advantage over existing anticonvulsants. However, definitive conclusions about the role of vigabatrin in epilepsy treatment should await the completion of ongoing Phase II and Phase III trials.