Gentamicin dosing in elderly patients based on bioelectrical impedance analysis.

The relationship between gentamicin pharmacokinetics and measures of bioelectrical impedance (BI) in elderly patients was investigated with the aim of developing a potential noninvasive means of individualising gentamicin dosage. Linear regression analyses identified height/resistance2 as a statistically significant predictor of gentamicin distribution volume, V, [adjusted (adj)r2 = 0.53, coefficient of variation (CV) = 15.2%], and resistance/reactance and creatinine clearance (CLcr) as predictors of total systemic clearance, CL, adj r2 = 0.52, CV = 20.1%. Individualisation of gentamicin dosage regimens based on these relationships to achieve steady-state (SS), peak gentamicin concentrations, Css,max, and SS trough concentrations, Css,min, of 7.0 and 1.0 micrograms/ml, respectively, in an independent group of elderly patients resulted in serum gentamicin levels of 5.9 +/- 0.7 and 0.8 +/- 0.4 micrograms/ml. Mean absolute prediction errors averaged 0.7 +/- 0.5 micrograms/ml for Css,max and 0.5 +/- 0.3 micrograms/ml for Css,min. Measures of BI provided the best predictions of Css,max, whereas models based on CLcr alone were the best predictors of Css,min. This technique provides a means of complementing routine pharmacokinetic monitoring of gentamicin pharmacotherapy in the elderly hospitalised patient with reductions in patient discomfort and potential savings in time and cost.

Maximal expiratory flow volume curves in workers exposed to asbestos.

We have studied 40 workers with varying industrial exposure to asbestos, using routine spirometry and maximal expiratory flow volume curves (MEFVC). Abnormalities of MEFVC were common and seen in those with normal spirometry and total lung capacity. The high incidence of abnormal MEFVC suggests that air flow dysfunction in small airways may follow prolonged asbestos exposure. Our findings support, therefore, the idea that asbestos exposure may cause an obstruction to airflow arising particularly in small airways, and that one of the common functional abnormalities attributable to asbestos exposure is airways obstruction.

Assessment of the value of positive pressure breathing apparatus in inducing cough.

In the last decade, numerous papers have discussed what has been called the indiscriminate use of intermittent positive pressure breathing therapy (IPPB) for the treatment of obstructive airways disease (Curtis et al., 1968; Loke and Anthonisen, 1974; Cheney et al., 1976; Baker, 1974; Murray, 1974; Barach and Segal, 1975; Sheldon and Gold, 1976; Dolovich et al., 1977). These papers have all failed to show any advantage of positive pressure breathing therapy, either in the acute or chronic stages of obstructive airways disease. IPPB apparatus is expensive, requires careful maintenance and cleaning and may lead to patient dependence. However, physiotherapists in this hospital gained the impression that patients who were receiving nebulisation with positive pressure appeared to cough more frequently, and to produce greater volumes of sputum, suggesting that IPPB apparatus may be a useful adjunct of physiotherapy. Therefore a study was designed to compare the effectiveness of nebulisation therapy, with and without positive pressure, on the production of cough and sputum volume in patients with chronic obstructive airways disease.

Sleeping ventilatory patterns in patients with severe chronic airflow obstruction causing respiratory failure.

During sleep some patients with airways obstruction and hypoxaemia developed tachypnoea. This could not be explained by the severity of their abnormality of lung function, their CO2 responsiveness, the nature of their lung disease or their personality. This nocturnal tachypnoea correlated best with a raised resting arterial blood PCO2, and was not seen hypoxaemic patients with a normal PCO2 who showed the usual fall in respiratory rate when asleep. We suggest that in patients with both hypoxaemia and hypercapnia sleep removes a cortical inhibitory mechanism which slows breathing durigng waking hours, and is linked to the arterial blood PCO2.

A case of primary alveolar hypoventilation associated with mild proximal myopathy.

A 34-year-old man presented with clinical features of primary alveolar hypoventilation, but was found additionally to have an adult onset myopathy caused by acid maltase deficiency. This was not severe, as judged clinically, and was initially overlooked. His vital capacity and sprint maximal ventilatory volume were only slightly reduced, and the ventilatory response to CO2 was virtually absent. There was, however, a mild impairment in the ability to decrease Pco2 to normal by voluntary hyperventilation. The relation of myopathy and alveolar hypoventilation is discussed, and it is proposed that the primary muscle disease predisposed the patient to the development of the ventilatory abnormality.