Since almost all urinary creatinine is derived from the muscle mass, the amount of creatinine in the urine will be proportional to muscle mass, and it will show an almost constant decrease with age.

Although aminoglycosides are generally infused every 8 or 12 h, recent data suggest that administration of the total daily dose every 24 h may reduce the risk of oto- and nephrotoxicity and improve efficacy. Aminoglycosides kill bacteria in a dose-dependent manner (i.e. the higher the drug level, the more rapid and complete the bactericidal effect), and exert a post-antibiotic effect (delay in regrowth after the drug concentration falls below its minimum inhibitory concentration for the strain). Moreover, survivors after initial aminoglycoside exposure are temporarily relatively insensitive to the drug, so longer interdose intervals allow recovery of greater sensitivity. Thus, dosing to achieve higher peak drug levels less often would seem desirable. In several animal models of infection, greater efficacy and less oto- and nephrotoxicity have been associated with once daily dosing of aminoglycosides. Several clinical studies have indicated the importance of high peak serum aminoglycoside levels for efficacy. Limited studies of once daily dosing of these drugs in man have suggested that it is at least as favourable as conventional dosing. Nonetheless, despite the obvious advantages of cost and convenience and the theoretical and experimental indication that once daily dosing is advantageous, we need to test this concept in the clinical situation. Large prospective, randomized, double-blind, comparative studies of once daily and conventional dosing regimens in the treatment of various infections in different patient populations are required.

We studied 17 patients, with unilateral lesions in lung or thoracic wall, during thoracotomy performed in the full lateral position. Balanced anaesthesia was used with pethidine and 50% nitrous oxide, in oxygen. The procedure included a period of one-lung ventilation (OLV). Haemodynamic and gas exchange measurements were performed before and after pleurotomy, during OLV, after re-expansion of the lung and after closure of the thoracic wall. The function of each lung was assessed separately during the first and last stages. Mean venous admixture was 9-12% before and after OLV and 31% during OLV. There was a positive correlation between venous admixture and pulmonary arterial pressure during OLV. End-tidal PCO2, carbon dioxide elimination and compliance of the operated side were reduced significantly at the end of the procedure; this is consistent with reduced blood flow and increased water content in that lung.

Mean hemispheric cerebral blood flow (CBF) was studied following intravenous or intraarterial administration of xenon-133, in 10 men admitted for coronary artery bypass grafting. Repeated CBF measurements were performed to evaluate autoregulation before, during, and after cardiopulmonary bypass (CPB). During CPB mean CBF remained unchanged compared with the pre-CPB level, without evidence of cerebral hyperemia or impairment of autoregulation. A marked increase in CBF occurred after CPB and was followed by a time-dependent reduction toward the pre-CPB level. The data support the alpha-stat regulation theory but cannot explain the cerebral vasodilation observed after CPB.

A 14-year-old boy with a mediastinal tumour large enough to cause dyspnoea at rest was anaesthetised for a biopsy. The tumour was believed to compress the tracheal bifurcation. After tracheal intubation, the expiratory breath sounds were heard to be intermittent. The expiratory flow pattern showed irregularities synchronous with the electrocardiogram. With constant flow inflation, the inspiratory pressure profile was suggestive of mechanical obstruction with a resistance which decreased during inspiration. The airway deadspace was greatly reduced, suggesting that the obstruction was near the tracheal tube opening and that there was pooling of carbon dioxide behind this obstruction. The alveolar deadspace fraction was increased and the shape of the carbon dioxide single breath test suggested severe airway obstruction. These findings can be explained on the basis of large airway obstruction, partly intermittent because of the heart's movement, and also reduced lung volume and uneven gas distribution caused by the tumour and pleural fluid.

Clonidine was administered intravenously in an attempt to limit sympatico‐adrenal activity and thereby reduce the incidence of arterial hypertension associated with coronary artery by‐pass graft surgery (CABG). Forty patients scheduled for CABG were assigned to two groups. Twenty patients received clonidine 4μg kg ‐1 before surgery, 2 μg kg ‐1 after cardiopulmonary by‐pass and 1 μg kg ‐1 when the skin was sutured. The other 20 patients served as controls. All patients were anesthetized with fentanyl, droperidol, nitrous oxide and alcuronium. During surgery 5 min after sternotomy, mean arterial pressure was 13 mmHg lower ( P <0.01) in the clonidine group, while after operation the difference between the groups was negligible. Both during and after surgery the plasma catecholamine concentrations were significantly lower in the clonidine group ( P <0.01). The greatest difference between the groups was seen 90 min after operation, when plasma noradrenaline and plasma adrenaline concentrations in the clonidine group were less than 1/ 3 of those in the control group ( P <0.01). As judged by catecholamine concentrations clonidine was effective in attenuating sympatico‐adrenal hyperactivity during and after surgery. Postoperative arterial hypertension was not reduced, however, and it is concluded that other factors besides sympatico‐adrenal hyperactivity must be important.

The ventilation and carbon dioxide elimination of each lung, and pulmonary arterial pressure, were studied in 17 patients during the early phases of anaesthesia for pulmonary surgery. The patients were ventilated mechanically to moderate hypocapnia. Expired tidal volume and carbon dioxide elimination rate of the lung to be operated on, and of the other lung, were similar in the supine position. There was a significant (P less than 0.01) increase in ventilation and a decrease in end-tidal PCO2 of the upper lung after turning the patient on to the side. Simultaneously, the physiological deadspace fraction of tidal volume (VD/VT) increased from 42 to 45% (P less than 0.05). Mean pulmonary arterial pressure (MPAP) increased slightly as surgery on the chest wall commenced. A concomitant increase of carbon dioxide elimination from the upper lung occurred also, although the distribution of ventilation, between the lungs, was unchanged in comparison with the conditions during undisturbed anaesthesia. Individual changes in MPAP (delta MPAP) and corresponding changes in VD/VT (delta (VD/VT)) were negatively correlated (r = -0.68, P less than 0.01). The regression equation was delta (VD/VT) (%) = 0.7 - 0.83 X delta MPAP (mmHg). It was concluded that variations in pulmonary arterial pressure during surgical stimulation may significantly affect the pattern of carbon dioxide elimination in the lungs. However, there was no evidence that these effects were important clinically.

Cardiac index, systemic and pulmonary arterial pressures, carbon dioxide elimination and ventilation of each lung were studied during thoracotomy. Seventeen patients, placed in the full lateral position, were ventilated mechanically through a Carlens' tube to moderate hypocapnia. Mean cardiac index increased by 12% as the pleura was opened (P less than 0.05), with no further change during surgery on the still ventilated upper lung. Mean arterial pressure was unchanged after opening the pleura, but decreased from 114 +/- 15 mm Hg (mean +/- 1 SD) to 104 +/- 18 mm Hg during surgery on the lung (P less than 0.01). Mean pulmonary artery pressure was unchanged. There was a significant (P less than 0.01) increase in carbon dioxide elimination from the upper lung when the pleura was opened. In addition, the ventilation of this lung increased significantly (P less than 0.05). Mean end-tidal PCO2 of the lower lung increased from 4.1 to 4.2 kPa after opening the pleura, while that of the upper lung increased from 3.0 to 3.6 kPa (P less than 0.01). VD/VT decreased from 43 to 38% as the pleura was opened (P less than 0.01). During surgical handling of the lung, marked decreases in ventilation, compliance, carbon dioxide elimination and end-tidal PCO2 were observed in the upper lung. We conclude that ventilation-perfusion mismatch decreased on opening the pleura, and that neither opening the pleura nor the subsequent lung surgery (both lungs being ventilated) caused any clinically important derangements in haemodynamics or oxygenation.

The Siemens-Elema CO2 Analyzer 930 allows calculation of carbon dioxide elimination from the instantaneous measurement of expired gas flow (VE) and carbon dioxide fraction (FECO2). VE is measured in the ventilator and FECO2 at the Y-piece. The most important source of error in the measurement of carbon dioxide elimination is rebreathing, which corresponds to about 24 ml of end-expiratory gas per breath with the standard Y-piece and tubing. This problem may be decreased by the use of non-return valves in the Y-piece. Allowance must be made for the effects of intermolecular interaction between carbon dioxide and the carrier gas, as the reading is about 20% greater with nitrous oxide than with oxygen. This problem can be largely circumvented by calibration with appropriate gas mixtures. Errors resulting from analyser delay are small, and are eliminated completely by the inclusion of fast electronic components. Carbon dioxide analysis is linear with air as carrier gas, but slightly alinear with nitrous oxide in oxygen mixtures. This error can be minimized by using calibration gases with a carbon dioxide content close to that of expired gas. The expiratory flow meter is linear if kept in good condition. Variations in temperature and water content of expired gas cause overestimation of mean expired carbon dioxide fraction (FECO2) by a factor of 1.01-1.02. Compressed gas in the tubing causes a small error which may be neglected at normal airway pressures with tubing of low compliance. Carbon dioxide measurement is slightly affected by barometric pressure. During mechanical ventilation of the lungs in 10 patients with air, FECO2 obtained after corrections for known errors agreed well with Scholander analysis of mixed expired gas.

We describe a new portable infra-red analyses for use with the Siemens-Elema Servo ventilator. The sensor head constitutes a Y-piece connecting the patient to the ventilator tubing, and gives instant carbon dioxide determination. It is based upon simple principles that can be realized with modern techniques, offering for instance freedom from interference by anaesthetic gases, and eliminating the need for calibration. A non-zero inspired carbon dioxide concentration interferes with the measurements. Integration of the carbon dioxide signal with the flow signal from the Servo ventilator yields data about carbon dioxide excretion, and additional calculation yields VD/VT if PaCO2 is known. The accuracy of determination of end-tidal carbon dioxide and carbon dioxide elimination was found to be adequate for research purposes, and that of VD/VT for clinical purposes. The device is considered to be of value in the operating theatre and intensive care unit, for monitoring, as a guide to ventilatory needs, and for the investigation of the magnitude and causes of increased deadspace.