1 This study aimed (1) to measure the whole blood to plasma (WB:P) and red blood cell to plasma (RBC:P) concentration ratios of propranolol in healthy volunteers and two types of patients, and (2) to compare the concentration ratios of the lipophilic drug propranolol with moderately lipophilic pindolol and hydrophilic atenolol. 2 There was no significant difference between the WB:P and RBC:P ratios of propranolol concentration in healthy volunteers and neurological patients compared with hypertensive patients. The mean ± s.d. WB:P ratios of propranolol concentration in the three groups were 0.74 + 0.03, 0.71 + 0.05, and 0.76 + 0.08 respectively. The mean RBC:P ratios were 0.39 + 0.08, 0.36 + 0.11, and 0.47 ± 0.15 respectively. WB:P and RBC:P concentration ratios of propranolol were linearly correlated with the free fraction of drug in plasma. Propranolol was 90% bound in plasma. 3 The mean WB:P and RBC:P ratios of pindolol in seven volunteers were 0.69 + 0.08 and 0.37 ± 0.14 respectively. Pindolol was 71.4 + 8.6% bound to plasma proteins. The concentration of pindolol in the RBC was linearly correlated with that unbound in plasma. 4 In four healthy volunteers, the mean WB :P concentration ratio of atenolol was 1.07 ± 0.25 and the mean RBC:P ratio was 1.15 + 0.55. 5 The similarity of the RBC:free plasma drug concentration ratios for all three drugs suggests that the use of organic solvent partition coefficients for the prediction of in vivo distribution may be unreliable.

The influence of beta-adrenoceptor antagonism on the effects of a single experimental stress was investigated in 12 healthy volunteers, using a double-blind protocol. A single oral dose of 80 mg propranolol reduced the stress-induced increase in heart rate and systolic blood pressure to 49.9 per cent and 8.3 per cent respectively compared to 61.0 per cent and 17.4 per cent with placebo. The rise in diastolic blood pressure was small and unaffected by beta-adrenoceptor blockade. The rise in temperature of the skin of the trunk was significantly reduced by propranolol. The self-rating of anxiety, alertness and concentration by the subjects was unaffected by propranolol.

SummarySixty-two children undergoing cardiac surgery were surveyed for the presence of external jugular veins. When present, these were used as a route for central venous catheterisation using a 'J' wire Seldinger technique. Only 54% of attempted insertions were successful but the results support greater efJacy in older children. Key wordsVeins; jugular, external, cannulationThe external jugular vein (EJV) provides a safe and reliable route for central venous access in adults especially where a 'J' wire technique is employed [1,2]. A lower success rate was reported in a small series of children and showed no correlation with patient size [3]. We aimed to assess the suitability of this approach in children in a larger paediatric series. MethodThe presence of EJVs was determined in children presenting for cardiac surgery. After induction of anaesthesia, the child was tilted 15" head down and the EJV was cannulated with a 20 G Abbocath cannula, using full aseptic technique. A J-shaped guidewire (radius of curvature of J = 3 mm) was then inserted into the cannula and manoeuvred into a central vein. Finally, after removal of the short cannula, a 22 G hydromer-coated polyurethane catheter was advanced over the guidewire and secured in place. Satisfactory placement was ascertained initially by aspiration of blood through the catheter and after the procedure was confirmed by chest radiography. Duration in situ and any complications were noted. All central line tips were sent after removal for bacterial culture. ResultsThe children's range of age and weight are illustrated in Figures 1 and 2. The mean age was 41 months and mean 7n " , . , . , , , , . . weight was 13.9 kg. Twenty-nine subjects were male and 33 were female. Fifty-eight of the 62 subjects (93.5%) had one or more visible EJV and initial cannulation was successful in 50 children (80.6%). Only 33 'J' wires (53.2%) were successfully manipulated into a central vein. Catheters passed easily over the 'J' wires, but two were subsequently found to be malpositioned. In both of these cases the catheters had passed in a cephalad direction along the internal jugular vein, one ipsilaterally, the other contralaterally. The ages, in years, of the successes and failures are shown in Fig. 3, and suggest increased success with age. This was confirmed when the ages in months were compared by calculating the Spearman Rank Correlation Coefficient (r, = 0.84) which showed that age had a statistically significant effect (p < 0.001) upon success. This result is more easily appreciated by comparing the success rate in those subjects less than 3 years old (37%) and those above this age (71%). Despite all cannulations being performed by the same anaesthetist, the success rate did not improve with greater experience of the technique over the course of the study. No pneumothorax or carotid puncture occurred. Staphyloccoccus albus was cultured from three of the catheter tips, but none of the children had evidence of systemic sepsis. The duration that successful cannulations remained in s...

1 The effects of several (8-adrenoceptor antagonists and lignocaine on blood oxyhaemoglobin dissociation curves have been studied in healthy non-smoking subjects. 2 The P at 50% saturation (P50) did not significantly change after oral propranolol 80 mg (single dose, andollowing 2 weeks' administration of 80 mg twice daily), or following separate intravenous injection of propranolol (0.2 mg/kg), practolol (1 mg/kg), atenolol (0.2 mg/kg) and SL 75212 (0.15 and 0.6 mg/kg).3 Increases in P50 were found after the addition of propranolol 100 and 500 ,ug/ml, and lignocaine 5 ,ug/ml to whole blood, but incubation with propranolol at 1000 ng/ml or less, or sotalol 5 and 500,ug/ml and 5 mg/ml resulted in no significant change in P50. 4 These results suggest that to increase P50 with propranolol requires plasma propranolol concentrations far in excess of concentrations normally achieved, and that the therapeutic effect of propranolol in patients with ischaemic heart disease cannot be attributed to an increase in P5o.

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