To determine whether epinephrine-induced hypokalemia is due to beta2-adrenoceptor stimulation, and whether hypokalemia can occur at physiologic concentrations of the agonist, epinephrine was infused into six normal volunteers at a rate of 0.1 microgram per kilogram of body weight per minute. The circulating epinephrine concentration was increased to 1.74 +/- 0.65 ng per milliliter, plasma potassium was reduced by 0.82 +/- 0.19 meq per liter, plasma insulin fell by 12 +/- 4 mU per liter, plasma renin activity was elevated, and tachycardia occurred. Isoproterenol infused at 0.02 micrograms per kilogram per minute caused similar tachycardia (25 beats per minute) and elevation in plasma renin activity (6.0 to 6.5 ng per milliliter per hour), but no hypokalemia. The difference in responses to the two catecholamines was ascribed to the relative beta2-selectivity of epinephrine. This hypothesis was tested in six subjects given infusions of epinephrine (0.05 micrograms per kilogram per minute) after administration of either 2.5 or 5 mg of ICI 118551--a selective beta2-receptor antagonist--or placebo. After placebo, epinephrine infusion elevated the circulating epinephrine concentration and reduced plasma potassium; hypokalemia was prevented by the beta2-antagonist. This drug only partially inhibited the rises in plasma renin and glucose and the shortening of systolic time intervals; there was no tachycardia. Fifteen-fold to 30-fold increases in circulating epinephrine concentration appear to cause hypokalemia by a specific beta2-receptor effect distinct from other actions of epinephrine. This phenomenon may be of physiologic importance after severe myocardial infarction, when similar increases in plasma epinephrine have occurred.

SUMMARY The operation of total pancreatectomy is performed rarely. Its role in the management of patients with chronic pancreatitis remains to be elucidated. We have reviewed our series of 29 total pancreatectomies for benign disease [14 women median age 39 years; 15 men median age 34 years]. Twelve underwent standard total pancreatectomy, in 17 duodenum preserving total pancreatectomy (DPTP) was performed. There was one death (mortality 3.4%). In no patient was the total pancreatectomy the first operative procedure. The patients were compared with age and sex matched diabetic control subjects selected on a best fit basis from the diabetic clinic database. The aetliology of the pancreatitis was idiopathic nine, pancreas divisum nine, alcohol eight and other causes three. The indication for surgery was pain 27, acute pancreatitis one and cholangitis with pancreatitis one. The complications of the procedures were mainly caused by infection [wound three, chest six and central line sepsis four] and in two there was a leak from the duodenum; no patient required re-operation. The postoperative stay [standard total, median 21 days (range 13-98) DPTP median 31 days (range 17-49)] has lengthened over the period due to greater attention to analgesic, diabetic and enzyme deficiency control before discharge. In standard total pancreatectomy there were five major hypoglycaemic episodes with only two in 17 DPTP patients. The per cent ideal body weight, the insulin requirement and the HbAl compared less well in standard total pancreatectomy group compared with controls than did DPTP. With both groups large doses of enzyme replacement were required, and this proved of importance in diabetic control. Our experience with total pancreatectomy suggests that pain will be improved in over 80% of patients and that the results of surgery will improve with prolonged follow up provided attention is given to analgesic abuse, enzyme deficiency and diabetes.The role of surgery in the management of chronic pancreatitis is a subject of debate.' Most would agree that the place for surgery is clear when there is a complication of chronic pancreatitis amenable to surgical intervention. Unfortunately the problem often facing the clinician is that of a patient with chronic pain, on an increasing dosage and strength of analgesia, whose quality of life is destroyed by the effects of both pain and analgesia. There is a group of patients who fail to respond to, or who relapse after, non-surgical procedures such as nerve blocks and endoscopic sphincterotomies: of these, there are some whose symptoms are not relieved by pancreatic

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1 Two studies were performed each in six normal volunteers in order to find evidence of either a physiological or pharmacological role of presynaptic ax-and presynaptic P-adrenoceptors in man.2 In Study 1 subjects received a 60 min infusion of guanfacine 3 mg (a2-adrenoceptor agonist) preceded by either idazoxan (oL2-adrenoceptor antagonist) or vehicle. 3 Guanfacine reduced plasma noradrenaline concentration by approximately 30% and this fall was not antagonised by the a2-receptor antagonist. The 30-fold increase in plasma growth hormone, measured as a marker of the central action of guanfacine, was almost completely blocked by idazoxan. 4 A comparison of the drug concentrations of idazoxan and guanfacine, together with their relative affinities for c.2-adrenoceptors, suggested that the idazoxan could not block the peripheral actions of guanfacine and that these were responsible for the fall in plasma noradrenaline concentration. 5 In Study 2 adrenaline 0.05 ,ug kg-1 min--was infused for 80 min preceded by either idazoxan or vehicle. 6 After vehicle, adrenaline caused no change in plasma noradrenaline concentration whereas it rose approximately 25% after administration of idazoxan. This was probably due to unmasking of presynaptic f-adrenoceptor stimulation by adrenaline when the opposing inhibitory autoreceptor was blocked.