Recognition and management of phaeochromocytoma

Phaeochromocytomas are catecholamine-secreting neuroendocrine tumours arising from the chromaffin cells in the adrenal medulla. These tumours may be identified incidentally, as part of a workup for multiple endocrine neoplasia or during unrelated surgery. Better understanding of catecholamine physiology and advances in preoperative preparation has significantly reduced surgical mortality from around 40% to less than 3%. Surgery is the definitive treatment in most cases and laparoscopic resection is associated with reduced hospital stay and earlier mobilisation. Phaeochromocytomas are of particular interest to anaesthetists as it presents a unique haemodynamic challenge both before and after adrenal resection. In this article we describe the physiology of these tumours, their diagnosis and perioperative management.     

Sodium-calcium exchange in Purkinje fibers: Electrical and mechanical effects

Summary The role of Na and Ca in the modulation of electrical and mechanical events was studied in canine cardiac Purkinje fibers perfusedin vitro. The results show that: 1) A low Na–Ca solution (Na 80.8 mM, Ca 1.08) increased contractile force and shortened the action potential transiently; during the recovery, the force decreased below and increased transiently above control; the action potential lengthened transiently. 2) A low Na solution increased force and transiently shortened the action potential; during the recovery, the force transiently decreased and the action potential lengthened again. 3) A low Ca solution decreased force and prolonged the action potential; during the recovery, the force increased transiently and the action potential shortened. 4) In low Na–Ca solution, verapamil, manganese or a fast driving rate did not prevent the transient increase in force but in the steady state the force was lower. 5) If the low Na–Ca solution was begun during quiescence resuming activity after one minute already resulted in a higher force. 6) Caffeine and high K decreased force but only caffeine markedly decreased the inotropic effects of low Na. 7) The initial increase in force was reversed in calcium-overloaded fibers. And 8) The Na–Ca ratio necessary to maintain force is smaller for Purkinje than myocardial fibers. It is concluded that a low Na–Ca solution increases force by increasing cellular calcium stores probably in the sarcoplasmic reticulum, that the maintenance of force is critically dependent on a smaller slow inward current, and that there are substantial differences between Purkinje and ventricular muscle fibers.Supported by grants HL17451 and 27038 from the National Institutes of Health, Heart and Lung Institute.During this work Dr. Li was a New York Heart Postdoctoral Fellow. Dr. Li's present address is Searl Research and Development, 4901 Searl Parkway, Skokie, Ill. 60077.     

Short-term treatment of gastric ulcer

Gastric ulcer is relatively infrequent, and clinical trials are often based on small-sized samples. The aim of this study was to define the gold standard therapy of active gastric ulcer. We included all single- or double-blind clinical trials on the short-term treatment of gastric ulcer. All the articles published over the period 1977–1994 were reviewed. Meta-analysis was done with both fixed and random effect models; results were shown using Galbraith's radial plot. Forty-eight papers comprising 52 studies were evaluated. Cimetidine, ranitidine, and famotidine proved significantly better than placebo [odds ratio (OR) and 95% confidence interval (CI 95%) at four to six weeks were: 2.67 (2.03–3.52), 3.94 (2.28–6.80), 1.76 (1.08–2.88), respectively]. Cimetidine and ranitidine had results comparable with the newer H₂ blockers [OR (CI 95%) at four weeks: 1.16 (0.91–1.47), 1.11 (0.80–1.55), respectively]. H₂ blockers were proved comparable with either sucralfate [OR (CI 95%) at eight weeks: 0.81 (0.37–1.79)] or bismuth [OR (CI 95%) at four to six weeks: 0.67 (0.37–1.20)]. Omeprazole is more effective than H₂ blockers [OR (CI 95%) at four weeks: 2.00 (1.57–2.55)]. It is concluded that H₂ blockers are preferred to either a placebo or sucralfate for short-term gastric ulcer treatment; the newer H₂ blockers do not have significant advantages over the older types; omeprazole can be regarded as the gold standard for active gastric ulcer treatment.The statistical analysis and computing with plot program was performed by G. Leandro, MD, Biostatistician. This work was performed under the auspices of the Roberto Farini Foundation for Gastroenterological Research.     

Serotonin antagonism reduces the adverse symptoms of beta blockade

Summary Beta-adrenoceptor antagonists (beta blockers) are a well-established first-line treatment for hypertension, but they have been associated with unwanted symptoms including cold extremities, lethargy, and nightmares. Ketanserin is a serotonin S₂-receptor antagonist that has previously been shown to reduce blood pressure in hypertensive patients by reducing systemic vascular resistance. Hypertensive patients whose sitting diastolic blood pressure was 95 mmHg, despite at least 4 weeks therapy with an optimal dose of beta blocker, were selected for the study. The beta-blocker dose remained constant throughout the study, but patients were randomly allocated to receive ketanserin 20 mg twice daily, ketanserin 40 mg twice daily, or bendrofluazide 5 mg each morning plus placebo at night in addition to the beta-blocker therapy. One hundred and forty two patients completed the symptom questionnaire at randomization and after 12 weeks treatment. The treatment groups were well matched for age, sex, weight, and blood pressure. Blood pressure was reduced significantly by all treatments, and there were no between-group differences. Bendrofluazide adversely affected alertness (p<0.05) and concentration (p<0.01) whereas ketanserin had no significant effect and the ketanserin 20 mg twice daily group had better concentration than the bendrofluazide group (p<0.05). Ketanserin treatment reduced the incidence of nightmares (p<0.05 for 20 mg twice daily and 40 mg twice daily) and was an improvement over bendrofluazide treatment in this respect (p<0.05).Leg pain on walking (p<0.01) and at rest (p<0.05) was worse on bendrofluazide, whereas ketanserin treatment 20 mg twice daily improved incidence of leg pain on walking (p<0.05) and was an improvement over bendrofluazide treatment in this respect (p<0.05). Incidence of flushing was reduced by ketanserin 40 mg twice daily (p<0.01) more effectively than by bendrofluazide treatment (p<0.05).The present study indicated that serotonin antagonism by ketanserin can reduce the nightmares and sleep disturbance and reverse the deterioration in peripheral circulation that may accompany treatment with beta blockers.representing the KTN 165 study group     

Withdrawal of Neurohumoral Blockade After Cardiac Resynchronization Therapy

BackgroundThe necessity of neurohumoral blockers in patients with heart failure who demonstrate normalized ejection fractions after cardiac resynchronization therapy remains unclear.ObjectiveSThe aim of this study was to investigate the feasibility and safety of neurohumoral blocker withdrawal in patients with normalized ejection fractions after cardiac resynchronization therapy.MethodsIn this prospective, open-label, randomized controlled pilot trial with a 2 × 2 factorial design, subjects were randomized to withdrawal of renin-angiotensin-aldosterone system inhibitors and/or beta-blockers versus continuation of treatment. The primary endpoint was a recurrence of negative remodeling, defined as an increase in left ventricular end-systolic volume index of >15% at 24 months. The secondary endpoint was a composite safety endpoint of all-cause mortality, heart failure–related hospitalizations, and incidence of sustained ventricular arrhythmias at 24 months.ResultsEighty subjects were consecutively enrolled and randomized among 4 groups (continuation of neurohumoral blocker therapy, n = 20; withdrawal of renin-angiotensin-aldosterone system inhibitors, n = 20; withdrawal of beta-blockers, n = 20; and withdrawal of renin-angiotensin-aldosterone system inhibitors and beta-blockers, n = 20). Of the 80 subjects, 6 (7.5%) met the primary and 4 (5%) the secondary endpoint. However, re-initiation of neurohumoral blockers occurred in 17 subjects because of hypertension or supraventricular arrhythmias.ConclusionsThe incidence of the primary and secondary endpoints over a follow-up period of 2 years was low in both the control group and in the groups in which neurohumoral blockers were discontinued. However, neurohumoral blocker withdrawal was hampered by cardiac comorbidities. (Systematic Withdrawal of Neurohumoral Blocker Therapy in Optimally Responding CRT Patients [STOP-CRT]; NCT02200822)