The Management of Hyponatremia in Cirrhosis: Should it Be Pharmacologic?

Hyponatremia is a common complication of patients with advanced cirrhosis that is associated with increased morbidity and mortality. Patients with cirrhosis may develop two types of hyponatremia: hypovolemic or hypervolemic hyponatremia. Hypervolemic hyponatremia is the most frequent type of hyponatremia that develops in patients with advanced liver disease and is the consequence of impairment in the renal capacity to eliminate solute-free water. The pathogenesis of these increased solute-free water retention involves several factors, but the most important one is a non-osmotic hypersecretion of vasopressin. The treatment of choice for hypervolemic hyponatremia is fluid restriction. Vaptans, drugs that are selective antagonists of vasopressin V2 receptors, emerged as the first pharmacological treatment of hypervolemic hyponatremia in cirrhosis with promising results. However, satavaptan was withdrawn from development for safety reasons and tolvaptan is not recommended in patients with liver disease. Therefore, currently there is no effective and safe pharmacological approach available for the management of hypervolemic hyponatremia in cirrhosis.     

Neurohormonal Intervention to Reduce Sudden Cardiac Death in Heart Failure: What is the Optimal Pharmacologic Strategy?

Sudden cardiac death (SCD) accounts for up to 50% of deaths in patients with heart failure (HF), depending on severity of symptomatic impairment and left ventricular dysfunction. Neurohormonal therapy directed at the renin-angiotensin-aldosterone system may reduce the propensity to SCD through improved hemodynamic responsiveness, reduced sympathetic tone in the myocardium and inhibition of cardiac remodelling. Angiotensin converting enzyme (ACE) inhibitors reduce overall mortality in chronic HF, the greatest benefit appearing to arises from reduction of HF progression rather than SCD. In HF patients who experience myocardial infarction (MI) reduced incidence in SCD may make a more marked contribution to the mortality benefits of ACE inhibition. Addition of beta-blocker therapy to ACE inhibition has consistently resulted in a reduction in SCD in patients with either mild-to-moderate or severe HF, and in the presence or absence of MI; the reduction in SCD is of the order of one-third versus placebo. Aldosterone blockade reduces the risk of SCD in advanced chronic heart failure (when added to ACE inhibitor) and in HF associated with acute MI (when given in addition to both ACE inhibitor and beta blocker). The evidence base suggests that for maximal SCD risk reduction in HF, beta-blocker therapy is advisable in combination with standard ACE inhibitor therapy, with addition of aldosterone blockade to this regimen for particular groups of heart failure patients.     

Does the level of stapled ileoanal anastomosis influence physiologic and functional outcome?

PURPOSE: The aim of this investigation was to ascertain how the length of anal canal preserved above the dentate line in stapled end-to-end ileoanal anastomosis influenced late outcome. METHODS: Two groups, high cuff group and low cuff group of nine subjects with stapled anastomosis, matched for sex, age, pouch configuration, and mean follow-up, representing the highest (median, 2.5 cm) and lowest (median, 0.7 cm) anal cuff lengths in our series, were selected. Physiologic and functional parameters were appraised preoperatively, at the time of ileostomy closure, and at 1, 3, 6, and 12 months after reestablishment of intestinal continuity. RESULTS: At one year, the drop in mean anal canal resting pressure was 13 percent in the high cuff group (not signficant) and 31 percent in the low cuff group (P <0.05); mean maximum squeezing pressure did not differ significantly from preoperative values in both groups. The mean volume of the ileal pouch was higher in the low cuff group at all insufflation pressures. The rectoanal inhibition reflex reappeared in four high cuff group patients and in none of the low cuff group patients. Mean distention pressure (cm H ₂ O) and volume (ml) eliciting urge sensation were 80 and 360 in the low cuff group compared with 40 and 240 in the high cuff group (P ?0.05). Daytime bowel movements and night incontinence were significantly better in the low cuff group. No statistical differences were observed for night stool frequency, daytime incontinence, pad use (day and night), discrimination between gas and feces, ability to defer evacuation, and difficulty in emptying the pouch. CONCLUSION: Patients with stapled anastomoses and a low rectal cuff length, despite presenting lower anal resting pressure and absence of rectoanal inhibition reflex, had a better functional outcome in terms of continence than those with a high cuff length.     

Direct physiologic assessment of anomalous aortic origin of a coronary artery: Enhanced diagnostics or illusion of insight?

• Fractional flow reserve and intravascular ultrasound evaluation are technically feasible in patients with congenitally abnormal coronary arteries arising from the wrong aortic sinus, including those with a slitlike orifice and presumed intramural course.
• Incorporation of fractional flow reserve and intravascular ultrasound into the evaluation of adults with anomalous coronary artery origins will provide additional data and may be useful in risk assessment, although these data should be interpreted with caution, as the validity of fractional flow reserve findings in this population has not been established.
• The applicability of fractional flow reserve thresholds for acute coronary syndromes to patients with anomalous coronary artery origins is unknown. Further study will be needed to determine how best to incorporate fractional flow reserve data in the evaluation and management of these patients.

     

Recovery of physiologic and clinical function after low anterior resection of the rectum for carcinoma: Myth or reality?

PURPOSE: The aim of this study was to examine the serial changes that take place in the first year after low anterior resection for rectal carcinoma, in terms both of anorectal physiology and clinical bowel function. Our hypothesis was that some patients never regain satisfactory anorectal function, because the operative procedure leads to permanent impairment of anorectal reflex and motor function. METHOD: Nineteen patients underwent serial tests of anorectal function, before and for one year after low anterior resection. The median level of the anastomosis above the anal high-pressure zone was 3 (range, 1–6) cm. RESULTS: Anal resting pressure (median (interquartile range)) was significantly decreased three months after operation (62 (46–72) cm H2O) and one year after operation was still significantly less (58 (48–73) cm H2O) than before operation (77 (58–93) cm H2O)(P<0.01). Maximum tolerated volume in the neorectum decreased from 130 (88–193) ml before operation to 80 (51–89) ml three months after operation (P<0.005) but returned to preoperative values by six months (125 (60–140) ml) (P=not significant) and remained at these values one year after operation. The volume in the neorectal balloon required to elicit a maximum rectoanal inhibitory reflex was significantly less three months after operation than before operation (50 (43–60) ml compared with 100 (73–100) ml;P<0.005); one year after operation, the volume required was still significantly less than before operation (50 ml vs.100 ml) (P<0.015). Bowel frequency increased from 1 (1–2) in 24 hours before operation to 4 (2–5) times in 24 hours after operation and remained at 4 times in 24 hours throughout the first year after operation. Three months after operation, 53 percent of patients experienced some degree of fecal leakage and 24 percent experienced urgency of defecation. These aspects of bowel function improved with time, but even one year after operation, 29 percent of patients continued to experience fecal leakage and 18 percent wore a protective pad. CONCLUSIONS: Anal resting pressure decreased significantly after low anterior resection and did not recover in the course of the first year after operation. Moreover, the volume of an air-filled balloon in the neorectum that was required to elicit maximum inhibition of the anal sphincter was significantly less after anterior resection than before operation. These long-term and presumably permanent changes in physiologic behavior of the anoneorectum after low anterior resection provide an explanation for the failure of some patients to regain satisfactory bowel function following that procedure.Read at the meeting of The American Society of Colon and Rectal Surgeons, Orlando, Florida, May 8 to 13, 1994.     

Pharmacologic approaches to rhythm versus rate control in atrial fibrillation--where are we now?

Until recently, contemporary drug treatment of atrial fibrillation (AF) focused primarily on restoration and maintenance of sinus rhythm, predicated on the belief that if AF is abolished then problems associated with AF would be abolished too. Recently completed clinical trials using drug therapy and comparing maintenance of sinus rhythm with control of ventricular rate have challenged this assumption, showing that simple control of ventricular rate with anticoagulation is an acceptable primary therapy, notably in older patients with persistent AF, minimally symptomatic or asymptomatic, and at increased risk for thromboembolic events. However, rate control and anticoagulation is not a panacea; existing trial results should not be interpreted to mean all patients should be treated with the rate control approach. Despite the limited efficacy and poor safety of current antiarrhythmic drugs, strategies for maintenance of sinus rhythm remain justified in many patients, such as those with first-episode AF, highly symptomatic patients, younger patients, and those with a history of congestive heart failure (CHF). Commonly used current and some investigational agents designated for “rhythm control” have enough pharmacologic overlap with rate control agents to be considered to have a dual mode of action, simultaneously addressing both rhythm and rate control. Furthermore, there is much interest in non-pharmacologic therapies, such as radiofrequency ablation, for rhythm control. The lack of appropriately designed and controlled trials at this time makes it difficult to determine the place of radiofrequency ablation and its impact on the rhythm versus rate question.     

The interruption of thyroid and interrenal and the inter-hormonal interference in fish: does it promote physiologic adaptation or maladaptation?

Endocrines, the chief components of chemical centers which produce hormones in tune with intrinsic and extrinsic clues, create a chemical bridge between the organism and the environment. In fishes also hormones integrate and modulate many physiologic functions and its synthesis, release, biological actions and metabolic clearance are well regulated. Consequently, thyroid hormones (THs) and cortisol, the products of thyroid and interrenal axes, have been identified for their common integrative actions on metabolic and osmotic functions in fish. On the other hand, many anthropogenic chemical substances, popularly known as endocrine disrupting chemicals, have been shown to disrupt the hormone–receptor signaling pathways in a number fish species. These chemicals which are known for their ability to induce endocrine disruption particularly on thyroid and interrenals can cause malfunction or maladaptation of many vital processes which are involved in the development, growth and reproduction in fish. On the contrary, evidence is presented that the endocrine interrupting agents (EIAs) can cause interruption of thyroid and interrenals, resulting in physiologic compensatory mechanisms which can be adaptive, though such hormonal interactions are less recognized in fishes. The EIAs of physical, chemical and biological origins can specifically interrupt and modify the hormonal interactions between THs and cortisol, resulting in specific patterns of inter-hormonal interference. The physiologic analysis of these inter-hormonal interruptions during acclimation and post-acclimation to intrinsic or extrinsic EIAs reveals that combinations of anti-hormonal, pro-hormonal or stati-hormonal interference may help the fish to fine-tune their metabolic and osmotic performances as part of physiologic adaptation. This novel hypothesis on the phenomenon of inter-hormonal interference and its consequent physiologic interference during thyroid and interrenal interruption thus forms the basis of physiologic acclimation. This interfering action of TH and cortisol during hormonal interruption may subsequently promote ecological adaptation in fish as these physiologic processes ultimately favor them to survive in their hostile environment.