General Approach to the Poisoned Patient

Poisoning and ingestions constitute an increasing amount of morbidity and mortality nationwide. According to the American Association of Poison Control Centers (AAPCC), 2.2 million exposures were reported in 2013, and ingestions are currently the leading cause of injury-related death in the United States. Exposures include intentional overdose or suicide attempts, accidental overdose in drug abusers or children, and work-related injuries or acts of terrorism. According to the AAPCC, 50% of exposures are in children less than 5 years old and 80% of exposures are unintentional. When it comes to the unstable undifferentiated and possibly poisoned patient, one must take a stepwise approach similar to that for any critically ill patient, This review covers the pathophysiology, stabilization and assessment, diagnosis and treatment, and disposition and outcomes of poisoning. Figures show The Full Outline of Unresponsiveness (FOUR) scale, a patient with methemoglobinemia, a hand with scaling due to mercury poisoning, an electrocardiogram with examples of QT prolongation and QRS widening, and an electrocardiogram of bidirectional ventricular tachycardia, pathognomonic of digitalis glycoside poisoning. Tables list a stepwise approach to a potentially poisoned patient, a general approach to the poisoned patient, heart rate, toxidromes, anticholinergic toxidrome, cholinergic toxidrome, Glasgow Coma Scale, toxins and associated odors, electrocardiogram findings, causes of anion-gap metabolic acidosis, and antidotes. This review contains 5 highly rendered figures, 13 tables, and 23 references Key words: Poison ingestion, Accidental poisoning, Toxidrome, Accidental overdose

Electrochemical Na+ and Ca2+ gradients drive coupled-clock regulation of automaticity of isolated rabbit sinoatrial nodal pacemaker cells

Coupling of an intracellular Ca2+ clock to surface membrane ion channels, i.e., a “membrane clock, ” via coupling of electrochemical Na+ and Ca2+ gradients ( ENa and ECa, respectively) has been theorized to regulate sinoatrial nodal cell (SANC) normal automaticity. To test this hypothesis, we measured responses of [Na+]i, [Ca2+]i, membrane potential, action potential cycle length (APCL), and rhythm in rabbit SANCs to Na+/K+ pump inhibition by the digitalis glycoside, digoxigenin (DG, 10–20 μmol/l). Initial small but significant increases in [Na+]i and [Ca2+]i and reductions in ENa and ECa in response to DG led to a small reduction in maximum diastolic potential (MDP), significantly enhanced local diastolic Ca2+ releases (LCRs), and reduced the average APCL. As [Na+]i and [Ca2+]i continued to increase at longer times following DG exposure, further significant reductions in MDP, ENa, and ECa occurred; LCRs became significantly reduced, and APCL became progressively and significantly prolonged. This was accompanied by increased APCL variability. We also employed a coupled-clock numerical model to simulate changes in ENa and ECa simultaneously with ion currents not measured experimentally. Numerical modeling predicted that, as the ENa and ECa monotonically reduced over time in response to DG, ion currents ( ICaL, ICaT, If, IKr, and IbNa) monotonically decreased. In parallel with the biphasic APCL, diastolic INCX manifested biphasic changes; initial INCX increase attributable to enhanced LCR ensemble Ca2+ signal was followed by INCX reduction as ENCX ( ENCX = 3 ENa − 2 ECa) decreased. Thus SANC automaticity is tightly regulated by ENa, ECa, and ENCX via a complex interplay of numerous key clock components that regulate SANC clock coupling.

Management of digoxin poisoning

Despite a gradual decline in the clinical use of digitalis glycosides, digitalis toxicity continues to be responsible for substantial morbidity and mortality, particularly among the elderly. Digitalis poisoning may occur acutely, after intentional overdose, but is more often seen as the result of chronic intoxication among patients receiving digitalis therapy. Clinical findings in chronic digitalis poisoning are often subtle. The astute clinician will enquire about digitalis use in older patients with vague complaints and will not be dissuaded from considering digitalis toxicity in the face of a ‘therapeutic’ digitalis blood concentration. Two digitalis preparations continue to be used with frequency, depending on geography. Digoxin is the digitalis glycoside of choice in the USA, while digitoxin prevails in some parts of Europe. While the methods and half-lives of elimination differ markedly for these two substances, the approach to poisoning by either is similar. Advanced age, underlying cardiovascular disease, and severe hyperkalaemia represent poor prognostic factors in digitalis poisoning. Early administration of digitalis Fab fragments should be undertaken when life-threatening symptoms are present. Prophylactic therapy with reduced doses of Fab fragments should be strongly considered for less serious toxicity.

Angiotensin-Converting Enzyme Inhibitors in Congestive Heart Failure: Practice versus Guidelines

Background: Angiotensin-converting enzyme (ACE) inhibitors decrease morbidity and mortality in patients with systolic heart failure. In the practice of cardiology, ACE inhibitors are insufficiently prescribed by cardiologists. Objective: To measure the deviation between observed practice and clinical practice guidelines (CPGs), and to identify factors contributing to the deviation. Methods: CPGs have been developed from available international guidelines via a procedure involving a consensus group. A practice survey was conducted on 208 patients less than 75 years old hospitalized in public hospital cardiology units. Factors associated with nonadherence to CPGs were identified among characteristics of patients, practitioners, and cardiology units in logistic regression models. Results: In patients for whom the prescription of ACE inhibitors was not contraindicated, ACE inhibitor therapy was not initiated in 14%, and the CPR dosages were not attained in 51.2% of the cases. Factors associated with treatment not being initiated were age over 60 years (p = 0.001), increased ejection fraction (p = 0.005), and treatment with diuretics (p = 0.001) and digitalis glycosides (p = 0.008) at hospital admission. Factors associated with prescription of subtarget doses were age over 60 years (p = 0.024), low serum potassium concentration (p = 0.014), and absence of digitalis glycoside treatment (p = 0.039) at the start of ACE inhibitor administration. Conclusions: Our work has shown that cardiologists tend to adapt their prescription of ACE inhibitors to clinical situations that are not considered relevant in international guidelines. The implementation of CPGs in cardiology units should target adequate information about these situations.

Management of congestive heart failure: is the role of positive inotropic therapy fading?

Significant strides have been made in the medical therapy of chronic CHF in the past two decades. Treatment has evolved from therapy based on the older concepts of the pathophysiology of CHF to evidence-guided therapy supported by results of major landmark studies that expand the understanding of the pathophysiology. Attenuation of neurohumoral activation is now a goal of pharmacological therapy, and we know that agents that offer hemodynamic and early clinical improvement may not necessarily prolong survival-unless they also modulate these neurohormonal systems. Positive inotropic therapy (e.g., use of a digitalis glycoside) is no longer considered essential in patients with CHF in sinus rhythm. Although impressive hemodynamic benefits can be observed with the use of positive inotropic agents, long-term treatment with these drugs has not produced clinical benefits and may increase mortality. Long before the current concerns about the use of positive inotropic therapy for CHF, cardiovascular physiologists had advised that contractility does not equate with overall cardiac performance. Stimulation of myocardial contractility is a property of digoxin therapy. However, cardiac function is governed by four determinants: preload, afterload, rhythm, and contractility. All four require control. Treatment aimed at reducing preload and afterload and improving arrhythmias can achieve cardiac compensation by reducing cardiac work without the need for digoxin therapy or other inotropic drugs.

Altered vagal and sympathetic control of heart rate in left ventricular dysfunction and heart failure

We investigated alterations in autonomic control of heart rate in conscious dogs with left ventricular (LV) dysfunction in the presence and absence of heart failure (HF) due to rapid pacing. In dogs with LV dysfunction but no HF, indexes of parasympathetic control decreased significantly after only 4 days of pacing. In dogs with fully developed HF, both vagal and sympathetic contributions were small. Vagomimetic doses of atropine increased both R-R interval (419 ± 25 to 466 ± 34 ms, P < 0.05) and standard deviation (SD) of the R-R interval (13 ± 2 to 34 ± 9 ms, P < 0.05). The digitalis glycoside deslanoside (Cedilanid-D) alone prolonged R-R interval (420 ± 33 to 492 ± 44 ms, P < 0.01) and tended to increase SD (14 ± 4 to 28 ± 8 ms, P = 0.08). After Cedilanid-D, low-dose atropine resulted in no significant further change in R-R interval or SD. These data indicate that changes in vagal control of heart rate become apparent at a very early developmental stage of LV dysfunction, and we speculate that this may provide important prognostic information in patients who are at risk for developing progressive myocardial dysfunction and HF. autonomic nervous system; digitalis glycoside; -blockade; low-dose atropine; pacing-induced heart failure Submitted on March 25, 1994 Accepted on August 17, 1994