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Pathophysiology of Circulatory Failure

circulatory failure
Circulatory failure, or the inability of the heart to provide sufficient cardiac output to sat­isfy tissue metabolic requirements, is the most important and most common cause of altered pharmacokinetics during cardiac emergencies. Circulatory failure may result from decreased myocardial contractility, arrhythmias that allow insufficient time for diastolic filling or impair atrioventricular synchrony, circulatory stresses such as increased afterload or hypovolaemia, valvular dysfunction, tamponade, or a variety of less common insults.

Regardless of the aetiology, circulatory fail­ure elicits characteristic compensatory haemodynamic adjustments, mediated in large part by activation of the sympathetic nervous system [Peniel & Benowitz 1984; Benowitz & Meister 1978]. Enhanced sympathetic tone in­creases cardiac contractility and peripheral vas­cular resistance, both of which serve to main­tain arterial blood pressure. The increase in peripheral vascular resistance, however, is not uniform among different vascular beds.

Synopsis of Important Principles

intensive supportive therapy1. Specific antidotal therapy is available for very few poisons. The mainstay of treatment of severe poisoning is intensive supportive therapy and good nursing care.

2. The great majority of poisoned patients recover with intensive supportive therapy alone, and enthusiastic claims for the success of other treatment often cannot be justified.

3. With some important exceptions, the management of poisoning is not altered by knowledge of plasma drug concentrations. There are many pitfalls in the interpretation of drug concen­trations in poisoned patients, especially when nonspecific analytical methods are used.

Gastric Aspiration and Lavage

Gastric AspirationAlthough unabsorbed drug in the stomach may be removed by gastric aspiration and lav­age its usefulness in practice has been seriously questioned (Proudfoot 1984). Most drugs and poisons seem to be absorbed rapidly and this technique is unlikely to be productive more than 4 hours after ingestion, unless gastric emptying has been delayed by opioid analgesics, anti­cholinergic agents, central nervous system de­pressants, and possibly salicylates. In such circumstances gastric lavage may be worthwhile up to 12 hours after ingestion.

It is said to be contraindicated after ingestion of corrosives and hydrocarbons such as paraffin because of the risks of perforation and lipoid pneumonia, respectively.

Medical LabThe idea that drug concentrations could be measured and used to guide therapeutic deci­sions was first applied to quinidine when it was used to convert the cardiac rhythm of patients with atrial fibrillation to sinus rhythm (Sokolow & Ball 1956).

Although quinidine is rarely used for this purpose today, because of the advent of DC cardioversion, this study is still almost unique because it defined a target concentration based upon both the probability of therapeutic success and of toxicity.

Therapeutic drugTherapeutic drug monitoring is based upon the collaboration between a health care provider (clinician, pharmacist, nurse) responsible for making quantitative and qualitative decisions about drug treatment and the clinical labora­tory providing analytical services for the measurement of drug concentrations. The in­formation provided by a drug concentration measurement is generally greater than for other substances measured by the laboratory.

This is because, unlike say sodium or glucose, the in­take of a drug is quite well known and the pro­cesses of distribution and elimination are usu­ally very simple and not under the control of a multitude of homeostatic controlling reflexes.