Controlled hypotension: a guide to drug choice.

For half a century, controlled hypotension has been used to reduce bleeding and the need for blood transfusions, and provide a satisfactory bloodless surgical field. It has been indicated in oromaxillofacial surgery (mandibular osteotomy, facial repair), endoscopic sinus or middle ear microsurgery, spinal surgery and other neurosurgery (aneurysm), major orthopaedic surgery (hip or knee replacement, spinal), prostatectomy, cardiovascular surgery and liver transplant surgery. Controlled hypotension is defined as a reduction of the systolic blood pressure to 80-90 mm Hg, a reduction of mean arterial pressure (MAP) to 50-65 mm Hg or a 30% reduction of baseline MAP. Pharmacological agents used for controlled hypotension include those agents that can be used successfully alone and those that are used adjunctively to limit dosage requirements and, therefore, the adverse effects of the other agents. Agents used successfully alone include inhalation anaesthetics, sodium nitroprusside, nitroglycerin, trimethaphan camsilate, alprostadil (prostaglandin E1), adenosine, remifentanil, and agents used in spinal anaesthesia. Agents that can be used alone or in combination include calcium channel antagonists (e.g. nicardipine), beta-adrenoceptor antagonists (beta-blockers) [e.g. propranolol, esmolol] and fenoldopam. Agents that are mainly used adjunctively include ACE inhibitors and clonidine. New agents and techniques have been recently evaluated for their ability to induce effective hypotension without impairing the perfusion of vital organs. This development has been aided by new knowledge on the physiology of peripheral microcirculatory regulation. Apart from the adverse effects of major hypotension on the perfusion of vital organs, potent hypotensive agents have their own adverse effects depending on their concentration, which can be reduced by adjuvant treatment. Care with use limits the major risks of these agents in controlled hypotension; risks that are generally less important than those of transfusion or alternatives to transfusion. New hypotensive drugs, such as fenoldopam, adenosine and alprostadil, are currently being evaluated; however, they have disadvantages and a high treatment cost that limits their development in this indication. New techniques of controlled hypotension subscribe to the use of the natural hypotensive effect of the anaesthetic drug with regard to the definition of the ideal hypotensive agent. It must be easy to administer, have a short onset time, an effect that disappears quickly when administration is discontinued, a rapid elimination without toxic metabolites, negligible effects on vital organs, and a predictable and dose-dependent effect. Inhalation agents (isoflurane, sevoflurane) provide the benefit of being hypnotic and hypotensive agents at clinical concentrations, and are used alone or in combination with adjuvant agents to limit tachycardia and rebound hypertension, for example, inhibitors of the autonomic nervous system (clonidine, beta-blockers) or ACE inhibitors. When they are used alone, inhalation anaesthetics require high concentrations for a significant reduction in bleeding that can lead to hepatic or renal injury. The greatest efficacy and ease-of-use to toxicity ratio is for techniques of anaesthesia that associate analgesia and hypotension at clinical concentrations without the need for potent hypotensive agents. The first and oldest technique is epidural anaesthesia, but depending on the surgery, it is not always appropriate. The most recent satisfactory technique is a combination treatment of remifentanil with either propofol or an inhalation agent (isoflurane, desflurane or sevoflurane) at clinical concentrations. In light of the current literature, and because of their safety and ease of use, these two techniques are preferred.