P Pu ur rp po os se e: : This two-part review summarizes the current knowledge of physiological mechanisms, pharmacological modalities and controversial issues surrounding preemptive analgesia.S So ou ur rc ce e: : Articles from 1966 to present were obtained from the MEDLINE databases. Search terms included: analgesia, preemptive; neurotransmitters; pain, postoperative; hyperalgesia; sensitization, central nervous system; pathways, nociception; anesthetic techniques; analgesics, agents.P Pr ri in nc ci ip pa al l f fi in nd di in ng gs s: : The physiological basis of preemptive analgesia is complex and involves modification of the pain pathways. The pharmacological modalities available may modify the physiological responses at various levels. Effective preemptive analgesic techniques require multi-modal interception of nociceptive input, increasing threshold for nociception, and blocking or decreasing nociceptor receptor activation. Although the literature is controversial regarding the effectiveness of preemptive analgesia, some general recommendations can be helpful in guiding clinical care. Regional anesthesia induced prior to surgical trauma and continued well into the postoperative period is effective in attenuating peripheral and central sensitization. Pharmacologic agents such as NSAIDs (non-steroidal anti-inflammatory drugs) opioids, and NMDA (Nmethyl-D-aspartate) -and alpha-2-receptor antagonists, especially when used in combination, act synergistically to decrease postoperative pain.C Co on nc cl lu us si io on n: : The variable patient characteristics and timing of preemptive analgesia in relation to surgical noxious input requires individualization of the technique(s) chosen. Multi-modal analgesic techniques appear most effective.Objectif : La présente revue, en deux parties, résume les connaissances actuelles sur les mécanismes physiologiques et les modalités pharmacologiques de lanalgésie préventive ainsi que sur les questions controversées qui lentourent.Sources : Des articles, de 1966 à aujourdhui, obtenus à partir des bases de données MEDLINE. Les termes de la recherche compren-
Principal findings: In Part I of this review article, techniques and agents that attenuate or prevent central and peripheral sensitization were reviewed. In Part II, the conditions required for effective preemptive techniques are evaluated. Specifically, preemptive analgesia may be defined as an antinociceptive treatment that prevents establishment of altered central processing of afferent input from sites of injury. The most important conditions for establishment of effective preemptive analgesia are the establishment of an effective level of antinociception before injury, and the continuation of this effective analgesic level well into the post-injury period to prevent central sensitization during the inflammatory phase. Although single-agent therapy may attenuate the central nociceptive processing, multimodal therapy is more effective, and may be associated with fewer side effects compared with the high-dose, single-agent therapy.
More than 26 million Americans suffer with cataracts, and with 3.6 million cataract extractions performed annually in the United States, it is the most common surgical procedure. The integrity of the delicate structures of the eye that mediate vision is dependent on the intraocular pressure (IOP). Yet, IOP acts to compress the vessels within the globe-akin to a Starling resistor-and is a key component that determines the ocular perfusion pressure, defined as the difference between arterial pressure and IOP. The retina is one of the most metabolically active tissues in the body, and its functional integrity is dependent on an adequate blood supply, with retinal function linearly related to the ocular perfusion pressure. Retinal cell death has been demonstrated at low perfusion pressures (below 50 mm Hg). Modern ophthalmic surgery involves globe irrigation, manipulation, and instrumentation, resulting in dynamic pressure fluxes within the eye. Marked elevations of IOP (up to 4-5 times the normal value) with consequent borderline retinal and optic disk perfusion pressures occur for prolonged periods during many ophthalmic procedures. General surgeries, including laparoscopic, spinal, and cardiac procedures, especially, with their demand for steep Trendelenburg or prolonged prone positioning and/or hypotensive anesthesia, can induce IOP changes and ocular perfusion imbalance. These rapid fluctuations in IOP, and so in perfusion, play a role in the pathogenesis of the visual field defects and associated ocular morbidity that frequently complicate otherwise uneventful surgeries. The exact etiology of such outcomes is multifactorial, but ocular hypoperfusion plays a significant and frequently avoidable role. Those with preexisting compromised ocular blood flow are especially vulnerable to intraoperative ischemia, including those with hypertension, diabetes, atherosclerosis, or glaucoma. However, overly aggressive management of arterial pressure and IOP may not be possible given a patient's comorbidity status, and it potentially exposes the patient to risk of catastrophic choroidal hemorrhage. Anesthetic management significantly influences the pressure changes in the eye throughout the perioperative period. Strategies to safeguard retinal perfusion, reduce the ischemic risk, and minimize the potential for expulsive bleeding must be central to the anesthetic techniques selected. This review outlines: important physiological principles; ophthalmic and general procedures most likely to develop damaging IOP levels and their causative factors; the effect of anesthetic agents and techniques on IOP; recent scientific evidence highlighting the significance of perfusion changes during surgery; and key aspects of postoperative visual loss and management approaches for high-risk patients presenting for surgery.
Neuroleptic malignant syndrome (NMS) and malignant hyperthermia (MH) may have a common pathogenic mechanism; therefore, it has been suggested that known triggering agents for MH (such as succinylcholine) should be avoided in patients with NMS. Electroconvulsive therapy (ECT) continues to play a major therapeutic role in contemporary psychiatry, and succinylcholine has been the muscle relaxant of choice in attenuating violent muscle contractions induced by ECT. Mivacurium is a non-depolarizing muscle relaxant with a relatively rapid onset and a short duration of action, and to date it has been proved safe in MH-susceptible patients. In this case report, following succinylcholine use during ECT, a patient with NMS developed an increase in temperature and serum creatine kinase (CK) level, possibly due to an MH reaction. Since the patient's mental status necessitated further ECT, mivacurium was administered during subsequent treatment and resulted in effective attenuation of muscle contractions without elevation of patient temperature or CK levels. In addition, there was no marked prolongation of the anaesthetic. Mivacurium is a suitable agent for patients with NMS undergoing ECT, as it has not been associated with precipitation of an MH response.
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