Anesthetics toxicity

Postoperative hepatic dysfunction is typically associated with factors such as blood transfusions, hypovolemic shock, and other surgical stresses rather than volatile anesthetic toxicity. However, a small subset of individuals who have been previously exposed to halothane may develop potentially life-threatening hepatitis. The incidence of severe hepatotoxicity following exposure to halothane is in the range of one in 20,000-35,000. Obese patients who have had more than one exposure to halothane during a short time interval may be the most susceptible. There is no specific treatment for halothane hepatitis, and therefore liver transplantation may ultimately be required in the most severe cases. 

The two major forms of local anesthetic toxicity are (1) systemic effects following absorption of the local anesthetic from their site of administration and (2) direct neurotoxicity from the local effects of these drugs when high concentrations are administered in close proximity to the spinal cord and other major nerve trunks. When blood levels of local anesthetics rise rapidly, adverse effects on several major organ systems may be observed. 

All local anesthetics have the ability to produce sleepiness, light-headedness, visual and auditory disturbances, and restlessness when high plasma concentrations are produced after rapid absorption or inadvertent intravascular administration. An early symptom of local anesthetic toxicity is circumoral and tongue numbness and a metallic taste. At higher concentrations, nystagmus and muscular twitching occur, followed by tonic-clonic convulsions. Local anesthetics... 

If seizures do occur, it is important to prevent hypoxemia and acidosis. Although administration of oxygen does not prevent seizure activity, hyperoxemia may be beneficial after onset of seizures. Hypercapnia and acidosis may lower the seizure threshold, and so hyperventilation is recommended during treatment of seizures. In addition, hyperventilation increases blood pH, which in turn lowers extracellular potassium. This action hyperpolarizes the transmembrane potential of axons, which favors the resting (or low-affinity) state of the sodium channels, resulting in decreased local anesthetic toxicity. 

Neuromuscular blocking drugs (ie, succinylcholine) are occasionally used to attenuate the peripheral (motor) manifestations of convulsions associated with status epilepticus or local anesthetic toxicity. Although this approach is effective in eliminating the muscular manifestations of the seizures, it has no effect on the central processes because neuromuscular blocking drugs do not cross the blood-brain barrier. 

Postoperative hepatic dysfunction is usually associated with factors such as blood transfusions, hypovolemic shock, and other surgical stresses rather than anesthetic toxicity. However, a very... 

Two major forms of local anesthetic toxicity are recognized direct neurotoxicity from the local effects of certain agents administered around the cord or other major nerve trunks, and systemic... 

A healthy 17-year-old man received an interscalene brachial plexus block using mepivacaine 600 mg and bupivacaine 150 mg. He became disorientated and showed signs of local anesthetic toxicity, for which he was given midazolam 5 mg. Flumazenil 0.5 mg was given 23 minutes after the end of the procedure, causing opisthotonos. 

Watanabe S, Satumae T, Takeshima R, Taguchi N. Opisthotonos after flumazenil administered to antagonize midazolam previously administered to treat developing local anesthetic toxicity. Anesth Analg 1998 86(3) 677-8. 

A 59-year-old woman, grade ASA I, had psychiatric effects associated with local anesthetic toxicity after receiving bupivacaine 50 mg and mepivacaine 75 mg for an axillary plexus block. She complained of dizziness and a near death experience (464). 

Marsch SC, Schaefer HG, Castelli I. Unusual psychological manifestation of systemic local anesthetic toxicity. Anesthesiology 1998 88(2) 531-3. 

Levitt, J.D. (1975). The biochemical basis of anesthetic toxicity. Surg. Clin. North Am. 55 801-18. 

In California, six cases of cardiac arrest or severe hypoxemia associated with outpatient liposuction resulted in four deaths over a 3.5-year period, all in women aged 38-62 years one had a cardiac arrest after sedation and the administration of local anesthetic but before liposuction was started, four had respiratory difficulties and cardiac arrest after liposuction, and one had respiratory difficulties during liposuction (50). Whether the cause of morbidity and mortality in any of these cases was related to local anesthetic toxicity was not mentioned. 

A weak solution of hdocaine has sometimes been injected into excess fat before liposuction, so that the procedure can be carried out without general anesthesia. The technique is generally regarded as safe (51). However, deaths are increasingly reported, associated with local anesthetic toxicity or drug interactions (49). 

Z4. Zsigmond, E. K., and Eilderton, T. E., Survey of local anesthetic toxicity in the families of patients with atypical plasma cholinesterase. /. Oral Surg. 33, 833-837 (1975). 

Early uses of trichloroethylene included degreasing, and by 1940, a formulation of trichloroethylene named Trilene had widespread use as an anesthetic. Toxicity soon became apparent, especially after cranial nerve injuries and activated latent herpes infections resulted from anesthesia (Defalque 1961 Humphrey and McClelland 1944). Other important halogenated hydrocarbons include methylene chlo-... 

Lidocaine, mexiletine, and tocainide rarely cause typical local anesthetic toxicity (ie, CNS stimulation, including convulsions) cardiovascular depression (usually minor) and allergy (usually rashes but may extend to anaphylaxis). Tocainide may cause agranulocytosis. These drugs may also precipitate arrhythmias, but this is less common than with class lA drugs. Hyperkalemia increases cardiac toxicity. 

Acidosis due to tissue h) xia favors local anesthetic toxicity because these drugs bind more avidly (or release less rapidly) from the sodium channel binding site when they are in the charged state. (Note that onset of therapeutic effect may be slower because charged local anesthetics penetrate the membrane less rapidly see text.) Hyperkalemia depolarizes the membrane, which also favors local anesthetic binding. Oxygenation reduces both acidosis and hyperkalemia. The answer is (D). 

A, Sweitzer BJ, Cutter TW. Was case report a case of unrecc nized local anesthetic toxicity In respc se AncsthAnalg (2003) 96,1 5... 

The authors noted that the exact etiology of the cardiogenic shock could not be elucidated, as it could have been caused by local anesthetic toxicity, or adrenaline, or a combination of the two. 

Nervous system Local anesthetic toxicity, including seizures and prolonged anesthesia, has been reported as a complication of interscalene plexus block, even within safe dose limits and without intravascular placement [5", 6" ]. Two further cases have been reported [7" ]. 

The authors suggested, in line with current recommendations, that early and sufficient use of lipid emulsion after a presumptive diagnosis of local anesthetic toxicity can produce a good outcome. 

Plasma lidocaine concentrations and symptoms of local anesthetic toxicity have been reported in five oriental patients after tumescent local anesthesia [41 ]. The patients received lidocaine in total doses of 20-35 mg/kg. The plasma lidocaine concentration 3 hours later did not exceed the toxic concentration of 5 pg/ml and was significantly lower at 8 hours. 

Nishiyama T, Komatsu K. Local anesthetic toxicity in interscalene block clinical series. Minerva Anestesiol 2010 76 1088-90. 

Nervous system A 22-year-old woman developed paresthesia, a metallic taste, and hot flushes within 20 minutes of administration of intravenous spiramycin for toxoplasmosis during labor [80" ]. The adverse reactions were initially attributed to local anesthetic toxicity associated with epidural analgesia however, epidural catheter aspiration was negative, suggesting that the catheter was not placed intravenously and the temporal relation to spiramycin administration suggested that the drug was the more probable cause. 

Julliac B, Theophile H, Begorre M, Richez B, Haramburu F. Side effects of spiramycin masquerading as local anesthetic toxicity during labor epidural analgesia. Int J Obstet Anesth 2010 19(3) 331-2. 

Evaluate for toxicity due to intravascular placement symptoms such as lightheadedness, dizziness, a metallic taste, ringing in the ears, or perioral numbness signify potential intravascular injection and risk for toxicity. Local anesthetic toxicity can also cause late symptoms such as hypotension, blurry vision, seizures, and cardiac arrhythmias. Stay with the patient for the first 10 minutes after a test dose or bolus. 

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