Liver anaesthesia

Hughes HM, George IM, Evans JC, et al. 1991. The role of the liver in the production of free radicals during halothane anaesthesia in the rat. Biochem J 277 795-800. 

The development of alcoholism is often insidious, proceeding from frequent drunkenness to dependence over years. Since this is so, and since alcohol may interact with other treatment (other psychoactive substances and via its effects on the liver), a careful check of a patient s intake is an important part of the medical history. It is vital to know about alcohol abuse before anaesthesia, since it may make the anaesthetic difficult and alcohol withdrawal may complicate the recovery period. 

Enflurane is metabolised by the cytochrome P-450 series, specifically P-450 2E1, but the agent is much less extensively metabolised than halothane (see above). Metabolites include trifluoroacetic acid (TEA) and inorganic fluoride ion. A small number of cases of enflurane hepatitis have been reported but the overall incidence of liver damage following enflurane anaesthesia is estimated to be 1 in 800000. Clinical studies have failed to detect any significant effects of enflurane on liver function even when given repeatedly. 

Halothane-related hepatitis was first reported in 1958 just two years after the drug s introduction. During subsequent years it became clear from the volume of reports that there was a very small excess risk of liver failure after halothane anaesthesia, particularly when the drug was administered more than once over a short time period. The medicolegal implications of this were profound and did much to promote the search for a safer alternative agent. 

Onset of anaesthesia is as rapid though not as smooth as after thiopentone administration, but recovery is more rapid with methohexitone and occurs within 2-5 minutes through redistribution. Drowsiness persists for much longer as the drug is slowly metabolised in the liver. While methohexitone has been reported to cause occasional EEG seizure-like activity in epileptics the drug also possesses anticonvulsant properties. 

Most drugs used in anaesthesia are metabolised in the liver by phase I reactions, mediated by cytochrome P-450 enzymes. These are susceptible to destruction by cirrhosis, so that the biotransformation of drugs, such as opioids (except morphine), benzodiazepines, barbiturates, and inhalational agents, may be markedly altered in severe liver disease. These enzymes are found in the centrilobular areas, which are more prone to hypoxia. In contrast, the enzymes responsible for phase II reactions, found predominantly in the peripheral areas, often function normally even in advanced disease. The disposition of benzodiazepines that are eliminated primarily by glucuronidation, e.g. lorazepam and oxazepam, are unaffected by chronic liver disease. For drugs with low hepatic extraction, advanced hepatocytic dysfunction decreases phase I and II biotransformation with a reduced clearance and prolongation of the elimination half-life. This is often partially offset by an increased free fraction due to decreased protein binding. 

The best anaesthetic vapour was found to be a 1 2 3 mixture of alcohol, chloroform, and ether, known as ACE. Despite being widely used, it was always known that ACE presented a risk, and yet it was the anaesthetic of choice for more than 100 years. Ether caused serious fires and explosions in operating theatres and while the risk of this was small - about one serious incident every 100,000 operations - it was alarming when it happened. Chloroform was not a fire risk but it could be deadly to some patients, killing them within minutes in certain tragic cases, and seriously damaging the liver of others. (Nitrous oxide was less risky, and continues to be used even today, but it does not produce deep anaesthesia.)... 

Newaz MA, Yousefipour Z, Nawa NN (2005) Modulation of nitric oxide synthase activity in brain, liver, and blood vessels of spontaneously hypertensive rats by ascorbic acid protection from free radical injury. Qin Exp Hypertens 27(6) 497-508 Nunn JF, Chanarin I, Taimer AG, Owen ER (1986) Megaloblastic bone marrow changes after repeated nitrous oxide anaesthesia. Reversal with fofinicacid. Br J Anaesth 58(12) 1469-1470 Parker WD Jr, Hass R, Stumpf DA, Parks J, Eguren LA, Jackson C (1984) Brain mitochondrial metabolism in experimental thiamine deficiency. Neurology 34(11) 1477-1481... 

Radiofrequency thermal ablation (RFTA) S. Rossi et al. (1990, 1993) were the first to introduce this procedure. Under analgosedation and local anaesthesia, an expandable, cooled-tip needle electrode is inserted per-cutaneously into the tumour with the help of US, CT or MR guidance. There are various types of probes with some differences. Due to high-frequency alternating current (480-500 kHz), the tumour tissue is gradually heated (up to max. 105 °C). A necrosis voume of 4(-5) cm in diameter can be achieved. An indication is given for 1-3 foci, each with a maximum size of 5 cm in diameter. This also applies to compromised liver func-... 

Brown TC, Gregory M, Bell B, Campbell PC. Liver tumours and muscle relaxants. Electromyographic studies in children. Anaesthesia 1987 42(12) 1284-6. 

Abdel Salam AR, Drummond GB, Bauld HW, Scott DB. Clearance of indocyanine green as an index of liver function during cyclopropane anaesthesia and induced hypotension. Br J Anaesth 1976 48(3) 231-8. 

Pumford N R, Halmes N C, Hinson J A 1997 Covalent binding of xenobiotics to specific proteins in the liver. Drug Metabolism Reviews 29 39-57 Purchase I F 1966 Cardiac arrhythmias occur during halothane anaesthesia in cats. British Journal of Anaesthesia 38 13-22... 

These act almost instantaneously, i.e., within a few seconds after administration. Because of this peculiar characteristics they are usually employed to produce general anaesthesia and to control convulsions. They may be used either alone or in conjimction with inhalation anaesthesia. After administration, they are first deposited in adipose tissues but are eventually dependent on the liver and kidney for their ultimate metabolic degradation and elimination. 

Another study found that 26 ehronie aleoholies (drinkers of about 40 g of aleohol daily, with no evidenee of liver impairment) needed about one-third more propofol to induee anaesthesia than another 20 patients who only drank soeially. However, there was great interindividual variation in the aleoholie group. ... 

A randomised, placebo-controlled study involving 60 patients found that a 5000 unit/kg intravenous bolus dose of ulinastatin given before induction of anaesthesia, and again 2 minutes before intravenous vecuronium lOOmicrograms/kg, delayed the onset of neuromuscular blockade compared with placebo (250 compared with 214 seconds). The recovery from neuromuscular block (measured as return of post-tetanic count) was significantly shorter after ulinastatin than placebo (11 compared with 17.7 minutes). The effects of ulinastatin were thought to be due to an increase in the release of acetylcholine at the neuromuscular junction and enhanced vecuronium elimination due to increases in liver blood flow and urine volume. ... 

Several other cases of hepatitis resulting from occupational exposure to halo-thane have been reported. Thus, there is little doubt that hepatitis may follow the inhalation of this anaesthetic. Extensive surveys of post-operative jaundice have also been carried out. A summary of the findings will be given here. Despite numerous reports in the literature of liver damage in patients who had halothane anaesthesia, there is still considerable controversy between anaesthetists and pathologists as to whether the hepatitis and halothane are causally related. 

Smith MGM, Golding PL, Eddleston ALWF, Mitchell CG, Kemp A, Williams R (1972) Cell-mediated immune responses in chronic liver diseases. Br Med J 1 527-530 Stier A (1968) The biotransformation of halothane. Anesthesiology 29 388-390 Sutton JA (1972) A brief history of steroid anaesthesia before althesin (CT 1341). Postgrad Med J [Suppl 2] 48 9-12... 

Trowell J, Peto R, Crampton Smith A (1975) Controlled trial of repeated halothane anaesthetics in patients with carcinoma of the cervix treated with radium. Lancet 1 821-824 Vergani D, Tsantoulas D, Eddleston ALWF, Davis M, Williams R (1978) Sensitization to halothane-altered liver components in severe hepatic necrosis after halothane anaesthesia. Lancet 2 801-803... 

Mongar JL, Whelan RF (1953) Histamine release by adrenaline and d-turbocurarine in the human subject. J Physiol (Lond) 120 146-154 Nana A, Cardan E, Leitersdorfer T (1972) Pancuronium bromide, its use in asthmatics and patients with liver disease. Anaesthesia 27 154-158 Paton WDM (1957) Histamine release by compounds of simple chemical structure. Pharmacol Rev 9 269-328... 

Liver biopsies showed moderate to severe fatty infiltration, thereby possibly increasing uptake of methoxyflurane and exposed more methoxyflurane to hepatic microsomal enzymes [208]. Control halothane-nitrous oxide anaesthesia with 12 obese patients led to a peaking in the serum fluoride level after 3 h anaesthesia (10.4 1.5 /tmol dm" ) [208]. 

The above terms are used in combination, for example a corrosive skin burn is an acute, local, irreversible effect, liver cancer is a chronic, systemic, irreversible effect and anaesthesia is an acute, systemic effect, usually reversible unless exposure has been very severe. 

Fig. 325. A Kupffer cell (top) showing many tubular invaginations and a fat storing Ito cell (bottom) in the liver (block 559) of an unmedicated 235 g female rat. Under pentobarbital anaesthesia (30 mg/kg), the animal was perfused from the abdominal aorta with 2.5 % glutaraldehyde in 0.1 M sodium ca-codylate buffer (pH 7.4). Postfixation with 1 % osmium te-troxide in sodium cacodylate buffer. Embedded in Epon 812 and sectioned at 50 nm. Lead citrate and uranyl acetate. Film 258/84...

Fig. 344. Uniform distribution of glycogen in the liver lobule (CV = central vein PV = portal vein branch) an unmedicated 465 g old male Wistar rat MR 2000 (No. 2) exsanguinated under ether anaesthesia on March 14, 1977. The tissue was fixed by immersion in Carno/s fluid (ethanol-chloroform-glacial acetic acid) and embedded in Paraplast. Periodic acid-Schiff reaction. Objective Leitz PI 40/0.65. Leitz Orthomat (eyepiece 2X). Film Agfa Pan 25...

Fig. 2.1.7. a The metastases from a breast cancer, subcapsular located in the left liver lobe, were treated via an oblique access route with the skin entry point at the epigastrium (former selective internal radiation therapy i.e. SIRT caused the parenchymal irregularities in the right liver lobe where active metastases could no longer be appreciated). Note the gas within the treated lesion and gas bubbles along the electrode s pathway. Extensive capsular anaesthesia caused the soft-tissue swelling between peritoneal wall and hepatic surface, b Due to an insulation defect, a grade 3 burn occurred at the skin entry point, about 5 cm distant from the electrode s tip. The burn was not appreciated until the end of the procedure because the entry point was draped with a swab and the patient did not feel the burn due to local anaesthesia... 

Liver Liver dysfxmction secondary to halogenated vapour anaesthesia has again been reported. 

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