liver enzymes and anaesthesia,BY MOHAMED ANWER RIFKY.pptx

An md discussion in zagazig medical school,about elevated liver enzymes in anaesthesia,by mohamed anwer rifky.

1. Ciprofol has high efficacy, good selectivity, and fewer adverse reactions, indicating good clinical application potential.Ciprofol adds a cyclopropyl group to the side chain of the core structure

2. ISCHEMIA-REPERFUSION INJURY Ischemia-reperfusion injury results from both hypoxia during an ischemic episode and cytotoxic events during reperfusion. Reperfusion induces the production of highly reactive chemicals that can cause necrosis or **apoptosis, such as superoxide, hydrogen peroxide, and hydroxyl radicals. After relatively brief ischemic intervals, most of the injury is due to reperfusion. With more prolonged ischemia, hypoxia accounts for a larger fraction of the overall injury from ischemia-reperfusion. ** A type of cell death in which the cell uses specialized cellular machinery to kill itself; a cell suicide mechanism that enables metazoans to control cell number and eliminate cells that threaten the animal's survival. t . Ratios of aminotransferases may hold keys to the diagnosis of hepatic disorders. For example, when both AST and ALT are elevated, an AST-to-ALT ratio higher than 4 is characteristic of Wilson disease, ratios between 2 and 4 are typical of alcoholic liver disease, and a ratio below 1 suggests nonalcoholic steatohepatitis (without cirrhosis).On the other hand, patients with florid liver failure can have normal enzyme levels when the liver damage is so extensive that too few viable hepatocytes remain to bring about increases in ALT or AST. In addition, chronic, ** smoldering liver diseases such as hepatitis C can destroy the liver, slowly and silently, without overt increases in ALT or AST. ** Have strong suppressed feelings Abnormal liver enzyme test results may be seen in up to 4% of normal individuals and up to 36% of psychiatric patients, although the prevalence of clinically significant hepatic dysfunction in these individuals is less than 1%, thus suggesting that further costly preoperative testing is unnecessary in asymptomatic patients. plasma clearance of indocyanine green is most commonly used to assess hepatic blood flow. Transesophageal echocardiography can also evaluate hepatic vein flow , but it is only an indirect measurement of hepatic perfusion and oxygenation. A novel technique involving pulsed Doppler probes implanted in animals and in humans undergoing cholecystectomy has allowed accurate measurement of hepatic arterial and portal vein blood flow. .

3. 1- With halothane, the mechanism of hepatic damage is thought to be immunologic . Desflurane is metabolized to a small, but variable, extent by cytochrome P450 2E1 (CYP2E1) in the liver to generate a trifluoroacetyl chloride reactive intermediate. This intermediate combine to multiple intracytoplasmic proteins, such as 58 kDa endoplasmic reticulum protein (ERp58) and CYP2E1 itself, forming potentially immunogenic ** adducts and inducing immune responses .Autoantibodies to CYP2E1 and ERp58 have been recently reported after desflurane anesthesia . Although only 0.01% of desflurane is metabolized even a small amount of biotransformation to immunogenic metabolites may cause hepatotoxicity. ** A compound formed by an addition reaction In conclusion ( of a Study) , anesthesiologists should be aware of this potential complication in morbidly obese patients following desflurane anesthesia. 2- Sevoflurane can induce malignant hyperthermia :In patients with ryanodine receptor (RYR1) or dihydropyridine receptor (CACNA1S) variants. 3- Using a vital capacity induction technique, inspired concentrations of 8% sevoflurane in combination with oxygen ( 1 L/minute) and nitrous oxide ( 2 L/minute) were used to obtain loss of consciousness followed by a 30 second IV injection of remifentanil ( 1 to 1.5 mcg/kg). Induction time was 3.4 +/- 2.2 minutes. 4- The inspired sevoflurane concentration was reduced to 4% when the pupils were divergent and to 2% when the pupils were central .

4. sevoflurane had favorable effects on hepatic function through an ischemic-preconditioning effect. These data are consistent with the favorable cardiac ischemic-preconditioning effect of sevoflurane. . Xenon, an inert gas first described as having anesthetic properties in 1951, has been considered to be an ideal inhaled anesthetic because it is non -explosive and nonflammable, exhibits low toxicity, has no known teratogenic effects, and has rapid induction and recovery profiles resulting from its extremely low blood gas coefficient of 0.115. Xenon has no significant effect on left ventricular function, systemic vascular resistance, or systemic blood pressure. Its hemodynamic profile is similar to that of propofol anesthesia in humans, and it caused less hypotension and had no effect on left ventricular function when compared with isoflurane in human studies. Although animal investigations suggested a substantial increase in cerebral perfusion with xenon when compared with intravenous anesthetics, xenon has no effect on other regional organ perfusion, including liver perfusion. It does not alter HABF, and given the absent effect on cardiac output, it should, in theory, have no impact on THBF (unlike all other volatile anesthetics). It also does not alter liver function tests . Xenon may therefore prove to be an ideal anesthetic with regard to hepatic perfusion. Arterial pH should be maintained near normal because systemic alkalemia is also noted to increase the diffusion of ammonia across the blood-brain barrier, a process that can potentially worsen the degree of encephalopathy. Recently, an isoform of ALT2 has been cloned in a separate chromosome (chr. 16) from the classic ALT .ALT2 has a wider organ distribution , including skeletal muscles and adipose tissue . .

5. 1- Fresenius Propoven 2 % , which the FDA has permitted for emergency use under an Emergency Use . 2- Contraindications : Egg hypersensitivity peanut hypersensitivity soya lecithin hypersensitivity . 3- Formulations of propofol contain sodium metabisulfite >> sulfite that may cause allergic-type reactions. 4- Consider zinc supplementation during prolonged therapy with propofol for patients predisposed to zinc deficiency, including those with burns, diarrhea, or sepsis. Do not infuse propofol for more than 5 days without providing a drug holiday to safely replace estimated or measured urine zinc losses. Certain formulations of propofol (e.g., Diprivan ) contain ethylenediaminetetraacetic acid (EDTA), which is a strong chelator of trace metals including zinc. 5- Certain formulations of propofol contain benzyl alcohol. Excessive amounts of benzyl alcohol in neonates have been associated with hypotension , metabolic acidosis, and kernicterus 6- Avoid abrupt discontinuation of propofol before weaning or for daily evaluation of sedation levels. This may result in rapid awakening with associated anxiety, agitation, and resistance to mechanical ventilation. 7- There are reports of the abuse of propofol for ** recreational and other improper purposes , which have resulted in fatalities and other injuries. Instances of self-administration of propofol by health care professionals have also been reported, which have resulted in fatalities and other injuries. ** ENJOYMENT 8- Propofol is excreted in human milk . Variable concentrations in human milk have been reported with administration of propofol to breast-feeding mothers in the postpartum period. ** Hyperpolarization-activated and cyclic nucleotide-gated ( HCN) channels belong to the superfamily of voltage-gated pore loop channels. HCN channels are unique among vertebrate voltage-gated ion channels, in that they have a reverse voltage-dependence that leads to activation upon hyperpolarization.  **In animal studies , propofol has been shown to directly depress the dorsal horn neurons in the spinal cord ,inhibit the phosphorylation of N-methyl-D-aspartate receptor NR1 subunit ,and inhibit the cannabinoid CB1 and CB2 receptors . In human volunteers, hypnotic doses of propofol at 3.5 mcg/ml decreased pain-related regional blood flow to the thalamus and anterior cingulate cortex ,Propofol significantly decreased pain scores by 40% and areas of hyperalgesia and allodynia in human volunteers . Work on propofol ’ s preferential binding to the **HCN1 pacemaker channels further reinforce its anti- hyperalgesic effects , Propofol has been shown to be anti-inflammatory , both in vitro ,and in human studies ,which may play an essential role in post-operative analgesia .

6. **Intraoperatively, it is advisable to avoid the placement of a transesophageal echocardiography probe, to avoid initiation of bleeding in patients with esophageal varices . . **CTP scores of A, B, and C are correlated with MELD scores of 10, 10-14, and >14 in that order. 1- The volume of distribution for nondepolarizing muscle relaxants is increased, and larger doses than usual may be required. 2- Those eliminated by glucuronidation ( oxazepam, lorazepam ) are not affected by liver disease. 3- Of the induction agents, etomidate and thiopental decrease hepatic blood flow, but ketamine does not. 4- Other diseases associated with elevated ALT and AST include musculoskeletal disorders such as polymyositis as well as acute myocar - dial infarction and hypothyroidism. 5- many laboratories use higher upper limit of normal values as high as 55 unit/L for ALT. 6- Drug ILI can be categorized as either intrinsic (predictably causes liver injury at certain high doses, eg , acetaminophen ), or more commonly, idiosyncratic (with an inconsistent relationship to dose and variable laboratory/clinical presentation). 7- The fulminant form of hepatotoxicity, commonly known as halothane hepatitis , is characterized by elevated ALT, AST , bilirubin, and alkaline phosphatase levels, and massive hepatic necrosis following the administration of halothane. Halothane hepatitis is rare( 1 in 5000-35,000 administrations in adults) but is fatal in between 50% to 75% of cases. Because of the potential for fatal hepatitis, halothane is no longer used in adult patients in most countries. **Sinusoid,  irregular tubular space for the passage of blood, taking the place of capillaries and venules in the liver, spleen, and bone marrow . The sinusoids form from branches of the portal vein in the liver and from arterioles (minute arteries) in other organs.

7. Case Report A 35-year-old Caucasian woman, who underwent anesthesia with a total dose of 540 mg of propofol for the stripping of varicose veins of the right leg, was admitted to our hospital with the clinical diagnosis of ALFailure . One week after surgery, four- to six ,fold elevated transaminases were documented for the first time. After hospital admission a liver biopsy was performed due to elevated liver enzymes, impaired coagulation and progredient jaundice ,Histologic findings revealed florid and lobar accentuated as well as chronically persistent hepatitis with hepatocyte death, hepatocellular cholestasis and micro vesicular fatty degeneration of 90% of the liver parenchyma .These findings were consistent with the diagnosis of toxic liver damage , most likely caused by propofol. Because of the continuously elevated transaminases, bilirubin, INR and encephalopathy, the patient was referred to the liver transplant centre of the University of Essen for transplant evaluation. Furthermore, two patients developed jaundice and severe hepatic injury within 3 days of surgery under sevoflurane anesthesia. The clinical course was typical of halogenated anesthetic liver injury with a rapid onset, mild eosinophilia, a hepatocellular pattern of injury and severe course. Risk factors included previous anesthesia (although the agent used was not known).  ** CHI : The 22nd letter of the Greek alphabet 1,1,1,3,3,3-Hexafluoro-2-( fluoromethoxy )propane Sevoflurane is metabolized to a small extent by the microsomal drug metabolizing enzyme CYP 2E1 to a t rifluoroacetylated reactive intermediate (TFA)

8. MANN – WHITNNY U TEST

9. FISHER EXACT TEST