Intravenous anesthetics

Toxicity of General Anesthesia

Hepatotoxicity: Hepatotoxicity is rarely seen after Anesthesia and hepatic dysfunction mainly result from factors such as blood transfusion, hypovolemic shock, and other surgical stress. The mechanism underlying hepatoxicity from Halothane remain unclear, but studies with animals have implicated the formation of radioactive metabolites that either cause direct hepatocellular damage or initiate immune mediated responses.

Nephrotoxicity: The nephrotoxic potential of methoxyflurane has limited its clinical use in anesthesia, renal dysfunction following methoxyflurane is caused by inorganic fluoride released during the extensive metabolism of the anesthetic by hepatic and renal enzymes. Metabolism of enflurane and sevoflurane also leads to the formation of fluride ions. Studies have showed that enflurane causes Nephrotoxicity but not sevoflurane.

Chronic toxicity: Mutagenicity: Under normal conditions, most modern and many older inhaled anesthetics are not mutagens and probably not carcinogens. However, older anesthetics that contain the vinyl moiety may be mutagens. These agents are rarely used or never used. Carcinogenicity: Anesthetic agents may cause Carcinogenicity to operating room personnel who have been exposed to trace level of it. Such theory have not been proved at 100%.

Effects of reproduction: The probability of miscarriage amongst pregnant women increases more than expected level. Hematotoxicity: Prolonged exposure to nitrous oxide decreases methionine synthesis activity and may cause megaloblastic anemia.

CLINICAL USE OF INHALED ANESTHETICS Inhaled anesthetics are rarely used alone. They are usually combined with intravenous agents, the combination with intravenous agents, the combination called “balanced anesthesia”. Nitrous oxide, Desflurane, Sevoflurane and isoflurane are the most commonly used in the USA. Halothane is still used in pediatric anesthesia, although sevoflurane is replacing halothane. Methoxyflurane is occassionaly used mainly in case of obstetric anesthesia- but not for prolonged procedure for Nephrotoxicity. Chloroform is not used for its Hepatotoxicity. Cyclopropane and diethyl ether are no longer used because of their flammable and explosive characteristics.

Difference between Intravenous anesthetics and Inhaled anesthetics Intravenous AnestheticsInhaled Anesthetics Specialized Equipments are not necessary for their delivery or expensive facilities for the recovery and disposal of exhaled gas. Special Equipments are necessary for their delivery or expensive facilities required for the recovery and disposal of exhaled gas. Onset of action for drugs such as Propofol, thiopental is faster than newest inhaled drugs such as desflurane and sevoflurane. Most of the Inhaled Anesthetics has a onset of action slower than the Intravenous anesthetics. Rate of recovery is faster.Rate of recovery is slower. Extensive use in the outpatients.Less use in outpatient. Can be used solely to conduct anesthesia in short surgical procedure. E.g., Thiopental, Propofol, Ketamine. Cannot be used solely. Intravenous Opioids contribute cardiovascular stability, sedation and marked analgesia to anesthesia protocols and Opioid receptor antagonist can be used to hasten their actions. Have to be used in combination. Special procedures required for their reversal.

ULTRA SHORT ACTION BARBITURATES (THIOPENTAL) Thiopental is the most commonly used anesthetics for the induction of anesthesia, often used in combination with inhaled anesthetics. Following intravenous administration, thiopental rapidly crosses blood brain barrier and if given sufficient dosage, produces hypnosis in one circulation time. Similar drugs such as thiamylal and methohexital, causes plasma brain equilibrium occurs rapidly( within 1 min) because of high lipid solubility.

Metabolism of thiopental is much slower than its redistribution and takes place primarily in the liver. Less than 1% of an administered dose of thiopental is excreted unchanged by the kidney. Thiopental is metabolized at a rate of 15-16% per hour in human following a single dose. With large dosage thiopental causes dose dependent decreases in arterial blood pressure, stroke volume and cardiac output, this is due to its myocardial depressant effect and increased venous capacitance.

Cerebral metabolism and oxygen utilization are decreased after thiopental administration in proportion to the degree of cerebral depression. Thiopental may also reduce hepatic blood flow and glomerular filtration rate. Thiopental has participated porphyric crisis when used as a induction agent.

OPIOID ANALGESIS Intravenous Morphine 1-3 mg/kg, or high potency Opioid fentanyl, µg/kg have been used. Intravenous may increase chest wall rigidity, which may impair ventilation and post operative respiratory depression may occur requiring assisted ventilation and administration of Opioid antagonistic (e.g., Naloxane).

PROPOFOL Propofol or disprofol is an extremely important intravenous anesthetic. It produces anesthesia at a rate similar to that of intravenous barbiturates and recovery is more rapid. In particular patients are able to ambulate sooner after Propofol. Patient feel better, postoperative vomiting is uncommon, Propofol is reported to have antiemetic action.

Propofol is used both in induction and maintenance of anesthesia. The drug is also effective in producing prolonged sedation in patients After intravenous administration, distribution occur with half life of 2-8 min, the elimination half life of Propofol is approximately min. The drug is rapidly metabolize in liver by conjugation to glucuronide and sulfate and excreted in the urine. Less than 1% of the drug is excreted unchanged.

Propofol causes marked decrease in systemic blood pressure during induction of anesthesia, primarily through decreased peripheral resistance. In addition Propofol has greater negative iontropic effects on the heart than etomidate and thiopental. Apnea and pai at the site of injection also occur. Propofol is very costly.