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ENFLURANE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Enflurane is a volatile fluorinated methyl ethyl ether used as an inhalational anesthetic, and was developed in 1963.

Specific Substances

    1) Anesthetic compound no. 347
    2) 2-Chloro-1-(difluoromethoxy)-1,1,2-trifluoroethane
    3) 2-Chloro-1,1,2-trifluoroethyl difluoromethyl ether
    4) Compound 347
    5) Enflurane
    6) Ethane, 2-chloro-1-(difluoromethoxy)-1,1,2-trifluoro-
    7) Ethrane
    8) Methylflurether
    9) NSC 115944
    10) OHIO 347
    11) Molecular Formula: C3-H2-Cl-F5-O
    12) CAS 13838-16-9
    1.2.1) MOLECULAR FORMULA
    1) CHF2OCF2CHFCl

Available Forms Sources

    A) FORMS
    1) Enflurane is available as an easily vaporized liquid for use as an anesthetic gas. It is a clear, colorless, volatile and stable liquid with a mild sweet odor. It is non-flammable (ACGIH, 1991) Budavari, 1996; Prod Info Ethrane (R), 1999; Sittag, 1991).
    B) SOURCES
    1) Production: From chlorotrifluoroethylene + methanol + hydrogen fluoride by addition, photochlorination and fluorination (Ashford, 1994).
    C) USES
    1) Enflurane is used as an anesthetic gas (Budavari, 1996).
    2) Enflurane is a liquid, used as a general anesthetic compound in the induction of inhalation anesthesia (Hathaway et al, 1996; ACGIH, 1991; Sittig, 1991). It has fewer side-effects than halothane, chloroform or trichloroethylene (ACGIH, 1991). Biological effects are seen in the central nervous system and cardiovascular system (ACGIH, 1991).
    a) Exposure to concentrations of 4200 to 5300 ppm for 30 minutes results in decreased performance in cognitive tests (remembering word pairs) (Hathaway et al, 1996). At exposure of 2500 ppm, a trend towards more risky strategies in decision-making were observed (ACGIH, 1991).
    b) Anesthesia in humans is induced at levels of 15,000 to 20,000 ppm (Hathaway et al, 1996).
    c) For anesthesia, the usual adult dose via inhalation is a 0.5 to 3% mixture with oxygen (MSDS , 1999).
    3) Twitching indicates considerable depth of anesthesia; exposure to high levels of enflurane may cause seizures (ACGIH, 1991).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) WITH THERAPEUTIC USE
    1) Enflurane may cause CNS and respiratory depression, coughing, laryngospasm, hypotension, hepatotoxicity, renal toxicity, and seizures. ECG changes, nausea and vomiting, and malignant hyperthermia have occurred with enflurane anesthesia. Rhabdomyolysis with acute renal failure is a rare effect.
    0.2.3) VITAL SIGNS
    A) WITH THERAPEUTIC USE
    1) Hypotension has been reported with enflurane anesthesia. Tachypnea, hyperthermia, hypotension, and tachycardia may develop with malignant hyperthermia.
    0.2.5) CARDIOVASCULAR
    A) WITH THERAPEUTIC USE
    1) Hypotension, dysrhythmias, and cyanosis have been reported with enflurane anesthesia.
    0.2.6) RESPIRATORY
    A) WITH THERAPEUTIC USE
    1) Coughing, laryngospasm, ventilatory depression, elevated PaCO2 levels, and acute asthma have been reported with enflurane use.
    B) WITH POISONING/EXPOSURE
    1) Acute overdose has produced asphyxia.
    0.2.7) NEUROLOGIC
    A) WITH THERAPEUTIC USE
    1) Increased motor activity with or without seizures may occur at deep levels of anesthesia. Shivering may also occur during the postoperative period, as well as severe headache, dizziness, drowsiness or lightheadedness.
    0.2.8) GASTROINTESTINAL
    A) WITH THERAPEUTIC USE
    1) Nausea, vomiting (sometimes bloody), abdominal pain, or constipation may occur during the postoperative period.
    0.2.9) HEPATIC
    A) WITH THERAPEUTIC USE
    1) Hepatotoxicity develops infrequently following enflurane anesthesia, but may be severe.
    0.2.10) GENITOURINARY
    A) WITH THERAPEUTIC USE
    1) Serum inorganic fluoride concentrations of greater than 50 mcmol have been associated with subclinical renal toxicity.
    0.2.11) ACID-BASE
    A) WITH THERAPEUTIC USE
    1) Metabolic acidosis may develop with malignant hyperthermia.
    0.2.12) FLUID-ELECTROLYTE
    A) WITH THERAPEUTIC USE
    1) Hyperkalemia or hypokalemia may occur in cases of malignant hyperthermia.
    0.2.13) HEMATOLOGIC
    A) WITH THERAPEUTIC USE
    1) Leukocytosis and porphyria been observed with enflurane anesthesia. Self-limited CO formation may occur following enflurane use in the presence of desiccated soda lime.
    0.2.15) MUSCULOSKELETAL
    A) WITH THERAPEUTIC USE
    1) Enflurane anesthesia has been associated with malignant hyperthermia, a skeletal muscle hypermetabolic state which may cause muscle rigidity and rhabdomyolysis.
    0.2.16) ENDOCRINE
    A) WITH THERAPEUTIC USE
    1) Enflurane and surgery may increase serum glucose, impair glucose tolerance and inhibit insulin secretion.
    0.2.18) PSYCHIATRIC
    A) WITH THERAPEUTIC USE
    1) Mood changes and nightmares have been reported following enflurane anesthesia.
    0.2.20) REPRODUCTIVE
    A) Enflurane is classified as FDA pregnancy category B. No fetal abnormalities have been reported in humans exposed to enflurane. Enflurane crosses the placenta and appears in umbilical venous blood at about half the concentration in maternal venous blood. Dose-dependent birth defects have occurred in one animal study; however, other studies in rats and rabbits produced no evidence of fetal harm.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, the manufacturer does not report any carcinogenic potential with enflurane.

Laboratory Monitoring

    A) Monitor ECG and pulse oximetry. Serum fluoride concentrations and renal function should be monitored in cases of significant overexposure.
    B) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count, urinalysis, and liver and kidney function tests is suggested for patients with significant exposure.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) SUMMARY
    1) Enflurane is an inhalational anesthetic; ingestion is unlikely. DO NOT induce emesis.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    B) MALIGNANT HYPERTHERMIA
    1) ADULTS AND CHILDREN - Administer dantrolene sodium in an initial dose of 1 mg/kg by rapid IV infusion.
    a) If symptoms persist or reappear, the dose may be repeated, to a cumulative dose of 10 mg/kg.
    b) Reversal is usually achieved with a cumulative dose of 2.5 mg/kg.
    c) Oral doses of 1 to 2 mg/kg QID for 1 to 3 days may be necessary to prevent the recurrence of the manifestations of malignant hyperthermia.
    2) Reduce body temperature with cooling blankets or ice, monitor serum potassium and CK levels.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    2) Dermal absorption may cause systemic poisoning. Carefully observe patients with dermal exposure for systemic effects and treat symptomatically.

Range Of Toxicity

    A) Toxic dose is not established. Recreational abuse or any non medical use may cause life threatening respiratory depression.

Clinical Effects

Vital Signs

    3.3.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Hypotension has been reported with enflurane anesthesia. Tachypnea, hyperthermia, hypotension, and tachycardia may develop with malignant hyperthermia.
    3.3.2) RESPIRATIONS
    A) WITH THERAPEUTIC USE
    1) Rapid breathing may accompany malignant hyperthermia which has occurred in 1 out of 725,000 enflurane anesthetics (Prod Info Ethrane(R), enflurane, 1999).
    3.3.3) TEMPERATURE
    A) WITH THERAPEUTIC USE
    1) Effects of malignant hyperthermia may include muscle rigidity, tachypnea, tachycardia, cyanosis, dysrhythmias, unstable blood pressure, and increased CPK (Prod Info ETHRANE(TM) inhalation liquid, 2006; Caropreso et al, 1975).
    a) The incidence of malignant hyperthermia is low, occurring in only 1 of 725,000 enflurane anesthetics (Prod Info ETHRANE(TM) inhalation liquid, 2006).
    3.3.4) BLOOD PRESSURE
    A) WITH THERAPEUTIC USE
    1) Hypotension may accompany isorhythmic atrioventricular dissociation (Sigurdsson et al, 1983; Willatts et al, 1983).
    2) Unstable blood pressure may occur during malignant hyperthermia (Prod Info ETHRANE(TM) inhalation liquid, 2006).
    3.3.5) PULSE
    A) WITH THERAPEUTIC USE
    1) The hypercapnia associated with spontaneous ventilation during enflurane anesthesia increases heart rate (Stevens et al, 1971).

Heent

    3.4.3) EYES
    A) ANIMAL STUDIES
    1) In rabbits, administration of 100 mg to the eye produced a moderate reaction (RTECS , 1999).
    B) WITH THERAPEUTIC USE
    1) Blurred vision or double vision may be a reversible effect of enflurane anesthesia (Prod Info Ethrane(R), enflurane, 1999).
    2) Enflurane produces a significant dose-dependent decrease in intraocular pressure (Scheurecker, 1978).
    3.4.6) THROAT
    A) WITH THERAPEUTIC USE
    1) Coughing and laryngospasm may occur with enflurane anesthesia (Prod Info Ethrane(R), enflurane, 1999).

Cardiovascular

    3.5.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Hypotension, dysrhythmias, and cyanosis have been reported with enflurane anesthesia.
    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) Hypotension and cyanosis may accompany isorhythmic atrioventricular dissociation (Sigurdsson et al, 1983; Willatts et al, 1983), and is sometimes seen with malignant hyperthermia.
    b) Cardiac output is slightly diminished and some arterial hypotension is not uncommon during anesthesia. Enflurane also produces significant depression of baroreflex control of heart rate (Morton & Duke, 1980).
    B) CONDUCTION DISORDER OF THE HEART
    1) WITH THERAPEUTIC USE
    a) ISORHYTHMIC ATRIOVENTRICULAR DISSOCIATION - A dysrhythmia that is usually brief and resolves spontaneously. This is an electrocardiographic finding where the PR interval gradually shortens until the P wave disappears into the QRS complex. It was observed in 16 of 105 patients (15%) receiving enflurane anesthesia in one study (Sigurdsson et al, 1983; Willatts et al, 1983; Chander, 1982).
    b) Sinus tachycardia may commonly be seen during enflurane anesthesia (Rodrigo et al, 1987).
    c) Tachycardia, unstable blood pressure, and dysrhythmias may be seen in cases of malignant hyperthermia (Prod Info ETHRANE(TM) inhalation liquid, 2006).

Respiratory

    3.6.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Coughing, laryngospasm, ventilatory depression, elevated PaCO2 levels, and acute asthma have been reported with enflurane use.
    B) WITH POISONING/EXPOSURE
    1) Acute overdose has produced asphyxia.
    3.6.2) CLINICAL EFFECTS
    A) COUGH
    1) WITH THERAPEUTIC USE
    a) Coughing and laryngospasm have been reported frequently, particularly when enflurane is used for short surgical procedures in pediatric patients (Steward, 1977).
    B) ACUTE RESPIRATORY INSUFFICIENCY
    1) WITH THERAPEUTIC USE
    a) Enflurane anesthesia is accompanied by ventilatory depression. Ventilatory depression is the result of shortened duration of inspiration; respiratory rate is unchanged (Wahba, 1980).
    C) ACIDOSIS
    1) WITH THERAPEUTIC USE
    a) PaCO2 - Elevated PaCO2 levels are also seen with deeper anesthesia (Wahba, 1980).
    D) BRONCHOSPASM
    1) WITH THERAPEUTIC USE
    a) Lowry & Fielden (1976) reported 3 cases of severe bronchospasm in known asthmatics given enflurane anesthesia (Lowry & Fielden, 1976).
    2) WITH POISONING/EXPOSURE
    a) Acute asthma has been reported after occupational exposure. Asthma occurred in an anesthetist on 6 separate occasions. In each case, symptoms began 8 to 12 hours after the subject had administered enflurane (Schwettmann & Casterline, 1976).
    E) INJURY DUE TO ASPHYXIATION
    1) WITH POISONING/EXPOSURE
    a) Asphyxia has resulted from enflurane misuse. A fatality resulting from the misuse of enflurane has been reported by Lingenfelter (1981). A 29-year-old student nurse anesthetist had applied enflurane topically with a 4 by 4 gauze to her lower lip in an effort to treat herpes simplex labialis.
    1) The patient had apparently used the entire contents of a 250 mL enflurane bottle over a 3 to 4-hour period and was later found unconscious in the women's restroom. Cardiopulmonary resuscitation was performed unsuccessfully.
    2) Autopsy findings were normal with the exception of high enflurane concentrations in the skin, gastric contents, blood, and lungs. The death was attributed to airway obstruction and subsequent asphyxia (Lingenfelter, 1981a).
    F) PARALYSIS
    1) WITH POISONING/EXPOSURE
    a) General muscle relaxation and respiratory paralysis resulted in the death of a 21-year-old male following the abuse of enflurane. Lack of tissue damage at autopsy was probably indicative of a one time abuse of this substance. One empty bottle and one partial bottle were found as well as an inflating bellows with an attached filter. Autopsy showed moderate lung edema and inflammation in the bronchi (Jacob et al, 1989).
    G) HYPERVENTILATION
    1) WITH THERAPEUTIC USE
    a) Rapid breathing may accompany malignant hyperthermia due to enflurane use (Prod Info Ethrane(R), enflurane, 1999).

Neurologic

    3.7.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Increased motor activity with or without seizures may occur at deep levels of anesthesia. Shivering may also occur during the postoperative period, as well as severe headache, dizziness, drowsiness or lightheadedness.
    3.7.2) CLINICAL EFFECTS
    A) SEIZURE
    1) WITH THERAPEUTIC USE
    a) Immediate or delayed seizure activity in patients emerging from enflurane anesthesia may occur. Enflurane has been reported to induce cerebral hyperexcitability which appears as a burst-suppression pattern on an EEG and may progress to seizure (Burchiel, 1980).
    b) The onset of convulsive symptoms after the end of anesthesia has ranged from within 5 minutes (Jenkins & Milne, 1984) to as long as 8 days (Ohm et al, 1975). Up to 80% of patients who experience seizures will have them within the first 24 hours following surgery (Christys et al, 1989).
    1) The duration of symptoms has also varied; from 90 seconds to greater than 48 hours.
    c) Conditions reported have included prolonged myoclonic contractions (Ng, 1980), focal seizures (Parke & Jago, 1992; Sprague & Wolf, 1982), generalized tonic/clonic seizures (Kruczek et al, 1980) Yazji & Seed, 1984; (Grant, 1986; Allan, 1984; Fahy, 1987), and life-threatening status epilepticus (Nicoll, 1986).
    d) Patients with pre-existing seizure disorders may be at a higher risk for enflurane-induced seizures. Yamashiro et al (1985) demonstrated abnormal EEG findings, differing from background activity, following enflurane anesthesia in patients with an antecedent seizure disorder (Yamashiro et al, 1985).
    B) CHILL
    1) WITH THERAPEUTIC USE
    a) Shivering may occur in the postoperative period (Prod Info ETHRANE(TM) inhalation liquid, 2006).
    C) CENTRAL NERVOUS SYSTEM DEFICIT
    1) WITH THERAPEUTIC USE
    a) Signs of CNS depression such as dizziness, drowsiness, or lightheadedness may occur following enflurane anesthesia (Prod Info Ethrane(R), enflurane, 1999).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) OPISTHOTONOS
    a) ANIMAL STUDIES - Komatsu & Ogli (1987) reported the incidence of opisthotonus in mice treated with 1.2% isoflurane, 2.0% enflurane or 1.0% halothane to be isoflurane > enflurane > halothane (no opisthotonus reported in halothane group). The concentrations used were considered close to the MAC for mice (Komatsu & Ogli, 1987).

Gastrointestinal

    3.8.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Nausea, vomiting (sometimes bloody), abdominal pain, or constipation may occur during the postoperative period.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH THERAPEUTIC USE
    a) Vomiting (sometimes bloody) may occur during the first 2 to 24 hours after surgery. In the first 2 hours, 27 of 60 patients (45%) receiving enflurane experienced some degree of nausea, and/or vomiting. By 24 hours after surgery 46 of 60 patients (77%) had vomited (Hovorka et al, 1988).

Hepatic

    3.9.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Hepatotoxicity develops infrequently following enflurane anesthesia, but may be severe.
    3.9.2) CLINICAL EFFECTS
    A) TOXIC HEPATITIS
    1) WITH THERAPEUTIC USE
    a) Hepatitis with fever, jaundice, and elevated liver enzymes may occur, possibly due to a hypersensitivity reaction (Christ et al, 1988).
    b) ONSET - Symptoms of hepatitis vary in onset from 5 to 19 days in reported cases, with some fatalities reported (Denlinger et al, 1974; Sadone & Kim, 1974; Tsang, 1975; Paull & Fortune, 1987; Kline, 1980; Danilewitz et al, 1980; Masone et al, 1982; Gogus et al, 1991).
    c) Hepatic coma and encephalopathy have been reported (White et al, 1981). Liver biopsies in fatalities have been characteristic for centrilobular necrosis and fatty changes (Paull & Fortune, 1987; Lewis et al, 1983).
    d) The incidence of liver damage following enflurane anesthesia is low (Eger et al, 1986).
    e) DURATION - Most patients recover in 3 to 4 weeks with malaise being the only sequelae (Christ et al, 1988). Fever and elevated liver enzymes are generally observed, while jaundice and eosinophilia may or may not be present.
    f) RISK FACTORS - Patients with repeated exposures to enflurane are more likely to develop a hepatitis-like reaction (Ona et al, 1980).
    B) LIVER ENZYMES ABNORMAL
    1) WITH THERAPEUTIC USE
    a) Elevations in ALT, LDH, and GGT, but not AST, may be seen with frequent exposure.
    b) Fee et al (1979) studied the effects of repeat enflurane administration on liver enzyme activity. Alanine aminotransferase (ALT) levels were significantly increased, while aspartate aminotransferase (AST) levels were not significantly affected.
    1) Lactate dehydrogenase levels (LDH) were increased in up to 17% of patients, while gamma glutamyl transferase levels were elevated in as many as 19% of enflurane recipients (Fee et al, 1979).
    c) The incidence of abnormal liver function tests increases with the number of enflurane exposures .

Genitourinary

    3.10.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Serum inorganic fluoride concentrations of greater than 50 mcmol have been associated with subclinical renal toxicity.
    3.10.2) CLINICAL EFFECTS
    A) TOXIC NEPHROPATHY
    1) WITH THERAPEUTIC USE
    a) Enflurane appears to be safe in patients with normal renal function and in those with mild to moderate renal impairment. Elevations in serum fluoride may be seen, and produce toxicity. Oliguria and anuria may occur due to fluoride toxicity.
    1) Serum inorganic fluoride concentrations of greater than 50 mcmol have been associated with subclinical renal toxicity (Carter et al, 1976).
    b) CASE REPORT - A 66-year-old male with carcinoma of the bladder developed oliguria and anuria unresponsive to furosemide following a second course of enflurane.
    1) Following the second course of enflurane anesthesia, the patient was found to have peak fluoride levels of 25 millimoles per liter with peak inorganic fluoride concentration of 93 millimoles per liter, which is considered nephrotoxic (Eichhorn et al, 1976).

Acid-Base

    3.11.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Metabolic acidosis may develop with malignant hyperthermia.
    3.11.2) CLINICAL EFFECTS
    A) ACIDOSIS
    1) WITH THERAPEUTIC USE
    a) An increase in overall metabolism leads to high oxygen demand, elevated temperature, possible hyperkalemia, and a base deficit (Prod Info ETHRANE(TM) inhalation liquid, 2006).

Hematologic

    3.13.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Leukocytosis and porphyria been observed with enflurane anesthesia. Self-limited CO formation may occur following enflurane use in the presence of desiccated soda lime.
    3.13.2) CLINICAL EFFECTS
    A) PORPHYRIA DUE TO TOXIC EFFECT OF SUBSTANCE
    1) WITH THERAPEUTIC USE
    a) Porphyria has been observed with enflurane anesthesia (Prod Info Ethrane(R), enflurane, 1999).
    B) LEUKOCYTOSIS
    1) WITH THERAPEUTIC USE
    a) Elevation of the white blood cell count has been observed with enflurane anesthesia (Prod Info ETHRANE(TM) inhalation liquid, 2006).
    C) CARBOXYHEMOGLOBINEMIA
    1) WITH THERAPEUTIC USE
    a) Self-limited production of carbon monoxide (CO) via the degradation of enflurane in the presence of desiccated soda lime has been demonstrated under the following conditions: (1) use of a clinical absorber with a large amount of soda lime, (2) use of a continuous gas flow, (3) allowing the soda lime temperature to increase during the reaction, and (4) following the reaction for a long period of time. It was found that total CO production was linearly dependent on the amount of desiccated soda lime and that the very large absorber systems commonly used in the United States may have the disadvantage of having the potential to produce particularly large amounts of CO. This could potentially cause carbon monoxide poisoning, particularly in children, after mask induction or initial wash-in with enflurane (Wissing et al, 2001).

Musculoskeletal

    3.15.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Enflurane anesthesia has been associated with malignant hyperthermia, a skeletal muscle hypermetabolic state which may cause muscle rigidity and rhabdomyolysis.
    3.15.2) CLINICAL EFFECTS
    A) INCREASED MUSCLE TONE
    1) WITH THERAPEUTIC USE
    a) Enflurane anesthesia has been associated with a skeletal muscle hypermetabolic state known as malignant hyperthermia, which causes muscle rigidity (Prod Info ETHRANE(TM) inhalation liquid, 2006). The incidence is very low.
    B) DRUG-INDUCED MYOPATHY
    1) WITH THERAPEUTIC USE
    a) Caccia et al (1978) reported a case of massive paroxysmal myoglobinuria with focal muscle necrosis following cardiac arrest in a 13-year-old child after enflurane and succinylcholine anesthesia. The clinical picture resembled "Evans myopathy" (Caccia et al, 1978).
    C) RHABDOMYOLYSIS
    1) WITH THERAPEUTIC USE
    a) Rhabdomyolysis with acute renal failure is a rare event which may occur following enflurane anesthesia. It generally presents as an incomplete form of malignant hyperthermia. Effects have included jaw tightness, cardiac dysrhythmias, metabolic acidosis, and increased body temperature. Myoglobinuria is generally present (Lee et al, 1987).

Endocrine

    3.16.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Enflurane and surgery may increase serum glucose, impair glucose tolerance and inhibit insulin secretion.
    3.16.2) CLINICAL EFFECTS
    A) ABNORMAL GLUCOSE TOLERANCE TEST
    1) WITH THERAPEUTIC USE
    a) General anesthesia with enflurane and surgery are reported to increase serum glucose, impair glucose tolerance, and inhibit insulin secretion (Young et al, 1975).

Reproductive

    3.20.1) SUMMARY
    A) Enflurane is classified as FDA pregnancy category B. No fetal abnormalities have been reported in humans exposed to enflurane. Enflurane crosses the placenta and appears in umbilical venous blood at about half the concentration in maternal venous blood. Dose-dependent birth defects have occurred in one animal study; however, other studies in rats and rabbits produced no evidence of fetal harm.
    3.20.2) TERATOGENICITY
    A) ANIMAL STUDIES
    1) RATS, RABBITS: Enflurane administration in rats and rabbits at doses up to 4 times the human dose produced no evidence of fetal harm (Prod Info ETHRANE(R) inhalation liquid, 2010).
    2) Exposure of pregnant mice to anesthetic concentrations (1%) resulted in an increase in birth defects in the offspring, consisting of cleft palate, ventriculomegaly, and hydronephrosis. Lower concentrations of 0.01% to 0.5% produced no teratogenic changes (Wharton, 1981).
    3.20.3) EFFECTS IN PREGNANCY
    A) PLACENTAL BARRIER
    1) Enflurane crosses the placenta and appears in umbilical venous blood at about half the concentration in maternal venous blood. Inhalation of enflurane for analgesia during the first stage of labor appears to not be associated with adverse effects on the parturient or fetus (Abboud, 1985).
    B) PREGNANCY CATEGORY
    1) Enflurane is classified as FDA pregnancy category B (Prod Info ETHRANE(R) inhalation liquid, 2010).
    C) LACK OF EFFECT
    1) Inhalation of enflurane for analgesia during the first stage of labor appears to not be associated with adverse effects on the parturient or fetus (McGuinness & Rosen, 1984).
    2) Enflurane caused no delayed adverse effects upon infant development or renal function 6 to 12 months after exposure to enflurane during Cesarean section (Kristianson et al, 1980; Wickstrom et al, 1980).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) Lactation studies with enflurane have not been conducted in humans; therefore, it is unknown whether enflurane is excreted into human milk (Prod Info ETHRANE(R) inhalation liquid, 2010).
    3.20.5) FERTILITY
    A) ANIMAL STUDIES
    1) Studies in mice have shown that prolonged exposure to high doses of enflurane may result in sperm abnormalities (Prod Info ETHRANE(R) inhalation liquid, 2010).

Summary Of Exposure

    A) WITH THERAPEUTIC USE
    1) Enflurane may cause CNS and respiratory depression, coughing, laryngospasm, hypotension, hepatotoxicity, renal toxicity, and seizures. ECG changes, nausea and vomiting, and malignant hyperthermia have occurred with enflurane anesthesia. Rhabdomyolysis with acute renal failure is a rare effect.

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS13838-16-9 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed
    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, the manufacturer does not report any carcinogenic potential with enflurane.
    3.21.4) ANIMAL STUDIES
    A) CARCINOMA
    1) In mice, enflurane is a carcinogenic compound according to RTECS criteria. In this species, intermittent inhalation exposure to 3000 parts per million for 4 hours for 78 weeks resulted in tumors in the respiratory system and liver (RTECS , 1999).
    B) NEOPLASIA
    1) Enflurane was given to Swiss ICR mice at 1/2, 1/8, and 1/32 minimum alveolar concentration (MAC) for 4 in-utero exposures plus 24 exposures during the first 9 weeks of life. The incidence of tumors was the same in the treated mice compared with untreated control mice which received the same background gases (Prod Info ETHRANE(R) inhalation liquid, 2010).

Genotoxicity

    A) DNA damage has been described in human lymphocytes stimulated with pokeweed mitogen following exposure to enflurane at concentrations of 0.2% volume. The rate of DNA damage was increased at higher concentrations. DNA single-strand breaks were shown by nucleoid sedimentation (Reitz et al, 1992).
    B) No mutagenic effects were associated with enflurane in the Ames test, sister chromatid exchange test, or the 8-azaguanine system (Prod Info ETHRANE(R) inhalation liquid, 2010).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor ECG and pulse oximetry. Serum fluoride concentrations and renal function should be monitored in cases of significant overexposure.
    B) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count, urinalysis, and liver and kidney function tests is suggested for patients with significant exposure.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Monitor renal function and serum fluoride concentrations in patients with significant overexposure.
    2) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count, urinalysis, and liver and kidney function tests is suggested for patients with significant exposure.
    4.1.3) URINE
    A) URINALYSIS
    1) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring urinalysis is suggested for patients with significant exposure.
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) Monitor arterial blood pressure and pulse oximetry, institute continuous cardiac monitoring.
    b) Respiratory rate (respiratory failure) should be monitored during enflurane anesthesia.
    c) Levels of enflurane in urine were useful for monitoring occupational enflurane exposure in operating rooms (Imbriani et al, 1994).
    1) A urinary level of 153 mcg/L corresponded to an airborne enflurane concentration of 75 ppm, a urinary level of 22 mcg/L corresponded to an airborne concentration of 10 ppm, and a urinary level of 3.5 mcg/L corresponded to an airborne concentration of 1 ppm (Imbriani et al, 1994).

Methods

    A) CHROMATOGRAPHY
    1) Enflurane may be detected and quantitated in blood and tissue samples with gas chromatography/mass spectrometry (GC/MS) methods (Jacob et al, 1989; Walker & Morano, 1990).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.3) DISPOSITION/INHALATION EXPOSURE
    6.3.3.5) OBSERVATION CRITERIA/INHALATION
    A) SEIZURES - The onset of convulsive symptoms after the end of anesthesia has ranged from within 5 minutes (Jenkins & Milne, 1984) to as long as 8 days (Ohm et al, 1975). The duration of symptoms has also varied; from 90 seconds to greater than 48 hours.
    B) HEPATITIS - The symptoms of hepatitis vary in onset from 5 to 19 days in reported cases (Denlinger et al, 1974; Sadone & Kim, 1974; Tsang, 1975). Most patients recover in 3 to 4 weeks with malaise being the only sequelae (Christ et al, 1988).

Monitoring

    A) Monitor ECG and pulse oximetry. Serum fluoride concentrations and renal function should be monitored in cases of significant overexposure.
    B) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count, urinalysis, and liver and kidney function tests is suggested for patients with significant exposure.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) Enflurane is an inhalational anesthetic. Although ingestion is unlikely, it may occur.Because of the rapid absorption of enflurane and rapid onset of CNS depression, prehospital decontamination is not recommended.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Because of rapid absorption and CNS depression, emesis and activated charcoal are of questionable value. Enflurane is an inhalational anesthetic. Ingestion is unlikely to occur.
    B) EMESIS/NOT RECOMMENDED
    1) Inducing emesis is not recommended
    C) ACTIVATED CHARCOAL
    1) May be of use if administered early and if the patient's airway is protected.
    2) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    3) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) GENERAL TREATMENT
    1) Information on ingestions is limited.
    2) Treatment should include recommendations listed in the INHALATION EXPOSURE section when appropriate.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.
    D) SPEED OF RECOVERY
    1) Black et al (1977) reported a rapid return of consciousness occurring in less than 5 minutes after discontinuing anesthesia.
    6.7.2) TREATMENT
    A) SEIZURE
    1) Seizures have been successfully treated with barbiturates, phenytoin, and diazepam (Allan, 1984) Yazji & Seed, 1984; (Grant, 1986; Parke & Jago, 1992; McManus, 1992; Ohm et al, 1975; Nicoll, 1986). Studies in cats have suggested that diazepam and barbiturates may lower the threshold for enflurane induced EEG changes (Darimont & Jenkins, 1977; Jenkins & Milne, 1984), but the clinical relevance of this has yet to be determined.
    2) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    3) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    4) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    5) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).
    6) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    7) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    8) PHENYTOIN/FOSPHENYTOIN
    a) Benzodiazepines and/or barbiturates are preferred to phenytoin or fosphenytoin in the treatment of drug or withdrawal induced seizures (Wallace, 2005).
    b) PHENYTOIN
    1) PHENYTOIN INTRAVENOUS PUSH VERSUS INTRAVENOUS INFUSION
    a) Administer phenytoin undiluted, by very slow intravenous push or dilute 50 mg/mL solution in 50 to 100 mL of 0.9% saline.
    b) ADULT DOSE: A loading dose of 20 mg/kg IV; may administer an additional 5 to 10 mg/kg dose 10 minutes after loading dose. Rate of administration should not exceed 50 mg/minute (Brophy et al, 2012).
    c) PEDIATRIC DOSE: A loading dose of 20 mg/kg, at a rate not exceeding 1 to 3 mg/kg/min or 50 mg/min, whichever is slower (Loddenkemper & Goodkin, 2011; Prod Info Dilantin(R) intravenous injection, intramuscular injection, 2013).
    d) CAUTIONS: Administer phenytoin while monitoring ECG. Stop or slow infusion if dysrhythmias or hypotension occur. Be careful not to extravasate. Follow each injection with injection of sterile saline through the same needle (Prod Info Dilantin(R) intravenous injection, intramuscular injection, 2013).
    e) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over next 12 to 24 hours for maintenance of therapeutic concentrations. Therapeutic concentrations of 10 to 20 mcg/mL have been reported (Prod Info Dilantin(R) intravenous injection, intramuscular injection, 2013).
    c) FOSPHENYTOIN
    1) ADULT DOSE: A loading dose of 20 mg phenytoin equivalent/kg IV, at a rate not exceeding 150 mg phenytoin equivalent/minute; may give additional dose of 5 mg/kg 10 minutes after the loading infusion (Brophy et al, 2012).
    2) CHILD DOSE: 20 mg phenytoin equivalent/kg IV, at a rate of 3 mg phenytoin equivalent/kg/minute, up to a maximum of 150 mg phenytoin equivalent/minute (Loddenkemper & Goodkin, 2011).
    3) CAUTIONS: Perform continuous monitoring of ECG, respiratory function, and blood pressure throughout the period where maximal serum phenytoin concentrations occur (about 10 to 20 minutes after the end of fosphenytoin infusion) (Prod Info CEREBYX(R) intravenous injection, 2014).
    4) SERUM CONCENTRATION MONITORING: Monitor serum phenytoin concentrations over the next 12 to 24 hours; therapeutic levels 10 to 20 mcg/mL. Do not obtain serum phenytoin concentrations until at least 2 hours after infusion is complete to allow for conversion of fosphenytoin to phenytoin (Prod Info CEREBYX(R) intravenous injection, 2014).
    B) BODY TEMPERATURE ABOVE REFERENCE RANGE
    1) MALIGNANT HYPERTHERMIA - Enflurane anesthesia has been associated with a skeletal muscle hypermetabolic state known as MALIGNANT HYPERTHERMIA. Dantrolene and ice have been recommended.
    2) DANTROLENE SODIUM (ADULT OR PEDIATRIC) - Initial recommended dose is 1 milligram per kilogram by rapid IV infusion.
    a) If symptoms persist or reappear, the dose may be repeated, to a cumulative dose of 10 milligrams per kilogram.
    b) Reversal is usually achieved with a cumulative dose of 2.5 milligrams per kilogram.
    c) Oral doses of 1 to 2 milligrams per kilogram four times daily for 1 to 3 days may be necessary to prevent the recurrence of the manifestations of malignant hyperthermia (Prod Info, 1985; (Cain & Bell, 1989).
    3) ICE - Apply ice to lower body temperature.
    C) CONDUCTION DISORDER OF THE HEART
    1) VENTRICULAR DYSRHYTHMIAS SUMMARY
    a) Obtain an ECG, institute continuous cardiac monitoring and administer oxygen. Evaluate for hypoxia, acidosis, and electrolyte disorders (particularly hypokalemia, hypocalcemia, and hypomagnesemia). Lidocaine and amiodarone are generally first line agents for stable monomorphic ventricular tachycardia, particularly in patients with underlying impaired cardiac function. Amiodarone should be used with caution if a substance that prolongs the QT interval and/or causes torsades de pointes is involved in the overdose. Unstable rhythms require immediate cardioversion.
    2) LIDOCAINE
    a) LIDOCAINE/INDICATIONS
    1) Ventricular tachycardia or ventricular fibrillation (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010; Vanden Hoek et al, 2010).
    b) LIDOCAINE/DOSE
    1) ADULT: 1 to 1.5 milligrams/kilogram via intravenous push. For refractory VT/VF an additional bolus of 0.5 to 0.75 milligram/kilogram can be given at 5 to 10 minute intervals to a maximum dose of 3 milligrams/kilogram (Neumar et al, 2010). Only bolus therapy is recommended during cardiac arrest.
    a) Once circulation has been restored begin a maintenance infusion of 1 to 4 milligrams per minute. If dysrhythmias recur during infusion repeat 0.5 milligram/kilogram bolus and increase the infusion rate incrementally (maximal infusion rate is 4 milligrams/minute) (Neumar et al, 2010).
    2) CHILD: 1 milligram/kilogram initial bolus IV/IO; followed by a continuous infusion of 20 to 50 micrograms/kilogram/minute (de Caen et al, 2015).
    c) LIDOCAINE/MAJOR ADVERSE REACTIONS
    1) Paresthesias; muscle twitching; confusion; slurred speech; seizures; respiratory depression or arrest; bradycardia; coma. May cause significant AV block or worsen pre-existing block. Prophylactic pacemaker may be required in the face of bifascicular, second degree, or third degree heart block (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010).
    d) LIDOCAINE/MONITORING PARAMETERS
    1) Monitor ECG continuously; plasma concentrations as indicated (Prod Info Lidocaine HCl intravenous injection solution, 2006).
    3) AMIODARONE
    a) AMIODARONE/INDICATIONS
    1) Effective for the control of hemodynamically stable monomorphic ventricular tachycardia. Also recommended for pulseless ventricular tachycardia or ventricular fibrillation in cardiac arrest unresponsive to CPR, defibrillation and vasopressor therapy (Link et al, 2015; Neumar et al, 2010). It should be used with caution when the ingestion involves agents known to cause QTc prolongation, such as fluoroquinolones, macrolide antibiotics or azoles, and when ECG reveals QT prolongation suspected to be secondary to overdose (Prod Info Cordarone(R) oral tablets, 2015).
    b) AMIODARONE/ADULT DOSE
    1) For ventricular fibrillation or pulseless VT unresponsive to CPR, defibrillation, and a vasopressor therapy give an initial dose of 300 mg IV followed by 1 dose of 150 mg IV. For stable ventricular tachycardias: Infuse 150 milligrams over 10 minutes, and repeat if necessary. Follow by a 1 milligram/minute infusion for 6 hours, then a 0.5 milligram/minute. Maximum total dose over 24 hours is 2.2 grams (Neumar et al, 2010).
    c) AMIODARONE/PEDIATRIC DOSE
    1) Infuse 5 milligrams/kilogram as a bolus for pulseless ventricular tachycardia or ventricular fibrillation; may repeat twice up to 15 mg/kg. Infuse 5 milligrams/kilogram over 20 to 60 minutes for perfusing tachycardias. Maximum single dose is 300 mg. Routine use with other drugs that prolong the QT interval is NOT recommended (Kleinman et al, 2010).
    d) ADVERSE EFFECTS
    1) Hypotension and bradycardia are the most common adverse effects (Neumar et al, 2010).
    4) PROCAINAMIDE
    a) PROCAINAMIDE/INDICATIONS
    1) An alternative drug in the treatment of PVCs or recurrent ventricular tachycardia when lidocaine is contraindicated or not effective. It should be avoided when the ingestion involves agents with quinidine-like effects (e.g. tricyclic antidepressants, phenothiazines, chloroquine, antidysrhythmics) and when the ECG reveals QRS widening or QT prolongation suspected to be secondary to overdose(Neumar et al, 2010; Vanden Hoek,TL,et al).
    b) PROCAINAMIDE/ADULT LOADING DOSE
    1) 20 to 50 milligrams/minute IV until dysrhythmia is suppressed or toxicity develops from procainamide (hypotension develops or the QRS is widened by 50%), or a total dose of 17 milligrams/kilogram is given (1.2 grams for a 70 kilogram person) (Neumar et al, 2010).
    2) ALTERNATIVE DOSING: 100 mg every 5 minutes until dysrhythmia is controlled, or toxicity develops from procainamide (hypotension develops or the QRS is widened by 50%) or 17 mg/kg have been given (Neumar et al, 2010).
    3) MAXIMUM DOSE: 17 milligrams/kilogram (Neumar et al, 2010).
    c) PROCAINAMIDE/CONTROLLED INFUSION
    1) In conscious patients, procainamide should be administered as a controlled infusion (20 milligrams/minute) because of the risk of QT prolongation and its hypotensive effects (Link et al, 2015)
    d) PROCAINAMIDE/ADULT MAINTENANCE DOSE
    1) 1 to 4 milligrams/minute via an intravenous infusion (Neumar et al, 2010).
    e) PROCAINAMIDE/PEDIATRIC LOADING DOSE
    1) 15 milligrams/kilogram IV/Intraosseously over 30 to 60 minutes; discontinue if hypotension develops or the QRS widens by 50% (Kleinman et al, 2010).
    f) PROCAINAMIDE/PEDIATRIC MAINTENANCE DOSE
    1) Initiate at 20 mcg/kg/minute and increase in 10 mcg/kg/minute increments every 15 to 30 minutes until desired effect is achieved; up to 80 mcg/kg/minute (Bouhouch et al, 2008; Ratnasamy et al, 2008; Mandapati et al, 2000; Luedtke et al, 1997; Walsh et al, 1997).
    g) PROCAINAMIDE/PEDIATRIC MAXIMUM DOSE
    1) 2 grams/day (Bouhouch et al, 2008; Ratnasamy et al, 2008; Mandapati et al, 2000; Luedtke et al, 1997; Walsh et al, 1997).
    h) MONITORING PARAMETERS
    1) ECG, blood pressure, and blood concentrations (Prod Info procainamide HCl IV, IM injection solution, 2011). Procainamide can produce hypotension and QT prolongation (Link et al, 2015).
    i) AVOID
    1) Avoid in patients with QT prolongation and CHF (Neumar et al, 2010).
    D) AIRWAY MANAGEMENT
    1) Enflurane may cause abrupt respiratory failure. Administer oxygen and endotracheally intubate as clinically indicated.
    E) FLUID/ELECTROLYTE BALANCE REGULATION
    1) Fluid and electrolyte replacement may be necessary in cases of metabolic acidosis, hyperkalemia, and myoglobinemia.
    F) ACIDOSIS
    1) METABOLIC ACIDOSIS: Treat severe metabolic acidosis (pH less than 7.1) with sodium bicarbonate, 1 to 2 mEq/kg is a reasonable starting dose(Kraut & Madias, 2010). Monitor serum electrolytes and arterial or venous blood gases to guide further therapy.
    2) Repeat doses of no more than one-half the original amount may be given no more often than every 10 minutes if required (American Heart Association, 1987). Monitor blood gases to adjust dose.
    G) HYPOTENSIVE EPISODE
    1) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    2) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    3) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
    H) RHABDOMYOLYSIS
    1) SUMMARY: Early aggressive fluid replacement is the mainstay of therapy and may help prevent renal insufficiency. Diuretics such as mannitol or furosemide may be added if necessary to maintain urine output but only after volume status has been restored as hypovolemia will increase renal tubular damage. Urinary alkalinization is NOT routinely recommended.
    2) Initial treatment should be directed towards controlling acute metabolic disturbances such as hyperkalemia, hyperthermia, and hypovolemia. Control seizures, agitation, and muscle contractions (Erdman & Dart, 2004).
    3) FLUID REPLACEMENT: Early and aggressive fluid replacement is the mainstay of therapy to prevent renal failure. Vigorous fluid replacement with 0.9% saline (10 to 15 mL/kg/hour) is necessary even if there is no evidence of dehydration. Several liters of fluid may be needed within the first 24 hours (Walter & Catenacci, 2008; Camp, 2009; Huerta-Alardin et al, 2005; Criddle, 2003; Polderman, 2004). Hypovolemia, increased insensible losses, and third spacing of fluid commonly increase fluid requirements. Strive to maintain a urine output of at least 1 to 2 mL/kg/hour (or greater than 150 to 300 mL/hour) (Walter & Catenacci, 2008; Camp, 2009; Erdman & Dart, 2004; Criddle, 2003). To maintain a urine output this high, 500 to 1000 mL of fluid per hour may be required (Criddle, 2003). Monitor fluid input and urine output, plus insensible losses. Monitor for evidence of fluid overload and compartment syndrome; monitor serum electrolytes, CK, and renal function tests.
    4) DIURETICS: Diuretics (eg, mannitol or furosemide) may be needed to ensure adequate urine output and to prevent acute renal failure when used in combination with aggressive fluid therapy. Loop diuretics increase tubular flow and decrease deposition of myoglobin. These agents should be used only after volume status has been restored, as hypovolemia will increase renal tubular damage. If the patient is maintaining adequate urine output, loop diuretics are not necessary (Vanholder et al, 2000).
    5) URINARY ALKALINIZATION: Alkalinization of the urine is not routinely recommended, as it has never been documented to reduce nephrotoxicity, and may cause complications such as hypocalcemia and hypokalemia (Walter & Catenacci, 2008; Huerta-Alardin et al, 2005; Brown et al, 2004; Polderman, 2004). Retrospective studies have failed to demonstrate any clinical benefit from the use of urinary alkalinization (Brown et al, 2004; Polderman, 2004; Homsi et al, 1997).
    I) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).
    6.8.2) TREATMENT
    A) GENERAL TREATMENT
    1) Treatment should include recommendations listed in the INHALATION EXPOSURE section when appropriate.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    6.9.2) TREATMENT
    A) GENERAL TREATMENT
    1) Treatment should include recommendations listed in the INHALATION EXPOSURE section when appropriate.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Abstracts

Case Reports

    A) ADULT
    1) ASPHYXIA - A fatality resulting from the misuse of enflurane has been reported by Lingenfelter (1981). A 29-year-old student nurse anesthetist had applied enflurane topically with a 4 by 4 gauze to her lower lip in an effort to treat herpes simplex labialis.
    a) The patient had apparently used the entire contents of a 250 mL enflurane bottle over a 3 to 4 hour period and was later found unconscious in the women's restroom. Cardiopulmonary resuscitation was performed unsuccessfully.
    b) Autopsy findings were normal, with the exception of high enflurane concentrations in the skin, gastric contents, blood, and lungs. The death was attributed to airway obstruction and subsequent asphyxia (Lingenfelter, 1981a).
    2) LIVER TOXICITY - A predominantly cholestatic reaction to enflurane was described by Foutch et al (1987). A 60-year-old male developed preicteric fever 8 days following enflurane anesthesia, followed by the occurrence of jaundice on the 22nd day.
    a) Eosinophilia with mixed hepatocellular-cholestatic liver injury was observed initially, however by day 31 biochemical cholestasis predominated.
    b) Biopsy at this time was consistent with a mixed hepato-cannalicular drug reaction. The patient recovered within approximately 10 weeks. This appears to be the first case report of predominantly cholestatic features occurring late in the clinical course of enflurane-induced hepatitis (Foutch et al, 1987).
    3) RENAL TOXICITY - Eichhorn (1976) reported a case of a 66-year-old male with carcinoma of the bladder who developed oliguria and anuria unresponsive to furosemide following a second course of enflurane.
    a) Following the second course of enflurane anesthesia, the patient was found to have peak fluoride levels of 25 millimoles per liter with peak inorganic fluoride concentration of 93 millimoles per liter, which is considered nephrotoxic.
    b) With supportive therapy, the patient's urine output spontaneously returned and gradually increased from the fourth postanesthetic day on (Eichhorn et al, 1976).

Range Of Toxicity

Summary

    A) Toxic dose is not established. Recreational abuse or any non medical use may cause life threatening respiratory depression.

Therapeutic Dose

    7.2.1) ADULT
    A) ANALGESIA: 0.25% to 1% of enflurane inspired concentrations provides analgesia for vaginal delivery. This concentration provides analgesia equivalent to that provided by 30% to 60% nitrous oxide (Prod Info ETHRANE(R) inhalation liquid, 2010).
    B) CESAREAN SECTION: The recommended enflurane concentration is 0.5% to 1% as supplementation to other general anesthetics (Prod Info ETHRANE(R) inhalation liquid, 2010).
    C) INDUCTION OF ANESTHESIA: 2% to 4.5% of enflurane inspired concentrations produces surgical anesthesia within 7 to 10 minutes (Prod Info ETHRANE(R) inhalation liquid, 2010).
    D) MAINTENANCE OF ANESTHESIA: 0.5% to 3% of enflurane inspired concentrations maintains surgical levels of anesthesia; MAX concentration, 3% (Prod Info FORANE(R) inhalation liquid, 2010).
    7.2.2) PEDIATRIC
    A) GENERAL
    1) HYPERKALEMIA
    a) In pediatric patients, rare cases of increased serum potassium levels resulting in cardiac arrhythmias, including fatalities, during the postoperative period have been associated with inhaled anesthetic agent use. Patients with latent or overt neuromuscular disease, particularly Duchenne muscular dystrophy, appear to have an increased risk. In most cases, succinylcholine was coadministered. There were also significant serum creatinine kinase levels in these patients. In some cases, there were also changes in urine consistent with myoglobinuria. Although this condition was similar to malignant hyperthermia in presentation, there were no signs or symptoms of muscle rigidity or hypermetabolic states in any of these patients. It is recommended that hyperkalemia and resistant arrhythmias be treated early and aggressively as would be the standard subsequent evaluation for latent neuromuscular disease (Prod Info ETHRANE(R) inhalation liquid, 2010)
    2) FLUORIDE CONCENTRATIONS DURING THERAPEUTIC ADMINISTRATION
    1) Serum inorganic fluoride concentrations in children anesthetized with enflurane 0.8% to 1% for 20 to 200 minutes were comparable to levels found in adult patients receiving this anesthetic for equal duration (Oikkonen & Meretaja, 1989).
    2) In 40 children (aged 22 days to 11 years), increases in serum fluoride concentration ranged from 2 to 10 micromoles/liter, with a highest individual value of 12.5 micromoles/liter (Oikkonen & Meretaja, 1989).
    3) In another 23 children, increases in serum fluoride concentration ranged from 3 to 9 micromoles/liter; increases did not clearly correlate with age (Oikkonen & Meretaja, 1989).

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) The minimum lethal human dose to this agent has not been delineated.
    2) Fatalities have been reported following the inhalational abuse of one entire bottle of enflurane (Jacob et al, 1989; Walker & Morano, 1990).

Maximum Tolerated Exposure

    A) SPECIFIC SUBSTANCE
    1) FLUORIDE
    a) Serum inorganic fluoride concentrations of greater than 50 mcmol have been associated with subclinical renal toxicity (Carter et al, 1976).
    2) The maximum tolerated human exposure to this agent has not been delineated.
    B) ANIMAL STUDIES
    1) In rats, intermittent exposure via inhalation to 170 ppm for 3H for 4W resulted in changes in liver weight (RTECS , 1999).

Serum Plasma Blood Concentrations

    7.5.1) THERAPEUTIC CONCENTRATIONS
    A) THERAPEUTIC CONCENTRATION LEVELS
    1) ADULT
    a) O'Neill et al (1982) recorded a mean enflurane plasma concentration of 100 mcg/mL in 20 pediatric patients receiving enflurane 3% to 4% in nitrous oxide:oxygen, 70:30. Anesthesia was reported to be smooth and uncomplicated.
    b) Plasma concentrations following inspiration of enflurane 1.5% fell from 68.4 micrograms per milliliter at 40 minutes to 3.5 micrograms per milliliter 6 hours after anesthesia was stopped (Imbenotte et al, 1987).
    c) Maximum blood concentrations of enflurane were 70 mcg/mL 20 minutes after uptake of enflurane 1.5% (Imbenotte et al, 1987).
    d) The minimum alveolar concentration (MAC) of enflurane in man is 1.68% in pure oxygen, 1.17% in 30% nitrous oxide/70% oxygen, and 0.57% in 70% nitrous oxide/30% oxygen (Prod Info Ethrane(R), enflurane, 1989).
    2) PEDIATRIC
    a) FLUORIDE CONCENTRATIONS -
    1) Serum inorganic fluoride concentrations in children anesthetized with enflurane 0.8% to 1% for 20 to 200 minutes were comparable to levels found in adult patients receiving this anesthetic for equal duration (Oikkonen & Meretoja, 1989).
    2) In 40 children (aged 22 days to 11 years), increases in serum fluoride concentration ranged from 2 to 10 micromoles/liter, with a highest individual value of 12.5 micromoles/liter (Oikkonen & Meretoja, 1989).
    3) In another 23 children, increases in serum fluoride concentration ranged from 3 to 9 micromoles/liter; increases did not clearly correlate with age (Oikkonen & Meretoja, 1989).
    b) ENFLURANE CONCENTRATIONS -
    1) O'Neill et al (1982) recorded a mean enflurane plasma concentration of 100 mcg/mL in 20 pediatric patients receiving enflurane 3% to 4% in nitrous oxide:oxygen, 70:30. Anesthesia was reported to be smooth and uncomplicated.
    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) ADULT
    a) Blood enflurane level of 71 milligrams/deciliter was reported post-mortem in a 29-year-old male following the inhalational abuse of one bottle. Blood concentrations most likely do not correlate with blood concentrations at the time of death due to redistribution in the body as well as evaporation between the time of death and autopsy (Walker & Morano, 1990).

Workplace Standards

    A) ACGIH TLV Values for CAS13838-16-9 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.
    a) Adopted Value
    1) Enflurane
    a) TLV:
    1) TLV-TWA: 75 ppm
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: A4
    2) Codes: Not Listed
    3) Definitions:
    a) A4: Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    c) TLV Basis - Critical Effect(s): CNS impair; card impair
    d) Molecular Weight: 184.5
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:

    B) NIOSH REL and IDLH Values for CAS13838-16-9 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: Enflurane
    2) REL:
    a) TWA:
    b) STEL:
    c) Ceiling: 2 ppm (15.1 mg/m(3)) [60-minute]
    d) Carcinogen Listing: (Not Listed) Not Listed
    e) Skin Designation: Not Listed
    f) Note(s): [*Note: REL for exposure to waste anesthetic gas.]
    3) IDLH: Not Listed

    C) Carcinogenicity Ratings for CAS13838-16-9 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A4 ; Listed as: Enflurane
    a) A4 :Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: Enflurane
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS13838-16-9 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) References: ACGIH, 1991 Lewis, 1996 MSDS, 1999 RTECS, 2002
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 3900 mg/kg
    b) 3900 mcL/kg - Acute pulmonary edema and other changes
    2) LD50- (ORAL)MOUSE:
    a) 5 g/kg
    b) 5 mL/kg - Acute pulmonary edema and other changes
    3) LD50- (SUBCUTANEOUS)MOUSE:
    a) 38,800 mg/kg
    b) 38,800 mcL/kg - Acute pulmonary edema and other changes
    4) LD50- (INTRAPERITONEAL)RAT:
    a) 6 g/kg
    b) 6 mL/kg - Acute pulmonary edema and other changes
    5) LD50- (ORAL)RAT:
    a) 5450 mg/kg
    b) 5450 mcL/kg - Acute pulmonary edema and other changes
    6) LD50- (SUBCUTANEOUS)RAT:
    a) 19,500 mg/kg
    b) 19,500 mcL/kg - Acute pulmonary edema and other changes
    7) TCLo- (INHALATION)HUMAN:
    a) 1 pph for 6H - Urine volume decreased
    8) TCLo- (INHALATION)MOUSE:
    a) Female, 1 pph for 4H at 6-15D of pregnancy - Fetotoxicity and developmental abnormalities in musculoskeletal system
    b) Female, 10,000 ppm for 4H at 6-15D of pregnancy - Developmental abnormalities in urogenital and central nervous sytem, craniofacial
    c) 3000 ppm for 4H / 78W-I - Tumors in respiratory system and liver
    d) 170 ppm for 3H / 4W-I - Changes in weight of liver and other changes
    9) TCLo- (INHALATION)RAT:
    a) Female, 1500 ppm for 6H at 1-20D of pregnancy - Effects on newborn
    b) Female, 16,500 ppm for 6H at 8-10D of pregnancy - Fetotoxicity
    c) Female, 16,500 ppm for 6H at 11-13D of pregnancy - Developmental abnormalities in musculoskeletal system
    d) Female, 20 ppm for 8H at 28D prior to mating and 1-21D of pregnancy - Fetotoxicity

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Enflurane is indicated for induction and maintenance of general anesthesia. Clinical anesthesia produced by enflurane resembles halothane or methoxyflurane, except that it produces a more pronounced muscular relaxation. A graded impairment of central nervous system function is obtained with increasing enflurane anesthesia (Thornton et al, 1983).
    B) Enflurane produces a similar degree of central respiratory depression as the other halogenated anesthetics. However, tachypnea is uncommon, making enflurane superior when spontaneous ventilation is permitted, as in abdominal surgery (Gilman et al, 1990).

Physicochemical

Physical Characteristics

    A) Enflurane is a clear, colorless, stable, volatile, nonflammable, liquid that easily vaporizes. The boiling point is 56.5 degrees C (at 760 mmHg); vapor pressure is 175 mmHg (at 20 degrees C), 218 mmHg (at 25 degrees C), and 345 mmHg (at 36 degrees C); specific gravity is 1.517 (at 25/25 degrees C); refractive index is 1.3026 to 1.303 (at 20 degrees C); blood/gas coefficient is 1.91 (at 37 degrees C); oil/gas coefficient is 98.5 (at 37 degrees C); partition coefficients are 74 in conductive rubber and 120 in polyvinyl chloride (at 25 degrees C) (Prod Info ETHRANE(R) inhalation liquid, 2010).
    1) Enflurane is used in liquid form (Hathaway et al, 1996).
    2) It is clear and colorless and has a mild, sweet odor (ACGIH, 1991).
    B) It contains 19.53% carbon (C), 1.09% hydrogen (H), 19.22% chloride (Cl), 51.49% fluoride (F), and 8.67% oxygen (O) (Budavari, 1996).

Molecular Weight

    A) 184.49 (Prod Info COMPOUND 347(TM) liquid inhalation, 2001)

References

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