a) ACUTE EFFECTS: Household propellant (eg, whipping cream) abuse occurs when the gas emitted from the nozzle is sprayed into a plastic bag and breathed or sniffed directly. Acute effects are usually due to asphyxia (ie, headache, dizziness, seizures, and possibly death). Acute neurologic effects of poisoning are primarily due to asphyxia. Signs and symptoms may include excitation and euphoria that can progress to CNS depression, loss of consciousness and even death. Asphyxia can also lead to cardiac dysrhythmias and hypotension.
b) CHRONIC EFFECTS: CNS: Chronic abuse can cause myeloneuropathy. Findings may include numbness and tingling of the hands and legs, ataxia, peripheral sensory neuropathy, and weakness. In some cases, patients have complained of an electric-shock feeling that starts when the neck is flexed and radiates down the back to the legs. RESPIRATORY: Respiratory irritation may be noted. Interstitial emphysema and pneumomediastinum have been reported following inhalation from whipped cream dispensers. HEMATOLOGIC: Hematologic effects (ie, leukopenia, thrombocytopenia, severe megaloblastic anemia, myelosuppression) and neuropathy can follow chronic inhalation. OTHER: Vitamin B12 deficiency may have a role in toxicity.

a) Nitrous oxide has been reported to cause mild hypertension when used as an anesthetic (Hardman et al, 1996).

a) CARDIAC DYSRHYTHMIAS may occur and may be the result of hypoxia. In one study of 103 procedures using inhalation of halothane-nitrous oxide- oxygen mixture, cardiac dysrhythmias were recorded in 44 procedures (42.7%) (Fisch et al, 1969). The patients in this study were not intubated.

a) AV DISSOCIATION: A study of 100 patients receiving isoflurane anesthesia and epinephrine/lidocaine hemostasis during hypophysectomy found a significantly higher incidence of isorhythmic AV dissociation among those patients that also received nitrous oxide (Lampe et al, 1990a).

a) Homemade nitrous oxide, using ammonium nitrate fertilizer as a reagent, may be contaminated with nitrogen dioxide which can cause reversible bronchiolitis when inhaled (Messina & Wynne, 1982).

a) INTERSTITIAL EMPHYSEMA: The direct inhalation of nitrous oxide from the nozzle of an empty whipped cream dispenser has been reported to result in interstitial emphysema from the rupture of the intra-alveolar walls, and pneumomediastinum caused by the dissection of the interstitial gases centrally along the bronchovascular tree (LiPuma et al, 1982).
b) CASE REPORT: A 17-year-old girl intentionally ingested MDMA and inhaled nitrous oxide and was admitted to the ED with significant neck swelling along with neck, chest and throat pain. Although the patient had extensive subcutaneous emphysema, airway compromise was not present. Vital signs and laboratory studies were normal. Chest x-ray was suggestive of a pneumomediastinum with no pneumothorax. A CT of the chest showed extensive surgical emphysema in the neck and chest, with pneumomediastinum and a small anterior pneumothorax. Since the patient was clinically stable, the patient was treated conservatively and monitored closely due to the high risk for mediastinitis. Diagnostic studies showed no evidence of esophageal injury or perforation. Treatment included high flow oxygen and prophylactic antibiotic therapy. Following 3 days of close monitoring, a follow-up x-ray showed improvement in the pneumomediastinum. In this case, the combination of MDMA and nitrous oxide led to alveolar rupture and dissection of gas along the mediastinal planes. Rapid diffusion of nitrous oxide in a closed space likely led to extensive pneumomediastinum (McDermott et al, 2015).

a) Individuals abusing this agent generally purchase it in a can of cooking oil preparation or whipping cream, where it is used as a propellant. The can is inverted and sprayed for a short time until no further oil or whipping cream comes out and only the gas is being emitted from the nozzle. The gas is sprayed into a plastic bag and breathed or sniffed directly. Fatalities are usually due to suffocation and a plastic bag may be found near the victim's head.
b) CASE REPORT: A 32-year-old man was found deceased in his home after an apparent intentional inhalation of nitrous oxide from whipped cream cans. A backpack filled with whipped cream cans labelled as containing E-942 propellant (nitrous oxide) was found near his body. In addition, numerous cans emptied of the propellant were discovered in his home. His body was found connected to an anesthesia system built using rubber pipes and tubing that connected to a face mask and a blood pressure monitoring system connected to a can of whipped cream. It was determined that the face mask was fitted so tightly that it prohibited airflow and lead to hypoxia during inhalation of the nitrous oxide. The end result was cardiorespiratory failure and death (Potocka-Banas et al, 2011).

a) Main complications immediately following the use of nitrous oxide are due to lack of oxygen, asphyxia. Symptoms may include headache, dizziness, excitation proceeding to possible depression.

a) Many of the neurological and hematopoietic effects of nitrous oxide are presumed to be due to the selective inactivation of vitamin B12 (Deacon et al, 1978; Brodsky, 1983; Brodsky & Cohen, 1987; Pema et al, 1998). One study found several defects in cobalamin metabolism due to nitrous oxide administered to rats. This has also been reported in an infant with cobalamin deficiency (Kondo et al, 1981; Felmet et al, 2000).
b) CASE REPORT/PEDIATRIC: An 8-month-old, with a history of mild developmental delay, developed progressive lethargy and athetoid movements 6 days after elective surgery. Anesthesia was maintained for 80 minutes with inhaled isoflurane and nitrous oxide. The infant was found to be severely cobalamin deficient (less than 20 pg/mL; normal 200-950 pg/mL) with pancytopenia present. Forty-eight hours after treatment with intramuscular hydroxocobalamin the infant was more alert and had decreased athetosis. At 12 months, the child was regaining developmental milestones, but remained significantly delayed with a head circumference remaining below the 5th percentile.

a) Many of the neurological and hematopoietic effects of nitrous oxide are presumed to be due to the selective inactivation of vitamin B12 (Morris et al, 2015; Hsu et al, 2012; Deacon et al, 1978; Brodsky, 1983; Brodsky & Cohen, 1987; Pema et al, 1998). One study found several defects in cobalamin metabolism due to nitrous oxide administered to rats. This has also been reported in an infant with cobalamin deficiency (Kondo et al, 1981; Felmet et al, 2000).
b) CASE REPORT: ADULT: A 24-year-old vegetarian woman who had abused nitrous oxide developed decreased sensitivity to pinprick and temperature in a glove-and-stocking distribution with proximal lower-extremity weakness, but reflexes remained brisk (Lai et al, 1997). The authors speculated that the symptoms were exacerbated by a dietary deficiency of vitamin B12 related to the patient's vegetarianism. Symptoms gradually resolved with drug cessation and treatment with hydroxocobalamin and folate supplements.
c) CASE REPORT: A 22-year-old man, who had abused nitrous oxide (up to 20 to 30 canisters daily) for a month, developed progressive gait instability, numbness of the feet, and buckling at the knees resulting in episodes of falling 2 to 3 times daily. Physical examination included mild distal loss of vibration and proprioception, diminished ankle and extensor plantar reflexes, a Romberg sign and normal strength. An initial vitamin B12 level was 138 pg/mL (reference range, 250 to 900 pg/mL) and an elevated homocysteine level of 113.1 micromol/L (reference range, 0 to 14 micromol/L). Other laboratory studies were essentially within normal limits and a MRI of the spine was normal. Treatment included vitamin B12 (1000 mcg daily for 7 days, followed by 1000 mcg orally weekly) repletion along with thiamine and a multivitamin daily. Symptoms improved but 3 weeks (4 weeks after discontinuation of nitrous oxide) later the patient developed a new onset of progressive weakness in the lower extremities; physical exam was consistent with symptoms. Vitamin B12 and homocysteine levels were normal. Over the next 7 months, the patient's motor strength and reflexes gradually improved. The delayed motor deterioration in this patient may suggest that nitrous oxide may produce severe motor neuropathy or neuronopathy separate from vitamin B12 deficiency dorsal column myelopathy (Morris et al, 2015).
d) CASE REPORT: A 19-year-old man, with a history of nitrous oxide abuse for one month, developed polyneuropathy and myelopathy. Symptoms included general muscular weakness, areflexia, and wide-based, ataxic, steppage gait. Sensory tests revealed diminished superficial sensation below the cervical-thoracic junction and a glove-and-stocking pattern of sensory loss in all 4 extremities. The patient was treated with vitamin B12 (1000 mcg/day) injections for 5 days and received further B12 injections (1000 mcg) once per week for 2 months. Numbness resolved within the first 5 days and the patient was symptom free after 2 months of therapy (Hsu et al, 2012).
f) Neurological symptoms occurred in 15 patients exposed to nitrous oxide by either self-administration or professional use. The most common initial symptom, present in all individuals, was numbness and tingling of the hands and legs. Twelve of the patients reported an electric shock-like feeling produced by neck flexion that radiated up or down the back and legs. The side effects began to appear after 3 months to 5 years of nitrous oxide abuse. After administration was discontinued, improvement was noticed in a few weeks or months (Layzer et al, 1978).

a) CASE REPORT: A 27-year-old woman, with a history of depression, anxiety and chronic nitrous oxide abuse over approximately 3 years with an average use of 100 to 200 whipped cream charger cartridges per day on 3 to 4 days per week, was admitted with urinary retention (over 12 hours) and worsening lower extremity weakness. A urinary catheter was inserted and 1800 mL of urine was returned. A physical examination was significant for decreased vibration sensation and reduced proprioception in both lower extremities, a positive Romberg, and inability to balance without support. She was alert and oriented. A MRI was performed and showed an abnormal signal beginning at C3 to C4 and extending caudally to T11 to T12 which was highly suggestive of subacute combined degeneration (SCD) in the presence of nitrous oxide abuse. Her serum vitamin B12 concentration was normal (683 pg/mL, therapeutic range, 210-950) and no hematologic abnormalities. A drug screen was positive for opiates and benzodiazepines. The patient admitted using cyanocobalamin 1000 to 5000 mcg daily and cyanocobalamin injection (1000 to 2000 mcg IM daily as a 7 day course; the drug was received from a family member living in Europe) as needed. She started using this therapy after reading about it on the Internet. During her hospitalization she was treated with cyanocobalamin 1000 mcg IM daily for 5 days and to be followed by 1000 mcg IM weekly for 4 weeks. Other treatments included physical and occupational therapy. She was discharged on day 3 in stable condition, despite a lack of improvement in her neurologic symptoms. Despite extensive plans for outpatient care, the patient was lost to follow-up (Pugliese et al, 2015).

a) CASE REPORT: A 27-year-old man with a history of depression and self-harm was admitted with progressive lower limb weakness over a 6-week period. He was seen regularly in the ED for recurrent patellar dislocation. Nerve conduction studies were consistent with a primary demyelinating neuropathy. He was treated with immunoglobulin and showed some improvement and was discharged to a rehabilitation center with normal upper limb function and the ability to walk with a frame. The patient was readmitted 6 months later, with severe areflexic flaccid paraparesis, a B12 concentration of 108 ng/L (range, 180 to 700) and evidence of slow conduction velocities by nerve biopsy. During this admission, the patient admitted to intentionally dislocating his patella by using his fist or a hammer to receive nitrous oxide analgesia. B12 therapy was started; however, the patient remained a paraplegic requiring a wheelchair after 6 years of inconsistent follow-up (Thompson et al, 2015).
b) CASE REPORT: A woman in her 20s with a history of intravenous drug use had been inhaling nitrous oxide from whipped-cream bulbs for 10 days for pain secondary to a sprained ankle and was found living in a car for over 3 days prior to admission. An estimated 60 empty "bulbs" were found on the floor of the car. The patient was alert and oriented with 1/5 flaccid proximal weakness of the lower limbs. Neurological exam included an absent plantar and knee-jerk reflexes, with an intermittent sensory level to T10. A proprioception deficit to her feet, knees, and hips was also present bilaterally. Urinary retention was present with 1800 mL drained from an indwelling catheter. Laboratory evidence of rhabdomyolysis (creatine kinase 9000 Units/L), acute renal failure and vitamin B12 deficiency (level of 124 pmol/L (reference range: greater than 210 pmol/l) were also reported. Her clinical course was complicated by a cardiopulmonary arrest (secondary to dehydration) and bilateral deep venous thrombosis (DVT) to the level of the femoral arteries. Following successful resuscitation, the patient was treated with vitamin B12 replacement therapy, methionine and anticoagulation therapy. Over the next 5 months, the patient gradually regained partial motor function of her limbs and normal sensory levels. She was discharged after 2 months of rehabilitation and was able to walk short distances with a walking frame, but continued to have residual neurological deficits affecting the distal lower limb muscle groups (Cartner et al, 2007).

a) Anxiolytic, euphoric, and analgesic effects and central nervous system depression may occur (Kunkel, 1987).

a) Anxiolytic, euphoric, and analgesic effects and central nervous system depression may occur (Kunkel, 1987).

a) SUMMARY: Myeloneuropathy has been reported following chronic exposure (Hsu et al, 2012; Miller et al, 2004; Layzer et al, 1978; Pema et al, 1998). Onset of symptoms may be delayed 6 months or more following discontinuation of extensive usage (Heyer et al, 1986). Early sensory complaints include leg weakness, loss of balance, numbness and tingling in peripheral extremities and trunk, sphincter disturbance, and electric shock sensation radiating down the back on flexion of the neck (Lhermitte's sign) (Layzer et al, 1978; Hayden et al, 1983; Pema et al, 1998).
b) Physical findings may include ataxia with a wide based gait, increased deep tendon reflexes, a positive Rhomberg test, decreased vibratory sensation, proprioception and decreased sense of light touch in the lower extremities (Miller et al, 2004a).
c) Polyneuropathy has occurred from inhalation of nitrous oxide delivered from cartridges through a whipped cream dispenser, sometimes called "nanging" (Ng & Frith, 2002; Lai et al, 1997; Sahenk et al, 1978).
d) Several reports of neuropathy have occurred following abuse of nitrous oxide, primarily by dentists (Blanco & Peters, 1983) (Gutmann & Johnsen, 1981) (Paulson, 1979) (Sahenk et al, 1978; Layzer et al, 1978; Layzer et al, 1978).
e) Chronic abuse of nitrous oxide by health professionals or from chronic exposure to over-the-counter preparations containing the drug (ie, whipped cream dispensers) can result in megaloblastic anemia, polyneuropathy, bone marrow depression, and possibly reproductive system changes (Winek et al, 1995) (Wagner, 1992) (Kunkel, 1987).
f) CASE REPORT: A 24-year-old man, with a history of inhaling nitrous oxide from bottles (1000 L per bottle) at the rate of 4 bottles per week, was admitted with unsteady gait. His symptoms were consistent with myelopathy involving the posterior column and the bilateral corticospinal tract and possible polyneuropathy. He was initially treated with vitamin B12 (level was low (149 pg/mL)) supplementation with little response. It was suggested that the patient may have had a superimposed inflammatory neuropathy and was treated with plasmapheresis and ongoing B12 supplementation. Approximately, one week later the patient had improved and was able to walk independently with only mild unsteadiness. At one year follow-up, his condition was stable and diagnostic studies (including MRI) were within normal limits (Lin et al, 2011).
g) CASE REPORT: A 19-year-old man, with a history of nitrous oxide abuse for one month, developed polyneuropathy and myelopathy. Symptoms included general muscular weakness, areflexia, and wide-based, ataxic, steppage gait. Sensory tests revealed diminished superficial sensation below the cervical-thoracic junction and a glove-and-stocking pattern of sensory loss in all 4 extremities. The patient was treated with vitamin B12 (1000 mcg/day) injections for 5 days and received further B12 injections (1000 mcg) once per week for 2 months. Numbness resolved within the first 5 days and the patient was symptom free after 2 months of therapy (Hsu et al, 2012).
h) CASE REPORT: After abusing nitrous oxide (4 to 5 cans/daily, about 2000 mL/can) for more than 10 years, a 41-year-old man presented with progressive motor clumsiness and distal paresthesia in the four limbs. Laboratory tests showed megaloblastic red blood cells (102.3 fL, normal 80 to 94 fL) and serum vitamin B12 concentration of 143 pg/nL (normal 160 to 970 pg/mL). MRI of the brain revealed conspicuous changes in the posterior and lateral columns at the C2 to C7 level. In addition to sensori-motor axonal polyneuropathy, multimodal evoked potentials (EPs) showed the following abnormalities: abnormal visual EPs with delayed peak latencies of P100 bilaterally; abnormal brainstem auditory EPs characterized by inconsistent waveform of I and II and delayed peak latencies of wave V; abnormal somatosensory EPs of median and tibial nerve stimulation with markedly decreased peak amplitudes and delayed peak latencies of cortical potentials bilaterally; and abnormal motor EPs to transcranial magnetic stimulation with prolonged central motor conduction time (Lin et al, 2007).

a) Nausea and vomiting may occur with therapeutic use. In one study using 70% nitrous oxide and 30% oxygen, 3/124 patients had nausea and only 1/124 had vomited (Nieto & Rosen, 1980).

a) Impotence has been reported as an early sensory complaint associated with nitrous oxide-induced myeloneuropathy (Layzer et al, 1978; Hayden et al, 1983).

a) Bone marrow depression with resultant leukopenia, thrombocytopenia and megaloblastic anemia has been noted following chronic or intermittent inhalation of nitrous oxide (Anon, 1982; Amess et al, 1978; Nunn et al, 1982; Sweeney et al, 1985) and in one infant with cobalamin deficiency (not previously diagnosed) (Felmet et al, 2000).
b) Many of the neurological and hematopoietic effects of nitrous oxide are believed to be due to the selective inactivation of vitamin B12 (Deacon et al, 1978; Brodsky, 1983; Brodsky & Cohen, 1987; Pema et al, 1998). One study found several defects in cobalamin metabolism due to nitrous oxide administered to rats (Kondo et al, 1981).
c) CASE SERIES: A study comparing 25 patients who received nitrous oxide during anesthesia and 23 who did not revealed no changes in red cell mass, neutrophil production, or leukocyte levels after a 6 to 9 hour surgery. Both groups included elderly patients with mild B12 or folate deficiencies, but some patients were transfused during surgery and this may have masked nitrous oxide effects (Waldman et al, 1990).
d) CASE REPORT/PEDIATRIC: An 8-month-old, with a history of mild developmental delay, developed progressive neurological symptoms and pancytopenia (hematocrit 21% to 16.4%, leukocyte count of 1700/mm(3) with an absolute neutrophil count of 220/mm(3) and a platelet count of 26000/mm(3)) 9 days after elective surgery. The anesthetic agent used during surgery was isoflurane and nitrous oxide for 80 minutes. The infant was found to be severely cobalamin deficient (less than 20 pg/mL; normal 200-950 pg/mL). Forty-eight hours after treatment with intramuscular hydroxocobalamin the infant was more alert. Blood count and marrow recovery were evident within one week.

a) Bone marrow depression with resultant leukopenia, thrombocytopenia and severe megaloblastic anemia has been noted following chronic or intermittent inhalation of nitrous oxide (Anon, 1982; Amess et al, 1978; Nunn et al, 1982; Sweeney et al, 1985) and in one infant with cobalamin deficiency (not previously diagnosed) (Felmet et al, 2000).
b) Many of the neurological and hematopoietic effects of nitrous oxide are believed to be due to the selective inactivation of vitamin B12 (Deacon et al, 1978; Brodsky, 1983; Brodsky & Cohen, 1987; Pema et al, 1998). One study found several defects in cobalamin metabolism due to nitrous oxide administered to rats (Kondo et al, 1981).
c) Chronic abuse of nitrous oxide by health professionals or from chronic exposure to over-the-counter preparations containing the drug (ie, whipped cream dispensers) can result in megaloblastic anemia, polyneuropathy, bone marrow depression, and possibly reproductive system changes (Winek et al, 1995; Wagner et al, 1992; Kunkel, 1987).

a) Methemoglobinemia has resulted from contaminants of nitrous oxide canisters in anesthesia (Clutton-Brock, 1967). It was demonstrated that in vitro exposure of human blood to low concentrations of nitrous oxide (as low as 6 parts/million) oxidized 17% of hemoglobin to methemoglobin after 3 hours of exposure, and exposure to nitrous oxide concentrations at 45 ppm oxidized 50% of total hemoglobin to methemoglobin in the first hour (Chiodi et al, 1983).

a) CASE REPORT: A 76-year-old woman with a short bowel underwent anesthesia with nitrous oxide 60% in oxygen, isoflurane, and fentanyl for an operation that lasted just over 2 hours. She subsequently developed increasing pain, numbness, fatigue, and weakness in both arms. Five months after the operation her hematocrit had dropped from 41.3 to 30.3%. The authors suggest that vitamin B12 absorption was marginal due to her short bowel and her exposure to nitrous oxide oxidized enough vitamin B12 to depress methionine synthetase activity (Berger et al, 1988).

a) CASE REPORT: After abusing nitrous oxide (4 to 5 cans/daily, about 2000 mL/can) for more than 10 years, a 41-year-old man presented with progressive motor clumsiness and distal paresthesia in the four limbs. Laboratory tests showed megaloblastic red blood cells (102.3 fL, normal 80 to 94 fL) and serum vitamin B12 concentration of 143 pg/nL (normal 160 to 970 pg/mL) (Lin et al, 2007).

a) In one case, a man presented to the emergency department with frostbite injury to his left cheek after sniffing nitrous oxide directly from the cylinder (Hwang et al, 1996).

a) Fujinaga et al (1987) reported a greater incidence of early resorptions, late resorptions, total fetal wastage, major visceral malformations, and any visceral abnormality in the 50% nitrous oxide treated rats than in controls.
b) Prolonged exposure of male rats to 20% nitrous oxide produced a reduced sperm count and multinucleated cells (Kripke et al, 1976).
c) Pregnant rats exposed to 24 hours of 60% nitrous oxide demonstrated a specific period of susceptibility to teratogenic effects on days 8 and 9 of gestation. Defects included skeletal malformations of the ribs and vertebrae (Fujinaga et al, 1989).
d) A decrease in startle reflex and reactivity (both tactile and acoustic) was found in a group of mice prenatally exposed to nitrous oxide. Dams were exposed to 5, 15, and 35% nitrous oxide for 4 hours per day on gestational days 6 to 15. No skeletal teratogenic effects were observed (Rice, 1990).
e) CNS, cardiovascular, and renal abnormalities have been reported in nitrous oxide-exposed experimental animals (Fink et al, 1967) RTECS, 1996; HSDB, 1996).
f) Cultured rat embryos demonstrated growth retardation, morphological abnormalities, and altered body laterality after 24-hour exposures to nitrous oxide (Baden & Fujinaga, 1991). Similar findings in vivo were reported by the same group with 24 hours of exposure to 75 percent nitrous oxide on day 8 of gestation (Fujinaga et al, 1990).
g) No behavioral changes were noted in the offspring of rats exposed for six hours per day at 0.1 to 1.0 percent nitrous oxide in air throughout pregnancy (Holson et al, 1995).
h) Fetal loss and growth retardation have been observed among the offspring of rats chronically treated with nitrous oxide during pregnancy (Corbett et al, 1973; Pope et al, 1978; Vieira et al, 1980) 1983). A small but dose-related trend for increasing resorptions and decreased live births has been reported with six hour per day full gestation exposures to 0.1 to 1.0 percent nitrous oxide in air (Holson et al, 1995).

a) Other epidemiologic reports of occupational exposure to waste anesthetic agents have been negative (Hathaway et al, 1996).

a) Nerve conduction studies demonstrated slowed sensory potentials, reduced amplitude, and mildly prolonged late responses (Heyer et al, 1986).
b) Sensory evoked potentials showed prolonged latency of scalp-evoked potentials from nerve stimulation of tibia with normal median nerve values (Heyer et al, 1986).
c) Normal visual acuity, funduscopic examination, and spatial contrast sensitivity were reported. Foveal visual evoked potentials were noted to be delayed in the right eye (Heyer et al, 1986).

a) ACUTE EXPOSURE: Treatment is primarily supportive. Asphyxiation is a major risk in patients that abuse nitrous oxide (eg, "nanging") due to displacement of oxygen by nitrous oxide leading to hypoxia. Supplemental oxygen is the mainstay of treatment, and most patients recover rapidly once exposure ceases and oxygen is administered. Monitor vital signs, pulse oximetry continuously and cardiac monitoring. Obtain baseline ABGs; repeat as needed. Patients may initially have tachypnea and tachycardia followed by bradycardia, respiratory depression and hypotension. Initially treat hypotension with IV fluids; infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine or norepinephrine; titrate to desired response. Nausea and vomiting can develop following its use as an anesthetic. Monitor fluid status and electrolytes; correct electrolyte abnormalities as indicated.

a) Supportive treatment. Administer supplemental oxygen. In cases of severe CNS and/or respiratory depression, consider orotracheal intubation. Early symptoms may include delirium and euphoria (signs of hypoxemia) that can lead to respiratory depression and coma. Avoid benzodiazepines or other respiratory depressant agents. Patients who do not recover rapidly have likely sustained hypoxic end organ damage, which may be irreversible. OTHER: HEMATOLOGIC: Chronic exposure (ie intermittent or chronic inhalation) can produce leukopenia, thrombocytopenia, and megaloblastic anemia. NEUROLOGIC: Neurologic events including numbness, gait disturbances, paresthesia, myeloneuropathy have developed after long periods of exposure. Cyanocobalamin (vitamin B12) has been used successfully in patients with chronic toxicity. RARE: Methemoglobinemia has occurred as a result of contaminants found in nitrous oxide canisters. Obtain a methemoglobin level in a patient that is cyanotic despite adequate oxygenation.

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.

a) LIDOCAINE/INDICATIONS
b) LIDOCAINE/DOSE
c) LIDOCAINE/MAJOR ADVERSE REACTIONS
d) LIDOCAINE/MONITORING PARAMETERS

a) AMIODARONE/INDICATIONS
b) AMIODARONE/ADULT DOSE
c) AMIODARONE/PEDIATRIC DOSE
d) ADVERSE EFFECTS

a) Folinic acid has also been shown to have a protective effect against the metabolic toxicity associated with nitrous oxide exposure (Louis-Ferdinand, 1994).
b) FOLINIC ACID is the active form of folate. A single IV dose of 30 mg has been effective in reversing bone marrow toxicity after repeated use of nitrous oxide anesthesia (Nunn et al, 1986).

a) Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (ie, dyspnea, headache, fatigue, CNS depression, tachycardia, metabolic acidosis). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin concentrations above 20% to 30%, but may occur at lower methemoglobin concentrations in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy.

a) INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules (Prod Info PROVAYBLUE(TM) intravenous injection, 2016) and 10 mg/1 mL (1% solution) vials (Prod Info methylene blue 1% intravenous injection, 2011). REPEAT DOSES: Additional doses may be required, especially for substances with prolonged absorption, slow elimination, or those that form metabolites that produce methemoglobin. NOTE: Large doses of methylene blue may cause methemoglobinemia or hemolysis (Howland, 2006). Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection (Prod Info methylene blue 1% intravenous injection, 2011; Herman et al, 1999). NEONATES: DOSE: 0.3 to 1 mg/kg (Hjelt et al, 1995).
b) CONTRAINDICATIONS: G-6-PD deficiency (methylene blue may cause hemolysis), known hypersensitivity to methylene blue, methemoglobin reductase deficiency (Shepherd & Keyes, 2004)
c) FAILURE: Failure of methylene blue therapy suggests: inadequate dose of methylene blue, inadequate decontamination, NADPH dependent methemoglobin reductase deficiency, hemoglobin M disease, sulfhemoglobinemia, or G-6-PD deficiency. Methylene blue is reduced by methemoglobin reductase and nicotinamide adenosine dinucleotide phosphate (NADPH) to leukomethylene blue. This in turn reduces methemoglobin. Red blood cells of patients with G-6-PD deficiency do not produce enough NADPH to convert methylene blue to leukomethylene blue (do Nascimento et al, 2008).
d) DRUG INTERACTION: Concomitant use of methylene blue with serotonergic drugs, including serotonin reuptake inhibitors (SRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), triptans, and ergot alkaloids may increase the risk of potentially fatal serotonin syndrome (U.S. Food and Drug Administration, 2011; Stanford et al, 2010; Prod Info methylene blue 1% IV injection, 2011).

a) DOSE: 2 to 4 mg/kg intravenously over 5 minutes. Dose may be repeated in 30 minutes (Nemec, 2011; Lindenmann et al, 2006; Kiese et al, 1972).
b) SIDE EFFECTS: Hypotension with rapid intravenous administration. Vomiting, diarrhea, excessive sweating, hypotension, dysrhythmias, hemolysis, agranulocytosis and acute renal insufficiency after overdose (Dunipace et al, 1992; Hix & Wilson, 1987; Winek et al, 1969; Teunis et al, 1970; Marquez & Todd, 1959).
c) CONTRAINDICATIONS: G-6-PD deficiency; may cause hemolysis.

a) Five fatalities due to nitrous oxide abuse demonstrated postmortem blood concentrations of 46 to 180 milliliters/liter (Baselt RC, 1976; DiMaio & Garriott, 1978).
b) Administration of 20 to 40 percent nitrous oxide produces analgesia in conscious patients. General anesthesia occurs with levels of 60 to 80 percent. Nitrous oxide should be administered with a minimum of 20 percent oxygen to prevent irreversible anoxic damage (Rogo & Lupovici, 1986).

1) Nitrous oxide

a) TWA: 25 ppm (46 mg/m(3)) (over the time exposed)
b) STEL:
c) Ceiling:
d) Carcinogen Listing: (Not Listed) Not Listed
e) Skin Designation: Not Listed
f) Note(s): [*Note: REL for exposure to waste anesthetic gas.]

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.

a) Female 14D post, 5000 ppm for 4H -- REP
b) Female 14D post, 75 pph for 6H -- TER