NEFAZODONE

6.4 MONITORING

A. Nefazodone plasma levels are not widely available and their clinical usefulness has not been determined.
B. Following nefazodone overdose, monitor heart rate, ECG, blood pressure, liver function tests, neurologic and respiratory status.

6.5 ORAL EXPOSURE

6.5.1 PREVENTION OF ABSORPTION/PREHOSPITAL

A. EMESIS/NOT RECOMMENDED -

1. Mild drowsiness and lethargy have occurred 30 minutes to 2 hours postingestion (Lesar et al, 1984; Root & Ohlson, 1984). Ipecac is not recommended.

B. ACTIVATED CHARCOAL -

1. PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION

a. Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion.

(1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should be administered by medical or paramedical personnel capable of airway management to prevent aspiration in the event of spontaneous emesis.

2. 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; and 1 gram/kilogram in infants up to 1 year old (USP DI, 2000; Chyka & Seger, 1997).

(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 (Barceloux et al, 1997).

b. ADVERSE EFFECTS/CONTRAINDICATIONS

(1) Complications: emesis, aspiration (Chyka & Seger, 1997). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
(2) Contraindications: unprotected airway, gastrointestinal tract not anatomically intact, therapy may increase the risk or severity of aspiration; ingestion of most hydrocarbons (Chyka & Seger, 1997).

6.5.2 PREVENTION OF ABSORPTION

A. GASTRIC LAVAGE

1. INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).

a. Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.

2. PRECAUTIONS:

a. SEIZURE CONTROL: Is mandatory prior to gastric lavage.
b. AIRWAY PROTECTION: Alert patients - place in Trendelenburg and left lateral decubitus position, with suction available. Obtunded or unconscious patients - cuffed endotracheal intubation.

3. LAVAGE FLUID:

a. Use small aliquots of liquid. Lavage with 150 to 200 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in children over 5 or adults) and 10 milliliters/kilogram body weight of normal saline in young children. Continue until lavage return is clear.
b. The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
c. CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.

4. COMPLICATIONS:

a. Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications.
b. Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).

5. CONTRAINDICATIONS:

a. Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.

B. ACTIVATED CHARCOAL

1. CHARCOAL ADMINISTRATION

a. Consider administration of activated charcoal after a potentially toxic ingestion (Chyka & Seger, 1997). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

2. 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; and 1 gram/kilogram in infants up to 1 year old (USP DI, 2000; Chyka & Seger, 1997).

(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 (Barceloux et al, 1997).

b. ADVERSE EFFECTS/CONTRAINDICATIONS

(1) Complications: emesis, aspiration (Chyka & Seger, 1997). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
(2) Contraindications: unprotected airway, gastrointestinal tract not anatomically intact, therapy may increase the risk or severity of aspiration; ingestion of most hydrocarbons (Chyka & Seger, 1997).

6.5.3 TREATMENT

A. SUPPORTIVE CARE

1. There is no specific treatment for nefazodone overdose other than supportive care. Nefazodone overdose alone has not prolonged QRS duration and there is no evidence that therapies used in tricyclic antidepressant overdose (bicarbonate, phenytoin) are useful.
2. There is only a small risk for seizures in overdose, thus prophylactic treatment with anticonvulsants is not recommended. Hypotension has responded to intravenous fluids.

B. HYPOTENSION

1. SUMMARY

a. Infuse 10 to 20 milliliters/kilogram of isotonic fluid and place in Trendelenburg position. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

2. DOPAMINE

a. PREPARATION: Add 200 or 400 milligrams to 250 milliliters of normal saline or dextrose 5% in water to produce 800 or 1600 micrograms per milliliter or add 400 milligrams to 500 milliliters of normal saline or dextrose 5% in water to produce 800 micrograms per milliliter.
b. DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed. Norepinephrine should be added if more than 20 micrograms/kilogram/minute of dopamine is needed.
c. CAUTION: If VENTRICULAR DYSRHYTHMIAS occur, decrease rate of administration. Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred.

3. NOREPINEPHRINE

a. PREPARATION: Add one milligram norepinephrine to 250 milliliters of dextrose 5% in water to produce 4 micrograms/milliliter.
b. DOSE

(1) ADULT: 2 to 3 milliliters (8 to 12 micrograms)/minute
(2) ADULT AND CHILD: 0.1 to 0.2 microgram/kilogram/minute. Titrate to maintain adequate blood pressure.
(3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised.

C. BRADYCARDIA

1. ATROPINE - may be indicated if significant bradycardia or heart block are present.
2. ATROPINE/DOSE

a. ADULT ASYSTOLIC ARREST: Give 1 milligram intravenously and repeat in three to five minutes if asystolic cardiac arrest persists. Three milligrams (0.04 milligram/kilogram) intravenously is a fully vagolytic dose in most adults.
b. ADULT BRADYCARDIA: Give 0.5 milligram to 1 milligram intravenously or intratracheally every five minutes up to a maximum total dose of 0.04 milligram/kilogram. Doses less than 0.5 milligram may cause paradoxical bradycardia in adults.
c. PEDIATRIC DOSE: Give 0.02 milligram/kilogram intravenously or intraosseously (maximum single dose: CHILD: 0.5 milligram; ADOLESCENT: 1 milligram) repeating every five minutes if needed.

(1) MINIMUM DOSE: 0.1 milligram. Doses less than 0.1 milligram may cause paradoxical bradycardia in children.
(2) MAXIMUM DOSE: 1 milligram in children; 2 milligrams in adolescents.

d. ENDOTRACHEAL ADMINISTRATION: Optimum dose is not established as systemic absorption is unreliable. Administer two to three times the recommended intravenous dose and dilute in a volume of 3 to 5 milliliters of 0.9% saline. Follow with several positive pressure breaths.

D. TORSADE DE POINTES

1. Since nefazodone is pharmacologically related to trazodone, which is known to produce a dose-related prolongation of the QTc interval, ventricular arrhythmias, including torsades de pointes, are possible (Augenstein et al, 1987).
2. SUMMARY

a. Withdraw the causative agent. Hemodynamically unstable patients require electrical cardioversion. Emergent treatment with magnesium, isoproterenol, or atrial overdrive pacing is indicated. Detect and correct underlying electrolyte abnormalities (hypomagnesemia, hypokalemia, hypocalcemia) (Smith & Gallagher, 1980; Keren et al, 1981; AHA, 2000).

3. MAGNESIUM SULFATE

a. ADULT DOSE: No clearly established guidelines exist. Administer 2 grams (16 mEq) mixed in 50 to 100 milliliters D5W intravenously over 5 minutes, followed if needed by a second 2 gram bolus and infusion of 3 to 50 milligrams/minute in patients not responding to the initial bolus or with recurrence of dysrhythmias (AHA, 2000; Perticone et al, 1997).
b. PEDIATRIC DOSE: 25 to 50 milligrams/kilogram diluted to 10 milligrams/milliliter for intravenous infusion over 5 to 15 minutes.
c. PRECAUTIONS: Use with caution in patients with renal insufficiency.
d. MAJOR ADVERSE EFFECTS: High doses may cause respiratory depression, weakness, neuromuscular blockade, and hypotension.
e. MONITORING PARAMETERS: Heart rate and rhythm, blood pressure, respiratory rate, motor strength, deep tendon reflexes, serum magnesium, phosphorus, and calcium.

4. ISOPROTERENOL

a. DOSE: 2 to 10 micrograms/minute (children: 0.1 to 1 microgram/kilogram/minute) by continuous monitored intravenous infusion; titrate to heart rate and rhythm response. A 2-microgram/milliliter solution may be prepared by mixing 1 milligram isoproterenol hydrochloride in 500 milliliters of dextrose 5 percent in water.
b. AVAILABLE FORMS: Isuprel(R) (parenteral solution) 1:100,000; 1:50,000; 1:5000
c. PRECAUTIONS: Correct hypovolemia before using; do not administer simultaneously with epinephrine; contraindicated in patients with acute cardiac ischemia; may precipitate fatal ventricular fibrillation if the rhythm is not torsade de pointes.

(1) Use caution in patients with coronary insufficiency, diabetes, hyperthyroidism, or sensitivity to sympathomimetics; contraindicated in patients with pre-existing dysrhythmias.

d. MAJOR ADVERSE EFFECTS: Cardiac dysrhythmias, dizziness, nervousness, tremor.
e. MONITORING PARAMETERS: Heart rate and rhythm, blood pressure, central venous pressure

5. OVERDRIVE PACING

a. Institute overdrive pacing at a rate of 130 to 150 beats per minute, and decrease as tolerated.

6. PHENYTOIN

a. ADULT DOSE: 15 milligrams/kilogram intravenous infusion at a rate not exceeding 50 milligrams/minute.
b. PEDIATRIC DOSE: 15 to 20 milligrams/kilogram by intravenous infusion at a rate not exceeding 1 to 3 milligrams/kilogram/minute to a maximum of 50 milligrams/minute.
c. PRECAUTIONS: Too rapid infusion may induce hypotension and dysrhythmias. Extravasation may cause significant tissue injury.
d. MAJOR ADVERSE EFFECTS: Hypotension and dysrhythmias may develop with too rapid infusion. Mild central nervous system depression, nystagmus, and ataxia are common.
e. MONITORING PARAMETERS: Heart rate and rhythm, blood pressure

7. AMIODARONE

a. Despite its prolongation of the QT interval, amiodarone has been reported to be effective in both treating acute episodes of torsades de pointes and preventing recurrences (Mattioni et al, 1989; Lazzara, 1989).

8. OTHER DRUGS

a. Lidocaine, mexiletine, verapamil, bretylium, propranolol, and labetalol have also been used to treat torsade de pointes, but results have been inconsistent.

9. AVOID

a. Avoid class Ia antiarrhythmics (quinidine, disopyramide, procainamide, aprindine) and most class III antiarrhythmics (N- acetylprocainamide, sotalol) since they may further prolong the QT interval and have been associated with torsade de pointes.

E. SEIZURES

1. SUMMARY - Attempt initial control with a benzodiazepine (diazepam or lorazepam). If seizures persist or recur administer phenobarbital.

a. Monitor for respiratory depression, hypotension, dysrhythmias, and the need for endotracheal intubation.
b. Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or treat with intravenous dextrose ADULT: 100 milligrams IV, CHILD: 2 milliliters/kilogram 25% dextrose).

2. DIAZEPAM

a. MAXIMUM RATE: Administer diazepam intravenously over 2 to 3 minutes (maximum rate = 5 milligrams/minute).
b. ADULT DIAZEPAM DOSE: 5 to 10 milligrams initially, repeat every 5 to 10 minutes as needed. Monitor for hypotension, respiratory depression and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after diazepam 30 milligrams.
c. PEDIATRIC DIAZEPAM DOSE: 0.2 to 0.5 milligram per kilogram repeat every 5 minutes as needed. Monitor for hypotension, respiratory depression and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after diazepam 10 milligrams in children over 5 years or 5 milligrams in children under 5 years of age.
d. RECTAL USE: If an intravenous line cannot be established, diazepam may be given per rectum (generally use twice the usual initial dose because of decreased absorption), or lorazepam may be given intramuscularly.
e. MIDAZOLAM: has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. PEDIATRIC MIDAZOLAM DOSE: INTRAMUSCULAR: 0.2 milligram/kilogram (maximum 7 milligrams) (Chamberlain et al, 1997); INTRANASAL: 0.2 milligram/kilogram (Lahat et al, 2000). Buccal midazolam, 10 milligrams, 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).

3. LORAZEPAM

a. MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 milligrams/minute (Prod Info Ativan(R), 1999).
b. ADULT LORAZEPAM DOSE: 2 to 8 milligrams intravenously. Initial doses may be repeated in 10 to 15 minutes if seizures persist (Prod Info, Ativan(R), 1999; AMA, 1991).
c. PEDIATRIC LORAZEPAM DOSE: 0.05 to 0.1 milligram/kilogram intravenously, (maximum 4 milligrams/dose) repeated twice at intervals of 10 to 15 minutes (Benitz & Tatro, 1995).

4. PHENOBARBITAL

a. ADULT PHENOBARBITAL LOADING DOSE: 600 to 1200 milligrams of phenobarbital intravenously initially (10 to 20 milligrams per kilogram) diluted in 60 milliliters of 0.9 percent saline given at 25 to 50 milligrams per minute.
b. ADULT PHENOBARBITAL MAINTENANCE DOSE: Additional doses of 120 to 240 milligrams may be given every 20 minutes.
c. MAXIMUM SAFE ADULT PHENOBARBITAL DOSE: No maximum safe dose has been established. Patients in status epilepticus have received as much as 100 milligrams/minute until seizure control was achieved.
d. PEDIATRIC PHENOBARBITAL LOADING DOSE: 15 to 20 milligrams per kilogram of phenobarbital intravenously at a rate of 25 to 50 milligrams per minute.
e. PEDIATRIC PHENOBARBITAL MAINTENANCE DOSE: Repeat doses of 5 to 10 milligrams per kilogram may be given every 20 minutes.
f. MAXIMUM SAFE PEDIATRIC PHENOBARBITAL DOSE: No maximum safe dose has been established. Children in status epilepticus have received doses of 30 to 120 milligrams/kilogram within 24 hours. Vasopressors and mechanical ventilation were needed in some patients receiving these doses.
g. MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation.
h. NEONATAL PHENOBARBITAL LOADING DOSE: 20 to 30 milligrams/kilogram intravenously at a rate of no more than 1 milligram/kilogram per minute in patients with no preexisting phenobarbital serum levels.
i. NEONATAL PHENOBARBITAL MAINTENANCE DOSE: Repeat doses of 2.5 milligrams/kilogram every 12 hours may be given; adjust dosage to maintain serum levels of 20 to 40 micrograms/milliliter.
j. MAXIMUM SAFE NEONATAL PHENOBARBITAL DOSE: Doses of up to 20 milligrams/kilogram/minute up to a total of 30 milligrams/kilogram have been tolerated in neonates.
k. CAUTIONS: Adequacy of ventilation must be continuously monitored in children and adults. Intubation may be necessary with increased doses.
l. SERUM LEVEL MONITORING: Monitor serum levels over next 12 to 24 hours for maintenance of therapeutic levels (20 to 40 micrograms per milliliter).

5. Phenytoin should be avoided due to the potential effect of nefazodone on the QTc interval.

F. PULMONARY EDEMA/NON-CARDIOGENIC

1. ONSET: Respiratory tract irritation or injury can progress to pulmonary edema which may be delayed in onset up to 24 to 72 hours after exposure in some cases.
2. NON-PHARMACOLOGIC TREATMENT: Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 milliliters/kilogram) is preferred if ARDS develops.

a. To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 milliliters/kilogram) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000).

3. FLUIDS: Crystalloid solutions must be administered cautiously, AVOIDING a net positive fluid balance. Monitor fluid status through a central line or Swan Ganz(R) catheter.
4. DIURETICS: May be needed to avoid a net positive fluid balance.
5. ANTIBIOTICS: Indicated only when there is evidence of infection.
6. EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).

G. MEDICAL FACILITY MANAGEMENT

1. PRIAPISM - is a medical emergency requiring immediate consult with a urologist.
2. It has been suggested that administration of anticholinergics (ie, benztropine) or beta-blockers may be effective in reversing trazodone-induced priapism, which is also theoretically possible, but not as likely, with nefazodone since it has less alpha-blocking activity. Clinical studies will be needed to verify efficacy (Fishbain, 1989; Ware et al, 1994).

H. SEROTONIN SYNDROME

1. HYPERTHERMIA

a. Control agitation and muscle activity. Undress patient and enhance evaporative heat loss by keeping skin damp and using cooling fans.
b. MUSCLE ACTIVITY - Benzodiazepines may be useful. Diazepam: Adult: 5 to 10 milligrams IV every 5 to 10 minutes as needed, monitor for respiratory depression and need for intubation. Child: 0.25 milligram/kilogram IV every 5 to 10 minutes; monitor for respiratory depression and need for intubation.
c. Non-depolarizing paralytics may be used in severe cases.

2. HYPERTENSION

a. Monitor vital signs regularly. For mild/moderate asymptomatic hypertension, pharmacologic intervention may not be necessary. For hypertensive emergencies (emergent need to lower mean BP 30 percent within 30 minutes and achieve diastolic BP of 100 mmHg or less within one hour), nitroprusside is preferred.
b. NITROPRUSSIDE

(1) NITROPRUSSIDE/INDICATIONS

(a) Nitroprusside is preferred for hypertensive emergencies (emergent need to lower mean BP 30 percent within 30 minutes and achieve a diastolic BP of 100 mmHg or less within one hour).

(2) NITROPRUSSIDE/DOSE

(a) 0.1 to 5 microgram/kilogram/minute intravenous infusion; up to 10 micrograms/kilogram/minute may be required (AHA, 1992).

(3) NITROPRUSSIDE/SOLUTION PREPARATION

(a) Dilute a 50-milligram vial in 500 milliliters of dextrose 5 percent in water (100 micrograms/milliliter). Prepare fresh every 24 hours; wrap in aluminum foil. Discard discolored solution.

(4) NITROPRUSSIDE/MAJOR ADVERSE REACTIONS

(a) Severe hypotension; cyanide toxicity; methemoglobinemia; lactic acidosis; chest pain or arrhthymias (high doses).

(5) NITROPRUSSIDE/MONITORING PARAMETERS

(a) Monitor blood pressure every 30 to 60 seconds at onset of drip; once stabilized, monitor every 30 minutes.

c. NITROGLYCERIN

(1) In theory, nitroglycerin may help alleviate the serotonin syndrome through nitric oxide mediated downregulation of serotonin.
(2) ADULT - Begin continuous infusion at 5 micrograms/minute and titrate to desired effect.
(3) CHILD - Begin infusion at 0.25 to 0.5 micrograms/kilogram/minute and titrate to desired effect.

3. HYPOTENSION

a. Administer 10 to 20 milliliters/kilogram 0.9% saline bolus and place patient in Trendelenburg position. Further fluid therapy should be guided by central venous pressure or right heart catheterization to avoid volume overload.
b. Control hyperthermia.
c. Pressor agents with dopaminergic effects may theoretically worsen serotonin syndrome and should be used with caution.
d. DOPAMINE

(1) PREPARATION: Add 200 or 400 milligrams to 250 milliliters of normal saline or dextrose 5% in water to produce 800 or 1600 micrograms per milliliter or add 400 milligrams to 500 milliliters of normal saline or dextrose 5% in water to produce 800 micrograms per milliliter.
(2) DOSE: Begin at 2 to 5 micrograms per kilogram per minute progressing in 5 to 10 micrograms per kilogram per minute increments as needed.
(3) CAUTION: If VENTRICULAR ARRHYTHMIAS occur, decrease rate of administration.

e. NOREPINEPHRINE

(1) PREPARATION: Add 4 milliliters of 0.1 percent solution to 1000 milliliters of dextrose 5% in water to produce 4 micrograms/milliliter.
(2) INITIAL DOSE

(a) ADULTS: 2 to 3 milliliters (8 to 12 micrograms)/minute
(b) ADULT AND CHILD: 0.1 to 0.2 microgram/kilogram/minute. Titrate to maintain adequate blood pressure.

(3) MAINTENANCE DOSE

(a) 0.5 to 1 milliliter (2 to 4 micrograms)/minute

4. SEIZURES

a. DIAZEPAM

(1) MAXIMUM RATE: Administer diazepam intravenously over 2 to 3 minutes (maximum rate = 5 milligrams/minute).
(2) ADULT DIAZEPAM DOSE: 5 to 10 milligrams initially, repeat every 5 to 10 minutes as needed. Monitor for hypotension, respiratory depression and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after diazepam 30 milligrams.
(3) PEDIATRIC DIAZEPAM DOSE: 0.2 to 0.5 milligram per kilogram, repeat every 5 minutes as needed. Monitor for hypotension, respiratory depression and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after diazepam 10 milligrams in children over 5 years or 5 milligrams in children under 5 years of age.
(4) RECTAL USE: If an intravenous line cannot be established, diazepam may be given per rectum (not FDA approved), or lorazepam may be given intramuscularly.

b. LORAZEPAM

(1) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 milligrams/minute (Prod Info Ativan(R), 1991).
(2) ADULT LORAZEPAM DOSE: 4 to 8 milligrams intravenously. Initial doses may be repeated in 10 to 15 minutes if seizures persist (AMA, 1991).
(3) PEDIATRIC LORAZEPAM DOSE: 0.05 to 0.1 milligram/kilogram intravenously, repeated twice at intervals of 15 to 20 minutes (Benitz & Tatro, 1988; Giang & McBride, 1988).