VENLAFAXINE

 

• 2. Withdrawal reactions, characterized by nausea, dizziness, headache, agitation, nightmares, diaphoresis, and positional vertigo have been reported in several patients following abrupt discontinuation of venlafaxine (Boyd, 1998; Dallal & Chouinard, 1998; Johnson et al, 1998).
• 4.0 LABORATORY/MONITORING
• 4.1 MONITORING PARAMETERS/LEVELS
• 4.1.1 SUMMARY
• A. Monitor blood pressure and ECG in symptomatic patients.
• 4.1.4 OTHER
• A. MONITORING
• 1. Monitor blood pressure for possible hypotension or hypertension.
• 2. Monitor temperature for possible hyperthermia.
• 3. Monitor fluid status and electrolytes as indicated in patients with profuse sweating.
• 4. ECG should be monitored for possible tachycardia.
• 4.3 METHODS
• A. CHROMATOGRAPHY
• 1. Venlafaxine and its major active metabolite, O-desmethylvenlafaxine, have been measured in plasma by high-performance liquid chromatography with ultraviolet detection (Klamerus et al, 1992).
• 5.0 ABSTRACTS
• 5.1 CASE REPORTS
• A. ADULT
• 1. Fantaskey & Burkhart (1995) reported a case of a 41-year-old female who ingested 4.5 grams venlafaxine, 500 mg diphenhydramine, and 50 mg thiothixene and subsequently developed severe CNS depression requiring intubation. On presentation to the ED, she was also hypertensive (BP 168/101 mmHg) and tachycardic (106 bpm). Serum electrolytes were normal. ECG revealed sinus tachycardia and nonspecific T wave changes. An arterial blood gas showed a pH of 7.34, PaCO2 38, and PaO2 377. Decontamination with activated charcoal and sorbitol was administered following normal saline gastric lavage. The patient was responsive to verbal commands approximately one hour after admission to the ED. Supportive care was continued and she was extubated 9 hours post-ingestion with subsequent full recovery.
• 5.2 CASE SERIES
• A. ACUTE EFFECTS
• 1. In premarketing testing, 14 cases of venlafaxine acute overdoses, alone or in combination with other drugs or alcohol, were reported. The three highest estimated doses reported taken were 6.75 g, 2.75 g, and 2.5 g. Resultant peak plasma levels for the latter two were 6.24 and 2.35 mcg/mL, respectively, and peak plasma levels of O-desmethylvenlafaxine were 3.37 and 1.30 mcg/mL, respectively. All patients recovered with no sequelae and most reported no symptoms. Among those reporting symptoms, somnolence was the most common. One patient was observed to have two generalized seizures and a prolongation of QTc to 500 msec, compared with 405 msec baseline. Two other patients were reported to have a sinus tachycardia (Prod Info Effexor(R), 2000).
• 6.0 TREATMENT
• 6.1 LIFE SUPPORT
• A. Support respiratory and cardiovascular function.
• 6.3 PATIENT DISPOSITION
• 6.3.1 DISPOSITION/ORAL EXPOSURE
• 6.3.1.2 HOME CRITERIA/ORAL
• A. In a retrospective series of 63 pediatric cases of venlafaxine ingestion with doses ranging from 18.75 to 75 milligrams (2.1 to 5.5 milligrams/ kilogram), only one patient developed minor effects (lethargy) (Herrington & Gorman, 1996). Children ingesting 5.5 milligrams/kilogram or less can be managed at home.
• 6.3.1.5 OBSERVATION CRITERIA/ORAL
• A. Carefully observe patients with ingestion exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
• 6.4 MONITORING
• A. Monitor blood pressure and ECG in symptomatic patients.
• 6.5 ORAL EXPOSURE
• 6.5.1 PREVENTION OF ABSORPTION/PREHOSPITAL
• A. EMESIS/NOT RECOMMENDED -
• 1. EMESIS: Ipecac-induced emesis is not recommended because of the potential for CNS depression and seizures.
• 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. EMESIS/NOT RECOMMENDED
• 1. EMESIS: Ipecac-induced emesis is not recommended because of the potential for CNS depression and seizures.
• 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).
• C. 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.
• D. WHOLE BOWEL IRRIGATION (WBI)
• 1. Consider the use of whole bowel irrigation after ingestion of extended release products.
• 2. ADULTS - Administer two liters of polyethylene glycol electrolyte solution initially followed by one to two liters per hour until rectal effluent is clear. May be given by nasogastric tube if patient is unable to drink large volumes.
• 3. CHILDREN - Administer 20 milliliters/kilogram of polyethylene glycol electrolyte solution initially followed by 10 to 20 milliliters/kilogram per hour until rectal effluent is clear. May be given by nasogastric tube if patient is unable to drink large volumes.
• 6.5.3 TREATMENT
• A. SUMMARY
• 1. Treatment is symptomatic and supportive. Seizures may occur and should be treated aggressively. Cardiac monitoring is recommended.
• 2. Physostigmine may INDUCE SEIZURES in the venlafaxine poisoned patient and should NOT be used.
• B. SEIZURES
• 1. SUMMARY
• a. Attempt initial control with a benzodiazepine (diazepam or lorazepam). If seizures persist or recur administer phenobarbital. Benzodiazepines and barbiturates are generally preferred over phenytoin for the control of overdose or withdrawal related seizures.
• b. Monitor for respiratory depression, hypotension, dysrhythmias, and the need for endotracheal intubation.
• c. Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or treat with intravenous dextrose ADULT: 50 milliliters 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/FOSPHENYTOIN
• a. Benzodiazepines and/or barbiturates are generally preferred to phenytoin or fosphenytoin in the treatment of drug or withdrawal induced seizures.
• b. PHENYTOIN
• (1) PHENYTOIN INTRAVENOUS PUSH VERSUS INTRAVENOUS INFUSION: Manufacturer does not recommend intravenous infusions due to lack of solubility and resultant precipitation, however infusions are commonly used.
• (a) Administer phenytoin undiluted, by very slow intravenous push or dilute 50 milligrams per milliliter solution in 50 to 100 milliliters of 0.9 percent saline.
• (2) PHENYTOIN ADMINISTRATION RATE: Rate of administration by either method should not exceed 0.5 milligram per kilogram per minute or 50 milligrams per minute.
• (3) ADULT PHENYTOIN LOADING DOSE: 15 to 18 milligrams per kilogram of phenytoin initially. Rate of administration by very slow intravenous push or diluted to 50 milligrams per milliliter should not exceed 0.5 milligram per kilogram per minute or 50 milligrams per minute.
• (4) ADULT PHENYTOIN MAINTENANCE DOSE: Manufacturers recommend a maintenance dose of 100 milligrams orally or intravenously every 6 to 8 hours. The goal is to maintain a serum concentration between 10 to 20 micrograms/milliliter.
• (5) PEDIATRIC PHENYTOIN LOADING DOSE: 15 to 20 milligrams per kilogram or 250 milligrams/square meter of phenytoin. Rate of intravenous administration should not exceed 0.5 to 1.5 milligrams per kilogram per minute.
• (6) PEDIATRIC PHENYTOIN MAINTENANCE DOSE: Repeat doses of 1.5 milligrams per kilogram may be given every 30 minutes to a maximum daily dose of 20 milligrams per kilogram.
• (7) CAUTIONS: Administer phenytoin while monitoring ECG. Stop or slow infusion if arrhythmias or hypotension occur. Be careful not to extravasate. Follow each injection with injection of sterile saline through the same needle.
• (8) SERUM LEVEL MONITORING: Monitor serum levels over next 12 to 24 hours for maintenance of therapeutic levels (10 to 20 micrograms per milliliter).
• c. FOSPHENYTOIN
• (1) ADULT DOSAGE AND ADMINISTRATION: The dose, concentration in dosing solutions, and infusion rate of fosphenytoin are expressed as phenytoin sodium equivalents.
• (2) ADULT LOADING DOSE FOSPHENYTOIN: 15 to 20 milligrams/kilogram of phenytoin sodium equivalents at a rate of 100 to 150 milligrams phenytoin equivalent/minute.
• (3) Fosphenytoin should not be infused at rates greater than 150 milligrams phenytoin equivalent/minute because of the risk of hypotension.
• (4) CAUTIONS: Perform continuous monitoring of respiratory function, cardiac rhythm, and blood pressure throughout infusion and for at least 30 minutes thereafter.
• (5) ADULT MAINTENANCE DOSING: 4 to 6 milligrams phenytoin equivalents/kilogram/day. Rate of administration should not exceed 150 milligrams phenytoin equivalent/minute.
• (6) SERUM LEVEL MONITORING: Monitor serum phenytoin levels over the next 12 to 24 hours; therapeutic levels 10 to 20 microgram/milliliter. Do not obtain serum phenytoin concentrations until at least 2 hours after infusion is complete to allow for conversion of fosphenytoin to phenytoin.
• C. PVCS/VENTRICULAR DYSRHYTHMIAS
• 1. Treatment of ventricular dysrhythmias may include lidocaine, phenytoin, or overdrive transvenous pacing.
• a. VENTRICULAR DYSRHYTHMIAS SUMMARY
• (1) 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. Sotalol is an alternative for stable monomorphic ventricular tachycardia. Amiodarone and sotalol 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 cardioversion. Consider phenytoin if ventricular dysrhythmias persist. Atropine may be used when severe bradycardia is present and PVCs are thought to represent an escape complex.
• 2. LIDOCAINE
• a. LIDOCAINE/INDICATIONS
• (1) Ventricular tachycardia or ventricular fibrillation. Consider in patients with frequent PVCs (greater than 5 per minute), coupled, multifocal, or R on T phenomenon associated with ingestion.
• b. LIDOCAINE/DOSE
• (1) ADULT: 1 to 1.5 milligram/kilogram intravenously push; begin maintenance infusion of 1 to 4 milligrams per minute; repeat 0.5 milligram/kilogram bolus 10 minutes after initial load.
• (2) CHILD: 1 milligram/kilogram initial bolus intravenously; followed by a continuous infusion of 20 to 50 micrograms/kilogram/minute.
• c. LIDOCAINE/PREPARATION
• (1) Add 1 gram of lidocaine to 250 milliliters of dextrose 5 percent in water, to make a 4 milligram/milliliter solution. An increase in the infusion rate of 1 milliliter/minute increases the dose by 4 milligrams/minute.
• d. LIDOCAINE/DOSING IN SPECIAL SITUATIONS
• (1) Although the loading dose of lidocaine does not need to be reduced, the maintenance dose should be decreased by 50% in the presence of impaired hepatic blood flow (acute myocardial infarction, congestive heart failure, or circulatory shock) and in patients over 70 years of age.
• e. LIDOCAINE/MAJOR ADVERSE REACTIONS
• (1) Paresthesias; muscle twitching; confusion; seizures; respiratory depression or arrest; 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.
• f. LIDOCAINE/MONITORING PARAMETERS
• (1) ECG; plasma concentrations.
• 3. AMIODARONE
• a. AMIODARONE/INDICATIONS
• (1) Effective for the control of hemodynamically stable ventricular tachycardia, polymorphic ventricular tachycardia, and wide complex tachycardia of unclear origin. Also recommended after defibrillation and epinephrine in cardiac arrest with persistent ventricular tachycardia or ventricular fibrillation (AHA, 2000). It should be used with caution 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.
• b. AMIODARONE/ADULT DOSE
• (1) Infuse 150 milligrams over 10 minutes, followed by a 1 milligram/minute infusion for 6 hours then 0.5 milligram/minute. Subsequent infusion of 150 milligrams can be repeated as needed for recurrent or resistant dysrhythmias to a maximum total daily dose of 2 grams (AHA, 2000).
• c. AMIODARONE/PEDIATRIC DOSE
• (1) Infuse 5 milligrams/kilogram as a bolus for pulseless ventricular tachycardia or ventricular fibrillation. Infuse 5 milligrams/kilogram over 20 to 60 minutes for perfusing tachycardias. Maximum total dose is 15 milligrams/kilogram per day. Routine use with other drugs that prolong the QT interval is NOT recommended.
• d. ADVERSE EFFECTS
• e. Hypotension and bradycardia are the most common adverse effects. Treat by slowing infusion, intravenous crystalloid administration, pressors or pacing (AHA, 2000).
• 4. BRETYLIUM
• a. BRETYLIUM/INDICATIONS
• (1) Ventricular tachycardia or ventricular fibrillation refractory to defibrillation, epinephrine, and lidocaine.
• b. BRETYLIUM/ADULT DOSE
• (1) VENTRICULAR TACHYCARDIA LOADING DOSE: 5 to 10 milligrams/kilogram of a 10-milligrams/milliliter solution intravenously over 8 to 10 minutes.
• (2) VENTRICULAR TACHYCARDIA MAINTENANCE DOSE: A continuous infusion of 2 milligrams/minute can be used following the loading dose.
• (3) REFRACTORY VENTRICULAR FIBRILLATION DOSE: 5 milligrams/kilogram intravenous bolus, followed by defibrillation; if VF persists, administer 10 milligrams/kilogram 5 minutes later. Doses of 10 milligrams/kilogram may be repeated twice at 5 to 30 minute intervals.
• (4) MAXIMUM DOSE: 30 to 35 milligrams/kilogram; reduce dose in impaired renal function.
• c. BRETYLIUM/PRECAUTIONS
• (1) Caution in renal insufficiency; severe pulmonary hypertension; aortic stenosis. Maximal antiarrhythmic effect may not be apparent for 20 minutes to 12 hours postinjection; may aggravate digitalis toxicity.
• d. BRETYLIUM/MAJOR ADVERSE REACTIONS
• (1) Hypotension (usually 1 hour postinjection) preceded by hypertension; respiratory depression; hyperthermia; bradycardia; anginal attacks.
• e. BRETYLIUM/MONITORING PARAMETERS
• (1) ECG, blood pressure
• D. 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.