(proh-METH-ah-zeen hy-droh-KLOR-eyed)
Phenergan
Phenothiazine
Antiemetic
Sedative-hypnotic
pH 4 to 5.5
Usual dose
A vesicant; see Dilution, Rate of Administration, Contraindications, Precautions, Monitor, and Antidote. Deep IM injection is the preferred route of administration.
All uses:
The Institute for Safe Medication Practices (ISMP) recommends 6.25 to 12.5 mg as a starting IV dose and suggests considering the use of alternate drugs (e.g., 5-HT3 receptor antagonists [e.g., dolasetron (Anzemet), granisetron (Kytril), ondansetron (Zofran)]).
Nausea and vomiting:
12.5 to 25 mg every 4 to 6 hours as needed.
Allergic conditions:
25 mg. May repeat in 2 hours if necessary. Change to oral therapy as soon as possible.
Sedation, nighttime:
25 to 50 mg.
Sedation, perioperative:
25 to 50 mg. May combine with a reduced dose of narcotic analgesic and an anticholinergic drug (e.g., atropine).
Sedation, labor and delivery:
50 mg during early stage of labor. When labor fully established, may administer 25 to 75 mg with a reduced dose of a narcotic analgesic. May repeat every 4 hours to a maximum dose of 100 mg in a 24-hour period.
Pediatric dose
IV use is rare and is limited to pediatric patients 2 years of age or older; see Contraindications and Maternal/Child. Adjust dose to the age, weight, and severity of condition. Use the minimum effective dose and avoid concomitant administration with other drugs with respiratory depressant effects. Do not exceed one half of adult dose. One source suggests a maximum dose of 25 mg. If given IV, administer separately from other medications (e.g., appropriately reduced doses of barbiturates or narcotics, and an appropriate dose of an anticholinergic agent).
Adjunct to premedication:
1.1 mg/kg/dose.
Nausea and vomiting (unlabeled):
0.25 to 1 mg/kg/dose every 6 hours as needed.
Dose adjustments
Reduced dose may be indicated in the elderly. See Drug/Lab Interactions.
Dilution
May be given undiluted or may dilute with NS. Concentration should never exceed 25 mg/mL. 1 mL (25 to 50 mg) diluted with 9 mL of NS equals 2.5 to 5 mg/mL. The ISMP recommends further dilution with an additional 10 to 20 mL of NS or in a 50-mL minibag of NS. Slightly yellow color does not alter potency. Discard if greatly discolored. Administer through Y-tube or three-way stopcock of a free-flowing IV.
Storage:
Store at CRT. Protect from light.
Compatibility (underline indicates conflicting compatibility information)
Consider any drug NOT listed as compatible to be INCOMPATIBLE until consulting a pharmacist; specific conditions may apply.
May form a precipitate with heparin; flush heparinized infusion sets with SWFI or NS before and after administration.
One source suggests the following compatibilities:
Additive:
Amikacin, ascorbic acid, hydromorphone (Dilaudid), penicillin G potassium.
Y-site:
Amifostine (Ethyol), aztreonam, bivalirudin (Angiomax), ceftaroline (Teflaro), ciprofloxacin (Cipro IV), cisatracurium (Nimbex), cladribine (Leustatin), dexmedetomidine (Precedex), docetaxel (Taxotere), etoposide phosphate (Etopophos), fenoldopam (Corlopam), filgrastim (Neupogen), fluconazole (Diflucan), fludarabine (Fludara), gemcitabine (Gemzar), granisetron (Kytril), heparin, hetastarch in electrolytes (Hextend), hydrocortisone sodium succinate (Solu-Cortef), linezolid (Zyvox), melphalan (Alkeran), ondansetron (Zofran), oxaliplatin (Eloxatin), palonosetron (Aloxi), pemetrexed (Alimta), potassium chloride (KCl), remifentanil (Ultiva), sargramostim (Leukine), teniposide (Vumon), thiotepa, vinorelbine (Navelbine).
Rate of administration
The ISMP recommends administration of a single dose over 10 to 15 minutes administered at a port farthest from the patient vein; observe continuously if given in a peripheral vein.
A maximum rate of 25 mg or fraction thereof over 1 minute is suggested by the manufacturer.
Actions
A phenothiazine derivative with effects on the central, autonomic, and peripheral nervous systems. It has antihistaminic, antiemetic, anticholinergic, and sedative effects. As an antihistamine, it competitively blocks the H1 histamine receptor, antagonizing most of the effects of histamine to at least some degree. Potentiates respiratory depression, sedative, and hypotensive effects of narcotics and other CNS depressants. Has no analgesic effects and does not potentiate analgesic effects of narcotics. Onset of action is prompt. Duration of action is 4 to 6 hours. Half-life ranges from 9 to 16 hours. Primarily metabolized in the liver and excreted in the urine.
Indications and uses
Prophylaxis or treatment of minor transfusion reactions. ■ Treatment of or an adjunct to the treatment of hypersensitivity reactions (including anaphylaxis and other immediate-type reactions) after acute symptoms have been controlled with epinephrine and other standard measures. Consider for use if oral administration is impossible or contraindicated. ■ Treatment of acute nausea, vomiting, and motion sickness. ■ Sedation to meet surgical and obstetric needs. ■ Adjunct to analgesics for control of postoperative pain. ■ Sedation and relief of apprehension; production of a light sleep from which a patient can be easily aroused. ■ An adjunct to anesthesia and analgesia in selected surgical situations (e.g., repeated bronchoscopy, ophthalmologic surgery, and poor-risk patients). Given in conjunction with reduced amounts of narcotic analgesics.
Contraindications
Comatose or severely depressed states, hypersensitivity or an idiosyncratic reaction to phenothiazines, and pediatric patients under 2 years of age. Never inject into an artery; may cause arteriospasm resulting in gangrene. Do not administer SC; chemical irritation may result in necrotic lesions.
Precautions
Ampule must state “for IV use.” Deep IM injection preferred. ■ Use with extreme caution in pediatric patients and the elderly; see Maternal/Child and Elderly. ■ Can cause severe chemical irritation and tissue damage regardless of route of administration. Irritation and damage can result from perivascular extravasation, unintentional intra-arterial injection, and intraneuronal or perineuronal infiltration. Adverse event reports include abscesses, burning, erythema, gangrene, pain, palsies, paralysis, sensory loss, severe spasm of the distal vessels, swelling, thrombophlebitis, tissue necrosis, and venous thrombosis. ■ Use should be avoided in patients with compromised respiratory function or in patients at risk for respiratory failure (e.g., COPD, sleep apnea); risk of potentially fatal respiratory depression is increased. ■ May cause paradoxical excitation in pediatric patients and the elderly. ■ Use phenothiazines with extreme caution in pediatric patients with a history of sleep apnea, a family history of sudden infant death syndrome, or in the presence of Reye’s syndrome. ■ Use with caution in patients with asthma, bladder neck obstruction, bone marrow suppression, cardiovascular disease, glaucoma, liver dysfunction, prostatic hypertrophy, pyloroduodenal obstruction, or stenosing peptic ulcer disease. ■ May produce ECG changes (e.g., prolonged QT interval, changes in T waves). ■ May mask diagnosis of other conditions, including Reye’s syndrome, brain tumor, drug intoxication, and intestinal obstruction. ■ May lower seizure threshold; use extreme caution in patients with known seizure disorders and with narcotics or local anesthetics that also lower seizure threshold. ■ May contain sulfites; use caution in patients with allergies. ■ Neuroleptic malignant syndrome (NMS), a rare syndrome manifested by hyperpyrexia, muscle rigidity, irregular BP and HR, and altered mental status, has been reported in association with promethazine alone or in combination with antipsychotic drugs.
Monitor:
A vesicant; determine absolute patency of vein; extravasation will cause necrosis; see Contraindications and Precautions. ISMP suggests administering through large-bore veins but prefers use of a central venous catheter. Administration through hand or wrist veins is strongly discouraged. ■ Monitor frequently for S/S of extravasation (e.g., burning, erythema, pain, palsies, sensory loss, and swelling along IV site), especially along peripheral sites. ■ Keep patient in supine position. Monitor BP and pulse before administration and between doses. ■ Sedative effect may require ambulation to be monitored. ■ See Drug/Lab Interactions.
Patient education:
Avoid use of alcohol or other CNS depressants (e.g., antihistamines, barbiturates). ■ Request assistance for ambulation; may cause dizziness or fainting. ■ Use caution performing tasks that require alertness. ■ May cause skin and eye photosensitivity. Avoid unprotected exposure to sun. ■ Report stinging or burning at IV site promptly. ■ Report any involuntary muscle movements.
Maternal/child:
Category C: safety for use in pregnancy and pediatric patients not established. Use only when clearly needed. ■ Discontinue breast-feeding. ■ Contraindicated in pediatric patients under 2 years of age. Post-marketing cases of respiratory depression and death (not directly related to individualized weight-based dosing) have been reported. Concomitant administration with other respiratory depressants increases this risk. ■ Use caution in pediatric patients 2 years of age or older. Use the minimum effective dose. ■ Do not use for vomiting of unknown etiology in pediatric patients. Antiemetics are not recommended for treatment of uncomplicated vomiting in pediatric patients. Use should be limited to prolonged vomiting of known etiology. Extrapyramidal symptoms that can occur secondary to promethazine administration may be confused with CNS signs of an undiagnosed primary disease (e.g., encephalopathy or Reye’s syndrome). ■ Avoid use in pediatric patients with S/S suggestive of Reye’s syndrome or other hepatic diseases. ■ Excessively large doses of antihistamines in pediatric patients have caused hallucinations, convulsions, and death. ■ Pediatric patients metabolize antipsychotic agents more rapidly than adults. ■ Incidence of extrapyramidal reactions is relatively high in pediatric patients, especially in the presence of acute illness (e.g., measles, chickenpox, gastroenteritis). ■ See Precautions and Contraindications.
Elderly:
See Dose Adjustments and Precautions. ■ Have a reduced capacity to metabolize and eliminate. ■ May cause confusion, dizziness, hyperexcitability, hypotension, and/or sedation. ■ Increased sensitivity to anticholinergic effects (e.g., dry mouth, urinary retention). ■ Increased risk of extrapyramidal side effects (e.g., tardive dyskinesia, parkinsonism).
Drug/lab interactions
Increased CNS depression and hypotensive effects with narcotics, alcohol, anesthetics, and barbiturates; reduced doses of these agents usually indicated. ■ Additive effects with MAO inhibitors (e.g., selegiline [Eldepryl]), anticholinergics, antihistamines, antihypertensives, hypnotics, muscle relaxants, and propranolol; dose adjustments may be necessary. ■ Use with epinephrine not recommended; may cause precipitous hypotension. ■ Risk of cardiotoxicity increased with pimozide (Orap), quinidine, and sparfloxacin (Zagam); concurrent use not recommended. ■ Risk of additive QT interval prolongation, cardiac depressant effects, and cardiac arrhythmias increased with amiodarone (Nexterone), disopyramide (Norpace), erythromycin, procainamide (Pronestyl), and quinidine. ■ Concurrent use with antidepressants (e.g., fluoxetine [Prozac], paroxetine [Paxil]), tricyclic antidepressants (e.g., amitriptyline [Elavil]), or MAO inhibitors may increase effects of both drugs. ■ Concurrent use with other neuroleptic agents (e.g., haloperidol [Haldol]) may increase the risk of NMS. ■ May lower seizure threshold. Dose adjustment of anticonvulsants may be necessary. ■ Capable of innumerable other interactions. ■ Selected pregnancy tests may show a false-negative or false-positive result. ■ May cause an increase in blood glucose; consider when a glucose tolerance test is indicated.
Side effects
Average dose:
Blurring of vision, bradycardia, confusion, dizziness, drowsiness, dryness of mouth, extrapyramidal symptoms, faintness, hallucinations, hematologic side effects (e.g., agranulocytosis, leukopenia, thrombocytopenia, thrombocytopenic purpura), hyperexcitability, hypersensitivity reactions, hypertension (rare), hypotension (mild), lassitude, nightmares, photosensitivity, sedation, somnolence, tachycardia, tinnitus, tremors.
Overdose:
Anaphylaxis, cardiac arrest, coma, convulsions, deep sedation, respiratory depression. All side effects of phenothiazines are possible, but rarely occur. See prochlorperazine (Compazine).
Antidote
Discontinue the drug immediately at onset of any side effect and notify the physician. Sympathetic block and heparinization have been used during acute management of promethazine extravasation (unintentional intra-arterial injection or perivascular extravasation). In some cases surgical intervention, including fasciotomy, skin graft, and/or amputation, has been required. Counteract hypotension with IV fluids, Trendelenburg position, norepinephrine (Levophed), or phenylephrine (Neo-Synephrine); counteract extrapyramidal symptoms with benztropine mesylate (Cogentin) or diphenhydramine (Benadryl). Epinephrine is contraindicated for hypotension; further hypotension will occur. Use diazepam (Valium) or phenobarbital for convulsions or hyperactivity. In treating respiratory depression and unconsciousness, avoid analeptics such as doxapram (Dopram); they may cause convulsions. Treatment of NMS includes discontinuation of all unnecessary drugs and intensive symptomatic treatment and monitoring. Dialysis does not appear to be helpful in overdose situations. Resuscitate as necessary.
Propofol injection
(PROH-poh-fohl in-JEK-shun)
Diprivan
General anesthetic
Anesthesia adjunct
Sedative-hypnotic
pH 7 to 8.5
Usual dose
Lidocaine may be administered to minimize pain on injection of propofol. Administer before propofol injection or add to propofol immediately before administration. Do not exceed more than 20 mg lidocaine to 200 mg propofol.
Induction of anesthesia
Must be individualized and titrated to desired response. Allow 3 to 5 minutes between dose adjustments to allow for and assess clinical effects.
Healthy adults under 55 years of age:
40 mg every 10 seconds until induction onset (approximately 2 to 2.5 mg/kg).
Adults over 55 years of age, debilitated, or ASA III or IV risk patients:
20 mg every 10 seconds until induction onset (approximately 1 to 1.5 mg/kg).
Cardiac anesthesia:
20 mg every 10 seconds until induction onset (0.5 to 1.5 mg/kg).
Neurosurgical patients:
20 mg every 10 seconds until induction onset (approximately 1 to 2 mg/kg). Infusion or slow injection (20 mg over 10 seconds) is used to avoid significant hypotension and decrease in cerebral perfusion pressure. If increased intracranial pressure is suspected, hyperventilation and hypocarbia should accompany administration.
Maintenance of anesthesia
Must be individualized and titrated to desired response. Allow 3 to 5 minutes between dose adjustments to allow for and assess clinical effects.
Adults under 55 years of age:
Immediately follow induction with an infusion of 100 to 200 mcg/kg/min (6 to 12 mg/kg/hr) or an intermittent bolus in increments of 25 to 50 mg as needed.
Adults over 55 years of age, debilitated, or ASA III or IV risk patients:
Immediately follow induction with an infusion of 50 to 100 mcg/kg/min (3 to 6 mg/kg/hr). Do NOT use a rapid intermittent bolus in these patients.
Cardiac anesthesia:
Most patients require 100 to 150 mcg/kg/min in combination with an opioid (primary propofol with an opioid secondary). An alternate regimen is an opioid primary with low-dose propofol 50 to 100 mcg/kg/min (3 to 6 mg/kg/hr).
Neurosurgical patients:
Immediately follow induction with an infusion of 100 to 200 mcg/kg/min (6 to 12 mg/kg/hr). Do NOT use a rapid intermittent bolus in these patients.
Initiation of monitored anesthesia care (MAC) sedation
Must be individualized and titrated to desired response. Allow 3 to 5 minutes between dose adjustments to allow for and assess clinical effects. MAC sedation rates are approximately 25% of those used for anesthesia.
Healthy adults under 55 years of age:
An infusion of 100 to 150 mcg/kg/min (6 to 9 mg/kg/hr) over 3 to 5 minutes or a slow injection of 0.5 mg/kg over 3 to 5 minutes. Slow infusion or slow injection techniques are preferable to rapid bolus administration.
Adults over 55 years of age, debilitated, or ASA III or IV risk patients:
Most patients require doses similar to healthy adults. Must be given over 3 to 5 minutes as a slow infusion (preferred) or as a slow injection over 3 to 5 minutes. Do NOT give as a rapid bolus.
Maintenance of MAC sedation
Healthy adults under 55 years of age:
Maintain with an infusion (preferred) of 25 to 75 mcg/kg/min (1.5 to 4.5 mg/kg/hr) or incremental bolus doses of 10 to 20 mg.
Adults over 55 years of age, debilitated, or ASA III or IV risk patients:
Reduce dose to 80% of usual dose; an infusion of 20 to 60 mcg/kg/min (1.2 to 3.6 mg/kg/hr). Do NOT use bolus doses.
Sedation of intubated, mechanically ventilated ICU patients
Must be individualized and titrated to desired response. Given as a continuous infusion. Begin with an initial dose of 5 mcg/kg/min (0.3 mg/kg/hr) for 5 minutes. Allow at least 5 minutes between adjustments to reach peak drug effect and to avoid hypotension. Increase slowly over 5 to 10 minutes by 5 to 10 mcg/kg/min (0.3 to 0.6 mg/kg/hr) to desired level of sedation. Individualize to patient condition, response, blood lipid profile, and vital signs. Some clinicians recommend reducing dose by approximately one half for elderly (over 55 years) and debilitated. Check urinalysis and urine sediment before administration of propofol in patients at risk for renal failure; see Precautions and Monitor.
Maintenance of sedation in mechanically ventilated or respiratory-controlled ICU patients
5 to 50 mcg/kg/min (0.3 to 3 mg/kg/hr) or higher as a continuous infusion slowly titrated to desired level of sedation. Use caution with doses higher than 50 mcg/kg/min; may increase risk of hypotension. Bolus doses of 10 to 20 mg may be used to rapidly increase the depth of sedation in patients in whom hypotension is not likely to occur. Temporarily reduce dose once each day to assess neurologic and respiratory function and to determine minimum dose required for desired level of sedation. Average maintenance dose under 55 years is 38 mcg/kg/min; over 55 years, 20 mcg/kg/min. Average maintenance dose for post–coronary artery bypass graft (CABG) patients is usually low (median of 11 mcg/kg/min) because of high intraoperative opiates.
Relief of pruritus associated with use of spinal opiates or cholestasis (unlabeled)
Subhypnotic doses of 10 to 15 mg as an IV injection or 0.5 to 1.5 mg/kg/hr as an infusion.
Management of refractory status epilepticus (unlabeled)
Administer doses of 1 to 2 mg/kg as an IV injection over 5 minutes; may be repeated if seizure activity recurs. If indicated, follow with a maintenance infusion of 2 to 10 mg/hr. Adjust to achieve the lowest rate needed to suppress seizure activity. Decrease gradually to prevent withdrawal seizures.
Pediatric dose
To minimize pain on injection of propofol in pediatric patients, administer through larger veins or pretreat smaller veins with lidocaine. See Maternal/Child.
Induction of anesthesia in healthy pediatric patients 3 to 16 years of age
Must be individualized and titrated to desired response. 2.5 to 3.5 mg/kg administered over 20 to 30 seconds. Induction with propofol is indicated only in pediatric patients 3 years of age or older. In pediatric patients from 2 months to 3 years of age, induction must be achieved by supplementing with another agent (literature suggests nitrous oxide 60% to 70%). See Dose Adjustments.
Maintenance of anesthesia in healthy pediatric patients from 2 months to 16 years of age
Must be titrated to desired clinical effect. (See statement under induction in healthy pediatric patients in the previous paragraph, and see Indications and Uses.) Administered as a variable-rate infusion supplemented with nitrous oxide 60% to 70% for most pediatric patients.
Pediatric patients 2 months of age and older:
Immediately follow induction dose with an infusion of 125 to 300 mcg/kg/min (7.5 to 18 mg/kg/hr). Initially, a rate of 200 to 300 mcg/kg/min may be indicated and can usually be reduced to 125 to 150 mcg/kg/min after the first half-hour. Decrease infusion rate if clinical signs of light anesthesia are not present after 30 minutes of maintenance; see Rate of Administration. Younger pediatric patients may require higher maintenance infusion rates than older pediatric patients. See Dose Adjustments.
Dose adjustments
All situations:
Reduce induction and maintenance doses for pediatric patients classified as ASA III or IV. ■ See Usual Dose for specific reduced doses required for adults over 55 years of age; debilitated, ASA III, or ASA IV risk patients; or patients with circulatory disorders. ■ Reduced dose required in presence of other CNS depressants. See Drug/Lab Interactions. ■ No dose adjustment required for gender, chronic hepatic cirrhosis, or chronic renal failure.
ICU sedation:
Adjust infusion to maintain a light level of sedation through the wake-up assessment or weaning process.
Dilution
Supplied in ready-to-use vials containing 10 mg/mL. Shake well before use. May be further diluted only with D5W. Do not dilute to a concentration less than 2 mg/mL (4 mL diluent to 1 mL propofol yields 2 mg/mL). More stable in glass than in plastic. Strict aseptic technique imperative; emulsion supports rapid growth of microorganisms. Failure to use strict aseptic technique has been associated with microbial contamination of the product with resultant fever, infection, sepsis, other life-threatening illnesses, and/or death. Do not use with evidence of emulsion separation. Prepare immediately before each use. Flush IV line at end of every 6 hours in extended procedures to remove residual propofol.
Filters:
Use filters with caution. The pore size should be equal to or greater than 5 microns. Filters with a pore size less than 5 microns may impede the flow of propofol and/or cause a breakdown of the emulsion.
Storage:
Protect from light and store below 22° C (72° F) but do not refrigerate. Discard infusion and tubing every 12 hours or every 6 hours if propofol has been transferred from the original container.
Compatibility (underline indicates conflicting compatibility information)
Consider any drug NOT listed as compatible to be INCOMPATIBLE until consulting a pharmacist; specific conditions may apply.
Manufacturer states, “Should not be mixed with other therapeutic agents prior to administration. Compatibility with blood/serum/plasma has not been established.”
Y-site:
Manufacturer lists as compatible at the Y-site with the following solutions: D5W, LR, D5LR, D51/2NS, D51/4NS. Other sources list acyclovir (Zovirax), alfentanil, aminophylline, ampicillin, atracurium (Tracrium), atropine, aztreonam (Azactam), bumetanide, buprenorphine (Buprenex), butorphanol (Stadol), calcium gluconate, carboplatin (Paraplatin), cefazolin (Ancef), cefotaxime (Claforan), cefotetan, cefoxitin (Mefoxin), ceftaroline (Teflaro), ceftazidime (Fortaz), ceftriaxone (Rocephin), cefuroxime (Zinacef), chlorpromazine (Thorazine), cisatracurium (Nimbex), cisplatin, clindamycin (Cleocin), cyclophosphamide (Cytoxan), cyclosporine (Sandimmune), cytarabine (ARA-C), dexamethasone (Decadron), dexmedetomidine (Precedex), diphenhydramine (Benadryl), dobutamine, dopamine, doxycycline, droperidol (Inapsine), enalaprilat (Vasotec IV), ephedrine, epinephrine (Adrenalin), esmolol (Brevibloc), famotidine (Pepcid IV), fenoldopam (Corlopam), fentanyl, fluconazole (Diflucan), fluorouracil (5-FU), furosemide (Lasix), ganciclovir (Cytovene IV), glycopyrrolate (Robinul), granisetron (Kytril), heparin, hydrocortisone sodium succinate (Solu-Cortef), hydromorphone (Dilaudid), 6% hydroxyethyl starch (Voluven), ifosfamide (Ifex), imipenem-cilastatin (Primaxin), insulin (regular), isoproterenol (Isuprel), ketamine (Ketalar), labetalol, lidocaine, lorazepam (Ativan), magnesium sulfate, mannitol, meperidine (Demerol), midazolam (Versed), milrinone (Primacor), morphine, nafcillin (Nallpen), nalbuphine, naloxone, nitroglycerin IV, nitroprusside sodium, norepinephrine (Levophed), paclitaxel (Taxol), pancuronium, pentobarbital (Nembutal), phenobarbital (Luminal), phenylephrine (Neo-Synephrine), potassium chloride (KCl), prochlorperazine (Compazine), propranolol, ranitidine (Zantac), sodium bicarbonate, succinylcholine, sufentanil (Sufenta), telavancin (Vibativ), ticarcillin/clavulanate (Timentin), vancomycin, vecuronium.
Rate of administration
Use of a syringe pump or volumetric pump recommended to provide controlled infusion rates. See Usual Dose for specific rates for specific age and/or indication. Decrease rate based on age, debilitation, or calculated risk. Must be individualized and titrated to desired level of sedation and changes in vital signs. Monitor respiratory function continuously. Continuous administration preferable to intermittent to avoid periods of undersedation or oversedation. Too-rapid administration (bolus dosing, too-rapid increase in infusion rate, overdose) can cause severe cardiorespiratory complications, especially in pediatric patients, adults over 55 years, debilitated or ASA III or IV risk patients. In all anesthesia, higher rates are generally required for the first 15 minutes, then appropriate responses can usually be maintained with a decrease of 30% to 50%. Always titrate rates downward until there is a mild response to surgical stimulation. This avoids administration at rates higher than clinically necessary. Control increased response to surgical stimulation or lightening of anesthesia (increased pulse rate, BP, sweating and/or tearing) with bolus injections of 25 to 50 mg (adults under 55 years of age only), slow injection of reduced doses, or by increasing the infusion rate (adults under or over 55 years of age) or by increasing the infusion rate (pediatric patients). If control not effective within 5 minutes, consider use of an opioid, barbiturate, or inhalation agent.
Actions
A potent emulsified IV sedative hypnotic agent. Action is dose dependent and rate dependent. Can provide conscious (verbal contact maintained) or unconscious sedation, depending on dose. Produces hypnosis rapidly and smoothly with minimal excitation, usually within 40 seconds. Depth of sedation easily and rapidly controlled by adjusting rate of infusion. Rapid onset of action facilitates accurate titration and minimizes oversedation. Due to extensive redistribution from the central nervous system to other tissues and high metabolic clearance, recovery from anesthesia or sedation is rapid. Time to awakening is dependent on duration of infusion. Discontinuation of an infusion after maintenance of anesthesia for 1 hour or sedation in the ICU for 1 day will result in rapid awakening. Prolonged infusions (e.g., 10 days in ICU) will result in drug accumulation and an increased time to awakening. Terminal half-life after a 10-day infusion is 1 to 3 days. Other effects include decreased systemic vascular resistance, myocardial blood flow, and oxygen consumption; a decrease in cerebral blood flow and intracranial pressure; and a decrease in intraocular pressure. Also has antiemetic properties. Has minimal impact on cardiac output, but changes may occur because of assisted or controlled ventilation. Hypotension, oxyhemoglobin desaturation, apnea, and airway obstruction can occur. Addition of an opioid may further decrease cardiac output or respiratory drive. Metabolized in the liver and excreted as metabolites in urine. Crosses placental barrier. Secreted in breast milk.
Indications and uses
Adults:
Induce and/or maintain anesthesia as part of a balanced anesthetic technique for inpatient and outpatient surgery. ■ Initiate and maintain monitored anesthesia care (MAC) during diagnostic procedures (e.g., colonoscopy, dental procedures) and in conjunction with local/regional anesthesia during surgical procedures. ■ Continuous sedation and control of stress responses in intubated, mechanically ventilated ICU patients (e.g., post-CABG, postsurgical, neuro/head trauma, ARDS, COPD, asthma, status epilepticus, tetanus). Continuous infusion of low doses allows controlled recovery of consciousness when required and for assessment.
Pediatric patients:
Induction of anesthesia as a part of a balanced anesthetic technique for inpatient and outpatient surgery in pediatric patients over 3 years of age. ■ Maintenance of anesthesia as part of a balanced anesthetic technique for inpatient and outpatient surgery in pediatric patients over 2 months of age. ■ Not recommended for induction of anesthesia for pediatric patients under 3 years of age or for maintenance of anesthesia under 2 months of age. ■ Not indicated for use in pediatric patients for ICU sedation or for MAC sedation for surgical, nonsurgical, or diagnostic procedures.
Unlabeled uses:
Subhypnotic doses used for relief of pruritus associated with use of spinal opiates or cholestasis; treatment of status epilepticus refractory to standard anticonvulsant therapy.
Contraindications
Known hypersensitivity to propofol or its components (e.g., soybean oil, glycerol, egg lecithin, sodium hydroxide) or any time general anesthesia or sedation is contraindicated.
Precautions
All situations:
For IV use only. ■ Administered by or under the direct observation of the anesthesiologist. Must have responsibility only for anesthesia during surgery and/or procedures. In the ICU setting, may be administered to intubated, mechanically ventilated patients by persons skilled in medical management of critically ill patients and trained in cardiovascular resuscitation and airway management. Both life-threatening and fatal anaphylactoid and anaphylactic reactions have been reported. ■ Strict aseptic technique required; see Dilution. ■ Use caution in patients with compromised myocardial function, intravascular volume depletion, or abnormally low vascular tone (e.g., sepsis); may be more susceptible to hypotension. ■ Avoid rapid bolus administration in the elderly, debilitated, or ASA-PS III or IV patients. May cause undesirable cardiopulmonary depression, including apnea, airway obstruction, hypotension, and oxygen desaturation. ■ An emulsion; use caution in patients with lipid metabolism disorders (e.g., diabetic hyperlipidemia, pancreatitis, and primary hyperlipoproteinemia). ■ May cause convulsions during recovery phase in patients with epilepsy. ■ Use caution in patients with increased intracranial pressure or impaired cerebral circulation. Decrease in mean arterial pressure may cause decreases in cerebral perfusion. ■ Propofol infusion syndrome has been reported and is characterized by severe metabolic acidosis, hyperkalemia, lipemia, rhabdomyolysis, hepatomegaly, and cardiac and renal failure. Deaths have occurred. Most often associated with prolonged, high-dose infusions in ICU but has been observed following large-dose, short-term infusions during surgical anesthesia. Consider alternative means of sedation when there is a prolonged need for sedation, when large doses of propofol are required to maintain a desired level of sedation, or if a patient develops metabolic acidosis. ■ Has no analgesic properties; provide pain relief or local anesthetic as indicated. Has been used successfully with midazolam (Versed), 1 to 3 mg, for initial induction. Midazolam provides better amnesia and causes less pain on injection, whereas propofol sustains sedation and allows more rapid recovery. ■ May contain sulfites; use caution in patients with allergies.
Monitor:
All situations:
Correct fluid volume deficiencies before administration. ■ Will cause transient local pain during IV injection; minimize by using larger veins and lidocaine previous to injection. Use with midazolam reduces awareness of this pain. ■ Apnea may occur during induction and last for more than 60 seconds. Intubation equipment, controlled ventilation equipment, oxygen, and facilities for resuscitation and life support must be available. Maintain a patent airway and ascertain adequate ventilation at all times. ■ All vital signs must be monitored continuously. Use of a respiratory monitor required. ■ Hypotension common during first 60 minutes; monitor closely. Significant hypotension or cardiovascular depression can be profound. ■ To prevent profound bradycardia, anticholinergic agents (e.g., atropine, glycopyrrolate) may be required to modify increases in vagal tone due to concomitant agents (e.g., succinylcholine) or surgical stimulation. ■ Bed rest required for a minimum of 3 hours after IV injection, or satisfy specific hospital rules for discharge. ■ See Precautions and Drug/Lab Interactions.
ICU sedation:
Observe for signs and symptoms of pain; may indicate need for opioids or analgesia, not an increase in propofol dose. ■ Benzodiazepines (e.g., diazepam [Valium]) and/or neuromuscular blocking agents (e.g., atracurium [Tracrium], succinylcholine) may also be used. ■ Monitor triglycerides with long-term use (ICU sedation). Adjust if fat is inadequately cleared from body, and reduce other lipid administration. 1 mL of propofol contains approximately 0.1 Gm of fat (1.1 kcal). ■ Dose may be reduced carefully to allow patient to awaken to a lighter level of sedation, allowing neurologic and respiratory assessment daily. Avoid rapid awakening; will cause anxiety, agitation, and resistance to mechanical ventilation. ■ Monitor urinalysis and urine sediment on alternate days in patients at risk for renal impairment. ■ Some formulations contain EDTA, a trace metal chelator. Formulations containing EDTA should not be infused for longer than 5 days without providing a drug holiday to safely replace estimated or measured zinc losses. Consider zinc supplementation in patients who may be predisposed (e.g., patients with burns, diarrhea, or major sepsis). ■ Discontinue opioids and paralytic agents and optimize respiratory function before weaning from mechanical ventilation. ■ Maintain light sedation until 15 minutes before extubation.
Patient education:
Avoid alcohol or other CNS depressants (e.g., antihistamines, benzodiazepines) for 24 hours following anesthesia. ■ Do not perform tasks requiring mental alertness (e.g., driving, operating hazardous machinery, or signing legal documents) until the day after surgery or longer. All effects must have subsided.
Maternal/child:
Category B: use during pregnancy only if clearly needed. ■ Not recommended for use in obstetric procedures, including cesarean section; no assurance of safety for fetus. ■ Not recommended for use during breast-feeding. ■ Has been approved for induction of anesthesia in pediatric patients 3 years to 16 years of age. Has been approved for maintenance of anesthesia in pediatric patients 2 months to 16 years of age. ■ Distribution and clearance in pediatric patients 3 years to 12 years of age is similar to that seen in adults. ■ Serious bradycardia may result with concomitant administration of fentanyl. ■ Serious adverse effects (e.g., metabolic acidosis) occurred during ICU sedation in pediatric patients with respiratory infections and/or with doses in excess of recommendations for adults. Fatalities have occurred. ■ A recent study identified an increase in deaths with propofol versus standard sedative agents. Manufacturer has issued a warning letter stating that propofol should not be used for sedation of pediatric patients in ICU. ■ See Side Effects.
Elderly:
Dose requirements decrease after age 55 due to reduced clearance and volume distribution and higher blood levels. Minimize undesirable cardiorespiratory depression (hypotension, apnea, airway obstruction, and/or oxygen desaturation) by using reduced doses and rates of administration. Avoid rapid single or repeated bolus doses; see Precautions. See Usual Dose and Dose Adjustments.
Drug/lab interactions
Potentiated by inhalational anesthetics (e.g., enflurane, halothane, isoflurane, nitrous oxide), narcotics (e.g., morphine, meperidine [Demerol], fentanyl), sedatives (e.g., barbiturates, benzodiazepines [e.g., diazepam (Valium), midazolam (Versed)], chloral hydrate, droperidol [Inapsine]). Anesthetic and sedative effects increased; systolic, diastolic, mean arterial pressure, and cardiac output are decreased. Dose adjustment may be indicated with concomitant use. ■ No significant adverse interactions noted to date with neuromuscular blocking agents (e.g., atracurium [Tracrium], succinylcholine). ■ Competition for chemoreceptor binding sites may occur if used in combination with droperidol; use of propofol as a single agent is suggested to control nausea and vomiting. ■ In pediatric patients, serious bradycardia may result with concomitant administration of fentanyl.
Side effects
Adults and pediatric patients:
More likely to occur during loading boluses, with supplemental boluses, or during higher rate of administration. Apnea; bradycardia (profound); cough; dyspnea; headache; hypotension; hypoventilation; injection site burning, pain, stinging; nausea, and upper airway obstruction are most common. Urine may be green. Abdominal cramping, anaphylaxis (including bronchospasm, erythema, and hypotension), bucking/jerking/thrashing, clonic/myclonic movement (rarely including convulsions and opisthotonus), dizziness, fever, flushing, hiccups, hypertension, tingling/numbness/coldness at injection site, twitching, and vomiting may occur.
Pediatric patients:
Increased incidences of agitation, bradycardia, and jitteriness have occurred; apnea has been observed frequently. Abrupt discontinuation following prolonged infusion may result in agitation, flushing of the hands and feet, hyperirritability, and tremulousness.
Overdose:
Cardiorespiratory depression (hypotension, apnea, airway obstruction, and/or oxygen desaturation).
Antidote
Keep physician informed of all side effects. Reduction of dose may be required or will be treated symptomatically. Discontinue the drug for major side effects, paradoxical reactions, or accidental overdose. A short-acting drug, a patent airway, and continuous controlled ventilation with oxygen until normal function assured should be adequate. Treat bradycardia and/or hypotension with increased rate of IV fluids, Trendelenburg position, vasopressors (e.g., dopamine). Anticholinergic agents (e.g., atropine or glycopyrrolate) may be required. Treat hypersensitivity reactions and resuscitate as necessary.
Propranolol hydrochloride
(proh-PRAN-oh-lohl hy-droh-KLOR-eyed)
Beta-adrenergic blocking agent
Antiarrhythmic
pH 2.8 to 3.5
Usual dose
1 to 3 mg given 1 mg at a time under careful monitoring (e.g., CVP, ECG); see Monitor and Rate of Administration. Do not give additional propranolol if the desired change in rate or rhythm is achieved. If there is no change in rhythm for at least 2 minutes after the initial dose, cycle may be repeated one time. (AHA recommends 0.5 to 1 mg over 1 minute, repeated as needed up to a total dose of 0.1 mg/kg.) No further propranolol may be given by any route for at least 4 hours. Best results achieved if administered within 2 to 4 hours of symptom onset or thrombolytic therapy. Transfer to oral therapy as soon as possible.
Pediatric dose (unlabeled)
0.01 to 0.1 mg/kg/dose over 10 minutes. Maximum dose is 1 mg for infants and 3 mg for other pediatric patients. Repeat at 6- to 8-hour intervals if needed.
Tetralogy spells (hypercyanotic spells):
0.15 to 0.25 mg/kg/dose may be given slowly. May repeat once in 15 minutes. Another source recommends 0.01 to 0.2 mg/kg/dose. Should not exceed 5-mg dose.
Dose adjustments
Lower-end initial doses may be indicated in the elderly based on potential for decreased organ function and concomitant disease or drug therapy. ■ Consider dose reduction in patients with impaired hepatic function. ■ See Drug/Lab Interactions. ■ Reduce dose gradually to avoid rebound angina, myocardial infarction, or ventricular arrhythmias.
Dilution
May be given undiluted; however, further dilution of each 1 mg in 10 mL D5W or NS is preferred to facilitate titration of an exact dose while monitoring effect. May be diluted in 50 mL of D5W, D5/1/2NS, D5NS, or NS for infusion.
Storage:
Store at CRT. Protect from freezing or excessive heat.
Compatibility
Consider any drug NOT listed as compatible to be INCOMPATIBLE until consulting a pharmacist; specific conditions may apply.
One source suggests the following compatibilities:
Additive:
Dobutamine, verapamil.
Y-site:
Alteplase (tPA, Activase), fenoldopam (Corlopam), heparin, hydrocortisone sodium succinate (Solu-Cortef), linezolid (Zyvox), meperidine (Demerol), milrinone (Primacor), morphine, nesiritide (Natrecor), potassium chloride (KCl), propofol (Diprivan), tacrolimus (Prograf), tirofiban (Aggrastat).
Rate of administration
Each 1 mg or fraction thereof must be given over 1 minute to avoid excessive hypotension and/or cardiac standstill. A single dose may be given as an infusion over 10 to 15 minutes. Allow adequate time for distribution; consider slow circulation time. Observe monitor and discontinue propranolol as soon as rhythm change occurs.
Pediatric rate:
Extend rate of administration of a single dose by injection to a minimum of 5 minutes in pediatric patients.
Actions
Propranolol is a nonselective beta-adrenergic blocker with antiarrhythmic effects. Cardiac response to sympathetic nerve stimulation is inhibited, slowing the HR (especially ventricular rate) by inhibiting atrioventricular conduction. Decreases the force of cardiac contractility, and decreases arterial pressure and cardiac output. Blockade of beta2-adrenergic receptors found predominantly in smooth muscle (e.g., vascular, bronchial, gastrointestinal, and genitourinary); leads to constriction in these tissues. Well distributed throughout the body, the onset of action occurs within 1 to 2 minutes and lasts about 4 hours. Half-life is 2 to 5.5 hours. Metabolized in the liver. Excreted primarily in the urine. Secreted in breast milk.
Indications and uses
Reserve IV use for life-threatening situations or for those occurring under anesthesia. ■ Short-term treatment to decrease the ventricular rate in supraventricular tachycardia, including Wolff-Parkinson-White syndrome and thyrotoxicosis. ■ Treatment of persistent and symptomatic PVCs that do not respond to conventional measures. ■ Use in patients with atrial flutter or atrial fibrillation should be reserved for arrhythmias unresponsive to standard therapy or when more prolonged control is required. ■ Control of ventricular rate in life-threatening, digoxin-induced arrhythmias (severe bradycardia may occur). ■ Treatment of tachyarrhythmias due to excessive catecholamine action during anesthesia when other measures fail. ■ Not the drug of first choice for treatment of ventricular arrhythmias unless the arrhythmia is induced by catecholamines or digoxin. In critical situations, when cardioversion or other drugs are not indicated or effective, propranolol may be used with caution. (Use a low dose and administer very slowly so the failing heart maintains some sympathetic drive to maintain myocardial tone. May respond with NSR, but a reduction in ventricular rate is more likely.) ■ Numerous other uses PO.
Unlabeled uses:
Other beta-blockers (e.g., atenolol, esmolol) have been used in the perioperative period to reduce cardiac morbidity and mortality in patients at risk; propranolol was not used in these studies. ■ Has been used for adjunctive treatment of pheochromocytoma following primary treatment with an alpha-adrenergic blocking agent (e.g., phenoxybenzamine [Dibenzyline], phentolamine [Regitine]) and for treatment of other refractory arrhythmias when benefit outweighs risk.
Contraindications
Cardiogenic shock, sinus bradycardia, greater than first-degree heart block, bronchial asthma, known hypersensitivity to propranolol.
Precautions
Oral administration is preferred. Use IV administration only when necessary. ■ Not considered the drug of choice for arrhythmias in myocardial infarction. ■ Used concurrently with digoxin or alpha-adrenergic blockers as indicated. ■ Use with caution in overt CHF. May precipitate more severe failure. ■ Use with extreme caution in asthmatics or in patients with lung disease or bronchospasm; can block bronchodilation produced by endogenous and exogenous catecholamine stimulation of beta receptors. ■ Use with caution in patients with diabetes or in patients with a history of hypoglycemia. May cause hypoglycemia and mask the symptoms. ■ Beta blockade can mask symptoms of hyperthyroidism. Abrupt withdrawal of propranolol may be followed by exacerbation of symptoms, including thyroid storm. ■ Use caution in patients with hepatic or renal impairment. ■ May cause arrhythmia, angina, MI, or death if stopped abruptly. ■ Beta-adrenergic receptor blockade can cause a reduction in intraocular pressure. Withdrawal of propranolol may lead to a return of elevated intraocular pressure. May also interfere with the screening test for glaucoma. ■ IV dose used during surgery to replace an oral dose should be one-tenth of the oral dose. ■ May cause severe bradycardia in patients with Wolff-Parkinson-White syndrome. See Drug/Lab Interactions.
Monitor:
Continuous ECG and BP monitoring is mandatory during administration of IV propranolol. Monitoring of pulmonary wedge pressure or central venous pressure is recommended. Discontinue the drug when a rhythm change is noted and wait to note full effect before giving additional medication if indicated. ■ See Precautions and Drug/Lab Interactions.
Patient education:
Report any breathing difficulty promptly.
Maternal/child:
Category C: safety for use in pregnancy and breast-feeding and in pediatric patients not established. Use only when clearly indicated. ■ Bradycardia, hypoglycemia, and respiratory depression have been seen in neonates whose mothers received propranolol during labor or delivery.
Elderly:
Lower-end initial doses may be indicated; see Dose Adjustments. ■ Response of elderly versus younger patients not documented. ■ Use with caution in age-related peripheral vascular disease; risk of hypothermia increased. ■ May exacerbate mental impairment.
Drug/lab interactions
Metabolism involves multiple pathways in the cytochrome P450 system. Interactions with inhibitors, inducers, or substrates of this system are documented. ■ Blood levels of propranolol increased when administered concurrently with substrates or inhibitors such as amiodarone (Nexterone), cimetidine (Tagamet), ciprofloxacin (Cipro IV), delavirdine (Rescriptor), fluconazole (Diflucan), fluoxetine (Prozac), fluvoxamine (Luvox), imipramine (Tofranil), isoniazid (INH), paroxetine (Paxil), quinidine, ritonavir (Norvir), rizatriptan (Maxalt), teniposide (Vumon), theophylline, tolbutamide, zileuton (Zyflo), zolmitriptan (Zomig). ■ Blood levels of propranolol decreased when administered concurrently with inducers such as cigarette smoke, ethanol, and rifampin (Rifadin). ■ Concurrent use with propafenone may produce additive negative inotropic and beta-blocking effects. ■ Concurrent administration with quinidine results in additive negative inotropic effects and beta-blockade and postural hypotension. ■ Concurrent use with disopyramide (Norpace) has been associated with additive hypotension, severe bradycardia, asystole, and heart failure. ■ Concurrent use with amiodarone (Nexterone) results in additive negative chronotropic properties. ■ Decreases lidocaine clearance; lidocaine toxicity has been reported with concurrent use. ■ Effects additive when given with other agents that slow A-V nodal conduction (e.g., digoxin [Lanoxin], lidocaine). ■ Concurrent use with calcium channel blockers that have negative inotropic and/or chronotropic activity (e.g., diltiazem [Cardizem], verapamil) may further depress myocardial contractility and A-V nodal conduction. Bradycardia, heart failure, and cardiovascular collapse have been reported with verapamil and beta-blockers. Bradycardia, hypotension, heart block, and heart failure have been reported with coadministration of diltiazem and beta-blockers. ■ Antihypertensive effects of clonidine may be antagonized by propranolol. Use with clonidine may precipitate acute hypertension or aggravate rebound hypertension if clonidine is stopped abruptly; discontinue propranolol several days before gradual withdrawal of clonidine. Monitor BP with concurrent use. ■ First-dose hypotension may be prolonged with prazosin (Minipress). Postural hypotension has been reported when used concurrently with doxazosin (Cardura) and terazosin (Hytrin). ■ Coadministration with reserpine (a catecholamine-depleting drug) may result in hypotension, bradycardia, vertigo, syncope, or orthostatic hypotension. ■ Avoid concurrent use with epinephrine. Beta-blockade may lead to unopposed alpha-receptor stimulation, resulting in uncontrolled hypertension. ■ Dobutamine or isoproterenol (Isuprel) may be administered to reverse the effects of propranolol. However, patients may experience protracted, severe hypotension. ■ Anesthetic agents (e.g., methoxyflurane and trichloroethylene) may depress myocardial contractility when administered with propranolol. ■ ACE inhibitors (enalapril [Vasotec], lisinopril [Zestril]) may increase bronchial hyperactivity when given concurrently with propranolol. ■ Hypotension and cardiac arrest have been reported with concurrent use of haloperidol and propranolol. ■ Propranolol may increase serum levels of theophylline and diazepam (Valium). ■ Potentiates ergot alkaloids (e.g., dihydroergotamine [D.H.E. 45]); monitor for peripheral ischemia; reduce ergot dose or discontinue beta-blocker. ■ Added hypotensive effect with diuretics (e.g., furosemide), other antihypertensive agents (e.g., enalapril, nitroglycerin), some phenothiazines (e.g., chlorpromazine [Thorazine]), and reserpine. Reduced dose of one or both drugs may be indicated. ■ May prolong effects of nondepolarizing muscle relaxants (e.g., pancuronium). ■ May increase anticoagulant effects of warfarin. ■ May mask symptoms of hypoglycemia with insulin and sulfonylureas and result in prolonged hypoglycemia. ■ Can interfere with numerous diagnostic and physiologic tests. Consult literature. ■ May alter thyroid function tests and cause elevations in BUN, serum potassium, triglycerides, serum transaminases, and alkaline phosphatase. ■ Metabolism and release of catecholamines increased in smokers; increased doses may be required. May also interfere with therapeutic effects in treatment of angina. ■ Patients taking beta-blockers who are exposed to a potential allergen may be unresponsive to the usual dose of epinephrine used to treat a hypersensitivity reaction.
Side effects
AV conduction delays, bradyarrhythmias, bronchospasm, cardiac failure, cardiac standstill, erythematous rash, hallucination, hypotension, laryngospasm, nausea, paresthesia of the hands, respiratory distress, syncopal attacks, vertigo, visual disturbances. Many other side effects have been reported with oral propranolol and could be seen with the IV route; see manufacturer’s literature.
Antidote
For any side effect or excessive dosage, discontinue the drug and notify the physician immediately. Treat bradycardia with atropine 0.25 to 1 mg. Isoproterenol (Isuprel) may be used with caution if no response to vagal blockade. Serious bradycardia may require pacing. Treat cardiac failure with digitalization and diuretics. Treat hypotension or depressed myocardial function with glucagon. Administer 50 to 150 mcg/kg IV followed by an infusion of 1 to 5 mg/hr (see glucagon monograph for correct dilution). Isoproterenol (Isuprel) and dopamine may also be useful; see Drug/Lab Interactions. Treat bronchospasm with isoproterenol and aminophylline. Treat other side effects symptomatically. Monitor ECG, HR, neurobehavioral status, and intake and output until stable. Not significantly removed by hemodialysis or peritoneal dialysis. Resuscitate as necessary.
Protamine sulfate 
(PROH-tah-meen SUL-fayt)
Antidote (heparin antagonist)
pH 6 to 7
Usual dose
Following a serious heparin overdose, discontinue heparin and administer protamine immediately.
Pretreatment:
Corticosteroids and antihistamines can be used for patients at risk for protamine hypersensitivity.
IV heparin overdose:
1 mg of IV protamine neutralizes approximately 100 USP units of heparin. May be repeated if needed in 10 to 15 minutes. Never exceed 50 mg in any 10-minute period. Dose adjusted as indicated by coagulation studies. Any dose over 100 mg in 2 hours should be justified by coagulation studies (has its own anticoagulant effect). Because heparin disappears rapidly from the circulation, the dose of protamine required decreases rapidly with the time elapsed after heparin injection (e.g., 30 minutes after IV heparin, 0.5 mg [or one half of the dose] of protamine may be sufficient to neutralize 100 USP units of heparin).
Subcutaneous heparin overdose:
1 to 1.5 mg IV protamine per 100 units of heparin. Some clinicians recommend a loading dose of 25 to 50 mg given slowly over 10 minutes followed by administration of the remainder of the calculated dose as a continuous infusion over 8 to 16 hours (the continuous infusion covers the absorption time seen with administration of SC heparin). See comments under IV heparin overdose.
Low-molecular-weight heparin overdose (unlabeled):
1 mg IV protamine for every 100 antifactor Xa units of LMWH. If PTT remains prolonged 2 to 4 hours after the first dose, or if bleeding continues, consider administration of a second dose of 0.5 mg protamine for every 100 antifactor Xa units. Only 60% to 75% of antifactor Xa activity is neutralized. Excessive protamine doses can worsen bleeding potential. See comments under IV heparin overdose.
Dose adjustments
Because heparin disappears rapidly from the system, reduce dose of protamine based on length of time elapsed since heparin dose (up to one half if 30 minutes has elapsed). ■ Prompt administration of protamine sulfate may also decrease dose requirements.
Dilution
May be given undiluted or may be further diluted with NS or D5W.
Storage:
Store at CRT. Do not freeze. Discard remaining medication or diluted solution.
Compatibility
Consider any drug NOT listed as compatible to be INCOMPATIBLE until consulting a pharmacist; specific conditions may apply.
Manufacturer recommends not mixing with other drugs unless compatibility is known, and lists as incompatible with some antibiotics, including several cephalosporins and penicillins. Consider individualized rate adjustment necessary to produce desired effects.
One source suggests the following compatibilities:
Additive:
Ranitidine (Zantac), verapamil.
Rate of administration
50 mg (5 mL) or fraction thereof over 10 minutes. Do not exceed 50 mg in 10 minutes. As an infusion, may be given over 2 to 3 hours with dosage titrated according to coagulation studies. Increase duration of infusion to 8 to 16 hours for treatment of SC heparin overdose. Use infusion pump or microdrip (60 gtt/mL) to administer. Too-rapid administration, high doses, or repeated doses can cause anaphylaxis, bradycardia, cardiovascular collapse, catastrophic pulmonary vasoconstriction, pulmonary hypertension, dyspnea, flushing, noncardiogenic pulmonary edema, sensation of warmth, or severe hypotension. Hypertension has also occurred.
Actions
An anticoagulant if administered alone. In the presence of heparin, protamine forms a stable salt, neutralizing the anticoagulant effect of both drugs. Does not bind to low-molecular-weight fragments of LMWH preparations, leading to incomplete neutralization of antifactor Xa. Each 1 mg of protamine can neutralize approximately 100 USP units of heparin. Onset of action is within 0.5 to 1 minute. Neutralization of heparin occurs within 5 minutes. Duration of action is about 2 hours.
Indications and uses
To neutralize the anticoagulant activity of heparin in severe heparin overdosage.
Unlabeled uses:
Neutralization of heparin administered during extracorporeal circulation in arterial and cardiac surgery or dialysis procedures. ■ Heparin neutralization in pregnant women near delivery. ■ Treatment of overdose of low-molecular-weight heparin (e.g., dalteparin, enoxaparin, tinzaparin). Neutralization of LMWH is not complete.
Contraindications
Known hypersensitivity to protamine. ■ Do not use for bleeding that occurs without prior exposure to heparin.
Precautions
For IV use only. Can cause severe hypotension, cardiovascular collapse, noncardiogenic pulmonary edema, catastrophic pulmonary vasoconstriction, and pulmonary hypertension. Risk factors include high dose or overdose, rapid administration, repeated doses, previous administration of protamine, and current or previous use of protamine-containing drugs (e.g., NPH insulin, protamine zinc insulin, and certain beta-blockers). Allergy to fish, previous vasectomy (may have antiprotamine antibodies), severe left ventricular dysfunction, and abnormal preoperative pulmonary hemodynamics also may be risk factors. In patients with any of these risk factors, the risk versus benefit of protamine sulfate administration should be carefully considered. See Rate of Administration and Usual Dose. ■ Must be administered in a facility equipped to monitor the patient and respond to any medical emergency. ■ Pulmonary edema and/or circulatory collapse may occur in patients undergoing cardiac bypass surgery; etiology unknown. ■ Protamine sulfate should not be given when bleeding occurs without prior heparin use.
Monitor:
Coagulation studies (e.g., aPTT, ACT, heparin titration test with protamine, plasma thrombin time) may be indicated to monitor therapeutic response. ■ Facilities to treat shock must be available; see Precautions. ■ After cardiac surgery or dialysis procedures, even with adequate neutralization, further bleeding may occur any time within 24 hours (heparin “rebound”). Observe the patient continuously. Additional protamine sulfate may be indicated.
Maternal/child:
Category C: safety for use in pregnancy, breast-feeding, or pediatric patients not established.
Drug/lab interactions
Specific information not available.
Side effects
Occur more frequently with too-rapid injection; anaphylaxis, back pain, bradycardia, dyspnea, feeling of warmth, flushing, lethargy, nausea, vomiting, severe hypertension or hypotension. Acute pulmonary hypertension, noncardiogenic pulmonary edema, catastrophic pulmonary vasoconstriction, circulatory collapse, capillary leak, or pulmonary edema may occur.
Antidote
Discontinue the drug and notify the physician, who may recommend a decrease in rate of administration or, if side effects are severe, symptomatic treatment such as administration of whole blood, vasopressors (e.g., dopamine) for hypotension, atropine for bradycardia, and oxygen for dyspnea. Resuscitate as necessary.
Protein amino acids, dextrose, fat emulsion, and electrolytes 
(PROH-teen ah-MEE-noh AS-ids)
Kabiven ■ Perikabiven
Nutritional therapy
Usual dose
Obtain baseline labs; see Monitor. Correct severe fluid, electrolyte, and acid-base disorders before initiating therapy.
Kabiven:
19 to 38 mL/kg/day. Do not exceed 40 mL/kg/day.
Perikabiven:
27 to 40 mL/kg/day. Do not exceed 40 mL/kg/day.
Maximum infusion rate is based on the dextrose component. Individualize dose based on patient’s clinical condition (ability to adequately metabolize amino acids, dextrose, and lipids), on patient’s body weight and nutritional/fluid requirements, as well as on additional energy given orally/enterally to the patient. Dosage selection is based on fluid requirements, which can be used in conjunction with the nutritional requirements to determine final dosage. Products meet total nutritional requirements for protein, dextrose, and lipids in stable patients and can be individualized to meet specific needs with the addition of nutrients. Treatment may be continued for as long as is required by the patient’s condition.
The recommended daily nutritional requirements for protein, dextrose, and lipids compared to the amount of nutrition provided by each product are shown in the following chart. See Rate of Administration for additional dosing instructions.
| Nutritional Comparison | ||||
| Nutrition Provided by Kabiven Recommended Dosage | Nutrition Provided by Perikabiven Recommended Dosage | Recommended Nutritional Requirements | ||
| Stable Patients | Critically Ill Patients* | |||
| Fluid (mL/kg/day) | 19 to 38 | 27 to 40 | 30 to 40 | Minimum needed to deliver adequate macronutrients |
| Protein† (Gm/kg/day) | 0.6 to 1.3 | 0.64 to 0.94 | 0.8 to 1 | 1.5 to 2 |
| Nitrogen (Gm/kg/day) | 0.1 to 0.2 | 0.1 to 0.15 | 0.13 to 0.16 | 0.24 to 0.3 |
| Dextrose (Gm/kg/day) | 1.9 to 3.7 | 1.8 to 2.7 | ≤10 | ≤5.8 |
| Lipids (Gm/kg/day) | 0.7 to 1.5 | 0.95 to 1.4 | 1 | ≤1 |
| Total energy requirement (kcal/kg/day) | 16 to 32 | 18 to 27 | 20 to 30 | 25 to 30 |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
