AHFS Class:

• Neuromuscular Blocking Agents 12:20.20

Generic Name(s):

• Vecuronium Bromide

Vecuronium bromide is an aminosteroid nondepolarizing neuromuscular blocking agent.1,3,4,5,420

Skeletal Muscle Relaxation

Vecuronium bromide is used to produce skeletal muscle relaxation during surgery after general anesthesia has been induced.1,420 The drug also is used to facilitate endotracheal intubation;1,15,16,30,39,40,41,46,54,63,68,71,77,80,113,117,124,129,131,142 however, a neuromuscular blocking agent with a more rapid onset of action (e.g., succinylcholine, rocuronium) generally is preferred in emergency situations when rapid intubation is required.110,111,112,141,145,421,424

Vecuronium has produced adequate neuromuscular blockade in patients undergoing cesarean section,11,94,95,96,97,143 vagotomy,41 and other types of surgery, including otolaryngologic,37 cardiovascular (e.g., coronary artery bypass),1,65,69,71,122,143 facial,98 dental and oral,98,119 ophthalmic,53,54 orthopedic,48,60,62,69,90 abdominal (i.e., gynecologic, splenic, pancreatic, exploratory, and hernia procedures, as well as adrenalectomy, colostomy, sigmoidectomy, laparotomy, cholecystectomy, and gastrectomy),15,41,42,43,46,48,62,64,69,71,82,87,113,115,117,124 and routine minor procedures.114,123 The drug has also produced adequate blockade with minimal adverse effects in patients with renal74,84,116 or hepatic failure,79,90,102 critically ill or high-risk patients,18,19,64,118,126 and children 7 weeks of age and older.27,28,34,78

Vecuronium also has been used to facilitate mechanical ventilation in the intensive care unit (ICU);1,186,187,188,189,190,191,192,193,341,421 however, the manufacturer states that insufficient data are available to support dosage recommendations for such use.1 Whenever neuromuscular blocking agents are used in the ICU, the benefits versus risks of such therapy must be considered and patients should be assessed frequently to determine the need for continued paralysis.1,421 (See Cautions: Precautions and Contraindications.)

Compared with other neuromuscular blocking agents, vecuronium has an intermediate onset and duration of action, and exhibits minimal cardiovascular effects.1,3,18,49,143,145,420,421 Because of its slow onset of paralysis, vecuronium is not suitable for rapid sequence intubation, but may be used for procedures requiring profound muscle relaxation for short durations (e.g., laryngoscopy, bronchoscopy) or for maintenance of neuromuscular blockade during the postintubation period.18,145,421,424 Although vecuronium is mostly metabolized, cumulative effects attributed to its active 3-desacetyl metabolite may occur in patients with renal or hepatic dysfunction.1,18,143,145,151,420,421 Because vecuronium has minimal effects on the heart, it may be a suitable neuromuscular blocking agent during surgery.420,421

For additional information on uses and treatment principles of neuromuscular blocking agents, see Uses in the Neuromuscular Blocking Agents General Statement 12:20.20.

Reconstitution and Administration

Vecuronium bromide is administered IV only.1 The initial (intubating) dose is administered by rapid IV injection;1,2 maintenance doses may be administered by intermittent IV injection or by continuous IV infusion.1,30,33,39,76,80,113,118 Vecuronium should not be administered by IM injection ,144 since there are no clinical data to support this route of administration.

While reactions associated with histamine release are unlikely with vecuronium, if the drug is used in patients in whom substantial histamine release would be particularly hazardous (e.g., patients with clinically important cardiovascular disease) or in patients with any history suggesting a greater risk of histamine release (e.g., a history of severe anaphylactoid reactions or asthma), it may be prudent to administer the drug slowly over a period of 1-2 minutes or longer and discontinue administration if any signs of histamine release occur.141,144

For IV injection, commercially available vecuronium bromide for injection should be reconstituted with a compatible IV solution (e.g., 5% dextrose, 5% dextrose and 0.9% sodium chloride, 0.9% sodium chloride, lactated Ringer's, bacteriostatic water for injection).1 When reconstituted with bacteriostatic water for injection, the solution should be used within 5 days; when reconstituted with other compatible solutions, the solution should be used within 24 hours and any unused portions should be discarded.1 (See Chemistry and Stability: Stability.)

For continuous IV infusion, the reconstituted vecuronium solution should be further diluted to the desired concentration (usually 0.1 or 0.2 mg/mL) in a compatible IV infusion solution such as 5% dextrose, 5% dextrose and 0.9% sodium chloride, 0.9% sodium chloride, or lactated Ringer's.1,2,30,80,113 Use of a controlled-infusion device is recommended to ensure precise control of the flow rate during continuous IV infusion of the drug.359

Reconstituted solutions of vecuronium and diluted solutions of the drug should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.1 Vecuronium should not be mixed in the same syringe nor administered simultaneously through the same needle as an alkaline solution (e.g., barbiturate solution).144 (See Chemistry and Stability: Stability.)

Dispensing and Administration Precautions

Neuromuscular blocking agents should be administered only by individuals who are adequately trained in their use and complications.1,359 For specific procedures and techniques of administration, specialized references should be consulted. Facilities and personnel necessary for intubation, administration of oxygen, and respiratory support should be immediately available whenever these drugs are used.1,359,424 In addition, a reversal agent should be readily available in the event of a failed intubation or to accelerate neuromuscular recovery after surgery.1,359,421 (See Dosage and Administration: Reversal of Neuromuscular Blockade.)

Because neuromuscular blocking agents can cause respiratory arrest, precautions (e.g., storage segregation, warning labels, access limitations) should be taken to ensure that these drugs are not administered without adequate respiratory support.425 Affixing warning labels to storage containers and final administration containers is recommended to clearly communicate that respiratory paralysis can occur and ventilator support is required.425 The Institute for Safe Medication Practices (ISMP) recommends the following wording for these containers: “Warning: Paralyzing agent—causes respiratory arrest—patient must be ventilated.”425

Neuromuscular blocking agents have no known effect on consciousness, pain threshold, or cerebration, and should therefore be used in conjunction with adequate levels of anesthesia, and only after appropriate analgesics and sedatives are administered.1,359,421,423,424 To avoid distress to the patient, vecuronium should be administered only after unconsciousness has been induced.141,424

Standardize 4 Safety

Standardized concentrations for vecuronium have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. 249,250Multidisciplinary expert panels were convened to determine recommended standard concentrations. 249,250Because recommendations from the S4S panels may differ from the manufacturer's prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label. 249,250 For additional information on S4S (including updates that may be available), see [Web].249,250

Dosage

Dosage of vecuronium bromide must be carefully adjusted according to individual requirements and response.1,2 The use of a peripheral nerve stimulator is recommended to accurately monitor the degree of neuromuscular blockade and recovery, determine the need for additional doses, and minimize the possibility of overdosage.1,421

The possible need for substantially increased doses of vecuronium bromide in burn patients should be considered.175 (See Cautions: Precautions and Contraindications.)

Initial Dose

The usual initial (intubating) adult dose of vecuronium bromide is 0.08-0.1 mg/kg (1.4-1.75 times the dose necessary to induce 90% neuromuscular blockade).1,2 Following administration of this initial dose, endotracheal intubation for nonemergency surgical procedures can be performed within 2.5-3 minutes in most patients1,61,75 and maximum neuromuscular blockade generally occurs within 3-5 minutes.1,2 When used concomitantly with balanced anesthesia, this initial dose usually results in clinically sufficient neuromuscular blockade for about 25-30 minutes;1,2 spontaneous recovery to about 25% of baseline generally occurs within 25-40 minutes and is usually 95% complete 45-65 minutes after administration.1 When used concomitantly with inhalation anesthesia, this initial dose usually results in clinically sufficient neuromuscular blockade for 30-40 minutes.144 When administration of a larger initial dose is considered necessary, the manufacturer states that vecuronium bromide has been administered in initial doses ranging from 0.15-0.28 mg/kg in patients undergoing halothane anesthesia with minimal adverse cardiovascular effects as long as ventilation was adequately maintained.1,2 Although onset of action may be delayed with usual initial doses in patients with impaired circulation or in whom volume of distribution of the drug may be increased (e.g., patients with cardiovascular disease or edema), larger than usual initial doses are not recommended for these patients.1,2,141

When vecuronium is used concomitantly with general anesthetics (e.g., enflurane, isoflurane, halothane) that potentiate its neuromuscular blocking activity, dosage of vecuronium bromide may need to be reduced.1,2,14,23,89 The manufacturer states that the initial adult dose of vecuronium bromide may be reduced by about 15% (i.e., to 0.06-0.085 mg/kg) when the drug is administered more than 5 minutes after administration of enflurane, isoflurane, or halothane has been initiated or after steady-state anesthesia has been achieved.1,2

When used following succinylcholine, vecuronium bromide should be administered at a reduced initial dose and its administration should be delayed until the patient begins recovering from the neuromuscular blockade induced by succinylcholine.1,2 Following use of succinylcholine for endotracheal intubation in adults, a reduced initial vecuronium bromide dose of 0.05-0.06 mg/kg with balanced anesthesia or 0.04-0.06 mg/kg with inhalation anesthesia may be necessary.1,2

Because even small doses of vecuronium may cause profound neuromuscular blockade in patients with neuromuscular diseases (e.g., myasthenia gravis, Eaton-Lambert syndrome), response should be monitored carefully with a peripheral nerve stimulator;1 use of a small test dose of vecuronium bromide (e.g., 0.005-0.02 mg/kg)141,144 may be of value in monitoring the response to administration of skeletal muscle relaxants in these patients.1

Maintenance Dosage

Intermittent IV Injection

For maintenance of neuromuscular blockade during prolonged surgical procedures in adults receiving balanced anesthesia, additional vecuronium bromide doses of 0.01-0.015 mg/kg may be administered by intermittent IV injection as necessary.1,2 In patients receiving inhalation anesthesia, the usual maintenance dose is 0.008-0.012 mg/kg, administered as necessary.144 The manufacturer states that a maintenance dose of 0.01 mg/kg during enflurane anesthesia is approximately equivalent to a dose of 0.015 mg/kg during balanced anesthesia.1 In patients undergoing balanced or inhalation anesthesia, the first maintenance dose of vecuronium bromide generally is necessary 25-40 minutes after administration of the initial dose.1,2 Because the drug lacks clinically important cumulative effects at usual doses, the manufacturer states that repeated maintenance doses of vecuronium bromide may be administered at relatively regular intervals, generally ranging from 12-15 minutes in patients undergoing balanced anesthesia and at slightly longer intervals in patients undergoing enflurane or isoflurane anesthesia.1,2 When longer intervals between doses are desirable, the size of each maintenance dose may be increased (i.e., to greater than 0.01-0.015 mg/kg).1

Continuous IV Infusion

After the initial intubating dose is administered, patients may receive a continuous IV infusion of vecuronium to maintain neuromuscular blockade during prolonged surgical procedures; the infusion should be initiated approximately 20-40 minutes after administration of the initial dose when early spontaneous recovery from this dose is evident.1,30,33,39,76,80,113,118 The wide interindividual range in dosage requirements of vecuronium with continuous IV infusions requires that patients be very closely monitored to avoid excessive dosage when this method of administration is employed.30,33,39,113 Following rapid IV injection of an initial dose of vecuronium, required infusion rates of the drug initially decrease progressively and become relatively constant within 30-50 minutes.30,39,113 When administered by continuous IV infusion in adults, an initial vecuronium bromide infusion rate of 1 mcg/kg per minute is recommended by the manufacturer.1 Subsequently, the infusion rates should be adjusted to maintain 90% neuromuscular blockade; maintenance infusion rates of 0.8-1.2 mcg/kg per minute usually are adequate to maintain continuous neuromuscular blockade in most patients.1,39 Following rapid IV administration of an initial 0.1-mg/kg dose in a limited number of patients undergoing general surgery with nitrous oxide and halothane anesthesia, the rate of continuous IV infusion necessary to maintain 95% neuromuscular blockade at steady state ranged from approximately 0.55-1.67 mcg/kg per minute (mean: 1 mcg/kg per minute).39

The rate of spontaneous recovery from vecuronium-induced neuromuscular blockade following discontinuance of the infusion is likely to be comparable to that following administration of a single IV injection of the drug.1

When vecuronium is administered by IV infusion in patients receiving general anesthetics that potentiate its neuromuscular blocking activity, a reduction in the infusion rate of vecuronium bromide may be required.1 The manufacturer states that the infusion rate may need to be reduced by about 25-60% approximately 45-60 minutes following the initial IV dose when the drug is administered in the presence of steady-state anesthesia with enflurane or isoflurane.1 However, a reduction in the vecuronium bromide infusion rate may not be necessary in the presence of steady-state anesthesia with halothane.1

The manufacturer states that prolonged use of continuous IV infusions of vecuronium during mechanical ventilation in the ICU has not been adequately studied to date to establish dosage recommendations for this use.1

Pediatric Dosage

Recommendations for initial and maintenance doses of vecuronium bromide administered by intermittent IV injection in pediatric patients 10-16 years of age and older are the same as those for adults.1,2 (See Initial Dose and Maintenance Dosage: Intermittent IV Injection under Dosage and Administration: Dosage.) Slightly higher initial doses of vecuronium bromide and more frequent administration of maintenance doses may be necessary in children 1-9 years of age than in older children and adults.1,2,28 Infants older than 7 weeks but less than 1 year of age appear to be more sensitive than adults to the neuromuscular blocking effects of vecuronium and may experience a longer period of time (about 1.5 times longer) to neuromuscular recovery;1,2,27,148 although these children may receive doses comparable to those used in adults, less frequent administration of maintenance doses may be necessary.27,148

Safety and efficacy of vecuronium in children younger than 7 weeks of age have not been established.1,144 In addition, the manufacturer states that administration of the drug by continuous IV infusion has not been adequately studied to date to establish dosage recommendations for this route of administration in any pediatric age group.1

Dosage in Renal and Hepatic Impairment

The manufacturer states that vecuronium is well tolerated and neuromuscular blockade induced by the drug is not substantially prolonged in patients with renal failure who are optimally prepared with dialysis prior to surgery;1,2 although experience with these patients is limited, most clinicians use the usual initial and maintenance doses of the drug, with the interval between doses based on careful monitoring of the patient.141,149 Since prolongation of blockade may occur in patients with severe renal failure (i.e., creatinine clearance less than 10 mL/minute) who are not optimally prepared with dialysis, the manufacturer cautions that a lower than usual initial dose of vecuronium bromide should be considered if emergency surgery is necessary in these patients;1,2 however, most clinicians believe that the usual initial dose can be administered, anticipating that the duration of blockade may be prolonged, with maintenance dosing adjusted carefully according to the patient's response.141

Data currently are insufficient for specific dosage recommendations in patients with hepatic impairment.1 The duration of and rate of recovery from vecuronium-induced neuromuscular blockade appear to be prolonged in these patients.1,38,79,90 If vecuronium is used in patients with impaired hepatic function, some clinicians suggest that the usual initial dose of the drug may be given141,151 while others suggest giving a reduced initial dose;141 maintenance dosing (probably with reduced doses) would be adjusted carefully according to the patient's response.141,151

Reversal of Neuromuscular Blockade

Neuromuscular blockade induced by vecuronium can be reversed by administering a cholinesterase inhibitor (e.g., neostigmine, pyridostigmine, edrophonium) in conjunction with an anticholinergic agent such as atropine or glycopyrrolate to block the adverse muscarinic effects of the cholinesterase inhibitor.1,2,11,16,17,18,19,28,39,40,41,43,44,45,46,47,88,137,143 Alternatively, sugammadex may be used for the reversal of vecuronium-induced neuromuscular blockade after surgery.340,343,345 For specific information on the uses and dosage and administration of these other drugs, see the individual monographs .

To minimize the risk of residual neuromuscular blockade, reversal should only be attempted after some degree of spontaneous recovery has occurred; patients should be closely monitored until adequate recovery of normal neuromuscular function is assured (i.e., ability to maintain satisfactory ventilation and a patent airway).1,355,356,357,358,421

Adverse Effects

Adverse effects of vecuronium bromide generally are manifestations of the usual pharmacologic actions of the nondepolarizing neuromuscular blocking agents, including skeletal muscle weakness or paralysis and respiratory insufficiency or apnea.1,2 However, the respiratory depression that occurs during or following anesthesia that includes vecuronium bromide may also result at least in part from concomitantly administered drugs, including opiate agonists, barbiturates, and other CNS depressants.1

Prolonged to profound extensions of paralysis and/or muscle weakness as well as muscle atrophy have been reported after long-term use of the drug to support mechanical ventilation in intensive care settings.1 Prolonged paralysis has been associated with electrolyte disturbances (e.g., increased plasma magnesium concentrations), metabolic acidosis, and renal failure (which may result in high plasma concentrations of 3-desacetyl vecuronium); limited data indicate that prolonged paralysis may occur more frequently in female patients.186,187,189,190 (See Cautions: Precautions and Contraindications, in the Neuromuscular Blocking Agents General Statement 12:20.20.)

Following intradermal administration of vecuronium in several healthy individuals, minimal induration, redness, and itching, which are characteristic manifestations of cutaneous histamine release, have been observed, but these effects were less severe than those seen with other neuromuscular blocking agents.19,52,147,161,162 Rarely, hypersensitivity reactions associated with histamine release (e.g., bronchospasm, flushing, erythema, acute urticaria, hypotension, tachycardia) have been reported following IV administration of usual doses of the drug.1,12,18,48 Redness (flare) in skin proximal to the injection site, with subsequent urticaria, occurred in one patient following IV injection of vecuronium; subsequent intradermal testing with the drug produced a wheal and flare.161 In another patient, bronchospasm occurred following IV injection of the drug; subsequent intradermal testing with the drug was positive, although other immunologic studies, including basophil degranulation tests, revealed no evidence that the reaction was mediated by IgE or direct histamine release.162

Cardiovascular effects, including changes in heart rate,12,21,41,60,63,118,122,143 cardiac index,122 cardiac output,65,143 filling pressure of the heart,122 mean systolic blood pressure,41 mean arterial pressure,63 and systemic vascular resistance,65,143 have been observed occasionally following administration of vecuronium; however, these effects appear to be minimal and transient.12,21,60,65 Some cardiovascular effects may be associated with endotracheal intubation rather than with the drug.41,63,83,122,125,141 Systolic blood pressure, diastolic blood pressure, and/or mean arterial pressure reportedly did not change substantially in healthy patients following administration of doses of vecuronium bromide up to 0.15 mg/kg (up to 3 times the doses necessary for clinical relaxation); heart rate remained unchanged or decreased by an average of up to 8% from baseline values.1,12,63 The drug did not produce changes in heart rate or rhythm, mean arterial pressure, central venous pressure, or pulmonary wedge pressure when administered in a dose of 0.28 mg/kg in patients undergoing preparation for coronary artery bypass surgery; systemic vascular resistance decreased 12% and cardiac output increased 9% in these patients.1,65 Vecuronium did not produce tachycardia or changes in blood pressure in several patients undergoing surgery for pheochromocytoma.1,64 In comatose patients not receiving anesthesia who were administered vecuronium bromide doses of 0.1 mg/kg, the drug did not increase heart rate or cardiac output; in doses of 0.3 mg/kg, the drug caused only a very slight, transient increase in heart rate and cardiac output.58,60

Serious hypersensitivity reactions, including anaphylaxis, have been reported rarely with all neuromuscular blocking agents; such reactions were life-threatening or fatal in some cases.1,422

Precautions and Contraindications

Vecuronium bromide shares the toxic potentials of the nondepolarizing neuromuscular blocking agents, and the usual precautions of neuromuscular blocking agent administration should be observed.1 (See Cautions in the Neuromuscular Blocking Agents General Statement 12:20.20.)

When used inappropriately, neuromuscular blocking agents can severely compromise respiratory function and cause respiratory paralysis; special precautions should be taken during and after administration of these drugs.1,110,111,127,128 (See Dispensing and Administration Precautions under Dosage and Administration: Reconstitution and Administration.) The degree of neuromuscular blockade produced by vecuronium should be monitored with a peripheral nerve stimulator, particularly in patients with conditions that may potentiate (e.g., neuromuscular diseases) or cause resistance to (e.g., burns) the neuromuscular blocking effects of the drug.1

Data from some clinical studies and intradermal skin testing indicate that histamine-like hypersensitivity reactions, including bronchospasm, flushing, redness, hypotension, and tachycardia, are not likely to occur following administration of vecuronium;1,12,18,48,143 however, this does not preclude the rare development of a hypersensitivity reaction and the possibility of histamine release should be considered.1,141 (See Pharmacology: Effects on Histamine.)

Since vecuronium exhibits minimal effects on heart rate,1,3,4,6,12,18,19,21,46,47,58,60,61,62,64,65,68 especially at recommended doses, the drug will not counteract the bradycardia induced by many anesthesia agents1,21,59 (e.g., high-dose fentanyl)122,143 or by vagal stimulation;141 as a result, bradycardia may be more common when vecuronium is used concomitantly during anesthesia with agents that may cause bradycardia than when certain other neuromuscular blocking agents are used concomitantly.141

Many drugs administered during anesthesia are suspected of being capable of initiating the development of malignant hyperthermia.1 The manufacturer states that data from screening in susceptible animals are insufficient to determine whether vecuronium is capable of initiating the development of this condition.1 However, because malignant hyperthermia can occur even in the absence of a recognized precipitating factor, clinicians should be vigilant for its possible development and prepared for its management in any patient undergoing general anesthesia.168

Resistance to nondepolarizing neuromuscular blocking agents,168,169,170,171,172,173,174,176,177,178,179,180,181,182,183,184 including vecuronium,175 can develop in burn patients and may be substantial. The magnitude of resistance depends on the extent of thermal injury and elapsed time since the burn.168,169,170,171,172,173,174,175 The possible need for substantially increased doses of vecuronium bromide in burn patients should be considered.175

Vecuronium is well tolerated and neuromuscular blockade induced by the drug is not substantially prolonged in patients with renal dysfunction who have undergone adequate dialysis prior to surgery.1,2 Since blockade may be prolonged in patients with severe renal failure (i.e., creatinine clearance less than 10 mL/minute)144 who are undergoing emergency surgery and cannot be adequately prepared with dialysis preoperatively, the manufacturer cautions that a lower than usual initial dose of vecuronium bromide be considered in these patients.1 (See Dosage and Administration: Dosage in Renal and Hepatic Impairment.) The manufacturer also cautions that inadvertent overdosage in patients with renal dysfunction may be avoided by careful monitoring with a peripheral nerve stimulator.1

Since the onset of neuromuscular blockade and maximum effect of vecuronium may be delayed secondary to impaired circulation or an increased volume of distribution of the drug, larger than usual doses of the drug are not recommended in patients with these conditions (e.g., patients with cardiovascular disease or edema)1 and caution should be used when administering a subsequent dose of the drug in such patients before the maximum effect of the initial dose is attained.141 Vecuronium should be administered with caution in patients with hepatic dysfunction (e.g., cirrhosis, cholestasis),1 since the drug appears to be eliminated principally via bile and recovery from neuromuscular blockade may be prolonged in these patients.1,38,79,90,143 The manufacturer cautions that inadvertent overdosage in patients with impaired circulation or hepatic dysfunction may be avoided by careful monitoring with a peripheral nerve stimulator.1

Vecuronium should be administered with caution in severely obese patients; maintenance of an adequate airway and ventilation support prior to, during, and following administration of neuromuscular blocking agents may require particular care in these patients.1

Patients with neuromuscular diseases (e.g., myasthenia gravis, Eaton-Lambert syndrome) may have an exaggerated response to vecuronium.1 In patients with neuromuscular diseases, the degree of neuromuscular blockade induced by vecuronium should be monitored with a peripheral nerve stimulator; use of a small test dose of the drug (e.g., 0.005-0.02 mg/kg)141,144 may be of value in monitoring the response to administration of skeletal muscle relaxants in these patients.1 The degree of neuromuscular blockade produced by vecuronium should also be monitored with a peripheral nerve stimulator in patients with severe electrolyte disturbances (i.e., hypermagnesemia, hypokalemia, hypocalcemia)141 or diseases that result in electrolyte disturbances (e.g., adrenal cortical insufficiency)141 and in patients with severe debilitation1 or carcinomatosis.1 For other conditions associated with increased response to neuromuscular blocking agents, see Cautions: Precautions and Contraindications, in the Neuromuscular Blocking Agents General Statement 12:20.20.

Long-term use of neuromuscular blocking agents to support mechanical ventilation in the intensive care unit (ICU) has been associated with prolonged paralysis and/or skeletal muscle weakness.1,341 Although confounding factors were present and a causal relationship has not been definitively established, the risks versus benefits of neuromuscular blockade should be considered whenever there is a need for long-term mechanical ventilation.1 Continuous monitoring of neuromuscular transmission with a peripheral nerve stimulator is recommended whenever vecuronium is used in the ICU.1 Additional doses of vecuronium or any other neuromuscular blocking agent should not be administered before there is a definite response to nerve stimulation tests.1 If no response is elicited, administration of the drug should be discontinued until a response returns.1

Since neuromuscular blocking agents have been reported to cause severe anaphylactic reactions, appropriate emergency treatment should be readily available whenever these drugs are administered.1 Vecuronium is contraindicated in patients with known hypersensitivity to the drug.1 Because of the possibility of cross-sensitivity, vecuronium should be used with caution in patients who have experienced previous anaphylactic reactions to other neuromuscular blocking agents (depolarizing or nondepolarizing).1

Pediatric Precautions

Safety and efficacy of vecuronium in children younger than 7 weeks of age have not been established.1,144 The drug has been used safely and effectively in children older than 7 weeks of age who were undergoing surgery.27,28 Vecuronium bromide that has been reconstituted with bacteriostatic water for injection containing benzyl alcohol should not be used in neonates.1,163,164,165,166,167

Mutagenicity and Carcinogenicity

Long-term animal studies to determine the mutagenic and carcinogenic potentials of vecuronium bromide have not been performed to date.1

Pregnancy, Fertility, and Lactation

Pregnancy

Animal reproduction studies have not been performed to date with vecuronium.1 It is not known whether administration of neuromuscular blocking agents during vaginal delivery has immediate or delayed adverse effects on the fetus or whether it increases the likelihood that resuscitation of the neonate will be necessary.146 Vecuronium should be used with caution and dosage reduced as necessary in pregnant women receiving magnesium sulfate during delivery, since the neuromuscular blockade may be potentiated1,141,154,155 and its reversal impeded.1,141,155 When vecuronium was administered to pregnant women during delivery by cesarean section, no adverse effects attributed to the drug were observed in neonates born to these women.94,95,96,97 In 2 limited studies, Apgar scores were 9 or greater at 5 minutes after birth in neonates born to women who received vecuronium bromide 0.04 or 0.06-0.08 mg/kg (after tracheal intubation with succinylcholine) during cesarean delivery.1,94,97 However, the drug crosses the placenta minimally,94,95,96,97 and the possibility of respiratory depression in neonates should be considered following cesarean section in which a neuromuscular blocking agent is administered to the mother.141,146 It is not known whether vecuronium can cause fetal harm when administered to pregnant women.1 The drug should be used during pregnancy only when clearly needed.1

Fertility

It is not known if vecuronium affects fertility.1

Lactation

Since it is not known if vecuronium is distributed into milk, the drug should be administered with caution to nursing women.1,141 However, since animal studies suggest that GI absorption of vecuronium is negligible,2 any drug that may be present in milk is not likely to be of any clinical importance to a nursing infant.141

Concurrent administration of some drugs, including general anesthetics (i.e., enflurane, isoflurane, halothane),1,2,3,13,14,18,23,73,87,89,123,129 antibiotics (e.g., aminoglycosides, tetracyclines, bacitracin, polymyxins, clindamycin),1,2,3,13,18,156 skeletal muscle relaxants (e.g., succinylcholine, pancuronium),1,2,3,21,33,62,124 magnesium salts,1,141,154,155 and quinidine,1 may affect the neuromuscular blocking activity of vecuronium bromide. Concurrent administration of barbiturates, opiate agonists, nitrous oxide, or droperidol appears to have little effect on the intensity or duration of the neuromuscular blockade induced by vecuronium.1 For additional information on potential drug interactions of vecuronium, see Drug Interactions in the Neuromuscular Blocking Agents General Statement 12:20.20.

General Anesthetics

Enflurane and isoflurane reportedly increase the potency and prolong the duration of the neuromuscular blockade induced by vecuronium by about 30-50%;1,2,3,13,14,18,23,73,89,129,143 halothane appears to have only a marginal effect on the potency and duration of neuromuscular blockade induced by vecuronium, prolonging the duration by about 20%.1,2,3,13,14,18,23,87,123 In a study comparing concomitant administration of vecuronium and either enflurane, isoflurane, or halothane with 60% nitrous oxide anesthesia, the ED₅₀ (dose required to produce 50% suppression of the control twitch response) of vecuronium decreased by about 50, 33, or 18% when the MAC (minimal alveolar anesthetic concentration) of enflurane, isoflurane, or halothane anesthesia, respectively, was increased from 1.2 to 2.2.14,18 When the MAC of the inhalation anesthetic was increased to 2.2 in this study, the duration of neuromuscular blockade was increased twofold by enflurane but only minimally by isoflurane or halothane; the potentiating effect of an increasing MAC is markedly less for vecuronium than for pancuronium.14

Skeletal Muscle Relaxants

Administration of succinylcholine prior to vecuronium appears to increase the potency and prolong the duration of neuromuscular blockade induced by vecuronium.1,2,3,21,33,62,124,131,132 In one study, when a 0.04-mg/kg dose of vecuronium bromide was given 15 or 30 minutes after complete recovery from the blockade of a 1-mg/kg dose of succinylcholine, the duration of neuromuscular blockade to 90% recovery was about 26 minutes compared with 12 minutes when vecuronium was administered alone; the onset of blockade was more rapid in patients receiving vecuronium subsequent to succinylcholine.131,132 In another study, a 1-mg/kg dose of succinylcholine followed 9-14 minutes later by a 0.036-mg/kg dose of vecuronium bromide induced a 91% neuromuscular blockade compared with a 72-78% blockade when vecuronium was administered alone; the time for recovery from 25% to 75% of the control twitch tension was about 10 or 8 minutes in patients who received both succinylcholine and vecuronium or vecuronium alone, respectively.62,124 If succinylcholine is administered prior to vecuronium, the manufacturer states that administration of vecuronium should be delayed until the effects of succinylcholine begin to dissipate.1 The manufacturer states that the administration of vecuronium prior to succinylcholine in order to attenuate some of the adverse effects of succinylcholine has not been fully evaluated.1

Concomitant use of vecuronium and other nondepolarizing neuromuscular blocking agents (e.g., pancuronium bromide) may result in additive or synergistic effects.1,141 The manufacturer states that data are insufficient to support concomitant administration of vecuronium and other nondepolarizing neuromuscular blocking agents.1 In healthy adults in one study, concomitant administration of vecuronium and pancuronium did not result in potentiation,134 whereas in another study concomitant administration of vecuronium and tubocurarine (no longer commercially available in the US) did result in potentiation.135

Anti-infective Agents

IV and/or intraperitoneal injection of high doses of certain anti-infective agents, including aminoglycosides,1,2,3,18,139,140,185 metronidazole,138 tetracyclines,1 bacitracin,1 clindamycin,156 lincomycin,156 and polymyxins (i.e., polymyxin B sulfate, colistin, sodium colistimethate),1 has been shown to induce neuromuscular blockade.1,2 If these anti-infective agents are used before, during, or after surgical procedures in which vecuronium is administered, the possibility of prolonged duration of neuromuscular blockade (or recurarization, particularly postoperatively)141 should be considered.1,2,141,156 For additional information, see see Drug Interactions: Anti-Infective Agents, in the Neuromuscular Blocking Agents General Statement 12:20.20.

Intraoperative administration of acylaminopenicillins, including piperacillin, reportedly prolongs vecuronium-induced neuromuscular blockade,158,159 increasing the duration of skeletal muscle relaxation by an average of 40-55%.159 Acylaminopenicillins should be used perioperatively with caution in patients receiving vecuronium and the possibility of prolonged neuromuscular blockade should be considered.158,159

Other Drugs

When magnesium sulfate is administered for the management of toxemia of pregnancy, the neuromuscular blockade induced by vecuronium may be potentiated1,154,155 and its reversal impeded.1,141,155 If used in pregnant women receiving magnesium sulfate, vecuronium should be used with caution and its dosage reduced as necessary.1,141,155

Experience with skeletal muscle relaxants other than vecuronium suggests that recurrence of paralysis may occur in patients following parenteral administration of quinidine during recovery from neuromuscular blockade.1 The manufacturer states that the possibility of recurrence of paralysis following parenteral administration of quinidine during recovery from vecuronium-induced neuromuscular blockade should be considered.1

Although further documentation is needed, a difficult and prolonged recovery from vecuronium-induced neuromuscular blockade in a patient receiving IV verapamil suggests that calcium-channel blocking agents may be capable of prolonging the duration of neuromuscular blockade induced by vecuronium.43 Similarly, a prolonged duration of vecuronium-induced blockade was reported in a patient who received oral dantrolene preoperatively, but further evaluation of a potential interaction is needed.157

Acute Toxicity

The manufacturer states that there has been no experience to date with overdosage following parenteral administration of vecuronium bromide.1 The possibility of overdosage can be minimized by assessing the vecuronium-induced effect on the response to peripheral nerve stimulation.1

Overdosage of vecuronium is likely to produce symptoms that are mainly extensions of the usual pharmacologic effects of the drug.1 The duration of neuromuscular blockade produced by an overdose of vecuronium may be longer than that following usual doses and skeletal muscle weakness, decreased respiratory reserve, low tidal volume, or apnea beyond the period of surgery and anesthesia may occur.1 A peripheral nerve stimulator should be used to monitor recovery from blockade and may be used to differentiate prolonged neuromuscular blockade from other causes of diminished respiratory reserve.1

In vecuronium overdosage, supportive and symptomatic treatment should be initiated.1 An adequate, patent airway should be maintained, using assisted or controlled respiration as necessary.1 The possibility that other drugs (e.g., general anesthetics, opiate agonists, barbiturates) used during the surgical procedure may be wholly or partially responsible for respiratory depression should be considered.1 If cardiovascular support is necessary, treatment should include proper patient positioning, IV fluid administration, and, if necessary, use of vasopressors.141 Reversal of the neuromuscular blockade produced by vecuronium may be achieved by administration of a cholinesterase inhibitor such as neostigmine, pyridostigmine, or edrophonium.1,11,16,17,18,19,28,39,40,41,43,44,45,46,47,88,137 (See Dosage and Administration: Reversal of Neuromuscular Blockade.)

Pharmacology

Neuromuscular Blockade

Vecuronium bromide is a nondepolarizing neuromuscular blocking agent that produces pharmacologic effects similar to those of other nondepolarizing neuromuscular blocking agents.1,3,6,18 (See Pharmacology in the Neuromuscular Blocking Agents General Statement 12:20.20). On a weight basis, vecuronium bromide is about 1.2-1.7 or 4-5 times as potent as pancuronium bromide1,13,16,17,20,26,62,145 or atracurium besylate,7,12,15,21,26,145 respectively. The duration of neuromuscular blockade induced by initially equipotent doses of vecuronium bromide is about 33-50%3,4,5,6,16,17,20,29,62,68,82,87,93 or 25-33%62 that induced by pancuronium bromide or tubocurarine chloride (no longer commercially available in the US), respectively, and about 70-100% that induced by atracurium besylate.12,18,20,51,82 The neuromuscular blocking activity of vecuronium is enhanced in the presence of some inhalation general anesthetics (e.g., enflurane, isoflurane).1,13,14,18,19,23,129 (See Drug Interactions: General Anesthetics.)

The effects of patient age on vecuronium-induced neuromuscular blockade in adults remain to be clearly determined.30,31,32,33,100,143 The time of onset of neuromuscular blockade appears to be increased31 and the dose of vecuronium bromide necessary to maintain steady-state neuromuscular blockade30,32,33 and the rate of recovery30,32,33 appear to be decreased in older adults compared with younger adults. In one study in anesthetized patients younger than 40, 40-60, and older than 60 years of age, mean steady-state vecuronium bromide dosage requirements were approximately 3, 2.4, and 1.8 mg/m² per hour, respectively, and the mean times for the recovery of twitch height to 75% of the original twitch height were approximately 25, 31, and 60 minutes, respectively.30,33 However, other preliminary data suggest that vecuronium dosage requirements and the rate of recovery from neuromuscular blockade are similar in young and older adults.100 Further studies are needed to fully evaluate the effects of age on vecuronium-induced neuromuscular blockade in adults.143 Young (1-10 years of age) children may require slightly larger doses of vecuronium bromide than adolescents and adults, when calculated on a weight basis, to achieve the same degree of neuromuscular blockade during comparable techniques of anesthesia;1,27,28 however, children younger than 1 year of age may require smaller doses of the drug or doses similar to adults, administered at longer time intervals.1,27,148 (See Pediatric Dosage in Dosage and Administration: Dosage.)

The ED₅₀ (dose required to produce 50% suppression of the control twitch response) of vecuronium bromide in patients undergoing balanced or nitrous oxide and halothane anesthesia reportedly ranges from 0.015-0.036 mg/kg.12,14,15,17,21,26,27,48,58,69,70,76,81 The manufacturer states that the ED₉₀ (dose required to produce 90% suppression of the control twitch response) of the drug in patients undergoing balanced anesthesia averages 0.057 mg/kg;1 in several studies in patients undergoing balanced anesthesia, the ED₉₀ has ranged from 0.043-0.062 mg/kg.1,12,21 The ED₉₅ (dose required to produce 95% suppression of the control twitch response) of vecuronium bromide in patients undergoing balanced anesthesia has ranged from 0.037-0.065 mg/kg.15,18,58,76

The ED₅₀ in children 7-45 weeks, 1-9 years, and 10-17 years of age undergoing nitrous oxide and halothane anesthesia has reportedly averaged 0.0165,27 0.019-0.033,27,28 and 0.023 mg/kg,28 respectively; the ED₉₅ in children 2-9 and 10-17 years of age undergoing nitrous oxide and halothane anesthesia has reportedly averaged 0.06 and 0.045 mg/kg, respectively.28,78

In animals, metabolic or respiratory acidosis substantially increases and metabolic alkalosis substantially decreases the intensity of vecuronium-induced neuromuscular blockade; respiratory alkalosis only slightly decreases the intensity of neuromuscular blockade.36 The effects of acid-base balance on vecuronium-induced neuromuscular blockade in humans have not been fully determined.37,143 In anesthetized patients receiving vecuronium by an infusion sufficient to produce a continual 50% depression of the control twitch tension, induced hypercapnia or hypocapnia decreased or increased twitch tension, respectively; however, changes in Paco₂ induced prior to administration of vecuronium had little effect on the maximal depression of twitch tension induced by the drug or the time necessary for spontaneous recovery from 25% to 75% of control twitch tension.37

Effects on Histamine

Vecuronium appears to have little histamine-releasing activity when administered at usual clinical doses.1,4,12,18,19,48,49,50,52,143,147 In studies comparing vecuronium bromide, atracurium besylate, metocurine iodide (no longer commercially available in the US), pancuronium bromide, and tubocurarine chloride (no longer commercially available in the US), vecuronium was the least potent stimulator of histamine release as determined by cutaneous reaction (i.e., induration, redness, itching) to intradermal injection of the drugs.52,147 While the risk of a histamine-induced sensitivity reaction to vecuronium appears to be low, anaphylaxis and anaphylactoid reactions have been reported rarely in patients receiving the drug.1 (See Cautions: Precautions and Contraindications.)

Other Effects

Despite its steroidal structure, vecuronium apparently exhibits no hormonal activity.141

The effect of vecuronium on intraocular pressure (IOP) in patients undergoing elective ophthalmic surgery has not been clearly determined.53,54 In one study, a 0.12-mg/kg dose of vecuronium bromide caused an additional reduction in IOP following an initial anesthesia-induced reduction,53 while in another study, a 0.1-mg/kg dose of the drug appeared to slightly reverse the initial anesthesia-induced reduction in IOP.54

Vecuronium is about 10 times less potent than pancuronium bromide and about 1000 times more potent than succinylcholine chloride in its ability to inhibit plasma pseudocholinesterase;57,99 vecuronium's activity appears to be of no clinical importance.11,55,56,141 Although probably of no clinical relevance,141 vecuronium is also about 5 times more potent than pancuronium bromide or atracurium besylate in its ability to inhibit erythrocyte cholinesterase.57

In animals, the effects of vecuronium on adrenergic receptors, cardiac muscarinic receptors, or norepinephrine reuptake mechanisms are minimal and occur only at dosages many times in excess of those required for neuromuscular blockade.19

Unlike most other nondepolarizing neuromuscular blocking agents, vecuronium exhibits minimal cardiovascular effects.1,3,5,6,19,143 The drug does not appear to substantially affect heart rate or rhythm,1,3,4,6,12,18,19,21,46,47,58,60,61,62,64,65,68 systolic or diastolic blood pressure,1,4,18,19,47,58,64 mean arterial pressure,1,12,21,46,58,60,62,63,65 cardiac output,1,18 systemic vascular resistance,1,18 or pulmonary capillary wedge pressure.1,58,65 (See Cautions: Adverse Effects.) In animals, 50% vagal blockade occurs only at vecuronium bromide doses 50-80 times greater than those required for 50% neuromuscular blockade.49,55,56,66,67

Pharmacokinetics

Absorption

The onset and duration of and the rate of recovery from neuromuscular blockade induced by vecuronium bromide vary among individuals, are dose dependent, and may be altered by the anesthetic agent (e.g., enflurane, isoflurane, halothane) employed.1,2,14,17,26,33,47,70,73,77,80,89 (See Drug Interactions: General Anesthetics.) The onset and duration of and rate of recovery from neuromuscular blockade generally do not appear to be substantially altered by renal dysfunction;1,74,84,149 however, the duration of blockade may be prolonged in patients with severe renal impairment who have not undergone dialysis prior to surgery.1,2 The duration of and rate of recovery from neuromuscular blockade appear to be prolonged by hepatic dysfunction (i.e., cirrhosis, cholestasis).1,38,79,90 The duration of blockade may also be prolonged in patients undergoing cardiopulmonary bypass surgery under induced hypothermia.152

As with other nondepolarizing neuromuscular blocking agents, the time from injection to maximum blockade decreases as the dose of vecuronium bromide increases.1,2,17,18,26,46,69,70,87 The manufacturer states that following IV administration of a vecuronium bromide dose of 0.08-0.1 mg/kg, neuromuscular blockade begins within 1 minute and is maximal at 3-5 minutes.1,2 Following concomitant administration of vecuronium bromide and halothane or nitrous oxide in adults, the time from injection to maximum blockade ranges from 3.3-6.7 minutes with doses of 0.01-0.05 mg/kg12,17,21,26,27,46,58,62,69,80,87 and 2.2-5.9 minutes with doses of 0.06-0.2 mg/kg.12,21,26,27,40,46,47,61,70,71,75,76,80,82 Following concomitant administration of a vecuronium bromide dose of 0.07 mg/kg and halothane and nitrous oxide anesthesia in children 7-45 weeks and 1-8 years of age, the time from injection to maximum blockade has reportedly averaged 1.5 and 2.4 minutes, respectively.27

The duration of neuromuscular blockade increases as the dose of vecuronium bromide increases.1,2,17,47,70,80,87 In animals, the intensity of vecuronium-induced neuromuscular blockade has been shown to be increased by acidosis;36 however, the effects of acid-base balance on vecuronium-induced blockade in humans have not been fully determined.37,143 (See Pharmacology: Neuromuscular Blockade.) The duration of neuromuscular blockade induced by initially equipotent doses of vecuronium bromide is about 33-50%3,4,5,6,16,17,20,29,62,68,82,87,93 or 25-33%62 of that induced by pancuronium bromide or tubocurarine chloride (no longer commercially available in the US), respectively, and about 70-100% of that induced by atracurium besylate.12,18,20,51,82 The manufacturer states that the duration of clinically sufficient neuromuscular blockade (i.e., time from injection to 25% spontaneous recovery of control twitch response) induced by initial vecuronium bromide doses of 0.08-0.1 mg/kg under balanced (e.g., thiopental [no longer commercially available in the US], nitrous oxide, fentanyl) or halothane anesthesia is about 25-30 or 30-40 minutes, respectively.2 Following intubation with succinylcholine, the duration of clinically sufficient neuromuscular blockade of initial vecuronium bromide doses of 0.05-0.06 mg/kg under balanced anesthesia is 20-25 minutes and the duration of initial doses of 0.03-0.06 mg/kg under inhalation anesthesia is 25-30 minutes.2 In various studies, the duration of vecuronium-induced blockade (time from injection to 90% spontaneous recovery of control twitch response) under nitrous oxide, halothane, or enflurane anesthesia has reportedly averaged from 14-32 minutes with initial doses of approximately 0.01-0.05 mg/kg12,17,58,62,80,87 and 34-60 minutes with initial doses of approximately 0.06-0.12 mg/kg.27,73,80,87 In children 7-45 weeks and 1-8 years of age, the duration of blockade (time from injection to 90% spontaneous recovery of control twitch response) under halothane and nitrous oxide anesthesia has reportedly averaged 73 and 35 minutes, respectively, following administration of a vecuronium bromide dose of 0.07 mg/kg.27 The prolonged duration of action in children younger than 1 year of age appears to be related to the larger volume of distribution of, and possibly an increased sensitivity to, the drug in this age group.148 Repeated administration of maintenance doses of vecuronium bromide appears to have little, if any, cumulative effect on duration of the neuromuscular blockade.1,16,17,40,51,62,71,72,80,93,143 In addition, since the time necessary to recover from maintenance doses of the same size generally does not change with each additional dose, doses may be administered at relatively regular intervals with predictable neuromuscular blocking results;1,30,61,62,68,71,77,80,93 however, the interval between maintenance doses depends on the size of the dose2,80 and concomitant anesthesia.2

Recovery from the neuromuscular blocking effects of vecuronium bromide occurs more rapidly than recovery from those of pancuronium bromide1,3,17,20,62,68,71,92,93 or tubocurarine chloride.62,92 Recovery from neuromuscular blockade may be enhanced slightly by alkalosis1,2,3,36,49 and prolonged by acidosis.1,2 The manufacturer states that the recovery time (the time necessary for spontaneous recovery of the twitch response from 25% to 75% of the control response) following administration of vecuronium bromide doses of 0.08-0.1 mg/kg under balanced or halothane anesthesia is about 15-25 minutes;1,144 the recovery time following initial doses of vecuronium bromide appears to be dose dependent.17,141 In children 7-45 weeks and 1-8 years of age, the recovery time following administration of a vecuronium bromide dose of 0.07 mg/kg under halothane and nitrous oxide anesthesia has reportedly averaged 20 and 9 minutes, respectively.27 Following administration of a single vecuronium bromide dose of 0.2 mg/kg in patients with cirrhosis, the recovery time reportedly averaged 44 minutes.38 Repeated administration of maintenance doses of vecuronium bromide appears to have little, if any, cumulative effect on the rate of recovery from neuromuscular blockade.48,68,69,72 The rate of recovery from vecuronium-induced blockade is more rapid than that from pancuronium-induced blockade3,17,20,62,68,71,92,93 and is similar to that from atracurium-induced blockade.51,72

Good to excellent conditions for performing endotracheal intubation generally are present within 2.5-3.7 minutes after administration of a 0.08- to 0.1-mg/kg dose of vecuronium bromide in most patients;1,47,61,75,80,150 however, intubation has been performed successfully within 1.5-2.5 minutes in some patients after administration of 0.07- to 0.2-mg/kg doses of the drug.22,40,46,47,68,70,71,77,85,150

In adults, mean plasma vecuronium concentrations of 0.09-0.1498,100,101 and 0.2 mcg/mL98 at steady-state are reportedly associated with 50% and 90% neuromuscular blockade, respectively.

Distribution

Distribution of vecuronium into human body tissues and fluids has not been fully characterized.2,100,144 Following IV administration, vecuronium appears to rapidly distribute into the extracellular space.2,100 Limited data indicate that the drug undergoes rapid and extensive hepatic extraction.116 Following administration of a single 0.025- to 0.28-mg/kg dose in adults with normal renal and hepatic function, the volume of distribution of vecuronium in the central compartment (V_c) and at steady-state (V_ss) reportedly ranges from 50-120 and 179-400 mL/kg, respectively.1,2,3,84,90,95,98,100,101 The V_c and V_ss averaged 50 and 200-210 mL/kg, respectively, following an initial 0.06-mg/kg dose and continuous infusion at 1 mcg/kg per minute in adults with normal renal and hepatic function undergoing inhalation or balanced anesthesia.160 The volume of distribution of vecuronium is increased in children younger than 1 year of age148 and may be decreased in geriatric patients;100 although not clearly established, the volume of distribution may be slightly increased in patients with renal failure.74,84,104

Vecuronium is approximately 60-90% bound to plasma proteins;1,2,57,99 however, in one study, the drug was reportedly 30 and 24% bound to serum proteins in healthy patients and patients with cirrhosis, respectively.102 The wide range in reported values may have resulted from the different methods used to determine the extent of protein binding.57,99,102,141 Vecuronium crosses the placenta minimally;94,95,96,97 placental transfer of the drug appears to be about 50% that of pancuronium.2,94,95,96 Umbilical venous plasma concentrations of vecuronium were 11% of maternal concentrations at delivery in 2 limited studies in women undergoing cesarean section who received 0.04 or 0.06-0.08 mg/kg of vecuronium bromide after tracheal intubation with succinylcholine.1,94,97 It is not known if vecuronium distributes into milk.144

Elimination

Plasma concentrations of vecuronium generally appear to decline in a biphasic manner.1,3,18,26,38,84,94,95,98,104 In adults with normal renal function, the plasma half-life in the distribution phase (t_½α) averages 3.3-9 minutes1,18,26,38,84,95,98,104 and in the terminal elimination phase (t_½β) averages 31-80 minutes.1,2,18,38,84,90,94,95,98,104 Some pharmacokinetic data indicate that plasma concentrations of vecuronium decline in a triphasic manner, with the drug undergoing a very rapid initial distribution.100,101,103,106,116 In adults with normal renal function, the plasma half-life in the initial distribution phase reportedly averages 1.1-3 minutes, the plasma half-life in the redistribution phase (t_½α) reportedly averages 9-14 minutes, and the plasma half-life in the terminal elimination phase (t_½β) reportedly averages 58-103 minutes.100,101,103,106,160 In a few children 3-11 months or 1-5 years of age, the t_½β of vecuronium reportedly averaged 65 or 41 minutes, respectively.148 The t_½α and t_½β of vecuronium are not substantially altered in patients with renal failure, the t_½α averaging 4-11 minutes and the t_½β averaging 68-97 minutes.84,104 In one study in patients with cirrhosis, the t_½β averaged 84 minutes.38 The t_½β is reportedly decreased to about 35-40 minutes during late pregnancy.1,2,94,95

The metabolic fate of vecuronium in humans has not been fully characterized.1,2,3,106,116,143 In aqueous solution in vitro, vecuronium undergoes spontaneous deacetylation at the 3α- and/or 17β-positions to form the hydroxy derivatives.9 The neuromuscular blocking activity of the 3α-hydroxy derivative appears to be at least 50% that of the unchanged drug;1,2,3,67 in animals, equipotent doses of vecuronium bromide and the 3α-hydroxy derivative induce neuromuscular blockade of similar duration.1,2 In vitro, the 3α-hydroxy derivative undergoes rapid conversion to the 3α,17β-dihydroxy derivative.3,18 The 17β-hydroxy and 3α,17β-dihydroxy derivatives appear to have about 5 and 2% of the neuromuscular blocking activity of the unchanged drug, respectively.3,18,22,67 The extent of spontaneous deacetylation and/or metabolism of vecuronium in vivo in humans remains to be clearly determined.1,106,116,143

Vecuronium and its metabolite(s) appear to be excreted principally in feces via biliary elimination; the drug and its metabolite(s) are also excreted in urine.1,2,106,116 Although only unchanged drug has been detected in plasma in patients receiving the drug as an adjunct to surgical anesthesia,1,2,106 up to 10% of a dose of vecuronium has been excreted in urine and 5-25% in bile as the 3α-hydroxy derivative in some patients.1,116 Another metabolite, 3-desacetyl vecuronium, has been detected rarely in plasma following prolonged clinical use of the drug in an intensive care setting.1 Studies in rabbits with orally administered drug indicate that enterohepatic circulation of vecuronium and its active metabolites probably does not occur.2 Approximately 20-30% (range: 3-36%) of an IV dose of vecuronium bromide is excreted in urine within 24 hours after administration in humans,1,2,103,106,116 principally as unchanged drug and to a lesser extent as the 3α-hydroxy derivative;103,106,116 most urinary excretion occurs within the first 4-6 hours.106,116 In patients with a T-tube in the common bile duct, 12-45% of an IV dose of vecuronium was reportedly excreted in bile within 18-42 hours after administration, almost completely as unchanged drug,103,106,116 with most biliary excretion occurring within the first 4-6 hours.2,106 Since excretion of the drug occurs mainly via biliary elimination, temporary or permanent exclusion of the liver in animals results in increased intensity and duration of the neuromuscular blockade induced by vecuronium bromide and prolongs recovery.2,18,105,108

Total body clearance of vecuronium reportedly averages 2.9-6.4 mL/minute per kg in patients with normal renal function.1,2,4,26,90,94,95,100,101,104,106,116,160 Total body clearance reportedly averages 2.5-4.5 mL/minute per kg in patients with renal dysfunction74,84,104,116 and 0.97-2.7 mL/minute per kg in patients with hepatic dysfunction (i.e., cirrhosis, biliary obstruction).4,38,90

The manufacturer states that the effect of hemodialysis or peritoneal dialysis on plasma concentrations of vecuronium and its metabolite(s) is unknown.1

Chemistry and Stability

Chemistry

Vecuronium bromide is a synthetic, nondepolarizing neuromuscular blocking agent.1,3,4,5 Vecuronium bromide differs structurally from pancuronium bromide only by the absence of an N -methyl group on the piperidine ring at position 2, resulting in a monoquaternary rather than bisquaternary compound.2,4,6,7,9 Vecuronium, like pancuronium bromide, contains the steroid or androstane nucleus.7,8

Vecuronium bromide occurs as white to off-white or slightly pink crystals or crystalline powder and has solubilities of 9 and 23 mg/mL in water and in alcohol, respectively.2 The drug has a pK_a of 8.97 in distilled water at 25°C.2 The commercially available powders for injection occur as a lyophilized cake of very fine microscopic crystals.1 Anhydrous citric acid, anhydrous dibasic sodium phosphate, sodium hydroxide, and/or phosphoric acid are added during manufacture of the powders for injection to buffer and adjust the pH.1,2 Mannitol is also added during manufacture of the powders for injection to adjust tonicity.1,2 Following reconstitution with sterile water for injection, vecuronium bromide solutions containing 2 mg/mL are clear,141 colorless,141 and isotonic1,2 and have a pH of 4.1,2

Stability

Vecuronium bromide is unstable in the presence of bases10,11 and undergoes gradual hydrolysis in aqueous solutions,2 alcohol,2 and chlorinated hydrocarbons.144 Vecuronium bromide solutions should not be administered in the same syringe as an alkaline solution nor should vecuronium bromide and an alkaline solution be administered simultaneously through the same needle.144

Commercially available vecuronium bromide powder for injection should be stored at 20-25°C and protected from light.1,2

When reconstituted with 5% dextrose, 5% dextrose and 0.9% sodium chloride, 0.9% sodium chloride, or lactated Ringer's, resulting vecuronium bromide solutions are stable for 24 hours when refrigerated.1 Since vials of the drug do not contain a preservative and are designed for single use only, unused portions of the reconstituted solution should be discarded.1,2 Following reconstitution with bacteriostatic water for injection, vecuronium bromide solutions are stable for 5 days at room temperature or when refrigerated.1 Vecuronium bromide solutions are stable for 48 hours after reconstitution with sterile water for injection when stored in plastic or glass syringes at 2-8°C or 15-30°C, but the manufacturer recommends that they be used within 24 hours.2

Vecuronium bromide is physically and chemically compatible with the following IV solutions: 5% dextrose, 0.9% sodium chloride, 5% dextrose and 0.9% sodium chloride, or lactated Ringer's.1

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

1. Pfizer. Vecuronium bromide for injection prescribing information. New York, NY; 2011 Feb.

2. Organon Inc. Product information form for American Hospital Formulary Service on Norcuron^®. West Orange, NJ; 1984 May.

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4. AMA Division of Drugs. AMA drug evaluations. 5th ed. Chicago: American Medical Association; 1983:419-44.

5. Miller RD. Is atracurium an ideal neuromuscular blocking drug? Anesth Analg (Cleveland) . 1982; 61:721-2. Editorial. (IDIS 157359)

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8. Booij LHDJ, Vree TB, Crul JF. Org-NC₄₅: a new steroidal non-depolarizing muscle relaxant. Pharm Weekbl Sci Ed . 1982; 1-4. (IDIS 145892)

9. Savage DS, Sleigh T, Carlyle I. The emergence of Org NC 45, 1-[(2β,3α,5α,16β,17β)-3, 17 bis(acetyloxy)-2-(1-piperidinyl) -androstan-16-yl]-1-methylpiperidinium bromide, from the pancuronium series. Br J Anaesth . 1980; 52(Suppl 1):3-9S.

10. Torda TA. Drug interactions with vecuronium and other competitive neuromuscular blockers. In: Agoston S, Bowman WC, Miller RD, Viby-Mogensen J, eds. Clinical experiences with Norcuron^® (Org NC 45, vecuronium bromide). Amsterdam: Excerpta Medica; 1983:72-8.

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