Vecuronium


The designing of pancuronium started the hunt for the ‘ideal neuromuscular blocking drug’. Savarese and Kitz in 1975 defined their ideal agent as one that would have ‘brief, noncumulative, nondepolarising neuromuscular action with rapid onset and recovery; it would be reversible by an appropriate antagonist and it would lack clinically important side effects’[1]. The perceived shortcomings of pancuronium were its slow onset, its cardiac vagolytic effects and its long duration of action. Pancuronium blocked the cardiac muscarinic receptors and caused tachycardia. Savage recognized that the muscarinic receptor activity resided in the quaternary group at one end (the A ring) and the neuromuscular blocking activity resided separately in the other quaternary group (the D ring)[2]. By demethylation of the A ring nitrogen Savage came up with vecuronium, a ‘clean drug’ devoid of cardiac effects. Vecuronium had an intermediate duration of action and a slow onset. The two aminosteroidals were both metabolized in the body, and the duration of their activity was unpredictable in patients with renal or hepatic failure. This was a disadvantage.

aminosteroids

Uses for Vecuronium Bromide

1 -Skeletal Muscle Relaxation

Vecuronium is NDMB aminosteroid  used for skeletal muscle relaxation during surgery after general anesthesia has been induced. its also can be used for Facilitation of endotracheal intubation  though Succinylcholine generally is preferred in emergency situations where rapid intubation is required (RSI).

A single dose should not be used in place of succinylcholine for rapid sequence induction of anesthesia.

Endotracheal intubation for nonemergency surgical procedures generally can be performed within 2.5–3 minutes following administration of 0.08- to 0.1-mg/kg dose

its also used to Treat increase pulmonary compliance during assisted or controlled respiration after general anesthesia and also used in ICU to facilitate Mechanical ventilation

Maintenance of Neuromuscular Blockade

  • Repeated administration of maintenance doses appears to have little, if any, cumulative effect on duration of neuromuscular blockade
  • Rate of spontaneous recovery from neuromuscular blockade following discontinuance of maintenance infusion usually is comparable to that following administration of a single IV injection.
  • Close monitoring recommended to avoid excessive dosage when continuous infusion is employed.

in general the dose should be Adjusted  carefully according to individual requirements and response.

 

for that Assessment of the  neuromuscular blockade and recovery in patients undergoing anesthesia using using  peripheral nerve stimulator is recommended to accurately monitor the degree of muscle relaxation and to minimize the possibility of overdosage. 

To avoid patient distress,  never administer in conscious patient 

Usual  Dose for Anesthesia

All age groups can receive the same dose somehow children 1–9 years of age may require slightly higher initial doses than adults

Initial dose: 0.08 to 0.1 mg/kg. Maintenance dose during prolonged surgical procedures: 0.01 to 0.015 mg/kg 25 to 40 minutes later, then as frequently as every 12 to 15 minutes.
Continuous infusion: Initiate with an intubating dose of 80 to 100 mcg/kg followed 20 to 40 minutes later with 0.8 to 1.2 mcg/kg/minute.

Note that about  15% reduction in the initial dosage  (i.e., to 0.06–0.085 mg/kg) when administered after administration of enflurane, isoflurane, or halothane has been initiated or after steady-state anesthesia has been achieved

If administering following succinylcholine,  dose should be reduced to  0.05–0.06 mg/kg with balanced anesthesia or 0.04–0.06 mg/kg with inhalation anesthesia or regular dosage after succinylcholine effect is vanished.

Renal Dose Adjustments

Vecuronium is well tolerated without clinically significant prolongation of neuromuscular blocking effect in patients with renal failure who have been optimally prepared for surgery by dialysis.

Though Data currently insufficient for specific dosage recommendations. Some clinicians suggest usual initial dose.  others suggest a reduced initial dose.Adjust maintenance dosing (probably with reduced doses) carefully according to patient’s response

 

Liver Dose Adjustments

Vecuronium is not recommended for use in patients with hepatic disease/failure.

current data is  insufficient for specific dosage recommendations. Some clinicians suggest usual initial dose while others suggest a reduced initial dose. 

Adjust maintenance dosing (probably with reduced doses) carefully according to patient’s response.

Because vecuronium is excreted in bile and in urine,  vecuronium should be used with caution in patients with clinically significant hepatic and/or biliary diseases and/or renal failure. In these patient groups prolongation of action has been observed, especially when high doses of vecuronium (0.2 mg/kg) were administered in patients with hepatic disease. [3]

Precautions

This drug should be administered by or under the supervision of experienced clinicians familiar with the use of neuromuscular blocking agents (NMBAs). Dosage must be individualized in each case. The dosage information provided is derived from studies based upon units of drug per unit of body weight and is intended to serve as a guide only, especially regarding enhancement of neuromuscular blockade of vecuronium by volatile anesthetics and by prior use of succinylcholine.

To obtain maximum clinical benefits of vecuronium and to minimize the possibility of overdosage, the monitoring of muscle twitch response to peripheral nerve stimulation is advised.

Severe anaphylactic reactions to vecuronium, have been reported. These reactions have in some cases been life-threatening and fatal. Due to the potential severity of these reactions, the necessary precautions, such as the immediate availability of appropriate emergency treatment, should be taken. Precautions should also be taken in those individuals who have had previous anaphylactic reactions to other NMBAs since cross-sensitivity between NMBAs has been reported.

Safety and effectiveness have not been established in pediatric patients less than 7 weeks of age.

Dialysis

Vecuronium is well tolerated without clinically significant prolongation of neuromuscular blocking effect in patients with renal failure who have been optimally prepared for surgery by dialysis. Under emergency conditions in anephric patients some prolongation of neuromuscular blockade may occur; therefore, if anephric patients cannot be prepared for non-elective surgery, a lower initial dose of vecuronium should be considered.

Manufacturer recommends consideration of decreased initial dose if emergency surgery is necessary in patients with severe renal failure (i.e., Clcr <10 mL/minute) who are not optimally prepared with dialysis however, most clinicians believe that usual initial dose may be given. Adjust maintenance doses carefully according to patient’s response.

Others

Residual neuromuscular blockade 

As with other neuromuscular blocking agents, residual neuromuscular blockade has been reported for Vecuronium. In order to prevent complications resulting from residual neuromuscular blockade, it is recommended to extubate only after the patient has recovered sufficiently from neuromuscular block. Other factors which could cause residual neuromuscular blockade after extubation in the post-operative phase (such as drug interactions or patient condition) should also be considered. If not used as part of standard clinical practice, the use of a reversal agent should be considered, especially in those cases where residual neuromuscular blockade is more likely to occur.

Drug hypersensitivity reactions

High rates of cross-sensitivity between neuromuscular blocking agents have been reported. Therefore, where possible, before administering Norcuron, hypersensitivity to other neuromuscular blocking agents should be excluded. Vecuronium should only be used when absolutely essential in susceptible patients. Patients who experience a hypersensitivity reaction under general anaesthesia should be tested subsequently for hypersensitivity to other neuromuscular blockers.

Vagal reactions

Since Vecuronium has no cardiovascular effects within the clinical dosage range, it does not attenuate bradycardia that may occur due to the use of some types of anaesthetics and opiates or due to vagal reflexes during surgery. Therefore, reassessment of the use and/or dosage of vagolytic drugs such as atropine for premedication or at induction of anaesthesia, may be of value for surgical procedures during which vagal reactions are more likely to occur (e.g. surgical procedures where anaesthetic drugs with known vagal stimulatory effects are used, opthalmic, abdominal or anorectal surgery, etc.).

Use in the internsive care unit (ICU)

In general, following long term use of neuromuscular blocking agents in the ICU, prolonged paralysis and/or skeletal muscle weakness has been noted. In order to help preclude possible prolongation of neuromuscular block and/or overdosage it is strongly recommended that neuromuscular transmission is monitored throughout the use of neuromuscular blocking agents. In addition, patients should receive adequate analgesia and sedation. Furthermore, muscle relaxants should be titrated to effect in the individual patients by or under supervision of experienced clinicians who are familiar with their actions and with appropriate neuromuscular monitoring techniques.

Myopathy after long term administration of non-depolarising neuromuscular blocking agents in the ICU in combination with corticosteroid therapy has been reported frequently. Therefore, for patients receiving both neuromuscular blocking agents and corticosteroids, the period of use of the neuromuscular blocking agent should be limited as much as possible.

The following conditions may influence the pharmacokinetics and/or pharmacodynamics of Vecuronium:

Prolonged circulation time

Conditions associated with prolonged circulation time such as cardiovascular disease, old age, oedematous state resulting in an increased volume of distribution, may contribute to an increase in the onset time of neuromuscular block. The duration of action may also be prolonged due to a reduced plasma clearance.

Neuromuscular disease

As with other neuromuscular blocking agents, Vecuronium should be used with extreme caution in patients with neuromuscular disease or after poliomyelitis since the response to neuromuscular blocking agents may be considerably altered in these cases. The magnitude and direction of this alteration may vary widely. In patients with myasthenia gravis or the myasthenic (Eaton Lambert) syndrome, small doses of Vecuronium may have profound effects and Vecuronium should be titrated to the response.

Hypothermia

In operations under hypothermia, the neuromuscular blocking effect of Vecuronium is increased and the duration is prolonged.

Obesity

Like other neuromuscular blocking agents,Vecuronium may exhibit a prolonged duration and a prolonged spontaneous recovery in obese patients, when the administered doses are calculated on actual body weight.

Burns

Patients with burns are known to develop resistance to non-depolarising agents. It is recommended that the dose is titrated to response.

Other conditions which may increase the effects of Norcuron are

Hypokalaemia (e.g. after severe vomiting, diarrhoea, and diuretic therapy), hypermagnesaemia, hypocalcaemia (after massive transfusions), hypoproteinaemia, dehydration, acidosis, hypercapnoea, cachexia. Severe electrolyte disturbances, altered blood pH or dehydration should therefore be corrected when possible.

Based on preclinical findings, Vecuronium may cause a reduction in the partial thromboplastin time and the prothrombin time, like pancuronium bromide, d-tubocurarine or other non-depolarising neuromuscular blocking agents.

Side Effects

Uncommon/rare (<1/100, >1/10 000) Very rare (<1/10 000)
Immune system disorders Hypersensitivity
Anaphylactic reaction
Anaphylactoid reaction
Anaphylactic shock
Anaphylactoid shock
Nervous system disorders Flaccid paralysis
Cardiac disorders Tachycardia
Vascular disorders Hypotension Circulatory collapse and shock
Flushing
Respiratory, thoracic and mediastinal disorders Bronchospasm
Skin and subcutaneous tissue disorders Angioneurotic edema
Urticaria
Rash
Erythematous rash
Musculoskeletal and connective tissue disorders Muscular weakness
Steroid myopathy
General disorders and administration site conditions Drug ineffective Face oedema
Decreased drug effect/ therapeutic response Injection site pain
Increased drug effect/ therapeutic response Injection site reaction
Injury, poisoning and procedural complications Prolonged neuromuscular block Airway complication of anaesthesia
Delayed recovery from anaesthesia

MedDRA version 8.0

 

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