Pharmacology: Pharmacodynamics: Bupivacaine is a long acting, amide-type local anaesthetic with both anaesthetic and analgesic effects. At high doses it produces surgical anaesthesia, while at lower doses it produces sensory block (analgesia) with less pronounced motor block. Onset and duration of the local anaesthetic effect of bupivacaine depend on the dose and site of administration. The presence of adrenaline may prolong the duration of action for infiltration and peripheral nerve blocks but has less marked effect on epidural blocks. Bupivacaine, like other local anaesthetics, causes a reversible blockade of impulse propagation along nerve fibres by preventing the inward movement of sodium ions through the cell membrane of the nerve fibres. The sodium channel of the nerve membrane is considered a receptor for local anaesthetic molecules. Local anaesthetics may have similar effects on other excitable membranes e.g. in the brain and myocardium. If excessive amounts of drug reach the systemic circulation, symptoms and signs of toxicity may appear, emanating from the central nervous and cardiovascular systems. Central nervous system toxicity usually precedes the cardiovascular effects as central nervous system toxicity occurs at lower plasma concentrations. Direct effects of local anaesthetics on the heart include slow conduction, negative inotropism and eventually cardiac arrest. Indirect cardiovascular effects (hypotension, bradycardia) may occur after epidural administration depending on the extent of the concomitant sympathetic block.
Pharmacokinetics: Bupivacaine has a pKa of 8.2 and a partition coefficient of 346 (25°C n-octanol/ phosphate buffer pH 7.4). The metabolites have a pharmacological activity that is less than that of bupivacaine. The plasma concentration of bupivacaine depends upon the dose, the route of administration and the vascularity of the injection site. The addition of adrenaline to bupivacaine may decrease the peak plasma concentration, whereas the time to peak plasma concentration usually is little affected. The effect varies with the type of block, dose and concentration. Bupivacaine shows complete and biphasic absorption from the epidural space with half-lives in the order of 7 min and 6 h, respectively. The slow absorption is rate-limiting in the elimination of bupivacaine, which explains why the apparent half-life after epidural administration is longer than that after intravenous administration. Bupivacaine has a total plasma clearance of 0.58 l/min, a volume of distribution at steady state of 73 l, a terminal half-life of 2.7 h and an intermediate hepatic extraction ratio of 0.38 after IV administration. It is mainly bound to alpha-l-acid glycoprotein with plasma binding of 96%. Clearance of bupivacaine is almost entirely due to liver metabolism and more sensitive to changes in intrinsic hepatic enzyme function that to liver perfusion. In children between 1 to 7 years the pharmacokinetics is similar to that in adults. An increase in total plasma concentration has been observed during continuous epidural infusion. This is related to a postoperative increase in alpha 1-acid glycoprotein. The unbound, i.e. pharmacologically active, concentration is similar before and after surgery. Bupivacaine readily crosses the placenta and equilibrium with regard to the unbound concentration is rapidly reached. The degree of plasma protein binding in the foetus is less than in the mother, which results in lower total plasma concentrations in the foetus. Bupivacaine is extensively metabolised in the liver, predominately by aromatic hydroxylation to 4-hydroxy-bupivacaine and N-dealkylation to PPX, both mediated by cytochrome P4503A4. About 1% of bupivacaine is excreted in the urine as unchanged drug in 24 h and approximately 5% as PPX. The plasma concentrations of PPX and 4-hydroxy-bupivacaine during and after continuous administration of bupivacaine are low as compared to the parent drug.
Bupivacaine hydrochloride (SENSORCAINE) is intended for surgical anaesthesia, post-operative analgesia, other therapeutic pain blocks and obstetric anaesthesia, particularly where long-acting anaesthesia is required. The choice of 0.5% makes it possible to vary the degree of motor blockade. Bupivacaine can be used for a number of anesthetic techniques including local infiltration, minor and major nerve blocks, epidural block, and arthroscopy.
Adults and children above 12 years of age: Please refer to the full product information for the dosage guide for the more commonly used techniques. The clinician's experience and knowledge of the patient's physical status are of importance in calculating the required dose. When prolonged blocks are used, either by continuous infusion or by repeated bolus administration, the risks of reaching a toxic plasma concentration or inducing a local neural injury must be considered. The doses in the table are those considered to be necessary to produce a successful block and should be regarded as a guide for use in adults. Individual variations in onset and duration occur. The figures reflect the expected average dose range needed. Standard textbooks should be consulted for factors affecting specific block techniques and for individual patient requirements. N.B. Risk of systemic effects of adrenaline with large volumes of adrenaline containing solutions should be considered. In order to avoid intravascular injection, aspiration should be repeated prior to and during administration of the main dose, which should be injected slowly or in incremental doses, at a rate of 25-50 mg/min, while closely observing the patient’s vital functions and maintaining verbal contact. When an epidural dose is to be injected, a preceding test dose of 3-5 ml bupivacaine containing adrenaline is recommended. An inadvertent intravascular injection may be recognised by a temporary increase in heart rate and an accidental intrathecal injection by signs of a spinal block. If toxic symptoms occur, the injection should be stopped immediately. Experience to date indicates that 400 mg administered over 24 hours is well tolerated in the average adult. In children the dosage should be calculated on a weight basis up to 2 mg/kg.
Hypersensitivity to local anaesthetics of the amide type or to any of the excipients. Hypersensitivity to sodium metabisulphite in solutions containing adrenaline. Intravenous regional anaesthesia (Bier's block) since unintentional leakage of bupivacaine into the circulation might cause acute systemic toxic reactions.
There have been reports of cardiac arrest or death during use of bupivacaine for epidural anaesthesia or peripheral nerve blockade. In some instances, resuscitation has been difficult or impossible despite apparently adequate preparation and management. Like all local anaesthetic drugs, bupivacaine may cause acute toxicity effects on the central nervous and cardiovascular systems, if utilised for local anaesthetic procedures resulting in high blood concentrations of the drug. This is especially the case after unintentional intravascular administration or injection into highly vascular areas. Ventricular arrhythmia, ventricular fibrillation, sudden cardiovascular collapse and death have been reported in connection with high systemic concentrations of bupivacaine. Regional or local anaesthetic procedures should always be performed in a properly equipped and staffed area. Equipment and drugs necessary for monitoring and emergency resuscitation should be immediately available. Patients receiving major blocks should be in an optimal condition and have an I.V. line inserted before the blocking procedure. The clinician responsible should take the necessary precautions to avoid intravascular injection and be appropriately trained and familiar with the diagnosis and treatment of side effects, systemic toxicity and other complications. Major peripheral nerve blocks may imply the administration of a large volume of local anaesthetic in areas of high vascularity, often close to large vessels where there is an increased risk of intravascular injection and/or systemic absorption which can lead to high plasma concentrations. Although regional anaesthesia is frequently the optimal anaesthetic technique, some patients require special attention in order to reduce the risk of dangerous side effects: The elderly and patients in poor general condition; Patients with partial or complete heart block - due to the fact that local anaesthetics may depress myocardial conduction; Patients with advanced liver disease or severe renal dysfunction; Patients in late stages of pregnancy; and Patients treated with anti-arrhythmic drugs class III (e.g. amiodarone) should be under close surveillance and ECG monitoring considered, since cardiac effects may be additive. Certain local anaesthetic procedures may be associated with serious adverse reactions, regardless of the local anaesthetic drug used. Central nerve blocks may cause cardiovascular depression, especially in the presence of hypovolaemia and therefore epidural anaesthesia should be used with caution in patients with impaired cardiovascular function. Retrobulbar injections may very occasionally reach the cranial subarachnoid space causing temporary blindness, cardiovascular collapse, apnoea, convulsions etc. Retro- and peribulbar injections of local anaesthetics carry a low risk of persistent ocular muscle dysfunction. The primary causes include trauma and/or local toxic effects on muscles and/or nerves. The severity of such tissue reactions is related to the degree of trauma, the concentration of the local anaesthetic and the duration of exposure of the tissue to the local anaesthetic. For this reason, as with all local anaesthetics, the lowest effective concentration and dose of local anaesthetic should be used. Vasoconstrictors may aggravate tissue reactions and should be used only when indicated. Injections in the head and neck regions may be made inadvertently into an artery may cause immediate cerebral symptoms even at low doses. Paracervical block can sometimes cause foetal bradycardia/tachycardia, and careful monitoring of the foetal heart rate is necessary. There have been reports of chondrolysis in patients receiving post-operative intra-articular continuous infusion of local anaesthetics. The majority of reported cases of chondrolysis have involved the shoulder joint. Due to multiple contributing factors and inconsistency in the scientific literature regarding mechanism of action, causality has not been established. Intra-articular continuous infusion is not an approved indication for Bupivacaine hydrochloride (SENSORCAINE). Epidural anaesthesia may lead to hypotension and bradycardia. The risk can be reduced by pre-loading the circulation with crystalloidal or colloidal solutions. Hypotension should be treated promptly with a sympathomimetic intravenously and repeated as necessary. Children should be given doses commensurate with their age and weight. When bupivacaine is administered as intra-articular injection, caution is advised when recent major intra-articular trauma is suspected or extensive raw surfaces within the joint have been created by the surgical procedure, as that may accelerate absorption and result in higher plasma concentrations. Solutions containing adrenaline should be used with caution in patients with severe or untreated hypertension, poorly controlled hyperthyroidism, ischemic heart disease, heart block, cerebrovascular insufficiency, advanced diabetes and any other pathological condition that might be aggravated by the effects of adrenaline. These solutions should also be used cautiously and in carefully restricted quantities in areas of the body supplied by end arteries, such as digits, or otherwise having a compromised blood supply. Bupivacaine hydrochloride (SENSORCAINE) adrenaline solutions contain sodium metabisulphite that may cause allergic reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulphite sensitivity in the general population is unknown and probably low. Sulphite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.
Reference to Special Groups of Patients: Pregnancy & Lactation.
The adverse reaction profile for Bupivacaine hydrochloride (SENSORCAINE) is similar to those for other long acting local anaesthetics. Adverse reactions caused by the drug per se are difficult to distinguish from the physiological effects of the nerve block (e.g. decrease in blood pressure, bradycardia), events caused directly (e.g. nerve trauma) or indirectly (e.g. epidural abscess) by the needle puncture.
Very Common (> 1/10): Vascular disorders: hypotension; Gastrointestinal disorders: nausea.
Common (> 1/100 < 1/10): Nervous system disorders: paraesthesia, dizziness; Cardiac disorders: bradycardia; Vascular disorders: hypertension; Gastrointestinal disorders: vomiting; Renal and urinary disorders: urinary retention.
Uncommon (> 1/1,000 < 1/100): Nervous system disorders: Signs and symptoms of CNS toxicity (convulsions, paraesthesia circumoral, numbness of the tongue, hyperacusis, visual disturbances, loss of consciousness, tremor, light-headedness, tinnitus, dysarthria).
Rare (< 1/1,000): Immune system disorders: Allergic reactions, anaphylactic reaction/shock; Nervous system disorders: Neuropathy, peripheral nerve injury, arachnoiditis, paresis and paraplegia; Eye disorders: Diplopia; Cardiac disorders: Cardiac arrest, cardiac arrhythmias; Respiratory disorders: Respiratory depression.
Bupivacaine should be used with caution in patients receiving other local anaesthetics or agents structurally related to amide-type local anaesthetics, e.g. certain anti-arrhythmics, such as lidocaine and mexiletin since the systemic toxic effects are additive. Specific interaction studies with bupivacaine and anti-arrhythmic drugs class III (e.g. amiodarone) have not been performed, but caution should be advised. Solutions containing adrenaline should generally be avoided or used with care in patients receiving tricyclic antidepressants since severe, prolonged hypertension may be the result. In addition, the concurrent use of adrenaline-containing solutions and oxytocic drugs of the ergot type may cause severe, persistent hypertension and possibly cerebrovascular and cardiac accidents. Neuroleptics such as phenothiazines may reduce or reverse the pressor effect of adrenaline. Solutions containing adrenaline should be used with caution in patients undergoing general anaesthesia with inhalation agents such as halothane and enflurane due to the risk of serious cardiac arrhythmias. Non-selective beta-blockers such as propranolol enhance the pressor effects of adrenaline, which may lead to severe hypertension and bradycardia.
N01BB01 - bupivacaine ; Belongs to the class of amides. Used as local anesthetics.
Sensorcaine Plain soln for inj 0.5%
10 mL x 1's (P1,898.79/polyamp)