Adrenaline with local anaesthetics

In patients with cardiac arrest, for example as a result of an intoxication with local anaesthetics, quinine or other cardiodepressant drugs, the stimulatory action of adrenaline on the impulse formation and propagation in the heart can be life saving. 

Systemic reactions to added adrenaline (norepinephrine) are unusual, but can occur and are usually expressed as temporary blood pressure increase, palpitations and anxiety. These reactions rarely require any other treatment than calming explanations. Adrenaline containing local anaesthetics should only be given with particular caution to individuals with increased susceptibility to adrenaline effects - e.g. patients treated with noradrenaline reuptake inhibitors or patients with certain heart diseases. 

Adrenaline along with local anaesthetics may be used for infiltration, nerve block and spinal anaesthesia for prolonging the action and to reduce the systemic toxicity of local anaesthetics. 

LIDOCAINE BETA-BLOCKERS 1. Risk of bradycardia (occasionally severe), l BP and heart failure with intravenous lidocaine 2. Risk of lidocaine toxicity due to T plasma concentrations of lidocaine, particularly with propranolol and nadolol 3. t plasma concentrations of propranolol and possibly some other beta-blockers 1. Additive negative inotropic and chronotropic effects 2. Uncertain, but possibly a combination of beta-blocker-induced 1 hepatic blood flow (due to 1 cardiac output) and inhibition of metabolism of lidocaine 3. Attributed to inhibition of metabolism by lidocaine 1. Monitor PR, BP and ECG closely watch for development of heart failure when intravenous lidocaine is administered to patients on beta-blockers 2. Watch for lidocaine toxicity 3. Be aware. Regional anaesthetics should be used cautiously in patients with bradycardia. Beta-blockers could cause dangerous hypertension due to stimulation of alpha-receptors if adrenaline is used with local anaesthetic... 

Intravenous. A double cuff is applied to the arm, inflated above arterial pressure after elevating the limb to drain the venous system, and the veins filled with local anaesthetic, e.g. 0.5-1% lidocaine without adrenaline (epinephrine). The arm is anaesthetised in 6-8 min, and the effect lasts for up to 40 min if the cuff remains inflated. The cuff must not be deflated for at least 20 minutes. The technique is useful in providing anaesthesia for the treatment of injuries speedily and conveniently, and many patients can leave hospital soon after the procedure. The technique must be meticulously conducted, for if the full dose of local anaesthetic is accidentally suddenly released into the general circulation severe toxicity and even cardiac arrest may result. Bupivacaine is no longer used for intravenous regional anaesthesia as cardiac arrest caused by it is particularly resistant to treatment. Patients should be fasted and someone skilled in resuscitation must be present. 

Some local anaesthetics, lidocaine and bupivacaine, can be used in combination with adrenaline. Adrenaline is a vasoconstrictor and its use increases the speed of onset and prolongs the duration of action of the local anaesthetic. Vasoconstrictors should never be used with local anaesthetics in digits or appendages, because of the risk of vasoconstriction leading to ischaemic necrosis. See page 277 for a list of local anaesthetics and other injectable drugs that can be administered by podiatrists. 

Note that drugs such as adrenaline (epinephrine), which are used with local anaesthetics, may interact with inhalational anaesthetics such as ha-... 

Patients taking tricyclic antidepressants show a grossly exa er-ated response (hypertension, cardiac arrhythmias, etc.) to parenteral noradrenaline (norepinephrine), adrenaline (epinephrine) and to a lesser extent to phenylephrine. Case reports suggest that this interaction only occurs rarely with local anaesthetics containing these vasoconstrictors. 

Noradrenaline and adrenaline are the classic catecholamines and neurotransmitters in the sympathetic nervous system. Noradrenaline stimulates the following subtypes of adrenoceptors P, a, U2. It has positive inotropic and chronotropic activities as a result of /3i-receptor stimulation. In addition, it is a potent vasoconstrictor agent as a result of the stimulation of both subtypes (ai,a2) of a-adrenoceptors. After intravenous infusion, its effects develop within a few minutes, and these actions disappear within 1-2 minutes after stopping the infusion. It may be used in conditions of acute hypotension and shock, especially in patients with very low vascular resistance. It is also frequently used as a vasoconstrictor, added to local anaesthetics. Adrenaline stimulates the following subtypes of adrenoceptors /3i, P2, oil, 0L2. Its pharmacological profile greatly resembles that of noradrenaline (see above), as well as its potential applications in shock and hypotension. Like noradrenaline, its onset and duration of action are very short, as a result of rapid inactivation in vivo. Both noradrenaline and adrenaline may be used for cardiac stimulation. Their vasoconstrictor activity should be kept in mind. A problem associated with the use of /3-adrenoceptor stimulants is the tachyphylaxis of their effects, explained by the /3-adrenoceptor downregulation, which is characteristic for heart failure. 

Infiltration anaesthesia is applied fan-shaped, with as few needle punctures as possible, in close proximity of the wound or the skin area to be treated. An aspiration should always take place to avoid intravascular injection. Suitable alternatives are lidocaine (lignocaine) or prilocaine for injection 5-10 mg/ml, with or without adrenaline. When making an incision of an abscess it is sometimes difficult to use a local anaesthetic if there is a pronounced inflammatory reaction, since the effect of the anaesthetic is reduced due to an increased acidity level. While adrenaline reduces bleeding and delays dispersion of the anaesthetic, local anaesthetic/adrenaline combinations are contraindicated for local anaesthesia of digits, on the face or where the skin survival is at risk. 

Dental anaesthesia—The total amount of local anaesthetics injected is much smaller (20-80 mg of lignocaine) than that used for othr purpose. Lignocaine (2%) with adrenaline (1 80,000) is the standard local anaesthetic preparation used in dentistry which produces good soft tissue and pulpal anaesthasia and also reduce postextraction bleeding. 

The duration of action of a local anaesthetic is proportional to the time that the drug remains bound to the sodium channels. Measures that prolong contact time will prolong the duration of the local anaesthetic effect. Cocaine has a vasoconstricting effect on blood vessels and prevents its own absorption. Many local anaesthetics are prepared with adrenaline (epinephrine) in order to achieve this effect. Concentrations are usually of the order of 1 200000 or more dilute than this. Care should be exercised when using adrenaline-containing solutions in the presence of halothane as it is known to sensitise the myocardium to the effects of catecholamines. 

This is an amide local anaesthetic and is widely used on account of its rapid onset, medium duration of effect, and low toxicity. It is less highly protein-bound than the longer-acting amides (Table 5.1) but it has a useful duration of effect and is the most versatile of all local anaesthetics. It is of intermediate potency and has less toxic potential than bupivacaine. It is available in aqueous solution as the hydrochloride salt in concentrations of 0.5-2.0% with and without adrenaline (epinephrine). Topical preparations are also available as gels or aerosols in 2-4% concentrations. 

Vasoconstriction will reduce local blood flow so that distribution of drug away from an injection site is retarded, e.g. local anaesthetic action is prolonged by combination with adrenaline (epinephrine). 

The effect of a local anaesthetic is terminated by its removal from the site of application. Anything that delays its absorption into the circulation will prolong its local action and can reduce its systemic toxicity where large doses are used. Most local anaesthetics, with the exception of cocaine, cause vascular dilation. The addition of a vasoconstrictor such as adrenaline (epinephrine) reduces local blood flow, slows the rate of absorption of the local anaesthetic, and prolongs its effect the duration of action of lidocaine is doubled from one to two hours. Normally, the final concentration of adrenaline (epinephrine) should be 1 in 200 000, although dentists use up to 1 in 80 000. 

Anaphylactoid reactions are very rare with amide local anaesthetics and some of those reported have been due to preservatives. Most reported reactions to amide local anaesthetics are due to co-administration of adrenaline (epinephrine), intravascular injection or psychological effects (vasovagal episodes). Reactions with ester local anaesthetics are more common. 

Adrenaline is an example of a sentry drug which acts on a receptor rather than an enzyme. This drug is used along with the injectable local anaesthetic procaine to prolong its action (Fig. 8.22). Adrenaline constricts the blood vessels in the vicinity of the injection and so prevents procaine being washed away by the blood supply. 

Considerable interest has recently been aroused by reports that patients treated with monoamine oxidtise inhibitors may suffer severe hypertensive attacks after taking certain foods, notably cheese - , beans and extracts of yeast . Some of these attacks have proved fatal. The hypertensive crises arise as a result of pressor substances in the offending foods (such as tyramine in cheese) which are absorbed unchanged into the blood stream when intestinal and liver monoamine oxidase is inhibited . Some of the inhibitors (tranylcypromine is an example) also have sympathomimetic actions which will contribute to the hypertensive effect. The administration of sympathomimetic substances—such as adrenaline in a local anaesthetic—to patients treated with monoamine oxidase inhibitor also creates a dangerous situation. The possibility of hypertensive crises clearly constitutes a serious hazard of therapy with these enzyme inhibitors. In many instances their limited effectiveness would not justify the exposure of patients to these hazards. 

Propranolol reduces the clearance of bupivacaine and so theoretically the toxicity of bupivacaine may be increased. There has been a single report of enhanced bupivacaine cardiotoxicity in a patient also receiving metoproioi and digoxin. The coronary vasoconstriction caused by cocaine is increased by propranolol. Beta blockers may interact with adrenaline (epinephrine)-containing local anaesthetics. 

The use of adrenaline with topical cocaine is controversial. Some consider that the addition of adrenaline is of doubtful value and that the combination should not be used, especially in the form of a concentrated paste. However, others consider the combination to be safe and useful. Whether or not adrenaline is combined with cocaine, the BNF considers that topical cocaine should be used only by those skilled in the precautions needed to minimise absorption and the consequent risk of arrhythmias. Note also that the use of local anaesthetics containing adrenaline should be avoided in patients who abuse cocaine, unless it is certain that they have not used cocaine for at least 24 hours. ... 

Note that local anaesthetic preparations of lidocaine often contain adrenaline (epinephrine), which may interact with beta blockers, see Beta blockers -I- Inotropes and Vasopressors , p.848. 

The blood pressme-raising effect of adrenaline is caused by a constriction of the blood-vessels. If, for example, mucous membranes are brushed with a highly diluted adrenaline solution (1 10,000), these become completely bloodless. To take advantage of this effect for small surgical procedures, adrenaline is added to local anaesthetics. 

Stimulant effect was reported [302]. In pharmacological tests, (119) potentiated many adrenaline like compounds and antagonized reserpine, tetrabenazine and phenothiazine. It has no anticholinergic, depressive, analgesic or local anaesthetic properties [303]. Notwithstanding structural analogy with harmaline (120), data on MAO inhibition were not presented. 

The tetraphenylboron method for small quantities of bases, given under Atropine, p. 116, has also been applied successfully to some preparations of local anaesthetics. Procaine in Injection of Procaine and Adrenaline can be determined by diluting 2 ml of sample to 20 ml with dilute buffer solution, pH 3 7, and taking 10 ml for the assay each ml of cetylpyridinium chloride is equivalent to 0 001364 g. Amethocaine, however, tends to give high results if the reagent is added in large excess, probably due to the tendency to partial formation of a di-tetraphenylborate. 

The local risks of vasoconstrictors in local anaesthetic solutions, particularly when the latter are used in the fingers or other extremities, have long been recognized. In addition, it is well known that the use of adrenaline or noradrenaline for this purpose can lead to marked rises in blood pressure, especially in patients who are taking MAO inhibitors the cardiovascular effects can be dangerous in patients with existing cardiovascular disease or where there is simultaneous treatment with either a tricyclic antidepressant (SED VIII) or with those general anaesthetics which sensitize the myocardium to the effects of catecholamines (e.g. chloroform, cyclopropane, halothane). 

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