Local anesthetic toxicity
Encyclopedia
While generally safe, local anesthetic
agents can be toxic if used in excessive doses or administered improperly. Even when administered properly, patients may still experience unintended reactions to local anesthetics.
Excessive doses may be unintentionally administered in several ways.
The toxic effects of local anesthetics can be classified by localized and systemic effects.
(PABA). These reactions range from urticaria
to anaphylaxis
.
PABA is a metabolic product of the degradation of Ester class of local anesthetics, such as procaine
(Novocaine), benzocaine
, and, to a lesser degree, amide class anesthetics such as lidocaine
, and prilocaine
. It is also a metabolic by-product of pramod methylparaben
, a preservative in multi-dose vials of lidocaine. When allergic response to injected anesthetics does occur, it is most likely due to the ester class local anesthetics. The amide class of local anesthetics is far less likely to produce allergic reaction.
(CNS), the cardiovascular system, and the immune system.
It can be described by the direct effects on the immune system, blood (hematologic), and cardiovascular system.
.
is a process where iron in hemoglobin is altered, reducing its oxygen-carrying capability, which produces cyanosis
and symptoms of hypoxia
. Benzocaine, lidocaine, and prilocaine all produce this effect, especially benzocaine.
, which may lead to cardiovascular collapse.
Systemic toxic reactions to locally administered anesthetics are progressive as the level of the anesthetic agent in the blood rises. Initial symptoms suggest some form of central nervous system excitation such as a ringing in the ears (tinnitus
), a metallic taste in the mouth, or tingling or numbness of the mouth. advanced symptoms include motor twitching in the periphery followed by grand mal seizures, coma
, and eventually respiratory arrest. At extremely high levels, cardiac arrhythmia or hypotension
and cardiovascular collapse occur.
This treatment is termed lipid rescue. This method of toxicity treatment was invented by Dr. Guy Weinberg in 1998, and had not been widely used until after the first published successful rescue in 2006. Since then more than a dozen case reports have been published. Recently, lipid therapy held the cover of the May 2008 issue of Anesthesia & Analgesia, where the bulk of the issue had to do with this life saving technique.
Though most reports to date have used Intralipid
, a commonly available intravenous lipid emulsion, other emulsions, such as Liposyn and Medialipid have also been shown to be effective.
There is ample supporting animal evidence and human case reports of successful use in this way. In the UK, efforts have been made to publicise this use more widely and lipid rescue has now been officially promoted as a treatment by the Association of Anaesthetists of Great Britain and Ireland. There is now one published case report of successful treatment of refractory cardiac arrest
in bupropion
and lamotrigine
overdose using lipid emulsion.
The design of a 'home made' lipid rescue kit has been described
Although lipid rescue mechanism of action is not completely understood it may be that the added lipid in the blood stream acts as a sink, allowing for the removal of lipophilic toxins from affected tissues. This theory is compatible with two studies on lipid rescue for clomipramine toxicity in rabbits and with a clinical report on the use of lipid rescue in veterinary medicine to treat a puppy with moxidectin toxicosis.
Local anesthetic
A local anesthetic is a drug that causes reversible local anesthesia, generally for the aim of having local analgesic effect, that is, inducing absence of pain sensation, although other local senses are often affected as well...
agents can be toxic if used in excessive doses or administered improperly. Even when administered properly, patients may still experience unintended reactions to local anesthetics.
Excessive doses may be unintentionally administered in several ways.
- Repetitive (small) doses of local anesthetic to achieve an adequate level of anesthesia may lead to eventual administration of toxic doses.
- Injection of anesthesia in a confined space may result in excessive fluid pressure that may damage nerves.
- Doses intended for epidural or intra-support-tissue administration may be accidentally delivered as intravascular injection, resulting in accelerated systematic absorption.
The toxic effects of local anesthetics can be classified by localized and systemic effects.
Localized
A cause of local toxicity is allergic reaction to para-aminobenzoic acid4-Aminobenzoic acid
4-Aminobenzoic acid is an organic compound with the formula H2NC6H4CO2H. PABA is a white grey crystalline substance that is only slightly soluble in water...
(PABA). These reactions range from urticaria
Urticaria
Urticaria is a kind of skin rash notable for pale red, raised, itchy bumps. Hives is frequently caused by allergic reactions; however, there are many non-allergic causes...
to anaphylaxis
Anaphylaxis
Anaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure...
.
PABA is a metabolic product of the degradation of Ester class of local anesthetics, such as procaine
Procaine
Procaine is a local anesthetic drug of the amino ester group. It is used primarily to reduce the pain of intramuscular injection of penicillin, and it was also used in dentistry. Owing to the ubiquity of the trade name Novocain, in some regions procaine is referred to generically as novocaine...
(Novocaine), benzocaine
Benzocaine
Benzocaine is a local anesthetic commonly used as a topical pain reliever, or in cough drops. It is the active ingredient in many over-the-counter anesthetic ointments...
, and, to a lesser degree, amide class anesthetics such as lidocaine
Lidocaine
Lidocaine , Xylocaine, or lignocaine is a common local anesthetic and antiarrhythmic drug. Lidocaine is used topically to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic or as a local anesthetic for minor surgery.- History :Lidocaine, the first amino...
, and prilocaine
Prilocaine
Prilocaine is a local anesthetic of the amino amide type first prepared by Claes Tegner and Nils Lofgren. In its injectable form , it is often used in dentistry. It is also often combined with lidocaine as a preparation for dermal anesthesia , for treatment of conditions like paresthesia...
. It is also a metabolic by-product of pramod methylparaben
Methylparaben
Methylparaben, also methyl paraben, one of the parabens, is a preservative with the chemical formula CH3. It is the methyl ester of p-hydroxybenzoic acid.-Occurrence:...
, a preservative in multi-dose vials of lidocaine. When allergic response to injected anesthetics does occur, it is most likely due to the ester class local anesthetics. The amide class of local anesthetics is far less likely to produce allergic reaction.
Systemic
Systemic toxicity of anesthetics involves the central nervous systemCentral nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
(CNS), the cardiovascular system, and the immune system.
It can be described by the direct effects on the immune system, blood (hematologic), and cardiovascular system.
Immune system
As noted previously, allergic reaction to metabolic break-down of anesthetic agents and preservatives (PABA) can cause anaphylaxisAnaphylaxis
Anaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure...
.
Hematologic
MethemoglobinemiaMethemoglobinemia
Methemoglobinemia is a disorder characterized by the presence of a higher than normal level of methemoglobin in the blood. Methemoglobin is an oxidized form of hemoglobin that has an increased affinity for oxygen, resulting in a reduced ability to release oxygen to tissues. The oxygen–hemoglobin...
is a process where iron in hemoglobin is altered, reducing its oxygen-carrying capability, which produces cyanosis
Cyanosis
Cyanosis is the appearance of a blue or purple coloration of the skin or mucous membranes due to the tissues near the skin surface being low on oxygen. The onset of cyanosis is 2.5 g/dL of deoxyhemoglobin. The bluish color is more readily apparent in those with high hemoglobin counts than it is...
and symptoms of hypoxia
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
. Benzocaine, lidocaine, and prilocaine all produce this effect, especially benzocaine.
Cardiovascular
Cardiovascular effects are primarily those of direct myocardial depression and bradycardiaBradycardia
Bradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...
, which may lead to cardiovascular collapse.
Systemic toxic reactions to locally administered anesthetics are progressive as the level of the anesthetic agent in the blood rises. Initial symptoms suggest some form of central nervous system excitation such as a ringing in the ears (tinnitus
Tinnitus
Tinnitus |ringing]]") is the perception of sound within the human ear in the absence of corresponding external sound.Tinnitus is not a disease, but a symptom that can result from a wide range of underlying causes: abnormally loud sounds in the ear canal for even the briefest period , ear...
), a metallic taste in the mouth, or tingling or numbness of the mouth. advanced symptoms include motor twitching in the periphery followed by grand mal seizures, coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
, and eventually respiratory arrest. At extremely high levels, cardiac arrhythmia or hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
and cardiovascular collapse occur.
Management
Intravenous lipid emulsions may be useful for cardiotoxicity however the evidence at this point is still limited.This treatment is termed lipid rescue. This method of toxicity treatment was invented by Dr. Guy Weinberg in 1998, and had not been widely used until after the first published successful rescue in 2006. Since then more than a dozen case reports have been published. Recently, lipid therapy held the cover of the May 2008 issue of Anesthesia & Analgesia, where the bulk of the issue had to do with this life saving technique.
Though most reports to date have used Intralipid
Intralipid
Intralipid is a brand name for the first safe fat emulsion for human use, approved in 1962 in Europe and invented by Professor Arvid Wretlind, Sweden. The FDA initially would not approve the product due to prior experience with another fat emulsion. It was approved in the United States in 1972...
, a commonly available intravenous lipid emulsion, other emulsions, such as Liposyn and Medialipid have also been shown to be effective.
There is ample supporting animal evidence and human case reports of successful use in this way. In the UK, efforts have been made to publicise this use more widely and lipid rescue has now been officially promoted as a treatment by the Association of Anaesthetists of Great Britain and Ireland. There is now one published case report of successful treatment of refractory cardiac arrest
Cardiac arrest
Cardiac arrest, is the cessation of normal circulation of the blood due to failure of the heart to contract effectively...
in bupropion
Bupropion
Bupropion is an atypical antidepressant and smoking cessation aid. The drug is a non-tricyclic antidepressant and differs from most commonly prescribed antidepressants such as SSRIs, as its primary pharmacological action is thought to be norepinephrine-dopamine reuptake inhibition...
and lamotrigine
Lamotrigine
Lamotrigine, marketed in the US and most of Europe as Lamictal by GlaxoSmithKline, is an anticonvulsant drug used in the treatment of epilepsy and bipolar disorder. It is also used as an adjunct in treating depression, though this is considered off-label usage...
overdose using lipid emulsion.
The design of a 'home made' lipid rescue kit has been described
Although lipid rescue mechanism of action is not completely understood it may be that the added lipid in the blood stream acts as a sink, allowing for the removal of lipophilic toxins from affected tissues. This theory is compatible with two studies on lipid rescue for clomipramine toxicity in rabbits and with a clinical report on the use of lipid rescue in veterinary medicine to treat a puppy with moxidectin toxicosis.