Systemic Complications

of Local Anesthetics

Done By: Alaa Mourad

Course title: Anesthesia
Term: Fall 2015/2016
Outline:
- Introduction
- Overdose reactions, Allergy, and Idiosyncrasy
- Systemic Complications
Cardiovascular system complications
Nervous system complications
Endocrine system complications
Hematologic complications
Liver complications
Immunologic complications
- References

Introduction

The administration of local anesthetics is considered essential whenever potentially

painful procedures are contemplated.

Local anesthetics are extremely safe drugs when used as recommended. However,
whenever any drug, including local anesthetics, is used, the potential for unwanted
and undesirable responses exists.

Harmful effects of drugs range from:

Inconsequential to the patient and entirely reversible once the drug is withdrawn.
Uncomfortable but not seriously harmful
Seriously incapacitating or proven fatal to the patient.

Whenever any drug is administered, two types of actions may be observed:

a. Desirable actions, which are sought and beneficial
b. Undesirable actions, which are additional and are not sought.

Three principles are essential to be aware of:

-

Principle 1: No drug ever exerts a single action.

Principle 2: No clinically useful drug is entirely devoid of toxicity.
Principle 3: The potential toxicity of a drug lies in the hands of the user.

Overdose reactions, Allergy, and Idiosyncrasy

Overdose reactions

Local anesthetics are drugs that act to depress excitable membranes (e.g., the CNS
and myocardium are the target organs for local anesthetics).
With all local anesthetics, the dose administered varies with the anesthetic
procedure, the vascularity of the tissues, the depth of anesthesia and degree of
muscle relaxation required, the duration of anesthesia desired, and the physical
condition of the patient. The smallest dose and concentration required to produce
the desired result should be used.

When administered properly and in therapeutic dosages, they cause little or no

clinical evidence of CNS or CVS depression. However, signs and symptoms of
selective CNS and CVS depression develop with increased blood levels in the
cerebral circulation or myocardium.

Allergy

Clinical manifestations of allergy vary and include the following:

- Fever
- Angioedema
- Urticaria
- Dermatitis
- Depression of blood-forming organs
- Photosensitivity
- Anaphylaxis
Ester-type local anesthetics are much more likely to cause an allergic reaction
compared to the amide-type local anesthetics because of the formation of
PABA during the metabolic process. PABA may cause allergic reactions that
range from urticaria to anaphylaxis.
If a patient has an allergic response to either class, attempt using a product from
the other class. Example: patient develops a rash with procaine switch to lidocaine.
Alternatively, if a patient has a reaction to both classes, try using a preservativefree formulation such as lidocaine-MPF.

Idiosyncrasy

A qualitatively abnormal, unexpected response to a drug, differing from its usual

pharmacologic actions and thus resembling hypersensitivity. However, idiosyncrasy
does not involve a proven, or even suspected, allergic mechanism.

Any adverse response that is neither overdose nor an allergic reaction.

It is almost impossible to predict which persons will have idiosyncratic reactions or

the nature of the resulting idiosyncrasy.

Instances of idiosyncratic reaction have an underlying genetic mechanism. These

aberrations remain undetected until the individual receives a specific drug, which
then produces its nonpharmacological clinical expression.

Specific management of idiosyncratic reactions is difficult to discuss because of the

unpredictable nature of the response. Treatment is symptomatic and includes:
-

Positioning

Airway

Breathing

Circulation

The adverse effects of local anesthetics can be classified as:

1. Technique effects, such as needle trauma to a vessel.
2. Local effects of the drug, could be associated with its anesthetic activity or a
consequence of irritation or allergy.
3. Systemic effects, most commonly observed if the agent is inadvertently injected into a
blood vessel in sufficient quantities.
4. Additives effects, mostly vasoconstrictors to prolong the local effect, hyaluronidase to
promote penetration, and preservatives to prevent bacterial contamination

Systemic Complications
Cardiovascular

Cardiovascular complications are not uncommon, however, most changes are

moderate, involving:
- Mild peripheral vasodilatation
- Reduced cardiac output with a change in HR.
Local anesthetics:
- Reduce myocardial contractility and rate of conduction.
- Cause direct vasoconstriction or vasodilatation of vascular smooth muscle
- Cause central stimulation of the ANS.
Cardiac arrest and marked myocardial depression, in which hypoxia plays a
critical role, have been reported.
CV collapse can be severe and refractory to treatment; most fatal cases involve
bupivacaine.
The CVS is more resistant to the toxic effects of LA than the nervous system.
Mild circulatory depression can precede nervous system toxicity, but seizures
are more likely to occur before circulatory collapse. The IV dose of lidocaine
required to produce CV collapse is 7x that which causes seizures.

Nervous system

CNS effects of:

- Low concentrations of local anesthetics: sedation and confusion
- High concentrations of local anesthetics: seizures.
The first signs of systemic toxicity:
- mild sedation
- diminished alertness
- dizziness
- tinnitus
- metallic tastes
- muscle twitching
- perioral numbness
- visual disturbances
- disorientation
- light-headedness
Because the blood concentrations reached are sometimes higher than one would
predict, toxicity can occasionally prove much more severe than expected, for
example frank convulsions, sometimes progressing to respiratory arrest and
loss of consciousness.
LA-induced seizures have been reported more often with bupivacaine, particularly
in combination with chloroprocaine

Endocrine
Local anesthetics generally have only slight endocrine and metabolic adverse
effects, without clinical repercussions.

Hematologic
Methemoglobinemia has been reported with benzocaine, Cetacaine, cocaine,
lidocaine, novocaine, and prilocaine.
Acquired methemoglobinemia can result from exposure to chemicals that
contain an aniline group, such as benzocaine and procaine, or to those that are
transformed to metabolites that contain an aniline group, such as lidocaine and
prilocaine.
Factors that favor the onset of methemoglobinemia:
- Toxic blood concentrations of LA
- Aberrant hemoglobin
- NADH-methemoglobin reductase deficiency

Liver
Reduced hepatic clearance, in addition to relative over-dosage, of LA can lead
to systemic toxicity.

Immunologic
Systemic hypersensitivity reactions are not a frequent problem in local
anesthesia.
Systemic toxicity or allergy to additives (hyaluronidase, bisulfate, parabens) has
sometimes been improperly classified as hypersensitivity to LA
True allergy occurrence is very low, most likely < 1% of all the adverse effects
attributed to these substances.
Type I hypersensitivity reactions and life-threatening anaphylaxis can rarely
occur.
Cross-reaction between amides also occurs, ex: articaine, bupivacaine, lidocaine,
and prilocaine.
Type IV delayed hypersensitivity reactions are uncommon, but allergic contact
dermatitis and localized erythema and blistering have been reported.
Contact hypersensitivity also occurs. Benzocaine is a potent skin sensitizer, and
several cases of contact dermatitis to lidocaine have been reported.
Pseudo-allergic reactions are often caused by LA when injected into the skin, w/
similar symptoms to immediate type allergy. However, true immediate
hypersensitivity to LA is extremely rare.

References:
Meyler's Side Effects of Drugs Used in Anesthesia By J. K.
Aronson, Pages: 79 84
Handbook of Local Anesthesia By Stanley F. Malamed, Chapter
18 (Systemic Complications)
Figures: All images are copyrighted material and are the property of
- The authors of Handbook of Local Anesthesia
- Globalrph.com
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- Therichardcopley.wordpress.com
- Dreamstime.com
- Sagecreekhospital.ca
- Accelrys.com
- Iyad Abou Rabii, Immediate Past President at IADRPharmacology Therapeutic and Toxicology Scientific Group