Action And Clinical Pharmacology: Local anesthetics block the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse and by reducing the rate of rise of the action potential. In general, the progression of anesthesia is related to the diameter, myelination, and conduction velocity of affected nerve fibres. Clinically, the order of loss of nerve function is as follows: pain, temperature, touch, proprioception, and skeletal muscle tone. Procaine lacks topical anesthetic activity.
The rate of systemic absorption of local anesthetics is dependent upon the total dose and concentration of drug administered, the route of administration, the vascularity of the administration site, and the presence or absence of epinephrine in the anesthetic solution. A dilute concentration of epinephrine (1:200 000 or 5 g/mL) usually reduces the rate of absorption and plasma concentration of procaine. It also will promote local hemostasis and increase the duration of anesthesia.
Onset of anesthesia with procaine is rapid, the time of onset for sensory block ranging from about 2 to 5 minutes depending upon such factors as the anesthetic technique, the type of block, the concentration of the solution, and the individual patient. The degree of motor blockade produced is dependent on the concentration of the solution.
The duration of anesthesia also varies depending upon the technique and type of block, the concentration, and the individual. Procaine will normally provide anesthesia which is adequate for 1 hour.
Local anesthetics are bound to plasma proteins in varying degrees. Generally, the lower the plasma concentration of drug, the higher the percentage of drug bound to plasma.
Local anesthetics appear to cross the placenta by passive diffusion. The rate and degree of diffusion is governed by the degree of plasma protein binding, the degree of ionization, and the degree of lipid solubility. Fetal/maternal ratios of local anesthetics appear to be inversely related to the degree of plasma protein binding, because only the free, unbound drug is available for placental transfer. The extent of placental transfer is also determined by the degree of ionization and lipid solubility of the drug. Lipid, soluble nonionized drugs readily enter the fetal blood from the maternal circulation.
Depending upon the route of administration, local anesthetics are distributed to some extent to all body tissues, with high concentrations found in highly perfused organs such as the liver, lungs, heart, and brain. Various pharmacokinetic parameters of the local anesthetics can be significantly altered by the presence of hepatic or renal disease, addition of epinephrine, factors affecting urinary pH, renal blood flow, the route of drug administration, and the age of the patient. The in vitro plasma half-life of procaine in adults is 40±9 seconds and in neonates 84±30 seconds.
Procaine is readily absorbed following parenteral administration and is rapidly hydrolyzed by plasma cholinesterase to para-aminobenzoic acid and diethylaminoethanol.
The para-aminobenzoic acid metabolite inhibits the action of the sulfonamides (see Precautions).
For procaine, approximately 90% of the para-aminobenzoic acid metabolite and its conjugates and 33% of the dimethylaminoethanol metabolite are recovered in the urine, while less than 2% of the administered dose is recovered unchanged in the urine.
Indications And Clinical Uses: Local infiltration and peripheral nerve block.
Contra-Indications: Sensitivity to PABA esters; sensitivity to procaine.
Manufacturers’ Warnings In Clinical States: Local anesthetics should only be employed by clinicians who are well versed in diagnosis and management of dose-related toxicity and other acute emergencies which might arise from the block to be employed, and then only after insuring the immediate availability of oxygen, other resuscitative drugs, cardiopulmonary resuscitative equipment, and the personnel resources needed for proper management of toxic reactions and related emergencies. Delay in proper management of dose-related toxicity, underventilation from any cause, and/or altered sensitivity may lead to the development of acidosis, cardiac arrest, and, possibly, death.
Precautions: In general, reactions and complications are best averted by using the minimal effective dosage and lowest concentration of the anesthetic agent. Injections should always be made slowly and with frequent aspiration. When procaine is used with epinephrine, the caution required by any vasopressor drug is in order, especially in cases of patients with hypertension, diabetes mellitus and thyrotoxicosis.
Pregnancy: Animal reproduction studies have not been conducted with procaine. It is not known whether procaine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Procaine should be given to a pregnant woman only if clearly needed and the potential benefits outweigh the risk. This does not exclude the use of procaine at term for obstetrical anesthesia or analgesia.
Labor and Delivery: Local anesthetics rapidly cross the placenta, and when used for paracervical or pudendal block anesthesia, can cause varying degrees of maternal, fetal, and neonatal toxicity. The incidence and degree of toxicity depend upon the procedure performed, the type and amount of drug used, and the technique of drug administration. Adverse reactions in the parturient, fetus, and neonate involve alterations of the CNS, peripheral vascular tone, and cardiac function.
Paracervical or pudendal anesthesia may alter the forces of parturition through changes in uterine contractility or maternal expulsive efforts.
Fetal bradycardia which frequently follows paracervical block may be indicative of high fetal blood concentrations of procaine with resultant fetal acidosis.
Added risk appears to be present in prematurity, toxemia of pregnancy, and fetal distress.
Cases compatible with unintended fetal intracranial injection of local anesthetic solution have been reported following intended paracervical or pudendal block or both. Babies so affected present with unexplained neonatal depression at birth, which correlates with high local anesthetic serum levels, and usually manifest seizures within 6 hours. Prompt use of supportive measures combined with forced urinary excretion of the local anesthetic has been used successfully to manage this complication.
Adverse Reactions: Characteristic of those associated with other ester-type local anesthetics. CNS stimulation followed by depression. Cardiac depression. Allergic skin rashes or urticaria may occur.
Dosage And Administration: For infiltration anesthesia: 0.25 or 0.5% solution, 350 to 600 mg is generally a safe total single dose. 15 mL of 2% solution diluted with 45 mL of sterile saline make up 60 mL of 0.5% solution (5 mg/mL). 0.5 mL to 1 mL of epinephrine 1:1 000 per 100 mL anesthesia solution may be added for vasoconstrictive effect (1:200 000 to 1:100 000).
Peripheral nerve block: 0.5% (up to 200 mL), 1% (up to 100 mL) or 2% solution (up to 50 mL) may be employed. Dilutions may be prepared by taking appropriate volumes of 2% solutions and saline as diluent (see infiltration anesthesia for dilution procedure). Use should usually be limited to cases requiring a small amount (200 to 500 mg) of anesthetic in solution. Epinephrine 1:1 000 (0.5 to 1 mL/100 mL) may be added for vasoconstrictive effect. The usual total dose should not exceed 1 000 mg.
Availability And Storage: Each mL of 2% solution contains: procaine HCl 20 mg in water for injection. Nonmedicinal ingredients: acetone, chlorobutanol anhydrous, sodium bisulfite and sodium chloride. Vials of 30 mL, boxes of 5.
NOVOCAIN® Sanofi Procaine HCl Local Anesthetic