Sensorcaine -MPF

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 fibers. Clinically, the order of loss of nerve function is as follows: (1) pain, (2) temperature, (3) touch, (4) proprioception, and (5) skeletal muscle tone.

Systemic absorption of local anesthetics produces effects on the cardiovascular and central nervous systems (CNS).  At blood concentrations achieved with normal therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance are minimal.  However, toxic blood concentrations depress cardiac conduction and excitability, which may lead to atrioventricular block, ventricular arrhythmias and cardiac arrest, sometimes resulting in fatalities.  In addition, myocardial contractility is depressed and peripheral vasodilation occurs, leading to decreased cardiac output and arterial blood pressure.  Recent clinical reports and animal research suggest that these cardiovascular changes are more likely to occur after unintended intravascular injection of bupivacaine.  Therefore, incremental dosing is necessary.

Following systemic absorption, local anesthetics can produce central nervous system stimulation, depression, or both.  Apparent central stimulation is manifested as restlessness, tremors and shivering progressing to convulsions, followed by depression and coma progressing ultimately to respiratory arrest.  However, the local anesthetics have a primary depressant effect on the medulla and on higher centers.  The depressed stage may occur without a prior excited state.

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 mcg/mL) usually reduces the rate of absorption and peak plasma concentration of bupivacaine, permitting the use of moderately larger total doses and sometimes prolonging the duration of action.

The onset of action with bupivacaine is rapid and anesthesia is long lasting.  The duration of anesthesia is significantly longer with bupivacaine than with any other commonly used local anesthetic.  It has also been noted that there is a period of analgesia that persists after the return of sensation, during which time the need for strong analgesics is reduced.

The onset of action following dental injections is usually 2 to 10 minutes and anesthesia may last two or three times longer than lidocaine and mepivacaine for dental use, in many patients up to 7 hours.  The duration of anesthetic effect is prolonged by the addition of epinephrine 1:200,000.

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 proteins.

Local anesthetics appear to cross the placenta by passive diffusion.  The rate and degree of diffusion is governed by (1) the degree of plasma protein binding, (2) the degree of ionization, and (3) 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.  Bupivacaine with a high protein binding capacity (95%) has a low fetal/maternal ratio (0.2 to 0.4).  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.

Pharmacokinetic studies on the plasma profile of bupivacaine after direct intravenous injection suggest a three-compartment open model.  The first compartment is represented by the rapid intravascular distribution of the drug.  The second compartment represents the equilibration of the drug throughout the highly perfused organs such as the brain, myocardium, lungs, kidneys, and liver.  The third compartment represents an equilibration of the drug with poorly perfused tissues, such as muscle and fat.  The elimination of drug from tissue distribution depends largely upon the ability of binding sites in the circulation to carry it to the liver where it is metabolized.

After injection of Sensorcaine (bupivacaine HCl) for caudal, epidural, or peripheral nerve block in man, peak levels of bupivacaine in the blood are reached in 30 to 45 minutes, followed by a decline to insignificant levels during the next 3 to 6 hours.

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 half-life of bupivacaine in adults is 2.7 hours and in neonates 8.1 hours.

In clinical studies, elderly patients reached the maximal spread of analgesia and maximal motor blockade more rapidly than younger patients.  Elderly patients also exhibited higher peak plasma concentrations following administration of this product.  The total plasma clearance was decreased in these patients.

Amide-type local anesthetics such as bupivacaine are metabolized primarily in the liver via conjugation with glucuronic acid.  Patients with hepatic disease, especially those with severe hepatic disease, may be more susceptible to the potential toxicities of the amide-type local anesthetics. Pipecoloxylidine is the major metabolite of bupivacaine.

The kidney is the main excretory organ for most local anesthetics and their metabolites.  Urinary excretion is affected by urinary perfusion and factors affecting urinary pH.  Only 6% of bupivacaine is excreted unchanged in the urine.

When administered in recommended doses and concentrations, Sensorcaine (bupivacaine HCl) does not ordinarily produce irritation or tissue damage and does not cause methemoglobinemia.

Acute emergencies from local anesthetics are generally related to high plasma levels encountered during therapeutic use of local anesthetics or to unintended subarachnoid injection of local anesthetic solution (see ADVERSEREACTIONS, WARNINGS, and PRECAUTIONS).

Management of Local Anesthetic Emergencies
The first consideration is prevention, best accomplished by careful and constant monitoring of cardiovascular and respiratory vital signs and the patient’s state of consciousness after each local anesthetic injection. At the first sign of change, oxygen should be administered.

The first step in the management of systemic toxic reactions, as well as underventilation or apnea due to unintentional subarachnoid injection of drug solution, consists of immediate attention to the establishment and maintenance of a patent airway and effective assisted or controlled ventilation with 100% oxygen with a delivery system capable of permitting immediate positive airway pressure by mask. This may prevent convulsions if they have not already occurred.

If necessary, use drugs to control the convulsions. A 50 mg to 100 mg bolus IV injection of succinylcholine will paralyze the patient without depressing the central nervous or cardiovascular systems and facilitate ventilation. A bolus IV dose of 5 mg to 10 mg of diazepam or 50 mg to 100 mg of thiopental will permit ventilation and counteract central nervous system stimulation, but these drugs also depress central nervous system, respiratory, and cardiac function, add to postictal depression and may result in apnea. Intravenous barbiturates, anticonvulsant agents, or muscle relaxants should only be administered by those familiar with their use. Immediately after the institution of these ventilatory measures, the adequacy of the circulation should be evaluated. Supportive treatment of circulatory depression may require administration of intravenous fluids, and when appropriate, a vasopressor dictated by the clinical situation (such as ephedrine or epinephrine to enhance myocardial contractile force).

Endotracheal intubation, employing drugs and techniques familiar to the clinician, may be indicated after initial administration of oxygen by mask if difficulty is encountered in the maintenance of a patent airway, or if prolonged ventilatory support (assisted or controlled) is indicated.

Recent clinical data from patients experiencing local anesthetic-induced convulsions demonstrated rapid development of hypoxia, hypercarbia, and acidosis with bupivacaine within a minute of the onset of convulsions. These observations suggest that oxygen consumption and carbon dioxide production are greatly increased during local anesthetic convulsions and emphasize the importance of immediate and effective ventilation with oxygen which may avoid cardiac arrest.

If not treated immediately, convulsions with simultaneous hypoxia, hypercarbia, and acidosis plus myocardial depression from the direct effects of the local anesthetic may result in cardiac arrhythmias, bradycardia, asystole, ventricular fibrillation, or cardiac arrest. Respiratory abnormalities, including apnea, may occur. Underventilation or apnea due to unintentional subarachnoid injection of local anesthetic solution may produce these same signs and also lead to cardiac arrest if ventilatory support is not instituted. If cardiac arrest should occur, successful outcome may require prolonged resuscitative efforts.

The supine position is dangerous in pregnant women at term because of aortocaval compression by the gravid uterus. Therefore during treatment of systemic toxicity, maternal hypotension or fetal bradycardia following regional block, the parturient should be maintained in the left lateral decubitus position if possible, or manual displacement of the uterus off the great vessels should be accomplished.

The mean seizure dosage of bupivacaine in rhesus monkeys was found to be 4.4 mg/kg with mean arterial plasma concentration of 4.5 mcg/mL. The intravenous and subcutaneous LD50 in mice is 6 mg/kg to 8 mg/kg and 38 mg/kg to 54 mg/kg respectively.

• If you have an allergy to bupivacaine or any other part of Sensorcaine-MPF (bupivacaine).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Bleeding, a heartbeat that is not normal, an infection in the blood or where this medicine will be given, or low blood pressure.
• If your child is younger than 12 years of age. Do not give Sensorcaine-MPF to a child younger than 12 years of age.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Sensorcaine-MPF with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

For all uses of this medicine:

• Tell all of your health care providers that you take Sensorcaine-MPF. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how this medicine affects you.
• If you are 65 or older, use Sensorcaine-MPF with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Mouth:

• Do not eat while your mouth feels numb. You may bite your tongue.

Spinal:

• This medicine may cause short-term loss of feeling and motor activity in the lower half of your body. Do not try to get out of bed or do other tasks or actions until feeling and motor activity have returned to normal.