Binding of local anesthetics to proteins is reduced in a fetus with asphyxia compared to a healthy fetus, and lidocaine becomes trapped as a result of tissue acidosis [ 24 ]. Local anesthetics must be used with caution for fetuses at high risk of asphyxia or with poor general conditions since they are likely to experience side effects from local anesthetics.
The severity of the effects of a local anesthetic on a fetus is determined by the amount of local anesthetic delivered across the placenta. The amount of local anesthetic delivered during local anesthesia is determined not only by the amount of local anesthetic administered, but also the method of administration, whether vasoconstrictors have been used, the metabolic rate and half-life of the local anesthetic in the mother, the extent of fetal and maternal protein binding, and the pKa acid dissociation constant of the local anesthetic [ 25 ].
Local anesthetics can be classified as two types: ester or amide. Ester-type local anesthetics are hydrolyzed by esterase in the plasma and have a shorter duration of action than the amide-types. Ester-types are rapidly hydrolyzed in the mother's plasma, and thus have few effects on the fetus. Allergic reactions caused by local anesthetics can pose a danger for both the mother and the fetus, and ester-types are more likely to induce these allergic reactions.
In comparison, the likelihood of amide-type local anesthetics inducing allergic reactions is very low. Amide-type local anesthetics, which are widely used clinically, exert different kinds of effects depending on their type. The amount of amide-type anesthetic delivered to a fetus is largely affected by the extent of maternal protein binding. Only free compounds that do not bind proteins are transferred to the fetus through the placenta.
Therefore, the fetal-to-maternal ratio of a local anesthetic is determined by the extent of protein binding of the local anesthetic. Among the amide types, bupivacaine is known to have the lowest fetal-to-maternal ratio [ 26 ].
Theoretically, bupivacaine should have the smallest effects on the fetus among all amide types. For this reason, bupivacaine is widely used as a local anesthetic in the field of obstetrics.
However, at toxic levels, bupivacaine inhibits cardiac conduction, which leads to cardiac arrest with low chances of survival. For this reason, high-concentration bupivacaine is currently not used to induce local anesthesia in dental treatment. Lidocaine is the most commonly used local anesthetic in a dental cartridge. The extent of protein binding of lidocaine is smaller than that of bupivacaine. The proportion of free lidocaine is relatively high, so the amount of lidocaine transferred from the mother to the fetus is also relatively high.
As a result, lidocaine has a relatively high fetal-to-maternal ratio [ 26 ]. Vasoconstrictors are added to lidocaine to reduce the absorption of the local anesthetic, reduce toxicity, and increase the analgesic effects.
Epinephrine is commonly added to lidocaine contained in a dental cartridge as a vasoconstrictor. Vasoconstriction induced by epinephrine delays the absorption of local anesthetics by the mother, allowing the absorption of lidocaine to gradually occur in the maternal systemic circulation, while also allowing blood levels of lidocaine to gradually increase. The local anesthetic is transferred to the fetus slowly, and its margin of safety is also increased.
Considering how local anesthetics have small direct effects on the fetus even at submaximal doses [ 27 ], lidocaine may be considered relatively safe for use in pregnant women. However, epinephrine can reduce blood flow within the uterus to an extent that is proportional to its dose and reduce uterine contractile force [ 28 ].
The Food and Drug Administration FDA has proposed a classification system that classifies drugs according to their risk [ 29 ] Table 1. Drugs under categories A and B are considered to pose no danger to humans.
Categories A and B differ by whether the drug has been tested in human subjects or not. Drugs whose teratogenic risk cannot be eliminated are classified under category C. Category D includes drugs with positive evidence of human fetal risk. Drugs in category X are not recommended for use by pregnant women. The FDA categories and maximal dose of local anesthetics are presented in Table 2 [ 26 , 30 ]. Toxic concentrations of local anesthetics are similar between the fetus and the mother, and the toxicity of drugs is equipotent in the fetus and the mother.
When using local anesthetics in pregnant women, the effects of the local anesthetics on the mother and the fetus must be considered, and the drug dose must be determined carefully. The mother and the fetus undergo different changes as pregnancy progresses. Following the implantation of a fertilized egg on the uterine wall, the fetus undergoes various stages of development as gestational age increases.
Organs develop in the early pregnancy period, and the formed organs and tissues undergo volumetric growth in the middle and late stages of pregnancy [ 31 ]. Therefore, an identical drug may have different effects on the fetus and the mother depending on gestational age. Understanding the difference in the potential effects of a maternally administered drug according to gestational age will allow local anesthetics to be safely used in dental treatments associated with pregnancy.
Starting from 1 month after fertilization, a closed neural tube, a beating heart, and blood cells form. The embryonic stage is the period until 10 weeks after implantation, and the first trimester is the period until 13 weeks after implantation.
During this period, the development of the most important structures is complete, limbs form, and the fetus starts to move. Important structures formed during this period undergo further growth throughout the pregnancy period, and the likelihood of an organ deformity developing after this period is relatively low.
A fetus may develop a birth defect when exposed to chemicals that can induce mutations in the process of cell growth and chromosome proliferation. Organogenesis is actively underway during weeks gestational age , so teratogenic effects may appear upon fetal exposure to drugs during this period.
Therefore, postponement of elective dental treatment until the end of the first trimester is generally recommended. The second trimester is the weeks 14 through 27 in terms of gestational age. The risk of the teratogenic effects of drugs is lower during this period than during the first trimester. Most dentists tend to be extremely careful about performing dental treatments even during this period [ 32 ]. However, elective dental treatment has been reported to be relatively safe during this period.
Moreover, as the extent of physiological changes that occur during the second trimester is not too considerable, anesthesia is safer to perform in pregnant women for non-obstetric surgery in the second trimester than in the first or third trimester [ 33 ].
However, starting from week 20 gestational age , the risk of hypotension in the supine position increases because of aortocaval compression. Aortocaval compression also decreases blood flow into the uterus and may negatively affect the fetus.
These risks must be considered when performing dental treatments in pregnant women during this pregnancy period.
In the third trimester, aortocaval compression in the supine position is even more likely to occur because of the enlarged uterus. By placing a cushion on one side of the back to support the lateral position, symptoms, including hypotension and light-headedness, that may occur when lying in the supine position can be alleviated.
Pregnancy itself can affect neurological function [ 34 ]. Furthermore, conduction blockade occurs at a significantly faster rate during pregnancy than when not pregnant [ 35 ]. This demonstrates that the effects of local anesthetics may present more prominently as gestational age increases. Use of local anesthetics at low doses may be possible for pregnant women in the third trimester and may reduce the expression of the toxic effects of local anesthetics.
Research on whether surgical procedures and anesthesia performed on the mother in preparation for non-obstetric treatments induce pregnancy complications and negatively affect the fetus is important for the safety of the fetus and the mother. Poor management of oral health of the mother is reported to increase the incidence of premature birth, geriatric diabetes, and preeclampsia [ 36 , 37 , 38 ]; for this reason, proper oral health management during pregnancy is an important issue.
The American Congress of Obstetricians and Gynecologists and the American Academy of Pediatrics strongly recommend pregnant women to undergo dental treatment [ 39 ].
However, research on whether dental treatment during pregnancy is associated with negative pregnancy outcomes or not is rare. In a study conducted between and that involved 60, pregnant women, administration of local anesthetics such as benzocaine, procaine, tetracaine, and lidocaine did not increase the incidence of complications in the fetus [ 27 ]. In a study on pregnant women who required periodontal and dental treatments, dental treatment was found not to increase the rates of negative fetal and pregnancy outcomes [ 32 ].
Hagai et al. These results provide no clear evidence that use of local anesthetics in pregnant women for routine dental treatment increases complication rates for the mother and the fetus. Therefore, dentists who are concerned [ 3 , 41 , 42 ] and reluctant [ 2 , 43 ] about performing dental treatments in pregnant women should change their perception about dental treatments in pregnant women and believe that women can undergo all necessary dental procedures during pregnancy. However, special care is needed in many cases.
When the dose of a local anesthetic exceeds the maximum permissible dose, toxic reactions may occur. Toxic effects of local anesthetics that are associated with the central nervous system, such as reduced consciousness and seizure, occur first.
Seizure during pregnancy is associated with increased rates of negative pregnancy complications. Following a seizure, catecholamine secretion is increased, and subsequently, blood flow into the placenta is reduced.
Systemic seizures can lead to tissue acidosis and hypoxia. Anticonvulsants used to treat seizures can be transferred to the fetus through the placenta and negatively affect the fetus. Therefore, when performing dental treatments in pregnant women, the doses of local anesthetics must be maintained below the maximal permissible dose while negative aspiration is monitored to make sure the local anesthetics are not injected in blood vessels. Some pregnant women may contract diseases that increase the risk of pregnancy in the second trimester, although most women may not.
Major examples of these diseases include preeclampsia and eclampsia. They develop starting at week 20 gestational age and are accompanied by hypertension and diabetes. The mother is diagnosed with eclampsia if she experiences a seizure. When the dilation of the blood vessels entering the uterus and, subsequently, placenta perfusion are reduced, complications, including premature birth, may develop.
Many pregnant women with hypertensive diseases have poor oral health and require dental treatment during pregnancy [ 44 , 45 ]. However, theoretically, rates of complications associated with the use of local anesthetics are high for these women. Protein binding of local anesthetics is reduced in pregnant women with preeclampsia or eclampsia; therefore, a large amount of local anesthetics can be transferred to the fetus. Moreover, epinephrine included in a dental cartridge can significantly contract the blood vessels inside the uterus and reduce the blood flow to the placenta.
Therefore, local anesthetics must be used with caution in pregnant women with geriatric hypertensive diseases. When local anesthetics are administered to pregnant women with fetal compromise resulting from reduced placenta perfusion, the amounts of local anesthetics not bound to proteins increase, tissue acidosis occurs, and the local anesthetics may get trapped in the fetus, causing complications.
Therefore, if the general condition of the fetus is poor because of the mother's pregnancy-related medical conditions, use of local anesthetics at doses that are commonly used may still have negative effects on the fetus. The types and doses of the local anesthetics for dental treatments must be carefully determined for high-risk pregnant women who are likely or are planning to undergo dental treatment during pregnancy.
When local anesthetics are administered to pregnant women during dental treatments, both the woman and her fetus become exposed to the local anesthetics. Therefore, the effects of local anesthetics on the mother and the fetus must be considered when planning dental treatments to improve the mother's oral health. Fortunately, lidocaine, which is the most commonly used local anesthetic during dental treatments, is under category B and considered to have almost no negative effect on the mother and the fetus.
In addition, the likelihood of the use of local anesthetics in dental treatments for pregnant women negatively affecting the women and their fetuses appears to be low. Therefore, pregnant women are reluctant to undergo and dentists reluctant to perform dental treatments when the oral health of the pregnant women has been compromised by physiological changes related to pregnancy; thus, delaying the needed dental treatment is not advisable.
However, as exposure to drugs in the first trimester has a high risk of teratogenic effects, dental treatment is advised only after the second trimester as long as it is a regular and not an emergency treatment.
In addition, pregnant women who have contracted medical conditions that can induce serious pregnancy-related complications are also more prone to experience side effects from local anesthetics even at commonly administered doses. Thus, the dose and type of the local anesthetic must be carefully determined for these women.
National Center for Biotechnology Information , U. J Dent Anesth Pain Med. Published online Jun Find articles by Ji Min Lee. Find articles by Teo Jeon Shin. Author information Article notes Copyright and License information Disclaimer.
Corresponding author. This article has been cited by other articles in PMC. Avoid getting this medication in your eyes. Avoid swallowing the gel, liquid, or ointment while applying it to your gums or the inside of your mouth. The throat spray or oral lozenge may be swallowed gradually during use. Use Orajel Benzocaine Topical exactly as directed on the label, or as prescribed by your doctor.
Do not use in larger or smaller amounts or for longer than recommended. Use exactly as directed on the label, or as prescribed by your doctor. Read all medication guides or instruction sheets. Your body may absorb more of this medicine if you use too much, if you apply it over large skin areas, or if you apply heat, bandages, or plastic wrap to treated skin areas.
Skin that is cut or irritated may also absorb more topical medication than healthy skin. Use the smallest amount needed to numb the skin or relieve pain. Do not use large amounts of benzocaine topical. Do not cover treated skin areas with a bandage or plastic wrap without medical advice.
Do not use benzocaine topical to treat large skin areas or deep puncture wounds. Avoid using the medicine on skin that is raw or blistered, such as a severe burn or abrasion. To treat minor skin conditions, apply a thin layer of benzocaine topical to the affected area. If using the spray, hold the container 6 to 12 inches away from the skin. Do not spray this medication onto your face. Spray it instead on your hands and then rub it onto the face, avoiding contact with your eyes.
Clean the area with soap and water before applying benzocaine topical. Wash your hands before and after inserting a rectal suppository. Remove the wrapper, but avoid handling the suppository too long or it will melt.
Lie on your back with your knees up toward your chest. Gently insert the suppository into your rectum about 1 inch, pointed tip first. Stay lying down for a few minutes while the suppository melts. You should feel little or no discomfort. Back Submit. Uses of Benzocaine Updated: November 25, Benzocaine Brand Names Back to Top.
Benzocaine Drug Class Back to Top. Benzocaine is part of the drug class: Anesthetics for topical use. Benzocaine Interactions Back to Top. Benzocaine and Pregnancy Back to Top. Tell your doctor if you are pregnant or plan to become pregnant. Benzocaine falls into category C: In animal studies, pregnant animals were given this medication and had some babies born with problems. OR There are no well-controlled studies that have been done in pregnant women.
OR No studies have been done in animals, and no well-controlled studies have been done in pregnant women. Benzocaine Dosage Back to Top. The Benzocaine dose your doctor recommends will be based on the following use any or all that apply : the condition being treated other medical conditions you have other medications you are taking how you respond to this medication your weight your height your age your gender.
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