a) Wash exposed skin with soap and water.

a) BUPIVACAINE: Ventricular tachycardia was reported in a pediatric patient 10 hours after starting a continuous epidural infusion of 0.25% bupivacaine (2.5 mg/kg/hr). Serum bupivacaine level was 5.6 mcg/mL (McCloskey et al, 1992).
b) BUPIVACAINE: Ventricular tachycardia occurred in an 11-month-old, 8 kg infant who received 8 mL (1 mL/kg) of 0.5% bupivacaine prior to undergoing a circumcision. Following administration of 20% intralipid at an IV bolus dose of 12 mL, followed by an infusion at a dose of 2 mL/min (0.25 mL/kg/min), the patient recovered uneventfully (Buck et al, 2014).
c) PRAMOXINE: A 4-year-old child experienced frequent premature supraventricular complexes several hours after ingesting 100 mL of a lotion containing pramoxine (Stancavage et al, 1995).
d) LIDOCAINE: Supraventricular tachycardia was reported in a 2-year-old after apparently aspirating and swallowing a small amount of 2% viscous lidocaine (Garrettson & McGee, 1992).
e) DIBUCAINE: Two toddlers (aged 18 months and 21 months) developed generalized tonic-clonic seizures and severe dysrhythmias (bradycardia, ventricular tachycardia, ventricular fibrillation, asystole) following ingestions (15 mg/kg to 19 mg/kg) of 1% dibucaine ointment. Despite aggressive supportive measures, both children died within hours after ingestion (Dayan et al, 1996).

a) LIDOCAINE: Sinus tachycardia and hypotension occurred (with tourniquet deflation) in a 28-year-old pregnant woman following intravenous regional anesthesia administration of lignocaine for hand surgery. The patient recovered following supportive care (Coleman & Kelly, 1998). In a similar case, a 35-year-old pregnant woman, undergoing hand surgery using a tourniquet technique, also developed sinus tachycardia and hypotension following intravenous regional anesthesia administration of lidocaine and after deflation of the tourniquet (Cooper & May, 2009).
b) LIDOCAINE: A 21-year-old man developed hypotension and severe bradycardia that rapidly progressed to asystole after gargling 20 mL of a 4% lidocaine solution (containing 800 mg of lidocaine) in preparation for an upper gastrointestinal endoscopy. Despite aggressive resuscitative measures, the patient subsequently died (Zuberi et al, 2000). Although the patient was advised not to swallow the solution, it is believed that some of the solution did enter the gastrointestinal tract, resulting in lidocaine toxicity.
c) MEPIVACAINE: Severe bradycardia (10 to 15 bpm), requiring implantation of a pacemaker, was reported in a 30-year-old woman, with a history of AV block with a mild mitral prolapse, who received 400 mg of mepivacaine paracervically during an in-vitro fertilization procedure. The patient recovered following the pacemaker implantation (Ayestaran et al, 2000).
d) LIDOCAINE: Cardiac arrest occurred after an adult woman was given a lidocaine block followed by a bupivacaine block in the axillary space to facilitate hand surgery (Long et al, 1989).
e) LIDOCAINE: Toxicity was seen in a 22-year-old man during daily use of 240 mL viscous lidocaine for a severe tongue ulcer. His serum lidocaine concentration was 6.7 mcg/mL (Yamashita et al, 2002).
f) ROPIVACAINE: A 25-year-old man developed isolated sinus tachycardia (130 beast per minute) and tonic-clonic seizures approximately 1 minute following unintentional intravascular administration of 10 mL (75 mg) of ropivacaine for a sciatic nerve block. The patient recovered following supportive therapy (Petitjeans et al, 2002). Plasma ropivacaine concentrations, obtained 15, 90, and 150 minutes after onset of symptoms, were 13.1, 11.6, and 3.6 mcmol/L, respectively.
g) LIDOCAINE: A 57-year-old man with progressive heart failure developed ventricular tachycardia that recurred despite treatment with amiodarone and cardioversion. He was administered IV lidocaine bolus, as well as overdrive pacing, and cardioversion, followed by a continuous lidocaine infusion, at an initial dose of 1 mg/min increasing to 2 mg/min due to recurrent episodes of ventricular tachycardia. The patient developed mental status changes and tremor. A lidocaine level, obtained due to suspected lidocaine toxicity, was 7.6 mcg/mL (therapeutic range 2 to 5 mcg/mL), and his lidocaine infusion was discontinued. Over the next several hours, the patient became increasingly somnolent and confused, and an ECG showed normal sinus rhythm with progressive QRS widening, with subsequent cardiac arrest. Aggressive resuscitative measures were initiated without significant clinical improvement in the patient. Approximately 55 minutes after beginning resuscitation, 20% lipid emulsion therapy was started, with a return of normal sinus rhythm and narrowing of the QRS complex 5 minutes later. Repeat lidocaine levels, obtained 25 minutes and 55 minutes after the lipid infusion, were 3.5 mcg/mL and 3 mcg/mL, respectively (Dix et al, 2011).
h) BUPIVACAINE: A 37-year-old man, undergoing shoulder surgery, developed bradycardia, seizures, and cardiac arrest immediately after receiving bupivacaine as a nerve block. Despite undergoing cardiopulmonary resuscitation for approximately 2 hours and being placed on cardiopulmonary bypass, the patient died approximately 7 hours post-injection. An autopsy revealed several cardiac abnormalities, including cardiomegaly, myocardial bridging, and lipomatous hypertrophy of the intra-atrial septum. Rash and laryngeal edema were also present. Post-mortem toxicology results revealed cardiac blood bupivacaine concentration of 1.1 mcg/mL and an elevated total serum tryptase concentration of 45.1 ng/mL in cardiac blood (reference range, less than 11.4 ng/mL). The abrupt onset of seizures and the elevated bupivacaine concentration suggest inadvertent intravascular injection instead of administration as a peripheral nerve block, although the elevated tryptase concentration and the presence of rash and laryngeal edema also suggest the possibility of bupivacaine hypersensitivity as a possible contributing factor (Dudley et al, 2011).

a) DIBUCAINE: An 18-month-old infant was unresponsive and developed cyanosis and intermittent generalized tonic-clonic seizures approximately 30 minutes after ingesting approximately 150 mg (12.5 mg/kg) of a sunburn ointment containing 1% dibucaine. An ECG revealed a wide-complex rhythm with frequent paroxysmal ventricular contractions. A repeat ECG approximately 1 hour postingestion demonstrated AV blockade with a prolonged QRS interval (200 msec) and a QTc interval of 513 msec. With supportive care, including sodium bicarbonate IV boluses and IV magnesium sulfate, the patient's cardiac status normalized with narrowing of the QRS complex, and subsequently a complete recovery without sequelae (Nelsen et al, 2009).
b) CASE REPORT/LIDOCAINE: A 15-year-old girl developed seizures after ingesting up to 2 grams (49 mg/kg) of viscous lidocaine. She was tachycardic (160 bpm) with a Glasgow Coma Scale of 3, and fixed and dilated pupils. An ECG revealed a QRS of 110 ms, that narrowed to 80 ms within 80 minutes after administration of IV fluids and IV sodium bicarbonate, and an arterial blood gas analysis indicated severe metabolic acidosis. A serum lidocaine concentration at 2 hours post-ingestion was 16.6 mcg/mL (reference range 1.2 to 5 mcg/mL) that decreased to 0.7 mcg/mL 6 hours post-ingestion. There was no evidence of epileptiform activity on an EEG, and a brain MRI showed hypoxic ischemic injury approximately 40 hours post-ingestion. The patient was apneic with no brainstem reflexes on hospital day 9, and brain death was subsequently declared (Drapkin et al, 2015).
c) ROPIVACAINE: A 5-week-old preterm infant, born at gestational age of 36 weeks and scheduled for inguinal hernia repair, inadvertently received ropivacaine at a dose of 10 mg/kg, injected into the caudal space. The total ropivacaine dose received was 40 mg instead of the prescribed 8 mg. Within minutes, the patient developed bradycardia (50 bpm), widening of QRS complexes, elevated T waves, and hypotension (50/30 mmHg). With external chest compressions, administration of IV fluids and epinephrine, and controlled ventilation and sedation, the patient recovered and was discharged home 2 days later without neurologic sequelae (Hubler et al, 2010).

a) CASE REPORT/ROPIVACAINE: Hypotension, refractory to IV ephedrine, occurred in a 26-year-old pregnant woman who inadvertently received epidural administration of ropivacaine, 111 mL/hour instead of 11 mL/hour (a 10-fold dosing error), during labor. The total dose of ropivacaine received during a 38-minute period was 140 mg. With supportive treatment including an infusion of phenylephrine, the patient recovered and, approximately 2 hours later, vaginally delivered a male infant with Apgar scores of 9 at 1 minute and at 5 minutes (Thyen et al, 2010).

a) LIDOCAINE: Hypotension was reported in a 2-year-old approximately 24 hours after apparently aspirating and swallowing a small amount of 2% viscous lidocaine (Garrettson & McGee, 1992).

a) BUPIVACAINE: Following the accidental administration of 337.5 mg bupivacaine and 180 mcg sufentanil epidurally in less than 30 minutes, a 62-year-old patient suffered severe hypotension and moderate bradycardia. No dysrhythmias occurred and the patient recovered (Wolff et al, 1992).
b) LIGNOCAINE: A pregnant 28-year-old patient received intravenous regional anesthesia (tourniquet technique) using lignocaine for hand surgery. Surgery was uneventful and, 45 minutes later, the tourniquet was deflated. Sixty seconds later, the patient developed hypotension and sinus tachycardia. Effects resolved following supportive care (Coleman & Kelly, 1998).
c) LIDOCAINE: Hypotension was reported in a 21-year-old man after gargling with 20 mL of a 4% lidocaine solution (containing 800 mg lidocaine) in preparation for an upper gastrointestinal endoscopy (Zuberi et al, 2000).
d) LIDOCAINE: A pregnant 35-year-old woman (at 25 weeks gestation) received intravenous regional anesthesia with lidocaine for hand surgery. Prior to lidocaine administration, a tourniquet was applied to the upper arm and inflated. Following lidocaine administration, the tourniquet was deflated in phases. Approximately 10 minutes following the final deflation, the patient developed hypotension, sinus tachycardia, tinnitus, and a metallic taste in her mouth. An ultrasound indicated that the fetal heart rate was normal. With supportive care, the patient recovered (Cooper & May, 2009).

a) BUPIVACAINE/LIDOCAINE: In a rat model, bupivacaine was 2 to 4 times more potent in inducing adverse cardiovascular effects than lidocaine (Thomas et al, 1986).

a) LIDOCAINE/INFANT: ARDS developed in a 2-year-old 2 days after apparently aspirating a small amount of 2% viscous lidocaine (Garrettson & McGee, 1992).

a) LIDOCAINE: Adult respiratory syndrome was reported following administration of less than 30 mL of 1% lidocaine solution for topical anesthesia prior to fiberoptic bronchoscopy (Promisloff & Dupont, 1983).
b) LIDOCAINE: Respiratory distress was reported in a 21-year-old man after gargling with 20 mL of a 4% lidocaine solution (containing 800 mg of lidocaine) in preparation for an upper gastrointestinal endoscopy (Zuberi et al, 2000).

a) ORAL ADMINISTRATION: Oral ingestion of 5 to 30 mL of a 2% to 4% viscous Xylocaine (lidocaine) solution has resulted in seizures in children (Smith et al, 1992; Hess & Walson, 1988; Mofenson et al, 1983)Bowman et al, 1982; (Rothstein et al, 1982; Sakai & Lattin, 1980) . Seizures are most common following repeated ingestion (instead of mucous application) of recommended or excessive amounts of the viscous Xylocaine preparations (Smith et al, 1992; Rothstein et al, 1982) .

a) Seizures may occur following intravenous administration (Selden & Burke, 1988; Edgren et al, 1986; Brown & Skiendzielowski, 1980) .

a) Seizures may occur (Malone et al, 1988).

a) BUPIVACAINE/CASE SERIES: Four cases of seizures with hypoxia and acidosis occurred following intercostal and epidural bupivacaine administration. Seizures occurred within 2 to 10 minutes of injection. The incidence of bupivacaine induced seizures following this procedure appears to be less than 0.2% (Moore et al, 1982a).
b) BUPIVACAINE/CASE REPORTS (CHILDREN): There are several reports of tonic-clonic seizures occurring in pediatric patients 10 to 56 hours after starting a continuous epidural infusion. Serum bupivacaine levels ranged from 5.4 to 10.2 mcg/mL (McCloskey et al, 1992).
c) ROPIVACAINE: Generalized seizures have occurred within minutes following accidental intravenous (during attempted epidural) ropivacaine administration in a child and in an adult. Both patients recovered without neurologic sequelae (Abouleish et al, 1998; Plowman et al, 1998).

a) LIDOCAINE/INFANT: A 7-week-old developed seizures 20 to 30 minutes after receiving 3 ml of 1% lidocaine (6.7 mg/kg) in a dorsal penile nerve block for a circumcision (Donald & Derbyshire, 2004).
b) LIDOCAINE/CHILD: Seizures have been reported following subcutaneous injection of 31 mg/kg of lidocaine in a 2-year-old child (Alfano et al, 1984).
c) BUPIVACAINE/ADOLESCENT: A 13-year-old girl developed generalized tonic-clonic seizures followed by ventricular fibrillation approximately 30 minutes after subcutaneous administration of bupivacaine (total dose 30 mg) for wound debridement. The patient recovered following supportive measures (Yan & Newman, 1998).

a) Seizures have also occurred following topical application of local anesthetics to burn patients (Wehner & Hamilton, 1984) or patients with multiple erosive skin lesions (Lie et al, 1990).
b) CASE REPORTS - PEDIATRIC

a) LIDOCAINE/CASE REPORT: An 80-year-old, previously seizure-free man experienced generalized tonic-clonic seizures after each of 2 intraurethral instillations of 20 mL of 2% lidocaine jelly (Sundaram, 1987).
b) LIDOCAINE/CASE REPORT: An 87-year-old man suffered cardiac arrest after intraurethral administration of lidocaine for cystourethroscopy (Chang et al, 2005).

a) INCIDENCE: Wulf et al (1991), in a survey of German hospitals, reported that 0.76 out of every 1000 stellate ganglion blocks resulted in seizures.
b) LIDOCAINE/CASE REPORT: Generalized seizures, cyanosis, and nystagmus occurred in 2 patients, a 28-year-old woman and a 51-year-old man while they were undergoing stellate ganglion blockade with 1% lidocaine injection (Mahli et al, 2002).

a) PROPARACAINE/CASE REPORT: A 28-year-old woman with a corneal abrasion was given 2 drops of proparacaine hydrochloride in the conjunctival sac and experienced a tonic-clonic seizure. She was not on any other medication, nor did she have a history of seizures. This appears to have been an unusual adverse effect of this medication (Cydulka & Betzelos, 1990).

a) BUPIVACAINE: Tonic-clonic seizures were reported in a pediatric patient 21 hours after starting a continuous intrapleural infusion (0.25 to 0.5 mg/kg/hr). Serum bupivacaine level was 5.6 mcg/mL (Agarwal et al, 1992).
b) LIDOCAINE/CASE REPORT: A 40-year-old woman experienced 3 to 4 episodes of generalized tonic-clonic seizures within minutes after intraureteral administration of diluted lidocaine jelly for ureteral stone manipulation (Pantuck et al, 1997).

a) Seizures have occasionally been described after overdose (Eledjam, 2000; Mardirosoff & Dumont, 2000) or with therapeutic doses (Bisschop et al, 2001) of ropivacaine.
b) CASE REPORT: A 25-year-old woman developed numbness of her lip, lost consciousness, and experienced a generalized seizure within 13 minutes of receiving a 300 mg dose injection (6.25 mg/kg) of ropivacaine as an axillary brachial plexus block for preparation of surgery on her finger. During the patient's seizure, her heart rate increased from 85 to 140 beats per minute, and her systolic blood pressure increased from 104 to 160 mmHg. The seizure spontaneously resolved after approximately 20 seconds and, during surgery, her heart rate and blood pressure normalized. Laboratory analysis of a blood sample, obtained 28 minutes postinjection, revealed a plasma ropivacaine concentration of 3.65 mcg/mL (Kimura et al, 2007).
c) CASE REPORT: A 25-year-old man developed isolated sinus tachycardia (130 beats per minute) and tonic-clonic seizures approximately 1 minute following unintentional intravascular administration of 10 mL (75 mg) of ropivacaine for a sciatic nerve block. The patient recovered following supportive therapy (Petitjeans et al, 2002). Plasma ropivacaine concentrations, obtained 15, 90, and 150 minutes after onset of symptoms, were 13.1, 11.6, and 3.6 mcmol/L, respectively.

a) LIDOCAINE: Signs may occur at total lidocaine serum concentrations of 3.5 to 5 mcg/mL.

a) ADULTS
b) PEDIATRIC

a) CASE REPORT: Two elderly, terminally ill cancer patients receiving lidocaine for palliative pain control developed severe somnolence following therapeutic doses (300 mg and 200 mg daily, respectively) with serum concentrations of more than 8.0 mcg/mL (therapeutic 1.5 to 5 mcg/mL). Both improved with drug withdrawal. Routine monitoring and modified dosing may be required in terminally ill patients (Tei et al, 2005).

a) CASE REPORT: A 28-year-old woman became unresponsive with flaccid extremities after receiving an accidental spinal injection (intended for the paracervical area) of a mixture containing Bupivacaine and triamcinolone. The patient gradually recovered without neurologic sequelae (Wang & Chang, 1993).

a) CASE REPORT: A 55-year-old man went almost immediately into a coma following inadvertent intraarterial injection of 26 mL 0.75% bupivacaine with epinephrine (5 mcg/mL) (Tuominen et al, 1991).

a) CASE REPORT/INFANT: An 18-month-old infant became comatose with a Glasgow Coma Scale score of 3 following ingestion of approximately 150 mg (12.5 mg/kg) of a sunburn ointment containing 1% dibucaine. The patient also experienced generalized tonic-clonic seizures and ECG abnormalities, including AV nodal blockade with widening of the QRS complex. With supportive care, the patient recovered without sequelae (Nelsen et al, 2009).

a) CASE REPORT: A 4-year-old boy ingested 100 mL of a lotion containing pramoxine and, several hours later, experienced vomiting, somnolence, dysrhythmias, tremulousness, hypertonia, and periods of unresponsiveness with tonic flexion of the extremities. The patient completely recovered 3 days after ingestion (Stancavage et al, 1995).

a) LIDOCAINE: Ataxia, dysarthria, dysmetria, involuntary movements, loss of balance, and transient aphasia have been reported rarely after use of topical lidocaine for endoscopic procedures. Signs and symptoms resolved within 2 to 5 hours (Perney et al, 2003).

a) PRAMOXINE: In a retrospective series of 177 poison center cases of ingestion of pramoxine-containing products, diarrhea developed in 2 patients and persisted for up to 4 hours (Spiller et al, 2006).

a) BENZOCAINE
b) LIDOCAINE
c) BUPIVACAINE/LIDOCAINE
d) CETACAINE
e) EMLA CREAM
f) PRILOCAINE
g) PROPITOCAINE
h) TETRACAINE

a) There are no adequate or well-controlled trials for the use of the combination oxymetazoline hydrochloride/tetracaine hydrochloride or the single agent tetracaine in pregnant women. However, limited data from epidemiologic studies of oxymetazoline used intranasally as a decongestant during pregnancy in humans did not show any associated teratogenicity (Prod Info KOVANAZE(TM) nasal spray, 2016).

a) There were no teratogenic effects in animals given subQ doses up to 1200 times the single dermal administration of 0.5 mg lidocaine in a 60 kg person (Prod Info Zingo(TM) intradermal injection powder, 2014).

a) In animal studies, structural abnormalities, including short forelimb digits, fused and irregular shaped arches in thoracic vertebrae, fused ribs, irregular number of ribs, and unossified forelimb phalanx, and reduced fetal weights were observed following the subQ administration of oxymetazoline to rats during organogenesis at a maternally toxic dose approximately 7.6 times the exposure from oxymetazoline at the maximum recommended human dose (MRHD) of the combination (Prod Info KOVANAZE(TM) nasal spray, 2016).

a) There are no adequate and well-controlled studies of bupivacaine liposome use in pregnant women. Bupivacaine rapidly crosses the placenta by passive diffusion, and the degree of plasma protein binding, ionization, and lipid solubility determine the rate and extent of diffusion. The fetal/maternal ratio is inversely related to the degree of plasma protein binding. Bupivacaine has a high protein binding capacity of 95% and a low fetal/maternal ratio of 0.2 to 0.4. Being lipid soluble and nonionized, bupivacaine rapidly diffuses to fetal blood from the maternal circulation (Prod Info EXPAREL(R) injection suspension, 2015).

a) There are no adequate or well-controlled trials for the use of the combination oxymetazoline hydrochloride/tetracaine hydrochloride or the single agent tetracaine in pregnant women (Prod Info KOVANAZE(TM) nasal spray, 2016).

a) LIDOCAINE: Similar toxicity has occurred with lidocaine (Bozynski et al, 1987; Selden & Burke, 1988).

a) The US Food and Drug Administration has recommended that 0.75% bupivacaine solutions not be used for obstetrical epidural anesthesia because there have been reports of cardiac arrest and death occurring with this concentration. As a result of this recommendation, the manufacturer has withdrawn the obstetric indications for bupivacaine 0.75% solution (Prod Info Marcaine(R), bupivacaine, 1991). However, this decision has been heavily criticized (Writer et al, 1984; Scott, 1984). It is felt that with proper use of bupivacaine 0.75% in obstetrics, toxic effects can be avoided.

a) Toxicity often appears around 15 minutes after birth, with the baby becoming suddenly apneic, hypotonic, and with fixed pupils and decreased reflexes.
b) Toxicity may occur with venous lidocaine levels as low as 3 mcg/mL. The usual lidocaine dose given for episiotomy is around 200 mg; this may result in a blood level of around 14 mcg/mL in the neonate.
c) Intravenous lidocaine overdose may result in immediate cardiorespiratory arrest (Brown & Skiendzielowski, 1980; Edgren et al, 1986; Selden & Burke, 1988). Complete maternal and fetal recovery has been reported despite prolonged cardiac arrest (Selden & Burke, 1988).

a) Bupivacaine crosses the placental barrier. Use during pregnancy only if the potential maternal benefit outweighs the potential fetal risk. Use of bupivacaine as obstetrical paracervical block anesthesia is contraindicated (Prod Info Sensorcaine(R)-MPF with Epinephrine parenteral injection, 2013; Prod Info Sensorcaine(R) with Epinephrine parenteral injection, 2013; Prod Info Sensorcaine(R)-MPF parenteral injection, 2013; Prod Info Sensorcaine(R) parenteral injection, 2013).

a) SubQ administration of bupivacaine hydrochloride in animals at doses comparable to the maximum recommended human dose (MRHD) resulted in an increase in embryofetal deaths. In postnatal development studies, decreased pup survival was reported at doses comparable to the MRHD (Prod Info Sensorcaine(R)-MPF with Epinephrine parenteral injection, 2013; Prod Info Sensorcaine(R) with Epinephrine parenteral injection, 2013; Prod Info Sensorcaine(R)-MPF parenteral injection, 2013; Prod Info Sensorcaine(R) parenteral injection, 2013).
b) SubQ doses of bupivacaine up to 1.6 times the maximum recommended human dose (MRHD) resulted maternal lethality, in a decrease in pup survival, and an increase in embryo-fetal deaths (Prod Info EXPAREL(R) injection suspension, 2015).

a) Lidocaine containing 1:100,000 epinephrine at a subQ dose of 120 times the single dermal administration caused temporary developmental delays in the neonate offspring of animals (Prod Info Zingo(TM) intradermal injection powder, 2014).

a) No evidence of altered postnatal development, viability, or reproductive capacity in any offspring was reported in rats administered up to 2.8 times the maximum recommended human dose of prilocaine on a mg/m(2) basis from gestation day 6 to weaning (Prod Info Oraqix(R) oral transmucosal gel, 2010).
b) In studies in which animals were treated with a lidocaine and prilocaine 1:1 mixture based on weight, there was no evidence of fetal harm at subQ doses of up to approximately equivalent to the maximum recommended human dose of lidocaine. Intramuscular prilocaine doses of up to approximately 11 times the maximum recommended human dose did not impair fertility or result in fetal harm. Similarly, approximately 1.5 times the maximum recommended human dose each of lidocaine and prilocaine administered subQ produced no teratogenic, embryotoxic, or fetotoxic effects (Prod Info Oraqix(R) oral transmucosal gel, 2010; Prod Info EMLA(R) cream, 2005).
c) In a study of animals treated with lidocaine 5 mg/kg subQ, fetal harm was not noted. When animals were treated with lidocaine 15 mg/kg, there was maternal toxicity and delayed fetal development, including a nonsignificant 7% decrease in fetal weight and an increase in minor skeletal anomalies (skull and sternebral defects, reduced ossification of the phalanges). In a study where animals were treated with lidocaine or prilocaine up to 1.4-fold the maximum recommended human dose for 8 months (3 mating periods), there was no abnormal postnatal development in any offspring. However, the average number of pups per litter surviving until weaning of offspring (from the first 2 mating periods) was significantly reduced with both doses of either drug (Prod Info Oraqix(R) oral transmucosal gel, 2010).

a) Lidocaine and tetracaine administered both individually and in combination in doses less than one-fold higher than the single dermal administration were not teratogenic in animals (Prod Info PLIAGLIS(R) topical cream, 2012; Prod Info Synera (TM) topical patch, 2005).

a) In animal studies, reduced implantation sites and live litter sizes were noted following subQ administration of oxymetazoline at approximately 1.5 times the MRHD and increased pup mortality at 6 times the MRHD in a prenatal and postnatal development study. SubQ administration of tetracaine hydrochloride to rats and rabbits during organogenesis at 32 and 6 times, respectively, the exposure from tetracaine hydrochloride at the MRHD of the combination did not result in adverse developmental effects (Prod Info KOVANAZE(TM) nasal spray, 2016)

a) The effect of bupivacaine on breastfed infants or breast milk production has not been studied (Prod Info EXPAREL(R) injection suspension, 2015).

a) It is unknown whether oxymetazoline, tetracaine, or their metabolites are excreted into human breast milk (Prod Info KOVANAZE(TM) nasal spray, 2016).

a) Bupivacaine is excreted into human breast milk. Discontinue bupivacaine or discontinue nursing taking into account the importance of the drug to the mother (Prod Info Sensorcaine(R)-MPF with Epinephrine parenteral injection, 2013; Prod Info Sensorcaine(R) with Epinephrine parenteral injection, 2013; Prod Info Sensorcaine(R)-MPF parenteral injection, 2013; Prod Info Sensorcaine(R) parenteral injection, 2013).
b) Bupivacaine and its metabolite (pipecolylxylidide) are present in breast milk at low levels. When deciding whether to continue treatment in a breastfeeding patient, consider the benefits of breastfeeding, the mother's need for bupivacaine, and the potential adverse effects on the infant (Prod Info EXPAREL(R) injection suspension, 2015).

a) Consider the developmental and health benefits of breastfeeding, along with the mother's clinical need for the drug, and potential adverse effects on the nursing infant from the combination agent or from the mother's underlying condition when administering the oxymetazoline hydrochloride/tetracaine hydrochloride combination to a lactating woman (Prod Info KOVANAZE(TM) nasal spray, 2016).

a) Local anesthetics are present in breast milk, but concentrations (roughly 40% of serum levels) would not be expected to produce detectable effects (Giuliani et al, 2001; Briggs et al, 1998; Zeisler et al, 1986).

a) In one study assessing the magnitude of excretion of lidocaine, bupivacaine, and PPX (a metabolite of bupivacaine) in the breast milk of 27 patients undergoing cesarean delivery, the milk/serum ratios based on AUC values were 1.07 +/- 0.82, 0.34 +/- 0.24, and 1.37 +/- 0.61, respectively. The majority of the infants appeared to be in good health and there were no adverse effects to the infants related to the local anesthetic agents (Ortega et al, 1999).

a) In one study assessing the magnitude of excretion of lidocaine, bupivacaine, and PPX (a metabolite of bupivacaine) in the breast milk of 27 patients undergoing cesarean delivery, the milk/serum ratios based on AUC values were 1.07 +/- 0.82, 0.34 +/- 0.24, and 1.37 +/- 0.61, respectively. The majority of the infants appeared to be in good health and there were no adverse effects to the infants related to the local anesthetic agents (Ortega et al, 1999).
b) A 34-year-old woman received 20 mg of lidocaine injection for dental surgery while breastfeeding. Samples of milk and plasma were tested for lidocaine and monoethylglycinexylidide by high performance liquid chromatography. Milk concentrations for the lidocaine ranged from 44 to 66 mcg/L, giving a milk/plasma ratio of 1.1. Milk concentrations for the metabolite monoethylglycinexylidide ranged from 35 to 41 mcg/L giving a milk/plasma ratio of 1.8. The infant levels for the parent drug and metabolite were estimated to be less than 0.01 mg/kg/day; these levels were not considered to be pharmacologically significant (Lebedevs et al, 1993).
c) Lidocaine is considered compatible with breastfeeding by the American Academy of Pediatrics. The majority of uses of lidocaine are acute, and although some lidocaine appears in breast milk after IV administration, the concentration is not considered to be pharmacologically significant. Any amount found in breast milk is further reduced by poor oral bioavailability to the breastfeeding infant (Gilman et al, 1990).

a) Lidocaine is excreted into human milk with a milk:plasma ratio of 0.4. It has not been determined if tetracaine is excreted into human milk. Lidocaine milk-plasma ratios have ranged from 1.07 using AUC values when used as epidural anesthetic for cesarean section (n=27) to 1.1 when measured 5 to 6 hours after a 20 mg single dose injection for a dental procedure. This translates into an estimated maximum daily lidocaine exposure via breast milk of 36 mcg/kg, which is deemed unlikely to cause adverse effects in a nursing infant (Prod Info PLIAGLIS(R) topical cream, 2012; Prod Info Synera (TM) topical patch, 2005)

a) Following subQ administration of the oxymetazoline hydrochloride/tetracaine hydrochloride combination during the period of organogenesis through parturition and subsequent pup weaning, detectable levels of oxymetazoline, tetracaine, and the major tetracaine metabolite, p-butylaminobenzoic acid (PBBA), were present in the milk of lactating rats. The concentrations of oxymetazoline were dose dependent, with 2.5, 7, and 33.8 ng/mL of oxymetazoline corresponding to doses of 0.6, 1.5, and 7.6 times, respectively, the oxymetazoline exposure at the maximum recommended human dose (MRHD) of the combination. The concentrations of tetracaine and PBBA were generally consistent across all tetracaine dosing groups receiving 12 times the exposure as measured by PBBA at the MRHD, regardless of the oxymetazoline dose, with tetracaine concentrations ranging from 54.2 to 72.9 ng/mL and PBBA concentrations 100.5 to 131.2 ng/mL. However, animal data does not accurately predict human results (Prod Info KOVANAZE(TM) nasal spray, 2016).

a) The effect of bupivacaine on fertility has not been studied (Prod Info EXPAREL(R) injection suspension, 2015).

a) Lidocaine delivered via continuous subcutaneous infusion or subcutaneous injection did not affect the overall fertility of male or female rats at doses up to 2-fold and less than one-fold higher, respectively, than the single dermal administration (based on a 1 g single dermal administration applied to 10 cm(2) for 60 minutes to a 60 kg person). Male rats, however, experienced dose-related decreases in daily sperm production, spermatogenic efficiency, and decreased homogenization-resistant sperm head count (Prod Info PLIAGLIS(R) topical cream, 2012).

a) In animal fertility studies, reduced percentage of mobile sperm and sperm counts were observed in rats administered subQ oxymetazoline hydrochloride at doses 2 times the oxymetazoline exposure at the maximum recommended human dose (MRHD) of the combination. No effect on male mating behavior were noted at any dose tested in this study. A reduction in the number of viable embryos occurred when female rats were administered oxymetazoline hydrochloride, alone or in combination with tetracycline hydrochloride, at doses equivalent to or greater than 0.7 times the MRHD. With oxymetazoline hydrochloride administration as monotherapy or in combination with tetracaine hydrochloride at doses 7.5 times the MRHD, the numbers of corpora lutea and implantation sites were reduced; however, when tetracaine hydrochloride was given alone, these effects were not observed. In fact, no effects on male or female fertility were observed following tetracaine hydrochloride administration to rats at doses 28 and 33 times the exposure for males and females, respectively, as measured by the major tetracaine metabolite, p-butylaminobenzoic acid, at the MRHD of the combination (Prod Info KOVANAZE(TM) nasal spray, 2016).

a) Subcutaneous administration of tetracaine to male and female rats, at doses less than one-fold higher than the single dermal administration, did not affect fertility (Prod Info PLIAGLIS(R) topical cream, 2012).

a) Monitor vital signs and electrolytes.

a) Obtain an ECG and institute continuous cardiac monitoring in symptomatic patients.

a) Monitor for respiratory depression, hypotension, dysrhythmias, and the need for endotracheal intubation.
b) Evaluate for hypoglycemia (or treat with intravenous dextrose ADULT: 100 mg IV, CHILD: 2 mL/kg 25% dextrose), electrolyte disturbances, and hypoxia.

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

a) Phenytoin may worsen or precipitate cardiac arrhythmias from local anesthetics and should be avoided (Wood, 1971).

a) Initial intravenous bolus of 1.5 mL/kg 20% lipid emulsion (eg, Intralipid) over 2 to 3 minutes. Asystolic patients or patients with pulseless electrical activity may have a repeat dose, if there is no response to the initial bolus.
b) Follow with an intravenous infusion of 0.25 mL/kg/min of 20% lipid emulsion (eg, Intralipid). Evaluate the patient's response after 3 minutes at this infusion rate. The infusion rate may be decreased to 0.025 mL/kg/min (ie, 1/10 the initial rate) in patients with a significant response. This recommendation has been proposed because of possible adverse effects from very high cumulative rates of lipid infusion. Monitor blood pressure, heart rate, and other hemodynamic parameters every 15 minutes during the infusion.
c) If there is an initial response to the bolus followed by the re-emergence of hemodynamic instability during the lowest-dose infusion, the infusion rate may be increased back to 0.25 mL/kg/min or, in severe cases, the bolus could be repeated. A maximum dose of 10 mL/kg has been recommended by some sources.
d) Where possible, LRT should be terminated after 1 hour or less, if the patient's clinical status permits. In cases where the patient's stability is dependent on continued lipid infusion, longer treatment may be appropriate.

a) In vitro studies have suggested that administration of a lipid emulsion infusion to treat toxicity of highly lipophilic drugs may create a 'lipid sink' where the lipophilic drug is removed from the tissues by partitioning into a plasma lipid phase that was created by the infusion. This is evidenced by an in vitro study that compared the effects of 1% lipid emulsion with a standard buffer after inducing asystole into isolated rats hearts following administration of bupivacaine. The rat hearts that received the lipid emulsion returned to spontaneous contractions more rapidly (average time to first heart beat 44.6 +/- 3.5 seconds vs 63.8 +/- 4.3 seconds in controls), with complete cardiac function. The lipid-treated hearts also showed a more rapid decline in the myocardial bupivacaine content (Leskiw & Weinberg, 2009; Weinberg, 2006; Weinberg et al, 2006).
b) However, lipid rescue performed in vivo, particularly with bupivacaine-induced cardiac toxicity, appears to occur more rapidly than could be explained with the in vitro method of extracting a highly lipophilic drug across several tissue diffusion barriers into equilibrium with a plasma phase, indicating that there may be other alternative mechanisms of action. One such mechanism involves reversal of mitochondrial fatty acid transport inhibition.

a) In a systemic review of the effect of ILE therapy for local anesthetic toxicity, it was determined that ILE was effective in reversing cardiovascular or neurological features in some patients with local anesthetic overdose; however, the information was limited from very low quality studies (n=113; 76 human studies, including 2 randomized control trials and 74 case reports or case series; 38 animal studies, including 29 randomized control studies, 3 observational studies, and 6 case reports or case series) and the authors could not determine if ILE therapy was more effective than vasopressors (Hoegberg et al, 2016).

a) Propofol (which contains 10% lipids) should not be used in local anesthetic-induced cardiac toxicity. The large doses necessary for lipid rescue would actually result in propofol overdoses. In addition, propofol can lower blood pressure and is considered a mitochondrial poison (Felice & Schumann, 2008; Weinberg, 2006).

a) ELDERLY
b) ADULT
c) ADOLESCENT
d) PEDIATRIC
e) PREGNANT

a) In a dog model of severe bupivacaine overdose, cardiovascular collapse occurred following a single 10 mg/kg IV bolus of bupivacaine. Three of 9 dogs were treated immediately with infusion of a 20% lipid emulsion and cardiac massage, while in 6 the infusion of 20% lipid emulsion was begun 10 minutes after cardiovascular collapse. Normal hemodynamics returned in all 9 dogs, without electrical cardioversion. The authors' recommended dose to treat bupivacaine-associated cardiac arrest was 1 mL/kg intravenous injection of 20% lipid emulsion as a bolus, followed by an infusion of 0.25 mL/kg/min for 10 minutes, while continuing life support measures. Bolus may be repeated every 5 minutes, for two to three doses. Patients require monitoring to avoid volume overload (Weinberg et al, 2004).
b) Using a rat model, a study was conducted to evaluate the use of epinephrine with lipid infusion on the recovery from bupivacaine overdose. Following receipt of an IV bolus dose of bupivacaine 20 mg/kg, rats received one of six treatments (n=5 for all groups): saline, saline bolus plus 30% lipid emulsion (control), or 30% lipid emulsion plus epinephrine at 1 mcg/kg, 2.5 mcg/kg, 10 mcg/kg, or 25 mcg/kg. Initially, the addition of epinephrine resulted in a rapid return of spontaneous circulation in all animals within 5 minutes at epinephrine doses of 2.5 mcg/kg and greater; however, only 3 of the 5 rats at 10 mcg/kg, and 1 of the 5 rats at 25 mcg/kg achieved a sustained return of spontaneous circulation by 15 minutes. In contrast, the lipid control group resulted in a slower but more sustained recovery, with all animals achieving sustained return of spontaneous circulation at 10 and 15 minutes. In addition to a poor recovery at 15 minutes as compared with the lipid control, epinephrine administration at doses of 10 mcg/kg or greater resulted in increased lactate levels and worsening acidosis (Hiller et al, 2009).

a) Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (ie, dyspnea, headache, fatigue, CNS depression, tachycardia, metabolic acidosis). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin concentrations above 20% to 30%, but may occur at lower methemoglobin concentrations in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy.

a) INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules (Prod Info PROVAYBLUE(TM) intravenous injection, 2016) and 10 mg/1 mL (1% solution) vials (Prod Info methylene blue 1% intravenous injection, 2011). REPEAT DOSES: Additional doses may be required, especially for substances with prolonged absorption, slow elimination, or those that form metabolites that produce methemoglobin. NOTE: Large doses of methylene blue may cause methemoglobinemia or hemolysis (Howland, 2006). Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection (Prod Info methylene blue 1% intravenous injection, 2011; Herman et al, 1999). NEONATES: DOSE: 0.3 to 1 mg/kg (Hjelt et al, 1995).
b) CONTRAINDICATIONS: G-6-PD deficiency (methylene blue may cause hemolysis), known hypersensitivity to methylene blue, methemoglobin reductase deficiency (Shepherd & Keyes, 2004)
c) FAILURE: Failure of methylene blue therapy suggests: inadequate dose of methylene blue, inadequate decontamination, NADPH dependent methemoglobin reductase deficiency, hemoglobin M disease, sulfhemoglobinemia, or G-6-PD deficiency. Methylene blue is reduced by methemoglobin reductase and nicotinamide adenosine dinucleotide phosphate (NADPH) to leukomethylene blue. This in turn reduces methemoglobin. Red blood cells of patients with G-6-PD deficiency do not produce enough NADPH to convert methylene blue to leukomethylene blue (do Nascimento et al, 2008).
d) DRUG INTERACTION: Concomitant use of methylene blue with serotonergic drugs, including serotonin reuptake inhibitors (SRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), triptans, and ergot alkaloids may increase the risk of potentially fatal serotonin syndrome (U.S. Food and Drug Administration, 2011; Stanford et al, 2010; Prod Info methylene blue 1% IV injection, 2011).

a) DOSE: 2 to 4 mg/kg intravenously over 5 minutes. Dose may be repeated in 30 minutes (Nemec, 2011; Lindenmann et al, 2006; Kiese et al, 1972).
b) SIDE EFFECTS: Hypotension with rapid intravenous administration. Vomiting, diarrhea, excessive sweating, hypotension, dysrhythmias, hemolysis, agranulocytosis and acute renal insufficiency after overdose (Dunipace et al, 1992; Hix & Wilson, 1987; Winek et al, 1969; Teunis et al, 1970; Marquez & Todd, 1959).
c) CONTRAINDICATIONS: G-6-PD deficiency; may cause hemolysis.

a) If symptomatic and heart rate is less than 60, consider administration of atropine.
b) ATROPINE/DOSE

a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).

a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
b) DOSE

a) Bupivacaine: 2 mg/kg
b) Chloroprocaine: 10 mg/kg
c) Etidocaine: 4 mg/kg
d) Lidocaine: 5 mg/kg
e) Mepivacaine: 5 mg/kg
f) Prilocaine: 8 mg/kg
g) Procaine: 10 mg/kg
h) Ropivacaine: 3 mg/kg
i) Tetracaine: 3 mg/kg

a) MAXIMUM SINGLE DOSE
b) CONTINUOUS EPIDURAL INFUSION
c) MAXIMUM DAILY DOSE

a) BUNIONECTOMY: The recommended dose is 106 mg (8 mL) injected slowly by infiltration into the tissues surrounding the osteotomy (7 mL) and into the subcutaneous tissue (1 mL). MAXIMUM DOSE: 266 mg (20 mL (13.3 mg/mL) undiluted suspension) (Prod Info EXPAREL(TM) injection suspension, 2011).
b) HEMORRHOIDECTOMY: The recommended dose is 266 mg (20 mL) diluted with 10 mL saline (total 30 mL), divided into 6 5-mL aliquots, with each aliquot injected slowly by infiltration into the tissues. MAXIMUM DOSE: 266 mg (20 mL (13.3 mg/mL) undiluted suspension) (Prod Info EXPAREL(TM) injection suspension, 2011).
c) NOTE: Bupivacaine liposome is NOT bioequivalent with other formulations of bupivacaine even if the mg dosage is the same. Dosing cannot be converted from one formulation to another and different formulations should not be substituted for one another (Prod Info EXPAREL(TM) injection suspension, 2011).

a) Available as 0.5% and 1% ointment
b) SPINAL ANESTHESIA: 2.5 to 10 mg
c) MAXIMAL DAILY DOSE: 100 mg (Egfjord et al, 1988)

a) THERAPEUTIC DOSE (Adults and children over 2): 1 to 3 mg orally every 2 hours as needed; MOUTHRINSE: 0.5% solution as a rinse or swab for relief of discomfort associated with painful oral lesions or ulcerations or as a swallow (5 to 15 mL) for pain relief associated with esophageal lesions (Prod Info Sucrets(R) Maximum Strength Sore Throat Lozenges, 1996; Prod Info Dyclone(R), dyclonine topical solution 0.5%, 1997).
b) MAXIMAL SINGLE DOSE: 200 mg (S Sweetman , 2001)

a) INFILTRATION/NERVE BLOCK: 300 mg without epinephrine; 400 mg with epinephrine (Prod Info Duranest(R) injection, etidocaine, 1997)
b) CAUDAL EPIDURAL BLOCK: up to 300 mg (Prod Info Duranest(R) injection, etidocaine, 1997)

a) MAXIMUM DOSE
b) TOPICAL DOSE

a) SUPERFICIAL DERMATOLOGICAL PROCEDURES: Apply sufficient amount of topical cream to cover treated area (1 to 53 g; 3 to 121 cm) to a thickness of 1 mm; based on procedure, wait 20 to 60 minutes and remove pliable peel from skin (Prod Info PLIAGLIS(R) topical cream, 2012).

a) MAXIMUM SINGLE DOSE
b) TOTAL DAILY DOSE

a) A 0.4% solution is used for topical ophthalmic application (S Sweetman , 2001).

a) Pramoxine cream for hemorrhoids should be applied up to 5 times daily, usually after bowel movements, morning and night. The cream may be instilled in the rectum via an applicator or externally applied to the affected area (Prod Info Anusol(R), 1999; Prod Info Tronolane(R), 1996). The aerosol foam may be rectally administered as 1 applicatorful 3 or 4 times daily and after bowel evacuation. Aerosol containers must not be inserted into the rectum (Prod Info Proctofoam(R), 1990).

a) DENTAL INFILTRATION/NERVE BLOCK: Usual adult dose of prilocaine without felypressin (a vasoconstrictor) is 40 to 80 mg. The adult dose of prilocaine with felypressin (0.03 units/mL) is 30 to 150 mg (1 to 5 mL) as a 3% solution (S Sweetman , 2001).

a) INFILTRATION ANESTHESIA: 0.25% to 0.5% solutions of procaine hydrochloride have been used in doses of 350 to 600 mg (S Sweetman , 2001).
b) PERIPHERAL NERVE BLOCK: 500 mg is the usual dose, but doses up to 1 gram have been given (S Sweetman , 2001).

a) Used as a 0.5% solution for topical anesthesia of the eye (S Sweetman , 2001).

a) Used as a 0.4% solution in combination with 2% procaine (S Sweetman , 2001).

a) Available as 0.5% and 1% solutions and ointments for mucosal and ophthalmic use (S Sweetman , 2001).
b) PROLONGED SPINAL ANESTHESIA

a) INTRANASAL: 2 sprays ipsilateral (on the same side) to the maxillary tooth where the dental procedure will be performed 4 to 5 minutes apart; initiate dental procedure 10 minutes following second spray; if a test drill 10 minutes after administration of a second initial spray does not provide adequate anesthesia, may give 1 additional spray (Prod Info KOVANAZE(TM) nasal spray, 2016)

a) CONTINUOUS EPIDURAL INFUSION: A bupivacaine dose of 0.5 mL/kg of 0.25% without epinephrine prior to surgery, followed in 30 minutes by an infusion of 0.08 mL/kg/hour was reported effective and safe for postoperative pain relief in children following major lower extremity and genitourinary surgery (Desparmet et al, 1987).
b) CAUDAL ANALGESIA: A dose of 3 mg/kg of 0.25% bupivacaine was effective in producing caudal epidural analgesia in 45 children (Eyres et al, 1983).

a) Safety and effectiveness in pediatric patients below 18 years of age have not been established (Prod Info EXPAREL(TM) injection suspension, 2011).

a) THERAPEUTIC DOSE (Adults and children over 2): 1 to 3 mg orally every 2 hours as needed (Prod Info Sucrets(R) Maximum Strength Sore Throat Lozenges, 1996).

a) IV
b) INTRADERMAL
c) ORAL
d) TOPICAL

a) Less than 3 months of age or less than 5 kg: applied to maximum application area of 10 cm(2) for maximum application time of 1 hour; Maximum total dose of 1 g (Prod Info EMLA(R) topical cream, 2006)
b) 3 months to less than 12 months of age and greater than 5 kg: applied to maximum application area of 20 cm(2) for maximum application time of 4 hours; Maximum total dose of 2 g (Prod Info EMLA(R) topical cream, 2006)
c) 1 to 6 years of age and greater than 10 kg: applied to maximum application area of 100 cm(2) for maximum application time of 4 hours; Maximum total dose of 10 g (Prod Info EMLA(R) topical cream, 2006).
d) 7 to 12 years of age and greater than 20 kg: applied to maximum application area of 200 cm(2) for maximum application time of 4 hours; Maximum total dose of 20 g (Prod Info EMLA(R) topical cream, 2006).

a) Safety and effectiveness of the topical cream have not been established in pediatric patients (Prod Info PLIAGLIS(R) topical cream, 2012).

a) MAXIMUM SINGLE DOSE: Should not exceed 5 to 6 mg/kg in children. In children less than 3 years of age or 30 pounds, the concentration should be less than 2% (Prod Info Carbocaine(R), mepivacaine HCL, 1987a).

a) INTRANASAL (WEIGHING 40 KG OR MORE): 2 sprays ipsilateral (on the same side) to the maxillary tooth where the dental procedure will be performed 4 to 5 minutes apart; initiate dental procedure 10 minutes following second spray (Prod Info KOVANAZE(TM) nasal spray, 2016)

1) An accidental injection of a 1 gram bolus of lidocaine intravenously resulted in asystole apnea and multiple grand mal seizures which responded to intravenous epinephrine, isoproterenol, dopamine and diazepam (Finkelstein & Kreeft, 1979).
2) There have been over 5 case reports of lidocaine overdose in which a 800 to 2000 mg intravenous bolus of lidocaine was mistakenly injected when a lower dose was ordered. There was confusion over the two types of prepackaged syringes (100 mg and 1000 to 2000 mg). In all five patients seizures occurred and cardiopulmonary arrest. Three survived (Bryant et al, 1983).
3) Unresponsiveness, respiratory arrest, marked vasodilation, seizures, and hypotension occurred in an infant following accidental intravenous administration of 12 mg/kg of lidocaine. Recovery was complete with supportive care (Jonville et al, 1990).

1) Ingestion of 5 to 25 milliliters of a 2% viscous Xylocaine (lidocaine) solution has resulted in seizures in children (Sakai & Lattin, 1980; Rothstein et al, 1982).
2) Of 28 cases of lidocaine (lignocaine) ingestion in pediatric patients (mean ingested dose was 2.7 mg/kg), only two patients developed adverse effects. The first patient was an 8-month-old boy who developed agitation, increased salivation, and difficulty with solid food after ingesting a total lidocaine dose of 4.1 mg/kg and 0.1 mg/kg of chlorhexidine. The other patient was a 7-month-old girl who vomited twice within 30 minutes after ingesting a total lidocaine dose of 3.3 mg/kg and 0.08 mg/kg of chlorhexidine. The highest lidocaine dose ingested, within the 28 cases, was 5.9 mg/kg, indicating that doses under 6 mg/kg are unlikely to cause serious adverse effects and can be managed at home (Balit et al, 2006).

1) Infants less than 1 square meter in body surface area were more likely to develop elevated serum lidocaine concentrations following subcutaneous infiltration prior to cardiac catheterization in a study of 10 children (Palmisano et al, 1991).
2) CASE REPORT: A 37-year-old woman experienced agitation, aggressiveness, and a sensation of a near-death experience following infiltration of 0.1% lidocaine subcutaneously in her abdomen prior to liposuction. Total lidocaine dose was 1 g (13 mg/kg). Laboratory data revealed a lidocaine concentration of 9.7 mcg/mL (therapeutic, 1 to 5 mcg/mL). Following supportive therapy, the patient recovered and was discharged the next day without sequelae (Hines et al, 2015).

1) Delayed hypotension and tachycardia with cardiovascular collapse and adult respiratory syndrome has been reported following the administration of less than 30 milliliters of 1% lidocaine solution for topical anesthesia prior to fiberoptic bronchoscopy (Promisloff & Dupont, 1983).
2) An 11-month-old male infant developed seizures and a plasma lidocaine concentration of 10 micrograms/milliliter, following the application of 2% viscous lidocaine to his gums 5 to 6 times daily for a week (Mofenson et al, 1983).

a) BUPIVACAINE
b) DIBUCAINE
c) ETIDOCAINE
d) LIDOCAINE
e) LIGNOCAINE
f) MEPIVACAINE
g) PROCAINE
h) ROPIVACAINE

a) SEIZURES/LARGE ANIMALS: May be controlled with diazepam.
b) SEIZURES/DOGS & CATS:

a) SUMMARY
b) Treatment should always be done on the advice and with the consultation of a veterinarian.
c) Additional information regarding treatment of poisoned animals may be obtained from a Veterinary Toxicologist or the National Animal Poison Control Center.
d) ASPCA ANIMAL POISON CONTROL CENTER