In: Anesthesia8 Dec 2009
Although plasma levels of local anesthetic are usually low in adults, plasma concentrations can be an important concern in the delivery of local anesthetics to children. The dose as a proportion of total body weight in the adult is relatively small, and thus the chance of local anesthetic toxicity is low. However, in children, particularly when premedicated with sedative drugs, the systemic effects of local anesthetic can be toxic. Therefore, it is important to determine the plasma levels of lidocaine from all sources, including the transoral lidocaine patch.
Initial symptoms of CNS toxicity, such as lightheadedness and visual and auditory disturbances, begin at approximately 5 |xg/mL. Higher plasma concentrations of 10-12 |xg/mL produce unconsciousness, convulsions, and coma. If the maximum recommended dose of 4.4 mg/kg is used, toxicity is rare. However, several factors, compromised liver function for example, can result in lidocaine toxicity being reached at normally safe dosages. Also, because of variability among individual patients, plasma levels could be significantly higher than the mean value. For example, in this study, we recorded a peak plasma lidocaine concentration of 128 ng/mL (compared with a mean value of 82 ng/mL).
Results indicated that lidocaine absorbed from a 5-minute application of a single 20% lidocaine (46.1 mg) transoral patch did not reach toxic plasma concentrations in children. This is consistent with studies measuring plasma lidocaine concentrations after lidocaine patch application in adults. In addition, our results indicated plasma levels much lower than those reported in studies evaluating plasma lidocaine concentrations in adults after topical application with an 2% oral lidocaine rinse and considerably lower than concentrations reached after topical spray in the pharynx before intubation in children.
Although data from our pediatric subjects show mean plasma lidocaine concentrations well below toxic levels, our results did indicate that the mean peak plasma concentration in children was 4 to 5 times higher than the mean peak concentration found in adult patients (82 vs 16.5-22.3 ng/mL). Studies conducted on adults by Noven Pharmaceuticals found the peak lidocaine concentration to be 16.5 ng/mL after a 15-minute application. Houpt and coworkers found the mean lidocaine plasma concentration in adults to be 22.3 ng/mL 15 minutes after patch application. Also of interest is the mean time at which peak concentration was attained in children and adults. In children, the mean time at which peak concentration was achieved was approximately the same as that in adults (approximately 15 minutes after patch application); this was most likely because of our shorter application time (5 vs 15 minutes). This suggests that a 15-minute application in children would have produced a peak concentration at an earlier time than that observed in adults. erectalis 20 mg
Several factors may explain the increased concentration of lidocaine we found in children compared with adults. The most likely explanation is that of the smaller body mass and blood volume in children compared with adults. However, it is possible for a patient in a state of general anesthesia to experience changes in body temperature, blood pressure, hemodynamics, and pharmacokinetics that could influence the plasma concentration of lidocaine. Halothane was the major anesthetic agent administered and is expected to have had little effect on plasma protein binding but may have affected hemodynamics. As a vasodilator, halothane may have increased local tissue clearance resulting in increased uptake and redistribution, thereby causing lidocaine plasma levels to peak earlier. Also, lidocaine’s high hepatic extraction ratio would make it susceptible to the reduced hepatic blood flow and thereby result in elevated plasma levels. Despite these potential effects on lidocaine plasma levels, because of the low dose delivered, it is expected that the general anesthetic agents had little effect on the measured plasma levels. Therefore, these results should correlate well to plasma levels found in an ambulatory patient.
The possibility of toxic effects may be increased by other factors; for example, as noted previously, coadministration of sedative drugs, lower patient weight, or liver dysfunction. This increased risk may require a reduction of the total lidocaine dose. Also, it is important to note that the estimates listed previously were calculated on the basis of a 5-minute application of the patch. The 15-minute application recommended by the manufacturer may produce even greater plasma levels in children. In addition, care must be taken when comparing the mean values, reported here and by others, because of the large individual variability in plasma levels, as demonstrated by the large standard deviations shown in Figures 1 and 2. buy antibiotics canada
Peak plasma concentrations after application of topical anesthetics are ultimately determined by the rate of tissue distribution and the rate of clearance of the drug. High doses associated with rapid absorption and distribution and a prolonged elimination half-life will increase toxicity. Although rare, toxic levels can be reached through topical mucosal administration of li docaine. In fact, systemic uptake of topical lidocaine has been shown to be faster than subcutaneous injection and similar to intravenous administration.. Together, these findings indicate the importance of evaluating the cumulative accumulation of both lidocaine and its metabolites in the plasma when potential toxicity is being determined.
Plasma concentrations of MEGX after DentiPatch® application have not been reported previously. However, plasma concentrations of MEGX after lidocaine administration (intravenous and topical) have been examined. A single 120-mg intravenous dose in adults produced a peak plasma MEGX concentration of 80 ng/mL. In adults, submucosal injection of 3.6-7.2 mL of 2% lidocaine without epinephrine produced a mean plasma MEGX concentration of 58.9 ng/mL 2 hours after injection. In children, an epidural lidocaine bolus of 5 mgAg followed by 2.5 mg (kg/hr) produced an MEGX plasma concentration of 400 ng/mL after 1 hour and continued to increase for up to 5 hours. In our study, the maximum MEGX level was 11.98 ng/ mL, substantially less than the amounts measured by other studies. However, our results showed that plasma levels of MEGX were at their highest in each subject at the latest time point, 45 minutes after patch removal. In fact, several subjects had very low or no measurable plasma MEGX until the 45-minute time point. This suggests that higher levels may actually have been produced at time points later than 45 minutes, but they could not be measured because of the limitations of this study protocol. eriacta tablets
The results reported here provide an indication of the plasma concentrations that can be expected after application of the DentiPatch® transoral lidocaine patch. These values can serve as an aid in calculating the maximum total lidocaine dose that can be used safely in a pediatric dental patient.
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