Effect of a trial pharmaceutical solution on reversing sensations after using lidocain: An animal study.

INTRODUCTION: Local anesthesia has a paramount role in any branches of medical sciences specially dentistry. Soft tissue irritations and lips biting are adverse side-effects in some cases. This study tried out to represent a new pharmaceutical solution in returning sensations faster.
MATERIALS AND METHODS: Five New Zealand laboratory rabbits were anesthetized with 1 cc Ketamine and Xilosine intramuscularly in thigh site. Electrodes were attached to the palms and wrists. Then, 0.2 cc lidocain 2% was injected in forearm origin in order to block median proximal nerve in both forelegs. The nerves conduction study (NCS) was recorded before and after lidocain injection, plus 30 min and once again 1 h after calcium gloconate 10%, dextrose 50%, citric acid solution injection. The recorded data were analyzed using Wilcoxon test and using SPSS software (version 11.5) at significant level of 0.05.
RESULTS: The NCS of left and right forearms was 1.4 ± 1.35 mV and 0.48 ± 0.45 mV. According to the statistical test, there was no significant difference between two groups (P > 0.05).
CONCLUSION: Calcium gloconate 10%, dextrose 50%, citric acid solution did not reverse the effect of anesthetic drugs. Possible reasons were pressure to the nerves, which were caused by drug volume, and low sample size.

INTRODUCTION

Local anesthesia has a dramatic role in modern dentistry due to its pain relief and preventing over-reactions.[12]

Soft tissue irritation is one of the major problems after using local anesthetics, which would be caused by unintentional lips biting especially in children and disables.[34]

Significant percentages of inferior alveolar nerve blocks were associated with unintentional biting of the lips particularly in younger patients. The frequency of trauma to the lips was reported 18% (in ages < 4 years), 16% (4–7 years), 13% (8–11 years), and 7% (>12 years). Besides, mentally handicapped adults are just as likely to experience self-inflicted soft tissue irritations. Moreover, most patients dislike their diminished ability to speak (lisping), to smile (asymmetric), to drink (liquid runs from the mouth), and drooling during numbness.[34567] So, fear of numbness associated with the dental injection makes patients to avoid local anesthesia.[8]

Now a day, local anesthesia armamentariums consist of drugs which provide a range of numbness durations (30 min to 12 h) for pain control.[6] However, the usual length of dental treatment is approximately 44 min and prolonged soft tissue numbness (for 2–3 h) are mostly seen in nerve block techniques. Extent and the choice of technique play a paramount role in duration of local anesthetic. New techniques have been introduced to provide localized areas of pulpal anesthesia with minimal association of the soft tissues. The examples are periodontal ligament (or intra ligamentary injection) and the intraosseous injections.[79]

The other way, to prevent those unpleasant feelings and irritations, is to return sensation as fast as possible. Literature reported that OraVerse (Septodont, Pennsylvania, USA) is an effective component in reversing anesthetics.[101112131415] However, the drug meets some limitations in case of: Invasive procedures like endodontic treatment or surgery; children less than 6 years old or weighing less than 15 kg; patients suffering from myocardial infarction, coronary insufficiency, angina, or other coronary artery disorders. Furthermore, Phentoaminemesylate breaks down through liver and the kidneys, so some adverse side-effects might occur like: Diarrhea, facial swelling, increased blood pressure or hypertension, reactions to injection site, jaw pain, oral pain, paresthesia, pruritus, tenderness, upper abdominal pain and vomiting.[16]

Ujhelyi et al. surveyed the effect of hypertonic saline to reverse the blockage of Na channels of the nerves. The study was conducted on the swine, and the results suggested no significant effects of hypertonic saline in inducing repolarization.[17] In one hand, it is reported that local anesthetics affect the Ca channels by slowing their functions[18] and in the other hand, low pH reduces the concentration of anesthetic drugs in the fibers.[19]

Hence, this study tried a new pharmaceutical solution to return sensations faster by providing hypertonic, acidic and Ca ions containing the environment. The positive results would be helpful in returning sensation after mistaken injections, which may lead to prolonged paralysis,[2021] and diagnosis of recurrent, vague generalized pains without any specific reasons.

MATERIALS AND METHODS

Based on neurophysiologic science, there are theories which explain the required conditions for changing the pattern of canals and nerve membrane electric potentials.

Meyers-Overton: Pressure to the nerve membrane, which can be induced by hyperosmolar condition, causes malfunction and distortions of canals and leads to inactivation of lipid soluble anesthetics.[22] Hence, dextrose 50% was considered in the test pharmaceutical solution

Hyper acidic condition: Lower pH makes higher numbers of cationic forms of anesthetics and eliminates the effective penetration of drugs to the nerve cells. Some local anesthetics are prepared as water soluble hydrochloride ions and generally have a pH of 5–6. If a drug contains epinephrine, the test solution must be higher acidic (pH of 3–4) to maintain a stable environment. Conventional preparations with epinephrine have less free base to slow the onset of action. Also, high perineural sodium concentration may displace the local anesthesia from the bindings.[1923] Citric acid would be helpful to maintain lower pH

Hypercalcium condition: Higher amount of Ca ions around nerve cells makes the membrane hyperpolarized and low affinity for initiation of rest phase.[1824] Therefore, calcium gloconate 10% was registered in this pharmaceutical solution.

Preparing calcium gloconate 10%, dextrose 50%, citric acid solution

In order to make hyper calcium and hyperosmolar condition, 10 cc calcium gloconate 10% (Sina Daroo, Tehran, Iran) was diluted with 10 cc dextrose 50% (Mehban Daroo, Tehran, Iran). Then, Citric acid (Jovin Co., Eslamshahr, Iran) was added to the solution to make 3.6 of pH. These doses of drugs do not have any toxicity and interaction with each other.

In the next stage, five New Zealand laboratory rabbits, weighting about 1.5–2 kg, were included in this experimental and interventional study. The specimens were anesthetized with 1 cc Ketamine and Xilosine (Alfasan, Woerden, The Netherlands) intramuscularly in thigh site. The forelegs were shaved, ground's electrodes were attached to the palms and wrists, then the stimulator electrodes were attached and normal amplitude (mV) were recorded from each foreleg.

In the next stage 0.2 cc lidocain 2% (Daroopakhsh, Tehran, Iran) was injected to block median proximal nerve in both forelegs. Due to the effect of anesthesia, the recorded amplitude was zero by then. So, 0.2 cc calcium gloconate 10%, dextrose 50%, citric acid (CGD) solution was injected in the right foreleg (test) in the site of previous injection. The left foreleg was regarded as control and the amplitudes were recorded in these following intervals: After injection of CGD solution, 30 and 60 min later from both forelegs. Finally, the data were analyzed with Wilcoxon test by using SPSS software version 11.5 (IBM Corporation, NY, USA) at significant level of 0.05.

Ethics

This study was approved by the animal Department of Torabinejad Dental Research Center and Local Ethical Committee of Isfahan University of Medical Science with ID number of 21879.

RESULTS

Based on the analyzed results by Wilcoxon test, the mean base amplitudes were 6.02 ± 2.58 and 6.64 ± 4.24 mV for the test and control forelegs. Furthermore, the highest amplitudes were found in control forelegs 60 min after solution injection in all the rabbits. However the amplitudes were 0 in the other time spots [Table 1].

Table 1

The recorded values of amplitudes (mV) from test and control forelegs during different intervals Specimens

The mean amplitude of the control forelegs (1.4 ± 1.35 mV) was higher than test forelegs (0.48 ± 0.04 mV) 60 min after solution injection, but no significant differences was found (P = 0.46).

DISCUSSION

Trying to return sensitivity might be useful in mistaken injections, diagnosing vague generalized pains and recurrent pains without any specific reasons.

Although different drugs with different time duration have been produced, there is not any definite solution to reverse the effect of local anesthetics completely without side effects. The Oravers is a very effective drug, but it has some limitations as mentioned before.

Adverse reactions of one drug which is observed in its clinical trials cannot be directly compared to the clinical trials of another drug.

Intervening in peripheral environment of nerve makes reversal faster. Local anesthetics inhibit Na canals reversibly and dose-dependently. Hence, lidocaine molecules bond to membrane's receptors dynamically and unattached alternatively.[25] Some surveys used nerve physiology and designed studies to reach their goals in making sensation or faster blockage,[2126] but using natural ions has been paid attention for a while.

Ujhelyi et al. conducted a study to reverse the impact of lidocaine by using hypertonic normal saline on blocked Na canals.[17] The result showed similarities with the present study.

Lehavi et al. reported a case who suffered from a prolonged paralysis following an uneventful infraclavicular block for hand surgery. They tried lithium orally to lower the physiologic concentrations of Na and the results were hopeful.[27]

Although our results did not reverse the effect of anesthetic drugs apparently, it did not ignore the role of perinoural environment on physiology of nerve. Still there are some hopes to make the benefits of natural ions with the lowest side-effects as the results showed lower amplitudes 1 h after solution injection. The below factors might be the reasons:

Hyperosmolar environments would make the pressure on nerve's membrane and plasmolysis of the nerve. Hence, blockage of the impulses could be predicted, and that could be one of the reasons why diabetic patients manifest neuropathy[28]

The volume of drug might have pressure on nerves so it would have been better if the study had been conducted with different volumes[29]

Time limitation, low sample size and lack of facility might have affected the result.