Katsuhisa Sunada

Effects of Epinephrine on Lidocaine Pharmacokinetics and Blood Volume in the Dental Pulp

INTRODUCTION Epinephrine potentiates and prolongs the efficacy of local anesthetics by reducing blood flow. We investigated the effect of epinephrine on the pharmacokinetics of lidocaine and the pulpal blood volume after maxillary infiltration anesthesia in rats. METHODS We measured the (14)C-radioactivity and (14)C-distribution in the maxilla and the dental pulp after the injection of 2% (14)C-lidocaine with or without 10 μg/mL epinephrine (n = 7) into the palatine mucosa proximal to the first molar. The blood volume in the pulp was measured using (99m)Tc-pertechnetate (n = 5). RESULTS When lidocaine was injected together with epinephrine, the lidocaine became widely distributed throughout the maxilla and was observed mainly in the first molar pulp. The lidocaine amount in the dental pulp at 10-60 minutes was more than 2 times higher than that after the injection of lidocaine alone. The relative pulpal blood volume after 20 minutes decreased to 63.1% of the value after the injection of lidocaine alone. CONCLUSIONS We found that lidocaine had infiltrated into the molar pulp after infiltration anesthesia. Furthermore, our results suggested that epinephrine augmented the retention of lidocaine in the pulp.

Can nerve regeneration on an artificial nerve conduit be enhanced by ethanol-induced cervical sympathetic ganglion block?

This study aimed to determine whether nerve regeneration by means of an artificial nerve conduit is promoted by ethanol-induced cervical sympathetic ganglion block (CSGB) in a canine model. This study involved two experiments—in part I, the authors examined the effect of CSGB by ethanol injection on long-term blood flow to the orofacial region; part II involved evaluation of the effect of CSGB by ethanol injection on inferior alveolar nerve (IAN) repair using polyglycolic acid-collagen tubes. In part I, seven Beagles were administered left CSGB by injection of 99.5% ethanol under direct visualization by means of thoracotomy, and changes in oral mucosal blood flow in the mental region and nasal skin temperature were evaluated. The increase in blood flow on the left side lasted for 7 weeks, while the increase in average skin temperature lasted 10 weeks on the left side and 3 weeks on the right. In part II, fourteen Beagles were each implanted with a polyglycolic acid-collagen tube across a 10-mm gap in the left IAN. A week after surgery, seven of these dogs were administered CSGB by injection of ethanol. Electrophysiological findings at 3 months after surgery revealed significantly higher sensory nerve conduction velocity and recovery index (ratio of left and right IAN peak amplitudes) after nerve regeneration in the reconstruction+CSGB group than in the reconstruction-only group. Myelinated axons in the reconstruction+CSGB group were greater in diameter than those in the reconstruction-only group. Administration of CSGB with ethanol resulted in improved nerve regeneration in some IAN defects. However, CSGB has several physiological effects, one of which could possibly be the long-term increase in adjacent blood flow.

Effect of cervical sympathetic ganglionectomy on facial nerve reconstruction using polyglycolic acid-collagen tubes

A polyglycolic acid-collagen (PGA-c) tube was used as an artificial nerve guide during facial nerve reconstruction performed in a canine model of stellate ganglion block (SGB). The model was generated using a cervical sympathetic ganglionectomy. We evaluated the effects of blood flow on nerve regeneration. First, we resected the left cervical sympathetic ganglion in beagles (n=6). We assessed buccal mucosal blood flow and nasal skin temperatures once per week for 12weeks and Horners sign 2, 4, and 6months after resection. We compared these values to those measured prior to resection. Blood flow was increased for 6-11weeks, but sympathetic control remained blocked after 6months. Second, we divided beagles into 3 groups: resection models (negative control), from which 7mm of the left facial nerve buccal branch was resected (n=5); reconstruction models, which underwent nerve reconstruction using PGA-c tubes (n=6); and SGB+reconstruction models, which underwent a left cervical sympathetic ganglionectomy immediately after reconstruction (n=6). The right side of the face served as control (n=17). Nerve regeneration was significantly greater in the SGB+reconstruction model dogs than in the reconstruction model dogs, as measured by both electrophysiological and morphological analyses at postoperative week 12. In particular, motor nerve conduction velocity was increased approximately 2-fold (p=0.018). We were able to generate an SGB model with long-term increased blood flow facilitated by the promotion of facial nerve regeneration by PGA-c tubes.

Long-Term Evaluation of Continuous Epidural Anesthesia in an Improved Canine Model

Background Continuous epidural analgesia with catheterization is a useful technique, because it has a wide adaptation range and provides prolonged analgesia. Problems that may arise from long-term epidural analgesia are changes in the analgesic area, duration of analgesia and catheter-related problems. Few articles have evaluated gradual changes of long-term epidural analgesia. In the animal models used in those studies, the catheter was inserted by an invasive surgical procedure. In the present study, we evaluated changes in a canine model in which the catheter was inserted by a minimally invasive procedure. Objectives To evaluate long-term changes in the efficacy of epidural analgesia in an improved canine model in which the epidural catheter was inserted and fixed for 5 weeks using a minimally invasive procedure. Materials and Methods Six beagles underwent epidural catheterization under general anaesthesia. The catheter tip was located in the sixth lumbar region; the catheter peripheral end was passed subcutaneously through the neck. Physiological saline was continuously infused (1.0 mL/h) via the catheter throughout the study. The efficacy of epidural analgesia was assessed weekly with 2% lidocaine once a week in 5 weeks. Peripheral blood analysis including interleukin-6 (IL-6) level in the cerebrospinal fluid (CSF), histological evaluations and epidurography were performed to evaluate the mechanisms underlying the changes. Results No dog died and the catheters were kept in place. The efficacy of analgesia was well maintained until 4 weeks; at 5th week, the efficacy decreased by half. The spread of injected medium was not observed in the cranial direction at 5th week and the tip of catheter was capped with granulation tissue. Throughout the study period, white blood cell counts and C-reactive protein levels were slightly high for catheterization and the IL-6 level in CSF was below detectable limits. Conclusions This was the longest study period with continuous epidural analgesia administered in canines. The effective period of epidural anesthesia was 4 weeks in this study. We speculate that time-dependent decrease in the anaesthetic efficacy was attributed to formation of granulation tissue surrounding the catheter tip.

Epinephrine Affects Pharmacokinetics of Ropivacaine Infiltrated Into Palate

Pulpal anesthesia success rates for ropivacaine following maxillary infiltration anesthesia seem to be low. We investigated the hypothesis that the addition of epinephrine would affect the pharmacokinetics of ropivacaine by retaining ropivacaine in the mucosa of the injected area through the time-dependent distribution of ropivacaine in the rat maxilla and serum following maxillary infiltration anesthesia using (3)H-labeled ropivacaine. We then examined the vasoactivity of ropivacaine with or without epinephrine on local peripheral blood flow. The addition of epinephrine to ropivacaine increased ropivacaine concentrations in the palatal mucosa and adjacent maxilla by more than 3 times that of plain ropivacaine at 20 minutes. By observing the autoradiogram of (3)H-ropivacaine, plain ropivacaine in the maxilla was remarkably reduced 20 minutes after injection. However, it was definitely retained in the palatal mucosa, hard palate, adjacent maxilla, and maxillary nerve after the administration with epinephrine. Ropivacaine with epinephrine significantly decreased labial blood flow. This study suggests that 10 μg/mL epinephrine added to 0.5% ropivacaine could improve anesthetic efficacy and duration for maxillary infiltration anesthesia over plain ropivacaine.

Are Muscle Relaxants Needed for Nasal Intubation in Propofol and Remifentanil Anesthesia

PURPOSE The authors hypothesized that a muscle relaxant would have no meaningful difference in intubation conditions during nasal intubation under remifentanil and propofol anesthesia. MATERIALS AND METHODS This parallel-group, double-blinded, randomized controlled trial included 44 patients who received saline (S group; n = 22) or rocuronium (R group; n = 22). In addition to remifentanil 0.5 μg/kg per minute and propofol 5 mg/kg per hour, propofol 0.5 mg/kg was administered until loss of consciousness. Nasal intubation was performed 10 minutes after administration of R or S 0.6 mg/kg. Significant differences in intubation conditions and salivary amylase levels before and after intubation were tested (P < .05). RESULTS Vocal cord status (P = .003) and response to intubation or cuff filling (P = .008) were significantly different, but intubation conditions were not. Salivary amylase level was significantly lower with R administration (P = .022). No patient complained of postoperative throat pain and hoarseness. CONCLUSION Muscle relaxants during nasal intubation performed after bolus administration of propofol 0.9 mg/kg in addition to 10 minutes of remifentanil 0.5 μg/kg per minute plus propofol 5 mg/kg per hour are unnecessary.

Changes in blood flow at the mandibular angle and Horner syndrome in a rat model of superior cervical ganglion block

Background A stellate ganglion block (SGB) causes increased blood flow in the maxillofacial region, exhibiting the potential for regenerative effects in damaged tissue. The focus of this study was to understand the efficacy of SGB for regenerative effects against nerve damage. A rat model of the superior cervical ganglion block (SCGB) was created instead of SGB, and facial blood flow, as well as sympathetic nervous system function, were measured. Methods A vertical incision was made on the left side of the neck of a Wistar rat, and a 5-mm resection of the superior cervical ganglion was performed at the back of the bifurcation of the internal and external branches of the left common carotid artery. Blood flow in the skin at the mandibular angle and mean facial temperature were measured using a laser-Doppler blood flow meter and a thermographic camera, respectively, over a 5-week period after the block. In addition, the degree of ptosis and miosis were assessed over a period of 6 months. Results The SCGB rat showed significantly higher blood flow at the mandibular angle on the block side (P < 0.05) for 3 weeks, and significantly higher skin temperature (P < 0.05) for 1 week after the block. In the SCGB rat, ptosis and miosis occurred immediately after the block, and persisted even 6 months later. Conclusions SCGB in rats can cause an increase in the blood flow that persists over 3 weeks.

Dexmedetomidine Enhances the Pulpal Anesthetic Effect of Lidocaine: A Pilot Study

Dexmedetomidine hydrochloride (DEX) demonstrates analgesic, sedative, and hypotensive effects. DEX may also enhance the effect of local anesthetics used in the oral cavity, although this has not been well established in combination with lidocaine. We conducted a single-blind crossover study in 8 healthy volunteers to investigate whether DEX enhances the anesthetic effect of lidocaine in the oral cavity. DEX or DEX + lidocaine was injected into the labial gingiva corresponding to the root apex of the maxillary left central incisor and into the buccal gingiva corresponding to the root apex of the mandibular right first molar. Pain threshold, blood pressure, pulse rate, oxygen saturation, and bispectral index were measured 5 minutes after treatment and at 10-minute intervals for 60 minutes. DEX + lidocaine caused pulpal anesthesia in more subjects than lidocaine alone; this difference was significant for both central incisors and first molars up to 40 minutes after treatment. Following DEX + lidocaine treatment, blood pressure and bispectral index were significantly reduced at several time points, and pulse rate significantly reduced at all time points. Neither treatment caused changes in oxygen saturation. In conclusion, administering DEX with lidocaine for dental local anesthesia caused sedation and enhanced local anesthesia compared to lidocaine alone.

Imidazoline 1 receptor activation preserves respiratory drive in spontaneously breathing newborn rats during dexmedetomidine administration

Dexmedetomidine is an alpha‐2 (α2) adrenoceptor and imidazoline 1 (I1) receptor agonist that provides sedation without loss of respiratory drive.

Dexmedetomidine Increases the Latency of Thermal Antinociception in Rats

Recent reports have stated that dexmedetomidine (DEX), an α2-adrenoreceptor agonist, enhances the local anesthetic effects of ropivacaine and prolongs its effective duration. However, little is known about the effect of a combination of DEX and lidocaine on anesthetic duration. Therefore, we investigated whether DEX can prolong the local anesthetic effect of lidocaine, using the thermal paw withdrawal test in Wistar rats in order to measure local anesthetic duration. We subcutaneously injected 50 μL of either normal saline, 2% lidocaine, a combination of 0.5 μg/kg DEX and 2% lidocaine, or a combination of 2% lidocaine with 1:80,000 epinephrine into the plantar surface of the left hind paw of the rats. The plantar region was stimulated using heat. We measured the perceived acute pain according to paw movement in response to stimulation. We found DEX significantly prolonged the paw withdrawal latency of lidocaine. Moreover, we found that DEX can prolong the local anesthetic duration of lidocaine as much as 1:80,000 epinephrine, up to 35 minutes after injection. In conclusion, this study concluded that a combination of DEX and lidocaine may be useful as a local anesthetic, similar to a combination of epinephrine and lidocaine, for short procedures.