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Anesth Prog. 2010 Spring; 57(1): 35–39.
PMCID: PMC2844238


Statistical Analysis of Lidocaine and Dexmedetomidine Interaction with Isobologram

Yukako Tsutsui, Satoko Hoshiai, and Katsuhisa Sunada 2009;37(5):543–547.

It has been recently reported that dexmedetomidine (DEX), an alpha-2 adrenergic receptor agonist, enhanced local anesthetic effect of lidocaine on peripheral nerve. We previously reported that the combination of lidocaine and DEX decreased the action potential (AP) amplitude of the sciatic nerve in rats. These reports suggested that combination of lidocaine and DEX could be more effective for increasing pain threshold. Although recent reports have described the effect of DEX for lidocaine, to our knowledge, the pharmacological relationship of lidocaine and DEX has not been known. Thus, we identified the pharmacological relationship of lidocaine and DEX by isobologram analysis on the rat sciatic nerve.

The isolated sciatic nerve of wistar rats were placed on a nerve chamber made of plastic with two connecting wells and three compartment rooms. The sciatic nerve was stimulated and recorded via two platinum electrode wires. Stimuli with duration of 0.5 msec and frequency of 1 Hz were given. 50% effect concentration (EC50) was performed by probit analysis. The local anesthetic effect of DEX combined with lidocaine was assessed by the isobologram analysis.

We measured the AP amplitude after each drug application to the isolated rat sciatic nerve. Lidocaine decreased the AP amplitude and EC50 was 95.63 ± 11.16 μM. DEX also decreased the AP amplitude and EC50 was 12.19 ± 1.07 μM. The EC50 of the combination was 37.08 μM (lidocaine) + 3.67 μM (DEX), which was calculated according to our dose ratio. Lidocaine EC50 was 10 times higher than DEX EC50. Therefore, we considered that the dose ratio of the combination was 10 : 1. Point for EC50 of combined lidocaine with DEX was located below the additive line on the isobologram. Thus, the pharmacological relationship between lidocaine and DEX appears to be synergistic by the isobologram analysis. These results showed that the combination of lidocaine and DEX can induce synergistic analgesia which may increase the pain threshold.

Figure 1
Time response curve of DEX (n  = 5).
Figure 2
Dose response curve of lidocaine (n  = 8).
Figure 3
Dose response curve of DEX (n  = 8).
Figure 4
Dose response curve of lidocaine with DEX (n  = 9).
Figure 5
Isobologram analysis of EC50 for lidocaine, DEX, and lidocaine with DEX.

Department of Dental Anesthesiology, The Nippon Dental University, School of Life Dentistry at Tokyo

Use of Structured Teaching Method and Behavior Management for a Patient with Autism Undergoing General Anesthesia

Yukie Nitta, Makiko Shibuya, Nobuhito Kamekura, Toshiaki Fujisawa, and Kazuaki Fukushima 2009;37(5):548–553.

Physical restraint is often needed when a patient with autism spectrum disorder panics during induction of general anesthesia. Enforced anesthesia induction with physical restraint has many risks such as injury to the patient and staff, as well as emotional trauma for the patient. We tried to avoid physical restraint at the induction of general anesthesia in a 32-year-old male patient with autism using a structured teaching method and behavior management. Because the patient had refused dental treatment since turning 18, he required dental treatment under general anesthesia. For the first five visits, he underwent anesthesia without physical restraint, but on the 6th visit, he required strong restraint. To avoid enforced anesthesia induction with restraint in subsequent visits, we attempted to use a visual guide based on structured teaching. Structured teaching is described in TEACCH (Treatment and Education for Autistic and Communication in Handicapped Children), which is a well-known program for autism spectrum disorder (Table 1). The visual guide consists of a series of pictures of the places, tools and the processes that the patient will see and experience during induction of anesthesia. Each card contains a written description in two or three words (Fig. 1).

Figure 1
Visual guide (picture cards).
Table 1
Principles and concepts of TEACCH

At preoperative consultation, we showed the picture cards and practiced the induction of anesthesia using them. Tell-Show-Do and count methods were used at the same time. We lent his mother the picture cards and facemask and asked her to practice repeatedly with them at home. For all three subsequent visits, we planned to manage him in the same procedure and with the same staff, as patients with autism prefer routines and sameness over changes and novelty.

As a result of using these devices and procedures, we were able to manage him without any restraint. It appears that people with autistic spectrum disorders are affected with panic because they cannot understand how to perform and cannot readily adapt to new changes or situations (Fig. 2). To avoid inducing panic, a structured teaching method with behavior management is effective for patients with autism spectrum disorders, even if they had previously experienced physical restraint for the induction of general anesthesia in the past.

Figure 2
Two factors that cause patients with autism spectrum disorder to panic and the corresponding actions for anesthesia management.

Department of Dental Anesthesiology, Graduate School of Dental Medicine, Hokkaido University

Optimum Level of Propofol Sedation Indicators for Behavior Management in Uncooperative Patients with Disabilities: Eye Closure, Loss of Eyelash Reflex, and Smooth Insertion of Bite Block

Soichiro Kawase, Sachi Sumida, Hisanori Okada, Koichiro Matsuo, Kazuo Hosaka, and Tadashi Ogasawara 2009;37(5):554–559.

We studied the usefulness of “eye closure”, “loss of eyelash reflex”, and “smooth insertion of bite block” to be considered as the optimum level of propofol sedation indicators for behavior management in uncooperative patients with disabilities.

The subjects were 16 patients with Down's syndrome, autism or mental retardation who needed intravenous sedation because of their uncooperativeness in dental treatment. Pure oxygen was given for one minute, and nitrous oxide (N2O) concentration was increased every other minute in a stepwise fashion by 10% increments. At the 30% concentration level, anesthesia was maintained for seven minutes, and then a tourniquet was applied and venipuncture was performed. After obtaining venous access, infusion of normal saline was started and an infusion of propofol was initiated using a TCI (Target Controlled Infusion) pump at a predicted brain concentration of 3.0 μg/ml. N2O was turned off immediately after securing venous access and ventilation was continued with pure oxygen.

During the propofol infusion, examination was performed. The estimated brain concentrations of propofol at the time when the three indicators (“eye closure”, “loss of eyelash reflex”, and “smooth insertion of bite block”) appeared were recorded, and the estimated brain concentrations at the time when the three indicators could be confirmed was maintained, while respiratory depression, body motion, etc. of the patients under dental treatment were observed.

  1. The lowest concentration was for “eye closure”, followed by “loss of eyelash reflex”, and the highest concentration required was for “smooth insertion of bite block”.
  2. By maintaining the estimated brain concentration for “smooth insertion of bite block”, dental treatment was completed without any problem in 80% of the cases.

This study suggests that “smooth insertion of bite block” can be considered as an effective optimum level indicator of propofol sedation for uncooperative dental patients with disabilities. The depth of sedation level was indicated by “eye closure”, “loss of eyelash reflex”, and then “smooth bite block insertion (in order of increasing depth)”. By inserting the bite block after loss of eyelash reflex, body motions did not occur in 62.5% of the patients. This allows undesirable stimuli to be avoided, and enables dental treatment levels of sedation to be reached smoothly.

Figure 1
The predicted brain concentration (eye closed).
Figure 2
The predicted brain concentration (loss of eyelash reflex).
Figure 3
The predicted brain concentration (smooth insertion of a bite block).
Figure 4
Comparison of predicted brain concentration; eye closed, loss of eyelash reflex, and smooth insertion of a bite block.
Figure 5
Comparison between each predicted brain concentrations.

Department of Special Patient and Oral Care, School of Dentistry, Matsumoto Dental University

Articles from Anesthesia Progress are provided here courtesy of American Dental Society of Anesthesiology