Anesth Analg 2002;94:271-274
© 2002 International Anesthesia Research Society
PEDIATRIC ANESTHESIA
Anesthesia for Patients with Congenital Insensitivity to Pain and Anhidrosis: A Questionnaire Study in Japan
Toshiya Tomioka, MD, PhD*,
Yutaka Awaya, MD, PhD
,
Kenji Nihei, MD, PhD
,
Hiroshi Sekiyama, MD*,
Shigehito Sawamura, MD, PhD*, and
Kazuo Hanaoka, MD, PhD*
*Department of Anesthesiology, Faculty of Medicine, The University of Tokyo; Department of Pediatrics, Seibo International Catholic Hospital; and Department of Pediatric Neurology, National Pediatric Hospital, Tokyo, Japan
Address correspondence and reprint requests to Toshiya Tomioka, Department of Anesthesiology, Faculty of Medicine, The University of Tokyo, 3-1 Hongo 7-chome, Bunkyo-ku, Tokyo, 113-8655, Japan. Address e-mail to tomiokat-ane{at}h.u-tokyo.ac.jp
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Abstract
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We investigated the anesthetic management of patients with congenital insensitivity to pain and anhidrosis (CIPA) in Japan. CIPA is a rare inherited disease characterized by a lack of pain sensation and thermoregulation. Although lacking pain sensation, some patients do have tactile hyperesthesia. Thus, anesthetics are a necessity during operations. We also determined that because patients with CIPA have problems with thermoregulation, temperature management is a concern during the perioperative period and sufficient sedation is necessary to avoid accidental fractures. Additionally, it was found that the use of muscle relaxants does not present a problem, malignant hyperthermia is not associated with CIPA, and that the possibility of abnormalities in the autonomic nervous system must be taken into consideration. Therefore, patients with CIPA can be safely managed with anesthesia.
IMPLICATIONS: We investigated the anesthetic management of patients with congenital insensitivity to pain and anhidrosis. We clarified the following three important points: anesthesia is necessary, temperature management must be maintained, and there must be sufficient perioperative sedation in the anesthetic management of patients with congenital insensitivity to pain and anhidrosis.
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Introduction
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Congenital insensitivity to pain and anhidrosis (CIPA) is an inherited disease and is classified as a hereditary sensory and autonomic neuropathy type IV (HSAN-IV). There have been many reports of CIPA in Japanese patients (1–3). CIPA is characterized by episodes of unexplained fever, systemic analgesia, anhidrosis, and mental distress. These symptoms occur because of an abnormality of the trkA gene, a receptor tyrosine kinase of nerve growth factor (4). Patients with CIPA often experience trauma, bony fractures, and osteomyelitis because of an insensitivity to pain. Therefore, such patients may undergo surgery such as osteotomy and amputation. However, there have been few reports concerning the anesthetic management of patients with CIPA because it is a rare disease (5,6). Using a questionnaire survey, we investigated the use of anesthesia in CIPA patients during surgery, and propose standards and future indications for anesthetic management of patients with CIPA.
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Methods
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Fifty-seven questionnaires were mailed to all current members of the HSAN-IV Association in Japan. Thirty-four (59.6%) of the questionnaires were returned which revealed 23 patients who had operations under general anesthesia. To examine the use of anesthesia on these patients, questionnaires were also sent to the medical centers that treated them. Twenty-one questionnaires accounting for 15 patients were completed and returned. There were 45 anesthesia records regarding these 15 patients and the following perioperative variables were evaluated: age, sex, preanesthetic medication, induction and maintenance of anesthesia, and the use of muscle relaxants and other drugs such as atropine and fentanyl. In addition, we reviewed body temperature and instances of nausea or vomiting, as well as the anesthesiologist’s impression of the needed depth of anesthesia, and other factors. To understand the patients’ present condition, we also questioned their parents, who were familiar with their conditions, regarding general pain, headache, abdominal pain, hot or cold sensation, tactile sensation, titillation, itching, sweating, and mental state as well as their anesthetic family history. In regard to general pain, headache, abdominal pain, hot or cold sensation, tactile sensation, titillation, and itching, the answer was chosen from the following: "none," "feel a little," "feel most," and "feel sensitive."
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Results
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Patient characteristics are summarized in Figure 1. Fourteen of 15 patients felt little or no pain, including headache and abdominal pain. Most of the patients also felt little or no hot or cold sensation. However, all of the patients had tactile sense and six patients complained of tactile hyperesthesia. Six patients also complained of hypersensitivity to titillation. Regarding the itching sensation, the range varied from normal to none. All of the patients had damaged sweating mechanisms; eight patients had little sweating and in seven patients sweating was absent. Most of the patients had some degree of mental deficiency; nine patients were moderate to severe, five were mild, and one was normal.
Forty-five surgical procedures were performed under general anesthesia on 15 patients with CIPA. Of the 15 patients, 14 were <15 yr of age with their initial anesthetic. Of the 45 anesthetics, only 2 were patients older than 20 yr. Of the procedures performed, there were 40 orthopedic surgeries, 2 abdominal surgeries, 1 dental surgery, 1 ophthalmologic surgery, and 1 urological surgery. Because of insensitivity to pain, osteomyelitis induced by injury was responsible for a large majority of the procedures.
A variety of preanesthetic medications were given to the patients at the various medical facilities. In 19 of the 45 cases, atropine was given as a preanesthetic medication; however, none of the patients displayed signs of heat. In 19 cases, sedatives such as a benzodiazepine or hydroxyzine were given as preanesthetic medications, and in 1 case, meperidine was given as a preanesthetic medication. These medications all had a normal effect on the patients. All of the procedures were performed under general anesthesia.
Regional anesthesia was not used in any of the cases. Anesthesia was induced either IV or by inhalation according to clinical requirements. The IV anesthetics included barbiturates, benzodiazepine, propofol, and ketamine. The inhaled anesthetics were halothane, enflurane, and sevoflurane in oxygen. All of the induction anesthetics had the usual effect on the patients. Usual monitoring was used including rectal body temperature. Anesthesia was maintained with various techniques with inhaled anesthetics being the preferred method. The inhaled anesthetics used were halothane, enflurane, isoflurane, sevoflurane in oxygen, and nitrous oxide. In three cases, anesthesia was maintained with nitrous oxide in oxygen. In two cases, anesthesia was maintained with propofol. In four cases, patients received fentanyl or pentazocine to supplement the nitrous oxide anesthesia, and in two cases, patients received a fentanyl-supplemented inhaled anesthesia. Muscle relaxants were used to facilitate tracheal intubation in 25 cases. Of these, 6 cases received succinylcholine, 15 cases vecuronium, and 4 cases pancuronium. Maintenance by nontracheal intubation techniques included mask ventilation in five cases and laryngeal mask in two cases. The muscle relaxants all had the usual effect on patients and no problems occurred with the use of neuromuscular antagonists. The concentration of inhaled anesthetics varied. The concentration range of anesthetic maintenance was 0.3% to 1.0% for halothane, 0.5% to 2.0% for enflurane, 0.5% for isoflurane, and 0.2% to 3.0% for sevoflurane. There was a wide variation in anesthetic requirements for each procedure.
Perioperative body temperatures were almost within the normal range. Some cases became hyper- or hypothermic, but body temperature was returned to normal with the use of warm or cool blankets and regulation of the operating room temperature. In three cases, body temperature increased during the postoperative period, but returned to normal with simple cooling. For treating hyperthermia, the nonsteroidal antiinflammatory drugs diclofenac sodium and indomethacin had no effect. Except for two patients, most patients did not experience nausea or vomiting. One patient felt the need to vomit during the postoperative period, but antiemetics were ineffective. However, this patient tended to feel the need to vomit frequently in daily life. None of the cases displayed clear autonomic nervous system dysfunction.
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Discussion
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HSAN is divided into five classifications: sensory radicular neuropathy, congenital sensory neuropathy, familial dysautonomia or Riley-Day syndrome, CIPA, and hereditary sensory neuropathy with predominant loss of small myelinated nerve fibers. CIPA corresponds to type IV HSAN (7). CIPA is a hereditary disease caused by an abnormality of the TrkA gene, which causes inactivation of nerve growth factor during the embryonal period (4). As a result, there are defects in pain sensation and impairment of peripheral sympathetic nerves. A defect in pain sensation causes analgesia. Impairment of peripheral systemic nerves causes anhidrosis and, consequently, excessive fever because of problems with thermoregulation. Anesthesia is composed of the following four elements: sedation, analgesia, muscle relaxation, and prevention of excessive autonomic reflexes. In patients with CIPA, the nervous system through which analgesia and autonomous reflex are controlled is lacking. Therefore, patients with CIPA present an interesting challenge in the management of anesthesia. From our survey, we clarified the following three points: (a) anesthesia is necessary, (b) temperature management must be maintained, and (c) sufficient perioperative sedation is necessary.
It may be thought that anesthetics are unnecessary in patients with CIPA because they do not feel pain; however, this is not the case. Most patients with CIPA display tactile hyperesthesia, which is thought to compensate for algesthesia. We speculate that nociceptive stimuli from the operation act on hypersensitive taction to cause unpleasant sensations in patients with CIPA. Based on animal experiments, it has been determined that anesthetics affect both taction and algesthesia (8). Therefore, it is possible that the use of anesthetics can prevent undue taction.
Okuda et al. (5) described the difference in concentration of inhaled anesthetics needed for orthopedic surgery and dental surgery. According to their report, the inhaled anesthetic was >1.0 minimum alveolar anesthetic concentration for orthopedic surgery, and <1.0 minimum alveolar concentration for dental surgery. They speculated that these differences were caused by the nociceptive stimulus of each operation. However, a detailed report of the orthopedic surgeries was not given, and it is possible that tactile hyperesthesia might influence the need for larger inhaled anesthetic concentrations. An accurate level of anesthetic needed for patients with CIPA has yet to be determined. Therefore, a standard level of anesthetic should be maintained until further study.
It is interesting to note reports of audio-hypersensitivity in patients with CIPA who were maintained under light anesthesia. Audio-hypersensitivity in patients with CIPA might have some relation to tactile hyperesthesia. Also, because of the small number of patients with abdominal surgery in this study, we do not have a detailed understanding of visceral pain.
In patients with CIPA, management of body temperature is difficult in daily life because the sympathetic nervous system, which rules the sweat glands, is lacking. However, patients with CIPA can control their body temperature by strict management of room temperature and use of a heat insufflation device. It is therefore necessary to adjust the room temperature and use a heat insufflation apparatus during surgical operations. Moreover, sufficient preanesthetic medication is necessary to reduce fevers caused by excitement. The management of body temperature is simple if appropriate measures are taken and routine prevention is maintained.
Some points concerning sedation of patients with CIPA during the perioperative should be noted. Patients with fractures do not feel pain because of their insensitivity to it. Therefore, patients may become excited and sometimes become enraged. Care must be taken when preanesthetic medication is administered or emergent excitement appears. Otherwise, new fractures from excessive movement may be caused. Therefore, it is necessary to maintain moderate sedation during the perioperative period. Sevoflurane and propofol, which are widely used anesthetics, allow early recovery from anesthesia. However, these anesthetics do not function as long-term sedatives during the postoperative period and other preemptive long-term sedatives are necessary.
Our study also clarified other points for anesthetic management in patients with CIPA. There is no problem with the use of either depolarizing or nondepolarizing muscle relaxants. Also, none of the cases had any problems attributed to anesthetic family history, and there was no relation to any diseases that cause abnormal body temperature, e.g., malignant hyperthermia. No cases in our study showed heat accumulation because of atropine administration. Moreover, no abnormalities occurred through the use of neuromuscular antagonists, similar to a report by Okuda et al. (5). There may be differences in patients with HSAN-III (9–11). In the anesthetic management of patients with CIPA, it is necessary to consider the possibility of abnormalities in the autonomic nervous system. Postoperative nausea and vomiting should not be caused by the usual mechanisms.
In conclusion, in the anesthetic management of patients with CIPA, it is important to note the following three points: (a) anesthesia is necessary, (b) temperature management must be maintained, and (c) there must be sufficient perioperative sedation. In addition, no problems were associated with the use of muscle relaxants, malignant hyperthermia is not associated with CIPA, and possible abnormalities in the autonomic nervous system should be considered.
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Accepted for publication October 1, 2001.
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Abstract
Introduction
