Paths of thoracic epidural catheters in children undergoing the Nuss procedure for pectus excavatum repair.

PURPOSE: To investigate the paths of thoracic epidural catheters in children, this retrospective study was performed. METHODS: We investigated 73 children aged 4 to 12 (mean ± SD 7.8 ± 2.3) years, who underwent the Nuss procedure for pectus excavatum repair under combined general and epidural anesthesia over a 5-year period at Tokyo Metropolitan Police Hospital. Following induction of general anesthesia, we inserted a radiopaque epidural catheter via the T5/6 or T6/7 interspace and advanced for 5 cm cephalad in the thoracic epidural space. We evaluated the paths of the epidural catheters on plain chest radiographs after surgery. RESULTS: The median level for the catheter tip location was T3 (range C6-T7), while the median number of vertebrae crossed by the catheter tips was 2.5. In most children, the catheters advanced straight for the first 2-3 cm (1-1.5 vertebrae) in the thoracic epidural space. However, they continued to advance straight in only 25 children, while they exhibited curved or coiled paths in the remaining 48. The catheter tips were located at higher levels in children with straight epidural catheter paths [median (range) T2 (C6-T4)] than in those with curved or coiled paths after the initial 2-3 cm [median (range) T4 (T2-T7)] (p < 0.0001). CONCLUSIONS: Our findings indicate that the course of epidural catheters in children is unpredictable after the first 2-3 cm in the thoracic epidural space. Clinicians should be aware of such findings, although further studies are required for confirmation.

Practical guidelines for the response to perioperative anaphylaxis.

Perioperative anaphylaxis is a severe adverse event during anesthesia that requires prompt diagnosis and treatment by physicians, including anesthesiologists. Muscle relaxants and antibiotics are the most common drugs that cause perioperative anaphylaxis in Japan, as in many countries. In addition, sugammadex appears to be a primary causative agent. Obtaining previous anesthesia records is necessary in a patient with a history of allergic reactions during anesthesia, whenever possible, to avoid recurrence of anaphylaxis. Although medical staff are likely to notice abnormal vital signs because of complete monitoring during anesthesia, surgical drapes make it difficult to notice the appearance of skin symptoms. Even if there are no skin symptoms, anaphylaxis should be suspected, especially when hypotension resistant to inotropes and vasopressors persists. For improving the diagnostic accuracy of anaphylaxis, it is helpful to collect blood samples to measure histamine/tryptase concentrations immediately after the events and at baseline. The first-line treatment for anaphylaxis is adrenaline. In the perioperative setting, adrenaline should be administered through the intravenous route, which has a faster effect onset and is secured in most cases. Adrenaline can cause serious complications including severe arrhythmias if the appropriate dose is not selected according to the severity of symptoms. The anesthesiologist should identify the causative agent after adverse events. The gold standard for identifying the causative agent is the skin test, but in vitro tests including specific IgE antibody measurements and basophil activation tests are also beneficial. The Working Group of the Japanese Society of Anesthesiologists has developed this practical guide to help appropriate prevention, early diagnosis and treatment, and postoperative diagnosis of anaphylaxis during anesthesia.Grade of recommendations and levels of evidence Anaphylaxis is a relatively rare condition with few controlled trials, and thus a so-called evidence-based scrutiny is difficult. Therefore, rather than showing evidence levels and indicating the level of recommendation, this practical guideline only describes the results of research available to date. The JSA will continue to investigate anaphylaxis during anesthesia, and the results may lead to an amendment of this practical guideline.

Sugammadex and rocuronium-induced anaphylaxis.

Perioperative anaphylaxis is a life-threatening clinical condition that is typically the result of drugs or substances used for anesthesia or surgery. The most common cause of anaphylaxis during anesthesia is reportedly neuromuscular blocking agents. Of the many muscle relaxants that are clinically available, rocuronium is becoming popular in many countries. Recent studies have demonstrated that succinylcholine (but also rocuronium use) is associated with a relatively high rate of IgE-mediated anaphylaxis compared with other muscle relaxant agents. Sugammadex is widely used for reversal of the effects of steroidal neuromuscular blocking agents, such as rocuronium and vecuronium. Confirmed cases of allergic reactions to clinical doses of sugammadex have also been recently reported. Given these circumstances, the number of cases of hypersensitivity to either sugammadex or rocuronium is likely to increase. Thus, anesthesiologists should be familiar with the epidemiology, mechanisms, and clinical presentations of anaphylaxis induced by these drugs. In this review, we focus on the diagnosis and treatment of anaphylaxis to sugammadex and neuromuscular blocking agents. Moreover, we discuss recent studies in this field, including the diagnostic utility of flow cytometry and improvement of rocuronium-induced anaphylaxis with the use of sugammadex.

[Usefulness of ultrasound sonography in performing posterior sacroiliac ligament injection in elderly patients].

BACKGROUND: The sacroiliac joint (SIJ) is recognized as a potential source for low back pain especially in elderly people. Previous studies indicated that in patients with SIJ pain, posterior sacroiliac ligament injections are more effective than intra articular injections. The aim of this study was to assess usefulness of ultrasound sonography (US) in performing posterior sacroiliac ligament injection. METHODS: We examined SIJ and ligaments, and injected local anesthetics using ultrasonography. US guided needle insertions were performed. We also examined the cadevar of a 74-year-old woman to examine SIJ anatomy. RESULTS: US was performed in 61 male and 97 female outpatients (N = 158) with a mean age of 72.8 ± 10.9. US examination of the SIJ is difficult to perform because of its complex anatomy, and wide range of normal variations, and relative inaccessibility by surface scanning. The long posterior sacroiliac ligament (LPSL) is visualized as a hyper echoic laminated linear structure. We were able to confirm needle placement and area affected by local anesthetics. CONCLUSIONS: Our study suggests that US can be useful in performing posterior sacroiliac ligament injections. Sufficient anatomical knowledge and extensive US experience are essential in performing these injections.

Antiallodynic effect of herbal medicine yokukansan on peripheral neuropathy in rats with chronic constriction injury.

Yokukansan, one of the traditional Japanese herbal medicines, ameliorated neuropathic pain symptoms in patients. In this study, we investigated the effects of yokukansan on neuropathic pain in chronic constriction injury (CCI) model. Oral administration of yokukansan significantly inhibited mechanical and cold allodynia in the von Frey hair or acetone test, respectively. In comparison, amitriptyline, a tricyclic antidepressant, demonstrated moderate, but not significant, antiallodynic effects in the mechanical and cold tests. Yokukansan significantly inhibited the cerebrospinal fluid dialysate level of glutamate that had increased by the stimulation of brush or acetone. Glutamate transporter inhibitors, DL-threo-beta-hydroxy aspartate and dihydrokainate, decreased the yokukansan-induced antiallodynic actions in CCI rats. Our results suggest that yokukansan was confirmed to have antiallodynic effects in CCI rats, which are related to a blockade of glutamatergic neurotransmission via activation of glutamate transporters in the spinal cord.

[Case of pneumonitis caused by Yokukansan].

A 74-year-old man was admitted to our hospital complaining of severe neck pain and general fatigue. He had been undergoing treatment for post-operative neck pain at the out-patient clinic of our hospital, but was now complaining of pain more intense than usual. Chest X-rays revealed diffuse ground glass shadows in bilateral lung fields, and computed tomography revealed diffuse intestinal shadows. A drug lymphocyte stimulation test (DLST) was also performed at that time. Steroid pulse therapy improved the clinical symptoms, hypoxemia and chest X-ray findings. DLST performed again with Yokukansan and Hachimijiogan 133 days after the initial diagnosis of pneumonitis showed Yokukansan was positive. This result showed Yukukansan may be a causative drug for allergic drug-induced pneumonitis. Any drugs including kanpo may be possible to induce allergic pneumonitis.

[Effect of the sacroiliac ligament block on intractable low back pain in elderly patients].

BACKGROUND: Lumbar spine disease in the elderly people is complicated by a variety of pathophysiology in the spine and the cause of the pain is unclear. Diagnosis of pain may be difficult in patients with pain in the thigh and groin area. Sacroiliac joint is supporting the trunk and movable joint. We examined the effect of the sacroiliac joint block for intractable low back pain. METHODS: Retrospectively we examined the duration of disease in patients with hip and leg pain visiting the hospital for eight months, and we questioned the site of pain awareness. Newton test, Gaenslen test, Patrick test and Fadire test were carried out for sacroiliac joint pain in patients with at least one positive finding. When performing sacroiliac ligaments block local anesthetics was injected to check the position of the dorsal sacroiliac ligaments under ultrasonic echo whenever possible. The block is performed with the patients prone at a point one finger from the posterior superior iliac spine level at an angle of 30-45 degrees downward toward the outside. Injecting the drugs penetrating the ligament continued to give a feel slightly outward to avoid the iliac Cattelan 23 G needle. We confirmed pain assessment NRS at 11 (0-10), and the improvement of pain was assessed with the change of the NRS on the next return. RESULTS: NRS showed a significant decrease at all points in time before block, their pain decreased gradually. The patients showed NRS improvement of more than 50% of the first block in 15 of 24 patients. CONCLUSIONS: Block at the posterior sacroiliac ligament region significantly reduced pain for chronic intractable low back pain. The block was shown to be effective as a treatment and for diagnosis.

[Comparison of intraoperative stress hormones release between propofol-remifentanil anesthesia and propofol with epidural anesthesia during gynecological surgery].

BACKGROUND: Remifentanil recently comes to be used for intraoperative analgesia instead of epidural anesthesia in gynecological surgery. It seems to offer the same stability in vital signs, but stress response during remifentanil anesthesia has not been evaluated. Therefore, we compared remifentanil anesthesia with epidural anesthesia regarding stress hormones. METHODS: Fifty-one patients scheduled for surgery were randomized into two groups (epidural group: E and remifentanil group: R). Anesthesia was maintained with propofol and epidural ropivacaine in E, and with propofol and remifentanil in R. Plasma concentrations of adrenaline, noradrenaline, dopamine (DOA), cortisol, adorenocorticotropic hormone (ACTH), and blood glucose were measured at five points during the perioperative period. RESULTS: Adrenaline, noradrenaline and blood glucose were not significantly different between the groups at any point. DOA was significantly higher in R than E at skin closure. Cortisol was significantly higher in R than E at three points during operation. ACTH was significantly higher in E than R at skin closure. CONCLUSIONS: The inhibition of stress hormone secretion during operation was less in R than E. Regarding stress response, total intravenous anesthesia with remifentanil seems to be a proper method, but to have less potency than general anesthesia using epidural block.

[The direction and the position of epidural catheter tips inserted 5 cm or 7 cm cephalad did not differ].

BACKGROUND: Epidural catheter insertion is a common procedure in gynecological surgeries. At a previous study, we investigated the catheter's direction and position, inserted 7cm cephalad from T12-L1, with postoperative plain X-P using picture archiving communication system (PACS). 74% of the catheters advanced in cephalad direction and 71.4% of the catheter tips stayed within one vertebra from the puncture level. We estimated that the catheters were too long to advance straight. Then, we planned another prospective study to compare the catheter advanced 7 cm or 5 cm regarding its direction and tip position. METHODS: Fifty-one female patients receiving gynecological surgery were enrolled. Epidural catheters were inserted from T12-L1 intervertebral space in cephalad direction for the length of 5 cm confirmed with postoperative plain X-P using PACS. The catheter's direction, the length, and the position were verified and compared with the result of the previous study. RESULTS: The catheters going cephalad appeared more frequently among 5 cm group than 7 cm group. Those going caudalad appeared more frequently among 7 cm group than 5 cm group. However, the catheter tip final position and the length from the puncture levels were not significantly different between the groups. CONCLUSIONS: The direction and the position of epidural catheter inserted 5 cm or 7 cm cephalad did not differ.

[Assessment of the quality of the newly developed rapid oscillometric blood pressure measurement].

BACKGROUND: The purpose of this study is to examine the accuracy of the Fukuda Denshi DS-7000 noninvasive blood pressure measurement device equipped with two cuff deflation mode: a normal mode and quick mode. METHODS: Twenty-one patients undergoing elective surgery were divided into two groups by using cardio-ankle vascular index (CAVI): no atherosclerotic group and atherosclerotic group. During anesthesia, two modes of blood pressure measurements were examined with the normal mode followed by the quick mode. RESULTS: All the patients completed the study, resulting in a total of 1034 paired blood pressure measurements. In both no atherosclerotic group and atherosclerotic group, there were statistically significant correlations among systolic, diastolic and mean blood pressure in two modes. This results certified the accuracy of the quick mode measurement. CONCLUSIONS: The newly developed rapid oscillometric blood pressure measurement can be useful for perioperative management especially in atherosclerotic patients.

[Anaphylactic reaction to epidural block in an outpatient].

A healthy 29-year-old woman received epidural block for severe lumbago in an outpatient clinic. Fifteen minutes after injection of mepivacaine 0.5% with dexamethasone into the epidural space, the patient complained of itching of eyelids followed by generalized pruritus. Hypotension, erythema and generalized urticaria were observed. Initial treatment was with 100% oxygen through face mask, and additional intravenous fluids, followed by administration of adrenaline, chlorpheniramine and dopamine. Cardiac ultrasound examination showed mildly impaired movement of inferior to septal wall. Her plasma histamine level was transiently elevated during the anaphylactic event; however the serum tryptase level was not. Biological assays for confirming the causative agent and cutaneous test were all negative, but clinical symptoms positivity showed nonimmunological anaphylactic reaction to mepivacaine or dexamethasone. This case report confirms the need for systematic allergological investigation in a case of immediate hypersensitivity reaction occurring during nerve block in patients who had even received similar nerve blocks repeatedly. Pain clinician should be aware of the possibility of anaphylactic reactions involving any drug or substance used for an outpatient.

[Confirmation of the position of the epidural catheter regarding its intended direction and location for lumbar epidural block].

BACKGROUND: Epidural catheter insertion is a common procedure for gynecological surgeries. Epidural puncture is usually performed according to the anatomical landmarks without radiographic means. The aim of his study was to confirm the actual level of puncture, and the distance as well as the direction of epidural catheters threaded. METHODS: Seventy-seven female patients receiving epidural anesthesia were enrolled. Epidural catheter was inserted from T12-L1 intervertebral space in cephalad direction for the length of 7 cm. The catheter was confirmed with postoperative plain X-P using picture archiving communication system. The intended direction and length were compared with the actual data. In addition, we retrospectively analyzed the factors including the performers (resident vs. specialist), the approaches of puncture (median vs. paramedian), and patient physical factors (age, height, body weight, and BMI). RESULTS: Of the catheters 54.6% was inserted from T12-L1, and 74% of them were advanced in cephalad direction. Of the tip of the catheter 71.4% stayed within one vertebra from the puncture level. The puncture accuracy, the frequency of catheter threaded over one vertebra, and the frequency of catheters threaded in cephalad direction did not differ significantly among performers, approaches and patients physical factors. CONCLUSIONS: Only 11.7% of the catheters were actually inserted from T12-L1 and advanced in cephalad direction over one vertebra as we had intended.

[Efficacy of traditional herbal medicine, Yokukansan on patients with neuropathic pain].

BACKGROUND: Neuropathic pain that is the chronic, severe, and intractable pain, interferes with activities of daily living (ADL) and consequently reduces quality of life (QOL). We reported the efficacy of Yokukansan in patients with neuropathic pain, including acute herpetic pain, postherpetic neuralgia, central poststroke pain, post-traumatic spinal cord injury pain, thalamic syndrome, complex regional pain syndrome and symptomatic trigeminal neuralgia. Yokukansan was more effective compared with traditional medicines, such as tricyclic antidepressants, carbamazepine, gabapentin, and opioids etc., which are recommended to treat neuropathic pain. Recently, effects of Yokukansan is reported on the behavioral and psychological symptoms of dementia (BPSD) in elderly patients with dementia. Repeated administration of Yokukansan decreases expression of 5-hydroxytryptamine (5-HT) 2A receptors in the prefrontal cortex in mice, and Yokukansan also protects destruction of myelin sheaths in rats with thiamine deficient-induced encephalopathy. Mechanism of effectiveness of Yokukansan on neuropathic pain has not been established; however, efficacy of Yokukansan on neuropathic pain has been shown clinically. CONCLUSIONS: As far as we know, this is the first report that Yokukansan was effective on neuropathic pain. Yokukansan without serious adverse reactions may be a possible medicine for treatment of neuropathic pain in future.

[Retrospective evaluation of optimal doses of fentanyl by patient-controlled epidural analgesia in management of postoperative pain after gynecological surgery in the elderly].

BACKGROUND: Patient controlled epidural analgesia (PCEA) is a useful method in alleviation of postoperative pain; however, PCEA sometimes provided inadequate pain relief in the elderly. Therefore, we investigated optimal doses of fentanyl by PCEA in management of postoperative pain after gynecological surgery in the elderly. METHODS: We investigated the pain at rest using 100 mm visual analogue scale (VAS) on the 1st day and 2nd day after the operations. Patients were divided into two groups ; one was well-controlled group (WC group, VAS < 20 mm) and the other was poorly-controlled group (PC group, VAS > or =20 mm). In two groups, we retrospectively compared doses of fentanyl in PCEA, number of demand-PCEA, postoperative nausea as well as vomiting, and delirium during 48 hrs after the operations. RESULTS: The mean age in WC group was significantly higher than that in PC group. The total dosage of epidural fentanyl did not differ significantly between the groups. In WC group fentanyl of 0.172 microg x kg(-1) hr(-1) was given, and fentanyl 0.197 microg x kg(-1) x hr(-1) in PC group. CONCLUSIONS: We found that fentanyl 0.172 microg x kg(-1) x 1 hr(-1) by PCEA was the most appropriate dose for alleviation of postoperative pain after gynecological surgery in the elderly.

[Yokuininto improves treatment resistant burning pain in legs].

Yokuininto was effective in treating burning pain in both lower legs of a 58-year-old woman. She felt her lower legs feverish: however, no neurological deficit or abnormal finding in angiography was found. The burning pain was increased by cold and decreased by warm, but was alleviated by epidural block with local anesthetics. After 2-week medication of Yokuininto, burning pain was reduced to 20 to 30% and fever in legs disappeared. Yokuininto has been used for chronic pain in muscle and joint accompanied by swelling or local fever. This patient had no joint pain or swelling, but her burning pain was considered to have resulted from some abnormality in blood circulation due to disorder in discharge of water in the body.

[Effective treatment of acute pain and related symptoms in elderly with herpes zoster].

BACKGROUND: The incidence of herpes zoster increases with age. Immediate pain relief is required for prevention of postherpetic neuralgia (PHN) and also its related symptoms that worsen the general condition because acute herpetic pain often interferes with sleep, mood, and general activities in elderly patients. Nerve block is useful to relief acute pain and recommended for prevention of PHN. Tricyclic antidepressant drugs have antinoticeptive effect in acute pain in experimental models, in addition to its antidepressant effect. METHODS: Forty elderly patients with herpes zoster within 3 months after the onset underwent nerve blocks and received tricyclic antidepressant drugs. We assessed the effect of treatments and adverse effects. RESULTS: No significant adverse effects were found in elderly patients who had received nerve blocks and/or tricyclic antidepressant drugs. Alleviation of acute pain was obtained in more than 80% of patients, and in all patients depressive state and/or disturbance of the general condition were significantly improved. CONCLUSIONS: With careful technique and assessment of patients, both nerve block and tricyclic antidepressant drugs were beneficial and safe treatments in elderly patients with herpes zoster.

Vasopressin may be useful in the treatment of systemic anaphylaxis in rabbits.

Recent studies demonstrate that vasopressin is useful when treating hemorrhagic and septic shock. The effect of vasopressin on systemic anaphylaxis has not been investigated except in clinical case reports. Vasopressin increases blood pressure because of vasoconstriction through the V1 receptor. Thus, we evaluated the effect of vasopressin on circulatory depression and bronchoconstriction provoked by systemic anaphylaxis and survival rates in rabbits. In the first set of experiments, 15 nonsensitized rabbits received normal saline (control) and vasopressin at 0.8 or 0.08 U/kg. In the second set, 40 sensitized rabbits received horse serum to induce anaphylaxis, and then received the same drugs as in the first set. In the first set, mean arterial pressure (MAP) in vasopressin groups increased by 18% to 24% compared with the control. Vasopressin at 0.8 U/kg decreased MAP insignificantly before the increases of MAP occurred. In the second set, vasopressin at 0.08 U/kg improved the survival rate. At 45 min after antigen challenge, 69% of the rabbits that received vasopressin at 0.08 U/kg were alive, whereas 29% of the control rabbits and 23% of the rabbits that received vasopressin at 0.8 U/kg were alive. Vasopressin increased MAP by 36% to 109% compared with the control within 5 min, however, at 2 min, vasopressin at 0.8 U/kg had no effect on MAP. Pulmonary dynamics were similar. In conclusion, vasopressin at 0.08 U/kg improved survival rates and severe hypotension provoked by systemic anaphylaxis, suggesting that this agent may be useful in the treatment of systemic anaphylaxis.

Addition of 0.1% bupivacaine to buprenorphine and droperidol in patient-controlled epidural analgesia improved postoperative pain scores on coughing after gynecological surgery.

STUDY OBJECTIVE: To compare the analgesic efficacy of additional 0.1% bupivacaine to patient-controlled epidural analgesia (PCEA) using buprenorphine and droperidol after gynecological surgery. DESIGN: Randomized, double-blinded study. SETTING: Operating theater and general ward at Jichi Medical School Hospital. PATIENTS: Thirty patients with American Society of Anesthesiologists physical status I and II scheduled for gynecological surgery. INTERVENTIONS: Patients received combined general and epidural anesthesia for surgery and epidural analgesia for postoperative analgesia. Patients were assigned to receive PCEA with or without 0.1% bupivacaine. Group 1 (n = 15) received buprenorphine 20 microg and droperidol 0.1 mg diluted with saline, and group 2 (n = 15) received bupivacaine 2 mg, buprenorphine 20 microg, and droperidol 0.1 mg diluted with saline (0.1% bupivacaine solution) in a bolus dose of the PCEA, respectively. No background epidural infusion was used. MEASUREMENTS: Visual analog pain scale (VAPS) scores at rest and on coughing, and cumulative frequency of self-administrated analgesic solution in PCEA were recorded at 24 and 48 hours postoperatively. MAIN RESULTS: There were no significant differences noted between the groups in VAPS scores at rest or in cumulative volumes of PCEA solution in 24 or 48 hours postoperatively. Median VAPS scores on coughing in group 2 were significantly lower than those values in group 1 at 24 hours (36 vs 65 mm, P < .001) and 48 hours (32 vs 54 mm, P = .036) postoperatively. CONCLUSIONS: Addition of 0.1% bupivacaine to PCEA using buprenorphine and droperidol provides better analgesia on coughing after gynecological surgery.

[Diphenhydramine is useful in a parturient with hypersensitivity to local anesthetics to manage her delivery].

We did an obstetric management of a parturient, aged 32 years, with a history of local anesthetic hypersensitivity. The results of histamine release test, and cellular antigen stimulation test with lidocaine, mepivacaine, bupivacaine and preservative-free lidocaine during her pregnancy showed that all local anesthetics studied were positive. We used diphenhydramine as an alternative local anesthetic for episiotomy to the parturient during the delivery. Infiltration with diphenhydramine provided adequate analgesia without noticeable adverse reaction. One month after the delivery, we performed provocative challenge test with local anesthetics, and confirmed she had positive tests to lidocaine, mepivacaine and preservative-free lidocaine, and negative test to bupivacaine. Diphenhydramine is an adequate alternative of local anesthetics in patients with history of hypersensitivity to local anesthetics.

Hypotension associated with systemic aggregated anaphylaxis is not attenuated by a selective endothelin-A receptor antagonist, BQ 610, in rabbits in vivo.

PURPOSE: The present study was done to investigate the role of endothelin-1 (ET-1) in hypotension and bronchospasm provoked by anaphylaxis in rabbits in vivo. METHODS: Forty-five rabbits sensitized to horse serum were randomly allocated to five groups: Group 1 (n = 10) received 0.5 nmol x kg(-1) of ET-1; Group 2 (n = 10) received 0.5 nmol x kg(-1) of ET-1 and 200 nmol x kg(-1) of a selective ETA receptor antagonist, BQ 610, without anaphylaxis; Group 3 (n = 5) received 200nmol x kg(-1) of BQ 610 alone without anaphylaxis, Group 4 (n = 10) received normal saline alone before being antigen challenged to induce anaphylaxis; Group 5 (n = 10) received 200 nmol x kg(-1) of BQ 610 before antigen challenge. RESULTS: Mean arterial pressure (MAP) values were significantly different between Groups 1 and 2. Heart rate (HR), central venous pressure (CVP), dynamic pulmonary compliance (C(dyn)), and pulmonary airway resistance (R(L)) did not differ significantly between Groups 1 and 2. MAP values were significantly decreased compared with baseline in both Groups 4 and 5; however, the values were not significantly different between two groups. CVP values were significantly different between Groups 4 and 5 only at the 15-min time point following antigen challenge. HR, R(L), and C(dyn) values were not significantly different between Groups 4 and 5, nor were the survival rates. CONCLUSION: BQ 610 does not improve hypotension or survival rates in systemic aggregated anaphylactic rabbits in vivo, implying that circulating ET-1 may not play an important role in anaphylaxis, although direct proof of production of circulating ET-1 or activation of ETA receptors is lacking in this study.