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This article presents a brief historical perspective of the F Breathing Circuit, a universal single-limb breathing circuit. The single-limb breathing circuit (tube within a tube configuration) comprises two tubes of sufficient size and compliance, so that either channel enables safe, unrestricted inspiration/expiration at all times in spontaneous and controlled ventilation. The single-limb circuit can function in various modes: as an anesthetic circle circuit as well as a Mapleson-type rebreathing circuit and as a non-rebreathing circuit (e.g., with ICU ventilators) in adult and pediatric patients. Therefore, it qualifies as a universal breathing circuit. Since its first introduction in Japan (1978), which was followed by further modifications and improvements, the circuit was made available in USA and worldwide.

Chronic orofacial pain is often refractory to conventional pain therapies. We conducted an open-label study to determine whether adenosine 5'-triphosphate (ATP) could alleviate chronic intractable orofacial pain, and if so, which type of pain could respond to ATP.In 8 and 16 patients with non-neuropathic and neuropathic intractable orofacial pain, respectively, ATP was intravenously infused at a rate of 100 microgxkg(-1)xmin(-1) over 120 min. The magnitudes of spontaneous pain and brush-evoked allodynia were graded with a visual analog scale (VAS). When a VAS score for spontaneous pain was decreased by 50% or more by ATP, the patient was classified as a responder.The patients could be clearly divided into 10 responders and 14 non-responders. Ten of the 16 patients (62.5%) with neuropathic pain, but none of the 8 patients with non-neuropathic pain, responded to ATP. In particular, all of 8 patients with neuropathic pain following pulpectomy, with or without subsequent tooth extraction, responded to ATP. In the 10 responders, VAS scores for spontaneous pain decreased slowly but progressively during the infusion period, and eventually, ATP reduced the VAS scores for spontaneous pain and allodynia by 82 +/- 15% and 74 +/- 9%, respectively. In these responders, the analgesic and anti-allodynic effects of ATP outlasted the infusion period for medians of 7 and 12 h, respectively.Intravenous ATP did not relieve non-neuropathic orofacial pain. However, it exerted slowly expressed but long-lasting analgesic and anti-allodynic effects in patients with neuropathic orofacial pain, especially in those suffering from neuropathic pain following pulpectomy and/or tooth extraction.

UNLABELLED With a traditional clamp test alone, quantitative evaluation of the level of surgical anesthesia/analgesia is not easy. We have developed a rabbit model that allows for repeated quantification of the varying level of surgical anesthesia/analgesia using both mechanical and electrical stimulation as simulated surgical stimuli. After tracheostomy and intravascular cannulations under isoflurane anesthesia, eight rabbits were placed on a sling that allowed for free movement of the head and extremities. The inspired isoflurane concentration was reduced from 3% to 1.5% and then to 0%. Remifentanil was then infused at 4 graded infusion rates (0.1-0.8 microg. kg(-1) x min(-1)). At each drug dose, analgesic variables were determined including the number of animals behaviorally unresponsive to clamping the forepaw (nonresponders) and threshold voltage of subcutaneous electrical stimulation (2 Hz, 5 Hz, and 50 Hz) required to evoke the head lift (HLT, pain detection/arousal threshold) and escape movement responses (EMT, pain tolerance threshold). With increasing drug doses, HLTs and EMTs at 5 Hz increased dose-dependently and most proportionately to increases in the number of nonresponders, a standard indicator of the anesthetic/analgesic level. Therefore, using the HLT and EMT at 5 Hz combined with a clamp test, this rabbit model allows for quantitative evaluation of the varying level of surgical anesthesia/analgesia. IMPLICATIONS We have developed a rabbit model of surgical anesthesia and analgesia using both mechanical and electrical stimulation as simulated surgical stimuli, which allows for repeated, quantitative, and qualitative evaluation of the varying level of surgical anesthesia and analgesia, differentiation between sedative/hypnotic and analgesic components of drug actions, and simultaneous monitoring of all the clinically relevant physiological variables including cardiovascular and respiratory variables.

In this study, by measuring bispectral index (BIS), we tested the hypothesis that intravenous adenosine 5′-triphosphate (ATP) infusion would deepen the level of midazolam-induced sedation. Ten healthy volunteers underwent 2 experiments with at least 2 weeks' interval: immediately after intravenous bolus administration of midazolam (0.04 mg/kg), they received continuous infusion of either ATP infusion (100 μg/kg/min) or placebo (saline) for 40 minutes in a double-blind, randomized, crossover manner. Changes in BIS values and responsiveness to verbal command as well as cardiorespiratory variables were observed throughout the study periods. Administration of midazolam alone reduced BIS value from control: 97 ± 1 to 68 ± 18 at 25 minutes, which was accompanied by significant cardiopulmonary depressant effects, while maintaining responsiveness to verbal command (consciousness) throughout the study period. Coadministration of ATP with midazolam further reduced BIS value to 51 ± 13, associated with complete loss of consciousness without adverse effect on the cardiorespiratory systems. We conclude that the addition of ATP infusion to midazolam significantly enhances midazolam sedation without disturbing cardiorespiratory functions.

Propofol is frequently used for intravenous sedation or anesthesia in ambulatory and office-based anesthesia. Although awakening is usually rapid, there are instances of delayed recovery from propofol anesthesia. It has been reported that aminophylline antagonizes the sedative effects of several anesthetic and analgesic drugs. The case reports presented here demonstrate that intravenous aminophylline effectively reversed prolonged propofol-induced sedation/anesthesia in the postoperative period. There were no side effects or delayed re-sedation after the administration of aminophylline. Our study suggests that aminophylline could be a clinically useful propofol antagonist.

BACKGROUND Adenosine and remifentanil are potent IV analgesics with ultrashort half-lives. The antinociceptive effect of IV adenosine has not been clearly characterized. We compared the antinociceptive effects of adenosine and remifentanil in rabbits. METHODS Sixteen rabbits, placed on a sling allowing reasonably free movement, received IV adenosine (400 microg x kg(-1) x min(-1)) or remifentanil (0.4 microg x kg(-1) x min(-1)) over 240 min. RESULTS Both drugs produced profound antinociception, as assessed by the number of animals unresponsive to clamping the forepaw and the electrical stimulation threshold of escape movement. With remifentanil, the antinociceptive effect increased rapidly, reaching its peak at 60 min, and then began to decline despite continued infusion. After stopping the infusion, it decreased rapidly and disappeared within 30 min. The vasodilating effect of IV adenosine was immediate in onset and ultrashort in duration. The antinociceptive effect of adenosine increased slowly but progressively during the infusion, reaching its peak only when the infusion ended. Then it decreased slowly over the following 360 min after terminating the infusion. CONCLUSION Remifentanil had a rapid onset and short duration of action, and probably showed signs of tolerance development, whereas the antinocieptive effect of adenosine was slow in onset and long-lasting, despite its ultrashort plasma half-life and the immediate on-off profiles of its vasodilating effect.

The use of low-flow anesthesia causes a discrepancy between the delivered fraction (FD) and the inspired fraction (FI) of inhaled gases. We compared the FI/FD ratios of a new circle (fresh gas inlet located between the inspiratory valve and the patient) to those of the conventional circle (fresh gas inlet located between the inspiratory valve and the CO2 absorber) in low-flow isoflurane and sevoflurane anesthesia, using three anesthetic machines (Drager NM-GS, Drager Fabius-GS, and ACOMA KMA-1300-III). Eighty-two patients were randomly assigned to three experimental groups. For experiment 1, 32 patients were allocated to the NM-GS conventional/new, NM-GS new/conventional, ACOMA conventional/new, and ACOMA new/conventional groups. For experiment 2, 14 patients were allocated to ACOMA conventional/conventional and ACOMA new/new groups to measure isoflurane FI/FD ratios. For experiment 3, 36 patients were allocated to ACOMA conventional/conventional, ACOMA new/new, Fabius conventional/conventional, and Fabius new/new to measure sevoflurane FI/FD ratios. In experiment 1, the NM-GS showed no significant changes in the FI/FD ratios. However, in the ACOMA, the new circle improved the FI/FD ratio. In experiment 2, the isoflurane FI/FD ratios in the new circle of the ACOMA were significantly higher than those in the conventional circle. In experiment 3, the sevoflurane FI/FD ratios in the new circle of both the ACOMA and the Fabius were significantly higher than those in the conventional circles. The positioning of the fresh gas inlet between the inspiratory valve and the patient improved the FI/FD ratios of both isoflurane and sevoflurane during low-flow anesthesia in two decoupling-style anesthetic machines (ACOMA and Fabius).

This review summarizes clinical application of adenosine and adenosine 5'-triphosphate (ATP) in pain conditions. Investigations have been performed in patients with acute perioperative pain or chronic neuropathic pain treated with intravenous adenosine or ATP, or intrathecal adenosine. Characteristic central adenosine A1 receptor-mediated pain-relieving effects have been observed after intravenous adenosine infusion in human inflammation/sensitization pain models and in patients with chronic neuropathic pain. Adenosine compounds, in low doses, can reduce allodynia/hyperalgesia more consistently than spontaneous pain, suggesting that these compounds affect neuronal pathophysiological mechanisms involved in central sensitization. Such pain-relieving effects, which are mostly mediated via central adenosine A1 receptor activation, have a slow onset and long duration of action, lasting usually for hours or days and occasionally for months. With acute perioperative pain, treatment with a low-dose infusion of adenosine compounds and the A1 receptor-mediated central antisensitization mechanisms may play only a minor part in the total perioperative pain experience. By administering sufficient doses of adenosine compounds during surgery, however, significant and long-lasting perioperative pain relief can be achieved via central A1 receptor-mediated antinociceptive/analgesic actions as well as via peripheral A2a or A3 receptor-mediated antiinflammatory actions. Thus, adenosine compounds have significant potential for alleviating various types of pain.

No study has been performed on the analgesic effect of adenosine 5'-triphosphate (ATP) on postherpetic neuralgia (PHN). We conducted an open-label trial of ATP in patients with PHN, and compared ATP with ketamine and lidocaine.Twelve patients with PHN were studied. On separate days, ketamine (0.3 mg.kg(-1)), lidocaine (2 mg.kg(-1)), and ATP (100 microg.kg(-1).min(-1) or less for 120 min) were administrated intravenously. The intensity of spontaneous pain as well as tactile allodynia was assessed using a visual analog scale (VAS). When the VAS score for spontaneous pain was decreased by more than 50%, the patient was classified as a responder.Five, 6, and 6 patients responded to ketamine, lidocaine, and ATP, respectively. In 6 ATP responders, pain relief developed slowly and lasted for 9 (median) h (range: 3-72 h). All 5 ketamine responders and only 1 of 7 ketamine nonresponders responded to ATP (5/5 vs 1/7, P0.05, chi2 test) whereas 2 of 6 responders to lidocaine and 4 of 6 nonresponders to lidocaine responded to ATP (2/6 vs 4/6, P0.05). The ketamine responders responded to ATP more often than did the lidocaine responders (5/5 vs 2/6, P0.05).Intravenous ATP exerted slowly developing and long-lasting analgesic effects in half of patients with PHN. Patients with ketamine-responsive PHN were likely to respond to ATP.

UNLABELLED Although acute tolerance to analgesia develops rapidly with remifentanil, it is unknown whether acute tolerance also develops to its nonanalgesic effects. We investigated the analgesic and cardiorespiratory effects of remifentanil during a continuous infusion in a rabbit model. Ten tracheotomized New Zealand White rabbits with arterial and venous accesses were placed on a sling that allowed for reasonably free movement. In spontaneously breathing conscious animals, remifentanil was infused IV at a constant-rate of 0.3 microg kg(-1)x min(-1) for 360 min. Sedative/analgesic and cardiorespiratory variables were assessed repeatedly during remifentanil infusion, including the number of animals behaviorally unresponsive to clamping the forepaw (nonresponders) and subcutaneous electrical stimulation thresholds required to elicit head lift (HLT: pain detection/arousal threshold) and escape movement responses (EMT: pain tolerance threshold). Within 60-120 min of starting the infusion, the number of nonresponders, HLT, EMT, and PaCO(2) increased significantly, whereas blood pressure, heart rate, and respiratory rate decreased. Thereafter, all variables returned towards preinfusion levels despite continuing infusion. These results indicate that during a remifentanil infusion acute tolerance develops for both its analgesic and cardiorespiratory effects. IMPLICATIONS Using a new rabbit model, we found that during continuous, constant-rate remifentanil infusion acute tolerance developed within the first few hours, not only to its analgesic but also to its cardiovascular and respiratory effects, albeit in slightly different time courses.

Perioperative pain is still a major problem, and new pharmacological means should be explored to mitigate such pain. Adenosine is an ubiquitous endogenous substance; when exogenously administered, it provides a number of salutary effects including neuromodulation, antinociception, and cytoprotective actions. The aim of this study was to characterize the perioperative antinociceptive-analgesic effects of intraoperative adenosine infusion and determine the duration of actions in the postoperative period, and compare them to those of remifentanil in patients undergoing major surgical procedures in a double-blind study.Sixty-two patients were randomly assigned to one of the two treatments. After standard induction of anesthesia, the lungs were mechanically ventilated. Anesthesia was maintained with a constant alveolar concentration of inhaled anesthetics (3% desflurane and 65% nitrous oxide in oxygen). A variable-rate of intravenous infusion of adenosine (50-500 microg kg(-1) x min(-1)) or remifentanil (0.05-0.5 microg kg(-1) x min(-1)) was initiated 5 min before the skin incision and was titrated to maintain systolic blood pressure and heart rate within 20% of baseline values during surgery. Postoperative evaluations included the level of sedation, degree of pain severity, opioid analgesic (fentanyl, morphine) consumption, and cardiorespiratory variables for 48 h. Intraoperative inhibition of the cardiovascular responses to surgical stimulation could be equally achieved by adenosine or remifentanil, and both could maintain excellent hemodynamic stability. Postoperatively, however, there were striking differences: (1). initial pain score was reduced by 60% (P0.001) in the adenosine group compared to the remifentanil group and it remained lower throughout the 48 h recovery period; (2). postoperative morphine requirements during the first 0.25, 2 and 48 h were consistently lower in the adenosine group as compared to the remifentanil group (78, 71 and 42%, P0.001, respectively); (3). adenosine patients remained significantly less sedated at all evaluations; (4) the end-tidal and arterial carbon dioxide values in the remifentanil group were significantly higher when patients were admitted to the postanesthesia care unit. No adverse effect of adenosine was observed at any time. Intraoperative adenosine infusion provided a salutary recovery from anesthesia associated with a pronounced and sustained postoperative pain relief. Compared to remifentanil, adenosine significantly reduced the opioid requirements and minimized the side effects including protracted sedation, cardiorespiratory instability, nausea, and vomiting in the postoperative recovery period.

Hemodynamic responses, blood gas, and metabolic changes were assessed when large dosages of a pre-mixed solution of adenosine or adenosine triphosphate (ATP) with catecholamine were intravenously administered in the conscious, spontaneously breathing rabbit. The present study offers a simple and effective approach to enabling safe administration of large doses of the potent vasodilators, adenosine or ATP with minimal cardio-respiratory and metabolic changes.

The effects of ATP on the isometric contractions of isolated rat left ventricular papillary muscle were studied. Exogenously administered ATP had an immediate onset, an abrupt response, progressive recovery and produced dose-related depression in the peak developed tension, maximum rate of tension development and relaxation, which were statistically significant. There were no significant changes in the resting tension, time to peak tension and relaxation time, except for a significantly prolonged relaxation time at the highest concentration of ATP. In the studies of interactions of ATP and either epinephrine or Ca(++), we observed that ATP seemed to interfere with the inotropic effect of epinephrine, while Ca(++) antagonized the negative inotropic action of ATP. We conclude that the site of negative inotropic action of ATP is most likely on the cell membrane, where ATP interferes with Ca(++) flux, and that ATP interferes with the positive inotropic action of epinephrine.

Adenosine triphosphate (ATP) has been reported to be a hypotensive agent similar in effect to sodium nitroprusside (SNP). The purpose of this study was to examine and compare the effects of both SNP and ATP on general coronary hemodynamics, myocardial O2 consumption, and circulating catecholamines. Twelve dogs were anesthetized with 1.0% halothane and given either SNP or ATP by controlled infusion to reduce their systemic blood pressure by 50% for a 2-h period followed by a (blood pressure) recovery period. The ATP-induced hypotension was rapid, easily controlled, not accompanied by tachyphylaxis over the 120 min studied, and resulted in an increase in coronary sinus blood flow (CSBF), which plateaued at 260% above control. The increase in CSBF was almost immediate and remained at this elevated level for the duration of the induced hypotension. During the ATP-induced hypotension, there was no change in heart rate or circulating catecholamines. A 60% reduction in myocardial O2 uptake was observed, presumably from the cardiac unloading. In contrast, SNP-induced hypotension required a marked increase in dose over time, did not significantly increase CSBF, did increase heart rate, and resulted in large increases in circulating plasma catecholamines. Neither agent affected cardiac output. ATP-induced hypotension resulted in no change in cardiac lactic acid uptake, while SNP caused lactic acid production, indicating possible cardiac ischemia or cyanide toxicity.

Adenosine triphosphate (ATP) has been reported to be a hypotensive agent similar in effect to sodium nitroprusside (SNP). The purpose of this study was to examine and compare the effects of both SNP and ATP on general coronary hemodynamics, myocardial O2 consumption, and circulating catecholamines. Twelve dogs were anesthetized with 1.0% halothane and given either SNP or ATP by controlled infusion to reduce their systemic blood pressure by 50% for a 2-h period followed by a (blood pressure) recovery period. The ATP-induced hypotension was rapid, easily controlled, not accompanied by tachyphylaxis over the 120 min studied, and resulted in an increase in coronary sinus blood flow (CSBF), which plateaued at 260% above control. The increase in CSBF was almost immediate and remained at this elevated level for the duration of the induced hypotension. During the ATP-induced hypotension, there was no change in heart rate or circulating catecholamines. A 60% reduction in myocardial O2 uptake was observed, presumably from the cardiac unloading. In contrast, SNP-induced hypotension required a marked increase in dose over time, did not significantly increase CSBF, did increase heart rate, and resulted in large increases in circulating plasma catecholamines. Neither agent affected cardiac output. ATP-induced hypotension resulted in no change in cardiac lactic acid uptake, while SNP caused lactic acid production, indicating possible cardiac ischemia or cyanide toxicity.

In the anesthetic management of five patients undergoing excision of pheochromocytoma, adenosine triphosphate (ATP) was used for the purpose of regulating systemic arterial pressure during the period of tumor manipulation. ATP was administered at doses of 0.05-0.4 mg/kg/min. Systemic arterial pressure showed a significant decrease from 162 +/- 17/103 +/- 11 mmHg before manipulation to 136 +/- 21/81 +/- 10 mmHg during the manipulation period. The plasma catecholamine levels showed significant increases in this period. Immediately after excision, the systemic arterial pressure was maintained at normal levels (118 +/- 13/75 +/- 16 mmHg) by fluid replacement and discontinuation of ATP administration, subsequently becoming 129 +/- 19/79 +/- 16 mmHg. The heart rate was very stable and tachycardia did not occur during the manipulation period. Only one arrhythmic episode occurred in one patient. The systemic vascular resistance index was significantly lower during the manipulation period than before it. It was therefore considered that ATP was useful as an agent for controlling arterial pressure during the anesthesia for pheochromocytoma.

The palpebral conjunctiva is a very special tissue. The mucous membrane epithelium overlying the conjunctival capillaries is only two to four cell layers thick with minimum oxygen consumption, and this presents a unique opportunity to measure tissue oxygen tension atraumatically [1]. The transconjunctival oxygen monitor measures tissue oxygen tension, which reflects both the oxygen content of the arterial blood and the regional blood flow. If arterial oxygen content remains constant, then any change in tissue oxygen tension should be secondary to a change in the blood flow to that tissue. The purpose of this study was to examine the relationship between the conjunctival PO2 (PcjO2, in millimeters of mercury) and carotid artery blood flow (CaBF, in millimeters per minute) in the dog during hemorrhagic hypotension.

Hypotensive effects of the intravenous injection of adenine compounds [adenosine triphosphate (ATP), adenosine] were compared with those of sodium nitroprusside (SNP) in rabbits during light, stable halothane anesthesia. ATP and adenosine were almost equipotent in their effects on blood pressure and heart rate. The hypotensive potencies of ATP and adenosine were approximately 1/6 (bolus injection) and 1/40 (continuous infusion) that of SNP, but the adenine compounds had a more rapid onset of action and shorter recovery times than SNP. With bolus injection, SNP invariably caused a baroreceptor-mediated reflex increase in heart rate. In contrast, ATP and adenosine caused a dose-related decrease in heart rate and hypotension. With continuous infusion, ATP and adenosine produced immediate onset of hypotension without tachycardia. Blood pressure remained remarkably stable throughout the infusion; neither tachyphylaxis nor rebound hypertension were observed. Thus, the adenine compounds offer possible advantages over SNP as they are physiologic agents with little or no acute toxicity and may be devoid of tachycardia, tachyphylaxis, and rebound hypertension.