磯野 史朗

On the basis of two observations that avoiding prone sleeping decreased incidence of sudden infant death syndrome and that obstructive sleep apnea is closely linked with the syndrome, we hypothesized that the prone position may increase upper airway collapsibility in infants and small children. Passive pharyngeal collapsibility of 19 infants and small children (10-101 weeks old) was examined in three postures: supine with face straight up, supine with neck rotated, and prone with neck rotated. The collapsibility was evaluated with the maximal distension of the most collapsible region, pharyngeal stiffness, and pharyngeal closing pressure, estimated from static pressure-area relationship of the passive pharynx. No significant changes in pharyngeal stiffness were detected; however, maximal distension was reduced in the prone position (mean +/- SD, 0.56 +/- 0.26 versus 0.44 +/- 0.20 cm(2); supine with face straight up versus prone position, p < 0.05). Pharyngeal closing pressure increased at neck rotation in the supine position (-4.5 +/- 2.4 versus -2.8 +/- 2.3 cm H(2)O; supine with face straight up versus supine with neck rotated, p < 0.05), and a further increase was observed in the prone position (-0.3 +/- 2.9 cm H(2)O, p < 0.05 versus supine with neck rotation). Pharyngeal closing pressure in the prone position was above atmospheric pressure in half of our subjects, whereas all subjects had negative pharyngeal pressure in the supine position. We conclude that the prone position increases upper airway collapsibility, although the mechanism is yet unclear.

Obesity and craniofacial abnormalities may contribute to the pathogenesis of obstructive sleep apnea. The purpose of this study was to evaluate the influence of body habitus and craniofacial characteristics on types of pharyngeal closure. The types of pharyngeal closure were determined by endoscopic evaluations of closing pressures of the passive pharynx in 54 paralyzed and anesthetized patients with sleep-disordered breathing (SDB). Assessment of craniofacial characteristics of the SDB patients and 24 normal subjects were made by lateral cephalometry. As compared with normal subjects, SDB patients demonstrated receded mandibles and long lower faces with downward mandible development. SDB patients with positive closing pressures at both the velopharynx and oropharynx (VP + OP group) demonstrated smaller maxillas and mandibles than those with positive closing pressures at the velopharynx only (VP-only group). Obesity was more prominent in the VP-only group than in the VP + OP group. Our results suggest that obesity and craniofacial abnormalities contribute synergistically to increases in collapsibility of the passive pharyngeal airway in patients with SDB. Furthermore, the relative contribution of obesity and craniofacial anomaly appears to determine the type of pharyngeal closure in SDB.

We studied the effects of minor surgery and endotracheal intubation on postoperative breathing patterns. We measured breathing patterns and laryngeal resistance during the periods immediately before intubation (preoperative) and immediately after extubation following minor surgery (postoperative) in eight patients anaesthetized with sevoflurane and eight patients anaesthetized with isoflurane, breathing spontaneously through a laryngeal mask airway at a constant end-tidal anaesthetic concentration (1.0 MAC). In both sevoflurane-anaesthetized and isoflurane-anaesthetized patients, expiratory time was reduced and inspiratory and expiratory laryngeal resistance increased after surgery. In sevoflurane-anaesthetized patients, occlusion pressure (P0.1) increased without changes in inspiratory time (T(I)). Occlusion pressure did not change and T(I) was greater in isoflurane-anaesthetized patients after surgery. Minor surgery may have a small but significant influence on breathing and increased laryngeal resistance following endotracheal intubation may modulate these changes. The difference in breathing pattern between sevoflurane and isoflurane may be a result of different responses of the central nervous system to different anaesthetics in the presence of increased laryngeal resistance.

1. We do not fully understand the pathogenesis of nocturnal laryngeal stridor in patients with multiple system atrophy (MSA). Recent studies suggest that inspiratory thyroarytenoid (TA) muscle activation has a role in the development of the stridor. 2. The breathing pattern and firing timing of TA muscle activation were determined in ten MSA patients, anaesthetized with propofol and breathing through the laryngeal mask airway, while the behaviour of the laryngeal aperture was being observed endoscopically. 3. Two distinct breathing patterns, i.e. no inspiratory flow limitation (no-IFL) and IFL, were identified during the measurements. During IFL, significant laryngeal narrowing was observed leading to an increase in laryngeal resistance and end-tidal carbon dioxide concentration. Development of IFL was significantly associated with the presence of phasic inspiratory activation of TA muscle. Application of continuous positive airway pressure suppressed the TA muscle activation. 4. The results indicate that contraction of laryngeal adductors during inspiration narrows the larynx leading to development of inspiratory flow limitation accompanied by stridor in patients with MSA under general anaesthesia.

We investigated the effects of changes in lung volume on coordination of respiration and swallowing in 11 healthy subjects. Swallowing reflexes were elicited by bolus injections of a small amount of distilled water (1 ml) and by continuous infusion of distilled water (3 ml/min) into the pharynx at three different levels of lung volume. The lung volume was changed by application of negative extrathoracic pressure (0, -20, and -40 cm H(2)O). We found that increases in lung volume prolonged the latency of swallows elicited by bolus injection of water and decreased the number of swallows during continuous infusion of water. In addition, the preponderant coupling of swallows with the expiratory phase observed before application of negative extrathoracic pressure was lost during application of negative extrathoracic pressure. These results may indicate that lung inflation has an inhibitory influence on the swallowing reflex, and modulates the timing of swallowing in reference to the respiratory cycle.

The upper airway configuration significantly changes during the first year of life in humans, possibly leading to alteration of collapsibility of the pharyngeal airway. The present study evaluated developmental changes of passive pharyngeal mechanics in nine normal infants ranging in age from 2 to 12 mo. The static pressure-area relationship of the passive pharynx was quantified under general anesthesia with complete paralysis. We found a direct association between age and maximal velopharyngeal area (r = 0.840, p = 0.005). Velopharyngeal closing pressure progressively decreased with increasing age (r = -0.809, p = 0.008) and the closing pressures were below atmospheric pressure in all infants (range: -0.7 to -9.8 cm H(2)O; mean +/- SD: -3.6 +/- 2.7 cm H(2)O). Shape of the pressure-area curves became steeper in slope with maturation, indicating increased pharyngeal wall stiffness during development. Accordingly, we conclude that anatomic properties of the pharynx gain stability in favor of maintaining patent airway during development in normal infants.

Precise determination of the site of obstruction is mandatory for improvement of surgical outcome. The size of the upper airway depends on the balance between the upper airway(UA) muscle activity and intraluminal pressure. Structural property of the UA is considered to be a fulcrum of the balance model. Our final goal is to identify structural abnormalities within the UA. State-dependent and individual variability of the UA muscle activity and luminal pressure makes interpretation of UA size difficult. Measurements of UA size and evaluation of UA collapsibility may be less valuable during wakefulness and sleep without controlling the variability. Two unique approaches to identify the anatomic abnormalities while controlling the UA muscle activity and luminal pressure were reviewed.

BACKGROUND: Severe complications associated with upper airway obstruction often occur during the perioperative period. Development of a simple and reliable technique for reversing the impaired airway patency may improve airway management. The purpose of the current study is to evaluate the usefulness of transtracheal oxygen insufflation (TTI) for management of upper airway obstruction during anesthesia and to explore the mechanisms of TTI in detail. METHODS: During propofol anesthesia in eight spontaneously breathing patients, the upper airway cross-sectional area and pressure-flow measurements during neck flexion with TTI were compared with those during triple airway maneuvers (TAM) without TTI. Blood gas analyses assessed efficacy of CO2 elimination during TTI in an additional nine patients. RESULTS: TTI achieved adequate PaCO2 and PaO2 levels equivalent to those during TAM. In addition to a significantly smaller cross-sectional area during TTI, the location and slope of the pressure-flow relation during TTI completely differed from those during TAM, indicating that upper airway resistance was much higher during TTI. Notably, minute ventilation during TTI was significantly smaller than that during TAM, suggesting reduced dead space or other mechanisms for CO2 elimination. CONCLUSIONS: TTI is capable of maintaining adequate blood gases through mechanisms different from those of conventional airway support in anesthetized subjects with upper airway obstruction.

Purpose: In order to numerically compare the morphological differences of the nasal cavity and nasal sinus between acromegalics and non-acromegalics, bone window CT scans sliced parallel to the transsphenoidal surgical route were performed. Material and cases: Acromegalic patients had small or large macroadenomas and were 13 (7 men and 6 women) in number, aged 53.2+/-16.1 years. Non-acromegalic patients had pituitary tumors and were 44 (21 men and 23 women) in number, aged 52.1+/-12.5 years. Results The results of acromegalics are described in comparison to non-acromegalics in parentheses. a) The width of the surgical corridor: piriform aperture, 27.6+/-2.7 (25.9+/-2.6) mm; origin of inferior nasal concha, 29.4+/-9.4 (26.6+/-4.0) mm; and origin of middle nasal concha, 29.8+/-3.2 (26.2 mm+/-4.2) mm. b) The depth of the surgical corridor: the upper lip thickness, 18.1+/-2.7 (13.3+/-1.4) mm; the distances between piriform aperture and sphenoid wall, 52.9+/-4.6 (49+/-4.2) mm; sphenoid wall and sellar floor, 17.3+/-4.1 (18.7+/-4.1)mm; and sellar floor to dorsum sellae, 17.6+/-3.4 (15.6+/-4.0)mm. c) Marked carotid prominence: 7/13=53.4% (8/44=18.25%). d) Sinusitis: 8/13=61.5% (12/44=27.3%). Discussion d; conclusion The data presented above show that morphological differences in bony nasal cavity and soft tissue may be responsible for a deeper and narrower surgical field for acromegalics. Acromegalics had a marked carotid prominence more frequently, which needs special attention to avoid carotid injury, when enlarging the surgical field. Knowing these morphological differences will provide useful information for peri-and intra-operative care.

Purpose Although routine mechanical nasal packing after transsphenoidal surgery (TS) is thought to increase respiratory disorders during sleep, there has been little in the literature about the pre-and post-operative airway assessment of acromegalics with sleep apnea. (SA) We describe 4 acromegalic patients with SA, who underwent transsphenoidal surgery. Methods and cases The patients were all men, aged from 47 to 59 years. The pre-and post-operative sleep study consisted with a computer calculated oximetry parameter of oxygen desaturation index (ODI), which was defined as the number/hour of oxygen desaturation episodes exceeding 4% from the base line (normal range <15). The postoperative (postop.) sleep study was carried out from the 1st postop. day to the 8th day, for 1 to 8 days, varying for each patient. Results Only the worst postop. result is shown. Patient 1 had 2 operations, 2 years apart. ODI was 39.6 before the 1st operation and 45.9 postop.. In the second operation ODI was 21.8 preoperatively (preop.) and 57.9 postop.. Preop. and postop. ODI was 18.1 and 22.2 in patient 2, 21.6 and 22.5 in patient 3 and 45.5 and 18.9 in patient 4, respectively. ODI of patient 4 was 39.6, 3 weeks later. Conclusion Our data showed that the postop. oxymetric study commonly showed worse results in acromegalics with nasal packing. The better result of patient 4 was probably due to a postop. sleepless state. REM sleep usually increases in the first several postop, days, when cardiopulmonary complications are more likely to occur. Since acromegalics with severe SA and postop. nasal packing may more readily suffer from cardiopulmonary complications, postoperative meticulous respiratory monitoring and care should be mandatory.

BACKGROUND: Pain and dyspnea frequently coexist in many clinical situations. However, whether the two different symptoms interact with each other has not been elucidated. To elucidate the interaction between pain and dyspneic sensations, the authors investigated separately the effects of pain on dyspnea and the effects of dyspnea on pain in 15 healthy subjects. METHODS: Subjects were asked to rate their sensation of pain or dyspnea using a visual analog scale (VAS) during pain stimulation produced by tourniquet inflation (inflation cuff pressure: 350 mmHg) around the calf, and/or the respiratory loading consisted of a combination of resistive load (77 cm H2O x l(-1) x s(-1)) and hypercapnia induced by extra mechanical dead space (255 ml). In addition to changes in VAS scores, changes in ventilatory airflow and airway pressure were continuously measured. RESULTS: Pain stimulation and loaded breathing increased VAS scores, ventilation, and occlusion pressure (P0.1). The addition of a pain stimulus during loaded breathing increased the dyspneic VAS score (median 56 [interquartile range 50-62] vs. 64 [55-77]: before vs. after addition of pain stimulus, P < 0.05) with concomitant increases in minute ventilation (10.8 [10.1-13.3] vs. 12.4 [11.0-14.8] l/min, P < 0.05) and P0.1 (5.5 [4.9-7.2] vs. 6.8 [5.8-9.0] cm H2O, P < 0.05). The addition of respiratory loading during pain stimulation did not cause a significant change in pain VAS score (40 [33-55] vs. 31 [30-44]: before vs. after addition of respiratory loading), although both additional burdens increased further minute ventilation (10.0 [8.8-10.9] vs. 12.0 [10.6-13.2] l/min, P < 0.05) and P0.1 (2.5 [2.0-3.0] vs. 6.2 [4.9-7.0] cm H2O, P < 0.05). CONCLUSION: The authors' findings suggest that pain intensifies the dyspneic sensation, presumably by increasing the respiratory drive, whereas dyspnea may not intensify the pain sensation.

The tongue plays a significant role in the maintenance of a patent airway. The purpose of this study was to examine the effects of tongue musculature contraction on the static mechanical properties of the pharynx in patients with obstructive sleep apnoea (OSA). During hyperventilation-induced apnoea in seven OSA patients anaesthetized with sevoflurane, the static pressure/area relationships of the oropharynx were obtained by means of step changes in airway pressure while endoscopically measuring cross-sectional area. At each airway pressure, the tongue was electrically stimulated via electrodes placed bilaterally. Tongue electrical stimulation (TES) did not further dilate the oropharyngeal area at higher airway pressure (3.2+/-1.9 versus 3.0+/-2.1 cm2), although the narrowed oropharyngeal area at lower airway pressures increased during TES (0.8+/-9.0) versus 1.7+/-1.8 cm2, p<0.05). Accordingly, the slope of the pressure/area relationship decreased during TES (0.24+/-0.20 versus 0.12+/-0.09 cm2 x cm H2O(-1), p<0.05). In conclusion, electrical stimulation of the tongue stiffens the retroglossal airway wall in patients with obstructive sleep apnoea.

Sleep-disordered breathing (SDB), either central or obstructive in nature, is common in patients with acromegaly. However, no study has systematically examined the collapsibility of the pharynx in acromegaly to date. We evaluated intrinsic mechanical properties of passive pharynx in 10 anesthetized and paralyzed patients with active acromegaly before transsphenoidal adenomectomy for their pituitary adenoma. Static pressure-area relationships of the velopharynx and oropharynx were obtained by step changes in airway pressure during endoscopic cross-sectional area measurement of each segment. Moreover, curve fitting analysis by an exponential function estimated the closing pressure (P'close) of each segment. Preoperative nocturnal oximetry identified five acromegalic patients with an oxygen desaturation index (ODI) greater than 10 h-1 and clinical symptoms suggesting presence of SDB. The pharyngeal airway of all five acromegalic patients with SDB was highly collapsible at both velopharynx and oropharynx with positive P'close. Compared with age-, body mass index (BMI)-, and ODI-matched SDB patients without acromegaly, SDB patients with acromegaly had a higher P'close of the oropharynx, indicating that the etiology of SDB in acromegaly appears to differ from that of ordinary sleep apnea. Our results suggest that anatomic abnormality, especially at the base of the tongue, appears to play a significant role in development of SDB in acromegaly.

In order to test the hypothesis that different types of respiratory mechanical loads may differently modify the coordination of respiration and swallowing, we investigated the coordination of respiration and swallowing during resistive and elastic loads in 14 healthy subjects. Ventilation was monitored with a pneumotachograph and reflex swallowing was elicited by continuous infusion of distilled water into the pharynx (3 ml/min) and recorded on a submental electromyogram while the subject breathed through a device with a flow-resistive load (180 cm H2O/L/s), an elastic load (70 cm H2O/L), or without any external load. We found that addition of a flow-resistive load did not influence the frequency of swallowing, whereas addition of an elastic load caused a significant increase in swallowing frequency during continuous infusion of water. Analysis of the timing of swallowing in relation to respiratory cycle phase revealed that with flow-resistive loading, swallows occurred preferentially during the inspiratory-expiratory (I-E) transition, whereas with elastic loading, swallows occurred preferentially during the expiratory-inspiratory (E-I) transition. Signs of laryngeal irritation were observed most often during the elastic loading following E-I swallows. These results indicate that different types of respiratory mechanical loads can differently modify this coordination of respiration and swallowing, and suggest that the coordination may be compromised more with elastic loading than with flow-resistive loading.

OBJECTIVES/HYPOTHESIS: Although uvulopalatopharyngoplasty (UPPP) is an attractive surgical treatment for obstructive sleep apnea (OSA), the unpredictable outcome limits application of the procedure. Since UPPP corrects only retropalatal airway (RP) patency, we hypothesized that response to UPPP is determined by collapsibility of the retroglossal airway (RG), where UPPP does not correct. METHODS: We estimated closing pressure (Pclose) for each pharyngeal segment by endoscopically obtaining the static pressure/area relationship of the passive pharynx in completely paralyzed and anesthetized patients with sleep-disordered breathing (n = 41) before UPPP. Preferable response to UPPP was defined as the number of oxygen dips (ODI), obtained by nocturnal oximetry, less than 10 h(-1) after UPPP. RESULTS: Patients with negative Pclose at RG responded to UPPP significantly better than those with positive Pclose at RG (22/30 [73%] vs. 3/11 [27%], P<.05). ODI after UPPP was significantly correlated with age, Pclose at RP, and Pclose at RG. CONCLUSIONS: Endoscopic assessment of anatomic abnormality of the pharynx in paralyzed patients with sleep-disordered breathing under general anesthesia has clinical value for the improvement of UPPP outcome.

Sleep-disordered breathing (SDB) is common in patients with growth hormone (GH) secreting pituitary adenomas. Since long-term untreated SDB aggravates systemic conditions (hypertension and arrhythmia etc.), the therapeutic outcome of SDB is important in reducing morbidity and mortality rates. But the results of a quantitative analysis of the lowered GH and IGF-1 levels in SDB in a relatively large number of patients are not detailed. Ten consecutive acromegalic patients were studied with a bedside oximeter. Preoperatively they were divided into two groups based on the presence (SDB group=6 patients) or absence (non-SDB group=4 patients) of clinical symptoms of SDB such as habitual snoring, excessive daytime somnolence and nocturnal apneic episodes. The serum IGF-1 averaged 931.7ng/ml in SDB group and 898.3ng/ml in non-SDB group. The oxygen desaturation index (ODI) (the number of oxygen desaturations exceeding 4% from the base line) was 29.1+/-15.4 in the SDB group and 2.5+/-1.8 in the non- SDB group (P=0.01). Other oximeter parameters such as the percent of the time spent at O₂ saturation <90% and the mean and the lowest O₂ saturations closely correlated with the degree of the clinical symptoms. A postoperative sleep study was conducted in 5 patients in the preoperative SDB group, 4 months or more after the surgery. The serum GH and IGF-1 levels normalized in 3 patients but remained slightly high in 2. ODI became 9.1+/-5.6, which was significantly lower than the preoperative value (P=0.026). One patient had a complete clinical resolution. The other 4 obtained slight to moderate improvement clinically and oximetrically despite normalized or decreased hormonal levels. This study clarified that the response of SDB to lowering of the GH level varies from one patient to another and persisting SDB despite the normalization of the hormonal levels suggests the involvement of other factors in the production of SDB.

We have measured how a low concentration of nitrous oxide affected respiratory sensation and ventilation. Severe dyspnoea was induced in nine normal subjects by a combination of hypercapnia and inspiratory elastic load (50 cm H2O litre-1). Subjects were asked to rate their sensation of respiratory discomfort using a visual analogue scale (VAS) while breathing either 20% nitrous oxide or 20% nitrogen gas mixture. We compared the effects of each gas mixture on respiratory sensation and ventilation using steady-state values of ventilatory variables and VAS scores obtained before, during and after inhalation of each gas mixture. Inhalation of 20% nitrous oxide reduced the sensation of respiratory discomfort from a median VAS score of 6.5 (range 5.0-8.1) before inhalation to 3.6 (2.4-5.9) during inhalation (P < 0.05). There was no significant change in minute ventilation but tidal volume increased during inhalation of 20% nitrogen did not alter VAS scores or ventilatory variables. We found that a low concentration of nitrous oxide greatly alleviated the intensity of dyspnoea without changing respiratory load compensation.

Although negative pressure assisted ventilation with an assist-control mode may have a potential therapeutic role in the treatment of severe dyspnoea, the effects of negative pressure assisted ventilation with the assist-control mode on dyspnoea and breathing patterns have not been examined. We examined the effects of negative pressure assisted ventilation with the assist-control mode on dyspnoea and breathing patterns produced by a combination of resistive loading and hypercapnia in nine healthy subjects breathing spontaneously. Subjects were asked to rate their sensation of respiratory discomfort using a visual analogue scale. Negative pressure assisted ventilation caused a significant reduction in sensation of respiratory discomfort from a visual analogue scale score of 74 (55-91) (median (range)) before negative pressure assisted ventilation to 34 (15-53) during negative pressure assisted ventilation (p<0.01). During negative pressure assisted ventilation, there were significant changes in breathing patterns characterized by an increase in tidal volume and a decrease in respiratory frequency, while neither minute ventilation nor end-tidal carbon dioxide tension changed. Our results indicate that negative pressure assisted ventilation with the assist-control mode is effective in relief of dyspnoea and that negative pressure assisted ventilation influences the control of breathing to minimize respiratory discomfort.

BACKGROUND: The effects of intravenous anesthetics on airway protective reflexes have not been fully explored. The purpose of the present study was to characterize respiratory and laryngeal responses to laryngeal irritation during increasing doses of fentanyl under propofol anesthesia. METHODS: Twenty-two female patients anesthetized with propofol and breathing through the laryngeal mask airway were randomly allocated to three groups: (1) eight patients who received cumulative total doses of 200 microg fentanyl given in the form of two doses of 50 microg and one dose of 100 microg spaced 6 min under mechanical controlled ventilation while end-tidal carbon dioxide tension (PCO2) was maintained at 38 mmHg (fentanyl-controlled ventilation group), (2) eight patients who received cumulative total doses of 200 microg fentanyl while breathing spontaneously while end-tidal PCO2 was allowed to increase spontaneously (fentanyl-spontaneous ventilation group), and (3) six spontaneously breathing patients who were anesthetized with propofol alone (propofol group). The laryngeal mucosa of each patient was stimulated by spraying the cord with distilled water, and the evoked responses were assessed by analyzing the respiratory variables and endoscopic images. RESULTS: Before administration of fentanyl, laryngeal stimulation caused vigorous reflex responses, such as expiration reflex spasmodic panting, cough reflex, and apnea with laryngospasm. Increasing doses of fentanyl reduced the incidences of all these responses, except for apnea with laryngospasm, in a dose-related manner in both the fentanyl-controlled ventilation and the fentanyl-spontaneous ventilation groups. Detailed analysis of endoscopic images revealed several characteristics of laryngeal behavior during the airway reflex responses. CONCLUSION: Incremental doses of fentanyl depress airway reflex responses in a dose-related manner, except for apnea with laryngospasm.

Proper anesthetic management is necessary to preserve renal function during anesthesia and surgery. Using ultra-sound color Doppler, we examined the influence of sevoflurane on renal medullary blood flow in 20 adult patients without renal dysfunction. After identifying an interlobar artery in the outer medulla, we measured the velocity of the arterial blood flow before induction of anesthesia, and during sevoflurane anesthesia (1 MAC, 1.5 MAC). The minimum velocity of the interlobar arterial blood flow (Vmin) during wakefulness correlated significantly with creatinine clearance measured preoperatively. We did not find any significant change in Vmin after induction of sevoflurane anesthesia, despite significant decreases in mean arterial blood pressure.

Severe postoperative hypoxaemia during sleep may increase the risk of postoperative cardiovascular complications. We hypothesized that the severity of hypoxic episodes after surgery are related to the presence of preoperative sleep-disordered breathing (SDB). We tested this hypothesis in a multicentre study designed to elucidate the major risk factors for development of postoperative nocturnal desaturations. We performed overnight oximetry before operation and for one night between the second and fourth day after operation in 80 patients undergoing major surgery. We calculated oximetry variables such as oxygen desaturation index (ODI), defined as the number of oxygen desaturations exceeding 4% below baseline, percentage time spent at SpO2 < 90% (CT90, %) and lowest SpO2 value. After operation, although the change in ODI was not significant (P = 0.34), deterioration in CT90 and lowest SpO2 values were significant (P = 0.036 and P = 0.007, respectively). Multivariate analysis of possible risk factors for postoperative desaturations revealed that preoperative hypoxaemia and apnoea witnessed by others were highly correlated with postoperative hypoxaemia.

Collapsibility of the active pharynx, where active contraction of the upper airway muscles is evident, was previously reported to be higher in children with obstructive sleep apnea (OSA) than in those with primary snoring during sleep. Contribution of neuromuscular and anatomic factors to the increased collapsibility, however, was not estimated. We therefore evaluated collapsibility of the passive pharynx, in which upper airway muscle activities were eliminated. Our aim in the present study was to test the hypothesis that children with sleep-disordered breathing (SDB) have a structurally narrowed and a more collapsible pharynx compared with normal children. The static pressure/area relationship of the passive pharynx was endoscopically quantified in 14 children with SDB and in 13 normal children under general anesthesia with complete paralysis. The majority of children with SDB primarily closed their airways at levels of enlarged adenoids and tonsils with positive closing pressure (Pclose) (3.5+/-4.3 cm H2O), whereas half of the normal children closed their airways at the soft palate edges and the other half at the tongue bases with subatmospheric Pclose (-7.4+/-4.9 cm H2O). Cross-sectional area of the narrowest segment was significantly smaller in SDB children than in normal children. Interestingly, collapsibility of the retropalatal and retroglossal segments significantly increased in SDB children, compared with the normal subjects. We conclude that anatomic factors play a significant role in the pathogenesis of pediatric OSA and that predisposing structural abnormalities of the entire pharynx are likely to contribute to manifestation of OSA in addition to enlarged adenoids and tonsils.

We investigated the effects of increasing CO2 ventilatory drive on the coordination of respiration and reflex swallowing elicited by continuous infusion of distilled water into the pharynx (2.5 ml/min) in 11 normal subjects. Ventilation was monitored using a pneumotachograph and swallowing was recorded by submental electromyogram. The CO2 ventilatory drive was increased by addition of external dead space, while ventilation, the frequency of swallows, and the timing of swallows in relation to the phases of the respiratory cycle were measured at steady-state conditions. We found that the CO2 ventilatory response is not influenced by continuous reflex swallowing but that hypercapnia influences the timing and frequency of these swallows. Signs of aspiration were never observed during continuous infusion of water at eucapnia, but seven of 11 subjects showed laryngeal irritation and/or pending aspiration during hypercapnia, and the incidence of laryngeal irritation was higher the greater the PCO2. Detailed analysis of laryngeal irritations consisting of single coughs in seven subjects revealed that the majority of laryngeal irritations occurred when swallows coincided with expiratory-inspiratory transition or when swallows coincided with inspiration, whereas laryngeal irritation after an expiratory swallow was never observed. These results suggest that the automatic respiratory control system is not influenced by continuous swallowing but that the coordination of swallowing and respiration may be compromised during hypercapnia.

BACKGROUND: During anesthesia in humans, anterior displacement of the mandible is often helpful to relieve airway obstruction. However, it appears to be less useful in obese patients. The authors tested the possibility that obesity limits the effectiveness of the maneuver. METHODS: Total muscle paralysis was induced under general anesthesia in a group of obese persons (n = 9; body mass index, 32 +/- 3 kg[-2]) and in a group of nonobese persons (n = 9; body mas index, 21 +/- 2 kg[-2]). Nocturnal oximetry confirmed that none of them had sleep-disordered breathing. The cross-sectional area of the pharynx was measured endoscopically at different static airway pressures. A static pressure-area plot allowed assessment of the mechanical properties of the pharynx. The influence of mandibular advancement on airway patency was assessed by comparing the static pressure-area relation with and without the maneuver in obese and nonobese persons. RESULTS: Mandibular advancement increased the retroglossal area at a given pharyngeal pressure, and mandibular advancement increased the retropalatal area in nonobese but not in obese persons at a given pharyngeal pressure. CONCLUSION: Mandibular advancement did not improve the retropalatal airway in obese persons.

Anatomic abnormalities of the pharynx are thought to play a role in the pathogenesis of obstructive sleep apnea (OSA), but their contribution has never been conclusively proven. The present study tested this anatomic hypothesis by comparing the mechanics of the paralyzed pharynx in OSA patients and in normal subjects. According to evaluation of sleep-disordered breathing (SDB) by nocturnal oximetry, subjects were divided into three groups: normal group (n = 17), SDB-1 (n = 18), and SDB-2 (n = 22). The static pressure-area relationship of the passive pharynx was quantified under general anesthesia with complete paralysis. Age and body mass index were matched among the three groups. The site of the primary closure was the velopharynx in 49 subjects and the oropharynx in only 8 subjects. Distribution of the location of the primary closure did not differ among the groups. Closing pressure (PC) of the velopharynx for SDB-1 and SDB-2 groups (0.90 +/- 1.34 and 2.78 +/- 2.78 cmH2O, respectively) was significantly higher than that for the normal group (-3.77 +/- 3.44 cmH2O; P < 0.01). Maximal velopharyngeal area for the normal group (2.10 +/- 0.85 cm2) was significantly greater than for SDB-1 and SDB-2 groups (1.15 +/- 0.46 and 1.06 +/- 0.75 cm2, respectively). The shape of the pressure-area curve for the velopharynx differed between normal subjects and patients with SDB, being steeper in slope near Pc in patients with SDB. Multivariate analysis of mechanical parameters and oxygen desaturation index (ODI) revealed that velopharyngeal Pc was the only variable highly correlated with ODI. Velopharyngeal Pc was associated with oropharyngeal Pc, suggesting mechanical interdependence of these segments. We conclude that the passive pharynx is more narrow and collapsible in sleep-apneic patients than in matched controls and that velopharyngeal Pc is the principal correlate of the frequency of nocturnal desaturations.

Complete paralysis under general anesthesia allowed separating anatomic factors from neural factors which influence pharyngeal patency. We compared static mechanical properties of the passive pharynx in normals and sleep apneics. The passive pharynx was narrower and more collapsible in sleep apneics than normal controls indicating significance of anatomic factors in the pathogenesis of obstructive sleep apnea.

The velopharynx is the most common site of obstruction in patients with obstructive sleep apnea (OSA). Advancement of the mandible effectively reverses the pharyngeal obstruction. Accordingly, we hypothesized that mandibular advancement increases cross-sectional area of several segments of the upper airway, including the velopharynx and the oropharynx. We examined the pressure-area properties of the pharyngeal airway in 13 patients with OSA. Under general anesthesia and total muscle paralysis, the pharynx was visualized with an endoscope connected to a video-recording system. During an experimentally induced apnea, we manipulated the nasal pressure from 20 cmH2O to the point of total closure at the velopharynx. The procedure was repeated after maximal forward displacement of the mandible. Measurements of the cross-sectional area at different levels of nasal pressure allowed construction of a static pressure-area relationship of the "passive pharynx," where active neuromuscular factors are suppressed. In 12 of 13 patients with OSA, advancement of the mandible stabilized the airway by reducing the closing pressure and increasing the area at any airway pressure. Thus the maneuver shifted the static pressure-area curve of the velopharynx and the oropharynx upward in these patients. We conclude that anterior movement of the mandible widens the retropalatal airway as well as that at the base of the tongue in the passive pharynx of OSA patients.

Effects of lumbar epidural block on maximum expiratory strength were studied in 12 healthy volunteers. Subjects performed maximum expiratory effort against occluded airway at functional residual capacity (FRC) and total lung capacity (TLC) while measuring airway pressure and electromyogram of the abdominal muscles (EMGab). Cough strength was assessed by maximum expiratory pressure (PEmax) and peak EMGab (peak-EMGab). Following injection of 2% lidocaine 17.8±1.1 ml into the lumbar epidural space (L2.3±0.4), upper levels of analgesia ranged from T11 to T4 (T7.8±1.3). Peak-EMGab and PEmax were significantly reduced by lumbar epidural block at both lung volumes. Compared with severe reduction in peak-EMGab, PEmax was well maintained at TLC, but changes in PEmax were identical to those in peak-EMGab at FRC. When analgesia spread to higher than T6, PEmax at TLC decreased considerably. We conclude that lumbar epidural block producing analgesia above T6 paralyzes the abdominal muscles and severely impairs the ability of effective cough in healthy young men.

The effect of isoflurane administration on diaphragmatic activity was investigated in six anaesthetized mechanically ventilated dogs. Diaphragmatic strength was assessed by measuring the transdiaphragmatic pressure (Pdi) generated during supramaximal stimulation of both cervical phrenic nerves at frequencies of 0.5, 10, 20, 50 and 100 Hz under partially isometric conditions at 1, 1.5 and 2 minimum alveolar anaesthetic concentrations (MAC), after maintaining 1 h of stable conditions. Pdi measurements were made at the start of the stimulation (initial) and at the end of a 2-s period (2-s). The force-frequency relationship was compared at each anaesthetic level. For single twitch (0.5 Hz) stimulation, the time constant of diaphragmatic relaxation was also assessed. The sequence of changing anaesthetic depth was altered in random fashion between animals. Pdi amplitude at single twitch stimulation was unchanged at the three anaesthetic concentrations. There was no significant difference in initial Pdi at various stimulus frequencies with increasing depth of isoflurane anaesthesia. In addition, no change in 2-s Pdi during low frequency stimulation (10 and 20 Hz) was noted during any of the three levels of anaesthesia. By contrast, 2-s Pdi with 50 Hz stimulation during 2 MAC isoflurane exposure decreased significantly below Pdi levels seen at 1 and 1.5 MAC (P < 0.01). Furthermore, 2-s Pdi at 100 Hz stimulation decreased significantly in a dose-dependent fashion. From these results, we conclude that isoflurane reduces diaphragmatic activity at higher stimulation frequencies of 50 and 100 Hz.

Mechanical influences independent of chemoreceptor function on ventilatory control were studied in halothane-anesthetized, artificially ventilated patients using the technique reported by Altose et al. (Respir Physiol 66: 171-180, 1986). Contribution of mechanical factor was indirectly assessed by comparing the values of arterial carbon dioxide tension at which the subjects started breathing efforts during CO(2) loading induced by the following two methods. 1) Partial rebreathing of expired gas and 2) Mechanical hypoventilation (successive decrease in inflation volume). These two maneuvers resulted in a similar rate of increase in end-expiratory carbon dioxide tension. However, contrary to the observation made by Altose et al. in awake volunteers, we found comparable values of ventilatory recruitment threshold for Pa(CO)(2). Thus, we speculate that halothane anesthesia and/or loss of consciousness impair transmission of afferent information from the lung and/or chest wall musculature. Such effects may be responsible for the depression of load compensatory mechanism during anesthesia.

The effect of sevoflurane on diaphragmatic contractility was investigated in 12 anesthetized, mechanically ventilated dogs with the thorax opened. Animals were divided into two groups of six each: the sevoflurane and time control groups. We assessed contractility by the transdiaphragmatic pressure (Pdi) during supramaximal stimulation of the phrenic nerve at frequencies of 0.5, 10, 20, 50, and 100 Hz under quasiisometric conditions. The integrated electrical activity (Edi) of the crural and costal parts of the diaphragm (Edi cru, Edi cost) was also measured. In the sevoflurane group, diaphragmatic contractility was determined during three levels of anesthesia, specifically 0, 1.0, and 1.5 minimum alveolar anesthetic concentration (MAC). Measurements were made at the start of the stimulation (initial) and at the end of the 2-s period (2-s). Increasing the depth of sevoflurane anesthesia did not cause any significant differences in Pdi and Edi at 0.5-, 10-, and 20-Hz stimulation. By contrast, at 50- and 100-Hz stimulation, initial Pdi during 1.0 and 1.5 MAC sevoflurane exposure decreased significantly compared with the 0 MAC value (P less than 0.05). In addition, there was a statistical difference in 2-s Pdi between 1.0 and 1.5 MAC at 100-Hz stimulation (P less than 0.05). The Edi cru showed similar changes in Pdi at both measurements, whereas there was no remarkable change in Edi cost. There was no significant change either in Pdi or in Edi with respect to time in the time control group. We conclude from these results that sevoflurane impairs diaphragmatic contractility through its inhibitory effect on neuromuscular transmission, predominantly of the crural part.

We have examined the sensitivity of the geniohyoid, an upper airway dilating muscle, to vecuronium in 12 anaesthetized dogs undergoing mechanical ventilation of the lungs and compared it with that of the diaphragm. Dogs were allocated randomly to two groups: pentobarbitone alone (group 1, n = 7); pentobarbitone combined with 0.2 MAC (0.44%) of enflurane anaesthesia (group 2, n = 5). Supramaximal single twitch stimulations (0.1 Hz) were applied to the phrenic nerves in the upper thorax and the geniohyoid branches of the hypoglossal nerves at the neck. The evoked responses were assessed by the transdiaphragmatic pressure (Pdi) and the isometric force of the geniohyoid muscles (Tgh) until complete recovery of these variables after i.v. administration of vecuronium 0.02 mg kg-1. In both groups, the magnitude of the depression of twitch response was greater and time required to reach control amplitude was longer in the geniohyoid than the diaphragm. The depression of Tgh was significantly greater in group 2 than in group 1, whereas no change was observed in Pdi between the two groups. We conclude that the geniohyoid is more sensitive to vecuronium than the diaphragm and the differential effects of vecuronium are facilitated by a low concentration of enflurane.

The ability to swallow may be affected by administration of a small dose of muscle relaxant. To test the hypothesis that a subparalyzing dose of a muscle relaxant can impair swallowing, effects of partial paralysis produced by pancuronium on the swallowing reflex were investigated in eight conscious subjects. The swallowing reflex was induced by a bolus injection or a continuous infusion of distilled water into the mesopharynx. The swallowing function was assessed by electromyogram of suprahyoid muscles (EMGSH), mesopharyngeal pressure (Pmeso), and hypopharyngeal pressure (Phypo). Peripheral muscle activity was simultaneously determined by train of four ratio (TOFR) of hypothenar muscles to electrical stimulation of ulnar nerve and by hand grip strength (HGS). Following control measurements, measurements during partial paralysis and after recovery from partial paralysis were performed after intravenous administration of pancuronium 0.02 mg/kg. Partial paralysis significantly depressed EMGSH (bolus injection 44.1 +/- 10.0%, continuous infusion 55.9 +/- 10.2% of control value, P less than 0.01). Pmeso also significantly decreased (bolus injection 64.9 +/- 6.7 to 47.8 +/- 5.8 mmHg, P less than 0.01; continuous infusion 63.4 +/- 7.7 to 52.5 +/- 5.8 mmHg, P less than 0.05). The TOFR of peripheral muscles decreased to 81.4 +/- 6.7% of control value (P less than 0.01), and HGS was reduced from 44.6 +/- 1.9 to 39.4 +/- 2.0 kg (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

To examine the ventilatory effects of sevoflurane, breathing pattern, airway occlusion pressure waveform, and the mechanical variables of the respiratory system were determined in seven subjects anesthetized with sevoflurane and in an additional seven subjects anesthetized with halothane. All patients breathed 1 MAC of anesthetic using oxygen as the carrier gas, and the measurements were performed in the absence of surgical stimulation. The durations of inspiration and expiration were significantly longer during sevoflurane than during halothane administration. Tidal volumes were larger in the sevoflurane group than in the halothane group. Occlusion pressure waveforms were also markedly different between the two groups. Occlusion pressure during the initial 300-400 ms tended to be less in the sevoflurane-anesthetized than in the halothane-anesthetized subjects. There was no evidence of an active Hering-Breuer reflex with either anesthetic. Mechanical variables of the respiratory system were essentially identical between the two anesthetics. We conclude that (a) the ventilatory effects of halothane and sevoflurane are different, (b) the difference in the respiratory timing and depth of breathing originates from the action of the anesthetics on the central respiratory neural network, and (c) the different shape of the tracheal occlusion pressure may be largely due to the different effects of halothane and sevoflurane on the muscles of the rib cage.

We examined the effects of enflurane on the diaphragmatic function in 15 pentobarbital-anesthetized, mechanically ventilated dogs. They were divided into three groups of five animals each, according to the administered concentration of enflurane. The diaphragmatic function was assessed from transdiaphragmatic pressure (Pdi) and integrated diaphragmatic electromyography (Edi) developed at functional residual capacity against an occluded airway during bilateral supramaximal phrenic nerve stimulation at 0.5, 10, 20, 50 and 100 Hz under quasiisometric condition. After a control measurement, enflurane was administered at a constant end-expired concentration (0, 0.5 and 1 MAC) and the measurement was repeated after 1 hour of exposure. The Pdi amplitude generated by single twitch (0.5 Hz) and during 10, 20 and 50 Hz stimulation was unchanged between the groups. No change in Pdi during 100 Hz stimulation was noted during 0 and 0.5 MAC exposure, while it was reduced by 1 MAC of enflurane. When the values of Pdi were expressed as % of maximum Pdi (%Pdi,max) that developed during control measurement and analyzed in terms of %Pdi,max-stimulus frequency relationship, a significant decrease in %Pdi,max was noted for 100 Hz stimulation in 0.5 and 1 MAC groups compared to the control. Similarly, Edi during 100 Hz stimulation obtained in 0.5 and 1 MAC groups was markedly depressed compared to the control. Edi during 50 Hz stimulation was also decreased at 1 MAC. Relative changes in Edi following enflurane administration were greater than the corresponding changes of Pdi. These results demonstrate that enflurane impairs diaphragmatic function through its inhibitory effects on neuromuscular transmission.

The effect of increasing the concentration of sevoflurane anaesthesia on diaphragmatic function was investigated in six mechanically ventilated dogs. Diaphragmatic function was assessed by measuring the transdiaphragmatic pressure (Pdi) generated during bilateral supramaximal stimulation of the cervical phrenic nerves at frequencies of 0.5, 10, 20, 50, and 100 Hz under quasi-isometric conditions. Measurements were performed at 1, 1.5 and 2 MAC concentrations after maintaining stable conditions for one hour. The Pdi-stimulus frequency relationship was compared at each anaesthetic concentration. The sequence of changing anaesthetic depth was altered in random fashion among animals. The Pdi amplitude generated by single twitch (0.5 Hz) was unchanged at the three concentrations. In addition, no change in Pdi during 10, 20, 50 Hz stimulation was noted at any of the three levels of anaesthesia. By contrast, Pdi with 100 Hz stimulation during 2 MAC sevoflurane exposure (28.1 +/- 5.0 cmH2O) decreased below Pdi levels seen at 1 and 1.5 MAC (35.3 +/- 4.3 cmH2O and 31.5 +/- 4.3 cmH2O, respectively) (P less than 0.05). From these results, we conclude that sevoflurane impairs diaphragmatic function in deep anaesthesia.

In order to determine the respiratory effects of sevoflurane in humans, breathing pattern and mechanical behavior of respiratory system were investigated in ten subjects at anesthetic depth of 1 MAC (minimum alveolar concentration). Average tidal volume and breathing frequency amounted to 275 ml and 20.9 breaths per minute. Arterial carbon dioxide tension amounted to 45.6 mmHg. Duration of inspiration was 1.06s and that of expiration was 1.92s. Mean inspiratory flow rate amounted to 259 ml.s(-1). Average value of passive respiratory elastance determined by the method of Zin et al. amounted to 21.8 cmH(2)O. l(-1), while those of active respiratory elastance and resistance obtained by the method of Behrakis et al. were 28.0 cmH(2)O. l(-1) and 3.15 cmH(2)O. l(-1).s(-1), respectively. Values of these variables were compared to those reported in halothane and enflurane anesthesia and possible explanations of the differences between the anesthetics are discussed.

We examined the effect of enflurane on diaphragmatic contractility in six anesthetized mechanically ventilated dogs. The diaphragmatic force was assessed from transdiaphragmatic pressure (Pdi) developed at functional residual capacity against an occluded airway during cervical phrenic nerve stimulation. Pdi-stimulus frequency relationship was compared at three levels of anesthesia, namely 1, 1.5, and 2 MAC (minimum alveolar concentration) of enflurane. The sequence of changing anesthetic concentration was randomized between animals. Pdi at 50 and 100 Hz stimulation was significantly decreased with increasing MAC while Pdi at 10 Hz stimulation was not affected by the depth of anesthesia. Pdi of 20 Hz stimulation was significantly decreased at 2 MAC as compared to those at 1 and 1.5 MAC. We conclude that enflurane decreases contractility of the diaphragm mainly through impairment of the neuromuscular transmission and/or membrane excitability. Part of its effects is, however, probably related to the impairment of excitation-contraction coupling, as suggested by the depression of Pdi at 2 MAC in response to 20 Hz stimulation.

The response of breathing patterns to increased expiratory resistance is not only of physiologic interest, with respect to the control of breathing, but also of clinical interest because of its clinical relevance to obstructive diseases such as asthma and emphysema. To elucidate the response of breathing patterns to increased expiratory resistance during anesthesia, the respiratory effects of expiratory flow-resistive loading on breathing patterns were studied in 15 conscious and 10 lightly anesthetized subjects. Inspiratory time, expiratory time, respiratory frequency, inspiratory duty cycle, tidal volume, minute ventilation, and mean inspiratory flow rate were determined from a respiratory inductive plethysmograph. End-tidal CO2 was continuously recorded. In awake subjects, respiratory frequency was reduced without change in tidal volume or mean inspiratory flow rate, and minute ventilation was significantly decreased; the synchrony between rib cage and abdomen wall motion was well maintained during the loads. In contrast, in anesthetized subjects, respiratory frequency was reduced with remarkable increases in tidal volume, mean inspiratory flow rate, and minute ventilation, whereas coordination between rib cage and abdomen compartments was disturbed. End-tidal CO2 did not change in conscious subjects, but it increased in anesthetized subjects during the loads. These results indicate that there are differences between conscious and anesthetized subjects in breathing patterns during expiratory loading, and suggest that the ability to coordinate rib cage-abdomen wall motion is easily disturbed during anesthesia in patients with expiratory flow limitation.

We examined the effects of halothane and enflurane on diaphragmatic contractility in 12 anesthetized, mechanically ventilated dogs. The diaphragmatic force was assessed from transdiaphragmatic pressure (Pdi) developed at functional residual capacity against an occluded airway during cervical phrenic nerve stimulation. Animals were randomly assigned to two groups, a halothane group (n = 6) and an enflurane group (n = 6). The Pdi stimulus-frequency relationship was compared at anesthetic levels of 1, 1.5, and 2 MAC (minimum alveolar concentration) in each group. The sequence of changing anesthetic concentration was randomized. In addition, the Pdi-frequency relationship was also compared between 1 MAC of halothane and enflurane in 8 of 12 dogs. In animals anesthetized with enflurane, Pdi significantly decreased with 50- and 100-Hz stimulation in the presence of increasing MAC values, whereas Pdi at 10-Hz stimulation was not affected by the depth of anesthesia. Pdi with 20-Hz stimulation during 2 MAC enflurane also decreased significantly below Pdi levels seen at 1 and 1.5 MAC. By contrast, with halothane there was no difference in Pdi at any of the stimulation frequencies during any of the three levels of anesthesia. There was no statistical difference, however, between Pdi-frequency relationships during 1 MAC of halothane and enflurane in eight animals. From these results, we conclude that halothane does not impair diaphragmatic contractility any more than enflurane does, but enflurane decreases force generation of the diaphragm at high stimulation frequencies in a dose-related fashion. This depressant effect of enflurane occurs mainly through the impairment of neuromuscular transmission and/or membrane excitability.(ABSTRACT TRUNCATED AT 250 WORDS)