Association between exposure to anaesthesia and surgery and long-term cognitive trajectories in older adults: report from the Mayo Clinic Study of Aging.

BACKGROUND: The link between exposure to general anaesthesia and surgery (exposure) and cognitive decline in older adults is debated. We hypothesised that it is associated with cognitive decline. METHODS: We analysed the longitudinal cognitive function trajectory in a cohort of older adults. Models assessed the rate of change in cognition over time, and its association with exposure to anaesthesia and surgery. Analyses assessed whether exposure in the 20 yr before enrolment is associated with cognitive decline when compared with those unexposed, and whether post-enrolment exposure is associated with a change in cognition in those unexposed before enrolment. RESULTS: We included 1819 subjects with median (25th and 75th percentiles) follow-up of 5.1 (2.7-7.6) yr and 4 (3-6) cognitive assessments. Exposure in the previous 20 yr was associated with a greater negative slope compared with not exposed (slope: -0.077 vs -0.059; difference: -0.018; 95% confidence interval: -0.032, -0.003; P=0.015). Post-enrolment exposure in those previously unexposed was associated with a change in slope after exposure (slope: -0.100 vs -0.059 for post-exposure vs pre-exposure, respectively; difference: -0.041; 95% confidence interval: -0.074, -0.008; P=0.016). Cognitive impairment could be attributed to declines in memory and attention/executive cognitive domains. CONCLUSIONS: In older adults, exposure to general anaesthesia and surgery was associated with a subtle decline in cognitive z-scores. For an individual with no prior exposure and with exposure after enrolment, the decline in cognitive function over a 5 yr period after the exposure would be 0.2 standard deviations more than the expected decline as a result of ageing. This small cognitive decline could be meaningful for individuals with already low baseline cognition.

What do recent human studies tell us about the association between anaesthesia in young children and neurodevelopmental outcomes?

Anaesthetic and sedative drugs transiently disrupt normal neural activity to facilitate healthcare procedures in children, but they can also cause long-term brain injury in experimental animal models. The US Food and Drug Administration (FDA) has recently advised that repeated or lengthy exposures to anaesthetic and sedative drugs prior to 3 yr of age have the potential to harm the development of children's brains and added warnings to these drug labels. Paediatric anaesthesia toxicity could represent a significant public health issue, and concern about this potential injury in children has become an important issue for families, paediatric clinicians and healthcare regulators. Since late 2015, important new data from five major clinical studies have been published. This narrative review aims to provide a brief overview of the preclinical and clinical literature, including a comprehensive review of these recent additions to the human literature. We integrate these new data with prior studies to provide further insights into how these clinical findings can be applied to children.

Postoperative delirium in elderly patients is associated with subsequent cognitive impairment.

BACKGROUND: We examined the risk for postoperative delirium (POD) in patients with mild cognitive impairment (MCI) or dementia, and the association between POD and subsequent development of MCI or dementia in cognitively normal elderly patients. METHODS: Patients ≥65 yr of age enrolled in the Mayo Clinic Study of Aging who were exposed to any type of anaesthesia from 2004 to 2014 were included. Cognitive status was evaluated before and after surgery by neuropsychological testing and clinical assessment, and was defined as normal or MCI/dementia. Postoperative delirium was detected with the Confusion Assessment Method for the intensive care unit. Logistic regression analyses were performed. RESULTS: Among 2014 surgical patients, 74 (3.7%) developed POD. Before surgery, 1667 participants were cognitively normal, and 347 met MCI/dementia criteria. The frequency of POD was higher in patients with pre-existing MCI/dementia compared with no MCI/dementia {8.7 vs 2.6%; odds ratio (OR) 2.53, [95% confidence interval (CI) 1.52-4.21]; P <0.001}. Postoperative delirium was associated with lower education [OR, 3.40 (95% CI, 1.60-7.40); P =0.002 for those with <12 vs ≥16 yr of schooling]. Of the 1667 patients cognitively normal at their most recent assessment, 1152 returned for postoperative evaluation, and 109 (9.5%) met MCI/dementia criteria. The frequency of MCI/dementia at the first postoperative evaluation was higher in patients who experienced POD compared with those who did not [33.3 vs 9.0%; adjusted OR, 3.00 (95% CI, 1.12-8.05); P =0.029]. CONCLUSIONS: Mild cognitive impairment or dementia is a risk for POD. Elderly patients who have not been diagnosed with MCI or dementia but experience POD are more likely to be diagnosed subsequently with MCI or dementia.

Driving performance of outpatients achieving discharge criteria after deep sedation is worse than these of their escort-driver: a prospective observational study on simulator.

Background: Achieving post-anesthesia discharge criteria after surgery or outpatient procedures does not mean that the patient has regained all his or her faculties, such as driving. Although mandated by many clinical guidelines, there is no evidence that escort-drivers reduce the risk of traffic accidents after deep sedation. The purpose of this study was to evaluate that hypothesis that driving performance as measured using a driving simulation would not differ between patients who had undergone deep sedation for gastrointestinal endoscopy meeting discharge criteria and their escorts. Methods: This prospective study included patients scheduled for ambulatory gastrointestinal endoscopy under deep propofol sedation (patient group) and their escorts (escort group). Driving performance of escorts and patients (when discharge criteria were met) was assessed using a driving simulator. Results: 30 patients and their escorts were included. Patients crossed the midline significantly more frequently than escorts (3 [2-4] (median [IQR]) and 2 [1-3] crossings, respectively, p=0.015]. Patients were speeding for a higher proportion of the distance traveled compared with escorts (37 (20)% (mean (SD)) and 24 (17)% in patients and escorts, respectively, p = 0.029). There were no significant differences between groups in other simulation parameters. Conclusions: The ability to stay within the traffic lanes, as measured by the number of midline crossing during a simulated driving performance, is impaired in patients who meet discharge criteria after gastrointestinal endoscopy under deep sedation compared with their escorts. This finding does not support a practice of allowing patients to drive themselves home after these procedures.

Obstructive sleep apnoea and perioperative complications in bariatric patients.

BACKGROUND: The objective of this study was to determine the relationship between perioperative complications and the severity of obstructive sleep apnoea (OSA) in patients undergoing bariatric surgery who had undergone preoperative polysomnography (PSG). METHODS: The records of 797 patients, age >18 yr, who underwent bariatric operations (442 open and 355 laparoscopic procedures) at Mayo Clinic and were assessed before operation by PSG, were reviewed retrospectively. OSA was quantified using the apnoea-hypopnoea index (AHI) as none (≤ 4), mild (5-15), moderate (16-30), and severe (≥ 31). Pulmonary, surgical, and 'other' complications within the first 30 postoperative days were analysed according to OSA severity. Logistic regression was used to assess the multivariable association of OSA, age, sex, BMI, and surgical approach with postoperative complications. RESULTS: Most patients with OSA (93%) received perioperative positive airway pressure therapy, and all patients were closely monitored after operation with pulse oximetry on either regular nursing floors or in intensive or intermediate care units. At least one postoperative complication occurred in 259 patients (33%). In a multivariable model, the overall complication rate was increased with open procedures compared with laparoscopic. In addition, increased BMI and age were associated with increased likelihood of pulmonary and other complications. Complication rates were not associated with OSA severity. CONCLUSIONS: In obese patients evaluated before operation by PSG before bariatric surgery and managed accordingly, the severity of OSA, as assessed by the AHI, was not associated with the rate of perioperative complications. These results cannot determine whether unrecognized and untreated OSA increases risk.

Comparison of two ventilatory strategies in elderly patients undergoing major abdominal surgery.

BACKGROUND: 'Open lung' ventilation is commonly used in patients with acute lung injury and has been shown to improve intraoperative oxygenation in obese patients undergoing laparoscopic surgery. The feasibility of an 'open lung' ventilatory strategy in elderly patients under general anaesthesia has not previously been assessed. METHODS: 'Open lung' ventilation (recruitment manoeuvres, tidal volume 6 ml kg(-1) predicted body weight, and 12 cm H(2)O PEEP) (RM group) was compared with conventional ventilation (no recruitment manoeuvres, tidal volume 10 ml kg(-1) predicted body weight, and zero end-expiratory pressure) in elderly patients (>65 yr) undergoing major open abdominal surgery with regard to oxygenation, respiratory system mechanics, and haemodynamic stability. We also monitored the serum levels of the interleukins (IL)-6 and IL-8 before and after surgery to determine whether the systemic inflammatory response to surgery depends on the ventilatory strategy used. RESULTS: Twenty patients were included in each group. The RM group tolerated open lung ventilation without significant haemodynamic instability. Intraoperative Pa(o(2)) improved in the RM group (P<0.01) and deteriorated in controls (P=0.01), but postoperative Pa(o(2)) was similar in both groups. The RM group had improved breathing mechanics as evidenced by increased dynamic compliance (36%) and decreased airway resistance (21%). Both IL-6 and IL-8 significantly increased after surgery, but the magnitude of increase did not differ between the groups. CONCLUSIONS: A lung recruitment strategy in elderly patients is well tolerated and improves intraoperative oxygenation and lung mechanics during laparotomy.

Intraoperative ventilator settings and acute lung injury after elective surgery: a nested case control study.

BACKGROUND: While acute lung injury (ALI) is among the most serious postoperative pulmonary complications, its incidence, risk factors and outcome have not been prospectively studied. OBJECTIVE: To determine the incidence and survival of ALI associated postoperative respiratory failure and its association with intraoperative ventilator settings, specifically tidal volume. DESIGN: Prospective, nested, case control study. SETTING: Single tertiary referral centre. PATIENTS: 4420 consecutive patients without ALI undergoing high risk elective surgeries for postoperative pulmonary complications. MEASUREMENTS: Incidence of ALI, survival and 2:1 matched case control comparison of intraoperative exposures. RESULTS: 238 (5.4%) patients developed postoperative respiratory failure. Causes included ALI in 83 (35%), hydrostatic pulmonary oedema in 74 (31%), shock in 27 (11.3%), pneumonia in nine (4%), carbon dioxide retention in eight (3.4%) and miscellaneous in 37 (15%). Compared with match controls (n = 166), ALI cases had lower 60 day and 1 year survival (99% vs 73% and 92% vs 56%; p<0.001). Cases were more likely to have a history of smoking, chronic obstructive pulmonary disease and diabetes, and to be exposed to longer duration of surgery, intraoperative hypotension and larger amount of fluid and transfusions. After adjustment for non-ventilator parameters, mean first hour peak airway pressure (OR 1.07; 95% CI 1.02 to 1.15 cm H(2)O) but not tidal volume (OR 1.03; 95% CI 0.84 to 1.26 ml/kg), positive end expiratory pressure (OR 0.89; 95% CI 0.77 to 1.04 cm H(2)O) or fraction of inspired oxygen (OR 1.0; 95% CI 0.98 to 1.03) were associated with ALI. CONCLUSION: ALI is the most common cause of postoperative respiratory failure and is associated with markedly lower postoperative survival. Intraoperative tidal volume was not associated with an increased risk for early postoperative ALI.

Perioperative tobacco use interventions in Japan: a survey of thoracic surgeons and anaesthesiologists.

BACKGROUND: Tobacco use interventions in surgical patients who smoke could benefit both their short-term outcome and long-term health. Anaesthesiologists and surgeons can play key roles in delivering these interventions. This study determined the practices, attitudes, and beliefs of these physicians regarding tobacco use interventions in Japan. METHODS: Questionnaires were mailed to a national random sampling of Japanese anaesthesiologists and thoracic surgeons (1000 in each group). RESULTS: The survey response rate was 62%. More than 80% of respondents agreed or strongly agreed with the statements affirming the benefits of abstinence to surgical patients. However, only 26% of surgeons and 6% of anaesthesiologists reported almost always providing help to their patients to quit smoking. Compared with anaesthesiologists, surgeons were more likely to perform the elements of current recommendations for brief intervention, and to have attitudes favourable to tobacco use interventions. The most significant barrier to intervention identified by both groups was a lack of time to perform counselling. Compared with non-smokers, physicians who smoked were less likely to perform each of the recommended tobacco interventions CONCLUSIONS: Although current rates of intervention provided by anaesthesiologists and surgeons are low, there is considerable interest among these physicians in learning more about interventions. Given the relatively high prevalence of smoking in Japan and the potential for surgery to serve as a 'teachable moment' to promote abstinence from smoking, leadership by these specialists in the area of tobacco control could have a major impact on public health in Japan.

Stereospecific effects of ketamine enantiomers on canine tracheal smooth muscle.

1. Ketamine is a potent bronchodilator which relaxes airway smooth muscle (ASM). Clinically, ketamine is used as a 1:1 racemic mixture of enantiomers that differ in their analgesic and anaesthetic effects. The aim of this study was to determine whether there was a difference between the enantiomers in their ability to relax isolated ASM and to explore mechanisms responsible for any observed differences. 2. Canine tracheal smooth muscle strips were loaded with fura-2 and mounted in a photometric system to measure simultaneously force and [Ca2+]i. Calcium influx was estimated by use of a manganese quenching technique. 3. In strips stimulated with 0.1 microM ACh (EC50) R(-)-ketamine (1-100 microM) caused a significantly greater concentration-dependent decrease in force (P<0.0001) and [Ca2+]i than S(+)-ketamine (1-100 microM) (P<0.0005). In contrast, there was no significant difference between the enantiomers in their ability to inhibit calcium influx (45% decrease in influx rate for R(-)-ketamine and 44% for S(+)-ketamine, P =0.782). In strips contracted with 24 mM isotonic KCI (which activates voltage-operated calcium channels), the enantiomers modestly decreased force and [Ca2+]i; there was no significant difference between the enantiomers in their effects on force (P=0.425) or [Ca2+]i (P=0.604). 4. The R(-)-enantiomer of ketamine is a more potent relaxant of ACh-induced ASM contraction than the S(+)-enantiomer. This difference appears to be caused by differential actions on receptor-operated calcium channels.

Outcomes of anesthesia and surgery in people 100 years of age and older.

OBJECTIVE: To assess the outcomes of anesthesia and surgery for men and women 100 years of age and older. DESIGN: Retrospective cohort study in the 20-year time period from 1975 to 1994, with follow-up through 1995. SETTING: Mayo-affiliated hospitals and Olmsted Community Hospital, Rochester, Minnesota. PARTICIPANTS: All men and women 100 years of age and older who underwent surgery at a participating hospital. MEASUREMENTS: Forty-eight-hour and 30-day perioperative morbidity and mortality; long-term survival. RESULTS: Thirty-one men and women aged 100 to 107 years underwent 42 procedures. One major complication (3%) within 48 hours was observed. The 48-hour, 30-day, and 1-year mortality rates were 0%, 16.1%, and 35.5%, respectively. When compared with survival rates for age-, gender-, and calendar year of birth-matched peers from the general population, the survival rate for centenarians who underwent surgery and anesthesia was comparable to the rate expected. CONCLUSION: These data suggest that people 100 years of age and older who have operable diseases or injuries should not be denied surgical interventions because of perceived risks associated with their advanced age.

Alveolar pressure inhomogeneity during low-frequency oscillation of excised canine lobes.

To quantify the inhomogeneity of alveolar pressures (PA) during cyclic changes in lung volume similar to those present during spontaneous breathing, inhomogeneity of PA was measured with an alveolar capsule technique in six excised canine lungs. The lungs were ventilated by a quasi-sinusoidal pump with a constant end-expiratory lung volume and tidal volumes of 10, 20, and 40% of vital capacity at breathing frequencies ranging from 5 to 45 breaths/min. Inhomogeneity of PA was quantified as the sample standard deviation of pressures measured in three capsules. A component of inhomogeneity in phase with flow and a smaller component out of phase with flow were present. The in-phase component increased approximately linearly with flow. The ratio of inhomogeneity to flow was smaller at large tidal volumes and, at the two higher tidal volumes studied, the ratio was greater during inspiration than during expiration. If these data are interpreted in terms of a simple circuit model, this degree of inhomogeneity implies an approximately twofold variation in regional time constants. Despite these considerable differences in time constants, the absolute amount of inhomogeneity as defined by the sample standard deviation of the three PA's was small (maximum 0.57 +/- 0.32 cmH2O at the highest breathing frequency and tidal volume) because airway resistance in the canine lung was small.

Inhomogeneity during deflation of excised canine lungs. I. Alveolar pressures.

Factors both intrinsic and extrinsic to the lung may cause inhomogeneity of alveolar pressures during deflation. Wilson et al. (J. Appl. Physiol. 59: 1924-1928, 1985) predicted that any such inhomogeneity would be limited by interdependence of regional expiratory flows. To test this hypothesis and to explore how the pleural pressure gradient might affect inhomogeneity of alveolar pressures, we deflated at submaximal flows excised canine lobes that first were suspended in air and then were immersed in foams that simulated the vertical gradient of pleural pressure. Interregional inhomogeneity of regional transpulmonary pressures was measured with use of an alveolar capsule technique. Flow-dependent inhomogeneity of alveolar pressures was present, with differences in alveolar pressure quickly relaxing to a constant limiting value at each flow. Foam immersion increased inhomogeneity at a given flow. We conclude that factors intrinsic to the lung cause significant inhomogeneity of alveolar pressures at submaximal expiratory flows and that this inhomogeneity is enhanced by the extrinsic gradient of pleural pressure. These observations are consistent with the interdependence of flow proposed by Wilson et al.

Inhomogeneity during deflation of excised canine lungs. II. Alveolar volumes.

We have previously demonstrated appreciable inhomogeneity of alveolar pressures measured by a capsule technique in excised canine lobes deflated at submaximal flows (J. Appl. Physiol. 65: 1757-1765, 1988). We further analyzed the results of these experiments by estimating alveolar volumes (VA) and regional flows from regional transpulmonary pressures, assuming that regional pressure-volume relationships were homogeneous. Deflation at submaximal flows of lungs suspended in air caused significant flow-dependent inhomogeneity of VA that increased as lung volume decreased. Immersion of lungs in stable foams that simulated the gradient of pleural pressure modified the pattern of emptying, but not always to a gravity-dependent sequence. Limitation of regional expiratory flow was often asynchronous during both air suspension and foam immersion. There was no evidence of a common regional flow-volume curve. Submaximal deflation is a complex heterogeneous process, with the interregional pattern of emptying determined by the interaction of factors that are both intrinsic and extrinsic to the lungs.

Inhomogeneity during deflation of excised canine lungs. III. Single-breath O2 tests.

Both interregional and intraregional mechanisms may cause changes in N2 concentration of expired gas during the phases of the single-breath O2 test (SBO2) that follow dead-space washout. To evaluate the possible importance of each mechanism, we performed the SBO2 in excised canine lungs that were first suspended in air and then immersed in stable foams that simulated the vertical gradient of pleural pressure. The lungs were deflated at constant submaximal flows. The slope of phase III diminished with increasing expiratory flow and increased with foam immersion. The onset of phase IV depended on flow, and a terminal decrease in N2 concentration (phase V) was often observed. Simultaneously measured estimates of regional flows and volumes (J. Appl. Physiol. 65: 1764-1774, 1988) were used to further interpret these results. The onset of phase IV at flows greater than quasi-static signified the onset of flow limitation of dependent regions. The onset of phase V corresponded to flow limitation of nondependent regions.

Regional ventilation in excised lobes exposed to a transpulmonary pressure gradient.

We performed the quasi-static single-breath oxygen test (SBO2) in 16 excised canine lower lung lobes while the lobes were first suspended in air and then later immersed in stable foams that provided a vertical transpulmonary pressure gradient. In lobes suspended in air, an approximately linear alveolar plateau (AP) was obtained. The AP during foam immersion was markedly curvilinear, with phase IV seen at end expiration. The observed AP during foam immersion could be predicted by a mathematical model that assumed a homogeneous transpulmonary pressure-regional volume relationship equal to the overall pressure-volume (PV) relationship measured with the lobe suspended in air. The accuracy of this model was further confirmed by measuring the washout of nitrogen injected into different lung regions through alveolar capsules. We also used the model to examine the relationship between the onset of dependent airway closure and two of its proposed indicators: the onset of phase IV and the inflection point of the overall PV relationship. In most lobes, the lung volume at the onset of phase IV was less than the modeled lung volume at dependent airway closure. The lung volume at the inflection point was always less than the modeled lung volume at dependent airway closure. We show that the overall PV relationship measured in lobes suspended in air provides an accurate estimate of regional PV relationships during foam immersion.

Simulation of the vertical gradient of transpulmonary pressure by stable foams.

We describe a simulation of the vertical gradient of transpulmonary pressure (VGTP) using a stable foam, which is suitable for use in studies of the effect of the VGTP on excised lungs. We generated foams that produced linear hydrostatic pressure gradients (HPGs) from 0.18 to 0.44 cmH2O/cm depth, which were stable over time and were reproducible. The HPG was similar under static and dynamic conditions. The foam did not affect lung elastic properties or cause histological changes. We conclude that these stable foams provide a practical, inexpensive simulation of the VGTP and should be useful in studying the effects of the VGTP on regional lung behavior.

Electrical activation of expiratory muscles increases with time in pentobarbital-anesthetized dogs.

Although the pentobarbital-anesthetized dog is often used as a model in studies of respiratory muscle activity during spontaneous breathing, there is no information regarding the stability of the pattern of breathing of this model over time. The electromyograms of several inspiratory and expiratory muscle groups were measured in six dogs over a 4-h period by use of chronically implanted electrodes. Anesthesia was induced with pentobarbital sodium (25 mg/kg iv), with supplemental doses to maintain constant plasma pentobarbital concentrations. Phasic electrical activity increased over time in the triangularis sterni, transversus abdominis, and external oblique muscles (expiratory muscles). The electrical activity of the costal diaphragm, crural diaphragm, and parasternal intercostal muscles (inspiratory muscles) was unchanged. These changes in electrical activity occurred despite stable plasma levels of pentobarbital and arterial PCO2. They were associated with changes in chest wall motion and an increased tidal volume with unchanged breathing frequency. We conclude that expiratory muscle groups are selectively activated with time in pentobarbital-anesthetized dogs lying supine. Therefore the duration of anesthesia is an important variable in studies using this model.

Chest wall motion during spontaneous breathing and mechanical ventilation in dogs.

We measured the volume change of the thoracic cavity (delta Vth) and the volumes displaced by the diaphragm (delta Vdi) and rib cage (delta Vrc) in six pentobarbital-anesthetized dogs lying supine. A high-speed X-ray scanner (dynamic spatial reconstructor) provided three-dimensional images of the thorax during spontaneous breathing and during mechanical ventilation with paralysis. Tidal volume (VT) was measured by integrating gas flow. Changes in thoracic liquid volume (delta Vliq, presumably caused by changes in thoracic blood volume) were calculated as delta Vth - VT. Absolute volume displaced by the rib cage was not significantly different during the two modes of ventilation. During spontaneous breathing, thoracic blood volume increased during inspiration; delta Vliq was 12.3 +/- 4.1% of delta Vth. During mechanical ventilation, delta Vliq was nearly zero. Configuration of the relaxed chest wall was similar during muscular relaxation induced by either pharmacological paralysis or hyperventilation. Expiratory muscle activity produced 50 +/- 11% of the delta Vth during spontaneous breathing. We conclude that at constant VT the volume displaced by the rib cage is remarkably similar during the transition from spontaneous breathing to mechanical ventilation, while both diaphragmatic volume displacement and changes in intrathoracic blood volume decrease by a similar amount.

Halothane decreases both tissue and airway resistances in excised canine lungs.

Studies of the anesthetic effects on the airway often use pulmonary resistance (RL) as an index of airway caliber. To determine the effects of the volatile anesthetic, halothane, on tissue and airway components of RL, we measured both components in excised canine lungs before and during halothane administration. Tissue resistance (Rti), airway resistance (Raw), and dynamic lung compliance (CL, dyn) were determined at constant tidal volume and at ventilatory frequencies ranging from 5 to 45 min-1 by an alveolar capsule technique. Halothane decreased RL at each breathing frequency by causing significant decreases in both Raw and Rti but did not change the relative contribution of Rti to RL at any frequency. Halothane increased CL,dyn at each breathing frequency, although there was little change in the static pressure-volume relationship. The administration of isoproterenol both airway and tissue components of RL; it may act by relaxing the contractile elements in the lung. Both components must be considered when the effects of volatile anesthetics on RL are interpreted.

Anesthesia and chest wall function in dogs.

Three anesthetics (pentobarbital, halothane, and isoflurane) were studied in six mongrel dogs to systematically compare their effects on chest wall function during spontaneous breathing. Each dog received each anesthetic on separate occasions. Electrical activities of several respiratory muscles were measured with chronically implanted electrodes, and chest wall motion was assessed by high-speed three-dimensional computed tomography scanning. Phasic expiratory muscle activity was markedly depressed by volatile anesthetics halothane and isoflurane compared with pentobarbital. In contrast, inspiratory activity in parasternal intercostal muscles was relatively well preserved during anesthesia with these volatile agents. The contribution of expiratory muscles to tidal volume was diminished during halothane and isoflurane compared with pentobarbital anesthesia. As anesthesia was deepened, expiratory muscle activity was unchanged during pentobarbital anesthesia, enhanced in some dogs during isoflurane anesthesia, and remained absent during halothane anesthesia. Activity in parasternal intercostal muscle was depressed as inspired concentration of halothane or isoflurane was increased, whereas diaphragmatic activity was unchanged. Depression of expiratory muscle activity by halothane persisted when breathing was stimulated by positive end-expiratory pressure, with significant mechanical consequences for chest wall configuration. Many of these findings are in contrast with previous observations in humans and suggest that the dog is not a suitable model for the study of the effects of anesthetic drugs on the pattern of human respiratory muscle activity.