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PubMed1977

Investigations of cigarette smoke dosages in inhalation experiments with Syrian hamsters. I. Concentration of cigarette smoke in the inhalation chamber and of carbon monoxide in the blood.

We tested 20 different smoke inhalation machines and determined that 60% of the gas phase and 40% of the total paritulate matter reached the inhalation chamber; the remainder was lost in the exhaust gases. After determining these concentration percentages, we were able to calculate precisely the dosage of each puff of smoke administered to Syrian hamsters in our smoking machine. We also determined that the CO-Hb content in the blood of the hamsters rose to 60%; this CO-Hb value was a limiting factor for time of exposure to smoke, since too-high concentrations of CO-Hb would have killed the animals. On the basis of these results, we concluded that the animals should be exposed as long as possible to attain a high dose of smoke, but because of toxic effects the exposure time should not exceed 20 minutes, and the CO-Hb content should not exceed 60%.

Air↗
PubMed1986

Cold air inhalation has a cumulative bronchospastic effect when inhaled in consecutive doses for progressively increasing degrees of ventilation.

In 12 asthmatic subjects, we compared the bronchoconstriction obtained with 3 methods of isocapnic inhalation of cold dry air (IICDA) on 6 visits, two visits for each method: Dose-response curves (DRC), which were obtained by asking the subjects to inhale at progressively increasing degrees of ventilation (7.5, 15, 30, 60 L/min and maximal voluntary ventilation [MVV] at a fixed breathing rate); free MVV, i.e., breathing frequency not set; same degree of ventilation as the last required for DRC (VEeq). Degrees of ventilation were significantly greater with the free MVV method. The percentage fall in FEV1 obtained by VEeq method was significantly lower than the changes recorded with the DRC and the MVV methods, the 2 latter being not significantly different. We conclude that IICDA induces a cumulative bronchoconstriction by the DRC method. However, the bronchoconstriction obtained with the latter method is not significantly different from the one obtained with the free MVV method.

Asthma↗
PubMedDate not supplied

Switch to non-CFC inhaled corticosteroids: a comparative efficacy study of HFA-BDP and CFC-BDP metered-dose inhalers.

Inhaled corticosteroids, such as beclomethasone dipropionate (BDP), recommended for the treatment of persistent, mild, moderate, or severe asthma, have traditionally been administered via chlorofluorocarbon (CFC) propellant. The imminent phasing out of CFCs from pharmaceutical preparations due to the Montreal Protocol means patients will have to switch to a CFC-free alternative. One such preparation is hydrofluoroalkane-BDP (HFA-BDP), a press-and-breathe metered-dose inhaler. This 8-week, open-label, multicentre study assessed asthma control in patients switching from CFC-BDP to HFA-BDP (QVAR). Patients with asthma, stabilised on 400-1600 micrograms/day CFC-BDP, were randomised to HFA-BDP (354 patients; 75%) at half their current daily dose of CFC-BDP, or to CFC-BDP (119 patients; 25%). HFA-BDP efficacy was found to be equivalent to that of CFC-BDP in that no statistically significant difference was observed between the two groups in the mean change from baseline in a.m. PEF (95% CI within +/- 11 l/min). No statistically significant differences were observed between the two groups for increased asthma symptoms or acute asthma episodes. We conclude that asthma control was maintained over 8 weeks, with few asthma exacerbations, in patients switching from previous CFC-BDP therapy to HFA-BDP at half the dose.

Adrenal Cortex Hormones↗
PubMed1990

Comparison of inhaled terbutaline and inhaled terbutaline plus ipratropium bromide in acute asthmatic children.

Twenty asthmatic children, aged 4 to 15 years, consisting of 14 boys and 6 girls, were studied during acute episodes of asthmatic attacks. A group of 10 children each received either inhaled terbutaline 0.5 mg or inhaled terbutaline 0.5 mg followed by ipratropium bromide 0.04 mg 15 minutes later through a 750-ml volumetric spacer. Significant increases in FEV1 over the baseline were observed from 2 minutes to 2 hours and from 2 minutes to 6 hours following the first and second regimen respectively. A slightly greater increase and longer duration in FEV1 were observed in the combined drug treatment and very slight decreases in systolic and diastolic blood pressure below the base-line were observed. Neither regimen showed any serious adverse effect on the heart rate and respiratory rate.

Acute Disease↗
PubMed1990

[Lung deposition of 300 and 600 mg pentamidine, inhaled with 3 different inhalers].

Intracorporal, especially pulmonary, and extracorporal deposition of pentamidine was studied following inhalation of 300 or 600 mg in 6 ml Aqua dest. each dose in six patients with one previous episode of pneumocystis carinii pneumonia. Three different nebulizers--two mechanical nebulizers (Respirgard II and Pari-IS-2) and one ultrasonic device (Portasonic) - were compared. The following results were obtained: 1.300 mg pentamidine in 6 ml Aqua dest. is a sufficient dose for prophylaxis provided an appropriately constructed nebulizer and an optimal respiratory manoeuvre (inspiratory vital capacity breathing) are employed. With the nebulizer Portasonic, the frequency of cough was higher compared with the two mechanical nebulizers, which is attributed to its higher mist density. 2. Application of 600 mg pentamidine in 6 ml Aqua dest. as an aerosol is difficult to apply owing to clinical and technical problems caused by severe respiratory tract irritation and a high viscosity of the nebulizer solution. We assume that ultrasonic nebulization is affected more by the high viscosity than mechanical pneumatic nebulization. 3. Inspiratory vital capacity breathing (12/min) leads to five- to eight-fold higher pulmonary and improved peripheral deposition rates compared with commonly used spontaneous respiration. We therefore recommend to shorten the duration of inhalation by applying this respiratory technique while maintaining a generally tolerated and optimally nebulizable concentration of pentamidine, i.e. about 300 mg in 6 ml Aqua dest.

Aerosols↗
PubMed2002

Inhalation delivery of anticancer agents via HFA-based metered dose inhaler using methotrexate as a model drug.

In the present study, the feasibility of delivering anticancer drugs via metered dose inhaler (MDI) was demonstrated using methotrexate (MTX) as a model anticancer drug. MDI formulations of MTX were prepared using hydrofluoroalkane-134a containing 0.67% MTX and 10% ethyl alcohol. The particle size of MTX was reduced by cryo milling with or without a surfactant (Pluronic F77) and the milled drug was employed for MDI formulations, which were subsequently evaluated for their medication delivery, mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD). Further, the efficacy of aerosolized MTX was evaluated by determining the in-vitro cytotoxicity of MTX against HL-60 cells using a six-stage viable impactor and the induction of apoptosis in HL-60 cells by acridine orange staining. Our results indicate that MTX aerosols having an MMAD varying between 2.2 and 3.2 microm (GSD 2.6-3.7) with a respirable fraction varying between 14.2 and 17.1% could be obtained by using MTX, which was cryo milled either alone or in combination with Pluronic F77. Exposure of HL-60 cells plated in third, fourth, fifth, and sixth stages of viable impactor to two actuations of MDI showed a cell kill of greater than 50%. Further, aerosolized MTX was found to induce apoptosis in HL-60 cells, as assessed by the morphological examination of the cells with fluorescent and confocal microscopy. Our results demonstrate that it is possible to deliver cytotoxic concentrations of MTX in an in vitro system simulating the lower respiratory tract (by using a six-stage viable impactor) via MDI and the cytotoxicity of the aerosolized MTX could be further improved by the optimization of the aerodynamic size.

Administration, Inhalation↗
PubMed2000

Inhalation toxicity of 1,6-hexamethylene diisocyanate homopolymer (HDI-IC) aerosol: results of single inhalation exposure studies.

The early acute pulmonary response of female Wistar rats exposed nose-only to a mixture of 1,6-hexamethylene diisocyanate homopolymer (HDI-IC) aerosol was examined. This study was designed to investigate the time course of the relationship between acute pulmonary irritation and ensuing disturbances of the air/blood barrier in rats exposed to concentrations of 3.9, 15.9, 54.3, or 118. 1 mg HDI-IC/m(3). The duration of exposure was 6 h, followed by serial sacrifices 0 h, 3 h, 1 day, 3 days, and 7 days postexposure. Concentrations were selected based on the results of a 4-h acute inhalation study in rats (LC(50) = 462 mg/m(3)). Bronchoalveolar lavage (BAL) fluid was analyzed for markers indicative of injury of the bronchoalveolar region, including phospholipids as proxy of altered surfactant homeostasis. Glutathione (GSH) was determined in BAL fluid and lung tissue. BAL cells with increased intracellular phospholipids were observed on day 1 and especially day 3, with some residual increase on day 7. Increased intracellular phospholipids and activity of acid phosphatases appear to suggest that phagocytized phospholipids may transiently affect lysosomal function. Following exposure to 15.9 mg/m(3), changes returned almost entirely to the level of the air-exposed control on day 7. Especially at higher exposure concentrations, lung weights and total number of cells in BAL were still statistically significantly elevated at this time point. Experimental evidence suggests that markers indicative of a dysfunction of the air/blood barrier, such as angiotensin-converting enzyme, total protein, and phospholipids engulfed by alveolar macrophages, were most sensitive to probe this type of changes. Although GSH in BALF was increased following exposure, there was an apparent depletion of tissue GSH immediately after cessation of exposure. In summary, this study suggests that respirable HDI-IC aerosol appears to cause a transient dysfunction of the air/blood barrier indicated by an increased extravasation of plasma constituents. Despite the remarkable extent of effects observed, most changes were reversible within a postexposure period as short as 7 days. First evidence of increased leakage of pulmonary epithelial barrier was observed at 3.9 mg/m(3). With respect to changes of early markers of pulmonary epithelial barrier dysfunction, approximately 3 mg HDI-IC/m(3) was considered to be the threshold concentration for acute pulmonary irritation.

Acid Phosphatase↗
PubMed2003

Comparative efficacy of terbutaline sulphate delivered by Turbuhaler dry powder inhaler or pressurised metered dose inhaler with Nebuhaler spacer in children during an acute asthmatic episode.

AIMS: To compare the efficacy of terbutaline sulphate delivered via Turbuhaler with a pressurised metered dose inhaler (pMDI) connected to Nebuhaler spacer in a population of asthmatic children presenting to emergency departments because of an acute episode of asthma. METHODS: Randomised double blind, double dummy, parallel study of acute asthma in the emergency department. A total of 112 children (6-16 years), who had a diagnosis of asthma, a baseline FEV1 of 25-60% of predicted normal value (PNV), and the ability to perform spirometry were studied. Patients received two doses of 0.5 mg/10 kg (maximum 2.0 mg) of terbutaline sulphate at time 0 minutes and time 30 minutes. The two groups were also stratified into subgroups based on FEV1: 25-45% and 45.1-60% PNV. FEV1 before treatment and at two 15-minute intervals after each treatment was the main outcome measure. PIF, PEF, heart rate, SpO2, and tremor were also measured at these times. RESULTS: Both the Turbuhaler and pMDI+Nebuhaler groups showed significant increases from baseline to final value in their FEV1 results, 49% and 50% change from baseline to t = 60 min, respectively (p < 0.001) using last value carried forward. No significant difference was found between the two groups for these results. Subanalysis of the stratified groups revealed similar results. In addition, no significant difference was found in the group and subgroup comparisons for heart rate, SpO2, and tremor. CONCLUSION: Results show that Turbuhaler and pMDI+Nebuhaler are similar in terms of benefit and side effects in the treatment of acute moderate to severe asthma attacks in this study population.

Acute Disease↗
PubMed1998

Effects of inhaled corticosteroids and inhaled cromolyn sodium on urinary growth hormone excretion in asthmatic children.

Over the past few years there has been an increasing awareness that asthma is a chronic inflammatory airways disease. The current therapeutic strategies for treating asthma focus on suppressing the inflammatory process by using cromones or inhaled corticosteroids (ICS). The beneficial effects of ICS in asthma are now well known, but its detrimental effect on linear growth remains a controversial issue. The aim of this open label, nonrandomized, cross-sectional, one-time study was to determine the influence of these drugs on urinary growth hormone (U-GH) levels in prepubertal asthmatic children. U-GH levels were measured in 47 prepubertal asthmatic children who had been treated for at least 6 months with either ICS (beclomethasone or budesonide at a mean daily dose of 360 microg) or with 80 mg daily dose of cromolyn sodium (CrS). There were also nine healthy children who served as a control. These three groups of children were matched for age and gender ratio. The mean level of U-GH in the CrS-treated group was 2.94 +/- 0.96 ng/night; this was significantly higher compared to the mean level of the ICS-treated group (1.99 +/- 0.83 ng/night; P < 0.001) and to the mean level of the control group (1.98 +/- 0.39 ng/night; P < 0.006). There was no significant difference between the mean level of U-GH in the group treated by ICS and the controls (P < 0.9). These results show that the mean levels of U-GH secretion of the children who were treated by CrS for 6 months was significantly increased, compared to the mean U-GH level of the ICS-treated group and the controls. The mean U-GH levels in the last two groups showed no statistically significant difference.

Administration, Inhalation↗
PubMed1996

An assessment of the systemic effects of single and repeated doses of inhaled fluticasone propionate and inhaled budesonide in healthy volunteers.

The systemic effects of single and multiple doses of inhaled fluticasone propionate (FP) and budesonide were examined in 24 healthy male volunteers (age range 18-29 years). The study was of an open, placebo-controlled, randomized, three-way crossover design. On each study day, multiple blood samples were taken over a 20 h period after drug administration (after a single dose and after the last of seven doses) and area under the curve (AUC(0-20)) for plasma cortisol and white blood cell (WBC) counts was calculated. RESULTS. The present study shows that multiple dosing with FP 1.0 mg b.i.d. for 3.5 days (seven doses) resulted in a marked cortisol suppression from placebo which, at 55%, was more than double that seen with a single dose (25% suppression). Multiple dosing with budesonide 0.8 mg b.i.d. resulted in a 34% suppression in plasma cortisol compared with a suppression of 26% with a single dose. The increase in systemic activity of FP after multiple dosing is confirmed by both the number of subjects with 0800 hours plasma cortisol values below normal limits and by the changes in WBC and differential counts. CONCLUSION. The results of the present study confirm previous findings with regard to the more marked systemic effect of FP following multiple dosing as compared with a single dose. This increase in systemic effect from single dosing to multiple dosing is significantly greater for FP than for budesonide.

Administration, Inhalation↗
PubMed1991

Assessment of systemic effects of inhaled glucocorticosteroids: comparison of the effects of inhaled budesonide and oral prednisolone on adrenal function and markers of bone turnover.

The effects of inhaled budesonide (BUD) and oral prednisolone (PRED) on markers of bone turnover and adrenal function were compared in a randomized, double-blind, double-dummy, crossover study. Twelve healthy subjects were treated for one week with 0.8, 1.6 and 3.2 mg/day BUD and 5, 10 and 20 mg/day PRED, the three doses being given in ascending order. Plasma cortisol and adrenal cortical androgens showed a significantly decreasing trend with the increasing doses of both drugs, although PRED caused a significantly greater decrease than BUD. Osteoblast function, reflected by serum osteocalcin and alkaline phosphatase was significantly reduced by PRED, but BUD had a significantly different effect as it affected only osteocalcin. Urinary hydroxyproline/creatinine, a marker of bone resorption, was not changed by either drug. The average potency ratio for equivalent systemic effects was PRED:BUD 3.9:1. During short-term treatment at equivalent anti-asthmatic doses, BUD has significantly less effect on adrenal function and bone turnover than PRED, and it may carry less risk of bone complications during long-term treatment.

Administration, Inhalation↗
PubMed1998

Disease-related response to inhaled nitric oxide in newborns with severe hypoxaemic respiratory failure. French Paediatric Study Group of Inhaled NO.

Inhaled nitric oxide (iNO) has been shown to improve oxygenation in severe persistent pulmonary hypertension of the newborn (PPHN). However, PPHN is often associated with various lung diseases. Thus, response to iNO may depend upon the aetiology of neonatal acute respiratory failure. A total of 150 (29 preterm and 121 term) newborns with PPHN were prospectively enrolled on the basis of oxygenation index (OI) higher than 30 and 40, respectively. NO dosage was stepwise increased (10-80 ppm) during conventional mechanical or high-frequency oscillatory ventilation while monitoring the oxygenation. Effective dosages ranged from 5 to 20 ppm in the responders, whereas iNO levels were unsuccessfully increased up to 80 ppm in the nonresponders. Within 30 min of iNO therapy, OI was significantly reduced in either preterm neonates (51+/-21 vs 23+/-17, P < .0001) or term infants with idiopathic or acute respiratory distress syndrome (45+/-20 vs 20+/-17, P < .0001), 'idiopathic' PPHN (39+/-14 vs 14+/-9, P < .0001), and sepsis (55+/-25 vs 26+/-20, P < .0001) provided there was no associated refractory shock. Improvement in oxygenation was less significant and sustained (OI=41+/-16 vs 28+/-18, P < .001) in term neonates with meconium aspiration syndrome and much less (OI=58+/-25 vs 46+/-32, P < .01) in those with congenital diaphragmatic hernia. Only 21 of the 129 term newborns (16%) required extracorporeal membrane oxygenation (57% survival). Survival was significantly associated with the magnitude in the reduction in OI at 30 min of iNO therapy, a gestational age > or =34 weeks, and associated diagnosis other than congenital diaphragmatic hernia. Conclusion, iNO improves the oxygenation in most newborns with severe hypoxaemic respiratory failure including preterm neonates. However, response to iNO is disease-specific. Furthermore, iNO when combined with adequate alveolar recruitment and limited barotrauma using exogenous surfactant and HFOV may obviate the need for extracorporeal membrane oxygenation in many term infants.

Administration, Inhalation↗
PubMed1996

Burns with inhalation injury and petrol aspiration in adolescents seeking euphoria through hydrocarbon inhalation.

We have recently managed four adolescent boys severely injured while aspirating petrol to achieve euphoria. This is a practice that occurs sporadically in this group in which alcohol and drugs are more difficult to procure by reason of their age and fiscal resources. The injuries sustained included extensive burns all with associated severe inhalation injury secondary to smoke and products of combustion, complicated by hydrocarbon pneumonitis.

Adolescent↗
PubMed1998

Establishing a therapeutic index for the inhaled corticosteroids: part I. Pharmacokinetic/pharmacodynamic comparison of the inhaled corticosteroids.

The inhaled corticosteroids contain physicochemical differences that alter both glucocorticoid receptor-binding characteristics and the pharmacokinetic variables of these drugs. Differences in receptor-binding affinity translate into differences in potency for different drugs. Differences in pharmacokinetics, however, determine the topical effect to systemic effect ratio, or the "pulmonary targeting" of the drug. Beneficial pharmacokinetic properties that may improve pulmonary targeting include low oral bioavailability, rapid systemic clearance, and slow absorption from the lung. Delivery devices can produce clinically significant differences in topical activity by altering the dose deposited in the lung and, for orally absorbed drugs, the amount deposited in the oropharynx and swallowed. Clinical trials have confirmed that differences in potency or drug delivery of 2-fold or more can be detected in patients with asthma. However, because of the relatively flat nature of the dose-response curve for morning peak expiratory flow and forced expiratory volume in 1 second, the trials must be adequately powered and well controlled. The use of bronchial provocation measures are problematic because of the prolonged lag time for response. Study design flaws can lead to misinterpretation of results. Clinical studies have indicated the following relative potency differences: fluticasone propionate > budesonide = beclomethasone dipropionate > triamcinolone acetonide = flunisolide. Current evidence suggests that potency differences can be overcome by giving larger doses of the less potent drug. However, because of these potency differences, studies of systemic effects should not be done in isolation of adequate topical activity studies to define the pulmonary targeting of the drugs.

Administration, Inhalation↗
PubMed2001

Inhalation toxicity of 1,6-hexamethylene diisocyanate homopolymers (HDI-IC and HDI-BT): results of subacute and subchronic repeated inhalation exposure studies.

This article addresses results of two 13-wk inhalation toxicity studies in Wistar rats with aerosolized 1,6-hexamethylene diisocyanate (HDI) homopolymers using either the isocyanurate (HDI-IC) type or biuret (HDI-BT) type. Groups of 10 rats/sex/level were exposed nose-only to breathing zone concentrations of 0.5, 3.3, and 26.4 mg HDI-IC/m(3) or 0.4, 3.4, and 21.0 mg HDI-BT/m(3) (MMAD = 1.4-3.3 microm). The exposure regimen was 6 h/day, 5 days/wk for 13 wk. Two control groups were used in each study; one was exposed to filtered air, and the other to the vehicle acetone. In subacute pilot studies, groups of rats were exposed under identical conditions for 3 consecutive weeks using concentrations of approximately 4, 15-18, and 77-90 mg homopolymer/m(3). All studies demonstrated that adverse effects were caused by irritation-related responses occurring predominantly in the lower respiratory tract. Following subchronic exposure, compound-related effects were found only at the highest concentrations used and were confined to mild respiratory distress, marginally decreased body weights, and increased lung weights. Hematological evaluation showed a marginal increase in leukocyte counts. Pulmonary function testing revealed minimal changes indicative of increases in functional residual capacity and total lung capacity but without evidence of increased bronchial hyperreactivity to acetylcholine aerosol. Histopathology demonstrated an increased recruitment of alveolar macrophages, focal interstitial fibrosis with round-cell infiltrations, and bronchiolo-alveolar proliferations at the high-level exposure groups. The no-observable-adverse-effect levels (NOAELs) of both the 3- and 13-wk studies were in the range of 3-4 mg/m(3). Appreciable differences between the two types of polyisocyanates were not observed.

Administration, Inhalation↗
PubMed2001

Inhalation toxicity of 4-ethoxyaniline (p-phenetidine): critical analysis of results of subacute inhalation exposure studies in rats.

This article addresses results from a single 4-h and repeated 1- and 4-wk inhalation exposure studies in Wistar rats with vapor and/or aerosol atmospheres of 4-ethoxyaniline (p-phenetidine). Groups of 10 rats/sex were exposed nose-only to mean analytical concentrations of 11.1, 86.2, and 882.6 mg p-phenetidine/m(3) using an exposure regimen of 6 h/day, 5 days/wk for 4 wk. Concentrations were selected based on results from a pilot study in which rats were exposed under identical conditions on 5 consecutive days for 6 h/day to mean analytical concentrations of 38.2, 133.0, and 1247.6 mg/m(3). In repeated exposure studies, the focus of endpoints was on hematotoxicity. The LC50 was not determined, but no rats died following a single 4-h exposure to 5085 mg/m(3) as a mixture of vapor and aerosol. No mortality was observed either in the 1- or 4-wk studies. Rats exposed to 882.6 mg/m(3) and above evoked characteristic signs of toxicity that included cyanosis, with no apparent progression of findings during the exposure period. Animals exposed to 86.2 mg/m(3) and above exhibited a concentration-dependent, significant increase in blood methemoglobin and reticulocyte counts as well as a significant decrease in hemoglobin, hematocrit, and red blood cell counts. Spleen weights were significantly increased in groups exposed to 133.0 mg/m(3) and above. Microscopic changes demonstrated an increased hematopoiesis (bone marrow smears) and splenic hemosiderosis at 86.2 and 882.6 mg/m(3) and a hepatic hemosiderosis only at 882.6 mg/m(3). These data suggest that the toxicity of p-phenetidine is similar to that of its structural analog aniline. Based on the erythrocytotoxicity occurring at 86.2 mg/m(3) and above, including the apparent reactive changes in bone marrow (increased erythropoiesis) and spleen (increased erythroclasia), the no-observed-adverse-effect level (NOAEL) of the 4-wk study was 11.1 mg/m(3) air and that of the 1-wk study was 38.2 mg/m(3) air. This difference in NOAELs is considered to be related to the selection of exposure concentrations rather than cumulative toxicity.

Aerosols↗
PubMed2003

Inhalational anthrax due to bioterrorism: would current Centers for Disease Control and Prevention guidelines have identified the 11 patients with inhalational anthrax from October through November 2001?

A panel of 10 physicians used the nominal group technique to assess the ability of the Centers for Disease Control and Prevention (CDC) interim guidelines for clinical evaluation of persons with possible inhalational anthrax (IA) to retrospectively identify the 11 patients with IA seen during the October 2001 bioterrorism outbreak. The guidelines would not have identified 10 of 11 of these patients, primarily because the guidelines were designed to address only those patients with a known history of exposure or clearly identified environmental or occupational risk. The panel suggested revisions to the guidelines, primarily consisting of broadening the criteria for evaluation to include either known exposure or environmental occupational risk, or to include clinical symptoms consistent with IA. These extensions of the guidelines retrospectively identified 8 of 11 of the patients with IA from October 2001.

Anthrax↗
PubMed1997

Reduced postoperative analgesic demand after inhaled anesthesia in comparison to combined epidural-inhaled anesthesia in patients undergoing abdominal surgery.

We studied the effect of epidural/general combination anesthesia, in comparison to inhaled anesthesia, on postoperative pain and analgesic consumption in patients undergoing upper abdominal surgery. Anesthesia was induced with propofol and maintained with enflurane in 70% N2O as necessary to maintain arterial blood pressure within 20% of baseline. Group I received bupivacaine 0.25% 0.2 mL/kg and sufentanil 1 microgram/kg 65 +/- 3 min before dermal incision and 0.1 mL/kg bupivacaine 0.25% + sufentanil 2 micrograms/mL (BS) every hour thereafter. Group II received 0.2 mL/kg of BS 316 +/- 15 min after dermal incision in the recovery room. Postoperative patient-controlled epidural analgesia (PCEA) with BS was provided. Pain intensities and consumption of PCEA BS were recorded on postoperative days (PODs) 1 to 5. Inspiratory fraction of enflurane was lower (0.5% +/- 0.01% vs 1.6% +/- 0.04%; P < 0.001) in Group I compared with Group II. Cumulative postoperative consumption of PCEA BS was higher in Group I compared with Group II from the evening of POD 2 until the end of the study (301 +/- 19 mL vs 249 +/- 17 mL; P < 0.001), while pain intensities were comparable at all times. The intraoperative effects of combined BS and enflurane/N2O (inspiratory fraction [Fi] approximately 1 minimum alveolar anesthetic concentration [MAC]) did not preempt postoperative pain in contrast to enflurane/N2O anesthesia (Fi approximately 2.8 MAC).

Abdomen↗