Comparison of intubating conditions after induction with propofol and remifentanil or sufentanil : Randomized controlled REMIDENT trial for surgical tooth extraction.

PURPOSE: The aim of this study was to compare tracheal intubation conditions after induction of anesthesia with a bolus of propofol-sufentanil or propofol-remifentanil and a rapid induction technique. MATERIAL AND METHODS: A total of 70 patients (American Society of Anesthesiologists (ASA) classification I­II) undergoing outpatient surgery under general anesthesia with intubation for tooth extraction were randomly assigned to two groups in this double-blind study. Patients received either a bolus of remifentanil (3 µg/kg) or sufentanil (0.3 µg/kg) together with 2.5 mg/kg propofol for intubation. The primary outcome was the percentage of excellent intubation conditions and the secondary outcomes were the percentage of patients with a decrease of over 20% in mean arterial pressure (MAP) or heart rate (HR), time to achieve spontaneous respiration, time between the end of surgery and extubation and time to achieve an Aldrete score of 10. VAS pain score was >3 or having laryngeal pain 15 min after arriving in the postanesthesia care unit (PACU) were also analyzed. RESULTS: Intubating conditions (perfect + good conditions) were significantly better with remifentanil than with sufentanil (88.5% vs. 68.6%; p = 0.01). When using remifentanil, the hemodynamic conditions were good. Using remifentanil did not significantly increase the pain score or the laryngeal pain in the recovery room. This was confirmed by no significant differences between the groups for morphine consumption. Remifentanil significantly decreased the time to achieve an Aldrete score of 10. CONCLUSION: When intubation without muscle relaxants is required, intubating conditions are much better when a remifentanil bolus is used compared to a sufentanil bolus. The remifentanil/propofol rapid induction technique is a valuable technique to quickly intubate and achieve good conditions.

Combined pectoralis and serratus anterior plane blocks with or without liposomal bupivacaine for minimally invasive thoracic surgery: A randomized clinical trial.

BACKGROUND: Minimally invasive thoracic surgery is associated with substantial pain that can impair pulmonary function. Fascial plane blocks may offer a favorable alternative to opioids, but conventional local anesthetics provide a limited duration of analgesia. We therefore tested the primary hypothesis that a mixture of liposomal bupivacaine and plain bupivacaine improves the overall benefit of analgesia score (OBAS) during the first three postoperative days compared to bupivacaine alone. Secondarily, we tested the hypotheses that liposomal bupivacaine improves respiratory mechanics, and decreases opioid consumption. METHODS: Adults scheduled for robotically or video-assisted thoracic surgery with combined ultrasound-guided pectoralis II and serratus anterior plane block were randomized to bupivacaine or bupivacaine combined with liposomal bupivacaine. OBAS was measured on postoperative days 1-3 and was analyzed with a linear mixed regression model. Postoperative respiratory mechanics were estimated using a linear mixed model. Total opioid consumption was estimated with a simple linear regression model. RESULTS: We analyzed 189 patients, of whom 95 were randomized to the treatment group and 94 to the control group. There was no significant treatment effect on total OBAS during the initial three postoperative days, with an estimated geometric mean ratio of 0.93 (95% CI: 0.76, 1.14; p = 0.485). There was no observed treatment effect on respiratory mechanics, total opioid consumption, or pain scores. Average pain scores were low in both groups. CONCLUSIONS: Liposomal bupivacaine did not improve OBAS during the initial postoperative three days following minimally invasive thoracic procedures. Furthermore, there was no improvement in respiratory mechanics, no reduction in opioid consumption, and no decrease in pain scores. Thus, the data presented here does not support the use of liposomal bupivacaine over standard bupivacaine to enhance analgesia after minimally invasive thoracic surgery. SUMMARY STATEMENT: For minimally invasive thoracic procedures, addition of liposomal bupivacaine to plain bupivacaine for thoracic fascial plane blocks does not improve OBAS, reduce opioid requirements, improve postoperative respiratory mechanics, or decrease pain scores.

Polyethylene glycol addition does not improve exogenous surfactant function in an experimental model of meconium aspiration syndrome.

Meconium (MEC) is a potent inactivator of pulmonary surfactant. The authors studied the effects of polyethylene glycol addition to the exogenous surfactant over the lung mechanics and volumes. Human meconium was administrated to newborn rabbits. Animals were ventilated for 20 minutes and dynamic compliance, ventilatory pressure, and tidal volume were recorded. Animals were randomized into 3 study groups: MEC group (without surfactant therapy); S100 group (100 mg/kg surfactant); and PEG group (100 mg/kg porcine surfactant plus 5% PEG). After ventilation, a pulmonary pressure-volume curve was built. Histological analysis was carried out to calculate the mean alveolar size (Lm) and the distortion index (DI). Both groups treated with surfactant showed higher values of dynamic pulmonary compliance and lower ventilatory pressure, compared with the MEC group (P < .05). S100 group had a larger maximum lung volume, V(30), compared with the MEC group (P < .05). Lm and DI values were smaller in the groups treated with surfactant than in the MEC group (P < .05). No differences were observed between the S100 and PEG groups. Animals treated with surfactant showed significant improvement in pulmonary function as compared to nontreated animals. PEG added to exogenous surfactant did not improve lung mechanics or volumes.

Evaluation of a novel inhalation exposure system to determine acute respiratory responses to tobacco and polymer pyrolysate mixtures in Swiss-Webster mice.

Modern cigarette production processes are highly automated and yield millions of cigarettes per day. The forming cigarette and its components contact many different materials in the production process, some of which may leave minute residues. The potential for small inclusions of non-cigarette materials such as wood, plastic, cardboard and other materials exists from the bulk handling and processing of tobacco, in spite of vigilant workers and numerous online systems designed to keep the tobacco stream clean. Currently, there are no published methods that describe an approach to evaluate the potential toxicological impact of these non-tobacco residues and inclusions on the biological activity from exposure to the complex mixture of tobacco smoke. There are, however, many methods which describe toxicological evaluation approaches for pure materials, particularly synthetic polymers. We used the Deutsche Institute fur Normung (DIN) 53-436 tube furnace and nose-only exposure chamber in combination to conduct pilot studies in Swiss-Webster mice in order to develop a standardized methodology for the evaluation of sensory irritation and other potentially useful biological endpoints for predicting any potential hazards. Sensory and/or pulmonary irritation was assessed based on respiratory function parameters using the ASTM E981-84 method described by Alarie (1966) in mice, exposed to test atmospheres of 100% tobacco pyrolysate or tobacco/polymer pyrolysate mixtures. Other biological evaluations included respiratory function parameters, clinical signs, body weights, bronchoalveolar lavage fluid analysis, carboxyhemoglobin, blood cyanide concentrations and histopathology of the respiratory tract. These pilot studies have demonstrated that such an approach can detect biological changes resulting from exposure to unique tobacco/polymer pyrolysates. Small differences were detected in the sensory irritation responses (respiratory function), activation state of pulmonary macrophages, and histopathological findings in the nose of mice exposed to 100% tobacco or tobacco/polymer pyrolysates. Analytical measurements were also performed in order to characterize the test atmospheric changes that could occur from inclusion of the polymer into the tobacco. These included DIN-generated wet total particulate matter (TPM) DIN-Generated wet TPM (DWTPM), nicotine, cyanide, formaldehyde, acetaldehyde, acrolein, carbon monoxide, carbon dioxide, and nitrogen oxides. We attempted to correlate analyte differences in the test atmospheres with the resulting biological findings in the mice. The results demonstrated that this approach could detect minimal toxicological effects in mice exposed to test atmospheres of 100% tobacco or 70%/30% tobacco/polymer pyrolysates.

Toxicological responses in SW mice exposed to inhaled pyrolysates of polymer/tobacco mixtures and blended tobacco.

Modern cigarette manufacturing is highly automated and produces millions of cigarettes per day. The potential for small inclusions of non-cigarette materials such as wood, cardboard packaging, plastic, and other materials exists as a result of bulk handling and high-speed processing of tobacco. Many non-tobacco inclusions such as wood, paper, and cardboard would be expected to yield similar pyrolysis products as a burning cigarette. The aircraft industry has developed an extensive literature on the pyrolysis products of plastics, however, that have been reported to yield toxic by-products upon burning, by-products that have been lethal in animals and humans upon acute exposure under some exposure conditions. Some of these smoke constituents have also been reported in cigarette smoke. Five synthetic polymers, nylon 6, acrylonitrile-butadiene-styrene (ABS), nylon 12, nylon 6,6, and acrylonitrile-butadiene (AB), and the natural polymer wool were evaluated by adding them to tobacco at a 3, 10, and 30% inclusion level and then pyrolyzing the mixture. The validated smoke generation and exposure system have been described previously. We used the DIN 53-436 tube furnace and nose-only exposure chamber in combination to conduct exposures in Swiss-Webster mice. Potentially useful biological endpoints for predicting hazards in humans included sensory irritation and pulmonary irritation, respiratory function, clinical signs, body weights, bronchoalveolar lavage (BAL) fluid analysis, carboxyhemoglogin, blood cyanide concentrations, and histopathology of the respiratory tract. Chemical analysis of selected smoke constituents in the test atmosphere was also performed in order to compare the toxicological responses with exposure to the test atmospheres. Under the conditions of these studies, biological responses considered relevant and useful for prediction of effects in humans were found for sensory irritation, body weights, BAL fluid analysis, and histopathology of the nose. There was a marked sensory irritation response that recovered slowly for some polymers. Sustained body weight depression, lesions of the respiratory epithelium of the nose, and morphological changes in pulmonary alveolar macrophages (PAM) were observed after exposure to some polymer/tobacco pyrolysates. These responses were increased compared to exposure to tobacco pyrolysate alone. No moribundity or mortality occurred during the study. The data suggest that polymeric inclusions pose a minimal additional toxicologic hazard in humans.

Effects of Eucalyptol in respiratory system mechanics on acute lung injury after exposure to short-term cigarette smoke.

Eucalyptol is a compound that has demonstrated antioxidant, anti-inflammatory and bronchodilator effects, but there are no investigations about the effects of this constituent on the respiratory system mechanics in relation to acute lung injury caused by short-term cigarette smoke (CS) exposure. In view of the above, this work investigated the effects of Eucalyptol on the mechanics of the respiratory system of mice in short-term CS exposure. For this, we used data from respiratory mechanics in vivo, and histopathology and lung parenchymal morphometry analysis in vitro. The experiments were performed on C57black/6 mice divided into 5 groups. One group exposed to ambient air (AA + T), and another to cigarette smoke (CS + T) for 5 consecutive days and treated with 1% Tween 80 solution. The other groups were exposed to cigarette smoke for 5 consecutive days, and treated with Eucalyptol at doses of 30 mg/kg (CS + E30), 100 mg/kg (CS + E100), 300 mg/kg (CS + E300). Our results demonstrated significant changes in all variables of respiratory mechanics and lung parenchyma morphometry analyzed for the AA + T group compared to the CS + T group, confirming the establishment of the lesion induced by exposure to cigarette smoke. We also observed that mice treated with Eucalyptol orally at a dose of 300 mg/kg (CS + E300) showed improvement in all variables compared to the group exposed to cigarette smoke and treated with 1% Tween 80 (CS + T) demonstrating the effectiveness of Eucalyptol in preventing lung injury induced by exposure to CS. In conclusion, our results demonstrated that the Eucalyptol was able to prevent the acute lung injury in mice submitted to short-term cigarette smoke exposure.

Effects of acute magnesium loading on pulmonary function of stable COPD patients.

BACKGROUND: Magnesium (Mg) use has the potential to promote bronchodilatation and to improve lung function in obstructive diseases. IV administration of Mg during exacerbations of chronic obstructive pulmonary disease (COPD) has led to improved peak flow. This study aimed to investigate the effects of acute IV Mg loading on respiratory parameters of stable COPD patients. MATERIAL/METHODS: This was a randomized, double-blind, placebo-controlled crossover study. Twenty-two male COPD patients (64+/-6 years old, FEV1: 49+/-20%) received an IV infusion of 2 g of magnesium sulfate or placebo on two distinct occasions. Spirometry and mouth maximal respiratory pressures were obtained before and 45 minutes after the infusions. RESULTS: Mg use led to significant changes in functional respiratory capacity (-0.48 l, 95%CI: -0.96, -0.01), inspiratory capacity (0.21 l, 95%CI: 0.04, 0.37), maximal inspiratory pressure (10 cmH2O, 95%CI: 1.6, 18.4), and maximal expiratory capacity (10.7 cmH2O, 95%CI: 0.20, 21.2). The treatment was also associated with a marginally significant decrease in residual volume (-0.47 L, 95%CI: -0.96, 0.02, p=0.06). CONCLUSIONS: Acute IV Mg loading in stable COPD patients was associated with a reduction in lung hyperinflation and improvement of respiratory muscle strength. The clinical potential for chronic magnesium supplementation in COPD deserves further investigation.

Low-dose AgNPs reduce lung mechanical function and innate immune defense in the absence of cellular toxicity.

Multiple studies have examined the direct cellular toxicity of silver nanoparticles (AgNPs). However, the lung is a complex biological system with multiple cell types and a lipid-rich surface fluid; therefore, organ level responses may not depend on direct cellular toxicity. We hypothesized that interaction with the lung lining is a critical determinant of organ level responses. Here, we have examined the effects of low dose intratracheal instillation of AgNPs (0.05 µg/g body weight) 20 and 110 nm diameter in size, and functionalized with citrate or polyvinylpyrrolidone. Both size and functionalization were significant factors in particle aggregation and lipid interaction in vitro. One day post-intratracheal instillation lung function was assessed, and bronchoalveolar lavage (BAL) and lung tissue collected. There were no signs of overt inflammation. There was no change in surfactant protein-B content in the BAL but there was loss of surfactant protein-D with polyvinylpyrrolidone (PVP)-stabilized particles. Mechanical impedance data demonstrated a significant increase in pulmonary elastance as compared to control, greatest with 110 nm PVP-stabilized particles. Seven days post-instillation of PVP-stabilized particles increased BAL cell counts, and reduced lung function was observed. These changes resolved by 21 days. Hence, AgNP-mediated alterations in the lung lining and mechanical function resolve by 21 days. Larger particles and PVP stabilization produce the largest disruptions. These studies demonstrate that low dose AgNPs elicit deficits in both mechanical and innate immune defense function, suggesting that organ level toxicity should be considered.

Comparison of the effects of dexmedetomidine and remifentanil on potential extreme haemodynamic and respiratory response following mask ventilation and laryngoscopy in patients with mandibular fractures.

OBJECTIVE: The safety profile and efficacy were compared for remifentanil and dexmedetomidine with respect to haemodynamic and respiratory response during mask ventilation and laryngoscopy in patients with mandibular fractures. PATIENTS AND METHODS: Seventy patients undergoing elective mandibular fracture surgery were randomly assigned to the remifentanil group (Group R, n = 35) or the dexmedetomidine group (Group D, n = 35). The primary outcomes were preoperative pain scores caused by jaw movement; haemodynamic response; intubation score; and side effects, such as the incidence of oxygen desaturation and muscle rigidity. Other side effects, such as tachycardia, bradycardia, hypertension and hypotension, were also compared. RESULTS: Preoperative pain scores caused by jaw movement were significantly high for both groups, but there were no statistically significant differences between the groups. The incidence of oxygen desaturation and muscle rigidity was significantly lower in Group D than in Group R (p = 0.025). No significant differences existed between the groups in terms of intubation score, haemodynamics, and other side effects (p > 0.05). DISCUSSION: Dexmedetomidine and remifentanil had equal effectiveness on the control of haemodynamic response due to mask ventilation and intubation in patients with mandibular fractures. However, at the doses used in this study, dexmedetomidine had a significant advantage over remifentanil in terms of respiratory stability.

Effects of levodopa on pulmonary function in Parkinson's disease.

STUDY OBJECTIVES: Upper-airway obstruction (UAO) may be present in patients with Parkinson's disease (PD), and its reversibility after levodopa therapy has been suggested. To investigate the effects of oral intake of levodopa on pulmonary function and UAO criteria in patients with PD, we studied 22 patients with PD. DESIGN: Pulmonary function tests were performed after a 12-h withdrawal of levodopa therapy, and 1 h after oral intake of placebo or levodopa, according to a double-blind, placebo-controlled, crossover study. Six UAO criteria were recorded to detect UAO in patients. UAO was found in 5 of 21 patients on baseline conditions (1 patient could not perform all tests). RESULTS: Among the patients with UAO, after levodopa therapy three of five patients did not meet the four of six required criteria for defining UAO. Levodopa produced its effects on UAO criteria by means of a saw-tooth pattern improvement and/or a decrease below the defined thresholds of the peak inspiratory flow and the FEV(1)/peak expiratory flow (PEF) and FEV(1)/forced expiratory flow after 50% of the FVC (FEV(0.5)) ratios. Levodopa PEF increased by 0.85 L/s in patients with UAO and by 0.24 L/s in patients without UAO, while after placebo it increased by 0.03 L/s in patients with UAO and decreased by 0.16 L/s in patients without UAO (p = 0.02). Whereas in patients without UAO an increase of the FEV(1)/PEF and FEV(1)/FEV(0.5) ratios was observed after placebo and levodopa intake, these ratios decreased after levodopa and increased after placebo in patients with UAO. CONCLUSIONS: These results show that levodopa administration in patients with PD induces significant variations in PEF and UAO ratios (FEV(1)/PEF and FEV(1)/FEV(0.5)).

Effect of a beta 2-agonist (broxaterol) on respiratory muscle strength and endurance in patients with COPD with irreversible airway obstruction.

The effect of broxaterol, a new beta 2-agonist, on respiratory muscle endurance and strength was studied in a double-blind, placebo-controlled, randomized crossover clinical trial in 16 patients with chronic obstructive pulmonary disease (COPD) with irreversible airway obstruction (FEV1 = 57.1 percent of predicted). One patient withdrew from the study because of acute respiratory exacerbation. Inspiratory muscle strength was assessed by maximal inspiratory pressure (MIP) and endurance time was determined as the length of time a subject could breathe against inspiratory resistance (target mouth pressure = 70 percent of MIP, Ti/Ttot = 0.4). Broxaterol (B) or placebo (P) was given orally for seven days at the dose of 0.5 mg three times a day with a washout period of 72 h between study treatments. Measurements were performed before administration of B or P and 2 h (six patients) or 8 h (nine patients) after the end of each treatment. No significant changes in FEV1 or FRC were observed after B or P suggesting that diaphragmatic length was maintained constant with each treatment. The MIP did not significantly change, while endurance time increased after B in the patients tested at 2 h (from 234.8 +/- 48.1 s to 284.0 +/- 48.0 s, p less than 0.05) and at 8 h (from 187.2 +/- 31.1 s to 258.2 +/- 40.4 s, p less than 0.005). No changes were observed after P. Minute ventilation, airway occlusion pressure (P0.1), integrated electromyographic activities of the diaphragm (Edi), and intercostal parasternals (Eic) (normalized to the value obtained during MIP) showed no change during the endurance run with different treatments. We conclude that in a group of COPD patients with irreversible airway obstruction, B significantly improves respiratory muscle endurance, and that this does not arise as a result of an effect on neuromuscular drive or pulmonary mechanics, but may be mediated by peripheral factors.

Comparing the subjective, psychomotor, and physiological effects of intravenous hydromorphone and morphine in healthy volunteers.

RATIONALE: The psychopharmacological profile of hydromorphone, an opioid that has been used extensively for many years for post-operative pain management, has not been adequately characterized in non-drug abusers. OBJECTIVES: To characterize the subjective, psychomotor, and physiological effects of a range of single doses of hydromorphone in non-drug-abusing volunteers and to compare the effects of hydromorphone with that of morphine, a benchmark mu opioid agonist. METHODS: Subjects in a six-session study were injected in an upper extremity vein with 0, 0.33, 0.65, 1.3 mg/70 kg hydromorphone, and 5 and 10 mg/70 kg morphine, using a randomized, double-blind, crossover design. RESULTS: Hydromorphone increased scores on the pentobarbital-chlorpromazine-alcohol group and lysergic acid diethylamide scales and decreased scores on the benzedrine group scale of the Addiction Research Center Inventory, increased adjective checklist ratings of ("dry mouth", "flushing", and "nodding", and increased visual analog scale ratings indicative of both pleasant (e.g., drug liking) and unpleasant (e.g., "feel bad") effects. The subjective effects of morphine at putatively equianalgesic doses to those of hydromorphone were similar to those of hydromorphone, but in some cases of lesser magnitude. Psychomotor impairment was modest with hydromorphone and absent with morphine. Both opioids produced dose-dependent decreases in pupil size. A relative potency analysis indicated that hydromorphone was 10 times as potent as morphine (1 mg hydromorphone=10 mg morphine). CONCLUSIONS: The results of this study demonstrate that 0.33-1.3 mg hydromorphone had orderly, dose-related effects on subjective, psychomotor, and physiological variables, and similar effects to those of a benchmark mu opioid agonist, morphine.

Breathing patterns in infants and children under halothane anesthesia: effect of dose and CO2.

We studied the amplitude, timing, and shape of the airflow waveform at the mouth of spontaneously breathing children under two sets of conditions: 1) in 30 children aged 9 wk-4.5 yr at 2, 1, and 0% inspired halothane concentration and 2) in 22 children aged 5 mo-7 yr during hyperoxic CO2 rebreathing while recovering from anesthesia. Compared with control values, the relative changes in breath parameters at 1 and 2% halothane were, respectively, as follows: total cycle time -19 and -31%, tidal volume (VT) -30 and -44%, minute ventilation -11 and -17%, and VT/inspiratory time (TI) -16 and -20%. Parameters of timing and breath shape did not change except for the significant but small increase in TI/total cycle time (by 6 and 8%, respectively). With CO2 rebreathing, parameters reflecting inspiratory drive increased significantly in all patients as shown by the slopes of the regressions of these parameters against end-tidal PCO2. Mean slopes expressed in %control value per millimeter of mercury CO2 were 12.1 for minute ventilation, 8.3 for VT, and 10.67 for VT/TI. Parameters reflecting the timing and breath shape remained essentially unchanged. Our results suggest that, in children under halothane anesthesia, the amplitude, timing, and shape of the breathing pattern are controlled independently. In particular, the amplitude and timing of the breath may vary widely without any significant change in the shape.

Effects of naloxone on the sensation of dyspnea during acute respiratory stress in normal adults.

To clarify whether endogenous opioids modulate the dyspnea intensity and, if so, by what mechanism they act on it, we examined 12 healthy male volunteers aged 19-27 yr for ventilatory and peak mouth pressure (Pm) responses to hypoxic progressive hypercapnia with inspiratory flow-resistive loading after the intravenous infusion of 3 mg of naloxone or saline. The intensity of dyspnea was simultaneously assessed by visual analogue scaling every 15 s. Naloxone administration increased both ventilatory and Pm responses to hypoxic progressive hypercapnia (P < 0.05 for both). The increase in dyspnea intensity for a given increase in end-tidal PCO2 was significantly greater after naloxone infusion than after saline (P < 0.05). However, there were no differences in the increase in dyspnea intensity for a given increase in minute ventilation or Pm. These results suggest that the endogenous opioid system suppresses the respiratory output under a strong, acute respiratory stress in normal adults and that this system may relieve the dyspnea sensation secondary to the suppression of the brain stem respiratory center without specific effects on the processing of respiratory sensations in the higher brain.

Artificial surfactant attenuates hyperoxic lung injury in primates. I. Physiology and biochemistry.

Prolonged exposure to O2 causes diffuse alveolar damage and surfactant dysfunction that contribute to the pathophysiology of hyperoxic lung injury. We hypothesized that exogenous surfactant would improve lung function during O2 exposure in primates. Sixteen healthy male baboons (10-15 kg) were anesthetized and mechanically ventilated for 96 h. The animals received either 100% O2 (n = 6) or 100% O2 plus aerosolized artificial surfactant (Exosurf; n = 5). A third group of animals (n = 5) was ventilated with an inspired fraction of O2 of 0.21 to control for the effects of sedation and mechanical ventilation. Hemodynamic parameters were obtained every 12 h, and ventilation-perfusion distribution (VA/Q) was measured daily using a multiple inert-gas elimination technique. Positive end-expiratory pressure was kept at 2.5 cmH2O and was intermittently raised to 10 cmH2O for 30 min to obtain additional measurements of VA/Q. After the experiments, lungs were obtained for biochemical and histological assessment of injury. O2 exposures altered hemodynamics, progressively worsened VA/Q, altered lung phospholipid composition, and produced severe lung edema. Artificial surfactant therapy significantly increased disaturated phosphatidylcholine in lavage fluid and improved intrapulmonary shunt, arterial PO2, and lung edema. Surfactant also enhanced the shunt-reducing effect of positive end-expiratory pressure. We conclude that an aerosolized protein-free surfactant decreased the progression of pulmonary O2 toxicity in baboons.

Mechanism of action of ozone on the human lung.

Fourteen healthy normal volunteers were randomly exposed to air and 0.5 ppm of ozone (O3) in a controlled exposure chamber for a 2-h period during which 15 min of treadmill exercise sufficient to produce a ventilation of approximately 40 l/min was alternated with 15-min rest periods. Before testing an esophageal balloon was inserted, and lung volumes, flow rates, maximal inspiratory (at residual volume and functional residual capacity) and expiratory (at total lung capacity and functional residual capacity) mouth pressures, and pulmonary mechanics (static and dynamic compliance and airway resistance) were measured before and immediately after the exposure period. After the postexposure measurements had been completed, the subjects inhaled an aerosol of 20% lidocaine until response to citric acid aerosol inhalation was abolished. All of the measurements were immediately repeated. We found that the O3 exposure 1) induced a significant mean decrement of 17.8% in vital capacity (this change was the result of a marked fall in inspiratory capacity without significant increase in residual volume), 2) significantly increased mean airway resistance and specific airway resistance but did not change dynamic or static pulmonary compliance or viscous or elastic work, 3) significantly reduced maximal transpulmonary pressure (by 19%) but produced no changes in inspiratory or expiratory maximal mouth pressures, and 4) significantly increased respiratory rate (in 5 subjects by more than 6 breaths/min) and decreased tidal volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Can a difference in chest wall mechanics explain the lower respiratory drive during propofol versus halothane anesthesia in children?

This article extends previous work which suggested that respiratory drive was lower during propofol compared with halothane anesthesia. The aim of this study was to assess simultaneously chest wall motion, measured with respiratory inductive plethysmography (RIP), and respiratory drive measured by P0.1 the pressure generated during the initial 100 msec of an occluded inspiratory effort. Ten healthy children age 3 to 6 years who presented for a dental restorative procedure that required in excess of 2.5 hours were recruited. Patients were anesthetized with propofol (2.5 mg x kg(-1); 15 mg x kg(-1) x hr) or halothane (1.25%), in a randomized crossover study design. Following induction of anesthesia, RIP bands were placed at the level of the nipples and the umbilicus for the measurement of rib cage and abdomen excursion, respectively. Flow and airway pressure were measured. A manually operated pneumatic balloon was used for brief airway occlusion. Following a 60-minute washin/out of the anesthetic, the children were removed from mechanical ventilation and spontaneous ventilation was reinstated. The RIP signals were calibrated by the method of simultaneous solution of equations. The phase lag was calculated. During airway occlusion the maximal excursion of the calibrated rib cage trace (RMAX) was measured; a negative value indicated retraction of the rib cage. Respiratory drive was assessed both at a fixed interval (100 msec) (P0.1) and fixed proportion (10%) (P10%) of the occluded inspiratory effort. Significance of differences were assessed with a paired t-test (P-value < 0.05). Thoracoabdominal asynchrony was greater during halothane than propofol anesthesia, as was the amount of rib cage retraction, evidenced by lower values of RMAX; respiratory drive was higher during halothane than propofol anesthesia, as evidenced by higher values of both P0.1, and P10%. We conclude that during halothane anesthesia altered chest wall mechanics may result in a greater respiratory drive than during propofol anesthesia.

Lung mechanics and gas exchange in ventilated preterm infants during treatment of hyaline membrane disease with multiple doses of artificial surfactant (Exosurf)

Eight premature infants ventilated for hyaline membrane disease and enrolled in the OSIRIS surfactant trial were studied. Lung mechanics, gas exchange [PaCO2, arterial/alveolar PO2 ratio (a/A ratio)], and ventilator settings were determined 20 minutes before and 20 minutes after the end of Exosurf instillation, and subsequently at 12-24 hour intervals. Respiratory system compliance (Crs) and resistance (Rrs) were measured by means of the single breath occlusion method. After surfactant instillation there were no significant immediate changes in PaCO2 (36 vs. 37 mmHg), a/A ratio (0.23 vs. 0.20), Crs (0.32 vs. 0.31 mL/cm H2O/kg), and Rrs (0.11 vs. 0.16 cmH2O/mL/s) (pooled data of 18 measurement pairs). During the clinical course, mean a/A ratio improved significantly each time from 0.17 (time 0) to 0.29 (time 12-13 hours), to 0.39 (time 24-36 hours) and to 0.60 (time 48-61 hours), although mean airway pressure was reduced substantially. Mean Crs increased significantly from 0.28 mL/cmH2O/kg (time 0) to 0.38 (time 12-13 hours), to 0.37 (time 24-38 hours), and to 0.52 (time 48-61 hours), whereas mean Rrs increased from 0.10 cm H2O/mL/s (time 0) to 0.11 (time 12-13 hours), to 0.13 (time 24-36 hours) and to (time 48-61 hours) with no overall significance. A highly significant correlation was found between Crs and a/A ratio (r = 0.698, P less than 0.001). We conclude that Exosurf does not induce immediate changes in oxygenation as does the instillation of (modified) natural surfactant preparations. However, after 12 and 24 hours of treatment oxygenation and Crs improve significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary mechanics in ventilated preterm infants with respiratory distress syndrome after exogenous surfactant administration: a comparison between two surfactant preparations.

The effects of two surfactant preparations on lung mechanics have been studied on 24 ventilated premature infants with respiratory distress syndrome (RDS): 13 were given artificial surfactant (Exosurf Neonatal, Burroughs-Wellcome) and 11 natural porcine surfactant (Curosurf, Laboratoire Serono France). Measurements of respiratory system compliance (Cdyn, Crs) and resistance (Rrs) were performed immediately before surfactant administration and repeated 6, 18, 24, 48, and 72 hours later. With Exosurf treatment, 6 hours after surfactant administration inhaled O2 concentration (FlO2) could be lowered from (0.72 +/- 0.20, to 0.62 +/- 0.33; P < 0.05), whereas Crs did not change (0.37 mL/cmH2O/kg, +/- 0.14 vs. 0.39 +/- 0.12, NS). After 24 hours and during the following days a significant increase in Crs occurred (24 hours post-Exosurf: 0.51 +/- 0.18, P < 0.05). With Curosurf treatment, the improvement in oxygenation was greater and FlO2 could be lowered much more after 6 hours (from FlO2, 0.78 +/- 0.23 to 0.34 +/- 0.11, P < 0.01). This was associated with an increase in Crs (from 0.39 +/- 0.09 to 0.59 +/- 0.17, P < 0.05). During the following days, Crs was significantly higher in the group treated with Curosurf. Resistance was not altered by the type of surfactant preparation used except after 72 hours, when Rrs increased in the group treated with Exosurf. In conclusion, Curosurf appears to be more effective than Exosurf with regard to immediate pulmonary changes in ventilator treated premature infants with RDS. A rapid increase in Crs after Curosurf treatment indicates that recruitment of new functional areas of the lung is likely to be associated with a stabilization of small airways and alveolar units.

Exposure to isocyanates and organic solvents, and pulmonary-function changes in workers in a polyurethane molding process.

The extent of adverse health effects of isocyanates when combined with other chemicals is not well documented. This study was conducted as a 2.5-year follow-up as well as to determine daily and weekly effects of exposure to isocyanates and organic solvents on pulmonary function. The concentrations of chemicals sampled were below the recommended exposure criteria. No daily or weekly reduction in the subjects' pulmonary function was observed. The isocyanate/solvent-exposed subjects showed significant long-term reduction in their forced vital capacity (P < 0.05) and expiratory volume in 1 second (P < 0.001). No such changes were observed in non-exposed subjects or in those exposed only to organic solvents. The proportion of subjects who developed respiratory symptoms in the isocyanate-exposed group was not significantly greater than that of the non-exposed group. The results of this study indicate that long-term exposure to isocyanates, even in very low concentrations, may contribute to impaired pulmonary function.