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Topical anesthesia with lidocaine aerosol in the control of postoperative pain.

Postoperative pain was assessed in patients undergoing inguinal hernia repair. Ten patients received lidocaine aerosol in the surgical wound before skin closure, ten patients received placebo aerosol devoid of lidocaine, and ten patients were untreated. The lidocaine-treated group had significantly lower pain scores and meperidine requirements during the first postoperative day compared to the control groups. During the second day after surgery, these variables did not differ between groups. Wound anesthesia, assessed by palpation of the wound 24 h after surgery by a blinded investigator, was significantly more pronounced in the group treated with lidocaine aerosol than in the control groups. Similarly, in patients undergoing bilateral herniorraphy, wound pain following palpation was significantly reduced on the lidocaine-treated side compared to the untreated side. Patients in the group receiving lidocaine aerosol indicated less pain in connection with mobilization than untreated patients, but not compared to patients treated with placebo aerosol. Plasma substance P (SP) and beta-endorphin (BE) measured in lidocaine-treated patients and in untreated patients before and after drug administration showed no significant differences regarding SP, while BE was significantly increased 1 h after surgery in the untreated group. Plasma lidocaine concentrations were well below toxic levels. Results show that lidocaine aerosol used as topical anesthetic in the surgical wound is simple to use, and results in a long-lasting reduction of pain after a single administration. Moreover, postoperative mobilization is facilitated, and the requirement for postoperative analgesics is reduced. Wound healing was normal, and no adverse reactions to lidocaine were reported.

Adult↗

Aerosolization of novel nitric oxide donors selectively reduce pulmonary hypertension.

OBJECTIVES: Inhaled nitric oxide (NO) reduces pulmonary hypertension in acute respiratory failure. Soluble nitric oxide donors (NO/nucleophile adducts-NONOates) are less cumbersome to deliver and may offer clinical advantage compared with inhaled NO. The objective of this study was to examine the pulmonary and systemic hemodynamic effects of tracheal aerosolization of a new class of NONOates in a porcine model of experimentally induced pulmonary hypertension. DESIGN: Prospective, randomized, controlled study. SETTING: Research laboratory. SUBJECTS: Yorkshire pigs (n = 18), weighing 11.4 to 16.4 kg. INTERVENTIONS: In anesthetized, mechanically ventilated, instrumented pigs, steady-state pulmonary hypertension (SSPH) was induced using a thromboxane agonist (U46619). Control animals received tracheal aerosolization of saline (n = 6); EP/NO animals received tracheal aerosolization of ethylputreanine NONOate (EP/ NO, n = 6); and DMAEP/NO animals received aerosolized 2-(dimethylamino) ethylputreanine NONOate (DMAEP/NO, n = 6). MEASUREMENTS AND MAIN RESULTS: Mean pulmonary (MPAP) and mean systemic arterial pressures (MAP), atrial pressures, cardiac output, and arterial blood gases were measured following drug instillation. DMAEP/NO animals had significant reductions in pulmonary vascular resistance index (PVRI) and MPAP at all time points compared with SSPH and control animals (p < .05), while systemic vascular resistance index did not change. EP/NO animals had a significant reduction in PVRI and MPAP at some time points compared with SSPH and control animals. For both NONOate-treated animal groups, MAP and cardiac index did not change significantly compared with SSPH and control animals (p < .05). CONCLUSIONS: In this porcine model of pulmonary hypertension, intratracheal aerosolization of soluble NO donors results in sustained reduction of pulmonary hypertension without reducing systemic arterial pressure. Intermittent aerosolization of NONOates may be an alternative to continuously inhaled NO in the treatment of acute pulmonary hypertension.

Acute Disease↗

Distribution, retention and dosimetry of plutonium and americium in the rat, dog and monkey after inhalation of an industrial-mixed uranium and plutonium oxide aerosol.

This study provides information on patterns of radiation dose in laboratory animals after inhalation exposure to an aerosol of one form of mixed uranium and plutonium oxide. The aerosol contained a mixture of UO2 and 750 degrees C heat-treated PuO2 obtained from the ball milling operation in a mixed-oxide fuel fabrication process. Americium-241 from the decay of 241Pu was also present in the PuO2 matrix. Fischer-344 rats, Beagle dogs, and Cynomolgus and Rhesus monkeys inhaled aerosols re-generated from dry mixed oxide powders with particle size distribution characteristics similar to those observed in samples collected at the industrial site. Clearance from the lung and distribution in other tissues of the plutonium from this UO2 + PuO2 admixture was similar to what has been observed for PuO2 from laboratory-produced aerosols. The UO2-PuO2 aerosol was relatively insoluble in the lungs of all species. Monkeys and rats cleared plutonium and americium from their lungs faster than dogs. Very little plutonium or americium translocated within the first 2 yr after exposure to tissues other than tracheobronchial lymph nodes. The greater accumulation of plutonium and americium in the tracheobronchial lymph nodes of dogs as compared to monkeys and rats combined with the more rapid initial clearance of these radionuclides from the lungs of rats and monkeys suggests that errors could result from using data from a single animal species to estimate risk to humans from inhalation of these industrial aerosols.

Aerosols↗

Generation of Li combustion aerosols for animal inhalation studies.

A system was developed for generating Li aerosols to determine the potential health hazards of postulated accidents associated with the use of Li as a fusion reactor blanket or coolant. The aerosol was generated by sweeping Ar through a stainless steel chamber filled with Li metal that was heated inductively to temperatures up to 1300 degrees C. Argon carried the Li vapor into a burning chamber where it was mixed with air. The reaction of Li vapor with air formed an intense white flame that produced typical branched-chain condensation aerosol particles. This system generated well-controlled concentrations up to 2500 mg/m3 for periods of 4 h. The mass median aeordynamic diameter of the aerosol was approximately 0.66 micron with a geometric standard deviation of 1.5. Aerosols could be generated that were greater than 96% Li2O and LiOH, LiOH.H2O, or Li2CO3 by controlling the CO2 and H2O concentrations in the supply air. The system is currently being used to investigate the acute toxicity of Li combustion aerosols in laboratory animals.

Accidents↗

Inhalation deposition and retention patterns of a U-Pu chain aggregate aerosol.

Chain aggregate aerosol particles are normally formed during many high-temperature combustion and vaporization processes. The shape of chain aggregate aerosol particles could have an effect on the pattern of inhalation deposition and retention of the particles in the respiratory tract. A chain aggregate aerosol of nuclear reactor fuel could be present as an inhalation hazard if it were released to the atmosphere after a meltdown, core-disruptive accident. Rats were exposed to a chain aggregate U-Pu aerosol made by laser vaporization of mixed-oxide, breeder reactor fuel (20% plutonium dioxide and 80% uranium dioxide), then sacrificed to measure the clearance and retention of the fuel aerosol particles. Deposition of the 0.7-micron (activity median aerodynamic equivalent diameter) aerosol particles resulted in an average initial lung burden of 4140 Bq alpha activity. The chain aggregate particle shape was not a major factor in the total deposition; however, it may have influenced the regional distribution of the activity deposited. Retention of the particles in the upper airways of the tracheobronchial tree was on the order of 1% of the concurrent lung burden, which is consistent with recent data of other investigations. This study indicates that insoluble chain aggregate particles are retained in the tracheobronchial airways to a degree similar to simple spherically shaped particles of equivalent volume diameter.

Aerosols↗

Influence of dust loading on the alpha-particle energy resolution of continuous air monitors for thin deposits of radioactive aerosols.

Alpha-particle continuous air monitors must sometimes be operated in dusty environments where significant dust loading of the filter can be anticipated. It is important to understand how this dust loading affects the response of the continuous air monitors. Not only must a filter be changed if there is a reduction in airflow, but a change may be necessary if the energy resolution deteriorates and the continuous air monitor loses sensitivity and specificity for the radioactive aerosols of interest. A series of experiments were conducted to investigate alpha-particle energy resolution of continuous air monitor filters, particularly under dust loading conditions. Aerosol particles of various sizes were tagged with radon decay products to serve as surrogates for radioactive aerosols of interest such as plutonium or uranium. While the size of radioactive aerosols, filter type, and dust type affected the energy resolution, the thickness of an underlying (nonradioactive) dust layer did not show significant effect for the materials studied and a loading range of 0.01-10 mg x cm(-2). Our results indicate that it is possible for continuous air monitors to detect the release of radioactive aerosols with little deterioration in energy resolution under conditions of significant dust loading provided that the deposited layer of radioactive aerosols remains thin (< or = 0.1 mg x cm(-2)).

Aerosols↗

Mechanical delivery of aerosolized gadolinium-DTPA for pulmonary ventilation assessment in MR imaging.

RATIONALE AND OBJECTIVES: To evaluate a new technique with mechanical administration of aerosolized gadolinium (Gd)-DTPA for MR visualization of lung ventilation. METHODS: Ten experimental procedures were performed in six domestic pigs. Gd-DTPA was aerosolized by a small-particle generator. The intubated animals were mechanically aerosolized with the nebulized contrast agent and studied on a 1.5-T MR imager. Respiratory gated T1-weighted turbo spin-echo images were obtained before, during, and after contrast administration. Pulmonary signal intensity (SI) changes were calculated for corresponding regions of both lungs. Homogeneity of aerosol distribution was graded independently by two radiologists. RESULTS: To achieve a comparable SI increase as attained in previous trials that used manual aerosol ventilation, a ventilation period of 20 minutes (formerly 30 minutes) was sufficient. Mean SI changes of 116% were observed after that duration. Contrast delivery was rated evenly distributed in all cases by the reviewers. CONCLUSIONS: The feasibility of applying Gd-DTPA as a contrast agent to demonstrate pulmonary ventilation in large animals has been described before. The results of this refined technique substantiate the potential of Gd-based ventilation MR imaging by improving aerosol distribution and shortening the nebulization duration in the healthy lung.

Aerosols↗

Investigation of pulmonary epithelial permeability in patients after hyperbaric oxygen therapy by 99mTc diethylenetriaminepentaacetic acid aerosol inhalation lung scintigraphy.

The aim of this study was to evaluate the possibility of pulmonary epithelial permeability damage in patients after hyperbaric oxygen therapy (HBOT) by 99mTc diethylenetriaminepentaacetic acid (99mTc-DTPA) aerosol inhalation lung scintigraphy. Twenty-five controls and 21 patients with normal chest X-rays and no cigarette smoking for at least 1 year were recruited for the study. 99mTc-DTPA aerosol inhalation lung scans were performed after 20 HBOT sessions in 21 patients with refractory osteomyelitis or diabetic foot. The HBOT with 100% oxygen at 2.5 atm absolute for 100 min was performed five times a week. Clearance rates (%/min) of 99mTc-DTPA aerosol in each lung field were calculated from the dynamic images for 30 min. Clearance rates of 99mTc-DTPA aerosol were compared between patients and controls by the unpaired t test. Thirteen patients who had 99mTc-DTPA aerosol lung scans before and after HBOT therapy studies were tested for statistical significance by using the paired t test. There was no statistically significant difference (P>0.05, unpaired t test) between patients and controls in every lung field. For the 13 patients who had 99mTc-DTPA aerosol studies both before and after 20 HBOT sessions, the results also showed no statistically significant difference (P>0.05, paired t test). It is concluded that there was no demonstrable pulmonary epithelial permeability change under current clinical HBOT protocol.

Administration, Inhalation↗

The pH of aerosol saline solution.

We evaluated the pH of eight brands of aerosol saline solution to determine if there is a change in pH during the normal usage of an aerosol canister. The pH measurements were taken over a period of 14 to 24 days with a Corning model 10 pH meter (accuracy +/- 0.05 pH units). The saline was expelled and measured daily in 15-ml increments, the approximate volume used each day by soft lens wearers. We found no significant change in pH within each brand evaluated over the test period. However, there was a statistically significant difference in the median pH of the buffered and the unbuffered aerosol saline solutions. The mean pH of the buffered aerosol saline solutions, which averaged 7.30 pH units, was within the ocular comfort range. The mean pH of the unbuffered aerosol saline solutions, which averaged 5.79 pH units, was outside the ocular comfort range. This indicates that all aerosol saline solutions should be buffered.

Aerosols↗

Environmental and body contamination through aerosols produced by high-speed cutters in lumbar spine surgery.

STUDY DESIGN: A cadaver study to evaluate contamination in the operating room through the use of a high-speed bone cutter. OBJECTIVES: To determine the grade of contamination of animate and inanimate objects through an aerosol intraoperatively, produced by a high-speed cutter during lumbar laminectomy. SUMMARY OF BACKGROUND: In spinal surgery, high-speed cutters are used that produce an aerosol consisting of a mixture of irrigation solution, blood, and tissue debris. Such aerosols can be contaminated with potential pathogens. The surgical personnel and the environment are therefore exposed to a contamination risk. METHODS: Laminectomies at three points (L2-L4) were performed on a human cadaver using a high-speed cutting device. The aerosol produced by the irrigation solution was contaminated with Staphylococcus aureus ATCC 12600. To detect the contamination of the environment and of the surgical team, surveillance cultures were used. RESULTS: By air sampling, staphylococci were detected in the operating room at an extension of 5 by 7 m. The surgical team showed extensive face and body contamination with S. aureus. Despite protection by a barrier drape, similar contamination was observed on both the cadaver's head and the anesthesiologist. CONCLUSIONS: The use of high-speed cutters in spinal surgery produces an aerosol that can be contaminated with blood-borne pathogens from infected patients. This aerosol is spread over the whole surgical room and contaminates the room and all personnel present. It is therefore critical to ensure that effective infection control measures are performed, not only by the surgeons but by everyone present in the operating room. The room itself must be sufficiently disinfected after such procedures.

Aerosols↗

Ionic surface active compounds in atmospheric aerosols.

Surfactants in the atmosphere have several potential roles in atmospheric chemistry. They can form films on aqueous surfaces, which lowers the surface tension and possibly delays water evaporation and gaseous transportation across the aqueous interface. They can also increase the solubility of organic compounds in the aqueous phase. Recently, the decrease of surface tension in cloud growing droplets has been suggested as relevant to increases in the number of droplets of smaller size, potentially enhancing cloud albedo. Natural surfactants in the lung aid gas transfer and influence the dissolution rate of aerosol particles, so surfactants in atmospheric aerosols, once inhaled, may interact with pulmonary surfactants. Ambient aerosols were collected from the edge of Norwich, a small city in a largely agricultural region of England, and analysed for surfactants. Methylene blue, a conventional dye for detecting anionic surfactants, has been used as a colorimetric agent. The concentration of surfactants expressed as methylene blue active substances (MBAS) is in the range of 6-170 pmol m(-3)(air). A negative correlation with chloride aerosol indicates that these surfactants are probably not the well-known surfactants derived from marine spray. A more positive correlation with aerosol nitrate and gaseous NOx supports an association with more polluted inland air masses. The surfactants found in aerosols seem to be relatively strong acids, compared with weaker acids such as the long-chain carboxylic acids previously proposed as atmospheric surfactants. Surfactants from the oxidation of organic materials (perhaps vegetation- or soil-derived) seem a likely source of these substances in the atmosphere.

Acids↗

The effect of beclomethasone dipropionate aerosol on allergen induced nasal stenosis.

Nasal resistance to air flow has been used to evaluate the effect of beclomethasone dipropionate aerosol on allergen induced nasal stenosis. Sixteen patients with allergic rhinitis due to pollen were investigated in a randomized double-blind cross-over study with beclomethasone dipropionate aerosol and placebo aerosol. Only patients reacting to challenge were chosen. The study was carried out in the pollen-free season. After 1 week on either active or placebo aerosol a basic resistance value was determined followed by allergen challenge. Nasal resistance was determined 15 min and 7 hr after challenge. The aerosols were changed and after another week the procedure was repeated. There was significant preference (P less than 0.01) for beclomethasone dipropionate aerosol.

Administration, Intranasal↗

Double-blind comparison between beclomethasone dipropionate as aerosol and as powder in patients with nasal polyposis.

Beclomethasone dipropionate as a pressurized aerosol is effective in nasal polyposis, but the efficacy is only moderate. In these partly-blocked noses, it seems possible that the insufflated drug in powder form is better distributed over the mucous membrane than the pressurized aerosol. To test this hypothesis, we treated forty-two patients with nasal polyposis with intranasal beclomethasone dipropionate as a powder and as a pressurized aerosol in a double-dummy, cross-over design. There was no difference between the treatments in sixteen patients, while in twelve cases there was a preference for beclomethasone dipropionate as aerosol, and in fourteen, for the powder form. Fourteen found the aerosol most irritating and nineteen, the powder. Thus, in a group of polyp patients there were no significant differences between the two application forms, but possibly there is a need for both aerosol and powder, as there appeared to be differences in the individual responsiveness to the two types of intranasal medication. Blind microscopy of wiped nasal-smears before and after beclomethasone dipropionate treatment showed a reduction of basophilic cells, and counting of sneezes after medication demonstrated a reduction in the number of sneezes. These results suggest that a reduction of epithelial mediator-cells and of irritant receptor-sensitivity are of importance for the efficacy of topical steroids in rhinitis.

Adult↗

A new aerosol formulation of sodium cromoglycate compared with conventional powder in the treatment of asthma.

Sodium cromoglycate formulated as a pressurised aerosol was compared with the conventional powder for a period of 12 weeks in a double-blind group comparison trial involving 48 patients. A double dummy technique was used; the dose of sodium cromoglycate was 2 mg four times daily by aerosol, and 20 mg four times daily by Spinhaler. Patients were able to use the correct technique for both aerosol and dry powder inhalation. Patients recorded the severity of their asthma symptoms, their morning and evening peak flow rate, and the amount of other asthma therapy used, on a daily diary card. They also attended the clinic every 4 weeks for assessment. A statistical comparison of the efficacy of the powder and aerosol forms found no significant differences in clinical assessment of severity, diary card symptom scores, morning and evening peak flow readings, or aerosol bronchodilator usage. Thirty-four patients considered that the aerosol was more convenient and easier to use than the dry powder inhaler.

Adolescent↗

A paediatric canopy system for aerosol administration and minimized environmental pollution.

BACKGROUND: A canopy system for ribavirin aerosol administration to infants has been developed in order to improve the control of aerosol treatment, facilitate access to the infant and minimize environmental pollution. The system comprises a transparent canopy, fitted with four sealable apertures. An evacuation flow that is 3 l/min higher than the gas supply was anticipated to prevent aerosol leakage from the canopy. METHOD: In a clinical evaluation, 10 infants with body weights of 1.8-7.1 kg were placed inside the canopy during 1 hour of simulated treatment. The temperature, relative humidity and carbon dioxide concentration within the canopy were measured repeatedly to study the stability of these variables and their dependence on body weight. Infant body temperature, skin temperature and the respiratory frequency were measured. In a laboratory evaluation, aerosol leakage was studied using an ambient air admixture procedure and smoke tests. The sound level inside the canopy was measured. RESULTS: All physical variables inside the canopy remained stable. The sound level was 52 dBA. The carbon dioxide concentration (1000-3900 PPM) correlated with infant body weight (P < 0.001), as did canopy temperature (25.1-29.6 degrees C, P < 0.05). The relative humidity was 52-88%. Infant body temperatures were not influenced. The respiratory frequency decreased by 13% (P < 0.01). No aerosol leakage was observed. CONCLUSION: The canopy system facilitates a controlled aerosol therapy with good infant surveillance and accessibility a minimum of environmental pollution and a comfortable physical environment without apparent risks of carbon dioxide rebreathing or cooling stress at body weights of 1.8-7.1 kg.

Administration, Inhalation↗

Failure of aerosolized endothelin (ET-1) to induce bronchial hyperreactivity in the guinea pig.

Aerosol administration of endothelin (ET-1) has been shown to provoke a potent bronchoconstriction in the guinea pig. We investigated whether or not, aerosolized ET-1 induces a bronchial hyperreactivity in the guinea pig. Aerosolized ET-1 (10 micrograms/ml for 60 min) did not alter the dose-response curve, established by successive aerosol administration of acetylcholine (ACh) 3-4 h and 18-24 h after challenge with the peptide. In a second protocol, aerosolized ET-1 (10 micrograms/ml for 3 min) induced, in anaesthetized guinea pigs a bronchopulmonary response but did not alter the dose-response curve to aerosolized ACh established 30 min after the challenge. These results suggest that ET-1 may participate to the early, but not the late alteration of the bronchopulmonary tone observed during pathophysiological conditions.

Acetylcholine↗

Aerosolized and intravenously administered leukotrienes: effects on the bronchoconstrictor potency of histamine in the guinea-pig.

The effects of leukotrienes C4 and D4 (LTC4 and LTD4), administered intravenously or by aerosol, on the bronchoconstrictor potency of intravenously administered histamine have been investigated in anaesthetized, mechanically ventilated guinea-pigs. LTC4 (2 nM) had no effect on either the EC50 or the maximum contractile response to histamine on the isolated trachea of the guinea-pig. At 10 nM, LTC4 induced a rightward shift in the histamine concentration-response curve without affecting the maximum response. LTD4 (0.05-0.20 nmol kg-1, i.v.) dose-dependently enhanced histamine (9-36 nmol kg-1, i.v.)-induced increases in airways resistance, whereas equibronchoconstrictor doses of LTC4 (0.1-0.4 nmol kg-1, i.v.), failed to enhance histamine-induced increases in airways resistance. Aerosols of LTC4 and LTD4 generated from solutions of 1-16 microM and administered for 30 s, elicited concentration-dependent bronchoconstrictions comprising decreases in dynamic compliance and increases in airways resistance. At 20 min after exposure to these aerosols, the potency of histamine (9-36 nmol kg-1, i.v.) was significantly increased on both airways resistance and dynamic compliance. The potentiation induced by LTC4 (4 microM, 30 s) was maintained up to 60 min after aerosol exposure whereas that induced by LTD4 (4 microM, 30 s) was maintained up to 40 min after aerosol exposure but was not significantly different (P greater than 0.05, unpaired Student's t test) to saline-exposed animals at 60 min. LTC4 as has been previously reported for LTD4, does not enhance the histamine-induced contraction of isolated airways smooth muscle. In contrast to LTD4, intravenously administered LTC4 does not appear to enhance histamine-induced bronchoconstriction. On the other hand, aerosols of either LTC4 or LTD4 potentiate histamine in vivo in a concentration-dependent manner. These data suggest that leukotrienes may contribute to the regulation of airways reactivity to histamine in the guinea-pig.

Aerosols↗

Comparison of the effects of intra-arterial and aerosol administration of endothelin-1 (ET-1) in the guinea-pig isolated lung.

1. Intra-arterial injection of endothelin-1 (ET-1, 400 pmol; 1 microgram) in guinea-pig isolated perfused lungs, induced increases in pulmonary inflation pressure (PIP) and perfusion pressure (PPP), associated with oedema formation and thromboxane B2 (TxB2) release but not with the generation of sulphidopeptide leukotrienes or release of histamine. In contrast, aerosol administration of ET-1 (3, 6, 10 micrograms ml-1, for 2 min) evoked a dose-dependent increase in PIP, without significant changes in PPP, oedema formation or TxB2 release. 2. Addition of indomethacin (5 microM) or BW 755C (10 or 100 microM), but not nordihydroguaiaretic acid (NDGA, 50 microM) or FPL 55712 (10 microM), to the perfusion medium led to a significant inhibition of the increases in PIP and PPP, TxB2 release and oedema formation evoked by intra-arterial injection of 400 pmol ET-1. In contrast, indomethacin (5 microM), BW 755C (100 microM) or FPL 55712 (10 microM), added to the perfusion medium 10 min prior to challenge, did not affect the increase in PIP induced by a 2-min aerosol of a solution of ET-1 10 micrograms ml-1. 3. In vivo aerosol administration of indomethacin (100 mg ml-1, for 20 min) to non-anaesthetized guinea-pigs, 15 min before lung removal, did not modify the bronchopulmonary response evoked in isolated perfused lungs by an aerosol of ET-1 10 micrograms ml-1. However, under the same experimental conditions, indomethacin significantly inhibited TxB2 release evoked by aerosolized arachidonic acid (2 mg ml-1). 4. In conclusion, the present study shows that when injected by the intra-arterial route, ET-1 effects are mediated primarily via the generation of cyclo-oxygenase metabolites of arachidonic acid, whereas when the aerosol route is used, the peptide appears to act on airway smooth muscle cells, through an indomethacin-insensitive process which may involve some other, as yet unidentified, mediator(s).

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗