[Can mesh nebulizers improve prehospital aerosol therapy? An in vitro study on simulated prehospital emergency patients suffering from respiratory distress]. / Können Mesh-Vernebler die prähospitale Aerosoltherapie verbessern? Eine In-vitro-Studie an simulierten Notfallpatient*innen mit Atemnot.

BACKGROUND: Nebulizers used to treat prehospital emergency patients should provide a high output efficiency to achieve a fast onset of therapeutic drug effects while remaining unaffected by the presence of supplementary oxygen flow or the patient's breathing pattern. On the other hand, nebulizer performance is directly influenced by differences in device design, gas flow and patients' breathing patterns. Several studies from emergency departments were able to demonstrate an improvement in patient outcome when using a mesh nebulizer instead of a jet nebulizer. Data or bench studies regarding prehospital care are non-existent. OBJECTIVE: The aim of the present in vitro study was to evaluate which type of aerosol generator would best address the requirements of a prehospital adult emergency patient suffering from respiratory distress. MATERIAL AND METHODS: We evaluated the performance of a jet nebulizer (Cirrus™ 2, Intersurgical®) and two mesh nebulizers (Aerogen Solo® with USB controller, Aerogen Limited and M­Neb® mobile, NEBU-TEC International med. Produkte Eike Kern GmbH) with the possibility of portable operation in an in vitro model of a spontaneously breathing adult emergency patient. One physiological and three pathological breathing patterns (distressed breathing pattern as well as stable and acute exacerbated chronic obstructive pulmonary disease) were simulated. Nebulizer output and salbutamol lung deposition were measured at different oxygen flow rates using a face mask as the delivery interface. RESULTS: The mesh nebulizers produced a significantly higher aerosol output when compared to the jet nebulizer. The M­Neb® mobile was able to significantly exceed the output of the Aerogen Solo®. Oxygen flow had the largest influence on the output of the jet nebulizer but hardly affected the mesh nebulizers. After a nebulization time of 10 min the M­Neb® mobile also achieved the highest total salbutamol lung deposition (P < 0.001). Aerosol drug deposition was therefore mainly determined by the nebulizer's drug output per unit time. The deposition could not be improved using a spacer but was strongly influenced by the simulated emergency patients' breathing pattern. CONCLUSION: The use of mesh nebulizers might have the potential to improve the aerosol therapy of prehospital emergency patients. In general, mesh nebulizers seem to be superior to jet nebulizers regarding aerosol output per unit time and total lung deposition. The present data suggest that aerosol output and drug deposition to the collection filter in this simulated setting are closely connected and crucial for total salbutamol deposition, as the deposition could not be improved by adding a spacer. Aerosol drug deposition in simulated emergency patients' lungs is therefore mainly determined by the nebulizer's drug output per unit time. The level of oxygen flow used had the largest influence on the output of the jet nebulizer but hardly affected the output of the tested mesh nebulizers. Mesh nebulizers could therefore enable a demand-adapted oxygen therapy due to their consistent performance despite the presence of oxygen flow. A high respiratory rate was associated with a high drug deposition, which is clinically desirable in the treatment of patients in respiratory distress; however, drug underdosing must also be expected in the treatment of bradypneic patients. Further clinical studies must prove whether our findings also apply to the treatment of real prehospital emergency patients.

[Nebulization of emergency medications in the south German rescue service]. / Vernebelung von Notfallmedikamenten im süddeutschen Rettungsdienst.

BACKGROUND: In German emergency rescue services, inhalation treatment is routinely carried out by qualified health personnel. Standard operating procedures (SOP) for nebulization are neither uniform throughout Germany nor available in all federal states. Standardized recommendations with respect to which nebulizer type should be used are missing. The aerosol output as well as the drug deposition rates of jet and mesh nebulizers, however, differ considerably. Mesh devices can achieve a threefold higher lung deposition. Their use in emergency departments has also been shown to be associated with a better patient outcome when compared to jet nebulizers. OBJECTIVE: This survey was designed to evaluate the type of nebulizer used in the south German rescue services. Special attention was paid to the influence of existing SOP on the decision to perform nebulization during emergency treatment. MATERIAL AND METHODS: A total of 4800 emergency paramedics working in Baden-Württemberg, Bavaria and Rhineland-Palatinate received a questionnaire with a total of 17 questions on the implementation of drug nebulization in the daily practice. RESULTS: Despite the existence of more efficient nebulizer types, the jet nebulizer was by far the most frequently used nebulizer in the south German rescue services. The deposition rates of both the jet and mesh nebulizers were considerably overestimated by most respondents; however, 77.5% of all respondents could not give any information about the deposition rates of the mesh nebulizer. Only two thirds of all respondents carried out nebulization treatment on the basis of SOP. The implementation of SOP, however, was pivotal to the application of nebulization during emergencies. If SOP were in place,76.9% of the responders used aerosol treatment compared to 23.1% when there were none. The perceived safety when using nebulization during emergencies was also significantly higher (p = 0.013) when SOP were implemented. CONCLUSION: The exclusive use of mesh nebulizers could standardize the treatment of emergency patients in the south German rescue services. The use of mesh devices might possibly improve patient outcomes, even if clinical studies are still lacking. Nebulizer treatment differs between the federal states. A comprehensive implementation of SOP for nebulization treatment might support this process and could increase the application frequency and the perceived safety of nebulization during emergencies. A better training of paramedic personnel could improve the knowledge of aerosols as a treatment option for emergency patients and help to classify the advantages and disadvantages of the different aerosol generators available.

Aerosolized semifluorinated alkanes as excipients are suitable for inhalative drug delivery--a pilot study.

Semifluorinated alkanes (SFAs) have been described as potential excipients for pulmonary drug delivery, but proof of their efficacy is still lacking. We tested whether SFA formulations with the test drug ibuprofen can be nebulised and evaluated their pharmacokinetics. Physico-chemical properties of five different ibuprofen formulations were evaluated: an aqueous solution (H2O), two different SFAs (perfluorohexyloctane (F6H8), perfluorobutylpentane (F4H5)) with and without ethanol (SFA/EtOH). Nebulisation was performed with a jet catheter system. Inhalative characteristics were evaluated by laser diffraction. A confirmative animal study with an inhalative single-dose (6 mg/kg) of ibuprofen with each formulation was performed in anaesthetised healthy rabbits. Plasma samples at defined time points and lung tissue harvested after the 6-h study period were analyzed by HPLC-MS/MS. Pharmacokinetics were calculated using a non-compartment model. All formulations were nebulisable. No differences in aerodynamic diameters (MMAD) were detected between SFA and SFA/EtOH. The ibuprofen plasma concentration-time curve (AUC) was highest with F4H5/EtOH. In contrast, F6H8/EtOH had the highest deposition of ibuprofen into lung tissue but the lowest AUC. All tested SFA and SFA/EtOH formulations are suitable for inhalation. F4H5/EtOH formulations might be used for rapid systemic availability of drugs. F6H8/EtOH showed intrapulmonary deposition of the test drug.

Semifluorinated alkanes--a new class of excipients suitable for pulmonary drug delivery.

INTRODUCTION: Semifluorinated alkanes (SFAs) are considered as diblock molecules with fluorocarbon and hydrocarbon segments. Unlike Perfluorocarbons (PFCs), SFAs have the potential to dissolve several lipophilic or water-insoluble substances. This makes them possibly suitable as new excipients for inhalative liquid drug carrier systems. PURPOSE: The aim of the study was to compare physico-chemical properties of different SFAs and then to test their respective effects in healthy rabbit lungs after nebulisation. METHODS: Physico-chemical properties of four different SFAs, i.e. Perfluorobutylpentane (F4H5), Perfluorohexylhexane (F6H6), Perfluorohexyloctane (F6H8) and Perfluorohexyldodecane (F6H12) were measured. Based on these results, aerosol characteristics of two potential candidates suitable as excipients for pulmonary drug delivery, i.e. F6H8 and F4H5, were determined by laser light diffraction. Tracheotomised and ventilated New Zealand White rabbits were nebulised with either a high- or a low dose of SFAs (F6H8(low/high) and F4H5(low/high)) or saline (NaCl). Ventilated healthy animals served as controls (Sham). Arterial blood gases, lung mechanics, heart rate and blood pressure were recorded prior to nebulisation and in 30 min intervals during the 6-h study period. RESULTS: Out of the four SFAs studied initially, no satisfactory behaviour as a solvent has to be expected because of low lipophilicity for F6H6. Output rate during aerosolisation was very low for F6H12. F6H8 and F4H5 presented comparable aerosolisation characteristics and lipophilicity and were therefore tested in the in vivo model. Aerosol therapy, either SFAs or saline, impaired paO2/FiO2 ratio, dynamic lung compliance and respiratory mechanics in all groups, except for F4H5(low) group which behaved like the control group (Sham). F4H5(low) had no adverse effects on gas exchange or pulmonary mechanics. CONCLUSIONS: Perfluorobutylpentane (F4H5) in a low-dose application may be suitable as a new inhalable excipient in SFA-based pulmonary drug delivery systems for lipophilic or water-insoluble substances.

[Negative-pressure pulmonary edema (NPPE)]. / Das pulmonale Negativdrucködem.

Negative-pressure pulmonary edema (NPPE) is a clinical entity of anaesthesiologic relevance, perioperatively caused by obstruction of the conductive airways (upper airway obstruction, UAO) due to laryngospasm in approx. 50% of the cases, its early recognition and treatment by the anaesthesist is mandatory. NPPE, also addressed as post-obstructive pulmonary edema (POPE) presents in most cases as a complex of symptoms with rapid onset, consisting of acute respiratory failure with dyspnea, tachypnea, and strained respiratory efforts. Additional signs are paradoxe ventilation, pink frothy sputum, stridor, and severe agitation. UAO produce extreme reduction of intrathoracic pressure during spontaneous ventilation, consecutively causing increase in venous return to the right ventricle and in intrathoracic blood volume, resulting in elevated hydrostatic pressures and interstitial transudation of fluids. Partially due to largely differing criteria used for diagnosis, opinions about incidence and prevalence of NPPE are unhomogenous in medical literature. It has been shown that generation of NPPE is not only limited to patients being intubated and ventilated, but occurs also in patients requiring higher fractions of oxygen.

Airway management with the Laryngeal Tube Suction II in a patient with cervical spine injury.

Supraglottic airway devices may offer alternative strategies for securing the airway in patients with cervical spine injuries. A case of airway management with the LTS II, a modified version of the laryngeal tube suction, in a patient with a paramedian atlas fracture scheduled for decompression of a haematoma on the forehead is described. Device insertion was successful in the first attempt and a gastric tube was inserted without problems. Ventilation was uneventful, no complaints were stated after surgery.