Carboxyhemoglobin half-life toxicokinetic profiles during and after normobaric oxygen therapy: On a swine model.

Investigations on acute carbon monoxide (CO) poisoning struggle to highlight a relevant discriminant criterion related to CO poisoning severity for predicting complications, such as delayed neurological syndromes. In this context, it remains difficult to demonstrate the superiority of one method of oxygen (O2) administration over others or to identify the optimal duration of normobaric 100% oxygen (NBO) treatment. Myoglobin, as hemoglobin, are a potential binding site for CO, which could be a source of extravascular CO storage that impacts the severity of CO poisoning. It is not possible in routine clinical practice to estimate this potential extravascular CO storage. Indirect means of doing so that are available in the first few hours of poisoning could include, for example, the carboxyhemoglobin half-life (COHbt1/2), which seems to be influenced itself by the level and duration of CO exposure affecting this store of CO within the body. However, before the elimination of CO can be assessed, the COHbt1/2 toxicokinetic model must be confirmed: research still debates whether this model mono- or bi-compartmental. The second indirect mean could be the assessment of a potential COHb rebound after COHb has returned to 5% and NBO treatment has stopped. Moreover, a COHb rebound could be considered to justify the duration of NBO treatment. On an experimental swine model exposed to moderate CO poisoning (940 ppm for ±118 min until COHb reached 30%), we first confirm that the COHb half-life follows a bi-compartmental model. Secondly, we observe for the first time a slight COHb rebound when COHb returns to 5% and oxygen therapy is stopped. On the basis of these two toxicokinetic characteristics in favor of extravascular CO storage, we recommend that COHbt1/2 is considered using the bi-compartmental model in future clinical studies that compare treatment effectiveness as a potential severity criterion to homogenize cohorts of the same severity. Moreover, from a general toxicokinetic point of view, we confirm that a treatment lasting less than 6 hours appears to be insufficient for treating moderate CO poisoning.

Effect of Pressure Support Ventilation on Carboxyhemoglobin Toxicokinetic after Acute Carbon Monoxide Intoxication: a Swine Model.

INTRODUCTION: In an experimental study on carbon monoxide (CO) exposure in swine, we aimed to compare the influence of oxygen therapy using a non-rebreathing mask (NRM) to continuous positive airway pressure (CPAP) and two pressure support ventilation (PSV) devices on the decrease of the terminal elimination half-life of carboxyhemoglobin (COHb t1/2). This was the primary outcome. METHODS: Eight spontaneously breathing pigs were sedated by propofol and exposed to 940 ppm CO several times (n = 25) to obtain COHb levels of 30%. CPAPb (high flow open system, CPAP Boussignac® [7.5 cmH2O]), PSV-Vy (open system, Vylife Boussignac®), and PSV-Leg (closed system, Legendair® [inspiratory/expiratory airway pressure 12/4 cmH2O]) devices were used in a randomized order and compared to NRM (O2 at 15 l min-1) and atmospheric air (AA). The primary outcome was COHb t1/2. Multiple comparisons were performed using Dunn's tests. RESULTS: Median FiO2 and minute ventilation were significantly higher in the PSV-Leg group than the NRM group (p < 0.05). Median COHb t1/2 was 251, 85, 82, 93, and 58 min for AA, NRM, CPAPb, PSV-Vy, and PSV-Leg, respectively. All the interventions were superior to AA in terms of CO elimination (p < 0.001), but there was no statistically significant difference between CPAP or PSV and NRM. There was only a trend between PSV-Leg and NRM (p = 0.18). The median AUCs for ln (COHb) × time (h) were 170, 79, 83, 100, and 64 for AA, NRM, CPAPb, PSV-Vy, and PSV-Leg respectively, with a statistically significant difference only between AA and PSV-Leg (p = 0.002). CONCLUSION: In conclusion, in our study on CO intoxication in swine, the use of the closed PSV-Leg system led to the shortest COHb t1/2. These results suggest that PSV-Leg can be more efficient than NRM in eliminating CO and support the design of a clinical study to assess this hypothesis.

[Mycobacterium avium tumoral infection mimicking a lung adenocarcinoma: A potential diagnostic pitfall]. / Infection à Mycobacterium avium simulant un adénocarcinome pulmonaire : un potentiel piège diagnostique.

INTRODUCTION: The incidence of atypical mycobacterial infection in Europe is estimated at one case per 100,000 persons/year. Despite the low incidence of Mycobacterium avium infection, it can result in a nodular lesion simulating lung cancer. We report a case of atypical mycobacteriosis, mimicking lung cancer, which led to a lobectomy. CASE REPORT: It was a right pulmonary upper lobe nodule found in a 63-year-old COPD patient, partially nephrectomized for renal carcinoma, and weekly treated by methotrexate for rheumatoid arthritis. FDG uptake was weakly positive on PET-CT (SUV=2.2) in the upper fissure. Bronchoscopy yielded no lesions and no bacteriological findings. Percutaneous transthoracic lung biopsy revealed lung adenocarcinoma stage T1 (a) N0M0. An upper lobectomy with lymphadenectomy was performed. Histological examination revealed epithelioid granuloma surrounded by giant cells suggestive of tuberculomas. The bronchial washing fluid culture was positive for Mycobacterium avium after 7 weeks. CONCLUSION: In pseudo-neoplastic forms of atypical mycobacteriosis, the presence of alveolar, inflammatory cytonuclear abnormalities can mimic an adenocarcinoma. Making the difference between the cytonuclears defects related to inflammation or neoplasia remains a daily challenge in histopathology.

Aerosol delivery to the lung is more efficient using an extension with a standard jet nebulizer than an open-vent jet nebulizer.

BACKGROUND: Open-vent jet nebulizers are frequently used to promote drug deposition in the lung, but their clinical efficacy and indications are not clear. Our study compared lung deposition of amikacin using two different configurations of a jet nebulizer (Sidestream(®)): one vented (N1) and one unvented with a corrugated piece of tubing (N2). METHODS: In vitro nebulizer performance was assessed by laser diffraction and filtering. Lung delivery was evaluated by scintigraphy in baboons as a child model, and by amikacin urinary drug concentration in seven healthy spontaneously breathing volunteers. Subjects were randomly assigned to the two nebulizer systems (N1 and N2). RESULTS AND CONCLUSIONS: In vitro results showed a higher efficiency of N2 than N1 in terms of lung deposition prediction (95±3 mg vs. 70±0 mg; p<0.0001). Radioactivity deposition in the baboons' lungs was lower with N1 than with N2 (1.8% vs. 4.7% of nebulizer charge; p<0.05). The total daily amount of amikacin urinary excretion was lower with N1 than with N2 (29.5 mg vs. 40.1 mg; p<0.01). Conversely, in vivo drug output rate was higher with N1 than with N2 (3.1 mg/min vs. 2.2 mg/min; p<0.05). Using a corrugated piece of tubing with standard jet nebulizers delivers higher doses to the lungs than open-vent jet nebulizers. The open-vent jet nebulizer might be recommended for rapid administration of a lower dose to the lungs and the standard jet nebulizer with corrugated piece of tubing for a higher dose in the lungs.

Aerosol delivery through tracheostomy tubes: an in vitro study.

BACKGROUND: Our study investigated the influence of the cannula's inner diameter (ID) and of its removal on the expected respiratory dose of amikacin, using three different jet nebulizer configurations (Sidestream(®)): vented (N1), unvented with a piece of corrugated tubing attached to the expiratory limb of the T attachment (N2), and unvented alone (N3). METHODS: The jet nebulizer was filled with amikacin (500 mg/4 mL) and was attached to the tracheostomy tube. A lung model simulating spontaneous breathing was connected to the tracheostomy tube. A filter was connected between the nebulizer and the tracheostomy tube to measure the inhaled dose, and between the tracheostomy tube and the lung model to measure the respiratory dose. Different cannula IDs were tested (6.5, 8, 8.5, and 10 mm), and aerosol lost in the cannulas was determined. RESULTS AND CONCLUSIONS: Respiratory dose varied between 96±1 mg and 44±3 mg, with higher values observed with N2. The aerosol lost in the cannula was significant and represented up to 63% of the inhaled dose. There was a negative correlation between the cannula's ID and the aerosol lost in the cannula. After removal of the internal cannula, an increase in the respiratory dose of up to 31.3% was observed. We recommend removing the inner tracheostomy cannula to nebulize a larger amount of drug through a tracheostomy tube. Among the three jet nebulizer configurations studied, we recommend the unvented one with a piece of corrugated tubing attached to the expiratory limb of the T attachment.

[Unsuspected danger of a medicinal preparation]. / Danger inattendu d'une préparation magistrale.

INTRODUCTION: Inhaled foreign bodies are commonly reported in childhood but less so among adults. We report the case of a patient who inhaled a medicinal preparation containing meprobamate and quinine sulfate. The consequence of this was caustic damage to the airways. CASE REPORT: A 64-year-old woman came to the emergency room because of dyspnea, oropharyngeal pain and sialorrhea. She reported that she had inhaled a capsule containing meprobamate and quinine sulfate the previous day. Flexible bronchoscopy showed evidence of caustic damage to the larynx and lower airways. The patient was treated by fasting, corticoids and intravenous broad-spectrum antibiotics. All the lesions recovered and she was discharged from the hospital 15 days after the event. CONCLUSIONS: Inhalation of drugs mostly leads to airway obstruction. Risk of harm is influenced by neurological status, the motility of the digestive system and the properties of the drug. To the best of our knowledge, this is the first time that caustic airway disease has been described following inhalation of a medicinal preparation containing meprobamate and quinine. It highlights the need to be familiar with the chemical properties of medications when prescribing them to patients who are at risk of aspiration.

Primary care spirometry.

Primary care spirometry is a uniquely valuable tool in the evaluation of patients with respiratory symptoms, allowing the general practitioner to diagnose or exclude chronic obstructive pulmonary disease (COPD), sometimes to confirm asthma, to determine the efficacy of asthma treatment and to correctly stage patients with COPD. The use of spirometry for case finding in asymptomatic COPD patients might become an option, once early intervention studies have shown it to be beneficial in these patients. The diagnosis of airway obstruction requires accurate and reproducible spirometric measurements, which should comply with the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines. Low acceptability of spirometric manoeuvres has been reported in primary care practices. This may hamper the validity of the results and affect clinical decision making. Training and refresher courses may produce and maintain good-quality testing, promote the use of spirometric results in clinical practice and enhance the quality of interpretation. Softening the stringent ATS/ERS criteria could enhance the acceptability rates of spirometry when used in a general practice. However, the implications of potential simplifications on the quality of the data and clinical decision making remain to be investigated. Hand-held office spirometers have been developed in recent years, with a global quality and user-friendliness that makes them acceptable for use in general practices. The precision of the forced vital capacity measurements could be improved in some of the available models.

Comparison of lung deposition of amikacin by intrapulmonary percussive ventilation and jet nebulization by urinary monitoring.

The intrapulmonary percussive ventilation (IPV), frequently coupled with a nebulizer, is increasingly used as a physiotherapy technique; however, its physiologic and clinical values have been poorly studied. The aim of this study was to compare lung deposition of amikacin by the nebulizer of the IPV device (Percussionaire; Percussionaire Corporation; Sandpoint, ID) and that of standard jet nebulization (SST; SideStream; Medic-Aid; West Sussex, UK). Amikacin was nebulized with both devices in a group of five healthy subjects during spontaneous breathing. The deposition of amikacin was measured by urinary monitoring. Drug output of both devices was measured. Respiratory frequency (RF) was significantly lower when comparing the IPV device with SST (8.2 +/- 1.6 breaths/min vs. 12.6 +/- 2.5 breaths/min, p < 0.05). The total daily amount of amikacin excreted in the urine was significantly lower with IPV than with SST (0.8% initial dose vs. 5.6% initial dose, p < 0.001). Elimination halflife was identical with both devices. Drug output was lower with IPV than with SST. The amount of amikacin delivered to the lung is sixfold lower with IPV than with SST, although a lower respiratory frequency was adopted by the subjects with the IPV. Therefore, the IPV seems unfavorable for the nebulization of antibiotics.

Continuous positive airway pressure treatment for sleep apnoea: compliance increases with time in continuing users.

Continuous positive airway pressure (CPAP) remains the best treatment for sleep apnoea syndrome (SAS). In the 1990s, many authors reported on daily compliance, but all of the studies utilised relatively short periods of follow-up that did not exceed a few years. The mean annual rate of CPAP use in patients with SAS was prospectively recorded. In the current study, the results are presented along with compliance data from patients who started CPAP between 1991 and 1998 and were still using it by the end of 2003. The cohort was chosen in order to obtain >or=5 yrs of follow-up for each patient. In total, there were 204 patients. For the whole group, mean+/-sd compliance reached 321+/-90 and 393+/-84 min after 1 and 10 yrs, respectively. There was no significant change in the first 2 yrs, with a significant increase from the third year onwards. Compliance, or its evolution over time, was not correlated either to the baseline polysomnographical data (except slightly for the CPAP pressure), to the difference of these data before and under CPAP therapy, to the age of retirement or to changes in the marital status. In conclusion, very long-term compliance with continuous positive airway pressure increases by a mean of 8 min.day-1 per year of follow-up in patients with sleep apnoea syndrome.

Nasal obstruction and its impact on sleep-related breathing disorders.

Upper airway patency is essential during sleep in order to avoid sleep-related breathing disorders (SRBD). Nasal obstruction may have a negative impact on sleep quality and must be considered to be a co-factor in the pathophysiology of SRBD. In this paper we will discuss the relation between nasal physiology at night and sleep quality and the possible mechanisms between nasal obstruction and obstructive sleep apnea-hypopnea syndrome (OSAS). We will review the effect of the relief of nasal obstruction (with nasal dilators, medication and/or surgery) on SRBD. Also an algorithm on the management of OSAS patients when nasal surgery is indicated will be proposed.

High Mallampati score and nasal obstruction are associated risk factors for obstructive sleep apnoea.

Induced nasal obstruction can cause obstructive apnoeas in healthy subjects during sleep, but the relationship between nasal resistance measured during wakefulness and obstructive sleep apnoea syndrome (OSAS) is weak. It was postulated that if the subjects could not breathe through the nose, the oral airway must be used, but if this airway is narrowed as well, then it could precipitate sleep-disordered breathing (SDB). Nasal patency, Mallampati score (MS), neck circumference and body mass index were measured in 202 subjects referred to the authors' hospital to undergo a full-night polysomnography for suspicion of SDB. A significant correlation was found between the MS and apnoea/hypopnoea index measured during sleep. However, the relationship between these parameters was only significant in patients with nasal obstruction. The relative risk of having OSAS with a MS of III or IV was 1.95 for the whole group and 2.45 in patients with nasal obstruction. In conclusion, a high Mallampati score represents a predisposing factor for obstructive sleep apnoea syndrome, especially if it is associated with nasal obstruction. These patients merit special attention from both the sleep physician and the anaesthetist.

Noninvasive ventilation for acute respiratory failure: a prospective randomised placebo-controlled trial.

The aim of the present study was to clarify whether the known effects of noninvasive positive-pressure ventilation (NPPV) in patients with respiratory failure are real or due to placebo effects and whether early application of NPPV in the emergency department leads to rapid improvement of the patients condition and outcome. A prospective randomised placebo-controlled study was conducted in 20 patients with severe acute respiratory failure (ARF) secondary to an acute exacerbation of chronic obstructive pulmonary disease (COPD) or acute pulmonary oedema, not improving under conventional medical therapy and on the edge of intubation. Patients received either conventional medical therapy plus two-level NPPV (hi-level NPPV) or conventional medical therapy plus "placebo" NPPV. The main outcome measures involved the need for endotracheal intubation in the bi-level NPPV arm and in the placebo arm after crossing over to active NPPV. Morbidity, length of stay, mortality and the effect of the ventilatory mode on clinical, arterial-blood gas parameters, and the sternocleidomastoid muscles electromyogram (EMG) activity were also measured. The 10 patients in the active NPPV group rapidly improved and none needed intubation. Placebo NPPV resulted in no change in the clinical condition of patients that continued to worsen and the 10 patients were crossed over to active NPPV. Three patients were intubated. No differences in terms of morbidity, length of stay or mortality between the two groups were observed. Active NPPV (but not placebo NPPV) led to a rapid and significant improvement in the clinical parameters, pH and the carbon dioxide tension in arterial blood and to a decrease in respiratory frequency and sternocleidomastoid EMG activity. Early application of bi-level noninvasive positive-pressure ventilation in patients with severe acute respiratory failure, due to chronic obstructive pulmonary disease and acute pulmonary oedema, leads to a rapid improvement in clinical status and blood gases. Noninvasive positive-pressure ventilation had no placebo effect.

Pathophysiology of upper airway obstruction during sleep.

The obstructive sleep apnoea syndrome (OSAS) is characterised by repetitive upper airway obstructions leading to snoring, hypopnoeas and apnoeas. Sleep fragmentation and arterial oxygen desaturations are the first consequences. Since the discovery of the OSAS, an impressive series of studies were done on upper airway physiology, and more specifically, on the pharyngeal airway. The objective of this article is to review the pathophysiological basis of upper airway obstruction during sleep.

Standard ENT clinical evaluation of the sleep-disordered breathing patient; a consensus report.

Sleep disordered breathing (SDB) patients usually undergo an ENT clinical examination before any therapeutic decision. This clinical examination would be predictive about the occurrence of Obstructive Sleep Apnea Syndrome, cost effective, reproducible and would determine the sites of obstruction in the upper airways. To achieve this, ENT specialists from Belgium, representatives of academic hospitals in the country, have tried to establish an updated work-up in the clinical evaluation of the SDB patients. History, risk factors evaluation, excessive daytime sleepiness, static and dynamic evaluation of the upper airways (velopharynx aspect, tonsils grading, Mallampati score, Müller's maneuver, fiberoptic evaluation) have been standardized in a consensus report easily accessible to the vast majority of ENT specialists. This consensus must be understood as a clinical work-up to perform before the monitoring of breathing during sleep.

Conservative and non surgical treatments for the sleep disordered breathing adult.

Obstructive sleep apnoea (OSA) syndrome is a chronic disease characterised by repetitive obstructive apnoeas and hypopnoeas during sleep leading to sleep fragmentation. The treatment of OSA consists of general and specific measures. The aim of this article is to review the different non surgical approaches to treat OSA in adults. The different therapeutical options can be used in combination, which underlines that the OSA patient needs a careful and multidisciplinary management.

Surgical treatment of the sleep-disordered breathing patient; a consensus report.

Sleep disordered breathing patients may undergo surgical treatment after history, clinical examination and polysomnographic study if they demonstrate upper airway obstruction. This article focus on the surgical treatment designed for these patients. Sino-nasal surgery, rhinopharyngeal procedure, velopharyngeal procedures (Uvulopalato-pharyngoplasty, Laser assisted uvulopalatoplasty, Radiofrequency tissue volume reduction) as well as base of the tongue procedures were discussed among a panel of Belgian ENT specialists offering their experience in this field. Algorithm on corrective surgery as well as guidelines for postoperative management are proposed in the management of sleep disordered breathing patients.

Determinants of Fi,O2 with oxygen supplementation during noninvasive two-level positive pressure ventilation.

To maintain arterial oxygen saturation (Sa,O2) above 90% in patients with acute respiratory failure, oxygen (O2) is often added to the circuit of two-level noninvasive positive pressure ventilation (NPPV). However, the final inspiratory oxygen fraction (Fi,O2) is not known. To clarify this issue, the effect of different inspiratory positive airway pressures (IPAP) of the oxygen tubing connection site and the flow rate of O2, on Fi,O2 was assessed. The effects of the tidal volume (VT) and the respiratory rate on the Fi,O2 were then clarified in a model study. The Fi,O2 varied depending on the point where O2 was added to the circuit. When all other variables were constant, the connection closest to the exhaust port (ventilator side) gave the highest Fi,O2. Increases in IPAP led to decreases in Fi,O2. Finally, Fi,O2 increased with O2 flow, although it was difficult to obtain an Fi,O2 >0.30 unless very high O2 flows were used. Paradoxically, NPPV with low IPAP values and without O2 supplementation led to a Fi,O2 <0.21 at the circuit-patient interface. VT and respiratory rate did not appear to influence Fi,O2. To conclude, when using noninvasive positive pressure ventilation with two-level respirators, oxygen should be added close to the exhaust port (ventilator side) of the circuit. If inspiratory airway pressure levels are >12 cmH2O, oxygen flows should be at least 4 L x min(-1).

Microsleep during a simplified maintenance of wakefulness test. A validation study of the OSLER test.

Daytime somnolence is both a symptom in many patients and a prevalent complaint in the general population, but its objective assessment remains elusive. The current available tests are technically complex and thus inadequate for routine clinical use or epidemiological studies. A simplified behavioral maintenance of wakefulness test (OSLER test) has been recently described that could allow for widespread availability of objective measurements of this symptom. We verified the occurrence of (micro)sleep (episodes of sleep of > or = 3 s duration) during the performance of the OSLER test in 10 normal subjects after a non-sleep-deprived night and a sleep-deprived night in randomized order. Sleep was assessed electrophysiologically according to standard methods. The OSLER test (mean of four measurements) was significantly shorter after the sleep-deprived night (25 min versus 38 min). Single missed stimuli were frequent with or without (micro)sleep, but (micro)sleep was almost always present when four or more consecutive stimuli were missed. The sensitivity and specificity of the test in detecting sleep (of > or = 3 s duration) are 85% and 94%, respectively. The total number of missed stimuli per minute duration of the test could add valuable information to the simpler mean test result. Sensitivity and specificity are not altered when only three measurements are performed. We conclude that the OSLER test appears as a simple, easy, and reliable method to objectively assess daytime somnolence.