Alain Harf

Reversal of acute exacerbations of chronic obstructive lung disease by inspiratory assistance with a face mask.

BACKGROUND Patients with acute exacerbations of chronic obstructive pulmonary disease may require endotracheal intubation with mechanical ventilation. We designed, and here report on the efficacy of, a noninvasive ventilatory-assistance apparatus to provide inspiratory-pressure support by means of a face mask. METHODS We assessed the short-term (45-minute) physiologic effects of the apparatus in 11 patients with acute exacerbations of chronic obstructive pulmonary disease and evaluated its therapeutic efficacy in 13 such patients (including 3 of the 11 in the physiologic study) who were treated for several days and compared with 13 matched historical-control patients. RESULTS In the physiologic study, after 45 minutes of inspiratory positive airway pressure by face mask, the mean (+/- SD) arterial pH rose from 7.31 +/- 0.08 to 7.38 +/- 0.07 (P less than 0.01), the partial pressure of carbon dioxide fell from 68 +/- 17 mm Hg to 55 +/- 15 mm Hg (P less than 0.01), and the partial pressure of oxygen rose from 52 +/- 12 mm Hg to 69 +/- 16 mm Hg (P less than 0.05). These changes were accompanied by marked reductions in respiratory rate (from 31 +/- 7 to 21 +/- 9 breaths per minute, P less than 0.01). Only 1 of the 13 patients treated with inspiratory positive airway pressure needed tracheal intubation and mechanical ventilation, as compared with 11 of the 13 historical controls (P less than 0.001). Two patients in each group died. As compared with the controls, the treated patients had a more transient need for ventilatory assistance (3 +/- 1 vs. 12 +/- 11 days, P less than 0.01) and a shorter stay in the intensive care unit (7 +/- 3 vs. 19 +/- 13 days, P less than 0.01). CONCLUSIONS Inspiratory positive airway pressure delivered by a face mask can obviate the need for conventional mechanical ventilation in patients with acute exacerbations of chronic obstructive pulmonary disease.

Inspiratory Pressure Support Compensates for the Additional Work of Breathing Caused by the Endotracheal Tube

Breathing through an endotracheal tube and a demand valve may increase the work performed by the respiratory muscles. Inspiratory pressure support (PS) is known to reduce this work and might therefore compensate for this increased requirement. To test this hypothesis, we measured the work of breathing (WOB) in 11 patients whose tracheas were intubated. Five had no intrinsic lung disease, but six had chronic obstructive lung disease. We compared WOB measurements taken under several sets of conditions: during assisted breathing at four levels of PS, during unassisted breathing and connection to a T-piece, and after extubation of the trachea. During unassisted breathing via the ventilator circuit (PS set at 0 cmH20), the WOB per minute was greater than that after extubation, with a mean increase (+/- standard deviation) of 68 +/- 38% (10.3 +/- 5.1 vs. 6.5 +/- 3.7 J.min-1, P less than 0.01). While breathing through the T-piece, the WOB was 27 +/- 18% greater than after tracheal extubation (8.2 +/- 5.1 vs. 6.5 +/- 3.7 J.min-1, P less than 0.05). The principal reason why inspiratory work decreased after extubation was that the ventilatory requirement decreased. For each patient, we determined retrospectively, after extubation, the level of PS that had reduced WOB to its postextubation value and obtained levels ranging from 3.4 to 14.4 cmH2O. The PS level at which additional WOB was compensated for, was greater in patients with chronic lung disease than in those free of lung disease (12.0 +/- 1.9 vs. 5.7 +/- 1.5 cm H2O, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Accuracy of pulse oximetry in the intensive care unit.

Abstract. Objective: Pulse oximetry (SpO2) is a standard monitoring device in intensive care units (ICUs), currently used to guide therapeutic interventions. Few studies have evaluated the accuracy of SpO2 in critically ill patients. Our objective was to compare pulse oximetry with arterial oxygen saturation (SaO2) in such patients, and to examine the effect of several factors on this relationship. Design: Observational prospective study. Setting: A 26-bed medical ICU in a university hospital. Patients: One hundred two consecutive patients admitted to the ICU in whom one or serial arterial blood gas analyses (ABGs) were performed and a reliable pulse oximeter signal was present. Interventions: For each ABG, we collected SaO2, SpO2, the type of pulse oximeter, the mode of ventilation and requirement for vasoactive drugs. Measurements and results: Three hundred twenty-three data points were collected. The mean difference between SpO2 and SaO2 was –0.02% and standard deviation of the differences was 2.1%. From one sample to another, the fluctuations in SpO2 to arterial saturation difference indicated that SaO2 could not be reliably predicted from SpO2 after a single ABG. Subgroup analysis showed that the accuracy of SpO2 appeared to be influenced by the type of oximeter, the presence of hypoxemia and the requirement for vasoactive drugs. Finally, high SpO2 thresholds were necessary to detect significant hypoxemia with good sensitivity. Conclusion: Large SpO2 to SaO2 differences may occur in critically ill patients with poor reproducibility of SpO2. A SpO2 above 94% appears necessary to ensure a SaO2 of 90%.

A knowledge-based system for assisted ventilation of patients in intensive care units.

The procedure for weaning a patient with respiratory insufficiency from mechanical ventilation may be complex and requires expertise obtained by long clinical practice. We designed a knowledge-based system for the management of patients receiving respiratory support and implemented a weaning procedure. The system is intended for patients whose spontaneous respiratory activity is assisted by a Hamilton Veolar ventilator delivering a positive pressure plateau during inspiration (Pressure Support Ventilation mode). Our closed-loop real-time system running on a Personal Computer continuously adapts the assistance provided by the ventilator to the patients evolution, and indicates when the patient can be withdrawn from the ventilator. Three parameters are used to appreciate the ‘respiratory comfort’ of the patient: breathing frequency, which we consider the most informative index, tidal volume and end-tidal CO2 pressure. A preliminary study of 19 patients was performed to evaluate the ability of our system to adapt the assistance to the patients needs, with the main objective of facilitating weaning by gradually lowering the level of assistance. In 10 of these patients, considered as good candidates for weaning on the strength of objective criteria, the system maintained the breathing pattern in a zone of comfort for 95% of the period of assisted ventilation and stated that they were ‘weanable’. This was consistent with the clinical evolution of all 10 patients. These results show that such a system can provide effective management for mechanically ventilated patients.

Altered balance between matrix gelatinases (MMP-2 and MMP-9) and their tissue inhibitors in human dilated cardiomyopathy: potential role of MMP-9 in myosin-heavy chain degradation.

End‐stage of human dilated cardiomyopathy (DCM) is characterized by myocyte loss and fibrosis, and associated with ventricular dilatation and reduced cardiac function. Matrix metalloproteinases (MMPs) and their natural tissue inhibitors (TIMPs) have been involved in the myocardial remodeling.

Radiofrequency Is a Safe and Effective Treatment of Turbinate Hypertrophy

Objective To evaluate the safety and efficacy of radiofrequency for reduction of inferior turbinate volume.

NéoGanesh: a working system for the automated control of assisted ventilation in ICUs.

Automating the control of therapy administered to a patient requires systems which integrate the knowledge of experienced physicians. This paper describes NéoGanesh, a knowledge-based system which controls, in closed-loop, the mechanical assistance provided to patients hospitalized in intensive care units. We report on how new advances in knowledge representation techniques have been used to model medical expertise. The clinical evaluation shows that such a system relieves the medical staff of routine tasks, improves patient care, and efficiently supports medical decisions regarding weaning. To be able to work in closed-loop and to be tested in real medical situations, NéoGanesh deals with a voluntarily limited problem. However, embedded in a powerful distributed environment, it is intended to support future extensions and refinements and to support reuse of knowledge bases.

Gelatinase expression in pulmonary arteries during experimental pulmonary hypertension

Structural remodelling of pulmonary vessels is an important feature of pulmonary hypertension (PH), which reflects distal artery muscularization and matrix remodelling. The matrix metalloproteinases (MMPs) are involved in extracellular matrix turnover and hence, in smooth muscle cell migration and endothelial cell migration and proliferation. Among the MMPs, gelatinases (MMP-2 and MMP-9) can degrade basement membrane components and promote cell proliferation and migration. This study evaluated gelatinases in pulmonary vessels during progressive PH in two rat models: exposure to hypoxia or monocrotaline. Zymography of tissue homogenates revealed an association of progression of hypoxic PH with a time-dependent increase in gelatinase MMP-2 activity, specific to pulmonary vessels. Increased MMP-2 activity was also found 30 days postmonocrotaline. Reverse transcription polymerase chain reaction demonstrated upregulation of MMP-2 messenger ribonucleic acid. Immunolocalization showed MMP-2 throughout the pulmonary vasculature, from the trunk to the distal vessels, with strong staining of the intima, media and adventitia. MMP-2 was found in its active form and gelatinolytic activity was correlated to PH severity. Activity localization by in situ zymography corroborated with the immunolocalization findings. In conclusion, the authors demonstrated that matrix metalloproteinase-2 activity is increased in pulmonary vessels during progression of pulmonary hypertension, probably as a result of involvement in the matrix turnover associated with vascular remodelling during pulmonary hypertension.

Increased expression of matrix metalloproteinase‐9 in nasal polyps

To investigate the role of gelatinases in nasal polyposis, a common and disabling airway disease characterized by chronic inflammation and tissue remodelling, matrix metalloproteinase‐2 (MMP‐2) and MMP‐9 expression was investigated in the nasal polyps (NP) of 24 patients undergoing ethmoidectomy and compared with 15 control nasal mucosal (CM) samples obtained from snorers during turbinectomy. Tissue samples were either frozen for enzymatic analysis or paraffin wax‐embedded for immunohistochemistry. Zymography and quantitative image analysis showed that MMP‐9 active forms were significantly increased (p<0.05) in NPs compared to CM (44±40 versus 13±19×103 AU/10 µg protein), while MMP‐2 expression was similar in both tissues. Concomitant studies of gelatinase immunoexpression showed that MMP‐9 expression was enhanced (4‐ to 16‐fold) in surface epithelium, glands (p<0.05), and submucosal inflammatory cells (p<0.05). In addition, MMP‐9 positivity was markedly increased in endothelial cells (p<0.01). In situ zymography demonstrated marked gelatinolytic activity, consistent with the immunolocalization of MMP‐2 and MMP‐9. These results suggest up‐regulation of active MMP‐9 in the glands and vessels characteristic of NPs. It is concluded that MMP‐9 may play a role in the upper airway remodelling observed during nasal polyposis. Copyright

Impairment of polymorphonuclear neutrophil functions precedes nosocomial infections in critically ill patients

Objective A postinjury immunodepression involving neutrophil functions has been described in critically ill patients. The aim of this prospective study was to search for a relationship between an impairment of neutrophil functions and the subsequent development of nosocomial infection. Design Twenty-one severely ill (simplified acute physiology score II >20 on admission), nonimmunosuppressed patients who were receiving no antibiotics active against methicillin-resistant Staphylococcus aureus and highly resistant Pseudomonas aeruginosa were included. Twelve healthy subjects constituted a control group. Measurements Neutrophil functions (phagocytosis and bactericidal activity toward S. aureus and P. aeruginosa in homologous plasma, reactive oxygen species secretion) were studied at day 4 ± 1 after admission, and occurrence of nosocomial infection was prospectively recorded over the following 5 days. Interleukin-10 concentration was assessed by enzyme-linked immunosorbent assay. Results are expressed as median (25th–75th percentiles). Main Results Six out of the 21 patients acquired a nosocomial infection during the 5 days after blood sampling (infected group). Compared with the patients who did not acquire nosocomial infection (noninfected group, n = 15), the neutrophils of the infected group demonstrated a higher percentage of intracellular bacterial survival (17% [2% to 67%] vs. infected: 62% [22% to 100%], p < .05), leading to an impairment of S. aureus killing in homologous plasma (killed bacteria: 4.93 log10 colony forming units/mL [4.24–5.29] vs. infected: 3.62 log10 colony forming units/mL [0.00–4.58], p < .05). Interleukin-10 plasma concentration was higher in infected patients (78 pg/mL [60–83]) compared with noninfected patients (22 pg/mL [14–58], p < .05). By contrast, P. aeruginosa killing was similar in patients whether or not they acquired a nosocomial infection. Conclusion A decrease in S. aureus killing capabilities of neutrophils can be evidenced within the days before occurrence of a nosocomial infection.