Jean I. Keddissi

Update on ARDS: Beyond the Low Tidal Volume

In 2000, the Acute Respiratory Distress Syndrome (ARDS) network1 published the results of a landmark trial in which a specific therapy was found to improve survival in patients with ARDS. This was the first trial to demonstrate an improvement in mortality since the original description of the syndrome over 30 years earlier. In 1967, Ashbaugh et al described 12 patients with “acute respiratory distress, cyanosis refractory to oxygen therapy, decreased lung compliance, and diffuse infiltrates evident on the chest radiograph.”2 These patients were so difficult to oxygenate that the term “adult respiratory distress syndrome” was used to describe their condition, analogous to the respiratory distress syndrome seen in premature infants with hyaline membrane disease. These physicians also noted that oxygenation was improved by the use of positive endexpiratory pressure (PEEP). Nonetheless, the outcome was poor because 7 of the 12 patients died. Since the original description, our understanding of the epidemiology and clinical features of ARDS has evolved, ultimately resulting in the ARDSnet trial that demonstrated an improvement in survival with low tidal volumes.1 As we will show in the following review, there has been a significant amount of progress in our understanding and treatment of ARDS since the publication of this pivotal trial.

Dornase Alpha Compared to Hypertonic Saline for Lung Atelectasis in Critically Ill Patients

BACKGROUND Despite the lack of randomized trials, nebulized Dornase alpha and hypertonic saline are used empirically to treat atelectasis in mechanically ventilated patients. Our objective was to determine the clinical and radiological efficacy of these medications as an adjunct to standard therapy in critically ill patients. METHODS Mechanically ventilated patients with new onset (<48 h) lobar or multilobar atelectasis were randomized into three groups: nebulized Dornase alpha, hypertonic (7%) saline or normal saline every 12 h. All patients received standard therapy, including chest percussion therapy, kinetic therapy, and bronchodilators. The primary endpoint was the change in the daily chest X-ray atelectasis score. RESULTS A total of 33 patients met the inclusion criteria and were randomized equally into the three groups. Patients in the Dornase alpha group showed a reduction of 2.18±1.33 points in the CXR score from baseline to day 7, whereas patients in the normal saline group had a reduction of 1.00±1.79 points, and patients in the hypertonic saline group showed a score reduction of 1.09±1.51 points. Pairwise comparison of the mean change of the CXR score showed no statistical difference between hypertonic saline, normal saline, and dornase alpha. Airway pressures as well as oxygenation, expressed as PaO(2)/F(I)O(2) and time to extubation also were similar among groups. During the study period the rate of extubation was 54% (6/11), 45% (5/11), and 63% (7/11) in the normal saline, hypertonic saline, and Dornase alpha groups, respectively (p=0.09). No treatment related complications were observed. CONCLUSIONS There was no significant improvement in the chest X-ray atelectasis score in mechanically ventilated patients with new onset atelectasis who were nebulized with Dornase alpha twice a day. Hypertonic saline was no more effective than normal saline in this population. Larger randomized control trials are needed to confirm our results.

Bronchial responsiveness in patients with restrictive spirometry.

Background. Improvement in PFT after bronchodilators is characteristic of obstructive airway diseases such as COPD. However, improvement in patients with restrictive pattern is occasionally seen. We aim to determine the clinical significance of a bronchodilator responsive restrictive defect. Methods. Patients with restrictive spirometry and a bronchodilator study were identified at the University of Oklahoma and Oklahoma City VAMC between September 2003 and December 2009. Restriction was defined as a decreased FVC and FEV1, with normal FEV1/FVC. Responsiveness to bronchodilators was defined as an improvement in FEV1 and/or FVC of at least 12% and 200 mL. Patients with lung volume measurements had their clinical and radiographic records reviewed. Results. Twenty-one patients were included in the study. Most were current or ex-smokers, with most being on bronchodilators. The average FVC and FEV1 were 65 ± 11% and 62 ± 10% of the predicted, respectively. Most patients (66%) had a normal TLC, averaging 90 ± 16% of the predicted. RV, RV/TLC, and the TLC-VA values strongly suggested an obstructive defect. Conclusions. Reversible restrictive pattern on spirometry appears to be a variant of obstructive lung disease in which early airway closure results in air trapping and low FVC. In symptomatic patients, a therapeutic trial of bronchodilators may be beneficial.

Use of pressors in the management of septic shock

In their study comparing the eff ect of norepinephrine plus dobutamine versus epinephrine alone in the management of septic shock (Aug 25, p 676), Djillali Annane and colleagues conclude that there is no evidence for a diff erence in effi cacy between the two groups. The primary endpoint, 28-day all-cause mortality, was not statistically diff erent (40% in the epinephrine group vs 34% in the norepinephrine plus dobutamine group, p=0·31). When doing a power analysis, the sample size is inversely proportional to the desired detectable diff erence in outcome between groups. In this study, it seems that the investigators grossly overestimated the mortality rates (60% vs 40%), as well as the diff erence in outcome (an absolute reduction in mortality of 20%). Such an absolute diff erence, if confi rmed, would have meant a number needed to treat (NNT) of fi ve. These estimates led to the study being underpowered to detect a more realistic, but still clinically important, diff erence. On the basis of the number of patients enrolled, the study had only around 18% power to detect an absolute reduction in mortality of 6%, such as the one actually seen. This diff erence would mean an NNT of 17, a number comparable to the NNT found in other critical care trials, such as the ARDSnetwork low tidal volume study (NNT of 12), or the PROWESS trial (NNT of 17). Therefore, we believe that Annane and colleagues’ trial was not powered enough to confi rm a diff erence in the primary endpoint between the two groups. To answer this question, a larger study would be needed.

Bronchoscopic advances in the management of aerodigestive fistulas

Malignant aerodigestive fistula (ADF) is an uncommon condition complicating thoracic malignancies. It results in increased morbidity and mortality and warrants therapeutic intervention. The management approach depends on symptoms, configuration, location, and extent of the fistula. This article will discuss the therapeutic considerations in the management of ADF.

Metastatic Lung Carcinoma Involving the Maxillary Gingiva

Metastatic spread of malignant tumors to the oral soft tissue is rare and account for 0.1% of all oral malignancies. Metastatic spread to the oral soft tissue can present as dental infections, which in turn can create a diagnostic challenge. Metastasis to the oral soft tissue from lung cancer is a rare situation. Here we describe a 52 year-old male patient treated initially with antibiotics for presumed oral abscess, who later was found to have metastatic lung cancer involving the maxillary gingiva.