Jonathan B. Waugh

Capnography enhances surveillance of respiratory events during procedural sedation: a meta-analysis.

STUDY OBJECTIVE To determine if capnography, in addition to standard monitoring, identified more respiratory complications than standard monitoring alone. DESIGN Meta-analysis. SETTING University medical center. MEASUREMENTS The electronic databases PubMed, CINAHL, and Cochrane Library (Cochrane Reviews, CENTRAL) were searched for studies published between 1995-2009 reporting adverse respiratory events during procedural sedation and analgesia (PSA) with clearly defined end-tidal carbon dioxide threshold, adult population, clear study design, P-value calculation, similar outcome and predictor variable definitions, and binary independent and dependent variable raw data. Five such studies were evaluated independently. A meta-analysis of these studies was performed. MAIN RESULTS During PSA, cases of respiratory depression were 17.6 times more likely to be detected if monitored by capnography than cases not monitored by capnography (95% CI, 2.5-122.1; P < 0.004). CONCLUSION End-tidal carbon dioxide monitoring is an important addition in detecting respiratory depression during PSA.

Stethoscopes: What Are We Hearing?

This paper develops an objective methodology to test the audio quality of stethoscopes, classifies stethoscopes into five functional categories, and compares the audio performance of each of the five categories. These categories, based on the manufacturers recommended use, are basic assessment, cardiology, disposable, high-end cardiology, and physical assessment. The classification into categories is based on the intended performance of the stethoscopes as provided by the manufacturers. After developing the procedures and running more than 500 tests, the stethoscope with the least amount of loss over the spectrum was chosen from each of the five categories; the five were then compared to one another. Thirty-nine stethoscopes from 11 manufacturers were used in this study. The objective test methodology allows for side-by-side comparison of stethoscopes from various manufacturers that is independent of the manufacturers published test results.

Bronchodilator response with use of OptiVent* versus Aerosol Cloud Enhancer† metered-dose inhaler spacers in patients receiving ventilatory assistance

OBJECTIVE This study compared the clinical effectiveness of the OptiVent (HealthScan Products, Inc, Cedar Grove, NJ) and the ACE (DHD, Inc, Canastota, NY) metered dose inhaler (MDI) in-line spacers. DESIGN Two-group, split-plot design with subjects serving as their own controls. SETTING Data were collected in a 1000-bed urban hospital. PATIENTS A convenience sample of 7 intubated patients receiving mechanical ventilation. INTERVENTION Patients received 4 and 8 puffs of albuterol with use of both the OptiVent and ACE devices. RESULTS Changes in expiratory airway resistance (Raw), passive peak expiratory flow rate (PEFR), and total work-of-breathing (WOBTOT) were determined using a Bicore monitor (Bicore Monitoring System; Irvine, Calif). With the ACE, Raw decreased an average of 20.2% and 8.8% in patients receiving 4 and 8 puffs, respectively. With the OptiVent, Raw decreased an average of 34.6% and 10.8% in patients receiving 4 and 8 puffs, respectively. Improvements in WOBTOT were less than those seen in Raw, and PEFR did not trend with the other 2 variables. The performances of the 2 spacer brands were comparable, with no statistical difference (P values > 0.05) for all 3 variables with use of the nonparametric Kolmogorov-Smirnov test. CONCLUSIONS These data suggest that use of the OptiVent spacer yields comparable clinical results with the ACE spacer in patients receiving mechanical ventilation and merits further evaluation.

Medical school curriculum characteristics associated with intentions and frequency of tobacco dependence treatment among 3rd year U.S. medical students

OBJECTIVE Physicians play a critical role in addressing tobacco dependence, yet report limited training. Tobacco dependence treatment curricula for medical students could improve performance in this area. This study identified student and medical school tobacco treatment curricula characteristics associated with intentions and use of the 5As for tobacco treatment among 3rd year U.S. medical students. METHODS Third year medical students (N=1065, 49.3% male) from 10 U.S. medical schools completed a survey in 2009-2010 assessing student characteristics, including demographics, tobacco treatment knowledge, and self-efficacy. Tobacco curricula characteristics assessed included amount and type of classroom instruction, frequency of tobacco treatment observation, instruction, and perception of preceptors as role models. RESULTS Greater tobacco treatment knowledge, self-efficacy, and curriculum-specific variables were associated with 5A intentions, while younger age, tobacco treatment self-efficacy, intentions, and each curriculum-specific variable were associated with greater 5A behaviors. When controlling for important student variables, greater frequency of receiving 5A instruction (OR=1.07; 95%CI 1.01-1.12) and perception of preceptors as excellent role models in tobacco treatment (OR=1.35; 95%CI 1.04-1.75) were significant curriculum predictors of 5A intentions. Greater 5A instruction (B=.06 (.03); p<.05) and observation of tobacco treatment (B=.35 (.02); p<.001) were significant curriculum predictors of greater 5A behaviors. CONCLUSIONS Greater exposure to tobacco treatment teaching during medical school is associated with both greater intentions to use and practice tobacco 5As. Clerkship preceptors, or those physicians who provide training to medical students, may be particularly influential when they personally model and instruct students in tobacco dependence treatment.

Current applications of capnography in non-intubated patients

Current clinical guidelines recommend capnography as one of the best non-invasive methods to assess adequacy of ventilation in the non-intubated patient. Alveolar hypoventilation or respiratory depression is a serious event that occurs in a variety of clinical settings where patients receive sedatives and opioids. With the large number of procedures performed outside the operating room under the effects of sedatives and the increased use of patient-controlled analgesia, the need for capnography for monitoring has dramatically increased. Despite the succesful use of capnography to monitor ventilation in the operating room over several decades, other clinical areas have been very slow adapters of the technology and still rely heavily upon pulse oximetry to detect hypoventilation. This article reviews the most current evidence for using capnography in the non-intubated patient and summarizes the results of outcome measures reported in recent clinical trials. Capnography should be routinely used for non-intubated patients at risk for respiratory depression, in particular those receiving supplemental oxygen.

Use of siRNA molecular beacons to detect and attenuate mycobacterial infection in macrophages

Tuberculosis is one of the leading infectious diseases plaguing mankind and is mediated by the facultative pathogen, Mycobacterium tuberculosis (MTB). Once the pathogen enters the body, it subverts the host immune defenses and thrives for extended periods of time within the host macrophages in the lung granulomas, a condition called latent tuberculosis (LTB). Persons with LTB are prone to reactivation of the disease when the bodys immunity is compromised. Currently there are no reliable and effective diagnosis and treatment options for LTB, which necessitates new research in this area. The mycobacterial proteins and genes mediating the adaptive responses inside the macrophage is largely yet to be determined. Recently, it has been shown that the mce operon genes are critical for host cell invasion by the mycobacterium and for establishing a persistent infection in both in vitro and in mouse models of tuberculosis. The YrbE and Mce proteins which are encoded by the MTB mce operons display high degrees of homology to the permeases and the surface binding protein of the ABC transports, respectively. Similarities in structure and cell surface location impute a role in cell invasion at cholesterol rich regions and immunomodulation. The mce4 operon is also thought to encode a cholesterol transport system that enables the mycobacterium to derive both energy and carbon from the host membrane lipids and possibly generating virulence mediating metabolites, thus enabling the bacteria in its long term survival within the granuloma. Various deletion mutation studies involving individual or whole mce operon genes have shown to be conferring varying degrees of attenuation of infectivity or at times hypervirulence to the host MTB, with the deletion of mce4A operon gene conferring the greatest degree of attenuation of virulence. Antisense technology using synthetic siRNAs has been used in knocking down genes in bacteria and over the years this has evolved into a powerful tool for elucidating the roles of various genes mediating infectivity and survival in mycobacteria. Molecular beacons are a newer class of antisense RNA tagged with a fluorophore/quencher pair and their use for in vivo detection and knockdown of mRNA is rapidly gaining popularity.

The Na+/Ca2+ exchanger: A possible link between oxidative stress and endogenous ouabain in hypertension

Oxidative stress-induced hypertension involves a number of membrane transport proteins that play a critical role in maintaining the cytosolic homeostasis of Na + and Ca 2+ . These transport proteins include Na + /K + -ATPase, the Na + /H + exchanger, Na channels, and the Na + /Ca 2+ exchanger. The exact link between these membrane transporters is not exactly known but appears to involve their location in microdomains called PLasmERosomes, oxidative stress and circulating ouabain levels. Oxidative stress stimulates the generation of ouabain from the adrenal glands which elevates circulating endogenous ouabain levels. At concentrations above 1nM, ouabain inhibits the activity of the Na + /K + -ATPase. At 1nM or lower concentrations, the Na + /K + -ATPase acts as a transducer which induces a cascade of events that begins with phosphorylation of the epidermal growth factor receptor (EGFR) by Src and activation of Ras, Raf, mitogen activated protein kinase kinase (MEK), mitogen activated protein kinase (MAPK), extracellular signal-regulated kinase1/2 (ERK1/2), and p90 ribosomal S6 kinase (p90RSK). p90RSK activates the Na + /H + exchanger through phosphorylation. Ouabain-mediated inhibition and activation of the Na + /K + -ATPase and Na + /H + exchanger, respectively, leads to elevation of Na + in the PLasmERosome which stimulates the Na + /Ca 2+ exchanger to extrude Na + in exchange for Ca 2+ . This elevates Ca 2+ in the PLasmERosome which stimulates junctional ER to release Ca 2+ . Ca 2+ influx through the Na + /Ca 2+ exchanger and release from junctional ER leads to Ca 2+ overload which can lead to a number of pathologies including increased vascular tone and hypertension.