John L. Stauffer

Complications and consequences of endotracheal intubation and tracheotomy: A prospective study of 150 critically ill adult patients

A prospective study of the complications and consequences of translaryngeal endotracheal intubation and tracheotomy was conducted on 150 critically ill adult patients. Adverse consequences occurred in 62 percent of all endotracheal intubations and in 66 percent of all tracheotomies during placement and use of the artificial airways. The most frequent problems during endotracheal intubation were excessive cuff pressure requirements (19 percent), self-extubation (13 percent) and inability to seal the airway (11 percent). Patient discomfort and difficulty in suctioning tracheobronchial secretions were very uncommon. Problems with tracheotomy included stomal infection (36 percent), stomal hemorrhage (36 percent), excessive cuff pressure requirements (23 percent) and subcutaneous emphysema or pneumomediastinum (13 percent). Complications of tracheotomy were judged to be more severe than those of endotracheal intubation. Follow-up studies of survivors revealed a high prevalence of tracheal stenosis after tracheotomy (65 percent) and significantly less after endotracheal intubation (19 percent)(p < 0.01). Thirty-nine of 41 (95 percent) patients with endotracheal intubation and 20 of 22 (91 percent) patients with tracheotomy had laryngotracheal injury at autopsy. Ulcers on the posterior aspect of the true vocal cords were found at autopsy in 51 percent of the patients who died after endotracheal intubation. There was no significant relationship between the duration of endotracheal intubation or tracheotomy and the over-all amount of laryngotracheal injury at autopsy, although patients with prolonged endotracheal intubation followed by tracheotomy had more laryngeal injury at autopsy (P = 0.06) and more frequent tracheal stenosis (P = 0.05) than patients with short-term endotracheal intubation followed by tracheotomy. Adverse effects of both endotracheal intubation and tracheotomy are common. The value of tracheotomy when an artificial airway is required for periods as long as three weeks is not supported by data obtained in this study.

Do autopsies of critically ill patients reveal important findings that were clinically undetected

OBJECTIVE To determine if autopsies performed on patients who die in the medical intensive care unit (ICU) provide clinically important new information. DESIGN Retrospective review. SETTING A 16-bed medical-coronary ICU. PATIENTS Patients who underwent autopsy during a 1-yr period. INTERVENTIONS Pre mortem diagnoses were determined from the medical record. Autopsy results were obtained from the final pathology report. A panel of three physicians with certification of added qualifications in critical care medicine reviewed the findings. MEASUREMENTS AND MAIN RESULTS These questions were asked: a) Is the primary clinical diagnosis confirmed? b) Are the clinical and pathologic causes of death the same? c) Are new active diagnoses revealed? and d) If the new findings had been known before death, would the clinical management have differed? Forty-one autopsies (31% of deaths) were done that showed: a) the same primary clinical diagnosis and post mortem diagnosis in 34 (83%) patients; b) the same clinical and pathologic cause of death in 27 (66%) patients; c) new active diagnoses in 37 (90%) patients; and d) findings that would have changed medical ICU therapy had the findings been known in 11 (27%) patients. CONCLUSIONS Although the primary clinical diagnosis was accurate in most cases before death, the cause of death was frequently unknown. Almost all autopsies demonstrated new diagnoses, and knowledge of these new findings would have changed medical ICU therapy in many cases. In the critical care setting, autopsies continue to provide information that could be important for education and quality patient care.

The Human mineral dust-induced gene, mdig, is a cell growth regulating gene associated with lung cancer

Environmental or occupational exposure to mineral dusts, mainly silica and asbestos, is associated with an increased incidence of lung inflammation, fibrosis, and/or cancer. To better understand the molecular events associated with these pulmonary diseases, we attempted to identify genes that are regulated by mineral dusts. Using a differential display reverse transcription polymerase chain reaction technique and mRNAs of alveolar macrophages from both normal individuals and coal miners, we identified a novel mineral dust-induced gene named mdig, which had not been fully characterized. The expression of mdig mRNA was detected in alveolar macrophages from coal miners but not from normal subjects. The inducible expression of mdig could be observed in A549 cells exposed to silica particles in a time-dependent manner. The full-length mdig mRNA was expressed in human lung cancer tissues but was barely detectable in the adjacent normal tissues. In addition, a number of lung cancer cell lines constitutively express mdig. Alternative spliced transcripts of mdig were detected in some lung cancer cell lines. Silencing mdig mRNA expression in A549 lung cancer cells by siRNA-mediated RNA interference inhibits cell proliferation and sensitizes the cells to silica-induced cytotoxicity. These results suggest that the mdig gene may be involved in the regulation of cell growth and possibly the development of cancer.

An inhibitor of thromboxane production attenuates tumor necrosis factor release by activated human alveolar macrophages

Tumor necrosis factor alpha (TNF alpha) and thromboxane A2 (TXA2) are major products of the activated alveolar macrophage and serve as key mediators of lung injury. In order to determine if the synthesis of TXA2 and the release of TNF alpha are associated, the production of these inflammatory agents by the human alveolar macrophage (AM), as a result of activation by lipopolysaccharide (LPS), was assessed in the absence and presence of the thromboxane synthase inhibitors UK 38,485 (Dazmegrel) and OKY 046. UK 38,485 and OKY 046 inhibited both LPS-stimulated TXA2 production and TNF alpha release in a dose-dependent manner. Prostaglandin E2 (PGE2) production was not increased by UK 38,485 or OKY 046. Neither LPS nor UK 38,485 had any effect on LTB4 production by AM. Neither UK 38,485 or OKY 046 had any effect on LPS-stimulated interleukin-1 beta release. However, the TXA2 mimetic, U46619, did not stimulate TNF alpha release by AM either in the absence or presence of UK 38,485. These findings suggest that 1) UK 38,485 and OKY 046 are inhibitors of both TXA2 production and TNF alpha release by activated human AM, 2) UK 38,485 probably does not exert its inhibitory action on TNF alpha release through effects on eicosanoid production and 3) the possibility that TNF alpha- and TXA2-induced lung injury may be subject to amelioration by imidazole-based compounds should be further evaluated.

Does measuring BHR add to guideline derived clinical measures in determining treatment for patients with persistent asthma

RATIONALE Little is known about the use of biomarkers in guiding treatment decisions in routine asthma management. The objective of this study was to determine whether adding a LABA to an ICS would control bronchial hyperresponsiveness (BHR) at an overall lower dose of ICS when titration of medication was based upon the assessment of routine clinical measures with or without the measurement of BHR. METHODS After a 2-week run-in period, subjects (> or = 12 years) were randomized to one of three treatment groups. Two groups followed a BHR treatment strategy (based on clinical parameters [lung function, asthma symptoms, and bronchodilator use] and BHR) and were treated with either fluticasone propionate/salmeterol (FSC(BHR) group) or fluticasone propionate (FP(BHR) group) (n=156 each). The third group followed a clinical treatment algorithm (based on clinical parameters alone) and were treated with fluticasone propionate (FP(REF) group; n=154). All treatments were administered via Diskus. Treatment doses were adjusted as needed every 8 weeks for 40 weeks according to the subjects derived severity class, which was based on clinical measures of asthma control with or without BHR. RESULTS The mean total daily inhaled corticosteroids (ICS) dose during the double-blind treatment period was lower, although not statistically significant, in the FSC(BHR) group compared with the FP(BHR) group (a difference of -42.9 mcg; p=0.07). Compared with the FP(REF) group, the mean total daily ICS dose was higher in the FSC(BHR) group (a difference of 85.2 mcg) and was significantly higher in the FP(BHR) group (a difference of 131.2 mcg, p=0.037). CONCLUSION This study demonstrated that for most subjects, control of BHR was maintained when treatment was directed toward control of clinical parameters. In addition, there was a trend towards control of BHR and clinical measures at a lower dose of ICS when used concurrently with salmeterol.

INTUBATION OF CRITICALLY ILL PATIENTS

Airway management of critically ill patients has been enhanced by the recent introduction of several new types of artificial airways and laryngoscopes. New drugs for sedation and neuromuscular blockade have been developed to facilitate care of the intubated patient. Guidelines for management of the difficult airway have been introduced. Several new prospective studies have improved our understanding of complications of intubation and how to avoid these sometimes tragic events. A consensus is evolving that TLI and tracheotomy each have clear advantages and disadvantages in prolonged airway maintenance and that multiple factors, not simply the duration of TLI, must be considered in the optimal timing of tracheotomy for each patient. Complex medicolegal and ethical issues directly impact intubation, perhaps more so than any other practice in critical care medicine. Physicians who care for critically ill patients should be familiar with these recent developments and concepts in airway management.

Characterization of alveolar macrophage eicosanoid production in a non-human primate model of mineral dust exposure

The relative activation of eicosanoid production which results from the exposure of the alveolar macrophage (AM) to mineral dusts is thought to be a key factor in the pathophysiology of occupational lung disease. We compared in vitro basal and silica-stimulated production of prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) by AM from normal humans and non-human primates (Macaca nemestrina). In addition, we instilled mineral dusts directly into one lung of the non-human primate and evaluated AM eicosanoid production at two week intervals following dust instillation. Unstimulated AM from humans produce more PGE2 and TXA2 than do AM from M. nemestrina. However, in vitro exposure of AM from both species to silica dust produced a qualitatively similar increase in TXA2 production accompanied by no change in PGE2 production. Sequential analysis of AM eicosanoid production following a single bolus exposure to bituminous or anthracite coal dusts, titanium dioxide (TiO2) dust or crystalline silica showed marked variability among individual non-human primates in qualitative and quantitative aspects of dust-induced eicosanoid production. However, the rank order of potency of the different dusts (silica > anthracite > bituminous) correlated with epidemiological evidence relating the type of dust mined to the incidence of pneumoconiosis. These studies suggest that the non-human primate may serve as a model for the study of both the role of eicosanoids in the etiology of dust-induced occupational lung disease and the biochemical basis for individual variability in the response of lung cells to mineral dust exposure.

Bacterial Endotoxin Primes the Human Alveolar Macrophage for Subsequent Stimulation by Silica but Silica Does Not Prime for Stimulation by Bacterial Endotoxin

Abstract It has been suggested that prior exposure to mineral dust may attenuate the ability of the alveolar macrophage (AM) to respond to subsequent provocative stimuli, thus compromising the host defense mechanism. On the contrary, prior exposure of the AM with lipopolysacharride (LPS) has been shown to sensitize the AM for subsequent stimuli, thereby enhancing the reactivity of the AM. Since AM-derived eicosanoids serve as important mediators of the lungs response to AM activation, we evaluated the relative effects of LPS and silica dust on the production of several key eicosanoids when these activating agents were administered in sequence. Prior exposure of AM to LPS, followed by exposure to silica dust, led to an enhanced production of thromboxane A2 (TXA2) and leukotriene B4 (LTB4) when results were compared to AM stimulated with silica alone. In contrast, prior exposure of AM to silica dust reduced the ability of AM to respond to LPS, since levels of PGE2 and TXA2 produced by silica-primed AM subs...

Eicosanoid and Cytokine Production by the Pulmonary Alveolar Macrophage

Eicosanoids and cytokines produced by the pulmonary alveolar macrophage (PAM) are key mediators for the defensive role this cell plays in neutralizing the inhalation of pariculate dusts and foreign microbes. However, these factors are also mediators of inflammation and their uncontrolled release may cause the lung injury and fibrotic changes observed in individuals exposed occupationally to mineral dust. In vitro studies have suggested a link between the production of certain eicosanoids and cytokines released from the activated PAM. To this end, we have studied the release of eicosanoids (PGE2, TXB2 and LTB4) and cytokines (IL-1 and TNF) by cultured PAM, obtained from healthy human volunteers by bronchoalveolar lavage under basal culture conditions and following acute exposure to provocative agents such as the endotoxin lipopolysaccharide (LPS) and mineral dusts including silica. Studies were also carried out in the presence of specific cyclooxygenase inhibitors. The addition of LPS (10 μg/ml) to the culture medium produced a significant increase in PAM release of the eicosanoids: PGE2 (3.5 fold over baseline), TXB2 (2.8 fold over baseline) and LTB4 (4 fold over baseline). LPS also elicited a 2.5 fold elevation in IL-1 from these cells and a 9 fold increase in TNF release. The cyclooxygenase inhibitor, ibuprofen, significantly inhibited the LPS-induced rise in PGE2, TXB2 and TNF but had only a modest suppressive effect on IL-1 release. Exposure of these cells to silica dust elicited a similar augmentation in eicosanoid and cytokine release which was neutralized by prior exposure of the cells to ibuprofen. These results suggest that the enhanced production of eicosanoids and cytokines by PAM exposed to endotoxins and/or mineral dusts may be linked and that inhibition of eicosanoid release is linked to the production of TNF. IL-1 release however is not effectively neutralized by cyclooxygenase inhibition.

Human Sleep-Disordered Breathing

obstructive sleep apnea is a common clinical disorder primarily affecting men who have a long history of heavy snoring. The incidence of the illness increases with both aging and obesity; its major clinical manifestation is the complaint of daytime hypersomnolence. This illness has received a great deal of clinical and investigative attention in the last ten years because its occurrence appears almost epidemic in nature. In addition, apnea-associated cardiac rhythm abnormalities raise the question of the possible influence of obstructive sleep apnea on unexplained nocturnal death. Recently other associated cardiovascular abnormalities, such as sustained pulmonary and systemic hypertension, have resulted in further interest in this recently discovered illness.