Transbronchial biopsy with virtual CT bronchoscopy and nodal highlighting.

Transbronchial biopsy to sample lymph nodes and tumors that are not visible at endoscopy has a poor (<50%) success rate. These nodes can be highlighted easily at virtual computed tomographic (CT) bronchoscopy to provide a guide. This study was performed to evaluate if the addition of this information to the bronchoscopist improved the success rate of transbronchial biopsy of subcarinal and aortopulmonary lymph nodes. The addition of virtual CT bronchoscopy with lymph node highlighting significantly (P < .5) increased biopsy success rates for pretracheal, hilar, and high pretracheal adenopathy.

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.

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.

Inflammatory and fibrotic mediator release by alveolar macrophages from coal miners.

Eicosanoids and cytokines produced by alveolar macrophages (AM) are key mediators of pulmonary inflammation and fibrosis. In order to determine if eicosanoid production and cytokine production are altered in AM obtained from coal miners, we compared production of prostaglandin E2 (PGE2), thromboxane A2 (TXA2), leukotriene B4 (LTB4), interleukin-1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF alpha) by cultured AM from normal human subjects and coal miners. The recovery of AM from miners' lungs by bronchoalveolar lavage was significantly greater than that from control subjects. Mean eicosanoid and cytokine production by AM from active miners was also increased compared to AM from control subjects, but this increase was not statistically significant. AM from control subjects produced significantly more TXA2 and TNF alpha when exposed to lipopolysaccharide than did AM from miners. The cyclooxygenase inhibitor suprofen reduced PGF2 and TXA2 production and TNF alpha release but had no effect on LTB4 production of IL-1 beta release by miners' AM. The lipoxygenase inhibitor nordihydroguaiaretic acid attenuated TNF alpha release, as well as that of LTB4, but had no effect on IL-1 beta release. Inhibition of thromboxane synthase by UK 38,485 also reduced TNF alpha release by active miners' AM but had no effect on PGE2, LTB4 production, or IL-1 beta release. The results of these studies suggest that occupational inhalation of coal dust may increase total lung eicosanoid and cytokine levels and reduce the reactivity of AM to bacterial endotoxin. Furthermore, coal dust-induced changes in both eicosanoid and cytokine release may be subject to pharmacological modulation.

Effects of alpha 2-agonists on intrauterine pressure and sedation in horses: comparison between detomidine, romifidine and xylazine.

The effect of three alpha 2-agonistic sedatives, Detomidine (0.04 mg/kg), Romifidine (0.08 mg/kg) Xylazine (1.1 mg/kg) and placebo (NaCl), on intrauterine pressure was investigated with an intrauterine balloon model in four non-pregnant warmblood mares. Within 6.0 (+/- 2.2) min mean pressure increases of 9.80 (+/- 3.74), 6.88 (+/- 3.95) and 13.95 (+/- 5.19) mmHg were recorded for Detomidine, Romifidine and Xylazine, respectively. Placebo had no significant effect. The mean duration of pressure increase was 30.0 (+/- 5.10), 17.67 (+/- 9.87) and 19.50 (+/- 13.78) min for Detomidine, Romifidine and Xylazine, respectively. There was no significant difference in the degree and duration of sedation between the three treatment groups. It is concluded that alpha 2-agonists exert a marked pressure increase in the uterus with no statistically significant differences in degree and duration between the three substances. With equipotent doses no difference in duration and degree of sedation could be calculated.

Survival following mechanical ventilation for acute respiratory failure in adult men.

STUDY DESIGN: Survival following mechanical ventilation for acute respiratory failure has important implications for medical decision-making and allocation of expensive resources for critical care. PROCEDURE: We reviewed a 5-year experience with mechanical ventilation in 383 men with acute respiratory failure and studied the impact of patient age, cause of acute respiratory failure, and duration of mechanical ventilation on survival. Survival rates were 66.6 percent to weaning, 61.1 percent to ICU discharge, 49.6 percent to hospital discharge, and 30.1 percent to 1 year after hospital discharge. When our data were combined with 10 previously reported series, mean survival rates were calculated to be 62 percent to ventilator weaning, 46 percent to ICU discharge, 43 percent to hospital discharge, and 30 percent to 1 year after discharge. Of 255 patients weaned from mechanical ventilation, 44 (17.3 percent) required an additional period of mechanical ventilation during the same hospitalization. RESULTS: Age had a significant influence on survival to hospital discharge and on that to 1 year after hospital discharge, and the cause of acute respiratory failure had a significant influence on survival only to weaning. Survival was best in younger patients and those with COPD or postoperative respiratory failure and worst in patients resuscitated after cardiac or respiratory arrest. Increased duration of mechanical ventilation significantly reduced survival only to hospital discharge. Overall survival was significantly affected by age and cause of acute respiratory failure, but not by duration of mechanical ventilation. CONCLUSION: We conclude that age, cause of acute respiratory failure, and duration of mechanical ventilation have specific influences on the generally poor outcome of mechanical ventilation for acute respiratory failure.

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.

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.

Medical management of the airway.

All critical care physicians should be adept at medical management of the airway, including basic and advanced life support measures. Proper head and neck positioning, use of non-definitive airways, and ability to oxygenate and ventilate the patient with bag-valve-mask should be part of the armamentarium of every critical care physician. Training, skill, and experience are fundamental to successful translaryngeal intubation. The nasal and oral routes of such intubation each have distinct advantages and disadvantages. Oral intubation is preferred for emergency establishment of a definitive airway in most situations. Skillful intubation technique and meticulous daily management of the upper airway should diminish the risk of complications of translaryngeal intubation.

Pulmonary function in obstructive sleep apnea. Relationships to pharyngeal resistance and cross-sectional area.

Reduction in the size of the pharynx and increased pharyngeal airflow resistance have been demonstrated in patients with obstructive sleep apnea (OSA). We evaluated 15 men with severe OSA and 10 nonapneic control subjects matched for age and weight in order to determine if PCSA, inspiratory pharyngeal airflow resistance, and abnormal breathing events during sleep were associated with alterations in the flow-volume relationship and other awake PFTs. Pharyngeal cross-sectional area was determined by CT, and pharyngeal resistance between choanae and epiglottis was measured during quiet awake breathing. In patients with OSA, there was an inverse relationship between the mean cross-sectional area of the oropharynx and the ratio of FEF50%/FIF50% (rs = -0.54; p = 0.03). In all subjects, pharyngeal resistance was inversely related to percentage of predicted values for FEF25-75% (rs = -0.56; p = 0.01). The frequency of apneas during sleep was significantly (p less than 0.05) related to the percentage of predicted values for MVV, TLC, FVC, and PIF. Obesity appears to account for the strength of these relationships. Flow-volume loops and other PFTs did not distinguish patients with OSA from controls.

Morphology of the uvula in obstructive sleep apnea.

Alterations in pharyngeal structure and function are considered fundamental in the pathogenesis of obstructive sleep apnea (OSA). However, little is known about morphologic features of the pharynx in patients with OSA. We therefore studied the tissue composition of the uvula (midsagittal section) in patients with OSA, using a quantitative, morphometric point-counting technique. Uvula tissue was obtained by uvulopalatopharyngoplasty (UPPP) in 33 patients (mean number of apneas per hour of sleep = 32.7 +/- 5.2) and by autopsy in 22 normal subjects not known to have OSA. All statistical comparisons were controlled for differences caused by age and body mass index. Patients with OSA had a significantly greater percentage of muscle in the uvula (18.1 +/- 1.9% versus 9.3 +/- 2.1%, p = 0.02) than did normal subjects. A significant difference in fat content was also found (9.5 +/- 1.4% in patients versus 4.0 +/- 1.0% in normal subjects, p less than 0.02). These differences between patients with OSA and control subjects could not be accounted for by anthropometric or sex differences. The percentage of uvula fat tissue was significantly related to the frequency of apneas and hypopneas in sleep (r = 0.43, p less than 0.01). Uvula morphology in 6 nonapneic snorers undergoing UPPP was similar to that of patients with OSA. We conclude that the uvula in patients with OSA contains more muscle and fat than the uvula in control subjects, possibly contributing to pharyngeal narrowing in OSA.

Cardiac dysrhythmias during anesthesia for cervical decompression in the dog.

In a retrospective study, the risk for cardiac dysrhythmias was evaluated in dogs undergoing ventral decompression and/or fenestration of the cervical spine (CERV) and compared with that for dogs undergoing dorsal laminectomy for decompression of the thoracic or lumbar spine (TL). The dogs in the CERV subset (48 dogs) tended to be heavier and older than the dogs in the TL subset (111 dogs). There was no apparent bias detected in treatment before anesthesia and surgery. The risk for dysrhythmias was 2.5 times greater in the CERV subset, compared with that in the TL subset (P less than 0.01). The risk for ventricular premature contraction was 3.5 times higher in the CERV group (P less than 0.05). Bradycardia was found in 6 dogs from the CERV subset and was not found in any dogs from the TL subset. A logistic model was derived from the data and may be used to evaluate the risk for dysrhythmias in similar patients undergoing similar surgery and anesthesia. This model uses age, preoperative heart rate, and site of surgery (CERV or TL) to estimate the risk.

Pharyngeal size and resistance in obstructive sleep apnea.

Although anatomic and physiologic abnormalities of the upper airway are thought to be important in the pathogenesis of obstructive sleep apnea (OSA), the relative contributions of these factors have not been elucidated. We therefore measured pharyngeal cross-sectional area (PCSA) and pharyngeal air-flow resistance (Rp) in 12 overweight men with severe symptomatic OSA (mean apnea plus hypopnea index [AHI], 66.9 +/- 6.0 events per hour) and in 17 age- and weight-matched control subjects without spontaneous complaints of OSA symptoms (mean AHI, 4.9 +/- 1.6 events per hour). During wakefulness, PCSA was assessed during breath cessation at FRC by computed tomography (CT) and Rp by measuring inspiratory air-flow resistance between the choanae and epiglottis. No measure of PCSA differed significantly between patients and control subjects, and only 1 measure of PCSA, minimal pharyngeal area, correlated with AHI in all subjects (r = -0.38, p less than 0.05). In contrast, Rp was significantly higher (p less than 0.05) in patients (6.9 +/- 1.0 cm H2O/L/s) than in all control subjects (4.2 +/- 0.5 cm H2O/L/s) and correlated significantly with AHI (r = 0.53, p less than 0.01). We conclude that increased inspiratory resistance to air flow in the naso-oropharynx is present during wakefulness in overweight men with OSA, when compared with matched control subjects without symptomatic OSA, and is associated with disordered breathing during sleep. This occurs even though computed tomography is unable to demonstrate that pharyngeal size during wakefulness at FRC is significantly different between patients and control subjects. These observations suggest that the ability to dilate the pharynx during inspiration may be defective in patients with OSA.

Sleep apnea in amyloidosis.

Obstructive sleep apnea (OSA) occurs in patients with narrowing of the pharyngeal airway due to a variety of pathologic conditions. We documented obstructive and mixed sleep apnea in a patient with narrowing of the airway caused by macroglossia associated with amyloidosis. Tracheostomy relieved the symptoms of OSA (hypersomnolence, confusion upon awakening, and hyperkinesis during sleep) despite the emergence of striking central sleep apnea following the procedure.

The pH of ascitic fluid in the diagnosis of spontaneous bacterial peritonitis in alcoholic cirrhosis.

Fifty-six patients with alcoholic cirrhosis and ascites were studied. The ascitic fluid was analyzed for pH, PO2, PCO2 glucose, protein, specific gravity, amylase, lactic dehydrogenase, white blood cell count, polymorphonuclear count, and cytology. It was also cultured aerobically and anaerobically. Simultaneously, arterial blood was analyzed for pH, PO2, and PCO2. Venous blood was analyzed for complete blood count, protein, aspartate transaminase, and it was also cultured under aerobic and anaerobic conditions. Six patients had spontaneous bacterial peritonitis (SBP), i.e., culture was positive for Escherichia coli in five and Streptococcus faecalis in one. The mean (+/- S.E.) ascitic fluid pH in the SBP group wa 7.25 +/- 0.06 with a range of 7.12 to 7.31, while the ascitic fluid pH in the group with sterile ascites was 7.47 +/- 0.07 with a range of 7.39 to 7.58. The pH of the blood in both groups was 7.47 +/- 0.03. The pH of the ascites in the SBP group was significantly different from the pH in the group with sterile ascites, p less than 0.001. It was also significantly different from the blood pH, p less than 0.001. Highly significant inverse correlations existed between the ascitic pH in the SBP group and the ascitic white blood cell count (r = 0.84, p less than 0.01) and between the ascite pH in the SBP group and the ascitic polymorphonuclear count (r = -0.87 ,p less than 0.01). The ascitic fluid pH is recommended as an easy, quick, sensitive, and specific means of diagnosing SBP and it overcomes the problem of the present SBP diagnostic methods of utilizing an absolute white blood cell count greater than 500 per mm3 or a polymorphonuclear count greater than 250 per mm3 in which false positive interpretations occur.

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.