Human platelets modulate edema formation in isolated rabbit lungs.

The role of platelet glucose-6-phosphate dehydrogenase (G-6-PD) in mediating the effects of human platelets on oxidant-induced edema in the isolated perfused rabbit lung was investigated using dehydroepiandrosterone, a specific steroidal inhibitor of G-6-PD. Xanthine oxidase (0.003 and 0.012 U/ml) caused lung edema that was attenuated by coinfusion of washed human platelets. Platelets that were incubated with DEA to inhibit G-6-PD activity augmented xanthine oxidase-induced lung edema and pulmonary hypertension at both doses of xanthine oxidase. Infusion of papaverine to maintain stable pulmonary artery (PA) pressures, incubation of G-6-PD-inhibited platelets with acetylsalicylate, or infusion of a thromboxane-prostaglandin endoperoxide receptor site antagonist, SQ 29548, into the lung perfusate prevented augmentation of lung edema and the PA pressor response by G-6-PD-inhibited platelets. It was concluded that antioxidant-intact platelets attenuate oxidant-induced lung edema by preventing increased membrane permeability, and that G-6-PD-inhibited platelets augment lung edema through hydrostatic mechanisms mediated by release of platelet cyclooxygenase products.

Acetyl glyceryl ether phosphorylcholine-stimulated human platelets cause pulmonary hypertension and edema in isolated rabbit lungs. Role of thromboxane A2.

Macrophages, neutrophils, and platelets may play a role in acute edematous lung injury, such as that seen in the adult respiratory distress syndrome (ARDS), but their potential actions and interactions are unclear. Because stimulated human macrophages and neutrophils can release acetyl glyceryl ether phosphorylcholine (AGEPC), a potent platelet activator, we hypothesized that in ARDS, leukocyte release of AGEPC might stimulate platelets to release thromboxane A2 (TXA2), which then produces pulmonary hypertension and lung edema. In support of this premise, we found that pulmonary hypertension and edema occurred in isolated rabbit lungs perfused with human platelets and AGEPC, but not with platelets or AGEPC alone. Infusion of a vasodilator (nitroglycerin) to maintain base-line pulmonary artery pressures in lungs perfused with platelets and AGEPC prevented the development of lung edema suggesting that platelet and AGEPC-induced edema was hydrostatic in nature. Additional experiments suggested that the increased pressure was a result of TXA2 release from platelets stimulated by AGEPC. Specifically, preincubation of platelets with imidazole, a thromboxane synthetase blocker, prior to infusion with AGEPC significantly diminished pulmonary hypertension and prevented lung edema. Furthermore, pretreating lung preparations with 13-azaprostanoic acid, a TXA2 antagonist, before infusion of AGEPC and untreated platelets also reduced the pulmonary hypertension and blocked the lung edema. The role of TXA2 was further suggested when perfusates from lungs infused with platelets and AGEPC developed high levels of TXA2, whereas perfusates from controls did not. These results suggest that platelet aggregation induced by AGEPC may contribute to ARDS by releasing TXA2, which raises microvascular pressure and increases edema formation, especially when an underlying permeability defect is present.

Challenges in the care of the acutely ill.

Health care providers, hospital administrators, and politicians face competing challenges to reduce clinical errors, control expenditure, increase access and throughput, and improve quality of care. The safe management of the acutely ill inpatient presents particular difficulties. In the first of five Lancet articles on this topic we discuss patients' safety in the acute hospital. We also present a framework in which responsibility for improvement and better integration of care can be considered at the level of patient, local environment, hospital, and health care system; and the other four papers in the series will examine in greater detail methods for measuring, monitoring, and improving inpatient safety.

Diaphragmatic paralysis following chiropractic manipulation of the cervical spine.

We present a case of phrenic nerve damage resulting in unilateral diaphragmatic paralysis following chiropractic manipulation of the neck. Related vascular and neurologic complications of spinal manipulation are reviewed.

Involvement of cardiovascular rehabilitation programs in advance directive education.

BACKGROUND: Cardiac rehabilitation programs represent opportunities to educate patients with cardiac disease about living wills and durable powers of attorney for health care. The extent of advance directive education that is currently provided in cardiac rehabilitation programs, however, is unknown. METHODS: A questionnaire was mailed to nonphysician directors of cardiac rehabilitation programs to determine the programs' involvement in educating enrollees about end-of-life issues and the directors' opinions regarding the appropriateness of such education in cardiac rehabilitation curricula. Data were presented as proportions with 95% confidence intervals (Cls). RESULTS: Of the 1013 cardiac rehabilitation program directors, 845 (83%) responded to the questionnaire, of which 48 stated they were no longer enrolling patients. Of the remaining 797 program directors (83%), 71% (95% CI, 67%-74%) informed patients of their prognosis, but only 18% (95% CI, 15%-20%) and 12% (95% CI, 9%-14%) asked patients if they had a living will or a durable power of attorney for health care, respectively. Only 9% (95% CI, 7%-11%) offered educational sessions on advance directives and 17% distributed advance directive informational material. Education about cardiopulmonary resuscitation was provided by 27% (95% CI, 23%-30%), but only 3% (95% CI, 2%-4%) provided information on do-not-resuscitate topics. Fifty percent (95% CI, 46%-53%) were in favor of including advance directive education and 49% (95% CI, 45%-52%) favored inclusion of do-not-resuscitate topics into curricula. CONCLUSIONS: Cardiac rehabilitation programs are potentially valuable but not widely used sites for educating patients with cardiac disease about advance directives.

Controlled hyperventilation in patients with intracranial hypertension. Application and management.

When elevated intracranial pressure (ICP) complicates the course of various forms of cerebral edema, the likelihood of survival with full recovery is greatly diminished. Controlled mechanical hyperventilation effectively lowers ICP in some patients by causing cerebral vasoconstriction. Improved survival occurs in patients with elevated ICP from head trauma and intracranial infection treated with hyperventilation; however, no benefit has been demonstrated in patients with increased ICP from strokes or hypoxic brain damage. Proper management of the hyperventilation requires knowledge of basic cerebral circulatory physiology. Arterial Paco2 tensions should be maintained between 25 and 30 mm Hg. Vasoconstrictive effects of hyperventilation diminish after 48 to 72 hours when renal mechanisms compensate for the respiratory alkalosis. When hyperventilation is discontinued, the Paco2 must be gradually returned to normal values, since sudden changes may cause a marked rise in ICP.

Bilateral vocal cord paralysis with respiratory failure. A presenting manifestation of bronchogenic carcinoma.

A patient with lung cancer presented with upper airway obstruction and hypercapnic respiratory failure resulting from bilateral vocal cord paralysis. Computed tomography demonstrated tumor extension into the superior mediastinum, with probable disruption of both recurrent laryngeal nerves. Unlike the more common unilateral cord paralysis, bilateral cord dysfunction is often associated with preservation of voice and varying degrees of stridor that may lead to potentially life-threatening delays in diagnosis and treatment. Proper management requires urgent translaryngeal intubation if airway obstruction is high grade, with subsequent consideration of laryngeal surgical procedures for long-term care.

Procedure-specific do-not-resuscitate orders. Effect on communication of treatment limitations.

BACKGROUND: Do-not-resuscitate (DNR) orders are often inaccurately communicated between physicians and nurses or residents. Structured, procedure-specific DNR order forms have been suggested to improve communication, but no data exist to support this impression. METHODS: The level of agreement between attending physicians and nurses or residents in their understanding of the DNR orders of critically ill patients was measured before and after instituting a structured DNR order form. Caregivers were asked (1) about the clinical events to which the DNR order applied, (2) whether the DNR order withheld all elements of cardiopulmonary resuscitation, and (3) whether other treatments were to be withheld. Results were reported as kappa +/- SE. RESULTS: Nurses (n=41) and residents (n=34) showed only fair to moderate agreement with attending physicians (n=53) for the 76 evaluable patients before initiation of the DNR order form. After initiation of the structured DNR order form, nurses showed higher levels of agreement for the second (0.67 +/- 0.14) and third (0.69 +/- 0.13) components but not the first (0.39 +/- 0.15) component of the DNR order. Residents showed higher levels of agreement for the second (0.90 +/- 0.10) and third components (0.81 +/- 0.13) but not the first (0.57 +/- 0.17) component. Nurses compared with residents had lower levels of agreement with attending physicians for most aspects of the DNR order. CONCLUSION: A structured DNR order form improves agreement in understanding of some but not all components of the DNR order.

The impact of respiratory failure on the diagnosis of tuberculosis.

Six patients with hypoxic respiratory failure (arterial PO2/alveolar PO2 less than 0.50) resulting from active tuberculosis were evaluated to assess the impact of respiratory failure on the diagnosis of the underlying tuberculosis. All patients demonstrated anemia (hematocrit [mean +/- SEM], 0.29 +/- 0.01 [29.0% +/- 1.0%]) and hypoalbuminemia (serum albumin, 22 +/- 2 g/L [2.2 +/- 0.2 g/dL]) and noted an illness longer than one week. Findings on chest roentgenograms varied from a miliary pattern, misinterpreted as congestive heart failure, to cavitary and noncavitary alveolar infiltrates, misdiagnosed as bacterial pneumonia. Tuberculosis was not considered as a diagnostic possibility on admission in any patient. The mean time from admission until consideration of tuberculosis was 4.7 +/- 1.0 days and the time to diagnosis was 7.2 +/- 1.7 days. In contrast, tuberculosis was considered on admission in 12 patients presenting with undiagnosed active tuberculosis without respiratory failure. We conclude that respiratory failure delays the diagnosis of active tuberculosis by suggesting nontuberculous pneumonia.

Diagnosis of adult respiratory distress syndrome associated with underlying severe emphysema.

Adult respiratory distress syndrome (ARDS) notably produces bilateral homogeneous alveolar infiltrates and decreased lung compliance. We encountered a patient whose severe underlying emphysema altered these distinctive clinical features. The chest roentgenogram showed bilateral infiltrates containing multiple radiolucencies that simulated a cavitary process. Also, lung-chest wall compliances measured during mechanical ventilation were higher than usually observed in patients with ARDS. We suggest that the pathologic features of the emphysematous lung with multiple blebs and decreased elastic recoil properties impart these unique findings. When ARDS develops in a patient with severe underlying emphysema, an atypical presentation may produce a confusing clinical picture.

Communicating do-not-resuscitate orders with a computer-based system.

BACKGROUND: Do-not-resuscitate (DNR) orders for critically ill patients are frequently miscommunicated between attending physicians, house staff, and nurses. A computer-based system was developed to improve the communication of a procedure-specific DNR order form. METHODS: Concordance of understanding of patients' DNR status was measured with the use of unstructured DNR orders (period 1), procedure-specific DNR order forms (period 2), and procedure-specific DNR order forms administered with a computer-based communication system (period 3). The 3 components of the DNR order assessed were (1) the clinical events to which the DNR order applied, (2) whether the DNR order withheld all elements of cardiopulmonary resuscitation, and (3) whether other treatments were to be withheld. RESULTS: For the 147 patients, the computer-based system in period 3 (n = 71) improved concordance for attending physicians and nurses or residents for all 3 of the DNR components compared with period 1 (n = 40) and some of the DNR components compared with period 2 (n = 36). Concordance was "substantial" or "almost perfect" as measured by the K statistic during period 3. The proportion of agreement for the composite of all 3 components of the DNR order increased during each period (P<.001, period 3 vs period 1). Overall agreement between all caregivers for the composite DNR order also improved from period 1 (22.2%) to period 2 (47.8%) and period 3 (61.9%; P<.001 vs period 1). Errors in order entry were detected by physicians because of the computer system and corrected in 9.9% of DNR orders in period 3. Progress note documentation of DNR status did not improve during period 3. The procedures of period 3 were considered acceptable by the physician and nursing staff. CONCLUSION: A computer-based system combined with a procedure-specific DNR order form improves communication of patients' DNR status in a critical care setting.

Publications in subspecialty journals on end-of-life ethics.

BACKGROUND: Factors that impede patient adoption of advance directives and inhibit physician-patient discussions about end-of-life issues remain incompletely defined. Determination of publication rates of articles on end-of-life ethics in different subspecialty journals may provide insight into physicians' reluctance to promote advance directives for their patients, which appears to vary between subspecialty fields. OBJECTIVE: To determine publication rates of items on end-of-life issues and other ethics topics. METHODS: We surveyed core journals from 1976 to 1995 in cardiology (n = 5), critical care medicine (n = 1), nephrology (n = 4), oncology (n = 7), and pulmonary medicine (n = 2). RESULTS: Critical care medicine (50.4%; 95% confidence interval [CI], 45.0%-55.8%) and pulmonary medicine (27.6%; 95% CI, 22.7%-32.5%) journals published considerably more articles on end-of-life issues than journals in cardiology (4.1%; 95% CI, 0.8%-7.4%), nephrology (11.0%; 95% CI, 7.9%-14.1%), or oncology (6.9%; 95% CI, 1.5%-12.3%). Oncology (30.7%; 95% CI, 25.3%-36.1%), critical care medicine (29.6%; 95% CI, 24.2%-35.0%), and pulmonary medicine (21.5%; 95% CI, 16.6%-26.4%) journals published more items pertaining to all ethics-related topics compared with cardiology (11.0%; 95% CI, 7.3%-14.7%) or nephrology (7.3%; 95% CI, 4.2%-10.4%) journals. Oncology journal ethics articles most often pertained to informed consent or research issues. CONCLUSIONS: Different internal medicine subspecialty fields demonstrate markedly different patterns of publishing items on topics pertaining to end-of-life issues.

Massive pleural effusions from prostatic lymphangitic carcinomatosis: resolution with endocrine therapy.

Pleural effusions are a rare complication of metastatic adenocarcinoma of the prostate and have not been noted to resolve with endocrine therapy. In a patient with massive bilateral pleural effusions as the initial manifestation of underlying prostatic cancer, lung biopsy specimens documented the presence of lymphangitic carcinomatosis and pleural biopsy tissue was normal. The effusions cleared on two occasions after diethylstilbestrol diproprionate therapy was started. We conclude that massive pleural effusions occasionally complicate prostatic lymphangitic carcinomatosis and that they may resolve with endocrine therapy.

Utility of routine admission chest radiographs in patients with acute gastrointestinal hemorrhage admitted to an intensive care unit.

PURPOSE: To determine the diagnostic yield of routine admission chest radiographs in patients with acute gastrointestinal (GI) hemorrhage and clinical predictors of radiographic abnormalities. PATIENTS AND METHODS: The study was a retrospective series of 202 adult patients with GI hemorrhage admitted to intensive care units at an academic medical center. Routine admission chest radiographs were obtained in 161 patients. These radiographs were reviewed by a study radiologist blinded to the study purpose. The radiologist scored radiographic abnormalities into categories of "minor" or "major," "new" or "previously known," and "with an intervention" or "without an intervention." Nominal logistic regression explored the data for clinical features that identified patients with major new radiographic abnormalities with or without an intervention. RESULTS: Minor radiographic abnormalities were noted in 23 (14.3%) patients, of whom 17 (10.6%) patients had "new" (previously unknown) abnormalities. No minor abnormality prompted a therapeutic or diagnostic intervention. Major radiographic abnormalities were detected in 21 (13.0%) patients, of whom 19 (11.8%) had new findings. Major new findings prompted interventions in only 9 (5.6%) of patients. A history of lung disease and an abnormal lung physical examination predicted major new radiographic findings (P = 0.0001, sensitivity 79%, negative predictive value 96%). These variables also identified major new abnormalities that prompted interventions (P = 0.007, sensitivity 89%, negative predictive value 99%). Use of the logistic regression model to select patients for admission chest radiographs decreased charges from $1,068 to $580 for each detected major new radiographic abnormality and from $2,254 to $1,087 for major new radiographic abnormalities that prompted an intervention. CONCLUSION: These data indicate that routine chest radiographs have a low yield in detecting major new radiographic abnormalities in patients with acute GI hemorrhage. Clinical criteria, available at the time of admission, may be useful for selecting patients for chest radiographic evaluations.

Transverse myelitis associated with restless legs syndrome and periodic movements of sleep responsive to an oral dopaminergic agent but not to intrathecal baclofen.

Periodic limb movement disorder (PLMD) and restless legs syndrome (RLS) are related sleep disorders that occur with increased frequency in spinal cord disease. Effective treatment may be obtained with dopaminergic or opioid drugs, while anticonvulsants, benzodiazepines, and possibly baclofen may be helpful. This report describes a patient who developed RLS and PLMD after acute transverse myelitis associated with infectious mononucleosis, and failed to respond to intrathecal baclofen. All symptoms of RLS/PLMD resolved after treatment with pergolide.

The role of tracheotomy in weaning.

Tracheotomy is commonly performed in ventilator-dependent patients. Disadvantages to the procedure are perioperative complications, long-term airway injury, and the cost of the procedure. Benefits ascribed to tracheotomy vs prolonged translaryngeal intubation include improved patient comfort, more effective airway suctioning, decreased airway resistance, enhanced patient mobility, increased potential for speech, ability to eat orally, a more secure airway, accelerated ventilator weaning, reduced ventilator-associated pneumonia, and the ability to transfer ventilator-dependent patients from the ICU. None of these benefits, however, have been demonstrated in large-scale, prospective, randomized studies. It is proposed that there should be an anticipatory approach wherein tracheotomy is considered after an initial period of stabilization with the patient receiving mechanical ventilation when it becomes apparent that the patient will require prolonged ventilator assistance. Tracheotomy then is performed when the patient appears likely to gain one or more of the benefits ascribed to the procedure.

Does evidence-based medicine help the development of clinical practice guidelines?

Formal methods for the development of clinical practice guidelines have emerged to address societal needs to decrease physician practice variation, slow the rise of health-care costs, monitor inappropriate care, assist clinicians to stay abreast of new clinical information, set research priorities, and promote better health-care outcomes. Evidence-based methods ensure that guidelines provide valid recommendations based on a critical appraisal of the best available evidence rather than informal, opinion-based processes.

End-of-life care preferences of patients enrolled in cardiovascular rehabilitation programs.

STUDY OBJECTIVES: The study assessed the interests of ambulatory cardiac patients in advance planning and their willingness to participate in rehabilitation program-based end-of-life education. DESIGN: Observational survey study. SETTING: Fourteen outpatient cardiac rehabilitation programs in 11 states. PARTICIPANTS: Four hundred fifteen subjects enrolled in cardiac rehabilitation. MEASUREMENTS AND RESULTS: A questionnaire determined patient preferences for advance planning, completion of advance directives, completion of patient-physician discussions on end-of-life care, and effects of health status on patient acceptance of life-sustaining interventions. Seventy-two percent of patients wanted to direct their own end-of-life care, 86% desired more information on advance directives, 62% wanted to learn about life-sustaining care, and 96% were receptive to advance-planning discussions with their physicians. Seventy-two percent of patients had considered that they might require life-sustaining care in the future; acceptability of resuscitative care depended on health status and probability of survival. However, only 15% had discussed advance planning with their physicians, and 10% were confident that their physicians understood their end-of-life wishes. Physicians and cardiovascular rehabilitation programs were considered desirable sources of information on advance planning. CONCLUSIONS: Cardiac patients enrolled in rehabilitation programs want to learn more about end-of-life care and need more opportunities to discuss advance planning with their physicians. Patients consider cardiovascular rehabilitation programs to be acceptable sites for advance planning education.

Clinical predictors of prolonged translaryngeal intubation in patients with the adult respiratory distress syndrome.

This study was designed to determine if clinical features apparent after seven days of mechanical ventilation predict long-term intubation beyond 14 days and subsequent need for tracheotomy in patients with ARDS. Twenty-four patients were entered into the study. Group 1 patients were successfully extubated in less than or equal to 14 days after onset of ARDS and group 2 patients remained intubated greater than 14 days. On day 7 of ARDS, group 1 had a higher PaO2/PAO2 ratio, a lower PEEP requirement, less severe chest radiographic abnormalities and a greater likelihood of an improved radiograph from the baseline study. None of group 1 and 11 group 2 patients eventually underwent tracheotomy. Clinical features apparent after seven days of mechanical ventilation in patients with ARDS suggest the likelihood of prolonged intubation beyond 14 days and eventual tracheotomy. Recognition of these features may allow more timely conversion of endotracheal intubation to tracheotomy.

Positive pressure mechanical ventilation augments left ventricular function in acute mitral regurgitation.

Although inconclusively established, positive pressure ventilation may augment cardiac function in congestive cardiomyopathies. We report a patient with acute mitral regurgitation who experienced enhanced myocardial performance and resolution of large pulmonary artery v waves during mechanical ventilation. This observation supports the existence of a cardiac booster effect from positive pressure ventilation.