Low tidal volume ventilation is associated with reduced mortality in HIV-infected patients with acute lung injury.

BACKGROUND: Respiratory failure remains the leading indication for admission to the intensive care unit (ICU) and a leading cause of death for HIV-infected patients in spite of overall improvements in ICU mortality. It is unclear if these improvements are due to combination anti-retroviral therapy, low tidal volume ventilation for acute lung injury, or both. A study was undertaken to identify therapies and clinical factors associated with mortality in acute lung injury among HIV-infected patients with respiratory failure in the period 1996-2004. A secondary aim was to compare mortality before and after introduction of a low tidal volume ventilation protocol in 2000. METHODS: A retrospective cohort study was performed of 148 consecutive HIV-infected adults admitted to the ICU at San Francisco General Hospital with acute lung injury requiring mechanical ventilation. Demographic and clinical information including data on mechanical ventilation was abstracted from medical records and analysed by multivariate analysis using logistic regression. RESULTS: In-hospital mortality was similar before and after introduction of a low tidal volume ventilation protocol, although the study was not powered to exclude a clinically significant difference (risk difference -5.4%, 95% CI -21% to 11%, p = 0.51). Combination antiretroviral therapy was not clearly associated with mortality, except in patients with Pneumocystis pneumonia. Among all those with acute lung injury, lower tidal volume was associated with decreased mortality (adjusted odds ratio 0.76 per 1 ml/kg decrease, 95% CI 0.58 to 0.99, p = 0.043), after controlling for Pneumocystis pneumonia, serum albumin, illness severity, gas exchange impairment and plateau pressure. CONCLUSIONS: Lower tidal volume ventilation is independently associated with reduced mortality in HIV-infected patients with acute lung injury and respiratory failure.

Implementation of a low tidal volume ventilation protocol for patients with acute lung injury or acute respiratory distress syndrome.

The ARDS (acute respiratory distress syndrome) Network study found 22% lower mortality in acute lung injury and ARDS patients ventilated with low tidal volumes (V(T)) than in those ventilated with traditional V(T) ventilation. Several points should be considered when using the low V(T) protocol for clinical practice. Prior to implementation, hemodynamic and acid-base status, minute ventilation, and adequacy of sedation should be assessed to minimize the potential for intolerance. The volume-preset, assist-control mode is recommended for better control of V(T), and the respiratory rate should be increased as V(T) is reduced, so as to maintain minute ventilation and prevent acute hypercapnia. When unavoidable, hypercapnia should be induced slowly. Ventilator inspiratory flow (V(I)) and trigger sensitivity settings should be optimized to limit the increase in work of breathing and dyspnea. When dyspnea results in double-triggered breaths, V(T) can be titrated to 7-8 mL/kg, provided end-inspiratory plateau pressure is < or = 30 cm H(2)O. In severe acidosis (pH < 7.15) V(T) also can be increased. However, every effort should be made to maintain plateau pressure and V(T) goals by buffering severe acidosis and treating patient-ventilator asynchrony with sedation. Evaluation for weaning should occur when adequate oxygenation can be maintained on 40% oxygen and a positive end-expiratory pressure of 8 cm H(2)O. Pressure support levels between 5 and 20 cm H(2)O (above 5 cm H(2)O positive end-expiratory pressure) are used for weaning and titrated to keep the respiratory rate < 35 breaths/min. Pressure support levels should be weaned aggressively, as long as the protocol's weaning tolerance criteria can be maintained.

Efficacy of low tidal volume ventilation in patients with different clinical risk factors for acute lung injury and the acute respiratory distress syndrome.

In patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), a recent ARDS Network randomized controlled trial demonstrated that a low tidal volume (VT) mechanical ventilation strategy (6 ml/kg) reduced mortality by 22% compared with traditional mechanical ventilation (12 ml/kg). In this study, we examined the relative efficacy of low VT mechanical ventilation among 902 patients with different clinical risk factors for ALI/ARDS who participated in ARDS Network randomized controlled trials. The clinical risk factor for ALI/ARDS was associated with substantial variation in mortality. The risk of death (before discharge home with unassisted breathing) was highest in patients with sepsis (43%); intermediate in subjects with pneumonia (36%), aspiration (37%), and other risk factors (35%); and lowest in those with trauma (11%) (p < 0.0001). Despite these differences in mortality, there was no evidence that the efficacy of the low VT strategy varied by clinical risk factor (p = 0.76, for interaction between ventilator group and risk factor). There was also no evidence of differential efficacy of low VT ventilation in the other study outcomes: proportion of patients achieving unassisted breathing (p = 0.59), ventilator-free days (p = 0.58), or development of nonpulmonary organ failure (p = 0.44). Controlling for demographic and clinical covariates did not appreciably affect these results. After reclassifying the clinical risk factors as pulmonary versus nonpulmonary predisposing conditions and infection-related versus non-infection-related conditions, there was still no evidence that the efficacy of low VT ventilation differed among clinical risk factor subgroups. In conclusion, we found no evidence that the efficacy of the low VT ventilation strategy differed among clinical risk factor subgroups for ALI/ARDS.

Perspectives on care at the close of life. Management of dyspnea in patients with far-advanced lung disease: "once I lose it, it's kind of hard to catch it... ".

Dyspnea is a common problem among patients with interstitial fibrosis, lung cancer, cystic fibrosis, and chronic obstructive pulmonary disease. The slow but steady progression of such diseases, often punctuated by acute exacerbations or secondary illnesses, can lead to decision-making dilemmas among patients and their caregivers, such as when to accept mechanical ventilation, when to forgoe aggressive therapies, and when to make formal end-of-life care plans. Two cases, a 74-year-old woman with dyspnea secondary to emphysema and a 65-year-old woman with recurrent lung cancer and severe exertional fatigue and dyspnea, illustrate how dyspneic patients approaching the end of life can be evaluated and treated. Four management strategies for dyspnea are discussed: reducing ventilatory impedance, reducing ventilatory demand, improving respiratory muscle function, and altering central perception. Physicians should encourage end-stage lung disease patients and their families to discuss issues such as hospitalization and mechanical ventilation, to prepare advance directives, and to participate in a plan to manage their dyspnea.

End-of-life care: what do the American courts say?

End-of-life care of critically ill patients generally consists of two closely related practices: the withholding and withdrawal of life support, and the administration of palliative care. In the United States, the withholding or withdrawal of life support is legally justified by the principles of informed consent and informed refusal. The U.S. Supreme Court has held that competent patients may refuse any and all treatments, including those that sustain life. All states sanction such refusal by competent patients, and most states allow surrogates to refuse treatment on behalf of incompetent patients. Although some physicians use the concept of futility to unilaterally withhold or withdraw life support, the Supreme Court has not heard a futility case, and the only clear legal rule on futile treatment is the traditional malpractice test, which measures physician actions against standards of medical care. However, the Supreme Court has furnished guidelines on the administration of palliative care. By using the principle of double effect, these guidelines allow physicians to give sedative and analgesic agents to dying patients if they intend to relieve pain and suffering but not to hasten death.

Effects of primary care coordination on public hospital patients.

OBJECTIVE: To evaluate the effect of primary care coordination on utilization rates and satisfaction with care among public hospital patients. DESIGN: Prospective randomized gatekeeper intervention, with 1-year follow-up. SETTING: The Adult General Medical Clinic at San Francisco General Hospital, a university-affiliated public hospital. PATIENTS: We studied 2,293 established patients of 28 primary care physicians. INTERVENTION: Patients were randomized based on their primary care physician's main clinic day. The 1,121 patients in the intervention group (Ambulatory Patient-Physician Relationship Organized to Achieve Coordinated Healthcare [APPROACH] group) required primary care physician approval to receive specialty and emergency department (ED) services; 1,172 patients in the control group did not. MEASUREMENTS AND MAIN RESULTS: Changes in outpatient, ED, and inpatient utilization were measured for APPROACH and control groups over the 1-year observation period, and the differences in the changes between groups were calculated to estimate the effect of the intervention. Acceptability of the gatekeeping model was determined via patient satisfaction surveys. RESULTS: Over the 1-year observation period, APPROACH patients decreased their specialty use by 0.57 visits per year more than control patients did ( P =.04; 95% confidence interval [CI] -1.05 to -0.01). While APPROACH patients increased their primary care use by 0.27 visits per year more than control patients, this difference was not statistically significant (P =.14; 95% CI, -0.11 to 0.66). Changes in low-acuity ED care were similar between the two groups (0. 06 visits per year more in APPROACH group than control group, P =. 42; 95% CI, -0.09 to 0.22). APPROACH patients decreased yearly hospitalizations by 0.14 visits per year more than control patients (P =.02; 95% CI, -0.26 to -0.03). Changes in patient satisfaction with care, perceived access to specialists, and use of out-of-network services between the 2 groups were similar. CONCLUSIONS: A primary care model of health delivery in a public hospital that utilized a gatekeeping strategy decreased outpatient specialty and hospitalization rates and was acceptable to patients.

The treatment of acidosis in acute lung injury with tris-hydroxymethyl aminomethane (THAM).

Mechanical hyperventilation of acidemic patients with acute lung injury (ALI) requires the use of high volumes and pressures that may worsen lung injury. However, permissive hypercapnia in the presence of shock, metabolic acidosis, and multi-organ system dysfunction may compromise normal cellular function. Tris-hydroxymethyl aminomethane (THAM) may be an effective method to control acidosis in this circumstance. Protonated THAM is excreted by the kidneys, so that carbon dioxide production is not raised. In an uncontrolled study, we administered THAM to 10 patients with acidosis (mean pH = 7.14) and ALI (mean lung injury score = 3.28) in whom adequate control of arterial pH could not be maintained during either eucapnic ventilation or permissive hypercapnia ventilation. THAM was given at a mean dose of 0.55 mmol/kg/h. Administration of THAM was associated with significant improvements in arterial pH and base deficit, and a decrease in arterial carbon dioxide tension that could not be fully accounted for by ventilation. Although further studies are needed to confirm these observations, THAM appears to be an effective alternative to sodium bicarbonate for treating acidosis during ALI.

Exacerbation of acute pulmonary edema during assisted mechanical ventilation using a low-tidal volume, lung-protective ventilator strategy.

STUDY OBJECTIVES: To assess the magnitude of negative intrathoracic pressure development in a patient whose pulmonary edema acutely worsened immediately following the institution of a low-tidal volume (VT) strategy. DESIGN: Mechanical lung modeling of patient-ventilator interactions based on data from a case report. SETTING: Medical ICU and laboratory. PATIENT: A patient with suspected ARDS and frank pulmonary edema. INTERVENTIONS: The patient's pulmonary mechanics and spontaneous breathing pattern were measured. Samples of arterial blood and pulmonary edema fluid were obtained. MEASUREMENTS: A standard work-of-breathing lung model was used to mimic the ventilator settings, pulmonary mechanics, and spontaneous breathing pattern observed when pulmonary edema worsened. Comparison of the pulmonary edema fluid-to-plasma total protein concentration ratio was made. RESULTS: The patient's spontaneous VT demand was greater than preset. The lung model revealed simulated intrathoracic pressure changes consistent with levels believed necessary to produce pulmonary edema during obstructed breathing. A high degree of imposed circuit-resistive work was found. The pulmonary edema fluid-to-plasma total protein concentration ratio was 0.47, which suggested a hydrostatic mechanism. CONCLUSION: Ventilator adjustments that greatly increase negative intrathoracic pressure during the acute phase of ARDS may worsen pulmonary edema by increasing the transvascular pressure gradient. Therefore, whenever sedation cannot adequately suppress spontaneous breathing (and muscle relaxants are contraindicated), a low-VT strategy should be modified by using a pressure-regulated mode of ventilation, so that imposed circuit-resistive work does not contribute to the deterioration of the patient's hemodynamic and respiratory status.

A national survey of end-of-life care for critically ill patients.

In some intensive care units (ICUs), fewer patients who die now undergo attempts at cardiopulmonary resuscitation (CPR), and many more have life support actively withdrawn prior to death than did a decade ago. To determine the frequency of withdrawal of life support, we contacted every American postgraduate training program with significant clinical exposure to critical care medicine, asking them prospectively to classify patients who died into one of five mutually exclusive categories. We received data from 131 ICUs at 110 institutions in 38 states. There were 6,303 deaths, of which 393 patients were brain dead. Of the remaining 5,910 patients who died, 1,544 (23%) received full ICU care including failed cardiopulmonary resuscitation (CPR); 1,430 (22%) received full ICU care without CPR; 797 (10%) had life support withheld; and 2,139 (38%) had life support withdrawn. There was wide variation in practice among ICUs, with ranges of 4 to 79%, 0 to 83%, 0 to 67%, and 0 to 79% in these four categories, respectively. Variation was not related to ICU type, hospital type, number of admissions, or ICU mortality. We conclude that limitation of life support prior to death is the predominant practice in American ICUs associated with critical care training programs. There is wide variation in end-of-life care, and efforts are needed to understand practice patterns and to establish standards of care for patients dying in ICUs.

Acute lung injury and the acute respiratory distress syndrome.

OBJECTIVE: To review acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) in light of recent information about the definitions, epidemiology, pathophysiology, management, and outcome of these conditions. DATA SOURCES: The author's personal files as well as the computerized MEDLINE database. STUDY SOLUTION: Studies were selected for their relevance to the conditions of ALI and ARDS. DATA EXTRACTION: The author extracted all applicable data. DATA SYNTHESIS: The diagnostic criteria for ALI and ARDS include a) acute onset; b) bilateral chest radiographic infiltrates; c) a pulmonary artery occlusion pressure of < or =18 mm Hg or no evidence of left atrial hypertension; and d) impaired oxygenation manifested by a PaO2/FIO2 ratio of < or =300 torr (< or =40 kPa) for ALI and < or =200 torr (< or =27 kPa) for ARDS. The incidence of ALI and ARDS are approximately 70 and 7 patients out of 100,000 of the total U.S. population per year, respectively. The conditions result from direct or indirect injury to the pulmonary epithelium and endothelium that causes edema, atelectasis, inflammation, and fibrosis. This "diffuse alveolar damage" is actually patchy in many patients. Therapy of ALI and ARDS is largely supportive, although new approaches in mechanical ventilation, patient positioning, and pharmacologic therapy have been introduced. The mortality rate of ARDS has improved to <50%, but the reasons for this improvement are unclear. CONCLUSION: ALI and ARDS are better defined and understood than ever before, and their outcome has improved for unclear reasons.

Making decisions about the forgoing of life-sustaining therapy.

The incidence of withholding and withdrawal of life support from critically ill patients has increased to the extent that these practices now precede well over half of all deaths in many intensive care units (ICUs). Although the forgoing of life-sustaining therapy is ethically acceptable and clinically desirable in certain instances, and although physicians do not have a responsibility to provide futile care even if a patient or surrogate insists on it, they must be cautious in exercising their influence, if not authority, over patients and surrogates in prompting the withholding and withdrawal of life support. Such caution is particularly indicated because managed care has made patients suspicious of healthcare institutions and physicians who are rewarded for restricting access to care. Most patients and surrogates agree with reasonable physician recommendations to forgo life-sustaining therapy. When they do not agree, physicians should not limit care on the basis of their own personal notions of futility, but should instead rely on institutional or multiinstitutional futility policies. Such policies should be developed by health professionals, patients, community leaders, and, when appropriate, participants in managed-care organizations. They should specify which ICU interventions are beneficial, address potential conflicts of interest, and be available to persons who could use such information in selecting the source of their care.

[Decrease of supercooling capacity during embryogenesis and larval growth in Coleoptera]. / Diminution de la capacité de surfusion au cours de l'embryogenèse et du développement larvaire chez un coléoptère.

Potential cold resistance of non-diapause eggs and first instar larvae of Osmoderma eremita (Coleoptera, Cetoniidae, Trichiinae) during embryogenesis and post-embryonic growth was assessed by measuring individual supercooling points (SCP): sterile eggs had a mean SCP of -24.3 +/- 2.0 degrees C; fertilized newly laid eggs a mean SCP of -23.4 +/- 3.2 degrees C and eggs about to hatch a mean SCP of -9.2 +/- 2.9 degrees C. Water absorption by fertilized eggs is a necessary requirement for the development of the embryo and results in an increase in weight and water content: fertilized newly laid eggs had a mean fresh weight of 10.687 +/- 1.072 mg and a mean water content (expressed as a percentage of the dry weight) of 79.5 +/- 10.83%; eggs about to hatch had a mean fresh weight of 19.127 +/- 3.183 mg and a mean water content of 250.10 +/- 74.15%. The ex-ovo larvae, hatched 30 days after oviposition, had a mean SCP of -10.1 +/- 3.6 degrees C (no significant difference with eggs about to hatch) and had gained in weight (24.845 +/- 3.911 mg) and in water content (499.72 +/- 55.49%). Feeding 1st instar larvae had a decreased supercooling ability (mean SCP = -5.7 +/- 0.4 degrees C) whereas their mean fresh weight (99.858 +/- 53.091 mg) and mean water content (665.83 +/- 82.74%) increased. The eggs and larvae of O. eremita are freezing intolerant. Before overwintering, all larvae switch to being freezing tolerant and can survive ice formation in their tissues and body fluids, whereas their mean SCP stays at around -5 degrees C. However, recent experiments in the winter of 1996 have shown that frozen larva mortality does occur at temperatures lower than about -12 degrees C.

Withholding and withdrawal of life support: ethical, legal, and clinical aspects.

The withholding and withdrawal of life support are processes by which various medical interventions either are not given to or are taken away from patients, with the expectation that they will die as a result. The propriety of withholding and withdrawal of life support has been supported by ethical statements from groups such as the Task Force on Ethics of the Society of Critical Care Medicine, and by a series of legal decisions beginning with the Quinlan case. Surveys of healthcare professionals indicate that most ICU physicians withhold and withdraw life support on a regular basis, that they consider these processes ethically equivalent, that they recommend withholding and withdrawal of life support based upon prognosis (which may be expressed as futility), and that they consider patient and surrogate wishes to be most important in deciding to forego life-sustaining treatment, but place these wishes in the context of their own assessment of prognosis. Observational studies show that: withholding and withdrawal of life support occur frequently, the frequency has increased over the past several years in some ICUs, patients and families generally agree with physician recommendations to limit care or request such limitation, disagreements sometimes occur on this issue, withdrawal of life support occurs more commonly than withholding of life support in most ICUs, cardiopulmonary resuscitation is the therapy most frequently withheld, mechanical ventilation is the therapy most frequently withdrawn, this withdrawal process usually is gradual, and it usually is facilitated by the administration of sedatives and analgesics. Clinical information such as this is helping to define a standard of care in the area of withholding and withdrawal of life support.