Martin J. Tobin

A COMPARISON OF FOUR METHODS OF WEANING PATIENTS FROM MECHANICAL VENTILATION

BACKGROUND: Weaning patients from mechanical ventilation is an important problem in intensive care units. Weaning is usually conducted in an empirical manner, and a standardized approach has not been developed. METHODS: We carried out a prospective, randomized, multicenter study involving 546 patients who had received mechanical ventilation for a mean (+/- SD) of 7.5 +/- 6.1 days and who were considered by their physicians to be ready for weaning. One hundred thirty patients had respiratory distress during a two-hour trial of spontaneous breathing. These patients were randomly assigned to undergo one of four weaning techniques: intermittent mandatory ventilation, in which the ventilator rate was initially set at a mean (+/- SD) of 10.0 +/- 2.2 breaths per minute and then decreased, if possible, at least twice a day, usually by 2 to 4 breaths per minute (29 patients); pressure-support ventilation, in which pressure support was initially set at 18.0 +/- 6.1 cm of water and then reduced, if possible, by 2 to 4 cm of water at least twice a day (37 patients); intermittent trials of spontaneous breathing, conducted two or more times a day if possible (33 patients); or a once-daily trail of spontaneous breathing (31 patients). Standardized protocols were followed for each technique. RESULTS: The median duration of weaning was 5 days for intermittent mandatory ventilation (first quartile, 3 days; third quartile, 11 days), 4 days for pressure-support ventilation (2 and 12 days, respectively), 3 days for intermittent (multiple) trials of spontaneous breathing (2 and 6 days, respectively), and 3 days for a once-daily trial of spontaneous breathing (1 and 6 days, respectively). After adjustment for other covariates, the rate of successful weaning was higher with a once-daily trial of spontaneous breathing than with intermittent mandatory ventilation (rate ratio, 2.83; 95 percent confidence interval, 1.36 to 5.89; P < 0.006) or pressure-support ventilation (rate ratio, 2.05; 95 percent confidence interval, 1.04 to 4.04; P < 0.04). There was no significant difference in the rate of success between once-daily trials and multiple trials of spontaneous breathing. CONCLUSIONS: A once-daily trial of spontaneous breathing led to extubation about three times more quickly than intermittent mandatory ventilation and about twice as quickly as pressure-support ventilation. Multiple daily trials of spontaneous breathing were equally successful.

A prospective study of indexes predicting the outcome of trials of weaning from mechanical ventilation

Abstract Background. The traditional predictors of the outcome of weaning from mechanical ventilation — minute ventilation (VE) and maximal inspiratory pressure (P1max) — are frequently inaccurate. We developed two new indexes: the first quantitates rapid shallow breathing as the ratio of respiratory frequency to tidal volume (f/VT), and the second is termed CROP, because it integrates thoracic compliance, respiratory ṟate, arterial oxygenation, and P1max. Methods. The threshold values for each index that discriminated best between a successful and an unsuccessful outcome of weaning were determined in 36 patients, and the predictive accuracy of these values was then tested prospectively in an additional 64 patients. Sensitivity and specificity were calculated, and the data were also analyzed with receiver-operating-characteristic (ROC) curves, in which the proportions of true positive results and false positive results are plotted against each other for a number of threshold values of an index; the area...

Sleep in the intensive care unit

Abnormalities of sleep are extremely common in critically ill patients, but the mechanisms are poorly understood. About half of total sleep time occurs during the daytime, and circadian rhythm is markedly diminished or lost. Judgments based on inspection consistently overestimate sleep time and do not detect sleep disruption. Accordingly, reliable polygraphic recordings are needed to measure sleep quantity and quality in critically ill patients. Critically ill patients exhibit more frequent arousals and awakenings than is normal, and decreases in rapid eye movement and slow wave sleep. The degree of sleep fragmentation is at least equivalent to that seen in patients with obstructive sleep apnea. About 20% of arousals and awakenings are related to noise, 10% are related to patient care activities, and the cause for the remainder is not known; severity of underlying disease is likely an important factor. Mechanical ventilation can cause sleep disruption, but the precise mechanism has not been defined. Sleep disruption can induce sympathetic activation and elevation of blood pressure, which may contribute to patient morbidity. In healthy subjects, sleep deprivation can decrease immune function and promote negative nitrogen balance. Measures to improve the quantity and quality of sleep in critically ill patients include careful attention to mode of mechanical ventilation, decreasing noise, and sedative agents (although the latter are double-edged swords).

Effects of prolonged controlled mechanical ventilation on diaphragmatic function in healthy adult baboons

OBJECTIVE To study diaphragmatic strength and endurance after a prolonged period of mechanical ventilation. DESIGN Prospective animal study. SETTING Animal research laboratory. SUBJECTS Seven uninjured adult baboons (Papio cynocephalus) were anesthetized with ketamine, sedated, paralyzed, and mechanically ventilated. Animals were monitored with pulmonary arterial and peripheral arterial catheters. INTERVENTIONS Mechanical ventilation was provided for 11 days with an FIO2 of 0.21 and tidal volume of 15 mL/kg. Pulmonary function tests, including lung volumes, arterial blood gases, and chest radiographs were also monitored. Nursing care procedures included frequent turning, chest physiotherapy, and endotracheal suction. Antacids and prophylactic antibiotics (intravenous penicillin, topical polymyxin B, and gentamicin sulfate) were administered. In three animals, fishhook electrodes were surgically placed around both phrenic nerves on both day 0 and after 11 days of mechanical ventilation for diaphragmatic stimulation. On day 0, the electrodes were removed after phrenic nerve stimulation studies were performed. After 11 days of mechanical ventilation, animals were electively killed and full autopsy performed. MEASUREMENTS AND MAIN RESULTS Hemodynamic and pulmonary function parameters were measured at baseline and every day during the 11 days of mechanical ventilation. Diaphragmatic strength and endurance were measured on days 0 and 11. Diaphragmatic endurance was determined by an inspiratory resistive loading protocol. There were no significant changes in hemodynamics, lung volumes, or gas exchange during the period of mechanical ventilation. On day 7, the chest radiographs showed patchy lobar atelectasis in six animals, which cleared by day 11 in all but two of the animals. Lung pathology showed mild, focal pneumonitis. By day 11, maximum transdiaphragmatic pressure had decreased by 25% from day 0 and diaphragmatic endurance had decreased by 36%. CONCLUSIONS Eleven days of mechanical ventilation and neuromuscular blockade in healthy baboons resulted in nonsignificant changes in hemodynamics, oxygenation, and/or lung function. However, significant impairment in diaphragmatic endurance and strength were seen. Based on these results, it is likely that prolonged mechanical ventilation by itself impairs diaphragmatic function independent of underlying lung disease.

The application of esophageal pressure measurement in patients with respiratory failure.

This report summarizes current physiological and technical knowledge on esophageal pressure (Pes) measurements in patients receiving mechanical ventilation. The respiratory changes in Pes are representative of changes in pleural pressure. The difference between airway pressure (Paw) and Pes is a valid estimate of transpulmonary pressure. Pes helps determine what fraction of Paw is applied to overcome lung and chest wall elastance. Pes is usually measured via a catheter with an air-filled thin-walled latex balloon inserted nasally or orally. To validate Pes measurement, a dynamic occlusion test measures the ratio of change in Pes to change in Paw during inspiratory efforts against a closed airway. A ratio close to unity indicates that the system provides a valid measurement. Provided transpulmonary pressure is the lung-distending pressure, and that chest wall elastance may vary among individuals, a physiologically based ventilator strategy should take the transpulmonary pressure into account. For monitoring purposes, clinicians rely mostly on Paw and flow waveforms. However, these measurements may mask profound patient-ventilator asynchrony and do not allow respiratory muscle effort assessment. Pes also permits the measurement of transmural vascular pressures during both passive and active breathing. Pes measurements have enhanced our understanding of the pathophysiology of acute lung injury, patient-ventilator interaction, and weaning failure. The use of Pes for positive end-expiratory pressure titration may help improve oxygenation and compliance. Pes measurements make it feasible to individualize the level of muscle effort during mechanical ventilation and weaning. The time is now right to apply the knowledge obtained with Pes to improve the management of critically ill and ventilator-dependent patients.

Culmination of an Era in Research on the Acute Respiratory Distress Syndrome

The acute respiratory distress syndrome is a form of noncardiogenic pulmonary edema that results from acute damage to the alveoli. Most patients with this syndrome will die if they do not receive s...

Weaning From Mechanical Ventilation

Although the majority of patients can be easily weaned from mechanical ventilation, a substantial minority pose considerable difficulty. These patients account for a disproportionate amount of health care costs, and they pose enormous clinical, economic, and ethical problems. The major determinants of weaning outcome include the adequacy of pulmonary gas exchange, respiratory muscle pump function, and psychological problems. Many of the physiologic indices that have been used to predict weaning outcome are frequently inaccurate. Several techniques of weaning can be used, and there are no data to suggest the superiority of one technique over another. Management of the problem patient should be directed at the underlying cause of ventilator dependency, and an organized plan should be followed.

Meta-analysis under the spotlight: focused on a meta-analysis of ventilator weaning.

Objective:Because the results of a meta-analysis are used to formulate the highest level recommendation in clinical practice guidelines, clinicians should be mindful of problems inherent in this technique. Rather than reviewing meta-analysis in abstract, general terms, we believe readers can gain a more concrete understanding of the problems through a detailed examination of one meta-analysis. The meta-analysis on which we focus is that conducted by an American College of Chest Physicians/American Association for Respiratory Care/American College of Critical Care Medicine Task Force on ventilator weaning. Data Source:Two authors extracted data from all studies included in the Task Force’s meta-analysis. Data Synthesis and Overview:The major obstacle to reliable internal validity and, thus, reliable external validity (generalizability) in biological research is systematic error, not random error. If systematic errors are present, averaging (as with a meta-analysis) does not decrease them—instead, it reinforces them, producing artifact. The Task Force’s meta-analysis commits several examples of the three main types of systematic error: selection bias (test-referral bias, spectrum bias), misclassification bias (categorizing reintubation as weaning failure, etc.), and confounding (pressure support treated as unassisted breathing). Several additional interpretative errors are present. Conclusions:An increase in study size, as achieved through the pooling of data in a meta-analysis, is mistakenly thought to increase external validity. On the contrary, combining heterogeneous studies poses considerable risk of systematic error, which impairs internal validity and, thus, external validity. The strength of recommendations in clinical practice guidelines is based on a misperception of the relative importance of systematic vs. random error in science.

Nosocomial lung infection and its diagnosis

Nosocomial pneumonia occurs in 0.5% to 5.0% of all hospital admissions and is responsible for 15% of hospital deaths. Up to 60% of ICU patients may develop pneumonia, depending on the severity of their underlying disease. Despite the availability of potent antibiotics, ICU patients who develop Gram-negative pneumonia have a disturbingly high mortality rate. Specific etiologic diagnosis is frequently lacking because microbiological samples are commonly contaminated by oropharyngeal secretions which are colonized by Gram-negative bacilli (GNB) in up to 100% of ICU patients. Great controversy surrounds the value of various methods used to diagnose nosocomial pneumonia. Clinical criteria of pneumonia include fever, leukocytosis, purulent tracheobronchial secretions, and a new infiltrate on chest x-ray—all of which are also frequently observed in patients free of pneumonia. Tracheobronchial secretions are often contaminated by microorganisms colonizing the upper airways and their examination may provide misleading information and result in patient mismanagement. Blood cultures are valuable but positive in only a small proportion of patients with nosocomial pneumonia. Transtracheal and transthoracic aspiration are unsatisfactory in the intubated patient requiring mechanical ventilation. Immunologic techniques like countercurrent immunoelectrophoresis are promising but presently inadequate to screen for a wide variety of organisms. Transbronchial or open-lung biopsy may be considered if the pneumonia is thought to be due to opportunistic organisms rather than bacteria. From a practical standpoint, the least misleading information is probably obtained by quantitative cultures obtained from the lower airways by fiberoptic bronchoscopy, employing the plugged telescoping-catheter brush technique.

Role of the respiratory muscles in acute respiratory failure of COPD: lessons from weaning failure

It is problematic to withhold therapy in a patient with chronic obstructive pulmonary disease (COPD) who presents with acute respiratory failure so that detailed physiological measurements can be obtained. Accordingly, most information on respiratory muscle activity in patients experiencing acute respiratory failure has been acquired by studying patients who fail a trial of weaning after a period of mechanical ventilation. Such patients experience marked increases in inspiratory muscle load consequent to increases in resistance, elastance, and intrinsic positive end-expiratory pressure. Inspiratory muscle strength is reduced secondary to hyperinflation and possibly direct muscle damage and the release of inflammatory mediators. Most patients recruit both their sternomastoid and expiratory muscles, even though airflow limitation prevents the expiratory muscles from lowering lung volume. Even when acute hypercapnia is present, patients do not exhibit respiratory center depression; indeed, voluntary activation of the diaphragm, in absolute terms, is greater in hypercapnic patients than in normocapnic patients. Instead, the major mechanism of acute hypercapnia is the development of rapid shallow breathing. Despite the marked increase in mechanical load and decreased force-generating capacity of the inspiratory muscles, patients do not develop long-lasting muscle fatigue, at least over the period of a failed weaning trial. Although the disease originates within the lung parenchyma, much of the distress faced by patients with COPD, especially during acute respiratory failure, is caused by the burdens imposed on the respiratory muscles.