Continuous and bilevel positive airway pressure in the treatment of acute cardiogenic pulmonary edema

Therapeutics

Continuous and Bilevel Positive Airway Pressure in the Treatment of Acute Cardiogenic Pulmonary Edema JOSHUA M. KOSOWSKY, MD, ALAN B. STORROW, MD, AND STEVEN C. CARLETON, MD, PHD Patients with acute cardiogenic pulmonary edema (ACPE) are commonly seen in the emergency department (ED). Although the majority of patients respond to conventional medical therapy, some patients require at least temporary ventilatory support. Traditionally,this has been accomplished via endotracheal intubation and mechanical ventilation, an approach that is associated with a small but significant rate of complications. The past 2 decades have witnessed increasing interest in methods of noninvasive ventilatory support (NVS), notably continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BiPAP). We review the physiological consequences, clinical efficacy, and practical limitations of CPAP and BiPAP in the management of ACPE. (Am J Emerg ied 2000;18:91-98. Copyright © 2000 by W.B. Saunders Company) Acute cardiogenic pulmonary edema (ACPE) is a common medical emergency. Although virtually all patients with ACPE present in respiratory distress, the majority can be stabilized in the emergency department (ED) with conventional pharmacological therapy aimed at reversing hypoxemia and improving cardiac function. 1 In a minority of patients, severe, persistent hypoxemia or progressive respiratory fatigue indicates a need for assisted ventilation. Traditionally this has been accomplished via endotracheal intubation (ETI) and mechanical ventilation. ETI is associated with well-known risks and liabilities. 2 The procedure itself can cause injury to the upper airway and entails a small but significant risk of aspiration. Failed attempts at intubation can have disastrous consequences. Once the endotracheal tube is secured in the airway, loss of anatomic barriers predisposes to ventilator-associated pneumonia, a highly morbid complication. 3 The presence of an endotracheal tube is uncomfortable for patients and precludes oral intake, expectoration, and speech. Patients

From the Department of Emergency Medicine and Center for Emergency Care, University of Cincinnati College of Medicine, Cincinnati, OH. Manuscript received August 4, 1998, accepted September 4, 1998. Address reprint requests to Joshua Kosowsky, MD, Department of Emergency Medicine, University of Cincinnati College of Medicine, PO Box 670769, Cincinnati, OH 45267-0769. Key Words: Emergency medical services; pulmonary edema; congestive heart failure; noninvasive ventilation; continuous positive airway pressure; bilevel positive airway pressure. Copyright © 2000 by W.B. Saunders Company 0735-6757/00/1801-0022510.00/0

frequently become agitated and require deep sedation, entailing additional potential morbidity. Noninvasive ventilatory support (NVS) has been advanced as a means of avoiding the morbidity of ETI in patients with acute respiratory failure. 4,5,6 NVS is easily instituted and generally well-tolerated by patients. With the development of improved masks and ventilator technologies, applications for NVS have proliferated. Over the past 2 decades, NVS has gained acceptance for the treatment of a variety of both acute and chronic respiratory conditions .7 In the setting of ACPE, accumulating evidence supports the use of NVS. 8 Two different modes of NVS have been applied in this context: continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BiPAP). Both CPAP and BiPAP have been promoted as improving pulmonary mechanics and hemodynamics, thereby modifying both the pathophysiology and clinical course of ACPE. CONTINUOUS POSITIVE AIRWAY PRESSURE (CPAP) CPAP is a method of NVS in which the patient breathes through a mask against positive pressure held constant throughout the respiratory cycle. To compensate for leaks, CPAP devices regulate airflow to maintain a set pressure. The amount of positive airway pressure can be adjusted according to the patient's clinical response. Pressures of 5 to 10 cmH20 are most commonly used, and pressures above 15 cmH20 are rarely needed or tolerated. CPAP improves lung mechanics by recruiting atelectatic alveoli, improving pulmonary compliance, and reducing the work of breathing. 9,1°At the same time, and particularly in patients with congestive heart failure, CPAP improves hemodynamics, by reducing preload and afterload, n In general, positive airway pressure reduces venous return to the left ventricle. In patients with normal left ventricular function, who are sensitive to changes in preload, this may lead to a decrease in cardiac output. However, in individuals with a failing left ventricle, a reduction in preload may actually improve cardiac function. 12More importantly, positive airway pressure is transmitted to the left ventricle, reducing transmural pressure and afterload, and resulting in enhanced left ventricular performance.13,14 The use of positive airway pressure delivered by face mask to treat ACPE was first reported in the 1930s. 15,16 91

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Interestingly, one of the original systems was described as follows: The machine as eventually designed consists of a blower--an Electrolux or Hoover vacuum cleaner answers the purpose ...--which supplies air under positive pressure through an opening to a mask;... When the household vacuum cleaner is employed the machine should be run for some minutes first of all to get rid of dust. 15 Partly because of practical issues, interest in such devices waned. In the late 1960s the benefits of continuous positive airway pressure became more fully appreciated with the advent of positive end-expiratory pressure (PEEP) to supplement mechanical ventilation. ~7 CPAP itself was first reintroduced in the neonatal intensive care unit, as a means of deriving the benefits of PEEP while avoiding the morbidity of ETI and positive pressure ventilation. 18With the introduction of better-fitting masks and improved ventilator technology, there was renewed interest in using CPAP for adults. 19 Over the past 2 decades there has been accumulating evidence in support of a role for CPAP in the management of ACPE. 2°,21,22,23 To date, three randomized studies have compared CPAP with standard medical therapy in the treatment of patients with ACPE. In the first trial, 40 hospitalized patients were randomized to either ambientpressure breathing or CPAP at 10 cm H20 by face mask, while inspired oxygen concentration was kept constant. Compared with controls, patients in the CPAP group showed more rapid improvement in oxygenation (PaQ), ventilation (PaCO2), respiratory rate, heart rate, and blood pressure. In the CPAP group six patients required ETI during the study period, versus 12 in the control group, a difference that failed to reach statistical significance. 24 In a second trial, 39 hospitalized patients were randomized to either oxygen supplementation alone or with the addition of CPAP at 10 cm H20 by face mask. Patients in the CPAP group experienced more rapid improvements in oxygenation, ventilation, respiratory rate, and heart rate. There was a statistically significant difference in the number of patients requiring ETI: seven patients in the control group, compared with none in the CPAP group. Intensive care unit (ICU) stay was significantly shorter for patients in the CPAP group (1.2 days, versus 2.7 days), but differences in overall hospital stay and in-hospital mortality did not reach statistical significance. 25 In the largest trial to date, 100 ICU patients were randomized to supplemental oxygen with or without CPAP fitrated to a maximum of 12.5 cm H20. The CPAP group showed a significantly lower rate-pressure product, intrapulmonary shunt fraction, and alveolar-arterial PaO2 gradient, with a significantly increased stroke volume index and PaO2. Again, there was a statistically significant difference in the number of patients requiring ETI: eight in CPAP group, compared with 18 in controls. There was, however, no significant difference in length of ICU or hospital stay, and no significant difference in in-hospital or 1-year mortality? 6 These three trials have recently been subjected to metaanalysis. Pooling the results, there was found to be a statistically significant 26% reduction in the need for ETI among patients treated with CPAR with a nonsignificant trend toward decreased mortality. Differences among the

studies seemed to suggest that patients with more severe respiratory failure might benefit most from CPAE 8 It is unlikely that there will be another large trial comparing CPAP with ambient-pressure breathing; therefore, benefits of CPAP with respect to secondary outcome measures will remain difficult to prove.

BILEVEL POSITIVEAIRWAYPRESSURE(BiPAP) BiPAP is a mode of NVS in which positive airway pressure increases during inspiration to assist the patient's spontaneous ventilation. BiPAP devices respond to the patient's respiratory cycle, alternating between a higher flow rate during inhalation and a lower flow rate during exhalation. The level of inspiratory flow must be matched to patient demand. If the ventilator does not generate adequate inspiratory flow, the patient will pull against the circuitry, increasing the work of breathing; on the other hand, if inspiratory flow exceeds demand, the patient may experience significant discomfort. Patients placed on BiPAP are often started at inspiratory pressures of 8 to 11 cm H20 and expiratory pressures of 3 to 5 cm H20, on the presumption that relatively low pressures enhance patient tolerance. 4 Titration is then achieved with incremental steps in inspiratory and expiratory pressure settings, in accordance with the patient's clinical response. Theoretically, when BiPAP is used in acute respiratory failure, positive expiratory pressure provides the physiological advantages of CPAP, while positive inspiratory pressure further decreases the work of breathing. These benefits have been shown most clearly in the setting of severe COPD. 27,28 In patients with ACPE, poor lung compliance and increased airway resistance add to the work of breathing. 29 Inspiratory muscles must generate large negative pleural pressure, which results in increased transmural pressure and afterload. 3° By unloading the work of breathing, BiPAP offers a theoretical advantage over CPAP in the setting of ACPE. On the other hand, excessive positive airway pressure can decrease venous return to the point of hemodynamic instability. 31 Since it's introduction in the late 1980s, BiPAP has been shown in several randomized trials to reduce the need for ETI in patients with acute respiratory failure. 3z33,34,35 The majority of patients in these trials had respiratory failure as a consequence of severe COPD or other noncardiac diagnoses. In one study it was found that among non-COPD, nonhypercapnic patients, BiPAP actually confelTed little or no benefit. 34A meta-analysis of randomized trials concluded that the use of BiPAP in patients with acute respiratory failure is associated with a decreased need for ETI and improved survival, but that these benefits are restricted to patients whose respiratory failure is related to an exacerbation COPD. 36 More recently, a trial comparing BiPAP with ETI and mechanical ventilation in patients with acute respiratory failure and without COPD, found noninvasive ventilation to be as effective as conventional mechanical ventilation in improving gas exchange but with less associated morbidity. However, in only a minority of patients (12 of 64) was respiratory failure caused by ACPE. 37 On the other hand, in a

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recent randomized clinical trial of BiPAP for ED patients with respiratory failure, among whom the most common diagnosis was ACPE (10 of 27 patients), BiPAP was associated with no reduction in need for ETI and a trend toward increased hospital mortality. 38 There are no randomized trials comparing BiPAP with standard medical therapy for ACPE, but several favorable case series have been reported. 39,4°,41,42 In one of the larger series, 22 ED patients with ACPE and in imminent need of ETI were placed on BiPAR with initial settings in the range of 5 to 8 cm H20 over 3 to 5 cm H20, subsequently titrated to patient response. All 22 patients tolerated the BiPAP mask. The investigators reported that only two of the 22 patients (9%) ended up requiring ETI, a percentage comparable with what had been reported in previous studies of CPAR 42 One small, randomized trial has compared BiPAP with CPAP for treatment of ACPE. Twenty-seven ED patients with ACPE and acute respiratory distress were randomized to receive either CPAP (starting at 10 cm H20), or BiPAP (starting at 15 cm H20 over 5 cm H20). Physicians, nurses, and patients were blinded to the ventilator mode, but respiratory therapists were unblinded and were allowed to make adjustments every 3 to 5 minutes to optimize patient comfort. The study found that there was a more rapid reduction of respiratory rate, less subjective dyspnea, and a more rapid improvement in both oxygenation and ventilation in the BiPAP group. Only one patient in each group required ETI. No difference was found in length of ICU stay, length of hospital stay, or in-hospital mortality. 43 A finding of concern in this trial was the unexpectedly high rate of acute myocardial infarction (AMI) in the BiPAP group. The excess rate of AMI is in part explained by unmatched baseline characteristics of the BiPAP patients, who, for example, were more likely to have presented with chest pain. On the other hand, the investigators did not rule out the possibility that the use of BiPAP itself made AMI more likely. Noting that a greater fall in blood pressure was observed in the BiPAP group, the investigators speculated that higher intrathoracic pressure may have induced a fall in cardiac output and myocardial perfusion. Because of this concern, the study was prematurely terminated. At present, there is a paucity of data regarding the safety and efficacy of BiPAP for the treatment of patients with ACPE. In particular, the evidence that BiPAP confers any advantage over CPAP in this setting remains inconclusive.

LIMITATIONSAND PRACTICALCONSIDERATIONS The success of NVS depends on appropriate patient selection and close monitoring of the response to treatment. Although there are no explicit guidelines as to when patients with acute respiratory failure should be given a trial of NVS, the presumption in the literature is that the earlier NVS is instituted, the better. 4,5,6 This differs from the approach to ETI, which, because of its invasive nature is often postponed until the late stages of respiratory failure. In the context of ACPE, the preemptive use of NVS is validated by experimental evidence. Randomized trials of NVS in ACPE have included patients with "respiratory failure," "incipient respiratory failure," or "respiratory

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distress" defined by clinical signs and symptoms. Clearly, not all of these patients were candidates for immediate ETI, as indicated by the fact that most patients in the control groups were never intubated. 24,25,26,43 On the other hand, NVS is not appropriate for all patients with ACPE. By definition, noninvasive modes of ventilatory support provide no control of the airway. For patients with compromised upper airway function or significantly altered level of consciousness, ETI remains the treatment of choice. Similarly, patients with cardiac arrest, unstable cardiac rhythms, or cardiogenic shock are generally felt not to be candidates for NVS and have been excluded from most clinical trials.4,5 In the setting of severe myocardial ischemia or infarction, ETI with full veutilatory support may be preferable to NVS, because any work of breathing increases myocardial oxygen demand. 8 Patients receiving NVS must be able to coordinate spontaneous breathing in the presence of an external source of positive pressure; for patients who are extremely agitated or otherwise uncooperative, NVS is not likely to be welltolerated. Patients with excessive secretions are poor candidates for NVS because there is no direct access for removal of secretions, and frequent expectoration interferes with the maintenance of positive airway pressure. Nausea and vomiting are relative contraindications to NVS, although the risk of aspiration is small when airway reflexes are intact. Recent gastric surgery is an uncommon but absolute contraindication to NVS. 4,5,6 In general, complications associated with NVS are uncommon. Clinically significant gastric insufflation is rare at pressures of less than 30 cm H20, and aspiration of gastric contents has a very low incidence (5% or less). Local complications such as skin abrasions, sinus complaints, and conjunctivitis are more common (15% to 70%), but are potentially avoidable and easily treatable. 44 Although no study has directly compared the two, both nasal and full-face masks are associated with similar rates of success and complications. High levels of pressure are more difficult to sustain with a nasal mask, because when the mouth opens the airway is depressurized. With either mask, a small degree of air leakage is preferable to an air-tight but poorly tolerated fit. For patients with lower pressure requirements, the nasal mask is more comfortable and less confining, allowing for speech and oral intake without removal of the mask. 5 NVS can be administered by self-contained, portable units or by some conventional ventilators. In the latter case, PEEP is set to achieve the desired expiratory pressure (or CPAP), and pressure support is set to achieve the desired inspiratory-expiratory pressure difference. With most NVS devices, supplemental oxygen can be supplied either through the tubing or directly into the face mask. Because supplemental oxygen is diluted by the high flow of air through the system, patients may require a higher flow of oxygen than they would with ambient pressure breathing. Some devices incorporate oxygen blenders that allow for more precise titration of inspired oxygen concentration. Devices that use a common inspiratory and expiratory line can cause rebreathing of exhaled gas and persistent hypercapnia. The use of an alternative exhalation device reduces rebreathing of carbon dioxide. 45

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Patients in whom the decision is made to institute a trial of NVS require close monitoring and frequent reevaluation. Devices designed for NVS often lack the advanced alarm systems found on modern conventional ventilators. For this reason, continuous pulse oximetry should be used and frequent clinical assessments should be made with respect to respiratory rate and work of breathing. Because positive airway pressure entails the risk of reducing cardiac output, all patients receiving NVS require careful monitoring of heart rate and blood pressure. When NVS is successful, patients usually appear more comfortable within a short period of time. 4 On the other hand, increasing dyspnea, rising respiratory rate, failure to maintain oxyhemoglobin saturation, deteriorating mental status, or hemodynamic instability indicate failure of NVS. A patient who would otherwise require ETI and is not improving clinically with NVS should not be allowed to progress to respiratory arrest before the trial of NVS is terminated. Although NVS is generally well tolerated, patients frequently experience initial discomfort and require coaching to leave the mask in place. Readjusting the mask fit and gradually titrating positive pressure can help improve patient comfort, but may require intensive respiratory therapist involvement. Some studies raise the concern that, compared with conventional mechanical ventilation, NVS unduly adds to nurse and respiratory therapist workload, especially during the initial period of therapy. 35,46 Other studies have not found this to be a significant problem. 32,47 The feasibility of NVS for the management of ACPE in the ED has been well documented in multiple clinical trials, 23,38,42,43,48 Whether NVS is workable in any particular ED, outside the context of a clinical trial, will depend on local technological expertise, accessibility of equipment and personnel, and other institutional factors.

CONCLUSION Over the past 2 decades, NVS has emerged as a therapeutic adjunct with the potential to reduce the morbidity of ACPE. Randomized controlled trials validate the use of CPAP in patients with ACPE because of a significant decrease in the need for ETI and a trend toward decrease mortality. Evidence from case series supports the use of BiPAP in ACPE, but there is currently no clear evidence that BiPAP confers additional benefit over CPAP in this setting. Appropriate patient selection and careful monitoring is critical to the success of any mode of NVS in the ED.

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