Patients with acute neurologic disease and respiratory failure are typically. Noninvasive Mechanical Ventilation in Acute Neurologic Disorders

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1 TREATMENT UPDATE Noninvasive Mechanical Ventilation in Acute Neurologic Disorders Eelco F.M. Wijdicks, MD Department of Neurology, Division of Critical Care Neurology, Mayo Clinic College of Medicine, Rochester, MN Mechanical ventilation and endotracheal intubation has raised concerns due to risk of infectious complications. Noninvasive ventilation is becoming the preferred method of ventilatory treatment. Neurologists should be aware of such devices as the bilevel positive airway pressure ventilator, as it helps to reduce respiratory distress and improve gas exchange without major complications or significant side effects. The device is small and easy to use, and may become increasingly popular in the treatment of patients with acute neurologic disease and respiratory failure. [Rev Neurol Dis. 2005;2(1):8-12] 2005 MedReviews, LLC Key words: Noninvasive ventilation Bilevel positive airway pressure Acute neurologic disease Intubation Patients with acute neurologic disease and respiratory failure are typically intubated not only for airway protection and to provide a better oxygen source but also to provide machine-supported breaths. The threshold to intubate patients with acute neurologic disease is generally low and, typically, outside the purview of neurologists. In some instances, the indication for intubation is undisputed, such as in hypoxemic hypercapnic acute respiratory failure. In other instances, it is debatable and, unfortunately, usually after the fact 8 VOL. 2 NO REVIEWS IN NEUROLOGICAL DISEASES

2 BiPAP for Acute Neurologic Disorders (eg, intubation after a single seizure). In acutely ill neurologic patients, maintaining an adequate airway is equally as important as providing a sufficient respiratory cycle. The signs that reflect a marginal condition and likely decompensation within a short period of time are desaturation signals on the pulse but it is uncertain if it would prevent reintubation. Respiration in Acute Neurologic Disorders Breathing is possible due to a complex neuronal circuit, controlled by respiratory centers in the pons and medulla. The centers in the pons are Noninvasive ventilation can be just as satisfactory and even better than endotracheal intubation. oximeter, weak spontaneous or triggered cough, weak gag reflex with touching the soft palate at the uvula, increasing sputum quantity with suctioning every hour, and thick sputum. 1 However, not only can the indication be in question but also the mode of ventilating support. Bilevel positive airway pressure (BiPAP) ventilators are becoming a first-line ventilatory treatment in various medical causes of acute respiratory failure. 2 With further sophistication of noninvasive ventilation, this mode may become more popular. Two recent reports from the medical intensive care unit prove that outcomes with noninvasive ventilation can be just as satisfactory and even better than endotracheal intubation; however, using noninvasive ventilation would require hospitals to have a respiratory therapy department. 3-5 BiPAP has been a staple in chronic treatment of amyotrophic lateral sclerosis, myotonic dystrophy, and obstructive sleep apnea in the chronic degenerative neurologic diseases, 5,6 but the use of noninvasive ventilation in acute neurologic disorders is new; therefore, it is important for neurologists to be aware of this device. It has also become an alternative option to intubation in patients with myasthenia gravis. Additionally, noninvasive ventilation may be a weaning mode, triggered by vagal reflexes, but unlike the medulla, do not have an oscillator to produce respiratory rhythm or polish and smooth out the respiratory cycle. The respiratory neurons in the medulla are located dorsally and ventrally to the nucleus ambiguus. Central hyperventilation has traditionally been linked to midbrain lesions, but this phenomenon, uncommonly due to neurologic lesions, may not have a specific localization. Pontine lesions could lead to prolonged inspiratory gasps, but involvement of consciousness could produce shallow breaths alone. Medullary lesions lead to ataxic breathing or apnea. When a patient with acute neurologic disease fails to breathe or venti- agents). Combinations of these abnormalities may occur (eg, aspiration in a postictal patient). Any patient with acute neurologic disease should have a complete assessment, and the following questions should be asked: Does the patient breathe on his own? Does the patient get air in and oxygenate well? Are the mechanics of breathing intact? For an initial assessment, a good history is needed (Has the patient been given sedatives or vecuronium?) as well as a chest x-ray, arterial blood gas and pulse oximeter, and, when appropriate, pulmonary function tests (vital capacity, maximal inspiratory pressure, and maximal expiratory pressure). Why Avoid Endotracheal Intubation? Endotracheal intubation and mechanical ventilation provide adequate oxygenation and improve gas exchange in a vast majority of patients. This is particularly important in patients who are unable to maintain their airway, have recently aspirated, or have developed a pneumonitis or neurogenic pulmonary edema. Severe aspiration pneumonia Ventilator-associated pneumonia is not only common, but the mortality rate is approximately 30%. late well, 3 major causes should be considered: abnormal respiratory drive (eg, sedatives, seizures), abnormal respiratory conduit (eg, upper airway obstruction, diffuse pulmonary infiltrates), and abnormal respiratory mechanics (eg, diaphragmatic failure from phrenic nerve injury or abnormal neuromuscular junction traffic, particularly paralytic and neurogenic pulmonary edema almost always go hand in hand in patients who are comatose. However, the duration of intubation, mode of mechanical ventilation, and use of tracheostomy are very controversial issues in patients with neurologic disorders, and no reproducible studies are available. There are certain important facts derived from other VOL. 2 NO REVIEWS IN NEUROLOGICAL DISEASES 9

3 BiPAP for Acute Neurologic Disorders continued intensive care unit (ICU) populations. Ventilator-associated pneumonia is not only common, but the mortality rate is approximately 30%. It is estimated to occur in 20 cases per 1000 ventilator days, and in 68% of the isolates, Staphylococcus aureus, Streptococcus pneumonia, or Pseudomonas aeruginosa are present. The time on the mechanical ventilator clearly increases the risk of developing pneumonia, and early extubation is a desired goal. It is well known that aggressive management of pulmonary complications after any acute brain injury is probably the most important issue in these patients. In addition, there is a concern that the use of mechanical ventilators can cause lung injury. Thus any ventilator mode that prevents or reduces time on the ventilator or even prevents endotracheal intubation and consequently reduces length of stay and costs in the ICU seems very appropriate. BiPAP: Principles and Use Noninvasive ventilator devices provide almost similar modes as mechanical ventilators. For example, the Respironics BiPaP-ST (Murrysville, PA) can be set on spontaneous, spontaneous timed (assist control), and timed (control). Some of the control variables in BiPAP ventilation are inspiratory positive airway pressure, expiratory positive airway pressure, or continuous positive airway pressure, depending on the rate and inspiratory time percent. Inspiration can be time- or flow-triggered and flow- or time-cycled. The systems used provide continuous flow and square wave pressure pattern as oxygen is delivered to the system. A pressure-controlled ventilator delivers noninvasive positive pressure ventilation. The device is small, simple to operate, and has only a few settings. When the mask is fitted, patients will obtain BiPAP by initiating a breath, or the machine may cycle between inspiration and expiration with time intervals that can be set manually. The goal of noninvasive ventilation is to reduce respiratory distress and improve gas exchange, but this can only be effective if there is good patient and ventilator synchrony. During noninvasive ventilation, the patient becomes comfortable and the work of breathing is reduced and noticed by the patient. Ideally, noninvasive ventilation should avert intubation. In patients with more chronic neurologic disease, noninvasive ventilation could improve quality of life, avoid hospitalization, stabilize gas exchange, reduce fatigue and somnolence, and may, depending on the underlying disorder, prolong survival. 2,6,7 The mask should be fitting but not tight (Figure 1). Unfortunately, a mask that lies over the nose and mouth may be very uncomfortable Figure 1. BiPAP fitted to support poor ventilatory drive and tidal volumes associated in a patient with stupor due to acute hydrocephalus. BiPAP, bilevel positive airway pressure. to a dyspneic patient. The patient, if alert, should be allowed to adjust to this mask but would certainly need reassurance that breathing will become more pleasant after a desirable level is found. Noninvasive positive pressure ventilation is usually started with low inspiratory pressures, and then adjusted to patient comfort. Typically, 6 to 8 cm H 2 O is initiated and then gradually increased to 10 to 16 cm H 2 O. In the acute setting, high initial pressures, in the order of 20 cm H 2 O, may sometimes be preferred to quickly unload inspiratory muscles. A reduction in pressure settings would then follow. The patient is clinically monitored and comfort is assessed not only by reducing respiratory rate but also by oxygen saturation. Hill 8 suggests coaching the patient by saying, Let the machine breathe for you, while also pointing out to the patient that endotracheal intubation will be avoided. The patient is monitored using several variables, but comfort and respiratory distress remain the most important guidelines. A trial in which a patient is struggling, restless, and unable to have the machine take over will fail. Another indicator of success is the reduction of the respiratory rate and the resolution of tachycardia. Gas exchange can be monitored with continuous arterial oxygen saturation using a pulse oximeter at the bedside. Patient/ ventilator synchrony is more difficult to judge and requires practical experience. Typically, the patient triggers flow with each breath, and the ventilator cycles simply into an expiratory phase. However, in some patients, poor synchronization with the device during rapid shallow breathing or pooling secretions from oropharyngeal weakness may frustrate physicians with its use. Some important side effects can be avoided, such as air leaking and 10 VOL. 2 NO REVIEWS IN NEUROLOGICAL DISEASES

4 BiPAP for Acute Neurologic Disorders mask discomfort. Mouth and nasal dryness and congestion could become a problem when BiPAP is used for prolonged periods of time. Indications of Noninvasive Positive Pressure Ventilation The clinical indication of BiPAP is severe dyspnea, clinical presence of accessory muscle use, abdominal paradox, presence of tachypnea with Acute Myasthenia gravis exacerbation Stupor from overdose Postictal period after generalized tonic-clonic seizure BiPAP, bilevel positive airway pressure. mean duration was 5 days, but some patients could be weaned within 4 hours after specific therapy was initiated. In this preliminary study, we found that BiPAP could prevent intubation in 70% of the trials; however, BiPAP failed in all patients who had hypercapnia at presentation. This would indicate that a more severe degree of neuromuscular respiratory failure exists in these patients. In In a preliminary study in patients with myasthenia gravis, BiPAP could prevent intubation in 70% of the trials. respiratory rates of more than 30 breaths per minute, and a gas exchange with oxygen pressure fraction of inspired oxygen of less than 200. Neurologic indications for BiPAP are listed in Table 1. In patients with an acute neuromuscular disorder, we have shown that myasthenia gravis can be treated with noninvasive mechanical ventilation, which may prevent intubation. In 11 episodes, BiPAP was started in patients in whom the vital capacities were markedly reduced and consistently below 10 ml/kg body weight. The mean BiPAP pressures were 13 5 cm H 2 O, and inspiratory expiratory with a range of 10 to cm H 2 O. Oxygen supplementation was provided, typically with the range of 2-10 L/min. In these patients, the addition, we were successful in weaning patients from the ventilator in myasthenia gravis. 9,10 This is a useful observation particularly because a recent study suggests that noninvasive positive pressure ventilation for Table 1 Some Neurologic Indications for BiPAP Chronic Amyotrophic lateral sclerosis Muscular dystrophy Diaphragmatic failure from phrenic nerve lesion needed.) Patients with a decreased level of consciousness were excluded from this trial, and most patients had pneumonia, postoperative failure sepsis, or acute respiratory distress syndrome. Neuromuscular disease was tested in only a small proportion of patients. One case example of BiPAP use in Guillain-Barré syndrome (GBS) has been published, indicating that noninvasive ventilation can be used safely and effectively in certain conditions. 12 Our initial experience with the use of BiPAP in GBS was different and more dramatic. We recently noted 2 instances of emergency intubation in patients with GBS. 13 In these 2 consecutive patients, BiPAP seemed to provide good comfort with marked improvement in gas exchange. However, both suddenly deteriorated with marked hypoxemia. BiPAP should be considered in acute neuromuscular disease and possibly in patients who have a decreased level of consciousness and reduced respiratory drive. respiratory failure after extubation in chronic obstructive pulmonary disease was not successful and did not prevent the need for reintubation. 11 (Our patient population with acute neuromuscular disease and generally good prior lung function is clearly different, but prospective studies are Both patients had to be intubated and were found to have very low inspiratory and expiratory pressures and vital capacities much lower than at the time of the start of noninvasive mechanical ventilation. These initial attempts were totally unsuccessful, and, therefore, its use in GBS is concerning. We would warn against its indiscriminate use in GBS and call for prospective study. It is clear that the rapid beneficial effect of plasma exchange on respiratory function in myasthenia gravis is not seen in GBS with respiratory failure, and both intravenous immunoglobulin and plasma exchange generally do not prevent intubation in GBS. Acute hypoxemia can be due to excessive secretions obstructing the airway, or sometimes the use of opioids VOL. 2 NO REVIEWS IN NEUROLOGICAL DISEASES 11

5 BiPAP for Acute Neurologic Disorders continued to control pain; in other patients, it is due to ventilation/perfusion mismatch as a result of microatelectasis. BiPAP: Not for Everyone BiPAP should be considered in acute neuromuscular disease and possibly in patients who have a decreased level of consciousness and reduced respiratory drive. Such patients would have had a single seizure, and may briefly become hypoxemic from use of benzodiazepines; have been intoxicated with alcohol or use of other drugs that will metabolize within 24 hours; or are recovering from the impact of acute brain injury (eg, subarachnoid hemorrhage). It may have an important use in patients with catastrophic brain injury to provide palliation. Providing noninvasive ventilation in patients with marked respiratory distress and do-not-resuscitate or intubate orders may cause significant improvement in comfort and also family assurance. Noninvasive ventilation is associated with complications, but when used in short periods of time, they are not of major concern. These complications are nasal congestion, eye irritation, nasal bridge ulceration, aspiration, and gastric distension. In addition, pneumothorax has been described in patients with Duchenne s muscular dystrophy. 14 This may be due to a predilection of patients with Duchenne s muscular dystrophy. Noninvasive mechanical ventilation could become an important adjunct in acutely ill neurologic patients. Neurologists should be aware of this mode, but respiratory care therapists should also be available to monitor and coach the patient. References 1. Coplin WM, Pierson DJ, Cooley KD, et al. Implications of extubation delay in brain-injured patients meeting standard weaning criteria. Am J Respir Crit Care Med. 2000;161: Paus-Jenssen ES, Reid JK, Cockcroft DW, et al. The use of noninvasive ventilation in acute respiratory failure at a tertiary care center. Chest. 2004;126: Girault C, Briel A, Hellot MF, et al. Noninvasive mechanical ventilation in clinical practice: a 2-year experience in a medical intensive care unit. Crit Care Med. 2003;31: Hillberg RE, Johnson DC. Noninvasive ventilation. N Engl J Med. 1997;337: Loube DI, Gay PC, Strohl KP, et al. Indications for positive airway pressure treatment of adult obstructive sleep apnea patients: a consensus statement. Chest. 1999;115: Bach JR, Ishikawa Y, Kim H. Prevention of pulmonary morbidity for patients with Duchenne muscular dystrophy. Chest. 1997;112: Eagle M, Baudouin SV, Chandler C, et al. Survival in Duchenne muscular dystrophy: improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. Neuromuscul Disord. 2002;12: Hill NS. Noninvasive Positive Pressure Ventilation: Principles and Applications. Armonk, NY: Futura Publishing Company, Rabinstein A, Wijdicks EFM. BiPAP in acute respiratory failure due to myasthenic crisis may prevent intubation. Neurology. 2002;59: Rabinstein AA, Wijdicks EFM. Weaning from the ventilator using BiPAP in myasthenia gravis. Muscle Nerve. 2003;27: Esteban A, Frutos-Vivar F, Ferguson ND, et al. Noninvasive positive-pressure ventilation for respiratory failure after extubation. N Engl J Med. 2004;350: Pearse RM, Draper A, Grounds RM. Noninvasive ventilation to avoid tracheal intubation in a patient with Guillain-Barre syndrome. Br J Anaesth. 2003;91: Wijdicks EFM, Roy TK. BiPAP in early Guillain- Barré syndrome may fail. Submitted for publication. 14. Simonds AK, Muntoni F, Heather S, Fielding S. Impact of nasal ventilation on survival in hypercapnic Duchenne muscular dystrophy. Thorax. 1998;53: Main Points The use of a mechanical ventilator may increase the risk of developing pneumonia or may cause lung injury; therefore, noninvasive ventilation may be a good alternative. The goal of noninvasive ventilation is to reduce respiratory distress and improve gas exchange. This can only be effective if there is good patient and ventilator synchrony. In patients with more chronic neurologic disease, noninvasive ventilation could improve quality of life, avoid hospitalization, stabilize gas exchange, reduce fatigue and somnolence, and may prolong survival. Bilevel positive airway pressure (BiPAP) ventilators may be used in patients with respiratory failure and myasthenia gravis only when hypercapnia is absent. BiPAP in central nervous system disorders with an improving level of consciousness may be a preferred mode rather than endotracheal intubation. BiPAP may serve as a good weaning mode. 12 VOL. 2 NO REVIEWS IN NEUROLOGICAL DISEASES