Respiratory Dysfunction Associated with Acute Cerebrovascular Events
Dr. Pablo R. Castillo, Dr. Mauricio A. Reinoso.
Pulmonary and Critical Care Medicine Section, Baylor College of Medicine and Houston
Veterans Affairs Medical Center, Houston, TX, U.S.A.
Cerebrovascular events (CDVE) are a major cause of morbidity and mortality worldwide.
Most patients with CVE do not develop significant respiratory problems but when present,
they may be a marker of severe neurologic derangement. In one study (1), only 8% of
patients presenting with acute carotid territory stroke were electively intubated and
mechanically ventilated due to neurologic deterioration. "Good" outcome in terms
of survival and neurological status of patients with hemispheric strokes who required
mechanical ventilation have been reported in approximately 20% of cases (2). Respiratory
disturbances associates with strokes can result from discrete or difuse lesions to key
componets of the respiratory controller. The clinical spectrum of respiratory disordes in
stroke include abnormal breathing patterns, hypoxemic and hypercapnic respiratory failure,
aspiration pneumonia due to an inability to protect the airways and clear the airway by
coughing, and acute pulmonary emblism due to prolonged inmobilization. There is a veriety
of altered respiratory patterns associated with strokes. There is a variety of altered
respiratory patterns associated with strokes (3-5). These changes are not only important
in determining the location of the neuroanatomic lesion, but they havealso been regarded
as outcome predictors in CVE. This paper reviews the evaluation, management, and effect of
respiratory care interventions, management, and effect of respiratory care interventions
on a variety of respiratory system problems in patients with CVE.
Hemis´jeroc oscje,oc strples jave beem associated with a modest reduction of the
contralateral chest wall and diaphragm movements (6,7). On the other hand, bilateral
hemispheric dysfunction has been typically associated with Cheyne-Stokes respiration (8);
a periodic breathing pattern characterized by progresive hyperpnea followed by hypopnea
and apnea. Cheyne-Stokes respiration is frequently described in patients with hemispheric
CVE and significant cardiac and pulmonary diseases but it has also been noted in patients
with brainstem strokes.
The exact mechanism of this form ob breathing pattern is not completely understood. In
patients with bilateral hemispheric lessions, an increased response to carbon dioxide
(CO2), presumably due to loss of the normal cortical inhibition, has been described (5).
In patients with congestive heart failure and pulmonary disorders, circulatory slowing and
hyperventilation with or without hypoxemia are instability. Cheyne- Stokes respiration is
typically present in the tranition from wakefulness to sleep (drowsiness). Cheyne-Stokes
respiration is typically present in stroke patients with reduced level of consciousness of
in the transition from wakefulness to sleep (drowsiness) and the first two stages of
non-rapid eye movement sleep (NREM). Cheyne-Stokes respiration with hypocapnia has been
associated with high mortality (9,10). Conversely, intermitten Cheyene-Stokes respiration
does not necesarily indicate a poor prognosis and it usually disappears with the
improvement in neurological status.
Central neurogenic hyperventilation (CNH), is described in patients with midbrain and
upper pontie tegmentum lesions (11,12). To be considered neurogenic in origin, such
hyperventilation must be accompanied by a normal PaO2, as response to hypoxic drive can
minic thies breathing pattern. True CNH seems to occur rarely and it has been associated
with por clinical outcome. Most hyperventilation in stroke patients can be explain by
reflex stimulation of the respiratory center by hypoxia, activation of lung and chest wall
receptors, and metabolic factors 8i.e., metabolic acidosis with Kussmaulís breating).
Apneustic breathing (13)with its prolonged inspiratory pauses indicates a pontine
stroke. Damage to the low pons or high medulla can produce an abnormal breathing pattern
characterized by normal breaths separated by irregular pauses or cluster breathing.
Grossly irregular breathing occurs in patient with medullary lesion. This ataxic breathing
pattern is an ominous sign and usually precedes the patientis demise.
A rare breathing disorder in which the volitional breathing controller is preserverd
but automatic breathing is impaired (Ondineis curse) (14m15) can be seen in ischemic
lessions involving the lateral tegmentum points and medulla due to distal vertebral artey
occlusion (lateral medullary stroke). Clinically, patients can maintain fair to adequate
ventilation while awake but they develop severe hypoventilation and life-threatening
central apneas during sleep (16). Invasive mechanical ventilation is often needed
initially to maintain ventilation. Stable patients can be managed by noninvasive positive
pressure ventilation during sleep. The opposite pattern, that is, preservation of
atuomatic breathing with inability to voluntarily modify the breathing depth or frecuency
has been described in patients with extensive midpontine infarcts ("locked-in
syndrome"), lacunar infarcts in the upper pontine corticospinal tract, and presumably
in bilateral hemispheric lesions (17).
Finally, increased intracranial pressure leading to transtentorial herniation produces
a typical rostrocaudal deterioration in which normal breathing is replaced by
Cheyne-Stokes respiration, followed by neurogenic hyperventilation and subsequetntly,
atacic respiration that precedes apnea (18).
RESPIRATORY FAILURE IN STROKE
Patients with acute strokes may not be able to maintain adequate oxygenation and/or
ventilation in the absence of an intracardiac shunt (acute respiratory failure) (19). In
fact, respiratory arrest represent a primary cause of death in the first few days after a
stroke (20). Depending on the pathophysiologic mechanism, patients may present with
hypercapnic (pump failure) or hypoxemic respiratory failure. The hallmark of ventilatory
pump failure is hypercapnia with acute respiratory acidosis. In acute stroke patients,
this hypoventilation is most commonly due to a decreased total minute ventilation
secondary to a reduced central respiratory drive. The alveolar-arterial oxygen gradient
(P(A-a)O2) is useful in determining in the hypoxemia present in this form of respoiratory
failure is only due to hypoventilation (normal gradient) or if there is additional
parenchymal lung disease (elevated gradient). Hypercapnia may also result from concomitant
abnormalities in one or several or the determinants of the carbon dioxide level in
arterial blood [PaCO2]=k VCO2/VE(1-VD/VT)] (Table 1).
Tabla 1. Causes and pathogenesis of respiratory failure in acute
Increased CO2 production (VCO2) in patients with fever , sepsis,
agitation or excessive carbohydrate load, associated with a limited ventilatory capacity
(e.g., high VD/VT, low minute ventilation)
Increased dead space (VD/VT) in severe COPD,
cystic fibrosis and severe asthma.
Decreased total minute ventilation (VE) due to other conditions associate with
ventilatory pump dysfunction:
Decreased central respiratory drive: drugs (narcotics, sedatives, anesthetics), central
Abdominal resoiratory efferents
Spinal Cord: traums, poliomyrliyis, amyotrophic lateral sclerosis, tetanus, rabies.
Neuromuscualr: Myasthenia gravis, multiple sclerosis, botulism, Guillain-Barre Syndrome,
hypophosphatemia, hypomagnesemia, drugs (streptomycin, amikacin, neuromuscular blockers),
polyneuropathy of critical illness, bilateral phrenic nerve injury.
Abnormal chest walla and/or muscles: Severe kyphoscoliosis, ankylosing spondylitis,
massive obesity, muscular dystrophy, polymyositis, respiratory muscles fatigue, acid
Airway obstruction: epiglotitis, fixed and variable upper airway obstrction due to
tummors, post-extubation, tracheomalacia, bilateral vocal cord paralysis.
The hallmark or hypoxemic respoiratory failure is an inability to adequately oxygenate
the blood. The main pathophysiologic mechanism involved are V/Q mismatch (respnd to 100%
02) and intrapulmonary shunting (no significant improvement with 100% O2). The patients
typically exhibit a rapid shallow breathing pattern and a low or normalCO2. This form of
respiratory failure is commonly the result of a diffuse acute lung injury with high
permeability pulmonary edema (ARDS), severe pneumonic infiltrates, or cardiogenic
pulmonary edema. Rarely, patients with acute brain injury, can present with a form of
non-cardiogenic pulmonary edema termed neurogenic pulmonary edema (NPE) (21). The exact
mechanism of NPE is unknown but massive addrenergic overacitivity with pulmonary
vasoconstriction has been implicated (22,23).
The management of acute respiratory failure is initally supportive aimed at the
correction of hypoxemia or hypercapnia until specific actions are implemented to correct,
if possible, the factors that lead to the respiratory failure. The main goal in managing
hypercapnic respiratory failure. The main goal in managing hypercapnic respiratory failure
is to improve alveolar ventilation through the use of mechanical ventilation. This is most
comonly done through an endotracheal tube using a volume-controlled ventilator (usual
initial settings are: tidal volume (VT) 10 ml/kg, assist-control mode (A/C), rate 8-10
breath per minute, and fractional concentration of inspired oxygen (FiO2) 1.0). Arterial
blood gases (ABGs) must be checked 10-20 min later to detect inadverted and potentially
life-threatening acute alkalosis secondary to overcorrection of the hypercapnia and to
adjust the FiO2. Non-invasive mechanical ventilation could only be tried for cooperative,
hemodynamically stable stroke patients with intact upper airway function without excessive
secretions, regurgitation, or vomiting.
Parients with V/Q mismatch abnormalities without significant intrapulmonary shunt will
usually respond to non-invasive O2 suplementation (i.e., nasal cannula, Venturi mask). In
patients with cardiogenic pulmonary edema, the use of CPAP (5-10 cmH20) via a face mask in
addition tooxygen supplementation can be beneficial by reducing the transmural pressure of
the left ventricle, and therefore afterload but also by decreasing the preload. The
ventilatory management of patients with diffuse acute lung injury (i.e., ARDS) requires
machanical vantilation and should be viewed as a balance between adequate oxygenation on
one hand, and the risk for barotrauma and cardiovascular compromise on the other. And
detailed discussion of the ventilatory management of acute lung injury/ARDS is beyond the
scope of this review, but a special effort should be made to deliver enough oxygenation
and maintain adequate mean arterial pressure in stroke patients to avoid further increased
intracraneal pressure and ischemia.
Adequate arterial oxygen saturation is usually archieved by raising the FiO2 and
increasing the end-expiratory lung volume to recruit collapsed or flooded alveolI. This
can be achieved by adding extrinsic end expiratory positive pressure (PEEP) and/or
setting the ventilator to create dynamic hyperinflation (auto-PEEP). It is unclear if one
strategy is more effective that the other in ARDS but in stroke patients with increased
intrathoracic pressure with its impedance of cerebral and systemic venous return (25,26).
Since the effects of PEEP are not easily estimated, intracranial pressure monitoring is
recommended if levels > 10 cm H20 are used. Concomitant elevation of the upper part of
the body 30 (with the head in neutral position also help to optimize cerebral venous
return. To avoid potiential oxygen toxicity, it is recommended not to use 100% O2 for more
than a few hours and to maintain an FiO2 for more than a few hours and to maintain an FiO2
SYMBOL 163\f "Symbol" 0.6. To avoid barotrauma, it is recommended to maintain
plateau pressure (end-inflation hold pressure) less than 25 cm H20. The VT chosen shoud be
one tha preents lung overinflation (i.e., plateau pressure <35 cm H20) and, alveolar
derecruitment at the end of expiration (inadequate oxygenation). This usually means an
initial VT of 7-8 ml/Kg that may need to be reduced to 5 ml/kg.
Allowing CO2 retention and respiratory acidemia in an effort to limit barotrauma
(through reductions in rate and VT) is referred as "Permisseve Hypercapnia".
Although, widely used for the majority or ARDS patients, this strategy should be avoided
in CVA patients due to the deleterous effect of CO2 and accidemia on cerebral blood flow
AIRWAY MANAGEMENT IN ACUTE STROKE
Strokes resulting in depressed level of consciousness or blbar dysfunction may cause
abnormal swallowing mechanism and altered cough and gag reflexes that compromise the
airway patency. Early identification of such high-risk patients may avoid aspiration of
gastric or oropharyngeal contents. Simple routine measures to reduce the risk of
aspiration include the use of frequent suctioning of secretions, elevation of the head of
the bed, and avoidance of oral intake, at least in the acute period. Nearly 30% of
patients experience neurogenic dysphagia following stroke (28,29). After the acute period
resolves, swallowing study with modified barium protocol should be obtained if abnormal
voluntary cough and gag reflexes or dysphonia are present (30,31), or if supervised
feeding is associated with coughing, regurgitation or respiratory distress. According to
the degree of dysphagia, oral feeding can still be possible if eating is done only in the
upright position, optimal dietary texture is selected, and small size boluses (i.e., <=
1 teaspoon) are given under direct supervision. With severe swallowing problems or
episodes of recurrent aspiration, placement of a gastric (i.e., percutaneous endoscopic
gastrostomy PEG) or small bowel tubes is indicated.
Prophylactic endotracheal intubation should be considered if patients are not able to
protect their airwais. This decision should take into consideration the severity and
prognosis of the neurological damage, co-morbid conditions, and prior patientsi and
proxyis wishes regarding invasive support (1,2,32,33). Other common indications for
endotracheal intubation in stroke patients are tonic-clonic seizures or status
epilepticus, respiratory failure due to pneumonia and pulmonary edema and therapeutic
Physicians should be aware of the potential risks of perfoming endotracheal intubation
in neurological patients who are prone to develop or already have increased intracranial
pressure (34-36). In this patients, use of thiopental, nebulized or intravenous lidocaine,
and an alpha/beta blocker such as labetalol would prevent further raising in intracranial
pressure, coughing and sympathetic response to intubation (37).
INCREASE INTRACRANIAL PRESSURE AND MECHANICAL HYPERVENTILATION
Mechanical hyperventilation will acutely and transiently loweir intracranial pressure
(24). Cerebral blood flow is linearly related to PaCOO2 between 25 and 80 mm. Hg in normal
brain. Lowering the PaCO2 level to 25-30 mm Hg remains a useful emergency therapy for
acutely elevated intracranial pressure although, worsening of ischemia due to
vasoconstriction in infarct penumbral areas has been postulated as a potential risk (1).
The effects of mechanical hyperventilation are short-lived, probably up to 24 hours.
Return to normocarbia should be done gradually over 24-48 hours. In patients with
otherwise normal lungs, noninvasive continuous monitoring with an infrared capnograph in
line with the ventilator can avoid multiple ABGs determinations.
PATIENT-VENTILATOR INTERACTIONS IN STROKE
The output of the respiratory center, clinically expressed as respiratory muscles
contraction, can be altered by an external stimuous such as mechanical ventilation. Most
patients intubated and mechanically ventilated continue to make spontaneous respiratory
efforts. If the magnitude of the inspiratory efforts is sufficent, each effort triggers a
machine breath, i.e., the respiratory pump entrains the ventilator. On the other hand,
when teh amplitude os spontaneous inspiratory efforts is small relative to the sensitivity
of the machine triggering mechanism, increases in spontaneous respiratory frequency are
not expressed as changes in actual machine rate and minute ventilation (Figure 1). This is
often the case in stroke patients requiring mechanical ventilation who have depresed
sensorium with reduced respiratory drive. These "wasted respiratory efforts"
repesent a form of patient-ventilator asynchrony that is not only associated with
increased in oxygen consumption and patient discomfort but they can also produce an
irregular breathing pattern which could mislead the evaluthing pattern wich could mislead
the evaluating physician.
Airway pressure (PAW) and flow (V)
tracings in an intubated mechanically ventilated patient. Nota asynchronous spontaneous
respiratory efforts (arrows) during machine deflation. (Dots: mechanical inflation)
Interactions betwen the ventilator and the patients respiratory system can mimic
breathing patterns observed in non-intubated patients with different levels of cenral
newrological dysfunction. Figure 2 shows airway pressure and flow tracing in one of our
patients with brainstem ischemic stroke. At first glance, it may seem that he exhibits a
form of irregular periodic breathing. Careful evaluation of respiratory muscles
contraction by physical exam and analysis of airway and flow tracings during the presumed
"apneic" intervals demonstrate a regular tachypneic intrinsic pattern (Figure
2-arrows). Here, some inspiratory efforts are able to trigger machine breaths (dots). With
each subsequent mechanical inflation, the operating lung volume increases (manifested by a
progressive increase in peak pressures) to a point that the patientis effort cannot
overcome the lung elastic recoil pressure plus the machine triggering sensitivity and
there is a failure to trigger a mechanical breath. When this patient was allowed to breath
spontaneously with the assitence of continuous positive airway pressure (CPAP), the
underlying tachypneic pattern was unvovered (Figure 3). This tachpnea was persistent
despite normal oxygenation and lung mechanics, leading to a diagnosis of central
Patient-ventilator asynchrony in a
patient with brainstem stroke mimicking irregular periodic breathing. (Dots: mechanical
inflation; arrows: spontaneous respiratory efforts. See text for explanation)
Tachypneic breathing pattern in an
intubated patient with brainstem stroke while breathing spontaneously with CPAP
assistance. See text for explanation.
An intrinsic periodic breathing pattern can be precipitated by the way physicians set
the mechanical ventilator. This is particulary seen in patients with central neurologic
damage and some degree of altered level of consciousness or during sleep. Most
mechanically ventilated patients are maintained at settings resulting in nearly
"normal" PaCO2 which in turn maintain recruitment of the respiratory muscles.
Following the transition to NREM sleep stage 1, the normal response s an incrase in the
recruitment threshold of respiratory muscles for CO2. If the ventilator settings are
unchanged during sleep time, it may be possible that PaCO2 now falls below the operating
recruitment threshold for CO2 and apnea develop. If the patientis backup ventilator rate
is low enough as it usual in stable ventilator dependent patients, anough as it is usual
in stable ventilator dependt patients (e.g., SIMV 4 breaths per minute or using pressure
support ventilation (PSV mode)) this prolonged central apnea can cause cortical arousal
and therefore, sleep disruption. The easiest way to overcome this ventilator-triggered
periodic breathing is to increase the ventilatoris frequency at night when using SIMV or
A/C modes of ventilation and avoiding using PSV at night as the sole mode of ventilation.
VENOUS THROMBOEMBOLISM IN ACUTE STROKE
The prevalence of deep venous thrombosis in patients with ischemic strokes is aroudn
42%. This number has been reduced to 26% with the use of low-dose unfractionated heparin
and further down to 17% with prophylactic use of low-molecular-weight heparin (38). The
efficacy of pneumatic leg compression and elastic stockings in ischemic stroke lis not
well establish. But in neurosurgical patients pneumatic compression has shown to be
effective. In high risk is contrindicated, an inferior vena cava filter (e.g., Greenfield
filter) should be considered.
Data on the prevalence of pulmonary embolism (PE) after strokes is incomplete but it is
estimated that 13% of all stroke patients or 22% of strokes patients with DVT will develp
PE. In one series (39), half of the stroke patients who developed PE died from this
complication. Moreover, when DVT was diagnosed, this was invariably present in the
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