Plum and posner’s diagnosis of stupor and coma fourth Edition series editor sid Gilman, md, frcp
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Central reflex hyperpnea (neurogenic pulmonary edema) Basis pontis damage Pseudobulbar paralysis of voluntary control Lower pontine tegmentum damage or dysfunction Apneustic breathing Cluster breathing Short-cycle anoxic-hypercapnic periodic respiration Ataxic breathing (Biot) Medullary dysfunction Ataxic breathing Slow regular breathing Loss of autonomic breathing with preserved voluntary control Gasping
46 Plum and Posner’s Diagnosis of Stupor and Coma pany coma (Table 2–2, Figure 2–3). Chapter 5 discusses respiratory responses to metabolic disturbances. Because neurogenic and meta- bolic influences on breathing interact exten- sively, respiratory changes must be interpreted cautiously if there is evidence of pulmonary disease. The pattern of respiration can give impor- tant clues concerning the level of brain dam- age. Once assured that there is adequate ex- change of oxygen, the physician should watch the patient spontaneously breathe. Irregulari- ties of the respiratory pattern that provide clues to the level of brain damage are described in the paragraphs below. PATHOPHYSIOLOGY Breathing is a sensorimotor act that integrates nervous influences arising from nearly every level of the brain and upper spinal cord. In hu- mans, respiration subserves two major func- ACh Muscarinic Medulla Midbrain
Spinal Cord: NE Xn. IX and X Nerves Cervical
Thoracic Lumbar
Sacral Cortex
Infralimbic Cortex
Insular Cortex
Hypothalamus Rostral Ventrolateral Medulla Nucleus of the Solitary Tract Caudal
Ventrolateral Medulla
Amygdala Parabrachial Nucleus VP Thalamus Nucleus Ambiguus 1-receptor ␣1-receptor Pons Figure 2–3. A diagram summarizing the cardiovascular control pathways in the brain. Visceral afferent information (gray) arrives from nerves IX and X into the nucleus of the solitary tract. This information is then distributed to the parabrachial nucleus, which relays it to the forebrain, and to the ventrolateral medulla, where it controls cardiovascular reflexes. These include both vagal control of heart rate (red) and medullary control (purple) of the sympathetic vasomotor control area of the rostral ventrolateral medulla (orange), which regulates sympathetic outflow to both the heart and the blood vessels (dark green). Forebrain areas that influence the cardiovascular system (brown) include the insular cortex (a visceral sensory area), the infralimbic cortex (a visceral motor area), and the amygdala, which produces autonomic emotional responses. All of these act on the hypothalamic sympathetic activating neurons (light green) in the paraventricular and lateral hypothalamic areas to provide behavioral and emotional influence over the blood pressure and heart rate. ACh, acetylcholine; NE, norepinephrine; VP, ventroposterior. Examination of the Comatose Patient 47
tions: one of metabolism and the other be- havioral. Metabolically, respiratory control is directed principally at maintaining tissue oxy- genation and normal acid-base balance. It is regulated mainly by reflex neural mechanisms located in the posterior-dorsal region of the pons and in the medulla. Behavioral control of breathing allows it to be integrated with swallowing, and in humans, with verbal and emotional communication as well as other behaviors. Respiratory rhythm is an intrinsic property of the brainstem that is generated by a network of neurons that lie in the ventrolateral medulla, including the pre-Bo¨tzinger complex 29,30
(see Figure 2–3). This rhythm is regulated in the intact brain by a number of influences that enter via the vagus and glossopharyngeal nerves. ACh Medulla
Midbrain Spinal Cord: Muscarinic ACh
ACh T2-T12: Intercostal Motor Neurons C3-5: Phrenic Motor Nucleus Hypoglossal Motor Nucleus Nicotinic IX and X Nerves Cervical Thoracic
Lumbar Sacral
Cortex Prefrontal Cortex Hypothalamus Ventral Respiratory Group Parabrachial Nucleus 2 adrenergic NE T2-8 Pons Nucleus
Ambiguus Figure 2–4. A diagram summarizing the respiratory control pathways in the brain. Afferents from the lung (pulmonary stretch), upper airway (cough reflexes), and carotid body arrive via cranial nerves IX and X in the nucleus of the solitary tract (gray), also called the dorsal respiratory group. These control airway and respiratory reflexes, analogous to the cardiovas- cular system, by inputs to the ventrolateral medulla. These include outputs to the airways via the vagus nerve (red) and outputs from the ventral respiratory group (orange) to the spinal cord, controlling sympathetic airway responses (green) and respiratory motor (phrenic motor nucleus, blue) and accessory motor (hypoglossal and intercostal, blue) outputs. The ventral respiratory group is responsible for generating respiratory rhythm. However, it is assisted in this process by the parabrachial nucleus (or pontine respiratory group, purple), which receives ascending respiratory afferents and integrates them with other brainstem reflexes (e.g., swallowing). The prefrontal cortex (brown) provides behavioral regulation of breathing, producing a continual breathing rhythm even in the absence of metabolic need. This influences the hypothal- amus (light green), which may vary respiratory pattern in coordination with behavior or emotion. ACh, acetylcholine; NE, norepinephrine. 48 Plum and Posner’s Diagnosis of Stupor and Coma The carotid sinus branch of the glossopharyn- geal nerve brings afferents that carry informa- tion about blood oxygen and carbon dioxide content, whereas the vagus nerve conveys pul- monary stretch afferents. These terminate in the commissural, ventrolateral, intermediate, and interstitial components of the nucleus of the solitary tract. 31–33 Chemoreceptor affer- ents can increase respiratory rate and depth, whereas pulmonary stretch receptors tend to inhibit lung inflation (the Herring-Breuer re- flex). These influences are relayed to reticular areas in the ventrolateral medulla that regulate the onset of inspiration and expiration. 34 In
medulla may also serve as chemoreceptors and directly influence the nearby circuitry that gen- erates the respiratory rhythm. 35,36
The medullary circuitry that controls respira- tion is under the control of pontine cell groups that integrate breathing with ongoing orofacial stimuli and behaviors. 37 Neurons in the para- brachial nucleus primarily increase the rate and depth of respiration, presumably in rela- tion to emotional responses or in anticipation of metabolic demand during various behaviors. On the other hand, neurons located more ven- trally in the intertrigeminal zone, between the principal sensory and motor trigeminal nuclei, produce apneas, which are necessary during swallowing and in response to noxious chemi- cal irritation of the airway (e.g., smoke or water in the nasal passages). 38 Superimposed upon these metabolic de- mands and basic reflexes, the forebrain can com- mand a wide range of respiratory responses. Respiration can be altered by emotional re- sponse, and it increases in anticipation of met- abolic demand during voluntary exercise, even if the muscle that is to be contracted has been paralyzed (i.e., as a consequence of central command rather than metabolic reflex). The pathways that control vocalization in humans appear to originate in the frontal opercular cor- tex, which provides premotor and motor inte- gration of orofacial motor actions. However, there is also a prefrontal contribution to the maintenance of respiratory rhythm, even in the absence of metabolic demand (the basis for posthyperventilation apnea, described below). These considerations make the recognition of respiratory changes useful in the diagnosis of coma (Figure 2–5). POSTHYPERVENTILATION APNEA If the arterial carbon dioxide tension is low- ered by a brief period of hyperventilation, a healthy awake subject will nevertheless con- tinue to breathe with a normal rhythm, at least initially, 39 albeit at reduced volume, until the PCO 2 returns to its original level. By contrast, subjects with diffuse metabolic impairment of the forebrain, or bilateral structural damage to the frontal lobes, commonly demonstrate post- hyperventilation apnea. 40 Their respirations stop after deep breathing has lowered the car- bon dioxide content of the blood below its usual resting level. Rhythmic breathing returns when endogenous carbon dioxide production raises the arterial level back to normal. The demonstration of posthyperventilation apnea requires that the patient voluntarily take several deep breaths, so that it is useful in dif- ferential diagnosis of lethargic or confused pa- tients, but not in cases of stupor or coma. One instructs the subject to take five deep breaths. No other instructions are given. It is useful for the examiner to place a hand on the pa- tient’s chest, to make it easier later to detect when breathing has restarted, and to count the breaths. If the lungs function well, the ma- neuver usually lowers the arterial carbon di- oxide by 8 to 14 torr. At the end of the deep breathing, wakeful patients without brain dam- age show little or no apnea (less than 10 sec- onds). However, in patients with forebrain im- pairment, the period of apnea may last from 12 to 30 seconds. The neural substrate that pro- duces a continuous breathing pattern even in the absence of metabolic need is believed to include the same frontal pathways that regu- late behavioral alterations of breathing patterns, as the continuous breathing pattern disappears with sleep, bilateral frontal lobe damage, or dif- fuse metabolic impairment of the hemispheres. CHEYNE-STOKES RESPIRATION Cheyne-Stokes respiration 41 is a pattern of periodic breathing with phases of hyperpnea alternating regularly with apnea. The depth of respiration waxes from breath to breath in a smooth crescendo during onset of the hyper- pneic phase and then, once a peak is reached, wanes in an equally smooth decrescendo until a period of apnea, usually from 10 to 20 seconds, Examination of the Comatose Patient 49
is reached. The hyperpneic phase usually lasts longer than the apneic phase (Figure 2–5). This rhythmic alternation in Cheyne-Stokes respiration results from the interplay of normal brainstem respiratory reflexes. 42–45
When the medullary chemosensory circuits sense ade- quate oxygen and carbon dioxide tension, they reduce the rate and depth of respiration, caus- ing a gradual rise in arterial carbon dioxide ten- sion. There is normally a short delay of a few seconds, representing the transit time for fresh blood from the lungs to reach the left heart and then the chemoreceptors in the carotid artery and the brain. By the time the brain be- gins increasing the rate and depth of respira- tion, the alveolar carbon dioxide has reached even higher levels, and so there is a gradual ramping up of respiration as the brain sees a rising level of carbon dioxide, despite its ad- ditional efforts. By the time the brain begins to see a fall in carbon dioxide tension, the levels in the alveoli may be quite low. When blood containing this low level of carbon dioxide reaches the brain, respiration slows or may even cease, thus setting off another cycle. Hence, the periodic cycling is due to the delay (hys- B C
E A B C D E A 1 min
Figure 2–5. Different abnormal respiratory patterns are associated with pathologic lesions (shaded areas) at various levels of the brain. Tracings by chest-abdomen pneumography, inspiration reads up. (A) Cheyne-Stokes respiration is seen with metabolic encephalopathies and with lesions that impair forebrain or diencephalic function. (B) Central neurogenic hyperventilation is most commonly seen in metabolic encephalopathies, but may rarely be seen in cases of high brainstem tumors. (C) Apneusis, consisting of inspiratory pauses, may be seen in patients with bilateral pontine lesions. (D) Cluster breathing and ataxic breathing are seen with lesions at the pontomedullary junction. (E) Apnea occurs when lesions en- croach on the ventral respiratory group in the ventrolateral medulla bilaterally. (From Saper, C. Brain stem modulation of sensation, movement, and consciousness. Chapter 45 in: Kandel, ER, Schwartz, JH, Jessel, TM. Principles of Neural Sci- ence. 4th ed. McGraw-Hill, New York, 2000, pp. 871–909. By permission of McGraw-Hill.) 50 Plum and Posner’s Diagnosis of Stupor and Coma teresis) in the feedback loop between alveolar ventilation and brain chemoreceptor sensory responses. The Cheyne-Stokes respiratory cycle is not usually seen in normal individuals because the circulatory delay between a change in alveolar blood gases and carbon dioxide tension in the brain is only a few seconds. Even as circulatory delay rises with cardiovascular or pulmonary disease, during waking the descending path- ways that prevent posthyperventilation apnea also ensure the persistence of respiration even during periods of low metabolic need, thus damping the oscillations that produce Cheyne- Stokes respiration. However, during sleep or with bilateral forebrain impairment, due either to a diffuse metabolic process such as uremia, hepatic failure, or bilateral damage such as ce- rebral infarcts or a forebrain mass lesion with diencephalic displacement, periodic breathing may emerge. 43–45
In patients with heart fail- ure, the transit time for blood from the lungs to reach the carotid and cerebral chemorecep- tors can become so prolonged as to produce a Cheyne-Stokes pattern of respiration, even in the absence of forebrain impairment. Thus, Cheyne-Stokes respiration is mainly useful as a sign of intact brainstem respiratory reflexes in the patients with forebrain impairment, but cannot be interpreted in the presence of sig- nificant congestive heart failure. HYPERVENTILATION IN COMATOSE PATIENTS Sustained hyperventilation is often seen in pa- tients with impaired consciousness, but is usu- ally a result of either hepatic coma or sepsis, conditions in which circulating chemical stim- uli cause hyperpnea, or a metabolic acidosis, such as diabetic ketoacidosis (see Chapter 5). Other patients have meningitis caused either by infection or subarachnoid hemorrhage, which stimulates chemoreceptors in the brain- stem, 46
Some patients hyperventilate when intrin- sic brainstem injury or subarachnoid hemor- rhage or seizures cause neurogenic pulmonary edema.
47 The ventilatory response is driven by pulmonary mechanosensory and chemosensory receptors. The pulmonary congestion lowers both the arterial carbon dioxide and the oxygen tension. Stimulation of pulmonary stretch re- ceptors is apparently sufficient to cause reflex hyperpnea, as oxygen therapy sufficient to raise the arterial oxygen level does not always cor- rect the overbreathing. Another small group of patients has been identified who have hyperventilation associ- ated with brainstem gliomas or lymphomas. 48,49
These patients have spinal fluid that is acellu- lar, but generally acidotic compared to arterial pH. In others, the lumbar CSF may have a nor- mal pH, but it is believed that the tumor causes local lactic acidosis, which may trigger brain che- moreceptors to cause hyperventilation (Figure 2–5). It is theoretically possible for an irritative lesion in the region of the parabrachial nu- cleus or other respiratory centers to produce hyperpnea. 37 The diagnosis of such true ‘‘cen- tral neurogenic hyperventilation’’ requires that with the subject breathing room air, the blood gases show elevated arterial oxygen tension, decreased carbon dioxide tension, and an ele- vated pH. The cerebrospinal fluid likewise must show an elevated pH and be acellular. The re- spiratory changes must persist during sleep to eliminate psychogenic hyperventilation, and one must exclude the presence of stimulating drugs, such as salicylates, or disorders that stim- ulate respiration, such as hepatic failure or un- derlying systemic infection. Cases fulfilling all of these criteria have rarely been observed, 50,51
and none that we are aware of has come to post- mortem examination of the brain. APNEUSTIC BREATHING Apneusis is a respiratory pause at full inspira- tion. Fully developed apneustic breathing, with each cycle including an inspiratory pause, is rare in humans, but of considerable localizing value. Experiments in animals indicate that ap- neusis develops with injury to the pontine re- spiratory nuclei described above, and experi- ence with rare human cases would support this view
52,53 (see Figure 2–5). Clinically, end-inspiratory pauses of 2 to 3 seconds usually alternate with end-expiratory pauses, and both are most frequently encoun- tered in the setting of pontine infarction due to basilar artery occlusion. However, apneustic breathing may rarely be observed in metabolic encephalopathies, including hypoglycemia, an- oxia, or meningitis. It is sometimes observed Examination of the Comatose Patient 51
in cases of transtentorial herniation, as the brainstem dysfunction advances. At least one patient with apneusis due to a brainstem in- farct responded to buspirone, a serotonin 1A receptor agonist. 53 ATAXIC BREATHING Irregular, gasping respiration implies damage to the respiratory rhythm generator at the pre- Bo¨tzinger level of the upper medulla. 30 This cell group can be specifically eliminated in ex- perimental animals by the use of a toxin that binds to neurons that express NK-1 receptors. The resulting irregular, gasping breathing is eerily similar to humans with bilateral rostral medullary lesions, and it indicates that suffi- cient neurons survive in the medullary reticu- lar formation to drive primitive ventilatory ef- forts, despite the loss of the neurons that cause smooth to-and-fro respiration. 54 More complete bilateral lesions of the ventrolateral medullary reticular formation cause apnea, which is not compatible with life unless the patient is artifi- cially ventilated (Figure 2–5). A variety of intermediate types of breathing patterns are also seen with high medullary le- sions. Some patients may breathe in irregular clusters or ratchet-like breaths separated by pauses. In other cases, particularly during in- toxication with opiates or sedative drugs, the breathing may slow and decline in depth grad- ually until it fades into complete arrest. There is a tendency in modern hospitals to intubate and ventilate patients with structural coma to protect the airway and permit treat- ment of respiratory failure. If the patient fights intubation or ventilation, paralytic drugs are often administered. This compromises the abil- ity of the neurologist to assess brainstem re- flexes, and in some cases may delay diagnosis and compromise care. Thus, it is important, whenever possible, to delay intubation until after the brief coma examination described here has been completed. SLEEP APNEA AND ONDINE’S CURSE
Obstructive sleep apnea is a common disorder in which the cross-section of the upper air- way is anatomically narrow. 55,56
During sleep, the muscles that keep the upper airway open, including the genioglossus muscle that pulls the tongue forward, undergo a gradual loss of tone. This results in critical narrowing of the airway and the increased rate of movement of air tends to further reduce airway pressure, resulting in sudden closure. Liable to the dis- order are obese patients, because deposition of fat in neck tissue reduces airway diameter; men, because the increased ratio of the length of the airway to its diameter predisposes to collapse; and middle aged or older patients, because muscle tone is more reduced during sleep with age. However, cases may occur in thin young adults, or even in children. Sleep apnea typically occurs in cycles lasting a few minutes each when the patient falls asleep, airway tone fails and an obstructive apnea oc- curs, blood oxygen levels fall, carbon dioxide rises, and the patient is aroused sufficiently to Yüklə 9,02 Mb. Dostları ilə paylaş:
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