Respiratory Pattern Disturbances in Ischemic

Cerebral Vascular DiseaseBY M. C. LEE, M.D., A. C. KLASSEN, M.D., AND J. A. RESCH, M.D.

Abstract:RespiratoryPatternDisturbancesin IschemicCerebralVascularDisease

• Impedance pneumography was used to monitor respiratory rates and patterns in 49 patientswith acute ischemic cerebral vascular disease. Nine patients had clinical evidence of bilateralischemic cerebral disease. In one of these, normal respiratory pattern was present at all times;in five, there was intermittent Cheyne-Stokes respiration; in two, there were variants of Cheyne-Stokes pattern, and one patient eventually developed sustained tachypnea with probablehyperpnea. Twenty-eight patients had unilateral cerebral infarct. In five of these, normalrespiratory pattern was present at all times; in 15, there was intermittent Cheyne-Stokesrespiration; six had a variant of Cheyne-Stokes respiration; two had sustained tachypnea withprobable hyperpnea. In 12 patients with brainstem infarcts, Cheyne-Stokes respiration was in-termittently present in four, Cheyne-Stokes variant patterns were observed in two, andsustained tachypnea with probable hyperpnea developed in six. Abnormalities of respiratorypatterns occurred more frequently during sleep, in the presence of a depressed sensorium, and inpatients with severe neurological deficits. Respiratory alkalosis of variable degree was presentin all patients with Cheyne-Stokes respiration or sustained tachypnea with probable hyperpnea.Cheyne-Stokes respiration was not always related to bilateral cerebral lesions. IntermittentCheyne-Stokes respiration was not closely related to immediate prognosis. Sustainedtachypnea with respiratory alkalosis was associated with the highest mortality rate amongpatients with respiratory pattern abnormalities.

Additional Key Wordstachypnea

impedance pneumographyhyperventilation

Cheyne-Stokes respirationrespiratory alkalosis

Introduction• Cerebral vascular disease may be associated with avariety of alterations in respiratory patterns. Thesechanges include Cheyne-Stokes respiration, ataxic,cluster, and apneustic respirations and centralneurogenic hyperventilation.16 The mechanisms un-derlying these changes of respiratory pattern are notwell understood.

Impedance pneumography is a simple andatraumatic method for continuous monitoring ofrespiratory patterns. Changes in transthoracic im-pedance are proportional to changes in tissue/airvolume ratios, and provide estimates of rate and, lessreliably, of volume of respiration. The method hasbeen used to detect abnormal respiratory patternsassociated with lesions of the central nervoussystem.7"9

In the present study the respiratory rates andpatterns were investigated in patients with acutecerebral or brainstem infarcts. The frequency andtypes of respiratory pattern abnormalities were

From the Department of Neurology, University of MinnesotaHospitals, Minneapolis, Minnesota 55455.

Presented at the 45th Scientific Sessions, American HeartAssociation, Dallas, Texas, November 16-19, 1972.

This investigation was supported by NINDS Grant No. NS-03364.

related to the clinical localization of the lesions and,where possible, with the pathological findings. In somepatients respiratory pattern changes were related tochanges in arterial gas values. The prognosticsignificance of respiratory pattern changes also wasconsidered.

MethodsForty-nine patients with acute cerebral or brainstem infarctsadmitted to the University of Minnesota HospitalsNeurological Intensive Care Unit within 72 hours after theonset of symptoms were studied during the first two weeks ofhospitalization (table 1). On the basis of the clinical ex-amination, the patients were classified as having unilateralor bilateral infarcts in the cerebral hemispheres or infarcts inthe brainstem.

A Beckman "Apnea Monitor" Model RM-10 was usedto provide continuous oscilloscopic monitoring ofrespiratory patterns as well as to obtain permanent record-ings. Permanent records of respiratory patterns were ob-tained with a chart recorder for approximately ten minutesper hour during the duration of the patients' stay in the in-tensive care unit. Arterial blood gas samples for pH, Pco2and Po2 were obtained in 25 patients soon after admissionand occasionally thereafter. The paper records ofrespiratory patterns were reviewed by the authors withoutknowledge of the presumed clinical localization of thelesions in these patients. Records were reviewed for thepresence or absence of Cheyne-Stokes respiration, Cheyne-Stokes variant patterns and tachypnea. Other types of

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RESPIRATORY PATTERN DISTURBANCES IN I5CHEMIC CVD

TABLE 1

Age Information of Patients

Oltmmtm group Ne. (y« Rang* of ago (yoars)

Unilateral cerebral infarctBilateral cerebral infarctBrainstem infarct

28912

687366

41-9263-9448-83

respiratory pattern changes were not included because offrequent difficulties in distinguishing them from artifactualchanges using this method. Respiratory pattern abnor-malities were not quantitated, although in individualpatients, the trend of the changes was studied. Cheyne-Stokes respiration was used to designate periods ofhyperpnea regularly alternating with a period of apnea. Theterm Cheyne-Stokes variant was used to designaterespiratory patterns in which phasic variations in depth ofrespiration without definite apneic periods occurred.Patients who showed both Cheyne-Stokes respiration andCheyne-Stokes variant patterns were classified as havingCheyne-Stokes respiration. Rapid, regular respiratory ratesgreater than 30 per minute were designated as tachypnea.

ResultsFigure 1 shows examples of various respiratory pat-tern changes studied in these patients.

In the majority of patients who showed abnormalrespiratory patterns, the abnormality was usually in-termittent and tended to occur more frequently in thepresence of severe neurological deficit and especiallywhen there was marked depression of sensorium. Asthe neurological status of the patient improved,respiratory pattern abnormalities tended to becomeless frequent and sometimes disappeared.

No abnormal patterns were detected in five of 28patients with unilateral cerebral infarcts and in one ofnine patients with bilateral cerebral infarcts (fig. 2).This absence of any observed abnormalities inrespiratory patterns occurred in patients with mildneurological deficit and minimal or no depression ofsensorium. Typical Cheyne-Stokes respiration waspresent intermittently in 15 of 28 patients with uni-lateral cerebral infarcts, in five of nine patients withbilateral cerebral infarcts, and in four of 12 patientswith brainstem infarcts. Cheyne-Stokes variantpatterns were present intermittently in six of 28patients with unilateral cerebral infarcts, in two ofnine patients with bilateral cerebral infarcts, and intwo of 12 patients with brainstem infarcts. Sustainedtachypnea with probable hyperpnea was observed intwo of 28 patients with unilateral cerebral infarcts, inone of nine patients with bilateral cerebral infarcts,and in six of 12 patients with brainstem infarcts.

In 42 patients there was evidence of cardiac,pulmonary or other systemic disease. There were onlyseven patients (four with unilateral cerebral, two withbilateral cerebral and one with brainstem infarcts) inwhom there was no clinical evidence of other signifi-cant systemic disease.

Ten patients died during the observed period.These patients consisted of two with unilateralcerebral, four with bilateral cerebral and four withbrainstem infarcts. Autopsy was performed in two

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Examples of various respiratory patterns recorded using impedancepneumography (rale: 1 mm per second). I. Eupnea. 2. and 3.Cheyne-Stokes respiration. 4. Cheyne-Stokes variant. 5.Tachypnea.

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LEE, KLASSEN, RESCH

E 3 Normol Respiratory Patternd Cheyne - Stokes Respiration• Cheyne - Stokes Variant• Tochypneo

Respiratory patterns observed in 49 patients with acute ischemiccerebral vascular disease.

patients with bilateral cerebral infarcts and in threewith brainstem infarcts.

Of the seven patients without evidence of othersystemic disease, four patients with unilateral cerebralinfarcts had normal respiratory patterns, while twopatients with bilateral cerebral infarcts and one withbrainstem infarct had intermittent Cheyne-Stokesrespiration. None of these seven patients died duringthe observed period.

Of the 25 patients who had one or more arterialgas studies performed (fig. 3), patients with normalrespiratory patterns had arterial gas values within nor-mal range. Patients with Cheyne-Stokes variantpatterns had normal values or mild respiratoryalkalosis. Respiratory alkalosis was present to asimilar degree in both unilateral and bilateral infarctgroups but was more severe in patients with sustainedtachypnea with probable hyperpnea. Pac>2 was lessthan 66 mm Hg in four patients with unilateralcerebral infarcts, three patients with bilateral cerebral

infarcts and three patients with brainstem infarcts. Allof these patients with low Pao2 values had Cheyne-Stokes respiration and in four of them sustainedtachypnea with probable hyperpnea eventuallydeveloped.

In three patients with cerebral infarcts (two uni-lateral, one bilateral) the development of sustainedtachypnea was preceded by Cheyne-Stokes respirationand respiratory alkalosis. The clinical course in thesethree patients appeared to be compatible with thetranstentorial herniation syndrome and associated up-per brainstem dysfunction. However, it is of interestthat postmortem examination in one of these cases didnot reveal evidence of significant transtentorial hernia-tion syndrome and associated upper brainstem lesions.Furthermore, in two patients with extensive pontineinfarction involving both the basal and tegmental por-tions as confirmed at autopsy, tachypnea was notobserved at any time, whereas typical Cheyne-Stokesrespiration was noted in both. In a third autopsiedpatient with a similar extensive pontine infarct,Cheyne-Stokes respiration preceded the developmentof sustained tachypnea.

DiscussionIn agreement with others,1'4-10~12 this study dem-onstrates the frequent occurrence of respiratorypattern abnormalities and arterial gas changes inpatients with acute ischemic cerebral vascular disease.Whether or not these respiratory pattern abnor-malities are directly related to the neurological lesionin these patients is difficult to ascertain. Othersystemic factors such as old age and cardiopulmonaryor metabolic dysfunction also may contribute tochanges in respiratory patterns and in arterial gasvalues. Such causes of respiratory dysfunction may beexpected to be present in a large proportion of patientsin the "stroke" age group. However, our study showedthat Cheyne-Stokes respiration occurred in threepatients (two with bilateral cerebral infarcts, one with

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pH, PaCO2 and Pao2 of patients with ischemic cerebral vascular disease. Transversebar indicates mean of values for each group.

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RESPIRATORY PATTERN DISTURBANCES IN ISCHEMIC CVD

brainstem infarct) without associated cardiac or othersystemic disease. This confirms the observations byBrown and Plum5 that Cheyne-Stokes respiration mayoccur in the absence of cardiac or other circulatory ab-normalities, and that extracerebral abnormalities,although they may increase the severity of periodicbreathing, are not usually the primary cause ofCheyne-Stokes respiration.

Previous studies2-4~6 have suggested that specificrespiratory pattern changes may be correlated withthe anatomical site of the central nervous system le-sion. When due to cerebral lesions, Cheyne-Stokesrespiration in humans has usually been considered tobe indicative of bilateral cerebral dysfunction.4-5-10 Inour series, however, Cheyne-Stokes respiration alsowas frequently observed in patients with unilateralcerebral and brainstem infarcts. However, Cheyne-Stokes respiration in patients with unilateral cerebralinfarct occurred only in association with cardiac orpulmonary abnormalities. Thus, while the presence ofbilateral cerebral lesions may not be essential for thedevelopment of Cheyne-Stokes respiration, systemicfactors may contribute to the development of Cheyne-Stokes respiration. Moreover, it is possible that ad-ditional unrecognized lesions were present in the othercerebral hemisphere, or that unilateral cerebral infarc-tion resulted in transtentorial herniation with subse-quent bilateral midbrain compression. An alternativeexplanation would be that unilateral cerebral lesionsmay result in bilateral cerebral dysfunctionmanifesting as altered respiratory sensitivity to CO2and subsequent Cheyne-Stokes respiration. This maybe analogous to other bilateral changes in central ner-vous system function such as depression of sensorium,bilateral electroencephalographical abnormalities andbilaterally decreased cerebral blood flow which mayoccur in patients with unilateral cerebral infarct.13- u

In support of this is the observation that in somepatients in our series Cheyne-Stokes respirationbecame less frequent or disappeared as the level ofsensorium and neurological status improved.

Other studies2-4-6 have demonstrated thathyperventilation attributed to the presence of centralnervous system lesions, often referred to as "centralneurogenic hyperventilation," is usually associatedwith midline lesions in the area of midbrain and upperpontine tegmentum. To be considered "primary" or"central" in origin, such "hyperventilation" must beaccompanied by normal levels of Pao2 (greater than 80mm Hg) and by a volume of breathing which is in-creased beyond the necessity of body demands. Reflexhyperpnea due to hypoxic drive could easily be mis-taken for "central neurogenic hyperventilation." Forexample, in all four patients with sustained tachypneaand probable hyperpnea in whom arterial gas deter-minations were obtained, low Pao2 values werepresent. It thus seems likely that true "centralneurogenic hyperventilation" occurs very rarely, if

ever.15 Therefore, tachypnea alone, even when com-bined with respiratory alkalosis, is not a satisfactoryindicator of the presence of "central neurogenichyperventilation." In the absence of accuratemeasurements of volumetric alveolar ventilation, itcan be speculated that the presence of tachypnea inmany of our cases might have been due to reflexhyperpnea rather than due to "central neurogenichyperventilation."

Other investigators11-12 have suggested that thepresence of either Cheyne-Stokes respiration or "cen-tral neurogenic hyperventilation" in combination withrespiratory alkalosis is associated with a very highmortality rate. In our study, the mere presence of in-termittent Cheyne-Stokes respiration or Cheyne-Stokes variant patterns did not necessarily indicate apoor immediate prognosis. Transient periods ofCheyne-Stokes respiration or Cheyne-Stokes variantpatterns were frequently observed in patients withrelatively mild neurological deficits, especially duringsleep. In these patients, as mentioned earlier, the inter-mittent respiratory pattern abnormalities usually dis-appeared as the neurological status improved. Thepresence of severe sustained tachypnea and probablehyperpnea with respiratory alkalosis in our series in-dicated a grave prognosis. The development of suchtachypnea in patients with massive cerebral infarctionwas associated with a fatal outcome in all three cases.Three out of six patients with brainstem infarcts inwhom severe tachypnea with respiratory alkalosis waspresent died during the observed period.

All cases with respiratory pattern abnormalitiesexcept for Cheyne-Stokes variant showed varyingdegrees of respiratory alkalosis regardless of the siteor the extent of the infarct. The underlying mechanismfor the development of respiratory alkalosis is notknown. Peripheral chemoreceptors are much less sen-sitive to changes in Pao2 than in Paco2, and reflexhyperpnea secondary to hypoxic drive probably doesnot occur unless Pao2 becomes less than 40 to 45 mmHg.16 In our series, however, all of the ten patientswho had Pao2 values less than 66 mm Hg showedrespiratory alkalosis and respiratory pattern abnor-malities. It is possible, therefore, that in these patientsrespiratory alkalosis and respiratory pattern abnor-malities were related to hypoxemia and the subsequenthypoxic drive of respiration.

Impedance pneumography appears to be usefulfor detecting respiratory pattern abnormalities whichwould otherwise often not be detected in the usualclinical setting. The method permits constantmonitoring of respiratory patterns although it doesnot provide accurate information on volumetricpulmonary changes. However, in conjunction with in-termittent measurements of total pulmonary ventila-tion and arterial gas studies, this technique may proveto be helpful in further elucidating complexneurogenic influences on respiration. The prognostic

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and therapeutic significance of the respiratory patternchanges seen in patients with cerebral vascular orother central nervous system lesions requires furtherelucidation.

AcknowledgmentsTechnical assistance was provided by Mrs. Lois Heaney,Department of Neurology. Biostatistical assistance was provided byDr. Ruth Loewenson and Maria Yam, Department of Neurology.

References1. Plum F, Brown HW: The effect on respiration of central ner-

vous system disease. Ann NY Acad Sci 109:915-931, 19632. Plum F, Swanson AG: Central neurogenic hyperventilation in

man. Arch Neurol Psychiat 81:535-549, 19593. Plum F, Alvord EC: Apneustic breathing in man. Arch Neurol

10:101-112, 19644. Plum F, Posner JB: The pathological physiology of signs and

symptoms of coma. In Plum F, Posner JB (eds): Diagnosis ofStupor and Coma. Second edition. Philadelphia, FA DavisCo, Chap. 1, pp 1-59, 1972

5. Brown HW, Plum F: The neurologic basis of Cheyne-Stokesrespiration. Amer J Med 30:849-860, 1961

6. Plum F: Neurological integration of behavioral andmetabolic control of breathing. In Porter R (ed): Breathing:Hering-Breuer Centenary Symposium (Ciba Symposium).London, J and A Churchill, pp 159-181, 1970

7. North JB, Jennett S: Impedance pneumography for thedetection of abnormal breathing patterns associated withbrain damage. Lancet 2:212-213, 1972

8. Geddes LA, Hoff HE, Hickman DM, et al: The impedancepneumograph. Aerosp Med 33:28-33, 1962

9. Hamilton LH, Beard JD, Kory RC: Impedance measurement oftidal volume and ventilation. J Appl Physiol 20:565-568,1965

10. Heyman A, Birchfield Rl, Sieker HO: Effects of bilateralcerebral infarction on respiratory center sensitivity. Neu-rology 8:694-700, 1958

11. Rout MW, Lane DJ, Wollner L: Prognosis in acute cere-brovascular accidents in relation to respiratory pattern andblood gas tensions. Brit Med J 3:7-9, 1971

12. Raudam E, Zupping R, Kaasik AE: Disturbances of gasmetabolism in patients with occlusive cerebrovascular dis-ease. Prog Brain Res 30:113-119, 1968

13. Meyer JS, Kanda T, Fukuuchi Y, et ah Diaschisis resultingfrom acute unilateral cerebral infarction. Arch Neurol23:241-247, 1970

14. Skinh^j E: Bilateral depression CBF in unilateral cerebral dis-eases. Acta Neurol Scand 4 1 (Suppl 14): 161-163, 1965

15. Plum F: Hyperpnea, hyperventilation and brain dysfunction.Ann Int Med 76:328, 1972

16. Comroe JH: The response to oxygen and oxygen lack. InComroe JH (ed): Physiology of Respiration. Chicago, Year-book Medical Publishers Inc, Chap. 4, pp 39-58, 1970

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M. C. LEE, A. C. KLASSEN and J. A. RESCHRespiratory Pattern Disturbances in Ischemic Cerebral Vascular Disease

Print ISSN: 0039-2499. Online ISSN: 1524-4628 Copyright © 1974 American Heart Association, Inc. All rights reserved.

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