December, 1972 T h e ]ournal o[ P E D I A T R I C S
1068
The respiratory status of children vith croup In a prospective investigation of 35 children with croup, an attempt was made to correlate arterial blood gas measurements with clinical and radiologic findings. In the 29 who were hypoxemic, the respiratory rate was the best indicator of the lowered arterial oxygen tension, which could last for several days. Hypercapnea, present in 19 patients, was not reflected by any of the clinical criteria. The degree of hypoxemia was greater than the degree of hypercapnea and is probably due to the development of alveolar-arterial oxygen differences secondary to abnormal distribution of ventilation/ perfusion ratios. Croup may, therefore, be associated with pulmonary disease as well as with upper airway obstruction; the resultant hypoxemia can be assessed accurately only by determination of arterial blood gases.
C.
J.
L. Newth, M.B., Ch.B., H. Levison, M.D.,* and A. C. Bryan, M.B., Ph.D.,
Toronto, Ontario, Canada
T H E N A T U R A L course of croup in childhood is often quite unpredictable. Most patients have a fairly benign course, but in some the condition can progress with startling rapidity to end in respiratory failure. Clinically, one tries to predict the onset of respiratory failure from: the severity of the dyspnea, the child's color, evidence of fatigue, increasing tachypnea and tachycardia, excessive restlessness, and poor air entry? Such indications are all rather vague and some are very subjective. A review of the literature led us to believe that no studies had attempted to correlate clinical parameters with arterial blood gas estimations, altl~ough OwenThomas, 2 in a study of eight patients with
severe croup, had concluded that venous carbon dioxide tension and p H were not guides to the severity of the upper airway obstruction and did not reflect the resulting hypoxia. We therefore made arterial blood
From the Departments of Paediatrlcs and Anaesthesia, University of Toronto, and The Research Institute, The Hospital [or Sick Children.
The 35 subjects (20 males and 15 females, between the ages of 6 months and 4 ~ years, studied on 41 occasions) were children with croup who had been brought to T h e Hospital for Sick Children, Toronto, where they were
*Reprint address: Room 4519, The Hospital tor ~ek Children, 555 University Ave. Toronto 2, Ontarlo~ Canada.
Vol. 81, No. 6, pp. 1068-1073
Abbreviations used P IO2: partial pressure of inspired oxygen Pao2: partial pressure of arterial oxygen Paco2: partial pressure of arterial carbon dioxide A-aO2: alveolar-arterial oxygen difference gas measurements in a prospective investigation of children with croup. M A T E R I A L S AND M E T H O D S
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Respiratory [unction in croup
1 06 9
Table I. Forty-one i n d i v i d u a l clinical, blood gas, a n d p H measurements on 35 patients with croup
Age (moo 21 42 19 24 33 28 18 15 9 15 30 17 21 21 21 13 10 18 35 16 13 20 8 54 15 15 28 28 18 7 14 14 22 40 40 15 18 46 17 17 28
Sex
Temperature (~ rectaO
Respiratory rate (~rain.)
Heart rate (~rain.)
Pao, (mm. Hg)
Paco8 (mm. Hg)
pH
M F M M M M M F F M M M M M M M M M M F M F F F F F F F M F M M F M M F M F F F F
39.0 38.2 37.9 38.9 37.5 37.2 37.6 38.0 36.5 37.5 37.0 37.3 37.0 38.2 38.5 38.5 38.2 40.0 39.7 37.8 37.0 37.8 37.5 36.0 40.2 37.6 38.8 36.0 38.8 37.9 39.5 39.5 38.0 37.2 37.2 39.0 37.9 37.1 39.6 39.6 36.0
24 2O 26 28 20 24 36 36 24 32 22 24 24 26 26 4O 36 40 3O 40 24 28 28 32 36 24 30 22 44 32 32 28 24 24 22 36 32 22 36 32 3O
96 132 108 140 108 110 132 160 t08 140 100 110 132 120 120 138 160 160 150 130 110 132 140 140 200 140 180 104 180 130 160 132 120 132 96 170 132 100 110 140 130
80 75 83 79 94 91 55 69 85 51 94 96 93 80 88 55 63 65 75 58 78 70 77 70 67 82 73 90 61 75 61 90 88 74 73 89 69 70 61 82 99
43 38 35 36 43 37 46 40 40 42 42 38 38 36 31 37 48 41 44 40 43 39 35 52 35 35 36 33 41 37 37 36 40 48 48 36 47 41 36 38 37
7.29 7.35 7.38 7.33 7.36 7.37 7.32 7.31 7.35 7.34 7.34 7.39 7.32 7.21 7.33 7.37 7.24 7.30 7.28 7.35 7.35 7.37 7.34 7.29 7.37 7.42 7.27 7.34 7.24 7.32 7.34 7.38 7.35 7.39 7.36 7.36 7.38 7.36 7.35 7.33 ).33
examined a n d assessed by one of us (C. N . ) . Croup is defined as a n u p p e r respiratory tract infection in which there is a sudden onset of inspiratory stridor, hoarseness, a n d typical cough following a 1 to 3 day history of a c o m m o n cold. T h e physical signs a n d symptoms are due to i n f l a m m a t o r y edema and spasm of the vocal cords or the subglottic area, a n d are said to cause varying degrees of laryngeal o b s t r u c t i o n ? F o r this investigation the criteria for a diagnosis of croup were: typical history, croup-like cough, inspiratory
stridor, a n d lack of evidence of lower airway disease or epiglottitis. Roentgenograms were m a d e of chest a n d neck in 30 patients a n d were assessed indep e n d e n t l y by one staff radiologist. I m m e d i a t e l y prior to arterial blood sampling assessments were m a d e of: the heart rate, the respiratory rate (average of 2 onem i n u t e recordings), the presence of cyanosis, air entry into the lungs, a n d degree of inspiratory stridor. T h e latter was difficult to measure a n d was done rather crudely by
10 7 0
Newth, Levis 9
and Bryan
110
PaO 2 (mm Hg) IO0
o
50-
100~176176 o
~o0 40-
o-o~
The Journal of Pediatrics December 1972
~
9
9
o
90-
90-
9
80-
~9149 176149
704
I9 9
~
8070-
9
60-
60 . . . . 30
~
50 PaCO2 (mm Hg)
9
50-
9
40-
PoO2 (mm Hg)
Fig. 1. Arterial oxygen and carbon dioxide tensions in croup. The shaded area indicates the mean and one standard deviation in normal subjects. noting those patients who had stridor at rest (usually sleeping) and those who had stridor only when stimulated. Blood samples were obtained by brachial or radial artery punctures and were taken in room air within six hours of admission; no complications arose and the procedures did not seem to add to the children's distress. Oxygen and carbon dioxide tension in the blood (Pao2, Paco2) were measured at 37 ~ C. with a Radiometer oxygen electrode, ~ type E 5046, and carbon dioxide electrode, "~ type E 5036, respectively. T h e p H was measured with the Astrup micro-pH-electrode, ~ model P H M - 2 7 G M . I n attempts to discover correlations, heart rate and respiratory rates were plotted against Pao2 and Paco2, and the corresponding correlation coefficients were calculated. Pao2 was also plotted against Paco2. The alveolar-arterial oxygen difference (A-aO2) was calculated using a modified alveolar air equation with an assumed R of 0.8: Alveolar Po~. z inspired Po2- arterial Pao2 R
To determine the duration ~)f hypoxemia arising from croup, another f o u r patients with croup had arterial blood gas estimations made daily for a period of 1 to 3 days, until the arterial oxygen tension returned to normal or until the child was discharged. ~Radlometer A / S , 72 E m d r u p v e j , Copenhagen N V , Denmark;
3020100
I
5
I
I
I
I
310
315
10 15 20 25 RESPIRATORY RATE
I
40 45
Fig. 2. Relation of arterial oxygen tension to respiratory rate (correlation coefficient ~ 0.66). The solid line represents the regression line. RESULTS T h e individual observations for age, sex, temperature, arterial blood gas tensions, and p H in the patients with croup are given in Table I. Twenty-nine patients were hypoxemic, having Pao2 less than the value represented by one standard deviation below the normal for the age group under study3; 19 patients w e r e hypercapneic, having Paco2 greater than the value represented by one standard deviation above the normal value for the age group 4, 5 (Fig. 1). O f all the clinical parameters assessed, the respiratory rate was by far the best indicator of the presence of hypoxemia, with correlation coefficient of 0.66 (Fig. 2). H e a r t rate was less reliable but still a statistically significant indicator, with a correlation coefficient of 0.41 (Fig. 3). N o correlation was found between the degree of hypercapnea and the respiratory or heart rates. Air entry and degree of stridor could not be objectively assessed in a reproducible manner, and hence were unreliable indicators of hypoxemia and hypercapnea. None of the patients h a d cyanosis. T h e solid line in the 02 - CO2 diagram
Volume 81 Number 6
Respiratory function in croup
PaCO 2 mmHg 80
Pa02 (turn HO)
100~
9080706050-
o.
70-
?
605040-
40-
30-
302010O- /,' ~ 100
10 7 1
2010-
0- -z/50 6'0 7'0 810 90 1(~0 110120 ~ ' 130 140 ' 140 ' 180 H E A R T RATE
i
220
Fig. 3. Relation of arterial oxygen tension to heart rate (correlation coefficient = 0.41). (Fig. 4) shows the relationship of Pao2 to Paco., in normal subjects when breathing air (P IO2 = 150 ram. H g ) . T h e slope of this line represents the respiratory exchange ratio, here assumed to be 0.8. The interrupted line represents the regression line for Pao2 versus Paao2 in the patients with croup (correlation coefficient = 0.32) ; the oxygen tension fell more than the carbon dioxide tension rose, and hence the pattern of events was different from that in simple alveolar hypoventilation secondary to upper airway obstruction. Fig. 5 shows that the relationship between the alveolar-arterial oxygen difference and the degree of hypoxemia is linear, with a correlation coefficient of 0.8. The chest and neck roentgenograms were read variously as showing minimal subglotic submucosal thickening, mild a i r trapping, minimal parenchymal hyperemia, or as being normal. No relationship between the radiologic findings and the degree of hypoxemia or hypercapnea could be established. Hypoxemia in children with croup lasted for several days in some instances (Table I I ) . One child had a normal Pao2 24 hours after her admission. Another patient's Pao2 returned to normal within 48 hours. Although the other two improved, t h e y were still hypoxemic after three days, when they were discharged with no clinical signs or symptoms of upper airway disease.
PaO 2
mmHg
Fig. 4. O2-CO~ diagram showing relationship of arterial oxygen tension to arterial carbon dioxide tension. The slope of the solid line depends on the respiratory exchange ratio, here assumed to be 0.8. The interrupted llne is the regression llne for values recorded in croup (correlation coefficient = 0.32). DISCUSSION
These results show that children with croup frequently have gas exchange failure, which does not correlate particularly well with the usual clinical criteria. Of the clinical parameters measured, the respiratory rate correlated best with the lowered arterial oxygen tension; but it is unlikely that chemical drive was responsible for the tachypnea observed in our patients. 6 A study in adults has indicated that the clinical appraisal of the level of alveolar ventilation is grossly inaccurate, and estimates of ventilatory volume are not reproducible. Neither duration of training nor clinieal experience had any influence on this fact. 7 The presence of cyanosis indicates that a child is already hypoxemlc, but absence of cyanosis does not preclude the possibility that moderate hypoxemia exists. For these reasons, we believe that arterial blood gases should be measured more frequently in this disease. The etiology of the gas exchange failure is of considerable interest. With upper airway obstruction one might think that the failure was due simply to alveolar hypoventilation and that the gas tensions should fall around the line representing respiratory quotient of
1 0 7 2 Newth, Levis 9
and Bryan
The Journal o/ Pediatrics December 1972
Table II. Serial determinations of Pao2 in four patients with croup
A-o 9 2 (mm Hg) 5O
Case No.
4540-
1
2 3 4
3530-
9 Discharged
259149
2015-
e9 e9
9
I
I
1050
//
F
I
I
J
I
4O 50 60 70 80 90 100 PaO 2 (ram Hg) Fig. 5. Relationship of alveolar-arterial oxygen differences to the arterial oxygen tensions in croup (correlation coefficient • 0.88). 0.8. However, the gas tensions fell considerably below this line (Fig. 4), and explanation of these values in terms of simple alveolar hypoventilation would require a fall in the respiratory exchange quotient to about 0.4, which seems a highly unlikely event. A more probable explanation is that an alveolar-arterial oxygen difference may have developed; the data in Fig. 5 confirm this hypothesis and suggest that the hypoxemia was due primarily to failure of gas exchange within the lung. A number of factors can contribute to an alveolar-arterial oxygen difference, including right-to-left shunting, imbalance between ventilation and perfusion, or a diffusion defect. However the most likely cause for such large differences as we observed is an abnormal distribution of ventilation/perfusion ratios. T h e nature of the actual disturbance of pulmonary function, is still uncertain. It is possible that infection of the upper airway extends into the lower airways, leading to a nonuniform distribution of airway resistance and hence to a maldistribution of ventilation, such as Pickens a n d associates s have recently
Paoz (ram. Hg) Day 1 [ Day 2 J Day 3 I Day 4 61 82 -55 72 84 70 68 65 * 67 74 73 * (asymtomatic).
shown to occur after minor upper respiratory tract infections in adults. Further evidence that croup in children involves the lower airways (although its primary clinical manifestation is upper airway obstruction) is furnished by Szpunar and associates, 9 who undertook gross and microscopic studies of the airways of 13 children who had died in the acute phase of croup subsequent to tracheostomy. These investigators found definite epithelial, mucosal, and submucosal inflammatory changes in the trachea, bronchi, and bronchioles in all cases; in some patients hyaline membranes covered the greater part of the alveolar surfaces, and three patients had dispersed atelectatic foci, mostly in one lung. A second explanation for the pulmonary dysfunction is that prolonged breathing through a high resistance produces pulmonary edema. T h e mechanics are not really clear, but the edema has been attributed to negative alveolar pressures which may "aspirate" intravascular fluid. Pulmonary edema has been shown to produce airway closure, which will also alter ventilation/distribution. The authors wish to thank the physicians of the Hospital for Sick Children, Toronto, for permission to study their patients, and Dr. B. Reilly, Staff Radiologist, for his assessment of the roentgenograrns. REFERENCES
1. Kendig, E. L." Disorders of the respiratory tract in children, Philadelphla, 1967, W. B. Sounders Company, pp. 261-266. 2. 9 J. B.: The management of acute upper airway obstruction in childhood, Proc. R. Soe. Med. 59: 1296, 1966. 3. Levis9 H., and Newth, C. J. L.: Unpublished data, 1971. 4. Winters, R. W., Engel, K., and Dell, R. B.:
Volume 81 Number 6
Acld-base physiology in medicine, ed. 2, London, Ontario, 1969, A. Talbot Co., p. 289. 5. Levison, H., Featherby, E. A., and Weng, T.-R.: Arterial blood gases, alveolar-arterial oxygen difference and physiologic dead space in children and young adults, Am. Rev. Resp. Dis. 10P 972, 1970. 6. Dripps, R. D., and Comroe, J. H., Jr.: The effect of the inhalation of high and low oxygen concentrations on respiration, pulse rate, ballistocardiogram and arterial oxygen saturation (oximeter) of normal individuals, Am. J. Physiol. 149: 277, 1947.
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7. Mithoeffer, J. C., Bassnian, O. G., Thibeault, D. W., and Mead, G. D.: The clinical estimation of alveolar ventilation, Am. Rev. Resp. Dis. 98: 869, 1968. 8. Pickens, J., Niewoehner, D., and Chester, E.: Frequency dependent compliance in viral upper respiratory infection, Clin. Res. 19: 518, 1971. 9. Szpunar, J'., Glowackl, J., Laskowski, A., and Miszek, A.: Fibrinous laryngotracheobronchitis in children, Arch. Otolaryngol. 93: 173, 1971.