Abstract
We used a noninvasive monitor of arterial pressure to determine the utility of pulsus paradoxus (PP) as an objective severity measure in croup. We performed a prospective, blinded comparison of PP in children with croup versus healthy control subjects, analyzed the relationship between PP and Westley croup score (WCS), and observed the effect of racemic epinephrine (RE) on PP and WCS in a subgroup of patients with severe croup. The PP and WCS were measured at presentation and in severe patients after treatment with RE. Mean PP was 6.1 ± 1.8 (SD) mm Hg (n = 29) in control subjects compared with a mean of 17.8 ± 11.2 (SD) mm Hg (n = 28) in patients with croup (p < 0.00001). There was significant concordance between baseline WCS and PP (Spearman's rho: 0.68; p = 0.0001). The mean decrease in PP after RE was 7.5 ± 11.8 (SD) mm Hg (p = 0.05; n = 12). The magnitude of decrease in PP after RE has significant concordance with the concurrent decrease in WCS (Spearman's rho: 0.73; p < 0.007). PP is elevated in children with croup, and the magnitude of elevation correlates with severity as measured by the WCS. PP may have utility as a research tool to objectively measure the severity of upper airway obstruction in croup.
Pulsus paradoxus (PP) is an exaggeration of the normal inspiratory drop in systolic blood pressure which reflects the large inspiratory fall in pleural pressure associated with airway obstruction (1). This phenomena occurs in asthma and has been recommended as an objective indicator of severity in asthma. The phenomenon has been reproduced in volunteer subjects breathing through external flow resistors to simulate airway obstruction (2-7). The upper airway obstruction present in viral croup would be expected to be associated with high negative intrapleural pressure swings and, therefore, PP. The relationship between severity of upper airway obstruction in viral croup and PP has not been well delineated. A Medline review from 1967 to 1996 found no reports that specifically addressed this issue and revealed only a single reference to “paradoxical pulse” by palpation in severe croup (8).
Unlike in asthma, noninvasive objective measures of severity of upper airways obstruction have been little studied. Currently, most published trials of therapeutic interventions in croup have relied on one of several clinical scores as outcome measures. Croup scores are a relatively subjective measure of severity. Evidence of improvement in more objective physiologic measures may decrease inter-observer variability in outcome measures and allow small but clinically significant effects to be discriminated (9). A noninvasive, objective measure of severity in croup, which could be applied in a continuous or repeated fashion, would be desirable. Previously described objective measures of severity include arterial blood gas analysis (10), transcutaneous Pco 2 (8), pressure time index utilizing an esophageal catheter-manometer (11), changes in tracheal diameter measured by fluoroscopy (12), and thoraco-abdominal asynchrony by noncalibrated inductance plethysmograph (13, 14). Of these, only transcutaneous Pco 2 and thoraco-abdominal asynchrony are noninvasive and suitable as ongoing continuous measures. Noninvasive, continuous determination of PP is an additional candidate for such an objective measure. In prior studies, we and others have measured PP in adult volunteers (6, 15) and in children (16) and adults (15) with acute asthma exacerbations using a finger arterial pressure monitor combined with a measure of respiratory excursion. This technique may allow measurement of PP in children with upper airway obstruction due to croup. As in asthma, the degree of PP may correlate with severity in croup.
The goals of this study were to determine: (1) normal values for PP in well children; (2) if patients with croup syndrome have higher values for PP than control children without respiratory illness; (3) the relationship between degree of PP and clinical severity as defined by the Westley croup score (WCS); (4) the change in PP after treatment with racemic epinephrine; and (5) whether the change in PP after racemic epinephrine correlates with changes in WCS.
This study was approved by the Institutional Review Board of Rhode Island Hospital. Informed consent was obtained from parents of children presenting with a chief complaint consistent with croup defined as inspiratory strider, “barky” cough, dyspnea, or retractions. Patients were excluded if they had findings consistent with acute epiglottitis, foreign body aspiration, or lower airway disease.
The croup score devised by Westley and associates was assigned by one of the investigators while blind to PP. This score (Table 1) is based on five clinical signs: (1) level of consciousness; (2) cyanosis; (3) stridor; (4) air entry; and (5) retractions. Each of these categories was assigned a numerical value to represent gradations of severity. The maximum possible score is 17, with a minimum of zero (17).
| Level of consciousness | ||
| Normal (including sleep) | 0 | |
| Disoriented | 5 | |
| Cyanosis | ||
| None | 0 | |
| Cyanosis with agitation | 4 | |
| Cyanosis at rest | 5 | |
| Stridor | ||
| None | 0 | |
| When agitated | 1 | |
| At rest | 2 | |
| Air entry | ||
| Normal | 0 | |
| Decreased | 1 | |
| Markedly decreased | 2 | |
| Retractions | ||
| None | 0 | |
| Mild | 1 | |
| Moderate | 2 | |
| Severe | 3 |
All patients were evaluated by one of the investigators after breathing room air mist for at least 10 min. A croup score was assigned and PP measured as described below. A subset of patients received nebulized racemic epinephrine at the discretion of the investigator. These patients had a second evaluation 15 to 30 min after the nebulization was complete. The investigator assigning the croup score remained blind to PP.
A FINAPRES® (finger arterial pressure monitor; Ohmeda, Englewood, CO) and a respiratory strain gauge were interfaced via an analog-to-digital converter (Biopac Systems, Inc., Santa Barbara, CA) to a computer. The finger arterial pressure monitor provides a continuous arterial blood pressure waveform, which when compared with the output from the respiratory strain gauge allows changes in blood pressure over the respiratory cycle to be measured. Pulsus paradoxus was defined as the lowest inspiratory systolic blood pressure subtracted from the peak expiratory systolic blood pressure averaged over 10 breaths. This procedure has been previously described in detail (6, 16) (Figure 1).
Fig. 1. Representative tracings of blood pressure and respiratory excursion in a patient with croup. I. Finger arterial blood pressure in millimeters of mercury. The maximum systolic blood pressure during expiration and the minimum systolic blood pressure during inspiration are indicated. The difference between these two points is the pulsus paradoxus. II. Chest wall motion: upward, expiration; downward, inspiration.
[More] [Minimize]Mean and SD are reported to summarize the continuous PP measurements, and median and interquartile range for the ordered categorical WCS. Statistical significance was assessed at the 5% level. The comparison between PP in patients with croup with PP in well children used a two-sample t test assuming unequal variances. The concordance between PP and the WCS for patients with croup was assessed by the nonparametric Spearman rank correlation statistic. The change in PP (pre-minus post-treatment PP) in patients treated with racemic epinephrine was assessed using a paired t test. The nonparametric sign test was used to test the significance of the change in median WCS. Finally, the concordance between the decrease in PP and decrease in WCS for the subjects treated with racemic epinephrine was assessed using the nonparametric Spearman rank correlation statistic. The statistical analysis of these data was performed using the computer program STATA (Version 4; Stata Corp., College Station, TX).
Twenty-nine control children were enrolled, ranging in age from 2.5 to 14 yr. The mean PP in 28 children with croup was 17.8 ± 11.2 (SD) mm Hg, compared with a mean value of 6.1 ± 1.8 (SD) mm Hg in 29 control children (Figure 2). The PP levels in these groups were significantly different (p < 0.00001).
Fig. 2. Box plots illustrate PP in the control subjects versus PP in children with croup. The line in the middle of the box represents the median. The box extends from the twenty-fifth to the seventyfifth percentile. The vertical whiskers extending from the box show the range and skewness of the data, with extreme points shown individually.
[More] [Minimize]As shown in Figure 3, in patients with croup, there was a significant association between the values of PP and WCS (Spearman's rho: 0.68; p = 0.0001).
Fig. 3. Plot of PP versus Westley Croup Score. The y-axis depicts the Westley croup score assigned to individual croup patients. The y-axis depicts PP measured for each of the croup patients prior to treatment.
[More] [Minimize]The mean initial PP in the 12 patients with croup who received nebulized racemic epinephrine was 24.1 ± 12.9 (SD) mm Hg. The mean decrease in PP after racemic epinephrine treatment was 7.5 ± 11.8 (SD) mm Hg (p = 0.05). The median decrease in WCS after racemic epinephrine treatment was 1.5 (interquartile range: −1 to −5; p = 0.58). Further, there was a significant positive relationship between the change in PP and the change in croup score (Spearman's rho: 0.73; p = 0.007).
Children presenting to the Emergency Department with signs and symptoms of croup had significantly greater mean PP compared with a control group of children without signs or symptoms of respiratory illness. This increase in PP is significantly correlated with the WCS, a clinical score that reflects severity of upper airway obstruction. Patients treated with nebulized racemic epinephrine had a significant decrease in PP, though not in WCS. The response to treatment with racemic epinephrine varied between patients and, importantly, the degree of change in PP was significantly correlated with the corresponding change in WCS.
The mechanisms that result in the normal inspiratory decrease in systolic blood pressure and the exaggerated decline present in airways obstruction (pulsus paradoxus) have been studied in an animal model of upper airway obstruction (18), in adult volunteers breathing through an external resistive load (4, 5, 7, 14, 15), and in adults with asthma (15). The reduction in pleural pressure results in an increase in left ventricular afterload and thus a fall in stroke volume and in arterial pressure roughly proportional to the fall in pleural pressure (1). Other mechanisms may contribute to this phenomenon, including increased venous return to the right heart with resulting shift of the ventricular septum to the left limiting left ventricular end-diastolic volume (1) and direct transmission of pleural pressure changes to the intrathoracic vasculature (5). Studies that have measured esophageal pressure via an esophageal balloon demonstrate a relationship between the magnitude of the swings in pleural pressure and the inspiratory decline in systolic blood pressure (4, 5, 12, 18). PP increases linearly with swings in pleural pressure up to 15 to 20 cm H2O after which larger changes in pleural pressure result in smaller declines in blood pressure (4, 5).
In asthma, the magnitude of the observed PP is significantly correlated with reductions in indices of airflow limitation (FEV1, FVC, PEFR) during bronchial challenge and spontaneous asthma attacks (15, 16). Several recent studies have questioned the usefulness of PP as a severity indicator, citing poor correlations between PP and spirometric measures during asthma exacerbations (19, 20). In part, observed poor correlations may be due to difficulties in accurate determination of PP using a sphygmomanometer. Our experience, as well as that of other investigators, has shown that manual determination of PP is inaccurate and difficult, particularly in young children (4, 6). However, assuming PP can be measured accurately, other variables influence the relationship between the degree of airway obstruction and its physiologic consequences. The inspiratory decrease in pleural pressure (ΔPpl) for a given degree of obstruction will be greater at higher inspiratory flow rates. In addition, increasing lung volume will alter the compliance at higher lung volumes, resulting in greater swings in ΔPpl (5). The rate of increase of PP slows when inspiratory ΔPpl exceeds 15 to 20 mm Hg; thus, increasingly severe obstruction may be associated with smaller increases in PP once pleural pressure swings exceed these values (4, 5, 12). Hypoxia has also been shown to increase PP (7), and some investigators have noted that different breathing patterns may affect the observed PP (15). Furthermore, in the late stages of respiratory failure, when respiratory muscles fatigue as a result of severe obstruction, PP begins to decrease. Thus, a low PP does not preclude severe clinical disease.
Given these provisos, we believe PP to be most useful as a within-subject index of therapeutic response over time. Several recent studies have utilized PP in this fashion. A placebo-controlled trial of dexamethasone versus placebo in pediatric patients with post-extubation stridor demonstrated significant reductions in PP in the dexamethasone group (21). Similarly, two studies have shown significant reductions in PP in response to breathing heliox in acute severe asthma in adult (22) and pediatric (23) patients.
Further development of continuous noninvasive blood pressure monitors may allow PP to be measured as an outcome in clinical trials and as an index of pleural pressure fluctuations in clinical practice. The technology for noninvasive continuous arterial blood pressure monitoring in children and adults is not yet mature. Several indirect noninvasive measures of this phenomenon have been suggested. Several investigators have noted inspiratory fluctuation in the pulse volume wave recorded with a pulse oximeter in patients with natural or induced airway obstruction (6, 24). These fluctuations correlated well with fluctuations in esophageal pressure in a canine model of obstructive sleep apnea (25). Similarly, pulse transit time (time from the R wave on the electrocardiogram to the pulse wave arrival at the finger) is inversely proportional to blood pressure and has been shown to correlate with inspiratory effort in patients with obstructive sleep apnea as measured by swings in esophageal pressure (26). These alternative measures merit further study to determine their relationship with the degree of airway obstruction.
In summary, a noninvasive measure of PP is elevated in children with croup, correlates with clinical severity, and improves with treatment. Noninvasive measurement of PP may be a useful research tool to objectively assess changes in the severity of upper airway obstruction in croup.
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