Respiratory Medicine

Use of the pleth variability index in children with obstructive respiratory disease

a b s t r a c t

Introduction: The phenomenon of pulsus paradoxus (PP) develops at varying rates in relation to the severity of the disease in obstructive respiratory tract disease. The pleth variability index (PVI) is the measurement value of perfusion index changes that occur with ventilation, which are determined during at least one respiratory cycle. Therefore, Noninvasive measurement of PVI can help in the measurement of PP. The current study aims to determine the role of PVI measurements before and after bronchodilator therapy during admission to the hos- pital in children with obstructive respiratory tract disease.

Methods: Age, gender, Pulmonary Index Score (PIS), and PVI data of patients aged 2-18 years who applied to the pediatric emergency department with signs of obstructive respiratory tract disease were recorded in triage. The PVI and PIS scores of the patients, who were divided into three groups according to their clinical severity scores, were recorded before and after bronchodilator treatment, and they were compared to the PVI values according to the disposition results.

Results: A total of 133 patients were included in this prospective, single-center study. The PVI values before and after treatment were significantly higher in patients with severe disease compared to the mild and moderate groups (p < 0.001). Post-treatment PVI values were significantly lower than pre-treatment values in all clinical severity groups (p < 0.001). While a total of 95 (71.43%) patients were discharged from the emergency depart- ment, 31 (23.31%) patients were admitted to the relevant department, and seven (5.26%) patients were admitted to the pediatric intensive care unit. The PVI values before and after treatment were significantly higher in the hos- pitalized group compared to the group discharged from the emergency department (p < 0.001). The areas under the ROCs were 0.940, 0.865, and 0.843 for the PVI measurements in patients with severe disease, moderate dis- ease, and hospitalization (p < 0.001).

Conclusions: Automated PVI measurement can be used as a noninvasive, rapid, and objective tool in the emer- gency department triage of patients admitted to the pediatric emergency department with signs of asthma attack or reactive respiratory tract disease.

(C) 2022

  1. Introduction

Although studies have shown that there is a decrease in the rate of hospitalization due to asthma, the number of emergency visits for asthma attacks in children under 18 years old has increased to 104.7 per 10,000 people [1-3]. acute asthma attacks in childhood can range in severity from mild to life-threatening and are one of the common causes of admission to emergency department [4,5]. In emergency de- partment triage, attack severity classification is needed to manage acute attack exacerbation and to determine initial treatment of the

* Corresponding author.

E-mail address: [email protected] (G. Demir).

patients. There are disease scoring systems that evaluate the severity of asthma attacks in children and are included in asthma attack manage- ment protocols in clinical practice [6-8]. However, none of these has been proven to be reliable. Recent studies have shown that asthma at- tack severity is associated with the degree of pulsus paradoxus (PP) [9,10]. A decrease of 10 mmHg or more in systolic blood pressure during inspiration is defined as PP. In obstructive respiratory tract diseases, such as asthma, blood flow returning to the left heart decreases due to hyperinflation in the lungs, and systolic blood pressure decreases during inspiration. Increased PP is associated with increasED asthma respira- tory scores and the severity of the asthma clinic. It has been shown that a pulsus paradoxus greater than 15 mmHg is correlated with Severe asthma attacks [11].

https://doi.org/10.1016/j.ajem.2022.03.019

0735-6757/(C) 2022

The Pleth Variability Index (PVI) is determined noninvasively and is the calculation of perfusion index changes that occur with ventilation during at least one respiratory cycle. Recent studies have shown that

Table 2

Criteria for discharge from the emergency department and hospitalization of patients admitted to the emergency department with an attack due to obstructive respiratory tract disease.

PVI is a noninvasive and accurate method for measuring PP [10,12].

These studies suggest that the higher the PVI value, the higher the PP. In this case, PVI measurement can be a guide in determining the severity of the disease in an asthma or reactive respiratory disease attack. In fact, PVI has mostly been investigated in the evaluation of fluid response in mechanically ventilated children [13-16]. In the literature, very few

Discharge – No oxygen requirement

  • A need for inhaled bronchodilator therapy not longer than four hours

Hospitalization in ward – FiO2 requirement <0.5

  • A need for inhaled bronchodilator therapy every 2-4 h

studies have been conducted on children with respiratory diseases, es- pecially those with spontaneous breathing and obstructive respiratory disease findings [10,12].

In this study, the role of PVI values, which are automatically mea-

sured in triage and after acute attack treatment, in determining the se- verity of attacks of patients who applied to the pediatric emergency department due to an asthma attack or reactive respiratory tract disease

Hospitalization in pediatric intensive care unit

  • FiO2 requirement >=0.5
  • A need for positive pressure ventilation (invasive or noninvasive)
  • <=2 h need for inhaled bronchodilator therapy
  • A need for bronchodilator infusion

attack was investigated. Their relationship with discharge from the pediatric emergency department was also determined.

  1. Methods

Patients between the ages of 2 and 18 who applied to the pediatric emergency department of our hospital between May 2020 and July 2021 and were diagnosed with an asthma attack or reactive respiratory tract disease attack after a doctor’s examination were included in the study. Patients with fever, dehydration, laryngitis, tracheitis, bronchiol- itis, non-agitating tachycardia, congenital respiratory disease, chronic lung disease, cardiopulmonary disease, or immunodeficiency were excluded from the study.

PVI levels were obtained automatically by means of a probe attached to the index finger of the hand using the Masimo Radical-7 monitor ap- proved by the US Food and Drug Administration. The Pulmonary Index Score (PIS), which is used in our routine clinical practice, was used to determine the severity of the attacks. Those with a PIS score of <7 were evaluated as mild, between 7 and 11 as moderate, and >=12 as hav- ing a severe attack [17] (Table 1). Demographic data, vital signs, oxygen saturation, and PIS and PVI levels of the patients were recorded simulta- neously in triage. Nebulized albuterol was given in the treatment of mild attacks, and those who needed repeated doses received them re- peatedly at 30-min intervals. Oral glucocorticoids (prednisolone/pred- nisone) were given to patients who did not improve after one dose of albuterol inhalation therapy, who worsened, or who had a history of se- vere or recurrent exacerbations. Three doses of ipratropium bromide and one dose of systemic glucocorticoid (prednisolone/prednisone) 20 min apart were given together with nebulized albuterol in the treat- ment of moderately severe attacks. Continuous nebulized albuterol to- gether with ipratropium bromide therapy, parenteral glucocorticoid (prednisolone/prednisone), and parenteral magnesium sulfate were given to those who did not respond adequately to the treatment for se- vere attacks. Two hours after the first evaluation of the patients, the PVI, oxygen saturation, and PIS values were reevaluated after the attack treatment. The decision for hospitalization (ward or pediatric intensive care unit) or discharge from the emergency department after acute at- tack treatment was made in accordance with the criteria shown in Table 2, regardless of the PVI values [10]. Patients were divided into two groups according to the disposition from the pediatric emergency

department: the group discharged from the emergency department and the Admitted group. Since the number of patients hospitalized in the pediatric intensive care unit for statistical analysis was low, the pa- tients in this group were included in the ward admitted group. The re- lationships between acute attack severity and PVI value in triage, and between PVI values after acute attack treatment and discharge from the emergency department and hospitalization, were investigated.

    1. Statistical analysis

All variables were analyzed using the SPSS v. 21 (SPSS Inc., Chicago, IL, USA) program. The Kolmogorov-Smirnov test was used to check for normality. The data were given as medians (inter-quartile range) for continuous variables due to the data was not normally distributed and frequencies (percent) for categorical variables. Analyses before and after treatment were performed using the Wilcoxon Signed Rank Test for continuous variables and the marginal homogeneity test for categor- ical variables. Intergroup comparisons of continuous variables were made with the Mann-Whitney U test or the Kruskal-Wallis test, de- pending on the number of groups. Intergroup comparisons of categori- cal variables were made using the chi-square test. Pairwise comparisons were made with the Bonferroni correction method. P values less than

0.05 were considered statistically significant. Receiver operating charac- teristic (ROC) curve analysis were performed to evaluate prediction per- formance of the PVI. Optimal cut-off points were determined by using Youden’s index and measurements of performance were calculated for optimal cut-off points.

  1. Results

A total of 133 patients, 68 (51.1%) male and 65 (48.9%) female, were included in the study. The median age was 5 years (inter-quartile range [IQR], 3-9 years). According to PIS, the severity of attacks was mild in 50 (37.6%) patients, moderate in 50 (37.6%) patients, and severe in 33 (24.8%) patients. The severity of attacks was reevaluated two hours after the treatment, and 85 (63.9%) of the patients had mild, 36 (27.1%) had moderate, and 12 (9.0%) had severe attacks. The median PVI values of the patients were 30 (IQR, 23-42) before the treatment and 24 (IQR, 18-32) after the treatment. After treatment, 95 (71.4%) of the patients were discharged home from the emergency department,

Table 1

Pulmonary Index Score.

Score

<6 years old respiratory rate

>=6 years old respiratory rate

Wheezing

Inspiratory/expiratory ratio

Accessory muscle use

Oxygen saturation

0

<=30

<=20

None

2:1

None

99-100

1

31-45

21-35

End expiration

1:1

+

96-98

2

46-60

36-50

Entire expiration

1:2

++

93-95

3

>60

>50

Inspiration and expiration

1:3

+++

<93

Mild exacerbation: <7, moderate exacerbation: 7 to 11, severe exacerbation: >=12.

Table 3

Summary of patients’ characteristics.

Age 5 (3-9)

Table 5

Summary of patients’ characteristics with regard to outcome.

Outcome p (between

Sex

Male 68 (51.13%)

Discharged (n = 95)

Hospitalized (n = 38)

groups)

Female 65 (48.87%)

Oxygen saturation

Before treatment 94 (92-96)

After treatment 96 (94-97)

PVI

Age 6 (3-9) 4 (2-10) 0.100

Sex

Male 47 (49.47%) 21 (55.26%) 0.681

Female 48 (50.53%) 17 (44.74%)

Moderate 36 (27.07%)

Before treatment

30 (23-42)

Oxygen saturation

After treatment

Disease severity, before treatment Mild

24 (18-32)

50 (37.59%)

Before treatment After treatment

p (before vs after)

95 (94-96)

96 (95-98)

<0.001

91 (88-92)

93 (92-95)

<0.001

<0.001

<0.001

Moderate

50 (37.59%)

PVI

Severe

Disease severity, after treatment Mild

33 (24.81%)

85 (63.91%)

Before treatment After treatment

p (before vs after)

26 (22-34)

21 (18-26)

<0.001

46.5 (39-49)

38 (29-44)

<0.001

<0.001

<0.001

Severe

12 (9.02%)

Outcome

Discharged

95 (71.43%)

Admitted to the ward

31 (23.31%)

Admitted to the pediatric intensive care unit

7 (5.26%)

PVI: Pleth variability index.

31 (23.31%) were admitted to the ward, and seven (5.26%) were admit- ted to the pediatric intensive care unit (Table 3).

Age was significantly higher in the group of patients with mild at- tacks (p = 0.005). There was no significant difference between the pre-treatment groups in terms of disease severity according to gender (p = 0.197). The PVI values before and after the treatment were found to be higher in the patient group with severe attacks compared to the groups with mild and moderate attacks, and higher in the group with moderate attacks compared to the group with mild attacks (p < 0.001). Post-treatment PVI values were found to be lower in all at- tack groups compared to the pre-treatment period (p < 0.001) (Table 4).

When the patients were examined in two groups discharged from the emergency department and hospitalized the oxygen saturation values before and after treatment were significantly higher in the discharged group than in the hospitalized group. The PVI values before and after attack treatment were significantly higher in the hospitalized group compared to the discharged group. In addition, post-treatment PVI values were significantly lower in both the discharged and hospital- ized groups compared to the pre-treatment period (p < 0.001 and

PVI: Pleth variability index.

p < 0.001). There was no significant difference between the groups in terms of age and gender (p = 0.681) (Table 5).

The areas under the ROCs were 0.940, 0.865, and 0.843 for the PVI measurements in patients with severe disease, moderate disease, and hospitalization (p< 0.001). Table 6 shows the sensitivities, specificities, and cut-offs for all PVI measurements. There was a negative correlation between PVI value and oxygen saturation before and after treatment (Table 7).

  1. Discussion

Important results were obtained in this study, which investigated the relationship between PVI values, attack severity, and treatment re- sponse in the acute attack management of obstructive respiratory tract disease. First, it was determined that PVI, which was measured blindly from clinical severity scoring in triage, increased as the severity of attacks increased, and there was a significant difference in PVI values between the groups. This result highlights that PVI measurements can be used in clinical practice not only in Mechanically ventilated patients but also in spontaneously breathing patients because of their relation- ship with PP. In fact, Frey et al. [11] reported a decrease in PP of more than 15 mmHg in patients who had an asthma attack, and a greater de- crease in PP as the severity of the attack increased. Arnold et al. [18], on the other hand, calculated the PP level according to the area under the

Table 4

Summary of patients’characteristics with regard to disease severity before treatment.

Disease severity before treatment

p (between groups)

Mild

(n = 50)

Moderate (n = 50)

Severe (n = 33)

Age Sex

7 (4-10)a

4.5 (3-8)b

4 (2-8)b

0.005

0.197

Male

21 (42.00%)

30 (60.00%)

17 (51.52%)

Female

29 (58.00%)

20 (40.00%)

16 (48.48%)

Oxygen saturation

Before treatment

96 (95-97)a

94 (93-95)b

90 (88-92) c

<0.001

After treatment

97 (96-98)a

96 (95-97)a

93 (92-94)b

<0.001

p (before vs after)

<0.001

<0.001

<0.001

PVI

Before treatment

24 (19-27)a

31.5 (26-39)b

47 (42-51) c

<0.001

After treatment

19.5 (17-22)a

25 (20-29)b

38 (32-44) c

<0.001

p (before vs after)

<0.001

<0.001

<0.001

Outcome Discharged

49 (98.00%)a

46 (92.00%)a

0 (0.00%)b

Admitted to the ward

1 (2.00%)

4 (8.00%)

26 (78.79%)

<0.001

Admitted to the PICU

0 (0.00%)

0 (0.00%)

7 (21.21%)

PVI: Pleth variability index.

PICU: Pediatric intensive care unit.

a,b,c: shows statistically significant differences.

Table 6

Prediction performance of the PVI.

Severe disease (n = 133)

Moderate & Severe disease (n = 133)

Hospitalization (n = 83)

PVI results of the patient group hospitalized in the pediatric intensive care unit. Furthermore, only seven patients in the study group were ad- mitted to the pediatric intensive care unit, and these patients were in- cluded in the patient group hospitalized in the ward for the correct

Cut-off >37.5 >28.5 >37.5

Sensitivity 100.00% 77.11% 91.89%

Specificity 85.00% 86.00% 71.74%

Accuracy 88.72% 80.45% 80.72%

PPV 68.75% 90.14% 72.34%

NPV 100.00% 69.35% 91.67%

AUC (95.0% CI) 0.940 (0.902-0.978) 0.865 (0.805-0.926) 0.843 (0.757-0.928)

p <0.001 <0.001 <0.001

PPV: Positive Predictive Value, NPV: Negative Predictive Value

AUC: Area Under ROC Curve, CI: Confidence Intervals, PVI: Pleth variability index

plethysmograph tracking curve and showed that there is a significant relationship between PP and Forced expiratory volume level.

In a study conducted with 117 patients aged 1-18 years, Brandwein et al. [10] manually measured the PVI level in triage and found the me- dian PVI value for all patients to be 29 (IQR, 20-44). In addition, when they analyzed the patients in three groups intensive care, hospitaliza- tion, and those who were sent home from the emergency they reported that PVI values were significantly higher in pediatric intensive care unit inpatients compared to hospital inpatients and patients who were discharged from the emergency department. The results of this study suggest that PVI may be a useful tool in the triage of children who pres- ent to the emergency department with obstructive airway disease. Sim- ilarly, in the current study, the median auto-measured PVI for all patients before triage treatment was 30 (IQR, 23-42). In addition, when patients were grouped in terms of attack severity according to PIS, pre-treatment PVI values were significantly higher than post- treatment PVI values in all three groups. This supports the view that PVI is correspondingly high in a severe attack with a higher degree of PP, and that PVI also decreases with resolution of the obstruction and decrease in PP after bronchodilator therapy. Again, the fact that the PVI value after treatment was lower in all disease severity groups com- pared to the pretreatment suggests that PIV could be a useful, objective, and Noninvasive tool in predicting the degree of PP.

In a study conducted with 38 patients for whom the PVI values be- fore and after acute asthma attack treatment were compared, it was de- termined that although the respiratory severity score was found to be significantly higher before treatment in hospitalized patients, the pre- treatment PVI values were not significant in terms of predicting patients who would be discharged from the emergency department and hospi- talized. In addition, it was reported that there was no significant differ- ence between PVI values before and after treatment. Despite these negative findings due to the insufficient number of patients in the se- vere exacerbation group for statistical analysis, they reported that PVI could be an objective tool that could help clinicians in Asthma severity triage [12]. In the current study, the median PVI values of the hospital- ized patient group, including those admitted to the pediatric intensive care unit, were almost twice as high from the PVI values of the group discharged from the emergency department. Such a significant differ- ence in PVI values between the two groups may be due to the high

Table 7

Correlations between oxygen saturation and PVI.

PVI

Before

After

Oxygen saturation

Before After

r p r p

-0.568

<0.001

-0.432

<0.001

-0.481

<0.001

-0.416

<0.001

r: spearman correlation coefficient. PVI: Pleth variability index.

statistical analysis of the final disposition results.

In our study, the PVI cut-off level, which predicts whether a patient will be hospitalized based on the PVI level before treatment, was found to be greater than 37.5%, with a PPV of 72.34%. Clinicians may find this objective value useful because it can be used as a numerical indicator of disease severity. At the same time, PVI measurements taken during a patient’s ongoing evaluation can serve as a guide. However, due to limited equipment availability and in- tense emergency department conditions, repetitive PVI measurements for the patients included in the study were not possible. As the severity of asthma worsens, air movement decreases with increasing obstruc- tion. As a result, the change in intrathoracic pressure reduces as well. Al- though high PVI values are recorded in patients with severe asthma attacks, the PVI value may decrease when respiratory failure or apnea occurs. When PVI was assessed before and after treatment, there was no evidence of respiratory failure in the patients in our study.

The oxygen saturation values before and after treatment were signif- icantly higher in the discharged group than in the hospitalized group. In this case, it is possible to believe that there is a negative relationship be- tween PVI value and oxygen saturation. In addition to determining dis- ease severity, we believe that PVI value, like oxygen saturation, can be used as an objective parameter in evaluating Treatment response and patient follow-up (except for patients with respiratory failure).

The current study has a number of limitations. The subsequent out- comes of patients who were hospitalized in the general pediatric ward or pediatric intensive care unit and discharged from the emergency de- partment were not collected. Some of the patients who were discharged may have applied to other hospitals with an increase in the severity of acute attacks, or the need for a pediatric intensive care unit may have arisen during the follow-up of the patients in ward. Due to the small number of patients admitted to the pediatric intensive care unit, the levels of PVI predicting pediatric intensive care unit hospitalization could not be analyzed. The fact that patients with reactive respiratory tract disease and asthma were included in the same study group may also be thought-provoking. However, due to overlapping features be- tween asthma, recurrent wheezing, and reactive respiratory tract dis- ease, especially in the younger age group, it is sometimes not possible to distinguish these specific obstructive respiratory tract diseases in clinical practice [19]. Moreover, both reactive respiratory tract disease and asthma cause physiologically similar bronchoconstriction of the small respiratory tracts with hyperinflation and increased PP. Continu- ous or repetitive PVI measurement were not possible due to limited equipment and intensive emergency room conditions. Instant PVI mea- surement was performed simultaneously with clinical severity scoring. In this regard, research comparing instantaneous and continuous PVI values is required. Finally, the use of PIS as the gold standard for disease severity scoring may have resulted in subjective results due to the diver- sity in the views of clinicians. A more objective measurement of peak expiratory flow (PEW) may be a better tool for comparison with PIV values. Despite all the limitations, the strength of the study is that PVI measurements were taken blindly from PIS before and after bronchodi- lator therapy, unlike in other studies. In addition, this study may shed light on the larger patient group hospitalized in the pediatric intensive care unit and further studies in which objective PEW measurement is used as the gold standard in asthma severity scoring.

  1. Conclusion

The severity of attacks of many patients who apply to the pediatric emergency department because of an attack due to obstructive respira- tory tract diseases can be accurately defined with certain clinical evalu- ation tools. Although PIS is a very important tool for assessing attack

severity, it includes some subjective parameters. Automatic PVI mea- surement can be useful in intensive emergency department conditions, especially in triage, in terms of predicting the response of patients to treatment and follow-up results by quickly determining the severity of attacks, and in terms of reducing subjective clinical decision varia- tions among physicians. This is because it provides objective data.

Funding

This research did not receive any specific grant from funding agen- cies in the public, commercial, or not-for-profit sectors.

Declaration of Competing Interest

None.

Acknowledgements

This study was presented as a speech statement in Turkey, in 17th National Pediatric Emergency Medicine and Intensive Care Congress, in 14 October 2021.

Approval for the study was obtained from the non-invasive clinical research ethics committee (dated 05/13/2020 and numbered 2020/ 6-22). Because the Plet Variability Index was measured routinely and noninvasively, patient consent to participate was not obtained.

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