SUDHANSHU GROVER, ARUN BANSAL
From Department of Pediatrics, Advanced Pediatric Centre, Postgraduate Institute of
Medical Education and Research, Chandigarh, India.
Background: Little is known about the profile and outcome of children with acute severe asthma admitted in pediatric intensive care unit (PICU) in developing countries. Objective: To study the clinical profile and outcome of children with acute severe asthma admitted in a PICU. Design: Retrospective analysis of 33 children admitted in PICU over a 4-year period. Data was collected for respiratory rate, oxygen saturation (in room air), retractions, wheeze and dyspnea and Clinical Asthma Severity
Scores (CASS) was calculated from the above. Setting: Pediatric ICU of a tertiary care teaching hospital of North India. Results: Median (interquartile range) age was 3.5 years (2.8-6), PRISM 6 (3-13.5), PRISM III 13 (10-14.5) and PICU stay was 2 days (2-3 days). Male to female ratio was 3.7. Twenty-eight of 33 (85%) children were known cases of asthma. Seven (25%) patients had previous admission for acute severe asthma. All but one were hemodynamically stable at admission; one child was in shock.
Median CASS at admission was 11 (8-12). All received nebulized salbutamol and budesonide while 27/33 (81.8%) received nebulized ipratropium. IV hydrocortisone was given to all. Thirty (90.9%) patients required IV bronchodilators. Magnesium sulfate (50 mg/kg over 20 mins) was used in 28 children, terbutaline (10 mcg/kg bolus over 30 mins then 0.1 mcg/kg/min) in 20, aminophylline (5 mg/kg loading then 0.9 mg/kg/h) in 9 and ketamine in 4 children. Mean number of MgSO4 doses used were 3.1 and mean

duration of terbutaline infusion was 31 hours. Adverse drug reaction was seen in 5 children, 4 had hypokalemia and 1 had nausea induced by aminophylline. Thirty-one
(93.9%) patients recovered normally, while 1 suffered post hypoxic sequelae, and one died. Both these patients were mechanically ventilated (14 and 3 days respectively), while no other patient required ventilation. Conclusion: ICU care provides an excellent setting for management of acute severe asthma not responding to standard initial management.

INTRODUCTION
Asthma is a common disease worldwide. It is the most common chronic disease in children. The prevalence of asthma in childhood is 10 to 30 % (1). It is the leading cause of hospitalizations in children less than 15 years of age, and the leading cause of school absence (2). In India, the estimated burden of asthma is believed to be more than 15 million (3). Studies have shown that acute asthma is one of the most common pediatric emergencies encountered along with acute diarrhea, pneumonia, seizures, and neonatal infections (4).
Most children admitted to the hospital because of acute asthma do not require intensive care treatment. Nevertheless, a small percentage of children with life-threatening asthma would develop progressive respiratory failure refractory to treatment and require admission to the pediatric intensive care unit
(PICU). Management in the ICU involves intensification of pharmacologic therapy, including nonstandard therapies, in an attempt to avoid invasive procedures, intubation and ventilation. Poorly controlled asthma is associated with significant morbidity and socioeconomic problems (3). Despite advancing knowledge of the pathophysiology and treatment of asthma, its morbidity and mortality are on the rise (5). Management of asthma is based on underlying pathophysiology, attempting to reverse bronchospasm, airway inflammation and mucus production (1). Treatment of acute exacerbation includes oxygen, inhaled bronchodilators and corticosteroids. Severe acute attacks sometimes bring difficulty to the physician. Little is known about the profile and outcome of children with acute severe asthma admitted in pediatric intensive care unit (PICU) in developing countries. This review is first of its kind from a pediatric ICU in India. There is also a dearth of similar studies from other developing countries. The objective of this

study is to assess the clinical profile and outcome of children admitted in pediatric intensive care unit.
MATERIAL AND METHODS
Study Design: Retrospective cohort study.
Study Setting: The study was conducted at the pediatric intensive care unit of a tertiary care hospital in north India.
Study Subjects: Children between 1 to 13 years of age admitted to pediatric intensive care unit.
Period of Study: August, 2006 to September, 2010.
Data collection: Analysis of 33 children admitted in PICU over a 4-year period. Demographic details were collected. Clinical details including duration of cough and respiratory distress before admission, PRISM and PRISM III scores at admission to
PICU, and past history of asthma and number of hospitalizations were noted. Other details collected at admission to PICU included respiratory rate, oxygen saturation (in room air), retractions, wheeze and dyspnea. Clinical Asthma Severity Score (CASS) which includes 5 parameters (tachypnea, hypoxia, retractions, wheeze and dyspnea)
(Table 1)(6) was calculated. Each parameter was scored from 0 to 3 (maximum total score was 15). A score of more than 7 was considered as severe. Also, the treatment given to each patient including individual drugs, their route of administration and duration of administration was noted.
Duration of ICU stay, duration of mechanical ventilation, duration of intravenous bronchodilator, adverse effects of drugs and outcome of patients was also taken into consideration.

Table 1 Clinical Asthma Severity Score (CASS) (6)
Score RR Room Air
Saturation*
Auscultation (wheeze) Retractions
2
3
0
1
<30
31-45
46-60
>60
97-100
94-96
91-93
<91
None
End expiration
All expiration
Inspiration and Expiration without stethoscope
* off oxygen for 5 minutes or until saturation drops less than 91%
# subjective assessment
None
+/-
++
+++
Dyspnea#
None
Full sentences
Partial sentences
Single word/grunt
Statistical analysis: Descriptive statistics was applied using SPSS software version 17.0
Results: Thirty three children (26 males and 7 females) in the age group of 1 to 13 years were admitted in the pediatric ICU during the study period. The male: female ratio was
3.7:1. Median (interquartile range) age was 3.5 years (2.8-6). Five patients (15%) presents as first episode while others (85%) were known cases of asthma (n=28).
However, only 16 out of these 28 patients were on regular treatment. Seven patients
(21%) had history of previous hospitalization due to asthma. Patients were symptomatic for an average 2.7 days before admission in hospital. History of fever (moderate grade) was present in 42% patients (n=14). The mean PRISM and PRISM II scores were 6 (3-
13.5) and 13 (10-14.5), respectively. All but one patients were hemodynamically stable at the time of admission, while one patient presented in hypoxemic shock. The mean respiratory rate and off oxygen saturation at admission in pediatric ICU were 55 per minute and 91.6% respectively. All (n=33) patients received salbutamol nebulization, while 32 and 27 received budesonide and ipratropium nebulizations also. All the

patients received at least one dose IV hydrocortisone, while 42% (n=14) received oral steroids later. The use of subcutaneous drugs was noted in a few patients. While 5
(15%) children received subcutaneous adrenaline, subcutaneous terbutaline was given to 2 (6%) children. Thirty (90.9%) patients required IV bronchodilators. Magnesium sulfate (50 mg/kg/dose over 20 to 30 minutes) was the most commonly used intravenous agent and was administered to 28 children (84%). While terbutaline (10 mcg/kg bolus over 30 mins followed by continuous infusion) was used in in 20 patients
(60%); aminophylline (5 mg/kg loading then 0.9 mg/kg/h) (n= 9; 27%) and ketamine
(n=4; 12%) were the other intravenous bronchodilators used. Mean number of MgSO4 doses used were 3.1 and mean duration of terbutaline infusion was 31 hours. The mean duration of IV drug/infusion usage was 34 hours. Nineteen children (57%) received more than one IV bronchodilator. Adverse drug effects were noted in 6 patients (18%).
While 5 patients had hypokalemic records due to terbutaline, aminophylline induced vomiting was noted in 1 patient. Magnesium sulfate was largely safe in all the patients with good efficacy and no significant side effects. Two patients required mechanical ventilation (6.1%). Of these, one patient suffered hypoxic sequel (duration of ventilation
14 days), while the other patient died at 65 hours of stay in ICU. While the course of other patients was relatively uncomplicated, the above mentioned 2 patients suffered complications in the form of pneumonia and pneumothorax, respectively. The
PRISM/PRISM III scores of these 2 patients were 14/23 and 14/13, respectively. The
CASS of both these patients at admission to PICU was 15 and 12 respectively; while the saturation (off oxygen) at admission to hospital was 66% and 88%. Both had silent chest at admission. Both these children received 3 intravenous bronchodilators

(magnesium sulfate, terbutaline and aminophylline during the hospital stay along with other drugs. Overall, 31 (93.9%) patients had normal outcome. The mean duration of
ICU stay was 2.9 days.
DISCUSSION
Asthma is the most common chronic disease of children. It contributes significantly to the number of cases in pediatric emergency. According to a large study comprising of
43,800 children presenting to pediatric emergency, acute exacerbation of asthma was the 3 rd most common diagnosis most common diagnosis (5.2%) after acute diarrhea and seizures (4). Data regarding the experience of managing acute severe asthma in pediatric intensive care units in India is lacking. This is the first study of its kind from an
Indian PICU. Data from western countries is, however, available. Most of the similar studies have been done over a variable period of time ranging from 12 months to 15 years. The number of patients in most of the comparable single centre studies is variable, ranging from 28 to 56 (7,8,9,10,11). Recently, a large retrospective cohort study comprising 1528 children admitted at 11 different centres over 5 years was conducted in the west (12). Our study period and the number of subjects is currently enough to know the trends of the disease and its outcome in an Indian PICU setting; although more such studies from different centres in India will be helpful.
Among the baseline variables, the sex distribution in our study population was quite uneven i.e. male:female ratio of 3.7. The sex distribution has been variable in the similar other studies (1.4 to 3.1) (10,12,13,14). But there has been a consistent male

preponderance in all of them. The mean PRISM III score of 13 in our study was significantly higher as compared to other studies (12).
The average duration of PICU stay was 2.9 days in our study which is similar to most of the studies (1 to 3 days) (7,8,9,10,11,12). However, the duration of hospital stay in the ventilated patients (n=2) was more in our study (14 days and 65 hours, respectively).
One such ventilated patient developed neurologic sequel while the other expired on at
65 hours of PICU stay. On the other hand, the average duration of stay in the ventilated patient was 1 to 2 days in the large multicentric trial from the west (12) and 3 to 4 days in the single centre studies from Taiwan and Israel (7,10). The number of ventilated patients in our study was significantly less (n=2; 6%) as compared to most of the other studies, a few of them having ventilation rates upto 20% (7,9,10,14,15). The death rate at our centre was low (n=1). This is similar to the mortality data from other centres (0 to
2.1%) (7,8,10,11,12).
The initial treatment given to the patients was similar at most of the centres including inhaled beta-2 agonists and IV steroids. However, the use of intravenous drugs has been variable both in terms of incidence and the choice of agent. In most of our patients, the intravenous drugs were started after the patient failed to show an adequate clinical response to the standard initial management consisting of inhaled bronchodilators and IV/oral steroids. This response was judged on the basis of the clinical score (CASS) mentioned above. Such a clinical exercise has not been performed in the other centres.

More than half (57%) of our patients received at least 2 IV drugs, the most common ones being magnesium sulfate and terbutaline. Similar data is lacking in all the comparative studies. Both these drugs have been proven to be effective in the various studies and meta analyses (16,17,18). Early use of intravenous bronchodilators (based on the clinical severity) has been our policy.
Additionally, we looked for the adverse effects of the intravenous drugs in each patient.
We found that magnesium sulfate was a safe and effective IV bronchodilator. No side effects were noted with its use. On the other hand, patients receiving terbutaline and aminophylline, however, suffered adverse effects (as mentioned above). Based on our previous experience, we recommend magnesium sulfate as a safe and fast acting drug in children with acute severe asthma not responding to conventional treatment. This view is also supported by various studies and meta-analyses (16). Overall, ninety four percent of our patients had favourable outcome.
In our experience, the use of clinical parameters would be far easier, faster and a more reliable way of assessing the patients rather than waiting for the lab investigations.
Lately, we have started using a clinical score (clinical asthma severity score) for assessing the severity of the illness, monitoring the response to treatment and taking decisions about the further management. Out of a total score of 15, a value of 7 or more was used to label a patient as having a severe exacerbation. The mean CASS at admission to PICU in our study was 10.54. The mean time period for significant clinical improvement in our patients was 20 hours.

According to our practices, the medical management of severe asthma is aggressive and is based on regular clinical monitoring based on objective parameters, so as to avoid the use of invasive lines and ventilation.
We conclude that the mortality and morbidity in children with severe asthma, who require PICU admissions are minimal, provided optimal early use of bronchodilators and intravenous steroids. Using this approach, it could also be possible to avoid mechanical ventilation and shorten the duration of hospital admission. Hence, management of such children may be improved by clear elucidation of the institutional practices, regular clinical monitoring, judicious use of various bronchodilators and fewer invasive interventions.
Table 2: Analysis of patients (n=33)
Demographic Characteristic s
Age (years)(mean)
Male: female
History
3.5 yr (2.8 to 6 yr)
26:7 (3.7)
Period of symptoms before admission (mean) 2.7 days
History of fever (moderate grade) 14/33 (42%)
Patients presenting as 1st episode
History of previous hospitalization
Patients on regular treatment
5/33 (15%)
7/33 (21%)
16/33 (48%)
At admission in PICU
PRISM (mean)
PRISM III (mean)
CASS at admission (mean)
6 (3-13.5),
13 (10-14.5)
10.54
55.1
per min Mean Respiratory rate
SpO2 at admission (mean)
Shock at admission
91.6%
1/33 (3.0%)

Treatment details
Period for significant improvement
Patients receiving salbutamol nebulization
Patients receiving ipratropium nebulization
Patients receiving oral steroid
Patients receiving IV steroid
33/33 (100%)
27/33 (81%)
14/33 (42%)
Patients receiving magnesium sulfate
33/33 (100%)
28/33 (84%)
3.1 doses per pt Average no. of magnesium sulfate doses
Patients receiving terbutaline infusion
Mean terbutaline infusion duration
20/33 (60%)
38.1 hr
Patients receiving aminophylline 9/33 (27%)
Patients receiving IV ketamine 4/33 (12%)
Patients receiving SC adrenaline 5/33 (15%)
Patients receiving SC terbutaline
20 hours
2/33 (6%)
2/33 (6.1%) Patients receiving mechanical ventilation
Mean duration of IV drug/infusion
Adverse drug effects
Death
Outcome
Normal
Hypoxic sequel
34.0 hours
6/33 (18%)
31/33 (94%)
1/33 (3%)
1/33 (3%)
ACKNOWLEDGEMENT: We are grateful to Dr. Sunit Singhi, professor and head, department of pediatrics, PGIMER, Chandigarh for his constant guidance and support.

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