Evidence Based Presentation

Critical Care 2

Claire Colvine

Infants under 2 years presenting to Accident and Emergency with

Bronchiolitis does 3% saline with Epinephrine improve oxygen saturations compared to 0.9% saline with Epinephrine

Rationale 15,000 infants in Scotland have bronchiolitis, 70% in the first year of life

3% under 1 year are admitted to hospital

www.sign.ac.uk/guidelines/bronchiolitis

Bronchiolitis is a disorder most commonly caused in infants by viral lower respiratory tract infection. Brand and Vassesn (2000)

Respiratory Syncytical Virus (RSV) is responsible for about 80% of the cases. Scarfone (2005)

It is characterized by acute inflammation, edema and necrosis of epithelial cells lining small airways, increased mucus production and bronchospasam.

Epinephrine contains alpha adrenergic properties and beta adrenergic effect. Bronchiolitis may benefit from the vasoconstricting effects and reduction of edema offered by the alpha adrenergic effect.Hariprakash (2003)

Hypertonic saline breaks ionic bonds within mucus gel, thereby reducing the degree of cross-linking and entanglements and lowering viscosity and elasticity of the mucus secretions. Hypertonic saline inhalation can theoretically reduce edema of the airway wall. Robinson (1997)

Does the evidence from the study and the existing research from the Cochrane review warrant changing management of infants with bronchiolitis within my workplace.

Cochrane Reviews

Epinephrine for Bronchiolitis (2009)

14 Studies in the review

Insufficient evidence to support the use of epinephrine for the treatment of brochiolitis among inpatients.

There is some evidence to suggest that epinephrine may be favourable to sulbutamol and placebo among outpatients.

More large multicenter studies recommended from the review.

Nebulized hypertonic solution for acute bronchiolitis in infants (2009)

4 Studies in the review

Current evidence from the review suggests nebulized 3% saline may significantly reduce the length of hospital stay and improve the clinical severity score in infants with acute viral

bronchiolitis.

Research Question

Improve Oxygen saturations

Outcome

0.9% saline with epinephrine

Comparison

3% hypertonic saline with epinephrine

Intervention

Under 2 yearsPatient

Search StrategySearch strategy between 10-12 April 2010Yields- Pub med= bronchiolitis 7828, epinephrine and bronchiolitis 103, Hypertonic Saline

and bronchiolitis 28, both hypertonic saline, bronchiolitis and epinephrine 5Elibrary (13 databases)= bronchiolitis, 5865, epinephrine and bronchiolitis 151Hypertonic saline and bronchiolitis 42, Epinephrine, hypertonic saline and bronchiolitis

8Out of the 13 articles which included all three core words 2 articles were chosen in regard

to type of study and similarities between the two.No Cochrane reviews or Best Bets done on all of inclusion criteria together

InclusionInclusion ExclusionExclusion

Bronchiolitis not being PCInfants under 2 years with bronchiolitis Infants over 2 yearsHypertonic saline Neb Infants requiring resus 0.9%saline Neb hypertonic saline vs. 0.9%Epinephrine Neb InpatientsAccident and Emergency Articles before 1995

Epinephrine vs. sulbutamol

Research Articles

Ayse, A, Anil, M, Saglam,A, Cetin, N, Bal,A and Asku, N. (2010)High volume Normal saline alone is as effective as Nebulized Salbutamol-Normal Saline, Epinephrine-Normal saline and 3% Saline in mild Bronchiolitis. Paediatric Pulmonology, 45, 41-47. (Turkish study over 6 months on the under 2 age group presenting to A+E with Bronchiolitis)

Grewal, S, Ali, S, McConnell, D, Vandermeer, B and Klassen, T. (2009) A Randomized Trial of Nebulized 3% Hypertonic Saline with Epinephrine in the Treatment of Acute Bronchiolitis in the Emergency Department. Archive of Paediatric Adolescent Medicine. 163 (11) 1007-1012. (Canadian Study taken over 14 months on infants under 1 presenting to A+E with bronchiolitis)

Critical Appraisal

Critical Appraisal Skills Programme (CASP 2004)

Designed by the Public Health Resource unit

10 Questions to help you make sense of a Randomised Controlled trials

Did the study ask a clearly-focused question?

Yes

6 weeks 1 year

0.9% saline or hypertonic saline with epinephrine

Relieve respiratory symptoms and monitor admission rates

Yes

6 week- 2 years

1st admission of bronchiolitis

0.9% saline, hypertonic saline with either sulbutamol or epinephrine

Relieve Respiratory symptoms and monitor admission rates

Grewal et al (2009)Anil et al (2010)

Was this a Randomised controlled trial (RCT) and was it appropriately so?

Yes

Randomised double-blinded controlled trial

Yes

Randomised double blinded controlled trial

Grewal et al (2009)

Anil et al (2010)

Were Participants appropriately allocated to intervention and control groups?

YesPatients randomised into blocks of 4 (both throughout the bronchiolitis season and from month to month). This was to guarantee a comparable distribution of patients with different viral pathogens in each group.

Two groups which were nebulised 0.9% saline with epinephrine and 3% hypertonic saline and epinephrine.

Randomisation scheme was generated by the pharmacy using the web site Randomisation.com www.randomisation .com

Randomisation list was concealed by pharmacy until completion.

YesAll eligible patients were randomly assigned to five different groups

Five groups were 0.9%saline and epinephrine, 3% hypertonic saline with epinephrine. Two groups differing saline and sulbutamol and 0.9% saline neat.

A random number table generated by computer was used by study coordinator to allocate patients to treatment groups and the study coordinator was the only person with access to the randomisation.

Numbers in each group ranged from 36 39.

Grewal et al (2009)Anil et al (2010)

Were participants and study personnel blind to participants study group?

YesRandomisation process controlled by pharmacy then physicians, house staff, nurses, study personnel and patients remained blinded to treatment allocation throughout the study.

Solutions similar in appearance and smell, stored in identical syringes, labelled only with code number and placed within research cupboard in ED.

YesStudy solutions were identical in appearance and odor

Identity of the study solutions were blinded to all participants, care providers and investigators.

Grewal et al (2009)Anil et al (2010)

Were all the participants who entered the trial accounted for at its conclusion?

YesEach family was contacted by telephone within 1 week to determine if any further treatment was sought after discharge from the ED.

Intention to treat analysis was used in all analysis.

YesThe investigators contacted the parents and guardians of discharged study patients via telephone 2 days after their ED visit to determine their readmission rate.

They were reassessed at 6 months by telephone contact in order to record wheezing attack rate.

No mention of intention to treat analysis

Grewal (2009)Anil et al (2010)

Were the participants in all groups followed up and data collected in the same way?

Both groups received either of the two drugs at 0 mins

Each nebuliser was given with continuous flow at 6 l.

All patients had measurements respiratory rate, oxygen saturation, Heart rate and RADI score. All recorded at baseline then 30,60,90 and 120 minutes.

Each measurements had been taken after the oxygen had been removed for 5 mins.

NPA taken

Two doses of study drug available if needed if physician felt it was needed during the 120 minute study

Emergency physicians felt free to withdraw amy one from the study to use other investigations or clinically necessary.

Drug was administered at 0 and 30 mins by same brand nebuliser 6l

Prior to each drug administration and at 60 and 120 mins the investigator assessed the childs condition, and recorded CS score SaO2 in room air, and heart rate.

Adverse events were defined as HR > 200, tremor withdrawal from the study due to worsening clinical status or discontinuation of any study medications due to side effects.

Patients were excluded from the study if administration was delayed by 10 mins or clinical deterioration.

At the end of the period the attending paediatrician determined need for admission depending on clinical condition

Grewal et al (2009)Anil et al (2010)

Did the study have enough participants to minimise the play of chance?

This study felt that anything less than a change of 3 points in the RACS would not be considered significantly different.

Assuming a power of 90% the study required a total sample size of 46 infants to be able to detect a difference of 3 in the RACS between the two groups.

A power analysis revealed that for detection of difference of 1 unit in CS score between five treatments with a power of 80%, the study requires 150 patients (30 per group)

Statistical significance was defined as p

How are the results and what is the main result?

Mean (95% CI)

Hypertonic saline with Epinephrine change in oxygen saturation 0.44 (-2.11to 1.23)

Normal saline with Epinephrine change in oxygen saturation was 1.34 (-0.29 to 2.99)

Total difference was 1.78 (-0.50to4.06)

24 patients received second dose of of the study drug.

The change in oxygen saturation was not significant when compared to control (0.95% saline)

0.9% with 1.5 mg Epinephrine (38) (mean +ranges)

Result 0 min-98.1%(94-100)

30min-98.0%(91-100)

60min- 98.5%(94-100)

120min- 98.7%94-100)

3% hypertonic saline with 1.5mg of epinephrine.(39)

Result

0 min- 97.4%(92-100)

30min-97.8%(91-100)

60min- 98.5%(95-100)

120min-98.5%(95-100)

No significant differences between the two groups .

Grewal et al (2009)Anil eta al (2010)

How precise are the results?

CI (95%)

Hypertonic saline group (-2.11 to 1.23)

0.9% Saline group (0.29 to 2.99)

Difference (0.50 to 4.06)

In all patients concerning the response to nebulized therapy, cs scores and SaO2 values after 30min were found to be significantly better than the base line values (P

Infants under 2 years presenting to A+E with Bronchiolitis does 3% saline

with Epinephrine improve oxygen saturations compared to 0.9% saline

with Epinephrine?

Answer- NO

Application to PracticeAs the research shows there is no significant difference in SP02 between hypertonic

saline and 0.9% saline with epinephrine when administered in accident and emergency.

Both studies were based in accident and emergency so the studies showed that there is no real significant change in condition in dealing with first line management.

Currently within Ayrshire and Arran we follow the SIGN guidelines so do not use any sort of nebulisation in Accident and Emergency for Bronchiolitis

This research is apparent to me working as an APNP in a DGH because although there is no significant difference in saline strengths with epinephrine in A+E. The Cochrane review shows that using hypertonic saline in inpatients can significantly reduce the symptoms and length of hospital stay.

Currently within Ayrshire and Arran we do not use hypertonic saline in treating bronchiolitis. This is obviously something that I need to take forward in developing as it has health and cost implications.

Both studies revealed that further multicenter trials need to be undertaken to assess epinephrine and saline use in immediate bronchiolitis treatment.

The Cochrane review did find small evidence that Epinephrine was favourable to sulbutamol and placebo among outpatients.

References Brand PLP, Vassen-Verbern.(2000)Differences in management of Bronchiolitis

between hospitals in the Netherlands. European Journal 0f Paediatrics,159:390-347

Hariprakash, S, Alexander, J, Carroll, W (2003) Randomised controlled trial of nebulized adrenaline in acute Bronchiolitis. Paediatric Allergy Immunology, 14:1-6

Hartling L, Russell, KF, Patel, H, Klassen, TP, Liang Y (2009) Epinephrine for bronchiolitis (Review). Cochrane Library.

Purcell, K,Fergie, J.(2004) Concurrent serious bacterial infections in 912 infants and children hospitalised for treatment of respiratory syncytial virus lower respiratory tract infection. Paediatric Infectious Disease Journal, 23:267-324.

Robinson, M, Hemming A,Regnis, J, Wong, A, Bailey, D, Bautotvich,G (1997) Effect of increasing doses of hypertonic saline on mucocilliary clearance in patients with cystic fibrosis. Thorax, 52 (10),900-903.

Scarfone, RJ. (2005) Controversies in the treatment of Bronchiolitis. Current opinion Paediatrics, 17:62-66

www.SIGN.ac.uk/Bronchiolitis acsessed 12/04/2010.

www.phru.nhs.uk/casp/apprasial.htm assessed 17/04/2004

Zhang, L, Mendoza-Sassi, RA, Wainwright, C, Klassen, TP. (2009) Nebulized hypertonic saline solution for acute bronchiolitis in infants (Review). Cochrane Library.

Questions