Study ID

Report ID

Review author name

First author

Full reference

Type of study

Is the study described as randomized?

Yes

Unclear

No

Next question

Next question

Exclude

Participants

Were the participants mechanically ventilated and:

‐        defined as adult by trialists

OR

‐        NOT identified as paediatric

Yes

Unclear

No

Next question

Next question

Exclude

Interventions

Did the study contain at least two interventions, comparing any model of nebulizer to MDI for aerosol bronchodilation?

Yes

Unclear

No

Next question

Next question

Exclude

Was the difference in bronchodilator delivery device the only planned difference between the comparison interventions?

Yes

Unclear

No

Next question

Next question

Exclude

Were the same bronchodilatory agents used in all comparison groups?

Yes

Unclear

No

Next question

Next question

Exclude

Were only bronchodilators delivered during the trial? (i.e. no other drug groups/agents mixed in with bronchodilator agent/s)

Yes

Unclear

No

Next question

Next question

Exclude

Was there any combination administration of bronchodilators of differing drug groups?

Yes

Unclear

No

Exclude

Next question

Next question

Outcomes

Did the study record airway responses∗?

Yes

Unclear

No

Include

Include

(subject to clarification of “unclear” points)

Exclude

Final decision

Include

Unclear

Exclude

If the study is to be excluded, record the reason and details to add to “Table of excluded studies”:

Authors  

Contact address  

Country of study 

Language of publication

Code

Authors

Full reference

Linked Study ID on p1?

(tick)

Linked Study ID in RevMan?

(tick)

A

B

C

Sequence generation

Was the allocation sequence adequately generated?

Give text which enabled your decision, including page no:

“YES” if used:

·  Random number table

·  Computer random number generator

·  Coin tossing

·  Shuffling cards/envelopes

·  Throwing dice

·  Minimization

“No” if used non‐random method such as:

·  Odd / even D.O.B

·  Date of admission

·  Hospital/clinic number

·  Clinician judgement

·  Participant preference

·  Lab test results

·  Availability of intervention

“Unclear” if there is insufficient information to permit “Yes” or “No” judgement.

Allocation concealment

Was the allocation adequately concealed?(i.e. participants/investigators enrolling participants could not foresee assignment)

Give text which enabled your decision, including page no:

“YES” if used:

·  Central allocation

·  Sequentially numbered containers of identical appearance

·  Sequentially numbered opaque, sealed envelopes

·  Or equivalent method

“No” if investigators could potentially foresee allocation such as:

·  Open random allocation scheme e.g. random list

·  Envelopes without safeguards e.g. unsealed, non opaque

·  Alteration / rotation

·  Date of birth

·  Case record number

·  Other unconcealed procedure

“Unclear” if there is insufficient information to permit “Yes” or “No” judgement.

Blinding of participants, personnel and outcome assessors

Was knowledge of allocated intervention adequately prevented during study?

Note: Blinding of personnel not possible with current review, but consider if a lack of blinding has potentially influenced results

Give text which enabled your decision, including page no:

“YES” if:

· No blinding, but unlikely to influence results

· Outcome assessment blinded

“No” if:

·  No blinding and is likely to influence result

·  Non‐blinding is likely to have introduced bias

“Unclear” if there is insufficient information to permit “Yes” or “No” judgement, OR study did not address this outcome

Incomplete outcome data

Were incomplete outcome data adequately addressed?

Give text which enabled your decision, including page no:

“YES” if missing data:

·  Complete ‐ none missing

·  Unlikely to be related to true outcome

·  Is balances across groups

·  Effect size not enough to have clinical relevance impact on observed effect size

·  Have been imputed appropriately

“No” if missing data:

·  Likely to be related to true outcome

·  Effect size enough to have clinical relevance impact on observed effect size

·  “as treated” analysis done with very different numbers than at outset

·  potentially inappropriate data imputation

“Unclear” if there is insufficient information to permit “Yes” or “No” judgement OR study did not address this outcome

Selective outcome reporting

Are study reports free of selective outcome reporting?

Give text which enabled your decision, including page no:

“YES” if:

·  Protocol available and pre‐set outcomes are reported in pre‐set way

·  No protocol, but clear published reports of all expected outcomes, including pre‐set ones

“No” if:

·  Not all pre‐set outcomes reported

·  1/1+ of primary outcomes reported in different methods, units, subsets of participants to protocol

·  1/1+ primary outcomes not pre‐set

·  1/1+ outcomes reported incompletely

·  Report does not include key outcome which would be expected

“Unclear” if there is insufficient information to permit “Yes” or “No” judgement.

Other potential threats to validity

Was the study free of anything else which may put it at risk of bias?

Give text which enabled your decision, including page no:

“YES” if:

·  Appears free from other sources

“No” if other potential source of bias e.g.:

·  Study design

·  Stopped early

·  Extreme baseline imbalance

·  Claims to be fraudulent

·  Other problem

“Unclear” if there is insufficient information to permit “Yes” or “No” judgement.

Cross – over trials

Consider these potential sources of bias if the study is a cross‐over design

Give text which enabled your decision, including page no:

Was the design appropriate?

Order of receiving treatments randomized?

Not biased from carry‐over effects?

Unbiased data available?

Participants

Age (mean, median, range)

Sex (numbers/%)

Any other ventilation/bronchodilation strategies? e.g.:

·  Heated humidification

·  Use of spacer devices

·  Helium oxygen mixtures

·  Nitric oxide mixtures

Pre‐existing lung pathology? e.g.:

·  COPD

·  Asthma

Other Include sources of funding, conflicts of interest and any unexpected findings

Outcomes

Reported in study?

Airway response:

  Airway resistance

(Rrs min, Rrs max, ΔRrs)

Yes / No

Patient outcome:

 Mortality

Yes / No

 Duration of mechanical ventilation

Yes / No

Adverse changes to haemodynamic observations

Yes / No

Reduction in wheezing

Yes / No

Freedom from contamination

Yes / No

Practitioner satisfaction

Yes / No

Associated cost

Yes / No

Quality of life measures

Yes / No

Continuous Outcomes ‐ RCTs

Unit of measurement

Intervention

Control

Details if outcomes are only described

n

Mean

(SD)

n

Mean

(SD)

Airway resistance

ΔRrs

Rrs max

Rrs min

Duration of mechanical ventilation

Practitioner satisfaction

Continuous Outcomes – Cross over trials

Unit of measurement

Intervention

Control

Cross over trial data

Record all that is available in the paper

Note – it is the within patient differences that you need the SD, standard error and CI for

n

Mean

(SD)

n

Mean

(SD)

SD

Standard error

CI

t

P value

Airway resistance

ΔRrs

Rint

Rrs max

Rrs min

Duration of mechanical ventilation

Practitioner satisfaction

Dichotomous Outcomes

Intervention (n)

Note: n = number of participants, NOT number of events

Control (n)

Note: n = number of participants, NOT number of events

Mortality – during critical care unit admission

Adverse changes to haemodynamic observations

Reduction in wheezing

Freedom from contamination

Any other relevant information about results

e.g. if data was obtained from the trialists, if results were estimated from graphs or are calculated by you (if so, state formula and calculations)

Freehand space for actions

Please document any contact with study authors and changes here

Trial characteristics

Single/multicentre?

Country/countries

Definition used of participant eligibility

How many people randomized?

Number of participants in each intervention group

Make and model of ventilator used

Ventilator settings used

Number of participants who received intended treatment

Number of participants who were analysed

Bronchodilator and make and model of each device used

Dose and frequency of administration

Detail administration process

e.g. use of spacer device, position of nebulizer/MDI in circuit, patient positioning etc for each intervention

Duration of treatment

How was the decision to withdraw mechanical ventilation made? (i.e. protocol, clinical judgement or a combination)

Length of follow up reported for patient outcome

Time points when measurements were taken during the study

Time points reported

Time points you are using in RevMan

Any additional information

Outcome measure: Reduction in ΔRrs (H₂O l^‐1s)

MDI

Nebulizer

Pre‐treatment

Post‐treatment

Pre‐treatment

Post‐treatment

Guerin 1999

(n = 18) ± SEM

11.46 ± 1.04

10.79 ± 0.88

12.80 ± 1.59

10.79 ± 1.11

Not significant

P <0.01

Outcome measure: Reduction in Rint (H₂0 l^‐1 s)

MDI

Nebulizer

Pre‐treatment

Post‐treatment

Pre‐treatment

Post‐treatment

Guerin 1999

(n = 18)

± SEM

5.03 ± 0.81

4.10 ± 0.60

5.23 ± 0.82

4.36 ± 0.62

P <0.05

Not significant

Outcome measure: Reduction in Rrs or Rint (cm H₂0)

MDI

Nebulizer

Pre‐treatment

Post‐treatment

Pre‐treatment

Post‐treatment

Manthous 1993

(n = 10)

± SEM

18.9 ± 2.6

19.6 ± 4.7

(estimate from a published figure)

21.5 ± 5.7

17.6 ± 5.4

Not significant

P <0.01