doument ontrol page

1

DOCUMENT CONTROL PAGE

Title

Title: Management of Acute Severe Asthma in Children >1yr Version: Version 2 Reference Number: PCCN3

Supersedes

Supersedes: Version 1 Description of Amendment(s): Repeat doses of magnesium; reduction in salbutamol dose; advice on arrhythmias; reduction of aminophylline dose per BNFc guidance;

Minor Amendment

Date: Notified To: Date: Summary of amendments:

Author

Originated By: North West and North Wales Paediatric Critical Care Network

Guideline authors:

Pete Murphy, Transport Consultant NWTS and Consultant Paediatric Anaesthetist, AHFT Rachael Barber, NWTS Consultant and PICU Consultant, RMCH Aradhana Ingley, Associate Specialist in Paediatrics, Glan Clwyd Hospital, North Wales Adam Sutherland, Senior Clinical Pharmacist, RMCH Fran Child, Consultant Paediatric Respiratory Consultant, RMCH Jon Couriel, Consultant Paediatric Respiratory Consultant, AHFT Version 2: Rachael Barber, NWTS Consultant and PICU Consultant, RMCH Carrick Allison, Paediatric Anaesthetic Trainee, RMCH Adam Sutherland, Lead Pharmacist, RMCH Elly Turner, Lead respiratory pharmacist, RMCH

Ratification

Ratified by: 1. MFT (Host Trust): - Paediatric Medicines Management Committee (MMC) on: 05/09/2018 2. AHFT: - Critical Care Clinical Business Unit on: - CDEG (Clinical Development & Evaluation Group) on: TBC

Application

Children only

Circulation

Issue Date: TBC Circulated by: Clinical Lead, North West & North Wales Paediatric Critical Care Net-work Dissemination and Implementation: NWTS & Network circulation lists

Review

Review Date: TBC—3 years Responsibility of: Clinical Lead & Network Manager, North West & North Wales Paediatric Critical Care Network

Date placed on the Intranet:

TBC

Please enter your EqIA Registration Number here: 150/12

2

1. Detail of Procedural Document Guidelines for Management of Acute Severe Asthma in Children >2yrs. 2. Equality Impact Assessment EqIA Registration Number: 150/12 3. Consultation, Approval and Ratification Process

This guideline was developed with input from: · North West and North Wales Paediatric Transport Service (NWTS). · Representatives from the North West and North Wales Paediatric Critical Care Network (PCCN). · Representatives from both Paediatric Intensive Care Units (Royal Manchester Children’s Hospital and

Alder Hey Children’s Hospital). · Representatives from the District General Hospitals within the PCCN. These guidelines were circulated amongst the North West and North Wales Paediatric Critical Care Network for comments on the All comments received have been reviewed and appropriate amendments incorporated. These guidelines were signed off by the Network’s Clinical Lead For ratification process see appendix 1. . 4. References and Bibliography

See guidelines. 5. Disclaimer These clinical guidelines represent the views of the North West and North Wales Paediatric Critical Care Network and North West and North Wales Paediatric Transport Service, which were produced after careful consideration of available evidence in conjunction with clinical expertise and experience. The guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient. Management of acute wheeze in children under 2 years of age : This guideline is not appro-

priate for this age group. Early consultant involvement is recommended. Patients may respond clini-

cally to magnesium and aminophylline rather than salbutamol. There is no evidence to support High

flow humidified oxygen at present.

Clinical advice is always available from NWTS on a case by case basis. Please feel free to contact NWTS (01925 853 550) regarding these documents if there are any queries.

http://www.nwts.nhs.uk

3

Guidelines for Management of Acute Severe Asthma in Children >2yr

SEVERE SaO2 <92% in air

Use of accessory muscles

Difficulty talking or eating

Agitated

Heart rate >140(under 5yr), >125bpm (over 5yr)

Resp rate >40(under 5yr), >30 (over 5yr)

LIFE THREATENING

NEAR FATAL SaO2 <92% in O2 plus any of:

Silent chest

Poor respiratory effort

Cyanosis

Altered Consciousness/Exhausted

Increased pCO2 or hypotension are

pre-terminal signs

Summon senior help (if life-threatening, contact Consultant Anaesthetist and Paediatrician)

Give high flow oxygen to achieve normal saturations (>94%)

Consider High Flow Humidified Oxygen

Nebulised β2agonist every 20 mins

Nebulised Ipratropium bromide every 20 mins

Oral prednisolone or intravenous hydrocortisone

If poor response after 3 nebules:

Give IV magnesium sulfate (unlicensed) 40mg/kg (Max 2g) (0.16mmol/kg, max 8mmol) over 20 mins

If not improving rapidly:

Give intravenous magnesium sulphate

Give intravenous salbutamol bolus

Start salbutamol infusion 2microgram/kg/min

If poor response after 1 hour:

Continuous nebulisers

Start salbutamol infusion at 2microgram/kg/min

Admit to ward

Oxygen to maintain saturations >94%

Nebulised salbutamol 1-4 hourly

Nebulised Ipratropium bromide 4 hourly

Continue Steroids

If no improvement within 30 minutes or

continuing to deteriorate:

Aminophylline loading 5mg/kg (max 500mg) over 20 mins if not on oral theophyllines

Aminophylline infusion 0.5 - 1mg/kg/hr

Consultant Anaes/Paeds Review

Still no improvement:

Consider second dose of intravenous magnesium sulphate (D/W NWTS)

Increase salbutamol infusion (max 5microgram/kg/min)

Consider CXR/antibiotics/alternative diagnosis

Blood gas + lactate

Prepare for intubation

Improving

Improving

Improving

Continuous monitoring:

ECG, SpO2, RR

Consultant review

Admit to Paeds HDU

4

Guidelines for Management of Acute Severe Asthma in Children <2 years

Oxygen: Children with life-threatening asthma or SpO2 <94% should receive high-flow oxygen via a

tight-fitting face mask or nasal cannula at sufficient flow rates to achieve normal saturations. High-flow humidified oxygen (optiflow or vapotherm) may be considered early and used on HDU aiming for flow 2 L/kg/min.

Nebulisers: Oxygen-driven nebulisation is recommended

Salbutamol: 2 to 5yrs 2.5mg 5yrs 5mg

Ipratropium bromide Under 12yrs 250 micrograms Over 12yrs 500 micrograms Combining nebulised ipratropium bromide with nebulised β2-agonist produces significantly more bronchodilatation than β2agonist alone. If a child has poor response to initial dose of β2agonist subse-quent doses should be given in combination with ipratropium every 20 minutes for the first hour then four hourly.

Steroids: Prednisolone: 2mgkg od started within 1 hour of presentation Max 40mg unless on maintenance steroids when max dose is 60mg Hydrocortisone: 4 mg/kg 6 hourly intravenously (max 100 mg per dose) started within 1 hour of presentation Higher doses may be given in patients on maintenance steroids. Benefits apparent within 3-4 hours. Oral and intravenous steroids are of equivalent efficacy so intravenous steroids should be reserved for those unable to retain oral medications or most severely affected. Continue until clinically improved. Tapering unnecessary unless course of steroids continues for >14 days.

Magnesium sulfate (unlicensed): 40mg/kg (max 2g) (0.16mmol/kg, max 8mmol) intravenous-

ly over 20 min. For ease of prescribing and administration, doses are banded according to patient weight (see page 10). In practice this is first intravenous therapy used as it is safe and causes less tachycardia. Dose may be repeated in severe cases.

Intravenous Salbutamol: Bolus: Over 2 years of age 15 microgram/kg (MAX DOSE 250 microgram). Give over 10 mins

Infusion: 1-2 microgram/kg/min (Rarely doses as high as 5microgrm/kg/min may be used on PICU) Start at 2 micrograms/kg/minute

Patients should be on continuous cardiac monitoring & have minimum of 12 hourly U&Es. Nebulised β2

-agonists should be continued 4 hourly whilst patient is receiving intravenous salbutamol unless there are signs of salbutamol toxicity when they should be stopped. Salbutamol (nebulised or iv infusion) may cause a marked metabolic and lactic acidosis especially if patient is underfilled due to poor fluid intake and increased insensible losses.

NB: Doses above 2microgram/kg/min MUST be discussed with paediatric/anaesthetic consultant and NWTS as they are associated with significant toxicity

Aminophylline Loading dose: 5 mg/kg over 20 min (Omit if on oral theophyllines/aminophylline)

MAX DOSE 500mg

Infusion: Child 1month to 11 years: 1mg/kg/hr

Child 12-17 years: 0.5mg/kg/hr

Doses should be adjusted according to plasma theophylline levels (see page 13)

Intravenous salbutamol and aminophylline are incompatible. Salbutamol is compatible with magnesium

5

Guidelines for Management of Acute Severe Asthma in Children >2yrs

CXR should be considered in following situations

Surgical emphysema

Persistent unilateral signs suggesting pneumothorax, lobar collapse or consolidation

Previous pneumothorax

Severe/Life-threatening asthma not responding to treatment

Mechanically ventilated patient

Blood gas measurements

Should be considered if there are life-threatening features not responding to treatment

Normal or raised pCO2 indicates worsening asthma and imminent respiratory failure

Capillary blood gases will give an accurate measure of pH and pCO2

Children receiving large doses of β2agonists may develop a lactic acidosis which will resolve as the

dose of β2agonist is reduced, but may need fluid bolus . Discuss with consultant.

Antibiotics

The majority of acute asthma attacks are triggered by viral infections

Decision for antibiotics should be made on clinical grounds

Non-pharmacological interventions in acute severe asthma

Physiotherapy

No role in unventilated asthmatic patient

Alternative Diagnoses to consider in child that is not improving

Anaphylaxis/Allergic Reaction Severe Pneumonia Atypical Infection

Hyperventilation Inhalational injury Foreign body

Pulmonary oedema

6


Intubation in Acute Severe Asthma is a High Risk Procedure

Indications for

Intubation

Cardiac/Respiratory Arrest

Exhaustion

Hypoxia despite high flow oxygen

Worsening respiratory acidosis

Altered sensorium (agitation, confusion, decreased GCS)

Risks of

Intubation

Low oxygen reserve

Rapid desaturation

Difficult to ventilate

Relative hypovolaemia

Delayed gastric emptying

Pre-oxygenation

Most experienced available operator

Use largest fitting/cuffed ET tube

Anticipate hypotension. Good iv access

Give 20ml/kg fluid bolus pre-induction

Prepare vasopressors e.g. 0.1 ml/kg adrenaline

1 in 10,000 made up to 10 mls 0.9% sodium

chloride (use 1-2 ml aliquots to maintain BP)

Rapid sequence induction

eg ketamine + suxamethonium

Drugs for

induction

Avoid histamine-releasing drugs if possible (atracurium, thiopentone, morphine)

Use ketamine or fentanyl

Volatile anaesthetic agent available for immediately post-intubation

Other

bronchodilators

Ketamine

Volatile anaesthetic agents

Adrenaline 1:10,000 0.1ml/kg iv/via ETT can be used in extremis

On-going sedation Use ketamine and fentanyl or midazolam

Avoid morphine as causes histamine release

7


Difficulties with Ventilation in Acute Severe Asthma

REMEMBER HYPOXIA KILLS, HYPERCAPNOEA DOES NOT!

High Peak Pressures causing barotrauma/pneumothorax/air leaks/reduced cardiac

output

Strategies: Try PCV or square wave ventilation

Limit Pmax(<35-40)

Permissive hypercapnia (pH>7.15)

Large, cuffed ETT will reduce resistance and leak

Keep muscle relaxed initially especially whilst high pCO2

Incomplete Expiration Slow emptying of alveolus causes poor gas exchange,

progressive gas trapping and ↑ residual volume

Strategies: Try low respiratory rates 10-20 and long expiratory times (I:E ratio ≥1:3 )

Manual decompression (disconnect ETT and manually compress chest)

Physiotherapy with saline lavage may help but use slow bagging rate

Intrinsic PEEP

Aim to match extrinsic PEEP to intrinsic PEEP to reduce gas trapping

Mucus Plugging

Suction and physiotherapy with saline lavage (can make worse if inadequately

sedated). In extreme cases, instillation of Dornase Alpha may improve severe mucous

plugging.

Discuss EARLY with NWTS

8


Discontinuing Intravenous Bronchodilators

Aminophylline: Elimination half-life 3-5 hours

Reduce dose by 50% of original dose every 6 hours

After discontinuing infusion, aminophylline will be cleared within 24hours

Salbutamol: Elimination half-life 4-6 hours

Reduce dose by 1microgram/kg/min every 6 hours

After discontinuing infusion, salbutamol will be cleared within 24 hours

NB: Substantial systemic absorption of salbutamol occurs via GI tract

when administered by inhalation so intravenous infusions should be

discontinued before stopping nebulised salbutamol

Patients should receive nebulised β2agonists every 2 hours and nebulised ipratropium

bromide every 4 hours whilst weaning off intravenous bronchodilators.

NB: Rebound may occur 24—48 hours after stopping either infusion so observe in hospi-

tal for this time. Some patients with particularly brittle asthma may require a slower

weaning regime.

Criteria for reducing bronchodilator therapy

Normal respiratory effort

Normal ability to speak

Reduction in oxygen requirement

Discharge planning after severe asthma attack:

Check inhaler technique

Start or review dosage of preventer treatment

Written asthma plan for subsequent attacks with clear instructions about use of bronchodila-

tors and need to seek urgent medical attention if worsening symptoms

Contact GP to arrange Primary care follow up within 48 hours

Paediatric team follow up within 2 months

Refer to Paediatric Respiratory Specialist if life-threatening features, required intra-

venous aminophylline or salbutamol or invasive ventilation.

9

Management of acute wheeze in children under

2 years of age This guideline is not appropriate for use in children under the age of 2 years. In such children, a

number of different diagnoses need to be considered and the response to treatment is variable.

Such children should be managed on an individualised basis and early consultant involvement

should be obtained.

If intravenous salbutamol is given to children under 2 years the loading dose should be

5 microgram/kg

Children under two years with a clinical picture consistent with asthma may respond better to mag-

nesium sulphate and aminophylline rather than salbutamol

Severe asthma Previous near-fatal asthma

Previous hospital admission for asthma

Requiring 3 or more classes of asthma medication

Repeated attendances at emergency department for asthma care

History of anaphylaxis

Plus Adverse behavioural/psychological features

Poor compliance

Failure to attend appointments

Fewer GP contacts

Self-discharge from hospital

Psychosis, depression, psychiatric illness or deliberate self harm

Alcohol or drug abuse

Obesity

Learning difficulties

Looked after children

Staff should have a lower threshold for admission to hospital for children with above risk

factors

Patients at risk of near-fatal/fatal asthma

10

Appendix 1: Additional Drug Information

Magnesium

Nebulised Magnesium: There is some limited evidence to support the use of nebulised magnesium in

addition to standard treatment (Cochrane review 2017) and its use does not seem to be associated with

adverse events.

Intravenous Magnesium Sulfate (unlicensed)

This can be given anywhere in the hospital if needed acutely. If the patient improves, they can continue

to be managed within the general ward environment. In practice this is often first intravenous therapy

used as is safe and causes less tachycardia.

All children who receive intravenous magnesium sulfate must be admitted to hospital.

There is some evidence that higher doses of magnesium may be of benefit clinically but this is not cur-

rently recommended in the BTS guidelines. In practice repeating the dose 1-2 hours after initial dose is

clinically safe. Patients requiring multiple doses should be discussed with NWTS.

Form: Magnesium sulfate 50% injection containing 500mg/ml of magnesium sulfate. This is

available in 2ml and 10ml ampoules. Caution if using other strengths as the table below will not be ap-

plicable

Dose: 40mg/kg over 20 minutes. The maximum dose is 2g. Can be administered centrally or pe-

ripherally. Dilute volumes below to 20ml for administration. Doses are banded by weight below for

ease of prescribing and administration.

Contra-indications: Myasthenia gravis

Severe renal impairment

Overdose: Hypermagnesaemia. Dependent on the size of the overdose, progressive muscle

weakness, significant hypotension and ultimately respiratory failure have been reported.

Patient WEIGHT (kg) DOSE Magnesium

sulfate (40mg/kg)

VOLUME Magnesium sulfate

50%

Further DILUTION

5-5.9kg 200mg 0.4mL

Then further dilute the

required dose of magnesi-

um sulfate 50% to 20ml

with sodium chloride

0.9% for administration

6-6.9kg 250mg 0.5mL

7-7.9kg 300mg 0.6mL

8-8.9kg 300mg 0.6mL

9-9.9kg 350mg 0.7mL

10-11.9kg 400mg 0.8mL

12-13.9kg 500mg 1 mL

14-15.9kg 550mg 1.1mL

16-17.9kg 600mg 1.3ml

18-19.9kg 700mg 1.4mL

20-21.9kg 800mg 1.6mL

22-23.9kg 900mg 1.8mL

24-25.9kg 950mg 1.9mL

26-27.9kg 1000mg 2 mL

28-29.9kg 1100mg 2.2mL

30-34.9kg 1200mg 2.4mL

35-39.9kg 1400mg 2.8mL

40-44.9kg 1600mg 3.2mL

45-49.9kg 1800mg 3.6mL

50kg & above 2g 4mL

11

.

Intravenous Salbutamol for Severe/Life-threatening Asthma

A bolus dose is recommended whilst the infusion is being drawn up (as infusion can take time to

prepare) to minimise delays, however this is not required if there is no delay in starting the

infusion.

Form: Salbutamol 1mg/ml Injection.

Bolus IV Salbutamol < 2 years of age 5 microgram/kg

>2 years of age 15 microgram/kg

(MAXIMUM DOSE 250 microgram)

Give over 10 minutes. Dilute injection to 50 microgram/ml (1ml of salbutamol 1mg/1ml diluted to

20ml with water for injection, sodium chloride 0.9% or glucose 5%)

15microgram/kg bolus over 10 minutes is equivalent to 1.5 microgram/kg/min infusion for the

same period

Continuous IV infusion: 1 to 2 microgram/kg/minute (Rarely doses up to 5microgram/

kg/min can be given on PICU)

Usual starting dose is 2micrograms/kg/min

Doses >2micrograms/kg/min should be used with extreme caution especially in

patients > 50kg as there is an increased incidence of side effects. We would strongly advise dis-

cussion with NWTS if increasing infusion above 2microgram/kg/min.

High doses of salbutamol (ie 3-5 microgram/kg/min) may cause tachycardia and SVT

without any additional benefit.

Management of SVT following Salbutamol Infusion

SVT has been reported in patients receiving salbutamol loading doses and infusions

at the higher dose range. Adenosine can cause bronchospasm in known patients

with asthma so should be used with caution in acute severe asthma. Please discuss

with NWTS/ Paeds cardiology consultant on call for further advice.

NOTE: CRASHCALL currently gives values for central administration of

salbutamol. If use of this is planned please discuss with NWTS first.

12

Guidelines for Management of Acute Severe Asthma in Children

Salbutamol infusion for Peripheral administration:

Draw up 10 mg of salbutamol (= 10ml of salbutamol 1 mg/ml)

Make up to 50mls with 5% glucose or 0.9% sodium chloride

Final concentration = 10 mg in 50 ml i.e. 200 micrograms/ml salbutamol

PERIPHERAL infusion rate: 0.3ml/kg/hr = 1microgram/kg/minute.

Example Dose Calculation:

For a 30kg child to run the infusion at 2microgram/kg/minute:

2microgram/kg/minute x 30kg = 60microgram/minute

60microgram/minute x 60minutes = 3600microgram/hour

Infusion contains 200microgram in 1ml therefore to calculate ml/hour:

3600 microgram/200microgram x 1ml = 18ml per hour

Weight 1microgram/kg/min 2microgram/kg/min 3microgram/kg/min (discuss with NWTS/PICU)

5kg 1.5mls/hr 3mls/hr 4.5mls/hr

10kgs 3mls/hr 6mls/hr 9mls/hr

15kgs 4.5mls/hr 9mls/hr 13.5mls/hr






45kg 13.5mls/hr 27mls/hr 40.5mls/hr

50kgs 15mls/hr 30mls/hr

55kgs 16.5mls/hr

60kgs 18mls/hr

13

Aminophylline infusion for Peripheral administration: Draw up 500mg of aminophylline and add to 500mls 0.9% sodium chloride

Final concentration = 500mg in 500mls i.e. 1mg/ml aminophylline

Aminophylline is compatible with up to 40mmol/litre of Potassium chloride

Loading Dose: 5mg/kg over 20 mins (max dose 500mg). Omit if on oral theophyllines

Infusion rate: 1 month to 11 years 1mg/kg/hr = 1ml/kg/hr

12-17 years 0.5mg/kg/hr = 0.5ml/kg/hr

Therapeutic monitoring: Check levels at 4-6 hours until stable and then every 24 hours

Therapeutic range 10-20mg/l

Plasma levels correlate well with clinical effect but NOT with toxicity

Response to monitoring: <5mg/L Increase dose by 50% and recheck in 6 hours

5-15mg/L Continue. Recheck 24 hours

15-20mg/L Half infusion rate and recheck in 6 hours

>20mg/L STOP infusion and recheck levels in 6 hours. Restart at half the previous infusion rate once levels <15mg/l

Weight 1mg/kg/hr

5kg 5mls/hr

10kgs 10mls/hr

15kgs 15mls/hr

20kgs 20mls/hr

25kgs 25mls/hr

30kgs 30mls/hr

35kgs 35mls/hr

40kgs 40mls/hr

45kg 45mls/hr

50kgs 50mls/hr

55kgs 55mls/hr

60kgs 60mls/hr

14


References

Magnesium sulfate for treating exacerbations of acute asthma in the emergency department

(Review) Griffiths B, Kew KM. Cochrane Database Syst Rev. 2016 Apr 29;4

Inhaled magnesium sulfate in the treatment of acute asthma (Review). Knightly R, Milan SJ.

Cochrane Database Syst Rev 2017, Issue 11 . CD003898

MAGNEsium Trial In Children (MAGNETIC): a randomised, placebo-controlled trial and economic

evaluation of nebulised magnesium sulphate in acute severe asthma in children. Powell CV, Ko-

lamunnage-Dona R. MAGNETIC study group. Health Technol Assess. 2013 Oct;17(45):v-vi, 1-216.

Clinical pharmacokinetics of magnesium sulphate in the treatment of children with severe acute

asthma. Rower JE, Liu X, Yu T, Mundorff M, Sherwin CM, Johnson MD. Eur J Clin Pharmacol. 2017

Mar;73(3):325-331. doi: 10.1007/s00228-016-2165-3. PMID:27909740

BTS/SIGN British Guideline on the Management of Asthma—a National Clinical Guideline May

2008, Revised September 2016

Management of Acute Severe Asthma in children (aged >2years) version 4 Royal Manchester Chil-

dren’s Hospital, CMFT. September 2015. Originated by Rachael Barber, PICU Consultant, Clare Mur-

ray, Respiratory Consultant.

Intravenous salbutamol for childhood asthma: evidence-based medicine? Starkey E, Mulla H, Pan-

dya H, Archives of Disease in Childhood 2014;99:873-877.

Lexicomp 18th Edition

British National Formulary for Children 2016-17

www.crashcall.net for drug doses

https://www.ncbi.nlm.nih.gov/pubmed/24144222

https://www.ncbi.nlm.nih.gov/pubmed/24144222

15

Appendix 1 Guidelines for Management of Acute Severe Asthma in Children >2yrs

16

Appendix 1 continued Guidelines for Management of Acute Severe Asthma in Children >2yrs

17

Resources www.crashcall.net - for intubation drugs / sedation regime Contact numbers: Regional Paediatric Intensive Care Unit Alder Hey Childrens Hospital 0151 252 5241 Regional Paediatric Intensive Care Unit Royal Manchester Childrens Hospital 0161 701 8000 NWTS (North West & North Wales Paediatric Transport Service) 01925 853 550 Guideline authors: Authors: Pete Murphy, Transport Consultant NWTS and Consultant Paediatric Anaesthetist, Alder Hey Rachael Barber, NWTS Consultant and PICU Consultant, Royal Manchester Children’s Hospital Aradhana Ingley, Associate Specialist in Paediatrics, Glan Clwyd Hospital, North Wales Adam Sutherland, Senior Clinical Pharmacist, Royal Manchester Children’s Hospital Fran Child, Consultant Paediatric Respiratory Consultant, Royal Manchester Children’s Hospital Jon Couriel, Consultant Paediatric Respiratory Consultant, Alder Hey Consulted parties: North West & North Wales Paediatric Transport Service (NWTS) North West and North Wales Paediatric Critical Care Network PICU, Royal Manchester Children’s Hospital PICU, Alder Hey Children’s Hospital

Guideline contact point: [email protected] Please visit our website for the most up to date version of this guideline: www.nwts.nhs.uk

Date of Approval by Host Trust:

Date of Review:


doument ontrol page

Documents