Minimal or Less Invasive Surfactant Treatment

2019
Quality Improvement of Neonatal Care: What Have We Learnt?
Minimal or Less Invasive Surfactant Treatment

MIST & LISA
Peter Dijk
Pediatrician-neonatologist
Beatrix Childrens Hospital
University Medical Center Groningen
2019
The Historical Perspective of RDS and Surfactant
1950’s Pattle and Clements discover pulmonary surfactants

1959 Avery and Mead: RDS is caused by surfactant deficiency
1964 Robillard and Chu: 1st trial with surfactant: by aerosol - no effect!
1971 Gregory developed 1st nasal CPAP device
1980s many Surfactant trials about dosing, timing, administration route
higher survival rate – but no reduction in BPD
neonatal ventilators further developed
2000 revival van CPAP after paper of Avery – CPAP reduction in BPD
ventilator induced lung injury acknowledged
>2000 combinations of surfactant and CPAP
INSURE – MIST – LISA - …
2019
SURFACTANT vs CPAP Dilemma
SURFACTANT has shown to be highly effective to improve survival

but you need to give it into the lungs
intubation needed (and ventilation)
=> VIL and more BPD
CPAP has shown to be effective and safe

less BPD (?)
We want to improve survival with less BPD!
COMBINATION OF CPAP and selective SURFACTANT
INSURE - MIST - LISA - other?

What method is better? Timing? Indications Surfactant?
2019
Summary of evidence – CPAP+SURFACTANT

Tomorrow – more about the evidence!
Surfactant administration with catheter during CPAP may be beneficial
Reduces the need for mechanical ventilation in individual studies

and meta-analyses – but not for the smallest infants (<26wks)
Reduces BPD in meta-analyses, but in none of the individual trials
Still debate about treatment thresholds (FiO2) in relation to GA,

What catheter/device/technique, role of analgesia/sedation.
Large studies are on their way – e.g. OPTIMIST (Australia)

2019
In European guideline on RDS
Lisa/MIST is preferred mode of

Surfactant administration in
Spontaneous breathing babies
2019
Surfactant administration on CPAP without intubation
LISA
Less Invasive Surfactant Administration
Angela Kribs method, Köln (Germany)
flexible catheter introduced using Magill Forceps
-story-
MIST
Minimal Invasive Surfactant Treatment
Hobart method, Peter Dargaville (Australia)
Angiocath introduced a vue, without Magill
2019
LISA
Flexible catheter (feeding) introduce catheter with

hold catheter
syringe with surfactant Magill under vision of
Close mouth
Magill forceps laryngoscope
Instillate surfactant 1-3 min
Laryngoscope While baby on CPAP
2019
MIST
stiff (angio)catheter introduce bend catheter hold catheter

syringe with surfactant under vision of close mouth
laryngoscope laryngoscope instillate surfactant
while baby on CPAP in 1-3 min
2019
LISA
https://youtu.be/0OmXlOXETZY
- open hyperlink -
2019
LISA with video laryngoscope
https://youtu.be/IYf92NN1kV0
- open hyperlink -
2019
MIST catheters
LISA Catheter Angio catheter 5F

(Chiesi)
which is MIST catheter….
SurfCath
(Vygon)
2019
Alternative “catheter” device – no need for Magill forceps

“combination of flexibele LiSA and “stiff” Hobart method
2019
LISA / MIST is part of a bundle non-invasive gentle approach
Antenatal transfer of mother to NICU center

Antenatal steroids
Avoid (general) anesthetics to the mother
Avoid hypothermia
Avoid unnecessary manipulations
Delayed cord-clamping
Minimal Handling – Soft landing
Early caffeine
Optimize CPAP from the start – do not interrupt
2019
Non-pharmalogical methods to avoid pain and discomfort
Positioning
Gentle handling
Holding – facilitated tucking – swaddling with blanket
Sucrose
Atropine - sometimes used to prevent bradycardia and secretion mucus

during procedure - may win some time
2019
Analgesia / Sedation
Procedure is likely to cause discomfort
But spontaneous breathing is essential for the idea of LISA/MIST
Preferably Positive Pressure Ventilation is be avoided – if possible
Evidence of safety and effect of drugs is lacking, but some use:

Propofol improves comfort but
longer desaturation and more pos press ventilation needed
Fentanyl Stiff thorax! Up to 10% (be prepared!)

more positive pressure ventilation needed
Ketamine high prevalence of apnea needing PPV
Remifentanil unpredictable and also stiff thorax
Morphine long half time – much longer than Naloxone!
If you use these – be prepared for emergency intubation

2019
Protocol of Netherlands Neonatal Network
Indication
24-40 wks with RDS (clinical and/or X-ray)*

24 wekers: not less need for ventilation, maybe less complications
> 32 weeks: not much evidence - more difficult (struggle)
nCPAP level 6-8 cm H2O
FiO2 < 30 weeks: >0,30
> 30 weeks: >0,35
PLUS
Patiënt is stable on nCPAP and has i.v. access
Patiënt breaths spontaneously
No signs of pneumothorax
No severe sepsis or circulatory failure
*UMCG participates in OPTIMIST: <29 wks only MIST when in trial

otherwise intubate, > 34 wks Intubate (struggle/other causes of RDS)
2019
Preparation
Premedication Caffeine - loading dose i.v. – if not given before
Atropine 10ug/kgBW i.v.
Sucrose 20% (0,2 ml/kgBW)
no standard analgetics or anesthesia
Catheter feeding cath or umbilical cath 5F (LISA)

or angiocath (or special surfactant catheter) (MIST)
MARKED on right insertion depth (water resistent marker)
<26 wks 1 cm >26 wks 1,5 cm
Laryngoscope or videoscope check power/battery and blade size
Magill forceps if using “soft flexible catheter”
Surfactant 100-200 mg/kg – depending on what surfactant/GA-BW
Materials and medication for emergency intubation must be prepared!

2019
Procedure
Nurse holds baby gently – facilated tucking in supine position

CPAP continues
Direct Laryngoscopy or videoscopy
Insert catheter orally between vocal cords on right moment
when glottis and vocal cords are open – to marked depth
Remove scope and keep catheter fixed in place
Close mouth – keep PEEP
Instill surfactant slowly in 1 to 3 min
look at infant: check saturation, heart rate, respiration
Remove catheter
Check surfactant spill to stomach
Continue CPAP – try to wean actively
2019
Possible complications
Apnea
Desaturation <60% or < 80% for more than 20 sec – despite increase FiO2
Bradycardia < 80 or <100 for more than 10 sec
Coughing – struggling
What to do (steps)
Stop instillation of surfactant and remove catheter
Give more oxygen
Increase PEEP
Give NIPPV – positive pressure ventilation
If this does not work sufficiently – intubate and ventilate
2019
Side effects
Need for more than one attempt 10-25%

Need for positive pressure ventilation 10-45%
Bradycardia or desaturation 10-35%
Dislocation of catheter
Reflux of surfactant
Depends on the experience of medical team

Practise
2019
21%
<6 hrs
>30%
<12-24 hrs
>30-35%
<24 hrs
2019
Exclusion
Severe RDS
Need for ventilation
FiO2 > 50% < 32?wks
FiO2 > 60% > 32?wks
Other reasons for RD
Malformations
No experience
Pneumothorax
Apnea’s
2019
Conclusions
Surfactant administration with catheter during CPAP by MIST or LISA is
probably the most beneficial way to treat RDS
Reduces the need for mechanical ventilation in individual studies

and meta-analyses – but not for the smallest infants (<26wks)
Reduces BPD in meta-analyses, but in none of the individual trials
Still debate about treatment thresholds (FiO2) in relation to GA,

Timing, what catheter or device or technique to use.
Early treatment seems appropriate
Role of analgesia/sedation is still unknown – but spontaneous

breathing infants on CPAP is the keystone of LISA/MIST
Large studies are on their way – e.g. OPTIMIST (Australia)

2019
And wait for real NON-invasive surfactant treatment

Minimal or Less Invasive Surfactant Treatment

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2019

Quality Improvement of Neonatal Care: What Have We Learnt?

Minimal or Less Invasive Surfactant Treatment

The Historical Perspective of RDS and Surfactant

1950’s Pattle and Clements discover pulmonary surfactants

SURFACTANT vs CPAP Dilemma

SURFACTANT has shown to be highly effective to improve survival

CPAP has shown to be effective and safe

We want to improve survival with less BPD!

COMBINATION OF CPAP and selective SURFACTANT

INSURE - MIST - LISA - other?

Summary of evidence – CPAP+SURFACTANT

Surfactant administration with catheter during CPAP may be beneficial

Reduces the need for mechanical ventilation in individual studies

Reduces BPD in meta-analyses, but in none of the individual trials

Still debate about treatment thresholds (FiO2) in relation to GA,

Large studies are on their way – e.g. OPTIMIST (Australia)

In European guideline on RDS

Lisa/MIST is preferred mode of

Surfactant administration on CPAP without intubation

Flexible catheter (feeding) introduce catheter with

stiff (angio)catheter introduce bend catheter hold catheter

LISA with video laryngoscope

LISA Catheter Angio catheter 5F

Alternative “catheter” device – no need for Magill forceps

LISA / MIST is part of a bundle non-invasive gentle approach

Antenatal transfer of mother to NICU center

Non-pharmalogical methods to avoid pain and discomfort

Atropine - sometimes used to prevent bradycardia and secretion mucus

Evidence of safety and effect of drugs is lacking, but some use:

Fentanyl Stiff thorax! Up to 10% (be prepared!)

Ketamine high prevalence of apnea needing PPV

Remifentanil unpredictable and also stiff thorax

Morphine long half time – much longer than Naloxone!

If you use these – be prepared for emergency intubation

24-40 wks with RDS (clinical and/or X-ray)*

*UMCG participates in OPTIMIST: <29 wks only MIST when in trial

Catheter feeding cath or umbilical cath 5F (LISA)

Laryngoscope or videoscope check power/battery and blade size

Magill forceps if using “soft flexible catheter”

Surfactant 100-200 mg/kg – depending on what surfactant/GA-BW

Materials and medication for emergency intubation must be prepared!

Nurse holds baby gently – facilated tucking in supine position

Need for more than one attempt 10-25%

Depends on the experience of medical team

Reduces the need for mechanical ventilation in individual studies

Still debate about treatment thresholds (FiO2) in relation to GA,

Early treatment seems appropriate

Role of analgesia/sedation is still unknown – but spontaneous

Large studies are on their way – e.g. OPTIMIST (Australia)

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