peri- Extubation Medication in a PICU Setting

Medication used for Extubation

1. Peri-Extubation Medications Hussain Ali AL-Lawati 2nd year General pediatric resident Neonatal Intensive Care Unit Block 10 2023/2024

2. Objectives Rationale of Peri-extubation medications Overview of medications Evidence based backing up the use of specific agent Specific scenarios

3. Introduction Choice of Peri-extubation medications largely depend on Gestational age Presence of risk factors which increases chance of unsucessful extubation Planned VS accidental extubation Availability of resources

4. Introduction The use of Methylxanthine is evidence based in very preterm and possibly moderate preterm newborns. Their use for term infants is limited to surgical cases. Other medications’s use, like steroids, depend on these risk factors Prolonged mechanical ventilation Failed or multiple extubations

5. Hagen- Poiseuille Law ETT is a foreign body in contact with Mucosal surfaces Multiple attempts of intubation can lead to trauma and inflammation, mainly at the larynx and subglottic space Edema of the airway will narrow the diamter and increase resistance This will result in respiratory insifficency Epnephrine causes vasoconstriction of the upper airway vasculature, reducing the edema Steroids reduces inflammation of the upper and lower airway

6. Rationale The rationale of use is currently limited to Improving respiratory drive Reducing airway and lower respiratory tract inflammation Preventing bronchospasm In a cohort study by Benneyworth BD, post cardiac surgical patients with extubation failure had high length of hospital stay and mortality rates (23 VS 33 days) and (8% vs 2%) respectively!

7. 1) Caffeine Caffeine is used for treatment and prevention of apnea of prematurity, to prevent mechanical ventilation and to enhance chances of successful Extubation. There is no supporting evidence for continuation of caffeine when the patient is on Mechanical ventilation. McPherson C et al. Concluded that high doses of Caffeine in the first 24 hours of life increase the risk of cerebellar bleed

8. Cont 18 RCTs included in 2023 Cochrane review on the use of caffeine in neonates 6 of which done specifically on its use before extubation Pooled evidence from 6 RCTs concluded that use of caffeine VS Placebo reduced extubation failure rates by >50% 3 of the trials included Aminophylline as an adjunt, and pooled even better outcomes ~60%

9. WHO recommendation

10. Standard Dose VS High dose Caffeine 2 Australian metanalyses concluded that high doses of Caffeine, up to 80mg/kg Loading followed by 30mg/kg Maintenance compared to standard dose halfed the rates of extubation failure. Follow up studies at 12 month corrected age of survivors showed better neurocognitive outcomes in the former group. Due to concerns of cerebellar bleed, it is advisable to administer high doses beyond 72 hours of life.

11. Dose monitoring and duration Generally, TDM is not recommended Some suggest that when caffeine is used for >7days, TDM is recommended to achive levels less than 20mg/L. 2019 NICE guid e lines suggest increasing the dose to 20mg/kg if therapuetic effects are not met, with careful drug level monitoring No data yet on ideal duration of Caffeine is proposed

12. Caffeine VS Other MethylXanthines Limited number of studies have compared Caffeine to Theophylline and aminophylline. 1 comparative study on 45 preterm infants, two patients required reintubation from both groups. Amino/Theophylline are cheeper and more readily avaliable in resource limited centers If Caffeine is available, it is preferred to be used in view of established long term safetry profile. “CAP”

13. Doxapram A respiratory stimulant Used for refractory apnea of prematurity that is not responding to Methylxanthines and non invasive ventilation 8 RCTs published on the effects of Doxapram, 2 of which focused on its effects in prevention of reintubation. Barrington Kj and Carrizales et al showed little or no difference on rates of extubation failure when used as an adjunt to methylxanthines. DOXA trial regarding efficacy and safety is ongoing

14. Adrenaline and Salbutamol No RCTs done on use of adrenaline post extubation in preterm infants. 2 studies done showed improvement in surrogate markers (pulmonary airway resistance), without comparing to placebo! However, the only recommendation to use it for post extubation stridor at doses of 0.2ml/kg. Salbutamol “ C ross over studies” showed no data in improving extubation outcomes

15. Corticosteroids Short duration of corticosteroids are less likely to affect neurodevelopmental outcomes compared to longer courses used as in “DART” 3 RCTs were included in the cochrane review O ne article showed reduction in extubation failures, with NNT=11 It is recommended to use Dexamethasone for patients with previous extubation failure due to stridor or any other cause. The dose is 0.25mg/kg/dose given at 8h intervals. The first dose is to be given 4 hours prior to extubation.

16. S pecific scenarios 1) Post surgical neonates A retrospective study on 120 neonates undergoing cardiac surgery showed increased risks of extubation failures in population with genetic abnormalitites, hypoplastic left heart syndrome and post op infections. However, a cohort study by Benneyworth BD et al, on 899 patients undergoing cardiac surgery, showed that an airway anomaly was the only independent risk factor of extubation failure. post cardiac surgical patients with extubation failure had high length of hospital stay and mortality rates (23 VS 33 days) and (8% vs 2%) respectively.

17. 2) Term and late preterm newborns WHO suggests that methylXanthines can be given to newborn 34-37 weeks of gestation, as they might be at risk of apnea of prematurity. No evidence of use for term infants beyonf 37 WOG

18. 3) Accidental extubation The current recommendation is to give Caffeine for all accidental extubations <34 WOG within 6 hours of the incident. Duration to be continued for 6 days afterwards. “Cuffed tubes” are used to prevent accidental extubations in older children. But no data supporting that in neonates. The smallest cuffed tube is 3mm in diameter! A n obervational study reported no difference in post extubation stridor risk regardless of the type of ETT.

19. Take Home Message All children <34 WOG shall be started on Caffeine Theophylline and aminophylline are suggested alternatives In case of complicated extubation after 72 hours of life, high dose caffeine is preferrable Other medications like adrenaline, CST and salbutamol can be used for management of post extubation stridor

20. Reference