Surfactant replacement therapy in acute respiratory ... - RM Solutions

Surfactant Replacement Therapyin Children with Acute RespiratoryDistress SyndromeDr Ali Al shehriPediatrics Critical care consultantAssistant professor pediatricsKing Saud Bin Abdulaziz for health sciencesKAMC/KFNGH

Disclosure

Case 1• 2 yrs boy 50% flam burn , inhalationinjury• COHb : 14 % on 100% FiO2 .• Hypoxic index: 568 .• ABC• Day 2 : OI : 53 PaO2/FiO2: 71• HFOV: MAP: 38 AMP: 80Hz : 7 FiO2 100% Sat : 85%• Permissive hypercapnea

Case 1• Dopamine : 10 micg/kg/mint.• UO : normal• Surfactant (servant) given 80 ml/m2/dose.• Improve oxygenation.• Day3 : OI: 20.• Multiple debridement and grafting.• Extubated week 5.• Discharge week 6.

Case 2• Preterm 24/52, CA 10 days, BPD referred forlaser photocoagulation.• Day 2 : RSV bronchiolitis.• Intubated : HFOV, OI :51, HI: 56• Dopamine : 15 micg/kg/mint• Surfactant (servant) 4ml/kg , two doses given.• Day 4 : shift to CMV.• OI : 10• Extubated : 18 days .• Discharge : one month.

Clinical Trials in Neonate• 2000-2005.• Birth –one month.• Children excluded .• 175 paper, 43 RCTs or SR.- Reduce mortality and pulmonary air leak- Severe meconium aspiration syndrome: reduce MV, O2 therapy ,time for hospitalization and need for ECMO.Halliday HL. Recent clinical trials of surfactanttreatment for neonates. Biol Neonate 2006; 89:323–329

Surfactant• Type II pneumocytes.• Lower alveolar surface tension.• 80% phospholipids (dipalmitoyl phosphatidylcholine 85% ).• 8% neutral lipids.• 12% proteins SP –A,B,C, and D- Surface tension (A,B,C )- Immune defense , particle clearance- Modulate lung inflammation ( D , A )

Type of SurfactantPed criti care medicine basic science and clinical evidence Derrk 2007

Type of SurfactantPhLip SPA SPB SPC SPDHumann surfactant 85% 5% 2% 2% 1%Exogenous naturel Surfactant 96% 0 2% 2% 0Infarsurf (Calfctant ) 0.9%Survanta (Beractant) 0.004%Synthetics Surfactant 100% 0 0 0 0Exosurf

Clinical trails• Outcome related :- Mode of delivery/dose(Better with entubation)- Direct vs indirect ALI(Better in direct )- Type of surfctant .-Time .(Natural better and moreresistant for inhibitionthan synthetics )(Early better than late )

Clinical trial adult• 4 RCT• Failed to demonstrate a mortality benefit.- Anzueto A, et al. Aerosolized surfactant in adults with sepsis-induced acute respiratorydistress syndrome: Exosurf Acute Respiratory Distress Syndrome Sepsis Study Group.N Engl J Med 1996; 334:1417–1421- Gregory TJ, Steinberg KP, Spragg R, et al. Bovine surfactant therapy for patients withacute respiratory distress syndrome. Am J Respir Crit Care Med 1997; 155:1309–1315- Lewis JF, Walmrath HD, et al. Effect of recombinant surfactant protein C-basedsurfactant on the acute respiratory distress syndrome. N Engl J Med 2004; 351:884–892- Jozef Kesecioglu1 et al, Exogenous Natural Surfactant for Treatment of Acute LungInjury and the Acute Respiratory Distress Syndrome Am J Respir Crit Care Med Vol180. pp 989–994, 2009-

Clinical trial in pediatrics• RCT6 ( 3 ALI/ARDS an 3 bronchiolitis)• Case report 20• Uncontrolled 7• Retrospective 3• Case control 1• Non randomized 1Duffett M, Choong K, Ng V, RandolphA,Cook DJ: Surfactant therapy for acuterespiratory failure in children: asystematic review and meta-analysis.Crit Care 2007.

Clinical trial in pediatrics ALI/ARDS• Improve gas exchange, reduce PIP and shorten CPPV and ICU stayLuchetti et al, Porcine-derived surfactanttreatment of severe bronchiolitis Scaactaaneasthesiol 1998 Aug;42(7):805-10.• Reduce PIP, , MV days p

Clinical trial in pediatrics ALI/ARDS• Douglas F. Willson et al. JAMA, January 26, 2005—Vol 293.- Improve oxygenation and mortality.- Minor transient hypoxia , hypotension around instillation

Clinical trial in pediatrics• Phase 3 multicenteral trail, randomized, blinded• Natural lung surfactant (calfactant) vs placebo .• 21 centers.• 153 patient.• 3 years study period.Wilson etal jama 293: 470-476, 2005

Clinical trial in pediatrics• Eligibility- Age 1 wk to 21 yrs.- Respiratory failure due to parynchymal lung disease .• Enrollment within 24 hours of initiation of mechanicalventilation( extended to 48 hours after the first 50 patient) .• OI > 7Wilson etal jama 293: 470-476, 2005

Clinical trial in pediatrics• Treatment regimen : 80 ml/m2 /dose calfcatant over 10 -15mint.• Retreatment ( 2 nd dose )At 12 hours if OI >7Wilson etal jama 293: 470-476, 2005

Clinical trial in pediatricsWilson etal jama 293: 470-476, 2005

Clinical trial in pediatrics• Subgroup analysis :- MR higher OI >13(37%) compared with OI >7 < 13(20%)- Less mortality in direct vs indirect lung injury placebo(8% vs 37%; P=.007)Wilson etal jama 293: 470-476, 2005

MortalityDuffett M, choong k etal meta-analysis. CritCare 2007.

Ventilator-free daysDuffett M, choong k etal meta-analysis. CritCare 2007

Duration of Mechanical ventilationDuffett M, choong k etal meta-analysis. CritCare 2007

Duration PCCU stayDuffett M, choong k etal meta-analysis. Crit Care2007

Clinical trial in pediatrics• RCT 1997 - 1999. pilot• PaO2/FIO2 < 100.• Result:- Improve oxygenation at 48 hrs dose (p 65• Patients with

Clinical trial in pediatricsInitial severity of hypoxemia correlated with mortalityPediatric Acute Lung InjuryProspective Evaluation of Risk Factors Associated withMortality Heidi R. Flori, Am J Respir Crit Care MedVol 171. pp 995–1001, 2005

Summery• ARDS/ ALI is life threatening disease .• Surfactant administration carry minimal adverse effectswith potential benefit .• RCT could NOT prove the efficacy.• Many confounders affecting the result of RCT.• Outcome surrogate variable other than mortality .

Summery• Surfactant not recommended as routine therapy .• May used in combination with other adjunct : if Protectivelung strategies and permissive hypercapnea optimized , maxand no benefit .• Consider in pt with potential max benefit with younger age ,high hypoxic index , direct lung injury, immunocompetent.• Further study .

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