1. Ventilation/Non-Dialytic Therapies in the Paediatric BMT Patient
Desmond Bohn
The Department of Critical Care Medicine, The Hospital for Sick Children, Toronto

2. Paediatric BMT and Critical Care
Sepsis
Respiratory
Airway obstruction
Pneumonia/pneumonitis
Pulmonary haemorrhage
Interstitial pneumonitis
ARDS
Neurological
Seizures
Intracranial haemorrhage

3. Paediatric BMT and Critical Care
Hepatic failure
Venocclusive disease
GVHD
Renal failure
Drug nephrotoxicity
Cardiac failure
Drug toxicity

4. ICU outcomes in paediatric BMT patients
Diaz de Heredia C Bone Marrow Transplantation 1999; 24:
31/176 patients admitted to ICU post BMT - 18%
n BMT BMT
allogenic autologous
ARF
Septic shock 5 3 2
Neurological disorders 5 5
Heart failure 2 2
Others 4 2 2
26 patients underwent mechanical ventilation - survival 46%

5. BAL in ventilated and non-ventilated in children after BMT
Ben-Ari J Bone Marrow Transplantation 2001; 27:191
non-ventilated
ventilated

6. Diffuse alveolar hemorrhage in pediatric BMT patients
Heggen J Pediatrics 2002; 109:965

7. Diffuse alveolar hemorrhage in pediatric BMT patients
Heggen J Pediatrics 2002; 109:965

8. Diffuse alveolar haemorrhage in BMT patients
Presents with cough and tachypneoa
No underlying infective aetiology
Pulmonary haemorrhage on BAL
Usually occurs following engraftment
Incidence %
Characterised by thrombocytopoenia but normal coagulation
Treated with high dose steroids and PEEP
High mortality

10. Markers of oxygenation defect
PaO2/FiO2
< 200 = ARDS
Oxygenation
Index
MAP x FiO2 x 100
>15 = severe ARDS
PaO2

11. Lung recruitment in ARDS

12. Goals: 1. Avoid Overdistention 2. Avoid Underinflation
3. Keep the lung open
4. Reduce FiO2
Froese AB, Crit Care Med 1997; 25:906

13. Responses of baboons to prolonged hyperoxia
Fracica PJ J Appl Physiol 1991; 71:2352
normal
lethal toxicity - FiO2 1.0 for 110 h
alveolus
PMN
interstitial matrix
PMN
alveolus
PMN
interstitial matrix
alveolus
alveolus

14. Pulmonary oxygen toxicity
Davis WB N Engl J Med 1983; 309:878
FiO2 0.9 for 17 hrs in healthy humans

15. THE ACUTE RESPIRATORY DISTRESS SYNDROME NETWORK
VOLUME MAY 4, NUMBER 18
VENTILATION WITH LOWER TIDAL VOLUMES AS COMPARED WITH TRADITIONAL TIDAL VOLUMES FOR ACUTE LUNG INJURY AND THE ACUTE RESPIRATORY DISTRESS SYNDROME
THE ACUTE RESPIRATORY DISTRESS SYNDROME NETWORK

17. Surfactant proteins B & C
Surfactant in ARDS
Willson D Crit Care Med 1999; 27:188
Infasurf
Surfactant proteins B & C
42 children with ARDS

18. Nitric oxide in ARDS Dobyns EL J Pediatr 1999;134:406 Control iNO 6010 50 5 *
4 hours 12 hrs 40 *
Change in P/F ratio from baseline 30
Change in OI from baseline -5 20
-10 * * 10
-15
-20
4 hours 12 hrs

19. Nitric oxide in ARDS n=40 n=177 n=30 Michael JR
Am J Respir Crit Care Med
1999; 157:1372
Dellinger RP
Crit Care Med 1998; 26:15
Troncy E
Am J Respir Crit Care Med
1997; 157:1483

20. Nitric oxide in ARDS 5 RCTs in adults
3 case series and 2 RCTs in pediatrics
Physiological endpoints - improved oxygenation & reduction in PAP
% of patients are “responders”
No data suggests any improvement in outcome

21. Steroids in ARDS
Meduri GU JAMA 1998; 280:159
MODS Score Outcome

23. Effect of prone position on survival in ARDS
Gattinoni L N Engl J Med 2001; 345:568

24. Effect of prone position on survival in ARDS
Gattinoni L N Engl J Med 2001; 345:568

25. RCT of prone vs supine ventilation in ARDS/ALI
Gattinoni L N Engl J Med 2001; 345:568
304 patients randomised in 3 yrs
Mortality (%) Supine Prone
Intention to treat
End of study 25 21
ICU discharge
Prone vs supine protocol
End of study 27 22
ICU discharge
*Patients with P/F <

27. HFOV in Paediatric ARDS
Arnold J. Crit Care Med 1994; 22:1530
CMV HFOV
No. of patients 29 29
Duration of CMV 80 ± ± 240
FiO ± ± 0.15
PEEP 21 ± 5 22 ± 3
OI 29 ± ± 10

28. MAP >5 cmH2O above CMV setting (25-30 cmH2O)
Algorithm for the use of HFOV
MAP >5 cmH2O above CMV setting (25-30 cmH2O)
High FiO2 (>0.8)
Maintain MAP for mins
Attempt to decrease FiO2
yes no
Decrease FiO2
in increments to <0.6
Increase the MAP
in increments of 2 cmH2O
Response usually at cmH20

29. Oxygen delivery/consumption
DO2 = Q x CaO2 .
As DO2 decreases VO2 maintained by increased extraction
Oxygen extraction ratio = (CaO2 - CvO2)/CaO2
VO2 = Q x (CaO2 - CvO2) .

30. Published outcomes in paediatric BMT patients admitted to ICU
Number of Number Survival
BMTs ventilated ventilated patients
Lamas (23%)
Hagen (37%)
Jacobe (41%)
Keenan (16%)
Rossi (44%)
Warwick (40%)
Diaz de Heredia (46%)
Hayes (15%)
Nichols (9%)
Bojko (12%)
Todd (11%)

31. AHRF: an integrated approach
Pressure control ventilation (PIP <35 cmH2O)
Negative fluid balance (furosimide)
HFOV
Prone position ventilation
iNO ppm
?ECMO

32. Prognosis of paediatric BMT patients requiring ventilation
Rossi R Crit Care Med 1999; 27:1181
n = 41

33. Prognosis of paediatric BMT patients requiring PPV
Rossi R Crit Care Med 1999; 27:1181

34. Ventilation in paediatric BMT patients
Hagen SA Pediatric Crit Care Med 2003; 4:206

35. Ventilation in paediatric BMT patients
Hagen SA Pediatric Crit Care Med 2003; 4:206

36. Ventilation/Non-Dialytic Therapies in the Paediatric BMT Patient
Acute respiratory failure requiring PPV in the BMT patient is associated with a high mortality
Therapy should be focused on minimising ventilation induced lung injury
Ventilation strategies that improve oxygenation may not improve O2 delivery
The development of hepato-renal failure is almost universally fatal