Ventilation/Non-Dialytic Therapies in the Paediatric BMT Patient

Desmond Bohn

The Department of Critical Care Medicine, The Hospital for Sick

Children, Toronto

Paediatric BMT and Critical Care

Sepsis

RespiratoryAirway obstructionPneumonia/pneumonitisPulmonary haemorrhageInterstitial pneumonitisARDS

NeurologicalSeizuresIntracranial haemorrhage

Hepatic failureVenocclusive diseaseGVHD

Renal failureDrug nephrotoxicity

Cardiac failureDrug toxicity

Paediatric BMT and Critical Care

ICU outcomes in paediatric BMT patients

31/176 patients admitted to ICU post BMT - 18%

ARF 15 10 5

Septic shock 5 3 2

Neurological disorders 5 5

Heart failure 2 2

Others 4 2 2

n BMT BMTallogenic autologous

Diaz de Heredia C Bone Marrow Transplantation 1999; 24:163-168

26 patients underwent mechanical ventilation - survival 46%

BAL in ventilated and non-ventilated in children after BMT

Ben-Ari J Bone Marrow Transplantation 2001; 27:191

non-ventilated ventilated

Diffuse alveolar hemorrhage in pediatric BMT patients

Heggen J Pediatrics 2002; 109:965

Diffuse alveolar hemorrhage in pediatric BMT patients

Heggen J Pediatrics 2002; 109:965

Diffuse alveolar haemorrhage in BMT patients

•Presents with cough and tachypneoa

•No underlying infective aetiology

•Pulmonary haemorrhage on BAL

•Usually occurs following engraftment

•Incidence 5 - 10%

•Characterised by thrombocytopoenia but normal coagulation

•Treated with high dose steroids and PEEP

•High mortality

Oxygenation Index

PaO2/FiO2

MAP x FiO2 x 100

PaO2

< 200 = ARDS

>15 = severe ARDS

Markers of oxygenation defect

Lung recruitment in ARDS

Froese AB, Crit Care Med 1997; 25:906Froese AB, Crit Care Med 1997; 25:906

Goals:Goals:1. Avoid Overdistention1. Avoid Overdistention2. Avoid Underinflation2. Avoid Underinflation3. Keep the lung open3. Keep the lung open4. Reduce FiO4. Reduce FiO22

Responses of baboons to prolonged hyperoxiaFracica PJ J Appl Physiol 1991; 71:2352

interstitial matrix

alveolus

PMN

PMN

PMNinterstitial matrix

alveolus

normal lethal toxicity - FiO2 1.0 for 110 h

alveolus

alveolus

Pulmonary oxygen toxicityDavis WB N Engl J Med 1983; 309:878

FiO2 0.9 for 17 hrs in healthy humans

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

VOLUME 342 MAY 4, 2000 NUMBER 18

Ventilation with low versus traditional tidalvolumes in ARDS

ARDS Network N Engl J Med 2000; 342:1301

Infasurf

Surfactant proteins B & C

42 children with ARDS

Willson D Crit Care Med 1999; 27:188

Surfactant in ARDS

Nitric oxide in ARDSDobyns EL J Pediatr 1999;134:406

60

50

40

30

20

10

0

10

5

0

-5

-10

-20

-15

4 hours 12 hrs

Cha

nge

in P

/F r

atio

fro

m b

asel

ine

Cha

nge

in O

I fr

om b

asel

ine

ControliNO

*

**

*

4 hours 12 hrs

Nitric oxide in ARDS

Dellinger RP Crit Care Med 1998; 26:15

Michael JR Am J Respir Crit Care Med1999; 157:1372

n=177n=40 n=30

Troncy EAm J Respir Crit Care Med1997; 157:1483

Nitric oxide in ARDS

5 RCTs in adults

3 case series and 2 RCTs in pediatrics

Physiological endpoints - improved oxygenation & reduction in PAP

40 - 60% of patients are “responders”

No data suggests any improvement in outcome

Steroids in ARDS

MODS Score Outcome

Meduri GU JAMA 1998; 280:159

Effect of prone position on survival in ARDSGattinoni L N Engl J Med 2001; 345:568

Effect of prone position on survival in ARDS

Gattinoni L N Engl J Med 2001; 345:568

304 patients randomised in 3 yrs

Intention to treat

End of study 25 21

ICU discharge 48 50.7

Prone vs supine protocol

End of study 27 22

ICU discharge 49.3 52.2

*Patients with P/F <88 40 20

Mortality (%) Supine Prone

RCT of prone vs supine ventilation in ARDS/ALIGattinoni L N Engl J Med 2001; 345:568

HFOV in Paediatric ARDS

CMV HFOV

No. of patients 29 29

Duration of CMV 80 ± 81 143 ± 240

FiO2 0.83 ± 0.18 0.84 ± 0.15

PEEP 21 ± 5 22 ± 3

OI 29 ± 14 26 ± 10

Arnold J. Crit Care Med 1994; 22:1530

Algorithm for the use of HFOV

MAP >5 cmH2O above CMV setting (25-30 cmH2O)High FiO2 (>0.8)

Maintain MAP for 10-15 minsAttempt to decrease FiO2

yes

Decrease FiO2 in increments to <0.6

no

Increase the MAP in increments of 2 cmH2O

Response usually at 30-35 cmH20

Oxygen extraction ratio = (CaO2 - CvO2)/CaO2

DO2 = Q x CaO2

Oxygen delivery/consumption

VO2 = Q x (CaO2 - CvO2).

As DO2 decreases VO2 maintained by increased extraction

.

Lamas 1991-2000 151 34 5(23%)

Hagen 1990-99 - 86 32(37%)

Jacobe 1994-98 210 36 15 (41%)

Keenan 1983-96 1080 121 19(16%)

Rossi 1986-95 355 39 17(44%)

Warwick 1976-92 869 196 79(40%)

Diaz de Heredia 1991-95 176 26 12(46%)

Hayes 1987-97 367 33 5(15%)

Nichols 1978-88 23 2(9%)

Bojko 1986-93 43 5(12%)

Todd 1973-90 54 6(11%)

Number of Number Survival BMTs ventilated ventilated patients

Published outcomes in paediatric BMT patients admitted to ICU

AHRF: an integrated approach

Pressure control ventilation (PIP <35 cmH2O)

Prone position ventilation

iNO 5 -20 ppm

?ECMO

HFOV

Negative fluid balance (furosimide)

Prognosis of paediatric BMT patients requiring ventilationRossi R Crit Care Med 1999; 27:1181

n = 41

Prognosis of paediatric BMT patients requiring PPV

Rossi R Crit Care Med 1999; 27:1181

Ventilation in paediatric BMT patientsHagen SA Pediatric Crit Care Med 2003; 4:206

Ventilation in paediatric BMT patientsHagen SA Pediatric Crit Care Med 2003; 4:206

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