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 Respiratory Airway obstruction Pneumonia/pneumonitis Pulmonary haemorrhage Interstitial pneumonitis ARDS Neurological Seizures Intracranial haemorrhage

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

ICU outcomes in paediatric BMT patients Diaz de Heredia C Bone Marrow Transplantation 1999; 24:163-168 31/176 patients admitted to ICU post BMT - 18% n BMT BMT allogenic autologous ARF 15 10 5 Septic shock 5 3 2 Neurological disorders 5 5 Heart failure 2 2 Others 4 2 2 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

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

Lung recruitment in ARDS

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

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

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

THE ACUTE RESPIRATORY DISTRESS SYNDROME NETWORK VOLUME 342 MAY 4, 2000 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

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

Nitric oxide in ARDS Dobyns EL J Pediatr 1999;134:406 Control iNO 60 10 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

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

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 Meduri GU JAMA 1998; 280:159 MODS Score Outcome

Effect of prone position on survival in ARDS Gattinoni 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

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 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

HFOV in Paediatric ARDS Arnold J. Crit Care Med 1994; 22:1530 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

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 10-15 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 30-35 cmH20

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) .

Published outcomes in paediatric BMT patients admitted to ICU Number of Number Survival BMTs ventilated ventilated patients 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%)

AHRF: an integrated approach Pressure control ventilation (PIP <35 cmH2O) Negative fluid balance (furosimide) HFOV Prone position ventilation iNO 5 -20 ppm ?ECMO

Prognosis of paediatric BMT patients requiring ventilation Rossi 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 patients Hagen SA Pediatric Crit Care Med 2003; 4:206

Ventilation in paediatric BMT patients Hagen 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