Is inhaled prophylactic heparin useful for prevention and Management of Pneumonia in ventilated ICU patients?: The IPHIVAP investigators of the Australian and New Zealand Intensive Care Society Clinical Trials Group.
To determine whether prophylactic inhaled heparin is effective for the prevention and treatment of pneumonia patients receiving mechanical ventilation (MV) in the intensive care unit.



A phase 2, double blind randomized controlled trial stratified for study center and patient type (non-operative, post-operative) was conducted in three university-affiliated intensive care units. Patients aged ≥18years and requiring invasive MV for more than 48hours were randomized to usual care, nebulization of unfractionated sodium heparin (5000 units in 2mL) or placebo nebulization with 0.9% sodium chloride (2mL) four times daily with the main outcome measures of the development of ventilator associated pneumonia (VAP), ventilator associated complication (VAC) and sequential organ failure assessment scores in patients with pneumonia on admission or who developed VAP.



Australian and New Zealand Clinical Trials Registry ACTRN12612000038897.



Two hundred and fourteen patients were enrolled (72 usual care, 71 inhaled sodium heparin, 71 inhaled sodium chloride). There were no differences between treatment groups in terms of the development of VAP, using either Klompas criteria (6-7%, P=1.00) or clinical diagnosis (24-26%, P=0.85). There was no difference in the clinical consistency (P=0.70), number (P=0.28) or the total volume of secretions per day (P=.54). The presence of blood in secretions was significantly less in the usual care group (P=0.005).



Nebulized heparin cannot be recommended for prophylaxis against VAP or to hasten recovery from pneumonia in patients receiving MV.
Department of Intensive Care Medicine, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia; Burns Trauma and Critical Care Research Centre, University of Queensland, QLD, Australia.
Hiran
H
Bandeshe
Department of Intensive Care Medicine, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia; Burns Trauma and Critical Care Research Centre, University of Queensland, QLD, Australia. Electronic address: r.boots@uq.edu.au.
Rob
R
Boots
Department of Intensive Care Medicine, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia; Burns Trauma and Critical Care Research Centre, University of Queensland, QLD, Australia.
Joel
J
Dulhunty
Department of Intensive Care Medicine, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia; Burns Trauma and Critical Care Research Centre, University of Queensland, QLD, Australia.
Rachael
R
Dunlop
Department of Intensive Care Medicine, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia; Burns Trauma and Critical Care Research Centre, University of Queensland, QLD, Australia.
Anthony
A
Holley
Department of Intensive Care Medicine, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia; Burns Trauma and Critical Care Research Centre, University of Queensland, QLD, Australia.
Paul
P
Jarrett
Prince of Wales Hospital, Chinese University of Hong Kong, Sha Tin, Hong Kong.
Charles D
CD
Gomersall
Department of Intensive Care Medicine, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia; Burns Trauma and Critical Care Research Centre, University of Queensland, QLD, Australia.
Jeff
J
Lipman
Prince of Wales Hospital, Chinese University of Hong Kong, Sha Tin, Hong Kong.
Thomas
T
Lo
Department of Intensive Care Medicine, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia; Burns Trauma and Critical Care Research Centre, University of Queensland, QLD, Australia.
Steven
S
O'Donoghue
Department of Intensive Care Medicine, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia; Burns Trauma and Critical Care Research Centre, University of Queensland, QLD, Australia; Heart Foundation Research Centre, Griffith University.
Jenny
J
Paratz
Department of Intensive Care Medicine, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia; Burns Trauma and Critical Care Research Centre, University of Queensland, QLD, Australia.
David
D
Paterson
Department of Intensive Care Medicine, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia; Burns Trauma and Critical Care Research Centre, University of Queensland, QLD, Australia.
Jason A
JA
Roberts
Department of Intensive Care Medicine, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia; Burns Trauma and Critical Care Research Centre, University of Queensland, QLD, Australia.
Therese
T
Starr
Intensive Care Unit. Royal Darwin Hospital, NT, Australia.
Di
D
Stephens
Department of Intensive Care Medicine, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia; Burns Trauma and Critical Care Research Centre, University of Queensland, QLD, Australia.
Janine
J
Stuart
Intensive Care Unit. Royal Darwin Hospital, NT, Australia.
Jane
J
Thomas
Department of Intensive Care and Hyperbaric Medicine, The Alfred, Prahran, Victoria, Australia.
Andrew
A
Udy
Intensive Care Unit. Logan Hospital, Queensland, Australia.
Hayden
H
White
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D004311:Double-Blind Method; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006493:Heparin / Q000008:administration & dosage*; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D009520:New Zealand; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy / Q000517:prevention & control*; D012121:Respiration, Artificial; D055815:Young Adult
D005343:Fibrinolytic Agents; D006493:Heparin
Nebulization; Unfractionated heparin; Ventilator associated complication; Ventilator associated pneumonia