Erratum to “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” Journal of Critical Care 34 (2016) 95–102

Bandeshe, Hiran; Dulhunty, Joel M.; Dunlop, Rachael; Holley, Anthony; Jarrett, Paul; Gomersall, Charles D; Lipman, Jeffrey; Lo, Thomas; O’Donoghue, Steven; Paratz, Jenny Davida; Paterson, David L.; Roberts, Jason A.; Starr, Therese; Stephens, Dianne P.; Stuart, Janine; Thomas, Jane; Udy, Andrew; White, Hayden

doi:10.1016/j.jcrc.2016.06.021

Cited by 9 publications

(11 citation statements)

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“…23,26 Our results are also consistent with a small, double-blind study 47 of intubated patients with acute exacerbation of chronic obstructive pulmonary disease that reported significantly more ventilator-free days with nebulised heparin, and a case-control study 48 of patients with inhalation injury that too reported an increase in ventilator-free days with nebulised heparin. A study of nebulised heparin 49 for ventilator-associated pneumonia did not find an improvement in clinical outcomes, but the heparin dose was 20% of the dose used in this study, and the nebulisation methodology was not standardised.…”

Section: Discussionmentioning

confidence: 71%

Nebulised heparin for patients with or at risk of acute respiratory distress syndrome: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial

Dixon

Smith

Campbell

et al. 2021

The Lancet Respiratory Medicine

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Background Mechanical ventilation in intensive care for 48 h or longer is associated with the acute respiratory distress syndrome (ARDS), which might be present at the time ventilatory support is instituted or develop afterwards, predominantly during the first 5 days. Survivors of prolonged mechanical ventilation and ARDS are at risk of considerably impaired physical function that can persist for years. An early pathogenic mechanism of lung injury in mechanically ventilated, critically ill patients is inflammation-induced pulmonary fibrin deposition, leading to thrombosis of the microvasculature and hyaline membrane formation in the air sacs. The main aim of this study was to determine if nebulised heparin, which targets fibrin deposition, would limit lung injury and thereby accelerate recovery of physical function in patients with or at risk of ARDS.Methods The Can Heparin Administration Reduce Lung Injury (CHARLI) study was an investigator-initiated, multicentre, double-blind, randomised phase 3 trial across nine hospitals in Australia. Adult intensive care patients on invasive ventilation, with impaired oxygenation defined by a PaO 2 /FiO 2 ratio of less than 300, and with the expectation of invasive ventilation beyond the next calendar day were recruited. Key exclusion criteria were heparin allergy, pulmonary bleeding, and platelet count less than 50 X 10⁹/L. Patients were randomly assigned 1:1, with stratification by site and using blocks of variable size and random seed, via a web-based system, to either unfractionated heparin sodium 25 000 IU in 5 mL or identical placebo (sodium chloride 0•9% 5 mL), administered using a vibrating mesh membrane nebuliser every 6 h to day 10 while invasively ventilated. Patients, clinicians, and investigators were masked to treatment allocation. The primary outcome was the Short Form 36 Health Survey Physical Function Score (out of 100) of survivors at day 60. Prespecified secondary outcomes, which are exploratory, included development of ARDS to day 5 among at-risk patients, deterioration of the Murray Lung Injury Score (MLIS) to day 5, mortality at day 60, residence of survivors at day 60, and serious adverse events. Analyses followed the intention-to-treat principle. There was no imputation of missing data. The trial is registered with the Australian and New Zealand Clinical Trials Register, number ACTRN12612000418875 .

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Section: Discussionmentioning

confidence: 71%

Nebulised heparin for patients with or at risk of acute respiratory distress syndrome: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial

Dixon

Smith

Campbell

et al. 2021

The Lancet Respiratory Medicine

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“…Unfractionated heparin has been used for intrapulmonary administration by several investigators utilizing different approaches. 35 –37 A pilot study of nebulized UFH for the prevention of ventilator-induced lung injury has been reported. 38 Inhaled prophylactic UFH has also been shown to be effective for the prevention and management of pneumonia and ventilated intensive care unit patients.…”

Section: Covid-19-associated Viral Coagulopathymentioning

confidence: 99%

Viral Coagulopathy in Patients With COVID-19: Treatment and Care

Kipshidze

Dangas

White

et al. 2020

Clin Appl Thromb Hemost

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COVID-19 has proven to be particularly challenging given the complex pathogenesis of SARS-CoV-2. Early data have demonstrated how the host response to this novel coronavirus leads to the proliferation of pro-inflammatory cytokines, massive endothelial damage, and generalized vascular manifestations. While SARS-CoV-2 primarily targets the upper and lower respiratory tract, other organ systems are also affected. SARS-CoV-2 relies on 2 host cell receptors for successful attachment: angiotensin-converting enzyme 2 and transmembrane protease serine 2. Clinicopathologic reports have demonstrated associations between severe COVID-19 and viral coagulopathy, resulting in pulmonary embolism; venous, arterial, and microvascular thrombosis; lung endothelial injury; and associated thrombotic complications leading to acute respiratory distress syndrome. Viral coagulopathy is not novel given similar observations with SARS classic, including the consumption of platelets, generation of thrombin, and increased fibrin degradation product exhibiting overt disseminated intravascular coagulation–like syndrome. The specific mechanism(s) behind the thrombotic complications in COVID-19 patients has yet to be fully understood. Parenteral anticoagulants, such as heparin and low-molecular-weights heparins, are widely used in the management of COVID-19 patients. Beyond the primary (anticoagulant) effects of these agents, they may exhibit antiviral, anti-inflammatory, and cytoprotective effects. Direct oral anticoagulants and antiplatelet agents are also useful in the management of these patients. Tissue plasminogen activator and other fibrinolytic modalities may also be helpful in the overall management. Catheter-directed thrombolysis can be used in patients developing pulmonary embolism. Further investigations are required to understand the molecular and cellular mechanisms involved in the pathogenesis of COVID-19-associated thrombotic complications.

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“…A recent multicenter trial, HEPBURN, focused in the safety and efficacy of burn patients receiving nebulized heparin, was stopped due to an elevated systemic clotting time (72,73). No convincing benefit of heparin nebulization was found under mechanical ventilation (74) or for prophylaxis for pneumonia patients receiving mechanical ventilation (75,76). In 16 patients with ventilator-induced lung injury, heparin was nebulized proving safety and increasing the number of ventilator-free days (77).…”

Section: Heparinmentioning

confidence: 99%

Anticoagulant therapy in acute respiratory distress syndrome

Camprubí-Rimblas¹,

Tantinyà²,

Bringué³

et al. 2018

Ann. Transl. Med.

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Acute respiratory distress syndrome (ARDS) presents a complex pathophysiology characterized by pulmonary activated coagulation and reduced fibrinolysis. Despite advances in supportive care of this syndrome, morbidity and mortality remains high, leading to the need of novel therapies to combat this disease. Focus these therapies in the inhibition of ARDS development pathophysiology is essential. Beneficial effects of anticoagulants in ARDS have been proved in preclinical and clinical trials, thanks to its anticoagulant and anti-inflammatory properties. Moreover, local administration by nebulization in the alveolar compartment increases local efficacy and does not produce systemic bleeding. In this review the coagulation and fibrinolytic pathway and its pharmacological targets to treat ARDS are summarized.

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Erratum to “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” Journal of Critical Care 34 (2016) 95–102

Cited by 9 publications

References 0 publications

Nebulised heparin for patients with or at risk of acute respiratory distress syndrome: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial

Nebulised heparin for patients with or at risk of acute respiratory distress syndrome: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial

Viral Coagulopathy in Patients With COVID-19: Treatment and Care

Anticoagulant therapy in acute respiratory distress syndrome

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