Maximal Recruitment Open Lung Ventilation in Acute Respiratory Distress Syndrome: The PHARLAP Trial

Author(s):  
C.L. Hodgson ◽  
D.J. Cooper ◽  
Y. Arabi ◽  
V. King ◽  
A.D. Bersten ◽  
...  
2021 ◽  
Vol 23 (2) ◽  
pp. 163-170
Author(s):  
Shailesh Bihari ◽  
◽  
Andrew Bersten ◽  
Eldho Paul ◽  
Shay McGuinness ◽  
...  

Background: The Permissive Hypercapnia, Alveolar Recruitment and Low Airway Pressure (PHARLAP) randomised controlled trial compared an open lung ventilation strategy with control ventilation, and found that open lung ventilation did not reduce the number of ventilator-free days (VFDs) or mortality in patients with moderate-to-severe acute respiratory distress syndrome (ARDS). Parsimonious models can identify distinct phenotypes of ARDS (hypo-inflammatory and hyperinflammatory) which are associated with different outcomes and treatment responses. Objective: To test the hypothesis that a parsimonious model would identify patients with distinctly different clinical outcomes in the PHARLAP study. Design, setting and participants: Blood and lung lavage samples were collected in a subset of PHARLAP patients who were recruited in Australian and New Zealand centres. A previously validated parsimonious model (interleukin-8, soluble tumour necrosis factor receptor-1 and bicarbonate) was used to classify patients with blood samples into hypo-inflammatory and hyperinflammatory groups. Generalised linear modelling was used to examine the interaction between inflammatory phenotype and treatment group (intervention or control). Main outcome measure: The primary outcome was number of VFDs at Day 28. Results: Data for the parsimonious model were available for 56 of 115 patients (49%). Within this subset, 38 patients (68%) and 18 patients (32%) were classified as having hypo-inflammatory and hyperinflammatory phenotypes, respectively. Patients with the hypo-inflammatory phenotype had more VFDs at Day 28 when compared with those with the hyperinflammatory phenotype (median [IQR], 19.5 [11–24] versus 8 [0–21]; P = 0.03). Patients with the hyperinflammatory phenotype had numerically fewer VFDs when managed with an open lung strategy than when managed with control “protective” ventilation (median [IQR], 0 [0–19] versus 16 [8–22]). Conclusion: In the PHARLAP trial, ARDS patients classified as having a hyperinflammatory phenotype, with a parsimonious three-variable model, had fewer VFDs at Day 28 compared with patients classified as having a hypo-inflammatory phenotype. Future clinical studies of ventilatory strategies should consider incorporating distinct ARDS phenotypes into their trial design.


Author(s):  
Renat R. Gubaidullin ◽  
◽  
Aleksandr P. Kuzin ◽  
Vladimir V. Kulakov ◽  
◽  
...  

ntroduction. The COVID-19 pandemic caused an outbreak of viral lung infections with severe acute respiratory syndrome complicated with acute respiratory failure. Despite the fact that the pandemic has a lengthened run, none of the therapeutic approaches have proved to be sufficiently effective according to the evidence-based criteria. We consider the use of surfactant therapy in patients with severe viral pneumonia and acute respiratory distress syndrome (ARDS) as one of the possible methods for treating COVID-19 related pneumonia. Objective. To prove the clinical efficacy and safety of orally inhaled Surfactant-BL, an authorized drug, in the combination therapy of COVID-19 related ARDS. Materials and methods. A total of 38 patients with COVID-19 related severe pneumonia and ARDS were enrolled in the study. Of these, 20 patients received the standard therapy in accordance with the temporary guidelines for the prevention, diagnosis and treatment of the novel coronavirus infection (COVID-19) of the Ministry of Health of the Russian Federation, version 9. And 18 patients received the surfactant therapy in addition to the standard therapy. Surfactant-BL was used in accordance with the instructions on how to administer the drug for the indication – prevention of the development of acute respiratory distress syndrome. A step-by-step approach to the build-up of the respiratory therapy aggressiveness was used to manage hypoxia. We used oxygen inhalation via a face mask with an oxygen inflow of 5–15 l/min, highflow oxygen therapy via nasal cannulas using Airvo 2 devices, non-invasive lung ventilation, invasive lung ventilation in accordance with the principles of protective mechanical ventilation. Results and discussion. Significant differences in the frequency of transfers to mechanical ventilation, mortality, Intensive Care Unit (ICU) and hospitalization length of stay (p <0.05) were found between the groups. Patients receiving surfactant therapy who required a transfer to mechanical ventilation accounted for 22% of cases, and the mortality rate was 16%. In the group of patients receiving standard therapy without surfactant inhalation 45% were transferred to mechanical ventilation, and 35% died. For patients receiving surfactant therapy, the hospital stay was reduced by 20% on average, and ICU stay by 30%. Conclusion. The inclusion of surfactant therapy in the treatment of COVID-19 related severe pneumonia and ARDS can reduce the progression of respiratory failure, avoid the use of mechanical ventilation, shorten the ICU and hospitalization length of stay, and improve the survival rate of this patient cohort.


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