The impact of the acute respiratory distress syndrome on outcome after oesophagectomy

Howells, P; Thickett, David; Knox, C; Park, D; Gao, Fang; Tucker, Olga; Whitehouse, Tony; McAuley, Daniel F.; Perkins, Gavin D.

doi:10.1093/bja/aew178

Cited by 21 publications

(17 citation statements)

References 31 publications

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“…Oesophagectomy patients were recruited into this trial as they represent a single cause with a reproducible and timed lung injury response that, historically, has been associated with increases in transpulmonary thermodilution-measured postoperative PVPI and EVLWI, inflammation and a high-rate of PPCs, including ARDS. 5 , 21 However, in contrast to previous trials in this population, 3 , 22 minimal postoperative increases in PVPI and EVLWI were observed in the placebo-treated patients, suggesting less lung injury and alveolar capillary leak in patients recruited to this trial.…”

Section: Discussioncontrasting

confidence: 66%

A nebulised antitumour necrosis factor receptor-1 domain antibody in patients at risk of postoperative lung injury: A randomised, placebo-controlled pilot study

Ryan

Bayliffe

McAuley

et al. 2020

European Journal of Anaesthesiology

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BACKGROUND Tumour necrosis factor receptor 1 (TNFR1) signalling mediates the cell death and inflammatory effects of TNF-α. OBJECTIVE The current clinical trial investigated the effects of a nebulised TNFR1 antagonist (GSK2862277) on signs of lung injury in patients undergoing oesophagectomy. DESIGN Randomised double-blind (sponsor unblind), placebo-controlled, parallel group study. SETTING Eight secondary care centres, the United Kingdom between April 2015 and June 2017. PATIENTS Thirty-three patients undergoing elective transthoracic oesophagectomy. INTERVENTIONS Patients randomly received a single nebulised dose (26 mg) of GSK2862277 ( n = 17) or placebo ( n = 16), given 1 to 5 h before surgery; 14 and 16, respectively competed the study. MAIN OUTCOME MEASUREMENTS Physiological and biochemical markers of lung injury, pharmacokinetic and safety endpoints were measured. The primary endpoint was the change from baseline in pulmonary vascular permeability index (PVPI) at completion of surgery, measured using single-indicator transpulmonary thermodilution. Adjusted point estimates and 95% credible intervals (analogous to conventional confidence intervals) were constructed for each treatment using Bayesian statistical models. RESULTS The mean change (with 95% credible intervals) from baseline in PVPI on completion of surgery was 0.00 (−0.23, 0.39) in the placebo and 0.00 (−0.24, 0.37) in the GSK2862277 treatment groups. There were no significant treatment-related differences in PaO 2 /F i O 2 or Sequential Organ Failure Assessment score. Levels of free soluble TNFR1, Macrophage Inflammatory Protein-1 alpha and total protein were significantly reduced in the bronchoalveolar lavage fluid of patients treated with GSK2862277 (posterior probability of decrease with GSK2862277 vs. placebo:≥0.977; equivalent to P < 0.05). The frequency of adverse events and serious adverse events were distributed evenly across the two treatment arms. CONCLUSION Pre-operative treatment with a single 26 mg inhaled dose of GSK2862277 did not result in significantly lower postoperative alveolar capillary leak or extra vascular lung water. Unexpectedly small increases in transpulmonary thermodilution-measured PVPI and extra vascular lung water index at completion of surgery suggest less postoperative lung injury than historically reported, which may have also compromised a clear assessment of efficacy in this trial. GSK2862277 was well tolerated, resulted in expected lung exposure and reduced biomarkers of lung permeability and inflammation. TRIAL REGISTRATION clinicaltrials.gov: NCT02221037.

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Section: Discussioncontrasting

confidence: 66%

A nebulised antitumour necrosis factor receptor-1 domain antibody in patients at risk of postoperative lung injury: A randomised, placebo-controlled pilot study

Ryan

Bayliffe

McAuley

et al. 2020

European Journal of Anaesthesiology

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“…Respiratory complications, mainly pneumonia, are a severe problem after esophageal surgery and at least in part responsible for the frequent need for postoperative critical care as well as for the high morbidity and mortality [2,[4][5][6][7][8][9][11][12][13][14][15][16][17][18][19][20]. A better understanding of the presumably multifactorial pathogenesis of postoperative pulmonary impairment [15] is mandatory for the development of new preventive and therapeutic strategies that are urgently needed.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, abdomino-thoracic esophagectomies are high-risk surgical procedures, facing high rates of postoperative morbidity and mortality, even in high-volume surgical centers [2][3][4][5][6][7][8][9][10]. Apart from anastomotic complications, high rates of postoperative respiratory complications, especially pneumonia, are reported after abdomino-thoracic esophagectomy that cause a high postoperative morbidity, a frequent need for critical care, and poor postoperative short-term as well as unsatisfactory long-term oncological outcomes [2,[4][5][6][7][8][9][11][12][13][14][15]. Multiple factors were proposed to contribute to the pathogenesis of postoperative pulmonary complications like perioperative atelectasis after single-lung ventilation, post-thoracotomy pain affecting respiratory physiology, as well as intraoperative injury to the thoracic cavity and the lung [10,[15][16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Early Respiratory Impairment and Pneumonia after Hybrid Laparoscopically Assisted Esophagectomy—A Comparison with the Open Approach

Reichert

Lang

Hecker

et al. 2020

JCM

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Patients undergoing esophageal cancer surgery are at high risk of developing severe pulmonary complications. Beneficial effects of minimally invasive esophagectomy had been discussed recently, but the incidence of perioperative respiratory impairment remains unclear. This is a retrospective single-center cohort study of patients, who underwent open (OE) or laparoscopically assisted, hybrid minimally invasive abdomino-thoracic esophagectomy (LAE) for cancer regarding respiratory impairment (PaO2/FiO2 ratio (P/FR) < 300 mmHg) and pneumonia. No differences were observed in the cumulative incidence of reduced P/FR between OE and LAE patients. Of note, until postoperative day (POD) 2, P/FR did not differ among both groups. Thereafter, the rate of patients with respiratory impairment was higher after OE on POD 3, 5, and 10 (p ≤ 0.05) and tended being higher on POD 7 and 9 (p ≤ 0.1). Although the duration of LAE procedure was slightly longer (total: p = 0.07, thoracic part: p = 0.004), the duration of surgery (Spearman’s rank correlation coefficient (rsp) = −0.267, p = 0.006), especially of laparotomy (rsp = −0.242, p = 0.01) correlated inversely with respiratory impairment on POD 3 after OE. Pneumonia occurred on POD 5 (1–25) and 8.5 (3–14) after OE and LAE, respectively, with the highest incidence after OE (p = 0.01). In conclusion, respiratory impairment and pulmonary complications occur frequently after esophagectomy. Although early respiratory impairment is independent of the surgical approach, postoperative pneumonia rate is reduced after LAE.

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“…8 Even in the VINDALOO cohort, the ARDS incidence remains higher than that defined by the Lung Injury Prediction Score 27 28 and the postoperative complication incidence is very high, with the advantages of an initial insult of surgery at a specific time and a defined postoperative care pathway, 3 which facilitates the conduct of efficacy trials. We believe this work demonstrates that oesophagectomy continues to be a useful model for trialling translational therapeutic and preventative strategies for critical illnesses prior to engaging in larger, more complex and expensive trials.…”

Section: Methodsmentioning

confidence: 99%

“…2 We have previously shown that ARDS following oesophagectomy is associated with more non-respiratory organ failure, longer critical care and hospital stays, 3 and other groups have demonstrated worse shortterm and long-term outcomes associated with ARDS 2 and other pulmonary complications. 4 Severe infection and cardiac dysrhythmias are common.…”

Section: Introductionmentioning

confidence: 99%

ARDS following oesophagectomy: a comparison of two trials

et al. 2017

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IntroductionThe Beta Agonist Lung Injury Trial-Prevention (BALTI-P) translational substudy and Vitamin D to Prevent Acute Lung Injury Following Oesophagectomy (VINDALOO) trials recruited patients undergoing oesophagectomy, 4 years apart. The acute respiratory distress syndrome (ARDS) rates were lower in the VINDALOO trial. We sought to identify changes between these two trials and identify risk factors for ARDS in oesophagectomy.MethodsThere were data available from 61 patients in the BALTI-P substudy and 68 from VINDALOO. Databases were available for both trials; additional data were collected. Multivariate logistic regression was used to analyse risk factors for ARDS and postoperative complications in the cohorts combined.ResultsLogistic regression analysis showed active smoking was associated with an increase in ARDS (OR 3.91; 95% CI 1.33 to 11.5) and dihydropyridine use (OR 5.34;95% CI 1.56 to 18.3). Hospital length of stay was longer for those who took dihydropyridines (median 29 days (IQR 17–42) vs 13 days (IQR 10–18), P=0.0007) or were diabetic (median 25 days (IQR 14–39) vs 13 (IQR 10–19), P=0.023) but not for current smokers (median in never/ex-smokers 13 (IQR 10–23) vs current smokers 15 (IQR 11–20), P=0.73).ConclusionsSmoking cessation trials should be promoted. Dihydropyridine effects perioperatively require further clinical and mechanistic evaluation. Patients undergoing oesophagectomy are a useful model for studying perioperative ARDS.

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The impact of the acute respiratory distress syndrome on outcome after oesophagectomy

Cited by 21 publications

References 31 publications

A nebulised antitumour necrosis factor receptor-1 domain antibody in patients at risk of postoperative lung injury: A randomised, placebo-controlled pilot study

A nebulised antitumour necrosis factor receptor-1 domain antibody in patients at risk of postoperative lung injury: A randomised, placebo-controlled pilot study

Early Respiratory Impairment and Pneumonia after Hybrid Laparoscopically Assisted Esophagectomy—A Comparison with the Open Approach

ARDS following oesophagectomy: a comparison of two trials

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