ECMO support may be associated with improved survival in tuberculosis associated severe ARDS

doi:10.21203/rs.3.rs-4925917/v1

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ECMO support may be associated with improved survival in tuberculosis associated severe ARDS

https://doi.org/10.21203/rs.3.rs-4925917/v1

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published 24 Oct, 2024

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Background

Data describing outcome of extracorporeal membrane oxygenation (ECMO) support in Tuberculosis (Tbc)-associated acute respiratory distress syndrome (ARDS) remain sparce and are mostly confined to singular case reports. The aim of this case series was to analyze intensive care unit (ICU) survival in patients with Tbc-associated ARDS receiving ECMO support and to compare those to patients not receiving ECMO.

Case presentation

ICU survival was analyzed retrospectively in 14 patients treated for Tbc-associated ARDS at three ECMO-referral university hospitals (Hannover Medical School, University Hospital Bonn (both Germany) and University Hospital Zurich (Switzerland)) during the last 14 years, of which eight patients received additional veno-venous (vv) ECMO support and six standard care only.

ICU survival was significantly higher in patients receiving additional ECMO support (62.5%, n=5/8) compared to those that did not (16.7%, n=1/6) (p=0.021). ECMO support was associated with reduced ICU mortality (Hazard ratio adjusted for baseline SOFA score [adj. HR] 0.125 (95% confidence interval (CI): 0.023-0.689), p=0.017). Median (IQR) time on ECMO and invasive ventilation in the ECMO group were 20 (11-26) and 37 (27-53) days, respectively. Major bleeding defined as transfusion requirement of 4 units of blood or more or surgical and/or radiologic intervention occurred only in one patient, in whom pulmonary bleeding was fatal. Thromboembolic events occurred in none of the ECMO patients.

Discussion and Conclusions:

This retrospective analysis from three large ECMO centers with similar SOPs suggests ECMO support as a feasible approach in patients with severe Tbc-associated ARDS. Although affiliated with extended runtimes, ECMO might be associated with improved survival in those patients. ECMO support should thus be considered in Tbc-associated ARDS to enable lung protective strategies during prolonged lung recovery.

Recently Idris et al. described in the Journal outcome of patients with tuberculosis (Tbc) associated critical illness, including those with severe acute respiratory distress syndrome (ARDS), supported by extracorporeal membrane oxygenation (ECMO) (1). In this systematic review and metanalysis of 43 patients receiving diverse modes of ECMO support, the authors reported encouraging clinical outcomes with an overall intensive care unit (ICU) survival of 81.4%. Data describing outcome of ECMO support in Tbc-associated ARDS in general remain sparce and are mostly confined to only singular case reports (2). However, the analysis by Idris et al. has some important limitations. First, patients were included based on singular case reports extracted over a wide time-period of 47 years, given rise to both reporting bias and significant heterogeneity in selection and provision of treatment as well as technology. Second, both patients with primarily respiratory as well as circulatory failure, consequentially receiving diverse modes of ECMO cannulation (vv-, va- and vav-ECMO), were included and analyzed together, thus further increasing clinical heterogeneity despite completely different primary clinical disorders.

Our study-group has therefore analyzed ICU survival in a more homogenous cohort of patients treated for Tbc-associated ARDS at three ECMO-referral university hospitals (Hannover Medical School, University Hospital Bonn (both Germany) and University Hospital Zurich (Switzerland)) during the last 14 years. A total of 14 patients with Tbc-associated ARDS were included in this present case series, of whom eight received additional veno-venous (vv) ECMO support and six received standard care only.

Baseline demographic and clinical characteristics at implementation of invasive ventilation were comparable between the two groups (Table 1). Three patients had HIV infection, two patients received medical immunosuppression, one had a congenital immune defect and five patients had chronic alcohol abuse. Patients later receiving ECMO support had significantly lower oxygenation index (Median (Interquartile range (IQR)) 71 (54–92) vs. 188 (146–236) mmHg, p < 0.001). Median (IQR) time to ECMO implantation was 2 (1–4) days.

Table 1

Demographic and clinical characteristics at start of invasive ventilation
Category	Median (interquartile range) / No (%)
	ECMO (n = 8)	no ECMO (n = 6)	p
Age - y	39 (27–48)	44 (35–68)	0.218
Sex - no (%)			0.733
male	6 (75)	4 (66.7)
female	2 (25)	2 (33.3)
BMI - kg/m²	19.9 (17.6–24.6)	22.2 (20-25.4)	0.61
Immunosuppression - no (%)	3 (37.5)	4 (66.7)	0.28
MDR-Tbc - no (%)	1 (12.5)	1 (16.7)	0.825
pO₂/FiO₂ - mmHg	71 (54–92)	188 (146–236)	< 0.001
pCO₂ - mmHg	49 (44–70)	56 (40–61)	0.707
Vasopressor therapy - no (%)	7 (87.5)	5 (83.3)	0.825
Vasopressor dose - ug/kg/min	0.38 (0.2-1.0)	0.33 (0.245–1.455)	0.613
Renal replacement therapy - no (%)	1 (12.5)	2 (33.3)	0.347
SOFA score - points	9 (7–10)	9 (8–11)	0.799
Lactate - mmol/l	1.4 (1.3–4.5)	4 (2.1–6.7)	0.228

Categorical variables are represented by number (n) and percentage (%), while continuous variables are expressed as median (25% to 75% Interquartile Range [IQR]). The normal distribution was checked using the D'Agostino-Pearson omnibus normality test and the Shapiro-Wilk normality test. Two-tailed p values of less than 0.05 were considered to indicate statistical significance. Comparisons of population characteristics between the ECMO and the no-ECMO group were performed using unpaired t-tests, Mann-Whitney tests and χ² tests, as appropriate. All reported p-values are two-sided unless indicated otherwise; p-values < 0.05 were considered statistically significant.

ARDS – Acute respiratory distress syndrome, ECMO – Extracorporeal membrane oxygenation, MDR – Multi drug resistant, SOFA – Sequential Organ Failure Assessment score, Tbc – Tuberculosis

ICU survival was significantly higher in patients receiving additional ECMO support (62.5%, n = 5/8) compared to those that did not (16.7%, n = 1/6) (FIGURE 1, p = 0.021). ECMO support was associated with reduced ICU mortality (Hazard ratio adjusted for baseline SOFA score [adj. HR] 0.125 (95% confidence interval (CI): 0.023–0.689), p = 0.017). Median (IQR) time on ECMO and invasive ventilation in the ECMO group were 20 (11–26) and 37 (27–53) days, respectively. Major bleeding defined as transfusion requirement of 4 units of blood or more or surgical and/or radiologic intervention occurred only in one patient, in whom pulmonary bleeding was fatal. Thromboembolic events occurred in none of the ECMO patients.

In the meta-analysis by Idris et al. 30 patients had ARDS, 27 were supported by vv-ECMO, of which 23 (85.1%) survived. However, outcomes were reported from a multitude of different centers dating back to 1975, making a reporting bias likely. Our outcome results with a survival of about 60% generated from three centers in a recent time period and similar standard operating procedures in the ECMO cohort are better in line with the more recent ECMO trials such as the CESAR (3) and EOLIA (4) study with regards to mortality. Idris et al. did not report on patients with Tbc-associated ARDS, treated at the same institutions but without ECMO support. The finding of an exceedingly high mortality in patients without ECMO support from this present cohort is provocative, but certainly needs confirmation in prospective studies. Of note, both ECMO runtime and ventilator-days were excessively long in either Idris et al. and our group, underlining the slow recovery from Tbc-associated ARDS (5) and the consequential need to optimize lung-protective strategies in this cohort.

In summary, this retrospective analysis from three large ECMO centers with similar SOPs suggests ECMO support as a feasible approach in patients with severe Tbc-associated ARDS. Although affiliated with extended runtimes, ECMO might be associated with improved survival in those patients. ECMO support should thus be considered in Tbc-associated ARDS to enable lung protective strategies during prolonged lung recovery.

ARDS = Acute respiratory distress syndrome

CI = Confidence Interval

ECMO = Extracorporeal membrane oxygenation

HR = Hazard Ratio

ICU = Intensive care unit

MDR = Multi drug resistant

SOFA = Sequential Organ Failure Assessment score

SOP = Standard operating procedure

Tbc = Tuberculosis

Va = Veno-arterial

Vav = Veno-arterial-venous

Vv = Veno-venous

Ethics approval and consent to participate

Due to a retrospective analysis ethics approval was waived. The study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The medical committee of Hannover Medical School (No. 11141_BO_K_2023), University Hospital Bonn (No 437/23-EP) and University Hospital Zurich (BASEC-No: 2024-00034) approved the study. All personal patient data were pseudonymized before data collection.

Consent of publication

Not applicable

Competing interests

None declared.

Clinical trial number

Not applicable

Funding

Not applicable

Author Contribution

KS and BN conceived the presented idea. BN, AB and LW obtained the retrospective data and performed the analysis. NB, AB, LW and KS discussed the data and generated figures. CB, SD, BS and KS wrote the manuscript; all authors discussed the results and contributed to the final manuscript. The BonHanZA study group is a three-center research consortium, that all authors are part of.

Acknowledgement

Further members of the BonHanZA (Bonn-Hannover-Zurich ARDS) study group, not directly contributing to the manuscript, are: Thorben Pape1,2,7, Jannik Ruwisch1,2,7, Marius M. Hoeper1,2,7, Pedro David Wendel-Garcia3,7, Daniel A. Hofmaenner3,7, Rolf Erlebach3,7, Mattia Mueller3,7, Rea Andermatt3,7, Konrad Peukert4,7, Andrea Sauer4,7We are grateful to the late Prof. Tobias Welte, who inspired this analysis and so many more. He and his influence on this study group will never be forgotten.

Data Availability

The datasets used and analyzed are during the current study are available from the corresponding author on reasonable request.

Idris R, Zielbauer AS, Koepsell J, Kloka J, Wetzstein N. Extracorporeal membrane oxygenation (ECMO) in patients with tuberculosis: systematic review and meta-analysis of 43 cases. BMC Pulm Med. 2024;24(1):47.
Besa S, Morales Á J, Salas P, Bravo MS, Garrido-Olivares L. Extracorporeal membrane oxygenation for tuberculosis pneumonia with empyema. Respir Med Case Rep. 2021;34:101481.
Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet. 2009;374(9698):1351-63.
Combes A, Hajage D, Capellier G, Demoule A, Lavoué S, Guervilly C, et al. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome. N Engl J Med. 2018;378(21):1965-75.
Agarwal R, Gupta D, Aggarwal AN, Behera D, Jindal SK. Experience with ARDS caused by tuberculosis in a respiratory intensive care unit. Intensive Care Med. 2005;31(9):1284-7.

No competing interests reported.

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You are reading this latest preprint version

ECMO support may be associated with improved survival in tuberculosis associated severe ARDS

Status:

Journal Publication

Version 1

Abstract

Figures

Background

Case presentation

Discussion and Conclusions

List of abbreviations

Declarations

Ethics approval and consent to participate

Consent of publication

Competing interests

Clinical trial number

Funding

Author Contribution

Acknowledgement

Data Availability

References

Additional Declarations

Status:

Journal Publication

Version 1