Efficacy of Adjunct Hemoperfusion Compared to Standard Medical Therapy on 28-Day Mortality in Leptospirosis Patients with Renal Failure and Shock: A Single-Center Randomized Controlled Trial
Abstract
1. Introduction
2. Methodology
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Rudd, K.E.; Johnson, S.C.; Agesa, K.M.; Shackelford, K.A.; Tsoi, D.; Kievlan, D.R.; Colombara, D.V.; Ikuta, K.S.; Kissoon, N.; Finfer, S.; et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: Analysis for the Global Burden of Disease Study. Lancet 2020, 395, 200–211. [Google Scholar] [CrossRef] [PubMed]
- Mehta, Y.; Paul, R.; Rabbani, R.; Acharya, S.P.; Withanaarachchi, U.K. Sepsis Management in Southeast Asia: A Review and Clinical Experience. J. Clin. Med. 2022, 11, 1. [Google Scholar] [CrossRef] [PubMed]
- Bauer, M.; Gerlach, H.; Vogelmann, T.; Preissing, F.; Stiefel, J.; Adam, D. Mortality in sepsis and septic shock in Europe, North America, and Australia between 2009 and 2019-results from a systematic review and meta-analysis. Crit. Care 2020, 24, 1–9. [Google Scholar] [CrossRef] [PubMed]
- Putzu, A.; Schorer, R.; Lopez-Delgado, J.C.; Cassina, T.; Landoni, G. Blood Purification and Mortality in Sepsis and Septic Shock: A Systematic Review and Meta-analysis of Randomized Trials. Anesthesiology 2019, 131, 580–593. [Google Scholar] [CrossRef] [PubMed]
- Cerdá, J.; Baldwin, I.; Honore, P.M.; Villa, G.; Kellum, J.A.; Ronco, C. Role of Technology for the Management of AKI in Critically Ill Patients: From Adoptive Technology to Precision Continuous Renal Replacement Therapy. Blood Purif. 2016, 42, 248–265. [Google Scholar] [CrossRef] [PubMed]
- Clark, W.R.; Gao, D.; Lorenzin, A.; Ronco, C. Membranes and Sorbents. Contrib Nephrol. 2018, 194, 70–79. [Google Scholar] [CrossRef] [PubMed]
- Ronco, C.; Bellomo, R. Hemoperfusion: Technical aspects and state of the art. Crit. Care 2022, 26, 135. [Google Scholar] [CrossRef] [PubMed]
- Huang, Z.; Wang, S.R.; Su, W.; Liu, J.Y. Removal of humoral mediators and the effect on the survival of septic patients by hemoperfusion with neutral microporous resin column. Ther. Apher. Dial. 2010, 14, 596–602. [Google Scholar] [CrossRef] [PubMed]
- Chu, L.; Li, G.; Yu, Y.; Bao, X.; Wei, H.; Hu, M. Clinical effects of hemoperfusion combined with pulse high-volume hemofiltration on septic shock. Medicine 2020, 99, e19362. [Google Scholar] [CrossRef] [PubMed]
- Lee, C.T.; Tu, Y.K.; Yeh, Y.C.; Chang, T.; Shih, P.Y.; Chao, A.; Huang, H.-H.; Cheng, Y.-J.; Yeh, Y.-C. Effects of polymyxin B hemoperfusion on hemodynamics and prognosis in septic shock patients. J. Crit. Care 2018, 43, 202–206. [Google Scholar] [CrossRef] [PubMed]
- Kaçar, C.K.; Uzundere, O.; Kandemir, D.; Yektaş, A. Efficacy of HA330 Hemoperfusion Adsorbent in Patients Followed in the Intensive Care Unit for Septic Shock and Acute Kidney Injury and Treated with Continuous Venovenous Hemodiafiltration as Renal Replacement Therapy. Blood Purif. 2020, 49, 448–456. [Google Scholar] [CrossRef] [PubMed]
- Huang, Z.; Wang, S.R.; Yang, Z.L.; Liu, J.Y. Effect on extrapulmonary sepsis-induced acute lung injury by hemoperfusion with neutral microporous resin column. Ther. Apher. Dial. 2013, 17, 454–461. [Google Scholar] [CrossRef] [PubMed]
- Pasamba, E.; Arakama, M.H.; Danguilan, R.; Mendoza, M.T. Outcome of Adults with Leptospirosis and Renal Failure Treated with Pulse Immunosuppression. J. Kidney 2018, 4, 1000161. [Google Scholar] [CrossRef]
- Kularatne, S.A.M.; Budagoda, B.D.S.S.; de Alwis, V.K.D.; Wickramasinghe, W.M.R.S.; Bandara, J.M.R.P.; Pathirage, L.P.M.M.K.; Gamlath, G.R.R.D.K.; Wijethunga, T.J.; Jayalath, W.A.T.A.; Jayasinghe, C.; et al. High efficacy of bolus methylprednisolone in severe leptospirosis: A descriptive study in Sri Lanka. Postgrad. Med. J. 2011, 87, 13–17. [Google Scholar] [CrossRef] [PubMed]
- Manipol-Larano, R. Effect of methylprednisolone and cyclophosphamide on the survival of patients with leptospirosis, renal failure, and pulmonary hemorrhage. Trop. Med. Surg. 2014, 2, 1000171. [Google Scholar] [CrossRef]
- Trivedi S, v.; Vasava, A.H.; Patel, T.C.; Bhatia, L.C. Cyclophosphamide in pulmonary alveolar hemorrhage due to leptospirosis. Indian J. Crit. Care Med. 2009, 13, 79–84. [Google Scholar] [CrossRef] [PubMed]
- So, R.A.Y.; Danguilan, R.A.; Chua, E.; Arakama, M.-H.I.; Ginete-Garcia, J.K.B.; Chavez, J.R. A Scoring Tool to Predict Pulmonary Complications in Severe Leptospirosis with Kidney Failure. Trop. Med. Infect. Dis. 2022, 7, 7. [Google Scholar] [CrossRef] [PubMed]
- Chu, L.; Xia, J.; Zhang, J.; Meng, Z.; Wang, F.; Liu, X.; Peng, Y.; Liu, D. Effects of high-volume hemofiltration combined with hemoperfusion on prognosis and inflammatory response in septic shock patients. Crit. Care Med. 2019, 47, e407–e413. [Google Scholar]
- Ronco, C.; Bellomo, R.; Kellum, J.A.; Ricci, Z. Blood purification in sepsis: Are we ready for it? Intensive Care Med. 2019, 45, 219–221. [Google Scholar]
Total (n = 37) | Hemoperfusion (n = 17) | Control (n = 20) | p-Value | |
---|---|---|---|---|
Mean ± SD; Median (Range); Frequency (%) | ||||
Age, years | 32.65 ± 10.77 | 30.94 ± 8.41 | 34.20 ± 12.46 | 0.381 * |
Sex | >0.999 † | |||
Male | 34 (91.89) | 16 (94.12) | 18 (90) | |
Female | 3 (8.11) | 1 (5.88) | 2 (10) | |
BMI | 22.98 ± 3.66 | 23.48 ± 4.74 | 22.55 ± 2.45 | 0.451 * |
Comorbidities | ||||
Diabetes Mellitus | 0 | 0 | 0 | - |
Hypertension | 0 | 0 | 0 | - |
Cardiovascular disease | 0 | 0 | 0 | - |
Obesity | 2 (5.41) | 2 (11.76) | 0 (0) | 0.204 † |
Cancer | 0 | 0 | 0 | - |
Pulmonary tuberculosis | 0 | 0 | 0 | - |
Other comorbidities | 0 | 0 | 0 | - |
APACHE score | 14.2 ± 2.15 | 13.5 ± 1.17 | 15 ± 1.35 | 0.1085 |
SOFA score | 12 (8–14); [n = 37] | 12 (9–14); [n = 17] | 12 (8–14); [n = 20] | 0.613 ‡ |
O2 support before admission (O2 support at emergency room) | 0.521 † | |||
None (room air) | 21 (56.76) | 11 (64.71) | 10 (50) | |
Face mask | 11 (29.73) | 5 (29.41) | 6 (30) | |
BIPAP | 0 | 0 | 0 | |
Mechanical ventilation | 5 (13.51) | 1 (5.88) | 4 (20) |
Total | Hemoperfusion | Control | Risk Difference (95% CI) | p-Value | |
---|---|---|---|---|---|
Frequency (%); | |||||
Intention-to-treat | (n = 37) | (n = 17) | (n = 20) | ||
28-day Mortality | 7 (18.92) | 0 (0) | 7 (35) | −0.35 (−0.56 to −0.14) | 0.007 |
Per protocol | (n = 31) | (n = 12) | (n = 19) | ||
28-day Mortality | 7 (22.58) | 0 | 7 (36.84) | −0.368 (−0.59 to −0.15) | 0.017 |
Total | Hemoperfusion | Control | Mean Difference (95% CI) | p-Value | |
---|---|---|---|---|---|
Mean ± SD | |||||
Intention-to-treat | (n = 37) | (n = 17) | (n = 20) | ||
Norepinephrine dose ΔD3–D0 | −0.14 ± 0.63; [n = 33] | −0.25 ± 0.34; [n = 17] | −0.03 ± 0.83; [n = 16] | −0.219 (−0.67 to 0.23) | 0.326 * |
Norepinephrine dose ΔD7–D0 | −0.43 ± 0.28; [n = 31] | −0.4 ± 0.25; [n = 17] | −0.46 ± 0.32; [n = 14] | 0.054 (−0.16 to 0.26) | 0.601 * |
Vasoactive score ΔD3–D0 | −14.39 ± 62.9; [n = 33] | −25 ± 34.23; [n = 17] | −3.13 ± 83.22; [n = 16] | −21.875 (−66.56 to 22.81) | 0.326 * |
Vasoactive score ΔD7–D0 | −43.5 ± 28.35; [n = 30] | −42.19 ± 24.9; [n = 16] | −45 ± 32.76; [n = 14] | 2.813 (−18.79 to 24.41) | 0.792 * |
Per protocol | (n = 31) | (n = 12) | (n = 19) | ||
Norepinephrine dose ΔD3–D0 | −0.16 ± 0.63; [n = 27] | −0.23 ± 0.31; [n = 12] | −0.1 ± 0.81; [n = 15] | −0.125 (−0.64 to 0.39) | 0.620 * |
Norepinephrine dose ΔD7–D0 | −0.42 ± 0.28; [n = 25] | −0.35 ± 0.22; [n = 12] | −0.48 ± 0.31; [n = 13] | 0.13 (−0.1 to 0.36) | 0.246 * |
Vasoactive score ΔD3–D0s | −15.56 ± 63.3; [n = 27] | −22.5 ± 31.01; [n = 12] | −10 ± 81.31; [n = 15] | −12.5 (−63.73 to 38.73) | 0.620 * |
Vasoactive score ΔD7–D0 | −43.54 ± 27.33; [n = 24] | −37.73 ± 21.72; [n = 11] | −48.46 ± 31.32; [n = 13] | 10.734 (−12.52 to 33.99) | 0.349 * |
Total | Hemoperfusion | Control | Mean or Median Difference (95% CI) | p-Value | |
---|---|---|---|---|---|
Median (Range) | |||||
Intention-to-treat | (n = 37) | (n = 17) | (n = 20) | ||
hsCRP ΔD3–D0 | −139.53 ± 91.37; [n = 32] | −138.52 ± 97.16; [n = 17] | −140.67 ± 87.73; [n = 15] | 2.144 (−65.05 to 69.34) | 0.949 * |
hsCRP ΔD7–D0 | −167.28 ± 106.89; [n = 30] | −167.21 ± 108.85; [n = 17] | −167.37 ± 108.68; [n = 13] | 0.164 (−81.93 to 82.26) | 0.997 * |
Procalcitonin ΔD3–D0 | −12.53 (−324–26.71); [n = 32] | −7.35 (−85.72–26.71); [n = 17] | −14.97 (−324–−0.08); [n = 15] | 7.62 (−17.4–32.64) | 0.539 ‡ |
Procalcitonin ΔD7–D0 | −19.24 (−249–−0.46); [n = 30] | −10.12 (−193.22–−1.03); [n = 17] | −22.54 (−249–−0.46); [n = 13] | 12.42 (−20.88–45.72) | 0.451 ‡ |
IL6 ΔD3–D0 | −4 (−3956–104); [n = 28] | −9 (−3956–22); [n = 15] | −3 (−378–104); [n = 13] | −6 (−133.74–121.74) | 0.924 ‡ |
IL6 ΔD7–D0 | −14 (−3981–141); [n = 24] | −20 (−3981–5); [n = 13] | −8 (−380–141); [n = 11] | −12 (−149.2–125.2) | 0.858 ‡ |
Lactate ΔD3–D0 | −2.88 (−98–21.5); [n = 32] | −2.6 (−28.6–21.5); [n = 17] | −4.01 (−98–4.7); [n = 15] | 1.41 (−5.24–8.06) | 0.668 ‡ |
Lactate ΔD7–D0 | −4.8 (−41–5.6); [n = 29] | −4.04 (−33.6–4.8); [n = 17] | −8.55 (−41–5.6); [n = 12] | 6.06 (−0.06–12.18) | 0.052 ‡ |
Per protocol | (n = 31) | (n = 12) | (n = 19) | ||
hsCRP ΔD3–D0 | −134.89 ± 91.41; [n = 26] | −135.6 ± 99.84; [n = 12] | −134.29 ± 87.36; [n = 14] | −1.313 (−77.06 to 74.43) | 0.972 * |
hsCRP ΔD7–D0 | −162.03 ± 102.86; [n = 24] | −168.67 ± 105.74; [n = 12] | −155.38 ± 104.14; [n = 12] | −13.293 (−102.14 to 75.56) | 0.759 * |
Procalcitonin ΔD3–D0 | −13.82 (−324–19.77); [n = 26] | −13.3 (−85.72–19.77); [n = 12] | −13.82 (−324–−0.08); [n = 14] | −2.93 (−31.79–25.93) | 0.836 ‡ |
Procalcitonin ΔD7–D0 | −22.04 (−249–−0.46); [n = 24] | −16.49 (−193.22–−7.16); [n = 12] | −22.04 (−249–−0.46); [n = 12] | −0.09 (−48.88–48.7) | 0.997 ‡ |
IL6 ΔD3–D0 | −2.55 (−378–104); [n = 22] | −4.5 (−357–22); [n = 10] | −2.55 (−378–104); [n = 12] | −5 (−128.59–118.59) | 0.934 ‡ |
IL6 ΔD7–D0 | −8 (−380–141); [n = 20] | −6.22 (−362–5); [n = 9] | −8 (−380–141); [n = 11] | 1.78 (−135.29–138.85) | 0.979 ‡ |
Lactate ΔD3–D0 | −2.7 (−98–21.5); [n = 26] | −1.8 (−28.6–21.5); [n = 12] | −5.26 (−98–4.7); [n = 14] | 4.2 (−3.83–12.23) | 0.291 ‡ |
Lactate ΔD7–D0 | −6.3 (−41–5.6); [n = 23] | −5.55 (−33.6–4.8); [n = 12] | −7 (−41–5.6); [n = 11] | 0.7 (−10.78–12.18) | 0.900 ‡ |
Total | Hemoperfusion | Control | Risk or Mean or Median Difference (95% CI) | p-Value | |
---|---|---|---|---|---|
Frequency (%); Median (Range) | |||||
Intention-to-treat | (n = 37) | (n = 18) | (n = 19) | ||
Serum creatinine ΔD7–D0 | −6.17 ± 2.49; [n = 30] | −6.77 ± 2.55; [n = 17] | −5.39 ± 2.28; [n = 13] | −1.38 (−3.22 to 0.46) | 0.135 * |
PF ratio ΔD3–D0 | −125 (-429–250); [n = 33] | −125 (-429–250); [n = 17] | −112 (−428–19); [n = 16] | 14 (−126.9–154.9) | 0.841 ‡ |
Per protocol | (n = 31) | (n = 12) | (n = 19) | ||
Serum creatinine ΔD7–D0 | −6.12 ± 2.38; [n = 24] | −7.11 ± 2.23; [n = 12] | −5.14 ± 2.19; [n = 12] | −1.972 (−3.84 to −0.1) | 0.040 * |
PF ratio ΔD3–D0 | −85 (−428–250); [n = 27] | 7.5 (−323–250); [n = 12] | −139 (−428–19); [n = 15] | 144 (3.54–284.46) | 0.045 ‡ |
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Leano, D.R.; Danguilan, R.; Arakama, M.-H.; Apelin, V.; Alamillo, P.P.; Chua, E. Efficacy of Adjunct Hemoperfusion Compared to Standard Medical Therapy on 28-Day Mortality in Leptospirosis Patients with Renal Failure and Shock: A Single-Center Randomized Controlled Trial. Trop. Med. Infect. Dis. 2024, 9, 206. https://doi.org/10.3390/tropicalmed9090206
Leano DR, Danguilan R, Arakama M-H, Apelin V, Alamillo PP, Chua E. Efficacy of Adjunct Hemoperfusion Compared to Standard Medical Therapy on 28-Day Mortality in Leptospirosis Patients with Renal Failure and Shock: A Single-Center Randomized Controlled Trial. Tropical Medicine and Infectious Disease. 2024; 9(9):206. https://doi.org/10.3390/tropicalmed9090206
Chicago/Turabian StyleLeano, Danice Romagne, Romina Danguilan, Mel-Hatra Arakama, Vince Apelin, Paolo Pinkerton Alamillo, and Eric Chua. 2024. "Efficacy of Adjunct Hemoperfusion Compared to Standard Medical Therapy on 28-Day Mortality in Leptospirosis Patients with Renal Failure and Shock: A Single-Center Randomized Controlled Trial" Tropical Medicine and Infectious Disease 9, no. 9: 206. https://doi.org/10.3390/tropicalmed9090206
APA StyleLeano, D. R., Danguilan, R., Arakama, M.-H., Apelin, V., Alamillo, P. P., & Chua, E. (2024). Efficacy of Adjunct Hemoperfusion Compared to Standard Medical Therapy on 28-Day Mortality in Leptospirosis Patients with Renal Failure and Shock: A Single-Center Randomized Controlled Trial. Tropical Medicine and Infectious Disease, 9(9), 206. https://doi.org/10.3390/tropicalmed9090206