Population pharmacokinetics of caspofungin in critically ill Chinese children: a prospective observational study.

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While caspofungin is increasingly used to treat invasive fungal infections in pediatric intensive care unit (PICU) patients, its pharmacokinetic profile in this population remains poorly understood, and current dosing regimens are not firmly supported by scientific evidence. This study aimed to characterize the population pharmacokinetics of caspofungin in critically ill children and to identify dosing strategies for optimal exposure. The prospective clinical study was conducted among pediatrics in PICU. Population pharmacokinetic analysis and Monte Carlo simulations were performed. A total of 138 plasma samples collected from 29 pediatric patients (0.33-16 years) were included in the final analysis. The two-compartment model with allometric scaling on body surface area (BSA, exponential 1 for volume of distribution and 0.66 for clearance) accurately described time courses of caspofungin. Extracorporeal membrane oxygenation (ECMO) significantly increased the central volume of distribution (effect coefficient 18.2). There was no significant difference in area under the concentration curve (AUC) between patients with and without ECMO support. Simulations demonstrated that tAUCss,24h/MIC-based PTA results showed no significant differences between ECMO and non-ECMO groups and supported the current dosing regimen. A fixed maintenance dose (MD) is appropriate for patients with BSA ≥ 1.4 m², while the standard BSA-based MD remains preferable for those with BSA <1.4 m². Our study confirmed the recommended caspofungin dosing regimen in Chinese critically ill PICU patients. Although the number of patients receiving ECMO in this study was limited, future studies with a larger ECMO population are warranted to further validate these findings.This study is registered with ClinicalTrials.gov as NCT04961593.

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  • Research Article
  • Cite Count Icon 13
  • 10.1038/s41598-022-14741-6
Outcome of post-traumatic acute respiratory distress syndrome in young patients requiring extracorporeal membrane oxygenation (ECMO)
  • Jun 23, 2022
  • Scientific Reports
  • Hassan Al-Thani + 4 more

We aimed to evaluate the outcomes of post-traumatic acute respiratory distress syndrome (ARDS) in young patients with and without Extracorporeal membrane oxygenation (ECMO) support. A retrospective analysis was conducted for trauma patients who developed ARDS at a level I trauma facility between 2014 and 2020. Data were analyzed and compared between ECMO and non-ECMO group. We identified 85 patients with ARDS (22 patients had ECMO support and 63 matched patients managed by the conventional mechanical ventilation; 1:3 matching ratio). The two groups were comparable for age, sex, injury severity score, abbreviated injury score, shock index, SOFA score, and head injury. Kaplan Meier survival analysis showed that the survival in the ECMO group was initially close to that of the non-ECMO, however, during follow-up, the survival rate was better in the ECMO group, but did not reach statistical significance (Log-rank, p = 0.43 and Tarone-Ware, p = 0.37). Multivariable logistic regression analysis showed that acute kidney injury (AKI) (Odds ratio 13.03; 95% CI 3.17–53.54) and brain edema (Odds ratio 4.80; 95% CI 1.10–21.03) were independent predictors of mortality. Sub-analysis showed that in patients with severe Murray Lung Injury (MLI) scores, non-ECMO group had higher mortality than the ECMO group (100% vs 36.8%, p = 0.004). Although ARDS is uncommon in young trauma patients, it has a high mortality. ECMO therapy was used in a quarter of ARDS cases. AKI and brain edema were the predictors of mortality among ARDS patients. ECMO use did not worsen the outcome in trauma patients; however, the survival was better in those who had severe MLI and ECMO support. Further prospective study is needed to define the appropriate selection criteria for the use of ECMO to optimize the outcomes in trauma patients.

  • Research Article
  • Cite Count Icon 4
  • 10.3760/cma.j.issn.0578-1310.2018.05.006
Continuous renal replacement therapy combined with extracorporeal membrane oxygenation for pediatric cardiopulmonary failure
  • May 2, 2018
  • Zhonghua er ke za zhi = Chinese journal of pediatrics
  • F Wang + 6 more

Objective: To explore the effectiveness and safety of continuous renal replacement therapy (CRRT) combined with extracorporeal membrane oxygenation (ECMO) on rescuing pediatric patients with cardiopulmonary failure. Methods: The medical records of patients treated with ECMO admitted to pediatric intensive care unit (PICU) in Shanghai Children's Hospital from December 2015 to November 2017 were retrospectively extracted. There were 14 patients treated with ECMO combined with CRRT (ECMO+ CRRT group) due to acute kidney injury (AKI) or fluid overload, while 11 cases treated with ECMO only. The demographics and clinical characteristics of patients, the indications, details and complications of ECMO and CRRT support, and the survival rates were analyzed. Results: A total of 25 cases including 15 boys and 10 girls with cardiopulmonary failure treated with ECMO were enrolled in this study, whose median age and body weight were 9 (1-117) months and 10 (2-42) kg. The median duration of ECMO support was 199.2 h, and the median duration of CRRT was 78.6 h. Among the 14 cases in ECMO + CRRT group, 12 cases were treated with CRRT connected to ECMO pipeline, and 2 other cases were treated with independently operated CRRT. The serum level of creatinine was significantly higher in ECMO+ CRRT group than that in ECMO group (53 (22- 126) vs. 29 (12- 92) μmol/L, Z=-2.208, P=0.043). There was no significant difference in running time between ECMO+CRRT group and ECMO group ((257±203) vs. (122± 83) h, t=-2.062, P=0.051). And the incidence of thrombocytopenia was higher in ECMO+CRRT group than that in ECMO group (10/14 vs. 3/11 , χ(2)=4.812, P=0.028). There were no differences in the successful weaning rate and discharge survival rate between ECMO + CRRT and ECMO group (9 vs. 8, χ(2)= 0.203, P= 0.652 and 8 vs. 8, χ(2)= 0.659, P= 0.417, respectively). Conclusion: The combination of CRRT and ECMO is an effective and safe treatment to alleviate fluid overload and improve kidney function in pediatric patients with cardiopulmonary failure.

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  • Cite Count Icon 31
  • 10.1097/00003246-199309000-00015
Effect of extracorporeal membrane oxygenation on neutrophil function in neonates.
  • Sep 1, 1993
  • Critical Care Medicine
  • Linda E Depuydt + 2 more

To study the effect of long-term extracorporeal membrane oxygenation (ECMO) support on neutrophil function. A prospective, clinical investigation. A pediatric intensive care unit. Four groups of patients: ECMO group 1, newborns after 1 day of ECMO support (n = 10); ECMO group 2, newborns after 5 days of ECMO support (n = 6); group 3, normal newborns (n = 20); group 4, normal adults (n = 30). Two mL of heparinized blood was obtained from patients in each group. A modification of the Smith and Rommel technique was used to measure neutrophil phagocytosis and killing utilizing live Candida tropicalis as the test organism. Neutrophils were incubated for 90 mins in normal adult serum with live Candida. Viability of Candida after phagocytosis was tested by vital fluorochrome staining. Phagocytic index (the number of neutrophils with intracytoplasmic Candida divided by the total neutrophils) and candidicidal ratio (neutrophils with dead Candida divided by total neutrophils with Candida) were determined daily. Neutrophils from ECMO group 1 (day 1) and ECMO group 2 (day 5) patients had significantly higher phagocytosis indices (72.8 +/- 20 and 76 +/- 18) and candidicidal ratios (0.15 +/- 0.1 and 0.16 +/- 0.09) compared with neutrophils from group 3 patients (normal neonates) (64 +/- 7 and 0.06 +/- 0.04). The phagocytosis indices were significantly lower in neutrophils from ECMO group 1 (day 1) and ECMO group 2 (day 5) patients compared with group 4 (adults) patients (86 +/- 9). However, the candidicidal ratios in neutrophils from ECMO groups 1 and 2 (ECMO day 1 and day 5) patients were equal to that value in group 4 (adults) (0.10 +/- 0.04). ECMO support for 5 days (ECMO group 2 vs. group 1) did not significantly change either the phagocytosis index or candidicidal ratio. Phagocytosis and intracellular killing by neutrophils of ECMO-supported neonates were significantly greater than those values found in normal newborns. ECMO support for 5 days produced no significant changes in neutrophil phagocytosis or killing.

  • Research Article
  • Cite Count Icon 8
  • 10.1016/j.jfma.2016.06.012
Extracorporeal membrane oxygenation for neonatal congenital diaphragmatic hernia: The initial single-center experience in Taiwan.
  • Oct 7, 2016
  • Journal of the Formosan Medical Association
  • Wan-Ting Hung + 12 more

Extracorporeal membrane oxygenation for neonatal congenital diaphragmatic hernia: The initial single-center experience in Taiwan.

  • Research Article
  • Cite Count Icon 16
  • 10.3390/jcm9113703
Association between Extracorporeal Membrane Oxygenation (ECMO) and Mortality in the Patients with Cardiac Arrest: A Nation-Wide Population-Based Study with Propensity Score Matched Analysis
  • Nov 18, 2020
  • Journal of Clinical Medicine
  • Su Jin Kim + 5 more

We attempted to determine the impact of extracorporeal membrane oxygenation (ECMO) on short-term and long-term outcomes and find potential resource utilization differences between the ECMO and non-ECMO groups, using the National Health Insurance Service database. We selected adult patients (≥20 years old) with non-traumatic cardiac arrest from 2007 to 2015. Data on age, sex, insurance status, hospital volume, residential area urbanization, and pre-existing diseases were extracted from the database. A total of 1.5% (n = 3859) of 253,806 patients were categorized into the ECMO group. The ECMO-supported patients were more likely to be younger, men, more covered by national health insurance, and showed, higher usage of tertiary level and large volume hospitals, and a lower rate of pre-existing comorbidities, compared to the non-ECMO group. After propensity score-matching demographic data, hospital factors, and pre-existing diseases, the odds ratio (ORs) of the ECMO group were 0.76 (confidence interval, (CI) 0.68–0.85) for 30-day mortality and 0.66 (CI 0.58–0.79) for 1-year mortality using logistic regression. The index hospitalization was longer, and the 30-day and 1-year hospital costs were greater in the matched ECMO group. Although ECMO support needed longer hospitalization days and higher hospital costs, the ECMO support reduced the risk of 30-day and 1-year mortality compared to the non-ECMO patients.

  • Front Matter
  • Cite Count Icon 32
  • 10.1016/j.xjtc.2021.02.024
Hybrid and parallel extracorporeal membrane oxygenation circuits
  • Feb 24, 2021
  • JTCVS Techniques
  • Aakash Shah + 3 more

Hybrid and parallel extracorporeal membrane oxygenation circuits

  • Research Article
  • Cite Count Icon 1
  • 10.1016/j.transproceed.2023.02.058
Early Gait Function After Lung Transplantation in Patients With and Without Pretransplant Extracorporeal Membrane Oxygenation Support
  • Apr 1, 2023
  • Transplantation Proceedings
  • Junghwa Do + 11 more

Early Gait Function After Lung Transplantation in Patients With and Without Pretransplant Extracorporeal Membrane Oxygenation Support

  • Research Article
  • Cite Count Icon 33
  • 10.1097/mat.0000000000001309
Extracorporeal Membrane Oxygenation in Children with Coronavirus Disease 2019: Preliminary Report from the Collaborative European Chapter of the Extracorporeal Life Support Organization Prospective Survey.
  • Oct 1, 2020
  • ASAIO Journal
  • Matteo Di Nardo + 15 more

Extracorporeal Membrane Oxygenation in Children with Coronavirus Disease 2019: Preliminary Report from the Collaborative European Chapter of the Extracorporeal Life Support Organization Prospective Survey.

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  • Cite Count Icon 146
  • 10.1097/mat.0000000000001172
Extracorporeal Membrane Oxygenation for Coronavirus Disease 2019 in Shanghai, China.
  • Apr 1, 2020
  • ASAIO Journal
  • Xin Li + 10 more

Severe cases of coronavirus disease 2019 (COVID-19) cannot be adequately managed with mechanical ventilation alone. The role and outcome of extracorporeal membrane oxygenation (ECMO) in the management of COVID-19 is currently unclear. Eight COVID-19 patients have received ECMO support in Shanghai with seven with venovenous (VV) ECMO support and one veno arterial (VA) ECMO during cardiopulmonary resuscitation. As of March 25, 2020, four patients died (50% mortality), three patients (37.5%) were successfully weaned off ECMO after 22, 40, and 47 days support, respectively, but remain on mechanical ventilation. One patient is still on VV ECMO with mechanical ventilation. The partial pressure of oxygen/fractional of inspired oxygen ratio before ECMO initiation was between 54 and 76, and all were well below 100. The duration of mechanical ventilation before ECMO ranged from 4 to 21 days. Except the one emergent VA ECMO during cardiopulmonary resuscitation, other patients were on ECMO support for between 18 and 47 days. In conclusion, ensuring effective, timely, and safe ECMO support in COVID-19 is key to improving clinical outcomes. Extracorporeal membrane oxygenation support might be an integral part of the critical care provided for COVID-19 patients in centers with advanced ECMO expertise.

  • Research Article
  • Cite Count Icon 12
  • 10.1016/j.thromres.2022.10.019
Neutrophil extracellular traps are increased after extracorporeal membrane oxygenation support initiation and present in thrombus: A preclinical study using sheep as an animal model
  • Nov 5, 2022
  • Thrombosis Research
  • Yang Zhang + 10 more

Neutrophil extracellular traps are increased after extracorporeal membrane oxygenation support initiation and present in thrombus: A preclinical study using sheep as an animal model

  • Research Article
  • Cite Count Icon 4
  • 10.1093/icvts/ivaa307
Financial implications of using extracorporeal membrane oxygenation following heart transplantation
  • Dec 11, 2020
  • Interactive CardioVascular and Thoracic Surgery
  • Bhuvaneswari Krishnamoorthy + 5 more

Primary graft dysfunction after heart transplant is associated with high morbidity and mortality. Extracorporeal membrane oxygenation (ECMO) can be used to wean patients from cardiopulmonary bypass. This study retrospectively reviews a single-centre experience of post-transplant ECMO in regard to outcomes and associated costs. Between May 2006 and May 2019, a total of 267 adult heart transplants were performed. We compared donor and recipient variables, ECMO duration and the incidence of renal failure, bleeding, infection and cost analysis between ECMO and non-ECMO groups. ECMO support was required postoperatively to manage primary graft dysfunction in 72 (27%) patients. The mean duration of ECMO support was 6 ± 3.2 days. Mean ischaemic times were similar between the groups. There was a significantly higher proportion of ventricular assist device explant to transplant in the ECMO group versus non-ECMO (38.2% vs 14.1%; P < 0.0001). ECMO patients had a longer duration of stay in the intensive care unit (P < 0.0001) and total hospital stay (P < 0.0001). Greater mortality was observed in the ECMO group (P < 0.0001). The median cost of providing ECMO was £18000 [interquartile range (IQR): £12750-£24000] per patient with an additional median £35225 (IQR: £21487.25-£51780.75) for ITU stay whilst on ECMO. The total median cost per patient inclusive of hospital stay, ECMO and dialysis costs was £65737.50 (IQR: £52566.50-£95221.75) in the non-ECMO group compared to £145415.71 (IQR: £102523.21-£200618.96) per patient in the ECMO group (P < 0.0001). Patients with primary graft dysfunction following heart transplantation who require ECMO are frequently bridged to a recovery; however, the medium and longer-term survival for these patients is poorer than for patients who do not require ECMO.

  • Research Article
  • Cite Count Icon 14
  • 10.1016/j.athoracsur.2022.12.038
Outcomes of Extracorporeal Membrane Oxygenation for Primary Graft Dysfunction After Lung Transplantation
  • Jan 10, 2023
  • The Annals of Thoracic Surgery
  • Tsuyoshi Takahashi + 9 more

Outcomes of Extracorporeal Membrane Oxygenation for Primary Graft Dysfunction After Lung Transplantation

  • Research Article
  • Cite Count Icon 1
  • 10.3389/fcvm.2022.938442
Impact of Extracorporeal Membrane Oxygenation on Right Ventricular Function After Heart Transplantation.
  • Jul 15, 2022
  • Frontiers in Cardiovascular Medicine
  • Cheng Zhao + 7 more

AimsAcute right ventricular failure remains a common challenging clinical syndrome in heart transplant (HTx) recipients. While extracorporeal membrane oxygenation (ECMO) is a proven strategy for the treatment of this condition, the outcomes after weaning and during follow up remain understudied. We aimed to evaluate the right-sided heart function in ECMO survivors following HTx.MethodsBetween September 2005 and December 2019, 205 patients with end-stage heart failure who underwent standard orthotopic HTx were enrolled. In total, 68 (33.2%) patients were included in the ECMO group and 137 (66.8%) patients were included in the non-ECMO group.ResultsOf the 68 patients in the ECMO group, 42 (61.8%) were successfully weaned from ECMO. After a median follow-up period of 53 months, there were 25 (59.5%) and 27 (23.7%) deaths in the ECMO and non-ECMO groups (P = 0.023), respectively. Systolic pulmonary artery pressure (SPAP) before discharge (P = 0.003) was the unique predictor of all-cause mortality during follow up. Meanwhile, patients in the ECMO group with more than moderate SPAP increase before discharge had higher mortality than patients in the non-ECMO group without such increase (P = 0.005).ConclusionsRecipient right-sided heart characteristics were strong predictors of ECMO need after HTx. ECMO patients had high mortality in the perioperative and follow-up periods, and the changes in right ventricular function in ECMO patients may be associated with pulmonary vessel injury before and after HTx.

  • Front Matter
  • Cite Count Icon 1
  • 10.1016/j.xjon.2020.02.008
Commentary: Extracorporeal membrane oxygenation: Is it life-saving and cost effective for all patients?
  • Mar 1, 2020
  • JTCVS open
  • Harold L Lazar

Commentary: Extracorporeal membrane oxygenation: Is it life-saving and cost effective for all patients?

  • Research Article
  • Cite Count Icon 25
  • 10.1016/j.resuscitation.2022.12.001
Outcome of extracorporeal membrane oxygenation use in severe accidental hypothermia with cardiac arrest and circulatory instability: A multicentre, prospective, observational study in Japan (ICE-CRASH study)
  • Dec 9, 2022
  • Resuscitation
  • Shuhei Takauji + 23 more

Outcome of extracorporeal membrane oxygenation use in severe accidental hypothermia with cardiac arrest and circulatory instability: A multicentre, prospective, observational study in Japan (ICE-CRASH study)

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