Hemolysis during Venovenous Extracorporeal Membrane Oxygenation in Neonates with Congenital Diaphragmatic Hernia: A Prospective Observational Study

Background: Extracorporeal membrane oxygenation (ECMO) treatment alleviates systemic cardiorespiratory failure. However, it is unclear whether ECMO also improves microcirculatory function, as the microcirculation can be disturbed despite normal systemic hemodynamics. We therefore aimed to study the sublingual microcirculation (SMC) throughout neonatal and pediatric ECMO treatment. We hypothesized that the SMC improves after starting ECMO, that the SMC differs between venovenous (VV) and venoarterial (VA) ECMO, and that insufficient recovery of microcirculatory disturbances during ECMO predicts mortality.Methods: This single-center prospective longitudinal observational study included 34 consecutive children (April 2016—September 2018). The SMC was assessed daily with a handheld vital microscope (integrated with incident dark field illumination) before, during, and after ECMO. Validated parameters of vessel density, perfusion, and flow quality were assessed for all vessels (diameter <100 μm) and small vessels (<20 μm). Linear mixed models and logistic regression models were built to assess changes over time and identify significant covariates. Using ROC curves, the predictive values of microcirculatory parameters were assessed for mortality on ECMO and overall mortality.Results: The study population comprised 34 patients (median age 0.27 years, 16 neonates, 16 females). Twelve patients were treated with VV and 22 with VA ECMO. Twelve patients died during ECMO (stopped due to futility) and 3 died after ECMO but before discharge. Microcirculatory parameters did not change significantly before, during or after ECMO. Except between microcirculatory flow index (MFI) and mean arterial pressure (MAP), no significant associations were found between microcirculatory parameters and global systemic hemodynamics. The probability of an undisturbed MFI (>2.6) increased with higher MAP (OR: 1.050, 95%CI: 1.008–1.094). Microcirculatory parameters did not significantly differ between VV and VA ECMO or between survivors and non-survivors. None of the microcirculatory parameters could predict mortality on ECMO or overall mortality.Conclusion: In this heterogeneous study population, we were not able to demonstrate an effect of ECMO on the sublingual microcirculation. Microcirculatory parameters did not change throughout ECMO treatment and did not differ between VV and VA ECMO or between survivors and non-survivors. Future research should focus on determining which neonatal and pediatric ECMO patients would benefit from microcirculatory monitoring and how.

Predictability model of the need for extracorporeal membrane oxygenation in neonates with meconium aspiration syndrome treated with inhaled nitric oxide

Before the use of extracorporeal membrane oxygenation (ECMO), infants with a severe form of congenital diaphragmatic hernia (CDH) had a high mortality and morbidity. Recent studies have shown an improvement in the survival of these infants after ECMO treatment; however, the existing data do not provide sufficient informations regarding the quality of survival and developmental outcome of these infants. The objective of this study was to evaluate survival, intracranial lesions, and the neurodevelopmental outcome of infants with CDH treated with ECMO. We retrieved data for 51 (n = 51) infants with CDH who were treated with ECMO at Huntington Memorial Hospital between 1985 and 1994. Their mean gestational age was 38.5 +/- 2.4 weeks (mean +/- SD); their mean birth weight was 3170 +/- 620 gm. Vital signs, arterial blood gases, chest radiographs, cranial and cardiac ultrasonography were routinely obtained before ECMO treatment. Cranial ultrasounds were performed daily on all infants while on ECMO; computerized tomography scans were obtained on all infants after completion of ECMO treatment. The surviving infants were followed at our neonatal follow-up clinic for neurodevelopmental assessment. A total of 39 infants were placed on venoarterial ECMO and 12 infants were placed on venovenous ECMO; a total of 35 infants had CDH repair before ECMO, whereas 16 infants had delayed surgery. A total of 31 infants (61%) survived. The infants who survived had a mean pH of 7.33 +/- 0.20, mean airway pressure of 19.6 +/- 5.8 cm H2O, and an oxygenation index (OI) of 87 +/- 55 before ECMO intervention. The infants who expired (n = 20) had a mean pH of 7.31 +/- 0.15, mean airway pressure of 23.1 +/- 5.5 cm H2O, and a mean oxygenation index of 127 +/- 56 before ECMO treatment. Before ECMO, survivors had a significantly lower oxygenation index and a higher Pao2 compared with nonsurvivors (p < 0.01). A total of 18 infants (35%) had abnormal central nervous system findings. Of the 51 infants, 10 had ventricular dilatation, 6 had intracranial hemorrhage, and 11 had focal or diffuse cerebral atrophy diagnosed by computerized tomography scan or at autopsy (1 patient had an infarct). Eight infants had more than one central nervous system abnormality. A total of 16 survivors had a neurodevelopmental evaluation at 12 months, and 11 of these survivors were evaluated at 24 months of age (Bayley Scales of Infant Development). The developmental progress of these infants falls within the low-average range of cognitive and motor abilities. Their mean Bayley Mental Developmental Index was 85 +/- 25 (50 to 145) at 24 months; their Psychomotor Developmental Index was 89 +/- 21 (50 to 113) at 24 months of age. Follow-up at 4 and 6 years of age is in progress. Our preliminary findings indicate that 35% of infants with severe CDH requiring ECMO had central nervous system abnormalities (intracranial lesions, including ventricular dilatation). The survival rate in our study population is consistent with recent reports. As a group, infants with severe CDH display mild neuromotor and cognitive delay in development at 24 months of age.

This study aimed to assess whether the proinflammatory markers procalcitonin (PCT), C-reactive protein (CRP), or interleukin 6 (IL-6) are associated with mortality in neonates with congenital diaphragmatic hernia (CDH) requiring extracorporeal membrane oxygenation (ECMO). Congenital diaphragmatic hernia neonates receiving venovenous ECMO between December 2012 and June 2022 were retrospectively reviewed and grouped by survival status. Longitudinal CRP, PCT, and IL-6 levels during the first 10 days on ECMO were analyzed using the Mann-Whitney U test. A PCT cut-off was determined to define a "high inflammatory response group," further evaluated with Kaplan-Meier curves and the log-rank test. Independent mortality risk factors were identified using Cox regression. Among nonsurvivors, PCT values were significantly higher on day 2 (p = 0.028), day 3 (p = 0.028), day 6 (p = 0.031), and day 10 (p = 0.017) after ECMO initiation. Infants in the high inflammatory response group had significantly shorter survival time (p = 0.006). C-Reactive protein and IL-6 were not significantly associated with mortality. In multivariable Cox regression analysis, high PCT on day 2 of ECMO (hazard ratio: 1.022; 95% confidence interval [CI]: 1.004-1.040) and severe pulmonary hypertension (hazard ratio: 3.270; 95% CI: 1.245-8.588) were independently associated with mortality. High PCT in CDH neonates receiving ECMO is significantly associated with increased mortality and reduced survival time.

Neonates with severe congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation (ECMO) have a high rate of mortality. There is controversy regarding optimal time of surgical intervention. We present our data over a 26-year period. We analysed data from our Extracorporeal Life Support Organization registry forms between 1989 and 2015, in order to determine the factors affecting survival outcome for repair of congenital diaphragmatic hernia with ECMO as a bridge to surgery and/or recovery. Ninety-eight neonates with congenital diaphragmatic hernia requiring ECMO were identified. In-hospital mortality was 32%. The overall mortality (47.9%) in our study was seen up to 7 months, after this point there was no mortality. There was no difference in survival in patients repaired using pre-, intra- or postoperative ECMO (P = 0.65). Requiring haemofiltration at any point was significantly associated with reduced survival [hazard ratio 2.7 (95% confidence interval 1.5-4.9); P = 0.01] as was the presence of neurological complications [hazard ratio 3.7 (95% confidence interval 1.6-8.5); P = 0.003]. Age, Apgar score, mode of delivery, side, associated cardiac comorbidities, pH, partial pressure of carbon dioxide, partial pressure of oxygen, oxygen saturations, bicarbonate, high-frequency oscillatory ventilation, mode of ECMO, inhaled nitric oxide, pulmonary complications and bleeding were not associated with any survival difference. We believe that all neonates with severe diaphragmatic hernia should be given the option of ECMO if clinically indicated. Provided these patients survive the initial postoperative period, they go on to have a sustained survival benefit. Long-term cost analysis and morbidity need to be taken into account to determine the true effect of ECMO on congenital diaphragmatic hernia.

BackgroundSurvival of neonates with intrauterine renal insufficiency and oligo- or anhydramnios correlates with the severity of secondary pulmonary hypoplasia. Early prenatal diagnosis together with repetitive amnioinfusions and modern intensive care treatment have improved the prognosis of these neonates. Extracorporeal membrane oxygenation is an established treatment option, mainly applied to neonates with pulmonary hypoplasia caused by congenital diaphragmatic hernia. However, a few case reports of extracorporeal membrane oxygenation in neonates with lower urinary tract obstruction have been published.Case presentationWe describe a case of a Caucasian male infant with prenatally diagnosed lower urinary tract obstruction and secondary pulmonary hypoplasia who was delivered spontaneously at 36 + 2 weeks of gestation. Venovenous extracorporeal membrane oxygenation was initiated on the first day of life for severe respiratory failure and consecutive hypoxemia despite treatment with inhaled nitric oxide and high-frequency oscillation. The patient was supported by extracorporeal membrane oxygenation for 10 days and extubated 6 weeks later. Hemofiltration was required on the second day of life because of renal insufficiency and was later replaced by peritoneal dialysis. The child was discharged after 4 months with nasal high-flow mild oxygen therapy and peritoneal dialysis.ConclusionNeonatal extracorporeal membrane oxygenation support is a possible treatment option for neonates with lower urinary tract obstruction and pulmonary hypoplasia.

Venovenous versus venoarterial extracorporeal membrane oxygenation in congenital diaphragmatic hernia

Venovenous extracorporeal membrane oxygenation in neonates with respiratory failure

Hybrid and parallel extracorporeal membrane oxygenation circuits

Cannulation for repeat extracorporeal membrane oxygenation (ECMO) in neonates with respiratory failure may be associated with technical difficulties, especially after the ligation of both the carotid artery and internal jugular vein. In a newborn who required repeat ECMO, the previously reconstructed right carotid artery was used for arterial access. The right atrium was cannulated through a small submammary thoracotomy incision after the internal jugular vein was found to be thrombosed. This approach is relatively simple, provides excellent bypass flow, and is not associated with significant bleeding.

Percutaneous, ultrasound-guided single- and multisite cannulation for veno-venous extracorporeal membrane oxygenation in neonates.

Results of extracorporeal membrane oxygenation in neonates with sepsis: The Extracorporeal Life Support Organization experience

Use of ECMO in Patients With Coronavirus Disease 2019: Does the Evidence Suffice?

Objective: To analyze the clinical effect of extracorporeal membrane oxygenation (ECMO) in the treatment of burn patients with acute respiratory distress syndrome (ARDS). Methods: The retrospective observational study and the systematic review were applied. From March 2014 to July 2020, five burn patients with ARDS received ECMO treatment in the First Affiliated Hospital of Army Medical University (the Third Military Medical University). All the five patients were male, aged from 40 to 62 years. The average total burn surface area was 58.8% total body surface area (TBSA) and four cases had severe inhalation injury. Patient's ECMO starting time, duration and mode, and whether successfully weaned or the cause of death, and others. were recorded. Furthermore, the changes of oxygenation and infection before, during, and after utilizing ECMO were analyzed. PubMed and Web of Science from the establishment of each database to August 2021 were searched using "Extracorporeal Membrane Oxygenation", "ECMO", "burn", "inhalation" as the search terms and "Title/Abstract" as the field to retrieve the clinical articles that meet the selection criteria . Basic information were extracted from the articles, including sample size, gender, age, total burn area, inhalation injury, the indication of ECMO, the start and lasting time of ECMO, ECMO mode, rate of successful weaning, complications of ECMO, mortality, the combined application of continuous renal replacement therapy (CRRT). Results: Five patients started venovenous ECMO on an average of 10.2 days after injury and lasted an average of 180.4 hours. Three out of 5 patients were weaned successfully with one patient survived. Four patients died of multiple organ dysfunction syndrome (MODS) and septic shock. Compared with those before ECMO treatment, the arterial oxygen partial pressure (PaO2) and oxygen saturation in arterial blood (SaO2) of three successfully weaned patients obviously increased during and after ECMO treatment. The fraction of inspired oxygen (FiO2) decreased below 50% and PaO2/FiO2 ratio increased above 200 mmHg (1 mmHg=0.133 kPa) during and after ECMO. Furthermore, lactic acid and respiratory rate decreased, basically. Compared with those before ECMO, PaO2 and SaO2 in the other two patients during ECMO, who failed to be weaned, continuously decreased while lactic acid increased. Before and during ECMO, the PaO2/FiO2 ratios of unsuccessfullg weaned cases were less than 200 mmHg, and partial pressure of carbon dioxide in arterial blood (PaCO2) were more than 40 mmHg. Compared with those before ECMO, there were no significant changes in body temperature during and after ECMO, which were less than 38 ℃. Compared with those before ECMO, the leucocyte number (the index without this in unsuccessfully weaned cases was omitted, the same as below) in four patients showed a significant decrease during ECMO, but rose after removal of ECMO. The proportion of neutrophils in three patients were slightly higher during ECMO than before ECMO, and did not change significantly after removal of ECMO. Compared with those before ECMO, platelet counts in three patients were significantly reduced during ECMO, and all five patients during ECMO were below normal levels. Compared with those before ECMO, the procalcitonin levels in four deaths were significantly increased during ECMO. Catheter culture of microorganism was performed in three successfully weaned patients, all of which were negative. A total of 13 literature were included, ranging from 1990 to 2019. The sample size in 6 studies was less than 10, and the sample size in 4 studies was between 10 and 20, and only 2 literatures had a sample size larger than 50. ECMO was applied in 295 burn patients with overall mortality of 48.8% (144/295), including 157 adults and 138 children. The most common indication of ECMO was severe ARDS. Among 157 adult burn patients (95 males and 65 females), 36 cases had inhalation injury. The average burn area was 27%-37%TBSA in 5 reported studies and was more than 50%TBSA in 2 reported studies. The most common mode was venovenous ECMO. ECMO treatment began 26.5 hours to 7.4 days after injury and lasted from 90 hours to 18 days, and the rate of successful weaning ranged from 50% to 100%. The most common complications were bleeding and infection. The mortality was 52.9% (83/157). MODS and sepsis were the leading causes of death. Among 138 pediatric burn patients (77 boys and 61 girls), 29 patients had inhalation injury. The average burn area was 17%-50.2%TBSA in 3 studies. ECMO treatment lasted from 165.2 hours to 324.4 hours. Bleeding was the most common complication. The mortality was 44.2% (61/138). Conclusions: ECMO is an effective strategy for the salvage treatment of burns complicated with ARDS. Furthermore, the prevention and treatment of bleeding, infection and organ dysfunction should be emphasized during the use of ECMO. More importantly, evidence-based guidelines for burns are urgently needed to further improve the clinical effect of ECMO.

Neonatal and pediatric extracorporeal membrane oxygenation (ECMO) is carried out commonly using occlusive blood pumps. Centrifugal pumps provide simple and safe technology for transportation on ECMO. The assistence respiratoire extra corporelle (AREC) system enables single needle venovenous ECMO for infants. We report on our experience with neonatal and pediatric ECMO treatments using nonocclusive blood pumps. One-hundred forty-six ECMO treatments were performed for cardiac, neonatal, and pediatric indications in 54, 19, and 27% of cases. Centrifugal pumps were used in 99, and the AREC system in 42 cases. Hospital mortality was estimated retrospectively and influence of type of pump, type of ECMO belonging to indication group, and lactate at ECMO installation were estimated. Irreversible organ failure leading to ECMO termination was investigated within groups of indications. Survival (recent 50 ECMO treatments) was 80, 70, 43, and 30% after meconium aspiration syndrome, acute respiratory distress syndrome, cardiac surgery, and prolonged resuscitation. Lactate exceeding 100 mg/dl at ECMO installation predicted significantly worse outcome. Cerebral damage was the main reason for ECMO termination in all but persistent circulatory failure in the cardiac group. Myocardial recovery resulted in all except 2 cardiac cases. Nonocclusive blood pumps can be used safely in neonatal and pediatric ECMO. Early installation may improve outcome markedly. In cardiac cases results of surgery should be thoroughly investigated on the table before ECMO installation to prevent hopeless ECMO treatments.