Neurological complications during veno-venous extracorporeal membrane oxygenation: Does the configuration matter? A retrospective analysis of the ELSO database.

BACKGROUND: Single- (SL) and double-lumen (DL) catheters are used in clinical practice for veno-venous extracorporeal membrane oxygenation (V-V ECMO) therapy. However, information is lacking regarding the effects of the cannulation on neurological complications. METHODS: A retrospective observational study based on data from the Extracorporeal Life Support Organization (ELSO) registry. All adult patients included in the ELSO registry from 2011 to 2018 submitted to a single run of V-V ECMO were analyzed. Propensity score (PS) inverse probability of treatment weighting estimation for multiple treatments was used. The average treatment effect (ATE) was chosen as the causal effect estimate of outcome. The aim of the study was to evaluate differences in the occurrence and the type of neurological complications in adult patients undergoing V-V ECMO when treated with SL or DL cannulas. RESULTS: From a population of 6834 patients, the weighted propensity score matching included 6245 patients (i.e., 91% of the total cohort; 4175 with SL and 20,270 with DL cannulation). The proportion of patients with at least one neurological complication was similar in the SL (306, 7.2%) and DL (189, 7.7%; odds ratio 1.10 [95% confidence intervals 0.91-1.32]; p = 0.33). After weighted propensity score, the ATE for the occurrence of least one neurological complication was 0.005 (95% CI - 0.009 to 0.018; p = 0.50). Also, the occurrence of specific neurological complications, including intracerebral hemorrhage, acute ischemic stroke, seizures or brain death, was similar between groups. Overall mortality was similar between patients with neurological complications in the two groups. CONCLUSIONS: In this large registry, the occurrence of neurological complications was not related to the type of cannulation in patients undergoing V-V ECMO.

Coagulation Factor Levels and Underlying Thrombin Generation Patterns in Adult Extracorporeal Membrane Oxygenation Patients.

BACKGROUND: There is a paucity of data on the underlying procoagulant-anticoagulant balance during extracorporeal membrane oxygenation (ECMO). We hypothesized that adult ECMO patients would have an imbalance between procoagulant and anticoagulant factors, leading to an abnormal underlying thrombin generation (TG) pattern. METHODS: Twenty adult venoarterial (VA) ECMO patients had procoagulant and anticoagulant factor levels measured temporally on ECMO day 1 or 2, day 3, and day 5. In heparin-neutralized plasma, underlying TG patterns, and sensitivity to activated protein C were assessed using calibrated automated thrombogram. TG parameters including lag time, peak TG, and endogenous thrombin potential (ETP) were compared against 5 normal plasma controls (3 males and 2 females) obtained from a commercial supplier. Thrombomodulin (TM) was added to some samples to evaluate for activated protein C resistance. RESULTS: Procoagulant factors (factor [F] II, FV, and FX) were mostly in normal reference ranges and gradually increased during the first 5 ECMO days (P = .022, <.001, <.001). FVIII levels were elevated at all time points and did not change (P = .766). In contrast, FXI was in the low-normal range but did not increase during ECMO (P = .093). Antithrombin (AT) and protein C levels were below normal but increased during the first 5 ECMO days (P = .002 and P = .014). Heparinase-treated samples showed prolonged lag time, increased peak TG, and increased ETP compared to controls; mean difference in lag time on ECMO day 1 or 2 = 6.0 minutes (99% confidence interval [CI], 2.8-9.2), peak TG = 193.4 (99% CI, 122.5-264.3), and ETP = 1170.4 (99% CI, 723.2-1617.6). After in vitro TM treatment, differences in TG parameters were accentuated and ECMO samples appeared insensitive to TM treatment; mean difference in lag time on ECMO day 1 or 2 = 9.3 minutes (99% CI, 6.2-12.4), peak TG = 233.0 (99% CI, 140.9-325.1), and ETP = 1322.5 (99% CI, 764.8-1880.2). Similar differences in TG parameters were observed on ECMO days 3 and 5. CONCLUSIONS: Contact activation occurs during ECMO, but procoagulant factor levels are generally preserved. Although heparin-neutralized TG is delayed, peak TG and ETP are supranormal in the setting of high FVIII and low AT and protein C levels. Resistance to TM is also apparent. These changes demonstrate a possible mechanism for hypercoagulability during adult VA ECMO.

Use of therapeutic plasma exchange as a rescue therapy in 2009 pH1N1 influenza A--an associated respiratory failure and hemodynamic shock.

OBJECTIVE: Acute pneumonitis with acute lung injury is a cause of significant mortality related to the 2009 pH1N1 influenza A virus. Widespread lung inflammation and increased pulmonary vascular permeability has been noted on autopsy. Also, many of these patients present with significant hemodynamic compromise suggesting systemic cytokine release. Therefore, attenuating circulating cytokines, and other mediators, by blood purification techniques is a theoretically attractive strategy. We report the use therapeutic plasma exchange in three children with 2009 H1N1 related acute lung injury with severe hemodynamic compromise that had failed conventional therapeutic interventions. DESIGN: Case series. SETTING: Pediatric intensive care unit in a university children's hospital. PATIENTS: Three children, aged 8, 11, and 17 yrs, with acute respiratory distress syndrome and hemodynamic compromise related to the 2009 pH1N1 influenza A virus documented by polymerase chair reaction. All patients were on mechanical ventilation and inhaled nitric oxide, and one patient was on extracorporeal membrane oxygenation. Therapeutic plasma exchange was used as a rescue strategy. INTERVENTIONS: Each patient received three exchanges of 35-40 mL/kg on consecutive days. MEASUREMENTS: All three patients had dramatic reduction in pediatric logistic organ dysfunction scores, oxygen requirements, and vasopressor requirements after two exchanges. All survived with good functional recovery. MAIN RESULTS: In this small series of patients with H1N1/acute respiratory distress syndrome and hemodynamic compromise, therapeutic plasma exchange appeared to benefit as a method of mitigating the associated cytokine storm. The procedure was well tolerated with no reported side effects. All three patients survived, defying the predicted mortality. Because these procedures used the filtration exchange method, it was performed in a timely fashion by intensive care unit personnel and on equipment already available in the intensive care unit for renal support. CONCLUSIONS: This very limited case series suggest there may be a role for therapeutic plasma exchange as a rescue therapy in severe shock and acute lung injury related to pH1N1 that has not responded to traditional therapy.

Continuous renal replacement therapies: a brief primer for the neurointensivist.

Continuous renal replacement therapy (CRRT) is a renal replacement modality that is often used in the ICU setting, including the neuro-ICU. This form of renal replacement therapy has been used classically for acute renal failure in patients with hemodynamic compromise, but is gaining acceptance as a method to control vascular and extra-vascular volume and mediate cytokines in non-renal diseases. Although these uses are briefly discussed, this review concentrates on the different forms of continuous renal replacement, mainly focusing on the technology of convective versus diffusive modalities and briefly on filter technology. There is also discussion on the various anticoagulation regimes used in CRRT including data on performing CRRT without anticoagulation. This review is not meant to be a discussion on the pros and cons of CRRT versus intermittent dialysis, but rather a primer on the technology of CRRT and how this therapy may affect general care of the ICU patient.