Challenges and pitfalls of extracorporeal membrane oxygenation in critically-ill pregnant and peripartum women with COVID-19: a retrospective case series.

BACKGROUND: Available data identify pregnancy as a strong determinant of a severe course of COVID-19 with increased mortality. Extracorporeal membrane oxygenation (ECMO) remains the last resort treatment in the critical course of COVID-19 yet may increase the risk of excessive bleeding, especially in the immediate post-cesarean section period. One in five patients receiving ECMO during the COVID-19 pandemic were women who were pregnant or postpartum. While the risk of critical respiratory failure in the peripartum period is high, in an early survey only 52% of pregnant patients intended to receive the COVID-19 vaccine. METHODS: Our study aimed to evaluate clinical characteristics and treatment modalities in a series of five pregnant and peripartum women supported with ECMO and anticoagulated with anti-Xa-guided nadroparin therapy in our center. We reviewed the full treatment courses; inflammatory, hemodynamic, and coagulation variables; and maternal and neonatal outcomes. We identified adverse events during the therapy. RESULTS: All five patients developed acute respiratory distress syndrome due to COVID-19 in the third trimester of pregnancy. Termination of pregnancy occurred between 28 and 36 gestational weeks. While four of five newborns survived to hospital discharge, only two of the five mothers survived to leave hospital. CONCLUSIONS: ECMO is feasible in the third trimester but not devoid of complications. The severity of respiratory failure during COVID-19 and extracorporeal support may not adversely impact neonatal outcomes.

7-Nitroindazole potentiates the anticonvulsant action of some second-generation antiepileptic drugs in the mouse maximal electroshock-induced seizure model.

The effects of 7-nitroindazole (7NI, a preferential neuronal nitric oxide synthase inhibitor) on the anticonvulsant activity of four second-generation antiepileptic drugs (AEDs: felbamate [FBM], lamotrigine [LTG], oxcarbazepine [OXC] and topiramate [TPM]) were studied in the mouse maximal electroshock-induced seizure (MES) model. Moreover, the influence of 7NI on the acute neurotoxic (adverse-effect) profiles of the studied AEDs, with regard to motor coordination, was determined in the chimney test in mice. Results indicate that 7NI (50 mg/kg; i.p.) significantly potentiated the anticonvulsant activity of OXC, but not that of FBM, LTG and TPM against MES-induced seizures and, simultaneously, it enhanced the acute neurotoxic effects of TPM, but not those of FBM, LTG and OXC in the chimney test in mice. 7NI at the lower dose of 25 mg/kg had no effect on the antiseizure activity and acute neurotoxic profiles of all investigated AEDs. Pharmacokinetic evaluation of interactions between 7NI and LTG, OXC and TPM against MES-induced seizures revealed no significant changes in free (non-protein bound) plasma AED concentrations following 7NI administration. Moreover, none of the examined combinations of 7NI with AEDs from the MES test were associated with long-term memory impairment in mice subjected to the step-through passive avoidance task. Based on our preclinical study, it can be concluded that only the combination of 7NI with OXC was beneficial, when considering its both anticonvulsant and acute neurotoxic effects. Moreover, the lack of impairment of long-term memory and no pharmacokinetic interactions in plasma of experimental animals make the combination of 7NI with OXC worthy of consideration for the treatment of patients with refractory epilepsy. The other combinations tested between 7NI and LTG, FBM and TPM were neutral, when considering their both anticonvulsant effects and acute neurotoxic profiles, therefore, no useful recommendation can be made for their clinical application.

Evaluation of interaction between valproate and baclofen in the formalin test in mice.

Valproate and baclofen dose-dependently inhibited both phases of the formalin test. Combination of valproate and baclofen exerted the additive antinociceptive effect on both phases of the formalin test.

Isobolographic analysis of interaction between vigabatrin and baclofen in the formalin test in mice.

Vigabatrin and baclofen given together, at doses not affecting motor performance, produced dose-dependent inhibition of both phases in the formalin test in mice. Isobolographic analysis revealed a significant synergy between both drugs in both phases of the forrmalin test.

Kynurenic acid does not protect against nicotine-induced seizures in mice.

Kynurenic acid, an antagonist of glutamatergic ionotropic receptors and alpha7 nicotinic cholinergic receptors failed to affect nicotine-induced convulsions in mice which may indicate that alpha7 nicotinic receptor-mediated events play no role in seizure activity produced by nicotine.