ABSTRACT
OBJECTIVE: Post-partum hemorrhage (PPH) is the leading preventable cause of worldwide maternal morbidity and mortality. Risk factors for psychological disorders following PPH are currently unknown. HELP-MOM study aimed to determine the incidence and identify risk factors for psychological disorders following PPH. METHODS: HELP-MOM study was a prospective, observational, national, and multicentre study including patients who experienced severe PPH requiring sulprostone. The primary endpoint was the occurrence of psychological disorders (anxiety and/or post-traumatic disorder and/or depression) following PPH, assessed at 1, 3, and 6 months after delivery using HADS, IES-R, and EPDS scales. RESULTS: Between November 2014 and November 2016, 332 patients experienced a severe PPH and 236 (72%) answered self-questionnaires at 1, 3, and 6 months. A total of 161 (68%) patients declared a psychological disorder following severe PPH (146 (90.1%) were screened positive for anxiety, 96 (58.9%) were screened positive for post-traumatic stress disorder, and 94 (57.7%) were screened positive for post-partum depression). In multivariable analysis, the use of intra-uterine tamponnement balloon was associated with a lower risk to be screened positive for psychological disorder after severe PPH (OR = 0.33 [IC95% 0.15-0.69], p = 0.004, and after propensity score matching (OR=0.34 [IC95% 0.12-0.94], p = 0.04)). Low hemoglobin values during severe PPH management were associated with a higher risk of being screened positive for psychological disorders. Finally, we did not find differences in desire or pregnancy between patients without or with psychological disorders occurring in the year after severe PPH. DISCUSSION: Severe PPH was associated with significant psychosocial morbidity including anxiety, post-traumatic disorder, and depression. This should engage a psychological follow-up. Large cohorts are urgently needed to confirm our results. REGISTRATION: ClinicalTrials.gov under number NCT02118038.
Subject(s)
Postpartum Hemorrhage , Stress Disorders, Post-Traumatic , Female , Humans , Pregnancy , Anxiety/epidemiology , Anxiety/etiology , Postpartum Hemorrhage/epidemiology , Postpartum Hemorrhage/therapy , Postpartum Period , Prospective Studies , Stress Disorders, Post-Traumatic/epidemiology , Stress Disorders, Post-Traumatic/etiologyABSTRACT
Local anesthetics have anti-inflammatory effects. Because most previous experiments were performed with supra-therapeutic concentrations, we measured the effects of clinically relevant concentrations of bupivacaine on the Toll like receptor 4 (TLR4)- and TLR2-myeloid differentiation primary response 88 (MyD88)-nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) pathways. We measured tumor necrosis factor alpha (TNF-α) and prostaglandin E2 (PGE2) release, p38 mitogen-activated protein kinase (MAP-kinase) phosphorylation and translocation of NF-κB in human peripheral blood mononuclear cells (hPBMCs) and human monocytes challenged with lipopolysaccharide (LPS) or tripalmitoylated lipopeptide Pam3CysSerLys4 (Pam3CSK4) in the presence or absence of bupivacaine. Similarly, we measured the effect of bupivacaine on HEK293 cells expressing the hTLR4 and the hTLR2 genes and challenged with LPS or Pam3CSK4. Finally, molecular docking simulations of R(+)- and S(-)-bupivacaine binding to the TLR4-myeloid differentiation protein 2 (MD-2) complex and to the TLR2/TLR1 heterodimer were performed. In PBMCs, bupivacaine from 0.1 to 100 µM inhibited LPS-induced TNF-α and PGE2 secretion, phosphorylation of p38 and nuclear translocation of NF-κB in monocytes. Bupivacaine similarly inhibited the effects of Pam3CSK4 on TNF-α secretion. Bupivacaine inhibited the effect of LPS on HEK293 cells expressing the human TLR4 receptor and the effect of Pam3CSK4 on HEK293 cells expressing the human TLR2 receptor. Molecular docking showed that bupivacaine binds to the MD-2 co-receptor of TLR4 and to the TLR2 receptor. Contrary to numerous experiments performed with supratherapeutic doses, our results were obtained with concentrations of bupivacaine as low as 0.1 µM. We conclude that bupivacaine modulates the inflammatory reactions such as those observed after surgery or trauma, at least partly by inhibiting the TLR4- and TLR2-NF-κB pathways.
Subject(s)
NF-kappa B , Toll-Like Receptor 4 , Humans , NF-kappa B/metabolism , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 2/genetics , Toll-Like Receptor 2/metabolism , Myeloid Differentiation Factor 88/genetics , Myeloid Differentiation Factor 88/metabolism , Myeloid Differentiation Factor 88/pharmacology , Signal Transduction , Leukocytes, Mononuclear/metabolism , Lipopolysaccharides/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Dinoprostone , Molecular Docking Simulation , Bupivacaine/pharmacology , HEK293 CellsABSTRACT
The curative role of sugammadex has been challenged in several observations of rocuronium-induced anaphylaxis because sugammadex may not completely encapsulate the molecule of rocuronium. In such conditions, rocuronium remains able to cause immunoglobulin E cross-linkage and the anaphylaxis mechanism can continue. We describe a case of rocuronium-induced anaphylaxis in which clinical improvement followed sugammadex administration. Intradermic skin tests confirmed rocuronium immunoglobulin E-mediated anaphylaxis but also showed intradermal injection of mixing in equal molecular ratio of sugammadex with rocuronium preventing rocuronium anaphylactic skin reaction. This observation demonstrates the efficacy of sugammadex to prevent rocuronium interaction with the skin immune system.
