Perioperative anaphylaxis management and testing: a quaternary centre audit.

BACKGROUND: Anaphylaxis is a severe, potentially life-threatening generalized or systemic hypersensitivity reaction. Sequential reports have cited anaphylaxis as the most common cause of anaesthesia-related deaths. We undertook an audit at a quaternary centre, examining the management of perioperative anaphylaxis and quality of referrals made to our anaesthesia allergy testing service. METHODS: The data of 41 patients consulted at St Vincent's Hospital Melbourne for perioperative anaphylaxis between 17th of January 2020 and 20th of January 2022 were analysed. Intervention outcomes included total intravenous fluid administered, adrenaline administration, instigation of CPR and the collection and the timing of serum tryptase samples. We also assessed referral quality, provision of institutional allergy alert and time elapsed from the anaphylaxis event to allergy testing. Contemporaneous Australian and New Zealand Anaesthetic Allergy Group (ANZAAG) guidelines were used as the reference standard for most outcomes. RESULTS: Our data reveals compliance of <80% with respect to intravenous fluid administration, referral quality and tryptase sampling, particularly at the 4-h timepoint. CONCLUSION: Surgical leadership and patient advocacy in the post-acute phase would likely facilitate requisite testing and improve the quality of counselling. We recommend institutions adopt a case-by-case review of management compliance with recommendations. Additionally, we advocate for the inclusion of a prompt to the ANZAAG referral form, that encourages the operator to update their patient's institutional allergy alert while awaiting allergy testing.

Endothelial Caspase-8 prevents fatal necroptotic hemorrhage caused by commensal bacteria.

Caspase-8 transduces signals from death receptor ligands, such as tumor necrosis factor, to drive potent responses including inflammation, cell proliferation or cell death. This is a developmentally essential function because in utero deletion of endothelial Caspase-8 causes systemic circulatory collapse during embryogenesis. Whether endothelial Caspase-8 is also required for cardiovascular patency during adulthood was unknown. To address this question, we used an inducible Cre recombinase system to delete endothelial Casp8 in 6-week-old conditionally gene-targeted mice. Extensive whole body vascular gene targeting was confirmed, yet the dominant phenotype was fatal hemorrhagic lesions exclusively within the small intestine. The emergence of these intestinal lesions was not a maladaptive immune response to endothelial Caspase-8-deficiency, but instead relied upon aberrant Toll-like receptor sensing of microbial commensals and tumor necrosis factor receptor signaling. This lethal phenotype was prevented in compound mutant mice that lacked the necroptotic cell death effector, MLKL. Thus, distinct from its systemic role during embryogenesis, our data show that dysregulated microbial- and death receptor-signaling uniquely culminate in the adult mouse small intestine to unleash MLKL-dependent necroptotic hemorrhage after loss of endothelial Caspase-8. These data support a critical role for Caspase-8 in preserving gut vascular integrity in the face of microbial commensals.

Inflammatory Biomarker Levels After Propofol or Sevoflurane Anesthesia: A Meta-analysis.

BACKGROUND: The perioperative inflammatory response may be implicated in adverse outcomes including neurocognitive dysfunction and cancer recurrence after oncological surgery. The immunomodulatory role of anesthetic agents has been demonstrated in vitro; however, its clinical relevance is unclear. The purpose of this meta-analysis was to compare propofol and sevoflurane with respect to biomarkers of perioperative inflammation. The secondary aim was to correlate markers of inflammation with clinical measures of perioperative cognition. METHODS: Databases were searched for randomized controlled trials examining perioperative inflammation after general anesthesia using propofol compared to sevoflurane. Inflammatory biomarkers investigated were interleukin (IL)-6, IL-10, tissue necrosis factor alpha (TNF-α), and C-reactive protein (CRP). The secondary outcome was incidence of perioperative neurocognitive disorders. Meta-analysis with metaregression was performed to determine the difference between propofol and sevoflurane. RESULTS: Twenty-three studies were included with 1611 participants. Studies varied by surgery type, duration, and participant age. There was an increase in the mean inflammatory biomarker levels following surgery, with meta-analysis revealing no difference in effect between propofol and sevoflurane. Heterogeneity between studies was high, with surgery type, duration, and patient age contributing to the variance across studies. Only 5 studies examined postoperative cognitive outcomes; thus, a meta-analysis could not be performed. Nonetheless, of these 5 studies, 4 reported a reduced incidence of cognitive decline associated with propofol use. CONCLUSIONS: Surgery induces an inflammatory response; however, the inflammatory response did not differ as a function of anesthetic technique. This absence of an effect suggests that patient and surgical variables may have a far more significant impact on the postoperative inflammatory responses than anesthetic technique. The majority of studies assessing perioperative cognition in older patients reported a benefit associated with the use of propofol; however, larger trials using homogenous outcomes are needed to demonstrate such an effect.