Questioning the Role of Carotid Artery Ultrasound in Assessing Fluid Responsiveness in Critical Illness: A Systematic Review and Meta-Analysis.

Background: A noninvasive and accurate method of identifying fluid responsiveness in hemodynamically unstable patients has long been sought by physicians. Carotid ultrasound (US) is one such modality previously canvassed for this purpose. The aim of this novel systematic review and meta-analysis is to investigate whether critically unwell patients who are requiring intravenous (IV) fluid resuscitation (fluid responders) can be identified accurately with carotid US. Methods: The protocol was registered with PROSPERO on the 30/11/2022 (ID number: CRD42022380284). Studies investigating carotid ultrasound accuracy in assessing fluid responsiveness in hemodynamically unstable patients were included. Studies were identified through searches of six databases, all run on 4 November 2022, Medline, Embase, Emcare, APA PsycInfo, CINAHL, and Cochrane Library. Risk of bias was assessed using the QUADAS-2 and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidelines. Results were pooled, meta-analysis was conducted where amenable, and hierarchical summary receiver operating characteristic models were established to compare carotid ultrasound measures. Results: Seventeen studies were included (n = 842), with 1048 fluid challenges. 441 (42.1%) were fluid responsive. Four different carotid US measures were investigated, including change in carotid doppler peak velocity (∆CDPV), carotid blood flow (CBF), change in carotid artery velocity time integral (∆CAVTI), and carotid flow time (CFT). Pooled carotid US had a pooled sensitivity, specificity, and AUROC with 95% confidence intervals (CI) of 0.73 (0.66-0.78), 0.82 (0.72-0.90), and 0.81 (0.78-0.85), respectively. ∆CDPV had sensitivity, specificity, and AUROC with 95% CI of 0.72 (0.64-0.80), 0.87 (0.73-0.94), and 0.82 (0.78-0.85), respectively. CBF had sensitivity, specificity, and AUROC with 95% CI of 0.70 (0.56-0.80), 0.80 (0.50-0.94), and 0.77 (0.78-0.85), respectively. Risk of bias and assessment was undertaken using the QUADAS-2 and GRADE tools. The QUADAS-2 found that studies generally had an unclear or high risk of bias but with low applicability concerns. The GRADE assessment showed that ∆CDPV and CBF had low accuracy for sensitivity and specificity. Conclusion: It appears that carotid US has a limited ability to predict fluid responsiveness in critically unwell patients. ∆CDPV demonstrates the greatest accuracy of all measures analyzed. Further high-quality studies using consistent study design would help confirm this.

Predicting Fluid Responsiveness Using Carotid Ultrasound in Mechanically Ventilated Patients: A Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies.

BACKGROUND: A noninvasive and accurate method of determining fluid responsiveness in ventilated patients would help to mitigate unnecessary fluid administration. Although carotid ultrasound has been previously studied for this purpose, several studies have recently been published. We performed an updated systematic review and meta-analysis to evaluate the accuracy of carotid ultrasound as a tool to predict fluid responsiveness in ventilated patients. METHODS: Studies eligible for review investigated the accuracy of carotid ultrasound parameters in predicting fluid responsiveness in ventilated patients, using sensitivity and specificity as markers of diagnostic accuracy (International Prospective Register of Systematic Reviews [PROSPERO] CRD42022380284). All included studies had to use an independent method of determining cardiac output and exclude spontaneously ventilated patients. Six bibliographic databases and 2 trial registries were searched. Medline, Embase, Emcare, APA PsycInfo, CINAHL, and the Cochrane Library were searched on November 4, 2022. Clinicaltrials.gov and Australian New Zealand Clinical Trials Registry were searched on February 24, 2023. Results were pooled, meta-analysis was conducted where possible, and hierarchical summary receiver operating characteristic models were used to compare carotid ultrasound parameters. Bias and evidence quality were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidelines. RESULTS: Thirteen prospective clinical studies were included (n = 648 patients), representing 677 deliveries of volume expansion, with 378 episodes of fluid responsiveness (58.3%). A meta-analysis of change in carotid Doppler peak velocity (∆CDPV) yielded a sensitivity of 0.79 (95% confidence interval [CI], 0.74-0.84) and a specificity of 0.85 (95% CI, 0.76-0.90). Risk of bias relating to recruitment methodology, the independence of index testing to reference standards and exclusionary clinical criteria were evaluated. Overall quality of evidence was low. Study design heterogeneity, including a lack of clear parameter cutoffs, limited the generalizability of our results. CONCLUSIONS: In this meta-analysis, we found that existing literature supports the ability of carotid ultrasound to predict fluid responsiveness in mechanically ventilated adults. ∆CDPV may be an accurate carotid parameter in certain contexts. Further high-quality studies with more homogenous designs are needed to further validate this technology.

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.