Sufentanil sublingual tablet system versus oral oxycodone for management of postoperative pain in enhanced recovery after surgery pathway for total knee arthroplasty: a randomized controlled study.

PURPOSE: Effectiveness of sufentanil sublingual tablet system (SSTS) compared to oral oxycodone in the management of postoperative pain after total knee arthroplasty (TKA) within an enhanced recovery after surgery (ERAS) protocol. METHODS: This pragmatic, parallel, open label, randomized controlled, trial enrolled 72 adult patients scheduled for TKA under spinal anesthesia following ERAS pathway. In addition to multimodal analgesia, patients received SSTS 15 mcg (SSTS group) or oral oxycodone extended release 10 mg twice daily and oral oxycodone immediate-release 5 mg up to four times daily on demand (Oxy group) to control pain during 48 h postoperatively. The primary endpoint was pain measured using a numeric rating scale at 24 h postoperatively. Time to first mobilization, side effects and patient satisfaction were also recorded. RESULTS: Median pain score at 24 h at rest was 3 [2-4] for Oxy group vs 2 [1.75-3] for SSTS group (p = 0.272) whereas median pain score on movement was 4 [3-6] vs 3 [2-5] respectively (p = 0.059). No difference in time to first mobilization was found between the two groups. The method of pain control was judged good/excellent for 83.9% of patients in the SSTS group compared with 52.9% in the Oxy group (p = 0.007). The incidence of nausea was 33% in SSTS group and 9% in Oxy group (p = 0.181). CONCLUSIONS: In complement to ERAS multimodal analgesia, sublingual sufentanil 15 mcg tablet system did not show clinically significant pain improvement compared to oral oxycodone after total knee arthroplasty. TRIAL REGISTRATION: Clinical Trials: NCT04448457 ; retrospectively registered on June 24, 2020. https://clinicaltrials.gov/ct2/show/NCT04448457?cond=sublingual+sufentanil&cntry=BE&draw=2&rank=3.

Comparison of the ability of esCCO and Volume View to measure trends in cardiac output in patients undergoing cardiac surgery.

BACKGROUND: Cardiac output (CO) is a physiological variable that should be monitored during cardiac surgery. The purpose of this study was to assess the trending ability of two CO monitors, esCCO (Nihon Kohden™, Tokyo, Japan) and Volume View (VV) (Edwards Lifesciences, Irvine, USA). METHODS: A total of 19 patients were included in the study. Before cardiopulmonary bypass (CPB), CO was measured simultaneously using both esCCO and VV devices before and after three CO-modifying manoeuvres (passive leg raise [PLR], the end expiratory occlusion test [EEOT] and positive end expiratory pressure [PEEP] at 10 cm H2O). Five CO values for esCCO and three for VV were averaged and compared during a one-minute period of time before and after each manoeuvre. RESULTS: A total of 114 paired readings were collected. Median CO values were 4.3 L min⁻¹ (IQR: 3.8; 5.2) and 3.8 L min⁻¹ (IQR: 3.5; 4.5) for esCCO and VV, respectively. The precision error was 1.4% (95% CI:1.0-1.7) for esCCO and 2.2% (95% CI: 1.8-2.7) for VV. The bias between esCCO and VV values was normally distributed (P = 0.0596). Between esCCO and VV, the mean bias was +0.6 L min⁻¹ with a Limit of Agreement (LOA) of -1.8 L min⁻¹ and +3.0 L min⁻¹. The concordance rate was 43% (95% CI: 29-58) between esCCO and VV. CONCLUSION: Both single and trended measurements of CO using esCCO and VV were not in agreement. This large discrepancy leads one to the conclusion that any outcome study conducted with one of these devices cannot be applied to the other.

Clinical application of the cardioprotective effects of volatile anaesthetics: CON--total intravenous anaesthesia or not total intravenous anaesthesia to anaesthetise a cardiac patient?

Although volatile anaesthetics show strong and easily reproducible cardioprotective effects in animal experiments, these effects are less obvious in clinical settings. Indeed, more than a decade after the first human clinical study, the number of publications has increased extensively, but the encouraging results from previous studies in terms of myocardial protection have failed to translate into an improvement in survival or a decrease the incidence of myocardial infarction. No consensus on the modalities of administration of volatile anaesthetics has been agreed and when the experimental protocols are transposed into daily clinical practice, their cardioprotective effects are still weak. The reasons for the disparities between experimental and clinical studies will be reviewed here, especially the role of patients' co-morbidities and medications as well as the limitations of the main positive clinical trials. Recent data showing anti-inflammatory properties of propofol will also be explained. One of the most important clinical benefits of propofol is that it can be used by target-controlled or continuous infusion for anaesthesia and sedation throughout the surgical and critical care periods without the risk of a transition failure. Further large multi-centre clinical investigations are still required.

Myeloid-derived suppressor cells: characterization and expansion in models of endotoxemia and transplantation.

CD11b+GR1+ myeloid-derived suppressor cells (MDSC) accumulate in several inflammatory conditions including cancer, infections, or trauma. MDSCs are found in bone marrow and lymphoid organs and suppress both innate and adaptive immune responses. Although mechanisms of suppression are not fully understood, they have been reported to require cell-cell contact and very often implicate L-arginine metabolism. We and others recently observed that lipopolysaccharide (LPS) administration, as other TLR ligands, induces MDSC. In this case, MDSC regulate immune response independently of L-arginine metabolism through heme oxygenase-1 activity. Manipulating MDSC as immunoregulators represents an attractive approach for cancer immunotherapy or transplantation. Herein, we describe methods for expanding and purifying MDSC, as well as in vitro and in vivo techniques to measure their suppressive functions.

Myeloid-derived suppressor cells in transplantation.

PURPOSE OF REVIEW: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature cells that are considered as potential therapeutic targets. Indeed, MDSCs have been shown to suppress immune responses to several types of tumor cells and blocking their suppressive activity may adequately enhance immune response against tumor antigens. On the contrary, the activity of MDSCs may be desirable in suppressing unwanted immune responses such as allograft rejection and might be involved as non-T regulatory cells in the induction and maintenance of transplantation tolerance. In addition, recent data reported that MDSC also control innate immune responses suggesting that MDSC might be important players in controlling ischemia reperfusion injury. RECENT FINDINGS: Herein, we focused on the few recent studies questioning the possible role played by MDSCs in solid-organ transplantation as well as in experimental models of graft versus host disease. SUMMARY: A growing body of evidence demonstrates that MDSCs are important physiological regulators of innate and adaptive immunity. Now, accumulating studies suggest that this concept can be transposed to the early and late transplantation immunity. Nevertheless, additional studies with mechanistic approaches in animal together with studies in human are required to better define their position and their interactions with immunosuppressive drugs.

Critical role of regulatory T cells in Th17-mediated minor antigen-disparate rejection.

Th17-mediated immune responses have been recently identified as novel pathogenic mechanisms in a variety of conditions; however, their importance in allograft rejection processes is still debated. In this paper, we searched for MHC or minor Ag disparate models of skin graft rejection in which Th17 immune responses might be involved. We found that T cell-derived IL-17 is critical for spontaneous rejection of minor but not major Ag-mismatched skin grafts. IL-17 neutralization was associated with a lack of neutrophil infiltration and neutrophil depletion delayed rejection, suggesting neutrophils as an effector mechanism downstream of Th17 cells. Regulatory T cells (Tregs) appeared to be involved in Th17 reactivity. We found that in vivo Treg depletion prevented IL-17 production by recipient T cells. An adoptive cotransfer of Tregs with naive monospecific antidonor T cells in lymphopenic hosts biased the immune response toward Th17. Finally, we observed that IL-6 was central for balancing Tregs and Th17 cells as demonstrated by the prevention of Th17 differentiation, the enhanced Treg/Th17 ratio, and a net impact of rejection blockade in the absence of IL-6. In conclusion, the ability of Tregs to promote the Th17/neutrophil-mediated pathway of rejection that we have described should be considered as a potential drawback of Treg-based cell therapy.