Background: Remifentanil-induced hyperalgesia (r-IH) involves an imbalance in the inhibitory and excitatory systems. As the transcranial Direct Current Stimulation (tDCS) modulates the thalamocortical synapses in a top-down manner, we hypothesized that the active (a)-t-DCS would be more effective than sham(s)-tDCS to prevent r-IH. We used an experimental paradigm to induce temporal summation of pain utilizing a repetitive cold test (rCOLDT) assessed by the Numerical Pain Score (NPS 0-10) and we evaluated the function of the descending pain modulatory system (DPMS) by the change on the NPS (0–10) during the conditioned pain modulation (CPM)-task (primary outcomes). We tested whether a-tDCS would be more effective than s-tDCS to improve pain perception assessed by the heat pain threshold (HPT) and the reaction time during the ice-water pain test (IPT) (secondary outcomes).Methods: This double-blinded, factorial randomized trial included 48 healthy males, ages ranging 19–40 years. They were randomized into four equal groups: a-tDCS/saline, s-tDCS/saline, a-tDCS/remifentanil and s-tDCS/remifentanil. tDCS was applied over the primary motor cortex, during 20 min at 2 mA, which was introduced 10 min after starting remifentanil infusion at 0.06 μg⋅kg-1⋅min-1 or saline.Results: An ANCOVA mixed model revealed that during the rCOLDT, there was a significant main effect on the NPS scores (F = 3.81; P = 0.01). The s-tDCS/remifentanil group presented larger pain scores during rCOLDT, [mean (SD) 5.49 (1.04)] and a-tDCS/remifentanil group had relative lower pain scores [4.15 (1.62)]; showing its blocking effect on r-IH. a-tDCS/saline and s-tDCS/saline groups showed lowest pain scores during rCOLDT, [3.11 (1.2)] and [3.15 (1.62)], respectively. The effect of sedation induced by remifentanil during the rCOLDT was not significant (F = 0.76; P = 0.38). Remifentanil groups showed positive scores in the NPS (0–10) during the CPM-task, that is, it produced a disengagement of the DPMS. Also, s-tDCS/Remifentanil compared to a-tDCS showed lower HPT and larger reaction-time during the IPT.Conclusion: These findings suggest that effects of a-tDCS prevent the summation response induced by r-IH during rCOLDT and the a-tDCS blocked the disengagement of DPMS. Thereby, tDCS could be considered as a new approach to contra-regulate paradoxical mechanisms involved in the r-IH. Clinical trials identification: NCT02432677. URL:https://clinicaltrials.gov/.

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The high mortality rate found may reflect the high complexity of the institution's patients. Knowing the profile of the patients assisted helps in the definition of management priorities, suggesting the need to create specific care lines for groups identified as high risk in order to reduce perioperative complications and deaths.

Summary Mortality and morbidity for high‐risk surgical patients are often high, especially in low‐resource settings. Enhanced peri‐operative care has the potential to reduce preventable deaths but must be designed to meet local needs. This before‐and‐after cohort study aimed to assess the effectiveness of a postoperative 48‐hour enhanced care pathway for high‐risk surgical patients (‘high‐risk surgical bundle’) who did not meet the criteria for elective admission to intensive care. The pathway comprised of six elements: risk identification and communication; adoption of a high‐risk post‐anaesthesia care unit discharge checklist; prompt nursing admission to ward; intensification of vital signs monitoring; troponin measurement; and prompt access to medical support if required. The primary outcome was in‐hospital mortality. Data describing 1189 patients from two groups, before and after implementation of the pathway, were compared. The usual care group comprised a retrospective cohort of high‐risk surgical patients between September 2015 and December 2016. The intervention group prospectively included high‐risk surgical patients from February 2019 to March 2020. Unadjusted mortality rate was 10.5% (78/746) for the usual care and 6.3% (28/443) for the intervention group. After adjustment, the intervention effect remained significant (RR 0.46 (95%CI 0.30–0.72). The high‐risk surgical bundle group received more rapid response team calls (24% vs. 12.6%; RR 0.63 [95%CI 0.49–0.80]) and surgical re‐interventions (18.9 vs. 7.5%; RR 0.41 [95%CI 0.30–0.59]). These data suggest that a clinical pathway based on enhanced surveillance for high‐risk surgical patients in a resource‐constrained setting could reduce in‐hospital mortality.

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