Non-Opioid Analgesics and Adjuvants after Surgery in Adults with Obesity: Systematic Review with Network Meta-Analysis of Randomized Controlled Trials.

Background/Objectives: Managing postoperative pain in patients with obesity is challenging. Although using a combination of pain relief methods is recommended for these patients, the true effectiveness of various intravenous non-opioid analgesics and adjuvants in multimodal anesthesia needs to be better defined. Methods: A systematic review and network meta-analysis was performed to evaluate the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, ketamine, α-2 agonists, lidocaine, magnesium, and oral gabapentinoids in adult surgical patients with obesity. The analysis aimed to compare these treatments to a placebo/no treatment or alternative analgesics, with a primary focus on postoperative pain and secondary endpoints including rescue analgesia, postoperative nausea and vomiting (PONV), and recovery quality. English-language randomized controlled trials across PubMed, Scopus, Web of Science, CINAHL, and EMBASE were considered. Quality and evidence certainty were assessed with the RoB 2 tool and GRADE, and data was analyzed with R software. Results: NSAIDs, along with acetaminophen, lidocaine, α-2 agonists, ketamine, and oral gabapentinoids, effectively reduce early postoperative pain. NSAIDs, particularly ibuprofen, as well as acetaminophen, ketamine, and lidocaine, also show benefits in later postoperative stages. Intravenous non-opioid analgesics and adjuvants show some degree of benefit in reducing PONV and the need for rescue analgesic therapy when using α-2 agonists alone or combined with oral gabapentinoids, notably decreasing the likelihood of PONV. Ketamine, lidocaine, and α-2 agonists are shown to enhance postoperative recovery and care quality. Conclusions: Intravenous non-opioid analgesics and adjuvants are valuable in multimodal anesthesia for pain management in adult surgical patients suffering from obesity.

Schnider and Eleveld Models for Propofol Target-Controlled Infusion Anesthesia: A Clinical Comparison.

BACKGROUND: Various pharmacokinetic/pharmacodynamic (PK/PD) models have been developed to accurately dose propofol administration during total intravenous anesthesia with target-controlled infusion (TIVA-TCI). We aim to clinically compare the performance of the Schnider model and the new and general-purpose Eleveld PK/PD model during TIVA-TCI. METHODS: We conducted a prospective observational study at a single center, enrolling 78 female patients, including 37 adults (aged < 65 years) and 41 elderly patients (aged ≥ 65 years). These patients underwent breast surgery with propofol-remifentanil TIVA-TCI guided by the bispectral index (BIS) for depth of anesthesia monitoring (target value 40-60) and the surgical plethysmographic index (SPI) for antinociception monitoring (target value 20-50) without neuromuscular blockade. The concentration at the effect site of propofol (CeP) at loss of responsiveness (LoR) during anesthesia maintenance (MA) and at return of responsiveness (RoR), the duration of surgery and anesthesia (min), the time to RoR (min), the propofol total dose (mg), the deepening of anesthesia events (DAEs), burst suppression events (BSEs), light anesthesia events (LAEs) and unwanted spontaneous responsiveness events (USREs) were considered to compare the two PK/PD models. RESULTS: Patients undergoing BIS-SPI-guided TIVA-TCI with the Eleveld PK/PD model showed a lower CeP at LoR (1.7 (1.36-2.25) vs. 3.60 (3.00-4.18) µg/mL, p < 0.001), higher CePMA (2.80 (2.55-3.40) vs. 2.30 (1.80-2.50) µg/mL, p < 0.001) and at RoR (1.48 (1.08-1.80) vs. 0.64 (0.55-0.81) µg/mL, p < 0.001) than with the Schnider PK/PD model. Anesthetic hysteresis was observed only in the Schnider PK/PD model group (p < 0.001). DAEs (69.2% vs. 30.8%, p = 0.001) and BSEs (28.2% vs. 5.1%, p = 0.013) were more frequent with the Eleveld PK/PD model than with the Schnider PK/PD model in the general patient population. DAEs (63.2% vs. 27.3%, p = 0.030) and BSEs (31.6% vs. 4.5%, p = 0.036) were more frequent with the Eleveld PK/PD model than with the Schnider PK/PD model in the elderly. CONCLUSIONS: The Schnider and Eleveld PK/PD models impact CePs differently. A greater incidence of DAEs and BSEs in the elderly suggests more attention is necessary in this group of patients undergoing BIS-SPI-guided TIVA-TCI with the Eleveld PK/PD than with the Schnider model.

Unwanted spontaneous responsiveness and burst suppression in patients undergoing entropy-guided total intravenous anesthesia with target-controlled infusion: An observational prospective trial.

STUDY OBJECTIVE: To estimate the incidence of unwanted spontaneous responsiveness and burst suppression (BSupp) in patients undergoing state entropy (SE) and surgical pleth index (SPI)-guided total intravenous anesthesia (TIVA) with target-controlled infusion (TCI). DESIGN: Observational, prospective, single-center study. SETTINGS: Operating room. PATIENTS: 107 adult (<65 years) and elderly (≥65 years) women undergoing breast surgery. INTERVENTIONS: Propofol-remifentanil TIVA-TCI-guided by SE for depth of anesthesia monitoring (target value 40-60) and SPI for antinociception monitoring (target value 20-50) without neuromuscular blockade. MEASUREMENTS: Age; body mass index; American Society of Anesthesiologists physical status classification; concentration at the effect site of propofol (CeP) and remifentanil (CeR) at loss of responsiveness (LoR), median during anesthesia maintenance (MdM), and at return of responsiveness (RoR); propofol infusion duration; incidence of postoperative delirium (POD) with Confusing Assessment Method for the Intensive Care Unit. MAIN RESULTS: During SE-SPI-guided TIVA-TCI, 13.1% of patients showed unwanted spontaneous responsiveness, whereas 45.8% showed BSupp. Unwanted spontaneous responsiveness was observed mainly in adults (p < 0.05), and higher CeP RoR (p < 0.05) was registered. BSupp was observed mainly in patients showing a lower CeP MdM (p < 0.01) and CeP RoR (p < 0.05). Unwanted spontaneous responsiveness and BSupp were not associated with significant differences in CeRs. An age-related hysteresis effect was observed, resulting in higher CeP LoR than CeP RoR (p < 0.001). 12.2% of patients showed POD. Only preoperative serum albumin was associated with increased likelihood of POD (p = 0.046). CONCLUSIONS: The SE-SPI-guided TIVA-TCI did not prevent unwanted spontaneous responsiveness and BSupp. CeP RoR may be used as a proxy for anesthetic sensitivity.

Influence of Previous General Anesthesia on Cognitive Impairment: An Observational Study Among 151 Patients.

Introduction: Preoperative neurocognitive disorder (preO-NCD) is a common condition affecting 14-51. 7% of the elderly population. General anesthesia has already been associated with the one-year post-operative neurocognitive disorder (PostO-NCD), specifically, a deficit in executive function, measured by the Trail Making Test B (TMT-B), but its long-term effects on cognitive function have not been investigated. We aimed to detect preO-NCD prevalence in patients scheduled for cardiac surgery and further investigate the possible role of previous general anesthesia (pGA) in general preoperative cognitive status [measured via the Montreal Cognitive Assessment (MoCA)] and/or in executive functioning (measured via TMT-B). Methods: In this observational, prospective study, 151 adult patients scheduled for elective cardiac surgery underwent MoCA and TMT-B. Data on age, education, pGA, comorbidities, and laboratory results were collected. Results: We discovered a general cognitive function impairment of 79.5% and an executive function impairment of 22%. Aging is associated with an increased likelihood (OR 2.99, p = 0.047) and education with a decreased likelihood (OR 0.35, p = 0.0045) of general cognitive impairment, but only education was significantly associated with a decreased likelihood (OR 0.22, p = 0.021) of executive function impairment. While pGA did not significantly affect preO-NCD, a noteworthy interaction between aging and pGA was found, resulting in a synergistic effect, increasing the likelihood of executive function impairment (OR 9.740, p = 0.0174). Conclusion: We found a high prevalence of preO-NCD in patients scheduled for cardiac surgery. General cognitive function impairment is highly associated with advancing age (not pGA). However, older patients with at least one pGA appeared to be at an increased risk of preO-NCD, especially executive function impairment, suggesting that TMT-B should be associated with MoCA in the preoperative cognitive evaluation in this population.

Targeted temperature management in cardiac surgery: a systematic review and meta-analysis on postoperative cognitive outcomes.

BACKGROUND: Postoperative cognitive decline occurs commonly after cardiac surgery. The available literature is inconclusive on the role of intraoperative causal or protective factors. METHODS: We systematically reviewed studies evaluating delayed neurocognitive recovery (DNR), postoperative neurocognitive disorder (NCD), stroke, and the mortality rates among patients undergoing hypothermic or normothermic cardiopulmonary bypass (CPB). We further performed a subgroup analysis for age, surgery type (coronary artery bypass grafting [CABG], valve surgery, or combined), and the mean arterial blood pressure (MAP) during CPB, and conducted a proportion meta-analysis after calculation of single proportions and confidence intervals (CIs). RESULTS: We included a total of 58 studies with 9609 patients in our analysis. Among these, 1906 of 4010 patients (47.5%) had DNR, and 2071 of 7160 (28.9%) had postoperative NCD. Ninety of 4625 patients (2.0%) had a stroke, and 174 of 7589 (2.3%) died. There was no statistically significant relationship between the considered variables and DNR, NCD, stroke, and mortality. In the subgroup analysis comparing hypothermic with normothermic CPB, we found higher NCD rates after combined surgery; for normothermic CPB cases only, the rates of DNR and NCD were lower after combined surgery compared with CABG surgery. A MAP >70 mm Hg compared with MAP=50-70 mm Hg during CPB was associated with a lower rate of DNR. CONCLUSIONS: Temperature, MAP during cardiopulmonary bypass age, and surgery type were not associated with neurocognitive disorders, stroke, and mortality in cardiac surgery. Normothermic cardiopulmonary bypass, particularly when performed with MAP >70 mm Hg, may reduce the risk of postoperative neurocognitive decline after cardiac surgery. PROSPERO REGISTRATION NUMBER: CRD42019140844.

Age influences on Propofol estimated brain concentration and entropy during maintenance and at return of consciousness during total intravenous anesthesia with target-controlled infusion in unparalyzed patients: An observational prospective trial.

PURPOSE: Aging affects pharmacodynamics/pharmacokinetics of anesthetics, but age effects on Entropy-guided total intravenous anesthesia with target-controlled infusions (TIVA-TCI) are not fully characterized. We compared aging effects on effective estimated brain concentration of Propofol (CeP) during TIVA-TCI Entropy-guided anesthesia, without neuromuscular blockade (NMB). METHODS: We performed an observational, prospective, single-center study enrolling 75 adult women undergoing Entropy-guided Propofol-Remifentanil TIVA-TCI for breast surgery. Primary endpoint was the relationship between age and CeP at maintenance of anesthesia (MA) during Entropy-guided anesthesia. Secondary endpoints were relationships between age and CeP at arousal reaction (AR), return of consciousness (ROC) and explicit recall evenience. We calculated a linear model to evaluate the age's impact on observational variable and performed pairwise tests to compare old (≥65 years, n = 50) and young (<65 years, n = 25) patients or patients with and without an AR. RESULTS: We did not observe age-related differences in CeP during MA, but CeP significantly (p = 0,01) decreased with age at ROC. Entropy values during MA increased with age and were significantly higher in the elderly (RE: median 56[IQR49.3-61] vs 47.5[42-52.5],p = 0.001; SE: 51.6[45-55.5] vs 44[IQR40-50],p = 0.005). 18 patients had an AR, having higher maximum RE (92.5[78-96.3] vs 65[56.5-80.5],p<0.001), SE (79[64.8-84] vs 61[52.5-69],p = 0.03, RE-SE (12.5[9.5-16.5] vs 6 [3-9],p<0.001. CONCLUSION: Older age was associated with lower CeP at ROC, but not during MA in unparalysed patients undergoing breast surgery. Although RE and SE during MA, at comparable CeP, were higher in the elderly, Entropy, and in particular an increasing RE-SE, is a reliable index to detect an AR.