Daily Anesthesiology Research Analysis
Analyzed 88 papers and selected 3 impactful papers.
Summary
Dose-optimized perioperative strategies emerged across three impactful studies: a network meta-analysis with Monte Carlo simulation defines a ketamine dosing window for pruritus and shivering prophylaxis in cesarean delivery; pooled prospective perioperative immune profiling links delayed recovery of innate immunity by POD3 with postoperative infection; and a very large retrospective cohort identifies a low intra-operative dexmedetomidine dose range associated with reduced delirium risk.
Research Themes
- Perioperative immunophenotyping to predict infectious complications
- Dose-optimization of anesthetic adjuvants (ketamine, dexmedetomidine)
- Delirium prevention strategies in non-cardiac surgery
Selected Articles
1. Estimated preventive dose of racemic ketamine for shivering and pruritus prophylaxis in cesarean delivery: a Monte Carlo simulation guided network meta-analysis.
Across 25 RCTs (n=3,842), dose–response modeling showed that low-dose racemic ketamine (~0.12 mg/kg IV bolus) effectively prevents neuraxial opioid-related pruritus with a favorable safety profile, while ~0.33 mg/kg is needed to prevent shivering but enters a range where neuropsychiatric adverse effects become common. These findings delineate a practical therapeutic window for goal-directed ketamine use in cesarean delivery.
Impact: Provides quantitative, clinically actionable dosing guidance using advanced network meta-analysis and Monte Carlo simulation, likely to standardize ketamine prophylaxis strategies in obstetric anesthesia.
Clinical Implications: Use ~0.12 mg/kg ketamine for pruritus prophylaxis when neuraxial opioids are used; weigh the narrower safety margin at ~0.33 mg/kg for shivering prevention against neuropsychiatric side effects. Incorporate patient-specific risk and shared decision-making.
Key Findings
- Low-dose ketamine (~0.12 mg/kg IV) effectively prevents neuraxial opioid–related pruritus with favorable tolerability.
- Shivering prophylaxis requires ~0.33 mg/kg, where neuropsychiatric side effects become common, indicating a narrow therapeutic window.
- Dose–response was quantified via network meta-analysis integrated with Monte Carlo simulation, enabling continuous ED parameter estimation.
Methodological Strengths
- PRISMA-compliant systematic review and network meta-analysis of RCTs with PROSPERO registration
- Advanced dose–response modeling using logistic regression and Monte Carlo simulation
Limitations
- Heterogeneity of trial protocols and outcome definitions across included RCTs
- Aggregate data meta-analysis without individual patient data may limit precision of covariate adjustments
Future Directions: Prospective dose-finding RCTs validating ~0.12 mg/kg for pruritus and comparing alternative regimens for shivering with standardized neuropsychiatric outcome measures.
BACKGROUND: The use of ketamine and esketamine in cesarean delivery is limited by their dose-dependent adverse effects. This study aimed to precisely quantify the dose-response relationships for the prevention of shivering and pruritus and to determine the associated risk of neuropsychiatric side effects, thereby defining its therapeutic window. METHODS: A systematic review and network meta-analysis were conducted. We searched databases for randomized controlled trials (RCTs) evaluating a single intravenous bolus of ketamine or esketamine during cesarean delivery under neuraxial anesthesia. Study quality was assessed using the Cochrane RoB 2 tool. We integrated traditional and network meta-analysis with logistic regression, Monte Carlo simulation, and polynomial regression to establish continuous dose-response models and calculate key dose parameters (ED RESULTS: 25 studies(3,842 participants) were included. The ED CONCLUSION: The benefits of low-dose ketamine (≈0.12 mg/kg) for pruritus prophylaxis clearly outweigh its risks. In contrast, the dose required for shivering prevention (≈0.33 mg/kg) falls within the range where side effects become common, resulting in a narrow therapeutic window. This study provides critical dose-finding evidence for individualized, goal-directed use of ketamine in cesarean delivery. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251073122, identifier CRD420251073122.
2. Perioperative immune dynamics and infectious complications: a pooled-data analysis of prospective studies.
Across 487 patients pooled from six prospective studies, surgery induced a stereotyped immune trajectory with early IL-6/IL-10 surges and suppression of ex vivo TNF/IL-1β production, most pronounced on POD1. Persisting innate immune suppression by POD3—especially after more invasive colorectal surgery—was associated with subsequent infection; proteomics corroborated inflammatory activation with downregulation of key immune signaling proteins.
Impact: Links time-resolved perioperative immune phenotypes to postoperative infections using multimodal assays, enabling mechanistically informed risk stratification and hypothesis generation for targeted immunomodulation.
Clinical Implications: Monitor early IL-6 and day-3 ex vivo TNF production to identify patients at risk for infection; consider tailoring surveillance and immunomodulatory strategies based on failure to recover innate immune function by POD3.
Key Findings
- Surgery induces an early inflammatory surge (IL-6/IL-10) with concurrent suppression of innate cytokine production (TNF, IL-1β) ex vivo, peaking at POD1.
- Failure to recover ex vivo TNF production by POD3 is associated with increased postoperative infection risk.
- Proteomics confirmed IL-6 upregulation and revealed downregulation of IFN-γ and lymphocyte-activating chemokines during suppression.
Methodological Strengths
- Pooled prospective datasets with consistent perioperative immune phenotyping across multiple modalities
- Integration of cytokine assays, ex vivo functional testing, and proteomics
Limitations
- Heterogeneity in surgical procedures and perioperative care across source studies
- Observational design limits causal inference and interventional thresholds are not established
Future Directions: Prospective validation of day-3 innate function recovery thresholds and trials testing targeted immunomodulators guided by perioperative immune profiling.
BACKGROUND: Major surgery elicits a complex immune response involving both systemic inflammation and innate immune suppression. These changes may contribute to postoperative infectious complications. This study aimed to determine whether perioperative immune activation and suppression patterns are associated with the development of postoperative infectious complications. MATERIALS AND METHODS: A pooled analysis of six prospective clinical studies was conducted to evaluate perioperative immune function in patients undergoing diverse surgical procedures. Immune monitoring included plasma danger-associated molecular pattern and cytokine concentrations, ex vivo cytokine production after lipopolysaccharide stimulation of whole blood, and proteomic profiling. Clinical outcomes included postoperative infections, pain scores, and quality of recovery. RESULTS: A total of 487 patients were included. Danger-associated molecular patterns generally increased following surgery. All surgical procedures induced a stereotypical immune trajectory, characterized by early plasma interleukin (IL)-6 and IL-10 elevation and suppression of ex vivo tumor necrosis factor (TNF) and IL-1β production, most pronounced on postoperative day 1. Immune suppression persisted through POD3 in patients undergoing colorectal surgery, but resolved more quickly after breast surgery, a less invasive procedure. Patients who developed post-operative infections had higher plasma IL-6 and TNF concentrations on postoperative day 1 and attenuated ex vivo TNF production on postoperative day 3. Proteomic profiling confirmed IL-6 upregulation and identified consistent downregulation of multiple immune signaling proteins, including IFN-γ and chemokines involved in lymphocyte activation. CONCLUSION: Surgical injury initiates a coordinated immune response with early inflammation and delayed innate immune suppression. Failure to recover innate immune function by postoperative day 3 is associated with increased infection risk. Perioperative immune profiling may enable early risk stratification and inform targeted immunomodulatory strategies.
3. Dose-dependent relationship between intra-operative dexmedetomidine and delirium after non-cardiac surgery: a retrospective cohort study.
In a retrospective cohort of 114,786 non-cardiac surgical patients, low cumulative intra-operative dexmedetomidine dosing (approximately 0.25–0.35 μg/kg) was associated with reduced postoperative delirium, whereas higher doses conferred no additional benefit versus no dexmedetomidine. Findings suggest a narrow, beneficial low-dose window for delirium prevention.
Impact: Provides dose-specific real-world evidence at unprecedented scale, informing safer dexmedetomidine use for delirium prevention and guiding future dose-finding RCTs.
Clinical Implications: Consider restricting intra-operative dexmedetomidine to low cumulative doses (~0.25–0.35 μg/kg) when aiming to reduce postoperative delirium; avoid dose escalation given lack of added benefit and potential adverse effects.
Key Findings
- Among 114,786 adults, only low-dose dexmedetomidine (~0.25–0.35 μg/kg cumulative) was associated with lower postoperative delirium risk.
- Higher cumulative doses did not reduce delirium compared with no dexmedetomidine exposure.
- Real-world dose–response characterization supports a narrow, beneficial dosing window.
Methodological Strengths
- Very large sample size with dose–response analysis
- Comparative evaluation across dose strata versus non-exposed controls
Limitations
- Retrospective observational design with potential confounding by indication
- Delirium ascertainment and intraoperative confounders (e.g., anesthetic depth) may vary across cases
Future Directions: Prospective randomized dose-finding trials testing low-dose dexmedetomidine (0.25–0.35 μg/kg) for delirium prevention with standardized outcomes.
INTRODUCTION: Dexmedetomidine can attenuate delirium in patients who are critically ill, but evidence with regards to its preventive effect on postoperative delirium remains equivocal. We hypothesised that the risk of delirium after intra-operative dexmedetomidine administration varies depending on the dose administered and aimed to identify the optimum dose to mitigate delirium. METHODS: We included 114,786 adults undergoing general anaesthesia for non-cardiac, non-transplant surgery. Primary exposure was intra-operative dexmedetomidine dose in cumulative μg.kg RESULTS: A total of 4804 (4.2%) patients received dexmedetomidine, with a median (IQR [range]) cumulative dose of 0.49 (0.28-0.84 [0.01-2.50]) μg.kg DISCUSSION: Low, but not high, dose dexmedetomidine administration was associated with lower risks of delirium, with optimal doses ranging between 0.25 μg.kg WHAT WE DID: We studied medical records from over 100,000 adults who underwent general anaesthesia for surgery. We looked at people who were given a medicine called dexmedetomidine during their operation and compared them with people who were not given this medicine. We also compared people who got a low dose with people who got a high dose. WHY DID WE DO IT: Some patients become confused or mixed up after surgery. This is called delirium. Dexmedetomidine may help prevent this confusion, but doctors are not sure what dose works best. We wanted to find out if the amount of medicine given changes the risk of delirium after surgery. WHAT WE FOUND: We found that patients who were given a low dose of dexmedetomidine were less likely to become confused after surgery. Patients who were given a high dose did not have less confusion than patients who were not given the medicine at all. The safest and most helpful dose was a small amount, between 0.25 and 0.35 micrograms per kilogram of body weight. This means that giving a small dose of dexmedetomidine during surgery may help reduce confusion afterwards but giving more than this does not seem to help.