BACKGROUND: Acute kidney injury (AKI) is a common complication after cardiac surgery and is a risk factor for long-term major adverse kidney events (MAKE). This study aimed to evaluate the association between postoperati...BACKGROUND: Acute kidney injury (AKI) is a common complication after cardiac surgery and is a risk factor for long-term major adverse kidney events (MAKE). This study aimed to evaluate the association between postoperative Nephrocheck AKI risk score with postoperative in-hospital AKI and MAKE up to 5 years after cardiac surgery. METHODS: The study included 610 patients who underwent nonemergent cardiac surgery with cardiopulmonary bypass (CPB). The Nephrocheck AKI risk score 6 hours after CPB was evaluated for association with AKI. The peak Nephrocheck AKI risk score that occurred between 6 hours post-CPB and postoperative day 4 was evaluated for association with MAKE. NephroCheck values were log2-transformed and mean-centered. Logistic and Cox regression were used to assess associations with AKI and MAKE, respectively. Models included linear terms and quadratic and cubic terms to evaluate nonlinearity. Optimal thresholds were derived using receiver operating characteristic (ROC) analysis and the Youden index. RESULTS: The incidence of postoperative all-stage in-hospital AKI was 110/610 (18.0%), and the incidence of MAKE was 257/610 (42.1%). For AKI, higher-order terms were not significant; therefore, linear models were retained. Each twofold increase in the 6-hour biomarker concentration was associated with increased odds of AKI in unadjusted (OR 1.49; 95% confidence interval [CI], 1.27-1.75; P < .001) and adjusted models (OR range 1.39-1.42; P < .001). An ROC-derived threshold >0.14 was associated with higher odds of AKI in unadjusted (OR 2.43; 95% CI, 1.60-3.69; P < .001) and adjusted models (OR range 2.28-2.34; P < .001). For MAKE, a nonlinear association was observed. The linear term was not significant, whereas the quadratic term was significant in both unadjusted (HR 1.09; 95% CI, 1.04-1.13; P < .001) and adjusted models (HR range 1.06-1.07; P < .008), indicating that the risk of MAKE increases disproportionately at higher peak NephroCheck concentrations. The cubic term was not significant. Patients with peak Nephrocheck AKI risk score >1.69 units had a higher risk of MAKE in unadjusted (HR 2.11; 95% CI, 1.55-2.85; P < .001) and adjusted models (HR range 1.75-2.04; P < .001). CONCLUSIONS: Nephrocheck AKI risk score 6 hours post-CPB was significantly associated with in-hospital postoperative AKI. Peak postoperative NephroCheck measurements were also significantly associated with MAKE up to 5 years after cardiac surgery.
Methadone is a long-acting opioid with multifaceted analgesic properties that is under increasing investigation as an intraoperative analgesic in cardiac surgery. A systematic search of United States National Library of...Methadone is a long-acting opioid with multifaceted analgesic properties that is under increasing investigation as an intraoperative analgesic in cardiac surgery. A systematic search of United States National Library of Medicine Database (MEDLINE) and Excerpta Medica Database (EMBASE) databases identified publications investigating the use of intraoperative methadone in adult cardiac surgical patients. The risk of bias and quality of evidence of these studies were assessed, and data from these reports were extracted and presented in a narrative format. Sixteen eligible publications were included. Although the quality of the studies was moderate to high, the certainty of the evidence is low due to the limited available data regarding optimal dosing strategies, timing of administration in relation to cardiopulmonary bypass, and long-term safety outcomes. The composite data suggest that a single dose of intraoperative methadone results in less postoperative pain and opioid consumption postoperatively without any increased risk for QTc prolongation or respiratory depression. Doses of 0.1 to 0.3 mg/kg are reported in the cardiac surgery literature; however, there is evidence of a dose-response relationship with methadone's analgesic benefits and increased deliriogenic side effects. Studies using 0.1 mg/kg reveal equivocal analgesia, whereas the studies administering ≥0.2 mg/kg consistently report lower postoperative pain scores and opioid consumption compared to short-acting intravenous (IV) opioids. Crucially, the use of cardiopulmonary bypass significantly impacts methadone's plasma concentrations and must be considered when determining the optimal dose and timing of administration. Further, recent observational studies offer valuable insight into methadone's role in multimodal enhanced recovery after cardiac surgery protocols. Additional trials are needed to refine methadone usage in this population.
BACKGROUND: Transfusion during orthotopic liver transplantation (OLT) is frequent and linked to adverse outcomes. However, the ability of the Model for End-Stage Liver Disease (MELD) 3.0 score to predict intraoperative t...BACKGROUND: Transfusion during orthotopic liver transplantation (OLT) is frequent and linked to adverse outcomes. However, the ability of the Model for End-Stage Liver Disease (MELD) 3.0 score to predict intraoperative transfusion use has not been well characterized. METHODS: We performed a single-center retrospective cohort study of 69 adult OLT recipients to evaluate the association between preoperative MELD 3.0 scores and intraoperative transfusion utilization. The primary outcome was total intraoperative blood component use. Secondary outcomes included estimated blood loss (EBL) and use of individual components (packed red blood cells, fresh frozen plasma, platelets, and cryoprecipitate). Analyses used descriptive statistics, Mann-Whitney U tests, and Kruskal-Wallis tests. Multivariable linear regression adjusted for age, birth sex, transplant indication, and preoperative hemoglobin (covariates selected a priori based on clinical relevance). Significance was set at P = .05. RESULTS: The cohort included 52 men and 17 women (median [IQR] age 57 [46-66] years; median MELD 3.0 score 27 [16-36]). The primary outcome, median intraoperative transfusion volume, was 34 (24-46) blood components. Median EBL was 5500 (3500-8000) mL. In univariable analysis, each one-point increase in MELD was associated with an additional 0.82 blood components transfused (ie, beta coefficient β 0.82; 95% confidence interval [CI], 0.48-1.2; P ≤ .001). In multivariable linear regression adjusted for age, birth sex, indication, and preoperative hemoglobin, higher MELD 3.0 remained independently associated with greater total utilization (β 0.92; 95% CI, 0.48-1.4; P < .001). Women had higher median MELD scores than men (33 [26-36.5] vs 23 [13-36]; P = .05) but similar total transfusion use (34 [24-45] vs 34 [24-46] units; P = .82) and EBL (5500 [4425-7420] vs 5000 [2800-8000] mL; P = .55). By indication, hepatocellular carcinoma (HCC) recipients had lower median MELD scores (13 [8-17]) than alcohol-related (34 [19.8-38], P < .001) or other (27 [21.5-32.5], P = .01) indications. Compared to alcohol-related recipients, HCC recipients received fewer median total blood components (24 [14-44] vs 38 [27-46.8] units, P = .04). EBL did not differ significantly across indications (P = .12). CONCLUSIONS: Preoperative MELD 3.0 is a robust independent predictor of intraoperative transfusion burden in OLT. Diagnosis-specific patterns-particularly lower transfusion among HCC recipients-support tailoring resource planning by indication and MELD 3.0. Prospective multicenter validation should compare MELD 3.0 against MELD-Na and clinical models to refine prediction of transfusion and evaluate postoperative outcomes.
Giannakis P, Restrepo M, Stone AB
… +10 more, Zhuang ST, Wang J, Cozowicz C, Illescas A, Rowe JE, Reisinger L, Poultsides L, Liu J, Poeran J, Memtsoudis SG
BACKGROUND: Frailty and age are major outcome drivers in hip fracture surgery, but their interaction has not been considered in neuraxial versus general anesthesia comparisons. Using the Hospital Frailty Risk Score (HFRS...BACKGROUND: Frailty and age are major outcome drivers in hip fracture surgery, but their interaction has not been considered in neuraxial versus general anesthesia comparisons. Using the Hospital Frailty Risk Score (HFRS), we examined this interaction. METHODS: In this retrospective cohort study (2016-2023, Premier Healthcare Database), adults undergoing hip fracture surgery with neuraxial or general anesthesia were included and stratified by age quantiles (≤71, 72-86, ≥87 years) and HFRS (low, intermediate/high). The primary outcome was an in-hospital composite of mortality and major system complications. Intensive care unit (ICU) admission and high opioid use or prolonged length of stay (LOS) ≥75th percentile were also assessed. We used mixed-effects models and reported odds ratios (OR) and 95% confidence intervals (CIs). RESULTS: Among 623,122 patients, neuraxial (versus general) anesthesia was associated with lower odds of the composite outcome in patients ≥87 years with intermediate/high frailty (OR, 0.88 and 95% CI, 0.83-0.94; P < .001). Overall, neuraxial anesthesia was linked to higher odds of respiratory complications (OR, 1.06 and 95% CI, 1.01-1.10; P = .03), driven by patients ≤71 years with intermediate/high frailty, and lower odds of renal failure (OR, 0.87 and 95% CI, 0.83-0.92; P < .001), primarily among those ≥72 years with intermediate/high frailty. Neuraxial anesthesia was also associated with higher cardiac complication odds (OR, 1.07 and 95% CI, 1.02-1.12; P = .008), particularly in patients aged 72 to 86 years with intermediate/high frailty. Mortality odds were lower overall (OR, 0.83 and 95% CI, 0.74-0.93; P = .003), driven by patients ≥87 years with intermediate/high frailty. Neuraxial anesthesia was associated with higher odds of prolonged LOS in patients aged 72 to 86 years with low frailty (OR, 1.16 and 95% CI, 1.04-1.31; P = .035), but lower odds in those ≥87 years with intermediate/high frailty (OR, 0.92 and 95% CI, 0.87-0.97; P = .012). It was associated with lower odds of high opioid use overall and within each subgroup. ICU admission odds were higher in patients ≤71 years with intermediate/high frailty (OR, 1.16 and 95% CI, 1.05-1.29; P = .019) but lower in those ≥87 years with intermediate/high frailty (OR, 0.82 and 95% CI, 0.75-0.90; P < .001). Neuraxial anesthesia was linked to higher odds of discharge home (OR, 1.08 and 95% CI, 1.04-1.12; P < .001), except among ≥87-year-old intermediate/high frailty patients, where odds were lower (OR, 0.90 and 95% CI, 0.81-0.99; P = .041). CONCLUSIONS: Neuraxial versus general anesthesia showed modest overall benefits after hip fracture, varying by age-frailty subgroup, supporting frailty-guided anesthetic decisions clinically.Level of evidence: III. Retrospective cohort study.
BACKGROUND: Dexamethasone is used in primary total joint arthroplasty (TJA) to reduce postoperative nausea and vomiting, and there is emerging evidence that it also ameliorates adverse events more broadly. Despite a lack...BACKGROUND: Dexamethasone is used in primary total joint arthroplasty (TJA) to reduce postoperative nausea and vomiting, and there is emerging evidence that it also ameliorates adverse events more broadly. Despite a lack of supporting data, a vocal minority has continued to question the appropriateness of dexamethasone in cases where the hyperglycemic burden and/or risk of infection are increased. This study sought to assess the benefits and potential harms of dexamethasone in a cohort of patients undergoing revision TJA for periprosthetic joint infection (PJI). We hypothesize that perioperative dexamethasone exposure is associated with fewer postoperative complications, regardless of diabetes status. METHODS: An all-payer, US hospital-based dataset was queried. Patients ≥18 years with a diagnosis of hip or knee PJI between 2015 and 2023 were identified using billing and procedural codes, and verified using hospital charges for antibiotics and spacers. The primary outcome was composite complications. Secondary outcomes (wound and infectious complications, as well as mortality) were evaluated to probe for potential safety signals. RESULTS: In total, 61,527 patients were identified. A total of 30,644 nondiabetic patients and 14,996 diabetic patients were 1:1 matched based on dexamethasone exposure, with good balance. Dexamethasone-treated patients had fewer aggregate complications in both cohorts (nondiabetic: adjusted odds ratio [aOR], 0.934 and 95% confidence interval [CI], 0.760-0.978; diabetic: aOR, 0.814 and 95% CI, 0.746-0.889). Dexamethasone was also associated with fewer wound complications (nondiabetic: aOR, 0.891 and 95% CI, 0.823-0.964; diabetic: aOR, 0.879 and 95% CI, 0.787-0.981) and infectious complications (nondiabetic: aOR, 0.891 and 95% CI, 0.823-0.964; diabetic: aOR, 0.827 and 95% CI, 0.754-0.908) . Only diabetic patients saw a statistically significant decrease in mortality (aOR, 0.692 and 95% CI, 0.532-0.901). CONCLUSIONS: As with any retrospective study, findings should be interpreted cautiously due to the possibility of residual confounding. Nevertheless, dexamethasone appears to be safe to use in patients undergoing first-stage revision for TJA for PJA regardless of diabetic status. Further, findings suggest that dexamethasone is associated with lower odds of aggregate complications, and contrary to conventional wisdom, these benefits may be even greater among diabetics.
BACKGROUND: Hip fracture carries high morbidity in elderly patients. While most efforts focus on single perioperative measures, we assessed whether a coordinated multidisciplinary algorithm could reduce early postoperati...BACKGROUND: Hip fracture carries high morbidity in elderly patients. While most efforts focus on single perioperative measures, we assessed whether a coordinated multidisciplinary algorithm could reduce early postoperative complications (EPOCs) within 7 days. The Advise, Surgery, Analgesia, Pharmacology (ASAP) bundle comprises four components: orthogeriatric consultation (Advise), surgery within 12 hours (Surgery), supra-inguinal fascia iliaca block (SFIB; Analgesia), and chronic therapy adjustment (Pharmacology). METHODS: In this retrospective, single-center interrupted time-series cohort study (January 2017-December 2022), we compared hip fracture patients admitted pre-ASAP (January 1, 2017-December 31, 2019) versus post-ASAP (January 1, 2020-December 31, 2022). Following ethics approval, we conducted interrupted time-series analysis of 7-day EPOC rates, stratified by Clavien-Dindo grades: all complications (1-4) and major complications (2-4). Kaplan-Meier and Cox proportional hazards models evaluated cumulative incidence and hazard ratios (HRs). RESULTS: Among 845 patients (480 pre-ASAP, 365 post-ASAP), all EPOCs declined immediately after ASAP implementation (P = .032) with a sustained negative trend over time (P = .008), and major EPOCs also decreased immediately (P < .001) with a flatter subsequent trend (P = .20). Kaplan-Meier curves confirmed a lower cumulative incidence of both all and major complications post-ASAP (log-rank P < .001). ASAP reduced the hazard for all EPOCs (HR, 0.58; 95% confidence interval [CI], 0.49-0.68) and major EPOCs (HR, 0.60; 95% CI, 0.49-0.73). Early surgery and SFIB each independently predicted fewer all EPOCs, whereas only early surgery predicted fewer major EPOCs. CONCLUSIONS: Implementation of the ASAP bundle significantly lowered EPOCs after hip fracture surgery. Early surgery and SFIB were especially impactful, supporting broader adoption of multimodal perioperative strategies in elderly patients.
BACKGROUND: Thromboxane A2 (TXA2), a metabolite of arachidonic acid, is well known for its role in vasoconstriction and platelet aggregation via activation of thromboxane prostanoid receptors (TPR). Although other prosta...BACKGROUND: Thromboxane A2 (TXA2), a metabolite of arachidonic acid, is well known for its role in vasoconstriction and platelet aggregation via activation of thromboxane prostanoid receptors (TPR). Although other prostanoid receptors have established roles in pain modulation, the contribution of TXA2-TPR signaling to nociceptive processing remains unclear. This study evaluated the analgesic effects of a TPR agonist in mouse models of pain. METHODS: Four-week-old male ddY mice, an outbred mouse strain, received intrathecal (i.t.) administration of (Z)-7-((1S,2R,3R,4R)-3-((R,E)-3-hydroxy-4-(4-iodophenoxy)but-1-en-1-yl)-7-oxabicyclo[2.2.1]heptan-2-yl)hept-5-enoic acid (I-BOP), a TPR agonist, in four pain models (n = 6-10 per group): hot plate test, formalin test, prostaglandin E2 (PGE2)-induced allodynia, and L5 spinal nerve transection (L5-SNT). Behavioral tests evaluated pain responses as the primary outcome. The mRNA expression levels of cyclooxygenase (COX)-1, COX-2, TXA2 synthase (TXAS), and TPR were analyzed by reverse transcription-polymerase chain reaction and compared between ipsilateral and contralateral L4-L6 spinal dorsal horns. TPR localization in the spinal dorsal horn was determined by immunohistochemistry. Data were analyzed using appropriate parametric or nonparametric tests based on the results of normality assessment. Comparisons between groups were performed using Student t test, the Mann-Whitney U test, 1-way analysis of variance (ANOVA) with Dunnett post hoc test, 2-way ANOVA with Bonferroni post hoc test, or Friedman test followed by Wilcoxon signed-rank tests with Bonferroni correction as appropriate. All behavioral assessments were conducted in a blinded manner. RESULTS: In the PGE2-induced allodynia model, coadministration of I-BOP dose dependently reduced the allodynia score compared with PGE2 alone. When the response to PGE2 alone was defined as 100%, the allodynia scores were reduced to 20% (95% confidence interval [CI], -7 to 47; P = .0012) at 1 ng and 10% (95% CI, -11 to 31; P < .001) at 10 ng I-BOP. In the L5-SNT neuropathic pain model, i.t. I-BOP produced a dose-dependent elevation of mechanical withdrawal thresholds, with significant main effects of dose (P < .001) and time (P < .001) and a significant dose × time interaction (P = .0012). In the formalin test, I-BOP selectively reduced nociceptive behavior during the second phase (I-BOP 140 ± 6.2 seconds; saline 623 ± 18.1 seconds, expressed as mean ± standard error of the mean [SEM]; P = .008), without affecting the first phase. The ipsilateral spinal dorsal horn of L5-SNT mice showed increased TPR mRNA expression. Immunohistochemistry revealed TPR localization in both the substantia gelatinosa and deep laminae of the spinal dorsal horn. CONCLUSIONS: These findings suggest that a TPR agonist exerts analgesic effects by acting on TPR expressed in the spinal cord, highlighting the potential role of TPR signaling in pain modulation.
BACKGROUND: The International Organization for Standardization (ISO) and US Food and Drug Administration (FDA) are updating regulations for pulse oximeters to reduce performance disparities linked to skin pigment. We tes...BACKGROUND: The International Organization for Standardization (ISO) and US Food and Drug Administration (FDA) are updating regulations for pulse oximeters to reduce performance disparities linked to skin pigment. We tested common oximeters with current and anticipated regulatory frameworks. We hypothesized that not all oximeters show more positive bias in darkly vs lightly pigmented participants and that few oximeters would "pass" the anticipated FDA regulations. METHODS: We used a controlled desaturation protocol to test 34 oximeters across arterial oxygen saturations (SaO2) 70% to 100% in healthy adults. Based on what FDA and ISO had shared at the time of study design, we studied cohort sizes of ≥24 with ≥25% of participants being darkly pigmented. We used the subjective Monk Skin Tone (MST) scale and the objective individual typology angle (ITA) derived from a spectrophotometer to characterize skin pigment. The accuracy root mean square error (ARMS), bias (mean of SpO2 - SaO2 error), and skin pigment differential bias were calculated. Monte Carlo simulation explored potential impacts of participant selection on device passing. RESULTS: For cohorts of 24 participants, 28/34 oximeters (82%) passed 2017 ISO Standard (ARMS < 4%), 22/34 (65%) passed 2013 FDA guidance (ARMS ≤ 3%), 21/34 (62%) oximeters passed both ARMS and differential bias criteria for anticipated ISO standards, and 1/34 (3%) passed anticipated FDA criteria. More devices passed when testing cohorts were increased beyond 24 participants. Eleven oximeters had more positive bias in participants with dark vs light (dorsal finger) pigmentation across 70% to 100% SaO2 (median difference 1.42, IQR: 1.35-1.90). Eighteen devices could pass or fail depending on cohorts selected for analysis. CONCLUSIONS: Pulse oximeters show variable performance across manufacturers and models. Notably, only some devices show more positive bias in people with darker skin. Anticipated updates to ISO and FDA frameworks yield strikingly different assessments and require refinement of cohort sizes and differential bias criteria. Whether new guidelines will translate into improved real-world performance or reduced health disparities is yet to be determined.
BACKGROUND: Glutamatergic neurons in the medial septum (MS) are identified to promote emergence from sevoflurane general anesthesia (GA), with the potential downstream neural circuit remaining to be explored. METHODS: Ra...BACKGROUND: Glutamatergic neurons in the medial septum (MS) are identified to promote emergence from sevoflurane general anesthesia (GA), with the potential downstream neural circuit remaining to be explored. METHODS: Rabies virus (RV)-mediated monosynaptic retrograde tracing and anterograde tracing were first used to identify the projection from glutamatergic MS neurons (MSGlu) to glutamatergic neurons in the lateral hypothalamus (LH, LHGlu). In vivo fiber photometry, optogenetic bidirectionally manipulations, electroencephalogram/electromyogram (EEG/EMG), and behavioral tests were further employed to investigate the role of the circuit from MSGlu neurons to the LH (MSGlu-LH circuit) in regulating states of consciousness under two different states of sevoflurane GA: continuous, steady-state general anesthesia (CSSGA) and burst-suppression (BS) oscillations. RESULTS: The retrogradely labeled upstream neurons of LHGlu neurons were extensively detected in the MS, and most RV-infected neurons in the MS were co-labeled by Vesicular glutamate transporter 2 (Vglut2, mean ± standard error of the mean [SEM], 86.3% ± 1.5%, n = 4 mice). And the MSGlu-LHGlu circuit constitutes the highest proportion among the three downstream LH neuronal populations (presynaptic boutons co-localized ratio: glutamatergic, 77.0% ± 2.2%; γ-aminobutyric acid-ergic, 59.6% ± 0.9%; orexinergic, 28.5% ± 2.0%; n = 4 mice). The calcium activity of the MSGlu-LH circuit was inhibited concurrently as the process of loss of consciousness during 2.4% sevoflurane induction. Optogenetic activation of the MSGlu-LH circuit promoted behavioral arousal and increased β power of EEG (stimulation vs pre-stimulation, 16.8% ± 2.3% vs 9.7% ± 1.7%, P =.0065; n = 8 mice) during CSSGA. In contrast, during CSSGA, optogenetic inhibition of the MSGlu-LH projection deepened cortical inhibition, characterized by increased δ power and decreased power of β and γ (inhibition vs pre-inhibition, δ: 62.4% ± 4.5% vs 55.3% ± 4.2%, P =.0404; β: 6.7% ± 0.8% vs 9.4% ± 1.3%, P =.0069; γ: 3.3% ± 0.6% vs 4.8% ± 0.8%, P =.0076; n = 8 mice). Optogenetic bidirectionally manipulations of the MSGlu-LH circuit induced similar effects during BS: activation of this projection resulted in cortical activation with decreased burst-suppression ratio (BSR; median [25%-75% percentiles], stim vs pre, 59.0% [43.8%-64.5%] vs 77.5% [74.0%-84.3%], P =.0121; n = 8 mice), while inhibition of this projection led to cortical inhibition with increased BSR (inhib vs pre, 76.1% ± 7.0% vs 64.5% ± 8.4%, P =.0382; n = 8 mice). CONCLUSIONS: This study reveals that activation of the glutamatergic MS-LH circuit promotes emergence from sevoflurane GA.