Wongsripuemtet P, Dong K, Vavilala MS
… +13 more, Miller JB, Minic Z, Ohnuma T, Laskowitz D, Goldstein B, Korley F, Meurer W, Kaakati A, Chaikittisilipa N, Kiatchai T, Wang Z, Hu X, Krishnamoorthy V
BACKGROUND: Weaning from cardiopulmonary bypass (CPB) is a critical step in cardiovascular surgery. Although ionized calcium (iCa) plays a crucial role in myocardial contractility, and hypocalcemia commonly occurs during...BACKGROUND: Weaning from cardiopulmonary bypass (CPB) is a critical step in cardiovascular surgery. Although ionized calcium (iCa) plays a crucial role in myocardial contractility, and hypocalcemia commonly occurs during CPB, only a few studies have examined the association between iCa levels and clinical outcomes following CPB. This study aimed to evaluate whether iCa levels during CPB weaning were associated with clinical outcomes. METHODS: This multicenter retrospective study was conducted in three Japanese hospitals. Adult patients (aged ≥ 18 years) who underwent cardiovascular surgery with CPB were included. Exposure was defined as iCa concentration during CPB weaning. The primary outcome was low cardiac output syndrome (LCOS) on ICU admission, which was determined when at least one of the following three criteria was met: (i) postoperative MCS use, (ii) cardiac index <2.0 L min-1 m-2, (iii) use of two or more inotropes (dopamine, dobutamine, adrenaline, and milrinone) at 1 hour following the end of the surgery. The patients were divided into four groups based on iCa quartile: low iCa group (iCa ≤ 1.05 mmol L-1), standard iCa group (1.05 < iCa ≤ 1.13 mmol L-1), moderate-high iCa group (1.13 < iCa ≤1.24 mmol L-1), and high iCa group (iCa > 1.24 mmol L-1). Multivariate logistic regression analyses were performed to calculate adjusted odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: In total, 2,382 patients were included between September 2012 and December 2022. The median age was 70 years (IQR: 60-76 years), and 1,464 patients (61%) were men. The overall LCOS incidence was 501 cases (21%). Compared to the standard iCa group, the adjusted ORs for LCOS were 1.45 (95% CI, 1.06 to 1.99, P = .020) in the low iCa group, 1.42 (95% CI, 1.01 to 2.00, P = .046) in the moderate-high iCa group, and 1.36 (95% CI, 0.95 to 1.94, P = .094) in the high iCa group. CONCLUSIONS: Both low and high iCa levels at CPB weaning were associated with an increased risk of postoperative LCOS in patients undergoing cardiovascular surgery.
BACKGROUND: Effective postoperative pain management in gynecological surgery is challenging because of complex visceral-somatic pain interactions and the adverse effects of conventional analgesics. HSK21542, a novel peri...BACKGROUND: Effective postoperative pain management in gynecological surgery is challenging because of complex visceral-somatic pain interactions and the adverse effects of conventional analgesics. HSK21542, a novel peripherally restricted kappa-opioid receptor (KOR) agonist that selectively targets visceral pain pathways enriched with KORs, may provide adequate analgesia without systemic adverse events. METHODS: We conducted a pooled post-hoc analysis of data from two phase III, multicenter, triple-blinded, randomized controlled trials (Study 301, HSK21542 vs placebo; Study 303, HSK21542 vs tramadol vs placebo). Eligible patients undergoing elective gynecological surgery were included. The primary outcome was the summed pain-intensity difference over 12 and 24 hours (SPID 12h and SPID 24h ). Secondary outcomes were pain-relief quality (proportion of patients relieved from severe pain with a pain numerical rating score ≤ 3 between 0 and 24 hours) and rescue-analgesic requirements (number of doses and time to first rescue analgesic). Adverse events were also assessed. RESULTS: A total of 370 patients were analyzed: 150 received HSK21542, 139 received a placebo, and 81 received tramadol. After inverse probability of treatment weighting (IPTW) adjustment, baseline characteristics were well-balanced across treatment groups (all standardized mean differences [SMD] <0.1; see Table 1 for 95% CIs). HSK21542 produced greater reductions in pain intensity over 12 and 24 hours than placebo (least-squares mean differences -8.1 and -16.3 for SPID 12h and SPID 24h , respectively. Both P < .001) and no statistically significant difference was observed between HSK21542 and tramadol ( P > .05). Significantly more patients in the HSK21542 group were relieved from severe pain at 0 to 12 hours (92.7% vs 82.7%, P < .001) and required fewer rescue doses at 0 to 12 hours (0.00 [IQR 0.00-1.00] vs 1.00 [IQR 0.00-2.00], P < .001) and 0 to 24 hours (0.00 [IQR 0.00-1.00] vs 1.00 [IQR 0.00-2.00], P < .001) than those in the placebo group, whereas no significant differences with tramadol both in 0 to 12 and 0 to 24 hours. HSK21542 was also associated with significantly lower incidences of nausea (24.7% vs 66.7%) and vomiting (21.3% vs 60.5%) than tramadol. Only one case of dizziness occurred in the tramadol group. CONCLUSIONS: HSK21542 could provide adequate postoperative analgesia with few adverse events in patients undergoing gynecological surgery.
BACKGROUND: Oscillatory high-frequency ventilation modalities, including high-frequency oscillatory, percussive, and jet ventilation, are commonly used during anesthesia and critical care to improve oxygenation or facili...BACKGROUND: Oscillatory high-frequency ventilation modalities, including high-frequency oscillatory, percussive, and jet ventilation, are commonly used during anesthesia and critical care to improve oxygenation or facilitate airway surgery. These techniques rely on rapid, small-amplitude pressure oscillations to sustain gas exchange while minimizing baro- or volutrauma. However, how effectively such oscillations transmit through the conducting airways to the alveoli in mechanically heterogeneous lungs remains poorly understood, particularly under perioperative conditions associated with atelectasis, airway narrowing, or altered chest wall mechanics. METHODS: We combined in vivo measurements in anesthetized, mechanically ventilated piglets with computational simulations to quantify pressure transmission and ventilation heterogeneity across controlled variations in airway and tissue mechanical properties. Airway opening, tracheal, and alveolar capsule pressures (n = 16) were recorded with miniature pressure transducers during multifrequency (0.5-20.75 Hz) oscillations at positive end-expiratory pressures (PEEP) of 5 and 10 cmH2O. The experimental data informed a simulation model comprising heterogeneous airway and tissue compartments to identify determinants of alveolar ventilation during oscillatory modes. RESULTS: The in vivo measurements revealed that the endotracheal tube accounted for most of the total flow resistance and inertance, whereas the chest wall contributed approximately two-thirds of tissue damping and elastance. Only 29% (95% confidence interval [CI], 22%-36%) to 43% (95% CI, 32%-54%) of tracheal oscillatory pressure reached the alveoli, showing strong frequency-dependent attenuation that was not significantly influenced by PEEP. Simulation results validated against measured pressure transfer functions indicated that airway heterogeneity dominated regional disparities in pressure and tidal volume, causing up to 250% differences in local volumes at high net resistance. Tissue heterogeneity exerted smaller (<100%) but distinct effects on pressure-volume relationships. CONCLUSIONS: Airway heterogeneity, common in perioperative atelectasis, bronchospasm, and acute lung injury, profoundly limits the efficiency of oscillatory ventilation. Understanding how airway and tissue properties modulate oscillatory pressure transmission provides a mechanistic basis for tailoring high-frequency ventilation to individual patients. These insights may inform more rational ventilation strategies to optimize gas exchange while minimizing regional overdistension and collapse.
BACKGROUND: Intraoperative blood salvage (IBS) and autotransfusion have been widely implemented to minimize allogenic blood transfusion in major surgery. Despite published literature, controversy exists around its use in...BACKGROUND: Intraoperative blood salvage (IBS) and autotransfusion have been widely implemented to minimize allogenic blood transfusion in major surgery. Despite published literature, controversy exists around its use in liver transplantation (LT) for patients with hepatocellular carcinoma (HCC) due to concern for oncological recurrence. METHODS: We retrospectively studied adults with HCC who underwent deceased donor LT at a single LT center in Australia (August 2007-July 2020), comparing those who received IBS and autotransfusion with those who did not. Leukodepletion filters were not used. The primary outcome was time to HCC recurrence. The secondary outcomes were HCC recurrence-free survival and overall survival post-LT. RESULTS: A total of 245 patients having concurrent LT and HCC were analyzed. Of these, 167 received IBS and 78 did not. HCC recurrence occurred in 22/245 (9.0%) after a median of 20 months (IQR 13.5-24.5). For the primary outcome, IBS and autotransfusion was not associated with a decrease in time to HCC recurrence on unadjusted analysis (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.34-1.92; P = .62). Independent predictors of time to HCC recurrence were: hepatitis C (adjusted HR [aHR] 3.57, 95% CI, 1.03-12.4, P = .04), number of HCCs (aHR 1.17 per lesion increase, 95% CI, 1.06-1.30, P < .01), higher alpha-fetal protein levels (aHR 1.002 per kIU/L increase, 95% CI, 1.0003-1.003, P = .01), and microvascular invasion (aHR 3.27, 95% CI, 1.26-8.50, P = .01). After adjusting for these confounders, there remained no relationship between IBS and autotransfusion and time to HCC recurrence (aHR 0.57, 95% CI, 0.23-1.44, P = .24). For the secondary outcomes, IBS and autotransfusion was not a predictor of HCC recurrence-free survival (aHR 0.75, 95% CI, 0.39-1.42, P = .38) or overall survival (aHR 0.68, 95% CI, 0.35-1.33, P = .26) on multivariable analysis. CONCLUSIONS: In this single-center study, IBS and autotransfusion during LT in patients with concurrent HCC was not associated with an increased risk of recurrence. No unexpected risk factors for HCC recurrence after LT were identified. This study provides further evidence to confirm the safety of IBS in LT for HCC without the use of leukodepletion filters.