AcumenTM hypotension prediction index guidance for prevention and treatment of hypotension in noncardiac surgery: a prospective, single-arm, multicenter trial.

BACKGROUND: Intraoperative hypotension is common during noncardiac surgery and is associated with postoperative myocardial infarction, acute kidney injury, stroke, and severe infection. The Hypotension Prediction Index software is an algorithm based on arterial waveform analysis that alerts clinicians of the patient's likelihood of experiencing a future hypotensive event, defined as mean arterial pressure < 65 mmHg for at least 1 min. METHODS: Two analyses included (1) a prospective, single-arm trial, with continuous blood pressure measurements from study monitors, compared to a historical comparison cohort. (2) A post hoc analysis of a subset of trial participants versus a propensity score-weighted contemporaneous comparison group, using external data from the Multicenter Perioperative Outcomes Group (MPOG). The trial included 485 subjects in 11 sites; 406 were in the final effectiveness analysis. The post hoc analysis included 457 trial participants and 15,796 comparison patients. Patients were eligible if aged 18 years or older, American Society of Anesthesiologists (ASA) physical status 3 or 4, and scheduled for moderate- to high-risk noncardiac surgery expected to last at least 3 h. MEASUREMENTS: minutes of mean arterial pressure (MAP) below 65 mmHg and area under MAP < 65 mmHg. RESULTS: Analysis 1: Trial subjects (n = 406) experienced a mean of 9 ± 13 min of MAP below 65 mmHg, compared with the MPOG historical control mean of 25 ± 41 min, a 65% reduction (p < 0.001). Subjects with at least one episode of hypotension (n = 293) had a mean of 12 ± 14 min of MAP below 65 mmHg compared with the MPOG historical control mean of 28 ± 43 min, a 58% reduction (p< 0.001). Analysis 2: In the post hoc inverse probability treatment weighting model, patients in the trial demonstrated a 35% reduction in minutes of hypotension compared to a contemporaneous comparison group [exponentiated coefficient: - 0.35 (95%CI - 0.43, - 0.27); p < 0.001]. CONCLUSIONS: The use of prediction software for blood pressure management was associated with a clinically meaningful reduction in the duration of intraoperative hypotension. Further studies must investigate whether predictive algorithms to prevent hypotension can reduce adverse outcomes. TRIAL REGISTRATION: Clinical trial number: NCT03805217. Registry URL: https://clinicaltrials.gov/ct2/show/NCT03805217 . Principal investigator: Xiaodong Bao, MD, PhD. Date of registration: January 15, 2019.

Integrated Feedforward and Feedback Mechanisms in Neurovascular Coupling.

Neurovascular coupling (NVC) is the mechanism that drives the neurovascular response to neural activation, and NVC dysfunction has been implicated in various neurologic diseases. NVC is driven by (1) nonmetabolic feedforward mechanisms that are mediated by various signaling pathways and (2) metabolic feedback mechanisms that involve metabolic factors. However, the interplay between these feedback and feedforward mechanisms remains unresolved. We propose that feedforward mechanisms normally drive a swift, neural activation-induced regional cerebral blood flow (rCBF) overshoot, which floods the tissue beds, leading to local hypocapnia and hyperoxia. The feedback mechanisms are triggered by the resultant hypocapnia (not hyperoxia), which causes cerebral vasoconstriction in the neurovascular unit that counterbalances the rCBF overshoot and returns rCBF to a level that matches the metabolic activity. If feedforward mechanisms function improperly (eg, in a disease state), the rCBF overshoot, tissue-bed flooding, and local hypocapnia fail to occur or occur on a smaller scale. Consequently, the neural activation-related increase in metabolic activity results in local hypercapnia and hypoxia, both of which drive cerebral vasodilation and increase rCBF. Thus, feedback mechanisms ensure the brain milieu's stability when feedforward mechanisms are impaired. Our proposal integrates the feedforward and feedback mechanisms underlying NVC and suggests that these 2 mechanisms work like a fail-safe system, to a certain degree. We also discussed the difference between NVC and cerebral metabolic rate-CBF coupling and the clinical implications of our proposed framework.

Evaluation of a modified ultrasound-assisted technique for mid-thoracic epidural placement: a prospective observational study.

BACKGROUND: Although mid-thoracic epidural analgesia benefits patients undergoing major surgery, technical difficulties often discourage its use. Improvements in technology are warranted to improve the success rate on first pass and patient comfort. The previously reported ultrasound-assisted technique using a generic needle insertion site failed to demonstrate superiority over conventional landmark techniques. A stratified needle insertion site based on sonoanatomic features may improve the technique. METHODS: Patients who presented for elective abdominal or thoracic surgery requesting thoracic epidural analgesia for postoperative pain control were included in this observational study. A modified ultrasound-assisted technique using a stratified needle insertion site based on ultrasound images was adopted. The number of needle passes, needle skin punctures, procedure time, overall success rate, and incidence of procedure complications were recorded. RESULTS: One hundred and twenty-eight subjects were included. The first-pass success and overall success rates were 75% (96/128) and 98% (126/128), respectively. In 95% (122/128) of patients, only one needle skin puncture was needed to access the epidural space. The median [IQR] time needed from needle insertion to access the epidural space was 59 [47-122] seconds. No complications were observed during the procedure. CONCLUSIONS: This modified ultrasound-assisted mid-thoracic epidural technique has the potential to improve success rates and reduce the needling time. The data shown in our study may be a feasible basis for a prospective study comparing our ultrasound-assisted epidural placements to conventional landmark-based techniques.

Blood-brain Barrier Permeability May Influence Vasopressor Effects in Anesthetized Patients With Brain Tumor: An Analysis of Magnetic Resonance Imaging Data.

OBJECTIVE: This is a secondary analysis of data from a previous study of anesthetized brain tumor patients receiving ephedrine or phenylephrine infusions. 18 patients with magnetic imaging verified tumor contrast enhancement were included. We hypothesized that vasopressors induce microcirculatory flow changes, characterized by increased capillary transit time heterogeneity (CTH) and decreased mean transit time (MTT), in brain regions exhibiting BBB leakage. METHODS: This is a secondary analysis of data from a previous study of anesthetized brain tumor patients receiving ephedrine or phenylephrine infusions. 18 patients with magnetic imaging verified tumor contrast enhancement were included. Postvasopressor to prevasopressor ratios of CTH, MTT, relative transit time heterogeneity (RTH), cerebral blood flow (CBF), cerebral blood volume, and oxygen extraction fraction (OEF) were calculated in tumor, peritumoral, hippocampal, and contralateral grey matter regions. Comparisons were made between brain regions and vasopressors. RESULTS: During phenylephrine infusion, ratios of CTH, RTH, and CBF were greater, and ratios of MTT and OEF were lower, in the tumor region with contrast leakage compared with corresponding contralateral grey matter ratios. During ephedrine infusion, ratios of CTH, MTT, RTH, CBF, and cerebral blood volume were higher in the tumor region with leakage compared with contralateral grey matter ratios. In addition, the ratio of CBF was higher in all regions, the ratio of RTH was lower in the leaking tumor region, and the ratio of OEF was lower in peritumoral, hippocampal, and grey matter regions with ephedrine compared with phenylephrine. CONCLUSIONS: Vasopressors can induce distinct microcirculatory flow alterations in regions with compromised brain tumor barrier or BBB. Ephedrine, a combined α and ß-adrenergic agonist, appears to result in fewer flow alterations and less impact on tissue oxygenation compared with phenylephrine, a pure α-adrenergic agonist.

Effect of Esketamine Added to Propofol Sedation on Desaturation and Hypotension in Bidirectional Endoscopy: A Randomized Clinical Trial.

Importance: Propofol sedation is widely used for endoscopic procedures, but it poses risks of hemodynamic and respiratory depression. The addition of esketamine as an adjuvant may reduce propofol requirements and associated adverse events. Objective: To evaluate the effects of low-dose esketamine added to propofol-based sedation on desaturation and hypotension during same-visit bidirectional endoscopy. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled randomized clinical trial assessed patients from 3 teaching hospitals in China who were scheduled for same-visit bidirectional endoscopy between February 8 and November 30, 2022, and randomly assigned to receive esketamine or normal saline (placebo). Interventions: After induction of sedation with 0.1 µg/kg of sufentanil and 0.5 mg/kg of propofol, patients in the esketamine group received 0.15 mg/kg of intravenous esketamine, whereas patients in the placebo group received an equivalent volume of saline. Sedation was achieved through propofol titration. Main Outcomes and Measures: The primary outcome was the composite of desaturation and hypotension during the procedures. Secondary outcomes included desaturation, hypotension, propofol requirements, postprocedure pain and fatigue, nausea or vomiting, dizziness or headache, hallucination or nightmare, endoscopist satisfaction, and patient satisfaction. Results: Among the 663 initially enrolled patients, 660 completed the study (median [IQR] age, 48 [36-57] years; 355 [53.8%] female), with 331 randomized to the esketamine group and 329 to the placebo group. The administration of esketamine compared with placebo significantly reduced the incidence of the composite outcome of desaturation and hypotension (8.2% vs 21.0%; difference, -12.8 percentage points; odds ratio [OR], 0.34; 95% CI, 0.21-0.54; P < .001). Additionally, esketamine led to significantly lower incidences of desaturation (OR, 0.36; 95% CI, 0.18-0.72; false discovery rate q = .01) and hypotension (OR, 0.33; 95% CI, 0.18-0.60; q < .001) and reduced propofol requirements (difference, -58.9 mg; 95% CI, -65.7 to -52.2 mg; q < .001), without significant effects on other secondary outcomes. Conclusions and Relevance: In this randomized clinical trial of patients undergoing same-visit bidirectional endoscopy, the administration of low-dose esketamine resulted in an approximately 61% reduction in the incidence of desaturation and hypotension, accompanied by decreased propofol requirements. These findings support the use of esketamine as an adjuvant to propofol-based sedation in endoscopic procedures. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200055938.

Causes of Perioperative Cardiac Arrest: Mnemonic, Classification, Monitoring, and Actions.

Perioperative cardiac arrest (POCA) is a catastrophic complication that requires immediate recognition and correction of the underlying cause to improve patient outcomes. While the hypoxia, hypovolemia, hydrogen ions (acidosis), hypo-/hyperkalemia, and hypothermia (Hs) and toxins, tamponade (cardiac), tension pneumothorax, thrombosis (pulmonary), and thrombosis (coronary) (Ts) mnemonic is a valuable tool for rapid differential diagnosis, it does not cover all possible causes leading to POCA. To address this limitation, we propose using the preload-contractility-afterload-rate and rhythm (PCARR) construct to categorize POCA, which is comprehensive, systemic, and physiologically logical. We provide evidence for each component in the PCARR construct and emphasize that it complements the Hs and Ts mnemonic rather than replacing it. Furthermore, we discuss the significance of utilizing monitored variables such as electrocardiography, pulse oxygen saturation, end-tidal carbon dioxide, and blood pressure to identify clues to the underlying cause of POCA. To aid in investigating POCA causes, we suggest the Anesthetic care, Surgery, Echocardiography, Relevant Check and History (A-SERCH) list of actions. We recommend combining the Hs and Ts mnemonic, the PCARR construct, monitoring, and the A-SERCH list of actions in a rational manner to investigate POCA causes. These proposals require real-world testing to assess their feasibility.

Overexpression of HSF2 binding protein suppresses endoplasmic reticulum stress via regulating subcellular localization of CDC73 in hepatocytes.

BACKGROUND: Endoplasmic reticulum (ER) stress plays an important role in the occurrence and development of various liver diseases. However, there are no effective prevention and treatment strategies. We aimed to determine the role of heat shock factor 2 binding protein (HSF2BP) in ER stress. METHODS: HSF2BP expression in mice and cultured hepatocytes was measured during ER stress induced by tunicamycin, and its importance in ER stress was evaluated in hepatocyte-specific HSF2BP transgenic (TG) and knockout (KO) mice. The effects and mechanisms of HSF2BP on ER stress were further probed in hepatic ischemia-reperfusion (I/R) injury. RESULTS: HSF2BP expression was significantly upregulated during tunicamycin-induced ER stress in mice and cultured hepatocytes. Liver injury and ER stress were reduced in HSF2BP overexpressing mice after treating with tunicamycin, but were aggravated in HSF2BP knockout mice compared to the controls. In hepatic I/R injury, HSF2BP expression was significantly upregulated, and HSF2BP overexpressing mice had reduced liver injury and inflammation. These improvements were associated with ER stress inhibition. However, these results were reversed in hepatocyte-specific HSF2BP knockout mice. HSF2BP overexpression increased cytoplasmic CDC73 levels and inhibited the JNK signaling pathway. CDC73 knockdown using siRNA eliminated the protection exerted by HSF2BP overexpression in hypoxia/reoxygenation (H/R)-induced ER stress in hepatocytes. CONCLUSION: HSF2BP is a previously uncharacterized regulatory factor in ER stress-likely acts by regulating CDC73 subcellular localization. The feasibility of HSF2BP-targeted treatment in ER stress-related liver disease deserves future research.

Correlation Between Cerebral Tissue Oxygen Saturation and Oxygen Extraction Fraction During Anesthesia: Monitoring Cerebral Metabolic Demand-supply Balance During Vasopressor Administration.

BACKGROUND: The speculation that cerebral tissue oxygen saturation (SctO 2 ) measured using tissue near-infrared spectroscopy reflects the balance between cerebral metabolic rate of oxygen and cerebral oxygen delivery has not been validated. Our objective was to correlate SctO 2 with cerebral oxygen extraction fraction (OEF) measured using positron emission tomography; OEF is the ratio between cerebral metabolic rate of oxygen and cerebral oxygen delivery and reflects the balance between these 2 variables. MATERIALS AND METHODS: This cohort study was based on data collected in a previously published trial assessing phenylephrine versus ephedrine treatment in anesthetized patients undergoing brain tumor surgery. The variables of interest were measured twice over the healthy hemisphere before surgery: the first measurement performed after anesthesia induction and the second measurement performed after induction of a ∼20% increase in blood pressure using either phenylephrine or ephedrine. RESULTS: Data from 24 patients were analyzed. The overall vasopressor-induced relative changes in SctO 2 (ΔSctO 2 ) and OEF (ΔOEF) were 3.16% [interquartile range, -0.73% to 6.04%] and -12.5% [interquartile range, -24.0% to -6.19%], respectively. ΔSctO 2 negatively correlated with ΔOEF after phenylephrine treatment (Spearman rank correlation coefficient [ rs ]=-0.76; P =0.007), ephedrine treatment ( rs =-0.76; P =0.006), and any treatment ( rs =-0.79; P <0.001). ΔSctO 2 significantly associated with ΔOEF based on multivariable analysis with ΔOEF, relative changes in mean arterial pressure, arterial blood oxygen tension, and the bispectral index as covariates ( P =0.036). CONCLUSIONS: The negative correlation between changes in SctO 2 and OEF suggests that SctO 2 may reflect the cerebral metabolic demand-supply balance during vasopressor treatment. The generalizability of our findings in other clinical scenarios remains to be determined.

Scalp Nerve Block, Local Anesthetic Infiltration, and Postoperative Pain After Craniotomy: A Systematic Review and Network Meta-analysis of Randomized Trials.

The most efficacious methods for controlling postoperative pain in craniotomy remain unknown. A systematic review and network meta-analysis were performed to compare the efficacies of different strategies of scalp nerve block (SNB), scalp infiltration (SI), and control in patients undergoing craniotomy. MEDLINE, Embase, and CENTRAL databases were searched for randomized controlled trials. The primary outcome was postoperative 24-hour pain score, and the secondary outcome was opioid consumption within the first 24 hour after surgery. The effect was estimated using the between-group mean difference and ranked using the surface under the cumulative ranking curve (SUCRA) score. Twenty-four randomized trials were identified for inclusion. SNB using ropivacaine reduced postoperative 24-hour pain score when compared with control (mean difference [95% credible interval], -2.04 [-3.13, -0.94]; low quality), and when compared with SI using ropivacaine (-1.77 [-3.04, -0.51]; low quality) or bupivacaine (-1.96 [-3.65, -0.22]; low quality). SNB using ropivacaine was likely the most efficacious method for pain control (SUCRA, 91%), and also reduced opioid consumption within the first postoperative 24 hours as compared with control (mean difference [95% credible interval], -11.91 [-22.42, -1.4]; low quality). SNB using bupivacaine, lidocaine, and epinephrine combined, and SNB using ropivacaine, were likely the most efficacious methods for opioid consumption reduction (SUCRA, 88% and 80%, respectively). In summary, different methods of SNB / SI seem to have different efficacies after craniotomy. SNB using ropivacaine may be superior to other methods for postcraniotomy pain control; however, the overall quality of evidence was low.

Sevoflurane Exposure in the Developing Brain Induces Hyperactivity, Anxiety-Free, and Enhancement of Memory Consolidation in Mice.

Background: Sevoflurane exposure at brain developmental stages has been reported to induce neurotoxicity and, subsequently, results in learning deficits at the juvenile age. In this study, we aimed to investigate the effects of prior early-age sevoflurane exposure on locomotor activity, anxiety, CA1-dependent learning, and spatial memory, as well as synapse changes in mice. Methods: Totally, 3% sevoflurane was given to neonatal mice at postnatal day 7 for 4 h. These sevoflurane-treated mice were later subjected to open field and Morris water maze tests at their adult age (postnatal days 60-90) to assess their motor activity and spatial learning ability, respectively. The brain slices of sevoflurane-treated and control mice were examined for dendritic spine density and long-term potentiation (LTP) features following behavior tests (postnatal day 60). Protein levels of N-methyl-D-aspartate (NMDA) receptor subtypes and PSD95 in brain lysate were measured by using immunoblotting at the same age (postnatal day 60). Results: Prior early-age sevoflurane exposure increased the overall moving distance, prolonged the central-area lingering time, and increased the central-area entries of adult mice. Sevoflurane-treated mice spent more time in the target quadrant during the probe test. An increase of the spine density of pyramidal neurons in the CA1 region was observed in sevoflurane-treated mice. NMDA receptor GluN2A subunit, but not the GluN2B or PSD95, was increased in the brain lysate of sevoflurane-treated mice compared with that of control mice. LTP in the hippocampus did not significantly differ between sevoflurane-treated and control mice. Conclusion: Exposure to sevoflurane for mice during an early brain developmental stage (P7) induces later-on hyperactivity, anxiety-free, and enhancement of memory retention. These observations shed light on future investigations on the underlying mechanisms of sevoflurane's effect on neuronal development.

Effect of Perioperative Dexmedetomidine on Delayed Graft Function Following a Donation-After-Cardiac-Death Kidney Transplant: A Randomized Clinical Trial.

Importance: Delayed graft function (DGF) is a risk factor for acute rejection and graft failure after kidney transplant. Previous studies have suggested that dexmedetomidine may be renoprotective, but whether the use of dexmedetomidine would improve kidney allograft function is unknown. Objective: To investigate the effects of perioperative dexmedetomidine on DGF following a donation-after-cardiac-death (DCD) kidney transplant. Design, Setting, and Participants: This single-center, double-blind, placebo-controlled randomized clinical trial was conducted at The First Affiliated Hospital of Soochow University in Suzhou, China. Adults (18 years or older) who were scheduled for DCD kidney transplant were enrolled between September 1, 2019, and January 28, 2021, and then randomized to receive either dexmedetomidine or normal saline (placebo). One-year postoperative outcomes were recorded. All analyses were based on the modified intention-to-treat population. Interventions: Patients who were randomized to the dexmedetomidine group received a 24-hour perioperative dexmedetomidine intravenous infusion (0.4 µg/kg/h intraoperatively and 0.1 µg/kg/h postoperatively). Patients who were randomized to the normal saline group received an intravenous infusion of the placebo with the same dose regimen as the dexmedetomidine. Main Outcomes and Measures: The primary outcome was the incidence of DGF, defined as the need for dialysis in the first posttransplant week. The prespecified secondary outcomes were in-hospital repeated dialysis in the first posttransplant week, in-hospital acute rejection, and serum creatinine, serum cystatin C, estimated glomerular filtration rate, need for dialysis, and patient survival on posttransplant day 30. Results: Of the 114 patients enrolled, 111 completed the study (mean [SD] age, 43.4 [10.8] years; 64 male patients [57.7%]), of whom 56 were randomized to the dexmedetomidine group and 55 to the normal saline group. Dexmedetomidine infusion compared with normal saline reduced the incidence of DGF (17.9% vs 34.5%; odds ratio [OR], 0.41; 95% CI, 0.17-0.98; P = .04) and repeated dialysis (12.5% vs 30.9%; OR, 0.32; 95% CI, 0.13-0.88; P = .02, which was not statistically significant after multiple testing corrections), without significant effect on other secondary outcomes. Dexmedetomidine vs normal saline infusion led to a higher median (IQR) creatinine clearance rate on postoperative days 1 (9.9 [4.9-21.2] mL/min vs 7.9 [2.0-10.4] mL/min) and 2 (29.6 [9.7-67.4] mL/min vs 14.6 [3.8-45.1] mL/min) as well as increased median (IQR) urine output on postoperative days 2 (106.5 [66.3-175.6] mL/h vs 82.9 [27.1-141.9] mL/h) and 7 (126.1 [98.0-151.3] mL/h vs 107.0 [82.5-137.5] mL/h) and at hospital discharge discharge (110.4 [92.8-121.9] mL/h vs 97.1 [77.5-113.8] mL/h). Three patients (5.5%) from the normal saline group developed allograft failure by the post hoc 1-year follow-up visit. Conclusions and Relevance: This randomized clinical trial found that 24-hour perioperative dexmedetomidine decreased the incidence of DGF after DCD kidney transplant. The findings support the use of dexmedetomidine in kidney transplants. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1900025493.

Effect of Electroencephalography Spectral Edge Frequency (SEF) and Patient State Index (PSI)-Guided Propofol-Remifentanil Anesthesia on Delirium After Laparoscopic Surgery: The eMODIPOD Randomized Controlled Trial.

BACKGROUND: The effect of SedLine electroencephalography (EEG)-guided anesthetic care on postoperative delirium (POD) has not been studied. METHODS: This single-center randomized EEG Monitoring tO Decrease the Incidence of Post-Operative Delirium (eMODIPOD) trial involved 1560 patients aged 50 years or above undergoing laparoscopic surgery. Propofol-remifentanil anesthesia was guided either by SedLine (EEG-guided care, n=779) or not (usual care, n=781). The goal of EEG-guided care was to maintain spectral edge frequency between 10 and 15 and patient state index (PSI) between 25 and 50. The primary outcome was the incidence of POD on postoperative days 1 to 5. The secondary outcomes included emergence delirium, composite moderate-to-severe complications, length of hospital stay, intensive care unit admission, 30-day hospital readmission and all-cause mortality, and intraoperative awareness. RESULTS: Of the 1560 randomized patients, 1545 were included in the modified intention-to-treat analysis. The median propofol administered for anesthesia maintenance was 900 mg and 1000 mg in the EEG-guided and usual care groups, respectively (P=0.21). POD occurred in 1.0% (8/771) and 1.2% (9/774) of patients in the EEG-guided and usual care groups, respectively (risk ratio: 0.89; 95% confidence interval: 0.35-2.30). There were no between-group differences in all secondary outcome measures. Emergence delirium occurred in 11.8% (91/771) and 13.2% (102/774) of the EEG-guided care and usual care groups, respectively (risk ratio: 0.90; 95% confidence interval: 0.69-1.17; P=0.41). Three patients from each group reported intraoperative awareness. CONCLUSIONS: Compared with usual care, SedLine spectral edge frequency-guided and patient state index-guided propofol-remifentanil anesthetic care neither alters anesthetic delivery nor decreases the unexpected low incidence of POD in relatively young Chinese patients undergoing laparoscopic surgery.

The effect of selective cerebral perfusion on cerebral versus somatic tissue oxygenation during aortic coarctation repair in neonates and infants.

BACKGROUND: Suboptimal tissue perfusion and oxygenation may be the root cause of certain perioperative complications in neonates and infants having complicated aortic coarctation repair. Practical, effective, and real-time monitoring of organ perfusion and/or tissue oxygenation may provide early warning of end-organ mal-perfusion. METHODS: Neonates/infants who were scheduled for aortic coarctation repair with cardiopulmonary bypass (CPB) and selective cerebral perfusion (SCP) from January 2015 to February 2017 in Children's Hospital of Nanjing Medical University participated in this prospective observational study. Cerebral and somatic tissue oxygen saturation (SctO2 and SstO2) were monitored on the forehead and at the thoracolumbar paraspinal region, respectively. SctO2 and SstO2 were recorded at different time points (baseline, skin incision, CPB start, SCP start, SCP end, aortic opening, CPB end, and surgery end). SctO2 and SstO2 were correlated with mean arterial pressure (MAP) and partial pressure of arterial blood carbon dioxide (PaCO2). RESULTS: Data of 21 patients were analyzed (age=75±67 days, body weight=4.4±1.0 kg). SstO2 was significantly lower than SctO2 before aortic opening and significantly higher than SctO2 after aortic opening. SstO2 correlated with leg MAP when the measurements during SCP were (r=0.67, p<0.0001) and were not included (r=0.46, p<0.0001); in contrast, SctO2 correlated with arm MAP only when the measurements during SCP were excluded (r=0.14, p=0.08 vs. r=0.66, p<0.0001). SCP also confounded SctO2/SstO2's correlation with PaCO2; when the measurements during SCP were excluded, SctO2 positively correlated with PaCO2 (r=0.65, p<0.0001), while SstO2 negatively correlated with PaCO2 (r=-0.53, p<0.0001). CONCLUSIONS: SctO2 and SstO2 have distinct patterns of changes before and after aortic opening during neonate/infant aortic coarctation repair. SctO2/SstO2's correlations with MAP and PaCO2 are confounded by SCP. The outcome impact of combined SctO2/SstO2 monitoring remains to be studied.

Treatments Associated with Lower Mortality among Critically Ill COVID-19 Patients: A Retrospective Cohort Study.

BACKGROUND: Mortality in critically ill COVID-19 patients remains high. Although randomized controlled trials must continue to definitively evaluate treatments, further hypothesis-generating efforts to identify candidate treatments are required. This study's hypothesis was that certain treatments are associated with lower COVID-19 mortality. METHODS: This was a 1-yr retrospective cohort study involving all COVID-19 patients admitted to intensive care units in six hospitals affiliated with Yale New Haven Health System from February 13, 2020, to March 4, 2021. The exposures were any COVID-19-related pharmacologic and organ support treatments. The outcome was in-hospital mortality. RESULTS: This study analyzed 2,070 patients after excluding 23 patients who died within 24 h after intensive care unit admission and 3 patients who remained hospitalized on the last day of data censoring. The in-hospital mortality was 29% (593 of 2,070). Of 23 treatments analyzed, apixaban (hazard ratio, 0.42; 95% CI, 0.363 to 0.48; corrected CI, 0.336 to 0.52) and aspirin (hazard ratio, 0.72; 95% CI, 0.60 to 0.87; corrected CI, 0.54 to 0.96) were associated with lower mortality based on the multivariable analysis with multiple testing correction. Propensity score-matching analysis showed an association between apixaban treatment and lower mortality (with vs. without apixaban, 27% [96 of 360] vs. 37% [133 of 360]; hazard ratio, 0.48; 95% CI, 0.337 to 0.69) and an association between aspirin treatment and lower mortality (with vs. without aspirin, 26% [121 of 473] vs. 30% [140 of 473]; hazard ratio, 0.57; 95% CI, 0.41 to 0.78). Enoxaparin showed similar associations based on the multivariable analysis (hazard ratio, 0.82; 95% CI, 0.69 to 0.97; corrected CI, 0.61 to 1.05) and propensity score-matching analysis (with vs. without enoxaparin, 25% [87 of 347] vs. 34% [117 of 347]; hazard ratio, 0.53; 95% CI, 0.367 to 0.77). CONCLUSIONS: Consistent with the known hypercoagulability in severe COVID-19, the use of apixaban, enoxaparin, or aspirin was independently associated with lower mortality in critically ill COVID-19 patients.

Heterogeneous impact of hypotension on organ perfusion and outcomes: a narrative review.

Arterial blood pressure is the driving force for organ perfusion. Although hypotension is common in acute care, there is a lack of accepted criteria for its definition. Most practitioners regard hypotension as undesirable even in situations that pose no immediate threat to life, but hypotension does not always lead to unfavourable outcomes based on experience and evidence. Thus efforts are needed to better understand the causes, consequences, and treatments of hypotension. This narrative review focuses on the heterogeneous underlying pathophysiological bases of hypotension and their impact on organ perfusion and patient outcomes. We propose the iso-pressure curve with hypotension and hypertension zones as a way to visualize changes in blood pressure. We also propose a haemodynamic pyramid and a pressure-output-resistance triangle to facilitate understanding of why hypotension can have different pathophysiological mechanisms and end-organ effects. We emphasise that hypotension does not always lead to organ hypoperfusion; to the contrary, hypotension may preserve or even increase organ perfusion depending on the relative changes in perfusion pressure and regional vascular resistance and the status of blood pressure autoregulation. Evidence from RCTs does not support the notion that a higher arterial blood pressure target always leads to improved outcomes. Management of blood pressure is not about maintaining a prespecified value, but rather involves ensuring organ perfusion without undue stress on the cardiovascular system.

Renal tissue desaturation and acute kidney injury in infant cardiac surgery: a prospective propensity score-matched cohort study.

BACKGROUND: Previous studies on the association between renal tissue desaturation and acute kidney injury (AKI) in infant cardiac surgery are limited by small sample sizes and inconsistent results. This prospective study aimed to determine the association between renal desaturation and AKI in infants undergoing surgical repair of an isolated ventricular septal defect (VSD). METHODS: Infants undergoing VSD repair involving cardiopulmonary bypass participated in this prospective cohort study. The exposure of interest was renal tissue desaturation, defined as at least 20% decrease in saturation from baseline for at least 60 consecutive seconds. Intraoperative care was not guided by renal oxygenation, as the anaesthesiologists were blinded to the monitor. The outcome was AKI arising within postoperative Days 1-3. The primary analysis was based on propensity score-matched infants with and without intraoperative renal desaturation. RESULTS: Intraoperative renal desaturation was detected in 38 of 242 infants using near-infrared spectroscopy. This group of infants was matched with 114 infants without intraoperative renal saturation after propensity score matching. Acute kidney injury occurred in 47% (18/38) and 27% (31/114) of infants with or without renal desaturation, respectively. Infants with renal desaturation had higher odds of developing AKI than infants without renal desaturation based on conditional logistic regression (odds ratio 2.79; 95% confidence interval: 1.21-6.44; P=0.016). The cumulative time of renal desaturation correlated moderately with the ratio of postoperative peak creatinine to preoperative baseline creatinine (r=0.51; P<0.001). CONCLUSIONS: Intraoperative renal desaturation is associated with increased odds of developing AKI after surgical repair of an isolated VSD involving cardiopulmonary bypass in infants. CLINICAL TRIAL REGISTRATION: NCT03941015.

Can a deep learning model based on intraoperative time-series monitoring data predict post-hysterectomy quality of recovery?

BACKGROUND: Intraoperative physiological monitoring generates a large quantity of time-series data that might be associated with postoperative outcomes. Using a deep learning model based on intraoperative time-series monitoring data to predict postoperative quality of recovery has not been previously reported. METHODS: Perioperative data from female patients having laparoscopic hysterectomy were prospectively collected. Deep learning, logistic regression, support vector machine, and random forest models were trained using different datasets and evaluated by 5-fold cross-validation. The quality of recovery on postoperative day 1 was assessed using the Quality of Recovery-15 scale. The quality of recovery was dichotomized into satisfactory if the score ≥122 and unsatisfactory if <122. Models' discrimination was estimated using the area under the receiver operating characteristics curve (AUROC). Models' calibration was visualized using the calibration plot and appraised by the Brier score. The SHapley Additive exPlanation (SHAP) approach was used to characterize different input features' contributions. RESULTS: Data from 699 patients were used for modeling. When using preoperative data only, all four models exhibited poor performance (AUROC ranging from 0.65 to 0.68). The inclusion of the intraoperative intervention and/or monitoring data improved the performance of the deep leaning, logistic regression, and random forest models but not the support vector machine model. The AUROC of the deep learning model based on the intraoperative monitoring data only was 0.77 (95% CI, 0.72-0.81), which was indistinct from that based on the intraoperative intervention data only (AUROC, 0.79; 95% CI, 0.75-0.82) and from that based on the preoperative, intraoperative intervention, and monitoring data combined (AUROC, 0.81; 95% CI, 0.78-0.83). In contrast, when using the intraoperative monitoring data only, the logistic regression model had an AUROC of 0.72 (95% CI, 0.68-0.77), and the random forest model had an AUROC of 0.74 (95% CI, 0.73-0.76). The Brier score of the deep learning model based on the intraoperative monitoring data was 0.177, which was lower than that of other models. CONCLUSIONS: Deep learning based on intraoperative time-series monitoring data can predict post-hysterectomy quality of recovery. The use of intraoperative monitoring data for outcome prediction warrants further investigation. TRIAL REGISTRATION: This trial (Identifier: NCT03641625 ) was registered at ClinicalTrials.gov by the principal investigator, Lingzhong Meng, on August 22, 2018.

Association Between Cerebral Desaturation and Postoperative Delirium in Thoracotomy With One-Lung Ventilation: A Prospective Cohort Study.

BACKGROUND: The association between cerebral desaturation and postoperative delirium in thoracotomy with one-lung ventilation (OLV) has not been specifically studied. METHODS: A prospective observational study performed in thoracic surgical patients. Cerebral tissue oxygen saturation (Scto2) was monitored on the left and right foreheads using a near-infrared spectroscopy oximeter. Baseline Scto2 was measured with patients awake and breathing room air. The minimum Scto2 was the lowest measurement at any time during surgery. Cerebral desaturation and hypersaturation were an episode of Scto2 below and above a given threshold for ≥15 seconds during surgery, respectively. The thresholds based on relative changes by referring to the baseline measurement were <80%, <85%, <90%, <95%, and <100% baseline for desaturation and >105%, >110%, >115%, and >120% baseline for hypersaturation. The thresholds based on absolute values were <50%, <55%, <60%, <65%, and <70% for desaturation and >75%, >80%, >85%, and >90% for hypersaturation. The given area under the threshold (AUT)/area above the threshold (AAT) was analyzed. Delirium was assessed until postoperative day 5. The primary analysis was the association between the minimum Scto2 and delirium using multivariable logistic regression controlled for confounders (age, OLV time, use of midazolam, occurrence of hypotension, and severity of pain). The secondary analysis was the association between cerebral desaturation/hypersaturation and delirium, and between the AUT/AAT and delirium using multivariable logistic regression controlled for the same confounders. Multiple testing was corrected using the Holm-Bonferroni method. We additionally monitored somatic tissue oxygen saturation on the forearm and upper thigh. RESULTS: Delirium occurred in 35 (20%) of 175 patients (65 ± 6 years old). The minimum left or right Scto2 was not associated with delirium. Cerebral desaturation defined by <90% baseline for left Scto2 (odds ratio [OR], 5.82; 95% confidence interval [CI], 2.12-19.2; corrected P =.008) and <85% baseline for right Scto2 (OR, 4.27; 95% CI, 1.77-11.0; corrected P =.01) was associated with an increased risk of delirium. Cerebral desaturation defined by other thresholds, cerebral hypersaturation, the AUT/AAT, and somatic desaturation and hypersaturation were all not associated with delirium. CONCLUSIONS: Cerebral desaturation defined by <90% baseline for left Scto2 and <85% baseline for right Scto2, but not the minimum Scto2, may be associated with an increased risk of postthoracotomy delirium. The validity of these thresholds needs to be tested by randomized controlled trials.