Remimazolam ameliorates postoperative cognitive dysfunction after deep hypothermic circulatory arrest through HMGB1-TLR4-NF-κB pathway.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a complication of deep hypothermic circulatory arrest (DHCA). Various amounts of neurologic dysfunctions have been shown after DHCA, which has often been attributed to systemic inflammatory response syndrome and cerebral ischemia/reperfusion injury. Remimazolam is one of the commonly used anesthetic drugs with protective actions against inflammatory diseases, such as sepsis and cerebral ischemia/reperfusion injury. Here, we determined the protective effect and potential mechanism of action of remimazolam against neuronal damage after DHCA. METHODS: A rat model of DHCA was established, and a gradient dosage of remimazolam was administered during cardiopulmonary bypass (CPB). The cognitive function of rats was evaluated by Morris water maze. Hematoxylin and eosin and TUNEL staining were performed to assess hippocampus tissue injury and neuronal apoptosis. Inflammatory cytokines concentration were analyzed by enzyme-linked immunosorbent assay. The protein expression was analyzed using automated electrophoresis western analysis and immunohistochemical analysis. RESULTS: The appropriate dosage of remimazolam reduced histologic injury, neuronal apoptosis, microglia activation, and secondary inflammatory cascades, as well as the downregulation of the expression of the HMGB1-TLR4-NF-κB pathway after DHCA, improved the memory and learning abilities in DHCA rats. Further, administration of a TLR4 antagonist TAK-242 had a similar effect to remimazolam, while the TLR4 agonist LPS attenuated the effect of remimazolam. CONCLUSIONS: Remimazolam could ameliorate POCD after DHCA through the HMGB1-TLR4-NF-κB signaling pathway.

Hematocrit and Renal Failure in Aortic Arch Surgery: A Society of Thoracic Surgeons Database Study.

BACKGROUND: This study examined the association between cardiopulmonary bypass (CPB) hematocrit and postoperative acute renal failure (ARF) in patients undergoing aortic arch surgery with hypothermic circulatory arrest. METHODS: The Society of Thoracic Surgeons Adult Cardiac Surgery Database was queried from 2011 to 2019 for patients undergoing aortic arch surgery with hypothermic circulatory arrest. A multivariable logistic regression model estimated the adjusted odds of postoperative ARF on the basis of CPB hematocrit. Effects were stratified by preoperative kidney function and the duration of hypothermic circulatory arrest by using interaction terms. The study also investigated the association between postoperative ARF and major postoperative outcomes by using multivariable regression models. RESULTS: On adjusted analysis, higher CPB hematocrit (>20%-25%, >25%-30%, >30%) was associated with lower odds of ARF as compared with lower CPB hematocrit (≤20%) (>20-25%, aOR, 0.78; 95% CI, 0.65-0.93; P = .006; >25%-30%, aOR, 0.65; 95% CI, 0.50-0.84; P = .0007; >30%, aOR, 0.45; 95% CI, 0.28-0.72; P = .0008). The predicted probability of postoperative ARF by CPB hematocrit was higher in patients with lower preoperative renal function (estimated glomerular filtration rate, <60 mL/min/1.73 m2) (interaction P = .03). The association between hematocrit and postoperative ARF was not significantly modified by hypothermic circulatory arrest time (interaction P = .74). All postoperative outcomes were significantly worse in patients with postoperative ARF (all P < .0001). CONCLUSIONS: Among patients undergoing aortic arch surgery, a higher CPB hematocrit level is associated with reduced likelihood of postoperative ARF. Preoperative renal function, but not hypothermic circulatory arrest duration, significantly modified this association. The maintenance of higher CPB hematocrit may reduce the incidence of postoperative ARF, especially for patients with poor preoperative renal function.

Outcomes of Deep Hypothermic Circulatory Arrest for Descending and Thoracoabdominal Aneurysm Repair.

BACKGROUND: Deep hypothermic circulatory arrest (DHCA) in patients undergoing descending thoracic (DTAA) or thoracoabdominal aortic aneurysm (TAAA) repair is associated with increased morbidity and mortality. We present our outcomes after open DTAA and TAAA repair with and without DHCA. METHODS: From 1999 to 2022, 81 (38.8%) patients undergoing DTAA or TAAA repair required DHCA because proximal cross-clamping was not feasible or aneurysmal pathology extended into the arch and 128 (61.2%) patients required only distal bypass. Because of intrinsic pathological differences in patients requiring DHCA, confidence intervals (CIs) were used to compare groups in lieu of formal hypothesis tests. RESULTS: DHCA patients had more chronic dissections (64.2% vs. 43.8%, 95% CI for difference: 6-35%) and higher body mass indices (29.5 ± 6.8 vs. 27.2 ± 6.6, CI: 26-421%). More non-DHCA patients had medial degeneration (9.9% vs. 31.3%, CI: -33 to -7%). There were 10 (12.4%) in-hospital deaths for the DHCA and 10 (7.8%) for the non-DHCA group (CI: -5 to 14%). Survival at 10 years was 52.6% (CI: 42.1-65.7%) for the non-DHCA group and 48.3% (CI: 40.3-57.9%) for the DHCA group. The only meaningful differences in postoperative outcomes were intensive care unit (5.5 days vs. 6 days, CI: 12-410%) and hospital stay (19 days vs. 12 days, CI: 74-470%), which were longer in the DHCA group. CONCLUSIONS: Despite longer intensive care unit and hospital length of stays, selective use of DHCA is safe and effective with comparable morbidity and mortality to non-DHCA in open DTAA and TAAA repair.

The optimal degree of core temperature for hypothermic circulatory arrest in complex aortic arch surgery: results from 1310 patients.

OBJECTIVES: The optimal core temperature for hypothermic circulatory arrest during aortic arch surgery remains contentious. This study aims to evaluate patient outcomes under various temperatures within a large single-centre cohort. METHODS: Between 2010 and 2018, patients diagnosed with type A aortic dissection underwent total arch replacement at Fuwai Hospital were enrolled. They were categorized into 4 groups: deep hypothermia group, low-moderate hypothermia group, high-moderate hypothermia group and mild hypothermia group. Clinical data were analysed to ascertain differences between the groups. RESULTS: A total of 1310 patients were included in this cohort. Operative mortality stood at 6.9% (90/1310), with a higher incidence observed in the deep hypothermia group [29 (12.9%); 35 (6.9%); 21 (4.8%); 5 (3.4%); all adjusted P < 0.05]. Overall 10-year survival was 80.3%. Long-term outcomes did not significantly differ among the groups. Multivariable logistic analysis revealed a protective effect of higher core temperature on operative mortality (odds ratio 0.848, 95% confidence interval 0.766-0.939; P = 0.001). High-moderate hypothermia emerged as an independent protective factor for operative mortality (odds ratio 0.303, 95% confidence interval 0.126-0.727; P = 0.007). Multivariable Cox analysis did not detect an effect of hypothermic circulatory arrest on long-term survival (all P > 0.05). CONCLUSIONS: High-moderate hypothermia (24.1-28°C) offers the most effective protection against surgical mortality and is therefore recommended. Different hypothermic circulatory arrest temperatures do not influence long-term survival or quality of life.

Type A Aortic Dissection Following Heart Transplantation.

Cannulation strategies in aortic arch surgeries are a matter of immense discussion. Majority of time deep hypothermic circulatory arrest (DHCA) is the way out, but it does come with its set of demerits. Here we demonstrate a case with aortic arch dissection dealt with dual cannulation strategy in axillary and femoral artery without need for DHCA and ensuring complete neuroprotection of brain and spinal cord without hinderance of time factor. Inception of new ideas like this may decrease the need for DHCA and hence its drawbacks, thus decreasing the morbidity and mortality associated.

Deep Circulatory Arrest and Left Thoracotomy Approach Allow Open Repair of Chronic IIIb Dissection Associated to a Large Aortic Arch: A Case Series.

Thoracic aortic aneurysms evolving within a type IIIb chronic aortic dissection are mostly treated with the deployment of an endograft. However, several cases of dissecting aneurysms are associated with a significant dilatation of the aortic arch. These cases are usually managed in 2 steps: arch reconstruction or supra-aortic trunk debranching at first and a secondary graft deployment for the descending thoracic aorta. We present through this case series an alternative approach for this severe condition which consists in the replacement of the thoracic aorta from its hemi-arch to the distal thoracic or visceral aorta using a left thoracotomy. We deliberately neglected the remaining dissecting aorta if its diameter was below 45 mm, hypothesizing its nonevolution after repair. From 2012 to 2021, 9 patients have been treated for a thoracic aneurysm evolving after a IIIb chronic aortic dissection using a left thoracotomy and a 19°C circulatory arrest. Immediate postoperative results show no mortality or neurological disorders, and the 7 years follow-up for all of these 9 cases enlightened the absence of aneurysmal evolution especially for the distal anastomosis and the remaining dissected aorta. This work suggests that this direct approach strategy can definitively treat a thoracic dissecting aneurysm unsuitable for a simple endovascular treatment.

Retrograde cerebral perfusion reduces embolic and watershed lesions after acute type a aortic dissection repair with deep hypothermic circulatory arrest.

BACKGROUND: To assess whether retrograde cerebral perfusion reduces neurological injury and mortality in patients undergoing surgery for acute type A aortic dissection. METHODS: Single-center, retrospective, observational study including all patients undergoing acute type A aortic dissection repair with deep hypothermic circulatory arrest between January 1998 and December 2022 with or without the adjunct of retrograde cerebral perfusion. 515 patients were included: 257 patients with hypothermic circulatory arrest only and 258 patients with hypothermic circulatory arrest and retrograde cerebral perfusion. The primary endpoints were clinical neurological injury, embolic lesions, and watershed lesions. Multivariable logistic regression was performed to identify independent predictors of the primary outcomes. Survival analysis was performed using Kaplan-Meier estimates. RESULTS: Clinical neurological injury and embolic lesions were less frequent in patients with retrograde cerebral perfusion (20.2% vs. 28.4%, p = 0.041 and 13.7% vs. 23.4%, p = 0.010, respectively), but there was no significant difference in the occurrence of watershed lesions (3.0% vs. 6.1%, p = 0.156). However, after multivariable logistic regression, retrograde cerebral perfusion was associated with a significant reduction of clinical neurological injury (OR: 0.60; 95% CI 0.36-0.995, p = 0.049), embolic lesions (OR: 0.55; 95% CI 0.31-0.97, p = 0.041), and watershed lesions (OR: 0.25; 95%CI 0.07-0.80, p = 0.027). There was no significant difference in 30-day mortality (12.8% vs. 11.7%, p = ns) or long-term survival between groups. CONCLUSION: In this study, we showed that the addition of retrograde cerebral perfusion during hypothermic circulatory arrest in the setting of acute type A aortic dissection repair reduced the risk of clinical neurological injury, embolic lesions, and watershed lesions.

Clinical outcome of a branch-first approach with a novel continuous whole-brain perfusion strategy for total arch surgery.

BACKGROUND: Cerebral protection strategies have been investigated since the introduction of aortic arch surgery and have been modified over the centuries. However, the cerebral protective effects of unilateral and bilateral antegrade cerebral perfusion are similar, with opportunities for further improvement. METHODS: A total of 30 patients who underwent total arch surgery were enrolled in this study. Patients were assigned to the novel continuous whole-brain or unilateral antegrade cerebral perfusion group according to the cerebral perfusion technique used. Preoperative clinical data and 1-year postoperative follow-up data were collected and analyzed. RESULTS: There were no significant differences between the two groups in terms of the incidence of permanent neurological deficit, mortality, or therapeutic efficacy. However, the incidence of temporary neurological dysfunction in the novel whole-brain perfusion group was significantly lower than that in the unilateral antegrade cerebral perfusion group. CONCLUSIONS: In this study, the branch-first approach with a novel whole-brain perfusion strategy had no obvious disadvantages compared with unilateral antegrade cerebral perfusion in terms of cerebral protection and surgical safety. These findings suggest that this new technique is feasible and has application value for total arch surgery.

Cannula Placement for Cerebral Protection Without Circulatory Arrest in Patients Undergoing Hemiarch Aortic Aneurysm Repair.

BACKGROUND: Aortic aneurysms involving the proximal aortic arch, which require hemiarch-type repair, typically require circulatory arrest with antegrade cerebral perfusion. Left carotid antegrade cerebral perfusion (LCP) via distal arch cannulation without circulatory arrest was used in this study's patient population. The goal was to assess the operative efficiency and clinical outcomes of using a distal arch cannulation technique that would not require any hypothermic circulatory arrest (HCA) time compared with more traditional brachiocephalic artery cannulation with right-sided unilateral antegrade cerebral perfusion (RCP) and HCA. METHODS: A single-center retrospective review of patients with replacement of the distal ascending aorta involving the proximal arch was performed. Patients with an intramural hematoma or dissection were excluded. Between January 2015 and December 2019, 68 adult patients had undergone a hemiarch repair because of aneurysmal disease. Analysis of baseline demographics, operative data, and clinical outcomes was performed. RESULTS: Comparing the 68 patients: 21 patients were treated with RCP (via brachiocephalic artery graft with HCA), and 47 patients were treated with LCP (via distal aortic arch cannulation with cross-clamp between the brachiocephalic and left common carotid arteries without HCA). Baseline characteristics and outcomes were evaluated for both groups. The LCP group was younger (LCP median [IQR] age, 60 [53-65] years vs RCP median [IQR] age, 67 [59-71] years]. Sex, race, body mass index, comorbidities, and ejection fraction were similar between the groups. Cardiopulmonary bypass time (LCP, 123 minutes vs RCP, 149 minutes) and unilateral cerebral perfusion time (LCP, 17 minutes vs RCP, 22 minutes) were longer in the RCP group. Bleeding, prolonged ventilatory support, kidney failure, and length of stay were similar. In-hospital mortality was 2% in the LCP group vs 0% in the RCP group. Stroke occurred in 2 patients (4.2%) in the LCP group and in 0% of the RCP group. Mortality at 6 months in the LCP and RCP groups was 3% and 10%, respectively. CONCLUSION: Distal arch cannulation with LCP without HCA is a reasonable and safe alternative strategy for patients requiring hemiarch replacement for aneurysmal disease. This technique may provide additional benefits by avoiding circulatory arrest in these complex cases.

Is Deep Hypothermic Cardiac Arrest Mandatory in Aortic Arch Surgeries?

Cannulation strategies in aortic arch surgeries are a matter of immense discussion. Majority of time deep hypothermic circulatory arrest (DHCA) is the way out, but it does come with its set of demerits. Here we demonstrate a case with aortic arch dissection dealt with dual cannulation strategy in axillary and femoral artery without need for DHCA and ensuring complete neuroprotection of brain and spinal cord without hinderance of time factor. Inception of new ideas like this may decrease the need for DHCA and hence its drawbacks, thus decreasing the morbidity and mortality associated.

Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest Trial (GOT ICE): A Randomized Clinical Trial Comparing Outcomes After Aortic Arch Surgery.

BACKGROUND: Deep hypothermia has been the standard for hypothermic circulatory arrest (HCA) during aortic arch surgery. However, centers worldwide have shifted toward lesser hypothermia with antegrade cerebral perfusion. This has been supported by retrospective data, but there has yet to be a multicenter, prospective randomized study comparing deep versus moderate hypothermia during HCA. METHODS: This was a randomized single-blind trial (GOT ICE [Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest]) of patients undergoing arch surgery with HCA plus antegrade cerebral perfusion at 4 US referral aortic centers (August 2016-December 2021). Patients were randomized to 1 of 3 hypothermia groups: DP, deep (≤20.0 °C); LM, low-moderate (20.1-24.0 °C); and HM, high-moderate (24.1-28.0 °C). The primary outcome was composite global cognitive change score between baseline and 4 weeks postoperatively. Analysis followed the intention-to-treat principle to evaluate if: (1) LM noninferior to DP on global cognitive change score; (2) DP superior to HM. The secondary outcomes were domain-specific cognitive change scores, neuroimaging findings, quality of life, and adverse events. RESULTS: A total of 308 patients consented; 282 met inclusion and were randomized. A total of 273 completed surgery, and 251 completed the 4-week follow-up (DP, 85 [34%]; LM, 80 [34%]; HM, 86 [34%]). Mean global cognitive change score from baseline to 4 weeks in the LM group was noninferior to the DP group; likewise, no significant difference was observed between DP and HM. Noninferiority of LM versus DP, and lack of difference between DP and HM, remained for domain-specific cognitive change scores, except structured verbal memory, with noninferiority of LM versus DP not established and structured verbal memory better preserved in DP versus HM (P = 0.036). There were no significant differences in structural or functional magnetic resonance imaging brain imaging between groups postoperatively. Regardless of temperature, patients who underwent HCA demonstrated significant reductions in cerebral gray matter volume, cortical thickness, and regional brain functional connectivity. Thirty-day in-hospital mortality, major morbidity, and quality of life were not different between groups. CONCLUSIONS: This randomized multicenter study evaluating arch surgery HCA temperature strategies found low-moderate hypothermia noninferior to traditional deep hypothermia on global cognitive change 4 weeks after surgery, although in secondary analysis, structured verbal memory was better preserved in the deep group. The verbal memory differences in the low- and high-moderate groups and structural and functional connectivity reductions from baseline merit further investigation and suggest opportunities to further optimize brain perfusion during HCA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02834065.

Early outcome of simplified total arch reconstruction under mild hypothermia (30-32 °C) with distal aortic perfusion.

OBJECTIVE: We designed a simplified total arch reconstruction (s-TAR) technique which could be performed under mild hypothermia (30-32 °C) with distal aortic perfusion. This study aimed to compare its efficacy of organ protection with the conventional total arch reconstruction (c-TAR). METHODS: We reviewed the clinical data of 195 patients who had ascending aortic aneurysm with extended aortic arch dilation and underwent simultaneous ascending aorta replacement and TAR procedure between January 2018 and December 2022 in our center. 105 received c-TAR under moderate hypothermia (25-28 °C) with circulatory arrest (c-TAR group); rest 90 received s-TAR under mild hypothermia (30-32 °C) with distal aortic perfusion (s-TAR group). RESULTS: The s-TAR group demonstrated shorter CPB time, cross-clamp time and lower body circulatory arrest time compared with the c-TAR group. The 30-day mortality was 2.9% for the c-TAR group and 1.1% for the s-TAR group (P = 0.043). The mean duration of mechanical ventilation was shorter in the s-TAR group. Paraplegia was observed in 4 of 105 patients (3.8%) in the c-TAR group, while no such events were observed in the s-TAR group. The incidence of temporary neurologic dysfunction was significantly higher in the c-TAR group. The incidence of permanent neurologic dysfunction also showed a tendency to be higher in the c-TAR group, without statistical significance. Furthermore, the incidence of reoperation for bleeding were significantly lower in the s-TAR group. The rate of postoperative hepatic dysfunction and all grades of AKI was remarkably lower in the s-TAR group. The 3-year survival rate was 95.6% in the s-TAR group and 91.4% in the c-TAR group. CONCLUSIONS: s-TAR under mild hypothermia (30-32℃) with distal aortic perfusion is associated with lower mortality and morbidity, offering better neurological and visceral organ protection compared with c-TAR.

Hypothermic Circulatory Arrest in Adult Aortic Arch Surgery: A Review of Hypothermic Circulatory Arrest and its Anesthetic Implications.

Diseases affecting the aortic arch often require surgical intervention. Hypothermic circulatory arrest (HCA) enables a safe approach during open aortic arch surgeries. Additionally, HCA provides neuroprotection by reducing cerebral metabolism and oxygen requirements. However, HCA comes with significant risks (eg, neurologic dysfunction, stroke, and coagulopathy), and the cardiac anesthesiologist must completely understand the surgical techniques, possible complications, and management strategies.

Risk Factors for Stroke Development After Thoracic Aortic Surgery.

OBJECTIVES: Stroke after thoracic aortic surgery is a complication that is associated with poor outcomes. The aim is to characterize the intraoperative risk factors for stroke development. DESIGN: A retrospective analysis. SETTING: Tertiary, high-volume cardiac surgery center. PARTICIPANTS: Patients who had surgical repair of thoracic aortic diseases from January 1, 2017, through December 31, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 704 patients were included, of whom 533 had ascending aortic aneurysms, and 171 had type A aortic dissection. The incidence of postoperative stroke was 4.5% (95% CI 2.9%-6.6%) for ascending aortic aneurysms compared with 12.3% (95% CI 7.8%-18.16%) in type-A aortic dissections. Patients who developed postoperative strokes had significantly lower intraoperative hemoglobin median (7.5 gm/dL [IQR 6.8-8.6] v 8.55 gm/dL [IQR 7.3-10.0]; p < 0.001). The median cardiopulmonary bypass time was 185 minutes (IQR 136-328) in the stroke group versus 156 minutes (IQR 113-206) in the nonstroke group (p = 0.014). Circulatory arrest was used in 57.8% versus 38.5% of the nonstroke patients (p = 0.017). The initial temperature after leaving the operating room was lower, with a median of 35.0°C (IQR 34-35.92) in the stroke group versus 35.5°C (IQR 35-36) in the nonstroke cohort (p = 0.021). CONCLUSIONS: This single-center study highlighted the potential importance of intra-operative factors in preventing stroke. Lower hemoglobin, longer duration of cardiopulmonary bypass, deep hypothermic circulatory arrest, and postoperative hypothermia are potential risk factors for postoperative stroke. Further studies are needed to prevent this significant complication in patients with thoracic aortic diseases.

Incidence and clinical impact of silent pancreatitis after aortic arch surgery.

BACKGROUND: This study was designed to investigate the incidence and types of pancreatic injury, risk factors, and time-course changes in computed tomographic findings following total aortic arch replacement with moderate hypothermic circulatory arrest. METHODS: Medical records of patients who underwent total arch replacement between January 2006 and August 2021 were retrospectively reviewed. A comparison study between the patients with (group P) and without pancreatic injury (group N) was conducted to elucidate the impact of pancreatic injury. Follow-up computed tomography of the patients in group P was reviewed to investigate time-course changes of the pancreatic injury. RESULTS: Of 353 patients, 14 (4.0%) had subclinical pancreatic injury. Computed tomographic findings were consistent with acute pancreatitis in all patients, of whom eight patients had interstitial edematous pancreatitis, whereas six patients had necrotizing pancreatitis. Although walled-off necrosis occurred in three patients, none of them required drainage. In-hospital mortality was 7.1% and 4.4% in groups P and N, respectively (p = 0.98). The 5-year actuarial survival rates were 77.9% and 81.0% in groups P and N, respectively (p = 0.51). Multivariate analysis revealed that pancreatic injury was associated with chronic obstructive pulmonary disease (p = 0.03). CONCLUSIONS: This study highlighted that silent pancreatic injury after aortic arch surgery is underrecognized. Potential arterial sclerosis of the pancreatic circulation seems to be related to pancreatic injury.

Transcriptomic Profiling of circRNAs in rat Hippocampus after Deep Hypothermic Circulatory Arrest.

Neurologic abnormalities occurring after deep hypothermic circulatory arrest (DHCA) remain a significant concern. However, molecular mechanisms leading to DHCA-related cerebral injury are still ill-defined. Circular RNAs (circRNAs) are a class of covalently closed non-coding RNAs and can play important roles in different types of cerebral injury. This study aimed to investigate circRNAs expression profiles in rat hippocampus after DHCA and explore the potential functions of circRNAs in DHCA-related cerebral injury. Hence, the DHCA procedure in rats was established and a transcriptomic profiling of circRNAs in rat hippocampus was done. As a result, a total of 35192 circRNAs were identified. Among them, 339 circRNAs were dysregulated, including 194 down-regulated and 145 up-regulated between DHCA and sham group. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed based on the host genes of all dysregulated circRNAs. Also, 4 circRNAs were validated by RT-qPCR (rno_circ_0028462, rno_circ_0037165, rno_circ_0045161 and rno_circ_0019047). Then a circRNA-microRNA (miRNA) interaction network involving 4 candidate circRNAs was constructed. Furthermore, functional enrichment analysis of the miRNA-targeting mRNAs of every candidate circRNA was conducted to gain insight into each of the 4 circRNAs. Our study provided a better understanding of circRNAs in the mechanisms of DHCA-related cerebral injury and some potential targets for neuroprotection.

Determination of selective antegrade perfusion flow rate in aortic arch surgery to restore baseline cerebral near-infrared spectroscopy values: a single-centre observational study.

OBJECTIVES: Neuroprotection during aortic arch surgery involves selective antegrade cerebral perfusion. The parameters of cerebral perfusion, e.g. flow rate, are inconsistent across centres and are subject of debate. The aim of this study was to determine the cerebral perfusion flow rate during hypothermic circulatory arrest required to meet preoperative awake baseline regional cerebral oxygen saturation (rSO2). METHODS: Patients scheduled for aortic arch surgery with hypothermic circulatory arrest were enrolled in this prospective observational study. After initiation of hypothermic circulatory arrest, bilateral selective antegrade cerebral perfusion was established and cerebral flow rate was continuously increased. The primary end point was the difference of cerebral saturation from baseline during cerebral perfusion flow rates of 6, 8 and 10 ml/kg/min. RESULTS: A total of 40 patients were included. During antegrade cerebral perfusion, rSO2 was significantly lower than the baseline at 6 ml/kg/min [-7.3, 95% confidence interval (CI): -1.7, -12.9; P = 0.0015]. In contrast, flow rates of 8 and 10 ml/kg/min resulted in rSO2 that did not significantly differ from the baseline (-2; 95% CI: -4.3, 8.3; P > 0.99 and 1.8; 95% CI: -8.5%, 4.8%; P > 0.99). Cerebral saturation was significantly more likely to meet baseline values during selective antegrade cerebral perfusion with 8 ml/kg/min than at 6 ml/kg/min (44.1%; 95% CI: 27.4%, 60.8% vs 11.8%; 95% CI: 0.9%, 22.6%; P = 0.0001). CONCLUSIONS: At 8 ml/kg/min cerebral flow rate during selective antegrade cerebral perfusion, regional cerebral oximetry baseline values are significantly more likely to be achieved than at 6 ml/kg/min. Further increasing the cerebral flow rate to 10 ml/kg/min does not significantly improve rSO2.

[Risk factors of hyperlactatemia during pulmonary endarterectomy under deep hypothermic circulatory arrest and its influence on prognosis].

Objective: To investigate the incidence, risk factors, and outcomes of hyperlactatemia after pulmonary endarterectomy (PEA) under deep hypothermic circulatory arrest (DHCA). Methods: From December 2016 to January 2022, patients receiving PEA in China-Japan Friendship Hospital were enrolled in the study. Arterial blood samples were analyzed intraoperatively. Multivariate logistic regression analysis was performed to identify the predictors of intraoperative lactate elevation as well as major factors influencing the clinical outcome of the surgery. Results: A total of 110 patients (69 males and 41 females) were enrolled, aged (50.6±12.8) years. Receiver operating characteristic curve yielded an optimal cut-off lactate level of 7 mmol/L for predicting major postoperative complications (re-operation, re-intubation, postoperative renal failure requiring renal replacement therapy, wound infection, stroke, atrial fibrillation, and perioperative extracorporeal membrane oxygenation usage within 48 hours after surgery). Thirty-nine patients (35.5%) had an intraoperative peak arterial lactate level of≥7 mmol/L. According to intraoperative peak arterial lactate level, the patients were divided into two groups (<7 mmol/L and≥7 mmol/L). There were no statistically significant differences in age, sex and body mass index between the two groups (all P>0.05). Intraoperative peak lactate level was associated with prolonged mechanical ventilation time (r=0.262, P=0.008) and intensive care unit length of stay (r=0.304, P=0.002). Multivariate logistic regression analysis identified three key variables associated with lactate level≥7 mmol/L: DHCA duration (OR=1.186, 95%CI: 1.027-1.370, P=0.020), nadir hematocrit (HCT) (OR=0.580, 95%CI: 0.341-0.988, P=0.045) and preoperative pulmonary vascular resistance (PVR) (OR=1.096, 95%CI: 1.020-1.177, P=0.012). Patients with lactate≥7 mmol/L carried a higher rate of major complications (P=0.001). For patients with lactate≥7 mmol/L, 41.0% (16 out of 39 cases) had major complications, while for patients with lactate<7 mmol/L, only 14.1% (10 out of 71) had major complications. There was no statistically significant difference in mortality (8.5% vs 10.3%, P=0.753) between patients with different lactate levels. Moreover, intraoperative peak lactate level was a predictor of postoperative combined morbidity (OR=1.625, 95%CI: 1.176-2.245, P=0.003). Conclusion: High intraoperative lactate levels are associated with higher preoperative PVR, lower nadir HCT, and longer DHCA duration. Intraoperative lactate levels are independently associated with increased combined morbidity.