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.

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.

Systematic review and network meta-analysis of various nadir temperature strategies for hypothermic circulatory arrest for aortic arch surgery.

BACKGROUND: The optimal nadir temperature for hypothermic circulatory arrest during aortic arch surgery remains unclear. We aimed to assess and compare clinical outcomes of all three temperature strategies (deep, moderate, and mild hypothermia) using a network meta-analysis. METHODS: After literature search with MEDLINE and EMBASE through December 2021, studies comparing clinical outcomes with deep (<20°C), moderate (20-28°C), or mild (>28°C) hypothermic circulatory arrest were included. The outcomes of interest were perioperative mortality, stroke, transient ischemia attack (TIA), acute kidney injury (AKI), postoperative bleeding, operative time, and length of hospital stay. RESULTS: Twenty-four comparative studies were identified, including 6018 patients undergoing aortic arch surgery using hypothermic circulatory arrest (deep: 2,978, moderate: 2,525, and mild: 515). Compared to deep hypothermia, mild and moderate hypothermia were associated with lower mortality (mild vs. deep: odds ratio [OR] 0.50; 95% confidence interval (CI) 0.29-0.87, moderate vs. deep: OR 0.68; 95% CI 0.54-0.86). In addition, mild hypothermia was associated with lower stroke (OR 0.50; 95% CI 0.28-0.89), AKI (OR 0.36; 95% CI 0.15-0.88) and postoperative bleeding (OR 0.55; 95% CI 0.31-0.97) compared to deep hypothermia. There was no significant difference between mild and moderate hypothermia in mortality, AKI or bleeding occurrence, while mild hypothermia was associated with shorter operative time and hospital stay. There was no significant difference in TIA rate among three groups. CONCLUSIONS: Mild hypothermia was associated with overall more favorable clinical outcomes with comparable neurological complications compared to deep hypothermia. Furthermore, considering the shorter operative time and hospital stay compared with moderate hypothermia, mild hypothermia may be warranted when appropriate adjunctive cerebral perfusion is employed.

Does methylprednisolone provide protective effect in total aortic arch replacement requiring hypothermia circulatory arrest and selective cerebral perfusion?

BACKGROUND: Glucocorticoids (GC)were applied in total aortic arch replacement (TAAR) at various dosages in many centers, but with limited evidence. METHODS: The retrospective study was aimed to evaluate whether methylprednisolone was associated with better postoperative outcomes in patients undergoing TAAR. Patients undergoing TAAR with moderate hypothermia and selective cerebral perfusion between 2017.1 to 2018.12 in Fuwai hospital were classified into three groups according to doses of methylprednisolone given in the surgery: large-GC group (1500-3000 mg); medium-GC group (500-1000 mg) and no-GC group (0 mg). Postoperative outcomes were compared among three groups. Multivariable analysis was performed to identify the association of methylprednisolone with outcomes. RESULTS: Three hundred twenty-eight patients were enrolled. Two hundred twenty-eight were in the large-GC group, 34 were in the medium-GC group, and 66 were in the no-GC group. The incidences of major adverse outcomes in large-GC, medium-GC and no-GC groups were 22.8%, 17.6% and 18.2%, respectively, with no statistical difference. A significant difference was observed in post-cardiopulmonary bypass (CPB) fresh frozen plasma (FFP) transfusion (p < .001) and chest drainage volume (p < .001). Multivariable analysis demonstrated that methylprednisolone was not associated with better outcomes (p = .455), while large doses of methylprednisolone were significantly associated with excessive chest drainage (over 2000 mL) [OR (99% CI) 4.282 (1.66-11.044), p < .001] and excessive post-CPB FFP transfusion (over 400 mL) [OR (99% CI) 2.208 (1.027-4.747), p = .008]. CONCLUSIONS: Large doses of methylprednisolone (1500-3000 mg) did not show a protective effect in TAAR with moderate hypothermia arrest plus selective cerebral perfusion and might increase postoperative bleeding and FFP transfusion.

Application of deep hypothermic circulatory arrest in open left chest aortic aneurysm repair.

OBJECTIVES: Deep hypothermic circulatory arrest (DHCA) is often required for patients undergoing repair of descending thoracic aortic aneurysm (DTAA) or thoracoabdominal aortic aneurysm via left thoracotomy when proximal crossclamping is not feasible or when aneurysmal disease extends into the transverse aortic arch. Historical literature suggests higher complications rates due to the technical complexity of this approach; we examined outcomes with this approach at our center. METHODS: Between January 2008 and May 2018, 84 patients with DTAA or Crawford extent I thoracoabdominal aortic aneurysm underwent open repair. DHCA was employed in 46 of 84 (55%) patients, of which 33 (72%) required repair of distal arch and DTAA, and 13 (28%) required repair of the distal arch and extent I thoracoabdominal aortic aneurysm. Patients who underwent DHCA had more chronic dissections than those in the non-DHCA group (70% vs 34%; P ≤ .05). RESULTS: Major adverse outcomes for the DHCA group versus non-DHCA group were as follows: early mortality 3 out of 46 (7%) versus 4 out of 38 (11%) (P = .70), stroke 3 out of 46 (7%) versus 1 out of 38 (3%) (P = .62), permanent spinal cord deficit 2 out of 46 (4%) versus 3 out of 38 (8%) (P = .65), permanent renal failure necessitating dialysis 1 out of 46 (2%) versus 2 out of 38 (5%) (P = .59). Freedom from major adverse outcomes was 38 out of 46 (83%) versus 31 out of 38 (82%) for DHCA versus non-DHCA (P = 1). CONCLUSIONS: DHCA can be employed via left thoracotomy for combined arch and DTAA or extent I thoracoabdominal aortic aneurysm open repair.

The use of blood and blood products in aortic surgery is associated with adverse outcomes.

OBJECTIVE: To report long-term outcomes after deep hypothermic circulatory arrest (DHCA) with or without perioperative blood or blood products. METHODS: All patients who underwent proximal aortic surgery with DHCA from 2011 to 2018 were propensity matched according to baseline characteristics. Primary outcomes included short- and long-term mortality. Stratified Cox regression analysis was performed for significant associations with survival. RESULTS: A total of 824 patients underwent aortic replacement requiring circulatory arrest. After matching, there were 224 patients in each arm (transfusion and no transfusion). All baseline characteristics were well matched, with a standardized mean difference (SMD) <0.1. Preoperative hematocrit (41.0 vs 40.6; SMD = 0.05) and ejection fraction (57.5% vs 57.0%; SMD = 0.08) were similar between the no transfusion and blood product transfusion cohorts. Rate of aortic dissection (42.9% vs 45.1%; SMD = 0.05), hemiarch replacement (70.1% vs 70.1%; SMD = 0.00), and total arch replacement (21.9% vs 23.2%; SMD = 0.03) were not statistically different. Cardiopulmonary bypass and cross-clamp time were higher in the blood product transfusion cohort (P < .001). Operative mortality (9.4% vs 2.7%; P = .003), stroke (7.6% vs 1.3%; P = .001), reoperation rate, pneumonia, prolonged ventilation, and dialysis requirements were significantly higher in the transfusion cohort (P < .001). In stratified Cox regression, transfusion was an independent predictor of mortality (hazard ratio, 2.62 [confidence interval, 1.47-4.67]; P = .001). One- and 5-year survival were significantly reduced for the transfusion cohort (P < .001). CONCLUSIONS: In patients who underwent aortic surgery with DHCA, perioperative transfusions were associated with poor outcomes despite matching for preoperative baseline characteristics.

Laboratory signatures differentiate the tolerance to hypothermic circulatory arrest in acute type A aortic dissection surgery.

OBJECTIVES: Our goal was to investigate whether laboratory signatures on admission could be used to identify risk stratification and different tolerance to hypothermic circulatory arrest in acute type A aortic dissection surgery. METHODS: Patients from 10 Chinese hospitals participating in the Additive Anti-inflammatory Action for Aortopathy & Arteriopathy (5A) study were randomly divided into derivation and validation cohorts at a ratio of 7:3 to develop and validate a simple risk score model using preoperative variables associated with in-hospital mortality using multivariable logistic regression. The performance of the model was assessed using the area under the receiver operating characteristic curve. Subgroup analyses were performed to investigate whether the laboratory signature-based risk stratification could differentiate the tolerance to hypothermic circulatory arrest. RESULTS: There were 1443 patients and 954 patients in the derivation and validation cohorts, respectively. Multivariable analysis showed the associations of older age, larger body mass index, lower platelet-neutrophile ratio, higher lymphocyte-monocyte ratio, higher D-dimer, lower fibrinogen and lower estimated glomerular filtration rate with in-hospital death, incorporated to develop a simple risk model (5A laboratory risk score), with an area under the receiver operating characteristic of 0.736 (95% confidence interval 0.700-0.771) and 0.715 (95% CI 0.681-0.750) in the derivation and validation cohorts, respectively. Patients at low risk were more tolerant to hypothermic circulatory arrest than those at middle to high risk in terms of in-hospital mortality [odds ratio 1.814 (0.222-14.846); odds ratio 1.824 (1.137-2.926) (P = 0.996)]. CONCLUSIONS: The 5A laboratory-based risk score model reflecting inflammatory, immune, coagulation and metabolic pathways provided adequate discrimination performances in in-hospital mortality prediction, which contributed to differentiating the tolerance to hypothermic circulatory arrest in acute type A aortic dissection surgery.Clinical Trials. gov number NCT04918108.

The Evaluation Value of Diffusion-Weighted Imaging for Brain Injury in Patients after Deep Hypothermic Circulatory Arrest.

Objective: Cerebral complications may occur after surgery with deep hypothermic circulatory arrest (DHCA). Diffusion-weighted imaging (DWI) has shown promising results in detecting early changes of cerebral ischemia. However, studies in human models are limited. Here, we examined the significance of DWI for detecting brain injury in postoperative patients after DHCA. Methods: Twelve patients who had undergone selective cerebral perfusion with DHCA were enrolled. All patients underwent magnetic resonance imaging (MRI) examinations before and after the operation with T1-weighted phase (T1W) and T2-weighted phase (T2W). Magnetic resonance angiography (3D TOF) was applied to observe intracranial arterial communication situations. DWI was employed to calculate the apparent diffusion coefficient (ADC) values. The neurocognitive function of patients was assessed preoperatively and postoperatively using the Montreal Cognitive Assessment Scale (MoCA), Hamilton Depression Scale (HAMD), and Hamilton Anxiety Scale (HAMA). Results: The ADC values of the whole brain of patients after surgery were significantly higher than before surgery (P = 0.003). However, no significant difference in the ADC values of other regions before and after the operation was observed. There was no significant effect on the postoperative cognitive function of patients after surgery, but visual-spatial and executive abilities were significantly reduced, while psychological anxiety (P = 0.005) and depression levels (P < 0.05) significantly increased. Correlation analysis revealed a significant association between ADC change values and depression change values (P < 0.05). Conclusion: DHCA demonstrated no significant effect on the cognitive function of patients but could affect the mood of patients. On the other hand, DWI demonstrated promising efficiency and accuracy in evaluating brain injury after DHCA.

Duration of regional cerebral oxygen saturation under 40% is a risk factor for neurological injury following pulmonary thromboendarterectomy: A prospective observational study.

BACKGROUND: Deep hypothermic circulatory arrest (DHCA) is nowadays commonly used in pulmonary thromboendarterectomy (PTE). Neurological injury related to DHCA severely impairs the prognosis of patients. However, the risk factors and predictors of neurological injury are still unclear. METHODS: We conducted a prospective observational study, including 82 patients diagnosed as chronic thromboembolic pulmonary hypertension and underwent PTE alone in our center from December 2016 to May 2021. Demographic characteristics, clinical and surgical data, and neurological adverse events were recorded prospectively. Univariate and multivariate analyses were conducted to identify the predictors of neurological injury. RESULTS: Eleven (13.4%) patients exhibited neurological injuries after surgery. Univariate analysis showed that the duration of regional cerebral oxygen saturation (rSO2 ) under 40% (p < .001), the minimum rSO2 (p = .006), and the percentage of decrease in rSO2 (p = .011) were significantly associated with neurological injury. Multivariate analysis showed that the duration of rSO2 under 40% was an independent predictor for postoperative neurological injury (odds ratio = 3.896, 95% confidence interval: 1.812-8.377, p < .001). The receiver operating characteristic curve showed that when the cut-off value was 1.25 min, its sensitivity for predicting neurological injury was 63.6% with a specificity of 88.7%. CONCLUSIONS: The duration of rSO2 under 40% is an independent predictor for neurological injury following PTE. For complicated lesions, more times of circulatory arrest were much safer and more reliable than a prolonged time of a single circulatory arrest. The circulation should be restored as soon as possible, when the rSO2 under 40% is detected, rather than waiting for 5 min.

Metabolomic profiling demonstrates evidence for kidney and urine metabolic dysregulation in a piglet model of cardiac surgery-induced acute kidney injury.

Acute kidney injury (AKI) is a common cause of morbidity after congenital heart disease surgery. Progress on diagnosis and therapy remains limited, however, in part due to poor mechanistic understanding and a lack of relevant translational models. Metabolomic approaches could help identify novel mechanisms of injury and potential therapeutic targets. In the present study, we used a piglet model of cardiopulmonary bypass with deep hypothermic circulatory arrest (CPB/DHCA) and targeted metabolic profiling of kidney tissue, urine, and serum to evaluate metabolic changes specific to animals with histological acute kidney injury. CPB/DHCA animals with acute kidney injury were compared with those without acute kidney injury and mechanically ventilated controls. Acute kidney injury occurred in 10 of 20 CPB/DHCA animals 4 h after CPB/DHCA and 0 of 7 control animals. Injured kidneys showed a distinct tissue metabolic profile compared with uninjured kidneys (R2 = 0.93, Q2 = 0.53), with evidence of dysregulated tryptophan and purine metabolism. Nine urine metabolites differed significantly in animals with acute kidney injury with a pattern suggestive of increased aerobic glycolysis. Dysregulated metabolites in kidney tissue and urine did not overlap. CPB/DHCA strongly affected the serum metabolic profile, with only one metabolite that differed significantly with acute kidney injury (pyroglutamic acid, a marker of oxidative stress). In conclusion, based on these findings, kidney tryptophan and purine metabolism are candidates for further mechanistic and therapeutic investigation. Urine biomarkers of aerobic glycolysis could help diagnose early acute kidney injury after CPB/DHCA and warrant further evaluation. The serum metabolites measured at this early time point did not strongly differentiate based on acute kidney injury.NEW & NOTEWORTHY This project explored the metabolic underpinnings of postoperative acute kidney injury (AKI) following pediatric cardiac surgery in a translationally relevant large animal model of cardiopulmonary bypass with deep hypothermic circulatory arrest. Here, we present novel evidence for dysregulated tryptophan catabolism and purine catabolism in kidney tissue and increased urinary glycolysis intermediates in animals who developed histological AKI. These pathways represent potential diagnostic and therapeutic targets for postoperative AKI in this high-risk population.

Safety of retrograde cerebral perfusion under moderate hypothermia for hemiarch replacement.

OBJECTIVES: Aortic surgeries performed under moderate hypothermia require antegrade cerebral perfusion. The influence of retrograde cerebral perfusion under moderate hypothermic circulatory arrest remains unknown. To clarify this effect, this study aimed to compare the early outcomes of retrograde versus antegrade cerebral perfusion under moderate hypothermia for hemiarch replacement. METHODS: Between March 2009 and April 2020, 391 hemiarch replacements under moderate hypothermic circulatory arrest via median sternotomy were performed at our institution. Of these, 70 involved retrograde perfusion and 162 involved antegrade perfusion. Propensity score matching was used to compare 61 pairs of retrograde and antegrade cases. RESULTS: Retrograde and antegrade strategy under moderate hypothermia resulted in comparable operative mortality (3.3% vs. 1.6%, P > 0.99), permanent neurological deficits (8.5% vs. 6.6%, P > 0.99), and temporary neurological deficits (24.6% vs. 39.3%, P = 0.33). Retrograde surgery was associated with shorter circulatory arrest times (31.4 ± 8.2 min vs. 37.4 ± 12.2 min, P = 0.005) and fewer red blood cell transfusions (4.6 ± 3.9 units vs. 8.2 ± 5.1 units, P < 0.001) than those with antegrade surgery. CONCLUSIONS: Retrograde cerebral perfusion under moderate hypothermia for hemiarch replacement yields excellent operative outcomes, equivalent to those achieved using an antegrade strategy.

Duration of deep hypothermic circulatory arrest for aortic arch surgery: is it a myth, fiction, or scientific leap?

INTRODUCTION: The use of deep hypothermic circulatory arrest (DHCA) to provide aortic surgeons with a bloodless operative field while simultaneously protecting the brain and peripheries from ischemic damage revolutionized cardiac and aortic surgery, and is currently used in specialist centers across the globe. However, it is associated with manifold adverse outcomes, including neurocognitive dysfunction and mortality. This review seeks to analyze the relationship between DHCA duration and clinical outcome, and evaluate the controversies and limitations surrounding its use. EVIDENCE ACQUISITION: We performed a review of available literature with statistical analysis to evaluate the relationship between DHCA duration (<40 min and >40 min) and key clinical outcomes, including mortality, permanent and temporary neurological deficit, renal damage, admission length, and reintervention rate. The controversies surrounding DHCA use and future directions for care are also explored. EVIDENCE SYNTHESIS: Statistical analysis revealed no significant association (P>0.05) between DHCA duration and clinical outcomes (early and late mortality rates, neurological deficit, admission length, and reintervention rate), both with and without adjunctive perfusion techniques. CONCLUSIONS: Available literature suggests that the relationships between DHCA duration (with and without adjunctive perfusion) and clinical outcomes are unclear, and at present not statistically significant. Alternative surgical and endovascular techniques have been identified as promising novel approaches not requiring DHCA, as have the use of biomarkers to enable early diagnosis and intervention for aortic pathologies.

Neuroprotection in aortic arch surgery: untold flaws and future directions.

The current paradigm of brain protection in aortic surgery falls short of delivering good outcomes with minimal complications. A renewed understanding of neuroprotective methods and biomarkers to predict brain injury and aortic disease are crucial towards the development of more effective clinical management strategies. A review of current literature was carried out to identify current flaws in our approach to neuroprotection in aortic surgery. Emerging evidence surrounding neuroprotective strategies, biomarkers for brain injury, and biomarkers for predicting aortic disease are evaluated in terms of their impact for future therapeutic approaches. Current literature suggests that the prevailing methods of neuroprotection need renewal. Clinical outcomes associated with deep hypothermic circulatory arrest remain varied. Branch-first and endovascular approaches to aortic repair are particularly promising alternatives. The use of biomarkers to identify and manage brain injury, as well as to diagnose aortic disease in the nonacute and acute settings, would further help to improve our overall paradigm of neuroprotection in aortic surgery. Though much prospective research is still required, the outlook for neuroprotection in aortic surgery is promising. Adopting alternative surgical techniques and exploiting predictive novel biomarkers will help us to gradually eliminate the risk of brain damage in aortic surgery.

The dynamic changes in autophagy activity and its role in lung injury after deep hypothermic circulatory arrest.

Deep hypothermic circulatory arrest (DHCA) can cause acute lung injury (ALI), and its pathogenesis mimics ischaemia/reperfusion (I/R) injury. Autophagy is also involved in lung I/R injury. The present study aimed to elucidate whether DHCA induces natural autophagy activation and its role in DHCA-mediated lung injury. Here, rats were randomly assigned to the Sham or DHCA group. The sham group (n = 5) only received anaesthesia and air intubation. DHCA group rats underwent cardiopulmonary bypass (CPB) followed by the DHCA procedure. The rats were then sacrificed at 3, 6 and 24 h after the DHCA procedure (n = 5) to measure lung injury and autophagy activity. Chloroquine (CQ) was delivered to evaluate autophagic flux. DHCA caused lung injury, which was prominent 3-6 h after DHCA, as confirmed by histological examination and inflammatory cytokine quantification. Lung injury subsided at 24 h. Autophagy was suppressed 3 h but was exaggerated at 6 h. At both time points, autophagic flux appeared uninterrupted. To further assess the role of autophagy in DHCA-mediated lung injury, the autophagy inducer rapamycin and its inhibitor 3-methyladenine (3-MA) were applied, and lung injury was reassessed. When rapamycin was administered at an early time point, lung injury worsened, whereas administration of 3-MA at a late time point ameliorated lung injury, indicating that autophagy contributed to lung injury after DHCA. Our study presents a time course of lung injury following DHCA. Autophagy showed adaptive yet protective suppression 3 h after DHCA, as induction of autophagy caused worsening of lung tissue. In contrast, autophagy was exaggerated 6 h after DHCA, and autophagy inhibition attenuated DHCA-mediated lung injury.

Neuroprotective strategies with circulatory arrest in open aortic surgery - A meta-analysis.

OBJECTIVE: Deep hypothermic circulatory arrest (DHCA) in aortic surgery is associated with morbidity and mortality despite evolving strategies. With the advent of antegrade cerebral perfusion (ACP), moderate hypothermic circulatory arrest (MHCA) was reported to have better outcomes than DHCA. There is no standardised guideline or consensus regarding the hypothermic strategies to be employed in open aortic surgery. Meta-analysis was performed comparing DHCA with MHCA + ACP in patients having aortic surgery. METHODS: A systematic review of the literature was undertaken. Any studies with DHCA versus MHCA + ACP in aortic surgeries were selected according to specific inclusion criteria and analysed to generate summative data. Statistical analysis was performed using STATS Direct. The primary outcomes were hospital mortality and post-operative stroke. Secondary outcomes were cardiopulmonary bypass time (CPB), post-operative blood transfusion, length of ICU stay, respiratory complications, renal failure and length of hospital stay. Subgroup analysis of primary outcomes for Arch surgery alone was also performed. RESULTS: Fifteen studies were included with a total of 5869 patients. There was significantly reduced mortality (Pooled OR = +0.64, 95% CI = +0.49 to +0.83; p = 0.0006) and stroke rate (Pooled OR = +0.62, 95% CI = +0.49 to +0.79; p < 0.001) in the MHCA group. MHCA was associated significantly with shorter CPB times, shorter duration in ICU, less pulmonary complications, and reduced rates of sepsis. There was no statistical difference between the two groups in terms of circulatory arrest times, X-Clamp times, total operation duration, transfusion requirements, renal failure and post-op hospital stay. CONCLUSION: MHCA + ACP are associated with significantly better post-operative outcomes compared with DHCA for both mortality and stroke and majority of the secondary outcomes.

Association of Ongoing Cerebral Oxygen Extraction During Deep Hypothermic Circulatory Arrest With Postoperative Brain Injury.

Cardiac surgery utilizing circulatory arrest is most commonly performed under deep hypothermia (∼18°C) to suppress tissue oxygen demand and provide neuroprotection during operative circulatory arrest. Studies investigating the effects of deep hypothermic circulatory arrest (DHCA) on neurodevelopmental outcomes of patients with congenital heart disease give conflicting results. Here, we address these issues by quantifying changes in cerebral oxygen saturation, blood flow, and oxygen metabolism in neonates during DHCA and investigating the association of these changes with postoperative brain injury. Neonates with critical congenital heart disease undergoing DHCA were recruited for continuous intraoperative monitoring of cerebral oxygen saturation (ScO2) and an index of cerebral blood flow (CBFi) using 2 noninvasive optical techniques, diffuse optical spectroscopy (DOS) and diffuse correlation spectroscopy (DCS). Pre- and postoperative brain magnetic resonance imaging (MRI) was performed to detect white matter injury (WMI). Fifteen neonates were studied, and 11/15 underwent brain MRI. During DHCA, ScO2 decreased exponentially in time with a median decay rate of -0.04 min-1. This decay rate was highly variable between subjects. Subjects who had larger decreases in ScO2 during DHCA were more likely to have postoperative WMI (P = 0.02). Cerebral oxygen extraction persists during DHCA and varies widely from patient-to-patient. Patients with a higher degree of oxygen extraction during DHCA were more likely to show new WMI in postoperative MRI. These findings suggest cerebral oxygen extraction should be monitored during DHCA to identify patients at risk for hypoxic-ischemic injury, and that current commercial cerebral oximeters may underestimate cerebral oxygen extraction.

Predictors of Neurological Outcome Following Infant Cardiac Surgery Without Deep Hypothermic Circulatory Arrest.

The aim of this study is to describe the clinical characteristics, perioperative course and neuroimaging abnormalities of infants with congenital heart disease (CHD) undergoing heart surgery without deep hypothermic circulatory arrest (DHCA) and identify variables associated with neurological outcome. Infants with CHD undergoing open-heart surgery without DHCA between 2009 and 2017 were identified from a cardiac surgery database. Full-term infants < 10 weeks of age at the time of surgery who had both a pre- and postoperative brain magnetic resonance imaging exam (MRI) were included. Clinical characteristics and perioperative variables were collected from the electronic medical record. Brain Injury Scores (BIS) were assigned to pre- and postoperative brain MRIs. Variables were examined for association with neurological outcome at 12 months of age or greater. Forty-two infants were enrolled in the study, of whom 69% (n = 29) had a neurological assessment ≥ to 12 months of age. Adverse neurological outcome was associated with longer intensive care unit (ICU) stay (P = 0.003), lengthier mechanical ventilation (P = 0.031), modified Blalock-Taussig (MBT) shunt procedure (P = 0.005) and postoperative seizures (P = 0.005). Total BIS scores did not predict outcome but postoperative infarction and/or intraparenchymal hemorrhage (IPH) was associated with worse outcome by multivariable analysis (P = 0.018). Infants with CHD undergoing open-heart surgery without DHCA are at increased risk of worse neurological outcome when their ICU stay is prolonged, mechanical ventilation is extended, MBT shunt is performed or when postoperative seizures are present. Cerebral infarctions and IPH on postoperative MRI are also associated with worse outcome.