Nitric Oxide in Selective Cerebral Perfusion Could Enhance Neuroprotection During Aortic Arch Surgery

BackgroundHypothermic circulatory arrest (HCA) in aortic arch surgery has a significant risk of neurological injury despite the newest protective techniques and strategies. Nitric oxide (NO) could exert a protective role, reduce infarct area and increase cerebral perfusion. This study aims to investigate the possible neuroprotective effects of NO administered in the oxygenator of selective antegrade cerebral perfusion (SCP) during HCA.MethodsThirty male SD adult rats (450–550 g) underwent cardiopulmonary bypass (CPB), cooling to 22°C body core temperature followed by 30 min of HCA. Rats were randomized to receive SCP or SCP added with NO (20 ppm) administered through the oxygenator (SCP-NO). All animals underwent CPB-assisted rewarming to a target temperature of 35°C in 60 min. At the end of the experiment, rats were sacrificed, and brain collected. Immunofluorescence analysis was performed in blind conditions.ResultsNeuroinflammation assessed by allograft inflammatory factor 1 or ionized calcium-binding adapter molecule 1 expression, a microglia activation marker was lower in SCP-NO compared to SCP (4.11 ± 0.59 vs. 6.02 ± 0.18%; p < 0.05). Oxidative stress measured by 8oxodG, was reduced in SCP-NO (0.37 ± 0.01 vs. 1.03 ± 0.16%; p < 0.05). Brain hypoxic area extent, analyzed by thiols oxidation was attenuated in SCP-NO (1.85 ± 0.10 vs. 2.74 ± 0.19%; p < 0.05). Furthermore, the apoptotic marker caspases 3 was significantly reduced in SCP-NO (10.64 ± 0.37 vs. 12.61 ± 0.88%; p < 0.05).ConclusionsNitric oxide administration in the oxygenator during SCP and HCA improves neuroprotection by decreasing neuroinflammation, optimizing oxygen delivery by reducing oxidative stress and hypoxic areas, finally decreasing apoptosis.

Use of On-Site Digital Subtraction Angiography for Left Subclavian Artery Management During Hybrid Aortic Arch Repair in DeBakey I Dissection

Purpose: A hybrid aortic repair using the frozen elephant trunk (FET) technique with an open distal anastomosis in zone 2 and debranching of the left subclavian artery (LSA) has been demonstrated to be favorable and safe. Although a transposition of the LSA reduces the risk of cerebellar or medullar ischemia, this may be challenging in difficult LSA anatomies. Case Report: We present the case of a 61-year old patient with DeBakey I aortic dissection, treated with FET in moderate hypothermic circulatory arrest (26°C) and selective cerebral perfusion using a Thoraflex-Hybrid (Vascutek Terumo) prosthesis anchored in zone 2, with overstenting of the LSA orifice and no additional LSA debranching. Sufficient perfusion of the LSA was proved intraoperatively using LSA backflow analysis during selective cerebral perfusion in combination with on-site digital subtraction angiography (ARTIS Pheno syngo software). No neurologic dysfunction or ischemia occurred in the postoperative course. An angiographic computed tomography revealed physiologic LSA perfusion, with subsequent thrombotic occlusion of the false lumen in the proximal descending aorta after 7 days. Conclusion: Using an angiography-guided management in patients with complex DeBakey I dissection and difficult anatomy may simplify a proximalization of the distal anastomosis in zone 2 for FET, even without an additional LSA debranching.

Hypertonic Saline Compared to Mannitol for the Management of Elevated Intracranial Pressure in Traumatic Brain Injury: A Meta-Analysis

Background: We performed a meta-analysis to evaluate the effect of hypertonic saline compared to mannitol for the management of elevated intracranial pressure in traumatic brain injury.Methods: A systematic literature search up to July 2021 was performed and 17 studies included 1,392 subjects with traumatic brain injury at the start of the study; 708 of them were administered hypertonic saline and 684 were given mannitol. They were reporting relationships between the effects of hypertonic saline compared to mannitol for the management of elevated intracranial pressure in traumatic brain injury. We calculated the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) to assess the effect of hypertonic saline compared to mannitol for the management of elevated intracranial pressure in traumatic brain injury using the dichotomous or continuous method with a random or fixed-effect model.Results: Hypertonic saline had significantly lower treatment failure (OR, 0.38; 95% CI, 0.15–0.98, p = 0.04), lower intracranial pressure 30–60 mins after infusion termination (MD, −1.12; 95% CI, −2.11 to −0.12, p = 0.03), and higher cerebral perfusion pressure 30–60 mins after infusion termination (MD, 5.25; 95% CI, 3.59–6.91, p < 0.001) compared to mannitol in subjects with traumatic brain injury.However, hypertonic saline had no significant effect on favorable outcome (OR, 1.61; 95% CI, 1.01–2.58, p = 0.05), mortality (OR, 0.59; 95% CI, 0.34–1.02, p = 0.06), intracranial pressure 90–120 mins after infusion termination (MD, −0.90; 95% CI, −3.21–1.41, p = 0.45), cerebral perfusion pressure 90–120 mins after infusion termination (MD, 4.28; 95% CI, −0.16–8.72, p = 0.06), and duration of elevated intracranial pressure per day (MD, 2.20; 95% CI, −5.44–1.05, p = 0.18) compared to mannitol in subjects with traumatic brain injury.Conclusions: Hypertonic saline had significantly lower treatment failure, lower intracranial pressure 30–60 mins after infusion termination, and higher cerebral perfusion pressure 30–60 mins after infusion termination compared to mannitol in subjects with traumatic brain injury. However, hypertonic saline had no significant effect on the favorable outcome, mortality, intracranial pressure 90–120 mins after infusion termination, cerebral perfusion pressure 90–120 mins after infusion termination, and duration of elevated intracranial pressure per day compared to mannitol in subjects with traumatic brain injury. Further studies are required to validate these findings.

Unilateral versus bilateral anterograde cerebral perfusion in acute type A aortic dissection repair: A systematic review and meta-analysis

Objectives: The aim of the study is to compare the safety and efficacy of unilateral anterograde cerebral perfusion (UACP) and bilateral anterograde cerebral perfusion (BACP) for acute type A aortic dissection (ATAAD). Methods: A systematic review of MEDLINE (PubMed), Scopus, and Cochrane Library databases (last search: August 7 , 2021) was performed according to the PRISMA statement. Studies directly comparing UACP versus BACP for ATAAD were included. Random-effects meta-analyses were performed. Results: Eight retrospective cohort studies were identified, incorporating 2416 patients (UACP: 843, BACP: 1573). No statistically significant difference was observed regarding in-hospital mortality (odds ratio [OR]:1.05 [95% Confidence Interval (95%CI):0.70-1.57]), permanent neurological deficit (PND) (OR: 0.94 [95%CI:0.52-1.70]), transient neurological deficit (TND) (OR: 1.37 [95%CI:0.98-1.92]), renal failure (OR: 0.96 [95%CI:0.70-1.32]), and re-exploration for bleeding (OR: 0.77 [95%CI:0.48-1.22]). Meta-regression analysis revealed that PND and TND were not influenced by differences in rates of total arch repair, Bentall procedure and concomitant CABG in UACP and BACP groups. Cardiopulmonary bypass time (Standard Mean Difference [SMD]:-0.11 [95%CI:-0.22, 0.44]), Cross clamp time (SMD:-0.04 [95%CI:-0.38, 0.29]) and hypothermic circulatory arrest time (SMD:-0.12 [95%CI:-0.55, 0.30]) were comparable between UACP and BACP. Intensive care unit stay was shorter in BACP arm (SMD:0.16 [95%CI:0.01, 0.31]), however, length of hospital stay was shorter in UACP arm (SMD:-0.25 [95%CI:-0.45, -0.06]). Conclusions: UACP and BACP had similar results in terms of in-hospital mortality, PND, TND, renal failure and re-exploration for bleeding rate in patients with ATAAD. ICU stay was shorter in the BACP arm while LOS was shorter in the UACP arm.

Characterising the dynamics of cerebral metabolic dysfunction following traumatic brain injury: A microdialysis study in 619 patients

Traumatic brain injury (TBI) is a major cause of death and disability, particularly amongst young people. Current intensive care management of TBI patients is targeted at maintaining normal brain physiology and preventing secondary injury. Microdialysis is an invasive monitor that permits real-time assessment of derangements in cerebral metabolism and responses to treatment. We examined the prognostic value of microdialysis parameters, and the inter-relationships with other neuromonitoring modalities to identify interventions that improve metabolism. This was an analysis of prospective data in 619 adult TBI patients requiring intensive care treatment and invasive neuromonitoring at a tertiary UK neurosciences unit. Patients had continuous measurement of intracranial pressure (ICP), arterial blood pressure (ABP), brain tissue oxygenation (PbtO2), and cerebral metabolism and were managed according to a standardized therapeutic protocol. Microdialysate was assayed hourly for metabolites including glucose, pyruvate, and lactate. Cerebral perfusion pressure (CPP) and cerebral autoregulation (PRx) were derived from the ICP and ABP. Outcome was assessed with the Glasgow Outcome Score (GOS) at 6 months. Relationships between monitoring variables was examined with generalized additive mixed models (GAMM). Lactate/Pyruvate Ratio (LPR) over the first 3 to 7 days following injury was elevated amongst patients with poor outcome and was an independent predictor of ordinal GOS (p<0.05). Significant non-linear associations were observed between LPR and cerebral glucose, CPP, and PRx (p<0.001 to p<0.05). GAMM models suggested improved cerebral metabolism (i.e. reduced LPR with CPP >70mmHg, PRx <0.1, PbtO2 >18mmHg, and brain glucose >1mM. Deranged cerebral metabolism is an important determinant of patient outcome following TBI. Variations in cerebral perfusion, oxygenation and glucose supply are associated with changes in cerebral LPR and suggest therapeutic interventions to improve cerebral metabolism. Future prospective studies are required to determine the efficacy of these strategies.

The Dynamic Relationship Between Cortical Oxygenation and End-Tidal CO2 Transient Changes Is Impaired in Mild Cognitive Impairment Patients

Background: Recent studies have utilized data-based dynamic modeling to establish strong association between dysregulation of cerebral perfusion and Mild Cognitive Impairment (MCI), expressed in terms of impaired CO2 dynamic vasomotor reactivity in the cerebral vasculature. This raises the question of whether this is due to dysregulation of central mechanisms (baroreflex and chemoreflex) or mechanisms of cortical tissue oxygenation (CTO) in MCI patients. We seek to answer this question using data-based input-output predictive dynamic models.Objective: To use subject-specific data-based multivariate input-output dynamic models to quantify the effects of systemic hemodynamic and blood CO2 changes upon CTO and to examine possible differences in CTO regulation in MCI patients versus age-matched controls, after the dynamic effects of central regulatory mechanisms have been accounted for by using cerebral flow measurements as another input.Methods: The employed model-based approach utilized the general dynamic modeling methodology of Laguerre expansions of kernels to analyze spontaneous time-series data in order to quantify the dynamic effects upon CTO (an index of relative capillary hemoglobin saturation distribution measured via near-infrared spectroscopy) of contemporaneous changes in end-tidal CO2 (proxy for arterial CO2), arterial blood pressure and cerebral blood flow velocity in the middle cerebral arteries (measured via transcranial Doppler). Model-based indices (physio-markers) were computed for these distinct dynamic relationships.Results: The obtained model-based indices revealed significant statistical differences of CO2 dynamic vasomotor reactivity in cortical tissue, combined with “perfusivity” that quantifies the dynamic relationship between flow velocity in cerebral arteries and CTO in MCI patients versus age-matched controls (p = 0.006). Significant difference between MCI patients and age-matched controls was also found in the respective model-prediction accuracy (p = 0.0001). Combination of these model-based indices via the Fisher Discriminant achieved even smaller p-value (p = 5 × 10–5) when comparing MCI patients with controls. The differences in dynamics of CTO in MCI patients are in lower frequencies (&lt;0.05 Hz), suggesting impairment in endocrine/metabolic (rather than neural) mechanisms.Conclusion: The presented model-based approach elucidates the multivariate dynamic connectivity in the regulation of cerebral perfusion and yields model-based indices that may serve as physio-markers of possible dysregulation of CTO during transient CO2 changes in MCI patients.