Effect of cerebrospinal fluid drainage pressure in descending and thoracoabdominal aortic repair: a prospective multicenter observational study.

PURPOSE: Cerebrospinal fluid drainage (CSFD) is recommended during open or endovascular thoracic aortic repair. However, the incidence of CSFD complications is still high. Recently, CSF pressure has been kept high to avoid complications, but the efficacy of CSFD at higher pressures has not been confirmed. We hypothesize that CSFD at higher pressures is effective for preventing motor deficits. METHODS: This prospective observational study included 14 hospitals that are members of the Japanese Society of Cardiovascular Anesthesiologists. Patients who underwent thoracic and thoracoabdominal aortic repair were divided into four groups: Group 1, CSF pressure around 10 mmHg; Group 2, CSF pressure around 15 mmHg; Group 3, CSFD initiated when motor evoked potential amplitudes decreased; and Group 4, no CSFD. We assessed the association between the CSFD group and motor deficits using mixed-effects logistic regression with a random intercept for the institution. RESULTS: Of 1072 patients in the study, 84 patients (open surgery, 51; thoracic endovascular aortic repair, 33) had motor deficits at discharge. Groups 1 and 2 were not associated with motor deficits (Group 1, odds ratio (OR): 1.53, 95% confidence interval (95% CI): 0.71-3.29, p = 0.276; Group 2, OR: 1.73, 95% CI: 0.62-4.82) when compared with Group 4. Group 3 was significantly more prone to motor deficits than Group 4 (OR: 2.56, 95% CI: 1.27-5.17, p = 0.009). CONCLUSION: CSFD is not associated with motor deficits in thoracic and thoracoabdominal aortic repair with CSF pressure around 10 or 15 mmHg.

Intranasal administration of polysulfide prevents neurodegeneration in spinal cord and rescues mice from delayed paraplegia after spinal cord ischemia.

BACKGROUND: Delayed paraplegia is a devastating complication of thoracoabdominal aortic surgery. Hydrogen sulfide (H2S) was reported to be protective in a mouse model of spinal cord ischemia and the beneficial effect of H2S has been attributed to polysulfides. The objective of this study was to investigate the effects of polysulfides on delayed paraplegia after spinal cord ischemia. METHODS AND RESULTS: Spinal cord ischemia was induced in male and female C57BL/6J mice by clamping the aortic arch and the left subclavian artery. Glutathione trisulfide (GSSSG), glutathione (GSH), glutathione disulfide (GSSG), or vehicle alone was administered intranasally at 0, 8, 23, and 32 h after surgery. All mice treated with vehicle alone developed paraplegia within 48 h after surgery. GSSSG, but not GSH or GSSG, prevented paraplegia in 8 of 11 male mice (73%) and 6 of 8 female mice (75%). Intranasal administration of 34S-labeled GSSSG rapidly increased 34S-labeled sulfane sulfur species in the lumbar spinal cord. In mice treated with intranasal GSSSG, there were increased sulfane sulfur levels, and decreased neurodegeneration, microglia activation, and caspase-3 activation in the lumbar spinal cord. In vitro studies using murine primary cortical neurons showed that GSSSG increased intracellular levels of sulfane sulfur. GSSSG, but not GSH or GSSG, dose-dependently improved cell viability after oxygen and glucose deprivation/reoxygenation (OGD/R). Pantethine trisulfide (PTN-SSS) also increased intracellular sulfane sulfur and improved cell viability after OGD/R. Intranasal administration of PTN-SSS, but not pantethine, prevented paraplegia in 6 of 9 male mice (66%). CONCLUSIONS: Intranasal administration of polysulfides rescued mice from delayed paraplegia after transient spinal cord ischemia. The neuroprotective effects of GSSSG were associated with increased levels of polysulfides and sulfane sulfur in the lumbar spinal cord. Targeted delivery of sulfane sulfur by polysulfides may prove to be a novel approach to the treatment of neurodegenerative diseases.

Oral Administration of Glutathione Trisulfide Increases Reactive Sulfur Levels in Dorsal Root Ganglion and Ameliorates Paclitaxel-Induced Peripheral Neuropathy in Mice.

Peripheral neuropathy is a dose-limiting side effect of chemotherapy with paclitaxel. Paclitaxel-induced peripheral neuropathy (PIPN) is typically characterized by a predominantly sensory neuropathy presenting with allodynia, hyperalgesia and spontaneous pain. Oxidative mitochondrial damage in peripheral sensory neurons is implicated in the pathogenesis of PIPN. Reactive sulfur species, including persulfides (RSSH) and polysulfides (RSnH), are strong nucleophilic and electrophilic compounds that exert antioxidant effects and protect mitochondria. Here, we examined the potential neuroprotective effects of glutathione trisulfide (GSSSG) in a mouse model of PIPN. Intraperitoneal administration of paclitaxel at 4 mg/kg/day for 4 days induced mechanical allodynia and thermal hyperalgesia in mice. Oral administration of GSSSG at 50 mg/kg/day for 28 days ameliorated mechanical allodynia, but not thermal hyperalgesia. Two hours after oral administration, 34S-labeled GSSSG was detected in lumber dorsal root ganglia (DRG) and in the lumber spinal cord. In mice treated with paclitaxel, GSSSG upregulated expression of genes encoding antioxidant proteins in lumber DRG, prevented loss of unmyelinated axons and inhibited degeneration of mitochondria in the sciatic nerve. In cultured primary neurons from cortex and DRG, GSSSG mitigated paclitaxel-induced superoxide production, loss of axonal mitochondria, and axonal degeneration. These results indicate that oral administration of GSSSG mitigates PIPN by preventing axonal degeneration and mitochondria damage in peripheral sensory nerves. The findings suggest that administration of GSSSG may be an approach to the treatment or prevention of PIPN and other peripheral neuropathies.

Hyperbaric phototherapy augments blood carbon monoxide removal.

BACKGROUND AND OBJECTIVES: Carbon monoxide (CO) poisoning is responsible for nearly 50,000 emergency department visits and 1200 deaths per year. Compared to oxygen, CO has a 250-fold higher affinity for hemoglobin (Hb), resulting in the displacement of oxygen from Hb and impaired oxygen delivery to tissues. Optimal treatment of CO-poisoned patients involves the administration of hyperbaric 100% oxygen to remove CO from Hb and to restore oxygen delivery. However, hyperbaric chambers are not widely available and this treatment requires transporting a CO-poisoned patient to a specialized center, which can result in delayed treatment. Visible light is known to dissociate CO from carboxyhemoglobin (COHb). In a previous study, we showed that a system composed of six photo-extracorporeal membrane oxygenation (ECMO) devices efficiently removes CO from a large animal with CO poisoning. In this study, we tested the hypothesis that the application of hyperbaric oxygen to the photo-ECMO device would further increase the rate of CO elimination. STUDY DESIGN/MATERIAL AND METHODS: We developed a hyperbaric photo-ECMO device and assessed the ability of the device to remove CO from CO-poisoned human blood. We combined four devices into a "hyperbaric photo-ECMO system" and compared its ability to remove CO to our previously described photo-ECMO system, which was composed of six devices ventilated with normobaric oxygen. RESULTS: Under normobaric conditions, an increase in oxygen concentration from 21% to 100% significantly increased CO elimination from CO-poisoned blood after a single pass through the device. Increased oxygen pressure within the photo-ECMO device was associated with higher exiting blood PO2 levels and increased CO elimination. The system of four hyperbaric photo-ECMO devices removed CO from 1 L of CO-poisoned blood as quickly as the original, normobaric photo-ECMO system composed of six devices. CONCLUSION: This study demonstrates the feasibility and efficacy of using a hyperbaric photo-ECMO system to increase the rate of CO elimination from CO-poisoned blood. This technology could provide a simple portable emergency device and facilitate immediate treatment of CO-poisoned patients at or near the site of injury.

Bronchovenous Fistula During Adult Cardiac Surgery: A Case Report.

Bronchovenous fistula (BVF) associated with adult cardiac surgery is a rarely reported life-threatening condition. We present a 75-year-old woman who developed a BVF during cardiac surgery. Dense adhesion in the pleural and pericardial cavities was noted. Restrictive pulmonary pathology required high airway pressure. Transesophageal echocardiography and hemoglobin measurement were helpful for the timely diagnosis of BVF, which was controlled by transection of the right upper pulmonary vein where a vent catheter had been inserted. Injuries around the cannulated site presumably initiated the BVF, which was worsened by high-pressure ventilation. Therefore, cannulation site might be a risk factor for BVF.

Hyperlactatemia of dialysis-dependent patients after cardiac surgery impacts on in-hospital mortality: a two-center retrospective study.

BACKGROUND: Lactate is a well-known marker to estimate prognosis after cardiac surgery and critically ill patients. The liver and kidney have a major role in lactate metabolism; however, there was less characterized about the change of lactate and threshold to predict in-hospital mortality in dialysis-dependent patients undertaking cardiac surgery. We conducted this retrospective observational study to characterize when and how lactate values after cardiac surgery affected in-hospital mortality. METHODS: This two-center retrospective study included dialysis-dependent patients who underwent cardiac surgery with a cardiopulmonary bypass from January 2014 to December 2018. Lactate values were collected at three points: at ICU admission (T1), the maximum level of lactate within 24 h postoperatively (T2), and 24 h after ICU admission (T3). We determined hyperlactatemia as more than 2 mmol/L following previous studies. RESULTS: We enrolled 122 dialysis-dependent patients. The mean age was 73 ± 8 years and hyperlactatemia was observed in 100 patients (81.9%). In-hospital mortality was 11.4%. Univariate analysis and area under curve in ROC suggested that T2 lactate was the most significantly associated with in-hospital mortality (AUC = 0.845). Multivariate logistic analysis showed a significant association between in-hospital mortality when patients showed early peak lactate levels of > 4.5 mmol/L after ICU admission (adjusted OR 8.35; 95% CI: 1.44-57.13). CONCLUSIONS: In dialysis-dependent patients after cardiac surgery, the early-onset of a maximum arterial lactate concentration of > 4.5 mmol/L was significantly associated with in-hospital mortality.

Intraoperative vasoplegic syndrome in patients with fulminant myocarditis on ventricular assist device placement.

PURPOSE: Fulminant myocarditis is uncommon, but life-threatening, and some patients need mechanical circulatory support. This study was performed to evaluate how different types of mechanical circulatory support-biventricular assist device (BiVAD) or left ventricular assist device (LVAD) placement-affect intraoperative hemodynamic status. METHODS: From January 2013 to September 2016, the patients who underwent BiVAD or LVAD placement for fulminant myocarditis were analyzed. The mean arterial pressure (MAP), mean pulmonary arterial pressure, central venous pressure (CVP), vasoactive score, and inotropic score were recorded at five time points: after the induction of anesthesia; at weaning, 30 min after weaning, and 60 min after weaning from cardiopulmonary bypass (CPB); and at the end of surgery. The vasoactive and inotropic scores were calculated as follows: vasoactive score = norepinephrine (µg/kg/min) × 100 + milrinone (µg/kg/min) × 10 + olprinone (µg/kg/min) × 25: inotropic score = dopamine (µg/kg/min) × 1 + dobutamine (µg/kg/min) × 1 + epinephrine (µg/kg/min) × 100. RESULTS: We enrolled 16 patients of fulminant myocarditis. Ten of them underwent BiVAD placement, and the other underwent LVAD placement. After weaning from CPB, the BiVAD group had a significantly lower MAP but no difference in CVP. The vasoactive score was significantly higher in the BiVAD group at weaning of CPB (p = 0.015), 30 min after weaning (p = 0.004), 60 min after weaning (p = 0.005), and at the end of surgery (p < 0.016). CONCLUSION: Patients with BiVAD placement required more vasoactive support to maintain optimal hemodynamic status compared with those with LVAD placement. This result indicates that BiVAD placement was more associated with vasoplegic syndrome.