The combination of hydrogen gas and hydrogen-rich solution does not protect against ischemic spinal cord injury in rabbits.

PURPOSE: This study aimed to determine whether the combination of H2 gas inhalation and administration of hydrogen-rich acetated Ringer's solution (HS) could protect against ischemic spinal cord injury in rabbits. METHODS: In Experiment 1, rabbits were randomly assigned to a 1.2% H2 gas group, HS group, 1.2% H2 gas + HS group (combination group), or control group (n = 6 per group). The H2 concentration of HS was 0.65 mM. H2 was inhaled for 60 min, starting 5 min before reperfusion. HS (20 mL/kg) was divided into six bolus injections at 10-min intervals, starting 5 min before reperfusion. Spinal cord ischemia was produced by occluding the abdominal aorta for 15 min. Neurologic and histopathologic evaluations were performed 7 days after reperfusion. In Experiment 2, H2 concentrations in spinal cord tissue according to the administration of 1.2% H2 gas or HS were compared by measuring the electric current through a platinum needle electrode (n = 2). In Experiment 3, rabbits were assigned to a 2% H2 gas group or control group (n = 6 per group). Spinal cord ischemia was produced and neurologic and histopathologic evaluations were performed as in Experiment 1. RESULTS: There were no significant differences among the groups in the neurologic and histopathologic outcomes in Experiments 1 and 3. Bolus administration of HS (10 mL) transiently increased the current to only 1/30th and 1/27th of the plateau current with 1.2% H2 gas inhalation in two animals. CONCLUSION: These results suggest that the combination of 1.2% H2 gas inhalation and administration of a hydrogen-rich solution does not protect against ischemic spinal cord injury and that the increase in H2 concentration in spinal cord tissue after administration of HS is very low compared to 1.2% H2 gas inhalation.

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.

Cerebrospinal fluid drainage to prevent postoperative spinal cord injury in thoracic aortic repair.

BACKGROUND: Cerebrospinal fluid drainage (CSFD) is recommended as a spinal cord protective strategy in open and endovascular thoracic aortic repair. Although small studies support the use of CSFD, systematic reviews have not suggested definite conclusion and a large-scale study is needed. Therefore, we reviewed medical records of patients who had undergone descending and thoracoabdominal aortic repair (both open and endovascular repair) at multiple institutions to assess the association between CSFD and postoperative motor deficits. METHODS: Patients included in this study underwent descending or thoracoabdominal aortic repair between 2000 and 2013 at 12 hospitals belonging to the Japanese Association of Spinal Cord Protection in Aortic Surgery. We conducted a retrospective study to investigate whether motor-evoked potential monitoring is effective in reducing motor deficits in thoracic aortic aneurysm repair. We use the same dataset to examine whether CSFD reduces motor deficits after propensity score matching. RESULTS: We reviewed data from 1214 patients [open surgery, 601 (49.5%); endovascular repair, 613 (50.5%)]. CSFD was performed in 417 patients and not performed in the remaining 797 patients. Postoperative motor deficits were observed in 75 (6.2%) patients at discharge. After propensity score matching (n = 700), mixed-effects logistic regression performed revealed that CSFD is associated with postoperative motor deficits at discharge [adjusted odds ratio (OR), 3.87; 95% confidence interval (CI), 2.30-6.51]. CONCLUSION: CSFD may not be effective for postoperative motor deficits at discharge.

Guidelines for the use of cerebral oximetry by near-infrared spectroscopy in cardiovascular anesthesia: a report by the cerebrospinal Division of the Academic Committee of the Japanese Society of Cardiovascular Anesthesiologists (JSCVA).

Cerebral Oximetry by Near-infrared Spectroscopy (NIRS) has been used in cardiovascular anesthesia, but there was no guideline of regional cerebral oxygen saturation measured by cerebral oximetry by NIRS. This guideline provides recommendations applicable to patients at a risk of developing cerebral ischemia in cardiovascular surgery. Guidelines are intended to define practices meeting the needs of patients in most, but not all, circumstances, and should not replace clinical judgment. The Japanese Society of Cardiovascular Anesthesiologists (JSCVA) Task Force on Guidelines make an effort to ensure that the guideline writing committee contains broad views in using cerebral oximetry. Adherence to recommendations could be enhanced by shared decision making between healthcare providers and patients. This guideline was focused on cerebral oximetry of pediatric and adult cardiovascular disease. We hope this guideline would play an important role in using cerebral oximetry by measured NIRS.

Clinical Utility of Intraoperative Motor-Evoked Potential Monitoring to Prevent Postoperative Spinal Cord Injury in Thoracic and Thoracoabdominal Aneurysm Repair: An Audit of the Japanese Association of Spinal Cord Protection in Aortic Surgery Database.

BACKGROUND: Spinal cord ischemic injury is the most devastating sequela of descending and thoracoabdominal aortic surgery. Motor-evoked potentials (MEPs) have been used to intraoperatively assess motor tract function, but it remains unclear whether MEP monitoring can decrease the incidence of postoperative motor deficits. Therefore, we reviewed multicenter medical records of patients who had undergone descending and thoracoabdominal aortic repair (both open surgery and endovascular repair) to assess the association of MEP monitoring with postoperative motor deficits. METHODS: Patients included in the study underwent descending or thoracoabdominal aortic repair at 12 hospitals belonging to the Japanese Association of Spinal Cord Protection in Aortic Surgery between 2000 and 2013. Using multivariable mixed-effects logistic regression analysis, we investigated whether intraoperative MEP monitoring was associated with postoperative motor deficits at discharge after open and endovascular aortic repair. RESULTS: We reviewed data from 1214 patients (open surgery, 601 [49.5%]; endovascular repair, 613 [50.5%]). MEP monitoring was performed in 631 patients and not performed in the remaining 583 patients. Postoperative motor deficits were observed in 75 (6.2%) patients at discharge. Multivariable logistic regression analysis revealed that postoperative motor deficits at discharge did not have a significant association with MEP monitoring (adjusted odds ratio [OR], 1.13; 95% confidence interval [CI], 0.69-1.88; P = .624), but with other factors: history of neural deficits (adjusted OR, 6.08; 95% CI, 3.10-11.91; P < .001), spinal drainage (adjusted OR, 2.14; 95% CI, 1.32-3.47; P = .002), and endovascular procedure (adjusted OR, 0.45; 95% CI, 0.27-0.76; P = .003). The sensitivity and specificity of MEP <25% of control value for motor deficits at discharge were 37.8% (95% CI, 26.5%-49.5%) and 95.5% (95% CI, 94.7%-96.4%), respectively. CONCLUSIONS: MEP monitoring was not significantly associated with motor deficits at discharge.

Cerebrovascular CO2 reactivity during isoflurane-nitrous oxide anesthesia in patients with chronic renal failure.

PURPOSE: We assessed the cerebrovascular CO2 reactivity (CO2R) in chronic renal failure (CRF) patients without diabetes mellitus (DM), uncontrolled hypertension, peripheral vascular disease, or neurological disease under isoflurane-nitrous oxide anesthesia. METHODS: Forty-nine patients undergoing surgery, including 36 CRF patients (30 receiving dialysis and six pre-dialysis patients) and 13 patients without CRF (controls). Middle cerebral artery flow velocity (VMCA) was measured by transcranial Doppler ultrasonography at an end-tidal CO2 of 35 to 45 mmHg. CO2R was calculated as an absolute value (change in VMCA per mmHg PaCO2) and a relative value (absolute CO2R/baseline VMCA × 100). Factors associated with CO2R were evaluated simultaneously. RESULTS: Despite no significant differences in the absolute and relative values of CO2R between the CRF (mean 2.5 cm/s/mmHg; median 5.0%/mmHg) and control (2.4 cm/s/mmHg; 5.0%/mmHg) groups, blood urea nitrogen (BUN) concentrations in the CRF group correlated inversely with both absolute and relative CO2R. BUN concentration was higher (mean 72 versus 53 mg/dl, p = 0.006) and relative CO2R was lower (mean 2.6 versus 5.7%/mmHg, p = 0.011) in patients with pre-dialysis CRF (n = 6) versus CRF patients receiving dialysis (n = 30). CONCLUSIONS: CO2R in CRF patients was not significantly different from that in controls. However, in CRF patients with high BUN concentrations, CO2R might be impaired, leading to reduced cerebrovascular reserve capacity. Because DM is a major cause of CRF and we excluded DM patients, our results might not be applicable to patients with DM-induced CRF.

Comparison of the protective effects of direct ischemic preconditioning and remote ischemic preconditioning in a rabbit model of transient spinal cord ischemia.

INTRODUCTION: This study aimed to determine the relative potency of direct ischemic preconditioning (DIPC) and remote ischemic preconditioning (RIPC) for protection against ischemic spinal cord injury in rabbits and to explore the mechanisms involved. METHODS: In experiment 1, we compared the neurological and histopathological outcomes of DIPC, kidney RIPC, and limb RIPC. The DIPC and kidney RIPC groups received two cycles of 5-min occlusion/15-min reperfusion of the abdominal aorta and left renal artery, respectively. The limb RIPC group received two cycles of 10-min occlusion/10-min reperfusion of the femoral arteries bilaterally. Thirty minutes after the conditioning ischemia, spinal cord ischemia was produced by occluding the abdominal aorta for 15 min. In experiments 2 and 3, we investigated whether pretreatment using a free-radical scavenger, dimethylthiourea (DMTU), an adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), or a mitochondrial ATP-sensitive potassium channel antagonist, 5-hydroxydecanoate (5HD), could attenuate the protective effects of DIPC. In experiment 4, comprehensive analysis of phosphorylated proteins in the spinal cord was performed using a Proteome Profiler Array followed by immunoblotting to elucidate the signal pathway activated by DIPC. RESULTS: In experiment 1, DIPC improved the neurological and histopathological outcomes, whereas kidney and limb RIPC had no protective effects. In experiments 2 and 3, strong protective effects of DIPC were reconfirmed but were not attenuated by DMTU, DPCPX, or 5HD. In experiment 4, DIPC induced phosphorylation of Akt2. CONCLUSIONS: DIPC, but not kidney or limb RIPC, protected against ischemic spinal cord injury in rabbits. Akt2 might contribute to this protective effect.

Correction to: Cerebrovascular CO2 reactivity during isoflurane-nitrous oxide anesthesia in patients with chronic renal failure.

In the original publication of the article, the first sentence was published incorrectly under the section "Patients and preoperative assessment". The correct sentence should read as, "The Yamaguchi University Graduate School of Medicine Ethics Committee for Human Study approved the study protocol (18th August 2004: H16-71)".

The combination of insulin-like growth factor 1 and erythropoietin protects against ischemic spinal cord injury in rabbits.

INTRODUCTION: Insulin-like growth factor 1 (IGF-1) and erythropoietin (EPO) have been reported to independently protect against ischemic spinal cord injury in rabbits. In the present study, we investigated whether the combination of IGF-1 and EPO protects against ischemic spinal cord injury in rabbits. METHODS: Animals were assigned to 1 of 4 groups (n = 6 in each): a control group (saline), an IGF-1 group (IGF-1 0.3 mg/kg), an EPO group (EPO 800 U/kg), or an IGF-1 + EPO group (IGF-1 0.3 mg/kg + EPO 800 U/kg). Spinal cord ischemia was produced by occluding the abdominal aorta for 15 min. Saline, IGF-1, and EPO were administered intravenously just after the start of reperfusion. Hindlimb motor function was assessed daily for 7 days, after which histopathological evaluation was performed. To analyze phosphorylation of signal transduction molecules, animals were assigned to 1 of the 4 groups (n = 8 in each). Spinal cord ischemia and the treatment were the same as those described above. The spinal cords were removed at 15 or 30 min after reperfusion and used to analyze phosphorylation of signal transduction molecules. Four animals served as the preischemic control, and the spinal cord was removed just before the start of ischemia. RESULTS: In the IGF-1 + EPO group, both neurological and histopathological outcomes were significantly improved as compared to the control group, which was consistent with the increase of Janus kinase-2 (JAK2) phosphorylation. CONCLUSIONS: The combination of IGF-1 and EPO protects against ischemic spinal cord injury in rabbits. JAK2 might contribute to the protective effect.

[Development of postoperative cognitive dysfunction following major vascular surgery].

The development of postoperative cognitive dysfunction (POCD) is a devastating complication, leading to a poor postoperative quality of life. Even though the number of patients undergoing major vascular surgery has increased, the development of POCD has not been well evaluated in these patients compared with patients undergoing coronary artery bypass graft surgery (CABG). According to previous reports, more patients undergoing major vascular surgery by deep circulatory arrest or retrograde cerebral perfusion, and an equal or even larger number of patients undergoing surgery by selective cerebral perfusion, seem to develop POCD when compared with patients after CABG. However, only a small numbers of patients have been assessed and the timing of evaluating POCD has varied in previous studies. Well-organized studies with a sufficient number of cases and systematic post-operative evaluation of POCD are necessary.

Neuroanesthesia: from bench to bed.

It has been over 40 years since the term "neuroanesthesia" emerged. The anesthesiologists specializing in neuroanesthesia have actively conducted basic research on cerebral ischemia as well as on cerebral blood flow and metabolism. However, translating the results of basic research using experimental animals into clinical applications has been often unsuccessful, especially in the area of cerebral ischemia. The negative results produced by a series of hugely costly and time-consuming collaborative multicenter trials have disappointed many researchers. It could be argued that discrepancies in the efficacy of an agent ought to be viewed in the context of the differences between experimental animals and humans since they have considerably different higher-order functions, and consequently the relevance of using experimental animals is brought into question. Nevertheless, the accuracy of basic research can be improved by taking measures to reduce bias. Taking such measures may enable more careful judgments to be made at the basic research stage and prevent unnecessary clinical studies. Although it could be seen as taking a slight detour, it is advisable to create a system that facilitates confirmation of the original findings by a multicenter basic research project before starting a collaborative multicenter clinical trial.

[Intraoperative neurophysiological monitoring of the spinal cord].

It is more than 60 years since averaged somatosensory evoked potentials (SEPs) were devised. During this period, other evoked potentials including spinal cord evoked potentials and motor evoked potentials (MEPs) were developed. In cases needing identification of the pathologic level of myelopathy and monitoring the function of the spinal cord, these evoked potentials are now indispensable. The combination of these evoked potentials (multimodality monitoring) has been demonstrated to be sensitive and specific for detecting intraoperative neurologic injury during spine surgery. Although there is still a low level of evidence that intraoperative evoked potentials reduce the rate of new or worsened perioperative neurologic deficits, it is recommended to monitor MEP for thoracoabdominal aortic surgery and multimodal evoked potentials including at least spinal cord evoked potentials and MEP for spine surgery, when the spinal cord is considered to be at risk.

Temporal profiles of aquaporin 4 expression and astrocyte response in the process of brain damage in fat embolism model in rats.

PURPOSE: Fat embolism syndrome is a serious complication observed after trauma, orthopedic surgery, and cardiac surgery. We investigated brain damage in relationship to temporal profiles of water channel aquaporin 4 (AQP4) and astrocyte response to fat embolism in rats. METHODS: Triolein (2 microl) was injected into the right internal carotid artery in rats. Neurological outcome (score: range, 0-5 = no deficit-dead), brain water content, histopathology, and immunohistochemistry for AQP4 and glial fibrillary acidic protein (GFAP) were evaluated at 2 h (2 h group, n = 12), 24 h (24 h group, n = 12), and 72 h (72 h group, n = 12) after triolein injection. Saline was injected in the control (C) group (n = 12). RESULTS: Neurological deficit score (median score of 2) and brain water content (mean value, 86.2%) increased significantly at 2 h with no progressive increase over 72 h. Damaged tissues with shrunken and triangular-shaped neurons with vacuole degeneration in cytoplasm and halo formation were distributed mainly, but not exclusively, to the ipsilateral hemisphere and were associated with increase in infiltration of inflammatory cells during the time course. Increases in immunostaining for AQP4 and GFAP were observed in the peri-affected region but not in the core. Reactive astrocytes with hypertrophy and dendrite elongation were detected at 72 h in the peri-affected region. CONCLUSION: The results suggest that brain damage with edema is induced very rapidly after triolein injection in association with increase in AQP4 expression and GFAP in the peri-affected region.

Excessive dynamic airway collapse during general anesthesia: a case report.

BACKGROUND: Excessive dynamic airway collapse (EDAC) is an uncommon cause of high airway pressure during mechanical ventilation. However, EDAC is not widely recognized by anesthesiologists, and therefore, it is often misdiagnosed as asthma. CASE PRESENTATION: A 70-year-old woman with a history of asthma received anesthesia with sevoflurane for a laparotomic cholecystectomy. Under general anesthesia, she developed wheezing, high inspiratory pressure, and a shark-fin waveform on capnography, which was interpreted as an asthma attack. However, treatment with a bronchodilator was ineffective. Bronchoscopy revealed the collapse of the trachea and main bronchi upon expiration. We reviewed the preoperative computed tomography scan and saw bulging of the posterior membrane into the airway lumen, leading to a diagnosis of EDAC. CONCLUSIONS: Although both EDAC and bronchospasm present as similar symptoms, the treatments are different. Bronchoscopy proved useful for distinguishing between these two entities. Positive end-expiratory pressure should be applied and bronchodilators avoided in EDAC.

Does high-dose opioid anesthesia exacerbate ischemic spinal cord injury in rabbits?

PURPOSE: Intrathecal morphine given during a post-ischemic period has been reported to have the potential to exacerbate ischemic spinal cord injury. However, it remains unknown whether synthetic opioids administered systemically exacerbate ischemic injury. We sought to compare the damage of the spinal cord after transient spinal cord ischemia in rabbits anesthetized with three different regimens; isoflurane, fentanyl with isoflurane, and remifentanil with isoflurane. METHODS: We assigned rabbits to three groups (n = 9 in each); an isoflurane group (isoflurane 1 minimum alveolar concentration [MAC]), a fentanyl group (isoflurane 0.5 MAC + 100 microg x kg(-1) i.v. fentanyl given over 30 min before aortic occlusion), and a remifentanil group (isoflurane 0.5 MAC + 1 microg x kg(-1) x min(-1) i.v. remifentanil started 30 min before aortic occlusion and maintained until 1 h after reperfusion). Spinal cord ischemia was produced by occluding the abdominal aorta for 13 min. Hindlimb motor function (score range: 4, normal to 0, paraplegia) was assessed daily for 7 days, and then the number of normal neurons in the anterior spinal cord was counted. RESULTS: Severe motor dysfunction (score < or = 1) was observed in seven, four, and five animals in the isoflurane, fentanyl, and remifentanil groups, respectively. There were no significant intergroup differences in neurological scores. There were no differences in the numbers of normal neurons among the three groups (22 +/- 22, 42 +/- 30, 33 +/- 28, respectively). CONCLUSION: Our results suggest that neither i.v. fentanyl nor i.v. remifentanil added to 0.5 MAC isoflurane exacerbated ischemic spinal cord injury in rabbits when compared to 1 MAC isoflurane.

[Hypertension and tachycardia during endoscopic radial artery harvesting in two patients undergoing coronary artery bypass grafting].

Hypertension and tachycardia occurred during endoscopic radial artery harvesting in two patients undergoing coronary artery bypass grafting. Despite anesthesia maintained with moderate doses of fentanyl and isoflurane, hypertension and tachycardia occurred 10-15 min after tourniquet application and graft harvesting procedure. Tourniquet pain or direct stimulation to radial nerve by CO2 insufflation might be the causes. Although endoscopic radial artery harvesting is reported excellent for cosmetics with low incidence of complications such as infection and hematoma, hemodynamic change can occur during harvesting. Careful evaluation and management of hemodynamic changes should be exercised during this procedure in the patient with unstable angina and low cardiac function.

[Brain and spinal cord preconditioning for the protection against ischemic injury].

Recent studies have suggested that the brain preconditioning could induce tolerance to ischemia in humans. It has been believed that newly synthesized proteins are required for the acquisition of delayed tolerance in the brain and spinal cord. However, the mechanism other than the synthesis of neuroprotective proteins may also play a pivotal role. Preconditioning may reprogram the response to ischemic injury as seen during hibernation. Preconditioning with hyperbaric oxygen, volatile anesthetics, and xenon seems to be the focus of the attention from the standpoint of the clinical setting. Strong neuroprotection by the preconditioning with isoflurane and xenon is reported in animal experiments and may change the traditional idea of neuroprotection by anesthetics. The discovery that erythropoietin exerts neuroprotective properties has opened new therapeutic avenues. Erythropoietin is induced in the brain by hypoxic preconditioning and by the pharmacological preconditioning. In addition, the intravenous administration of erythropoietin has been shown to be safe and beneficial for acute stroke in humans. Therefore, erythropoietin is now one of the most promising neuroprotective agents. The research in the brain and spinal cord preconditioning will contribute to the elucidation of the mechanism of ischemic injury and to the establishment of new therapies for neuroprotection.