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.

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.

Effect of Autotransfusion Using Intraoperative Predonated Autologous Blood on Coagulopathy during Thoracic Aortic Surgery: A Randomized Controlled Trial.

BACKGROUND: Intraoperative predonated autologous blood transfusion is thought to replenish platelets and coagulation factors and ameliorate coagulopathy. This study aimed to evaluate whether intraoperative predonated autotransfusion improves coagulopathy during thoracic aortic surgery. METHODS: Patients who underwent thoracic aortic surgery were randomized into two groups as follows: those who received intraoperative predonated blood (group A: n = 31) and those who did not receive (group N: n = 22). In group A, autologous blood was retransfused immediately after cessation of cardiopulmonary bypass (c-CPB). RESULTS: The mean intraoperative allogenic blood or blood product transfusion requirements were significantly lesser in group A than in group N (packed red blood cells [RBCs]: 6.3 ± 5.1 vs. 9.1 ± 4.3 units, p = 0.04; fresh frozen plasma [FFP]: 3.0 ± 4.1 vs. 6.1 ± 5.7 units, p = 0.03). After c-CPB, hemoglobin (Hb) level, platelet count, and coagulopathy became significantly worse than those at the start of surgery in both the groups. However, the values significantly improved 30 min after c-CPB only in group A. Renal function was significantly worse in group N. CONCLUSIONS: Intraoperative predonated autotransfusion significantly improved coagulopathy, with reduced allogeneic blood transfusion volume during thoracic aortic surgery. Furthermore, reduction of allogeneic blood transfusion may reduce the adverse effects on renal function.

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.

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)".

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.

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.

[Risk management in spinal anesthesia].

More than one hundred years have passed since Bier first succeeded in spinal anesthesia. Spinal anesthesia now spreads all over the world because it has many advantages. Spinal anesthesia requires both a simple technique and a small volume of drug, produces profound analgesia, and is devoid of systemic pharmacologic side effects. However, several complications after spinal anesthesia have been reported. Although some of them rarely occur, they cause serious consequences once they happen. Those include cardiac arrest, meningitis, intracranial subdural hematoma, spinal epidural hematoma and cauda equina syndrome. Patients should be informed in detail of the incidence, severity, and outcome of these complications, especially when alternative analgesic methods can be chosen. The prediction, early detection and prompt start of the treatment of the complications after spinal anesthesia are important to minimize the risk of adverse outcome.

[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.

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.

Tight glycemic control by insulin, started in the preischemic, but not postischemic, period, protects against ischemic spinal cord injury in rabbits.

BACKGROUND: It is not well established whether insulin protects against ischemic spinal cord injury. We examined the effects of a single dose of insulin that corrects mild hyperglycemia on the outcome after transient spinal cord ischemia in rabbits. METHODS: We assigned rabbits to four groups (n = 8 in each); untreated control (C) group, preischemic insulin (Pre-I) group, preischemic insulin with glucose (GI) group (glucose concentrations were maintained at levels similar to the C group by the administration of glucose), and postischemic insulin (Post-I) group. Insulin (0.5 IU/kg) was administered 30 min before ischemia in the Pre-I and GI groups, and just after reperfusion in the Post-I group. Spinal cord ischemia was produced by occluding the abdominal aorta for 13 min. Neurologic and histopathologic evaluations were performed 7 days after ischemia. RESULTS: The mean blood glucose concentration before ischemia in the Pre-I group (118 mg/dL) was significantly lower than in the other three groups (158-180 mg/dL) and those of 30 min after reperfusion in the Pre-I (92 mg/dL) and Post-I (100 mg/dL) groups were significantly lower than in the C (148 mg/dL) and GI (140 mg/dL) groups. The motor function score and number of normal neurons in the anterior lumbar spinal cord in the Pre-I group were significantly greater than in the other three groups. CONCLUSIONS: These results suggest that a relatively small dose of preischemic insulin protects against ischemic spinal cord injury, and that the protective effects result from tight glycemic control before ischemia.

The effects of cyclosporin A and insulin on ischemic spinal cord injury in rabbits.

We examined the effects of cyclosporin A (CsA), a drug that inhibits mitochondrial permeability transition pore, and insulin on ischemic spinal cord damage in rabbits. We assigned rabbits to 5 groups (n = 6 in each); sham barrier-opened group (sham BO), barrier-opened group (BO), barrier-opened-CsA group (BO-CsA), barrier-opened-insulin group (BO-I), and barrier-opened-CsA-insulin group (BO-CsA-I). The blood-spinal cord barrier was opened to facilitate drug penetration by a mild injury to the lumber spinal cord on day 1. CsA (10 mg/kg per day IV) was administered on day 3 to day 5 (total 30 mg/kg). Insulin was administered 30 min before ischemia. In all groups, spinal cord ischemia was produced on day 5 by occluding the abdominal aorta for 13 min. Neurological and histopathological evaluations were performed 4 days after ischemia. In group BO-CsA, blood glucose concentrations were significantly larger compared with the other four groups, and no protection was observed. In contrast, hindlimb motor function in groups BO-I and Bo-CsA-I and histopathology in group BO-CsA-I were significantly better than in groups sham BO, BO, and BO-CsA. The results indicate that insulin protects against ischemic spinal cord injury, whereas the effect of CsA is, at best, minimal.

The effects of an AMPA receptor antagonist on the neurotoxicity of tetracaine intrathecally administered in rabbits.

We have reported that large concentrations of intrathecal local anesthetics increase glutamate concentrations in the cerebrospinal fluid (CSF) and cause neuronal injury in rabbits. In the current study we determined whether an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist, YM872, administered intrathecally, reduces neuronal injury caused by tetracaine. We first examined the effects of intrathecal YM872 10, 30, 100, or 300 mug in rabbits (n = 3 in each). YM872 produced reversible motor and sensory block in a dose-dependent manner. Then, we evaluated modulatory effects of YM872 (300 mug) on tetracaine-induced glutamate release and neuronal injury. Pretreatment of YM872 did not attenuate 1% or 2% tetracaine-induced increases in cerebrospinal fluid glutamate concentrations (n = 3 in each). For evaluation of neuronal injury, rabbits were assigned to 4 groups (n = 6 in each) and intrathecally received 1% tetracaine and saline (1%T), 1% tetracaine and YM872 (1%TY), 2% tetracaine and saline (2%T), or 2% tetracaine and YM872 (2%TY). The volume of saline, YM872, and tetracaine was 0.3 mL. Saline or YM872 was administered 30 min before tetracaine administration. Neurological and histopathological assessments were performed 1 wk after the administration. Two and 1 animals respectively, showed motor and sensory dysfunction in 1%T, whereas 5 animals showed both motor and sensory dysfunction in 2%T. YM872 improved 2% tetracaine-induced motor dysfunction and neuronal damage (chromatolytic neurons, identified by round-shaped cytoplasm with loss of Nissl substance from the central part of the cell and eccentric nuclei). In 2%TY, 3 animals showed normal motor function and 3 showed mild dysfunction (ability to hop, but not normally), whereas 4 animals showed moderate dysfunction (inability to hop) in 2%T (P = 0.042). Only 2 animals showed one chromatolytic neuron in 2%TY, whereas 5 animals showed 4-16 chromatolytic neurons in 2%T (P = 0.020). These results suggest that AMPA receptor activation is involved, at least in part, in the tetracaine-induced neurotoxicity in the spinal cord.