The Japan Society for Surgical Infection: guidelines for the prevention, detection, and management of gastroenterological surgical site infection, 2018.

BACKGROUND: The guidelines for the prevention, detection, and management of gastroenterological surgical site infections (SSIs) were published in Japanese by the Japan Society for Surgical Infection in 2018. This is a summary of these guidelines for medical professionals worldwide. METHODS: We conducted a systematic review and comprehensive evaluation of the evidence for diagnosis and treatment of gastroenterological SSIs, based on the concepts of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The strength of recommendations was graded and voted using the Delphi method and the nominal group technique. Modifications were made to the guidelines in response to feedback from the general public and relevant medical societies. RESULTS: There were 44 questions prepared in seven subject areas, for which 51 recommendations were made. The seven subject areas were: definition and etiology, diagnosis, preoperative management, prophylactic antibiotics, intraoperative management, perioperative management, and wound management. According to the GRADE system, we evaluated the body of evidence for each clinical question. Based on the results of the meta-analysis, recommendations were graded using the Delphi method to generate useful information. The final version of the recommendations was published in 2018, in Japanese. CONCLUSIONS: The Japanese Guidelines for the prevention, detection, and management of gastroenterological SSI were published in 2018 to provide useful information for clinicians and improve the clinical outcome of patients.

Association between preoperative tumor necrosis factor alpha inhibitor and surgical site infection after surgery for inflammatory bowel disease: a systematic review and meta-analysis.

Tumor necrosis factor-alpha inhibitor (TNFi) treatment is effective for ulcerative colitis (UC) and Crohn's disease (CD). Although several meta-analyses have been performed to evaluate the association between TNFi treatment and surgical morbidity, the results are controversial. We conducted a systematic review and meta-analysis of the prevention of surgical site infection (SSI) after surgery for UC and CD in patients on TNFis, based on literature published between January 2000 and May 2019 (registered on PROSPERO, No. CRD42019134156). Overall, 2175 UC patients in 13 observational studies (OBSs) and 7084 CD patients in 16 OBSs were included. The incidences of incisional (INC) SSI and organ/space (O/S) SSI after surgery for UC were 179/1985 (9.0%) and 176/2175 (8.1%), respectively. TNFi use was not associated with the incidences of INC SSI (odds ratio (OR) 1.04, 95% confidence interval (CI) (0.47-2.32) or O/S SSI (OR 1.85, 95% CI (0.82-4.20)) after surgery for UC. The INC SSI and O/S SSI incidences after surgery for CD were 289/3089 (9.4%) and 526/7,084 (7.4%), respectively. Preoperative TNFi use was not associated with INC SSI (OR 0.98, 95% CI (0.52-1.83)) or O/S SSI incidence (OR 1.09, 95% CI (0.78-1.52)) after surgery for CD. We did not find a significant association between preoperative TNFi use and SSI in surgery for UC or CD.

Right single lung transplantation using an inverted left donor lung: interposition of pericardial conduit for pulmonary venous anastomosis - a case report.

BACKGROUND: Lung transplantation (LTx) is still limited by the shortage of suitable donor lungs. Developing flexible surgical procedures can help to increase the chances of LTx by unfolding recipient-to-donor matching options based on the pre-existing organ allocation concept. We report a case in which a successful left-to-right inverted LTx was completed using the interposition of a pericardial conduit for pulmonary venous anastomosis. CASE PRESENTATION: A left lung graft was offered to a 59-year-old male who had idiopathic pulmonary fibrosis with predominant damage in the right lung. He had been prescribed bed rest with constant oxygen inhalation through an oxymizer pendant and had been on the waiting list for 20 months. Considering the condition of the patient (LAS 34.3) and the scarcity of domestic organ offers, the patient was highly likely to be incapable of tolerating any additional waiting time for another donor organ if he was unable to accept the presently reported offer of a left lung. Eventually, we decided to transplant the left donor lung into the right thorax of the recipient. Because of the anterior-posterior position gap of the hilar structures, the cuff lengths of the pulmonary veins had to be adjusted. The patient did not develop any anastomotic complications after the transplantation. CONCLUSIONS: A left-to-right inverted LTx is technically feasible using an autologous pericardial conduit for pulmonary venous anastomosis in selected cases. This technique provides the potential benefit of resolving challenging situations in which surgeons must deal with a patient's urgency and the logistical limitations of organ allocation.

Local Anesthetic Systemic Toxicity Following General and Epidural Anesthesia in A patient with a History of Muscle Relaxant-induced Anaphylaxis.

We here report that a 71-year-old Japanese woman with a history of anaphylaxis induced by muscle relaxants had local anesthetic systemic toxicity (LAST) following an abdominal surgery under general anesthesia with combined spinal-epidural anesthesia without muscle relaxants. The total dosages of local anesthetics reached 0.67 mg/kg of ropivacaine and 11.5 mg/kg of lidocaine over 12.5 h to obtain sufficient muscle relaxation for surgery. Regional anesthesia is useful in cases in which muscle relaxants are to be avoided during a surgery. However, especially for a patient with risk factors and prolonged surgery, precautions should be taken to prevent LAST.

Feasibility of lung transplantation from donors mechanically ventilated for prolonged periods.

PURPOSE: When patients are mechanically ventilated for more than 5 days, they are usually declined as donors for lung transplantation (LTx); thus, the long-term outcomes of LTx from such donors remain unclear. We investigated the feasibility of LTx from donors that had been mechanically ventilated for prolonged periods. METHODS: The subjects of this retrospective comparative investigation were 31 recipients of LTx from donors who had been mechanically ventilated for < 5 days (short-term group) and 50 recipients of LTx from donors who had been mechanically ventilated for ≥ 5 days (long-term group). RESULTS: The median duration of donor mechanical ventilation was 3 days in the short-term group and 8.5 days in the long-term group. However, other than the difference in the duration of donor ventilation, there were no significant differences in the clinical characteristics of the donors or recipients between the groups. The overall survival rate after LTx was comparable between the long-term group and short-term group (5-year survival rate, 66.6% vs. 75.2%). CONCLUSION: The potential inclusion of donors who have been on mechanical ventilation for more than 5 days could be a feasible strategy to alleviate donor organ shortage.

Low-risk donor lungs optimize the post-lung transplant outcome for high lung allocation score patients.

PURPOSE: The lung allocation score (LAS) has been generally recognized as a contributor to the overall survival in lung transplant candidates. However, donor-related risks have never been taken into consideration in previous research that validated the LAS. This study aimed to determine whether or not the role of the LAS as a predictor of the posttransplant outcome is influenced by the quality of the donor lungs. METHODS: We retrospectively reviewed 108 patients who underwent lung transplantation at Okayama University Hospital since 1998. The cohort was divided into two groups based on the lung donor score (DS; ≤ 4/> 4). Correlations between the LAS and posttransplant outcomes were investigated in both groups. RESULTS: In the high-DS group, an elevated LAS was strongly associated with posttransplant PaO2/FiO2 (p = 0.018). However, in the low-DS group, no correlation was found between them. There was no significant difference in the long-term survival according to the LAS in the low-DS group. The LAS effectively predicted the posttransplant outcome only when lungs with DS > 4 were transplanted; the LAS was not reliable if high-quality lungs were transplanted. CONCLUSION: Lung transplantation can be feasible and provides a survival benefit even for high-LAS patients if lungs from a low-risk donor are transplanted.

Airway complications have a greater impact on the outcomes of living-donor lobar lung transplantation recipients than cadaveric lung transplantation recipients.

PURPOSE: Airway complications (ACs) after living-donor lobar lung transplantation (LDLLT) could have different features from those after cadaveric lung transplantation (CLT). We conducted this study to compare the characteristics of ACs after LDLLT vs. those after CLT and investigate their impact on outcomes. METHODS: We reviewed, retrospectively, data on 163 recipients of lung transplantation, including 83 recipients of LDLLT and 80 recipients of CLT. RESULTS: The incidence of ACs did not differ between LDLLT and CLT. The initial type of AC after LDLLT was limited to stenosis in all eight patients, whereas that after CLT consisted of stenosis in three patients and necrosis in ten patients (p = 0.0034). ACs after LDLLT necessitated significantly earlier initiation of treatment than those after CLT (p = 0.032). The overall survival rate of LDLLT recipients with an AC was significantly lower than that of those without an AC (p = 0.030), whereas the overall survival rate was comparable between CLT recipients with and those without ACs (p = 0.25). CONCLUSION: ACs after LDLLT, limited to bronchial stenosis, require significantly earlier treatment and have a greater adverse impact on survival than ACs after CLT.

Reverse Right Ventricular Remodeling After Lung Transplantation in Patients With Pulmonary Arterial Hypertension Under Combination Therapy of Targeted Medical Drugs.

BACKGROUND: Patients with pulmonary arterial hypertension (PAH) are currently treated with combination therapy of PAH-targeted drugs. Reverse right ventricular (RV) remodeling after lung transplantation (LTx) in patients with end-stage PAH despite combination therapy of PAH-targeted drugs has not been fully elucidated.Methods and Results:A total of 136 patients, including 32 with PAH, underwent LTx from 1998 to 2014. We enrolled 12 consecutive patients with PAH treated with combination therapy of PAH-targeted drugs who underwent LTx and retrospectively analyzed the temporal and serial changes in hemodynamics and echocardiography before LTx and at 3 and 12 months after LTx. Before LTx, the RV was markedly dilated with substantially reduced RV fractional area change (RVFAC). At 3 months after LTx, pulmonary artery pressure, pulmonary vascular resistance and RV stroke work index were significantly decreased, while left ventricular stroke work index was increased. RV size assessed by echocardiography also significantly decreased and RVFAC improved. At 12 months after LTx, RVFAC was further increased and RV wall thickness was decreased significantly. CONCLUSIONS: Although severe RV dysfunction and dilation were observed in patients with end-stage PAH despite combination therapy of PAH-targeted drugs, RV function and morphology were improved after reduction of RV pressure load by LTx.

Pregnancy and delivery after myelomeningocele repair, ventriculoperitoneal shunt implantation, and augmentation cystoplasty.

INTRODUCTION: Management of pregnancy and delivery of a patient with a history of myelomeningocele requires a multidisciplinary team approach. CASE REPORT: We report a case of pregnancy and delivery by a patient who had a history of myelomeningocele surgical repair, ventriculoperitoneal (VP) shunt, and bladder augmentation enterocystoplasty. Regarding types of delivery style, anesthesiologists recommended a Cesarean section under general anesthesia. However, urologists recommended a vaginal delivery because they were concerned that she would require a nephrostomy because of severe adhesion between her uterus and the neobladder if she had a Cesarean section. DISCUSSION: In a pregnant myelomeningocele patient with a VP shunt, neurosurgeons are expected to manage the VP shunt during pregnancy and delivery. The possible types of delivery style and the best options based on the neurological deficit should be discussed together with a medical team.

High Frequency of Acute Adverse Cardiovascular Events After Lung Transplantation in Patients With Pulmonary Arterial Hypertension Receiving Preoperative Long-Term Intravenous Prostacyclin.

Adverse cardiovascular events after lung transplantation (LT) increase the mortality in patients with pulmonary arterial hypertension (PAH). Long-term intravenous prostacyclin is the usual treatment in severe patients with PAH, but it may increase the risk of hemorrhage due to its antiplatelet aggregation effect or thrombocytopenia. We investigated the impact of length of intravenous prostacyclin therapy on acute adverse cardiovascular events including hemorrhagic complication after LT. We retrospectively compared the incidence of adverse events (death, intrathoracic hematoma and bleeding, cardiac congestion or shock, cerebral infarction and pulmonary embolism) within 30 days after LT between no/short-term (median 0.6 years, n = 13) and long-term (median 3.7 years, n = 15) intravenous prostacyclin groups. There were no differences in the dose of intravenous prostacyclin and pulmonary artery pressure between the two groups. Among 22 adverse events (0.8 ± 1.1 events/patient), 4 events occurred in the no/short-term intravenous prostacyclin group and 18 occurred in the long-term intravenous prostacyclin group. The event rate per patient in the long-term intravenous prostacyclin group (1.2 ± 1.3 events/patient) was significantly higher than that in the no/short-term intravenous prostacyclin group (0.3 ± 0.5 events/patient) (P < 0.05). Intrathoracic hematoma and bleeding was the most frequent adverse event (9 events, 41%). Preoperative long-term intravenous prostacyclin therapy increases acute adverse cardiovascular events after LT in patients with PAH.

Long-Term Cognitive Deficits After Subarachnoid Hemorrhage in Rats.

BACKGROUND: Cognitive dysfunction can be a long-term complication following subarachnoid hemorrhage (SAH). Preclinical models have been variously characterized to emulate this disorder. This study was designed to directly compare long-term cognitive deficits in the context of similar levels of insult severity in the cisterna magna double-blood (DB) injection versus prechiasmatic blood (PB) injection SAH models. METHODS: Pilot work identified blood injectate volumes necessary to provide similar mortality rates (20-25 %). Rats were then randomly assigned to DB or PB insults. Saline injection and naïve rats were used as controls. Functional and cognitive outcome was assessed over 35 days. RESULTS: DB and PB caused similar transient rotarod deficits. PB rats exhibited decreased anxiety behavior on the elevated plus maze, while anxiety was increased in DB. DB and PB caused differential deficits in the novel object recognition and novel object location tasks. Morris water maze performance was similarly altered in both models (decreased escape latency and increased swimming speed). SAH caused histologic damage in the medial prefrontal cortex, perirhinal cortex, and hippocampal CA1, although severity of injury in the respective regions differed between DB and PB. CONCLUSION: Both SAH models caused long-term cognitive deficits in the context of similar insult severity. Cognitive deficits differed between the two models, as did distribution of histologic injury. Each model offers unique properties and both models may be useful for study of SAH-induced cognitive deficits.

Isoflurane Induces Transient Impairment of Retention of Spatial Working Memory in Rats.

Postoperative cognitive dysfunction (POCD) occurs in nearly one-third of patients after non-cardiac surgery. Many animal behavior studies have investigated the effect of general anesthesia on cognitive function. However, there have been no studies examining the effects on working memory specifically, with a focus on the retention of working memory. We demonstrate here that isoflurane anesthesia induces deficits in the retention of spatial working memory in rats, as revealed by an increase in isoflurane- induced across-phase errors in the delayed spatial win-shift (SWSh) task with a 30-min delay in an 8-arm radial arm maze on post-anesthesia days (PADs) 1,2,4, and 10. A post-hoc analysis revealed a significant increase in across-phase errors on PAD 1 and recovery on PAD 10 in the isoflurane group. In contrast, within-phase errors independent of the retention of working memory were unaffected by isoflurane. These results demonstrate that isoflurane anesthesia transiently impairs the retention of spatial working memory in rats.

[Cross-sectoral Approach of a Perioperative Management Center for General Thoracic Surgery].

Perioperative assessment and care, such as enhanced recovery after surgery (ERAS), is very important for improving the clinical outcomes of patients who have undergone surgery. However, professional assessments and care cannot be achieved through the actions of only 1 surgical department. We established a perioperative management center(PERIO) comprised of surgeons, dedicated nurses, anesthesiologists, dentists, physiotherapists, pharmacists, and nutritionists to perform intensive cross-sectoral perioperative management. In this manuscript, we investigated the impact of PERIO on the clinical outcomes of 127 elderly patients who underwent thoracic surgery for the resection of non-small cell lung cancer (NSCLC). We categorized these 127 patients into 3 groups:① those treated before the introduction of PERIO (between January 2006 to August 2008), ② those treated during the early phase after PERIO introduction (September 2008 to December 2011), and ③ those treated during the late phase after PERIO introduction( January 2012 to December 2014). Radical operations were performed significantly more frequently after PERIO introduction than before PERIO introduction, while the postoperative complication rates were similar among the 3 groups. The duration of postoperative hospitalization was reduced after the introduction of PERIO, and the hospital surplus increased after the introduction of PERIO. In conclusion, PERIO may play an important role in improving the clinical outcomes of thoracic surgery, especially for elderly patients with NSCLC.

Association between skin suture devices and incidence of incisional surgical site infection after gastrointestinal surgery: A systematic review and network meta-analysis.

AIM: We aimed to compare which suture devices could reduce the incidence of incisional surgical site infections (SSIs) after gastrointestinal surgery using a systematic review and network meta-analysis. METHODS: The CENTRAL, PubMed, and ICHUSHI-Web databases were searched from January 1st, 2000, to December 31st, 2022, for randomised clinical trials (RCTs) comparing the incidence of incisional SSI after gastrointestinal surgery among patients treated with different surgical suture devices, including non-absorbable sutures, absorbable sutures, skin staplers, and tissue adhesives (last searched in August 23th 2023). The risk of bias was assessed using the criteria of the Cochrane Handbook for Systematic Reviews of Interventions. To estimate the pooled odds ratios (ORs) for each comparison, we employed a fixed-effect inverse-variance model based on the Mantel-Haenszel approach. This study was registered in PROSPERO and supported in part by the Japan Surgical Infection Society. RESULTS: A total of 18 RCTs with 5,496 patients were included in this study. The overall SSIs in absorbable sutures were significantly lower than the ones in skin staplers (OR: 0.77; 95% confidence intervals (CI): 0.63-0.95) and non-absorbable sutures (OR: 0.62; 95% CI: 0.39-0.99). On the other hand, SSIs in absorbable sutures were not statistically different from the SSIs in tissue adhesive. The highest P-score was 0.91 for absorbable sutures. A funnel plot for estimating the heterogeneity of the studies revealed that a publication bias would be minimal (Egger test, P = 0.271). CONCLUSION: This study showed that absorbable sutures reduced incisional SSIs in gastrointestinal surgical operations compared to any other suture devices.

Recent evidence for subcutaneous drains to prevent surgical site infections after abdominal surgery: A systematic review and meta-analysis.

BACKGROUND: Surgical site infections (SSIs) increase mortality, hospital stays, additional medical treatment, and medical costs. Subcutaneous drains prevent SSIs in gynecological and breast surgeries; however, their clinical impact in abdominal surgery remains unclear. AIM: To investigate whether subcutaneous drains were beneficial in abdominal surgery using a systematic review and meta-analysis. METHODS: The database search used PubMed, MEDLINE, and the Cochrane Library. The following inclusion criteria were set for the systematic review: (1) Randomized controlled trial studies comparing SSIs after abdominal surgery with or without subcutaneous drains; and (2) Studies that described clinical outcomes, such as SSIs, seroma formation, the length of hospital stays, and mortality. RESULTS: Eight studies were included in this meta-analysis. The rate of total SSIs was significantly lower in the drained group (54/771, 7.0%) than in the control group (89/759, 11.7%), particularly in gastrointestinal surgery. Furthermore, the rate of superficial SSIs was slightly lower in the drained group (31/517, 6.0%) than in the control group (49/521, 9.4%). No significant differences were observed in seroma formation between the groups. Hospital stays were shorter in the drained group than in the control group. CONCLUSION: Subcutaneous drains after abdominal surgery prevented SSIs and reduced hospital stays but did not significantly affect seroma formation. The timing of drain removal needs to be reconsidered in future studies.

Patients scheduled to undergo esophageal surgery should have the highest priority for perioperative oral management triage: a cross-sectional study.

OBJECTIVES: An increasing number of patients visiting the dental office have a growing need for perioperative oral management (POM) to prevent postoperative complications. Therefore, it is necessary to determine which patients should receive preferential POM. This study investigated the dental status of patients scheduled to undergo surgery and addressed the priority for POM. METHODS: This retrospective study included a total of 150 patients who were scheduled to undergo surgery at the Department of Respiratory Surgery (DRS), Department of Neurological Surgery (DNS), Department of Gynecological Surgery (DGS), Department of Breast and Endocrine Surgery (DBES), and Department of Esophageal Surgery (DES) managed by the Perioperative Management Center of Okayama University Hospital. We compared the general and dental status of patients among the five groups. RESULTS: The DES group had significantly fewer teeth than the DBES group (p = 0.012), more severe periodontitis than both the DBES (p = 0.005) and DNS groups (p = 0.020), and poorer molar occlusal support status than both the DBES (p = 0.002) and DGS groups (p = 0.041). The DES group exhibited a significantly higher median age (p = 0.002), a higher ratio of males (p < 0.001), a higher prevalence of malignant tumors (p < 0.001), and higher proportions of smokers (p < 0.001) and drinkers (p < 0.001) than the other groups. CONCLUSION: Patients who underwent surgery at the DES had more dental problems than other surgery patients. Accordingly, these patients should be given the highest priority for POM triage.

An Evaluation of the Safety and Feasibility of Adenosine-assisted Clipping Surgery for Unruptured Cerebral Aneurysms: Study Protocol.

The effectiveness of adenosine-induced flow arrest in surgical clipping for the cerebral aneurysms with difficulties in temporary clip placement to the proximal main trunk has been reported. This is the first clinical trial to evaluate the safety and feasibility of adenosine-assisted clipping surgery for unruptured cerebral aneurysms (UCAs) in Japan. The inclusion criteria are as follows: patients over 20 years old, patients who agree to be enrolled in this study after providing informed consent, patients who undergo clipping surgery for UCA in our institute, and patients in whom the surgeons (T.H. or I.D.) judge that decompression of the aneurysm is effective. The primary endpoint is a modified Rankin Scale (mRS) score 30 days after surgery. We plan to enroll 10 patients in this study. The original protocol of adenosine administration was established in this trial. Herein, we present the study protocol.

Favorable survival even with high disease-specific complication rates in lymphangioleiomyomatosis after lung transplantation-long-term follow-up of a Japanese center.

BACKGROUND: Lung transplantation (LT) is a reliable therapeutic option for end-stage pulmonary lymphangioleiomyomatosis (LAM). Long-term outcome of LAM recipients after LT remains unknown. The aim of this study was to describe the outcomes of LT for LAM with a long-term follow-up, comparing those for other diseases in the same period. METHODS: We retrospectively reviewed consecutive 145 LT recipients between 1998 and 2015 at Okayama University Hospital with minimum 3-year follow-up. RESULTS: Twelve LAM recipients including nine sporadic-LAM and three tuberous sclerosis complex -LAM were identified. Nine of 12 underwent bilateral LT including four living-donor lobar LT. There was no significant difference in overall survival between the two groups. (P = 0.15). Chronic lung allograft dysfunction free survival rate in LAM compared with other diseases tended to be better (P = 0.058). However, the rate of requiring hemodialysis was significantly higher in LAM recipients than in the recipients of other diseases (P = 0.047). Notably, 8 of 12 (67%) LAM patients encountered LAM-related complication including chylothorax and pneumothorax, seven (58%) had proliferative diseases consisting of renal angiomyolipoma and recurrent LAM. Nine patients required mTOR inhibitors for LAM-related problems, contributing to improved control of LAM-related problems. While all nine recipients of bilateral LT have still survived, two patients died of diseases in their native lungs and one required re-LT among three recipients of single LT. CONCLUSION: Although the rates of LAM-related complications were unexpectedly high in the long term, LT is a feasible therapeutic option for patients with advanced pulmonary LAM.

Lung transplantation via cardiopulmonary bypass: excellent survival outcomes from extended criteria donors.

OBJECTIVES: The role of intraoperative cardiopulmonary bypass (CPB) in lung transplant (LTx) surgery is controversial. CPB enables slow pulmonary reperfusion and initial ventilation with low oxygen concentrations, both theoretically protective of transplanted lungs. In this study, we explored clinical outcomes following extended criteria donor LTx surgery implementing a thoroughly protective allograft reperfusion strategy using CPB. METHODS: Thirty-nine consecutive adult patients who underwent bilateral LTx with elective CPB and protective allograft reperfusion were reviewed. Bilaterally implanted lungs were reperfused simultaneously, via slow CPB flow reduction and initial ventilation with 21% oxygen and nitric oxide, followed by a brief modified ultrafiltration. During weaning from CPB, mean pulmonary arterial pressure was strictly maintained at 10-15 mmHg by controlling CPB and pulmonary flow. The clinical outcomes in 23 patients who received lungs from extended criteria donors (ECD group) were elucidated and compared to 16 patients undergoing LTx from standard criteria donors (SCD group). RESULTS: No life-threatening deterioration was observed to graft functionality during the first 72 h after LTx in the ECD group; however, only one patient required post-transplant extracorporeal membrane oxygenation. In three of 23 ECD LTx patients (12%), surgical revision for bleeding was required. Survival outcomes for the ECD group were favorable, with 100% survival at 6-months, 87.0% at 1-year, and 80.7% at 5-years. Outcomes in the ECD group were comparable to those in the SCD group. CONCLUSIONS: Despite a certain extent of risk associated with full-dose heparinization, use of CPB does not undermine survival outcomes after ECD LTx surgery if protective allograft reperfusion is securely performed.

Effect of nitrous oxide on neuronal damage and extracellular glutamate concentration as a function of mild, moderate, or severe ischemia in halothane-anesthetized gerbils.

BACKGROUND: The effect of nitrous oxide on ischemic neuronal damage was quantitatively evaluated by use of logistic regression curves. METHODS: Seventy-two gerbils were anesthetized with 1% halothane and randomly assigned to receive 70% nitrous oxide or 70% nitrogen. Forebrain ischemia was performed for 3, 5, or 7 min, and direct-current potential in the hippocampal CA1 region was recorded. Histologic outcome was evaluated 5 days later. Relations of neuronal damage with ischemic duration and duration of ischemic depolarization were determined by logistic regression curves. In some animals, extracellular glutamate concentration was measured every 60 s during forebrain ischemia. RESULTS: Nitrous oxide increased neuronal damage only with 5 min of ischemia (nitrous oxide vs. nitrogen: 78.5 +/- 23.0 vs. 37.3 +/- 12.2%; P < 0.01). The percentages of neuronal damage with 3 and 7 min of ischemia were not different with or without nitrous oxide. Logistic regression curves indicated that nitrous oxide significantly increased neuronal damage during the period from 3.07 to 6.63 min of ischemia. Logistic regression curves also indicated that nitrous oxide increased neuronal damage in the condition of the same duration of ischemic depolarization. Nitrous oxide shortened the ischemic duration necessary for causing 50% neuronal damage by 0.82 min. Dynamic change in extracellular glutamate concentration was not different (mean maximum dialysate glutamate concentration: 4.29 +/- 3.09 vs. 4.63 +/- 1.83 microm). CONCLUSION: Administration of nitrous oxide caused an increase in ischemic neuronal damage, but a significant adverse effect was observed with a limited range of ischemic intervals.