Delayed Emergence from Total Intravenous Anesthesia Following Posterior Spinal Correction and Fusion for Scoliosis: A Case Report.

BACKGROUND Postoperative acute liver failure, a complication following spine surgery, can cause delayed emergence from total intravenous anesthesia. Here, we report a case of acute severe postoperative liver failure following posterior spinal correction and fusion in a patient with congenital scoliosis. CASE REPORT A girl's congenital scoliosis worsened, and posterior spinal correction and fusion was scheduled. General anesthesia was induced with sevoflurane, fentanyl, target-controlled-infusion with propofol, and rocuronium. General anesthesia was maintained using target-controlled-infusion with propofol and remifentanil. The operation was completed with no remarkable complications. The operative time was 516 min and the anesthesia time was 641 min in the prone position. Emergence from anesthesia was poor, and it took 68 min to remove the tracheal tube after discontinuation of the anesthetic agents. The patient was drowsy and was transferred to her room in a general ward without reporting any pain, nausea, or dyspnea. On postoperative day 1, the results of laboratory investigations were suggestive of acute liver failure; contrast-enhanced computed tomography revealed a poorly enhanced area in the umbilical portion of the left liver lobe portal vein, indicating ischemic liver damage. Although no additional treatment was administered for acute liver failure, the patient recovered over time, and laboratory values normalized. No other postoperative complications were observed, and the patient was discharged on postoperative day 1. CONCLUSIONS Delayed emergence from general anesthesia may be due to acute liver failure following posterior spinal correction and fusion. There are several possible causes of postoperative liver failure, including anesthetics, prone position, and spinal surgery.

The Japanese Epidemiologic Study for Perioperative Anaphylaxis, a prospective nationwide study: clinical signs, severity, and therapeutic agents.

BACKGROUND: Diagnosis of perioperative anaphylaxis is difficult because of its non-specific and variable signs and symptoms. Therapeutic agents used to treat anaphylaxis and anaesthesiologist responses also vary depending on the case, which might affect outcomes; however, only a few studies have focused on these factors. METHODS: This prospective study of perioperative anaphylaxis, a part of the Japanese Epidemiologic Study for Perioperative Anaphylaxis, investigated the clinical signs, its severity, therapeutic drugs, epinephrine administration, and anaesthesiologist responses in cases of perioperative anaphylaxis to assess trends and variability. Shock index was used to assess severity of cardiovascular collapse. RESULTS: In 43 patients analysed in this study, cardiovascular signs (88.4%) were the most frequent, followed by skin (81.4%) and respiratory signs (60.5%). The presence of signs increased during the clinical course. The median time from the first signs to diagnosis of anaphylaxis was 10 (5.0-17.8) min. The rates of epinephrine use were 30.2% (unused), 48.8% (i.v.), and 20.9% (i.m.). The median time from diagnosis of anaphylaxis to epinephrine administration was 7 (inter-quartile range: 1.5-8.0) min. Antihistamines and corticosteroids were each used in 69.8% of cases. The worst shock index was higher in patients who received i.v. epinephrine (2.77 [0.90] mean [standard deviation]) than in both no epinephrine use cases (1.35 [0.41]) and i.m. epinephrine cases (1.89 [0.77] (P<0.001]). CONCLUSIONS: The clinical signs and treatments of perioperative anaphylaxis are variable, and the choice regarding epinephrine administration is based on symptom severity. CLINICAL TRIAL REGISTRATION: UMIN000035350.

Lower-Leg Amputation Performed Under Regional Anesthesia in a Patient with Epidermolysis Bullosa: A Case Report.

BACKGROUND Epidermolysis bullosa (EB) is a group of rare genetic conditions that can cause eruption of blisters on the skin and mucous membranes by the slightest mechanical stimulus. In these patients particular attention should be paid to potential complications, from monitoring of vital signs to anesthesia procedures in the perioperative period. CASE REPORT A 31-year-old man with EB underwent lower-leg amputation for squamous cell carcinoma. Multiple blisters and scars had appeared all over his face and body, and his extremities were contracted. The patient's mouth could open only up to approximately 5 mm, and laboratory examination showed a high inflammatory response. In addition, he had anemia and hypoalbuminemia with a serum albumin concentration of 1.4 g/dL. We planned sciatic and femoral nerve blocks with sedation for anesthesia management because of the anticipated difficulty of intubation and concern about postoperative upper-airway obstruction due to changes in the oral cavity. While protecting the skin from external force application, we performed sciatic and femoral nerve blocks (1.7 mg/kg) using 0.25% levobupivacaine, 10 mL (3.5 mg/kg) of 1% mepivacaine, and 6.6 mg of dexamethasone. Good analgesia was achieved, and the patient was stable during the operation. The patient was discharged 12 days postoperatively without additional signs of infection or new blister formation, although surgical wound healing was delayed. CONCLUSIONS For patients with EB who have had repeated blistering and scarring, even from a minor external force, attention should be paid to airway management and avoidance of additional skin damage caused by external forces.

Low Positive Airway Pressure without Positive End-Expiratory Pressure Decreases Blood Loss during Hepatectomy in Living Liver Donors.

BACKGROUND/AIMS: Despite the development of strategies to minimize blood loss during hepatectomy challenges remain. Our aim was to determine whether low positive airway pressure (PAP) without positive end-expiratory pressure (PEEP) could minimize blood loss during hepatectomy. METHODS: Forty-one living liver donors who underwent extended left lobectomy or right lobectomy between December 2012 and November 2013 were retrospectively analyzed. In the standard PAP group (n = 18), tidal volume was 8-10 ml/kg, respiratory rate was 10-12/min and PEEP was maintained at 5 cm H2O. In the low PAP group (n = 23), tidal volume was reduced to 5 ml/kg, respiratory rate was increased to 15/min and PEEP maintained at 0 cm H2O. Low central venous pressure (CVP) was maintained during surgery in all cases. RESULTS: The low PAP group had significantly less blood loss (p = 0.0075) and shorter operation time (p = 0.0303) than the standard PAP group. In multiple regression analysis, ventilation mode and median CVP were found to be determining factors for blood loss. In no case did the ventilation mode affect perioperative management. CONCLUSIONS: Low PAP without PEEP is a safe mechanical ventilation mode that might help minimize blood loss along with CVP monitoring during hepatectomy.

Estrogen-mediated renoprotection following cardiac arrest and cardiopulmonary resuscitation is robust to GPR30 gene deletion.

INTRODUCTION: Acute kidney injury is a serious,sexually dimorphic perioperative complication, primarily attributed to hypoperfusion. We previously found that estradiol is renoprotective after cardiac arrest and cardiopulmonary resuscitation in ovariectomized female mice. Additionally, we found that neither estrogen receptor alpha nor beta mediated this effect. We hypothesized that the G protein estrogen receptor (GPR30) mediates the renoprotective effect of estrogen. METHODS: Ovariectomized female and gonadally intact male wild-type and GPR30 gene-deleted mice were treated with either vehicle or 17ß-estradiol for 7 days, then subjected to cardiac arrest and cardiopulmonary resuscitation. Twenty four hours later, serum creatinine and urea nitrogen were measured, and histologic renal injury was evaluated by unbiased stereology. RESULTS: In both males and females, GPR30 gene deletion was associated with reduced serum creatinine regardless of treatment. Estrogen treatment of GPR30 gene-deleted males and females was associated with increased preprocedural weight. In ovariectomized female mice, estrogen treatment did not alter resuscitation, but was renoprotective regardless of GPR30 gene deletion. In males, estrogen reduced the time-to-resuscitate and epinephrine required. In wild-type male mice, serum creatinine was reduced, but neither serum urea nitrogen nor histologic outcomes were affected by estrogen treatment. In GPR30 gene-deleted males, estrogen did not alter renal outcomes. Similarly, renal injury was not affected by G1 therapy of ovariectomized female wild-type mice. CONCLUSION: Treatment with 17ß-estradiol is renoprotective after whole-body ischemia-reperfusion in ovariectomized female mice irrespective of GPR30 gene deletion. Treatment with the GPR30 agonist G1 did not alter renal outcome in females. We conclude GPR30 does not mediate the renoprotective effect of estrogen in ovariectomized female mice. In males, estrogen therapy was not renoprotective. Estrogen treatment of GPR30 gene-deleted mice was associated with increased preprocedural weight in both sexes. Of significance to further investigation, GPR30 gene deletion was associated with reduced serum creatinine, regardless of treatment.

Extracranial hypothermia during cardiac arrest and cardiopulmonary resuscitation is neuroprotective in vivo.

There is increasing evidence that ischemic brain injury is modulated by peripheral signaling. Peripheral organ ischemia can induce brain inflammation and injury. We therefore hypothesized that brain injury sustained after cardiac arrest (CA) is influenced by peripheral organ ischemia and that peripheral organ protection can reduce brain injury after CA and cardiopulmonary resuscitation (CPR). Male C57Bl/6 mice were subjected to CA/CPR. Brain temperature was maintained at 37.5°C ± 0.0°C in all animals. Body temperature was maintained at 35.1°C ± 0.1°C (normothermia) or 28.8°C ± 1.5°C (extracranial hypothermia [ExHy]) during CA. Body temperature after resuscitation was maintained at 35°C in all animals. Behavioral testing was performed at 1, 3, 5, and 7 days after CA/CPR. Either 3 or 7 days after CA/CPR, blood was analyzed for serum urea nitrogen, creatinine, alanine aminotransferase, aspartate aminotransferase, and interleukin-1ß; mice were euthanized; and brains were sectioned. CA/CPR caused peripheral organ and brain injury. ExHy animals experienced transient reduction in brain temperature after resuscitation (2.1°C ± 0.5°C for 4 minutes). Surprisingly, ExHy did not change peripheral organ damage. In contrast, hippocampal injury was reduced at 3 days after CA/CPR in ExHy animals (22.4% ± 6.2% vs. 45.7% ± 9.1%, p=0.04, n=15/group). This study has two main findings. Hypothermia limited to CA does not reduce peripheral organ injury. This unexpected finding suggests that after brief ischemia, such as during CA/CPR, signaling or events after reperfusion may be more injurious than those during the ischemic period. Second, peripheral organ hypothermia during CA reduces hippocampal injury independent of peripheral organ protection. While it is possible that this protection is due to subtle differences in brain temperature during early reperfusion, we speculate that additional mechanisms may be involved. Our findings add to the growing understanding of brain-body cross-talk by suggesting that peripheral interventions can protect the brain even if peripheral organ injury is not altered.

Inhibition of soluble epoxide hydrolase after cardiac arrest/cardiopulmonary resuscitation induces a neuroprotective phenotype in activated microglia and improves neuronal survival.

Cardiac arrest (CA) causes hippocampal neuronal death that frequently leads to severe loss of memory function in survivors. No specific treatment is available to reduce neuronal death and improve functional outcome. The brain's inflammatory response to ischemia can exacerbate injury and provides a potential treatment target. We hypothesized that microglia are activated by CA and contribute to neuronal loss. We used a mouse model to determine whether pharmacologic inhibition of the proinflammatory microglial enzyme soluble epoxide hydrolase (sEH) after CA alters microglial activation and neuronal death. The sEH inhibitor 4-phenylchalcone oxide (4-PCO) was administered after successful cardiopulmonary resuscitation (CPR). The 4-PCO treatment significantly reduced neuronal death and improved memory function after CA/CPR. We found early activation of microglia and increased expression of inflammatory tumor necrosis factor (TNF)-α and interleukin (IL)-1ß in the hippocampus after CA/CPR, which was unchanged after 4-PCO treatment, while expression of antiinflammatory IL-10 increased significantly. We conclude that sEH inhibition after CA/CPR can alter the transcription profile in activated microglia to selectively induce antiinflammatory and neuroprotective IL-10 and reduce subsequent neuronal death. Switching microglial gene expression toward a neuroprotective phenotype is a promising new therapeutic approach for ischemic brain injury.

Estrogen protects renal endothelial barrier function from ischemia-reperfusion in vitro and in vivo.

Emerging evidence suggests that renal endothelial function may be altered in ischemia-reperfusion injury. Acute kidney injury is sexually dimorphic, and estrogen protects renal tubular function after experimental ischemic injury. This study tested the hypothesis that during ischemia-reperfusion, estrogen alters glomerular endothelial function to prevent hyperpermeability. Glomerular endothelial cells were exposed to 8-h oxygen-glucose deprivation (OGD) followed by 4- and 8-h reoxygenation-glucose repletion. After 4-h reoxygenation-glucose repletion, transendothelial permeability to Ficoll-70 was reduced, and transendothelial resistance increased, by 17ß-estradiol vs. vehicle treatment during OGD (OGD-vehicle: 91.0 ± 11.8%, OGD-estrogen: 102.6 ± 10.8%, P < 0.05). This effect was reversed by coadministration of G protein-coupled receptor 30 (GPR30) antagonist G15 with 17ß-estradiol (OGD-estrogen-G15: 89.5 ± 6.9, P < 0.05 compared with 17ß-estradiol). To provide preliminary confirmation of this result in vivo, Ficoll-70 was administered to mice 24 h after cardiac arrest and cardiopulmonary resuscitation (CA/CPR). Blood urea nitrogen (BUN) and serum creatinine (SCr) in these mice were elevated within 12 h following CA/CPR and reduced at 24 h by pretreatment with 17ß-estradiol (BUN/SCr 17ß-estradiol: 34 ± 19/0.2 ± 0.1 vehicle: 92 ± 49/0.5 ± 0.3, n = 8-12, P < 0.05). Glomerular sieving of Ficoll 70 was increased by CA/CPR within 2 h of injury and 17ß-estradiol treatment (θ; 17ß-estradiol: 0.74 ± 0.26 vs. vehicle: 1.05 ± 0.53, n = 14-15, P < 0.05). These results suggest that estrogen reduces postischemic glomerular endothelial hyperpermeability at least in part through GPR30 and that estrogen may regulate post CA/CPR glomerular permeability in a similar fashion in vivo.

Normothermic cardiac arrest and cardiopulmonary resuscitation: a mouse model of ischemia-reperfusion injury.

Acute Kidney Injury (AKI) is a common, highly lethal, complication of critical illness which has a high mortality and which is most frequently caused by whole-body hypoperfusion. Successful reproduction of whole-body hypoperfusion in rodent models has been fraught with difficulty. Models which employ focal ischemia have repeatedly demonstrated results which do not translate to the clinical setting, and larger animal models which allow for whole body hypoperfusion lack access to the full toolset of genetic manipulation possible in the mouse. However, in recent years a mouse model of cardiac arrest and cardiopulmonary resuscitation has emerged which can be adapted to model AKI. This model reliably reproduces physiologic, functional, anatomic, and histologic outcomes seen in clinical AKI, is rapidly repeatable, and offers all of the significant advantages of a murine surgical model, including access to genetic manipulative techniques, low cost relative to large animals, and ease of use. Our group has developed extensive experience with use of this model to assess a number of organ-specific outcomes in AKI.

Plasmin induces endothelium-dependent nitric oxide-mediated relaxation in the porcine coronary artery.

OBJECTIVE: Plasmin is a key enzyme in fibrinolysis. We attempted to determine the possible role of plasmin in the regulation of vascular tone, while also investigating the mechanism of plasmin-induced vasorelaxation. METHODS AND RESULTS: In porcine coronary artery, plasmin induced an endothelium-dependent relaxation. This relaxing effect was mostly abolished by a proteinase inhibitor, a plasmin inhibitor, or a nitric oxide (NO) synthase inhibitor. The preceding stimulation with plasmin significantly inhibited the subsequent relaxation induced by thrombin but not that induced by proteinase-activated receptor-1-activating peptide. The relaxation induced by trypsin and substance P remained unaffected by the preceding plasmin stimulation. The pretreatment with plasmin, thrombin, or trypsin significantly attenuated the plasmin-induced relaxation. In porcine coronary artery endothelial cells (PCAECs) and human umbilical vein endothelial cells (HUVECs), plasmin induced a transient elevation in the cytosolic Ca2+ concentrations ([Ca2+]i). The preceding stimulation with plasmin inhibited the subsequent [Ca2+]i elevation induced by thrombin but not that induced by trypsin. In PCAECs, plasmin concentration-dependently induced NO production. CONCLUSIONS: The present study demonstrated, for the first time, that plasmin induced an endothelium-dependent NO-mediated relaxation in the porcine coronary artery, while also showing plasmin to specifically inactivate the thrombin receptor.