Anesthetic management of ventricular-peritoneal shunt implantation in osteogenesis imperfecta type IIB: A case report.

INTRODUCTION: Osteogenesis imperfecta (OI), a rare congenital disorder, has a risk of bone fracture and progressive bone deformity. OI type II is the most serious subtype, and very few reports on its anesthetic management exist. Patients face several anesthetic difficulties, of which easy fracturing of OI-affected bones is critical. Herein, we report our experience with the anesthetic management of a patient with OI type II. PATIENT CONCERNS AND DIAGNOSES: Through genetic testing, a 14-month-old girl (height: 45 cm, weight: 3.9 kg) was diagnosed with OI type IIB due to COL1A gene abnormality. The clinical manifestations included hydrocephalus, blue sclera, dental dysplasia, short stature, limb deformity and shortening, thoracic hypoplasia, rabbit eye, left inguinal hernia, and tricuspid valve regurgitation. Physical examination revealed an enlarged head due to skull dysplasia and hydrocephalus. The pediatrician confirmed that mask ventilation was possible even under spontaneous breathing, and that there was no history of bone fracture during mask holding. INTERVENTIONS AND OUTCOMES: The patient was scheduled for gastrostomy and ventriculo-peritoneal shunt implantation. An arterial pressure line was inserted at the neonatal intensive care unit. Propofol and remifentanil were selected for general anesthesia. Confirming that mask-assisted ventilation was possible under sleep, rocuronium was administered. Attentive mask ventilation was performed via the 2-person method to avoid fractures. We were able to intubate successfully using a Macintosh laryngoscope. A microcuff endotracheal tube was used. For ventilation, pressure control ventilation was selected and sedative dosage was adjusted using the patient state index as an indicator. The patient was sedated, intubated, and returned to the neonatal intensive care unit. She was extubated on the sixth postoperative day. No bone fractures were noted. CONCLUSION: OI type II is the most severe subtype with high mortality, and there are few reports on its anesthetic management. Easy fractures can be a problem in airway maintenance, blood pressure measurement, and repositioning. We performed the procedure attentively, avoiding jaw and cervical fractures during mask ventilation and endotracheal intubation. For respiratory management, we chose pressure control ventilation using a cuffed tracheal tube and circulatory control was attained via an arterial line inserted preoperatively. No complications occurred.

Spinal fusion with motor evoked potential monitoring using remimazolam in Alström syndrome: A case report.

RATIONALE: Alström syndrome is a rare genetic disorder characterized by obesity, diabetes mellitus, cardiomyopathy, and liver dysfunction. Further, scoliosis, a common symptom of Alström syndrome, often requires surgical intervention for functional impairments. Motor evoked potential (MEP) monitoring and other electrophysiological tests are essential when performing surgery for functional scoliosis. However, there are few reports on how to maintain general anesthesia in Alström syndrome. Here, we describe a patient with Alström syndrome who underwent surgery for scoliosis under general anesthesia with remimazolam and MEP monitoring. PATIENT CONCERNS: A 17-year-old woman (height, 140 cm, weight, 64.5 kg) diagnosed with Alström syndrome was scheduled for a posterior spinal fusion for functional scoliosis. Other associated comorbidities of Alström syndrome present were dilated cardiomyopathy, type 2 diabetes mellitus, obesity (body mass index, 32.1 kg/m2), amblyopia (light perception), and hearing impairment (speech awareness threshold 50 dBHL in each ear). DIAGNOSES, INTERVENTIONS, AND OUTCOMES: Posterior spinal fusion was planned for functional scoliosis. While investigating the dilated cardiomyopathy, transthoracic echocardiography showed global wall hypokinesis, with 45% left ventricular ejection fraction. The left ventricle was dilated, with left ventricular end-diastolic and end-systolic diameters of 55 and 42 mm, respectively. This finding along with the hypertriglyceridemia associated with Alström syndrome led us to conclude that propofol should be avoided. Thus, we induced general anesthesia using remimazolam. MEP monitoring was performed, and the patient experienced no motor impairments during the surgery. LESSONS: Myocardial and hepatic dysfunction determine the prognosis of patients with Alström syndrome. Thus, anesthesia that preserves liver function should be selected in such cases. In patients with hypertriglyceridemia, propofol should be avoided, and using remimazolam, an ultrashort-acting benzodiazepine, may be appropriate. In this case, reviewing the Patient State Index with SedLine allowed us to perform MEP monitoring uneventfully, and the posterior spinal fusion was completed without any motor impairment.

Spinal parenchymal occupation by neural stem cells after subpial delivery in adult immunodeficient rats.

Neural precursor cells (NSCs) hold great potential to treat a variety of neurodegenerative diseases and injuries to the spinal cord. However, current delivery techniques require an invasive approach in which an injection needle is advanced into the spinal parenchyma to deliver cells of interest. As such, this approach is associated with an inherent risk of spinal injury, as well as a limited delivery of cells into multiple spinal segments. Here, we characterize the use of a novel cell delivery technique that employs single bolus cell injections into the spinal subpial space. In immunodeficient rats, two subpial injections of human NSCs were performed in the cervical and lumbar spinal cord, respectively. The survival, distribution, and phenotype of transplanted cells were assessed 6-8 months after injection. Immunofluorescence staining and mRNA sequencing analysis demonstrated a near-complete occupation of the spinal cord by injected cells, in which transplanted human NSCs (hNSCs) preferentially acquired glial phenotypes, expressing oligodendrocyte (Olig2, APC) or astrocyte (GFAP) markers. In the outermost layer of the spinal cord, injected hNSCs differentiated into glia limitans-forming astrocytes and expressed human-specific superoxide dismutase and laminin. All animals showed normal neurological function for the duration of the analysis. These data show that the subpial cell delivery technique is highly effective in populating the entire spinal cord with injected NSCs, and has a potential for clinical use in cell replacement therapies for the treatment of ALS, multiple sclerosis, or spinal cord injury.

Survival of syngeneic and allogeneic iPSC-derived neural precursors after spinal grafting in minipigs.

The use of autologous (or syngeneic) cells derived from induced pluripotent stem cells (iPSCs) holds great promise for future clinical use in a wide range of diseases and injuries. It is expected that cell replacement therapies using autologous cells would forego the need for immunosuppression, otherwise required in allogeneic transplantations. However, recent studies have shown the unexpected immune rejection of undifferentiated autologous mouse iPSCs after transplantation. Whether similar immunogenic properties are maintained in iPSC-derived lineage-committed cells (such as neural precursors) is relatively unknown. We demonstrate that syngeneic porcine iPSC-derived neural precursor cell (NPC) transplantation to the spinal cord in the absence of immunosuppression is associated with long-term survival and neuronal and glial differentiation. No tumor formation was noted. Similar cell engraftment and differentiation were shown in spinally injured transiently immunosuppressed swine leukocyte antigen (SLA)-mismatched allogeneic pigs. These data demonstrate that iPSC-NPCs can be grafted into syngeneic recipients in the absence of immunosuppression and that temporary immunosuppression is sufficient to induce long-term immune tolerance after NPC engraftment into spinally injured allogeneic recipients. Collectively, our results show that iPSC-NPCs represent an alternative source of transplantable NPCs for the treatment of a variety of disorders affecting the spinal cord, including trauma, ischemia, or amyotrophic lateral sclerosis.

Time-dependent, bidirectional, anti- and pro-spinal hyper-reflexia and muscle spasticity effect after chronic spinal glycine transporter 2 (GlyT2) oligonucleotide-induced downregulation.

The loss of local spinal glycine-ergic tone has been postulated as one of the mechanisms contributing to the development of spinal injury-induced spasticity. In our present study using a model of spinal transection-induced muscle spasticity, we characterize the effect of spinally-targeted GlyT2 downregulation once initiated at chronic stages after induction of spasticity in rats. In animals with identified hyper-reflexia, the anti-spasticity effect was studied after intrathecal treatment with: i) glycine, ii) GlyT2 inhibitor (ALX 1393), and iii) GlyT2 antisense oligonucleotide (GlyT2-ASO). Administration of glycine and GlyT2 inhibitor led to significant suppression of spasticity lasting for a minimum of 45-60 min. Treatment with GlyT2-ASO led to progressive suppression of muscle spasticity seen at 2-3 weeks after treatment. Over the subsequent 4-12 weeks, however, the gradual appearance of profound spinal hyper-reflexia was seen. This was presented as spontaneous or slight-tactile stimulus-evoked muscle oscillations in the hind limbs (but not in upper limbs) with individual hyper-reflexive episodes lasting between 3 and 5 min. Chronic hyper-reflexia induced by GlyT2-ASO treatment was effectively blocked by intrathecal glycine. Immunofluorescence staining and Q-PCR analysis of the lumbar spinal cord region showed a significant (>90%) decrease in GlyT2 mRNA and GlyT2 protein. These data demonstrate that spinal GlyT2 downregulation provides only a time-limited therapeutic benefit and that subsequent loss of glycine vesicular synthesis resulting from chronic GlyT2 downregulation near completely eliminates the tonic glycine-ergic activity and is functionally expressed as profound spinal hyper-reflexia. These characteristics also suggest that chronic spinal GlyT2 silencing may be associated with pro-nociceptive activity.

Subpial Adeno-associated Virus 9 (AAV9) Vector Delivery in Adult Mice.

The successful development of a subpial adeno-associated virus 9 (AAV9) vector delivery technique in adult rats and pigs has been reported on previously. Using subpially-placed polyethylene catheters (PE-10 or PE-5) for AAV9 delivery, potent transgene expression through the spinal parenchyma (white and gray matter) in subpially-injected spinal segments has been demonstrated. Because of the wide range of transgenic mouse models of neurodegenerative diseases, there is a strong desire for the development of a potent central nervous system (CNS)-targeted vector delivery technique in adult mice. Accordingly, the present study describes the development of a spinal subpial vector delivery device and technique to permit safe and effective spinal AAV9 delivery in adult C57BL/6J mice. In spinally immobilized and anesthetized mice, the pia mater (cervical 1 and lumbar 1-2 spinal segmental level) was incised with a sharp 34 G needle using an XYZ manipulator. A second XYZ manipulator was then used to advance a blunt 36G needle into the lumbar and/or cervical subpial space. The AAV9 vector (3-5 µL; 1.2 x 1013 genome copies (gc)) encoding green fluorescent protein (GFP) was then injected subpially. After injections, neurological function (motor and sensory) was assessed periodically, and animals were perfusion-fixed 14 days after AAV9 delivery with 4% paraformaldehyde. Analysis of horizontal or transverse spinal cord sections showed transgene expression throughout the entire spinal cord, in both gray and white matter. In addition, intense retrogradely-mediated GFP expression was seen in the descending motor axons and neurons in the motor cortex, nucleus ruber, and formatio reticularis. No neurological dysfunction was noted in any animals. These data show that the subpial vector delivery technique can successfully be used in adult mice, without causing procedure-related spinal cord injury, and is associated with highly potent transgene expression throughout the spinal neuraxis.

Potent spinal parenchymal AAV9-mediated gene delivery by subpial injection in adult rats and pigs.

Effective in vivo use of adeno-associated virus (AAV)-based vectors to achieve gene-specific silencing or upregulation in the central nervous system has been limited by the inability to provide more than limited deep parenchymal expression in adult animals using delivery routes with the most clinical relevance (intravenous or intrathecal). Here, we demonstrate that the spinal pia membrane represents the primary barrier limiting effective AAV9 penetration into the spinal parenchyma after intrathecal AAV9 delivery. We develop a novel subpial AAV9 delivery technique and AAV9-dextran formulation. We use these in adult rats and pigs to show (i) potent spinal parenchymal transgene expression in white and gray matter including neurons, glial and endothelial cells after single bolus subpial AAV9 delivery; (ii) delivery to almost all apparent descending motor axons throughout the length of the spinal cord after cervical or thoracic subpial AAV9 injection; (iii) potent retrograde transgene expression in brain motor centers (motor cortex and brain stem); and (iv) the relative safety of this approach by defining normal neurological function for up to 6 months after AAV9 delivery. Thus, subpial delivery of AAV9 enables gene-based therapies with a wide range of potential experimental and clinical utilizations in adult animals and human patients.

Thoracic 9 Spinal Transection-Induced Model of Muscle Spasticity in the Rat: A Systematic Electrophysiological and Histopathological Characterization.

The development of spinal hyper-reflexia as part of the spasticity syndrome represents one of the major complications associated with chronic spinal traumatic injury (SCI). The primary mechanism leading to progressive appearance of muscle spasticity is multimodal and may include loss of descending inhibitory tone, alteration of segmental interneuron-mediated inhibition and/or increased reflex activity to sensory input. Here, we characterized a chronic thoracic (Th 9) complete transection model of muscle spasticity in Sprague-Dawley (SD) rats. Isoflurane-anesthetized rats received a Th9 laminectomy and the spinal cord was transected using a scalpel blade. After the transection the presence of muscle spasticity quantified as stretch and cutaneous hyper-reflexia was identified and quantified as time-dependent changes in: i) ankle-rotation-evoked peripheral muscle resistance (PMR) and corresponding electromyography (EMG) activity, ii) Hoffmann reflex, and iii) EMG responses in gastrocnemius muscle after paw tactile stimulation for up to 8 months after injury. To validate the clinical relevance of this model, the treatment potency after systemic treatment with the clinically established anti-spastic agents baclofen (GABAB receptor agonist), tizanidine (α2-adrenergic agonist) and NGX424 (AMPA receptor antagonist) was also tested. During the first 3 months post spinal transection, a progressive increase in ankle rotation-evoked muscle resistance, Hoffmann reflex amplitude and increased EMG responses to peripherally applied tactile stimuli were consistently measured. These changes, indicative of the spasticity syndrome, then remained relatively stable for up to 8 months post injury. Systemic treatment with baclofen, tizanidine and NGX424 led to a significant but transient suppression of spinal hyper-reflexia. These data demonstrate that a chronic Th9 spinal transection model in adult SD rat represents a reliable experimental platform to be used in studying the pathophysiology of chronic spinal injury-induced spasticity. In addition a consistent anti-spastic effect measured after treatment with clinically effective anti-spastic agents indicate that this model can effectively be used in screening new anti-spasticity compounds or procedures aimed at modulating chronic spinal trauma-associated muscle spasticity.

[Anesthetic management of intra-aortic balloon occlusion (IABO) for seven cases of placenta accreta--a six year experience at our institute].

We studied retrospectively amount of bleeding, clamping time, and the presence or absence of ischemia-reperfusion injury in all seven cases of IABO performed for placenta accreta from 2007 to 2012 at our hospital. We also examined rSO2 change before and after clamping in four cases in which lower-limb rSO2 monitoring was performed with NIRS (near-infrared spectroscopy). There was no case suspected of ischemia-reperfusion injury during and after clamping with the amount of bleeding around 1,580-10,973 ml (mean 4,536 ml) and clamping time of 10-83 min (mean 44 min). No significant decrease was observed in lower-limb rSO2 with 73.5 ± 5.9% before clamping and 70.8 ± 5.6% (mean ± SD) after clamping.

[Case report : usefulness of the airwayscope for difficult intubations in a pediatric patients with Coffin-Siris syndrome].

We experienced management of general anesthesia in a patients with Coffin-Siris syndrome (CS syndrome) which is an autosomal dominant disorder characterized by mental retardation, growth failure, hypoplasia of the fifth finger's distal phalanx and limb, and syndrome-specific facial appearance. Anesthesia was induced by sevoflurane by mask. After obtaining muscle relaxation by rocuronium, laryngoscopy by Machintosh #2 failed to reveal the vocal cord. However, the vocal cord was revealed by AirwayScope (AWS) for the pediatrics and then tracheal intubation was successful. Surgical procedures and anes-thetic management were performed uneventfully. This case demonstrates usefulness of AWS in pediatric patients with difficult intubation.

[Utility of a bronchoscope and a gum elastic bougie for nasal intubation in a patient with a history of transsphenoidal surgery].

A 39-year-old man with a history of transsphenoidal surgery was scheduled for sagittal split ramus osteotomy. Nasal intubation was successfully performed using a bronchoscope (BF) and a gum elastic bougie (GB). inserted using a BE The BF was then replaced with a GB. We widened his nasal cavity using the nasal airway. Finally, intubation was performed with an endotracheal tube (7.0 mm) using a GB and a Macintosh laryngoscope. Thus, BF and GB could be safely used for nasal intubation in a patient with a history of transsphenoidal surgery.

Vascular hyperpermeability in pulmonary decompression illness: 'the chokes'.

Decompression illness (DCI) develops during or after diving. Pulmonary decompression illness ('Chokes') is rarely seen because the affected individual usually dies in the water. We encountered a rare and interesting case. A 60-year-old man complained of leg pain after diving. Despite rapid transfer to a nearby hospital, advanced respiratory failure and shock had set in. He was then transferred to our hospital for hyperbaric oxygen therapy (HBOT). On account of his poor general condition, we initially treated him in the intensive care unit without HBOT, where he showed extreme hyperpermeability and a high level of serum procalcitonin (PCT; 20.24 ng/mL). Despite large-volume fluid therapy, severe intravascular dehydration and shock status remained. We assume that the injured endothelial cells induced vascular hyperpermeability and increased levels of inflammatory cytokines leading to the high serum PCT level. PCT might be a useful stress marker of endothelial damage and severity in DCI, including Chokes.

[Utility of target controlled infusion technique for deciding the fentanyl infusion rate for post-cholecystectomy pain management in a patient on anticoagulant therapy].

The fentanyl infusion rate was controlled by employing a target controlled infusion (TCI) technique under anticoagulant therapy for postoperative pain management. A 59-year-old woman with atrial fibrillation and mitral stenosis was scheduled for open cholecystectomy. Heparin was continuously infused for anticoagulant therapy. Sevoflurane and remifentanil were used for induction and maintenance of anesthesia. At completion of the operation, her consciousness was checked and the endotracheal tube was then removed under fentanyl TCI (effect-site concentration: Ce = 2.0 ng x ml(-1)). In this case, the spontaneous breathing rate was stable (10-12 x min(-1)) under fentanyl TCI. She had no complaints of pain(pain at rest: VAS 20 mm). The breathing rate in this case provided indication for postoperative pain management. The TIVAtrainer simulation makes the exchange from TCI infusion to continuous infusion easy. And the spontaneous breathing monitoring is useful for postoperative pain measurement of laparotomy cases.

[Remifentanil can reduce intraoperative movement during tympanoplastic surgery--a retrospective analysis].

BACKGROUND: This retrospective study compared remifentanil-sevoflurane anesthesia (RG) with fentanyl-sevoflurane anesthesia (FG) to determine which is accompanied with the lower incidence of intraoperative movement during tympanoplastic surgery under intraoperative facial nerve monitoring. METHODS: We reviewed 91 patients undergoing elective tympanoplastic surgery under intraoperative facial nerve monitoring. All patients were allocated into two groups; RG (48 subjects) and FG (43 subjects). Although vecuronium was given to facilitate endotracheal intubation, additional muscle relaxants were administered in case of intraoperative movement. The intraoperative consumption of sevoflurane, the additional use of vecuronium, incidence of intraoperative movement, and the effect-site concentration of remifentanil or fentanyl were calculated from the anesthetic records. RESULTS: Both the consumption of sevoflurane and the additional use of vecuronium were significantly less in the RG group than in the FG group. Incidence of intraoperative movement in RS was lower than that in FG (RG:FG = 6.2:53.5%, P = 0.002). CONCLUSIONS: According to our data, remifentanil-sevoflurane anesthesia can reduce the incidence of intraoperative movement during tympanoplastic surgery. This lower incidence of intraoperative movement with RG may be owing to the higher effect-site concentration of remifentanil.

[Breathing pattern and postoperative analgesia at various effect-site concentrations of fentanyl].

BACKGROUND: We investigated how various effectsite concentrations of fentanyl could affect breathing pattern and postoperative analgesia. METHODS: This study enrolled 64 ASA physical status 1 and 2 patients, undergoing elective surgical procedures, including otologic, orthopedic, breast surgery and gynecological laparoscopic procedure. General anesthesia was performed with sevoflurane inhalation and target-controlled infusion for fentanyl. After the surgery, fentanyl was administered by a target-controlled infusion system to maintain one of the effect-site concentrations of fentanyl as follows ; 0.5, 0.8, 1.0, 1.2, 1.5, 1.8 and 2.0 ng x ml(-1) under 0.8% of the end-tidal sevoflurane concentration. We recorded spontaneous respiratory rate (RR), tidal volume (Vt), and minute volume (MV). After sevoflurane inhalation was finished, the end-tidal sevoflurane concentration at the time at which they responded to command was recorded. Postoperative pain was assessed right after extubation. RESULTS: Although RR decreased in a effect-site concentration of fentanyl dependent manner, V(T) increased gradually, resulting in relatively constant range between 0.5-2.0 ng x ml(-1) of effect-site concentration of fentanyl. Postoperative pain was adequately controlled in the range between 1.2-2.0 ng x ml(-1) of effect-site concentrations of fentanyl. CONCLUSIONS: According to our data, 1.2-2.0 ng x ml(-1) of effect-site concentration of fentanyl could provide adequate postoperative analgesia without respiratory depression in otologic, orthopedic, breast surgery and gynecological laparoscopic procedures.

Right coronary artery spasms triggered by mechanical compression during off-pump coronary artery bypass grafting surgery.

In this case report, we describe recurrent spasms of the right coronary artery with no apparent preexisting abnormal angiogram that caused second-degree atrioventricular (AV) block and inferior wall hypokinesis. These hemodynamic changes were induced by mechanical compression of the right coronary artery by a pericardium drain tube. From our experience, we should be aware that mechanical compression may trigger an exaggerated vasomotor response, leading to severe coronary artery spasms.