Short-Term Effects of Early Postoperative Celecoxib Administration for Pain, Sleep Quality, and Range of Motion After Total Knee Arthroplasty: A Randomized Controlled Trial.

BACKGROUND: We hypothesized that early postoperative administration of celecoxib would reduce pain scores and improve sleep quality and active range of motion after total knee arthroplasty (TKA) under general anesthesia. METHODS: Patients in the celecoxib group received 400 mg of celecoxib 2 hours after TKA, followed 6 hours later by 200 mg of celecoxib. Patients in the control group received 400 mg of celecoxib the second day after surgery. Patients in both group had access to patient-controlled analgesia fentanyl. The primary outcome measure was the patient-reported visual analog scale (VAS) pain score the second day after TKA. The secondary outcome measure was sleep quality (days 1, 2, and 7 postoperatively). Active knee joint range of motion was assessed on days 2 and 7 postoperatively, and VAS pain scores were evaluated on postoperative days 1 to 7. Total fentanyl consumption was also assessed. RESULTS: Compared to the control group, the celecoxib group had significantly lower median VAS pain scores on postoperative days 1 and 2, significantly less nocturnal awakening (in minutes) and frequency of body motion, and better sleep efficacy on postoperative day 1. The celecoxib group also had a significantly better median flexion angle (°) on postoperative days 2 and 7, and lower cumulative fentanyl consumption. CONCLUSION: Early administration of celecoxib after TKA was associated with significantly reduced early VAS pain scores and improved sleep quality and active knee flexion angles. Thus, the early administration of celecoxib after TKA under general anesthesia may reduce pain and improve sleep quality and functional recovery. LEVELS OF EVIDENCE: Level II, therapeutic study. TRIAL REGISTRATION: UMIN-CTR 000014624 (July 23, 2014).

Influence of prolonged translaryngeal intubation on airway complications: a retrospective comparative analysis.

PURPOSE: Tracheostomy is usually suggested to facilitate airway management of intensive care unit (ICU) patients requiring prolonged translaryngeal intubation (PTLI). While it is not uncommon for physicians to hesitate and delay to perform it for more than 2 weeks, clinically recognizable airway adverse effects following PTLI are rarely discussed. Therefore, we compared retrospectively the PTLI group with control to assess them in adult patients. METHODS: During a period of 1991-2012, patients aged older than 15 years that were admitted to University of Tsukuba Hospital ICU, underwent translaryngeal intubation (TLI) for 14 days or longer, were retrospectively studied as Group P. Patients whose tracheas were intubated for 13 days or less were set up as a control group (Group C). Patients were excluded if they had undergone any procedures that might have affected recurrent laryngeal nerves. RESULTS: Ninety-eight patients (M:F = 58:40) (group P) and 88 patients (M:F = 58:30) (group C) were included. There were no differences in patients' characteristics. Durations of TLI were 20.8 ± 6.8 days in group P and 3.8 ± 3.0 days in group C. There were no differences in the occurrence rates of severe airway adverse events. Although we found higher incidence rates of dysphagia and dysphonia/hoarseness in group P, the symptoms were mild and they were not prolonged. There were no differences in other signs and symptoms. CONCLUSIONS: We found no difference in the occurrence rates of severe airway adverse events in both groups. Translaryngeal intubation may be tolerable in adults even if the duration exceeds 2 weeks.

Sudden intraoperative pulmonary congestion in a patient with severe anemia transfused 3 days prior to surgery.

Preoperative blood transfusion is sometimes controversial. We describe a case of a 43-year-old woman who developed sudden pulmonary congestion during surgery despite a small amount of intravenous crystalloid administration. She had no allergic disorders. Preoperative examination revealed that her hemoglobin was 5.6 g/dl, and she was diagnosed as folate-deficiency anemia although she never felt any symptoms before. Therefore, blood transfusion was performed and her hemoglobin increased to 9.4 g/dl. Amid surgery, airway pressure increased suddenly and pulsed oxygen saturation dropped. Chest roentgenogram revealed that the lungs were congested and her heart was markedly enlarged indicating the state of circulatory overload. We suggest that preoperative transfusion in a patient with chronic anemia should be carefully considered, and strongly recommend the confirmation with chest roentgenogram.

Delayed inhibition of tonic inhibition enhances functional recovery following experimental ischemic stroke.

The current study focuses on the ability to improve cognitive function after stroke with interventions administered at delayed/chronic time points. In light of recent studies demonstrating delayed GABA antagonists improve motor function, we utilized electrophysiology, biochemistry and neurobehavioral methods to investigate the role of α5 GABAA receptors on hippocampal plasticity and functional recovery following ischemic stroke. Male C57Bl/6 mice were exposed to 45 min transient middle cerebral artery occlusion and analysis of synaptic and functional deficits performed 7 or 30 days after recovery. Our findings indicate that hippocampal long-term potentiation (LTP) is impaired 7 days after stroke and remain impaired for at least 30 days. We demonstrate that ex vivo administration of L655,708 reversed ischemia-induced plasticity deficits and importantly, in vivo administration at delayed time-points reversed stroke-induced memory deficits. Western blot analysis of hippocampal tissue reveals proteins responsible for GABA synthesis are upregulated (GAD65/67 and MAOB), increasing GABA in hippocampal interneurons 30 days after stroke. Thus, our data indicate that both synaptic plasticity and memory impairments observed after stroke are caused by excessive tonic GABA activity, making inhibition of specific GABA activity at delayed timepoints a potential therapeutic approach to improve functional recovery and reverse cognitive impairments after stroke.

Juvenile striatal white matter is resistant to ischemia-induced damage.

White matter injury following ischemic stroke is a major cause of functional disability. Injury to both myelinated axons and oligodendrocytes, the myelin producing cells in the central nervous system, occurs in experimental models of ischemic stroke. Age-related changes in white matter vulnerability to ischemia have been extensively studied and suggest that both the perinatal and the aged periods are times of increased white matter vulnerability. However, sensitivity of white matter following stroke in the juvenile brain has not been evaluated. Interestingly, the late pediatric period is an important developmental stage, as it is the time of maximal myelination. The current study demonstrates that neurons in late pediatric/juvenile striatum are vulnerable to ischemic damage, with neuronal injury being comparable in juvenile and adult mice following ischemia. By contrast, actively myelinating striatal oligodendrocytes in the juvenile brain are resistant to ischemia, whereas adult oligodendrocytes are quite sensitive. As a result, myelin sheaths are remarkably intact and axons survive well in the injured striatum of juvenile mice. In addition to relative resistance of juvenile white matter, other glial responses were very different in juvenile and adult mice following cerebral ischemia, including differences in astrogliosis, fibrosis, NG2-cell reactivity, and vascular integrity. Together, these responses lead to long-term preservation of brain parenchyma in juvenile mice, compared to severe tissue loss and scarring in adult mice. Overall, the current study suggests that equivalent ischemic insults may result in less functional deficit in children compared to adults and an environment more conducive to long-term recovery. GLIA 2016;64:1972-1986.

Extended therapeutic window of a novel peptide inhibitor of TRPM2 channels following focal cerebral ischemia.

INTRODUCTION: TRPM2 channels have been suggested to play a role in ischemic neuronal injury, specifically in males. A major hindrance to TRPM2 research has been the lack of specific TRPM2 inhibitors. The current study characterized the specificity and neuroprotective efficacy of a novel TRPM2 inhibitor. METHODS: Fluorescent calcium imaging (Fluo5F) was used to determine inhibitor efficacy of the TRPM2 peptide inhibitor (tat-M2NX) in HEK293 cells stably expressing hTRPM2. Adult (2-3months) and aged (18-20months) mice were subjected to 60min middle cerebral artery occlusion (MCAO) and injected with tat-M2NX, control scrambled peptide (tat-SCR) or clotrimazole (CTZ) either 20min prior or 3h after reperfusion. Infarct size was assessed using TTC staining. RESULTS: TRPM2 inhibition by tat-M2NX was observed by decreased Ca(2+) influx following H2O2 exposure human TRPM2 expressing cells. Male mice pre-treated with tat-M2NX had smaller infarct volume compared to tat-SCR. No effect of tat-M2NX on infarct size was observed in female mice. Importantly, male TRPM2(-/-) mice were not further protected by tat-M2NX, demonstrating selectivity of tat-M2NX. Administration of tat-M2NX 3h after reperfusion provided significant protection to males when analyzed at 24h or 4days after MCAO. Finally, we observed that tat-M2NX reduced ischemic injury in aged male mice. CONCLUSIONS: These data demonstrate the development of a new peptide inhibitor of TRPM2 channels that provides protection from ischemic stroke in young adult and aged male animals with a clinically relevant therapeutic window.

Arginase I release from activated neutrophils induces peripheral immunosuppression in a murine model of stroke.

Transient suppression of peripheral immunity is a major source of complication for patients suffering from ischemic stroke. The release of Arginase I (ArgI) from activated neutrophils has recently been associated with T-cell dysfunction in a number of pathologies. However, this pathway has not been previously explored in ischemic stroke. Using the murine model of transient middle cerebral artery occlusion, we explored effects of stroke on peripheral T-cell function and evaluated the role of neutrophils and ArgI. Stimulation of splenic T cells from post-stroke animals with anti-CD3/CD28 resulted in decreased proliferation and interferon-γ production when compared with sham-surgery controls. Flow cytometric analysis of intrasplenic leukocytes exposed the presence of a transient population of activated neutrophils that correlated quantitatively with elevated ArgI levels in culture media. In vitro activation of purified resting neutrophils from unmanipulated controls confirmed the capacity for murine neutrophils to release ArgI from preformed granules. We observed decreased expression of the L-arg-sensitive CD3ζ on T cells, consistent with decreased functional activity. Critically, L-arg supplementation restored the functional response of post-stroke T cells to mitogenic stimulation. Together, these data outline a novel mechanism of reversible, neutrophil-mediated peripheral immunosuppression related to ArgI release following ischemic stroke.

Androgen and PARP-1 regulation of TRPM2 channels after ischemic injury.

The calcium-permeable transient receptor potential M2 (TRPM2) ion channel was recently demonstrated to have a sexually dimorphic contribution to ischemic brain injury, with inhibition or knockdown of the channel protecting male brain preferentially. We tested the hypothesis that androgen signaling is required for this male-specific cell-death pathway. Additionally, we tested the hypothesis that differential activation of the enzyme poly (ADP-ribose) polymerase-1 (PARP-1) is responsible for male-specific TRPM2 channel activation and neuronal injury. We observed that administration of the TRPM2 inhibitor clotrimazole (CTZ) 2 hours after onset of ischemia reduced infarct volume in male mice and that protection from ischemic damage by CTZ was abolished by removal of testicular androgens (castration; CAST) and rescued by androgen replacement. Male PARP-1 knockout mice had reduced ischemic damage compared with WT mice and inhibition of TRPM2 with CTZ failed to reduce infarct size. Lastly, we observed that ischemia increased PARP activity in the peri-infarct region of male mice to a greater extent than female mice and the difference was abolished in CAST male mice. Data presented in the current study indicate that TRPM2-mediated neuronal death in the male brain requires intact androgen signaling and PARP-1 activity.

Experimental pediatric arterial ischemic stroke model reveals sex-specific estrogen signaling.

BACKGROUND AND PURPOSE: Pediatric stroke, birth to 18 years, is a significant cause of long-term disability in the United States; however, there is currently little experimental data on the pathophysiology of childhood stroke owing to lack of animal models. We developed a novel mouse model of experimental childhood-onset arterial ischemic stroke to characterize the sex-specific response of the adolescent brain to cerebral ischemia and assess the neuroprotective effect of estrogen at this developmental stage. METHODS: Postnatal day 20 to 25 mice were subjected to 90 minutes experimental stroke via the intraluminal filament middle cerebral artery occlusion model and ischemic damage assessed 22 hours after reperfusion. Real-time quantitative real-time polymerase chain reaction was performed 22 hours after middle cerebral artery occlusion to determine the effects of ischemia and estrogen treatment on the proapoptotic gene Bax. RESULTS: Ischemic injury did not differ between male and female juvenile (postnatal day 20-25) mice after middle cerebral artery occlusion. However, estrogen reduced ischemic injury in female mice, whereas having no effect in juvenile males. No differences in estrogen receptor expression were observed on postnatal day between 20 males and females. In contrast, estrogen minimized the ischemia-induced increase in the proapoptotic gene Bax in female mice, whereas having no effect on Bax induction in the male brain. CONCLUSIONS: Focal ischemia has fundamentally different effects in the juvenile brain compared with the adult, as evidenced by the lack of sex difference in ischemic injury in the murine postnatal day 20 to 25 middle cerebral artery occlusion model and the sexually dimorphic response to estrogen neuroprotection.

Rapid injection of propofol reduces vascular pain and facilitates Laryngeal Mask Airway insertion.

STUDY OBJECTIVE: To compare the clinical efficacy of a rapid injection of propofol in regard to pain and ability to facilitate Laryngeal Mask Airway (LMA) insertion. DESIGN: Randomized, single-blinded, placebo-controlled study. SETTING: University hospital. PATIENTS: 120 ASA physical status 1 and 2 patients undergoing elective orthopedic surgeries. INTERVENTIONS: Patients were randomly allocated to one of 4 groups. Group A patients were pretreated with normal saline followed by propofol 2.0 mg/kg at 3.3 mg/sec. Group B patients were pretreated with lidocaine 0.5 mg/kg followed by propofol 2.0 mg/kg at 3.3 mg/sec. In Group C, patients were pretreated with lidocaine 1.0 mg/kg followed by propofol 2.0 mg/kg at 3.3 mg/sec. In Group D, patients were pretreated with normal saline followed by propofol 2.0 mg/kg at 50 mg/sec. MEASUREMENTS: Pain on injection was measured using a 4-point scale. Scale and success rate of smooth LMA insertion also were recorded. MAIN RESULTS: Rapid injection was less painful than after pretreatment with lidocaine 0.5 mg/kg, but was similar to slow injection after pretreatment with lidocaine 1.0 mg/kg. Rapid injection facilitated LMA insertion, unlike slow injection with lidocaine 0.5 mg/kg pretreatment, and was similarly successful to slow injection after pretreatment with lidocaine 1.0 mg/kg. CONCLUSIONS: The rapid administration of propofol reduces pain and facilitates LMA insertion versus slow administration of propofol.

Intracranial hemorrhage from undiagnosed metastatic brain tumor during general anesthesia.

A patient with endometrial cancer presented with intracranial hemorrhage from an undiagnosed metastatic brain tumor during abdominal radical hysterectomy. Since she was neurologically intact, a systematic examination for brain metastasis had not been performed preoperatively. After the surgery, she had delayed recovery from general anesthesia with right hemiplegia and aphasia. Computed tomography and magnetic resonance imaging showed left putaminal hemorrhage from brain metastasis.

[Comparative study of oral tracheal tube extubation force in a baby manikin model: taping methods and tube diameters].

BACKGROUND: Adhesive tape is the standard method for securing tracheal tubes. There have been several studies about extubation forces in adult models. However, there have been few in pediatric models. Therefore, we examined the force required to extubate tracheal tube from a manikin using three methods. METHODS: A baby simulation manikin was orally intubated. The tracheal tube (3.0 to 4.5 mm internal diameter) was fixed at the right oral corner. The tracheal tube was secured with adhesive tape with three different methods as follows: 1) 0.63 cm-wide tape coiled around the tube twice, 2) 1.25 cm-wide tape coiled around the tube twice, 3) 1.25 cm-wide tape coiled up three times around the tube ("puttee style"). Adhesive tape was attached 10 cm on both sides of the tube along the lips. The tracheal tube was connected to a force-measuring device and pulled vertically until the tube was displaced 1 cm distally from the initial position. The required force was defined as the "extubation force". Each method was repeated 5 times. RESULTS: The extubation force was larger when the tape used was wider, and the contact area between the tracheal tube and tape was larger. The force was also larger as the tube diameter became larger. CONCLUSIONS: To fix a tracheal tube securely, adhesive tape should be wider and the contact area between the tube and the tape should be larger. In this regard, "puttee style" fixation seems to be effective.

Endotracheal tube extubation force: adhesive tape versus endotracheal tube holder.

BACKGROUND: Adhesive tape is commonly used to secure the endotracheal tube (ETT) in anesthesia and intensive-care settings. OBJECTIVE: To determine the force required to extubate when the ETT is secured with adhesive tape or commercially available ETT holders. METHODS: We orally intubated a simulation manikin with a standard 8.0-mm inner-diameter ETT, inflated the cuff to 20 cm H(2)O, and measured the force required to extubate with the ETT secured in several ways. We tested 3 brands of tape (Durapore, Multipore Dry, and Wardel) with 6 methods, and 2 commercially available ETT holders (LockTite and Thomas) with one method. We also tested a bite block (Universal Bite Block) with 2 methods. We used a releasable cable tie with the bite block and/or ETT holder. We connected the ETT to a digital force gauge and pulled perpendicular to the oral cavity, until the entire cuff was removed from the trachea. In each trial we considered the largest force recorded the extubation force. RESULTS: One of the conventional tape methods (with wider tape and longer tape strips) required the largest force to extubate. CONCLUSIONS: With tape strips of sufficient length and width, a conventional tape method was superior to the 2 tested commercial ETT holders in holding the ETT in place in the manikin.

Minimum alveolar concentrations of sevoflurane for maintaining bispectral index below 50 in children.

OBJECTIVE: To determine minimum alveolar concentration (MAC) of sevoflurane for maintaining bispectral index (BIS) below 50 (MAC(BIS50) ) in children. BACKGROUND: MAC(BIS50) of sevoflurane in adults was reported to be 0.97%, which has not been elucidated in children. METHODS/MATERIALS: Twenty children, American Society of Anesthesiologists physical status I or II, aged 1-8, were induced and anesthetized with sevoflurane in oxygen. After tracheal intubation, we started maintenance of anesthesia with endtidal sevoflurane concentrations of 2.6%. The endtidal sevoflurane concentration at which BIS was measured was predetermined by the up-down method (with 0.2% as a step size). After 10 min at predetermined endtidal sevoflurane concentrations, BIS was measured for 1 min. MAC(BIS50) was determined using Dixon's up-down method and probit test. RESULT: MAC(BIS50) of sevoflurane was 2.83% (95% confidence intervals: 2.70-3.14) in children. CONCLUSIONS: MAC(BIS50) of sevoflurane in children was calculated to be three times as high as in adults. This indicates that high endtidal sevoflurane concentration is required to suppress electroencephalogram activity in children.

A novel association of alveolar capillary dysplasia, atypical duodenal atresia, and subglottic stenosis.

Alveolar capillary dysplasia (ACD), which is a rare and lethal congenital pulmonary anomaly found in newborns, begins its onset or causes deterioration of the infant's condition some time after birth. Various congenital anomalies in combination with ACD have been reported, except for subglottic stenosis. Therefore, we aim to report a novel association in a case of ACD with the combination of atypical duodenal atresia and subglottic stenosis. The male infant was scheduled for duodeno-duodenostomy because a double-bubble sign was observed on a chest radiograph. He arrived at the operating theater without any symptoms. After induction of general anesthesia, although mask ventilation was performed without difficulties throughout the entire procedure, oxygen saturation values of the upper and lower extremities dissociated after several attempts of intubation. Surgery was canceled because of instability of the respiratory condition. Respiratory insufficiency worsened progressively, and the infant died at 5 days of age. An autopsy confirmed ACD and revealed cartilaginous subglottic stenosis, which had made intubation difficult. This report highlights the hazards of the onset and worsening of ACD, and the importance of thorough echocardiography before surgery when atypical duodenal atresia is suspected. Anesthesiologists should also be prepared for the difficulty of intubation.

[Airway management using i-gel in two patients for awake craniotomy].

The i-gel (Intersurgical Ltd., Wokingham, Berkshire, UK) is a new single-use noninflatable supraglottic airway device. It is composed of a soft, gel-like, transparent, thermoplastic elastomer, which provides a perilaryngeal seal without cuff inflation. In this case report, we describe the airway management using i-gel in two patients scheduled for awake craniotomy. One patient underwent the implantation of brain stimulator electrodes and the other patient underwent the removal of a glioma near Broca's area. After anesthesia was induced with propofol and remifentanil, airway was secured using i-gel. Anesthesia was maintained using oxygen, air and propofol, supplemented with an infusion of remifentanil. Anesthesia was discontinued after completion of craniotomy. The i-gel was removed when patients opened their eyes upon calling their names out. The i-gel was reinserted before the closure of the dura without difficulties despite the fact that necks were rotated about 30 degrees rightward, and remained in place until the end of surgery. All procedures finished uneventfully and without adverse events. We conclude that i-gel is effective in asleep-awake-asleep technique because of its easiness in reinsertion under condition of rotated neck.

[Anesthesia for cardiac resynchronization therapy in a child after cardiac surgery with dilated cardiomyopathy].

We report a case of anesthesia for cardiac resynchronization therapy (CRT) in a child with dilated cardiomyopathy who had undergone cardiac surgery for double outlet right ventricle. The patient was a 23-month-old boy, who had undergone pacing lead implantation as a part of CRT. His postoperative interventricular synchronization was improved significantly, and he was placed off mechanical ventilation at the early stage. However, heart failure developed slowly and his cardiac function deteriorated. Mechanical ventilation was required in consequence. We conclude that optimal time to initiate CRT as well as indications for CRT should be carefully examined.

[Unsuccessful anesthetic management for cesarean section in a patient with primary pulmonary hypertension].

A 31-year-old woman with primary pulmonary hypertension presented for an elective cesarean section at the 34-week gestation. After monitoring pulmonary artery, systemic artery blood pressures and an electrocardiogram, continuous lumbar epidural anesthesia was performed. Uneventful delivery was followed by a sudden decrease in systemic pressure and loss of consciousness. Her trachea was intubated and administration of epinephrine was started. Nitroprusside and milrinone were infused to decrease pulmonary artery pressure and to maintain systemic arterial pressure. However, she died after 16 hours due to an impairment of right ventricular function. Although the patient with PPH had been managed successfully using continuous epidural analgesia until delivery, sudden hemodynamic alterations following delivery could not be controlled by pharmacological interventions.