Genesis of "negative pressure" during hanging drop; the answer is positive pressure.

A drop of saline placed within the hub of an epidural needle is sucked in when the needle is advanced and penetrates through a polyurethane foam cube. This phenomenon might be explained by the release of compressed air inside of the needle into the air. The positive pressure inside of the needle may be generated by advancing of the needle. To prove this hypothesis, the pressure inside of the needle was measured during needle advancement, and it increased gradually and then dropped to zero suddenly when the needle fully penetrated the polyurethane foam block. We can speculate that the same phenomenon occurs during hanging-drop method of epidural anesthesia, and this may occur regardless of whether epidural subatmospheric pressure exists or not.

Biomechanical profiles of tracheal intubation: a mannequin-based study to make an objective assessment of clinical skills by expert anesthesiologists and novice residents.

BACKGROUND: Tracheal intubation (TI) is a key medical skill used by anesthesiologists and critical care physicians in airway management in operating rooms and critical care units. An objective assessment of dexterity in TI procedures would greatly enhance the quality of medical training. This study aims to investigate whether any biomechanical parameters obtained by 3D-motion analysis of body movements during TI procedures can objectively distinguish expert anesthesiologists from novice residents. METHODS: Thirteen expert anesthesiologists and thirteen residents attempted TI procedures on an airway mannequin using a Macintosh laryngoscope. Motion capturing technology was utilized to digitally record movements during TI procedures. The skill with which experts and novices measured biomechanical parameters of body motions were comparatively examined. RESULTS: The two groups showed similar outcomes (success rates and mean time needed to complete the TI procedures) as well as similar mean absolute velocity values in all 21 body parts examined. However, the experts exhibited significantly lower mean absolute acceleration values at the head and the left hand than the residents. In addition, the mean-absolute-jerk measurement revealed that the experts commanded potentially smoother motions at the head and the left hand. The Receiver Operating Characteristic (ROC) curves analysis demonstrated that mean-absolute-acceleration and -jerk measurements provide excellent measures for discriminating between experts and novices. CONCLUSIONS: Biomechanical parameter measurements could be used as a means to objectively assess dexterity in TI procedures. Compared with novice residents, expert anesthesiologists possess a better ability to control their body movements during TI procedures, displaying smoother motions at the selected body parts.

Downregulation of stanniocalcin 1 is responsible for sorafenib-induced cardiotoxicity.

Sorafenib is associated with adverse cardiac effects, including left ventricular dysfunction. However, the precise mechanism remains unclear. Here, we aimed to establish the genes responsible for this cardiotoxicity using zebrafish and human cardiomyocytes. Fluorescent cardiac imaging using pigmentless zebrafish with green fluorescent protein hearts revealed that the ventricular dimensions of the longitudinal axis with sorafenib were significantly shorter than those of the control group. Transcriptome analysis of their hearts revealed that stanniocalcin 1 (stc1) was downregulated by sorafenib. stc1 knockdown in zebrafish revealed that reduction of stc1 decreased the longitudinal dimensions of zebrafish ventricles, similar to that which occurs during sorafenib treatment. STC1 downregulation and cytotoxicity were also seen in human cardiomyocytes exposed to sorafenib. To clarify the molecular function of stc1 in sorafenib-induced cardiotoxicity, we focused on oxidative stress in cardiomyocytes treated with sorafenib. Reactive oxygen species (ROS) production significantly increased in both species of human cardiomyocytes and zebrafish exposed to sorafenib and STC1 knockdown compared with the controls. Finally, we found that forced expression of stc1 normalized impairment, decreasing the longitudinal dimensions in zebrafish treated with sorafenib. Our study demonstrated that STC1 plays a protective role against ventricular dysfunction and ROS overproduction, which are induced by sorafenib treatment. We discovered for the first time that STC1 downregulation is responsible for sorafenib-induced cardiotoxicity through activated ROS generation.

An approach to the intra-thoracic inferior vena cava through the abdominal cavity preparing for total hepatic vascular exclusion by sagittal diaphragmotomy.

BACKGROUND/AIMS: For resection of advanced liver tumors with tumor thrombus/invasion extending into the intra-thoracic inferior vena cava (IVC) above the diaphragm as well as huge liver tumors located at the root of hepatic vein, an appropriate approach to the intra-thoracic IVC through the abdominal cavity is the key to control the intraoperative massive bleeding. SURGICAL TECHNIQUE: The pericardium and diaphragm are separated by using fingers without injury of the pericardium. From just below the xiphoid process to the IVC, the diaphragm is vertically dissected without cutting the pericardium and doing median sternotomy. Then the intra-thoracic IVC is exposed easily and encircled with an umbilical tape. RESULTS: This technique was applied in four patients (hepatocellular carcinoma: n = 3, cholangiocellular carcinoma: n = 1). The mean patient's age was 69 (59-81) year old, and three were male. The median duration of surgery and blood loss was 490 min and 3600 mL, respectively. The median peaked aspartate aminotransferase and total bilirubin was 428 IU/mL and 2.75 mg/dL, respectively. The median duration of hospital stay was 22 days. CONCLUSIONS: This approach to intra-thoracic IVC through the abdominal cavity is very beneficial and helpful for many liver surgeons.

[Two cases of diaphragmatic surgery in children under artificial pneumothorax].

We reported two cases of thoracoscopic diaphragm repair in children. The first case was a 6-day old neonate undergoing thoracoscopic repair of congenital diaphragmatic hernia under general anesthesia. During operation, CO2 was insufflated with a pressure of 4 cmH2O into the thoracic cavity. Although end-tidal CO2 increased to 90 mmHg, Sp(O2) and blood pressure were maintained within normal ranges. The second case was a 20-month-old infant undergoing thoracoscopic repair of diaphragmatic laxity. During operation, end-tidal CO2 increased to around 50 mmHg. Sp(O2) and blood pressure were normal. But during the procedure, insufflation pressure increased up to 10 cmH2O accidentally and arterial blood pressure curve disappeared. Insufflation pressure was corrected quickly and the arterial blood pressure recovered to normal within 10 seconds. The physiological changes of CO2 insufflation in thoracic cavity is similar to tension pneumothorax and we must take care to keep insufflation pressure under 4 cmH2O.

[Reliability in detection of tracheal intubation using cricoid palpation method].

BACKGROUND: Unrecognized esophageal intubation remains a significant cause of anesthetic morbidity. Extensive data showed that clinical signs and methods for confirming proper tracheal tube placement were not always reliable. Advancing tracheal tube into the trachea can be detected by palpating the cricoid cartilage. We evaluated the reliability of detecting tracheal intubation by cricoid palpation methods (CPM) in this study. METHODS: Three hundred and twelve patients were enrolled. After induction of general anesthesia, patients' tracheae were intubated using rigid laryngoscope. Before tracheal intubation, an assistant applied gentle pressure over the cricoid cartilage to detect tracheal or esophageal intubation. Immediately after intubation, the assistant was asked to state whether the tracheal tube was in the trachea or in the esophagus on the basis of what had been felt as the tube passed. Tracheal intubation was confirmed by capnometer and auscultation. RESULTS: In 304 tracheal intubations, the CPM correctly detected 268 cases, giving sensitivity of 88%. In 26 esophageal intubation, the CPM correctly detected 11 esophageal cases, giving specificity of 42%. Positive predictive value and negative predictive values were 95% and 23%, respectively. Increasing body mass index decreased the sensitivity for detecting tracheal intubation by the CPM. CONCLUSIONS: The CPM alone is imperfect for tracheal tube placement confirmation. Multiple methods for detecting correct tube placement should be used, since no single method has perfect reliability.

Upper airway obstruction associated with flexed cervical position after posterior occipitocervical fusion.

Upper airway obstruction resulting from overflexion fixation of the cervical spine is a rare but life-threatening complication after cervical spine surgery. There are few reports of dyspnea after a posterior cervical fusion. We present the case of a 63-year-old woman with rheumatoid arthritis who developed an upper airway obstruction immediately after an O-C4 fusion. She was reintubated with a fiberoptic scope. Revision surgery allowing the angle to return to the neutral position was performed to ameliorate the overflexion of the cervical spine fixation and the consequent upper airway obstruction. After revision surgery, the upper airway obstruction disappeared. Our experience suggests that intraoperative use of fluoroscopy and extubation with a tube exchanger are recommended to avoid this complication, especially in patients at high risk of upper airway obstruction.

Bilateral vocal cord paralysis in a patient with chronic renal failure associated with Alport syndrome.

A 61-year-old woman with chronic renal failure (CRF) associated with Alport syndrome underwent coronary artery aneurysmectomy under general anesthesia. Hemorrhage control was difficult during the surgery, and she became hemodynamically unstable. The surgery and anesthesia lasted 446 and 552 min, respectively. On postoperative day 1, she developed severe respiratory distress several minutes after extubation. Her trachea was immediately reintubated. The second attempt to extubate her trachea also failed. Fiberoptic examination revealed bilateral vocal cord paralysis (VCP) due to recurrent laryngeal nerve (RLN) paralysis. Although she needed a temporary tracheostomy, vocal cord movement recovered without treatment 3 months after surgery. The mechanisms underlying her symptoms may be multifactorial: the first and foremost factor was that she had been receiving maintenance hemodialysis for 20 years since being diagnosed with Alport syndrome. We speculated that RLN vulnerability due to Alport syndrome and CRF strengthened her symptoms. We also recognized that the long-lasting mechanical stress and low perfusion to the RLN due to hemodynamic instability during surgery were indispensable contributory factors to the development of VCP. This is the first report of postoperative bilateral VCP in a patient with CRF related to Alport syndrome. Based on this experience, we strongly recommend preoperative detailed examination of vocal cord function in patients with CRF associated with Alport syndrome.

Volume manipulation by phlebotomy for cesarean section in a patient with pulmonary hypertension.

Pulmonary hypertension in a parturient is known for its high perioperative mortality. We describe a successful case of cesarean section performed under general anesthesia in a parturient with pulmonary hypertension. A distinctive feature of our management was active blood volume manipulation by phlebotomy and reinfusion of the blood. Just after the baby was delivered, about 250 ml of blood was phlebotomized to counteract autotransfusion by the contracting uterus. We stopped phlebotomy at this volume because moderate systemic hypotension occurred. The blood was slowly infused, with transesophageal echocardiography used to evaluate right ventricle filling. The patient was hemodynamically stable during the operation and had an uneventful postpartum period. Her baby's perioperative course was also uneventful.

[Compartment syndrome in the left lower leg following semiradical hysterectomy under general anesthesia combined with epidural anesthesia].

A 72-year-old woman, ASA physical status II, weighing 47 kg, with uterine cancer was scheduled for semiradical hysterectomy. She had uncontrolled diabetes mellitus with FBS 123 mg x dl(-1) and HbA1c 7.0%. After an epidural catheter had been placed at the L1-2 level, general anesthesia was induced with propofol 100 mg, fentanyl 50 microg and vecuronium 5 mg. The trachea was intubated, and ventilation was controlled. Anesthesia was maintained with 1.5% sevoflurane in 30% oxygen and epidural anesthesia. Systolic blood pressure was maintained between 80-120 mmHg throughout the operation and the total blood loss was 1260 g. Continuous epidural anesthesia was started 1 hour before the end of operation using 0.2% ropivacaine and 3.7 microg x ml(-1) fentanyl at 5 ml x hr(-1). She awoke in the operating room and her trachea was extubated. After awaking from anesthesia, she complained of weakness and numbness in the both lower extremities. We considered these as an influence of epidurally administered 5 ml of 0.5% ropivacaine 30 min before the end of surgery. However, 2 hours later, she complained of right lower leg pain. We removed the epidural catheter, considering the possibility of the epidural catheter tip stimulating nerve root. However, next morning, the frontal part of her right lower leg turned reddish and swollen, and the pain appeared with the pulse of dorsalis pedis artery hardly palpable. Taken together these symptoms and the elevation of creatine kinase to 20000 IU x l(-1), we diagnosed as a compartment syndrome. In the evening of the postoperative one day, emergent fasciotomy was performed under local anesthesia. She was discharged with full recovery of her right leg function, and a well healed fasciotomy scar. Magnetic resonance angiography (MRA) on the 10th postoperative day demonstrated the obstruction of the right superficial femoral artery and anterior tibial artery. Emergent fasciotomy is the recommended treatment for severe compartment syndrome. Early recognition, diagnosis, and surgical intervention averted potential neural and functional impairment in this patient.

K(+)-channel openers suppress epileptiform activities induced by 4-aminopyridine in cultured rat hippocampal neurons.

K(+) channels are key modulators of neuronal excitability, and mutations in certain types of these channels are known to cause epileptic seizures. Activation of K(+) channels is reported to suppress epileptic discharge; however, the types of K(+)-channel openers that are most effective as anti-epileptic agents are not well understood. We established a quantitative fluorescence assay using the Na(+) indicator sodium-binding benzofuran isophthalate (SBFI) for evaluation of various compounds on epileptiform activities induced by 4-aminopyridine (4-AP) in cultured rat hippocampal neurons. Among the K(+)-channel openers, the K(V)7.2/K(V)7.3-channel openers retigabine and flupirtine and K(Ca)2-channel openers NS309, DCEBIO, and 1-EBIO showed potent anti-epileptic effects similar to conventional antiepileptic drugs (AEDs). In contrast, the K(Ca)1.1-channel openers NS1619, isopimaric acid, and chlorzoxazone demonstrated moderate inhibition. The K(ir)6-channel openers minoxidil, cromakalim, and pinacidil did not show anti-epileptic effects. We concluded that K(V)7.2/K(V)7.3, K(Ca)2, and, to some extent, K(Ca)1.1-channel openers, but not K(ir)6-channel openers, suppress 4-AP-induced epileptiform activities in hippocampal neurons. These results suggest that the K(+)-channel openers for this category of K(+) channels might have therapeutic potential as new classes of antiepileptic drugs.

[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.

Unilateral adrenalectomy attenuates hemorrhagic shock-induced analgesia in rats.

PURPOSE: To assess the importance of the pituitary adrenal axis in producing stress-induced analgesia (SIA) after hemorrhagic shock, we performed formalin tests after hemorrhage and reinfusion in unilaterally adrenalectomized or sham-operated rats. METHODS: Fifty-two adult Sprague-Dawley rats were divided into seven groups: sham-operation normotensive (n = 8), sham-operation shock (n = 8), adrenalectomy normotensive (n = 7), adrenalectomy shock (n = 7), sham-operation shock + yohimbine (n = 7), sham-operation normotensive + corticosterone (n = 7), and adrenalectomy shock + corticosterone (n = 8). The left adrenal gland was cauterized 24 h before the experiment. The mean blood pressure in the shock groups was kept at 50-60 mmHg for 30 min by draining arterial blood. After the blood-reinfusion or observation period, 10% formalin was injected into the rear paw. Nociceptive behaviors and locomotion were observed and rated for 1 h, using the criteria of Dubuisson and Dennis. In 12 other sham-operated and adrenalectomized rats, plasma adrenalin, noradrenalin, and corticosterone concentrations were measured before and after hemorrhagic shock. RESULTS: Although the sham-operation shock group showed a lower pain score, the adrenalectomy shock group showed nociceptive behavior similar to that in the normotensive groups. Yohimbine did not affect the SIA; however, corticosterone administration reversed the effects of the adrenalectomy on the SIA. The plasma corticosterone levels in the unilaterally adrenalectomized rats were lower than those in the sham-operated rats and did not increase after hemorrhagic shock. CONCLUSION: These results suggest that adrenocortical systems play an important role in hemorrhagic shock-induced SIA.

Effect of propofol on ropivacaine metabolism in human liver microsomes.

A combination of the general anesthetic propofol and epidural anesthesia with a local anesthetic is widely used. The metabolism of ropivacaine and that of lidocaine are mediated by similar P450 isoforms. Previously, propofol was found to inhibit the metabolism of lidocaine in vitro. Here we investigated whether propofol inhibits the metabolism of ropivacaine using human liver microsomes in vitro. Ropivacaine (6.0 micromol.l(-1)) as the substrate and propofol (1-100 micromol.l(-1)) were reacted together using human microsomes. The concentrations of ropivacaine and its major metabolite 2',6'-pipecoloxylidide (PPX) were measured using high-performance liquid chromatography. The metabolic activity of ropivacaine was reflected in the production of PPX. The inhibitory effects of propofol on ropivacaine metabolism were observed to be dose-dependent. The IC50 of propofol was 34.9 micromol.l(-1). Propofol shows a competitive inhibitory effect on the metabolism of ropivacaine (i.e., PPX production mediated by CYP3A4) in human CYP systems in vitro.

CYP2C19 genotype affects diazepam pharmacokinetics and emergence from general anesthesia.

OBJECTIVES: Diazepam is widely used to relieve preoperative anxiety in patients. The objective of this study was to investigate the effects of polymorphism in CYP2C19 and the effects of CYP3A4 messenger ribonucleic acid (mRNA) content in blood on recovery from general anesthesia and on diazepam pharmacokinetics. METHODS: Sixty-three Japanese patients were classified into the following 3 genotype (phenotype) groups on the basis of polymerase chain reaction-restriction fragment length polymorphism analysis of CYP2C19 polymorphism: no variants, *1/*1 (extensive metabolizer [EM]); 1 variant, *1/*2 or *1/*3 (intermediate metabolizer [IM]); and 2 variants, *2/*2, *2/*3, or *3/*3 (poor metabolizer [PM]). We assessed the effects of these polymorphisms and of CYP3A4 mRNA content in the lymphocytes on the patients' recovery from general anesthesia. RESULTS: CYP2C19 genotyping analysis in the 63 subjects showed that 32%, 46%, and 22% of subjects were classified into the EM, IM, and PM groups, respectively. The PM subjects showed a larger area under the curve representing the concentration of diazepam over a 24-hour period (AUC(0-24)) (2088 +/- 378 ng/mL.h(-1), P = .0259), lower clearance of diazepam (0.049 +/- 0.009 L.h(-1).kg(-1), P = .0287), and longer emergence time (median, 18 minutes; 25th-75th percentile range, 13-21 minutes; P < .001) in comparison with subjects in the EM group (AUC(0-24), 1412 +/- 312 ng/mL; clearance, 0.074 +/- 0.018 L.h(-1).kg(-1); and emergence time, 10 minutes, 8-12 minutes [median and 25th-75th percentile range]). The IM group also showed a longer emergence time (median, 13 minutes; 25th-75th percentile range, 9-20 minutes; P < .001) and a larger variation in this parameter in comparison with the EM group. The distributions of the CYP2C19 genotype were significantly different between the 2 groups (rapid emergence <20 minutes, slow emergence >20 minutes) (P = .0148). The mean value of the CYP3A4 mRNA level in the slow-emergence group (mean +/- SD, 4.80 +/- 3.99 x10(-10)) was significantly lower than that of the rapid-emergence group (mean +/- SD, 12.50 +/- 11.90 x10(-10)) (P = .0315). However, there was no significant correlation between emergence time and CYP3A4 mRNA levels (r = 0.239, P = .0601). CONCLUSION: We found that the CYP2C19 genotype affects diazepam pharmacokinetics and emergence from general anesthesia and that the slow-emergence group possesses lower levels of CYP3A4 mRNA than are found in the rapid-emergence group.

Liquid chromatographic determination of plasma ropivacaine for assessing pharmacokinetics of the viscous preparation.

We developed assay method for determination of plasma ropivacaine by using reversed-phase high performance liquid chromatography (HPLC) equipped with ordinary octadecylsilyl silica-gel (ODS) column. Plasma samples spiked with internal standard (bupivacaine) were treated by ethylacetate to extract ropivacaine and internal standard. The ropivacaine and internal standard separated on ODS column were detected by an ultra violet (UV) detector set at 215 nm. The mobile phase solvent consisted of acetonitrile, methanol and 0.05 M phosphate buffer adjusted to pH 4.0 (10 : 30 : 60, v/v) was pumped at a flow rate of 0.8 ml/min. The calibration curve of ropivacaine was linear at the concentration of 25-1,000 ng/ml (r=0.9998). The recoveries of ropivacaine from plasma were greater than 87.9% with the coefficient of variations (CVs) less than 6.1%. The CVs for intra- and inter-day assay of ropivacaine were 2.0-12.0% and 1.7-14.8%, respectively. This HPLC method was applied to determining plasma ropivacaine in two healthy subjects after receiving 0.5% ropivacaine viscous preparation, which was prepared in our hospital. Our preliminary pharmacokinetic data showed that ropivacaine viscous could be used safely based on the plasma ropivacaine concentrations (C(max): 89-125 ng/ml) for pain relief in oral mucosa.

[Case of premature ventricular contraction immediately after electroconvulsive therapy in a depressive patient].

A 42-year-old woman with eating disorder underwent electroconvulsive therapy (ECT) under general anesthesia with thiamylal 150 mg and suxamethonium 60 mg. On her fourth ECT procedure, premature ventricular contraction (PVC) occurred immediately after the treatment. We speculate that increased release of catecholamine by ECT and hypokalemia caused PVC. It seems that she repeated self-vomiting, because she had hypokalemia, metabolic alkalosis, and weight loss of 3 kg in two weeks before arrhythmia episode. We conclude that in the anesthetic management of patients undergoing ECT a careful attention should be given to body weight change and serum electrolyte care before ECT because it is easy to develop electrolyte abnormality by eating disorder of self-emetic type.