Identification of hypothermia-inducing neurons in the preoptic area and activation of them by isoflurane anesthesia and central injection of adenosine.

Hibernation and torpor are not passive responses caused by external temperature drops and fasting but are active brain functions that lower body temperature. A population of neurons in the preoptic area was recently identified as such active torpor-regulating neurons. We hypothesized that the other hypothermia-inducing maneuvers would also activate these neurons. To test our hypothesis, we first refined the previous observations, examined the brain regions explicitly activated during the falling phase of body temperature using c-Fos expression, and confirmed the preoptic area. Next, we observed long-lasting hypothermia by reactivating torpor-tagged Gq-expressing neurons using the activity tagging and DREADD systems. Finally, we found that about 40-60% of torpor-tagged neurons were activated by succeeding isoflurane anesthesia and by icv administration of an adenosine A1 agonist. Isoflurane-induced and central adenosine-induced hypothermia is, at least in part, an active process mediated by the torpor-regulating neurons in the preoptic area.

Randomized controlled trial of remimazolam compared with placebo in Japanese patients undergoing upper gastrointestinal endoscopy: Phase III investigator-initiated clinical trial.

OBJECTIVES: To assess the effectiveness of remimazolam against normal saline (placebo) as a sedative agent for endoscopy in a multicenter, randomized, double-blind, investigator-initiated phase III controlled trial. METHODS: We included 48 Japanese patients undergoing upper gastrointestinal endoscopy. For the procedure, an initial remimazolam dose of 3 mg and additional doses of 1 mg were administered, as determined in the phase II clinical study. The primary study end-point was the successful sedation rate during gastrointestinal endoscopy, determined as a Modified Observer's Assessment of Alertness/Sedation score ≤4 before the start of endoscopy, the completion of gastrointestinal endoscopy, and two or fewer additional doses per 6 min. RESULTS: The successful endoscopy sedation rates were 91.9% and 9.1% in the remimazolam and placebo groups, respectively (P < 0.01). The time from the end of endoscopy to arousal was 0.0 (0.0-0.0) min for both groups. The number of additional doses required to achieve sedation was lower in the remimazolam group than that in the placebo group (P < 0.01). CONCLUSIONS: Remimazolam demonstrated a significantly higher sedation effect during upper gastrointestinal endoscopy in Japanese patients with safe and fast recovery compared with placebo.

Comparison of a new EMG module, AF-201P, with acceleromyography using the post-tetanic counts during rocuronium-induced deep neuromuscular block: a prospective, multicenter study.

Recent advances in neuromuscular monitors have facilitated the development of a new electromyographic module, AF-201P™. The purpose of this study was to investigate the relationship between post-tetanic counts (PTCs) assessed using the AF-201P™ and the acceleromyographic TOF Watch SX™ during rocuronium-induced deep neuromuscular block. Forty adult patients consented to participate in this study. The integrated AF-201P™ stimulating and sensing electrode was placed over the ulnar nerve on the distal volar forearm and the belly of the abductor digiti minimi muscle of one arm. The TOF Watch SX™ was applied with the provided hand adaptor on the opposite arm, to observe twitch responses of the adductor pollicis muscle. After stabilization of train-of-four (TOF) responses, rocuronium 0.9 mg kg-1 was administered intravenously. Then, PTCs were observed every 3 min using both monitors. Whenever the TOF count was detected with the TOF Watch SX™, rocuronium 0.2 mg kg-1 was administered, and successive PTC measurements were continued. A total of 1732 paired PTC data points were obtained and analyzed. Regression analysis showed no significant difference in PTCs between the two monitors (PTCs measured by the TOF Watch SX™ = 0.78·PTCs measured by AF-201P™ + 0.21, R = 0.56). Bland-Altman analysis also showed acceptable ranges of bias [95% CI] and limits of agreement (0.3 [0.2 to 0.5] and - 4.6 to 5.3) for the PTCs. The new EMG module, AF-201P™, showed reliable PTCs during deep neuromuscular block, as well as the TOF Watch SX™.

Successful intrathecal neurolytic block for the management of cancer pain in a 10-year-old child: a case report.

BACKGROUND: Cancer pain management in children is challenging owing to their unique patient characteristics. We present the case of a 10-year-old girl whose cancer pain was successfully managed using an intrathecal neurolytic block. CASE PRESENTATION: The patient experienced severe cancer pain due to recurrent right ilium osteosarcoma. The tumor progressed rapidly despite chemoradiotherapy and gradually invaded the right lumbar plexus, which resulted in severe neuropathic pain in the right lower extremity. Systemic analgesics failed to attenuate the pain. We performed an intrathecal neurolytic block using 10% phenol-glycerol. The neurolytic block completely relieved her right lower extremity pain. After the block, the patient's quality of life improved, and she spent her time with family. CONCLUSIONS: The intrathecal neurolytic block successfully relieved the patient's cancer pain. Successful intrathecal neurolytic blocks require meticulous pain assessment of individual patients, to avoid possible serious complications such as paresis/paralysis and bladder/bowel dysfunction.

Transient Receptor Potential Ankyrin 1 Mediates Hypoxic Responses in Mice.

Transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation channel that is broadly expressed in sensory pathways, such as the trigeminal and vagus nerves. It is capable of detecting various irritants in inspired gasses and is activated during hypoxia. In this study, the role of TRPA1 in hypoxia-induced behavioral, respiratory, and cardiovascular responses was examined through four lines of experiments using TRPA1 knockout (KO) mice and wild type (WT) littermates. First, KO mice showed significantly attenuated avoidance behavior in response to a low (15%) oxygen environment. Second, the wake-up response to a hypoxic ramp (from 21 to 10% O2 in 40 s) was measured using EEG electrodes. WT mice woke up within 30 s when oxygen was at 13-14%, but KO mice did not wake up until oxygen levels reached 10%. Histological analysis confirmed that mild (13% O2) hypoxia resulted in an attenuation of trigeminal neuronal activation in KO mice. Third, the ventilatory response to hypoxia was measured with whole body plethysmography. KO mice showed attenuated responses to mild hypoxia (15% O2) but not severe hypoxia (10% O2). Similar responses were observed in WT mice treated with the TRPA1 blocker, AP-18. These data clearly show that TRPA1 is necessary for multiple mild hypoxia (13-15% O2)-induced physiological responses. We propose that TRPA1 channels in the sensory pathways innervating the airway can detect hypoxic environments and prevent systemic and/or cellular hypoxia from occurring.

Comparison of the MultiViewScope Stylet Scope and the direct laryngoscope with the Miller blade for the intubation in normal and difficult pediatric airways: A randomized, crossover, manikin study.

BACKGROUND: Managing difficult pediatric airway is challenging. The MultiViewScope (MVS) Stylet Scope is reported to be useful in difficult pediatric airway. In this randomized crossover study, we compared the effectiveness of the MVS Stylet Scope to a standard direct laryngoscope with Miller #1 blade in simulated normal and difficult airways. METHODS: Fifteen expert anesthesiologists and Fifteen anesthesiology residents participated in the study. Participants were asked to perform intubation with the Airsim Baby manikin first, and then with the Airsim Pierre Robin manikin. Participants in each group used the intubation devices in a randomized order. The primary outcome was the time of successful intubation. The secondary outcomes were the force exerted on the incisors during intubation, Cormack-Lehane scale, the difficulty of intubation. RESULTS: There were no differences between MVS Stylet Scope and Direct laryngoscope in the time of successful intubation by the expert anesthesiologists or the anesthesiology residents in a normal or difficult pediatric airway. MVS Stylet Scope significantly improved the force exerted on the incisors during intubation in the expert anesthesiologists or the anesthesiology residents in a normal or difficult pediatric airway. MVS Stylet Scope significantly improved Cormack-Lehane scale, and the difficulty of intubation with difficult pediatric airway situation in both expert anesthesiologists and anesthesiology residents. CONCLUSIONS: Although less forces on the incisors and improved view of glottis were observed with the MVS Stylet Scope, MVS Stylet Scope did not shorten the time of intubation. The results of this study mean that the MVS Stylet Scope may be a less invasive airway devise than the direct laryngoscope with the Miller blade in the pediatric airway management. For the next step, we need to evaluate the MVS Stylet Scope in the real patients as an observational study.

Effects of dexmedetomidine on lipopolysaccharide-induced acute kidney injury in rats and mitochondrial function in cell culture.

PURPOSE: To investigate the mechanisms through which dexmedetomidine (DEX) could improve the renal injury in lipopolysaccharide (LPS)-induced acute kidney injury (AKI) and examine how TNF-α or DEX might affect mitochondrial function and renal injury. METHODS: In vivo experiments involved 24 rats randomly allocated to a sham group, an LPS group, and an LPS + DEX group. Serum creatinine, lactate, TNF-α, IL-1ß, and IL-6 concentrations, as well as urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, were measured 0, 3, and 6 h after the start of the experiments. Histopathological examinations were performed to determine the extent of LPS-induced renal injury and recovery by administration of DEX. in vitro, human embryonic kidney 293 cells were treated with or without (control) several concentrations of TNF-α and DEX for 24 h before measurements of the oxygen consumption rate (OCR) under basal conditions and with the addition of oligomycin, carbonylcyanide-p-trifluoromethoxyphenylhydrazone, antimycin A, and rotenone, as well as intracellular reactive oxygen species (ROS) levels. RESULTS: DEX attenuated LPS-induced increases in serum creatinine and IL-6 concentrations. LPS administration caused histological tissue damage in the kidney, but DEX prevented such damage. In vitro, DEX suppressed TNF-α-induced increases in basal OCR and ROS levels and inhibited decreases of ATP production induced by TNF-α. CONCLUSION: DEX has protective effects for cells and tissues of the kidney by inhibiting oxygen consumption and hypoxia or by improving mitochondrial dysfunction via TNF-α in the renal cells. These results might point to DEX being an important new therapeutic target for the treatment of septic AKI.

The effects of hemodynamic management using the trend of the perfusion index and pulse pressure variation on tissue perfusion: a randomized pilot study.

BACKGROUND: Intraoperative hemodynamic management is challenging because precise assessment of the adequacy of the intravascular volume is difficult during surgery. Perfusion index (PI) has been shown to reflect changes in peripheral circulation perfusion. Pulse pressure variation (PPV) reflects the preload responsiveness. The hypothesis of this study was that hemodynamic management using the trend of the PI and PPV would improve tissue perfusion. METHODS: This was a prospective, randomized, parallel design, single-blind, single-center pilot study. Patients undergoing elective open gynecological surgery requiring a direct arterial line were included. The patients were randomly allocated to two groups. The intervention group received hemodynamic management using the trend of the PI and PPV in an effort to improve tissue perfusion. The control group received hemodynamic management at the discretion of the anesthesia care provider. The primary outcome was the peak lactate level during surgery. The secondary outcomes were the duration of hypotension, intraoperative fluid balance, intraoperative urine output, and postoperative complication rate. Statistical analysis was performed using Student's t test and Fisher's exact test. A P value of < 0.05 was considered statistically significant. RESULTS: Although the intervention significantly decreased the duration of hypotension and intraoperative fluid balance, the peak lactate level was not different between the intervention group and the control group. Intraoperative urine output and postoperative complication rate were not different between the groups. CONCLUSION: Hemodynamic management using the trend of the PI and PPV does not improve tissue perfusion in patients undergoing open gynecological surgery. TRIAL REGISTRATION: This trial was prospectively registered on a publicly accessible database (UMIN Clinical Trials Registry ID: UMIN 000026957. Registered 12 April 2017, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000030916 ).

Effects of Landiolol in Lipopolysaccharide-Induced Acute Kidney Injury in Rats and In Vitro.

The mechanisms by which landiolol, an ultra-short-acting, selective ß-1 blocker, could improve septic acute kidney injury and how inflammation might affect mitochondrial function and cause the renal injury were examined. Male Wistar rats (250 g-300 g) were randomly allocated to three groups: a sham control group (n = 8); a lipopolysaccharide (LPS) group (n = 8); and an LPS + landiolol group (n = 8). LPS was administered intravenously at the start of the experiments; the LPS + landiolol group rats received LPS and continuous intravenous landiolol. Serum creatinine and lactate concentrations and hemodynamic parameters were measured 3 and 6 h after the experiments started. TNF-α, IL-1ß, and IL-6 levels and urinary 8-OHdG concentrations were determined. The extent of LPS-induced renal injury and recovery with landiolol were examined histopathologically. Metabolic analysis in human embryonic kidney cells was performed using Seahorse analysis. The effects of landiolol on cytokine-induced mitochondrial stress and glycolytic stress were examined. Treatment with landiolol was shown to normalize serum creatinine and lactate levels following intravenous LPS administration (Cr: LPS group 0.8 ±â€Š0.6 mg/mL, LPS + landiolol group 0.5 ±â€Š0.1 mg/mL; P < 0.05). In the in vitro experiments, TNF-α induced an increase in mitochondrial oxygen consumption, which was attenuated by landiolol, which could represent a mechanism for renal protection. Landiolol may have protective effects on the cells and tissues of the kidney by inhibiting oxygen consumption and hypoxia caused by TNF-α in renal cells. These results suggest that landiolol may be an important new therapeutic target for treating inflammation-associated kidney injury.

Heme oxygenase-1 inducer and carbon monoxide-releasing molecule enhance the effects of gabapentinoids by modulating glial activation during neuropathic pain in mice.

INTRODUCTION: Neuropathic pain is one of the most difficult-to-treat symptoms. Although gabapentinoids are classified as first-line drugs, they have only modest efficacy. OBJECTIVES: The aim of this study was to investigate whether treatment with the heme oxygenase-1 (HO-1) inducer cobalt protoporphyrin IX (CoPP) or the carbon monoxide-releasing molecule tricarbonyldichlororuthenium (II) dimer (CORM-2) can enhance the antinociceptive effects produced by gabapentinoids in mice with neuropathic pain. METHODS: Neuropathic pain was induced by spared nerve injury (SNI) of the sciatic nerve. The mechanical threshold was tested using von Frey filaments. The expression of spinal HO-1, HO-2, the Ca2+ channel α2δ1 subunit, microglial markers, and M1 or M2 microglial markers was examined using reverse transcription polymerase chain reaction. RESULTS: Treatment with CoPP or CORM-2 alleviated mechanical allodynia induced by SNI. CoPP or CORM-2 enhanced the antiallodynic effects of gabapentinoids (pregabalin or gabapentin) during SNI-induced mechanical allodynia. HO-1 inhibitor tin protoporphyrin IX (SnPP) prevented the antiallodynic effects of gabapentinoids (pregabalin or gabapentin) during SNI-induced mechanical allodynia. CoPP or CORM-2 increased HO-1 and Ca2+ channel α2δ1 subunit gene expression and the decreased gene expression of microglial markers, M1 microglial marker, or tumor necrosis factor in the ipsilateral spinal dorsal horn of mice with SNI. SnPP prevented HO-1 induction and glial inhibition, which were produced by gabapentinoids during SNI-induced mechanical allodynia. CONCLUSIONS: This study suggests that HO-1 plays crucial roles in the antiallodynic effects of gabapentinoids. Gabapentinoids attenuate the glial activation induced by SNI and some of these effects are mediated by HO-1.

Linalool Odor-Induced Anxiolytic Effects in Mice.

In folk medicine, it has long been believed that odorous compounds derived from plant extracts can have anxiolytic effects. Among them, linalool, one of the terpene alcohols in lavender extracts, has been reported to have the anxiolytic effects. However, the anxiolytic nature of the linalool odor itself as well as its potential action through the olfactory system has not been thoroughly examined. In this study, we examined the anxiolytic effects of linalool odor with light/dark box test and with elevated plus maze (EPM), and found that linalool odor has an anxiolytic effect without motor impairment in mice. The effect was not observed in anosmic mice, indicating that it was triggered by olfactory input evoked by linalool odor. Furthermore, the effect was antagonized by flumazenil, indicating that the linalool odor-induced anxiolytic effect was mediated by γ-aminobutyric acid (GABA)ergic transmission via benzodiazepine (BDZ)-responsive GABAA receptors. These results provide information about the potential central neuronal mechanisms underlying the odor-induced anxiolytic effects and the foundation for exploring clinical application of linalool odor in anxiety treatments.

Evaluation of the pharyngeal airway using computational fluid dynamics in patients with acromegaly.

OBJECTIVES: Perioperative airway management may be particularly challenging in patients with acromegaly undergoing trans-sphenoidal pituitary surgery (TSS). Management for airway obstruction is required prior to pituitary surgery to minimize perioperative hypoxia. The purpose of this retrospective study was to evaluate airway obstruction by simulation of computational fluid dynamics (CFD) using computed tomography (CT) images in patients who had undergone TSS. METHODS: CT images of the nasopharyngeal airways of patients with acromegaly (n = 5) or nonfunctional pituitary adenoma (n = 6) undergoing TSS from April 2012 to January 2017 were used to construct these airways in three dimensions. Estimated airflow pressure and velocity in the retropalatal airway (RA), oropharyngeal airway (OA), and hypopharyngeal airway (HA) were simulated using CFD. RESULTS: Estimated pharyngeal airflow pressure in the HA, OA, and RA was significantly greater in patients with acromegaly than in those with nonfunctional pituitary adenomas whereas the estimated pharyngeal airflow velocity was significantly impaired only in the RA of patients with acromegaly. Minimum postoperative SpO2 both within 3 hours and from 3 to 12 hours after the end of anesthesia was significantly lower in the patients with acromegaly. Additionally, estimated volume of tongue and pharyngeal airflow pressure in the HA, OA, and RA correlated with minimum postoperative SpO2. CONCLUSION: Pharyngeal airflow pressure estimated from CT images is high in patients with acromegaly, and these values correlate with postoperative minimum values for SpO2. Preoperative evaluation of CT images by CFD can predict difficulty in airway management and perioperative hypoxia. LEVEL OF EVIDENCE: 4.

Phenylephrine does not improve oxygenation during one-lung ventilation: A randomized, double-blind, cross-over study.

BACKGROUND: Phenylephrine is an α1 adrenergic receptor agonist that causes pulmonary vasoconstriction, and so may effectively enhance hypoxic pulmonary vasoconstriction (HPV). However, there is little evidence that phenylephrine augments HPV in clinical situations. This study aimed to evaluate the clinical effects of phenylephrine infusion on oxygenation during one-lung ventilation (OLV) in patients undergoing thoracic surgery. METHODS: This was a prospective, randomized, double-blind, cross-over study. Included patients were those undergoing elective thoracic surgery in the lateral decubitus position with OLV. Patients were randomly allocated to two groups. The N-P group initially had OLV with normal saline infusion for 30 minutes; after a 10 minute interval, OLV was then maintained with phenylephrine infusion for 30 minutes. The P-N group had the drug-infusion in the reverse order. The primary outcome was arterial partial pressure of oxygen. Secondary outcomes were mean arterial pressure, heart rate, pulse pressure variation, perfusion index, and difference between bladder and skin temperature. Statistical analysis was performed using the student t-test, Fisher's exact test, and ANOVA for Cross-over design. P < 0.05 was considered statistically significant. RESULTS: Twenty-nine patients were analyzed. Although phenylephrine infusion significantly increased mean arterial pressure (P < 0.001), arterial partial pressure of oxygen did not differ between the two timepoints (P = 0.19). There was no carryover effect in arterial partial pressure of oxygen (P = 0.14). Phenylephrine infusion significantly decreased heart rate (P = 0.02) and pulse pressure variation (P < 0.001). CONCLUSIONS: Phenylephrine infusion did not improve oxygenation during OLV. The present results indicate that phenylephrine does not have clinically meaningful effects on HPV. TRIAL REGISTRATION: University Hospital Medical Information Network 000024317.

Difficult airway associated with bifid glottis and coexistent subglottic stenosis in a patient with Pallister-Hall syndrome: a case report.

BACKGROUND: Pallister-Hall syndrome is a rare disorder characterized by hypothalamic hamartoma, hypopituitarism, bifid epiglottis, and micrognathia. CASE PRESENTATION: We describe the airway management under general anesthesia of a 15-year-old female with Pallister-Hall syndrome whose airway was compromised with bifid epiglottis and acquired subglottic stenosis. The three options considered for airway management were tracheal intubation, a supraglottic device, and surgical tracheotomy. Tracheal intubation provides a secured airway, but extubation can be difficult. A supraglottic device minimizes airway injury, but it does not completely protect the airway from aspiration. CONCLUSIONS: The patient's airway was successfully managed using a supraglottic device with aspiration prophylaxis. Airway management devices should be selected according to each patients' individual circumstances.

Unsuccessful tracheal intubation in a patient with Kniest dysplasia undergoing repeated general anesthesia: a case report.

BACKGROUND: Kniest dysplasia is a type of chondrodysplasia characterized by severe craniofacial abnormalities including tracheomalacia, midface hypoplasia, and cleft palate. CASE PRESENTATION: We previously described a 6-year-old girl with Kniest dysplasia, in whom glottic edema rapidly developed after tracheal intubation. At the age of 13 years, a reoperation was scheduled to correct talipes equinovarus but was subsequently canceled due to failure of tracheal intubation and subsequent glottic edema. Airway evaluation by endoscopy and computed tomography 1 month later revealed severe laryngeal narrowing. Therefore, the second anesthesia was maintained with spinal anesthesia combined with sciatic nerve block without tracheal intubation. CONCLUSION: Careful perioperative airway evaluation is required in patients with Kniest dysplasia, and alternative strategies for airway management other than tracheal intubation should be considered.

Orexin Receptor Blockade-Induced Sleep Preserves the Ability to Wake in the Presence of Threat in Mice.

Retention of the ability to wake from sleep in response to dangerous situations is an ideal characteristic of safe hypnotics. We studied the effects of a dual orexin receptor antagonist-22 (DORA-22) and the GABA-A receptor modulator, triazolam, on the ability to wake in response to aversive stimuli. We examined four modalities of sensory inputs, namely, auditory (ultrasonic sound), vestibular (trembling), olfactory (predator odor), and autonomic (hypoxia) stimuli. When the mice fell asleep, one of the four stimuli was applied for 30 s. In the case of auditory stimulation, latency to arousal following vehicle, DORA-22, and triazolam administration was 3.0 (2.0-3.8), 3.5 (2.0-6.5), and 161 (117-267) s (median and 25-75 percentile in the parentheses, n = 8), respectively. Latency to return to sleep after arousal was 148 (95-183), 70 (43-98), and 60 (52-69) s, respectively. Similar results were obtained for vestibular and olfactory stimulation. During the hypoxic stimulation, latencies for arousal and returning to sleep were not significantly different among the groups. The findings of this study are consistent with the distinct mechanisms of these sleep promoting therapies; GABA-A receptor activation by triazolam is thought to induce widespread central nervous system (CNS) suppression while DORA-22 more specifically targets sleep/wake pathways through orexin receptor antagonism. These data support the notion that DORA-22 preserves the ability to wake in response to aversive and consciousness-inducing sensory stimuli, regardless of modality, while remaining effective in the absence of threat. This study provides a unique and important safety evaluation of the potential for certain hypnotics.

Contralateral cerebral hemoglobin oxygen saturation changes in patients undergoing thoracotomy with general anesthesia with or without paravertebral block: a randomized controlled trial.

PURPOSE: Perioperative analgesia during thoracotomy is often achieved by combining paravertebral block (PVB) with general anesthesia (GA). Functional near-infrared spectroscopy (NIRS) can detect changes in cerebral oxygenation resulting from nociceptive stimuli in the awake state or under sedation. We used NIRS to measure changes in cerebral blood flow provoked by thoracotomy incision made under GA and determine how these changes were influenced by supplementation of GA with PVB. METHODS: Thirty-four patients undergoing elective thoracotomy were enrolled. Patients were randomly assigned to a group receiving only GA, or GA combined with PVB (GA + PVB). Changes in cerebral oxygenated hemoglobin (ΔO2Hb), deoxygenated-Hb (ΔHHb), and total-Hb (ΔtotalHb) were evaluated by NIRS as surgery began. RESULTS: In the GA group, ΔO2Hb was significantly higher in the hemisphere contralateral to the side of surgery when the incision was made and 2 min after incision compared with the ipsilateral side (start of surgery, P < 0.01; 2 min, P < 0.05). In contrast, there were no significant changes in the ΔO2Hb at any of the time points in the GA + PVB group. Comparable with ΔO2Hb, the concentration of ΔtotalHb was significantly higher in the contralateral hemisphere in the GA group at the start of surgery (P < 0.05). CONCLUSIONS: Changes in the cerebral O2Hb concentration were detected by NIRS immediately after surgical incision under GA, but not in the presence of a PNB. NIRS could be used to monitor surgical pain. PVB inhibited changes in oxygenation induced by incision-provoked pain.

Application of calibrated forceps for assessing mechanical nociception with high time resolution in mice.

In order to investigate the basic physiological mechanisms of pain and the anti-nociceptive effects of analgesics, development of pain assays in mice is critical due to the advances of genetic manipulation techniques. The von Frey hairs/Semmes-Weinstein monofilaments test (von Frey test) has long been applied to examine mechanical nociception in mice. Though the von Frey test is a well-established and standardized method, it is inappropriate to assess a rapid change in the nociceptive threshold because voluntary resting/sleeping states are necessary to examine the response. In this study, we assessed the effectiveness of calibrated forceps to determine the mechanical nociceptive threshold in mice. Repeated daily measurements of the threshold over 5 days indicated that the device obtained stable and reliable values. Furthermore, repeated measurements with 5 minute intervals revealed that the device detected the rapid change of the threshold induced by remifentanil, a short-acting µ-receptor agonist. These results indicate that the calibrated forceps are well-suited for measuring the mechanical nociceptive threshold in mice, and are useful in assessing the effects of short-acting analgesics on mechanical nociception.

A Case of Sudden Shock during Caesarean Section in whi ch Amniotic Fluid Embolism is Suspected.

We report a case of sudden shock during caesarean section under combined spinal epidural anesthesia. The patient was a 29-year-old woman. During the operation vital signs had been almost stable until a female-baby was born. But after the delivery of the placenta, the patient developed an episode of coughing and dyspnea followed by unconsciousness and bradycardia. She was given adrenaline and intubated, appearing ventricular fibrillation on a EKG. Cardiopulmonary resuscitation was immediately started and sinus rhythm returned. Hypotension followed and a small dose of adrenaline was infused for three days. She made good progress and was discharged without significant sequela. Cardiopulmonary collapse type of amniotic fluid embolism (AFE) is doubtful in this case. The necessity of rapid and appropriate treatment for emergency obstetric cases was discussed.