The arousal level of consciousness required for working memory performance: An anaesthesia study.

Regarding the stage of arousal level required for working memory to function properly, limited studies have been conducted on changes in working memory performance when the arousal level of consciousness decreases. This study aimed to experimentally clarify the stages of consciousness necessary for optimal working memory function. In this experiment, the sedation levels were changed step-by-step using anaesthesia, and the performance accuracy during the execution of working memory was assessed using a dual-task paradigm. Participants were required to categorize and remember words in a specific target category. Categorization performance was measured across four different sedative phases: before anaesthesia (baseline), and deep, moderate and light stages of sedation. Short-delay recognition tasks were performed under these four sedative stages, followed by long-delay recognition tasks after participants recovered from sedation. The results of the short-delay recognition task showed that the performance was lowest at the deep stage. The performance of the moderate stage was lower than the baseline. In the long-delay recognition task, the performance under moderate sedation was lower than that under baseline and light sedation. In addition, the performance under light sedation was lower than that under baseline. These results suggest that task performance becomes difficult under half sedation and that transferring information to long-term memory is difficult even under one-quarter sedation.

Moderate sedation induced by general anaesthetics disrupts audio-spatial feature binding with sustained P3 components in healthy humans.

Feature binding is considered to be the basis for conscious stimulus perception, while anaesthetics exert a gradient effect on the loss of consciousness (LOC). By integrating these two streams of research, the present study assessed the effect of two anaesthetic agents (i.e. propofol and midazolam) on audio-spatial feature binding. We also recorded the electrophysiological activity of the frontal channels. Using pharmacokinetic simulation, we determined the effect-site concentration (Ce) of the anaesthetics at loss of response to verbal command and eyelash reflex. We subsequently adjusted Ce to 75%, 50% and 25% of Ce-LOC to achieve deep, moderate and light sedation, respectively. Behavioural results showed that moderate sedation selectively disrupted feature binding. The frontal channels showed a P3 component (350-600 ms peristimulus period) following the presentation of audio-spatial stimuli at baseline and under moderate and light sedations. Critically, the late event-related potential component (600-1000 ms) returned to the pre-activated level (0-350 ms) at baseline and under light sedation but was sustained under moderate sedation. We propose that audio-spatial feature binding may require the presence of a P3 component and its subsequent and sufficient decline, as under anaesthetic-induced moderate sedation the P3 component was sustained and featured binding was impaired.

Effects of sedation on subjective perception of pain intensity and autonomic nervous responses to pain: A preliminary study.

Rather than relying solely on subjective pain evaluation using means such as the visual analogue scale (VAS), in clinical situations it is possible to observe evoked responses of the autonomic nervous system (ANS) as objective indicators. Few studies, however, have reported these relationships under finely controlled sedation. 16 healthy male participants were administrated in intravenous sedation with either propofol or midazolam randomly. We initially determined, using pharmacokinetic simulation, the effect-site concentration (Ce) of anaesthetic at loss of response to verbal command and eyelash reflex (Ce-LOR). Then subsequently adjusted Ce to 75%, 50%, and 25% of Ce-LOR to achieve deep, moderate, and light sedation. At awake control state and each sedation level, a noxious electrical stimulation was applied three times at the right forearm, an average pain intensity of the three stimuli was rated on a VAS (0-10). Changes in the peripheral perfusion index measured by oximetry were used as an indicator of ANS response. We analyzed the influence of sedation level on VAS and ANS responses compared to the awake control state. While ANS responses were similar in all conditions, VAS was statistically significantly lower in moderate (5.6±0.6, p <0.005) or deep (5.3±0.6, p <0.001) sedation than in the awake state (7.2±0.4). This study revealed that even when the ANS responds similarly to the same stimulation, subjective pain perception is attenuated by sedation. A cerebral mechanism other than that of the brainstem might determine subjective pain intensity.

Age-related and sex-related changes in perfusion index in response to noxious electrical stimulation in healthy subjects.

BACKGROUND: Even though pain is a subjective phenomenon, its objective evaluation in humans is important because subjects requiring pain evaluation may be unable to describe their pain intensity because of decreased awareness or impaired cognitive function. Previous reports indicate that the perfusion index (PI), which is calculated from pulse oximeter waveforms, has some utility in assessing pain. However, age-associated and sex-associated differences in change of PI have hitherto not been evaluated for assessment of pain. Therefore, we aimed to estimate the utility of age-related differences in PI change among healthy volunteers subjected to electrical stimulation. METHODS: We measured PI and pulse rate in 70 healthy volunteers exposed to gradually increasing electrical stimulation. The subjects were classified into four groups, ie, young men, young women, aged men, and aged women. Stimulation was stopped when subjects reached their pain tolerance threshold. The average PI and pulse rate were calculated 10 seconds before and after electrical stimulation and compared across the four groups. Changes in PI and pulse rate were analyzed using the paired t-test. RESULTS: The PI was significantly decreased in response to pain stimulation in young men (P<0.0001), young women (P=0.0002), and aged men (P=0.0158). However, aged women failed to show significant changes in PI before or after stimulation. The pulse rate was not significantly altered in any of the groups. CONCLUSION: PI may be an independent parameter reflecting the perception of noxious stimuli and could be used for objective evaluation of pain perception in healthy volunteers, except when it is used for pain evaluation in elderly women.

Antinociceptive effects of mirtazapine, pregabalin, and gabapentin after chronic constriction injury of the infraorbital nerve in rats.

AIMS: To clarify the antiallodynic effects of the α2-adrenergic receptor antagonist mirtazapine compared with those of gabapentin and pregabalin in a rat model of orofacial neuropathic pain. METHODS: Mirtazapine (10, 30, and 100 µg), gabapentin (10, 30, and 100 µg), and pregabalin (3, 10, and 30 µg) were administered intrathecally to eight male Sprague-Dawley rats with orofacial neuropathic pain induced by chronic constriction injury of the infraorbital nerve that had been carried out 2 weeks previously. Stimulation using von Frey filaments (1.0 to 15.0 g) applied to skin innervated by the injured infraorbital nerve enabled the measurement of mechanical thresholds 0 to 180 minutes after drug injection. Time-course data for the dose-response effects were analyzed using two-way analysis of variance and the posthoc Tukey-Kramer multiple-comparison test. RESULTS: Intrathecal administration of not only gabapentin and pregabalin but also mirtazapine reversed the lowered mechanical nociceptive thresholds produced by the nerve injury. The ED50 (95% confidence interval) was (in µg) 49.00 (39.71-58.29) for mirtazapine, 54.84 (46.12-63.56) for gabapentin, and 13.47 (11.24-15.69) for pregabalin. CONCLUSION: Intraspinal administration of either mirtazapine, gabapentin, or pregabalin reverses the lowered facial mechanical thresholds produced in a rat model of trigeminal neuropathic pain.

A meta-analysis of hypnosis for chronic pain problems: a comparison between hypnosis, standard care, and other psychological interventions.

Hypnosis is regarded as an effective treatment for psychological and physical ailments. However, its efficacy as a strategy for managing chronic pain has not been assessed through meta-analytical methods. The objective of the current study was to conduct a meta-analysis to assess the efficacy of hypnosis for managing chronic pain. When compared with standard care, hypnosis provided moderate treatment benefit. Hypnosis also showed a moderate superior effect as compared to other psychological interventions for a nonheadache group. The results suggest that hypnosis is efficacious for managing chronic pain. Given that large heterogeneity among the included studies was identified, the nature of hypnosis treatment is further discussed.

[Sugammadex reversal after extubation under muscle relaxation to prevent cough reflex in a patient with intractable spontaneous pneumothorax].

A 40-year-old man (168 cm tall and weighing 71 kg) with intractable pneumothorax was operated for resection of a bulla in the left lung. After insertion of epidural catheter via T 5-6 interspace, general anesthesia was induced and maintained with propofol, remifentanil and rocuronium. The duration of surgery was 1h 48 min and rocuronium given during surgery was 110 mg. After completion of surgery, the double-lumen tube was replaced with laryngeal mask airway to prevent cough reflex. However, infusion of sugammadex 200 mg induced mild cough reflex, resulting in air leakage from thoracic drainage. Because air leakage still continued after extubation, reoperation must be done and re-intubation was required. Since rocuronium 50 mg did not provide satisfactory muscle relaxation measured by train of four, additional dose of rocuronium 40 mg was administered and re-intubation was successfully performed without cough reflex. Reoperation lasted for 43 minutes and rocuronium infused was 100 mg. Nasal airway was inserted to prevent airway obstruction by the tongue and extubation was performed under muscle relaxation with infusion of rocuronium 10 mg. And then, immediate administration of sugammadex 400 mg could elicit spontaneous respiration without cough reflex.

The influence of working memory capacity on experimental heat pain.

UNLABELLED: Pain processing and attention have a bidirectional interaction that depends upon one's relative ability to use limited-capacity resources. However, correlations between the size of limited-capacity resources and pain have not been evaluated. Working memory capacity, which is a cognitive resource, can be measured using the reading span task (RST). In this study, we hypothesized that an individual's potential working memory capacity and subjective pain intensity are related. To test this hypothesis, we evaluated 31 healthy participants' potential working memory capacity using the RST, and then applied continuous experimental heat stimulation using the listening span test (LST), which is a modified version of the RST. Subjective pain intensities were significantly lower during the challenging parts of the RST. The pain intensity under conditions where memorizing tasks were performed was compared with that under the control condition, and it showed a correlation with potential working memory capacity. These results indicate that working memory capacity reflects the ability to process information, including precise evaluations of changes in pain perception. PERSPECTIVE: In this work, we present data suggesting that changes in subjective pain intensity are related, depending upon individual potential working memory capacities. Individual working memory capacity may be a phenotype that reflects sensitivity to changes in pain perception.

Propofol exerts anti-inflammatory effects in rats with lipopolysaccharide-induced acute lung injury by inhibition of CD14 and TLR4 expression.

We investigated the effect of propofol (Prop) administration (10 mg kg-1 h-1, intravenously) on lipopolysaccharide (LPS)-induced acute lung injury and its effect on cluster of differentiation (CD) 14 and Toll-like receptor (TLR) 4 expression in lung tissue of anesthetized, ventilated rats. Twenty-four male Wistar rats were randomly divided into three groups of 8 rats each: control, LPS, and LPS+Prop. Lung injury was assayed via blood gas analysis and lung histology, and tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels were determined in bronchoalveolar lavage fluid using ELISA. Real-time polymerase chain reaction was used to detect CD14 and TLR4 mRNA levels, and CD14 and TLR4 protein expression was determined by Western blot. The pathological scores were 1.2 ± 0.9, 3.3 ± 1.1, and 1.9 ± 1.0 for the control, LPS, and LPS+Prop groups, respectively, with statistically significant differences between control and LPS groups (P < 0.05) and between LPS and LPS+Prop groups (P < 0.05). The administration of LPS resulted in a significant increase in TNF-α and IL-1ß levels, 7- and 3.5-fold, respectively (P < 0.05), while treatment with propofol partially blunted the secretion of both cytokines (P < 0.05). CD14 and TLR4 mRNA levels were increased in the LPS group (1.48 ± 0.05 and 1.26 ± 0.03, respectively) compared to the control group (1.00 ± 0.20 and 1.00 ± 0.02, respectively; P < 0.05), while propofol treatment blunted this effect (1.16 ± 0.05 and 1.12 ± 0.05, respectively; P < 0.05). Both CD14 and TLR4 protein levels were elevated in the LPS group compared to the control group (P < 0.05), while propofol treatment partially decreased the expression of CD14 and TLR4 protein versus LPS alone (P < 0.05). Our study indicates that propofol prevents lung injury, most likely by inhibition of CD14 and TLR4 expression.

Propofol exerts anti-inflammatory effects in rats with lipopolysaccharide-induced acute lung injury by inhibition of CD14 and TLR4 expression

We investigated the effect of propofol (Prop) administration (10 mg kg-1 h-1, intravenously) on lipopolysaccharide (LPS)-induced acute lung injury and its effect on cluster of differentiation (CD) 14 and Toll-like receptor (TLR) 4 expression in lung tissue of anesthetized, ventilated rats. Twenty-four male Wistar rats were randomly divided into three groups of 8 rats each: control, LPS, and LPS+Prop. Lung injury was assayed via blood gas analysis and lung histology, and tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels were determined in bronchoalveolar lavage fluid using ELISA. Real-time polymerase chain reaction was used to detect CD14 and TLR4 mRNA levels, and CD14 and TLR4 protein expression was determined by Western blot. The pathological scores were 1.2 ± 0.9, 3.3 ± 1.1, and 1.9 ± 1.0 for the control, LPS, and LPS+Prop groups, respectively, with statistically significant differences between control and LPS groups (P < 0.05) and between LPS and LPS+Prop groups (P < 0.05). The administration of LPS resulted in a significant increase in TNF-α and IL-1β levels, 7- and 3.5-fold, respectively (P < 0.05), while treatment with propofol partially blunted the secretion of both cytokines (P < 0.05). CD14 and TLR4 mRNA levels were increased in the LPS group (1.48 ± 0.05 and 1.26 ± 0.03, respectively) compared to the control group (1.00 ± 0.20 and 1.00 ± 0.02, respectively; P < 0.05), while propofol treatment blunted this effect (1.16 ± 0.05 and 1.12 ± 0.05, respectively; P < 0.05). Both CD14 and TLR4 protein levels were elevated in the LPS group compared to the control group (P < 0.05), while propofol treatment partially decreased the expression of CD14 and TLR4 protein versus LPS alone (P < 0.05). Our study indicates that propofol prevents lung injury, most likely by inhibition of CD14 and TLR4 expression.

Continuous femoral versus epidural block for attainment of 120° knee flexion after total knee arthroplasty: a randomized controlled trial.

We conducted the prospective randomized controlled trial to test that continuous femoral nerve block (CFNB) improves attainment of 120° knee flexion compared to continuous epidural analgesia (CEA). Sixty-six patients scheduled for unilateral total knee arthroplasty were randomized into two groups; infusion of ropivacaine 0.15% into CEA or CFNB to third postoperative days. We studied the time required to attain 120° knee flexion, variations in thigh and calf circumferences around the treated knee, pain scores, rehabilitation milestones, the need for adjuvant analgesics, and side effects. CFNB patients attained earlier knee flexion to 120°, lower variations in thigh and calf circumferences, less pain during rehabilitation, and less need for adjuvant analgesics. CFNB is a better pain management strategy that accelerates knee flexion rehabilitation.

The comparison of spontaneous breathing and muscle paralysis in two different severities of experimental lung injury.

OBJECTIVES: The benefits of spontaneous breathing over muscle paralysis have been proven mainly in mild lung injury; no one has yet evaluated the effects of spontaneous breathing in severe lung injury. We investigated the effects of spontaneous breathing in two different severities of lung injury compared with muscle paralysis. DESIGN: Prospective, randomized, animal study. SETTING: University animal research laboratory. SUBJECTS: Twenty-eight New Zealand white rabbits. INTERVENTIONS: Rabbits were randomly divided into the mild lung injury (surfactant depletion) group or severe lung injury (surfactant depletion followed by injurious mechanical ventilation) group and ventilated with 4-hr low tidal volume ventilation with spontaneous breathing or without spontaneous breathing (prevented by a neuromuscular blocking agent). Inspiratory pressure was adjusted to control tidal volume to 5-7 mL/kg, maintaining a plateau pressure less than 30 cm H2O. Dynamic CT was used to evaluate changes in lung aeration and the regional distribution of tidal volume. MEASUREMENTS AND RESULTS: In mild lung injury, spontaneous breathing improved oxygenation and lung aeration by redistribution of tidal volume to dependent lung regions. However, in severe lung injury, spontaneous breathing caused a significant increase in atelectasis with cyclic collapse. Because of the severity of lung injury, this group had higher plateau pressure and more excessive spontaneous breathing effort, resulting in the highest transpulmonary pressure and the highest driving pressure. Although no improvements in lung aeration were observed, muscle paralysis with severe lung injury resulted in better oxygenation, more even tidal ventilation, and less histological lung injury. CONCLUSIONS: In animals with mild lung injury, spontaneous breathing was beneficial to lung recruitment; however, in animals with severe lung injury, spontaneous breathing could worsen lung injury, and muscle paralysis might be more protective for injured lungs by preventing injuriously high transpulmonary pressure and high driving pressure.

Serotonin 2C receptor alternative splicing in a spinal cord injury model.

Spinal cord injury can have debilitating consequences, commonly resulting in motor dysfunction below the lesion site and the development of chronic pain syndromes. The serotonin pathway is important for inhibiting noxious stimuli and facilitating motor function after spinal cord injury. The serotonin 2C receptor (5HTR2C) has several characteristic features, and is regulated by the amount of serotonin 2C receptor as well as RNA editing and alternative splicing. In this study, we used a rat model of spinal contusion injury to investigate the relationship between the pain threshold and 5HTR2C alternative splicing. The pain threshold was assessed using mechanical stimulation with von Frey filaments. We then used real-time PCR to examine the RNA levels of 5HTR2C in three sections of the spinal cord: the rostral, injury-core, and caudal positions. On postoperative day 12, the pain threshold in injured rats was significantly reduced compared with sham-operated and naïve rats. The total 5HTR2C levels were significantly lower in injured rats than in naïve rats at all positions, and significantly lower in injured rats compared with sham-operated rats at injury-core and caudal positions. The ratio of exon Vb-skipped nonfunctional 5HTR2C mRNA to total 5HTR2C was significantly higher in injured rats compared with naïve rats at the injury-core and caudal positions, and significantly higher in injured rats compared with sham-operated rats at the caudal position. These results indicate that spinal contusion injury, which causes neuropathic pain, induces serotonergic dysfunction. This dysfunction appears to be mediated by decreased 5HTR2C mRNA expression, and alternative splicing. These results confirm the importance of considering splice variants when examining 5HTR2C.

[Management of aneurysmal subarachnoid hemorrhage].

The annual incidence of aneurysmal subarachnoid hemorrhage (SAH) is approximately 20 per 100,000/ year in Japan, and it is suggested that approximately 40% of SAH patients have poor outcome. Rebleeding after SAH and delayed cerebral vasospasm are the most important causes of poor outcomes. Particularly, rebleeding significantly worsened the outcome, therefore, its prevention is of utmost importance. Preventive measures against rebleeding include open surgery and endovascular treatment without craniotomy. Selection of the measures to prevent rebleeding should be based on neurological assessment, location and shape of cerebral aneurysm, anticipated difficulties in the treatment, presence of complications, etc. At present, surgical clipping remains the method of choice in Japan. However, there has been growing acceptance that the efficacy of endovascular treatment is comparable to that of surgical treatment, suggesting endovascular treatment should be considered in suitable patients with ruptured cerebral aneurysms. In this report, we describe the proceedures for the standard management of SAH, in particular, treatment of ruptured cerebral aneurysm and selection of treatment measures, according to the Japanese guidelines for the management of aneurysmal subarachnoid hemorrhage.

The influence of initial target effect-site concentrations of propofol on the similarity of effect-sites concentrations at loss and return of consciousness in elderly female patients with the Diprifusor system.

BACKGROUND: Whether effect-site concentrations of propofol (Cep) at loss of consciousness and return of consciousness (LOC and ROC, respectively) in elderly women using Diprifusor are similar is unclear. We investigated whether differences in initial target Cep (Ctarget) alter similarities between Cep values at LOC and ROC. MATERIALS AND METHODS: In this study, female patients (n = 58, age = 72.5 ± 1.1 years) undergoing knee arthroplasty were administered propofol with Diprifusor. Cep at LOC and ROC were estimated for different Ctarget values (3.0-4.5 µg/ml). Pearson's correlation coefficient analysis and simple regression were performed to assess the relationship between Cep at LOC and ROC for each Ctarget. Differences in correlation coefficients of regression lines obtained from each Ctarget group were determined using the t-test. RESULTS: The different Ctarget groups did not show significant differences in total propofol levels and in Cep values at LOC or ROC. However, Cep at ROC was significantly higher than Cep at LOC when Ctarget was 4.0 and 4.5 µg/ml, whereas these Cep values were not significantly different in low Ctarget groups. Strong positive correlations were observed between Cep at LOC and ROC for all Ctarget groups. Regression coefficients for the different Ctarget groups were not significantly different. Compared to low (≤3.5 µg/ml) Ctarget groups, high Ctarget groups showed significantly shorter time until LOC. Induction quality was not significantly different among the groups. CONCLUSIONS: In elderly women, Cep values at LOC are strong predictors of Cep at ROC when Ctarget is 3.0-4.5 µg/ml. High Ctarget groups (≥4.0 µg/ml) exhibited shorter induction times with normal cardiovascular stability.

The impact of nitrous oxide on electroencephalographic bicoherence during isoflurane anesthesia.

BACKGROUND: We previously reported that electroencephalographic (EEG) bicoherence, the degree of phase coupling among the frequency components of a signal, showed 2 peaks during isoflurane anesthesia. Hayashi et al. (Br J Anaesth 2007;99:389-95) also revealed that the peak frequency of bicoherence around 10 Hz increased when ketamine was added. Because nitrous oxide (N(2)O) and ketamine share several common features, they are often treated as the same category of anesthetic. Here, we investigated the effect of N(2)O on EEG bicoherence and other EEG derivatives during isoflurane anesthesia. METHODS: Twenty patients (aged 34-72 years, ASA physical status I and II) of either gender who underwent elective laparoscopic surgery were included. Raw EEG data, along with EEG-derived parameters, were recorded using an A-1050 Bispectral Index (BIS) monitor and our self-authored Bispectral Analyzer for BIS software. We compared 2 peaks of EEG bicoherence (pBIC-low, around 4 Hz; and pBIC-high, around 10 Hz), as well as BIS and spectral edge frequency 95% (SEF95). Anesthesia was induced with 3 mg · kg(-1) thiopental and 3 µg · kg(-1) fentanyl. After tracheal intubation, anesthesia was maintained with isoflurane (expired concentration at 1.0%), oxygen, and nitrogen. Fentanyl was added and maintained at an estimated effect-site concentration of >1.5 ng · mL(-1). We obtained baseline data 1 hour after induction of anesthesia, then 70% N(2)O was added for 30 minutes. RESULTS: Before N(2)O, pBIC-low and pBIC-high were 49.3% ± 8.3% and 42.4% ± 11.0%. Ten minutes after starting N(2)O, pBIC-high decreased to 14.9% ± 5.9% (P < 0.001), and it was statistically significantly lower throughout the N(2)O period. Meanwhile, pBIC-low transiently decreased to 37.2% ± 12.8% (P = 0.01) during the early phase of N(2)O administration. Before N(2)O, BIS and SEF95 were 43.2 ± 4.9 and 13.1 ± 2.0 Hz, respectively. Both BIS and SEF95 slightly but statistically significantly decreased during N(2)O administration. Fifteen minutes after starting N(2)O, BIS and SEF95 were 35.7 ± 6.2 (P < 0.001) and 8.6 ± 1.8 Hz (P < 0.001) and they decreased more when large δ waves emerged. Fifteen minutes after stopping N(2)O, BIS, SEF95, as well as pBIC-low and pBIC-high returned to pre-N(2)O values. CONCLUSION: Dissimilar to the effect of ketamine, N(2)O significantly decreases pBIC-high during isoflurane anesthesia.

Spontaneous breathing during lung-protective ventilation in an experimental acute lung injury model: high transpulmonary pressure associated with strong spontaneous breathing effort may worsen lung injury.

OBJECTIVE: We investigated whether potentially injurious transpulmonary pressure could be generated by strong spontaneous breathing and exacerbate lung injury even when plateau pressure is limited to <30 cm H2O. DESIGN: Prospective, randomized, animal study. SETTING: University animal research laboratory. SUBJECTS: Thirty-two New Zealand White rabbits. INTERVENTIONS: Lavage-injured rabbits were randomly allocated to four groups to receive low or moderate tidal volume ventilation, each combined with weak or strong spontaneous breathing effort. Inspiratory pressure for low tidal volume ventilation was set at 10 cm H2O and tidal volume at 6 mL/kg. For moderate tidal volume ventilation, the values were 20 cm H2O and 7-9 mL/kg. The groups were: low tidal volume ventilation+spontaneous breathingweak, low tidal volume ventilation+spontaneous breathingstrong, moderate tidal volume ventilation+spontaneous breathingweak, and moderate tidal volume ventilation+spontaneous breathingstrong. Each group had the same settings for positive end-expiratory pressure of 8 cm H2O. MEASUREMENTS AND RESULTS: Respiratory variables were measured every 60 mins. Distribution of lung aeration and alveolar collapse were histologically evaluated. Low tidal volume ventilation+spontaneous breathingstrong showed the most favorable oxygenation and compliance of respiratory system, and the best lung aeration. By contrast, in moderate tidal volume ventilation+spontaneous breathingstrong, the greatest atelectasis with numerous neutrophils was observed. While we applied settings to maintain plateau pressure at <30 cm H2O in all groups, in moderate tidal volume ventilation+spontaneous breathingstrong, transpulmonary pressure rose >33 cm H2O. Both minute ventilation and respiratory rate were higher in the strong spontaneous breathing groups. CONCLUSIONS: Even when plateau pressure is limited to <30 cm H2O, combined with increased respiratory rate and tidal volume, high transpulmonary pressure generated by strong spontaneous breathing effort can worsen lung injury. When spontaneous breathing is preserved during mechanical ventilation, transpulmonary pressure and tidal volume should be strictly controlled to prevent further lung injury.

A case of hypogonadotropic hypogonadism caused by opioid treatment for nonmalignant chronic pain.

We report a case of 42-year-old male patient with hypogonadotropic hypogonadism. He suffered from general fatigue and erectile dysfunction after the treatment with transdermal fentanyl for chronic pain by traffic injury. Endocrine examinations and hormone stimulating tests showed that he had hypogonadotropic hypogonadism. Brain magnetic resonance imaging (MRI) showed no abnormal findings, and he had no past history of accounting for acquired hypogonadotropic hypogonadism. Therefore, his hypogonadism was diagnosed to be caused by opioid treatment. Although opioid-induced endocrine dysfunctions are not widely recognized, this case suggests that we should consider the possibility of endocrine dysfunctions in patients with opioid treatment.

Human brain activity associated with painful mechanical stimulation to muscle and bone.

PURPOSE: The purpose of this study was to elucidate the central processing of painful mechanical stimulation to muscle and bone by measuring blood oxygen level-dependent signal changes using functional magnetic resonance imaging (fMRI). METHODS: Twelve healthy volunteers were enrolled. Mechanical pressure on muscle and bone were applied at the right lower leg by an algometer. Intensities were adjusted to cause weak and strong pain sensation at either target site in preliminary testing. Brain activation in response to mechanical nociceptive stimulation targeting muscle and bone were measured by fMRI and analyzed. RESULTS: Painful mechanical stimulation targeting muscle and bone activated the common areas including bilateral insula, anterior cingulate cortex, posterior cingulate cortex, secondary somatosensory cortex (S2), inferior parietal lobe, and basal ganglia. The contralateral S2 was more activated by strong stimulation than by weak stimulation. Some areas in the basal ganglia (bilateral putamen and caudate nucleus) were more activated by muscle stimulation than by bone stimulation. CONCLUSIONS: The putamen and caudate nucleus may have a more significant role in brain processing of muscle pain compared with bone pain.