Yushi U. Adachi

Inhibiting NADPH oxidase protects against long-term memory impairment induced by neonatal sevoflurane exposure in mice

BACKGROUNDnNeonatal exposure to anaesthetics such as sevoflurane has been reported to result in behavioural deficits in rodents. However, while oxidative injury is thought to play an underlying pathological role, the mechanisms of neurotoxicity remain unclear. In the present study, we investigated whether the NADPH oxidase inhibitor apocynin protects against long-term memory impairment produced by neonatal sevoflurane exposure in mice.nnnMETHODSnPostnatal day six mice were divided into four groups; (1) non-anaesthesia, (2) intraperitoneal apocynin (50 mg kg(-1)) treatment, (3) 3% sevoflurane exposure for 6 h, and (4) apocynin treatment combined with sevoflurane exposure. Superoxide concentrations and NADPH oxidase expression in the brain were determined using dihydroethidium fluorescence and immunoblotting, respectively. Cleaved caspase-3 immunoblotting was used for the detection of apoptosis, and cytochrome c immunoblotting was performed to evaluate mitochondrial function. Long-term cognitive impairment was evaluated using the fear conditioning test in adulthood.nnnRESULTSnSevoflurane exposure increased concentrations of superoxide (109%) and the NADPH oxidase subunit p22phox (39%) in the brain, and apocynin abolished these increases. Neonatal sevoflurane exposure caused learning deficits in adulthood. Apocynin also maintained long-term memory function in mice given neonatal sevoflurane exposure, and it reduced apoptosis and decreased cytochrome c concentrations in the brains of these mice.nnnCONCLUSIONSnApocynin reduces neuronal apoptosis and protects against long-term memory impairment in mice, neonatally exposed to sevoflurane by reducing superoxide concentrations. These findings suggest that NADPH oxidase inhibitors may protect against cognitive dysfunction resulting from neonatal anaesthesia.

Dexmedetomidine-induced atrioventricular block followed by cardiac arrest during atrial pacing: a case report and review of the literature

Sinus bradycardia is a well-known consequence of stimulation of presynaptic α2 adrenergic receptors due the adminstration of dexmedetomidine. One of the most serious adverse effects of dexmedetomidine is cardiac arrest. Some cases demonstrating such an arrest due to the indiscriminate use of this drug were recently reported. We continuously administered dexmedetomidine to a 56-year-old male patient at a rate of 0.3xa0μg/kg/h (lower than the recommended dose) without initial dosing for sedation in an intensive care unit. The patient had undergone open cardiac surgery and atrial pacing was maintained at a fixed rate, 90/min. The PQ interval in electrocardiography gradually prolonged during the infusion; finally, complete atrioventricular block and subsequent cardiac arrest occurred. Immediate cardiopulmonary resuscitation was carried out, including re-intubation, and recovery of spontaneous circulation was attained 15xa0min after the event. The patient was discharged from hospital on the 25th postoperative day without any neurological complications.

Recurarization after sugammadex following a prolonged rocuronium infusion for induced hypothermia

To the Editor, Sugammadex encapsulates the steroidal neuromuscular blocking agents, rocuronium and vecuronium, and rapidly reverses their effect. Although recurarization is possible after administration of sugammadex, only a few cases have been documented clinically. We report here a patient showing signs of neuromuscular block in spite of repeated administration of sugammadex. Consent for publication of this report was obtained from the patient’s family. A 56-yr-old male patient with chronic renal failure was scheduled for a pancreatoduodenectomy. On the morning of the planned surgery, he underwent a cardiac arrest while still on the ward of our university hospital. After recovery of spontaneous circulation, tracheal intubation was performed, and emergency contrast-enhanced computed tomography revealed a pulmonary air embolism. He was admitted to the intensive care unit where therapeutic mild hypothermia was induced (day 1) and continuous hemodiafiltration therapy was initiated. To prevent shivering as one of the complications of hypothermia, rocuronium was infused continuously at a rate of 25 mg hr. The patient received 1,376 mg over 46.5 hr (day 3). Two days later (day 5), his body temperature had recovered, hemodynamic variables were stable, and consciousness had improved. Accordingly, weaning from mechanical ventilation was attempted for tracheal extubation; however, his tidal volume was small under pressure support mode (8 cm H2O). An accelomyographic monitor (TOF-Watch , NihonKoden, Tokyo, Japan) applied to the adductor pollicis muscle showed a train-of-four (TOF) count of four with a TOF ratio of 0.2. Consequently, sugammadex 400 mg was administered. Immediately after the injection, the patient’s responses to noxious stimuli and verbal commands showed improvement; however, 12 hr later, tidal volume in the pressure support mode (8 cm H2O) had decreased, and the patient’s response to stimuli was weak. A second injection of sugammadex (400 mg) was administered, and this clearly increased tidal volume and the response to noxious stimuli. On the next day (day 6), after confirmation of adequate ventilation, airway patency, and neurological recovery, the patient’s trachea was extubated without any difficulties, and oxygen was applied by face mask. Although oxygen saturation was maintained ([ 90%), the patient complained of dyspnea approximately 12 hr after tracheal extubation. Although the accelomyographic monitoring at the adductor pollicis appeared normal, the intensivist in charge, suspecting residual neuromuscular blockade, administered another dose of sugammadex 400 mg. Consciousness and spontaneous ventilation improved immediately after the injection, and dyspnea disappeared without apparent change in accelomyographic response. No complications were detected after the third administration of sugammadex. On day 8, continuous hemodiafiltration T. Murata, MD Department of Anesthesia, Daiyukai General Hospital, Nagoya City, Aichi, Japan

Landiolol reduces hemodynamic responses to bronchoscopy-assisted suctioning in intubated ICU patients

Landiolol is an ultra-short-acting β1-selective antagonist developed in Japan that was recently approved for the treatment of tachycardia in intensive care units (ICUs). This study investigated the protective effects of landiolol against the cardiovascular responses during bronchoscopic endotracheal suctioning. This study enrolled 15 patients requiring orotracheal intubation in an ICU. All of the patients required endotracheal suctioning using fiber bronchoscopy while sedated at a Ramsay Scale of 2–3. All subsequent suctioning procedures were assigned randomly to three groups using a cross-over design: saline as a placebo (group C) or 20 or 40xa0μgxa0kg-1xa0min-1 landiolol, respectively (groups L20 and L40). The infusion was started 3xa0min before bronchoscopy and continued for 6xa0min. The central venous pressure (CVP) heart rate (HR) and arterial blood pressure (BP) were recorded. Fourteen patients completed the investigation, and 30 procedures (nu2009=u200910/group) were analyzed. The suctioning significantly increased the CVP, HR, and BP in groups C and L20, although the changes in BP were of shorter duration in group L20. No significant increase in the hemodynamic parameters was observed in group L40. The administration of landiolol 40xa0μgxa0kg-1xa0min-1 prevented a harmful hyperdynamic circulatory response to bronchoscopic endotracheal suctioning, without obvious decreases in HR or BP after the intervention.

The determinants of propofol induction time in anesthesia.

Background The required dose of anesthetics is generally smaller in patients with low cardiac output (CO). A high CO decreases the blood concentration of anesthetics during induction and maintenance of anesthesia. However, a high CO may also shorten the delivery time of anesthetics to the effect site, e.g. the brain. We assessed the time required for induction of anesthesia with propofol administered by target-controlled infusion (TCI), and investigated factors that modify the pharmacodynamics of propofol. Methods After measuring CO and blood volume (BV) by dye densitometry, propofol was infused using TCI to simulate a plasma concentration of 3 µg/ml. After infusion, the time taken to achieve bispectral index (BIS) values of 80 and 60 was determined. Age, sex, lean body mass (LBM), and cardiovascular parameters were analyzed as independent variables. The dependent variables were the time taken to achieve each BIS value and the plasma concentration of propofol (Cp) 10 min after the commencement of infusion. Results Multiple regression analysis revealed that a high CO significantly reduced the time taken to reach the first end point (P = 0.020, R2 = 0.076). Age and LBM significantly prolonged the time taken to reach the second end point (P = 0.001). Cp was negatively correlated with BV (P = 0.020, R2 = 0.073). Conclusions Cardiac output was a statistically significant factor for predicting the time required for induction of anesthesia in the initial phase, whereas, age and LBM were significant variables in the late phase. The pharmacodynamics of propofol was intricately altered by CO, age, and LBM.

A low dose of droperidol decreases the desflurane concentration needed during breast cancer surgery: a randomized double-blinded study

Background Droperidol (DHB) reportedly reduces the dose of propofol needed to achieve hypnosis when anesthesia is induced and decreases the bispectral index (BIS) in propofol-sedated patients during spinal anesthesia. We reported previously that supplemental DHB decreased the BIS after the administration of sevoflurane and remifentanil. This study investigated the effect of DHB on desflurane (DES) consumption in a clinical setting. Methods We conducted a prospective, randomized double-blinded study of 35 women with American Society of Anesthesiologist physical status I or II who underwent a mastectomy. Either DHB (20 µg/kg) or a saline placebo was administered to patients 30 min after the induction of anesthesia. A blinded anesthesiologist maintained a BIS value of 50 during anesthesia by modulating inhaled DES concentrations that changed 0.5% at 2.5 min intervals and maintained analgesia via the constant administration of remifentanil by referring to vital signs. The primary endpoint was the effect of DHB on DES consumption. The secondary endpoints included blood circulatory parameters, the time from the end of surgery to extubation, and discharge time between the groups. Results The characteristics of the patients did not differ between the groups. The DHB group used a mean of 27.2 ± 6.0 ml of DES compared with 41.4 ± 9.5 ml by the placebo group (P < 0.05). Conclusions A small dose of DHB reduced the DES concentration needed to maintain a BIS of 50. Our results show that DHB reduced the consumption of DES without adverse effects.

Sugammadex-Enhanced Neuronal Apoptosis following Neonatal Sevoflurane Exposure in Mice

In rodents, neonatal sevoflurane exposure induces neonatal apoptosis in the brain and results in learning deficits. Sugammadex is a new selective neuromuscular blockade (NMB) binding agent that anesthesiologists can use to achieve immediate reversal of an NMB with few side effects. Given its molecular weight of 2178, sugammadex is thought to be unable to pass through the blood brain barrier (BBB). Volatile anesthetics can influence BBB opening and integrity. Therefore, we investigated whether the intraperitoneal administration of sugammadex could exacerbate neuronal damage following neonatal 2% sevoflurane exposure via changes in BBB integrity. Cleaved caspase-3 immunoblotting was used to detect apoptosis, and the ultrastructure of the BBB was examined by transmission electron microscopy. Exposure to 2% sevoflurane for 6u2009h resulted in BBB ultrastructural abnormalities in the hippocampus of neonatal mice. Sugammadex alone without sevoflurane did not induce apoptosis. The coadministration of sugammadex with sevoflurane to neonatal mice caused a significant increase (150%) in neuroapoptosis in the brain compared with 2% sevoflurane. In neonatal anesthesia, sugammadex could influence neurotoxicity together with sevoflurane. Exposure to 2% sevoflurane for 6u2009h resulted in BBB ultrastructural abnormalities in the hippocampus of neonatal mice.

Post-operative cardiac arrest induced by co-administration of amiodarone and dexmedetomidine: a case report

We firstly report a postoperative hemodialysis patient who was co-administered with amiodarone and dexmedetomidine and developed severe bradycardia followed by cardiac arrest. A 79-year-old male patient underwent an amputation of the right lower extremity. The electrocardiogram of the patient showed a complete right bundle branch block with left anterior fascicular block before the anesthesia, and paroxysmal atrial tachycardia over 200xa0beats/min lasting 15xa0min was observed during surgery. After admission to the intensive care unit, the intensivist and the consultant cardiologist decided to treat tachycardia using amiodarone. The initial dosing of amiodarone and the maintenance infusion succeeded to decrease the heart rate. Approximately 2xa0h and a half after the start of dexmedetomidine infusion for sedation, the heart rate gradually declined and severe bradycardia suddenly followed by cardiac arrest was observed. Resuscitation was promptly initiated and the patient regained sinus rhythm without delay. In retrospective analysis, the monitoring record of the electrocardiogram revealed the marked atrioventricular conduction abnormalities. This is the first case report concerning a cardiac arrest induced by amiodarone and dexmedetomidine.

Subcutaneous emphysema and ultrasound sonography.

Subcutaneous emphysema is not a rare complication in intensive care unit patients. Recently, ultrasound guidance for central venous puncture is becoming popular; however, the information on imaging for subcutaneous emphysema is limited. We encountered a patient complicated with severe pneumomediastinum and subsequent subcutaneous emphysema. The catheter replacement was attempted, and we examined the visuality of cervical vessels using ultrasound sonography before the intervention. Internal jugular vein itself was observed despite of subcutaneously migrated air bubble; however, the range of ultrasound image was limited, and the relationship between the vessel and the adjacent tissue was unclear.

Radial artery cannulation decreases the distal arterial blood flow measured by power Doppler ultrasound.

Radial arterial cannulation is a popular technique for continuous hemodynamic monitoring in an area of anesthesia and intensive care. Although the risk for invasive monitoring is considerable, there is scarce information about the change in blood flow of cannulated vessel after the catheterization. In the current investigation, we evaluated the change in the cannulated arterial blood flow. Six volunteers (study 1) and eight post-surgical patients (study 2) were enrolled into the studies. In the study 1, the both side of diameter of radial artery (RA), ulnar artery (UA) and dorsal branch of radial artery (DBRA) of participants were measured using power Doppler ultrasound (PDU) with or without proximal oppression. In the study 2, the diameter of RA, UA and DBRA of the both intact and cannulated side were compared. Study 1: The diameter of RA was 3.4 (0.52) [mean (SD)] mm and the proximal oppression significantly decreased the diameter to 1.8 (0.59) mm. The diameter of DBRA measured by PDU also decreased 2.0 (0.60)–1.3 (0.59) mm. Study 2: There was no difference between the diameters of right and left RA, however, the UA was larger [3.4 (0.60) vs. 2.8 (0.83) mm] and the DBRA was narrower [1.4 (0.43) vs. 2.0 (0.47) mm] in the cannulated side. The diameters of DBRA were different between the intact and cannulated side in the patients. Although there is no information of relationships between cause of severe complication and decreased flow, significant reduction of blood flow should be concerned.