Comparison between the effects of deep and moderate neuromuscular blockade during transurethral resection of bladder tumor on endoscopic surgical condition and recovery profile: a prospective, randomized, and controlled trial.

PURPOSE: To compare between deep neuromuscular blockade (NMB) and moderate NMB with respect to endoscopic surgical conditions and recovery profiles in patients with general anesthesia for transurethral resection of bladder (TURB). METHODS: 108 patients undergoing elective TURB were randomized into two groups: the moderate NMB (n = 54) or deep NMB (n = 54) group. After the operation, NMB was reversed with 2 mg/kg sugammadex at a train-of-four (TOF) count of 1 or 2 (moderate NMB group) or with 4 mg/kg sugammadex at post-tetanic count (PTC) of 2 (deep NMB group). Surgeons, who were blinded to the study design, rated the endoscopic surgical condition on a 5-point scale (1 = extremely poor, 2 = poor, 3 = acceptable, 4 = good, 5 = optimal) immediately following the operation. Recovery profiles, including postoperative residual curarization (PORC), respiratory complication, and recovery time, were recorded. RESULTS: No difference was observed between the two groups regarding patients and anesthesia characteristics. There were statistically significant differences in endoscopic surgical conditions between the two groups (P < 0.001). Thirty-eight patients in the deep NMB group (74%) showed optimal surgical conditions, whereas 16 patients in the moderate NMB group (30%) showed optimal endoscopic surgical conditions. No PORC and respiratory complications occurred in both groups, and no difference was found between the two groups in terms of recovery profiles, including recovery time and other adverse events. CONCLUSIONS: Deep NMB and reversal with sugammadex improved the endoscopic surgical condition without complications compared with moderate NMB and reversal with sugammadex in patients undergoing TURB.

Effects of depth of neuromuscular block on surgical conditions during laparoscopic colorectal surgery: a randomised controlled trial.

There have been few objective evaluations of the effects of deep neuromuscular blockade on intra-operative conditions. In this prospective randomised controlled study, we evaluated the effects of deep neuromuscular block on surgical conditions during laparoscopic colorectal surgery. Patients were randomly allocated using a computer-generated randomisation code to either moderate (train-of-four count 1-2 maintained and antagonised with neostigmine) or deep (post-tetanic count 1-2 maintained and reversed with sugammadex) levels of neuromuscular blockade. The primary outcome measure was the number of abrupt increases in intra-abdominal pressure intra-operatively. Secondary outcome variables were intra-operative restoration of spontaneous breathing, number of surgical requests for additional neuromuscular blockade, surgical rating of operating conditions and patient satisfaction. The surgeon who rated the surgical conditions score and investigator who checked the postoperative variables were blinded to patient allocation. In total, we recruited 70 patients of whom 64 (32 in each group) were analysed. Increases in intra-abdominal pressure (14/32 vs. 6/32; p = 0.031), intra-operative restoration of spontaneous breathing (16/32 vs. 2/32; p < 0.001) and request for additional neuromuscular blockade (21/32 vs. 8/32; p = 0.001) were more frequent in the moderate compared with the deep group. In patients undergoing elective laparoscopic colorectal surgery, deep neuromuscular blockade provided better surgical conditions than moderate neuromuscular blockade, as measured by a reduction in the incidence of intra-abdominal pressure alarms.

The Effect of Intraoperative Nefopam Administration on Acute Postoperative Pain and Chronic Discomfort After Robotic or Endoscopic Assisted Thyroidectomy: A Randomized Clinical Trial.

BACKGROUND: Acute postoperative pain and chronic discomfort are reported after robotic or endoscopic thyroidectomy. The purpose of this prospective, randomized, and double-blinded clinical trial was to investigate whether intraoperative infusion of nefopam decreases acute postoperative pain and chronic discomfort following either a robotic or endoscopic thyroidectomy via the bilateral axillo-breast approach (BABA). METHODS: Patients were randomized into two groups: The control group (n = 29) or the nefopam group (n = 29). Patients in each group were infused with the same volume of saline or nefopam (0.2 mg/kg bolus, 120 µg/kg/h continuous infusion) during surgery. Acute postoperative pain, the need for rescue analgesics, and other postoperative adverse effects were assessed at 1, 6, 24, and 48 h postoperatively. Chronic pain and discomfort was recorded at 3 months after surgery. RESULTS: Patients in the nefopam group reported lower pain scores in the neck, as well as the axilla and anterior chest areas at 1, 6, 24, and 48 h postoperatively, when compared with the control group (P < 0.05 at each time points). Rescue analgesics were required less in the nefopam group than in the control group (1.4 [1] vs. 2.3 [1.5]; P = 0.001). The degree of chronic pain and discomfort were relatively lower in the nefopam group (P < 0.05). CONCLUSION: We report that intravenous nefopam infusion during surgery decreased acute postoperative pain and the need for rescue analgesics, as well as chronic discomfort, following BABA robotic or endoscopic thyroidectomy without adverse events.

Comparison of reversal with neostigmine of low-dose rocuronium vs. reversal with sugammadex of high-dose rocuronium for a short procedure.

Some short procedures require deep neuromuscular blockade, which needs to be reversed at the end of the procedure. Forty-four patients undergoing elective laryngeal micro-surgery were randomly allocated into two groups: rocuronium 0.45 mg.kg-1 with neostigmine (50 µg.kg-1 with glycopyrrolate 10 µg.kg-1 ) reversal (moderate block group) vs. rocuronium 0.90 mg.kg-1 with sugammadex (4 mg.kg-1 ) reversal (deep block group). The primary outcome was the intubating conditions during laryngoscopy secondary outcomes included recovery of neuromuscular block; conditions for tracheal intubation; satisfaction score as determined by the surgeon; onset of neuromuscular block; and postoperative sore throat. The onset of neuromuscular block was more rapid, and intubation conditions and ease of intra-operative laryngoscopy were more favourable, and the satisfaction score was lower in the moderate block group compared with the deep block group. No difference was found in the incidence of postoperative sore throat. In laryngeal micro-surgery, the use of rocuronium 0.9 mg.kg-1 with sugammadex for reversal was associated with better surgical conditions and a shorter recovery time than rocuronium 0.45 mg.kg-1 with neostigmine.

Prospective, randomized and controlled trial on magnesium sulfate administration during laparoscopic gastrectomy: effects on surgical space conditions and recovery profiles.

BACKGROUND: The degree of neuromuscular blockade is one of the important factors that determine the condition of surgical space during laparoscopic surgery. Magnesium sulfate potentiates the actions of neuromuscular blocking agent, and we hypothesized that intraoperative magnesium sulfate infusion may improve surgical space condition during laparoscopic surgery. METHODS: Eighty-four patients undergoing elective laparoscopic gastrectomy were randomized to receive isotonic saline (group C) or magnesium sulfate (group M, loading dose with 50 mg/kg over 10 min and then 15 mg/kg/h by continuous infusion) to maintain the moderate neuromuscular blockade using rocuronium. Two experienced surgeons scored the quality of surgical space condition using a 5-point surgical rating scale (SRS). The secondary outcomes included recovery profiles, postoperative pain and adverse events. RESULTS: The SRS in group M was higher than that of group C. The proportion of patients with a SRS of 5 (optimal) was 2.7 % in the group C and 40.5 % in the group M (P < 0.0001) although a lower amount of rocuronium was required in group M than group C [24.2 (6.5) mg/h for group M vs. 27.5 (6) mg/h for group C; P = 0.017]. Pain after operation site was less severe in group M than in group C at postoperative 24 h (P = 0.009). Recovery profiles and adverse events were similar between the two groups. CONCLUSION: Intraoperative administration of magnesium sulfate improved the quality of surgical space conditions and decreased neuromuscular blocking agent requirement and postoperative pain in patients undergoing laparoscopic gastrectomy.

Optimum dose of neostigmine to reverse shallow neuromuscular blockade with rocuronium and cisatracurium.

We examined the use of neostigmine for reversing shallow (defined as train-of-four ratio of 0.5), cisatracurium- and rocuronium-induced neuromuscular block in 112 patients, by use of 0 µg.kg(-1) , 10 µg.kg(-1) , 20 µg.kg(-1) or 40 µg.kg(-1) dose of neostigmine for reversal. The times from neostigmine administration to train-of-four ratios of 0.7, 0.9 and 1.0 were evaluated. Analysis of variance showed that the duration of action was significantly longer after cisatracurium compared with rocuronium. The time to reach a train-of-four ratio of 1.0 was significantly shorter with neostigmine 40 µg.kg(-1) compared with lower neostigmine doses, and at this dose the time did not differ between cisatracurium and rocuronium. The recovery time from a train-of-four ratio of 0.5-1.0 did not differ between cisatracurium and rocuronium, and was significantly shortened by the administration of neostigmine. We conclude that a neostigmine dose of 40 µg.kg(-1) was the most effective at reducing recovery time after neuromuscular blockade.

Effect of preoperative autologous blood donation on patients undergoing bimaxillary orthognathic surgery: a retrospective analysis.

The efficacy of preoperative autologous blood donation (PABD) was evaluated according to preoperative haemoglobin (Hb) values. The records of 295 patients who underwent bimaxillary orthognathic surgery between July 2007 and August 2008 were reviewed. The records for autologous blood donation, intraoperative transfusion, and related laboratory studies were also evaluated. The transfusion trigger used during this period was Hb < 10 g/dl. A total of 189 patients (64.1%) made a PABD and 106 patients (35.9%) did not. The incidence of allogeneic blood transfusion was significantly lower in the PABD group than in the no PABD group (15.9% vs. 29.2%, P = 0.007). This difference was greater in patients with a preoperative Hb < 14 g/dl (20.3% vs. 62.5%, P < 0.0001), and no difference was found in patients with Hb ≥ 14 g/dl (13.3% vs. 14.9%, P = 0.83). PABD reduced the incidence of allogeneic blood transfusion in patients undergoing bimaxillary orthognathic surgery, particularly in patients with a preoperative Hb < 14 g/dl. PABD could be used to reduce the frequency of intraoperative allogeneic blood transfusion in these patients.

Timing of reversal with respect to three nerve stimulator end-points from cisatracurium-induced neuromuscular block.

After elective ear surgery with cisatracurium neuromuscular blockade, 48 adults were randomly assigned to receive neostigmine: (a) at appearance of the fourth twitch of a 'train-of-four'; (b) at loss of fade to train-of-four; or (c) at loss of fade to double-burst stimulation, all monitored using a TOF-Watch SX® on one arm. For each of these conditions, the recovery from train-of-four (TOF) ratio was measured in parallel objectively using a TOF-Watch SX placed on the contralateral arm. The median (IQR [range]) time from administration of reversal to a train-of-four ratio ≥ 0.9 was 11 (9-15.5 [2-28]) min, 8 (4-13.5 [1-25]) min and 7 (4-10 [2-15]) min in the three groups, respectively. This recovery time was significantly shorter when reversal was given at loss of fade to double-burst stimulation (c), than when given at the appearance of the fourth twitch (a), p = 0.046. However, the total time to extubation may be unaffected as it takes longer for fade to be lost after double-burst stimulation than for four twitches subjectively to appear.

Conversion of cell-survival activity of Akt into apoptotic death of cancer cells by two mutations on the BIM BH3 domain.

Survival and proliferation of cancer cells are often associated with hyperactivity of the serine/threonine kinase, Akt. Herein, we show that prosurvival activity of Akt can be converted into prodeath activity by embedding an Akt recognition sequence in the apoptogenic BH3 domain of human BIM. The recognition sequence was created by introducing two mutations, I155R and E158S, into the core region of the BIM BH3 domain. Although a 21-mer BIM BH3 peptide containing these two mutations bound weakly to BCL-XL and BCL-2, this peptide with phosphorylation of Ser158 bound to these proteins with a dissociation constant of <10 nM. The crystal structure of the phosphorylated peptide bound to BCL-XL revealed that the phospho-Ser158 makes favorable interactions with two BCL-XL residues, which cannot be formed with unphosphorylated Ser158. Remarkably, the designed peptide showed a cytotoxic effect on PTEN-null PC3 tumor cells whose Akt activity is aberrantly high. The cell-killing activity disappeared when the cellular Akt activity was lowered by ectopic PTEN expression. Thus, these results lay a foundation for developing a peptide or protein agent that is dormant in normal cells but is transformed into a potent apoptogenic molecule upon phosphorylation by hyperactivity of Akt in cancer cells.

Ultrasound-guided oblique subcostal transversus abdominis plane block for analgesia after laparoscopic cholecystectomy: a randomized, controlled, observer-blinded study.

BACKGROUND: The oblique subcostal transversus abdominis plane (OSTAP) block has been described as an effective analgesic method for upper abdominal surgery. We evaluated the postoperative analgesia of the OSTAP block and compared it with that of the transversus abdominis plane (TAP) block in patients undergoing laparoscopic cholecystectomy (LC). METHODS: Patients scheduled for elective LC were randomized to receive either standard care or to undergo an OSTAP or TAP block. All blocks were performed with ultrasound guidance, and 20 mL of 0.375% ropivacaine was injected bilaterally. The postoperative pain score and consumption of rescue analgesics were evaluated. RESULTS: The OSTAP block reduced postoperative verbal numerical rating scale pain scores (median [Interquartile range, IQR]) compared to standard care at 10 min (2 [1-4] vs. 7 [5-8]), 30 min (2 [1-5] vs. 6 [5-8]), 1 h (2 [1-3] vs. 5 [4-6]), and 3 h (2 [2-3] vs. 4 [3-5]). Pain scores were also lower in the OSTAP group than in the TAP group at 10 min (2 [1-4] vs. 4 [2-6]), 1 h (2 [1-3] vs. 3 [3-4]), 3 h (2 [2-3] vs. 3 [3-4]), 6 h (2 [2-3] vs. 3 [3-5]), and 24 h (1 [1-2] vs. 2 [2-3]) postoperatively. The total fentanyl requirement was reduced in the OSTAP group (p = 0.005). CONCLUSION: The OSTAP block can provide better analgesia than the TAP block or standard care during the postoperative 24 h period in patients undergoing LC.

Efficacy of butylscopolamine for the treatment of catheter-related bladder discomfort: a prospective, randomized, placebo-controlled, double-blind study.

BACKGROUND: Catheter-related bladder discomfort (CRBD) secondary to intraoperative catheterization of urinary bladder is one of the most distressing symptoms during recovery from anaesthesia. Butylscopolamine, a peripheral antimuscarinic agent, is effective for relieving the pain, which is because of smooth muscle contraction. The aim of this study was to assess the efficacy and safety profiles of butylscopolamine in treating CRBD after urological surgeries. METHODS: Adult male patients undergoing urological surgery requiring urinary bladder catheterization intraoperatively were enrolled. Induction and maintenance of anaesthesia were standardized. Patients were randomized into two groups after complaining of CRBD in the post-anaesthesia care unit. The control group (n=29) received normal saline and the butylscopolamine group (n=28) was administered butylscopolamine 20 mg i.v. The severity of CRBD, postoperative pain, and adverse effects were assessed at baseline, 20 min, 1, 2, and 6 h after administration of the study drug. RESULTS: The severity of CRBD observed in the butylscopolamine group was significantly lower than that of the control group at 1, 2, and 6 h after administration of the study drug [59 (12), 50 (16), 40 (21) in the control group vs 41 (22), 32 (25), 23 (18) in the butylscopolamine group, P<0.01]. Rescue analgesics were required less in the butylscopolamine group than in the control group (P=0.001). Adverse events were comparable between the two groups. CONCLUSION: Butylscopolamine 20 mg administered i.v. after complaining CRBD during recovery reduced both the severity of CRBD and the need for rescue analgesics without adverse effects in patients undergoing urologic surgeries.

The effect of the jaw-thrust manoeuvre on the ability to advance a tracheal tube over a bronchoscope during oral fibreoptic intubation.

During fibreoptic intubation, it is often difficult to advance a tracheal tube over the fibreoptic bronchoscope. We performed a prospective randomised study to investigate the effect of the jaw-thrust manoeuvre on the ability to advance a tracheal tube during oral fibreoptic intubation. After placing the bronchoscope in the trachea, an assistant randomly applied a jaw-thrust manoeuvre (jaw-thrust group) or sham manoeuvre (control group) in 82 patients during tube advancement. The jaw-thrust group had a higher success rate on the first attempt (70.7% vs 34.1%, p = 0.002), required fewer attempts (median (IQR [range]) 1 (1-2 [1-3]) vs 2 (1-3 [1-4]), p < 0.001), and took less time [6 (4-8 [2-16]) s vs 10 (7-15 [3-40]) s, p < 0.001] for tube advancement compared with the control group. The jaw-thrust manoeuvre facilitates the advancement of a tracheal tube over the bronchoscope during oral fibreoptic intubation.

Emergence agitation in children undergoing adenotonsillectomy: a comparison of sevoflurane vs. sevoflurane-remifentanil administration.

BACKGROUND: Sevoflurane is widely used in paediatric anaesthesia but frequently causes emergence agitation (EA). This study evaluated whether limiting the sevoflurane concentration by combining remifentanil with sevoflurane reduced the incidence of EA. METHODS: Eighty-four preschool children scheduled for adenotonsillectomy were randomly assigned to either the remifentanil or sevoflurane group. In the remifentanil group, anaesthesia was induced with thiopental, rocuronium, and 1% sevoflurane. It was maintained with 1% sevoflurane, 60% nitrous oxide in oxygen, and a continuous infusion of remifentanil. For the sevoflurane group, anaesthesia was induced with thiopental, rocuronium, and 8% sevoflurane, and was maintained with 2-3% sevoflurane. Both groups received ketorolac 1 mg/kg and dexamethasone 0.15 mg/kg. EA was measured using the paediatric anaesthesia emergence delirium (PAED) scale and a four-point EA scale in the post-anaesthesia care unit. RESULTS: The scores on the PAED scales were significantly lower in the remifentanil group than in the sevoflurane group [median (interquartile range); 6 (4.25-10.25) vs. 11 (7.75-14.0), P = 0.007], and the proportion of patients with PAED scores ≥ 10 was significantly lower in the remifentanil group than in the sevoflurane group [15 (35.7%) vs. 27 (64.2%), P = 0.009]. The incidence of EA evaluated using the four-point scale was also lower in the remifentanil group [11 (26.1%) vs. 21 (50%), respectively, P = 0.025]. CONCLUSION: The incidence of EA was lower in children undergoing adenotonsillectomy who received a lower concentration of sevoflurane combined with remifentanil than in those given a higher concentration of sevoflurane without remifentanil.

Influence of a prolonged lateral position on induction of spinal anesthesia for cesarean delivery: a randomized controlled trial.

BACKGROUND: Maternal hypotension occurs commonly during cesarean delivery under spinal anesthesia. We evaluated whether hypotension due to aortocaval compression could be prevented by maintaining a lateral position after an intrathecal injection. METHODS: Eighty-six women undergoing elective cesarean delivery were enrolled. Spinal anesthesia was conducted in the right lateral position using 8 mg of hyperbaric bupivacaine and 15 µg of fentanyl. Patients were randomly assigned to maintain the right lateral position for 6 min before assuming the wedged supine position (group L), or to assume the wedged supine position immediately after the spinal injection (group S). Hypotension was defined as a decrease in mean arterial pressure to <80% of baseline. Ephedrine was given if blood pressure decreased to <70% of baseline. The incidence of hypotension and nausea, ephedrine requirement, maximal block height, and neonatal outcomes were evaluated. RESULTS: No significant between-group differences were observed in the lowest blood pressure, total ephedrine dose, or incidence of hypotension or nausea. Onset of hypotension was delayed (6 ± 2 vs. 10 ± 3 min, P<0.001), and the sensory block level was more cephalad in group L than in group S (T2 [C8-T5] vs. T4 [T1-T6], P=0.001). Apgar scores did not differ between the groups. CONCLUSION: During spinal anesthesia for elective cesarean delivery, maintaining the lateral position for 6 min after an intrathecal injection of hyperbaric bupivacaine resulted in a more gradual and higher cephalad sensory block, without an increase in the incidence of maternal hypotension.

A randomised controlled trial comparing rocuronium priming, magnesium pre-treatment and a combination of the two methods.

We investigated whether magnesium sulphate combined with rocuronium priming shortens the onset of neuromuscular blockade, compared with these methods used alone. Ninety-two patients scheduled for general anaesthesia were randomly allocated to one of four groups: controls were given 0.6 mg.kg(-1) rocuronium; patients in the prime group were given 0.06 mg.kg(-1) rocuronium three minutes before a further dose of 0.54 mg.kg(-1) rocuronium; patients in the magnesium group were given an infusion of 50 mg.kg(-1) magnesium sulphate before rocuronium and patients in the magnesium and prime group were given both the magnesium sulphate and the priming dose of rocuronium. Tracheal intubation was attempted 40 s after the rocuronium injection. The time to onset of neuromuscular blockade was the primary outcome; duration of blockade and tracheal intubating conditions were also measured. The group allocation and study drugs were coded and concealed until statistical analyses were completed. The magnesium and prime group had the shortest mean (SD) onset time (55 (16)s; p < 0.001), and best tracheal intubating conditions (p < 0.05). No statistical difference was found for the duration of blockade. As for adverse events, a burning or heat sensation was reported in eight (35%) and six (26%) patients in the magnesium and magnesium and prime groups, respectively. The combination of magnesium sulphate and rocuronium priming accelerated the onset or neuromuscular blockade and improved rapid-sequence intubating conditions, compared with either magnesium sulphate or priming used alone.

Drug-administration sequence of target-controlled propofol and remifentanil influences the onset of rocuronium. A double-blind, randomized trial.

BACKGROUND: Remifentanil is known to cause bradycardia and hypotension, as well as the decreases of cardiac output (CO). We hypothesized that hemodynamic suppression by remifentanil would affect the onset time of rocuronium. This study investigated whether the onset of rocuronium was influenced by the drug-administration sequence during induction of anesthesia with target-controlled infusion of propofol and remifentanil. METHODS: Healthy adult patients (n = 126) undergoing elective surgery under general anesthesia were randomized into two groups according to drug-administration sequence. In Remi-Pro-Rocu group (n = 62), remifentanil was infused first, followed by propofol. Then, rocuronium was administered lastly. In Pro-Rocu-Remi group (n = 64), propofol, rocuronium, and remifentanil were given in that order. As a primary outcome, the onset time of rocuronium was measured. Mean arterial pressure (MAP), heart rate (HR), CO, and stroke volume were recorded before anesthesia (T1), at injection of rocuronium (T2), immediately before and after intubation (T3 and T4). RESULTS: In Remi-Pro-Roc group, the onset of rocuronium was delayed significantly compared with Pro-Rocu-Remi group [median (interquartile range); 130 (105-150) vs. 90 (71-100) s, P < 0.001]. At the time of rocuronium injection (T2), MAP, HR, and CO were significantly lower in Remi-Pro-Rocu group than Pro-Rocu-Remi group (P < 0.001). CONCLUSION: The onset time of rocuronium is prolonged significantly by early administration of remifentanil during target-controlled infusion of propofol and remifentanil, and it may be due to the decreased CO caused by remifentanil.

Novel tumor suppressive function of Smad4 in serum starvation-induced cell death through PAK1-PUMA pathway.

DPC4 (deleted in pancreatic cancer 4)/Smad4 is an essential factor in transforming growth factor (TGF)-ß signaling and is also known as a frequently mutated tumor suppressor gene in human pancreatic and colon cancer. However, considering the fact that TGF-ß can contribute to cancer progression through transcriptional target genes, such as Snail, MMPs, and epithelial-mesenchymal transition (EMT)-related genes, loss of Smad4 in human cancer would be required for obtaining the TGF-ß signaling-independent advantage, which should be essential for cancer cell survival. Here, we provide the evidences about novel role of Smad4, serum-deprivation-induced apoptosis. Elimination of serum can obviously increase the Smad4 expression and induces the cell death by p53-independent PUMA induction. Instead, Smad4-deficient cells show the resistance to serum starvation. Induced Smad4 suppresses the PAK1, which promotes the PUMA destabilization. We also found that Siah-1 and pVHL are involved in PAK1 destabilization and PUMA stabilization. In fact, Smad4-expressed cancer tissues not only show the elevated expression of PAK1, but also support our hypothesis that Smad4 induces PUMA-mediated cell death through PAK1 suppression. Our results strongly suggest that loss of Smad4 renders the resistance to serum-deprivation-induced cell death, which is the TGF-ß-independent tumor suppressive role of Smad4.

Isoflurane decreases death of human embryonic stem cell-derived, transcriptional marker Nkx2.5(+) cardiac progenitor cells.

BACKGROUND: Cardiac progenitor cells (CPCs) derived from human embryonic stem cells (hESCs) can multiply and generate cardiomyocytes, offering their tremendous potential for cardiac regenerative therapy. However, poor survival under stressful conditions is a major hurdle in the regeneration. We investigated whether isoflurane-induced preconditioning can increase hESC-derived CPC survival under oxidative stress. METHODS: Undifferentiated hESCs were cultured in suspension with 20% FBS (fetal bovine serum) and 20 ng/ml of BMP-4 (bone morphogenetic protein-4) to form embryoid bodies and grown onto Matrigel-coated plates for 2-3 weeks. To characterise the differentiated CPCs, immunostaining for Nkx2.5 (nonspecific transcriptional marker) and Isl-1 was performed. hESC-derived CPCs were exposed to oxidative stress induced by H(2) O(2) and FeSO(4) . For anaesthetic preconditioning, CPCs were exposed to isoflurane (0.25, 0.5, 1.0 mM). CPC survival was determined by trypan blue exclusion. A mitoK(ATP) channels inhibitor, 5-hydroxydecanoic acid (200 µM) and an opener, diazoxide (100 µM), were used to investigate the involvement of mitoK(ATP) channels. RESULTS: hESC-derived CPCs stained with Nkx2.5 were 95 ± 3% of total cell number. Isoflurane (0.5 and 1.0 mM)-preconditioned CPCs showed a significantly lower death rate compared with control (0.5 mM: 30.6 ± 10.7% and 1.0 mM: 28.5 ± 6.2% vs. control: 43.2 ± 9.9%). Inhibition of mitoK(ATP) channels with 5-HD completely abolished the protective effects of isoflurane. Diazoxide significantly decreased CPC death (29.5 ± 12.4%). However, when diazoxide was applied to CPC preconditioned with isoflurane, CPC death did not decrease further (28.7 ± 10.9%). CONCLUSION: Isoflurane increased hESC-derived Nkx2.5(+) CPC survival under oxidative stress, and mitoK(ATP) channels may be involved in the protective effect.

A short period of inhalation induction with sevoflurane prevents rocuronium-induced withdrawal in children.

BACKGROUND: the aim of this study was to determine whether or not inhalation induction with sevoflurane can prevent the withdrawal movement associated with the injection of rocuronium. METHODS: a total of 75 pediatric patients were randomly allocated to five groups (S 1.5, 2.0, 2.5, 3.0, and the control group). In the control group (n=15), 2.5% thiopental 5 mg/kg was injected intravenously. Rocuronium 0.4 mg/kg was injected immediately after loss of consciousness. In the S 1.5, 2.0, 2.5, or 3.0 group, rocuronium 0.4 mg/kg was injected at 1.5, 2, 2.5, or 3 min after inhalation induction, respectively, and the withdrawal response was recorded. End-tidal sevoflurane concentrations were recorded at the time of the rocuronium injection. The inhalation time of sevoflurane before rocuronium injection required to provide no withdrawal response in 50% and 95% of patients (IT(50) and IT(95) ) was calculated. RESULTS: the incidence of withdrawal was 80% (12/15), 71.4% (10/14), 21% (3/14), 0% (0/14), and 0% (0/15) in group C, group S 1.5, group S 2.0, group S 2.5, and group S 3.0, respectively. IT(50) of the rocuronium injection time was 1.7 min (95% CI: 1.5-1.9) and IT(95) was 2.3 min (95% CI: 2.0- 2.9). CONCLUSIONS: this study demonstrated that inhalation induction with sevoflurane can prevent the withdrawal movement induced by rocuronium in children, and IT(50) and IT(95) for the prevention of movement was 1.7 and 2.3 min, respectively.