Effects of Increased Optic Nerve Sheath Diameter on Inadequate Emergence from Anesthesia in Patients Undergoing Robot-Assisted Laparoscopic Prostatectomy: A Prospective Observational Study.

(1) Background: Robot-assisted laparoscopic prostatectomy (RALP) is preferred over open prostatectomy because it offers superior surgical outcomes and better postoperative recovery. The steep Trendelenburg position and pneumoperitoneum required in Robot-assisted laparoscopic prostatectomy, however, increase intracranial pressure (ICP). The present study aimed to evaluate the effects of elevated ICP on the quality of emergence from anesthesia. (2) Methods: Sixty-seven patients undergoing RALP were enrolled. We measured optic nerve sheath diameter at four timepoints during surgery. Primary outcome was inadequate emergence in the operating room (OR). Secondary outcomes were postoperative neurologic deficits of dizziness, headache, delirium, cognitive dysfunction, and postoperative nausea and vomiting (PONV). (3) Results: A total of 69 patients were screened for eligibility and 67 patients completed the study and were included in the final analysis. After establishing pneumoperitoneum with the Trendelenburg position, ONSD increased compared to baseline by 11.4%. Of the 67 patients, 36 patients showed an increase of 10% or more in optic nerve sheath diameter (ONSD). Patients with ΔONSD ≥ 10% experienced more inadequate emergence in the OR than those with ΔONSD < 10% (47.2% vs. 12.9%, p = 0.003). However, other variables related to the quality of emergence from anesthesia did not different significantly between groups. Similarly, neurologic deficits, and PONV during postoperative day 3 showed no significant differences. (4) Conclusions: ICP elevation detected by ultrasonographic ONSD measurement was associated with a transient, inadequate emergence from anesthesia.

The effect of preventive use of corticosteroids on postoperative complications after esophagectomy: A retrospective cohort study.

Corticosteroids have been empirically administered to reduce the rate of acute respiratory distress syndrome (ARDS) after esophagectomy. However, their efficacy remains controversial, and corticosteroids may increase the risk of graft dehiscence and infection, which are major concerns after esophagectomy. Therefore, we compared the incidence of composite complications (ARDS, graft dehiscence and infection) after esophagectomy between patients who received a preventive administration of corticosteroids and those who did not. All patients who underwent esophagectomy from 2010 to 2015 at a tertiary care university hospital were reviewed retrospectively (n = 980). Patients were divided into Steroid (n = 120) and Control (n = 860) groups based on the preventive administration of 100 mg hydrocortisone during surgery. The primary endpoint was the incidence of composite complications. The incidence of composite complications was not different between the Control and Steroid groups (17.4% vs. 21.7% respectively; P = 0.26). The incidence rates of complications in each category were not different between the Control and Steroid groups: ARDS (3.8% vs. 5.0%; P = 0.46), graft dehiscence (4.8% vs. 6.7%; P = 0.37), and infection (12.8% vs. 15.8%; P = 0.36). Propensity score matching revealed that composite complications (20.0% vs. 21.7%; P = 0.75), ARDS (4.3% vs. 5.2%; P = 0.76) and infection (16.5% vs. 15.7%; P = 0.86) were not different between the Control and Steroid group, but the incidence of graft dehiscence was higher in the Steroid group than in the Control group (0.9% vs. 7.0%; P = 0.0175). In conclusions, the preventive use of corticosteroids did not reduce the incidence of ARDS, but may be related to an increased incidence of graft dehiscence. Therefore, routine administration of corticosteroids to prevent ARDS is not recommended in esophagectomy.

Ascorbic acid improves thrombotic function of platelets during living donor liver transplantation by modulating the function of the E3 ubiquitin ligases c-Cbl and Cbl-b.

OBJECTIVE: To investigate the effect of ascorbic acid (AA) on hemostatic function during living donor liver transplantation (LDLT). METHODS: Blood samples from 21 LDLT recipients were taken within 30 minutes after induction and at 120 minutes after reperfusion. Rotational thromboelastography (TEG) and western blot analysis were used to analyze for fibrinolysis and functional changes in c-Cbl and Cbl-b, respectively. TEG test samples were prepared as one of three groups: C group (0.36 mL of blood), N group (0.324 mL of blood + 0.036 mL of 0.9% normal saline), and A group (0.324 mL of blood + 0.036 mL of 200 µmol/L-AA dissolved in 0.9% normal saline). RESULTS: AA decreased fibrinolysis and increased clot rigidity at baseline and 120 minutes after reperfusion. Cbl-b expression was significantly increased at baseline and 120 minutes after reperfusion in the A group compared with the C and N groups. However, c-Cbl phosphorylation was most significantly decreased in the A group at baseline and 120 minutes after reperfusion. CONCLUSION: AA can significantly decrease fibrinolysis and improve clot rigidity in LT recipients during LDLT, and functional changes in Cbl-b and c-Cbl might represent the underlying mechanism. AA may be considered for use during LDLT to decrease hyperfibrinolysis.

Incidence of tolerance in children undergoing repeated administration of propofol for proton radiation therapy: a retrospective study.

BACKGROUND: Propofol is an excellent hypnotic drug for use in repeated radiation procedures in young children. To date, tolerance to propofol generally does not develop in pediatric patients undergoing radiation therapy. However, several studies have suggested that there may be potential for development of tolerance to propofol. The aim of this study was to evaluate the development of a tolerance to propofol used for repeated deep sedation in children undergoing proton radiation therapy (PRT). METHODS: All children undergoing PRT at our institution between December 2015 and January 2018 were eligible for inclusion in this study. Sedation was induced by a bolus dose of propofol (2.0 mg.kg- 1) followed by a continuous infusion of 250 µg.kg- 1.min- 1 via an infusion pump to achieve deep sedation. Sedation was maintained with the propofol infusion of 200 µg.kg- 1.min- 1, which was adjusted in 25 µg.kg- 1.min- 1 increments up or down as necessary to ensure deep sedation. The primary outcome was mean doses of propofol over time. RESULTS: Fifty-eight children were analyzed. The mean (SD) age was 4.5 (2.1) years. The mean (SD) number of treatment sessions was 19 (7). Fifteen patients (26%) developed tolerance to propofol. However, there were no significant differences between the children who developed tolerance and the children who did not develop tolerance in mean propofol dose and awakening time over time (p = 0.887 and P = 0.652, respectively). Age, the number of PRT, and attending anesthesiologists was not significantly associated with the incidence of tolerance to propofol. CONCLUSION: Repeated prolonged deep sedation for PRT elicited multiple times over several weeks in young children using propofol did not develop tolerance in 74% of patients. Although the incidence of 26% tolerance to propofol may still be present, the increase in propofol dose was minimal. Therefore, the use of repeated propofol for children was safe.

Effects of propofol and isoflurane on excitatory amino acid carrier 1 mRNA and glutathione protein levels in rat hippocampus.

OBJECTIVE: We compared the effects of two anesthetics, isoflurane and propofol, on the nuclear or cytosolic localization of nuclear factor erythroid 2-related factor 2 (Nrf2), mRNA expression levels of excitatory amino acid carrier 1 (EAAC1), and glutathione (GSH) protein levels in the rat hippocampus. METHODS: Fifty-two adult male Sprague-Dawley rats were randomly divided into three groups: a control group, a group that received propofol for 240 minutes (P240), and a group that received isoflurane for 240 minutes (I240). We compared GSH protein and EAAC1 mRNA expression levels in the rat hippocampus and evaluated Nrf2 content in cytosolic and nuclear fractions in the three groups. RESULTS: GSH protein and EAAC1 mRNA expression levels were significantly higher in the I240 and P240 groups compared with the control group. The I240 and P240 groups showed lower Nrf2 protein levels in the cytosolic fractions, but higher levels in the nuclear fractions compared with the control group. CONCLUSION: Treatment with isoflurane or propofol may enhance GSH production by facilitating translocation of Nrf2 into the nucleus and increasing EAAC1mRNA expression in the rat hippocampus. Isoflurane and propofol show similar profiles in EAAC1 expression-associated GSH production.

Increased expression of the Cbl family of E3 ubiquitin ligases decreases Interleukin-2 production in a rat model of peripheral neuropathy.

BACKGROUND: Interleukin 2 (IL-2) influences the development and severity of pain due to its antinociceptive and immunomodulatory effects. Its production is influenced by the increased expression of c-Cbl (Casitas B-lineage lymphoma proto-oncogene) and Cbl-b E3 ubiquitin ligases. We evaluated the effects on IL-2-mediated changes in c-Cbl and Cbl-b expression in a rat model of chronic neuropathic pain. METHODS: Peripheral neuropathy was induced in adult male Sprague-Dawley rats weighing 250-300 g by chronic spinal nerve ligation. Half of the spinal cord ipsilateral to the nerve injury was harvested at 1, 3, and 6 weeks, and the expression levels of IL-2, c-Cbl, Cbl-b, phospholipase C-γ1 (PLC-γ1), ZAP70, and protein kinase Cθ (PKCθ), as well as ubiquitin conjugation, were evaluated. RESULTS: Total IL-2 mRNA levels were significantly decreased at 3 and 6 weeks after nerve injury compared to those in sham-operated rats. The mRNA levels of c-Cbl and Cbl-b, as well as the level of ubiquitin conjugation, were significantly increased at 3 and 6 weeks. In contrast, the levels of phosphorylated ZAP70 and PLC-γ1 were decreased at 3 and 6 weeks after spinal nerve ligation. Ubiquitination of PLC-γ1 and PKCθ was increased at 3 and 6 weeks. CONCLUSIONS: Our results suggest that ubiquitin and the E3 ubiquitin ligases c-Cbl and Cbl-b function as neuroimmune modulators in the subacute phase of neuropathic pain after nerve injury.

Isoflurane decreases interleukin-2 production by increasing c-Cbl and Cbl-b expression in rat peripheral blood mononuclear cells.

Objective To evaluate how isoflurane affects T-cell function by assaying interleukin (IL)-2 production and the expression of two Casitas B-lineage lymphoma (Cbl) family proto-oncogenes (c-Cbl and Cbl-b) in rat peripheral blood mononuclear cells (PBMCs). Methods Adult male Sprague-Dawley rats were randomly allocated to those that underwent blood collection after brief isoflurane anesthesia (control group), immediately after 4 hours of isoflurane general anesthesia (4I group), and 1 day after 4 hours of isoflurane general anesthesia (1D 4I group). IL-1, IL-2, and IL-6 mRNA levels and c-Cbl and Cbl-b levels in PBMCs were determined by polymerase chain reaction. Ubiquitination of protein kinase Cθ (PKCθ) and phospholipase C-γ1 (PLC-γ1) in PBMCs was assessed by immunoprecipitation. Results The IL-2 mRNA level in rat PBMCs was significantly lower in the 4I and 1D 4I groups than in the control group. c-Cbl, Cbl-b, and ubiquitin expression was significantly increased and zeta-chain-associated protein kinase 70, PLC-γ1, and PKCθ protein levels were significantly decreased in the 4I group. Ubiquitination of PLC-γ1 and PKCθ was significantly increased in the 4I group. Conclusion Isoflurane influences ubiquitin, c-Cbl, and Cbl-b expression in rat PBMCs, indicating suppression of receptor tyrosine kinase signaling pathways. These results suggest that isoflurane suppresses T-cell function.

Randomized trial of subfascial infusion of ropivacaine for early recovery in laparoscopic colorectal cancer surgery.

BACKGROUND: There is a need for investigating the analgesic method as part of early recovery after surgery tailored for laparoscopic colorectal cancer (LCRC) surgery. In this randomized trial, we aimed to investigate the analgesic efficacy of an inverse 'v' shaped bilateral, subfascial ropivacaine continuous infusion in LCRC surgery. METHODS: Forty two patients undergoing elective LCRC surgery were randomly allocated to one of two groups to receive either 0.5% ropivacaine continuous infusion at the subfascial plane (n = 20, R group) or fentanyl intravenous patient controlled analgesia (IV PCA) (n = 22, F group) for postoperative 72 hours. The primary endpoint was the visual analogue scores (VAS) when coughing at postoperative 24 hours. Secondary end points were the VAS at 1, 6, 48, and 72 hours, time to first flatus, time to first rescue meperidine requirement, rescue meperidine consumption, length of hospital stay, postoperative nausea and vomiting, sedation, hypotension, dizziness, headache, and wound complications. RESULTS: The VAS at rest and when coughing were similar between the groups throughout the study. The time to first gas passage and time to first rescue meperidine at ward were significantly shorter in the R group compared to the F group (P = 0.010). Rescue meperidine was administered less in the R group; however, without statistical significance. Other study parameters were not different between the groups. CONCLUSIONS: Ropivacaine continuous infusion with an inverse 'v ' shaped bilateral, subfascial catheter placement showed significantly enhanced bowel recovery and analgesic efficacy was not different from IV PCA in LCRC surgery.

Obesity is independently associated with spinal anesthesia outcomes: a prospective observational study.

The influence of body-mass index (BMI) on spinal anesthesia is still controversial, with discrepant results reported in previous studies. To compare spinal anesthesia in obese and non-obese subjects, the anesthesia profiles in patients who underwent spinal anesthesia using intrathecal hyperbaric bupivacaine were compared. A total of 209 patients undergoing elective total knee replacement arthroplasty (TKRA) surgery under spinal anesthesia were divided into an NO (non-obese) group (BMI < 30 kg/m2, n = 141) and an O (obese) group (BMI ≥ 30 kg/m2, n = 68). Anesthesia was deemed successful if a bilateral T12 sensory block occurred within 15 minutes of intrathecal drug administration, and if the level of sensory block was higher than T12 when the surgery ended. Logistic regression analysis with multiple variables known to influence spinal anesthesia was performed to identify which parameters independently determined the spinal anesthesia outcome. Similar doses of bupivacaine were administered to the NO and O groups. The incidence of anesthesia failure was significantly lower in the O group [n = 43 (30.5%) in the NO group vs. n = 10 (18.9%) in the O group, p = 0.014]. The independent predictors for successful anesthesia in all patients were dose of hyperbaric bupivacaine [odds ratio (OR) 2.12, 95% CI: 1.64-2.73] and obese status (BMI ≥ 30 kg/m2, OR 2.86, 95% CI: 1.25-6.52). Time to first report of postoperative pain and time to first self-void were significantly longer in the O group. These results suggest that the duration of block with hyperbaric bupivacaine is prolonged in obese patients and obesity is independently associated with spinal anesthesia outcomes, as is bupivacaine dosage. A further study enrolling patients with morbid obesity and using a fixed bupivacaine dosage is required to confirm the effect of obesity on spinal anesthesia.

A comparison among infusion of lidocaine and dexmedetomidine alone and in combination in subjects undergoing coronary artery bypass graft: a randomized trial.

BACKGROUND: Previous studies have reported the cardioprotective effect of dexmedetomidine and lidocaine. We compared the effect of lidocaine and dexmedetomidine infusion during off-pump coronary artery bypass graft (OPCAB). METHODS: 153 patients undergoing OPCAB were enrolled. The lidocaine group (n=36, Group LIDO) received an infusion of lidocaine 2 mg/kg/h after bolus 1.5 mg/kg; the dexmedetomidine group (n=40, Group DEX) received dexmedetomidine 0.3-0.7 µg/kg/h; the combined group (n=39, Group Combined) received infusion of both drugs; and the control group (n=38) received nothing. We measured serum creatinine kinase-myocardial band (CK-MB) and cardiac troponin I (cTnI) concentration before and immediately after the surgery, postoperative day (POD)#1 and #2. The complication rate and clinical outcomes were compared. RESULTS: The concentration of cTnI was significantly lower in the Group LIDO and Group Combined than the control group on POD#2. The concentration of CK-MB was significantly lower in the Group LIDO and Group Combined compared to the control group on POD#1 and #2 [CK-MB on POD#1: 7.67 (5.78-11.92) vs. 7.18 (5.01-11.72) vs. 13.19 (6.85-23.87) in the Group LIDO, combined and control, respectively, Group LIDO vs. control: p=0.003, Group Combined vs. control: p=0.015]. The AUC of CK-MB was significantly lower in the Group LIDO and Group Combined than the control group. However, clinical variables including complication rate, ICU stay and one-year mortality were not different. CONCLUSIONS: Lidocaine infused at 2 mg/kg/h, but not dexmedetomidine infused at 0.3-0.7 µg/kg/h reduced postoperative myocardial injury marker levels compared with the control group. However, no other clinical benefits were observed.

Comparison of respiratory mechanics between sevoflurane and propofol-remifentanil anesthesia for laparoscopic colectomy.

BACKGROUND: The creation of pneumoperitoneum and Trendelenburg positioning during laparoscopic surgery are associated with respiratory changes. We aimed to compare respiratory mechanics while using intravenous propofol and remifentanil vs. sevoflurane during laparoscopic colectomy. METHODS: SIXTY PATIENTS UNDERGOING LAPAROSCOPIC COLECTOMY WERE RANDOMLY ALLOCATED TO ONE OF THE TWO GROUPS: group PR (propofol-remifentanil group; n = 30), and group S (sevoflurane group; n = 30). Peak inspiratory pressure (PIP), dynamic lung compliance (Cdyn), and respiratory resistance (Rrs) values at five different time points: 5 minutes after induction of anesthesia (supine position, T1), 3 minutes after pneumoperitoneum (lithotomy position, T2), 3 minutes after pneumoperitoneum while in the lithotomy-Trendelenburg position (T3), 30 minutes after pneumoperitoneum (T4), and 3 minutes after deflation of pneumoperitoneum (T5). RESULTS: In both groups, there were significant increases in PIP and Rrs while Cdyn decreased at times T2, T3, and T4 compared to T1 (P < 0.001). The Rrs of group PR for T2, T3, and T4 were significantly higher than those measured in group S for the corresponding time points (P < 0.05). CONCLUSIONS: Respiratory mechanics can be adversely affected during laparoscopic colectomy. Respiratory resistance was significantly higher during propofol-remifentanil anesthesia than sevoflurane anesthesia.

Effects of two different doses of epidural steroid on blood glucose levels and pain control in patients with diabetes mellitus.

BACKGROUND: A high incidence of diabetes mellitus has been reported among patients diagnosed with lumbar degenerative spinal diseases. Although epidural steroid injections are known to increase the postprocedure blood glucose level, it has not been investigated whether a lower steroid dose can reduce blood glucose excursions and still be effective in controlling patients' subjective pain. OBJECTIVE: We compared the effects of 2 common doses of triamcinolone administered via epidural steroid injections on blood glucose levels and pain control in patients with diabetes mellitus to determine an adequate epidural steroid dose. STUDY DESIGN: A prospective observational study. METHODS: One hundred patients with diabetes mellitus were enrolled. They received lumbar transforaminal, lumbar interlaminar, or caudal epidural triamcinolone for radiculopathy, spinal stenosis, or failed back surgery syndrome. After the type of procedure was clinically determined, the doses of triamcinolone given were randomly chosen, either 40 mg (Group 40) or 20 mg (Group 20). The patients were asked to measure their finger stick blood glucose level twice daily (fasting and postprandial) for 3 days before the injection, on the day of the injection, for 7 days after the injection, and at 14 days after the injection. They also kept a blood glucose diary. Employment status and clinical outcome were evaluated at 8 weeks after the procedure. RESULTS: There were significant increases in fasting blood glucose (FBG) level on postprocedure day (PPD) #1 to PPD #3 in Group 40, but on PPD #1 in Group 20. Moreover, there was a significant difference in FBG between groups on PPD #1 and PPD #2 (FBG on PPD #1: 179 [51]) mg/dL in Group 40 versus 146 [50] mg/dL in Group 20, P < 0.001]. Postprandial blood glucose (PBG) level was significantly elevated in both groups from PPD #0 to PPD #3. Notably, the increase in PBG was significantly greater in Group 40 than Group 20 on PPD #0 and #1 (PBG on PPD #0: 288 [57] mg/dL versus 242 [94] mg/dL in Groups 40 and 20, respectively, P = 0.004). The numeric rating scale for pain reported by the patients decreased for 2 weeks after treatment with no difference between groups. Employment status and clinical outcome was not different between groups. LIMITATIONS: The patients who chose to participate in this study may be a cohort of well-controlled patients with diabetes mellitus. The type of procedure performed was determined by a clinical decision and not randomized. The different routes of administration and diagnosis of failed back surgery syndrome can result in different levels of systemic absorption, thereby influencing the degree and duration of hyperglycemia. In patients with FBSS, the epidural space may be destructed by surgery and adhesive changes in epidural space could be extensive. Therefore, we thought that the absorption of epidural space in these patients would be incomplete or slow compared with those without FBSS. CONCLUSION: Epidural steroid injections were associated with statistically significant elevations in PBG in patients with diabetes for up to 4 days after the procedure. The higher dose of triamcinolone increased FBG and PBG greater than a lower dose did without affecting pain control, employment status, or clinical outcome. Thus, with respect to glucose and pain control, 20 mg of triamcinolone appears to be recommended rather than 40 mg in patients with diabetes. Clinical Trials registration : NCT01435707.

Ethanol embolotherapy of hand arteriovenous malformations.

PURPOSE: Ethanol embolotherapy is one of the established methods in the treatment of extremity arteriovenous malformations (AVMs). The purpose of this study was to report the application of this method to hand AVMs and to assess retrospectively the therapeutic outcomes and complications. PATIENTS AND METHODS: From December 1998 to March 2009, we treated 31 patients with hand AVMs (16 women, 15 men, age range, 5-51 years; mean age, 27 years). With the patients under general anesthesia, they underwent staged ethanol embolotherapy (range, 1-11 sessions; mean, 2.8 sessions) by direct puncture and or intra-arterial approach. Therapeutic outcomes were evaluated by clinical responses of symptoms and signs, as well as the degree of devascularization on angiography. We also divided the patients into three groups according to the extent of involvement: a group involving fingers (n = 14), a group involving fingers and parts of the palm (n = 9), and a group involving parts of the palm (n = 8) and compared the therapeutic outcomes and complications among groups. RESULTS: One patient (3%) was cured, 22 patients (73%) showed improvement, and 7 patients (23%) showed no change or aggravation after the treatment. One patient was lost to follow-up. Nineteen patients (61%) had one or more complications, including skin necrosis in 14 patients (45%), bullae in 7 patients (23%), joint stiffness or contracture in 6 patients (19%), and transient nerve palsy in 4 patients (13%). All of the complications were resolved completely after 1 to 8 months' (average, 3.4 months) follow-up, except in 2 patients who underwent amputation. According to the location of AVMs, rates of therapeutic benefit and complications were 93% and 64% in the group involving fingers, 38% and 78% in the group involving fingers and the palm, and 88% and 38% in the group involving the palm, respectively. CONCLUSION: Ethanol embolotherapy of hand AVMs improves symptoms in a certain percentage of patients with a relatively high risk of complications. According to the extent of AVMs, there was a trend toward a higher complication rate in treatment of AVMs involving fingers and a lower rate of therapeutic benefit in AVMs involving both the fingers and the palm.

Novel Use of Hydromorphone as a Pretreatment Agent: A Double-blind, Randomized, Controlled Study in Adult Korean Surgical Patients.

BACKGROUND: Hydromorphone is a potent µ-opioid selective agonist that has an onset time within 5 minutes and reaches peak effect between 10 and 20 minutes. However, it may show immediate analgesic effect to rocuronium-induced pain because of its peripheral analgesic property and also may attenuate noxious stimuli from tracheal intubation during induction. The opioid receptors are known to be present in peripheral sensory nerve terminals as well as in the dorsal root ganglion and the central terminal of primary afferent nerves. Therefore, we hypothesized that hydromorphone may be considered a potent pretreatment or adjuvant drug during the induction of anesthesia with its peripherally and centrally mediated analgesia. OBJECTIVE: The aim of this study was to compare the effects of pretreatment with hydromorphone in reducing rocuronium-induced withdrawal movements and hemodynamic changes during tracheal intubation with the effects of fentanyl and normal saline. METHODS: In this double-blind, randomized, controlled study, consecutive adult patients aged 20 to 70 years who were scheduled to undergo general anesthesia for elective gastric or colorectal surgery at the Samsung Seoul Hospital (Seoul, Republic of Korea) were randomly assigned to receive 5 mL hydromorphone 0.03 mg/kg or fentanyl 2 µg/kg or normal saline. Thirty seconds after administering the study drug, anesthesia was induced with 2.5% thiopental sodium 5 mg/kg. After loss of consciousness, rocuronium 0.6 mg/kg was injected and immediate withdrawal movements were recorded. Two minutes after rocuronium injection, tracheal intubation was performed and hemodynamic changes were observed. RESULTS: A total of 194 patients were enrolled, with 65 in the hydromorphone group, 67 in the fentanyl group, and 62 in the saline group. The overall incidence of withdrawal movements was significantly lower in the hydromorphone group (2 patients; 3.1%) and the fentanyl group (5 patients; 7.5%) (both, P < 0.001) than in the saline group (36 patients; 58.1%). The mean arterial pressure (MAP) and heart rate (HR) after intubation (median [interquartile range]) in the fentanyl group (101.5 [84-115] mm Hg; 93.5 [82-102] beats per minute [bpm]) and the hydromorphone group (93.0 [83-106] mm Hg; 90.0 [86.3-93.6] bpm) were significantly lower than these measures in the saline group (111.5 [105-123] mm Hg; 103.5 [96-113] bpm) (fentanyl group MAP and HR, P < 0.001; hydromorphone group MAP and HR, P < 0.001). CONCLUSIONS: Pretreatment with hydromorphone and fentanyl may have similar effectiveness in reducing withdrawal movements in response to rocuronium injection pain and inducing immediate general anesthesia.

Downregulation of constitutive and cytokine-induced complement 3 expression by morphine in rat astrocytes.

BACKGROUND: The effect of opioids on inflammation and immune responses is an important subject of investigation because immunoregulatory cytokines are produced in the central nervous system and opioid receptors are widespread in these cells. OBJECTIVES: The aim of this study was to evaluate the immunomodulatory effect of morphine on the C3 expression (both constitutive and proinflammatory cytokine-induced C3 expression) in primary rat astrocytes. METHODS: Primary rat astrocytes were untreated or treated with morphine in different concentrations (10(-6) to 10(-2) M) before incubation without or with 5 U/mL tumor necrosis factor-α (TNF-α), and C3 protein and mRNA expressions were measured. Similarly, astrocytes were treated with 10(-3) M morphine and stimulated with other proinflammatory cytokines, including 10 ng/mL interleukin-8 (IL-8) and 5 U/mL IL-1ß. Astrocytes were exposed to 10(-5) M naloxone for 2 hours before adding morphine, and TNF-α and C3 protein was measured. Tumor growth factor-ß (TGF-ß) was measured from the supernatants of each proinflammatory cytokine. RESULTS: All results are expressed as mean percentages of C3 production by normalizing C3 without morphine or any cytokine treatment as 100%. Constitutive C3 protein production was decreased at morphine 10(-3) M (57.2%) and 10(-2) M (30.1%). Pretreatment with morphine suppressed induction of C3 expression at both the protein and mRNA levels in astrocytes stimulated with TNF-α, IL-8, and IL-1ß (P < 0.05) in a dose-dependent manner. The inhibition of C3 protein production by morphine (10(-3) M; 33%) was partially attenuated by naloxone (52.0%) (P < 0.05). The pretreatment of astrocytes with morphine (10(-3) M) before stimulation with TNF-α, IL-8, and IL-1ß increased by 33% (P < 0.05), decreased by 15.2% (P < 0.05), and did not change the production of TGF-ß protein, respectively. CONCLUSIONS: Morphine downregulated both constitutive and proinflammatory cytokine-induced C3 expression of astrocytes at the transcriptional level, but not in a cytokine-specific manner.

EAAC1 gene deletion alters zinc homeostasis and exacerbates neuronal injury after transient cerebral ischemia.

EAAC1 is a neuronal glutamate and cysteine transporter. EAAC1 uptake of cysteine provides substrate for neuronal glutathione synthesis, which plays a key role in both antioxidant defenses and intracellular zinc binding. Here we evaluated the role of EAAC1 in neuronal resistance to ischemia. EAAC1(-/-) mice subjected to transient cerebral ischemia exhibited twice as much hippocampal neuronal death as wild-type mice and a corresponding increase in microglial activation. EAAC1(-/-) mice also had elevated vesicular and cytosolic zinc concentrations in hippocampal CA1 neurons and an increased zinc translocation to postsynaptic neurons after ischemia. Treatment of the EAAC1(-/-) mice with N-acetyl cysteine restored neuronal glutathione concentrations and normalized basal zinc levels in the EAAC1(-/-) mice. Treatment of the EAAC1(-/-) mice with either N-acetyl cysteine or with zinc chelators reduced ischemia-induced zinc translocation, superoxide production, and neuron death. These findings suggest that cysteine uptake by EAAC1 is important for zinc homeostasis and neuronal antioxidant function under ischemic conditions.

Prospective analysis of the pattern and risk for severe vital sign changes during percutaneous radiofrequency ablation of the liver under opioid analgesia.

OBJECTIVE: The aims of this study were to evaluate the pattern of vital sign changes and to elucidate significant risk factors for severe cardiovascular inhibition caused by percutaneous hepatic radiofrequency ablation (RFA). SUBJECTS AND METHODS: A total of 102 patients (male-to-female ratio, 73:29; age range, 35-85 years; mean age, 58.1 years) with 119 malignant hepatic tumors were enrolled and analyzed prospectively. The patients underwent percutaneous RFA with IV infusion of opioid analgesics. Changes in blood pressure (BP) and heart rate (HR) and the occurrence of significant cardiovascular inhibition (BP or HR < 70% of baseline) were monitored during the procedure. Respiratory rate and skin body temperature were recorded before and after the procedure. RESULTS: Whereas the mean BP was elevated (36%, 43/119) or depressed (36%, 43/119) with a similar frequency, the HR was predominantly depressed (56%, 66/119) during the procedure. The BP and HR were stable in only 18% cases (21/119), respectively. The respiratory rate showed no significant change (p = 0.521) after RFA; however, body temperature decreased (p < 0.001) after RFA. Although significant cardiovascular inhibition occurred in 41 cases (35%), all of the cases could be managed successfully and the technical success rate was 100% (119/119). Among the risk factors analyzed, old age (B = -0.003, p = 0.019) was significant for systolic BP depression, and contact of the RFA zone with the central portal vein (B = -0.096, p = 0.014) and female sex (B = -0.078, p = 0.033) were significant risk factors for HR depression as determined by multivariate analysis. CONCLUSION: Changes in BP and HR, especially bradycardia, are common during percutaneous RFA of hepatic lesions. Significant risk factors for severe cardiovascular inhibition include contact of the RFA zone with the branches of the central portal vein, old age, and female sex.