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.

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.

Effect of Hyaluronidase Addition to Lidocaine for Trigger Point Injection in Myofascial Pain Syndrome.

INTRODUCTION: This randomized, double-blind study compared the efficacy of hyaluronidase co-injection with that of local anesthesia alone on the degree of pain and quality of life in patients with myofascial pain syndrome (MPS). METHODS: Sixty-one adults, aged 25 to 75 years, with MPS affecting both trapezius muscles were randomly assigned to one of the 2 treatment groups: lidocaine (group L: n = 31) or hyaluronidase (group H: n = 30). All patients received Trigger point injection (TPI). Group L received 3.2 mL 0.5% lidocaine alone. Group H received the same solution of lidocaine mixed with hyaluronidase (600 iu/mL). Patients were followed for 14 days (pre- and post-TPI days 0, 1, 4, 7, and 14) with the verbal numerical rating scale (VNRS), and the primary outcome was VNRS on day 7. Also, we evaluated the neck disability index (NDI) and the short form of brief pain inventory (BPI-SF) on pre- and post-TPI day 14. RESULTS: In both groups, VNRS decreased on days 4, 7, and 14 compared to the pre-TPI. However, in group H, VNRS decreased on day 1 also. There were no significant differences of VNRS between the 2 groups during 14 days. NDI and BPI-SF scores also significantly decreased after TPI in both groups. CONCLUSIONS: There were no significant differences between groups in terms of VNRS, NDI, or BPI-SF scores. However, TPI consisting of lidocaine mixed with hyaluronidase worked more effectively than lidocaine alone on post-TPI day 1. Further, hyaluronidase showed a tendency to reduce TPI-related soreness.

Epinephrine decreases the dose of hyperbaric bupivacaine necessary for tourniquet pain blockade during spinal anesthesia for total knee replacement arthroplasty.

PURPOSE: We quantified the dose-sparing effect of epinephrine by comparing the median effective dose (ED(50)) of intrathecal hyperbaric bupivacaine co-administered with epinephrine with the ED(50) of intrathecal hyperbaric bupivacaine alone. METHODS: Three groups were randomly generated from 162 patients undergoing total knee replacement arthroplasty under combined spinal and epidural anesthesia: Group B (bupivacaine), Group BE1 (bupivacaine plus epinephrine 100 µg), and Group BE2 (bupivacaine plus epinephrine 200 µg). Each group was further divided by bupivacaine doses of 6, 7, 8, 9, 10, or 11 mg. The anesthesia was defined as successful if a bilateral T12 sensory block occurred within 15 min, and no intraoperative epidural supplement was required. The ED(50) and ED(95) for successful anesthesia and successful tourniquet pain blockade were determined separately by probit regression analysis. RESULTS: The ED(50) and ED(95) of intrathecal hyperbaric bupivacaine for successful anesthesia were not different among the groups: the ED(50) values were 7.1 mg [95 % confidence interval (95 % CI) 6.0-8.0 mg] in Group B, 6.2 mg (95 % CI 4.8-7.2 mg) in Group BE1, and 6.3 mg (95 % CI 4.9-7.2 mg) in Group BE2. However, the ED(50) and ED(95) values for tourniquet pain control were significantly smaller in Groups BE1 and BE2 than in Group B: the ED(50) values were 7.2 mg (95 % CI 6.3-7.9 mg), 5.5 mg (95 % CI 4.1-6.3 mg), and 5.3 mg (95 % CI 3.7-6.2 mg) in Groups B, BE1, and BE2, respectively. The incidence of tourniquet pain was significantly lower in Groups BE1 and BE2 than in Group B. The time to patients' requests for supplemental analgesia was significantly longer in Groups BE1 and BE2 than in Group B. CONCLUSIONS: Intrathecal epinephrine did not decrease the dose of intrathecal hyperbaric bupivacaine required for successful anesthesia. However, it reduced the dose required for tourniquet pain blockade.

Predictive factors for response of peripheral arteriovenous malformations to embolization therapy: analysis of clinical data and imaging findings.

PURPOSE: To find a significant predictive factor for the efficacy of endovascular treatment of peripheral arteriovenous malformations (AVMs). MATERIALS AND METHODS: One hundred seventy-six patients (73 male patients and 103 female patients; mean age, 29.4 y) who underwent treatment for AVMs in the body or extremities were included. Per Schobinger classification, lesions in 31 patients (18%) were stage II, those in 136 (77%) were stage III, and those in nine (5%) were stage IV. AVMs were located in the extremities in 130 patients (74%) and in the trunk in 46 patients (26%). AVMs were angiographically classified as type I (n = 1), type II (n = 36), type IIIa (n = 6), type IIIb (n = 9 1), or complex type (n = 42). Demographic factors, clinical data, and imaging data were analyzed to determine a statistically significant relationship with overall clinical outcomes. RESULTS: Overall, 68 patients (39%) were cured, 91 patients (52%) showed a partial response, nine patients (5%) showed no response, treatment failed in seven patients (4%), and treatment aggravated the condition in one patient (1%). The overall complication rate was 45% (79 of 176 patients). Minor complications developed in 62 patients (35%) and major complications developed in 17 (10%). Statistically, the extent of AVMs (odds ratio, 0.199) and angiographic classification (odds ratio, 0.162) were significant predictive factors for overall clinical outcome. CONCLUSIONS: Endovascular treatment of peripheral AVMs, planned with consideration of anatomic extent and angiographic subtypes, is likely to yield good clinical results with low complication rates.

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.

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.

A comparison of the effects of preanesthetic administration of crystalloid versus colloid on intrathecal spread of isobaric spinal anesthetics and cerebrospinal fluid movement.

BACKGROUND: Movement of the cerebrospinal fluid (CSF) is one of the most important factors in determining the intrathecal spread of isobaric spinal anesthetics. Preanesthetic administration of either crystalloid or colloid immediately before spinal anesthesia (preload) may result in different CSF pulsatile movement because of their different physical properties. We examined whether preload of crystalloid versus colloid may have different effects on the intrathecal spread of isobaric spinal anesthetics as a result of their different CSF dynamics regarding its pulsatile movement. METHODS: In a clinical study of isobaric spinal anesthesia, patients were allocated into 1 of 2 groups according to preload with either crystalloid (n = 30) or colloid (n = 30) before spinal anesthesia with 0.5 isobaric tetracaine. The pulsatile movements of CSF at the L2-3 intervertebral space and midportion of the aqueduct of Sylvius were also examined by magnetic resonance images in healthy volunteers (n = 23) at 0, 30, and 60 minutes after administering either crystalloid or colloid. RESULTS: In the clinical study, the time to reach the peak sensory block level was delayed significantly in the crystalloid preload group (27.2 ± 17.8 minutes; P < 0.01) compared with the colloid preload group (13.9 ± 7.0 minutes). The median sensory block levels of the crystalloid preload group at 15 minutes (T10, P < 0.05) and 20 minutes (T9.5, P < 0.05) were significantly lower than those (T8, T7, respectively) of the colloid preload group. In the magnetic resonance imaging study, cranially directed CSF pulsatile movement decreased significantly at the L2-3 intervertebral intrathecal space at 30 minutes after crystalloid administration, but not after colloid administration. The CSF production rate significantly increased at 30 minutes (637 µL/min, P < 0.05) after crystalloid preload compared with the baseline measurement (448 µL/min), and then slightly decreased (609 µL/min) at 60 minutes. In the colloid preload group, the CSF production rate was not statistically significant compared with the baseline measurement (464, 512, and 542 µL/min at baseline, 30, and 60 minutes, respectively). CONCLUSIONS: Compared with a colloid preload, which may be comparable to the no-preload condition, crystalloid preload prolonged the time to reach the peak sensory block level in isobaric spinal anesthesia, which might have been caused by a significant decrease in CSF pulsatile movement. This attenuated CSF pulsatile movement in the crystalloid preload group might have resulted from significant increases of CSF production.

The optimal oblique angle of fluoroscope for thoracic sympathetic ganglion block.

OBJECTIVE: The target in the thoracic sympathetic ganglion block (TSGB) is the anterior edge of the costovertebral articulation along the lateral surface of vertebral bodies T2-4. The present study attempts to determine an optimal safe angle for fluoroscopy in fluoroscope-assisted TSGB through the use of chest CT scan images. Additionally, we seek to determine if differences in these measurements exist in patients with chronic obstructive pulmonary disease (COPD). METHODS: Chest CT scans from 320 patients were included. The range of angle and entry point distance to midline was measured in all subjects. The range of angle was from the minimum angle to thoracic sympathetic ganglion passing over the lateral aspect of body to the maximum angle to the thoracic sympathetic ganglion not puncturing the pleural space. Additionally, these measurements from 50 COPD patients were subsequently compared age-matched individuals without COPD. RESULTS: No significant difference in optimal angle was found for any of the levels between T2 and T4. The optimal angle was significantly different between right and left sides, although no such difference was identified between genders. The older patients had a significantly smaller optimal angle than the younger. Similarly, individuals with COPD had a significantly smaller optimal angle and entry distance. INTERPRETATION: The measurements derived from this study can be used as a reference for TSGB and radiofrequency lesioning to prevent the complications. Specifically, our data indicate that the optimal oblique angle of fluoroscopy is 18°-19° for non-COPD patients and 16°-17° for COPD patients.

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.

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.

Efficacy of milrinone versus nitroglycerin in controlling pulmonary arterial hypertension induced by intravenous injections of absolute ethanol in anesthetized dogs.

PURPOSE: To compare the attenuating effects of milrinone versus nitroglycerin on pulmonary artery pressure (PAP) increase caused by repeat intravenous bolus injection of absolute ethanol in anesthetized dogs. MATERIALS AND METHODS: Twenty-four dogs were randomly distributed into three groups: a control group (group C), a nitroglycerin group (treated with a continuous infusion of nitroglycerin at 5.0 microg/kg/min; group N), and a milrinone group (treated with a continuous infusion of milrinone at 3.0 microg/kg/min after an initial bolus dose of 100 microg/kg; group M). Absolute ethanol (0.1 mL/kg) was injected at 10-minute intervals via a 5-F angiographic catheter advanced into the proximal portion of the inferior vena cava. Immediately before and after each intravenous injection of absolute ethanol, hemodynamic values were obtained through a pulmonary arterial catheter. RESULTS: Group M showed more stable hemodynamic values of systolic, mean, and diastolic PAP and pulmonary vascular resistance (PVR) compared with groups C and N. In addition, group M showed significantly higher values of cardiac output versus group C at 10 minutes after the 10th bolus of ethanol. After restoration of spontaneous breathing, group M also showed the least hemodynamic changes in systolic, mean, and diastolic PAPs and PVR among the groups. CONCLUSIONS: Although a continuous infusion of nitroglycerin or milrinone effectively prevented cardiovascular deterioration, milrinone was superior to nitroglycerin in managing the acute hemodynamic changes that resulted from repeated intravenous bolus injections of absolute ethanol (0.1 mL/kg) in healthy anesthetized dogs.

Cardiovascular effects and predictability of cardiovascular collapse after repeated intravenous bolus injections of absolute ethanol in anesthetized pigs.

PURPOSE: To evaluate the effects of repeated intravenous bolus injections of absolute ethanol on cardiopulmonary hemodynamic changes and to investigate the predictability of ethanol-induced cardiovascular collapse in anesthetized pigs. MATERIALS AND METHODS: Twenty pigs aged 3-6 months and weighing 28-38 kg were enrolled in the study. Absolute ethanol (0.1 mL/kg of body weight) was repeatedly injected through the inferior vena cava central to the renal vein at 10-minute intervals up to a total volume of 1.0 mL/kg. The subjects were divided into a cardiovascular collapse group and a no-collapse group according to the development or absence of cardiac collapse. RESULTS: Among the 20 pigs, 12 died before the final injection. Hemodynamic parameters measured immediately before the injection of absolute ethanol did not differ between the cardiovascular collapse group and the no-collapse group except that among animals with cardiovascular collapse, the injection immediately before the one causing cardiovascular collapse resulted in significant increases in the following hemodynamic parameters: mean pulmonary arterial pressure (P < .01), pulmonary vascular resistance (P = .04), and right ventricular end-diastolic volume (P = .02). No such increases were observed in the no-collapse group. CONCLUSIONS: Hemodynamic profiles in pigs obtained immediately before intravenous injection of absolute ethanol did not predict the subsequent occurrence of cardiovascular collapse except after the injection immediately preceding the one resulting in cardiovascular collapse. In this animal model, significant increases in select hemodynamic parameters occurred after the injection immediately preceding the one resulting in cardiovascular collapse.

Effects of repeat bolus ethanol injections on cardiopulmonary hemodynamic changes during embolotherapy of arteriovenous malformations of the extremities.

PURPOSE: This study was designed to investigate the effects of repeat bolus absolute ethanol injections on cardiopulmonary hemodynamic changes during ethanol embolotherapy of inoperable congenital arteriovenous (AV) malformations in the extremities. MATERIALS AND METHODS: Thirty adult patients (14 male, 16 female; age range, 22-51 years) who underwent ethanol embolotherapy of extremity AV malformations were enrolled in the study. A pulmonary artery catheter was used to measure hemodynamic profiles at baseline (T(baseline)), immediately before (T(pre)) and after (T(post)) a bolus injection of absolute ethanol, at the time of the maximum mean pulmonary arterial pressure (PAP) value during a session (T(highest)), 10 minutes after the final injection (T(final)), and after restoration of spontaneous breathing (T(resp)). RESULTS: The systolic, mean, and diastolic PAP (P < .01, P < .01, and P < .01, respectively) and the systemic vascular resistance index (P < .05) and pulmonary vascular resistance index (PVRI; P < .05) of T(highest) and T(resp) were significantly higher than values for T(final). The volume of a single bolus injection of absolute ethanol from 0.023 to 0.175 mL/kg of body weight showed that the systolic PAP (P = .02), pulmonary capillary wedge pressure (P = .02), and PVRI (P < .01) significantly increased in accordance with the increased single volume of absolute ethanol. A significant increase of the right ventricular end-diastolic volume index and right ventricular end-systolic volume index were observed at a dose of more than 0.14 mL/kg of body weight for a single bolus injection of absolute ethanol. CONCLUSIONS: During ethanol embolotherapy of extremity AV malformations, significant hemodynamic changes can arise during a bolus injection of absolute ethanol. Cardiopulmonary hemodynamic profiles should be monitored closely after a bolus injection of more than 0.14 mL/kg of body weight of absolute ethanol.

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.

Analgesic effects of ketamine infusion therapy in korean patients with neuropathic pain: A 2-week, open-label, uncontrolled study.

BACKGROUND: The overexcitation of the N-methyl-D-aspartate receptor complex appears to play a critical role in the development of neuropathic pain, and ketamine acts as an antagonist to that receptor. Some publications have reported on the prominent relief of neuropathic pain with intravenous or subcutaneous ketamine infusions or a single-dose intravenous ketamine injection despite adverse effects. OBJECTIVES: The primary objective of this study was to determine the analgesic effect of intravenous ketamine infusion therapy for neuropathic pain refractory to conventional treatments. Secondary objectives included identifying the variables related to the analgesic effect and the pain descriptors susceptible to ketamine infusion. METHODS: This 2-week, open-label, uncontrolled study was conducted in Korean patients with neuropathic pain recruited from the Samsung Seoul Hospital (Seoul, Republic of Korea) outpatient pain management unit. Patients were required to have a pain severity score >5 (visual analog scale [VAS], where 0 = no pain and 10 = worst pain imaginable) over a period of ≥1 month while on standard treatment. The patients were required to have shown no benefit from standard treatment and no pain relief lasting over 1 month. The ketamine infusion therapy was composed of 3 sessions performed consecutively every other day. Midazolam was administered concomitantly to reduce the occurrence of central nervous system-related adverse events (AEs) secondary to ketamine. Each session was as follows: ketamine 0.2 mg/kg and midazolam 0.1 mg/kg were administered intravenously for 5 minutes as a loading dose, followed by a continuous infusion of ketamine 0.5 mg/kg/h and midazolam 0.025 mg/kg/h for 2 hours. AEs were assessed in the following ways: close monitoring of ECG, blood pressure, oxygen saturation, and evaluating the need for treatment of AEs during infu- sion and until discharge by an attending anesthesiologist; an open question about discomfort at the end of each session; spontaneous reports about AEs during each session; and the patients' and caregivers' checklist of AEs occurring at home for 2 weeks after discharge. All the descriptors of pain expressed by the patients in Korean were recorded and translated into appropriate English terminology on the basis of the literature on Korean verbal descriptors of pain. Each of the translated pain descriptors was then classified into 1 of 18 sensory items. RESULTS: The overall VAS score for pain decreased from a baseline mean (SD) of 7.20 (1.77) to 5.46 (2.29) (P < 0.001) 2 weeks after treatment in 103 patients (53 males and 50 females; mean age, 52.56 [17.33] years) who completed the study. Variables such as age, sex, and the duration and diagnosis of pain were not found to be associated with analgesic effect. Seven of the 18 pain descriptors were found to have a significant response to ketamine infusion treatment between baseline and 2 weeks follow-up: burning pain (P = 0.008); dull, aching pain (P < 0.001); overly sensitive to touch (P = 0.002); stabbing pain (P = 0.008); electric pain (P = 0.031); tingling pain (P < 0.001); and squeezing pain (P < 0.001). A total of 52 patients reported AEs: 33 during infusion and 44 during recovery and up to 2 weeks follow up. The most commonly reported AEs were snoring (15 [15%]) during infusion and dizziness (43 [42%]) during recovery. CONCLUSIONS: Ketamine infusion therapy was associated with reduced severity of neuropathic pain and generally well tolerated for up to 2 weeks in these patients with neuropathic pain refractory to standard treatment. Variables such as sex, age, and the diagnosis and duration of pain had no association with the analgesic effect of this treatment. Randomized controlled trials are needed to evaluate the efficacy and tolerability of treatment with ketamine infusion.

Glucose and NADPH oxidase drive neuronal superoxide formation in stroke.

OBJECTIVE: Hyperglycemia has been recognized for decades to be an exacerbating factor in ischemic stroke, but the mechanism of this effect remains unresolved. Here, we evaluated superoxide production by neuronal nicotinamide adenine dinucleotide phosphate (NADPH) oxidase as a possible link between glucose metabolism and neuronal death in ischemia-reperfusion. METHODS: Superoxide production was measured by the ethidium method in cultured neurons treated with oxygen-glucose deprivation and in mice treated with forebrain ischemia-reperfusion. The role of NADPH oxidase was examined using genetic disruption of its p47(phox) subunit and with the pharmacological inhibitor apocynin. RESULTS: In neuron cultures, postischemic superoxide production and cell death were completely prevented by removing glucose from the medium, by inactivating NADPH oxidase, or by inhibiting the hexose monophosphate shunt that generates NADPH from glucose. In murine stroke, neuronal superoxide production and death were decreased by the glucose antimetabolite 2-deoxyglucose and increased by high blood glucose concentrations. Inactivating NADPH oxidase with either apocynin or deletion of the p47(phox) subunit blocked neuronal superoxide production and negated the deleterious effects of hyperglycemia. INTERPRETATION: These findings identify glucose as the requisite electron donor for reperfusion-induced neuronal superoxide production and establish a previously unrecognized mechanism by which hyperglycemia can exacerbate ischemic brain injury.

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.

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.