The effects of etomidate on expression of high mobility group box 1 via the nuclear factor kappa B pathway in rat model of sepsis.

Etomidate is an anesthetic agent used in hemodynamically unstable patients, but its use has been controversial in septic patients. The response of high-mobility group box 1 (HMGB1), a late-phase lethal cytokine in sepsis, to etomidate has not been reported. This study investigated the effects of etomidate on the expression and release of HMGB1 and the underlying mechanism using a cecal ligation and puncture (CLP) model. Thirty-six male Sprague-Dawley rats were divided into sham, CLP, and Etomi groups. Sepsis was induced in the CLP and Etomi groups, and intravenous etomidate (4 mg/kg) was infused for 40 min immediately after operation in the Etomi group. Serum creatinine, alanine aminotransferase (ALT), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and HMGB1 levels were measured 6 and 24 hours after surgery. Activation of nuclear factor (NF)-ĸB and HMGB1 mRNA expression in the liver, lung, kidney, and ileum tissues were measured, and immunohistochemical staining of HMGB1 was implemented. Increases of the TNF-α level 6 h after CLP and ALT and IL-6 levels 24 h after CLP were significantly inhibited by etomidate treatment. Etomidate treatment also significantly attenuated the increase in serum HMGB1 level at 6 and 24 h after CLP and suppressed the NF-ĸB and HMGB1 mRNA in multiple organs 24 h after CLP. Immunohistochemical staining also revealed that etomidate treatment inhibited HMGB1 expression. Etomidate inhibited the systemic release of HMGB1 and its expression in various organs. The mechanism may be associated with the inhibitory effects of etomidate on pro-inflammatory cytokine release and NF-ĸB activity.

Successful management of a tracheomalacia patient with active endotracheal bleeding due to intraoperative innominate artery injury: A case report.

RATIONALE: Intraoperative innominate artery injury is life-threatening in tracheomalacia patients with prolonged tracheostomy. Anesthetic management is challenging in cases with massive hemorrhage into the endotracheal tube. We report a case in which we successfully managed a tracheomalacia patient with acute endotracheal bleeding due to innominate artery injury. PATIENT CONCERNS: A 24-year-old patient with tracheomalacia was scheduled to undergo exploratory thoracotomy for the treatment of intermittent bleeding at the tracheostomy site. During exploration, sudden active bleeding due to innominate artery injury was observed in the endotracheal lumen. DIAGNOSES: The patient was diagnosed with tracheomalacia. INTERVENTIONS: We immediately used the bronchoscope to place the tip of the endotracheal tube at the bleeding site and hyperinflated the cuff. OUTCOMES: The ballooned cuff compressed the active bleeding site, so no additional bleeding was detected by bronchoscopy, and no additional massive bleeding was observed in the operative field. LESSONS: Immediate and appropriate overinflation of the endotracheal tube cuff by an anesthesiologist may provide improved surgical field visibility and time for critical surgical procedures in cases of massive hemorrhaging.

Effects of Positive End-Expiratory Pressure on Intraocular Pressure during One-Lung Ventilation in the Lateral Decubitus Position-A Prospective Randomized Trial.

Background and Objectives: The effect of positive end-expiratory pressure (PEEP) on intraocular pressure (IOP) is debatable. There have been no studies investigating the effects of PEEP on IOP during one-lung ventilation (OLV). We aimed to investigate the effects of PEEP on IOP in patients undergoing OLV for video-assisted thoracoscopic surgery (VATs). Materials and Methods: Fifty-two patients undergoing VATs were divided into a zero-PEEP (ZEEP) and a 6 cmH2O of PEEP (PEEP) groups. IOP, ocular perfusion pressure (OPP), and respiratory and hemodynamic parameters were measured before induction (T1), immediately following endotracheal intubation (T2), 30 min (T3) and 60 min (T4) after a position change to the lateral decubitus position (LDP) and OLV, and 10 min following two-lung ventilation near the end of the surgery (T5). Results: There was no significant difference in IOP and OPP between the two groups. The IOP of the dependent eye was significantly higher than that of the non-dependent eye during LDP in both groups. Peak inspiratory pressure was significantly higher in the PEEP group than in the ZEEP group at T3-T5. Dynamic compliance was significantly higher in the PEEP group than in the ZEEP group at T2-T5. The ratio of arterial oxygen partial pressure to fractional inspired oxygen was significantly higher in the PEEP group than in the ZEEP group at T4. Conclusions: Applying 6 cmH2O of PEEP did not increase IOP but enhanced dynamic compliance and oxygenation during OLV. These results suggest that 6 cmH2O of PEEP can be safely applied during OLV in LDP.

Amitriptyline inhibits the MAPK/ERK and CREB pathways and proinflammatory cytokines through A3AR activation in rat neuropathic pain models.

BACKGROUND: The pain-relief properties of tricyclic antidepressants can be attributed to several actions. Recent observations suggest that adenosine is involved in the antinociceptive effect of amitriptyline. The A3 adenosine receptor (A3AR) is the only adenosine subtype overexpressed in inflammatory and cancer cells. This study was performed to investigate the role of A3AR in the anti-nociceptive effect of amitriptyline. METHODS: Spinal nerve-ligated neuropathic pain was induced by ligating the L5 and L6 spinal nerves of male Sprague-Dawley rats. The neuropathic rats were randomly assigned to one of the following three groups (8 per group): a neuropathic pain with normal saline group, a neuropathic pain with amitriptyline group, and a neuropathic pain with amitriptyline and 3-ethyl-5-benzyl- 2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS) group. Amitriptyline or saline was administered intraperitoneally and 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS-1191), an A3AR antagonist, was injected subcutaneously immediately before amitriptyline administration. The level of extracellular signal-regulated kinase P44/42 (ERK1/2), cyclic AMP response element-binding protein (CREB), and proinflammatory cytokines were assessed using immunoblotting or reverse-transciption polymerase chain reaction. RESULTS: Amitriptyline increased the mechanical withdrawal threshold of the neuropathic rats. The level of phospho-ERK1/2 and phospho-CREB proteins, and proinflammatory cytokines produced by spinal nerve ligation were significantly reduced by amitriptyline administration. However, the use of MRS-1191 before amitriptyline administration not only reduced the threshold of mechanical allodynia, but also increased the signaling protein and proinflammatory cytokine levels, which were reduced by amitriptyline. CONCLUSIONS: The results of this study suggest that the anti-nociceptive effect of amitriptyline involves the suppression of ERK1/2 and CREB signaling proteins, and A3AR activation also affects the alleviation of the inflammatory response.

Continuous administration of ramosetron with patient-controlled analgesia after laparoscopic distal gastrectomy does not delay postoperative bowel function recovery: A prospective, randomized, double-blinded study.

BACKGROUND: Currently, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists are indicated to slow gastrointestinal motility in the diarrhea-predominant subtype of irritable bowel syndrome. They are commonly used to prevent or treat postoperative nausea and vomiting (PONV) and opioid-induced nausea and vomiting (OINV). We conducted a prospective, randomized, double-blinded study to investigate whether the continuous administration of ramosetron, a selective 5-HT3 receptor antagonist, for preventing PONV and/or OINV after laparoscopic distal gastrectomy (LDG) might influence bowel function recovery. METHODS: Patients scheduled to undergo LDG were randomly assigned to 1 of 3 treatment regimens: no prophylactic ramosetron (Group C); ramosetron 0.6 mg added to 2-day intravenous patient-controlled analgesia (IV-PCA) (Group R0.6); and ramosetron 1.2 mg added to 2-day IV-PCA (Group R1.2). Postoperative recovery profiles of bowel function, incidence of postoperative nausea/vomiting and pain, and perioperative data that affected bowel function recovery were evaluated. RESULTS: Seventy-three patients completed the study protocol. Parameters associated with postoperative recovery of bowel function, such as time to first flatus, time to first bowel movement, time to first defecation, and time to commencement of soft diet, were not significantly different between the 3 groups. The incidence of nausea 2 to 24 hours after surgery was significantly lower in Group R0.6 (20.0%) and Group R1.2 (12.5%) than in Group C (45.8%) (P < .022). The ratio of complete response 2 to 24 hours after surgery was significantly higher in Group R0.6 (80.0%) and Group R1.2 (87.5%) than in Group C (54.2%) (P < .022). The incidence of retching 24 to 48 hours after surgery was significantly lower in Group R0.6 (0.0%) and Group R1.2 (4.2%) than in Group C (16.7%) (P < .043). CONCLUSION: Continuous administration of ramosetron with patient-controlled analgesia to prevent PONV and OINV after LDG did not delay postoperative bowel function recovery.

Optimal dose of perineural dexmedetomidine for interscalene brachial plexus block to control postoperative pain in patients undergoing arthroscopic shoulder surgery: A prospective, double-blind, randomized controlled study.

BACKGROUND: Adjuvant perineural dexmedetomidine can be used to prolong the analgesic effect of interscalene brachial plexus block (ISB). We investigated the optimal dose of dexmedetomidine in ISB for postoperative analgesia in patients undergoing arthroscopic shoulder surgery. METHODS: One hundred patients scheduled for elective shoulder arthroscopic surgery were enrolled in this randomized, double-blind study. Ultrasound-guided ISB was performed before general anesthesia using 22 mL of ropivacaine 0.5% combined with 1, 1.5, or 2 µg/kg of dexmedetomidine (group D1, D2, and D3, respectively) or with normal saline as a control (group R, n = 25 per group). The primary outcome was the duration of analgesia (DOA), numeric pain rating scale (NRS), and consumption of additional analgesics during 36 h after ISB. Secondary outcome included durations of motor and sensory block (DOM and DOS), hemodynamic variables and sedation and dyspnea scores. RESULTS: Ninety-seven patients completed the study. The DOS, DOM, and DOA were significantly longer in the dexmedetomidine groups than in group R. The DOA was significantly longer in group D3 than in groups D1 (P = .026) and D2 (P = .039). The DOA was 808.13 ±â€Š179.97, 1032.60 ±â€Š288.14, 1042.04 ±â€Š188.13, and 1223.96 ±â€Š238.06 min in groups R, D1, D2, and D3, respectively. The NRS score was significantly higher in group R than in the dexmedetomidine groups 12 h after ISB (P < .001) and significantly lower in group D3 than in the other groups 18 h after ISB (P = .02). The incidence of hypotension was higher in groups D2 and D3 than in group R during surgery (P = .008 and P = .011, respectively). There were no significant differences in consumption of rescue analgesics, sedation, and dyspnea scores between the study groups. CONCLUSION: Perineural dexmedetomidine 2 µg/kg could be the optimal dose in ISB for arthroscopic shoulder surgery in that it provides an adequate DOA. However, this dose was associated with increased risk of hypotension.

The Effects of Remifentanil on Expression of High Mobility Group Box 1 in Septic Rats.

High mobility group box 1 (HMGB1) is a pivotal mediator of sepsis progression. Remifentanil, an opioid agonist, has demonstrated anti-inflammatory effects in septic mice. However, it is not yet known whether remifentanil affects the expression of HMGB1. We investigated the effects of remifentanil on HMGB1 expression and the underlying mechanism in septic rats. Forty-eight male Sprague-Dawley rats were randomly divided into 3 groups; a sham group, a cecal ligation and puncture (CLP) group, and a CLP with remifentanil treatment (Remi) group. The rat model of CLP was used to examine plasma concentrations of proinflammatory cytokines, tissue HMGB1 mRNA and the activity of nuclear factor (NF)-κB in the liver, lungs, kidneys, and ileum. Pathologic changes and immunohistochemical staining of NF-κB in the liver, lungs, and kidneys tissue were observed. We found that remifentanil treatment suppressed the level of serum interleukin (IL)-6 and tumor necrosis factor (TNF)-α 6 hours after CLP, and serum HMGB1 24 hours after CLP. HMGB1 mRNA levels and the activity of NF-κB in multiple organs decreased by remifentanil treatment 24 hours after CLP. Remifentanil treatment also attenuated nuclear expression of NF-κB in immunohistochemical staining and mitigated pathologic changes in multiple organs. Altogether, these results suggested that remifentanil inhibited expression of HMGB1 in vital organs and release of HMGB1 into plasma. The mechanism was related to the inhibitory effect of remifentanil on the release of proinflammatory cytokines and activation of NF-κB.

Comparison of an Intraoperative Infusion of Dexmedetomidine, Fentanyl, and Remifentanil on Perioperative Hemodynamics, Sedation Quality, and Postoperative Pain Control.

We aimed to compare fentanyl, remifentanil and dexmedetomidine with respect to hemodynamic stability, postoperative pain control and achievement of sedation at the postanesthetic care unit (PACU). In this randomized double-blind study, 90 consecutive total laparoscopic hysterectomy patients scheduled for elective surgery were randomly assigned to receive fentanyl (1.0 µg/kg) over 1 minute followed by a 0.4 µg/kg/hr infusion (FK group, n = 30), or remifentanil (1.0 µg/kg) over 1 minute followed by a 0.08 µg/kg/min infusion (RK group, n = 30), or dexmedetomidine (1 µg/kg) over 10 minutes followed by a 0.5 µg/kg/hr infusion (DK group, n = 30) initiating at the end of main procedures of the operation to the time in the PACU. A single dose of intravenous ketorolac (30 mg) was given to all patients at the end of surgery. We respectively evaluated the pain VAS scores, the modified OAA/S scores, the BIS, the vital signs and the perioperative side effects to compare the efficacy of fentanyl, remifentanil and dexmedetomidine. Compared with other groups, the modified OAA/S scores were significantly lower in DK group at 0, 5 and 10 minutes after arrival at the PACU (P < 0.05), whereas the pain VAS and BIS were not significantly different from other groups. The blood pressure and heart rate in the DK group were significantly lower than those of other groups at the PACU (P < 0.05). DK group, at sedative doses, had the better postoperative hemodynamic stability than RK group or FK group and demonstrated a similar effect of pain control as RK group and FK group with patient awareness during sedation in the PACU. (World Health Organization registry, KCT0001524).

Aminophylline partially prevents the decrease of body temperature during laparoscopic abdominal surgery.

Aminophylline can elicit thermogenesis in rats or increase metabolic rate during cold stress in lambs. We tested the hypothesis that aminophylline would reduce the change in core body temperature during laparoscopic abdominal surgery requiring pneumoperitoneum. Fifty patients were randomly divided into an aminophylline group (n=25) and a saline control group (n=25). Esophageal temperature, index finger temperature, and hemodynamic variables, such as mean blood pressure and heart rate, were measured every 15 min during sevoflurane anesthesia. In the aminophylline group, esophageal temperatures at T45 (36.1±0.38 vs. 35.7±0.29, P=0.024), T60 (36.0±0.39 vs. 35.6±0.28, P=0.053), T75 (35.9±0.34 vs. 35.5±0.28, P=0.025), T90 (35.8±0.35 vs. 35.3±0.33, P=0.011), and T105 (35.8±0.36 vs. 35.1±0.53, P=0.017) and index finger temperatures at T15 (35.8±0.46 vs. 34.9±0.33, P<0.001), T30 (35.7±0.36 vs. 35.0±0.58, P=0.029), T45 (35.8±0.34 vs. 35.2±0.42, P=0.020), T60 (35.7±0.33 vs. 34.9±0.47, P=0.010), T75 (35.6±0.36 vs. 34.8±0.67, P=0.028), T90 (35.4±0.55 vs. 34.4±0.89, P=0.042), and T105 (34.9±0.53 vs. 33.9±0.85, P=0.024) were significantly higher than in the saline control group. Aminophylline is effective in maintaining the core temperature through a thermogenic effect, despite reduced peripheral thermoregulatory vasoconstriction.

Effect of milrinone on the inflammatory response and NF-kB activation in renal ischemia-reperfusion injury in mice.

BACKGROUND: Milrinone increases intracellular adenosine 3',5'-cyclic monophosphate concentration and enhances vascular relaxation. Nuclear factor-kappa B (NF-kB) plays a key role in inflammatory responses during ischemia-reperfusion (I/R) injury. We aimed to investigate the effect of milrinone on the inflammatory responses and NF-kB activation in renal I/R injury in mice. METHODS: Thirty C57BL/6 mice were allocated into 3 groups. In group S (n = 10), only right nephrectomy was done. In group C (n = 10), the left kidney was subjected to 30 min of ischemia after right nephrectomy. In group M (n = 10), milrinone (5 µg/kg) was administered before ischemia. After 24 hours of reperfusion, the serum creatinine was measured, kidney samples were obtained for histology, and expressions of NF-kB and proinflammatory cytokines were analyzed. RESULTS: In group C, the serum creatinine concentration was markedly elevated, compared with group S. Creatinine concentration in group M was also elevated, but it was significantly lower than that in group C. Histologic evidence of renal damage was severe in group C, but it was improved in group M. In groups C and M, expression of NF-kB, tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) mRNA increased significantly compared with group S (P < 0.05). But group M showed a lower expression of NF-kB, TNF-α, ICAM-1, MCP-1 and MIP-2 mRNA than group C (P < 0.05). CONCLUSIONS: Milrinone treatment attenuates the renal inflammatory response and activation of NF-kB, resulting in improvement of renal function and tissue injury.

The comparison of sedation quality, side effect and recovery profiles on different dosage of remifentanil patient-controlled sedation during breast biopsy surgery.

BACKGROUND: The patient-controlled sedation (PCS) allows for rapid individualized titration of sedative drugs. Propofol has been the most widely used IV adjuvant, during the monitored anesthesia care (MAC). This study was designed to compare the sedation quality, side effect and recovery of the propofol alone, and propofol-remifentanil combination, using PCS for breast biopsy. METHODS: Seventy five outpatients, undergoing breast biopsy procedures with local anesthesia, were randomly assigned to receive propofol alone (group P), propofol-25 ug/ml of remifentanil (group PR25), and propofol-50 ug/ml of remifentanil (group PR50), using PCS. Pain visual analogue scores (VAS) and digit symbol substitution test (DSST), Vital signs, bi-spectral index (BIS) and observer assessment of alertness and sedation (OAA/S) score were recorded. RESULTS: Apply/Demand ratio in the group PR50 had a significant increase over the other groups (P < 0.05). The incidence of excessive sedation and dizziness were significantly more frequent in the group PR50 (P < 0.05). BIS and OAA/S score significantly decreased in the group PR25, PR50 at 15 min after the operation, the end of surgery (P < 0.05). At 5 min after the start of PCS, patients in the group PR25 and PR50 gave significantly less correct responses on the DSST than that of the group P (P < 0.05). CONCLUSIONS: Compared with the propofol alone, intermittent bolus injection of propofol-remifentanil mixture could be used, appropriately, for the sedation and analgesia during MAC. The group PR25 in a low dose of remifentanil has more advantages in terms of sedation and satisfaction because of the group PR50's side effects.

Hepatic ischemic preconditioning provides protection against distant renal ischemia and reperfusion injury in mice.

We previously demonstrated that there are acute and delayed phases of renal protection against renal ischemia and reperfusion (IR) injury with renal ischemic preconditioning (IPC). This study assessed whether hepatic IPC could also reduce distant renal IR injury through the blood stream-mediated supply of reactive oxygen species (ROS). Male C57BL/6 mice were randomly divided into four groups: group I, sham operated including right nephrectomy; group II (IR), left renal ischemia for 30 min and reperfusion injury; group III (IPC-IR), hepatic ischemia for 10 min followed by 10 min of reperfusion before left renal IR injury; group IV (MPG - IPC + IR), pretreated with 100 mg/kg N-(2-mercaptopropionyl)-glycine (MPG) 15 min before hepatic IPC and left renal IR injury. Renal function, histopathologic findings, proinflammatory cytokines, and cytoprotective proteins were evaluated 15 min or 24 hr after reperfusion. Hepatic IPC attenuated the expression of proinflammatory cytokines, tumor necrosis factor α, intercellular adhesion molecule 1, and induced inducible nitric-oxide synthase, and the phosphorylation of Akt in the murine kidney. Renal function was better preserved in mice with hepatic IPC (group III) than groups II or IV. Hepatic IPC protects against distant renal IR injury through the blood stream-delivery of hepatic IPC-induced ROS, by inducing cytoprotective proteins, and by inhibiting inflammatory reactions.

Efficacy of epidural analgesia in patients with cancer pain: a retrospective observational study.

PURPOSE: Pain in terminal cancer patients may be refractory to systemic analgesics or associated with adverse drug reactions to analgesics. Epidural analgesia has been effectively used in such patients for pain control. However, this method does not provide pain relief to all patients. The efficacy and complications of continuous epidural analgesia were evaluated for expanding efficacy in terminal cancer patients. MATERIALS AND METHODS: The charts of patients who received epidural analgesia for over 5 years for the control of terminal cancer pain were reviewed retrospectively. RESULTS: Ninety-six patients received 127 epidural catheters. The mean duration for epidural catheterization was 31.5±55.6 (5-509) days. The dose of epidural morphine increased by 3.5% per day. The efficacy of epidural analgesia at 2 weeks follow up revealed improved pain control (n=56), as the morphine equivalent drug dose dropped from 213.4 mg/day to 94.1 mg/day (p<0.05) at 2 weeks follow up. Accordingly, after 2 weeks institution of epidural analgesia, there was a significant reduction in the proportion of patients with severe pain, from 78.1% to 19.6% (p<0.05). CONCLUSION: Epidural analgesia was an effective pain control method in patients with terminal cancer pain, however, a systematized algorithm for the control of cancer-related pain in needed.

Acute compartment syndrome of the forearm and hand in a patient of spine surgery -A case report-.

A 38-year-old woman underwent a 4-hour operation in the prone position for a laminectomy at C4-7 and posterior cervical decompressive fusion at C7-T1 under general anesthesia. After undraping at the end of surgery, considerable swelling with many blisters of the left forearm and hand was observed. The chest roll at the left side had moved cephalad into the axilla and compressed the axillary structures. An emergency fasciotomy to decompress the compartments of the forearm and dorsal surface of the hand was performed. In the post anesthesia care unit, the radial pulse of the left hand was palpable and the level of oxygen saturation was normal. Forearm and hand edema subsided gradually over several days and the patient was discharged with full function of her left arm. This compartment syndrome suggests careful attention should be paid to the position of the chest roll when the prone position is established for a long duration.

Polymorphisms in FOXO gene family and association analysis with BMI.

Forkhead transcription factors of the FOXO subfamily are emerging as shared components of pathways that regulate a variety of cellular functions. In an effort to identify genetic polymorphisms in candidate genes to determine associations with BMI, we sequenced all exons of the FOXO genes (FOXO1a, FOXO3a, and FOXO4) and examined their associations with BMI in a Korean population (n = 734). Sixteen polymorphisms were identified in FOXO genes: three in FOXO1a, seven in FOXO3a, and six in FOXO4. Associations of FOXO polymorphisms with BMI were analyzed using multiple regression, adjusting for age and sex as covariates. One promoter single nucleotide polymorphism in the 5' flanking region of FOXO3a showed significant association with BMI, e.g., the lowest BMI (23.3 +/- 2.69 kg/m2) was discovered in individuals who were carrying T/T, intermediate BMI (26.6 +/- 3.14 kg/m2) was found in heterozygous individuals (C/T), and the highest BMI (27.2 +/- 3.47 kg/m2) occurred in individuals who were homozygous for the major allele (C/C; p = 0.01).