Jin Deok Joo

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.

Comparison of the recovery and respiratory effects of aminophylline and doxapram following total intravenous anesthesia with propofol and remifentanil.

STUDY OBJECTIVE To compare the effects of aminophylline and doxapram on recovery, respiration, and bispectral index (BIS) values in patients after total intravenous anesthesia (TIVA) with propofol and remifentanil. DESIGN Prospective, randomized, blinded clinical trial. SETTING Operating room of a university hospital. PATIENTS 90 adult, ASA physical status 1 and 2 patients scheduled for elective laparoscopic vaginal hysterectomy. INTERVENTIONS TIVA was performed with the induction target of remifentanil 3 ng/mL and propofol 6 μg/mL, followed by the maintenance target of remifentanil 1-3 ng/mL and propofol 3-5 μg/mL at the effect site, and with BIS scores in 40-50 range. Patients were randomized to three groups to receive intravenous (IV) aminophylline 3 mg/kg (n = 30), IV doxapram 1 mg/kg (n = 30), or normal IV saline (control; n = 30). MEASUREMENTS AND MAIN RESULTS After administration of the study drugs, return to spontaneous ventilation differed significantly among the three groups. The times to eye opening and hand squeezing on verbal command were similar. The time to extubation was shortened in both the doxapram and aminophylline groups (P < 0.05). Tidal volumes were increased in the doxapram group at 5-14 minutes and the aminophylline group at 5-12 minutes (P < 0.05). Respiratory rates were increased at 2 to 8 minutes and then showed a decrease at the 12 to 14-minute mark in both the doxapram and aminophylline groups (P < 0.05). No difference was noted between the two groups. BIS values were increased in both the doxapram and aminophylline groups at 4-10 minutes (P < 0.05). Heart rates were increased in the doxapram group for the first 8 minutes and at 1-2 minutes in the aminophylline group (P < 0.05). CONCLUSION Aminophylline 3 mg/kg or doxapram 1 mg/kg shortened the time to spontaneous ventilation and improved early recovery from TIVA without appreciable side effects. The more rapid emergence correlates with higher BIS values when compared with the saline control group. The arousal and respiratory effects of aminophylline were comparable to those of doxapram.

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.

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 PR50s side effects.

Low dose ketamine reduces the induction of ERK1/2 and CREB signaling protein in a neuropathic pain model of rats

BACKGROUND In addition to causing the loss of voluntary sensory and motor function, spinal cord injury (SCI) often creates a state of central neuropathic pain. Rats given SCI display increases in the activated form of transcription factors ERK 1/2 MAPK and CREB in the spinal cord, which correspond to allodynia in a model of neuropathic pain. This study was conducted to determine if low dose ketamine had an effect on the activation of ERK 1/2 and CREB in the development of neuropathic pain. METHODS This study was conducted to evaluate ERK 1/2 and CREB protein in a sham operated (control) group, neuropathic pain and normal saline (NP + NS) group and neuropathic pain and ketamine (NP + Keta) group. To accomplish this, male Sprague-Dawley rats were anesthetized and then subjected to L5-L6 spinal nerve ligation (SNL, neuropathic rats). The total amounts of ERK 1/2 and CREB protein were then assessed by western blot analysis. In addition, changes in the amounts of ERK 1/2 and CREB mRNA were evaluated by RT-PCR. RESULTS There was a significant increase in the amount of ERK 1/2 and CREB in the NP + NS group when compared with the sham group. However, the amount of ERK 1/2 and CREB protein induced due to SNL were significantly reduced by continuous infusion with ketamine in the NP + Keta group. CONCLUSIONS The results of this study revealed a positive linkage between NMDA receptors and the ERK-CREB signaling pathway. Therefore, NMDA receptors could be the target of future therapeutic approaches. Additionally, the results of the present study provide additional evidence that low dose ketamine effectively prevents and treats central neuropathic pain following SNL.

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).

Effects of Dexmedetomidine Infusion on the Recovery Profiles of Patients Undergoing Transurethral Resection

Transurethral resection has been the gold standard in the operative management of benign prostatic hyperplasia and bladder tumor; however, it is associated with several complications that may cause patient discomfort. We evaluated the usefulness of continuous infusion of dexmedetomidine on emergence agitation, hemodynamic status, and recovery profiles in patients undergoing elective surgery by a randomized clinical trial. Sixty patients aged 30 to 80 yr who were scheduled for elective transurethral resection under general anesthesia were included in this study. Participants were randomly assigned to two groups (control group, group C; dexmedetomidine group, group D). A total of 60 male patients were enrolled in this study and randomly assigned to group C (n=30) or group D (n=30). The quality of emergence in group D was marked by a significantly lower incidence of emergence agitation than in group C (P=0.015). Patients in group D therefore felt less discomfort induced by the indwelling Foley catheter than those in group C (P=0.022). No statistically significant differences were found between the two groups with respect to side effects including bradycardia (P=0.085), hypotension (P=0.640), and postoperative nausea and vomiting (P=0.389). Our study showed that intraoperative dexmedetomidine infusion effectively reduced the incidence and intensity of emergence agitation and catheter-induced bladder discomfort without delaying recovery time and discharge time, thus providing smooth emergence during the recovery period in patients undergoing transurethral resection (Clinical Trial Registry No. KT0001683).

Lidocaine attenuates the expression of ERK1/2 and CREB in a neuropathic pain model of rats

BACKGROUND In addition to causing the loss of voluntary sensory and motor function, spinal cord injury (SCI) often creates a state of central neuropathic pain. Rats given SCI display increases in the activated form of transcription factors ERK 1/2, p38 MAPK, and CREB in the spinal cord, which correspond to allodynia in a model of neuropathic pain. The current study was designed to determine if lidocaine had an effect on the development of neuropathic pain in response to SCI. METHODS Male Sprague Dawley rats were anesthetized and then received a L5-L6 spinal nerve ligation (neuropathic rats). The levels of intracellular cell-signaling protein, ERK 1/2 and CREB were then assessed by western blot analysis of samples collected from a sham operated (control) group, a neuropathic pain and normal saline (NP + NS) group, and a neuropathic pain and 5% lidocaine (NP + Lido) group. RESULTS The increased levels of ERK 1/2 and CREB protein that were observed in the neuropathic pain model were reduced by continuous infusion of 5% lidocaine. CONCLUSIONS The current results suggest that lidocaine therapy may be an effective method of preventing and treating central neuropathic pain following SCI, and that these effects may occur via the reduced expression of ERK 1/2 and CREB in the intracellular cell-signaling pathway.

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. Graphical Abstract