Neuromuscular Pharmacodynamics of Mivacurium in Patients with Major Burns / 대한마취과학회지

BACKGROUND: Burned patients sometimes require rapid onset of neuromuscular paralysis to secure the airway in full stomach patients or to treat laryngospasm. Because of poor lung function and hypermetabolic state, they desaturate quite rapidly. Burned patients are usually resistant to the effects of nondepolarizing relaxants. Mivacurium can be potentially a good alternative for rapid onset of paralysis, since it is metabolized by plasma cholinesterase, an enzyme often decreased in subject with major burns. This prospective study was conducted to define the neuromuscular pharmacodynamic profile of a single bolus dose of mivacurium in adult patients with major burns. METHODS: Adults (M/F = 22/8), aged 44.0 +/- 10.2 years, with total body surface area (TBSA) burn of 35.0 +/- 12.5% were studied at 39.8 +/- 28.9 post burn days. Age and sex matched 30 non-burned patients served as controls. Anesthesia was consisted of propofol and fentanyl infusion with nitrous oxide and oxygen. Mivacurium 0.2 mg/kg was administered as a bolus. Using TOF Watch, neuromuscular block was monitored with T1 response after the initial tetanic stimulation to recruit all muscle fibers. Onset time was defined as the interval from the beginning of drug administration to maximal twitch suppression. Intubation was attempted at 1 minute after the drug administration to simulate the rapid sequence induction with recording of either failure or success of intubation. By allowing spontaneous recovery without reversal drug, recovery profiles of neuromuscular paralysis were also measured. RESULTS: Patients demographics were similar in both groups except for the burn. Onset times and all recovery profiles were significantly prolonged in the burned versus non-burned groups. Attempts at intubation at 1 minute after the drug administration were successful with difficulty in approximately 70% of patients in both groups. CONCLUSIONS: Mivacurium 0.2 mg/kg demonstrated the conflicting dual responses in the burned patients. The prolonged onset time suggests resistance to neuromuscular effects. The prolonged recovery suggests increased sensitivity. This can be partially explained by the acetylcholine receptor proliferation and decreased level of plasma pseudocholinesterase. In view of the prolonged onset time of almost two minutes for maximal paralysis, mivacurium does not appear to be a good drug for rapid onset of paralysis in burns.

Nonlinear Mixed Effect Modeling of Population Pharmacokinetics and Pharmacodynamics of Etomidate / 대한마취과학회지

BACKGROUND: Etomidate is used as a fast-acting hypnotic with few cardiovascular effects to induce anesthesia in patients with a poor cardiovascular reserve. The bispectral index (BIS) has been suggested to be a measure of the depth of anesthesia and correlates well with the level of consciousness. This study examined the population pharmacokinetics and pharmacodynamics of etomidate using nonlinear mixed effect (NONMEM) modeling and sigmoid Emax modeling. METHODS: Eighteen middle aged adults, with ASA physical status I or II, who were scheduled for elective surgery, were included. 0.2% etomidate was administerd at 150 ml/h until the patients lost consciousness. The patient recovered spontaneously until they regained consciousness, as determined by a verbal response. The BIS was determined and arterial blood samples were collected. The plasma concentrations were measured with high performance liquid chromatograhy (HPLC). NONMEM was used for population pharmacokinetic and sigmoid Emax model for pharmacodynamic analysis. RESULTS: The induction dose for the loss of eyelid reflexes was 0.38 mg/kg. The induction time from drug infusion to the loss of eyelash reflexes was approximately 3.5 minutes. This study took approximately 8.5 minutes from the start of drug infusion to the recovery of consciousness. The pharmacokinetic parameters were t(1/2alpha) = 1.1 min, t(1/2beta) = 1.9 min, t(1/2gamma) = 106.5 min, k(21) = 0.36 L/min, k(31) = 0.009 L/min, V(1) = 6.43 L, V(area) = 426 L, C(l) = 2.77 L/min. The pharmacodynamics were keo = 0.40 L/min, CE(50) = 1.0 microgram/mL, E(0) = 94, E(max) = 94 and gamma = 1.2. The performance error for the etomidate concentration was 0.14+/-0.99 (typical prediction) and -0.03+/-0.40 (individual prediction) and -0.09+/-1.00 and -0.001+/-0.13 for the BIS score. CONCLUSIONS: When compared with other previously published data, our pharmacokinetic parameters demonstrated a shorter half lives, a larger volume of distribution, and an increased clearance with significant interindividual differences. The pharmacodynamics showed a large interindividual variability. The reason for discrepancy might be the relatively short sampling time. However, further study will be warranted to improve the model performance in the future.

Nonlinear Mixed Effect Modeling of Population Pharmacokinetics and Pharmacodynamics of Etomidate / 대한마취과학회지

BACKGROUND: Etomidate is used as a fast-acting hypnotic with few cardiovascular effects to induce anesthesia in patients with a poor cardiovascular reserve. The bispectral index (BIS) has been suggested to be a measure of the depth of anesthesia and correlates well with the level of consciousness. This study examined the population pharmacokinetics and pharmacodynamics of etomidate using nonlinear mixed effect (NONMEM) modeling and sigmoid Emax modeling. METHODS: Eighteen middle aged adults, with ASA physical status I or II, who were scheduled for elective surgery, were included. 0.2% etomidate was administerd at 150 ml/h until the patients lost consciousness. The patient recovered spontaneously until they regained consciousness, as determined by a verbal response. The BIS was determined and arterial blood samples were collected. The plasma concentrations were measured with high performance liquid chromatograhy (HPLC). NONMEM was used for population pharmacokinetic and sigmoid Emax model for pharmacodynamic analysis. RESULTS: The induction dose for the loss of eyelid reflexes was 0.38 mg/kg. The induction time from drug infusion to the loss of eyelash reflexes was approximately 3.5 minutes. This study took approximately 8.5 minutes from the start of drug infusion to the recovery of consciousness. The pharmacokinetic parameters were t(1/2alpha) = 1.1 min, t(1/2beta) = 1.9 min, t(1/2gamma) = 106.5 min, k(21) = 0.36 L/min, k(31) = 0.009 L/min, V(1) = 6.43 L, V(area) = 426 L, C(l) = 2.77 L/min. The pharmacodynamics were keo = 0.40 L/min, CE(50) = 1.0 microgram/mL, E(0) = 94, E(max) = 94 and gamma = 1.2. The performance error for the etomidate concentration was 0.14+/-0.99 (typical prediction) and -0.03+/-0.40 (individual prediction) and -0.09+/-1.00 and -0.001+/-0.13 for the BIS score. CONCLUSIONS: When compared with other previously published data, our pharmacokinetic parameters demonstrated a shorter half lives, a larger volume of distribution, and an increased clearance with significant interindividual differences. The pharmacodynamics showed a large interindividual variability. The reason for discrepancy might be the relatively short sampling time. However, further study will be warranted to improve the model performance in the future.

Enhanced Clearance of Propofol in Patients with Major Burns / 대한마취과학회지

BACKGROUND: Major burns can alter the pharmacokinetics of the commonly used drugs during the perioperative period. This study was carried out to define the pharmacokinetics of propofol in the burned patients during the subacute hyperdynamic phase of the injury. METHODS: Twenty adults, aged 43.7+/-2.3 years, with total body surface area burn of 44.0+/-22.2%, were examined at 14.1+/-2 days after the injury (mean+/-SD). Age and sex gender matched unburned patients were used as controls. Propofol 2 mg/kg was given intravenously over 10 seconds as a single bolus in both groups. Blood samples (n = 20) were collectedat predetermined intervals. A noncompartmental approach was used for the pharmacokinetic analyses of the propofol concentrations, which were determined by HPLC. The cardiac index was measured by esophageal echocardiography. RESULTS: The burns patients had a significantly higher cardiac index (CI). The clearance (Cl) and total volume of distribution (Vd) of propofol were higher in the burns patients, compared with the controls, yielding a smaller area under the curve. The total half-life (t1/2) was similar in both groups. CONCLUSIONS: There is a large increase in Vd and Cl in the burns patients compared to with the controls. The increased Cl in the burns patients is most likely to be related to the increased CI. Therefore, the initial bolus dose and maintenance infusion may have to be increased in the burns patients, provided the pharmacodynamic sensitivity is unaltered.

Enhanced Clearance of Propofol in Patients with Major Burns / 대한마취과학회지

BACKGROUND: Major burns can alter the pharmacokinetics of the commonly used drugs during the perioperative period. This study was carried out to define the pharmacokinetics of propofol in the burned patients during the subacute hyperdynamic phase of the injury. METHODS: Twenty adults, aged 43.7+/-2.3 years, with total body surface area burn of 44.0+/-22.2%, were examined at 14.1+/-2 days after the injury (mean+/-SD). Age and sex gender matched unburned patients were used as controls. Propofol 2 mg/kg was given intravenously over 10 seconds as a single bolus in both groups. Blood samples (n = 20) were collectedat predetermined intervals. A noncompartmental approach was used for the pharmacokinetic analyses of the propofol concentrations, which were determined by HPLC. The cardiac index was measured by esophageal echocardiography. RESULTS: The burns patients had a significantly higher cardiac index (CI). The clearance (Cl) and total volume of distribution (Vd) of propofol were higher in the burns patients, compared with the controls, yielding a smaller area under the curve. The total half-life (t1/2) was similar in both groups. CONCLUSIONS: There is a large increase in Vd and Cl in the burns patients compared to with the controls. The increased Cl in the burns patients is most likely to be related to the increased CI. Therefore, the initial bolus dose and maintenance infusion may have to be increased in the burns patients, provided the pharmacodynamic sensitivity is unaltered.

Performance Characteristics of High Efficiency Fluid and Blood Warmer using Print Circuit Board Heater at Various Flow Rates / 대한마취과학회지

BACKGROUND: Currently available warming devices are often heavy and cumbersome, requiring development of more portable, user friendly, high efficiency fluid and blood warmer. The intravenous fluid heating capabilities of a new, heat-plate print circuit board (PCB) based warmer at various low flow rates were tested. METHODS: Model Joyother BM-1(R) was investigated for normal saline (0.9% NaCl) and colloid at various infusion rates (60-6000 ml/hr). Final temperatures were measured by electronic thermometer after passing through the warmer. Effective warming was defined as a fluid temperature > or = 32degrees C. Ambient temperature was maintained at 22-25degrees C. Degree of heating capability and temperature decrease were compared and correlated between different flow rates. RESULTS: The device warmed the room temperature crystalloid and colloid efficiently. Its warming capability was continuously improved as the flow rates increased in all tested flow rates, reaching maximum 41degrees C. After the warming, the temperature decrease showed high negative correlation with the flow rates. The extent of cooling was less in colloid. No overheating was noted at sudden brake. CONCLUSIONS: Joyother BM-1(R) heated crystalloid and colloid sufficiently and safely enough for clinical application (exit temperature > or = 35degrees C) at various flow rates. The warming capacity and the length of the intravenous tube infusion system determined the efficiency of the warmer. Further study is warranted for the efficiency of warming for the blood and its element changes.

Western Blot Analysis of Alterations of Skeletal Muscle Nicotinic Acetylcholine Receptor Subunits in the Major Burns: Burn vs. Nonburn Sites / 대한마취과학회지

BACKGROUND: Major burn injury causes aberrant responses to neuromuscular blocking agents, and an increase in fetal type nicotinic acetylcholine receptors (nAchR) has been speculated to contribute to the altered response. This study was conducted to test the hypothesis that the increases in nAchR are due to generalized systemic effects, not limited to area of burn in humans. Using the rectus abdominis muscle of the burned area and quadriceps muscle of nonburned area from the single major burn patient, the changes of nAchR subunits of alpha1, gamma and alpha7 were compared. METHODS: Twelve adults (M:F = 11:1) with total body surface area (TBSA) of 48.8 +/- 19.3% major burns, undergoing burn related elective surgery, were included at 30.8 +/- 16.4 days after the burn injury. Only those with burns in abdominal area and no burns in the lower extremity, were selected. Under general anesthesia, muscle biopsy was taken from the rectus abdominis muscle under the burned abdominal area as well as from the quadriceps muscle under the unburned thigh, at least 30 cm away from the closest burn wound margin. The nAchR changes in the muscles were assayed by western blot using subtype specific mouse antibody for alpha1, gamma and alpha7. RESULTS: The nAchR subunit quantitation (volume% compared to nonburn controls) of alpha1, gamma and alpha7 in the rectus and quadriceps by densitometry were 335.4 +/- 45.4 vs. 321.7 +/- 76.2, 298.3 +/- 234.3 vs. 290.0 +/- 202.3, 149.7 +/- 22.6 vs. 141.6 +/- 35.6, respectively, showing no significant statistical differences between burned and nonburned area (P > 0.05). However, large coefficients of variation were noted in both muscles of gamma group, which may suggest indirect evidence of proliferation of fetal type nAchR in the major burns. TBSA and days after the burn injury were poorly correlated with the amount of expression of subtypes of acetylcholine receptors tested. CONCLUSIONS: Our results confirm that systemic effects of thermal injury include an increase in nAchR at sites distant from the thermal injury, which may account for the skeletal muscle dysfunction and aberrant responses to neuromuscular relaxation. Further studies need to address the importance of burn size and its effects on quantitative and qualitative changes in receptor.

The Limited Immune Modulatory Effect of Early Escharectomy on Adhesion Molecules in Major Burn Patients / 대한마취과학회지

BACKGROUND: Early escharectomy has been shown to improve the survival rates and the treatment outcomes of major burn patients. However, its exact mechanism, especially in terms of the human immune system, has not been fully elucidated. This observational study, which placed a focus on adhesion molecules, was conducted to assess changes of soluble intercelluar adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and E-selectin in major burn patients undergoing early eschar excision. METHODS: Seventeen ASA physical status II or III adult major burn patients, admitted for plastic and reconstructive surgery for burn wound care, were initially recruited. When early escharectomy was scheduled, a series of blood samples were obtained four times at 72 and 24 hours preop and 24 and 72 hours postop, respectively. Changing levels of sICAM-1, sVCAM-1, and E-selectin were measured using quantitative sandwich immunoassay techniques. RESULTS: All patients suffered from major burns. Early escharectomy does not appear to have any significant impact on the levels of sICAM-1 and sVCAM-1. On the other hand, E-selectin levels showed a significant decrease after escharectomy. CONCLUSIONS: Major burn injury certainly induces a systemic inflammatory response. Adhesion molecules behave in such a way that escharectomy has a limited immunomodulatory effect in major burns. This is probably related to the timing and extent of surgery, and the complex nature of burn related inflammation.

Lung Injury Induced by Major Burns does not Affect Fentanyl Clearance / 대한마취과학회지

BACKGROUND: Major burns can alter the pharmacokinetics of opiate analgesics, which are commonly used perioperatively. Fentanyl undergoes a significant amount of pulmonary pharmacokinetic transition. This study was conducted to compare the pharmacokinetics of fentanyl in major burns, with and without lung injury, during the subacute hyperdynamic phase of recovery. METHODS: Twelve adults, with total body surface area (TBSA) 51.0 +/- 11.8% burns, aged 34.9 +/- 9.6 years, with a lung injury related to the burn, were studied at 15.4 +/- 9.4 days after the injury. Another 8 patients, aged 39.8 +/- 10.5 years, with TBSA 46.3 +/- 19.4%, at 19.3 +/- 10.9 days, without lung injury, served as controls. Fentanyl 200microgram was given intravenously over 10 seconds. Blood samples (n = 20) were collected at predetermined intervals. A two-compartment model was used for pharmacokinetic analyses of the fentanyl concentrations, as determined by LC/MS. The cardiac index (CI) was also measured using an esophageal Doppler monitor. RESULTS: There were no differences in the patient characteristics between the two groups. Those with burns had a significantly higher cardiac index (4.1 +/- 2.4 L/min/m2), clearance (Cl), central (V1) and total volume of distribution (Vd), but there were no differences between those with and without lung injury (30.2 +/- 14.3 vs. 30.1 +/- 5.8 ml/min/kg, 0.8 +/- 0.3 vs. 0.6 +/- 0.2 L/kg, 5.8 +/- 1.7 vs. 5.2 +/- 2.1 L/kg, respectively). Prolonged distribution (t1/2alpha) and elimination half-lives (t1/2beta) were noted in those with burns, but there were no differences between the two groups (3.2 +/- 1.3 vs. 3.3 +/- 1.3 minutes, 2.6 +/- 1.4 vs. 2.0 +/- 0.7 hours, respectively). CONCLUSIONS: The increased Cl of fentanyl in those with burns is primarily dependent upon the resultant increased hepatic blood flow. The pulmonary kinetics is a saturable process, which is not affected by a single bolus of fentanyl. The lung injury induced by major burns would have no influence on the elimination kinetics of fentanyl.

Pseudoaneurysm in the Superficial Femoral Artery Following Removal of a Femoral Vein Catheter: A case report / 대한마취과학회지

Central venous catheterization allows the measurement of hemodynamic variables, the delivery of medications, and nutritional support. The placement of central venous catheterization is associated with adverse events, such as, arterial puncture, hematoma, A-V fistula, pseudoaneurysm, etc. We report a case of a superficial femoral artery pseudoaneurysm after removing a femoral vein catheter in a 48-year-old female patient undergoing cervical spinal fusion. An insidious arterial puncture not noticed during femoral vein catheterization may produce complications immediately after catheter removal. Whenever a central venous catheter is removed, the importance of firm and even compression for a sufficient length of time cannot be overemphasized.

Onset Time and Duration of Action of Neuromuscular Blockade with Rocuronium in Major Burn Patients / 대한마취과학회지

BACKGROUND: It is well known that burn patients are resistant to the action of nondepolarizing muscle relaxants. Rocuronium, with a shorter onset time and freedom from electrolyte side effects, may be considered for rapid sequence induction in these circumstances. This randomized, double-blind study was conducted to assess the onset time, duration of action of neuromuscular blockades and the intubating conditions induced by rocuronium in major burn patients. METHODS: Adult patients, suffered from major burn injury, aged 18-59 years, ASA physical status I or II, more than 4 weeks and less than 6 months after the initial injury, were included. Propofol and fentanyl based intravenous anesthesia was conducted with nitrous-oxide and oxygen. Neuromuscular blockade was monitored by acceleromyography, TOF-Watch(R) (Organon Teknika B.V., Boseind, The Netherlands), using Train-of-Four (TOF) stimulation. Rocuronium (Esmeron, Organon Inc, USA), at ED95 x 3 (0.9 mg/kg) and ED95 x 4 (1.2 mg/kg) were given intravenously over 5 s in both groups of burn and nonburn patients, respectively. Onset time, duration of action, and intubating conditions were assessed and graded according to the Guidelines for Good Clinical Research Practice. RESULTS: Average burn TBSA were between 30% and 40%, and the elapsed time after the initial injury was approximately a month. Demographic data revealed no significant differences between burn and nonburn groups. The average time to 95% neuromuscular block was significantly prolonged in the burn group compared to the non-burn group (115.0 +/- 58.4 vs. 68.4 +/- 15.8 sec at 0.9 mg/kg, 86.1 +/- 19.7 vs. 56.9 +/- 10.9 sec at 1.2 mg/kg, P < 0.05). Time to reappearance of T1 and duration TOF ratios 0.1, 0.25, 0.75 and 0.8 with respect to baseline were significantly shorter in the burn group. Intubating conditions ranged from good to excellent in the majority. When the different dosages were compared in the burn groups, all measured parameters improved as the dose was increased. CONCLUSIONS: Rocuronium showed significant resistance in the neuromuscular blockade of burn patients, which appeared to improve as increasing the dosage.

The Comparison of Minimum Alveolar Concentration and BIS50 of Inhalation Anesthetics for Evaluation of Anesthetic Potency / 대한마취과학회지

BACKGROUND: The bispectral index (BIS) has been designed to objectively measure the degree of sedation and hypnosis for anesthesia. Although it has been well-known that BIS correlates highly with the concentration of inhalation anesthetics, it is not clear whether analgesic potency expressed as MAC is comparable to hypnotic potency described as BIS50 in inhaled anesthetics. This study was conducted to examine the degree of correspondence by correlating the changes of BIS according to the different MAC of commonly used inhalation anesthetics. METHODS: One hundred ASA class 1 or 2 patients, scheduled for laparoscopic knee surgery were included. Patients were equally divided into 4 groups (n = 25 each) according to the inhalational agent enflurane, isoflurane, desflurane, or sevoflurane. Anesthetic depth for each individual agent was controlled to 2.0, 1.75, 1.5, 1.25, 1.0, 0.75 and 0.5 MAC, respectively. After equilibration for each concentration, BIS values were measured three times at 30 second intervals and an average was obtained. In addition, MAC values for each agent were measured when the bispectral index showed 50. RESULTS: The concentrations of inhaled agents vs. BIS showed high negative correlations (enflurane; -0.91, isoflurane; -0.94, desflurane; -0.84, and sevoflurane; -0.86). BIS50 for each agent was enflurane, 0.93 (1.6 vol%); isoflurane, 0.71 (0.9 vol%); desflurane, 0.95 (5.7 vol%); and sevoflurane, 0.84 MAC (1.7 vol%). Isoflurane-BIS50 showed a significant difference to the others (P<0.05). CONCLUSIONS: We concluded that the MAC of inhalation anesthetics showed poor correlation with BIS, suggesting a difference between the hypnotic and analgesic potency of individual inhaled anesthetic agents.

Atypical Increases of BIS according to Effect Site Concentration of Propofol in Severely Burn Patients Undergoing Early Escharectomy / 대한마취과학회지

BACKGROUND: This bispectral index, which is used for intravenous anesthetics and inhalation anesthesia, is a scale of sedation and hypnotic effect, which is widely used in clinics. Atypical changes in BIS are expected due to increased cardiac output, decreased blood albumin concentrations and renal function in severe burn patients undergoing early escharectomy. The aim of this study was to compare BIS according to effected site concentrations of propofol during anesthetic induction using propofol TCI in severe burn and nonburn patients. METHODS: Forty patients were classified as twenty nonburn elective surgical patients (group 1) and twenty burn patients scheduled for escharectomy (group 2). For induction, a propofol TCI device incorporating a prefilled syringe was adjusted to a target concentration of 6mug/ml in flash mode. The bispectral index was checked before induction and at each effect site concentration of propofol (0.5mug/ml interval) until an effect site concentration of 4.5mug/ml. Other suspected contributory factors such as cardiac index, creatinine clearance and albumin were checked simultaneously. The unpaired t-test and repeated measures ANOVA were performed for the statistical analysis. RESULTS: Below an effect site concentration of propofol of 3mug/ml, no BIS difference was evident between group 1 and group 2. However, at 3.5mug/ml, group 1 was 41.1+/-13.5 and group 2 was 54.7+/-16.6 and at 4mug/ml, group 1 was 40.1+/-2.6 and group 2 was 50.1+/-13.1. Among the suspected contributing factors, cardiac index and albumin showed significant differences between groups 1 and 2 (cardiac index: 3.4+/-0.5 L/min/m2 vs 2.7+/-0.3 L/min/m2, albumin: 4.1+/-0.3 g/dl vs 2.6+/-0.3 g/dl, P<0.05). Creatinine clearance showed no significant difference between the groups. CONCLUSIONS: Severe burn patients who are expecting early escharectomy had higher BIS values than nonburn patients from an effect site concentration of propofol of 3.5mug/ml. This study suggest that cardiac index should be considered as a factor that influences propofol.

Inhibition by Norfluoxetine, the Major Metabolite of Fluoxetine, of Voltage-Gated K+ Channels in Primary Cultured Rat Hippocampal Neurons / 대한마취과학회지

BACKGROUND: Fluoxetine (Prozac), a selective serotonin reuptake inhibitor, has been shown to be effective in the treatment of depression. We investigated the effects of norfluoxetine, the major active metabolite of fluoxetine, on voltage-gated K+ currents in primary cultured hippocampal neurons, and determined the potency and modes of actions of norfluoxetine. METHODS: Voltage-gated K+ currents were studied in primary cultured rat hippocampal neurons using the whole-cell configuration of the patch-clamp technique. Electrophysiological recordings were done in hippocampal neurons between 5-10 days in culture. Transient A-type K+ currents (KA) and delayed-rectifier K+ (KDR) currents were isolated from whole-cell K+ currents using a pulse protocol. RESULTS: Norfluoxetine accelerated the decay rate of whole-cell K+ currents, and thus decreased the current amplitude at the end of a pulse in a concentration-dependent manner. Norfluoxetine inhibited KA and KDR currents in a concentration-dependent manner with IC50's of 0.93 and 0.70micro M, respectively. Norfluoxetine also reduced the areas of KA currents and the steady-state KDR current over the range of test potentials, and the reduction was voltage-dependent (greater increase at more positive potentials). From the onset of the fractional block of KA currents by norfluoxetine during the initial 40 ms of a clamp step, we calculated k1 = 53.26/micro M.s for the association rate constant, and k2 = 70.24/s for the dissociation rate constant. The resulting apparent KD was 1.32micro M, which is similar to the IC50 value obtained from the concentration-response curve. CONCLUSIONS: Our results indicate that norfluoxetine, the major metabolite of fluoxetine, at therapeutic levels, produces a concentration- and voltage-dependent inhibition of KA and KDR currents in primary cultured hippocampal neurons. These effects could perturb the neuronal excitability in the hippocampus, and may contribute to the therapeutic antidepressant action of fluoxetine.

Comparison of Transesophageal Doppler Monitor vs. Pulmonary Artery Catheter in the Hemodynamic Indices of Major Burn Patients Undergoing an Extensive Escharectomy / 대한마취과학회지

BACKGROUND: In major burn patients, many invasive monitors including a pulmonary artery catheter (PAC) are often required to assess hemodynamic status. An esophageal Doppler monitor (EDM), as a noninvasive method of measuring hemodynamic parameters, may be a substitute for a PAC in this clinical circumstance. This study was conducted to evaluate the validity of Doppler derived hemodynamic indices in comparison to that of a PAC. METHODS: A total of 20 critically ill, severe burn patients, scheduled for an elective escharectomy and application of artificial dermis, were enrolled for the placement of a PAC and EDM. Simultaneous data was collected in regular intervals and the various parameters were compared between the two methods. RESULTS: A total of 158 pairs of data in 20 patients were gathered. Among all the parameters, cardiac output (CO) and stroke volume (SV) showed consistently 20% less in EDM. Correlation coefficients of heart rate (HR), CO, SV and systemic vascular resistance (SVR) were 0.97, 0.54, 0.62, and 0.68 respectively. Corrected flow time (FTc) had poor correlations with central venous pressure (CVP) and pulmonary capillary wedge pressure (PCWP). In the mean time, significant, but very weak correlations with FTc vs. CO and SV were demonstrated. CONCLUSIONS: EDM may be a substitute for a thermodilution (TD) PAC technique, it can be used with usefulness for hemodynamic and preload assessment in major burn patients.

Temporary Cardiac Arrest during a Pulmonary Lobectomy / 대한마취과학회지

A 49-year-old man with a left upper lobe mass lesion was admitted for evaluation. An open thoracotomy biopsy confirmed tuberculosis. A left upper lobectomy was then performed under general anesthesia. The operative procedure was remarkable for a 15-second acute episode of cardiac asystole during the aortopulmonary window lymph node dissection. After injection of epinephrine and open cardiac massage, sinus rhythm was restored. The rest of the patient's hospital course was uneventful. A vasovagal reflex due to the operative procedure, anesthetic medications, and undiagnosed underlying heart disease could be considered for the possible etiology.

Evaluation of Safety and Usability of Low Pressure Carbon Dioxide Insufflation in Endoscopic Thyroidectomy / 대한마취과학회지

BACKGROUND: Carbon dioxide insufflation during an endoscopic thyroidectomy may cause an adverse effects on blood gas and hemodynamic status. This study was conducted to evaluate the safety of low pressure carbon dioxide insufflation during an endoscopic thyroidectomy. METHODS: Patients in ASA physical status I or II, scheduled for an endoscopic thyroidectomy (n = 70) were gathered for the evaluation. During the operative procedure, minute ventilation at a tidal volume 10 ml/kg and respiratory rate 10/minute was maintained. End-tidal carbon dioxide tension, blood pressure and heart rate were measured and compared before and at 10, 20, 30, 60 and 90 minutes after CO2 insufflation. RESULTS: End tidal carbon dioxide tension significantly increased up to 30 minutes and plateaued thereafter. Mean blood pressure significantly increased up to 30 minutes but there was no change in heart rate after CO2 insufflation. Complications were not reported. CONCLUSIONS: We concluded that low pressure carbon dioxide insufflation during an endoscopic thyroidectomy was safe and useful.

The Changes of Plasma Potassium Concentrations during Anesthesia Induction with Etomidate in Patients with Major Burns / 대한마취과학회지

BACKGROUND: Etomidate, an anesthetic induction agent, has dose-dependent involuntary myoclonic movement. This prospective, randomized study was conducted to determine the safety of etomidate in patients with major burn injury. METHODS: Twenty ASA physical status II or III adult patients, scheduled for an elective early escharectomy, were studied. These patients had varying degrees of myoclonic activity at the time of anesthesia induction with etomidate (0.3 mg/kg). The plasma concentrations of potassium before and after myoclonus were measured and compared. RESULTS: Incidence of myoclonus after the injection of etomidate induction dose was 31.7%. No significant changes in plasma concentrations of the potassium level before or after myoclonus were found in this study group. CONCLUSIONS: Myoclonus during induction of anesthesia with etomidate did not cause any change in the plasma concentration of potassium. It appears to be a safe anesthetic induction agent in patients with major burns, threatened by hemodynamic and pulmonary insufficiency.

The Effect of Propofol on Cytokine Release in Patients Undergoing Colo-rectal Cancer Surgery / 대한마취과학회지

BACKGROUND: The role of propofol on the inflammatory cytokine response during surgery has been contradictory. This study was conducted to evaluate the effect of propofol compared to that of enflurane on cytokine responses. Pro- and anti-inflammatory cytokines, interleukin (IL)-10 and IL-12, were measured. METHODS: Thirty patients, who underwent colo-rectal cancer surgery, were randomly assigned into two groups in double-blind fashion. One group (n = 15) was anesthetized with enflurane vapor anesthetic, whereas the other group (n = 15) was anesthetized with a propofol intravenous infusion. At predetermined time intervals, the changes of IL-10 and IL-12 were measured. In addition, vital signs, amount of fluid infused during the operation, estimated blood loss and total amount of pethidine given within 24 hours after the operation were also measured. RESULTS: There were no statistically significant differences in the changes of IL-10 and IL-12 concentrations at all intervals when compared between the two groups, although the IL-10 was significantly increased at 1 hour after incision within each group. No other measured variables showed any meaningful differences. CONCLUSION: This study has demonstrated that propofol anesthesia did not prevent the surgical stress provoked cytokine responses.

Gabapentin as a Adjuvant Analgesic in Central Pain Syndrome / 대한마취과학회지

BACKGROUND: This study was undertaken to investigate the analgesic efficacy and safety of gabapentin in central pain syndrome. METHODS: With a diagnosis of central pain syndrome, a total 24 patients were accumulated in the outpatient pain clinic. Patients had been stabilized in their analgesic regimen at least four weeks prior to the study. Anticonvulsants, if taken, were discontinued for two weeks for wash-out. Pretreatment baseline pain scores (visual analog scale and pain intensity score) were obtained. Oral administration of gabapentin 300 mg was started in all patients. Initial doses were given from 300 mg per day with gradual titration over two weeks until 1) the onset of analgesic effect, 2) the maximum of 2,400 mg per day, and 3) the onset of intolerable side effects. Dosage was adjusted weekly. At the four-week study end point, VAS, PIS, pain improvement scores judged by family members, drug efficacy, tolerability and overall evaluation were assessed. The incidence of side effects was also noted. RESULTS: Fifteen patients dropped out due to various reasons. Data was collected from 9 patients (male = 4, female = 5). Among these, 3 had strokes and 6 spinal cord lesions due to trauma, cancer metastasis or syringomyelia. The average disease duration was 4.2 years. Analgesic onset was within two weeks and the average dose taken was 477.7 mg. At the end of the study, the VAS score and PIS revealed significant pain relief. These results were objectively reflected in pain improvement scores observed by family members. The majority scored good or excellent in all scales of drug evaluation. Sedation was the most frequently reported side effect. Others included dry mouth, weakness, and diarrhea, which were spontaneously resolved with lower dose maintenance. CONCLUSIONS: Gabapentin showed analgesic effect for central pain syndrome at a lower dose range than any other neuropathic pain syndromes. It appears to have different analgesic dose requirements in this difficult pain syndrome.