Byung Hoon Yoo

Pharmacokinetics and pharmacodynamics of propofol microemulsion and lipid emulsion after an intravenous bolus and variable rate infusion.

Background:The aim of this trial was to evaluate the induction and recovery characteristics of microemulsion propofol (Aquafol; Daewon Pharmaceutical Co., Ltd., Seoul, Korea). Pharmacokinetics, pharmacodynamics, and safety profile were investigated. Lipid emulsion propofol (Diprivan®; AstraZeneca, London, United Kingdom) was used as a comparator. Methods:Thirty-one healthy volunteers aged 20–79 yr were given an intravenous bolus of propofol 2 mg/kg, followed by variable rate infusion for 60 min. Each volunteer was studied twice with different formulations at an interval of 1 week. Arterial concentrations of propofol were measured, and Bispectral Index was used as a surrogate measure of propofol effect. The induction and recovery characteristics including bioequivalence were evaluated by noncompartmental analysis. The pharmacokinetics and pharmacodynamics were investigated using a population approach with mixed effects modeling. The rate, severity, and causal relation of adverse events were analyzed. Results:Both formulations were bioequivalent. The observed time to peak effect after a bolus of both formulations was 1.5 min. Plasma concentration of propofol at loss of consciousness, time to loss of consciousness after a bolus, and time to recovery of consciousness after discontinuation of infusion did not show significant differences. The population pharmacokinetics and pharmacodynamics revealed a variety of differences between two formulations. Aquafol showed similar safety profile to Diprivan®. Conclusions:The efficacy and safety of Aquafol were not different from those of Diprivan® within the dose range in this study.

The effect of remifentanil versus N2O on postoperative pain and emergence agitation after pediatric tonsillectomy/adenoidectomy

Background Remifentanil can be an alternative to N2O in general anesthesia. Intraoperative remifentanil may lead to acute opioid tolerance. This study aims to assess the effect of remifentanil substituted for 70% N2O on postoperative pain in children undergoing tonsillectomy/adenoidectomy. In addition, we evaluated the effect of remifentanil infusion on incidence of emergence agitation in these patients. Methods Eighty children, aged 2-12 years, undergoing tonsillectomy/adenoidectomy were randomly allocated to the N2O group (Group N; n = 40, sevoflurane and 70% N2O) or remifentanil group (Group R; n = 40, sevoflurane with remifentanil infusion at the rate of 0.17 µg/kg/min). In the recovery room, severity of pain and agitation were assessed by an investigator blinded to the assigned group. Time to eye opening and incidence of severe pain and agitation were compared between groups. Logistic regression was used to identify factors related to occurrence of severe pain and agitation. Results Number of patients with severe postoperative pain was 6 and 16 in groups N and R, respectively (P = 0.012). Incidence of emergence agitation was not significantly different between groups. Remifentanil infusion was a significant factor related to the occurrence of severe postoperative pain (P = 0.015), and age was inversely related to occurrence of emergence agitation (P = 0.001). Conclusions In children undergoing tonsillectomy/adenoidectomy, intraoperative remifentanil infusion may increase incidence of severe postoperative pain compared to N2O, but it may not affect incidence of emergence agitation.

The comparative study to evaluate the effect of palonosetron monotherapy versus palonosetron with dexamethasone combination therapy for prevention of postoperative nausea and vomiting

Background 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists are effective and safe on postoperative nausea and vomiting (PONV). Palonosetron, the newest 5-HT3 antagonist, has potent antiemetic property. We hypothesized that a combination of palonosetron and dexamethasone could more decrease PONV than palonosetron alone. Methods Among the patients scheduled to undergo laparoscopic gynecologic surgery, mastoidectomy with tympanoplasty or thyroidectomy under general anesthesia, eighty four female patients with at least two PONV risk factors were enrolled in this study. They were received randomly 0.075 mg palonosetron and 4 mg dexamethasone (group C) or 0.075 mg palonosetron alone (group P). The severity of PONV using Rhodes index and the percentage of complete response during postoperative 24 hours were compared between groups. Results The frequency of mild/moderate/great/severe PONV based on Rhodes index were 9.8%/0%/0%/0% and 9.3%/2.3%/2.3%/0% in group P and group C, respectively. Complete response for PONV was observed in 90.2% and 86% of patients in group P and group C, respectively. The overall incidence of PONV in group P and C was 9.8% and 14%, respectively. There was no significant difference between the two groups. Conclusions There were no differences between palonosetron monotherapy and combination therapy of palonosetron and dexamethasone in patients with high emetogenic risk.

General anesthesia versus monitored anesthetic care with dexmedetomidine for closed reduction of nasal bone fracture

Background Reduction of nasal bone fracture can be performed under general or local anesthesia. The aim of this study was to compare general anesthesia (GA) and monitored anesthetic care (MAC) with dexmedetomidine based on intraoperative vital signs, comfort of patients, surgeons and nurses and the adverse effects after closed reduction of nasal bone fractures. Methods Sixty patients with American Society of Anesthesiologists physical status I or II were divided into a GA group (n = 30) or MAC group (n = 30). Standard monitorings were applied. In the GA group, general anesthesia was carried out with propofol-sevoflurane-N2O. In the MAC group, dexmedetomidine and local anesthetics were administered for sedation and analgesia. Intraoperative vital signs, postoperative pain scores by visual analog scale and postoperative nausea and vomiting (PONV) were compared between the groups. Results Intraoperatively, systolic blood pressures were significantly higher, and heart rates were lower in the MAC group compared to the GA group. There were no differences between the groups in the patient, nurse and surgeons satisfaction, postoperative pain scores and incidence of PONV. Conclusions MAC with dexmedetomidine resulted in comparable satisfaction in the patients, nurses and surgeons compared to general anesthesia. The incidence of postoperative adverse effects and severity of postoperative pain were also similar between the two groups. Therefore, both anesthetic techniques can be used during the reduction of nasal bone fractures based on a patient%s preference and medical condition.

Reversal of rocuronium induced neuromuscular blockade using sugammadex in a patient with eclampsia treated by magnesium intraoperatively.

Magnesium has been used frequently both as an anticonvulsant for preeclampsia and in the treatment of preterm labor. Magnesium also results in potentiation of the effects of neuromuscular blocking drugs, and attenuates their reversal with anticholinesterase [1]. Prolongation of the duration of the neuromuscular blockade (NMB) increases the risk of residual paralysis. Unlike anticholinesterase, sugammadex binds steroidal muscle relaxants by encapsulation, and it can rapidly and completely antagonize the action of the NMB. Theoretically, magnesium sulfate may reduce the efficacy of sugammadex [2]. We report a successful reversal of NMB with sugammadex in a patient with eclampsia who was treated with magnesium intraoperatively and showed incomplete reversal with anticholinesterase from rocuronium-induced NMB. A 30-year-old multipara (height 167 cm, weight 62 kg) at 27 weeks and 5 days of gestation visited the emergency room (ER) complaining of epigastric soreness, nausea, vomiting, and headache since the previous night. She had no specific medical history. Her blood pressure was 200/124 mmHg, heart rate 86 beats/min, and respiratory rate 24 breaths/min. According to a non-stress test, the fetal heart rate was 150 beats/min. After intravenous administration of hydralazine 5 mg, her blood pressure decreased to 140/100 mmHg. Forty minutes later, a seizure occurred. Diazepam 10 mg was immediately administered intravenously, and just an hour after the patient’s arrival at the ER, an emergency cesarean section was performed under general anesthesia.

Reversible airway obstruction caused by changing the size and length of an endotracheal tube in a premature neonate with suspected tracheomalacia -A case report-

Tracheomalacia is a malformation of the tracheal membranosa. It is maintained during spontaneous breathing but can be altered by bronchoscopy or positive airway pressure. Tracheomalacia is associated with a high mortality and may cause prolonged intubation and ventilation. Here, the case of a 13-day-old infant with jejunoileal stenosis that had surgery is reported. During induction of general anesthesia, endotracheal intubation was attempted several times with different sized endotracheal tubes. Airway obstruction occurred after the endotracheal intubation. After the airway was maintained, the operation was completed. Tracheomalacia was diagnosed after otolaryngology evaluation postoperatively.

A detection of unexpected blood antibody at the time of transfusion was needed, during the operation -A case report-

To avoid the occurrence of fatal complications of blood transfusion, several tests are implemented before transfusion. The tests include ABO typing, Rh typing, cross-matching test and blood antibody screening test, and in usual they are completed before transfusion. However in the case of repetitive operations done via brief distance, reexamination for blood antibody tends to be omitted. After 2 previous operations, 30 years old male patient showed positive blood antibody screening during the third operation. Although antibody screening test performed before the first operation, no unexpected blood antibody was detected. During the third operation, after the decision to start transfusion was made, it took two hours to find appropriate blood. There was no significant deterioration of patients condition but the loss of time could lead to critical consequences. We present this case to make anesthesiologists and surgeons aware of possibility of unexpected blood antibody detection after transfusion.

Massive bleeding despite tourniquet inflation in total knee replacement patient with a femoro-popliteal artery bypass graft

A tourniquet is used frequently in orthopedic surgeries, including total knee replacement, to reduce bleeding and enhance the visual field during surgery. Herein, we present a case with massive bleeding that occurred during a total knee replacement that had administered a tourniquet with adequate pressure. A 65-year-old man presented to the orthopaedic clinic for right total knee replacement due to osteoarthritis. The patient had right lower limb artery obstruction and a history of a right femoro-popliteal artery bypass graft 7 years prior to his visit. He was 169 cm tall weighing 68 kg. The patient had no other specific medical history, and no abnormal finding was covered on the preoperative examination. When the patient arrived at the operating room, his blood pressure was 150/90 mmHg. We provided propofol 120 mg and rocuronium 50 mg followed by induction with sevoflurane and 1 : 1 of oxygen and N2O. An inflation tourniquet with a pressure of 300 mmHg was applied to the right thigh. While the surgeon was making the skin incision to expose the joint, unpredicted massive bleeding occurred. Just before the tourniquet was applied, the patients blood pressure was 95/65 mmHg, and right after the tourniquet was inflated, it was 130/80 mmHg. Based on the assumption of a tourniquet function error, we applied a new tourniquet with 300 mmHg of pressure on the right thigh. However, the bleeding continued even when we the raised pressure up to 400 mmHg. The bleeding decreased considerably when we deflated the cuff. Furthermore, with ultrasonographic guidance, we found that the femoral artery flow was not blocked by the tourniquet; therefore, the surgeon proceeded with the surgery without use of a tourniquet. During the surgery, 1,200 ml of crystalloid solution, 500 ml of colloid solution and packed RBC 4 units were administered and the estimated blood loss was 2,500 ml. Upon searching for the cause of the unpredicted bleeding, we examined the blood flow of the right femoro-popliteal artery bypass graft with ultrasonography 6 months later. It showed that both the femoro-popliteal artery bypass graft with or without 350 mmHg of tourniquet pressure had good blood flow (Fig. 1). A tourniquet is frequently used in total knee joint replacement surgeries to block the vascular flow of the limb during surgery. However, complications such as thigh pain, nerve injury, compartment syndrome, and nonalignment of the patella as well as systemic complications such as deep venous thrombosis, hypertension, and arrhythmia may occur. Therefore, it is important to maintain an adequate pressure and duration while using a tourniquet. There is no absolute limit on the pressure and duration when using a tourniquet, but Flatt [1] reported 2 hours is an adequate time if the patient has no hemodynamic problems. Horlocker et al. [2] reported 300 mmHg for the tourniquet pressure as being adequate for the lower limb. In this case, bleeding continued with an initial tourniquet pressure of 300 mmHg and even continued after we applied 400 mmHg of pressure. The use of the tourniquet instead increased the blood flow in our case. It is believed that the use of the tourniquet was unable to block the graft artery flow but collapsed the venous flow, which resulted in the increased blood loss. In case of artery occlusion above the knee, a polytetrafluroethylene (PTFE) bypass graft is used in elderly when an artery is in poor condition or there is no venous graft. For a PTFE bypass graft, it has good short outcomes compared to the use of a venous graft. For long term outcomes, a PTFE bypass graft shows less patency though. This case also used a PTFE bypass graft and this may have affected the blood flow when compared with a venous graft. However, there is no report on this issue yet. Complications from femoro-popliteal bypass grafts are myocardial ischemia, cerebral infarct, infection on the graft site, peripheral venous thrombosis, and sexual dysfunction by autonomic nerve injury. Infection on the graft site may result in permanent adhesion or fibrosis [3]. Therefore, in our case, it is believed that the patient had an asymptomatic infection, which resulted in adhesion and fibrosis around the artificial vessel graft. The adhesion and fibrosis blocked vessel collapsed even under high pressure causing severe bleeding afterwards. There is controversy about the use of a tourniquet in patients with peripheral artery occlusion. Some say it is safe not to use a tourniquet [4]. Others say there is no difference in postoperative vascular complications by using a tourniquet [5]. Therefore, adequate discussion must be carried out with orthopedists before use of a tourniquet. Patients with a history of a femoro-popliteal bypass graft should be evaluated first with ultrasonography on whether vascular flow can be blocked with a tourniquet. If it is decided that a tourniquet should not be used during surgery, care should be taken for the bleeding during surgery and for postoperative vascular complications.

Effect of ulinastatin on the rocuronium-induced neuromuscular blockade

Background Ulinastatin is a glycoprotein derived from human urine and a serine protease inhibitor found in human urine and blood. Ulinastatin increases both liver blood flow and urine output. Rocuronium is eliminated mainly through the liver and partly through the kidney, hepatic elimination of rocuronium might be enhanced by ulinastatin. We examined the effect of ulinastatin on the neuromuscular block caused by rocuronium. Methods Forty four adult patients were randomly divided into two groups of 22 patients each, i.e. the study group and the control group. In the study group, a bolus dose of ulinastatin 5,000 U/kg was administered 2 min before the injection of rocuronium 0.6 mg/kg. In the control group, normal saline was administered instead of ulinastatin. For the monitoring of both onset and recovery from neuromuscular blockade, train-of-four (TOF) and post-tetanic count were used with TOF-Watch Sx. All patients underwent general anesthesia with total intravenous anesthesia (TIVA) of remifentanil and propofol, using the effect site target infusion system. Results In the study group, the onset of neuromuscular block was significantly slower than in the control group (P < 0.05). The recovery time from the rocuronium injection to the return of PTC was also significantly shorter in the study group than in the control group (P < 0.05). Similarly, times to the return of T1, T2, T3, and T4 (i.e. the first, second, third, and fourth response of TOF) were significantly shorter in the study group than in the control group (P < 0.05). Conclusions Ulinastatin significantly delays the onset of neuromuscular block and accelerates the recovery from the block caused by rocuronium.

Factors that influence awakening in coronary artery bypass graft using propofol and remifentanil

BACKGROUND The development of total intravenous anesthesia in coronary artery bypass graft (CABG) surgery has led to increased interest in the use of combination of propofol and remifentanil. Early extubation in post-cardiac surgery reduces the length of stay in intensive care unit and hospital and costs. The purpose of this study is to evaluate which anesthetic factors affect awakening time after anesthesia. METHODS We enrolled twenty patients of ASA physical status II or III, scheduled for CABG in this study. All patients received a standardized propofol/remifentanil anesthesia as an effect site target controlled infusion. We recorded times to awakening and tracheal extubation, duration of cardiopulmonary bypass (CPB) period, total time of anesthesia and operation. Also, we recorded dose of propofol, remifentanil, fentanyl and minimum body temperature during CPB. To predict the factors that affect awakening time as a dependent variable, we considered all measured parameters as independent variables, and analyzed multiple linear regressions. RESULTS The mean time responded to verbal command was 216.5 +/- 124.8 minutes after end of surgery. Among several parameters, minimum body temperature during CPB (P = 0.001) and total time of anesthesia (P = 0.003) were considered as significant factors that influence awakening time after CABG. CONCLUSIONS Minimum body temperature during CPB and the duration of anesthesia influence awakening time after CABG, significantly.