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1.  The effects of an insulin-glucose-potassium (IGK) pretreatment on the bupivacaine cardiotoxicity 
Background
The purpose of this study is to evaluate the effect of an IGK pretreatment on the cardiotoxicity of bupivacaine.
Methods
Twenty-one anesthetized mongrel dogs were randomly divided into the following three groups: the control group (CG, n = 7), the treatment group (TG, n = 7) and the pretreatment group (PTG, n = 7). For the 30 min of pretreatment period, CG and TG received normal saline, while PTG received an IV bolus of insulin 2 U/kg, followed by an IGK infusion (2 U/kg/hr of insulin, 0.5-1.5 g/kg/hr of glucose, 1-2 mEq/kg/hr of KCl). The bupivacaine infusion was started at the rate of 0.5 mg/kg/min in all groups after the pretreatment period. CG received normal saline only. In TG, insulin (2 U/kg) was injected simultaneously with bupivacaine infusion, followed by the IGK infusion as with PTG. The hemodynamic variables and the time duration to reach the mean arterial pressure (MAP) of 60 mmHg were compared.
Results
The bupivacaine infusion decreased the cardiac index, MAP, and heart rate in all three groups. Although insulin concentration was higher in TG than in PTG during bupivacaine infusion, the hemodynamic variables in PTG decreased at the slowest rate. The time taken to reach MAP of 60 mmHg in PTG, TG, and CG was 51.4 ± 8.5, 36.4 ± 9.6, and 27.1 ± 8.7 min, respectively (P < 0.05).
Conclusions
IGK delays the bupivacaine-induced cardiac depression. However, a pretreatment with IGK is more effective in delaying the bupivacaine-induced hypotension than simultaneous administration, regardless of insulin concentration.
doi:10.4097/kjae.2013.64.1.47
PMCID: PMC3558649  PMID: 23372886
Bupivacaine; Cardiotoxicity; Dog; Insulin
2.  Insulin effect on bupivacaine-induced cardiotoxicity in rabbits 
Korean Journal of Anesthesiology  2011;61(6):493-498.
Background
Resuscitation following bupivacaine-induced cardiovascular collapse is difficult and often refractory to conventional treatment. This study was performed to assess the effect of insulin on bupivacaine-induced cardiovascular collapse in pentobarbital-anesthetized rabbits.
Methods
Bupivacaine was administered at 0.75 mg/kg/min until the heart rate decreased to 65 beats/min. A bolus of regular insulin (2 U/kg) was administered intravenously at the bupivacaine infusion endpoint (BIE) in the insulin group (n = 8), and 2 mL of 0.9% NaCl was administered to the control group (n = 8).
Results
All animals in the insulin group survived and four animals died in the control group. Arrythymia was rare 10 minutes after the BIE in the insulin group.
Conclusions
Bupivacaine-induced cardiovascular collapse can be effectively reversed with an insulin injection, probably through facilitation of cardiac conduction and contraction.
doi:10.4097/kjae.2011.61.6.493
PMCID: PMC3249572  PMID: 22220227
Bupivacaine; Cardiac arrhythmia; Insulin
3.  The Hemodynamic Effects of Insulin Following Overdosage with Levobupivacaine or Racemic Bupivacaine in Dogs 
Journal of Korean Medical Science  2007;22(2):342-346.
Although levobupivacaine (LBUP) is less cardiotoxic than racemic bupivacaine (RBUP), the resuscitation from the LBUP-induced cardiovascular collapse (CVC) has not been easy as expected. Following the recent reports that proposed the resuscitative action of insulin for the RBUP-induced CVC, a controlled trial was performed to assess the feasibility of insulin for the LBUP-induced CVC. Fourteen dogs were randomly allocated into two groups: the RBUP and LBUP groups. Each group received continuous intravenous infusions of RBUP or LBUP until the mean arterial pressure (MAP) reached 40 mmHg. Then, an intravenous bolus of insulin (2 U/kg) was administered. Both groups were successfully resuscitated. At CVC, a decrease of cardiac output and an increase of systemic vascular resistance were observed but to a lesser degree in the LBUP group (p<0.05). After insulin injection, the MAP further declined to under 40 mmHg for several minutes, which was more protracted in the LBUP group (p<0.05). The CVCs induced by LBUP or RBUP in anesthetized dogs could be successfully resuscitated by insulin. Compared with RBUP, however, the less degree of vasoconstriction by LBUP and the innate vasodilatory property of insulin yielded a delayed increment of MAP during the immediate resuscitation period in the LBUP-induced CVC.
doi:10.3346/jkms.2007.22.2.342
PMCID: PMC2693605  PMID: 17449947
Bupivacaine; Cardiopulmonary Resuscitation; Insulin
4.  Public awareness about the specialty of anesthesiology and the role of anesthesiologists: a national survey 
Background
The aims of this national survey were to determine the views of Korean people regarding the specialty of anesthesiology and the role of anesthesiologists and to consider the ways in which individual anesthesiologists and the Korean Society of Anesthesiologists inform the public.
Methods
This off-line national survey was conducted by a professional research organization to obtain exact and reliable data. The questionnaire included structured questions to identify perceptions of the specialty of anesthesiology and the role of anesthesiologists inside and outside the operating room, people's desire for explanation of anesthesia by anesthesiologists, and their opinion about the best way to raise awareness about anesthesia and anesthesiologists.
Results
Of the respondents, 25.2% did not know that anesthesiologists are in charge of anesthesia during surgery. Furthermore, even respondents who knew that had very little knowledge of anesthesiologists' actual roles inside and outside the operating room. Respondents wanted their anesthesiologist to inform them about their anesthesia.
Conclusions
The public's awareness regarding the role of anesthesiologists seems to be inadequate. To improve this awareness, in hospitals, each anesthesiologist should provide patients with more exact and detailed information. Simultaneously, the National Society of Anesthesiology should provide systematic information reflecting the public's thoughts.
doi:10.4097/kjae.2014.66.1.12
PMCID: PMC3926994  PMID: 24567807
Anesthesia; Physician's role; Public opinion
5.  Torsade de pointes in liver transplantation recipient after induction of general anesthesia: a case report 
Torsade de pointes (TdP) is an uncommon and specific form of polymorphic ventricular tachycardia, associated with a prolonged QT interval. Prolongation of the QT interval is the most widely recognized electrophysiological abnormality in patients with liver cirrhosis. We observed a case of TdP leading to cardiopulmonary resuscitation after the induction of general anesthesia, in a patient with liver cirrhosis scheduled for emergency cadaveric donor liver transplantation. The patient had mild QT prolongation on preoperative electrocardiography with a corrected QT (QTc) interval of 455 ms. Drugs used in the preoperative period can elongate cardiac repolarization. Sevoflurane and 5-hydroxytryptamine type 3 receptor antagonists such as palonsetron, used during general anesthesia may have triggered further QT prolongation, producing a fatal condition such as TdP. More caution and consideration in selecting drugs for anesthetic management are necessary for liver cirrhosis patients, especially in patients with preoperative QT prolongation.
doi:10.4097/kjae.2014.66.1.80
PMCID: PMC3927008  PMID: 24567820
Heart arrest; Liver transplantation; Long QT syndrome; Torsades de pointes
6.  External Validation of the Acute Physiology and Chronic Health Evaluation II in Korean Intensive Care Units 
Yonsei Medical Journal  2013;54(2):425-431.
Purpose
This study was designed to validate the usefulness of the Acute Physiology and Chronic Health Evaluation (APACHE) II for predicting hospital mortality of critically ill Korean patients.
Materials and Methods
We analyzed data on 826 patients who had been admitted to nine intensive care units and were included in the Fever and Antipyretics in Critical Illness Evaluation study cohort.
Results
Among the patients enrolled, 62% (512/826) were medical and 38% (314/826) were surgical patients. The median APACHE II score was 17 (11 to 23 interquartile range), and the hospital mortality rate was 19.5%. Age, underlying diseases, medical patients, mechanical ventilation, and renal replacement therapy were independently associated with hospital mortality. The calibration of APACHE II was poor (H=57.54, p<0.0001; C=55.99, p<0.0001), and the discrimination was modest [area under the receiver operating characteristic (aROC)=0.729]. Calibration was poor for both medical and surgical patients (H=63.56, p<0.0001; C=73.83, p<0.0001, and H=33.92, p<0.0001; C=33.34, p=0.0001, respectively), while discrimination was poor for medical patients (aROC=0.651) and modest for surgical patients (aROC=0.704). At the predicted risk of 50%, APACHE II had a sensitivity of 36.6% and a specificity of 87.4% for hospital mortality.
Conclusion
For Koreans, the APACHE II exhibits poor calibration and modest discrimination for hospital mortality. Therefore, a new model is needed to accurately predict mortality in critically ill Korean patients.
doi:10.3349/ymj.2013.54.2.425
PMCID: PMC3575980  PMID: 23364977
APACHE II; calibration; discrimination; intensive care units; illness severity
7.  Insulin Facilitates the Recovery of Myocardial Contractility and Conduction during Cardiac Compression in Rabbits with Bupivacaine-Induced Cardiovascular Collapse 
Bupivacaine inhibits cardiac conduction and contractility. Insulin enhances cardiac repolarization and myocardial contractility. We hypothesizes that insulin therapy would be effective in resuscitating bupivacaine-induced cardiac toxicity in rabbits. Twelve rabbits were tracheally intubated and midline sternotomy was performed under general anesthesia. Cardiovascular collapse (CVC) was induced by an IV bolus injection of bupivacaine 10 mg/kg. The rabbits were treated with either saline (control) or insulin injection, administered as a 2 U/kg bolus. Internal cardiac massage was performed until the return of spontaneous circulation (ROSC) and the time to the return of sinus rhythm (ROSR) was also noted in both groups. Arterial blood pressure, and electrocardiography were continuously monitored for 30 min and plasma bupivacaine concentrations at every 5 min. The ROSC, ROSR and normalization of QRS duration were attained faster in the insulin-treated group than in the control group. At the ROSC, there was a significant difference in bupivacaine concentration between two groups. Insulin facilitates the return of myocardial contractility and conduction from bupivacaine-induced CVC in rabbits. However, recovery of cardiac conduction is dependent mainly on the change of plasma bupivacaine concentrations.
doi:10.1155/2012/878764
PMCID: PMC3332159  PMID: 22567005
8.  Analysis of expert consultation referrals for anesthesia-related issues (December 2008-July 2010): KSA legislation committee report 
Korean Journal of Anesthesiology  2011;60(4):260-265.
Background
Since 2009, database construction of anesthesia-related adverse events has been initiated through the legislation committee of the Korean Society of Anesthesiologists (KSA), based on expert consultation referrals provided by police departments, civil courts, and criminal courts.
Methods
This study was a retrospective descriptive analysis of expert consultation referrals on surgical anesthesia-related cases between December 2008 and July 2010.
Results
During the given period, 46 surgical anesthesia-related cases were referred to the KSA legislation committee for expert consultation. Because six cases were excluded due to insufficient data, 40 cases were included in the final analysis. Of 40 cases, 29 (72.5%) resulted in death. Respiratory events were most common in both surviving/disabled and dead patients (36.4 vs. 51.7%, respectively; P > 0.05). Overall, respiratory depression due to the drugs used for monitored anesthesia care (MAC) was the most common specific mechanism (25%), in which all but one case (profound brain damage) resulted in death. In all of these cases, surgeons or physicians provided MAC without the help of anesthesiologists.
Conclusions
Overall, the most common damaging mechanism was related to respiratory depression due to sedatives or anesthetics used for MAC. Almost all MAC injury cases are believed to be preventable with the use of additional or better monitoring and an effective response to initial physiological derangement. Thus, it is essential to establish practical MAC guidelines and adhere to these guidelines strictly to reduce the occurrence of severe anesthesia-related adverse outcomes.
doi:10.4097/kjae.2011.60.4.260
PMCID: PMC3092961  PMID: 21602976
Complications; Malpractice; Medical legislation; Outcome assessment
9.  Extrauterine incubation of fetal goats applying the extracorporeal membrane oxygenation via umbilical artery and vein. 
Journal of Korean Medical Science  2002;17(5):663-668.
The fetus is an unstable subject for an isolated physiological and biochemical study. To study the fetus in a controlled and stable environment, a trial was done using 12 goat fetuses. Extrauterine incubation system was devised using an extracorporeal membrane oxygenation system. The system consisted of a venous reservoir with a servo-controlled roller pump and a membrane oxygenator. The extra-corporeal circuit and membrane oxygenator were primed with the maternal whole blood of 200 mL. Fetal umbilical cords was exposed by Cesarean section. Fetal umbilical arterial blood was drained via the drainage cannula. The drained blood was perfused to the oxygenator by the roller pump. The highly oxygenated and decarboxylated blood was returned to an umbilical vein via the perfusion catheter. The blood flow rate was controlled manually using a roller pump. Fetal heart rate, blood pressure, and electrocardiogram were continuously recorded. Gas analysis of drained and perfused blood was performed hourly. With this system, the fetuses were able to survive under fairly stable physiological condition for periods of up to 34 hr. The extrauterine incubation system used in this study could therefore be a encouraging future experimental model in researching the artificial placenta for premature fetuses.
PMCID: PMC3054922  PMID: 12378020
10.  Living Donor Liver Transplantation for an Infant with Osteogenesis Imperfecta and Intrahepatic Cholestasis: Report of a Case 
Journal of Korean Medical Science  2014;29(3):441-444.
Osteogenesis imperfecta (OI) is a group of genetic disorders characterized by bone fragility and connective tissue manifestations. We report a successful liver transplantation (LT) in an 8-month-old boy with OI and cholestatic biliary cirrhosis. After 4 cycles of intravenous pamidronate, LT was performed under intravenous anesthesia using a left lateral section from his mother without mechanical retractors. The operation time was 420 min and estimated blood loss was 520 mL requiring one unit of RBC transfusion. He was discharged without surgical complications. Therefore, LT should be considered for patients with end stage liver disease and OI under organic multidisciplinary cooperation.
Graphical Abstract
doi:10.3346/jkms.2014.29.3.441
PMCID: PMC3945143  PMID: 24616597
Osteogenesis Imperfecta; Liver Transplantation; Cholestatic Liver Disease; Malignant Hyperthermia
12.  Association of body temperature and antipyretic treatments with mortality of critically ill patients with and without sepsis: multi-centered prospective observational study 
Critical Care  2012;16(1):R33.
Introduction
Fever is frequently observed in critically ill patients. An independent association of fever with increased mortality has been observed in non-neurological critically ill patients with mixed febrile etiology. The association of fever and antipyretics with mortality, however, may be different between infective and non-infective illness.
Methods
We designed a prospective observational study to investigate the independent association of fever and the use of antipyretic treatments with mortality in critically ill patients with and without sepsis. We included 1,425 consecutive adult critically ill patients (without neurological injury) requiring > 48 hours intensive care admitted in 25 ICUs. We recorded four-hourly body temperature and all antipyretic treatments until ICU discharge or 28 days after ICU admission, whichever occurred first. For septic and non-septic patients, we separately assessed the association of maximum body temperature during ICU stay (MAXICU) and the use of antipyretic treatments with 28-day mortality.
Results
We recorded body temperature 63,441 times. Antipyretic treatment was given 4,863 times to 737 patients (51.7%). We found that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen independently increased 28-day mortality for septic patients (adjusted odds ratio: NSAIDs: 2.61, P = 0.028, acetaminophen: 2.05, P = 0.01), but not for non-septic patients (adjusted odds ratio: NSAIDs: 0.22, P = 0.15, acetaminophen: 0.58, P = 0.63). Application of physical cooling did not associate with mortality in either group. Relative to the reference range (MAXICU 36.5°C to 37.4°C), MAXICU ≥ 39.5°C increased risk of 28-day mortality in septic patients (adjusted odds ratio 8.14, P = 0.01), but not in non-septic patients (adjusted odds ratio 0.47, P = 0.11).
Conclusions
In non-septic patients, high fever (≥ 39.5°C) independently associated with mortality, without association of administration of NSAIDs or acetaminophen with mortality. In contrast, in septic patients, administration of NSAIDs or acetaminophen independently associated with 28-day mortality, without association of fever with mortality. These findings suggest that fever and antipyretics may have different biological or clinical or both implications for patients with and without sepsis.
Trial registration
ClinicalTrials.gov: NCT00940654
doi:10.1186/cc11211
PMCID: PMC3396278  PMID: 22373120
body temperature; antipyretic; fever; critical illness; mortality

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