The ‘R’ principles in laboratory animal experiments / 한국실험동물학회지

Since the Three Rs of replacement, reduction and refinement was proposed by Russel and Birch in 1959, researchers have a moral duty to minimize harm to animals. Even though animal experiments are performed by the Three Rs concept, animal researches which do not comply with international rules and standards are not accepted as well. As animal welfare has been important global issues, the methods to assess animal welfare compromise and distress have been proposed. Humanity is accepted as the goal of the Three Rs, however, another fourth R, ‘Refusal’ of fruitless protocol or ‘Responsibility’ for the experimental animal and social, scientific status of the animal experiments has been proposed. After establishing goals of animal research in a respective society, reliable knowledge can be obtained while improving laboratory animal welfare.

The ‘R’ principles in laboratory animal experiments / 한국실험동물학회지

Since the Three Rs of replacement, reduction and refinement was proposed by Russel and Birch in 1959, researchers have a moral duty to minimize harm to animals. Even though animal experiments are performed by the Three Rs concept, animal researches which do not comply with international rules and standards are not accepted as well. As animal welfare has been important global issues, the methods to assess animal welfare compromise and distress have been proposed. Humanity is accepted as the goal of the Three Rs, however, another fourth R, ‘Refusal’ of fruitless protocol or ‘Responsibility’ for the experimental animal and social, scientific status of the animal experiments has been proposed. After establishing goals of animal research in a respective society, reliable knowledge can be obtained while improving laboratory animal welfare.

The State of Anesthetic Services in Korea: A National Survey of the Status of Anesthesia Provider in the 2011-2013 Period

Active involvement of anesthesiologists in perioperative management is important to ensure the patients' safety. This study aimed to investigate the state of anesthetic services in Korea by identifying anesthetic service providers. From the insurance claims data of National Health Insurance for 3 yr, the Korean state of anesthetic services was analyzed. The claims for anesthesia from the medical institutions which hire their own anesthesiologist or with an anesthesiologist invitation fee are assumed to be the anesthesia performed by anesthesiologists. The annual anesthetic data were similar during the study period. In 2013, total counts of 2,129,871 were composed with general anesthesia (55%), regional anesthesia (36%) and procedural sedation with intravenous anesthetics (9%). About 80% of total cases of general anesthesia were performed in general hospitals, while more than 60% of the regional anesthesia and sedation were performed in the clinics and hospitals under 100 beds. Non-anesthesiologists performed 273,006 cases of anesthesia (13% of total) including 36,008 of general anesthesia, 143,134 of regional anesthesia, and 93,864 of sedation, mainly in the clinics and hospitals under 100 beds. All procedural sedations in the institutions without direct employed anesthesiologist were performed by non-anesthesiologists. Significant numbers of anesthesia are performed by non-anesthesiologist in Korea. To promote anesthetic services that prioritize the safety of patients, the standard to qualify anesthetic service is required. Surgeons and patients need to enhance their perception of anesthesia, and the payment system should be revised in a way that advocates anesthesiologist-performed anesthetic services.

Experience of hemostasis in tracheal bleeding very close to the carina by the bronchial blocker: a case report / 대한마취과학회지

Massive hemoptysis is respiratory compromise which should be managed as a life-threatening condition. In our case, the bronchial blocker played a role in hemostasis of tracheal bleeding very close to the carina and prevented further spillage into the contralateral lung. Right-sided one-lung isolation in an 87-year-old female, who received cardiopulmonary resuscitation due to myocardial infarction, was requested due to hemoptysis. Right-sided bronchial bleeding was suspected on auscultation, but esophageal and tracheal bleeding due to violent intubation with a stylet was also considered. We attempted one-lung isolation with the bronchial blocker. The bronchial blocker was inadvertently advanced to the left mainstem bronchus, but the inflated balloon of the bronchial blocker compressed the site of bleeding, which was within 1 cm proximal and left posterior to the carina. Tracheal bleeding stopped, and we confirmed that hemostasis was achieved with the balloon of the bronchial blocker using a fiberoptic bronchoscope.

Public awareness about the specialty of anesthesiology and the role of anesthesiologists: a national survey / 대한마취과학회지

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.

Torsade de pointes in liver transplantation recipient after induction of general anesthesia: a case report / 대한마취과학회지

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.

Living Donor Liver Transplantation for an Infant with Osteogenesis Imperfecta and Intrahepatic Cholestasis: Report of a Case

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.

External Validation of the Acute Physiology and Chronic Health Evaluation II in Korean Intensive Care Units

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.

The effects of an insulin-glucose-potassium (IGK) pretreatment on the bupivacaine cardiotoxicity / 대한마취과학회지

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.

Application of a high respiratory rate with a low tidal volume during carbon dioxide-pneumoperitoneum in rabbits

BACKGROUND: During laparoscopic surgery, high airway pressures are generally followed by a diaphragmatic shift and hyperventilation. We hypothesize that normocapnea can be maintained with the same amount of CO2 output (VCO2) during pneumoperitoneum (PP). METHODS: Six anesthetized rabbits were mechanically ventilated at a respiratory rate of 20/min with FIO2 0.5. At the end of the expiratory limb of the ventilator, the mean partial pressure of CO2 was measured. The internal carotid artery was catheterized. Baseline values for blood pressure, heart rate, arterial blood gas analysis, and ventilatory variables were obtained. CO2 gas was introduced into the peritoneum with an intra-abdominal pressure of 12 mmHg. The measurements at baseline and at PP1 were compared. The respiratory rate was changed from (20/min PP1, to 40/min PP2, 80/min PP3 or 120/min PP4) while calculating VCO2 and comparing ventilatory variables under PP at the same time. RESULTS: The peak inspiratory pressure (PIP) and tidal volume (VT) at PP1 increased, compared with baseline. With the same PaCO2, the VT decreased significantly from (45 +/- 8 ml PP1 to 29 +/- 5 ml PP2, 19 +/- 4 ml PP3 and 15 +/- 2 ml PP4), respectively. The PIP was reduced. However, the dead space to tidal volume ratio (VD/VT) was greater at higher RR during PP. CONCLUSIONS: PP increased the PIP and VT for the removal of overloaded CO2. Less VT at a higher respiratory rate could be used with the same amount of VCO2 during PP. However, the VD/VT was elevated by the induction of PP and by the increase in respiratory rate.

Insulin effect on bupivacaine-induced cardiotoxicity in rabbits / 대한마취과학회지

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.

Analysis of expert consultation referrals for anesthesia-related issues (December 2008-July 2010): KSA legislation committee report / 대한마취과학회지

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.

Safety Evaluation of Human Fibroblasts in Mice: Tumorigenicity, 13-week Toxicity and Distribution Studies / 한국실험동물학회지

Human fibroblasts were developed for cellular therapy with the aim of correcting of depressed scars, but the safety of that in vivo is unclear. In this study, we assessed the safety of human fibroblasts by investigating the tumorigenicity, 13-week toxicity and through distribution studies. In the tumorigenicity test, nude mice were divided into three dosage level treatment groups with a negative/positive control group. At 6 months after intradermal transplantation, all of the treatment groups showed no development of a nodule on the injection sites and organs. Toxicity studies were performed using ICR and BALB/c mice for 13 weeks. The mice were divided into three dosage level treatment groups with a control and a syngeneic group. There was no treatment-related effect on clinical signs, mortality, body weight, food/water consumption, hematology, serum biochemistry, urine, necropsy findings and histopathological findings in any groups. These results suggest that the no-observed-effect level (NOEL) of the human fibroblasts was greater than 7.5x10(7) cells/kg for mice. In the distribution study, groups were treated with fibroblasts labeled with a fluorescent dye (CM-DiI) at low and high doses with a control and a syngeneic group. At 24 hours, a large percentage of the labeled fibroblasts were observed at the dermal layer. At 3 months, fluorescence of the labeled fibroblasts continued to be observed. Other tissues were not detected the fluorescence at any time. These studies demonstrate that the safety of human fibroblasts is reasonable with no toxic effect, no tumorigenicity and retention in the dermis. Our studies define preclinical safety testing standards relevant to the development of cellular therapeutics.

Anesthesia for synchronous liver and kidney transplantation in a child: A case report / 대한마취과학회지

Synchronous liver and kidney transplantation (SLK) is considered a treatment of choice for an end-stage liver disease patient with irreversible kidney disease. Several perioperative renal supportive treatments, especially continuous renal replacement therapy (CRRT), have contributed to the effective control of hypervolemia and electrolytes and acid-base disturbances leading to high success rate in adults. However, anesthesia for SLK in children is frequently difficult since the CRRT is seldom available because of difficulty in securing large venous lines. In addition, conventional techniques such as venovenous bypass and side-clamping of the inferior vena cava are less applicable in small children causing difficult volume control. Herein, we report a case of SLK in a child with glycogen storage disease type I with a review of literature.

Hypercapnic coma at the postanesthesia care unit: A case report / 대한마취과학회지

A 59-year-old woman underwent explorative laparotomy under general anesthesia for mechanical ileus. The patient had rectal cancer with multiple metastasis, and was receiving 1.5-2 mg of intravenous morphine per hour due to severe abdominal pain. After about 3 hours of general anesthesia, the patient was extubated and transferred to postanesthesia care unit. The patient was supplied with 6 L/min of oxygen by facial mask. In 30 minutes, the patient showed no response to verbal order and pain stimulus with sluggish eye reflex, although pulse-oximeter showed 98-99%. After emergent intubation, arterial blood gas was sampled, and the result showed severe acidosis with hypercapnia. The patient was transferred to intensive care unit, and after 1 hour of mechanical ventilation the patient became conscious then fully recovered without further complication.

The Change of the Serum Potassium K+ Level with the Use of Graft Preserved UW Solution or HTK Solution before and after Reperfusion in Liver Transplantation Recipients / 대한마취과학회지

BACKGROUND: In liver transplantation, an increase of serum potassium [K+] after reperfusion is related to components of the preservation solution. However, the histidine-tryptophan-ketoglutarate (HTK) solution, which is now popularly used, has a twelve times lower [K+] as compared to the UW solution. This retrospective study was performed to compare the use of the UW solution with the HTK solution for changes in the serum [K+] during the early reperfusion period in liver transplantation recipients. METHODS: Anesthesia medical records of 366 liver transplant patients were reviewed and patients were enrolled in one of the two groups; recipients who received a transplanted liver preserved with the UW solution (UW group), and recipients received a liver preserved with the HTK solution (HTK group). Serum [K+] changes 5 min before, 5 min after, and 20 min after reperfusion for recipients in each group were compared. RESULTS: In the UW group, [K+] increased 5 min after reperfusion and decreased 20 min after reperfusion as compared to [K+] 5 min before reperfusion (3.93, 4.07, and 3.76 mM in 5 min before, 5 min after, and 20 min after reperfusion respectively; P < 0.001). In the HTK group, [K+] significantly decreased 5 min and 20 min after reperfusion as compared to [K+] 5 min before reperfusion (4.12, 3.79, and 3.75 mM; P < 0.001). CONCLUSIONS: When the HTK solution was used, the serum [K+] 5 min after reperfusion decreased as compared to the [K+] before reperfusion and didn't further decrease until 20 min after reperfusion.

The pain caused by a 2% propofol target-controlled infusion during anesthesia induction in adults / 대한마취과학회지

BACKGROUND: An increasing number of cases of target-controlled infusion (TCI) of propofol have substituted 2% propofol for 1% due to the concerns about lipid deposition and the practical convenience. However, 2% propofol may possess a higher proportion of free aqueous propofol because of the relatively decreased lipid-solvent ratio as compared to that for 1% propofol. We performed a prospective, randomized, double-blind trial to evaluate the pain of 1% and 2% propofol TCI. The efficacy of lidocaine pretreatment to abolish the pain was also tested for each concentration of propofol. METHODS: Two hundred adult patients were randomly allocated to 4 groups according to the pretreatment drugs and propofol concentrations; placebo (normal saline) and 1% propofol group (group 1), placebo and 2% propofol group (group 2), lidocaine and 1% propofol group (group 1L), and lidocaine and 2% propofol group (group 2L). Administration of pretreatment drug was followed by TCI with using each concentration of propofol. Pain was assessed using a four-point scale during propofol infusion. RESULTS: Propofol pain was more frequent (82% vs. 63%, respectively, P = 0.026), and severe (P = 0.002) for the group 2 than for group 1. Pain was significantly reduced by lidocaine pretreatment in the group 2L (48%) and group 1L (19%), as compared with group 2 (82%) and group 1 (63%), respectively (P < 0.001, both). However, group 2L still showed considerable pain that was similar to the pain of group 1. CONCLUSIONS: TCI of 2% propofol caused more frequent and severe pain despite of lidocaine pretreatment.

The Hemodynamic Effects of Insulin Following Overdosage with Levobupivacaine or Racemic Bupivacaine in Dogs

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.

Anesthetic Management for Abdominal Aortic Aneurysm Surgey without Homologous Blood Transfusion in Adult Jehovah'sWitness : A case report

Jehovah's Witnesses present a challenge for the anesthesia professionals on account of their refusal to accept blood and blood products. Therefore, anesthesiologists must be able to individualize their treatment depending on the patients' condition. We report a case of a stent removal and aorto-biiliac bypass surgery in a Jehovah's Witness. A 69 year-old, hypertensive man presented with claudication of both lower extremities due to the distal migration of an endoaneurysmal stent. According to his previous medical history, he had a lacunar infarction in the right middle cerebral artery territory, ischemic coronary artery disease with a stent in situ, and a stent inserted for an abdominal aortic aneurysm by radiological intervention. Because he strongly refused a transfusion, human recombinant erythropoietin was used before surgery. After the erythropoietin treatment, hemoglobin level increased to 14.8 g/dl (hematocrit 47.6%). During the operation, closed-circuit cell saver was used and transfused autologous blood was saved by acute normovolemic hemodilution. The patient recovered uneventfully from the anesthesia and was transferred to the intensive care unit. He was discharged on the ninth postoperative day without complications with a hematocrit level of 28.9%.

Vancomycin-resistant Enterococcus and Methicillin-resistant Staphylococcus aureus Colonization in Liver Transplant Recipients : A Matched Control Study / 대한구급학회지

BACKGROUND: Despite improvements in surgical technique and immunosuppression, infection following liver transplantation (LT) remains a significant problem. Vancomycin-resistant Enterococcuscus (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) have become important nosocomial pathogens. This study was undertaken in attempt to evaluate clinical impact of VRE and MRSA in LT recipients. METHODS: LT recipients with VRE or MRSA colonization from 2001 to 2004 were identified and matched (age, gender, United Network for Organ Sharing status, liver disease, and transplant date) to control groups without MRSA or VRE colonization. Demographics, clinical factors, length of stay, duration of the use of the mechanical ventilator, complications and survival rates were compared with matched controls. RESULTS: Eleven patients were colonized by VRE (4.7%) and thirty patients by MRSA (13%). The common sites of VRE culture included the tip of the urinary catheter and urine. The VRE colonized group experienced more biliary complications, relaparotomies, longer length of stay at ICU and ward, and longer use of the mechanical ventilator. One year survival rate was lower in the VRE group. MRSA was commonly cultured from sputum, tip of the central venous catheter or intraarterial catheter, and blood. The MRSA group experienced more relaparotomies, pneumonia, longer stay at ICU and ward, and longer use of mechanical ventilator compared to the control. One year survival rate was lower in the MRSA group. Rejection was not associated with VRE or MRSA infection. CONCLUSIONS: VRE or MRSA colonization is associated with higher incidence of posttransplant complications and lower survival rate than LT recipients without VRE or MRSA colonization. The patients with VRE or MRSA colonization also utilized more hospital resources.