Comparative Evaluation of Pregabalin and Clonidine as Preemptive Analgesics for the Attenuation of Postoperative Pain Following Thoracolumbar Spine Surgery

STUDY DESIGN: Prospective, randomized, double blind, placebo-controlled study.PURPOSE: To compare clonidine and pregabalin with placebo for the attenuation of postoperative pain after thoracolumbar spinal surgery and instrumentationOVERVIEW OF LITERATURE: Spine surgery is associated with moderate to severe postoperative pain that needs to be controlled to improve patient’s outcome. Alpha 2 agonists (e.g., clonidine) and gabapentenoids (e.g., pregabalin) are successfully used as part of a multimodal analgesic regimen.METHODS: Total 75 patients were enrolled and randomly allocated into three groups. Group P received pregabalin (150 mg), group C received clonidine (150 mcg), and group N received placebo 90 minutes preoperatively. A standard anesthesia protocol comprising fentanyl, thiopentone, vecuronium, nitrous oxide, and oxygen in isoflurane was used for all patients. Postoperative recovery profile, pain, time for first analgesic, 24-hour analgesic requirement, sedation, and hemodynamic parameters were noted.RESULTS: Recovery profile was similar in all three groups; however, the patients in group P and C were more sedated (p<0.05). Group N patients had a higher Visual Analog Scale (VAS) score (p<0.05) and the time for first analgesic was also lower (p=0.02). Postoperative (24-hour) analgesic requirement was maximum in group N, followed by that in group C and group P. The VAS score was highest in the control group; however, after 12 hours, it was similar in all groups.CONCLUSIONS: Postoperative pain and analgesic requirement is significantly attenuated by preoperative administration of a single dose of clonidine (150 mcg) or pregabalin (150 mg); pregabalin was more effective. Thus, their use offers a reasonable strategy for pain management in patients undergoing spine surgery.

Estimation of the effect-site equilibration rate constant using the time-to-peak effect of muscle relaxants measured by train-of-four stimulation during general anesthesia induction / 대한마취과학회지

BACKGROUND: The concept of the effect-site concentration of anesthetic agents is important. The effect compartment model can be explained using the concepts of effect-site concentration and effect-site equilibration rate constant (k e0). This study confirms that the time-to-peak effect (tpe ) can be measured easily in clinical practice by applying a priming dose and train-of-four (TOF) during general anesthesia induction, and k e0 can be calculated from the tpe of the four muscle relaxants that are commonly used in general anesthesia. METHODS: Eighty patients who received general anesthesia were divided into the succinylcholine, rocuronium, atracurium, or vecuronium groups. Priming doses of muscle relaxants were administered. The effects of muscle relaxants were quantified by recording the twitch response of the adductor pollicis muscle after stimulating the ulnar nerve. The tpe was measured at the lowest TOF value. k e0 was calculated from the measured tpe . RESULTS: The k e0 values of the succinylcholine, rocuronium, atracurium, and vecuronium groups were 0.076 (0.030)/min, 0.228 (0.122)/min, 0.062 (0.011)/min, and 0.077 (0.019)/min, respectively. CONCLUSIONS: It is possible to estimate k e0 from the tpe of muscle relaxants using a priming dose and TOF during general anesthesia induction.

Comparing the effects of vecuronium and cisatracurium on electrophysiologic monitoring during neurosurgery: a randomized controlled study

BACKGROUND: The differences between neuromuscular blocking (NMB) drugs on the efficacy of intraoperative motor-evoked potential (MEP) monitoring have not been established through clinical study. We compared the effects of vecuronium and cisatracurium on the efficacy of intraoperative MEP monitoring. METHODS: We enrolled 72 patients who had undergone neurosurgery with MEP monitoring. We randomly allocated the subjects into one of two groups, in whom we maintained continuous intravenous vecuronium (Group V) or cisatracurium (Group C) infusion during the surgeries; the target partial NMB for maintenance was T1/Tc 50% (T1, first twitch of TOF response; Tc, control response of T1 before NMB drug injection). We compared the means and coefficients of variation (CV, %) of all measured MEP amplitudes and the frequencies of NMB drug dose changes. RESULTS: The means and CVs of MEP amplitude and latency in all four limbs did not differ significantly between the groups, although we did change the continuous NMB drug doses in group V significantly less often than in group C. CONCLUSIONS: There were no significant differences between vecuronium and cisatracurium on the MEP variability and mean amplitudes. However, cisatracurium needed more frequent dose changes to maintain T1/Tc 50%.

Detection of Metabolites of Vecuronium Bromide in Visceral Samples Solves A Typical Death Mystery- (Toxicokinetics- Studies Using Gc-Ms Technique).

Introduction: On Sudden death of a medical student (20 year old girl) of National Institute of Medical Science autopsy materials along with site of injection were sent to F.S.L. It was informed during investigation that the girl took tetanus vaccine before death. In crime scene investigation Forensic Team observed that it was a case of gross negligence of dispensing wrong injection. Material: Tests were performed on viscera material viz., liver, spleen, kidney, lungs, brain, skin and blood etc. Mystery of suspected death was solved when a new GC-MS application was designed to get the unknown drug and various fragments of extracted material were studied. Method: A new method was developed on gas-chromatography-mass spectrophotometer and TL.C using various solvent systems is explained. Results: Metabolite fragments of vecuronium bromide a muscle relaxant were surprisingly observed in Viscera material, Blood sample and Skin piece from Leftt cubital fossa from this young girl, whose death is questioned. Conclusion: Structural elucidations of fragments provide a new approach to toxicokinetics. Th e explanation of fragments obtained were structurally compared with other neuromuscular blocking groups like atracurium and succinyl choline Th e presence of bromide attached cholest-5-en-Br, hydroxylated cholest-5-en-ol as hydroxylated product, acetylated fragments as cholest-5-enacetate and piperidone-2-one present in visceral samples indicates structural part obtained from vecuronium bromide drug. Th ese metabolites studies makes the case studies highly informative. Beside this new method of extractions, TLC systems and colouring reagents are also explained.

Effects of magnesium sulfate on remifentanil requirements for achieving hemodynamic stability during laparoscopy assisted distal gastrectomy

BACKGROUND: Magnesium is known to reduce the requirement of analgesic agents by blocking calcium channels that exist at the neuronal and neuromuscular junctions. However, former studies have shown inconsistent results regarding this concept. Therefore, we investigated the effects of magnesium on remifentanil requirements for achieving hemodynamic stabilization in patients undergoing laparoscopic gastrectomy. METHODS: Laparoscopic gastrectomy patients (n = 30) were randomly divided into two groups. Group M received 50 mg/kg of magnesium sulfate for 15 minutes prior to the induction of anesthesia. Then, 20 mg/kg/h of magnesium was administered during the operation time. Group N was administered the same amount of saline. Anesthesia was maintained with intravenous propofol and remifentanil injection. Vecuronium (0.1 mg/kg) was administered before intubation, and an additional 0.02 mg/kg was administered if a T1 twitch response was observed during surgery. Anesthetic time was standardized to provide an appropriate comparison of all patients. During 100 minutes, total anesthetic requirements and anesthetic requirements at every 10 minutes were analyzed. Postoperative pain was controlled with a patient controlled analgesia device. RESULTS: The remifentanil and vecuronium requirements during 100 minutes were significantly lower in Group M. There was no significant difference in propofol requirements between the two groups. No significant difference was observed in mean arterial pressure and heart rate. Postoperative VAS, PONV, or shivering also did not show any difference between the two groups. CONCLUSIONS: Magnesium reduced remifentanil and vecuronium requirements but not propofol requirements. Magnesium seems to have antinociceptic properties and reduces remifentanil requirements.

Effectiveness of sugammadex in reversing prolonged neuromuscular block in a patient with acquired immune deficiency syndrome (AIDS) taking streptomycin: A case report

The duration of the effect of muscle relaxants is extended in patients with acquired immunodeficiency syndrome (AIDS); however, a specific mechanism for this effect has not yet been discovered. In addition, streptomycin is known to prolong the action of muscle relaxants by blocking activity at neuromuscular junctions. Here, we report the case of patient with AIDS taking streptomycin for pulmonary tuberculosis for which sugammadex was effective in reversing prolonged paralysis induced by rocuronium and vecuronium for video-assisted thoracoscopic surgery (VATS) lung wedge resection.

Streptozotocin Diabetes Attenuates the Effects of Nondepolarizing Neuromuscular Relaxants on Rat Muscles

The hypothesis of this study was that diabetes-induced desensitization of rat soleus (SOL) and extensor digitorum longus (EDL) to non-depolarizing muscle relaxants (NDMRs) depends on the stage of diabetes and on the kind of NDMRs. We tested the different magnitude of resistance to vecuronium, cisatracurium, and rocuronium at different stages of streptozotocin (STZ)-induced diabetes by the EDL sciatic nerve-muscle preparations, and the SOL sciatic nerve-muscle preparations from rats after 4 and 16 weeks of STZ treatment. The concentration-twitch tension curves were significantly shifted from those of the control group to the right in the diabetic groups. Concentration giving 50% of maximal inhibition (IC50) was larger in the diabetic groups for all the NDMRs. For rocuronium and cisatracurium in both SOL and EDL, IC50 was significantly larger in diabetic 16 weeks group than those in the diabetic 4 weeks group. For SOL/EDL, the IC50 ratios were significantly largest in the diabetic 16 weeks group, second largest in the diabetic 4 weeks group, and smallest for the control group. Diabetes-induced desensitization to NDMRs depended on the stage of diabetes and on the different kind of muscles observed while was independent on different kind of NDMRs. The resistance to NDMRs was stronger in the later stage of diabetes (16 versus 4 weeks after STZ treatment). Additionally, when monitoring in SOL, diabetes attenuated the actions of neuromuscular blockade more intensely than that in EDL. Nonetheless, the hyposensitivity to NDMRs in diabetes was not relevant for the kind of NDMRs.

Estudo de lidocaína a 0,5% e combinação de lidocaína a 0,25% com fentanil e vecurônio em anestesia regional intravenosa para cirurgias de membros superiores / Study of 0.5% lidocaine alone and combination of 0.25% lidocaine with fentanyl and vecuronium in intravenous regional anesthesia for upper limb surgeries / Estudio de la lidocaína al 0,5% y en combinación de lidocaína al 0,25% con fentanilo y vecuronio en anestesia regional intravenosa para cirugías de miembros superiores

JUSTIFICATIVA E OBJETIVOS: A anestesia regional intravenosa (ARIV) para cirurgias de membros superiores com a tradicional alta dose de lidocaína pode levar a efeitos colaterais potencialmente letais. A fim de evitar esses efeitos, muitas técnicas modificadas de ARIV foram experimentadas com o uso de uma dose baixa de lidocaína, relaxante muscular e opioide. MÉTODOS: O presente estudo foi feito com 60 pacientes não medicados previamente, com classificação ASA 1-2, para comparar as características sensoriais e motoras, os parâmetros cardiorrespiratórios e os efeitos colaterais durante o período intraoperatório e de deflação pós-torniquete entre os pacientes que receberam 40 mL de lidocaína a 0,5% (n = 30) e aqueles que receberam uma combinação de 40 mL de lidocaína a 0,25% com 0,05 mg de fentanil e 0,5 mg de vecurônio (n = 30) em ARIV para cirurgias ortopédicas de membros superiores. Os resultados foram analisados com o uso do teste t de Student pareado para identificar a significância estatística. RESULTADO: A diferença entre os dois grupos em relação ao tempo médio de início e completo bloqueio sensitivo e motor foi estatisticamente significante. Porém, houve completo bloqueio sensitivo e motor em ambos os grupos 15 minutos após a injeção da solução anestésica. CONCLUSÃO: Embora a pequena demora observada no início e na obtenção completa dos bloqueios sensitivo e motor possa, teoricamente, atrasar o início da cirurgia em 10-15 minutos, clinicamente esse tempo seria gasto na preparação do campo cirúrgico. Portanto, essa combinação pode ser usada com segurança e eficácia em anestesia regional intravenosa para cirurgias ortopédicas de membros superiores com menor possibilidade de toxicidade anestésica local.

BACKGROUND AND OBJECTIVE: Intravenous regional anesthesia (IVRA) for upper limb surgeries with traditional high dose of lidocaine can lead to life threatening side effects. In order to avoid these potential life threatening side effects, many modified techniques of IVRA have been attempted by using a low dose of lidocaine, muscle relaxant and opioid. METHOD: The present study is carried out in sixty unpremedicated ASA Class 1 and 2 patients to compare the sensory and motor characteristics, cardio-respiratory parameters and side-effects during intra-operative and post-tourniquet deflation period between the patients who received 40 mL of 0.5% lidocaine alone (n = 30) and those who received a combination of 40 mL of 0.25% lidocaine with 0.05 mg fentanyl and 0.5 mg vecuronium (n = 30) in IVRA for upper limb orthopedic surgeries. The results were analyzed for statistical significance using a paired student t test. RESULTS: The difference between the two groups regarding the mean time of onset and complete sensory and motor block was statistically significant. But 15 minutes after the injection of anesthetic solution, there was complete sensory and motor block in both groups. CONCLUSION: Although the short delay observed in the onset and attainment of complete sensory and motor block may theoretically delay the start of surgery for 10-15 minutes but clinically that time will be spent in the preparation of surgical field. So this combination can be used safely and effectively in intravenous regional anesthesia for upper limb orthopedic surgeries with reduced chance of local anesthetic toxicity.

JUSTIFICATIVA Y OBJETIVOS: La anestesia regional intravenosa (ARIV) para cirugías de miembros superiores con la tradicional dosis alta de lidocaína, puede conllevar a efectos colaterales que amenazan la vida. Para evitar esos efectos colaterales potencialmente amenazadores, muchas técnicas modificadas de ARIV fueron experimentadas con el uso de una dosis baja de lidocaína, relajante muscular y opioide. MATERIALES Y MÉTODOS: El presente estudio se hizo con 60 pacientes no medicados previamente, con clasificación ASA 1-2, para comparar las características sensoriales y motoras, los parámetros cardiorrespiratorios y los efectos colaterales durante el período intraoperatorio y de deflación pos torniquete, entre los pacientes que recibieron 40 mL de lidocaína al 0,5% sola (n = 30) y los que recibieron una combinación de 40 mL de lidocaína al 0,25% con 0,05 mg de fentanilo y 0,5 mg de vecuronio (n = 30) en ARIV para cirugías ortopédicas de miembros superiores. Los resultados se analizaron usando el teste t de Student pareado para identificar la significancia estadística. RESULTADO: La diferencia entre los dos grupos con relación al tiempo promedio de inicio y completo bloqueo sensitivo y motor, fue estadísticamente significativo. Sin embargo, hubo un completo bloqueo sensitivo y motor en ambos grupos 15 minutos después de la inyección de la solución anestésica. CONCLUSIONES: Aunque la pequeña demora observada al inicio y durante la obtención completa de los bloqueos sensitivo y motor, teóricamente pueda atrasar el inicio de la operación entre 10 y 15 minutos, clínicamente ese tiempo se gastaría en la preparación del campo quirúrgico. Por tanto, esa combinación puede ser usada con seguridad y eficacia en la anestesia regional intravenosa para las cirugías ortopédicas de miembros superiores con menor posibilidad de toxicidad anestésica local.

Antioxidant effect of muscle relaxants (vecuronium, rocuronium) on the rabbit abdominal aortic endothelial damage induced by reactive oxygen species / 대한마취과학회지

BACKGROUND: Muscle relaxants induce vascular smooth muscle relaxation by inducing synthesis of the prostaglandins that influence vasomotor tone. However, the effects of muscle relaxants on endothelial cells and tissues following injury by reactive oxygen species (ROS) are unclear. We tested the effects of the muscle relaxants vecuronium and rocuronium on impaired acetylcholine (ACh)-induced relaxation following induction of ROS in rabbit aorta in vitro. METHODS: Isolated rabbit abdominal aortic ring segments were pretreated with vecuronium or rocuronium at 10(-4), 3 x 10(-4), 10(-3) or 3 x 10(-3) M, with or without inhibitors of Cu/Zn superoxide dismutase (diethyldithiocarbamate; DETCA, 0.8 mM) or catalase (3-amino-1,2,4-triazole; 3AT, 50 mM). All groups of aortic rings were then exposed to ROS generated by electrolysis in the organ bath medium (Krebs-Henseleit solution). The effects of vecuronium and rocuronium on ROS-induced impairment of relaxation induced by ACh (10(-6) M) were assessed. RESULTS: Aortic rings treated with vecuronium or rocuronium at 10(-4), 3 x 10(-4), 10(-3) or 3 x 10(-3) M preserved the capacity for ACh-induced endothelial relaxation following ROS exposure in a dose-dependent manner. Pretreatment with DETCA partially inhibited the protective effects of vecuronium and rocuronium on ACh-induced relaxation (P < 0.001), but pretreatment with 3AT had no effect. CONCLUSIONS: Muscle relaxants protected the endothelium in isolated rabbit abdominal aorta from free-radical injury in a dose-dependent manner. These results suggest that vecuronium and rocuronium may act as superoxide anion scavengers.

Heart rate variability predicts the extent of corrected QT interval prolongation after tracheal intubation

BACKGROUND: Corrected QT (QTc) interval can be modulated by sympathetic and parasympathetic balance. Tracheal intubation causes significant prolongation of the QTc interval due to sympathetic stimulation. This study was designed to elucidate the relationship between baseline autonomic nervous system activity and QTc prolongation after endotracheal intubation using heart rate variability (HRV). METHODS: Sixty-six healthy patients were included and the baseline HRV data were recorded for 5 min before anesthesia. Power spectrum densities were calculated for low frequencies (LF, 0.04-0.15 Hz) and high frequencies (HF, 0.15-0.4 Hz), defined as either LF's or HF's relative part of the total power. Anesthesia was induced with sevoflurane and vecuronium was given. The QTc interval, heart rate (HR) and mean arterial pressure (MAP) were measured before induction (baseline), before laryngoscopy (pre-intubation) and immediately after the intubation (post-intubation). RESULTS: The QTc interval change at post-intubation from baseline (DeltaQTc) showed a significant negative correlation with the HF (r = 0.34, P = 0.006) and positive correlation with LF/HF ratio (r = 0.37, P = 0.005). Patients were retrospectively divided into low-HF/LF (2.5, n = 22). The DeltaQTc was statistically higher in the high-LF/HF group compared to that in the low-LF/HF group (P = 0.048). The HR and MAP at baseline, pre-intubation and post-intubation were not different between two groups. CONCLUSIONS: The QTc interval prolongation after endotracheal intubation is influenced by baseline autonomic conditions and can be exaggerated in patients with activated sympathetic activity or depressed parasympathetic activity.

The effect of intravenous labetalol administration on hemodynamic responses during desflurane inhalation / 대한마취과학회지

BACKGROUND: Inspired concentrations of desflurane > or = 1 minimum alveolar anesthetic concentration (MAC) have been related to sympathetic stimulation such as hypertension and tachycardia. The current study examined whether labetalol, an alpha1 and beta-adrenergic antagonist would blunt these hemodynamic responses. METHODS: Fifty-four ASA physical status I patients, aged 20-60 years, were enrolled in this study. The patients were randomly divided into 2 groups. The breathing circuit was primed with an end-tidal desflurane concentration of 1.2 MAC in 6 L/min O2. Normal saline 5 ml or labetalol 0.3 mg/kg was injected into groups S and L respectively. After 5 minutes, anesthesia was induced with intravenous etomidate 0.2 mg/kg and vecuronium 0.1 mg/kg. Each patient inhaled desflurane through a tight fitting facemask. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and end-tidal concentration of desflurane (et-des) were measured at 5 minutes after saline or labetalol injection (baseline) and every 1 minute for 5 minutes after desflurane inhalation and for 2 minutes after intubation. RESULTS: In the saline injection group (group S), desflurane inhalation increased heart rate and blood pressure, while labetalol 0.3 mg/kg attenuated the heart rate and blood pressure increase in group L. After tracheal intubation, heart rate and blood pressure were significantly lower in group L than in group S. CONCLUSIONS: These results demonstrate that administration of intravenous labetalol is effective in attenuating tracheal intubation and desflurane-induced hemodynamic responses.

Total intravenous anesthesia in a 10-month-old patient with congenital myotonic dystrophy undergoing endoscopic third ventriculostomy: A case report / 대한마취과학회지

Myotonic dystrophy is a rare genetic disorder characterized by muscle atrophy and weakness. Surgical treatment of this condition poses various problems for the anesthesiologist. We describe the anesthetic management of a 10-month-old infant with congenital myotonic dystrophy, who was scheduled for endoscopic third ventriculostomy under general anesthesia. Anesthesia was induced with thiopental sodium, fentanyl, and vecuronium, and thereafter maintained via continuous infusion of propofol and remifentanil. The train-of-four ratio was monitored throughout the operation, and muscle relaxation was reversed with pyridostigmine and glycopyrrolate at the end of the procedure. We show that total intravenous anesthesia using propofol and remifentanil is a satisfactory anesthetic technique in very young patients with congenital myotonic dystrophy.

SUGAMADEX: novos horizontes para a reversão do bloqueio neuromuscular / SUGAMMADEX: new horizons for the reversal of neuromuscular blockade

O sugamadex é uma droga nova e revolucionária desenvolvida como antagonista seletivo dos agentes bloqueadores neuromusculares (ABNM) esteroides (rocurônio > vecurônio ¼ pancurônio). O medicamento é uma y-ciclodextrina modificada e hidrossolúvel que forma um composto estável com o ABNM na razão de 1:1. Ele se liga ao ABNM livre no plasma, criando um gradiente de concentração que desloca o ABNM dos receptores nicotínicos na junção neuromuscular, levando à reversão completa e duradoura do BNM. O sugamadex não se liga às proteínas ou a qualquer outro receptor no organismo, o que lhe confere ótimo perfil de tolerância. O sugamadex pode ser usado na reversão do BNM profundo, promovendo recuperação mais rápida em relação à succinilcolina. Seu emprego pode diminuir a necessidade de monitorização do BNM, a incidência de bloqueio residual e ainda evitar os efeitos adversos causados pelos anticolinesterásicos e anticolinérgicos. Entretanto, também há limitações em relação à utilização 00 sugamadex. Ele impede o uso dos AB- NMs esteroides durante 24 horas, caso seja necessário novo BNM, e pode aumentar o risco do emprego desnecessário e indiscriminado dos ABNMs. Além disso, faltam dados da sua utilização em alguns grupos populacionais e de seu uso em larga escala. Por fim, deve-se considerar também o fator econômico, visto que se trata de uma droga nova e de valor ainda elevado no mercado...

Sugammadex is a novel and unique compaund designed as a selective antaganist ot steroidal neuromuscular blaeking agents (NMBA) (rocuronium>vecuronium¼pancuronium). The drug is a modified water-saluble y-cyclodextrin that forms a stable complex at a 1:1 ratio with the NMBA. It combines with the NMBA creating a concentration gradient favoring the movement ot the NMBA from the nicotine receptors ot the neuromuscular junction leading to the complete and lasting reversal af the neuromuscular blockade (NMB). Sugamadex does not bind to plasma proteins or any other receptors system in the body what provides him a great tolerance profile. Sugamadex can be used in the reversal af deep neuromuscular blockade with a faster recovery time in relation to succinylcholine. Its use can diminish the necessity af monitoring af the NMB, the incidence ot residual blockade and still prevent the adverse effects caused by the antiecholinesterase and anticholinergic drugs. However, there are limitatians regarding the use af Sugammadex. It hinders the use ot the steroidal NMBA during 24 hours if a new NMB must be restablished and it can increase the risk ot unnecessary and indiscriminate use af the NMBA. Mareaver, there is a laek ot data regarding the its use in some population groups and in large scale. Final/y, the economic factor must be also considered, since it is a new drug with a still raised value in market...

The effect of beta1-adrenergic receptor gene polymorphism on prolongation of corrected QT interval during endotracheal intubation under sevoflurane anesthesia / 대한마취과학회지

BACKGROUND: The hemodynamic responses to endotracheal intubation are associated with sympathoadrenal activity. Polymorphisms in the beta1-adrenergic receptor (beta1AR) gene can alter the pathophysiology of specific diseases. The aim of this study is to investigate whether the Ser49Gly and Arg389Gly polymorphism of the beta1AR gene have different cardiovascular responses during endotracheal intubation under sevoflurane anesthesia. METHODS: Ninety-one healthy patients undergoing general anesthesia were enrolled. Patients underwent slow inhalation induction of anesthesia using sevoflurane in 100% oxygen. Vecuronium 0.15 mg/kg was given for muscle relaxation. Endotracheal intubation was performed by an anesthesiologist. The mean arterial pressure (MAP), heart rate (HR), and the corrected QT (QTc) interval were measured before induction, before laryngoscopy, and immediately after tracheal intubation. Genomic DNA was isolated from the patients' peripheral blood and then evaluated for the beta1AR-49 and beta1AR-389 genes using an allele-specific polymerase chain reaction method. RESULTS: No differences were found in the baseline values of MAP, HR, and the QTc interval among beta1AR-49 and beta1AR-389, respectively. In the case of beta1AR-49, the QTc interval change immediately after tracheal intubation was significantly greater in Ser/Ser genotypes than in Ser/Gly genotypes. No differences were observed immediately after tracheal intubation in MAP and HR for beta1AR-49 and beta1AR-389. CONCLUSIONS: We found an association between the Ser49 homozygote gene of beta1AR-49 polymorphism and increased QTc prolongation during endotracheal intubation with sevoflurane anesthesia. Thus, beta1AR-49 polymorphism may be useful in predicting the risk of arrhythmia during endotracheal intubation in patients with long QT syndrome.

Recurrent unilateral lung ventilation disorder in a patient that experienced rocuronium-induced anaphylactic bronchospasm during laparoscopic rectal surgery: A case report / 대한마취과학회지

Rocuronium is the anesthetic agent most likely to cause anaphylaxis. Immediately after intravenous rocuronium administration, the authors experienced ventilatory impairment due to unilateral bronchospasm (left lung), which was relieved by emergency treatment. However, 80 minutes after beginning laparoscopic surgery for rectal cancer, the left lung suddenly re-collapsed under pneumoperitoneum in the Trendelenburg position. A postoperative intradermal test revealed that rocuronium, vecuronium, atracurium, succinylcholine, or thiopental could induce anaphylaxis in this patient, but it was not established whether the second incident during surgery was due to endobronchial intubation or anaphylactic bronchospasm. This case cautions that under pneumoperitoneum in the Trendelenburg position, patients suspected of being prone to anaphylactic bronchospasm should also be considered at risk of endobronchial intubation.

Response of cerebral oximetry to increase in alveolar concentration of desflurane: effect of remifentanil and cerebrovascular CO2 reactivity / 대한마취과학회지

BACKGROUND: It is known that sympathetic stimulation and increase in cerebral blood flow velocity can be induced by desflurane. Cerebral oxygen balance could be disturbed during desflurane induction. Aim of this study was to elucidate that cerebral oxygen imbalance induced by desflurane mask induction can be reduced by combination of remifentanil and hypocapnia. METHODS: Twenty ASA 1-2 subjects were allocated randomly into 5 groups divided by concentration of remifentanil (0.0, 0.5, 1.0, 1.5, and 2.0 ng/ml). After confirmation of attaining proposed concentration of remifentanil, propofol and vecuronium were administered and mechanical ventilation was done with 8% desflurane with facial mask. Subsequently, changes in regional cerebral oxygen saturation (DeltarSO2), arterial blood pressure, heart rate, cardiac index, estimated alveolar concentration of desflurane (PDESF), and end-tidal concentration of carbon dioxide (PETCO2) were recorded for the following 10 minutes. According to concentration of desflurane and remifentanil, DeltarSO2 and hemodynamic factors were checked. RESULTS: During desflurane induction, changes in cerebral oximetry reached up to +10% (6 [first quartile], 13 [third quartile]). Arterial blood pressure, heart rate, and cardiac index were changed within clinical ranges. The DeltarSO2 showed S-shaped increasing pattern according to increasing PDESF. Hypocapnia and concentration of remifentanil reduced the maximum DeltarSO2 (P = 0.0046, P = 0.0060). Hypocapnia also shifted the curve to left (P = 0.0001). CONCLUSIONS: During 8% desflurane induction, regional cerebral oxygen saturation (rSO2) increases maximum +25%. Hypocapnia and use of remifentanil can reduce the increase in regional cerebral oxygen saturation.

Analysis of the rocuronium-vecuronium interaction on tetanic fade based on a generalized response surface model with varying relative potencies / 대한마취과학회지

BACKGROUND: Some studies have shown that rocuronium and vecuronium have additive, or synergistic effects on muscle relaxation based on the Loewe additivity. Therefore, we performed a fit of tetanic fade data to a generalized response surface model with varying relative potencies proposed by Kong and Lee (KLGRS) to evaluate the usefulness of KLGRS for capturing the interspersed drug interactions and to characterize the interaction between the two drugs. METHODS: Left phrenic nerve-hemidiaphragms (Male Sprague-Dawley rats, 150-250 g) were mounted in Krebs solution. Supramaximal electrical stimulation (0.2 ms, rectangular) of 50 Hz for 1.9 s to the phrenic nerve evoked tetanic contractions that were measured with a force transducer. Each preparation was exposed to one of 4 vecuronium concentrations (0.0, 1.5, 2.5, and 3.0 microM), or one of 4 rocuronium concentrations (0.0, 3.0, 4.5, and 5.5 microM). Subsequently the adequate amount of rocuronium was added to a vecuronium bath and that of vecuronium was added to a rocuronium until an 80-90% increase in tetanic fade was achieved. We then fitted the modified KLGRS models to the above data, after which we selected the best model, based on 5 methods for determining goodness of fit. Using this method, we obtained the response surface, as well as contour plots for the response surface (i.e. isoboles), the polynomial function and the interaction index. RESULTS: The model with the constant relative potency ratio and 8 parameters was found to best describe the results, and this model reflected well the characteristics of the raw data. In addition, the two drugs showed a synergistic interaction in almost every area and an antagonistic one in a very narrow area. CONCLUSIONS: KLGRS was found to be a useful method of analyzing data describing interspersed drug interactions. The interaction between rocuronium and vecuronium was found to be synergistic.

Remifentanil and fentanyl combined with propofol administered by target controlled infusion in neurosurgery / 中南大学学报(医学版)

OBJECTIVE@#To compare the hemodynamics and post-anesthetic recovery of total intravenous anesthesia (TIVA) with remifentanil or fentanyl combined with propofol administered by target controlled infusion (TCI) in neurosurgery.@*METHODS@#A total of 80 patients undergoing selective neurosurgery were randomly divided into a remifentanil group (Group R, n=40) and a fentanyl group (Group F, n=40). In Group R,remifentanil and propofol was administered by TCI and the blood concentration were 3 approximately 5 microg/L and 3 approximately 5 mg/L each. In Group F, fentanyl was continuously infused at 2 approximately 3 microg/(kg.h) and propofol was administered by TCI with the same blood concentration as that in Group R.Vecuronium was injected at intervals to maintain muscle relaxant.Mean arterial pressure and heart rate during the anesthesia and post-anesthetic recovery were recorded.@*RESULTS@#Mean arterial pressure of all the patients was decreased significantly from induction of anesthesia to termination of operation compared with that before the induction( P0.05). The eyes opened and extubed time of Group R were decurtated obviously and the scores of pain were increased significantly (P<0.01).@*CONCLUSION@#TIVA with remifentanil or fentanyl combined with propofol administered by TCI in neurosurgical operation can provided steadible hemodynamics. Resuscitation of remifentanil with propofol administered by target controlled infusion were more quickly but the scores of pain were more higher than that of fentanyl.

Anesthetic management during cardiac bypass in fetal lambs / 南方医科大学学报

<p><b>OBJECTIVE</b>To summarize the anesthetic management in fetal lamb cardiac bypass.</p><p><b>METHODS</b>Five ewes at 120-140 days of gestation were anesthetized intramuscularly with katamine hydrochloride, intubated and ventilated with a respirator. Anesthesia was maintained with fentanyl and vecuronium. Lactated Ringer's solution and magnesium sulfate were infused to maintain the mean blood pressure (MAP) over 70 mmHg and uterine relaxation. The fetal lambs received anesthesia with fentanyl and vecuronium intramuscularly via the uterine wall. Fetal cardiac bypass was established with pulmonary artery and right atrium cannulation, lasting for 30 min. The hemodynamic and blood gas data of the ewes and fetal lambs were recorded before bypass, at 30 min during bypass, and at 1 and 2 h after cessation of bypass. The pulse index of the umbilical artery (PIua) and the ewe's uterine artery (PIeu) were monitored simultaneously.</p><p><b>RESULTS</b>The MAP and heart rate (HR) of the fetus remained normal during the anesthesia. PIua increased significantly after cessation of bypass (P<0.05). Although the fetal oxygen tension in the axillary artery remained normal, the fetal lambs showed hypercarbia and acidosis after cessation of bypass (P<0.05). The maternal MAP and HR remained normal. The PIeu decreased significantly during bypass (P<0.05) and recovered the normal level after cessation of bypass. The arterial blood gas of the ewes was normal during the experiment.</p><p><b>CONCLUSION</b>Maintaining high hemodynamics in the ewes, application of uterine relaxation and intensive care during anesthesia are crucial in anesthetic management of cardiac bypass in fetal lambs.</p>

Desenvolvimento, validação e comparação de métodos analíticos para determinação de bloqueadores neuromusculares derivados de esteróides / Development, validation and comparison of analytical methods for determination of neuromuscular blocking derivatives of steroids

Os relaxantes neuromusculares não despolarizantes são fármacos indispensáveis nos procedimentos cirúrgicos que requerem entubação endotraqueal, visto que diminuem o tônus muscular. Quimicamente são divididos em derivados isoquinolinicos e derivados de esteróides, esses últimos com maior aplicação clinica e comercialização no Brasil. Assim sendo, é importante a validação de métodos analíticos para o controle de qualidade com alternativas confiáveis que garantam sua eficácia e segurança. Os brometos de vecurônio, de pancurônio e de rocurônio são fármacos relaxantes neuromusculares não despolarizantes derivados de esteróides. As propriedades farmacológicas destes fármacos são significativamente diferentes entre si, porém, as propriedades químicas são bastante similares. Na presente pesquisa foram desenvolvidos e validados métodos analíticos de separação (cromatografia líquida de alta eficiência e eletroforese capilar) para cada fármaco. Estes métodos foram aplicados a medicamentos comercializados no Brasil. Para todos os métodos cromatográficos foi utilizada uma coluna amino devido a seu caráter polar. Em função da baixa absorção dos três fármacos na região ultravioleta, os métodos eletroforéticos foram aplicados com detecções indiretas utilizando substâncias cromóforas. Comparando-se as técnicas utilizadas para determinação dos fármacos nos medicamentos isoladamente, não houve diferença significativa com nível de confiança de 95,0%. Nos testes de hipótese aplicados (F-Snedecor e t-Student), não foram observadas diferenças na precisão (variâncias) e no valor encontrado dos fármacos contidos nas amostras estudadas (comparação de duas médias).

The non-depolarizing neuromuscular relaxant drugs are essential in surgical procedures requiring endotracheal intubation, as they decrease muscle tonics. These drugs are chemically divided in isoquinolines derivatives and steroid derivatives, this latter group, with greater clinical application and commercialization in Brazil. Therefore, the study and validation of analytical methods are important for quality control with reliable alternatives to ensure their effectiveness and safety. The vecuronium, pancuronium and rocuronium bromides are steroid derivatives presenting non-depolarizing neuromuscular relaxant action. Pharmacological properties of these drugs differ significantly, however, its chemical properties are quite similar. In this research, analytical separation methods (high performance liquid chromatography and capillary electrophoresis), for each drug, were developed and fully validated. The methods were applied to pharmaceutical formulations commercialized in Brazil. For all chromatographic methods, an amino column was used, due to its polar characteristics. Due to the low absorption of the three drugs in the ultraviolet region, electrophoretic methods has been applied with indirect detection using chromophoric substances. When comparing both techniques used for quantitative determination of these drugs in pharmaceutical products, no significant difference was observed using a confidence level of 95.0%. By applying hypothesis tests (F-Snedecor and t-Student), it was not observed difference in precision (variance) and in the found amount of drugs contained in the selected samples (comparison of two means).