Target-controlled infusion and population pharmacokinetics of landiolol hydrochloride in gynecologic patients.

PURPOSE: We previously determined the pharmacokinetic (PK) parameters of landiolol in healthy male volunteers. In this study, we evaluated the usefulness of target-controlled infusion (TCI) of landiolol hydrochloride and determined PK parameters of landiolol in gynecologic patients. METHODS: Nine patients who were scheduled to undergo gynecologic surgery were enrolled. After inducing anesthesia, landiolol hydrochloride was administered at the target plasma concentrations of 500 and 1,000 ng/mL for each 30 min. A total of 126 data points of plasma concentration were collected from the patients and used for the population PK analysis. Furthermore, a population PK model was developed using the nonlinear mixed-effect modeling software. RESULTS: The patients had markedly decreased heart rates (HRs) at 2 min after the initiation of landiolol hydrochloride administration; however, their blood pressures did not markedly change from the baseline value. The concentration time course of landiolol was best described by a 2-compartment model with lag time. The estimate of PK parameters were total body clearance (CL) 34.0 mL/min/kg, distribution volume of the central compartment (V 1) 74.9 mL/kg, inter-compartmental clearance (Q) 70.9 mL/min/kg, distribution volume of the peripheral compartment (V 2) 38.9 mL/kg, and lag time (ALAG) 0.634 min. The predictive performance of this model was better than that of the previous model. CONCLUSION: TCI of landiolol hydrochloride is useful for controlling HR, and the PK parameters of landiolol in gynecologic patients were similar to those in healthy male volunteers and best described by a 2-compartment model with lag time.

[Usefulness of a noncontact continuous tympanic thermometer in patients undergoing cardiac surgery using an artificial heart-lung machine].

BACKGROUND: Most of the thermometers used during operations are invasive and non-hygienic. The usefulness of a noncontact continuous tympanic thermometer under general anesthesia has been reported. We evaluated the usefulness of a noncontact continuous tympanic thermometer in patients undergoing cardiac surgery using an artificial heart-lung machine. METHODS: Twenty patients scheduled to undergo cardiac surgery using an artificial heart-lung machine were selected for this study. After induction of general anesthesia, thermistor probes were inserted into the rectum and esophagus for measurements of rectal and esophageal temperatures, respectively. A noncontact continuous tympanic thermometer was inserted into the ear canal on the right side. These temperatures were monitored and recorded at one-minute intervals. Regression analysis and Bland-Altman analysis were used to compare the data (tympanic/rectal temperatures) with esophageal temperature as a core temperature. RESULTS: Tympanic temperature showed a good correlation with esophageal temperature (r=0.983, P<0.05). Rectal temperature also showed a good correlation with esophageal temperature (r=0.923, P<0.05), but the coefficient of correlation was low compared to that of tympanic temperature. The mean difference between tympanic temperature and esophageal temperature was -0.022 degrees C, and standard deviation (SD) was 0.395 degrees C. The mean difference between rectal temperature and esophageal temperature was -0.299 degrees C, and standard deviation (SD) was 0.838 degrees C. CONCLUSIONS: A noncontact continuous tympanic thermometer is useful for measurement of core temperature during cardiac surgery using an artificial heart-lung machine.

[Postoperative analgesia of continuous intravenous fentanyl or dexmedetomidine for patients receiving anticoagulant therapy].

BACKGROUND: It is difficult to achieve good postoperative analgesia in patients who undergo abdominal aortic surgery without epidural analgesia and who have a bleeding tendency or are undergoing anticoagulation therapy. Intravenous fentanyl analgesia can be used in such patients, but it occasionally causes respiratory depression. Dexmedetomidine is used to achieve postoperative sedation and analgesia without respiratory depression. We compared the methods used to achieve postoperative analgesia after abdominal aortic surgery. METHODS: In the intravenous fentanyl analgesia group (group F, n = 15), 0.5 microg x kg(-1) x hr(-1) fentanyl infusion was initiated during operation and continued to the next morning. In the intravenous dexmedetomidine group (group D, n = 15), 0.4-0.7 microg x kg(-1) x hr(-1) dexmedetomidine infusion was commenced during the operation and decreased to 0.2-0.7 microg x kg(-1) x hr- in the next morning. In the control group (group C, n = 15), continuous intravenous analgesia was not used. The frequency of analgesic use, Ramsay score, PaCO2 value, and rate of nausea and shivering were evaluated on the next morning. RESULTS: The frequency of analgesic use and Ramsay score were similar in groups F and D. The Paco2 value was higher in group F than group D. CONCLUSIONS: With regard to respiratory depression, intravenous dexmedetomidine analgesia is safer and more useful than intravenous fentanyl analgesia.

[Utility of SVV (stroke volume variation) during abdominal aortic surgery].

BACKGROUND: Stroke volume variation (SVV) has been shown to be a reliable predictor of fluid responsiveness. It has been reported that SVV is useful for perioperative fluid management. We evaluated SVV and hemodynamics after aortic declamping during abdominal aortic surgery. METHODS: Patients scheduled to undergo abdominal aortic surgery were selected for this study. A FloTrac sensor was fitted to a 20 G cannula indwelled in the radial artery, and cardiac output (CO), central venous pressure (CVP) and SVV were continuously monitored. Patients were divided into two groups depending on pressure decrease after aortic declamping: above 50 mmHg (F group) and below 50 mmHg (N group). CO, CVP and SVV before and after the aortic declamping in the two groups were compared. RESULTS: Thirty patients were included in this study (15 in the F group and 15 in the N group). Measurement points were 26 points in the F group and 28 points in the N group. SVV before aortic declamping in the F group was significantly higher than that in the N group. Rate of decrease in CO after aortic declamping in the F group was significantly higher than that in the N group. There was no difference in CVP between the two groups. CONCLUSIONS: The results of this study suggest that monitoring SVV during abdominal aortic surgery is useful.

[Clinical usefulness of continuous cardiac output measurement: PulseCO].

BACKGROUND: PulseCO for continuous cardiac output measurement is a relatively noninvasive and effective monitor. PulseCO is obtained from the arterial pulse waveform, but calibration by another method is necessary. We performed calibration of PulseCO by CO measurement using TEE and examined the utility of PulseCO. METHODS: PulseCO was calibrated by TEE after induction of anesthesia, and PulseCO and continuous cardiac output with Vigilance (CCO) were measured continuously. Records were obtained every thirty minutes and were excluded from analysis when hemodynamics was unstable. RESULTS: Correlations of CCO with TEE (r = 0.88) and PulseCO (r = 0.86) were examined. PulseCO showed a significantly better correlation with CCO, and dispersion was small. CONCLUSIONS: The results suggest that PulseCO is very useful as an intraoperative cardiac output measurement monitor.

[Optimal dose of fentanyl for postoperative epidural analgesia after thoracic surgery].

BACKGROUND: We investigated the dose of fentanyl in ropivacaine for epidural anesthesia that will provide effective analgesia with minimal side effects after thoracic surgery. METHODS: Sixty patients scheduled to undergo thoracic surgery were randomly allocated to four groups according to fentanyl dose in epidural analgesia: group R (0 microg x hr(-1); n = 15), group F1 (5 microg x hr(-1); n = 15), group F2 (10 microg x hr(-1); n = 15) and group F3 (15 microg x hr(-1); n = 15). Pain scores (visual analogue scale: VAS) were assessed at 1, 3, 6, 12, 24, and 48 hrs after surgery. Degrees of satisfaction regarding pain relief and complications during a period of 48 hrs after surgery were compared. RESULTS: Pain scores in group F3 were significantly lower than those in the other groups at 3, 6, and 12 hrs after surgery. The number of postoperative analgesics used in group R was significantly more than the numbers used in other groups. The incidences of side effects were similar in the four groups. CONCLUSIONS: We conclude that continuous epidural administration of more than 15 microg x hr(-1) of fentanyl in ropivacaine provides pain relief and few side effects after thoracic surgery.

[Anesthesic management of thoracic aortic stent graft deployment using rapid ventricular pacing].

Controlled hypotension is useful for accurate deployment of an aortic endograft. We describe the use of rapid ventricular pacing during thoracic aortic stent graft deployment. Anesthesia was induced and maintained with intravenous propofol and remifentanil. A pulmonary artery catheter with pacing function was introduced, and rapid ventricular pacing was started before stent graft deployment. Pacing mode was VVI and pacing rate was 120-160 beats min(-1). Aortic pressure and flow decreased immediately and were maintained at low levels during surgical manipulation. After stopping rapid ventricular pacing, heart rate and aortic pressure recovered immediately. Rapid ventricular pacing was performed 4 times, and there were no complications such as entailed arrhythmia. With rapid ventricular pacing maneuver, which is thought to cause a rapid change in cardiac output, continuous cardiac output measurement can be a useful monitor. This procedure has advantages over pharmacologic or other methods of aortic pressure reduction. Rapid ventricular pacing is safe and effective during stent graft positioning and deployment.

[Esophageal intubation: Can it be avoided with the airway scope (Pentax-AWS)?].

Airway scope (AWS) is a rigid indirect laryngoscope with integrated tube guidance and can improve laryngeal exposure compared to the conventional direct laryngoscope. It is expected that the clear and improved laryngeal view obtained with AWS can eliminate the risk of esophageal intubation. We, however, experienced 3 cases of esophageal intubation out of 600 clinical cases with AWS in 15 month after its market release. Two cases were by novice anesthesiologists with fewer than 10 intubation experiences with AWS. Although they had had more than 100 intubation experiences with Macintosh laryngoscope, they did not have sharp eye for incorrect intubation with AWS. The third case was performed by an experienced laryngoscopist but it was difficult to identify the glottic opening because patient had distracted airway anatomy due to laryngeal tumor. In all cases esophageal intubation was immediately noticed and airway was secured uneventfully. We conclude that intubation under vision with improved laryngeal view is still not sufficient to prevent esophageal intubation.

[Sensory block levels for pain relief after cesarean section].

BACKGROUND: It has been proposed that sensory block from the 10 th thoracic nerve (T 10) to the 1 st lumbar nerve (L1) is necessary for pain relief after cesarean section. However, we have experienced complaints of unsatisfactory pain relief from some patients in whom T 10-L 1 sensory block was achieved. We evaluated the relation between range of sensory block and satisfaction regarding pain relief in patients after cesarean section. METHODS: Pregnant patients after cesarean sections using continuous epidural infusion of 0.2% ropivacaine were allocated into two groups depending on the level of sensory block 6 hrs after surgery: below the T 10 level (T 10 group) and beyond the T 9 level (T 9 group). Degrees of satisfaction regarding pain relief and complications during a period of 16 hrs after surgery were compared. RESULTS: Fifty patients were included in this study (21 in the T 10 group and 29 in the T 9 group). Sensory block in the T 9 group ranged from T 5 to T 9. The number of postoperative analgesics usage in the T 9 group was significantly less than that in the T 10 group. CONCLUSIONS: We propose that sensory block ranging from T 5 to T 9 in addition to T 10-L 1 is necessary to obtain satisfactory pain relief after cesarean section.

Target-controlled infusion and population pharmacokinetics of landiolol hydrochloride in patients with peripheral arterial disease.

PURPOSE: We previously determined the pharmacokinetic (PK) parameters of landiolol in healthy male volunteers and gynecological patients. In this study, we determined the PK parameters of landiolol in patients with peripheral arterial disease. METHODS: Eight patients scheduled to undergo peripheral arterial surgery were enrolled in the study. After inducing anesthesia, landiolol hydrochloride was administered at target plasma concentrations of 500 and 1,000 ng/mL for 30 minutes each. A total of 112 data points of plasma concentration were collected from the patients and used for the population PK analysis. A population PK model was developed using a nonlinear mixed-effect modeling software program (NONMEM). RESULTS: The patients had markedly decreased heart rates at 2 minutes after initiation of landiolol hydrochloride administration; however, systolic blood pressures were lower than the baseline values at only five time points. The concentration time course of landiolol was best described by a two-compartment model with lag time. The estimates of PK parameters were as follows: total body clearance, 30.7 mL/min/kg; distribution volume of the central compartment, 65.0 mL/kg; intercompartmental clearance, 48.3 mL/min/kg; distribution volume of the peripheral compartment, 54.4 mL/kg; and lag time, 0.633 minutes. The predictive performance of this model was better than that of the previous model. CONCLUSION: The PK parameters of landiolol were best described by a two-compartment model with lag time. Distribution volume of the central compartment and total body clearance of landiolol in patients with peripheral arterial disease were approximately 64% and 84% of those in healthy volunteers, respectively.

[Suppression of frequent ventricular fibrillation attacks after induction of anesthesia with fentanyl, sevoflurane and propofol: a case report].

We experienced emergency anesthetic management of a 51-year-old male for exchange of a battery in an implantable cardioverter defibrillator. He had repeated and intractable attacks of ventricular fibrillation (Vf) before induction of anesthesia. Infusion of propofol at 100 mg.hr-1 failed to suppress the Vf attacks in the ICU. However, the Vf attacks were suppressed by the addition of fentanyl 100 micrograms, nitrous oxide and sevoflurane to the infusion of propofol. It is speculated that general anesthetics inhibit Vf attacks by direct suppression of myocardium and reduction of sympathetic nervous activity.

Detection of landiolol using high-performance liquid chromatography/fluorescence: a blood esterase-sensitive ultra-short-acting beta(1)-receptor antagonist.

Landiolol hydrochloride, a new adrenergic beta(1)-selective antagonist having an ultra-short half-life, is used to prevent tachyarrhythmia during surgery. Since landiolol is thought to be rapidly hydrolyzed to an inactivate metabolite by esterases, quantification of the drug concentration in the blood is impractical. The landiolol concentration in blood was halved within 5 min after blood sampling. This degradation was effectively prevented by pre-treatment with neostigmine (100 microg) in the sampling tube, but not by EDTA pre-treatment, indicating that landiolol could be metabolized by pseudocholinesterase in plasma. After the one-step solid-phase extraction, fluorescence detection of landiolol reduced chromatographic background signals and then improved assay sensitivity to the lower limit of 10 ng/ml in blood; this reproducible approach yielded coefficient variation of less than 6%. The blood concentration-time profile of landiolol hydrochloride in patients of the present investigation afforded more practical assessment than previously reported studies, thus improving accuracy and facilitating detailed pharmacokinetic study in relation to the pharmacological action of drug.