Relationship between dexmedetomidine dose and plasma dexmedetomidine concentration in critically ill infants: a prospective observational cohort study.

BACKGROUND: Dexmedetomidine is a highly selective central α2-agonist used as a sedative in pediatric intensive care unit (PICU). However, little is known about the relationship between dexmedetomidine dose and its plasma concentration during long-term infusion. We have previously demonstrated that the sedative plasma dexmedetomidine concentration is moderately correlated with the administered dose in adults (r = 0.653, P = 0.001). We hypothesized that there would be a similar relationship between the sedative dexmedetomidine concentration and administered dose in infants. METHODS: All patients admitted to the PICU at Nagoya City University Hospital, Japan, between November 2012 and March 2013 were eligible for inclusion in the study. Plasma dexmedetomidine concentration was measured by ultra-performance liquid chromatography coupled with tandem mass spectrometry. RESULTS: We measured the plasma dexmedetomidine concentration in 203 samples from 45 patients. Of these, 96 samples collected from 27 patients < 2 years old were included in this study. All patients received dexmedetomidine at 0.12-1.40 µg/kg/h. The median administration duration was 87.6 hours (range: 6-540 hours). Plasma dexmedetomidine concentration ranged from 0.07 to 3.17 ng/ml. Plasma dexmedetomidine concentration was not correlated with the administered dose (r = 0.273, P = 0.007). The approximate linear equation was y = 0.690x + 0.423. CONCLUSIONS: In infants, plasma dexmedetomidine concentration did not exhibit any correlation with administered dose, which is not a reliable means of obtaining optimal plasma concentration.

Effects of landiolol on refractory tachyarrhythmia after total cavopulmonary connection: a retrospective, observational, cohort study.

The onset of tachyarrhythmia after the Fontan procedure (total cavopulmonary connection; TCPC) should be considered a medical emergency. Landiolol is an ultra-short-acting ß1-selective blocker whose effect on tachyarrhythmia after TCPC is unclear. We evaluated the efficacy and safety of landiolol for tachyarrhythmia after TCPC. Consecutive patients undergoing TCPC were enrolled from January 2007 to December 2011. Of 435 pediatric open heart surgeries, 28 patients underwent TCPC. Of the 28 patients, 13 were treated with landiolol for critical tachyarrhythmia. Excluding three patients who received landiolol during surgery, we investigated the remaining 10 patients and statistical analysis was performed without a 10-year-old patient as outlier. The median age was 4.08 years. The subjects comprised five patients with sinus tachycardia, four with junctional ectopic tachycardia and one with paroxysmal supraventricular tachycardia. The initial dose was 4.7 ± 2.3 µg/kg/min, without a loading dose. Landiolol reduced the heart rate from 151.8 ± 23.2 at the start to 132.9 ± 20.0 at 1 h and 126.1 ± 24.9 at 2 h (P < 0.01 and P < 0.01, respectively), without blood pressure decrease (P = 0.235). Landiolol was effective in treating critical tachyarrhythmia without hemodynamic deterioration. We believe that landiolol is a promising option for postoperative tachyarrhythmia after the Fontan procedure.

Estimation of the success rate of anesthetic management for thymectomy in patients with myasthenia gravis treated without muscle relaxants: a retrospective observational cohort study.

Although maintaining anesthesia for myasthenia gravis (MG) with minimal muscle relaxants (MR) is common, the success rate of anesthetic management for MG without MR is not clear. We therefore retrospectively examined the success rate of anesthetic management for MG without MR among 66 consecutive cases of thymectomy for MG performed at our hospital between January 2004 and April 2010, before approval of using sugammadex. A total of 60 patients (90.9 %) were treated without MR (N group). Among the 60 cases, 17 (28.3 %) patients were not extubated in the operating room due to postoperative respiratory depression or other reasons. Therefore, the success rate of anesthetic management for thymectomy in patients with MG without treating MR was 71.7 % (43/60) [95 % confident interval (CI): 65.9-77.5 %]. The reasons for using MR included coughing at intubation in one case, bucking during surgery in two cases, and MR was considered to be safer by the attending anesthesiologist in three cases. The number of cases of impossible extubation requiring ventilation on that day was three in the N group and none in the R group. Finally, the success rate of anesthetic management for MG without MR was estimated to be 71.1 % (95 % CI: 65.9-77.5 %).

Development of a stable isotope dilution UPLC-MS/MS method for quantification of dexmedetomidine in a small amount of human plasma.

Dexmedetomidine (Dex) is a selective central α2-agonist with anesthetic properties and has been used in clinical practice for sedation in the intensive care unit (ICU) after operations. In this study, an analytical assay for the determination of Dex in a small amount of plasma was developed for the application to pediatric ICU trials. The quantification of Dex was constructed using the original stable isotope Dex-d3 for electrospray ionization-tandem mass spectrometry (ESI-MS/MS) in the selected reaction monitoring mode. A rapid ultra-performance liquid chromatography technique was adopted using ESI-MS/MS with a runtime of 3 min. Efficacious concentration levels (50 pg/mL to 5 ng/mL) could be evaluated using a very small amount of plasma (10 µL) from patients. The lower limit of the quantification was 5 pg/mL in the plasma (100 µL). For sample preparation, a solid-phase extraction was used along with the OASIS-HLB cartridge type. Recovery values ranged from 98.8 to 100.3% for the intra- [relative standard deviation (RSD), 0.9-1.3%] and inter- (RSD, 0.9-1.5%) day assays. A stable test had recovery values that ranged from 97.8 to 99.7% with an RSD of 1.0-1.9% for the process/wet extract, bench-top, freeze-thaw and long-term tests. This method was used to measure the Dex levels in plasma from pediatric ICU patients. In the clinical ICU trial, the small amount of blood (approximate plasma volume, 200 µL) remaining from blood gas analysis was reused and targeted for the clinical analysis of Dex in plasma.

A comparison between dosages and plasma concentrations of dexmedetomidine in clinically ill patients: a prospective, observational, cohort study in Japan.

BACKGROUND: Dexmedetomidine is a highly selective central α2-agonist with anesthetic and analgesic properties for patients in intensive care units. There is little information about the relationship between dosage and plasma concentration during long drug infusions of dexmedetomidine in critically ill patients, especially in Asians. In addition, the administration of dexmedetomidine with a dosage of 0.2-0.7 µg/kg/h in Japan is different from that with a dosage of 0.2-1.4 µg/kg/h in European countries and the USA. There has been concern about obtaining an effective concentration with a small dosage and estimating the relationship between dosage and plasma concentration. We conducted a prospective, observational, cohort study measuring plasma dexmedetomidine concentrations. METHODS: Plasma dexmedetomidine concentrations of 67 samples from 34 patients in an intensive care unit for 2 months were measured by ultra performance liquid chromatography coupled with tandem mass spectrometry using single-blind method, and the correlation coefficient between dosages and plasma concentrations was estimated. Exclusion criteria included young patients (<16 years) and samples obtained from patients in which the dosage of dexmedetomidine was changed within 3 h. RESULTS: Among the patients, 20 (58.8%) of the 34 received dexmedetomidine at 0.20-0.83 µg/kg/h, and in 40 of the 67 samples for which dexmedetomidine had been administered, this occurred for a median duration of 18.5 h (range, 3-87 h). The range of the dexmedetomidine plasma concentration was 0.22-2.50 ng/ml. By comparison with other studies, with a dosage of 0.2-0.7 µg/kg/h, the patients in this setting could obtain an effective dexmedetomidine concentration. The plasma dexmedetomidine concentration was moderately correlated with the administered dosage (r = 0.653, P < 0.01). The approximate linear equation was y = 0.171x + 0.254. The range of Richmond Agitation-Sedation Scale was 0 to -5. CONCLUSIONS: We concluded that, with a dosage of 0.2-0.83 µg/kg/h, the patients in this setting could obtain an effective dexmedetomidine concentration of 0.22-2.50 ng/ml. In addition, the plasma dexmedetomidine concentration was moderately correlated with the administered dosage (r = 0.653, P < 0.01). TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) UMIN000009115.

[Reappraisal of current practice of preoperative fasting in Japan].

BACKGROUND: The American Society of Anesthesiologists (ASA) published a clinical practice guideline of preoperative fasting in 1999. A nationwide survey conducted in Japan in 2003 reveals that many hospitals have a much longer fasting period. We conducted a similar survey in three limited areas in Japan to assess the changes in fasting practice. METHODS: A written questionnaire for preoperative fasting was sent to 50 hospital in 3 prefectures. RESULTS: The duration of fasting for liquids tends to be shorter than those in the 2003 survey. The rates of application of the ASA guideline, however, are still low specifically in adults (4.2%), which is significantly lower than those in children (17.7%), or in infants (39.0%). The reasons for noncompliance are mainly due to organizational problems associated with scheduling of operation. Most hospitals aspire to have Japanese guideline about preoperative fasting periods. CONCLUSIONS: Longer preoperative fasting periods are still common practice in Japanese hospitals.