Therapeutic drug monitoring of intravenous busulfan in Thai children undergoing hematopoietic stem cell transplantation: A pilot study.

Busulfan (Bu) is commonly used in myeloablative conditioning regimens for children undergoing hematopoietic stem cell transplantation. The standard target area under the concentration-time curve (AUC) of Bu is approximately 900-1500 µM min. In previous studies using five fixed doses (0.8-1.2 mg/kg) for Bu without dose adjustment, 75% patients achieved the target AUC. The aim of this pilot study was to determine the percentage of target AUC for intravenous (IV) Bu in Thai children. IV Bu was administered every 6 h over 16 doses. Blood samples were collected for pharmacokinetic (PK) analysis after the first, ninth, and thirteenth doses of Bu. Seven patients (2-14 years; median 6 years) were diagnosed with thalassemia (n = 4), acute myeloid leukemia (n = 2), and pure red cell aplasia. Three, two, and two patients received Bu at 1.1, 1.2, and 0.8 mg/kg, respectively. The AUC of Bu varied from 292-1714 µM min (median = 804). Nine (42.86%), eleven (52.38%), and one (4.76%) AUC values were within, below, and above the target, respectively. The median (range) Bu clearance was 5.93 (1.91-14.65) mL/min/kg. In this study, 42.86% AUC value achieved the target, which was lower than that in previous studies. Therapeutic drug monitoring (TDM) of Bu should be considered in Thai children receiving five fixed doses of IV Bu, and dose adjustment should be performed as necessary. Further PK studies for Bu with a larger sample size are warranted for confirming the necessity of TDM in every step dose of Bu.(Trial registration numbers; TCTR20190528003).

A cluster of lysergic acid diethylamide (LSD) poisonings following insufflation of a white powder sold as cocaine.

OBJECTIVE: Adulteration, substitution or contamination of illicit substances can have clinically significant implications when other illicit substances are included. Such circumstances can present as clusters of poisonings, including severe toxicity and death following exposure to unexpected illicit substances. We report a cluster of laboratory-confirmed lysergic acid diethylamide (LSD) in a powder that was sold as cocaine and used recreationally. METHODS: The Prescription, Recreational and Illicit Substance Evaluation (PRISE) program established by the New South Wales Ministry of Health includes State-based hospital toxicology services, Poisons Information Centre, Forensic & Analytical Science Service and emergency services to identify clusters of severe and unusual toxicity associated with substance use. PRISE criteria include a known cluster (geographically or situationally related) of people with acute severe toxicity, especially when accompanied by a toxidrome that is inconsistent with the history of exposure. A timely comprehensive drug screen and quantification is performed in eligible cases and the results are related to the clinical features. The need for a public health response is then considered. Four individuals inhaled a white powder that was sold as cocaine and developed severe toxicity that was not consistent with cocaine which prompted transfer to hospital for further management. RESULTS: LSD was confirmed in four subjects, and the concentrations in 3 of the individuals were 0.04-0.06 mg/L which are among the highest reported in the literature. Common clinical features were hallucinations, agitation, vomiting, sedation, hypertension, and mydriasis. One subject required intubation and admission to the intensive care unit, two required overnight admission, and the fourth was discharged following oral diazepam after observation. No subject suffered persistent injury. CONCLUSIONS: A close working relationship between pre-hospital emergency services, hospital-based clinical services, public health authorities, and analytical laboratories appears to be advantageous. Favourable clinical outcomes are observed from LSD poisoning despite high exposures with good supportive care.

Comparison of the efficacy between lidocaine spray plus lidocaine jelly lubrication and lidocaine jelly lubrication alone prior to nasogastric intubation: a prospective double-blind randomized controlled study.

OBJECTIVE: Although a common procedure, nasogastric (NG) intubation is also painful and unsatisfactory. Previous studies showed the benefits of local anesthesia in various forms over lubricant jelly alone, but they are rarely used due to their inconvenience and unavailability. The authors conducted a double-blind randomized controlled study to compare a commercial-available 10% lidocaine spray plus 2% lidocaine jelly lubrication and 2% lidocaine jelly lubrication alone prior to NG intubation. MATERIAL AND METHOD: Patients who fulfilled the indications for NG intubation were randomized to receive either 10% lidocaine spray or placebo (normal saline) spray to the nostril and throat prior to NG intubation. NG tubes lubricated with 2% lidocaine jelly were then inserted by experienced physicians. Physician, who sprayed, inserted the NG tubes and collected the patient's data, did not know the content of the spray, while patients were also blinded against the information of the spray. RESULTS: Sixty patients were included in the present study. Thirty one randomly received lidocaine spray and 29 received placebo spray. There were more female patients in the lidocaine group (65% vs. 28%, p=0.04), but ages, indications for NG intubation, size of NG tube, and physicians' experience in the procedure were similar in both groups. Patients' discomfort after being sprayed was also similar in both groups. However during the NG intubation, the patients in the lidocaine group experienced less pain as measured by visual analog scale (23.6 +/- 16.6 vs. 43.1 +/- 31.4 mm, p=0.005) and less discomfort (30.0 +/- 24.4 vs. 51.4 +/- 30.0 mm, p=0.004) than the placebo group. Ninety-three percent of the patients in the lidocaine group favored the same spray for their next intubations, while 65% of the placebo group did (p = 0.009). In addition, there was more physicians' satisfaction in the lidocaine group as measured by 5-point Likert scale (p=0.041). Likewise, 61% of the physicians favored lidocaine spray compared to 34.5% of the placebo spray (p=0.038). Degree of difficulty, duration of intubation, number of attempts and success rates of NG intubations were as well similar in both groups. No complications were found in the present study. CONCLUSION: 10% lidocaine spray plus 2% lidocaine jelly lubrication was more effective in relieving patients' pain, discomfort, and resulted in higher physicians' satisfaction. There were also no additional side effects as compared to 2% lidocaine jelly lubrication alone. Therefore, it should be recommended for routine application.