Development of two fully automated quick, easy, cheap, effective, rugged, and safe pretreatment methods for the extraction of psychotropic drugs from whole blood samples.

Quick, easy, cheap, effective, rugged, and safe extraction strategies are becoming increasingly adopted in various analytical fields to determine drugs in biological specimens. In the present study, we developed two fully automated quick, easy, cheap, effective, rugged, and safe extraction methods based on acetonitrile salting-out assisted liquid-liquid extraction (method 1) and acetonitrile salting-out assisted liquid-liquid extraction followed by dispersive solid-phase extraction (method 2) using a commercially available automated liquid-liquid extraction system. We applied these methods to the extraction of 14 psychotropic drugs (11 benzodiazepines and carbamazepine, quetiapine, and zolpidem) from whole blood samples. Both methods prior to liquid chromatography-tandem mass spectrometry analysis exhibited high linearity of calibration curves (correlation coefficients, > 0.9997), ppt level detection sensitivities, and satisfactory precisions (< 8.6% relative standard deviation), accuracies (within ± 16% relative error), and matrix effects (81-111%). Method 1 provided higher recovery rates (80-91%) than method 2 (72-86%), whereas method 2 provided higher detection sensitivities (limits of detection, 0.003-0.094 ng/mL) than method 1 (0.025-0.47 ng/mL) owing to the effectiveness of its dispersive solid-phase extraction cleanup step. These fully automated extraction methods realize reliable, labor-saving, user-friendly, and hygienic extraction of target analytes from whole blood samples.

A Case of Paraplegia Treated with Cerebrospinal Fluid Drainage and Permissive Hypertension after Graft Replacement of the Ascending Aorta and the Total Aortic Arch for Acute Aortic Dissection Stanford Type A.

Paraplegia after an operation for acute aortic dissection Stanford type A (AADA) is fairly uncommon, and there is no consensus about optimal treatment. We present a case in which cerebrospinal fluid drainage (CSFD) and permissive hypertension were used for treatment of paraplegia. When the patient showed complete bilateral paraplegia after operation for AADA, we immediately began CSFD and maintained mean arterial blood pressure at over 90 mmHg. His neurological deficit gradually recovered, and he was eventually able to walk without support. The combination of CSFD and permissive hypertension could be a first-line emergent treatment for postoperative paraplegia after AADA surgery.

Regioisomer Differentiation of Ring-Substituted Chloromethcathinones and Bromomethcathinones Using Gas Chromatography/Electron Ionization-Triple Quadrupole Energy-Resolved Mass Spectrometry.

Positional isomers o-, m-, and p-chloromethcathinones (CMCs) and m- and p-bromomethcathinones (BMCs) were effectively differentiated using gas chromatography (GC) and energy-resolved mass spectrometry (ERMS) analyses. GC demonstrated that the free bases of CMC and BMC isomers were simultaneously baseline-separated at a slow column heating rate (5 °C/min) using a conventional low-polar capillary column. ERMS showed that the trifluoroacetyl derivatives of the positional isomers differed in mass spectral abundances of both halophenyl and halobenzoyl cations. Moreover, the logarithmic plots of the abundance ratio of the two cations as a function of the collision energy (CE) exhibited marked differences among the isomers at each CE, following the order of ortho < para < meta for CMCs and para < meta for BMCs. The performed theoretical calculations of dissociation energy agreed well with the ERMS measurements. The GC and ERMS methodologies enabled unambiguous and reliable differentiation of CMC and BMC isomers. The developed approach is expected to significantly contribute to the accurate structural identification of new psychoactive substances in forensic, toxicological, and clinical fields.

A fast paraquat quantitation method in human serum using probe electrospray ionization-tandem mass spectrometry for emergency settings.

INTRODUCTION: Paraquat (PQ) is one of the most toxic herbicides to humans. However, it is still in use in many countries, including Japan, and many incidents, such as homicides, intentional ingestions, and occupational accidents, have been reported thus far. In PQ poisoning cases, it is possible to predict severity and prognosis using nomograms. Therefore, if the serum PQ level is determined immediately, a treatment plan can be rapidly established. However, most known analytical methods are time-consuming and therefore hardly ever contribute to patient treatment. METHODS: We developed a new method for PQ quantitation in serum by combining a probe electrospray ionization technique with mass spectrometry. This method requires virtually no serum pretreatment and can yield quantitation values in 18 s. RESULTS: We applied the proposed method to samples from real poisoning cases and compared the results with those obtained via liquid-chromatography-tandem mass spectrometry, revealing the absence of any significant differences at the 5% significance level (t(8) = 1.000, p > .05). The limits of detection and quantitation were 0.004 and 0.015 µg/L, respectively, and the calibration curve exhibited good linearity over the concentration range of 0.015-4.0 µg/mL (r2 = 0.998). DISCUSSION: As the proposed method is fast and easy to perform, it should be useful in emergency medical settings.

Application of probe electrospray ionization-tandem mass spectrometry to ultra-rapid determination of glufosinate and glyphosate in human serum.

Glufosinate and glyphosate, which are non-selective herbicides that include an amino acid moiety in their structures, are frequently used worldwide to control unwanted vegetation. Unfortunately, these readily available herbicides are also used by people to commit suicide, and thus represent important chemicals of interest in the fields of clinical medicine and forensics. Because of the high water solubility of these herbicides, most analytical methods for their detection require a derivatization step, which results in longer analysis times. Therefore, derivatization-based methods do not currently contribute to judgements on treatment decisions in emergency medicine. In this study, we addressed this limiting factor by developing an ultra-rapid and simple analytical technique using a combination of probe electrospray ionization (PESI) and tandem mass spectrometry (MS/MS), which gives quantitative results within 0.3 min. Herbicide standards were added to human serum that was then subjected to analysis (N = 5 per concentration). The analysis was repeated daily over eight consecutive days. The limit of detection (LOD) was 0.59 µg/mL for glufosinate and 0.20 µg/mL for glyphosate. The limit of quantitation (LOQ), i.e., the lowest point on the calibration curves, was 1.56 µg/mL for both the herbicides. The matrix effects were observed at three different concentrations (between 95.7%-104% for glufosinate, and between 90.7%-95.7% for glyphosate). When applied to samples taken from actual poisoning cases (six samples for each herbicide), the present method gave almost the same quantitative values as those obtained by conventional high-performance liquid chromatography with fluorescence detection. Thus, we believe that PESI-MS/MS could emerge as a rapid diagnosis method in the clinical emergency field.

[Tooth Mobility Evaluation -A Comparison with Dental Assessment-].

BACKGROUND: Patients with mobile teeth are at an increased risk of tooth injury related to tracheal intu- bation. Although the presence/absence of mobile teeth is confirmed through interviews during preoperative visits, patients are frequently unaware of the presence of such teeth. In our facility, dental consultation is pro- vided for all patients undergoing thoracoscopically- assisted surgery as part of the management of oral hygiene. This study examined the presence/absence of mobile teeth reported by patients during preoperative visits and those identified on dental consultation, focus- ing on the inconsistency between them. METHODS: Patients who had undergone thoraco- scopically-assisted surgery in our facility between Janu- ary and October 2014 were retrospectively studied. Tooth mobility was evaluated using the Miller index. RESULTS: Among the 76 (46 males and 30 females) patients aged 36 to 88 (mean: 67.8), mobile teeth were identified on dental consultation in 13 and reported during preoperative visits by 8. CONCLUSIONS: Based on this findings, it may be nec- essary to pay sufficient attention when inserting tubes even when mobile teeth have not been reported by patients during preoperative visits.

[General Anesthesia for the Thoracoscopic Lung Resection Surgery in 12 Very Elderly Patients above 85 Years of Age].

We investigated perioperative management and clinical outcome of 12 patients who were 85 years old or older and received video-assisted thoracic surgery under general anesthesia. Although all the patients had preoperative respiratory complications or cardiovascular complications, they were discharged without any additional respiratory assistance such as home oxygen therapy. Our observation suggests that it is important to evaluate the indication of anesthesia from their daily activities and pulmonary function test even if they are oldest-old. If the patient demonstrates good physical function, he or she should not be excluded from anesthesia.

[Perioperative Management of Emergency Operation for a Patient with Carcinoid Syndrome].

We report a case of carcinoid syndrome requiring an emergency operation for an upper gastrointestinal perforation. A 46-year-old man had undergone left lower lobectomy for a lung carcinoid tumor seven years previously, and liver metastasis was found five years previously. He developed cutaneous flushing and watery diarrhea, and was diagnosed with carcinoid syndrome one year previously. Although he was treated with octreotid, his symptoms became worse and he was admitted to our hospital. During the hospital stay, he underwent an emergency operation for an upper gastrointestinal perforation. Before the operation, hemodynamics were unstable. Anesthesia was induced with sevoflurane and propofol, and maintained with sevoflurane and remifentanil. Only vasopressin was used for the treatment of hypotension. Landiolol was used for perioperative tachyarrythmia. During anesthesia, there was no severe hypotension or hypertension. After the operation, he was managed with intubation in the ICU. Octreotid was administered again for the carcinoid syndrome. Vasopressin was necessary for the treatment of hypotension in the ICU. After improvement of hemodynamics, extubation was performed on the 3rd ICU day and he was discharged from the ICU on the 4th ICU day. In conclusion, we were able to perform good perioperative management of carcinoid syndrome accompanied by hemodynamic instability.

Reliability of central venous pressure to assess left ventricular preload for fluid resuscitation in patients with septic shock.

BACKGROUND: Initial fluid resuscitation is an important hemodynamic therapy in patients with septic shock. The Surviving Sepsis Campaign Guidelines recommend fluid resuscitation with volume loading according to central venous pressure (CVP). However, patients with septic shock often develop a transient decrease in cardiac function; thus, it may be inappropriate to use CVP as a reliable marker for fluid management. METHODS: We evaluated 40 adult patients with septic shock secondary to intra-abdominal infection who received active treatment and were monitored using transthoracic echocardiography (TTE) and CVP for 2 days after admission to our intensive care unit (ICU). We measured left ventricular end-diastolic diameter (LVEDD), left atrial diameter (LAD), and the pressure gradient of tricuspid regurgitation (TR∆P). The shock status was treated with volume loading and inotrope/vasopressor administration according to the TTE findings. We assessed left ventricular fractional shortening (LVFS) as an index of left ventricular contractility and TR∆P as an index of right ventricular afterload and then examined the correlation between CVP and LVEDD/LAD/TR∆P. RESULTS: LVFS decreased to ≤30% in 42.5% and 27.5% of patients with septic shock, and severe left ventricular dysfunction with LVFS ≤20% developed in 12.5% and 15.0% of patients on the first and second ICU days, respectively, despite the use of inotropes/vasopressors. Mild pulmonary hypertension as indicated by TR∆P ≥30 mmHg was present in 27.5% and 30.0% of patients on their first and second ICU days, respectively. There was no significant correlation between CVP and LVEDD/LAD/TR∆P. The hospital mortality rate in this study was 10.0%, although the predicted mortality based on the Acute Physiology and Chronic Health Evaluation II score was 58.7%. CONCLUSIONS: Our results suggest that CVP is not a reliable marker of left ventricular preload for fluid management during the initial phase of septic shock. Assessment of left ventricular preload, right ventricular overload, and left ventricular contractility using TTE seems to be more informative than the measurement of CVP for fluid resuscitation since some patients developed left ventricular dysfunction and/or right ventricular overload.

[A case of rocuronium-induced anaphylactic shock successfully treated with sugammadex].

We report a case of a 19-year-old male with rocuronium-induced anaphylactic shock. He was scheduled for endoscopic sinus surgery for chronic sinusitis under general anesthesia. Induction of anesthesia was done with fentanyl, propofol and sevoflurane. Just after administration of rocuronium, he developed tachycardia with extended exanthema on the face, anterior chest wall and abdomen. He was difficult to ventilate manually with mask and then intubated without difficulty. The carotid arterial pulse was not palpable and adrenaline was given intermittently to maintain blood pressure. Although the systolic blood pressure increased to 80 mmHg, hemodynamics was unstable with adrenaline. Sugammadex was then given and the blood pressure became stable without adrenaline. Exanthema also disappeared gradually. He was then transferred to ICU and extubated without any sequela. The plasma beta-tryptase increased to 46 microg x l(-1) during the shock state and returned to 14.1 microg x l(-1) 8 hrs after the event. The blood hemoglobin level also increased to 21.3 g x dl(-1) during the shock state and returned to 17.2 g x dl(-1) during the recovery phase. The laboratory data showed a marked increase in vascular permeability caused by rocuronium-induced anaphylactic shock.