Update in perioperative medicine: practice changing evidence published in 2016.

This summary reviews 18 key articles published in 2016 which have significant practice implications for the perioperative medical care of surgical patients. Due to the multi-disciplinary nature of the practice of perioperative medicine, important new evidence is published in journals representing a variety of medical and surgical specialties. Keeping current with the evidence that drives best practice in perioperative medicine is therefore challenging. We set out to identify, critically review, and summarize key evidence which has the most potential for practice change. We integrated the new evidence into the existing body of medical knowledge and identified practical implications for real world patient care. The articles address issues related to anticoagulation, transfusion threshold, immunosuppressive medications, postoperative delirium, myocardial injury after noncardiac surgery, postoperative pain management, perioperative management of antihypertensives, perioperative fasting, and perioperative diabetic control.

Microwave-assisted on-spot derivatization for gas chromatography-mass spectrometry based determination of polar low molecular weight compounds in dried blood spots.

Dried blood spot (DBS) sampling and analysis is increasingly being applied in bioanalysis. Although the use of DBS has many advantages, it is also associated with some challenges. E.g. given the limited amount of available material, highly sensitive detection techniques are often required to attain sufficient sensitivity. In gas chromatography coupled to mass spectrometry (GC-MS), derivatization can be helpful to achieve adequate sensitivity. Because this additional sample preparation step is considered as time-consuming, we introduce a new derivatization procedure, i.e. "microwave-assisted on-spot derivatization", to minimize sample preparation of DBS. In this approach the derivatization reagents are directly applied onto the DBS and derivatization takes place in a microwave instead of via conventional heating. In this manuscript we evaluated the applicability of this new concept of derivatization for the determination of two polar low molecular weight molecules, gamma-hydroxybutyric acid (GHB) and gabapentin, in DBS using a standard GC-MS configuration. The method was successfully validated for both compounds, with imprecision and bias values within acceptance criteria (<20% at LLOQ, <15% at 3 other QC levels). Calibration lines were linear over the 10-100µg/mL and 1-30µg/mL range for GHB and gabapentin, respectively. Stability studies revealed no significant decrease of gabapentin and GHB in DBS upon storage at room temperature for at least 84 days. Furthermore, DBS-specific parameters, including hematocrit and volume spotted, were evaluated. As demonstrated by the analysis of GHB and gabapentin positive samples, "microwave-assisted on-spot derivatization" proved to be reliable, fast and applicable in routine toxicology. Moreover, other polar low molecular weight compounds of interest in clinical and/or forensic toxicology, including vigabatrin, beta-hydroxybutyric acid, propylene glycol, diethylene glycol, 1,4-butanediol and 1,2-butanediol, can also be detected using this method.

Urine drug testing of chronic pain patients. IV. prevalence of gabapentin and pregabalin.

Gabapentin and pregabalin are well established for the treatment of seizures and neuropathic pain. Both drugs are eliminated primarily unchanged by renal excretion. As part of an ongoing research program to improve and expand drug testing methods for compliance monitoring of pain patients, the prevalence and concentrations of gabapentin and pregabalin in urine specimens from chronic pain patients were determined by a validated liquid chromatography-tandem mass spectrometry assay. The study was approved by an Institutional Review Board. A total of 57,542 urine specimens from 231 pain clinics located in 19 states were analyzed over the period of November 24, 2009, through May 2010. The limit of quantitation (LOQ) and upper LOQ of the assays for both drugs were 2.5 and 1000 µg/mL, respectively. Gabapentin was identified in 7013 specimens (12.2% prevalence), and pregabalin was identified in 4799 patients (8.3% prevalence). Generally, gabapentin concentrations were more than twofold higher than pregabalin, consistent with their relative potencies. Interestingly, both drugs were found in specimens from 249 patients, likely representing switching of prescriptions by the prescriber.

Effects of genetic variation in the novel organic cation transporter, OCTN1, on the renal clearance of gabapentin.

Gabapentin is an anticonvulsant that is widely prescribed for epilepsy and other neuropathic disorders. The pharmacokinetics, particularly the absorption and renal elimination, of gabapentin appear to involve membrane transporters. In this study, we tested the hypothesis that organic cation transporter 1 (OCTN1), a multispecific transporter expressed at the apical membrane in intestine and kidney, plays a role in gabapentin pharmacokinetics and that the common variant of OCTN1, OCTN1-L503F, contributes to variation in the pharmacokinetics of the drug. We observed that OCTN1 facilitates the Na+-independent transport of gabapentin, and that the OCTN1-L503F variant is deficient in gabapentin transport activity in stably transfected HEK-293 cells (fourfold enhanced uptake of gabapentin by OCTN1-503L vs twofold enhanced uptake by OCTN1-L503F, compared to mock-transfected cells). In clinical studies, we found that in subjects homozygous for the L503F variant, gabapentin renal clearance (CL(R)) approximates the glomerular filtration rate (mean+/-SE: 110+/-12 ml/min, n=9), whereas in subjects homozygous for the reference allele, gabapentin undergoes net secretion in the kidney (141+/-7.8 ml/min, n=11, P<0.05). Creatinine clearance and OCTN1 genotype accounted for 56% of the variation in CL(R) and were the only significant predictors of CL(R) (P<0.05). Importantly, OCTN1 genotype was the only significant predictor of net secretion of gabapentin (P<0.008). Oral bioavailability of gabapentin was not affected by OCTN1 genotype. We conclude that OCTN1 contributes to active tubular secretion of gabapentin, and that this effect may be diminished or absent in individuals carrying the OCTN1-L503F polymorphism. These results provide clinical evidence of the role of genetic variation in renal drug transporters in active drug secretion in vivo.