For many years it has been customary to derive blood alcohol concentrations from the analysis of urine, and despite the fact that the accuracy of such derivations has often been questioned British courts have been content to accept them as evidence in prosecutions for drunken driving, presumably on the grounds that such evidence was merely confirmatory and not vital. However, with the impending change in the law which will make it an offence to drive with more than a stated amount of alcohol in the blood, the reliability of the method of determining blood alcohol concentrations assumes much greater significance, particularly as the use of urine analysis has not been excluded (Ministry of Transport, 1965).In the interpretation of blood levels derived from urine analysis two problems arise. The first concerns the accuracy of the analytical method used to measure the alcohol concentration in urine, and the second is related to the choice of the conversion factor for the derivation of blood level. In the case of urine analysis the accuracy of the Nickolls modification of the Cavett technique is well established, but the method is tedious, time-consuming, and critically dependent on the technical skill of the operator. Gas chromatography is free from these disadvantages (Chandela and Janaik, 1960), and it is claimed that when used in combination with an internal standard and an integrator the alcohol content of a minute sample of either blood or urine can be measured accurately within five minutes (Curry, Walker, and Simpson, 1966). One purpose of the investigation to be described was to determine the accuracy of the gas chromatographic method.In the case of the conversion factor no unanimity of opinion exists about the correct choice, and it was the second purpose of the investigation to examine the validity of the conversion factor of 1.33 recommended in the Report of a Special Committee of the British Medical Association (1965 The times at which the samples were obtained were noted and the samples themselves were divided into three equal parts for distribution to the suspect, the police laboratory, and this department. Anonymity was preserved by the designation of a reference number. Initially the samples were analysed both by the Nickolls (1960) modification of the Cavett technique and by the gas chromatographic technique described in detail by Curry et al. (1966) but modified to use a Poropak Q porous polymer bead column instead of a polyethylene glycol 400 column. The Poropak column offers the advantage of a much lower column bleed and elutes the water peak first after 30 seconds followed by ethanol at 1.5 minutes and n-propanol at 3.5 minutes. With polyethylene glycol, unless the column is carefully conditioned with water before use, a tailing water peak is produced which prolongs the analysis. Latterly the samples were analysed by the gas chromatographic method alone.For chromatographic analysis the blood or urine sample was diluted with ten times its volume of an aqueous solution containing 24 mg. of propra...

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Introduction Emerging off-label medical uses of ketamine for the treatment of persistent conditions such as depression and chronic pain often require repeated administration. Cases reported by other countries suggest that long-term and repeated exposure to ketamine may be associated with several risks, including but not limited to hepatobiliary damage. Objective We aimed (1) to characterize the association between repeated administration of ketamine for off-label medical use and hepatobiliary events and (2) to describe recent trends in the use of ketamine across different clinical settings. Methods We conducted a retrospective case series analysis, utilizing reports identified from the US Food and Drug Administration Adverse Event Reporting System database as well as the medical literature. We included all cases reported through July 2018 describing both repeated exposure to ketamine in a hospital or ambulatory setting and a hepatobiliary adverse event. We excluded cases describing ketamine abuse. We identified adverse hepatobiliary events using the Medical Dictionary for Regulatory Activities (MedDRA ® ) and summarized various case characteristics including: patient demographics, route of ketamine administration, dose, time to onset of event, type of event, and pre-existing risk factors for hepatobiliary disease. To assess trends in the demand for ketamine, we used IQVIA, National Sales Perspectives™ to provide the nationally estimated number of vials sold for ketamine from the manufacturer to all US channels of distribution from 2013 through 2017. Results We identified 14 unique cases that met selection criteria with 21 hepatobiliary adverse events including liver enzyme elevation in all cases, biliary dilation with liver cirrhosis ( n = 1), biliary dilation with cholangitis ( n = 1), and pericholeductal fibrosis ( n = 1). Most cases received ketamine for the treatment of complex regional pain syndrome or chronic pain. In cases with a reported time to onset, the majority of events occurred within 4 days. The nationally estimated number of ketamine vials sold in the USA from manufacturers to various channels of distribution increased from 1.2 million in 2013 to 2.1 million in 2017. Conclusions We report an association between repeated or continuous administration of ketamine and hepatobiliary adverse events. Increased awareness among clinicians may mitigate these adverse outcomes, especially in the context of growing ketamine sales. Supplementary Information The online version contains supplementary material available at 10.1007/s40264-021-01120-9.