The clinical toxicology of ketamine.

INTRODUCTION: Ketamine is a pharmaceutical drug possessing both analgesic and anaesthetic properties. As an anaesthetic, it induces anaesthesia by producing analgesia with a state of altered consciousness while maintaining airway tone, respiratory drive, and hemodynamic stability. At lower doses, it has psychoactive properties and has gained popularity as a recreational drug. OBJECTIVES: To review the epidemiology, mechanisms of toxicity, pharmacokinetics, clinical features, diagnosis and management of ketamine toxicity. METHODS: Both OVID MEDLINE (January 1950-April 2023) and Web of Science (1900-April 2023) databases were searched using the term "ketamine" in combination with the keywords "pharmacokinetics", "kinetics", "poisoning", "poison", "toxicity", "ingestion", "adverse effects", "overdose", and "intoxication". Furthermore, bibliographies of identified articles were screened for additional relevant studies. These searches produced 5,268 non-duplicate citations; 185 articles (case reports, case series, pharmacokinetic studies, animal studies pertinent to pharmacology, and reviews) were considered relevant. Those excluded were other animal investigations, therapeutic human clinical investigations, commentaries, editorials, cases with no clinical relevance and post-mortem investigations. EPIDEMIOLOGY: Following its introduction into medical practice in the early 1970s, ketamine has become a popular recreational drug. Its use has become associated with the dance culture, electronic and dubstep dance events. MECHANISM OF ACTION: Ketamine acts primarily as a non-competitive antagonist on the glutamate N-methyl-D-aspartate receptor, causing the loss of responsiveness that is associated with clinical ketamine dissociative anaesthesia. PHARMACOKINETICS: Absorption of ketamine is rapid though the rate of uptake and bioavailability is determined by the route of exposure. Ketamine is metabolized extensively in the liver. Initially, both isomers are metabolized to their major active metabolite, norketamine, by CYP2B6, CYP3A4 and CYP2C9 isoforms. The hydroxylation of the cyclohexan-1-one ring of norketamine to the three positional isomers of hydroxynorketamine occurs by CYP2B6 and CYP2A6. The dehydronorketamine metabolite occurs either by direct dehydrogenation from norketamine via CYP2B6 metabolism or non-enzymatic dehydration of hydroxynorketamine. Norketamine, the dehydronorketamine isomers, and hydroxynorketamine have pharmacological activity. The elimination of ketamine is primarily by the kidneys, though unchanged ketamine accounts for only a small percentage in the urine. The half-life of ketamine in humans is between 1.5 and 5 h. CLINICAL FEATURES: Acute adverse effects following recreational use are diverse and can include impaired consciousness, dizziness, irrational behaviour, hallucinations, abdominal pain and vomiting. Chronic use can result in impaired verbal information processing, cystitis and cholangiopathy. DIAGNOSIS: The diagnosis of acute ketamine intoxication is typically made on the basis of the patient's history, clinical features, such as vomiting, sialorrhea, or laryngospasm, along with neuropsychiatric features. Chronic effects of ketamine toxicity can result in cholangiopathy and cystitis, which can be confirmed by endoscopic retrograde cholangiopancreatography and cystoscopy, respectively. MANAGEMENT: Treatment of acute clinical toxicity is predominantly supportive with empiric management of specific adverse effects. Benzodiazepines are recommended as initial treatment to reduce agitation, excess neuromuscular activity and blood pressure. Management of cystitis is multidisciplinary and multi-tiered, following a stepwise approach of pharmacotherapy and surgery. Management of cholangiopathy may require pain management and, where necessary, biliary stenting to alleviate obstructions. Chronic effects of ketamine toxicity are typically reversible, with management focusing on abstinence. CONCLUSIONS: Ketamine is a dissociative drug employed predominantly in emergency medicine; it has also become popular as a recreational drug. Its recreational use can result in acute neuropsychiatric effects, whereas chronic use can result in cystitis and cholangiopathy.

Paratubal Cystectomy in a Pregnant Woman Using the Single-Incision Laparoscopic Surgery (SILS) Technique.

Introduction: The proliferation of prenatal ultrasound has enhanced the detection of adnexal masses during pregnancy. The presentation necessitates a clear approach to investigation and treatment that balances both maternal and fetal risk. Laparoscopy is a safe approach to surgical management in the pregnant patient, and SILS may contribute to minimising perioperative complications. Case Presentation. We present the case of a 21-year-old female in her second trimester of pregnancy presenting with a large 20 cm right adnexal cyst. We proceeded with laparoscopic cystectomy via the SILS technique. There were no intraoperative complications, and she recovered well postoperatively. Conclusion: Laparoscopic resection of adnexal lesions is safe during pregnancy and should be favoured over the open approach. SILS minimises incision sites and has potential for reduction in perioperative morbidity.

Three Cases of Severe Placental Abruption as a First Symptom of Preeclampsia.

Placental abruption is often referred to in the literature as a complication of preeclampsia. We report 3 recent cases where the first symptom of preeclampsia was placental abruption. All women were previously healthy and in their first ongoing pregnancy. All had been seen by obstetricians for regular pregnancy checkups. None of the patients had a preexisting diagnosis of preeclampsia. Only one of the patients had risk factors for preeclampsia and occasional hypertension. In all cases, laboratory signs of preeclampsia were abnormal intra- or immediately postpartum. One fetus died in utero, and the other two pregnancies fortunately showed a favourable outcome.

Oral Riboflavin to Assess Ureteral Patency During Cystoscopy: A Randomized Clinical Trial.

OBJECTIVE: To evaluate whether oral riboflavin is more effective than placebo as a marker of ureteric patency at cystoscopy. METHODS: Patients scheduled for gynecologic surgery where cystoscopy was a planned component of the procedure were randomized to receive riboflavin 400 mg or placebo orally the night before surgery. During cystoscopy, the operating surgeon visualized ureteric jets and video recorded the cystoscopy portion of the procedure. The primary outcome was to determine whether orally administered riboflavin produced stronger yellow color of urine seen on cystoscopy than placebo on a 3-point scale. Secondary outcomes were to assess whether riboflavin administration improved ease of identifying ureteric jets (5-point scale) and whether a greater proportion of patients had both ureteric jets visualized with riboflavin compared with placebo. A sample size of 33 per group was planned. RESULTS: From June 28, 2017, to February 19, 2018, 72 women were screened and 66 were randomized, with 33 patients in each study group. The groups were similar in age, weight, body mass index, and ethnicity. The patients in the riboflavin group had significant increase of yellow-colored urine as rated by the operating surgeon, with a median of 2 compared with 1 on a 3-point scale (P<.001). The ureteral jets were more easily visualized in the riboflavin group as rated by the operating surgeon, with a median of 5 compared with 4 on a 5-point scale (P<.013). Bilateral ureteral patency was confirmed in 30 of 33 women (91%) in the riboflavin group and in 28 of 33 women (85%) in the placebo group (P=.71). CONCLUSIONS: The administration of riboflavin before gynecologic surgery improves the ease of visualizing the ureteric jets by inducing yellow coloration of the urine. CLINICAL TRIALS REGISTRATION: Australian New Zealand Clinical Trials Registry, 12616001367437.

Primary endometrial uterine Burkitt lymphoma in a 65-year-old woman.

•Primary Burkitt lymphoma of the uterus is a rare disease.•Differential of postmenopausal bleeding and night sweats should include lymphoma.•Outpatient endometrial sampling expedites diagnosis of endometrial malignancy.