Use of Early Ketamine Sedation and Association With Clinical and Cost Outcomes Among Mechanically Ventilated Patients With COVID-19: A Retrospective Cohort Study.

OBJECTIVES: To describe the utilization of early ketamine use among patients mechanically ventilated for COVID-19, and examine associations with in-hospital mortality and other clinical outcomes. DESIGN: Retrospective cohort study. SETTING: Six hundred ten hospitals contributing data to the Premier Healthcare Database between April 2020 and June 2021. PATIENTS: Adults with COVID-19 and greater than or equal to 2 consecutive days of mechanical ventilation within 5 days of hospitalization. INTERVENTION: The exposures were early ketamine use initiated within 2 days of intubation and continued for greater than 1 day. MEASUREMENTS: Primary was hospital mortality. Secondary outcomes included length of stay (LOS) in the hospital and ICUs, ventilator days, vasopressor days, renal replacement therapy (RRT), and total hospital cost. The propensity score matching analysis was used to adjust for confounders. MAIN RESULTS: Among 42,954 patients, 1,423 (3.3%) were exposed to early ketamine use. After propensity score matching including 1,390 patients in each group, recipients of ketamine infusions were associated with higher hospital mortality (52.5% vs. 45.9%, risk ratio: 1.14, [1.06-1.23]), longer median ICU stay (13 vs. 12 d, mean ratio [MR]: 1.15 [1.08-1.23]), and longer ventilator days (12 vs. 11 d, MR: 1.19 [1.12-1.27]). There were no associations for hospital LOS (17 [10-27] vs. 17 [9-28], MR: 1.05 [0.99-1.12]), vasopressor days (4 vs. 4, MR: 1.04 [0.95-1.14]), and RRT (22.9% vs. 21.7%, RR: 1.05 [0.92-1.21]). Total hospital cost was higher (median $72,481 vs. $65,584, MR: 1.11 [1.05-1.19]). CONCLUSIONS: In a diverse sample of U.S. hospitals, about one in 30 patients mechanically ventilated with COVID-19 received ketamine infusions. Early ketamine may have an association with higher hospital mortality, increased total cost, ICU stay, and ventilator days, but no associations for hospital LOS, vasopressor days, and RRT. However, confounding by the severity of illness might occur due to higher extracorporeal membrane oxygenation and RRT use in the ketamine group. Further randomized trials are needed to better understand the role of ketamine infusions in the management of critically ill patients.

Benefit-Risk Assessment of Esketamine Nasal Spray vs. Placebo in Treatment-Resistant Depression.

This post hoc analysis assessed the benefit-risk profile of esketamine nasal spray + oral antidepressant (AD) induction and maintenance treatment in patients with treatment-resistant depression (TRD). The Benefit-Risk Action Team framework was utilized to assess the benefit-risk profile using data from three induction studies and one maintenance study. Benefits were proportion of remitters or responders in induction studies and proportion of stable remitters or stable responders who remained relapse-free in the maintenance study. Risks were death, suicidal ideation, most common adverse events (AEs), and potential long-term risks. Per 100 patients on esketamine + AD vs. AD + placebo in induction therapy, 5-21 additional patients would remit and 14-17 additional patients would respond. In maintenance therapy, 19-32 fewer relapses would occur with esketamine. In both cases, there was little difference in serious or severe common AEs (primarily dissociation, vertigo, and dizziness). These findings support a positive benefit-risk balance for esketamine + AD as induction and maintenance treatment in patients with TRD.

Esketamina intranasal en depresión mayor severa resistente / Intranasal esketamine in depression major severe resistant

CONTEXTO: El trastorno depresivo mayor (TDM) es un trastorno del estado de ánimo cuya prevalencia em Argentina se ha estimado en un 8,7%.1 Se caracteriza por presentar sentimientos de tristeza y desesperanza, cambios en el apetito y peso, alteraciones del sueño, fatiga, dificultad para concentrarse y tomar decisiones e ideación y/o intento de suicidio. Estos síntomas llevan a una disfunción social y laboral siendo una de las principales causas de discapacidad a nivel mundial. Según sus características clínicas se clasifica en leve, moderada o severa. El TDM severo se define por presentar ocho de los nueve síntomas que definen a la depresión mayor según el Manual de Diagnóstico Diferencial 5° edición (DSM-5, su sigla en inglés Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition).2 Estos pacientes reportan ideas suicidas, presentan deterioro evidente de la calidad de vida, deterioro socio-ocupacional y mayor probabilidade de desarrollar características psicóticas y catatónicas. Deben ser remitidos a un psiquiatra para su tratamiento y frecuentemente requieren hospitalización. Un tercio de los pacientes con TDM son resistentes al tratamiento considerándose así cuando no responden satisfactoriamente a dos esquemas (concomitantes o sucesivos) con antidepresivos orales a dosis y duración adecuada. TECNOLOGÍA: La esketamina, enantiómero de la ketamina, se postula como una alternativa de tratamiento en TDM severo resistente. Es un antagonista no selectivo y no competitivo del receptor NMDA, modula la transmisión glutaminérgica y cuenta con la ventaja de ser administrada por vía intranasal lo que permite una opción no invasiva y de rápida absorción. Se propone su administración dos veces por semana (día uno: 56 mg Dosis subsiguientes 56 u 84 mg) durante el primer mes, luego una vez por semana hasta el segundo mes y posteriormente administrar cada una a dos semanas. Los pacientes se podrían auto administrar el fármaco en el consultorio bajo supervisión médica. La Administración de Alimentos y Medicamentos de los Estados Unidos (FDA; su sigla del inglés Food And Drug Administration) aprobó en 2019 el uso solamente disponible a través de un sistema de distribución restringida. OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura del uso de esketamina intranasal asociado a tratamiento antidepresivo oral para trastorno depresivo mayor severo resistente en pacientes adultos. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas, en buscadores genéricos de internet, y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas, guías de práctica clínica (GPC) y políticas de cobertura de diferentes sistemas de salud. RESULTADOS: Se incluyeron cuatro ECAs, dos RS, cuatro GPC, cuatro evaluaciones económicas y 15 informes de políticas de cobertura de tecnología para indicación. CONCLUSIONES: Evidencia de baja calidad sugiere que esketamina intranasal asociada al ajuste de antidepressivos orales mejoraría de manera considerable los síntomas depresivos hasta los 28 días, en comparación con placebo asociado al ajuste de antidepresivos orales. La evidencia en relación a la eficacia para retrasar los episodios de recaída a más largo plazo no permite sacar conclusiones al respecto. Asimismo, se observa una tendencia a presentar mayor número de episodios de recaída luego de la suspensión de la misma. La evidencia en relación a la disminución de los síntomas relacionados al suicidio no permite sacar conclusiones al respecto. Se observó que el uso de esketamina se asoció a mayor abandono por intolerancia en comparación con placebo. Como limitante en todos aquellos ensayos clínicos contra placebo se menciona que mantener el cegamiento fue dificultoso dado los síntomas disociativos asociados a esketamina, además de otros riesgos de sesgos que aumentan la incertidumbre. Evidencia de baja calidad sugiere que esketamina intranasal asociada a antidepresivos orales podría mejorar los síntomas depresivos, en comparación con antipsicóticos de segunda generación asociados a antidepresivos orales. No se encontraron estudios que comparen el uso de esketamina intranasal versus terapia electroconvulsiva en pacientes con depresión mayor resistente al tratamiento. Los financiadores públicos de la salud Latinoamericanos relevados no mencionan o no brindan cobertura al uso de esketamina intranasal. Las evaluaciones de tecnologías sanitarias relevadas recomiendan no incluir esta tecnología debido a la incertidumbre sobre la eficacia y a no considerarla costo-efectiva. De los países de altos ingresos relevados Escocia, Francia y Estados Unidos brindan cobertura en la indicación evaluada. Las principales guías de práctica clínica se realizaron antes de la aprobación de comercialización por las principales agencias regulatorias. Un consenso de expertos europeo sugiere su uso como opción en conjunto con inhibidores de la recaptación de serotonina o inhibidores de la recaptación de serotonina y norepinefrina. En Argentina, el consenso argentino sobre el diagnóstico y tratamiento del trastorno depresivo mayor resistente al tratamento recomienda el uso de esketamina intranasal como una de las opciones de primera línea. Se desconoce la costo-efectividad de la esketamina intranasal en la depresión mayor en la Argentina, sin embargo, estudios realizados en países de altos ingresos (Estados Unidos y Reino Unido) concluyeron que no era una tecnología costo-efectiva.

Assessment of Relationship of Ketamine Dose With Magnetic Resonance Spectroscopy of Glx and GABA Responses in Adults With Major Depression: A Randomized Clinical Trial.

Importance: A single subanesthetic dose of ketamine produces an antidepressant response in patients with major depressive disorder (MDD) within hours, but the mechanism of antidepressant effect is uncertain. Objective: To evaluate whether ketamine dose and brain glutamate and glutamine (Glx) and γ-aminobutyric acid (GABA) level responses to ketamine are related to antidepressant benefit and adverse effects. Design, Setting, and Participants: This randomized, parallel-group, triple-masked clinical trial included 38 physically healthy, psychotropic medication-free adult outpatients who were in a major depressive episode of MDD but not actively suicidal. The trial was conducted at Columbia University Medical Center. Data were collected from February 2012 to May 2015. Data analysis was conducted from January to March 2020. Intervention: Participants received 1 dose of placebo or ketamine (0.1, 0.2, 0.3, 0.4, or 0.5 mg/kg) intravenously during 40 minutes of a proton magnetic resonance spectroscopy scan that measured ventro-medial prefrontal cortex Glx and GABA levels in 13-minute data frames. Main Outcomes and Measures: Clinical improvement was measured using a 22-item version of the Hamilton Depression Rating Scale (HDRS-22) 24 hours after ketamine was administered. Ketamine and metabolite blood levels were measured after the scan. Results: A total of 38 individuals participated in the study, with a mean (SD) age of 38.6 (11.2) years, 23 (60.5%) women, and 25 (65.8%) White patients. Improvement in HDRS-22 score at 24 hours correlated positively with ketamine dose (t36 = 2.81; P = .008; slope estimate, 19.80 [95% CI, 5.49 to 34.11]) and blood level (t36 = 2.25; P = .03; slope estimate, 0.070 [95% CI, 0.007 to 0.133]). The lower the Glx response, the better the antidepressant response (t33 = -2.400; P = .02; slope estimate, -9.85 [95% CI, -18.2 to -1.50]). Although GABA levels correlated with Glx (t33 = 8.117; P < .001; slope estimate, 0.510 [95% CI, 0.382 to 0.638]), GABA response did not correlate with antidepressant effect. When both ketamine dose and Glx response were included in a mediation analysis model, ketamine dose was no longer associated with antidepressant effect, indicating that Glx response mediated the relationship. Adverse effects were related to blood levels in men only (t5 = 2.606; P = .048; estimated slope, 0.093 [95% CI, 0.001 to 0.186]), but Glx and GABA response were not related to adverse effects. Conclusions and Relevance: In this study, intravenous ketamine dose and blood levels correlated positively with antidepressant response. The Glx response correlated inversely with ketamine dose and with antidepressant effect. Future studies are needed to determine whether the relationship between Glx level and antidepressant effect is due to glutamate or glutamine. Trial Registration: ClinicalTrials.gov Identifier: NCT01558063.

Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression: Assessment of Long-Term Safety in a Phase 3, Open-Label Study (SUSTAIN-2).

OBJECTIVE: To evaluate long-term safety and efficacy of esketamine nasal spray plus a new oral antidepressant (OAD) in patients with treatment-resistant depression (TRD). METHODS: This phase 3, open-label, multicenter, long-term (up to 1 year) study was conducted between October 2015 and October 2017. Patients (≥ 18 years) with TRD (DSM-5 diagnosis of major depressive disorder and nonresponse to ≥ 2 OAD treatments) were enrolled directly or transferred from a short-term study (patients aged ≥ 65 years). Esketamine nasal spray (28-mg, 56-mg, or 84-mg) plus new OAD was administered twice a week in a 4-week induction (IND) phase and weekly or every-other-week for patients who were responders and entered a 48-week optimization/maintenance (OP/MAINT) phase. RESULTS: Of 802 enrolled patients, 86.2% were direct-entry and 13.8% were transferred-entry; 580 (74.5%) of 779 patients who entered the IND phase completed the phase, and 150 (24.9%) of 603 who entered the OP/MAINT phase completed the phase. Common treatment-emergent adverse events (TEAEs) were dizziness (32.9%), dissociation (27.6%), nausea (25.1%), and headache (24.9%). Seventy-six patients (9.5%) discontinued esketamine due to TEAEs. Fifty-five patients (6.9%) experienced serious TEAEs. Most TEAEs occurred on dosing days, were mild or moderate in severity, and resolved on the same day. Two deaths were reported; neither was considered related to esketamine. Cognitive performance generally either improved or remained stable postbaseline. There was no case of interstitial cystitis or respiratory depression. Treatment-emergent dissociative symptoms were transient and generally resolved within 1.5 hours postdose. Montgomery-Åsberg Depression Rating Scale total score decreased during the IND phase, and this reduction persisted during the OP/MAINT phase (mean [SD] change from baseline of respective phase to endpoint: IND, -16.4 [8.76]; OP/MAINT, 0.3 [8.12]). CONCLUSIONS: Long-term esketamine nasal spray plus new OAD therapy had a manageable safety profile, and improvements in depression appeared to be sustained in patients with TRD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02497287.

The Effectiveness and Value of Esketamine for the Management of Treatment-Resistant Depression.

DISCLOSURES: Funding for this summary was contributed by the Laura and John Arnold Foundation, National Institute for Health Care Management, California Health Care Foundation, Blue Cross Blue Shield of Massachusetts, Harvard Pilgrim Healthcare, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, Anthem, AstraZeneca, Allergan, Alnylam, Biogen, Blue Shield of California, Cambia Health Services, CVS Caremark, Editas, Express Scripts, Genentech, GlaxoSmithKline, Harvard Pilgrim Health Care, Health Care Service Corporation, HealthPartners, HealthFirst, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinkrodt Pharmaceuticals, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Agboola, Fazioli, and Pearson are employed by ICER. Touchette reports grants from ICER during the course of this work and personal fees from Monument Analytics, unrelated to this work. Atlas has nothing to disclose.

Dissociating the Clinical Role and Economic Value of Intranasal Esketamine.

DISCLOSURES: No funding supported the writing of this commentary. The author has nothing to disclose.

[How we see the development of clinical trials from the investigators' side?]

This is a discussion paper on research in clinical pharmacology in the field of psychiatry. In addition to other factors the decline in discovery and development of new drugs in the field of psychiatry and the developments and growing complexity in the field of clinical trial technology, including outsourcing and risk based monitoring, reduced the number of young clinical researchers interested in this important field. The challenges posed by the restructuring within the pharmacological industry - including digitalization - should induce changes in the structure and in the processes of clinical pharmacology research and in the training of clinical research staff members. The approval of esketamine nasal spray for treatment resistant depression by the FDA and the results of research with psychedelics call for more education and training in this specific field.

Assessment of Ketamine Adult Anesthetic Doses in Pediatrics Using Pharmacokinetic Modeling and Simulations.

BACKGROUND: Although few studies have used ketamine for induction and maintenance of pediatric anesthesia, official dosage recommendations are lacking. This study evaluates the outcomes of adult anesthetic doses in a pediatric population through pharmacokinetic modeling and computer simulations in an attempt to recommend an adequate ketamine dosing regimen. METHODS: Ketamine plasma concentration-time data in 19 children (age 8 months to 16 years; weight 5.5 to 67 kg) were analyzed according to a non-compartmental pharmacokinetic approach. The relationship between pharmacokinetic parameters and demographic covariates was mathematically characterized. A one-compartment open model was implemented to simulate the plasma profile following administration of 1-4.5 mg/kg IV bolus dose and 0.1-0.5 mg/kg/min continuous infusion of ketamine and to predict anesthesia onset and offset. KEY RESULTS: Pharmacokinetic parameters determined were clearance 0.025 ± 0.008 L/kg/min; distribution volume 3.3 ± 1.3 L/kg; half-life 2.6 ± 1 h; and mean residence time 2.3 ± 0.64 h. Body weight was the best predictor of clearance and distribution volume according to a 0.75-power model. Using weight to scale doses was associated with limited variability in simulated concentrations. Ketamine administered as 2.25 mg/kg IV bolus dose, followed by 0.1 mg/kg/min continuous IV infusion enables anesthesia initiation within 3 minutes and maintains it for 3 hours. CONCLUSIONS & INFERENCES: Weight-based dosing minimizes age-dependent variation in the plasma concentration of ketamine. Low-to-intermediate adult doses are suitable for induction and maintenance of safe anesthesia in children undergoing short-term surgical operations. However, this finding requires validation in controlled clinical trials before it is adopted into surgical standard practices.

Intra-operative low-dose ketamine does not reduce the cost of post-operative pain management after surgery: a randomized controlled trial in a low-income country.

BACKGROUND: In developing countries, post-operative pain remains underestimated and undertreated due to economic constraints, lack of awareness and limited resources. In contrast, ketamine is an effective, readily available, easy to use and inexpensive drug frequently used in poor settings. OBJECTIVES: The aim of this study was to explore the overall reduction in the medication treatment cost of acute post-operative pain by adding intra-operative low-dose ketamine to traditional intravenous morphine for surgery in a low-income country. METHODS: A double blind randomized controlled trial with placebo-controlled parallel group was performed in Mulago National Hospital (Uganda). Consenting adults scheduled for elective surgery were randomized into two study arms: Group K received ketamine 0.15mg/kg bolus at induction and a continuous infusion of 0.12 mg/kg/hour till start of skin closure; Group C (control) received normal saline. Both groups received Morphine 0.1 mg/kg IV at debulking. The total medication cost was registered. NRS pain scores and other measurements such vital signs and incidence of major and minor side effects were also recorded. RESULTS: A total of 46 patients were included. Patients' baseline characteristics were comparable in both groups. No statistically significant difference was found between the groups concerning the overall medication cost of post-operative pain management. Pain scores, patients' satisfaction in the first 24 hours after surgery and hospital length of stay were similar in both groups. CONCLUSION: Our results do not support the utilization of intra-operative low dose ketamine as a cost-saving post-operative pain treatment strategy for all types of surgery in low-resource settings.

Effect of low-dose ketamine versus fentanyl on attenuating the haemodynamic response to laryngoscopy and endotracheal intubation in patients undergoing general anaesthesia: a prospective, double-blinded, randomised controlled trial.

BACKGROUND: The use of drugs to attenuate the haemodynamic response to laryngoscopy and endotracheal intubation is the standard of care during elective surgery. Current evidence is conflicting concerning the best agent and optimal dose for this purpose. In the majority of cases, fentanyl is widely utilized to attenuate haemodynamic responses. Ketamine, an established available drug, has been scarcely studied in this regard at low doses and against varying doses of other common agents. OBJECTIVE: To compare the overall occurrence of hypertension and tachycardia immediately pre-intubation (post-induction) until 10 minutes post intubation between the study group receiving fentanyl at 1.0 µg/kg and the other receiving ketamine at 0.5 mg/kg, to compare the occurrence of post-induction hypotension and the occurrence of neuropsychiatric phenomena during emergence between the two groups. METHODS: One hundred and eight ASA I and II patients aged 18-65 years scheduled for elective surgery under general anaesthesia were randomized into two groups: Control group: received fentanyl 1.0 µg/kg intravenously. Intervention group: received ketamine 0.5 mg/kg intravenously. General anaesthesia was standardized in both groups. The patients and physicians administering anaesthesia were blinded to the study. Haemodynamic responses were evaluated by determining heart rate and blood pressure immediately before laryngoscopy and at 2.5, 5, 7.5 and 10 minutes. Neuropsychiatric phenomena were assessed upon recovery from anaesthesia. RESULTS: One hundred and eight ASA I and II patients scheduled to undergo elective surgery were included in this study, 54 participants (50%) in the fentanyl arm and 54 (50%) in the ketamine arm. Baseline demographic characteristics were similar between the groups. There were more hypertensive episodes in the ketamine arm (11%) compared to the fentanyl arm (1.85%), but not achieving statistical significance: Fisher's exact test, p=0.06. There was no significant difference in the number of episodes of tachycardia between the Ketamine group 7/54 (13%) and the fentanyl group, 6/54 (11%); x2=0.05, p=0.82. Hypotensive episodes were more common in those who received Fentanyl, 41/54 (76%), compared to ketamine recipients, 21/54 (39%), X2=16.9, p<0.001. The use of Ketamine was associated with less episodes of hypotension, adjusted odds ratio = 0.18 (95% confidence interval 0.07, 0.45). CONCLUSION: We conclude, based upon findings in this study group, that there is no difference in the occurrence of hypertension with the use ketamine at 0.5 mg/kg in combination with Propofol at 2.0 mg/kg. In this regard, ketamine provides a viable alternative to fentanyl at 1.0 µg/kg for attenuating the pressor response to laryngoscopy and endotracheal intubation. Additionally, our results suggest that ketamine may protect against post-induction (pre-laryngoscopy) hypotension.

Intraoperative ketamine for prevention of depressive symptoms after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial.

BACKGROUND: Ketamine is a general anaesthetic with anti-depressant effects at subanaesthetic doses. We hypothesised that intraoperative administration of ketamine would prevent or mitigate postoperative depressive symptoms in surgical patients. METHODS: We conducted an international, randomised clinical trial testing the effects of intraoperative administration of ketamine [0.5 mg kg-1 (Lo-K) or 1.0 mg kg-1 (Hi-K)] vs control [saline placebo (P)] in patients ≥60 yr old undergoing major surgery with general anaesthesia. We administered the Patient Health Questionnaire-8 before the operation, on postoperative day (POD) 3 (primary outcome), and on POD30 to assess depressive symptoms, a secondary outcome of the original trial. RESULTS: There was no significant difference on POD3 in the proportion of patients with symptoms suggestive of depression between the placebo [23/156 (14.7%)] and combined ketamine (Lo-K plus Hi-K) [61/349 (17.5%)] groups [difference = -2.7%; 95% confidence interval (CI), 5.0% to -9.4%; P=0.446]. Of the total cohort, 9.6% (64/670; 95% CI, 7.6-12.0%) had symptoms suggestive of depression before operation, which increased to 16.6% (84/505; 95% CI, 13.6-20.1%) on POD3, and decreased to 11.9% (47/395; 95% CI, 9.1-15.5%) on POD30. Of the patients with depressive symptoms on POD3 and POD30, 51% and 49%, respectively, had no prior history of depression or depressive symptoms. CONCLUSIONS: Major surgery is associated with new-onset symptoms suggestive of depression in patients ≥60 yr old. Intraoperative administration of subanaesthetic ketamine does not appear to prevent or improve depressive symptoms. CLINICAL TRIALS REGISTRATION: NCT01690988.

Chemsex among men - a questionnaire study. / Chemsex blant menn ­ en spørreundersøkelse.

BAKGRUNN: Formålet med undersøkelsen var å kartlegge forekomsten av rusmiddelbruk under sex (chemsex) blant et utvalg av mannlige pasienter ved Olafiaklinikken i Oslo, en poliklinikk for seksuelt overførbare infeksjoner. Vi ønsket også å se hvilke variabler innen psykisk helse, seksuelt overførbare infeksjoner og seksualatferd som var assosiert med chemsex for menn som har sex med menn og menn som har sex med kvinner. MATERIALE OG METODE: Studien var anonym og spørreskjemabasert blant mannlige pasienter ved poliklinikken i perioden 1.7.2016-20.10.2016. RESULTATER: Svarprosenten var 96 (1 050 fikk utdelt skjema, 1 013 ble inkludert). Av disse rapporterte 144 (14 %) bruk av chemsex i løpet av det siste året - 87 (17 %) menn som har sex med menn og 57 (12 %) menn som har sex med kvinner. Av de som hadde hatt chemsex, oppga flere menn som har sex med menn hivinfeksjon, at de hadde hatt syfilis, over ti sexpartnere og hadde deltatt på sexfest det siste året. Flere menn som har sex med kvinner oppga psykiske plager. FORTOLKNING: Det bør utredes nærmere hvordan helsevesenet best kan møte chemsexbrukernes behov. Spesielt er det viktig med informasjon om skadereduksjonstiltak og støtte til de som ønsker å slutte eller redusere bruken av chemsex.

Ketamine Infusions for Outpatient Pain Management: A Policy Development Project.

Current literature supports using ketamine for both acute and chronic pain management. It is imperative that the development of evidence-based protocols and policies keep pace with health care delivery to ensure patient safety. This project's objective was to formulate an outpatient ketamine infusion policy that promotes consistent and evidence-based care within a specified hospital system. This policy addresses potential side effects and minimization of adverse events by addressing patient selection, level of nursing care required, appropriate monitoring, and staff education.

Anaesthesia for cleft lip surgeries in a resource poor setting: techniques, outcome and safety.

INTRODUCTION: Cleft lip and palate is one of the more common congenital malformation and the most common craniofacial anomalies in children. The treatment is expensive and requires specialised care. Access to this care in middle and low income countries is compounded by socioeconomic status of patients and their relation and also the inadequacy of expertise in medical personnel and infrastructure. Objective: the study aimed to review the techniques of anaesthesia used in a low resource setting in terms of the techniques, outcome, and safety. METHODS: This is a retrospective review of 79 cases done in a resource poor setting. Information regarding the patients, surgeries and modes of anaesthesia were retrieved from the case notes. RESULTS: A total of 62 patients were operated with incomplete cleft accounting for 37 (59.7%), complete 23(37.1%), and 2 (3.2%) as bilateral. Forty-six (74.2%) of patients had their surgery done with ketamine anaesthesia without endotracheal intubation, 14 (22.6%) had regional anaesthesia and 2 patients (3.2%) had general anaesthesia with endotracheal intubation. CONCLUSION: This study demonstrates that with careful planning and expertise, cleft lip repair can be done safely in resource poor setting.

Assessment of Ketamine Binding of the Serotonin Transporter in Humans with Positron Emission Tomography.

Background: Comprehensive description of ketamine's molecular binding profile becomes increasingly pressing as use in real-life patient cohorts widens. Animal studies attribute a significant role in the substance's antidepressant effects to the serotonergic system. The serotonin transporter is a highly relevant target in this context, because it is central to depressive pathophysiology and treatment. This is, to our knowledge, the first study investigating ketamine's serotonin transporter binding in vivo in humans. Methods: Twelve healthy subjects were assessed twice using [11C]DASB positron emission tomography. A total of 0.50 mg/kg bodyweight ketamine was administered once i.v. prior to the second positron emission tomography scan. Ketamine plasma levels were determined during positron emission tomography. Serotonin transporter nondisplaceable binding potential was computed using a reference region model, and occupancy was calculated for 4 serotonin transporter-rich regions (caudate, putamen, thalamus, midbrain) and a whole-brain region of interest. Results: After administration of the routine antidepressant dose, ketamine showed <10% occupancy of the serotonin transporter, which is within the test-retest variability of [11C]DASB. A positive correlation between ketamine plasma levels and occupancy was shown. Conclusions: Measurable occupancy of the serotonin transporter was not detectable after administration of an antidepressant dose of ketamine. This might suggest that ketamine binding of the serotonin transporter is unlikely to be a primary antidepressant mechanism at routine antidepressant doses, as substances that facilitate antidepressant effects via serotonin transporter binding (e.g., selective serotonin reuptake inhibitors) show 70% to 80% occupancy. Administration of high-dose ketamine is widening. Based on the positive relationship we find between ketamine plasma levels and occupancy, there is a need for investigation of ketamine's serotonin transporter binding at higher doses.