Plasma cyclic guanosine 3′,5′-monophosphate levels: A marker of glutamate-nitric oxide-guanyl cyclase activity?

Objectives: Remifentanil-based anesthesia can lead to acute opioid tolerance and/or hyperalgesia. A low-dose intraoperative infusion of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine did not result in reduced postoperative morphine consumption after remifentanil-based anesthesia in adolescents. This study investigates the potential role of the glutamate-nitric oxide-cyclic guanosine 3′,5′-monophosphate (cyclic GMP) pathway in the failure of low-dose ketamine to prevent remifentanil-induced acute opioid tolerance and/or hyperalgesia.Design and setting: Prospective, double-blind, placebo-controlled randomized clinical trial at a university teaching hospital.Patients, participants, and interventions: Thirty-four adolescents receiving remifentanil-based anesthesia for surgical correction of idiopathic scoliosis were randomly assigned to receive either intraoperative ketamine administered as a bolus dose of 0.5 mg/kg in 10 mL of normal saline and a continuous intravenous infusion of 4.0 μg/kg/min or an equal volume of saline.Main outcome measures: Blood samples were collected before and after the administration of ketamine for analyzing the concentrations of cyclic GMP, ketamine, and norketamine. Blood samples were analyzed using high-performance liquid chromatography and an enzyme immunoassay.Results: The median (interquartile range) value of the concentration of plasma cyclic GMP decreased from 23.7 (17.4-26.7) to 14.8 (14.0-17.3) nmol/L after ketamine infusion (p 0.005) and from 23.9 (16.3-29.2) to 16.3 (14.5-18.6) nmol/L after saline infusion (p 0.005). The median value of the concentration of plasma cyclic GMP at the end of ketamine infusion did not differ significantly when compared with that after saline infusion (p = 0.07). The concentration of plasma cyclic GMP was inversely correlated with the concentration of plasma ketamine (r = −0.61).Conclusions: This study suggests that the low dose of intraoperative ketamine infused was insufficient to suppress the NMDA receptor pathway. The concentrations of plasma cyclic GMP may serve as an indirect biological marker of ketamine-induced NMDA receptor antagonism.

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Low Dose Perioperative Ketamine Infusion and it's Effect on Postoperative Pain Score, Sedation Score and Narcotic Consumption in Patients Undergoing Spine Surgery: A Prospective Randomized Double Blind Control Trial.

Case Medical Research ◽

10.31525/ct1-nct04259476 ◽

2020 ◽

Author(s):

Keyword(s):

Postoperative Pain ◽

Pain Score ◽

Spine Surgery ◽

Low Dose ◽

Sedation Score ◽

Double Blind ◽

Ketamine Infusion ◽

Postoperative Pain Score

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Low Dose Ketamine Infusion for Comorbid Posttraumatic Stress Disorder and Chronic Pain: A Randomized Double-Blind Clinical Trial

Chronic Stress ◽

10.1177/2470547020981670 ◽

2020 ◽

Vol 4 ◽

pp. 247054702098167

Author(s):

Alisher R. Dadabayev ◽

Sonalee A. Joshi ◽

Mariam H. Reda ◽

Tamar Lake ◽

Mark S. Hausman ◽

...

Keyword(s):

Posttraumatic Stress Disorder ◽

Chronic Pain ◽

Posttraumatic Stress ◽

Outcome Measures ◽

Low Dose ◽

Stress Disorder ◽

Double Blind ◽

Impact Of Event Scale ◽

Event Scale ◽

Ketamine Infusion

Objective To date, treatment options (i.e. psychotherapy, antidepressant medications) for patients with posttraumatic stress disorder (PTSD), are relatively few, and considering their limited efficacy, novel therapies have gained interest among researchers and treatment providers alike. Among patients with chronic pain (CP) about one third experience comorbid PTSD, which further complicates their already challenging pharmacological regimens. Low dose ketamine infusion has shown promise in PTSD, and in treatment of CP, however they have not been studied in comorbid population and under rigorous control conditions. Methods We compared the effects of a single dose of either ketamine (0.5 mg/kg) or ketorolac (15 mg) over a 40-minute of IV infusion in CP patients with and without PTSD, in double blind, randomized study. Measures were collected before, during, one day and seven days after the infusion. A planned sample size of 40 patients randomly assigned to treatment order was estimated to provide 80% power to detect a hypothesized treatment difference after the infusion. Main Outcome and Measures: The primary outcome measures were change in PTSD symptom severity assessed with the Impact of Event Scale–Revised (IES-R) and Visual Analogue Scale (VAS) for pain administered by a study clinician 24 hours post infusion. Secondary outcome measures included Impact of Event Scale–Revised (IES-R), VAS and Brief Pain Inventory (Short Form) for pain 1 week after the infusion. Results Both treatments offered comparable improvement of PTSD and CP symptoms that persisted for 7 days after the infusion. Patients with comorbid PTSD and CP experienced less dissociative side effects compared to the CP group. Surprisingly, ketorolac infusion resulted in dissociative symptoms in CP patients only. Conclusions This first prospective study comparing effects of subanesthetic ketamine versus ketorolac infusions for comorbid PTSD and CP, suggests that both ketamine and ketorolac might offer meaningful and durable response for both PTSD and CP symptoms.

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Impact of an Herbal Dietary Supplement Containing Spilanthes acmella and Orchis latifolia on Testosterone in Young Men

Journal of Biology and Life Science ◽

10.5296/jbls.v8i1.10356 ◽

2016 ◽

Vol 8 (1) ◽

pp. 28

Author(s):

Ryan G. Moran ◽

Alex T. VonSchulze ◽

Richard J. Bloomer

Keyword(s):

Nitric Oxide ◽

Young Men ◽

Moderate Increase ◽

Herbal Preparation ◽

Double Blind ◽

Total Blood ◽

Blood Samples ◽

Healthy Men ◽

Spilanthes Acmella ◽

The Impact

Attention has been given recently to herbal dietary supplements proposed to elevate testosterone and nitric oxide. This study evaluated the impact of a supplement containing Spilanthes acmella extract and Orchis latifolia extract on total blood testosterone, cortisol, and nitrate/nitrite in healthy men. Methods: Thirteen men (25.0±1.0 years) were randomly assigned (double-blind, cross-over design) to ingest a supplement (containing Spilanthes acmella extract and Orchis latifolia extract) and a placebo daily for 14 days, with a 14-day washout period between assignments. Fasting blood samples were collected on the mornings of days 1, 4, 8, and 15 and analyzed for testosterone, cortisol, and nitrate/nitrite. On day 15, subjects ingested an acute dose of the supplement or placebo and blood was collected every 30 minutes for three hours, and analyzed for testosterone. Results: No increase of significance was noted for any biochemical variable (p>0.05). However, a mean increase in testosterone from day 1 to day 15 of 29% was observed for the 13 subjects when ingesting the supplement, with a mean increase of 56% noted when only considering the 8 subjects who “responded” to treatment. Cortisol was increased approximately 19% when subjects ingested the supplement, compared to only 9% with the placebo. Conclusion: Two weeks of supplementation with an herbal preparation containing Spilanthes acmella extract and Orchis latifolia extract can increase testosterone in selected young men. The supplement also results in a moderate increase in cortisol. Larger scale studies are needed to further evaluate the impact of this herbal combination on testosterone in men.

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