Anestesiologia kehittyy leikkaussalien ulkopuolella

Tutkimusta molekyylitason mekanismien selvittämisestä potilaan terveyden kokonaisvaltaiseen hoitoon</p

Olisiko hydromorfonista oksikodonin haastajaksi?

Hydromorfoni on lähes sata vuotta vanha opioidi, jonka käyttö maassamme on ollut melko vähäistä. Nyt hydromorfonista on tullut Suomen markkinoille myös parenteraalinen valmiste. Finnanest pyysi dosentti Teijo Saarta pohtimaan tämän meille uuden opioidin asemaa. Teijo on - ilmeisesti ainoana suomalaistutkijana - tehnyt myös alkuperäistutkimusta hydromorfonista työskennellessään Erlangenissa, Saksassa.</p

Deksmedetomidiinin uudet antamistavat laajentavat käyttöaiheita tehohoitosedaation ulkopuolelle

Laskimoon annettava deksmedetomidiini on Suomessa kehitetty alfa-2-adrenergisiä reseptoreja aktivoiva lääkeaine. Sen pääasiallisena käyttöaiheena on ollut aikuispotilaiden tehohoitosedaatio. Lääke sai vuonna 2011 myyntiluvan, joka laajeni vuonna 2018 koskemaan myös aikuispotilaiden toimenpidesedaatiota. Deksmedetomiinilla on potilasta rauhoittavan vaikutuksen lisäksi kipua ja pahoinvointia lieventäviä ominaisuuksia. Muihin sedatiiveihin verrattuna deksmedetomidiini vaikuttaa hyvin vähän potilaan hengitystoimintaan. Deksmedetomidiinin vaihtoehtoiset antamisreitit ovat viime vuosina herättäneet kiinnostusta, ja lääkkeen käyttöä on tutkittu sekä yleisanestesian että puudutteiden tehosteaineena. Näiden tutkimusten tuloksien perusteella deksmedetomidiinin käyttömahdollisuuksien voidaan olettaa tulevaisuudessa lisääntyvän

Semimechanistic Population Pharmacokinetic Model to Predict the Drug-Drug Interaction Between S-ketamine and Ticlopidine in Healthy Human Volunteers

Low-dose oral S-ketamine is increasingly used in chronic pain therapy, but extensive cytochrome P450 (CYP) mediated metabolism makes it prone to pharmacokinetic drug-drug interactions (DDIs). In our study, concentration-time data from five studies were used to develop a semimechanistic model that describes the ticlopidine-mediated inhibition of S-ketamine biotransformation. A mechanistic model was implemented to account for reversible and time-dependent hepatic CYP2B6 inactivation by ticlopidine, which causes elevated S-ketamine exposure in vivo. A pharmacokinetic model was developed with gut wall and hepatic clearances for S-ketamine, its primary metabolite norketamine, and ticlopidine. Nonlinear mixed effects modeling approach was used (NONMEM version 7.3.0), and the final model was evaluated with visual predictive checks and the sampling-importance-resampling procedure. Our final model produces biologically plausible output and demonstrates that ticlopidine is a strong inhibitor of CYP2B6 mediated S-ketamine metabolism. Simulations from our model may be used to evaluate chronic pain therapy with S-ketamine.Peer reviewe

Population Modelling of Dexmedetomidine Pharmacokinetics and Haemodynamic Effects After Intravenous and Subcutaneous Administration

Background and Objective: Dexmedetomidine is a potent agonist of α2-adrenoceptors causing dose-dependent sedation in humans. Intravenous dexmedetomidine is commonly used perioperatively, but an extravascular route of administration would be favoured in palliative care. Subcutaneous infusions provide desired therapeutic plasma concentrations with fewer unwanted effects as compared with intravenous dosing. We aimed to develop semi-mechanistic population models for predicting pharmacokinetic and pharmacodynamic profiles of dexmedetomidine after intravenous and subcutaneous dosing.Methods: Non-linear mixed-effects modelling was performed using previously collected concentration and haemodynamic effects data from ten (eight in the intravenous phase) healthy human subjects, aged 19–27 years, receiving 1 µg/kg of intravenous or subcutaneous dexmedetomidine during a 10-min infusion.Results: The absorption of dexmedetomidine from the subcutaneous injection site, and distribution to local subcutaneous fat tissue was modelled using a semi-physiological approach consisting of a depot and fat compartment, while a two-compartment mammillary model explained further disposition. Dexmedetomidine-induced reductions in plasma norepinephrine concentrations were accurately described by an indirect response model. For blood pressure models, the net effect was specified as hyper- and hypotensive effects of dexmedetomidine due to vasoconstriction on peripheral arteries and sympatholysis mediated via the central nervous system, respectively. A heart rate model combined the dexmedetomidine-induced sympatholytic effect, and input from the central nervous system, predicted from arterial blood pressure levels. Internal evaluation confirmed the predictive performance of the final models, as well as the accuracy of the parameter estimates with narrow confidence intervals.Conclusions: Our final model precisely describes dexmedetomidine pharmacokinetics and accurately predicts dexmedetomidine-induced sympatholysis and other pharmacodynamic effects. After subcutaneous dosing, dexmedetomidine is taken up into subcutaneous fat tissue, but our simulations indicate that accumulation of dexmedetomidine in this compartment is insignificant.</p

Intranasal low-dose dexmedetomidine reduces postoperative opioid requirement in patients undergoing hip arthroplasty under general anesthesia

Background: Patients undergoing total hip arthroplasty (THA) need substantial amount of opioids for postoperative pain management, which necessitates opioid-sparing modalities. Dexmedetomidine is a novel alpha-2-adrenoceptor–activating drug for procedural sedation. In addition to its sedative effect, dexmedetomidine has analgesic and antiemetic effects. We evaluated retrospectively the effect of intraoperatively administered intranasal low-dose dexmedetomidine on postoperative opioid requirement in patients undergoing THA.Methods: We included 120 patients with American Society of Anesthesiologists status 1-2, age between 35 and 80 years, and scheduled for unilateral primary THA under general anesthesia with total intravenous anesthesia. Half of the patients received 50 μg of intranasal dexmedetomidine after anesthesia induction, while the rest were treated conventionally. Postoperative opioid requirements were calculated as morphine equivalent doses for both groups. The impact of intranasal dexmedetomidine on postoperative hemodynamics and length of stay was evaluated.Results: The cumulative postoperative opioid requirement was significantly reduced in the dexmedetomidine group compared with the control group (26.3 mg, 95% confidence interval 15.6-36.4, P Conclusion: Compared with the control group, intraoperative use of intranasal low-dose dexmedetomidine decreases opioid consumption and sympathetic response during acute postoperative period in patients undergoing THA.</p

Intranasal Dexmedetomidine Reduces Postoperative Opioid Requirement in Patients Undergoing Total Knee Arthroplasty Under General Anesthesia

Background: Total knee arthroplasty (TKA) causes severe pain, and strong opioids are commonly used in postoperative analgesia. Dexmedetomidine is a novel alpha-2-adrenoceptor-activating drug indicated for procedural sedation, but previous studies have shown clinically relevant analgesic and antiemetic effects. We evaluated retrospectively the effect of intranasal dexmedetomidine on the postoperative opioid requirement in patients undergoing TKA.Methods: One hundred and fifty patients with ASA status 1-2, age between 35 and 80 years, and scheduled for unilateral primary TKA under total intravenous anesthesia were included in the study. Half of the patients received 100 μg of intranasal dexmedetomidine after anesthesia induction, while the rest were treated conventionally. The postoperative opioid requirement was calculated as morphine equivalent doses for both groups. The effect of dexmedetomidine on postoperative hemodynamics, length of stay (LOS), and incidence of postoperative nausea and vomiting (PONV), was evaluated.Results: The cumulative postoperative opioid consumption was significantly reduced in the dexmedetomidine group compared to the control group (-28.5 mg, 95% CI 12-47 mg P Conclusion: Intraoperatively administered intranasal dexmedetomidine reduces postoperative opioid consumption and may be associated with a shorter hospital stay in patients undergoing TKA under general anesthesia.</p

Effects of pre-emptive pregabalin and multimodal anesthesia on postoperative opioid requirements in patients undergoing robot-assisted laparoscopic prostatectomy

Background: Previous findings indicate that pre-emptive pregabalin as part of multimodal anesthesia reduces opioid requirements compared to conventional anesthesia in patients undergoing robot-assisted laparoscopic prostatectomy (RALP). However, recent studies show contradictory evidence suggesting that pregabalin does not reduce postoperative pain or opioid consumption after surgeries. We conducted a register-based analysis on RALP patients treated over a 5-year period to evaluate postoperative opioid consumption between two multimodal anesthesia protocols. Methods: We retrospectively evaluated patients undergoing RALP between years 2015 and 2019. Patients with American Society of Anesthesiologists status 1-3, age between 30 and 80 years and treated with standard multimodal anesthesia were included in the study. Pregabalin (PG) group received 150 mg of oral pregabalin as premedication before anesthesia induction, while the control (CTRL) group was treated conventionally. Postoperative opioid requirements were calculated as intravenous morphine equivalent doses for both groups. The impact of pregabalin on postoperative nausea and vomiting (PONV), and length of stay (LOS) was evaluated. Results: We included 245 patients in the PG group and 103 in the CTRL group. Median (IQR) opioid consumption over 24 postoperative hours was 15 (8-24) and 17 (8-25) mg in PG and CTRL groups (p = 0.44). We found no difference in postoperative opioid requirement between the two groups in post anesthesia care unit, or within 12 h postoperatively (p = 0.16; p = 0.09). The length of post anesthesia care unit stay was same in each group and there was no difference in PONV Similarly, median postoperative LOS was 31 h in both groups. Conclusion: Patients undergoing RALP and receiving multimodal analgesia do not need significant amount of opioids postoperatively and can be discharged soon after the procedure. Pre-emptive administration of oral pregabalin does not reduce postoperative opioid consumption, PONV or LOS in these patients.</div