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The capability of viscoelastic measurement parameters to screen anticoagulation activity of edoxaban in relation to its plasma concentrations was evaluated in 15 healthy male volunteers. Blood samples were drawn before the oral administration of edoxaban 60 mg and 2, 4, 6, 8, and 24 hours after administration. At each time, standard coagulation tests were performed, blood viscoelastic properties were measured with a thromboelastometry device ROTEM delta analyzer (Instrumentation Laboratory, Werfen, Barcelona, Spain), and edoxaban plasma concentrations were measured. Our primary interest was the possible correlation between edoxaban plasma concentrations and values for ROTEM ExTEM, and FibTEM. We also studied the correlation of edoxaban plasma concentrations with the results of standard coagulation tests. We saw the effect of a single dose of edoxaban most clearly in clotting time (CT) of ROTEM ExTEM and FibTEM. Changes in these parameters correlated significantly with edoxaban plasma concentrations up to 6 hours from the ingestion of the drug. Activated partial thromboplastin time, prothrombin time, and anti–factor Xa were also affected. Peak changes were observed 2 and 4 hours after administration of edoxaban. The changes were mostly reversed after 8 hours. In conclusion, ROTEM CT correlates significantly with edoxaban plasma concentrations and can be used to estimate the effect of edoxaban. ROTEM should be considered as part of the assessment of coagulation, with the big advantage of being readily available on site. [ABSTRACT FROM AUTHOR]

Aims: Ketorolac is a nonsteroidal anti‐inflammatory racemic drug with analgesic effects only attributed to its S‐enantiomer. The aim of this study is to quantify enantiomer‐specific maturational pharmacokinetics (PK) of ketorolac and investigate if the contribution of both enantiomers to the total ketorolac concentration remains equal between infants and adults or if a change in target racemic concentration should be considered when applied to infants. Methods: Data were pooled from 5 different studies in adults, children and infants, with 1020 plasma concentrations following single intravenous ketorolac administration. An allometry‐based enantiomer‐specific population PK model was developed with NONMEM 7.3. Simulations were performed in typical adults and infants to investigate differences in S‐ and R‐ketorolac exposure. Results: S‐ and R‐ketorolac PK were best described with a 3‐ and a 2‐compartment model, respectively. The allometry‐based PK parameters accounted for changes between populations. No maturation function of ketorolac clearance could be identified. All model parameters were estimated with adequate precision (relative standard error <50%). Single dose simulations showed that a previously established analgesic concentration at half maximal effect in adults of 0.37 mg/L, had a mean S‐ketorolac concentration of 0.057 mg/L, but a mean S‐ketorolac concentration of 0.046 mg/L in infants. To match the effective adult S‐ketorolac‐concentration (0.057 mg/L) in typical infants, the EC50‐racemic should be increased to 0.41 mg/L. Conclusion: Enantiomer‐specific changes in ketorolac PK yield different concentrations and S‐ and R‐ketorolac ratios between infants and adults at identical racemic concentrations. These PK findings should be considered when studies on maturational pharmacodynamics are considered. [ABSTRACT FROM AUTHOR]

The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine endorses the clinical practice guideline Transfusion strategies in bleeding critically ill adults: a clinical practice guideline from the European Society of Intensive Care Medicine. This trustworthy clinical practice guideline serves as a useful decision aid for Nordic anaesthesiologists caring for critically ill patients with bleeding. [ABSTRACT FROM AUTHOR]

The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine endorses the Living WHO guideline on therapeutics and COVID‐19. This trustworthy continuously updated guideline serves as a highly useful decision aid for Nordic anaesthesiologists caring for patients with COVID‐19. [ABSTRACT FROM AUTHOR]

The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine endorses the clinical practice guideline Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. The guideline serves as a useful bedside decision aid for clinicians managing adults with suspected and confirmed septic shock and sepsis‐associated organ dysfunction. [ABSTRACT FROM AUTHOR]

Aims Although ketorolac analgesia is linked only to the S-enantiomer, there is limited information on the stereo-selective pharmacokinetics of this agent. We studied the stereo-selective pharmacokinetics of ketorolac in a pooled dataset of two studies, with women at delivery and 4-5 months postpartum, and males and nonpregnant females. Methods Nonlinear mixed-effect modelling was used to evaluate the stereo-selective pharmacokinetics of ketorolac tromethamine after a single intravenous injection immediately after delivery ( n = 41), 4-5 months postpartum ( n = 8, paired), and in male ( n = 12) and nonpregnant female ( n = 14) subjects. All of the males and six of the nonpregnant females were recruited from another study, in which they were undergoing blood sampling for 24 h. All remaining cases underwent blood sampling for 8 h. Results For both the R- and S-enantiomers, body weight affected ketorolac clearance. In addition, clearance for both enantiomers was 36% [95% confidence interval (CI) 15%, 58%] higher in male than in female subjects of the same body weight, and 55% (95% CI 33%, 78%) higher in women at delivery than in nonpregnant women of the same body weight. Women at delivery also had a 27% (95% CI 8%, 46%) higher distribution volume than nonpregnant women. The proportional effects of the covariates were not significantly different for the two ketorolac enantiomers. Conclusions Besides the anticipated impact of body weight on clearance, R- and S-ketorolac clearance is increased in male subjects and in women at delivery. To reach an exposure equivalent to that in nonpregnant women, males should receive a 36% increased ketorolac dose and pregnant women a 55% increased dose, in addition to a dose adjustment by body weight. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the current population pharmacokinetic study was to quantify oxycodone pharmacokinetics in children ranging from preterm neonates to children up to 7 years of age. Methods: Data on intravenous or intramuscular oxycodone administration were obtained from three previously published studies ( n = 119). The median [range] postmenstrual age of the subjects was 299 days [170 days-7.8 years]. A population pharmacokinetic model was built using 781 measurements of oxycodone plasma concentration. The model was used to simulate repeated intravenous oxycodone administration in four representative infants covering the age range from an extremely preterm neonate to 1-year old infant. Results: The rapid maturation of oxycodone clearance was best described with combined allometric scaling and maturation function. Central and peripheral volumes of distribution were nonlinearly related to bodyweight. The simulations on repeated intravenous administration in virtual patients indicated that oxycodone plasma concentration can be kept between 10 and 50 ng/ml with a high probability when the maintenance dose is calculated using the typical clearance and the dose interval is 4 h. Conclusions: Oxycodone clearance matures rapidly after birth, and between-subject variability is pronounced in neonates. The pharmacokinetic model developed may be used to evaluate different multiple dosing regimens, but the safety of repeated doses should be ensured. [ABSTRACT FROM AUTHOR]

Purpose: The aim was to assess anterior pituitary hormone levels during the acute phase of aneurysmal subarachnoid hemorrhage (aSAH) and analyze the possible association with the clinical condition and outcome. Material and methods: Forty patients with aSAH whose aneurysm was secured by endovascular coiling were enrolled. Basal secretions of cortisol, testosterone, luteinizing hormone (LH), prolactin (PRL), and sex hormone binding globulin (SHBG) levels were measured up to 14 days after the incident. Results: The main finding was that hypocortisolism was rare whereas testosterone deficiency was common in male patients. Furthermore, various other hormone deviations were frequent and there was wide interindividual variability. We found no association between delayed cerebral ischemia (DCI), outcome of the patients or aneurysm location, and hormone abnormalities, while both Hunt & Hess and Fisher grade were associated with low PRL levels. Hunt & Hess 5 was associated with low PRL concentration when compared to grades 1 (OR = 4.81, 95% CI 1.15–20.14, p = 0.03), 3 (OR 7.73, 95% CI 1.33–45.01, p = 0.02), and 4 (OR = 6.86 95% CI 1.28–26.83, p = 0.02). Fisher grade 4 was associated with low PRL concentration when compared to grades 3 (OR 3.37, 95% CI 1.06–10.73, p = 0.03) and 2 (OR 9.71, 95% CI 1.22–77.10, p = 0.04). Conclusion: Deviations from normal and huge interindividual differences are common in hormone levels during the acute phase of aSAH. Routine assessment of anterior pituitary function in the acute phase of aSAH is not warranted. During the follow-up in the outpatient clinic, hormone concentrations were not measured, which would have brought a more long-term perspective into our findings. [ABSTRACT FROM AUTHOR]