Carl-Olav Stiller

The ‘Wise List’– A Comprehensive Concept to Select, Communicate and Achieve Adherence to Recommendations of Essential Drugs in Ambulatory Care in Stockholm

The aim was to present and evaluate the impact of a comprehensive strategy over 10 years to select, communicate and achieve adherence to essential drug recommendations (EDR) in ambulatory care in a metropolitan healthcare region. EDRs were issued and launched as a Wise List by the regional Drug and Therapeutics Committee in Stockholm. This study presents the concept by: (i) documenting the process for selecting, communicating and monitoring the impact of the Wise List; (ii) analysing the variation in the number of drug substances recommended between 2000 and 2010; (iii) assessing the attitudes to the Wise List among prescribers and the public; (iv) evaluating the adherence to recommendations between 2003 and 2009. The Wise List consistently contained 200 drug substances for treating common diseases. The drugs were selected based on their efficacy, safety, suitability and cost-effectiveness. The Wise List was known among one-third of a surveyed sample of the public in 2002 after initial marketing campaigns. All surveyed prescribers knew about the concept and 81% found the recommendations trustworthy in 2005. Adherence to recommendations increased from 69% in 1999 to 77% in 2009. In primary care, adherence increased from 83% to 87% from 2003 to 2009. The coefficient of variation (CV%) decreased from 6.1% to 3.8% for 156 healthcare centres between these years. The acceptance of the Wise List in terms of trust among physicians and among the public and increased adherence may be explained by clear criteria for drug recommendations, a comprehensive communication strategy, electronic access to recommendations, continuous medical education and involvement of professional networks and patients.

Pain control after total knee arthroplasty: a randomized trial comparing local infiltration anesthesia and continuous femoral block

Background and purpose Pain after total knee arthroplasty (TKA) is usually severe, and epidural analgesia or femoral nerve block has been considered to be an effective pain treatment. Recently, local infiltration analgesia (LIA) has become increasingly popular but the outcome of this method regarding the analgesic effect has not been fully evaluated. We compared local infiltration analgesia and femoral block with regard to analgesia and morphine demand during the first 24 h after TKA. Methods 40 patients undergoing TKA under spinal anesthesia were randomized to receive femoral nerve block (group F) or peri- and intraarticular infiltration analgesia (group LIA) with a mixture containing ropivacaine, ketorolac, and epinephrine. All patients had access to intravenous patient-controlled analgesia (PCA) with morphine postoperatively. Pain intensity at rest and upon movement was assessed on a numeric rating scale (0–10) on an hourly basis over 24 h if the patients were awake. Results The average pain at rest was marginally lower with LIA (1.6) than with femoral block (2.2). Total morphine consumption per kg was similar between the 2 groups. Ancillary analysis revealed that 1 of 20 patients in the LIA group reported a pain intensity of > 7 upon movement, as compared to 7 out of 19 in the femoral block group (p = 0.04). Interpretation Both LIA and femoral block provide good analgesia after TKA. LIA may be considered to be superior to femoral block since it is cheaper and easier to perform.

Maternal use of thyroid hormones in pregnancy and neonatal outcome

Objective. To describe neonatal outcome including the presence of congenital malformations in infants born to women substituted with thyroid hormones, and the maternal characteristics of these women. Design. Register study based on prospectively collected data in relation to delivery. Setting. Swedish Health Registers. Population. All pregnant women (n = 848,468) and all infants born (n = 861,989) in Sweden from 1 July 1995 to 31 December 2004. Methods. Women who reported the use of thyroid hormones in early pregnancy or obtained a prescription for thyroid hormones later in pregnancy (n = 9,866), as well as their infants (n = 10,055) were identified from the Swedish Medical Birth Register. The reference population consisted of all women giving birth and their offspring during the same time interval. Main outcome measures. Neonatal outcome, malformations and maternal characteristics. Data were analyzed with adjustments for identified confounders. Results. Women using thyroxine had an increased rate of pre‐eclampsia, diabetes (pre‐existing or gestational), cesarean sections and inductions of labour compared to women in the reference population. The risk for preterm birth was marginally increased (OR 1.13, 95% CI 1.03–1.25). Neonatal thyroid disease was found in eight infants (seven with thyreotoxicosis and one unspecified), the expected number was 0.2. No further anomalies in neonatal diagnoses were found. A small but statistically significant risk for congenital malformations (OR =1.14, 95% CI 1.05–1.26) was found. Conclusion. Women on thyroid substitution during pregnancy had an increased risk for some pregnancy complications, but their infants were only slightly affected.

Plasma concentration of ketorolac after local infiltration analgesia in hip arthroplasty.

Local infiltration analgesia (LIA) with local anaesthetic (ropivacaine), a nonsteroidal anti‐inflammatory drug (ketorolac) and epinephrine after lower extremity arthroplasty has gained increasing popularity during the last decade. This method has certain advantages, which include minimal systemic side effects, faster post‐operative mobilization, earlier post‐operative discharge from hospital and less opioid consumption. However, information regarding plasma concentrations of ketorolac after LIA mixture is insufficient to predict the risk of renal impairment in patients subjected to arthroplasty.

A randomized study comparing plasma concentration of ropivacaine after local infiltration analgesia and femoral block in primary total knee arthroplasty

Abstract Pain after total knee arthroplasty (TKA) is difficult to control. A recently developed and increasingly popular method for postoperative analgesia following knee and hip arthroplasty is Local Infiltration Analgesia (LIA) with ropivacaine, ketorolac and epinephrine. This method is considered to have certain advantages, which include administration at the site of traumatized tissue, minimal systemic side effects, faster postoperative mobilization, earlier postoperative discharge from hospital and less opioid consumption. One limitation, which may prevent the widespread use of LIA is the lack of information regarding plasma concentrations of ropivacaine and ketorolac. The aim of this academically initiated study was to detect any toxic or near-toxic plasma concentrations of ropivacaine and ketorolac following LIA after TKA. Methods Forty patients scheduled for primary total knee arthroplasty under spinal anaesthesia, were randomized to receive either local infiltration analgesia with a mixture of ropivacaine 300 mg, ketorolac 30mg and epinephrine or repeated femoral nerve block with ropivacaine in combination with three doses of 10mg intravenous ketorolac according to clinical routine. Plasma concentration of ropivacaine and ketorolac were quantified by liquid chromatography–mass spectrometry (LC–MS). Results The maximal detected ropivacaine plasma level in the LIA group was not statistically higher than in the femoral block group using the Mann–Whitney U-test (p = 0.08). However, the median concentration in the LIA group was significantly higher than in the femoral block group (p < 0.0001; Mann–Whitney U-test). The maximal plasma concentrations of ketorolac following administration of 30mg according to the LIA protocol were detected 1 h or 2 h after release of the tourniquet in the LIA group: 152–958 ng/ml (95% CI: 303–512 ng/ml; n = 20). The range of the plasma concentration of ketorolac 2–3 h after injection of a single dose of 10mg was 57–1216 ng/ml (95% CI: 162–420 ng/ml; n = 20). Conclusion During the first 24 h plasma concentration of ropivacaine seems to be lower after repeated femoral block than after LIA. Since the maximal ropivacaine level following LIA is detected around 4–6 h after release of the tourniquet, cardiac monitoring should cover this interval. Regarding ketorolac, our preliminary data indicate that the risk for concentration dependent side effects may be highest during the first hours after release of the tourniquet. Implication Femoral block may be the preferred method for postoperative analgesia in patients with increased risk for cardiac side effects from ropivacaine. Administration of a booster dose of ketorolac shortly after termination of the surgical procedure if LIA was used may result in an increased risk for toxicity.

The value of preoperative grade of radiographic and histological changes in predicting pain relief after total knee arthroplasty for osteoarthritis

PurposeMany attempts with contradictory results have been made to correlate different features of OA with pain. One reason may be that pain at rest and pain with movement are seldom considered separately although the mechanisms may be quite different. Furthermore, pain ratings are subject to individual interpretation making an inter-individual comparison questionable. By instead calculating the absolute and relative changes in pain on an intra-individual level after total knee arthroplasty (TKA), we aimed at exploring a relationship between pain and radiological and histological changes.MethodsIn 69 patients undergoing TKA, preoperative radiographs and perioperative histological samples of the synovial membrane were graded for severity of osteoarthritic and inflammatory changes. The findings were related to the intensity of pain at rest and with movement both preoperatively and 18xa0months postoperatively according to the visual analogue scale (VAS).ResultsThe radiographic and histological findings showed no significant correlation with the mean pre- or postoperative pain scores. Instead, change in pain with movement from pre- to postoperative was significantly related to the grade of radiographic osteoarthritis. Best pain relief by TKA was achieved in patients with severe radiographic changes. This, however, only applied to pain with movement.ConclusionsPain at rest and pain with movement may have different mechanisms. We believe that assessing the intensity of pain at rest and pain with movement separately and considering changes in pain on an individual level will be helpful strategies in future follow-up studies and efforts aimed at explaining the mechanisms of pain in OA.

Ropivacaine pharmacokinetics after local infiltration analgesia in hip arthroplasty.

In this study, we determined the plasma concentration of ropivacaine by liquid chromatography-mass spectrometry for 30 hours after local infiltration analgesia in 15 patients with elective hip arthroplasty. The 95% upper prediction bound of maximal unbound plasma concentration of ropivacaine was 0.032 mg/L. Side effects sufficient to stop an IV infusion have been reported at arterial concentrations of 0.34 to 0.85 mg/L. Alpha-1-acid glycoprotein did not correlate with the fraction of unbound ropivacaine during the first 24 hours after local infiltration analgesia. No signs or symptoms of systemic local anesthetic toxicity were observed. The Clopper-Pearson 95% upper confidence limit for adverse signs was 0.218.

Pharmacokinetics after a single intravenous dose of the opioid ketobemidone in neonates

Ketobemidone is often used as an alternative to morphine in children in the Scandinavian countries. In an earlier study, we have examined the pharmacokinetic properties in children in different age groups but have not focused on neonates. The aim of this clinical trial was to explore the pharmacokinetics of ketobemidone in neonates.

Adverse Drug Reactions in a Tertiary Care Emergency Medicine Ward - Prevalence, Preventability and Reporting.

Purpose To identify the prevalence and preventability of adverse drug reactions (ADRs) in an emergency ward setting in a tertiary hospital in Sweden and to what extent the detected ADRs were reported to the Medical Product Agency (MPA). Methods In this prospective cross sectional observational study, 706 patients admitted to one of the Emergency Wards, at the Karolinska University Hospital in Solna, Stockholm during September 2008 –September 2009, were included. The electronic patient records were reviewed for patients’ demographic parameters, prevalence of possible ADRs and assessment of their preventability. In addition, the extent of formal and required ADR reporting to national registers was studied. Results Approximately 40 percent of the patient population had at least one possible ADR (n = 284). In the multivariable regression model, age and number of drugs were significantly associated with risk of presenting with an ADR (p<0.01 and p<0.001, respectively). Sex was not identified as a significant predictor of ADRs (p = 0.27). The most common ADRs were cardiovascular, followed by electrolyte disturbances, and hemorrhage. In 18 percent of the patient population ADRs were the reason for admission or had contributed to admission and 24% of these ADRs were assessed as preventable. The under-reporting of ADRs to the MPA was 99%. Conclusions ADRs are common in Emergency Medicine in tertiary care in Sweden, but under-reporting of ADRs is substantial. The most frequent ADRs are caused by cardiovascular drugs, and significantly associated with age and number of drugs. However, only a minority of the detected serious ADRs contributing to admission could have been avoided by increased risk awareness.

Long-term pattern of opioid prescriptions after femoral shaft fractures

The use of opioids in non‐cancer‐related pain following skeletal trauma is controversial due to the presumed risk of dose escalation and dependence. We therefore examined the pattern of opioid prescriptions, that is, those actually dispensed, in patients with femoral shaft fractures.