Eija Kalso

Haukeland University Hospital, Bergen, Hordaland, Norway

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Publications (230)1062.45 Total impact

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    ABSTRACT: The effects of ketamine in attenuating morphine tolerance have been suggested to result from a pharmacodynamic interaction. We studied whether ketamine might increase brain morphine concentrations in acute coadministration, in morphine tolerance, and morphine withdrawal.
    British Journal of Pharmacology 10/2014; · 5.07 Impact Factor
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    ABSTRACT: Context Measuring opioid concentrations in pain treatment is warranted in situations where optimal opioid analgesia is difficult to reach. Objectives To assess the usefulness of oral fluid (OFL) as an alternative to plasma in opioid concentration monitoring in cancer patients on chronic opioid therapy. Methods We collected OFL and plasma samples from 64 cancer patients on controlled-release (CR) oral morphine, CR oral oxycodone or transdermal (TD) fentanyl for pain. Samples were obtained on up to five separate days. Results A total of of 213 OFL and plasma samples were evaluable. All patients had detectable amounts of the CR or TD opioid in both plasma and OFL samples. The plasma concentrations of oxycodone and fentanyl (determination coefficient R2 = 0.628 and 0.700, respectively), but not morphine (R2 = 0.292), were moderately well correlated to the daily opioid doses. In contrast to morphine and fentanyl (mean OFL/plasma ratio 2.0 and 3.0, respectively), the OFL oxycodone concentrations were significantly higher than the respective plasma concentrations (mean OFL/plasma ratio 14.9). An active transporter could explain the much higher OFL versus plasma concentrations of oxycodone compared with morphine and fentanyl. Conclusion OFL analysis is well suited for detecting the studied opioids. For morphine and fentanyl, an approximation of the plasma opioid concentrations is obtainable, whereas for oxycodone, the OFL/plasma concentration relationship is too variable for reliable approximation results.
    Journal of Pain and Symptom Management. 09/2014;
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    ABSTRACT: Most clinically used opioids are mu-opioid receptor agonists. Therefore, genetic variation of the OPRM1 gene that encodes the mu-opioid receptor is of great interest for understanding pain management. A polymorphism 118A>G (rs1799971) within the OPRM1 gene results in a missense mutation and affects the function of the receptor. We studied the association between the 118A>G polymorphism and oxycodone analgesia and pain sensitivity in 1,000 women undergoing breast cancer surgery. Preoperatively, experimental cold and heat pain sensitivities were tested. Postoperative pain was assessed at rest and during motion. I.v. oxycodone analgesia was titrated first by a research nurse and on the ward using a patient-controlled analgesia device. The primary endpoint was the amount of oxycodone needed for the first state of adequate analgesia. For each patient, the 118A>G polymorphism was genotyped using Sequenom MassArray. The association between this variant and the pain phenotypes was tested using linear regression. The 118A>G variant was associated significantly with the amount of oxycodone requested for adequate analgesia (P=0.001, β=0.016). Collectively, oxycodone consumption was highest in individuals having the GG genotype (0.16 mgkg(-1)), lowest for the AA genotype-group (0.12 mg kg(-)¹), and moderate for the AG genotype-group (0.13 mg kg(-)¹). Furthermore, the G allele was associated with higher postoperative baseline pain ratings (P=0.001, β=0.44). No evidence of association with other pain phenotypes examined was observed.
    The journal of pain : official journal of the American Pain Society. 09/2014;
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    ABSTRACT: This review evaluates trials of antidepressants for acute and chronic postsurgical pain.
    Anesthesiology 09/2014; 121(3):591-608. · 5.16 Impact Factor
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    ABSTRACT: We describe the frequency, duration, clinical characteristics, and radiologic correlates of central poststroke pain (CPSP) in young ischemic stroke survivors in a prospective study setting.
    Neurology 08/2014; · 8.25 Impact Factor
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    ABSTRACT: Are antiepileptic drugs associated with reduced pain intensity in patients with neuropathic pain or fibromyalgia?
    JAMA The Journal of the American Medical Association 07/2014; 312(2):182-3. · 29.98 Impact Factor
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    ABSTRACT: This article presents general considerations discussed at an IMMPACT consensus meeting regarding proof-of-concept (POC) clinical trials and major POC trial designs and their advantages and limitations when used to evaluate chronic pain treatments. Abstract Proof-of-concept (POC) clinical trials play an important role in developing novel treatments and determining whether existing treatments may be efficacious in broader populations of patients. The goal of most POC trials is to determine if a treatment is likely to be efficacious for a given indication and thus if it is worth investing the financial resources and participant exposure necessary for a confirmatory trial of that intervention. A challenge of designing POC trials is obtaining sufficient information to make this important go/no-go decision in a cost effective manner. An IMMPACT consensus meeting was convened to discuss design considerations for POC trials in analgesia with a focus on maximizing power with limited resources and participants. We present general design aspects to consider including patient population, active comparators and placebos, study power, pharmacokinetic-pharmacodynamic relationships, and minimization of missing data. Efficiency of single dose studies for treatments with rapid onset is discussed. The trade-off between parallel-group and cross-over designs with respect to overall sample sizes, trial duration, and applicability is summarized. The advantages and disadvantages of more recent trial designs including (1) N-of-1 designs, (2) enriched designs, (3) adaptive designs, and (4) sequential parallel comparison designs are summarized and recommendations for consideration are provided. More attention to identifying efficient yet powerful designs for POC clinical trials of chronic pain treatments may increase the percentage of truly efficacious pain treatments that are advanced to confirmatory trials while decreasing the percentage of ineffective treatments that continue to be evaluated rather than abandoned.
    Pain 05/2014; · 5.64 Impact Factor
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    ABSTRACT: Abstract Twenty years ago, the main barriers to successful cancer pain management were poor assessment by physicians, and patients' reluctance to report pain and take opioids. Those barriers are almost exactly the same today. Cancer pain remains under-treated; in Europe, almost three-quarters of cancer patients experience pain, and almost a quarter of those with moderate to severe pain do not receive any analgesic medication. Yet it has been suggested that pain management could be improved simply by ensuring that every consultation includes the patient's rating of pain, that the physician pays attention to this rating, and a plan is agreed to increase analgesia when it is inadequate. After outlining current concepts of carcinogenesis in some detail, this paper describes different methods of classifying and diagnosing cancer pain and the extent of current under-treatment. Key points are made regarding cancer pain management. Firstly, the pain may be caused by multiple different mechanisms and therapy should reflect those underlying mechanisms - not simply based on pain intensity, as recommended by the WHO three-step ladder. Secondly, a multidisciplinary approach is required which combines both pharmacological and non-pharmacological treatment, such as psychotherapy, exercise therapy and electrostimulation. The choice of analgesic agent and its route of administration are considered, along with various interventional procedures and the requirements of palliative care. Special attention is paid to the treatment of breakthrough pain (particularly with fast-acting fentanyl formulations, which have pharmacokinetic profiles that closely match those of breakthrough pain episodes) and chemotherapy-induced neuropathic pain, which affects around one third of patients who receive chemotherapy. Finally, the point is made that medical education should place a greater emphasis on pain therapy, both at undergraduate and postgraduate level.
    Current Medical Research and Opinion 05/2014; · 2.37 Impact Factor
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    ABSTRACT: Pregabalin (PRG) and gabapentin (GBP) are used in the treatment of neuropathic pain and epilepsy, and PRG also in generalized anxiety disorder. There is increasing evidence that PRG possesses considerable abuse potential. PRG may have a higher addiction potential than GBP due to its rapid absorption and faster onset of action. Our objective is to estimate the proportion of all PRG- and GBP-related fatalities attributable to PRG and GBP abuse. We investigated all medico-legal death cases in Finland in which PRG or GBP was found in postmortem toxicology during 2010-2011. PRG was found in 316 cases and GBP in 43 cases. Drug abuse was associated with 48.1% of the PRG and 18.6% of the GBP findings. PRG poisoning accounted for 10.1% of all PRG cases and GBP poisoning for 4.7% of all GBP cases. In the drug abuser cases, PRG poisoning represented 19.1%, and GBP poisoning 12.5%. The median blood concentration of PRG was 15mg/L in the abuser group and 5.8mg/L in the other cases. For GBP, these concentrations were 12mg/L and 8.3mg/L, respectively. In the PRG abuser group, 91.4% of cases showed concomitant opioid use, while in the rest of these cases neither alcohol nor opioids were detected, but other central nervous system acting drugs were found in each abuser case. In the GBP abuser group, 87.5% of cases showed concomitant opioid use. PRG abuse with high doses is increasingly common and can be fatal when combined with opioids.
    Forensic science international. 05/2014; 241C:1-6.
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    ABSTRACT: This is an update of a Cochrane review entitled 'Carbamazepine for acute and chronic pain in adults' published in Issue 1, 2011. Some antiepileptic medicines have a place in the treatment of neuropathic pain (pain due to nerve damage). This updated review considers the treatment of chronic neuropathic pain and fibromyalgia only, and adds no new studies. The update uses higher standards of evidence than the earlier review, which results in the exclusion of five studies that were previously included. To assess the analgesic efficacy of carbamazepine in the treatment of chronic neuropathic pain and fibromyalgia, and to evaluate adverse events reported in the studies. We searched for relevant studies in MEDLINE, EMBASE and CENTRAL up to February 2014. Additional studies were sought from clinical trials databases, and the reference list of retrieved articles and reviews. Randomised, double blind, active or placebo controlled trials (RCTs) investigating the use of carbamazepine (any dose, by any route, and for at least two weeks' duration) for the treatment of chronic neuropathic pain or fibromyalgia, with at least 10 participants per treatment group. Participants were adults aged 18 and over. Two study authors independently extracted data on efficacy, adverse events, and withdrawals, and examined issues of study quality. Numbers needed to treat for an additional beneficial effect (NNT) or harmful effect (NNH) with 95% confidence intervals (CIs) were calculated from dichotomous data.We performed analysis using three tiers of evidence. First tier evidence derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for dropouts, at least 200 participants in the comparison, at least 8 weeks' duration, parallel design), second tier from data that failed to meet one or more of these criteria and were considered at some risk of bias but with adequate numbers in the comparison, and third tier from data involving small numbers of participants that was considered very likely to be biased or used outcomes of limited clinical utility, or both. Ten included studies (11 publications) enrolled 480 participants with trigeminal neuralgia, diabetic neuropathy, and post stroke pain. Nine studies used a cross-over design, and one a parallel group design. Most of the studies were of short duration, lasting four weeks or less.No study provided first or second tier evidence for an efficacy outcome. Using third tier evidence, carbamazepine generally provided better pain relief than placebo in the three conditions studied, with some indication of pain improvement over mainly the short term, but with poorly defined outcomes, incomplete reporting, and in small numbers of participants. There were too few data in studies comparing carbamazepine with active comparators to draw any conclusions.In four studies 65% (113/173) of participants experienced at least one adverse event with carbamazepine, and 27% (47/173) with placebo; for every five participants treated, two experienced an adverse event who would not have done so with placebo. In eight studies 3% (8/268) of participants withdrew due to adverse events with carbamazepine, and none (0/255) with placebo. Serious adverse events were not reported consistently; rashes were associated with carbamazepine. Four deaths occurred in patients on carbamazepine, with no obvious drug association. Carbamazepine is probably effective in some people with chronic neuropathic pain, but with caveats. No trial was longer than four weeks, had good reporting quality, nor used outcomes equivalent to substantial clinical benefit. In these circumstances, caution is needed in interpretation, and meaningful comparison with other interventions is not possible.
    Cochrane database of systematic reviews (Online) 04/2014; 4:CD005451. · 5.70 Impact Factor
  • Journal of pain and symptom management 03/2014; · 2.42 Impact Factor
  • Eija A Kalso, Kaarlo Simojoki
    Nature Reviews Neurology 02/2014; · 15.52 Impact Factor
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    ABSTRACT: Abstract In many countries, the number of elderly people has increased rapidly in recent years and this is expected to continue; it has been predicted that almost a quarter of the population in the European Union will be over 65 years of age in 2035. Many elderly people suffer from chronic pain but it is regularly under-treated, partly because managing these patients is often complex. This paper outlines the extent of untreated pain in this population and the consequent reduction in quality of life, before articulating the reasons why it is poorly or inaccurately diagnosed. These include the patient's unwillingness to complain, atypical pain presentations, multiple morbidities and cognitive decline. Successful pain management depends upon accurate diagnosis, which is based upon a complete history and thorough physical examination, as well as an assessment of psychosocial functioning. Poor physician/patient communication can be improved by using standardised instruments to establish individual treatment targets and measure progress towards them. User-friendly observational instruments may be valuable for patients with dementia. In line with the widely accepted biopsychosocial model of pain, a multidisciplinary approach to pain management is recommended, with pharmacotherapy, psychological support, physical rehabilitation and interventional procedures available if required. Declining organ function and other physiological changes require lower initial doses of analgesics and less frequent dosing intervals, and the physician must be aware of all medications that the patient is taking, in order to avoid drug/drug interactions. Non-adherence to treatment is common, and various strategies can be employed to improve it; involving the elderly patient's caregivers and family, using medication systems such as pill-boxes, or even sending text messages. In the long term, the teaching of pain medicine needs to be improved - particularly in the use of opioids - both at undergraduate level and after qualification.
    Current Medical Research and Opinion 01/2014; · 2.37 Impact Factor
  • JAMA The Journal of the American Medical Association 01/2014; 311(1):90-2. · 29.98 Impact Factor
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    BMJ (online) 01/2014; 348:g1490. · 17.22 Impact Factor
  • Eija Kalso
    Scandinavian Journal of Pain 01/2014;
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    ABSTRACT: In 2010, a quarter of direct healthcare cost in Europe were spent on brain diseases. The importance of preventing and treating brain diseases and maintaining of functional capacity of the brain will increase in our society with ageing population and with increasing cognitive requirements of modern working life. Public funding of basic and clinical neuroscience has, however, frozen to levels achieved years ago, clinical research of brain diseases being at a particular risk. Research projects directed to prevention, treatment, and rehabilitation of brain diseases will pay off, also when assessed by economic measures.
    01/2014; 130(17):1721-30.
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    ABSTRACT: Background and aims Thoracotomies can cause severe pain, which persists in 21–67% of patients. We investigated whether NSAID + intravenous patient-controlled analgesia (IV-PCA) with morphine is an efficacious alternative to thoracic epidural analgesia (TEA). We also wanted to find out whether an extended controlled pain management protocol within a clinical study can decrease the incidence of persistent post-thoracotomy pain. Methods Thirty thoracotomy patients were randomized into 3 intervention groups with 10 patients in each. G1: preoperative diclofenac 75 mg orally + 150 mg/24 h IV for 44 h, then PO; G2: valdecoxib 40 mg orally + parecoxib 80 mg/24 h IV for 44 h, then PO. IV-PCA morphine was available in groups 1 and 2 during pleural drainage, and an intercostal nerve block at the end of surgery was performed; G3: paracetamol + patient controlled epidural analgesia (PCEA) with a background infusion of bupivacaine with fentanyl. After PCA/PCEA oxycodone PO was provided when needed. These patients were contacted one week, 3 and 6 months after discharge. Patients (N = 111) not involved in the study were treated according to hospital practice and served as a control group. The control patients’ data from the perioperative period were extracted, and a prospective follow-up questionnaire at 6 months after surgery similar to the intervention group was mailed. Results The intended sample size was not reached in the intervention group because of the global withdrawal of valdecoxib, and the study was terminated prematurely. At 6 months 3% of the intervention patients and 24% of the control patients reported persistent pain (p < 0.01). Diclofenac and valdecoxib provided similar analgesia, and in the combined NSAID group (diclofenac + valdecoxib) movement-related pain was milder in the PCEA group compared with the NSAID group. The duration of pain after coughing was shorter in the PCEA group compared with the NSAID + IV-PCA group. The only patient with persistent pain at 6 months postoperatively had a considerably longer duration of pain after coughing than the other Study patients. The patients with mechanical hyperalgesia had more pain on movement. Conclusions Both PCEA and NSAID + IV-PCA morphine provided sufficient analgesia with little persistent pain compared with the incidence of persistent pain in the control group. High quality acute pain management and follow-up continuing after discharge could be more important than the analgesic method per se in preventing persistent post-thoracotomy pain. In the acute phase the measurement of pain when coughing and the duration of pain after coughing could be easy measures to recognize patients having a higher risk for persistent post-thoracotomy pain. Implications To prevent persistent post-thoracotomy pain, the extended protocol for high quality pain management in hospital covering also the sub-acute phase at home, is important. This study also provides some evidence that safe and effective alternatives to thoracic epidural analgesia do exist. The idea to include the standard “as usual” care patients as a control group and to compare them with the intervention patients provides valuable information of the added value of being a study patient, and deserves further consideration in future studies.
    Scandinavian Journal of Pain 01/2014;
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    ABSTRACT: Catechol-O-methyltransferase (COMT) metabolizes catecholamines in different tissues. Polymorphisms in COMT gene can attenuate COMT activity and increase sensitivity to pain. Human studies exploring the effect of COMT polymorphisms on pain sensitivity have mostly included small, heterogeneous samples and have ignored several important single nucleotide polymorphisms (SNPs). This study examines the effect of COMT polymorphisms on experimental and postoperative pain phenotypes in a large ethnically homogeneous female patient cohort. Intensity of cold (+2-4°C) and heat (+48°C) pain and tolerance to cold pain were assessed in 1,000 patients scheduled for breast cancer surgery. Acute postoperative pain and oxycodone requirements were recorded. Twenty-two COMT SNPs were genotyped and their association with six pain phenotypes analyzed with linear regression. There was no association between any of the tested pain phenotypes and SNP rs4680. The strongest association signals were seen between rs165774 and heat pain intensity as well as rs887200 and cold pain intensity. In both cases, minor allele carriers reported less pain. Neither of these results remained significant after strict multiple testing corrections. When analyzed further, the effect of rs887200 was, however, shown to be significant and consistent throughout the cold pressure test. No evidence of association between the SNPs and postoperative oxycodone consumption was found. SNPs rs887200 and rs165774 located in the untranslated regions of the gene had the strongest effects on pain sensitivity. Their effect on pain is described here for the first time. These results should be confirmed in further studies and the potential functional mechanisms of the variants studied.
    Anesthesiology 12/2013; 119(6):1422-33. · 5.16 Impact Factor
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    ABSTRACT: This article describes the methods and results of the early part (experimental pain tests and postoperative analgesia) of a study that assesses genetic and other factors related to acute pain and persistent pain after treatment of breast cancer in a prospective cohort of 1,000 women. One thousand consenting patients were recruited to the study. Before surgery (breast resection or mastectomy with axillary surgery), the patients filled in questionnaires about health, life style, depression (Beck Depression Inventory), and anxiety (State-Trait Anxiety Inventory). They were also exposed to experimental tests measuring heat (43° and 48°C, 5 s) and cold (2-4°C) pain intensity and tolerance. Anesthesia was standardized with propofol and remifentanil, and postoperative analgesia was optimized with i.v. oxycodone. The patients showed significant interindividual variation in heat and cold pain sensitivity and cold pain tolerance. There was a strong correlation between the experimental pain measures across the tests. Presence of chronic pain, the number of previous operations, and particularly state anxiety were related to increased pain sensitivity. Previous smoking correlated with decreased heat pain sensitivity. These factors explained 4-5% of the total variance in pain sensitivity in these tests. Oxycodone consumption during 20 h was significantly higher in patients who had axillary clearance. Oxycodone consumption had only a weak correlation with the experimental pain measures. Contact heat and cold pressure tests identify variability in pain sensitivity which is modified by factors such as anxiety, chronic pain, previous surgery, and smoking. High levels of anxiety are connected to increased pain sensitivity in experimental and acute postoperative pain.In a study of 1,000 women undergoing breast surgery for cancer, a small portion of the variance in preoperative response to noxious heat and cold testing could be explained by anxiety, the presence of chronic pain, and the number of previous operations. There was a weak correlation between response to experimental pain testing and acute postoperative pain, with largely similar predictive factors across both.
    Anesthesiology 12/2013; 119(6):1410-21. · 5.16 Impact Factor

Publication Stats

9k Citations
1,062.45 Total Impact Points


  • 2003–2014
    • Haukeland University Hospital
      • Department of Anesthesia and Intensive Care
      Bergen, Hordaland, Norway
    • University of California, San Francisco
      San Francisco, California, United States
  • 1990–2014
    • University of Helsinki
      • • Faculty of Medicine
      • • Institute of Biomedicine
      • • Division of Pharmacology and Toxicology
      • • Department of Physiology
      • • Department of Anaesthesia
      Helsinki, Southern Finland Province, Finland
  • 1982–2014
    • Helsinki University Central Hospital
      • • Department of Psychiatry
      • • Department of Oncology
      • • Department of Clinical Pharmacology
      • • Surgical Hospital
      Helsinki, Southern Finland Province, Finland
  • 2013
    • Boston Children's Hospital
      Boston, Massachusetts, United States
    • University of Turku
      • Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine
      Turku, Western Finland, Finland
    • Finnish Institute of Occupational Health
      Helsinki, Southern Finland Province, Finland
  • 1998–2013
    • University of Oxford
      • • Nuffield Department of Clinical Neurosciences
      • • Nuffield Division of Anaesthetics (NDA)
      Oxford, ENG, United Kingdom
  • 2011
    • Central Hospital Central Finland
      Jyväskylä, Province of Western Finland, Finland
  • 2008
    • Uppsala University Hospital
      Uppsala, Uppsala, Sweden
  • 2005
    • University of Bergen
      • Department of Surgical Sciences
      Bergen, Hordaland Fylke, Norway
  • 2004
    • Turku University Hospital
      Turku, Province of Western Finland, Finland
  • 1999
    • McGill University
      • Department of Anesthesia
      Montréal, Quebec, Canada
  • 1997
    • Åbo Akademi University
      • Department of Biology
      Turku, Province of Western Finland, Finland
  • 1996
    • Vaasa Central Hospital
      Vaasa, Province of Western Finland, Finland