Staffan Eksborg

Karolinska Institutet, Сольна, Stockholm, Sweden

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Publications (212)748.81 Total impact

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    ABSTRACT: A phase Ia/b dose-escalation study was performed to characterize the safety, efficacy and pharmacokinetic properties of the oral small molecule insulin-like growth factor-1-receptor pathway modulator AXL1717 in patients with advanced solid tumors. This was a prospective, single-armed, open label, dose-finding phase Ia/b study with the aim of single day dosing (phase Ia) to define the starting dose for multi-day dosing (phase Ib), and phase Ib to define and confirm recommended phase II dose (RP2D) and if possible maximum tolerated dose (MTD) for repeated dosing. Phase Ia enrolled 16 patients and dose escalations up to 2900 mg BID were successfully performed without any dose limiting toxicity (DLT). A total of 39 patients were treated in phase Ib. AXL1717 was well tolerated with neutropenia as the only dose-related, reversible, DLT. RP2D dose was found to be 390 mg BID for four weeks. Some patients, mainly with NSCLC, demonstrated signs of clinical benefit, including four partial tumor responses (one according to RECIST and three according to PET). The 15 patients with NSCLC with treatment duration longer than two weeks with single agent AXL1717 in third or fourth line of therapy showed a median progression-free survival of 31 weeks and overall survival of 60 weeks. Down-regulation of IGF-1R on granulocytes and increases of free serum levels of IGF-1 were seen in patients treated with AXL1717. AXL1717 had an acceptable safety profile and demonstrated promising efficacy in this heavily pretreated patient cohort, especially in patients with NSCLC. RP2D was concluded to be 390 mg BID for four weeks. Trial number is NCT01062620.
    Acta oncologica (Stockholm, Sweden) 07/2015; DOI:10.3109/0284186X.2015.1049290 · 3.00 Impact Factor
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    ABSTRACT: Background: Sodium selenite at high dose exerts antitumor effects and increases efficacy of cytostatic drugs in multiple preclinical malignancy models. We assessed the safety and efficacy of intravenous administered sodium selenite in cancer patients' refractory to cytostatic drugs in a phase I trial. Patients received first line of chemotherapy following selenite treatment to investigate altered sensitivity to these drugs and preliminary assessment of any clinical benefits. Materials and methods: Thirty-four patients with different therapy resistant tumors received iv sodium selenite daily for consecutive five days either for two weeks or four weeks. Each cohort consisted of at least three patients who received the same daily dose of selenite throughout the whole treatment. If 0/3 patients had dose-limiting toxicities (DLTs), the study proceeded to the next dose-level. If 2/3 had DLT, the dose was considered too high and if 1/3 had DLT, three more patients were included. Dose-escalation continued until the maximum tolerated dose (MTD) was reached. MTD was defined as the highest dose-level on which 0/3 or 1/6 patients experienced DLT. The primary endpoint was safety, dose-limiting toxic effects and the MTD of sodium selenite. The secondary endpoint was primary response evaluation. Results and conclusion: MTD was defined as 10.2 mg/m(2), with a calculated median plasma half-life of 18.25 h. The maximum plasma concentration of selenium from a single dose of selenite increased in a nonlinear pattern. The most common adverse events were fatigue, nausea, and cramps in fingers and legs. DLTs were acute, of short duration and reversible. Biomarkers for organ functions indicated no major systemic toxicity. In conclusion, sodium selenite is safe and tolerable when administered up to 10.2 mg/m(2) under current protocol. Further development of the study is underway to determine if prolonged infusions might be a more effective treatment strategy.
    Nutrients 06/2015; 7(6):4978-4994. DOI:10.3390/nu7064978 · 3.27 Impact Factor
  • Peter G Larsson · Staffan Eksborg · Per-Arne Lönnqvist ·
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    ABSTRACT: Clonidine has been advocated as a valid alternative for premedication in children but one of the few limitations is its association with reduced heart rate (HR), which thus raises the question of the safety of clonidine as premedication in children. The aim of this study was to investigate the incidence of bradycardia in children premedicated with oral or intravenous clonidine as compared to children not receiving pharmacologic premedication. An open, nonrandomized, observational study design was used. During the preoperative assessment visit the children were prescribed no premedication, intravenous or oral clonidine. On arrival to the operating room (OR) HR was recorded by connecting the patient to standard monitoring with pulseoximetry and/or Electrocardiogram. The primary outcome measure was the number of patients with a HR below 85% of the lower limit of the normal range (1st centile), which was defined as bradycardia that might need clinical intervention. One thousand five hundred and seven patients were included in the analysis. 600 and 85 patients did not receive any premedication (Group 0), 305 patients received iv Clonidine (Group CIV), and 517 patients were given oral Clonidine (Group CPO). One patient in Group 0 (0.15%; 95% CI: 0-0.81%), none in Group CIV (0%; 95% CI: 0.00-0.98%), and 5 patients in Group CPO (0.97%; 95% CI: 0.31-2.24%) were observed to have a HR of <85% of the 1st centile. The incidence of bradycardia following oral or intravenous premedication with clonidine in a pediatric population scheduled for anesthesia is low. Thus, it does not appear rational to refrain from using clonidine as premedication in children only due to fear of bradycardia. © 2015 John Wiley & Sons Ltd.
    Pediatric Anesthesia 06/2015; 25(9). DOI:10.1111/pan.12695 · 1.85 Impact Factor
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    ABSTRACT: Adult meta-analysis has identified dexmedetomidine as a potentially useful adjunct to prolong the duration of peripheral nerve blocks. However, no data exist regarding the adjuvant use of dexmedetomidine in the setting of pediatric peripheral nerve blocks. Using a prospective, randomized, double-blind design, children (1½-8 years, ASA 1-2) scheduled for outpatient inguinal hernia repair were randomized to receive either an ultrasound-guided ilioinguinal/iliohypogastric nerve block (IINB) with plain ropivacaine 0.197% (Group LA; n = 21) or ropivacaine 0.197% with adjunct dexmedetomidine 0.3 μg·kg(-1) (Group LAD; n = 22). The primary endpoint of the study was time to first postoperative administration of supplemental analgesia (FPASA) triggered by a pain score ≥4 (CHIPPS or NRS scale). Intention-to-treat (ITT) analysis was decided as the primary statistical analysis of the data. The median time to FPASA was prolonged by 88% following the use of adjunct dexmedetomidine (4.0 and 7.6 h in group LA and LAD, respectively) (P = 0.0717). Patients in Group LA displayed a significantly higher number of patients with a CHIPPS score ≥4 in the PACU (7 vs 0; P = 0.0029) as well as a higher incidence of PAED (4 vs 0; P = 0.0485) when compared to patients in Group LAD. No adverse events were recorded in any of the study groups. The use of dexmedetomidine as an adjunct to an IINB resulted in reduced incidences of CHIPPS pain scores ≥4 and PAED scores of ≥11 during early recovery following pediatric inguinal hernia repair. In addition, the use of adjunct dexmedetomidine was associated with a prolongation of the period to first supplemental analgesia demand. The results of the present exploratory study must be viewed as preliminary and need further validation by future larger sized studies and/or meta-analysis. © 2015 John Wiley & Sons Ltd.
    Pediatric Anesthesia 06/2015; 25(9). DOI:10.1111/pan.12704 · 1.85 Impact Factor
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    R El Edelbi · S Eksborg · S Lindemalm ·
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    ABSTRACT: Getting children to swallow tablets and capsules is a challenge and factors that influence their ability to swallow include taste, smell and texture. The aim of this study was to explore how well paediatric patients tolerated and accepted the MedCoat(®) in-situ coating for tablets and capsules. A non-randomised intervention study was performed at the Astrid Lindgren Children's Hospital, Karolinska University Hospital, Sweden. We identified 78 paediatric patients - 43 females and 35 males - who had problems swallowing tablets and capsules and evaluated their abilities with questionnaires. The median age of the patients was nine-years-old and the range was two to 18-years-old. Swallowing ability and palatability was improved by in-situ coating. The results showed that 66 out of 77 paediatric patients (86%, 95% confidence interval: 76 to 93%) were able to take the drugs they had been prescribed after in-situ coating. Swallowing improved in 87% of cases and palatability improved in 85%. A study of 77 paediatric patients with a median age of nine years, and a range of two to 18 years, found that 86% were able to take the tablets and capsules they had been prescribed after they were coated with the MedCoat. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Acta Paediatrica 05/2015; 104(9). DOI:10.1111/apa.13041 · 1.67 Impact Factor
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    Ranaa El Edelbi · Staffan Eksborg · Synnöve Lindemalm ·
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    ABSTRACT: Abstract Aim: To study tolerance and acceptance in pediatric patients for MedCoat® in-situ coating of tablets/capsules. Methods: A non-randomized intervention study was performed at Astrid Lindgren Children´s Hospital, Karolinska University Hospital. A total number of 78 pediatric patients were included in the study (43 females and 35 males). The ability of patients (median age 9 years; range 2-17 years) to swallow tablets/capsules was evaluated by questionnaires. Results: Swallowing ability and palatability was improved by in-situ coating. Sixty-six out of 77 pediatric patients (86%; 95%CI: 76 to 93%) reported facilitated drug treatment after in-situ coating. Conclusion: Drug therapy was facilitated and in-situ coating was well accepted and tolerated for most pediatric patients.
    Barnveckan 2015, , Stockholm; 04/2015
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    ABSTRACT: Postoperative nausea and vomiting (PONV) still represents one of the most distressing side effects of anaesthesia and surgery. Clinical risk scores e.g. Apfel score is today commonly used to identify patients at risk. We found in a previous study different platelet counts in patients with and without PONV. The aim of the present explorative study was to assess whether females experiencing PONV after breast surgery had any difference in preoperative platelet count and/or volume assessed by platelet testing. All women scheduled for elective breast cancer surgery at Danderyds Hospital, Stockholm, Sweden, during one year were asked to participate in this study. Occurrence of PONV during the 24 first postoperative hours was studied. Blood samples collected preoperatively were analysed by platelet counts determined by impedance (PTLi) and optical (PTLo) methods, mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT). Platelet data were compared between patients with and without PONV. In all 183 patients were included in the study, 65 (35%) suffered from PONV, increasing incidence with increased risk score 4 out 5 with 4 risk factors. Mean platelet count was 266 [114-538], mean platelet volume 8.59 [5.94-12.1] and mean platelet weight 16.17 [14.2-25.9] but no differences in any platelet test variables studied were found between patients with or without PONV or with increasing risk factors. One third of patients' experienced PONV, increased incidence associated to Apfel score but platelet numbers and simple platelet test provided no additional information around risk for PONV. Copyright © 2015. Published by Elsevier Ltd.
    International Journal of Surgery (London, England) 04/2015; 18. DOI:10.1016/j.ijsu.2015.03.006 · 1.53 Impact Factor
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    ABSTRACT: Administration of local anesthetics by a surgically placed wound catheter has recently been shown to reduce the need for postoperative morphine administration in extremely preterm infants undergoing ductus ligation. The primary aim of this randomized safety study was to define the plasma levels of levobupivacaine (LB) following two different intermittent infusion regimens. Eighteen preterm infants 23-27 gestational weeks, median birthweight 721 g scheduled for ductus ligation were included in the study. All patients were anesthetized according to a standardized protocol based on high-dose fentanyl (25-50 μg·kg(-1) ). Before skin closure, a subcutaneous catheter was inserted into the wound. The patients were randomized to receive one of the two intermittent infusion regimens: Group BII: Initial bolus plus early start of the intermittent infusion or Group DII: No bolus plus delayed start (8 h) of the intermittent infusion. Blood samples for determination of LB plasma concentrations were obtained on six occasions during the 24-h postoperative observation period, as well as hourly postoperative pain assessments using the Echelle Douleur Inconfort Noveau (EDIN) pain scale. Plasma concentrations of LB ranged from 0.094 to 1.682 μg·ml(-1) and 0 to 0.549 μg·ml(-1) in group BII and DII, respectively. Both regimens were associated with low postoperative EDIN pain scores (24 h median of 0 and 1 in group BII and DII, respectively). No signs of systemic local anesthetic toxicity were noted. The two studied intermittent infusion regimens were associated with plasma levels below potentially toxic levels and were both associated with adequate postoperative pain scores. © 2015 John Wiley & Sons Ltd.
    Pediatric Anesthesia 03/2015; 25(7). DOI:10.1111/pan.12634 · 1.85 Impact Factor
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    ABSTRACT: - Copyright © 2014, Ferrata Storti Foundation.
    Haematologica 12/2014; 100(4). DOI:10.3324/haematol.2014.116111 · 5.81 Impact Factor
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    ABSTRACT: Background 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. AimTo determine the maximal plasma concentration and the exposure of ketorolac during the first 30h following LIA in hip arthroplasty. Methods Thirteen patients scheduled for primary total hip arthroplasty with LIA (ropivacaine 200mg, ketorolac 30mg and epinephrine 0.5mg in a volume of 106ml) were included. Plasma concentration of ketorolac was quantified by liquid chromatography-mass spectrometry. In addition, we assessed the effect of increasing age and decreasing glomerular filtration rate on the maximal plasma concentration and the total exposure to ketorolac during 30h. ResultsThe range of the maximal plasma concentration, 0.3-2.2mg/l, was detected 30min-4h after completing the infiltration. Similar plasma levels have been reported after intramuscular injection of the same dose of ketorolac to healthy elderly volunteers. Conclusion Exposure to ketorolac after LIA may be comparable to an intramuscular injection of the same dose. Decision of dose reduction should be based on clinical assessment of risk factors.
    Acta Anaesthesiologica Scandinavica 07/2014; 58(9). DOI:10.1111/aas.12371 · 2.32 Impact Factor
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    ABSTRACT: 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.
    Anesthesia & Analgesia 07/2014; 119(4). DOI:10.1213/ANE.0000000000000364 · 3.47 Impact Factor
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    ABSTRACT: Background We have recently described a bi-directional bulk flow of cerebrospinal fluid (CSF) (coined ‘the CSF rebound mechanism’) after the use of high-volume caudal block in infants, which may explain the secondary longitudinal spread of the block. If important the initial cephalad transfer of CSF should be of such a magnitude that it would cause a transient reduction in cerebral blood flow (CBF) and cerebral oxygenation. The primary aim of this observational study was to delineate the magnitude of the reduction of CBF velocity (CBFV) associated with high-volume caudal block in infants.
    BJA British Journal of Anaesthesia 06/2014; 113(4). DOI:10.1093/bja/aeu161 · 4.85 Impact Factor
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    ABSTRACT: Bortezomib is a proteasome inhibitor currently studied in clinical trials of childhood cancers. So far, no side effects on bone growth have been reported in treated children. However, bortezomib was recently found to induce apoptosis in growth plate chondrocytes and impair linear bone growth in treated mice. We hypothesize that [Gly(14)]-humanin (HNG), a 24-amino acid synthetic antiapoptotic peptide, can prevent bortezomib-induced bone growth impairment. Mice with human neuroblastoma or medulloblastoma tumor xenografts (9-13 animals/group) received one 2-week cycle (2 injections/week) of bortezomib (0.8mg/kg or 1.0mg/kg), or HNG (1 µg/mouse), or the combination of HNG/bortezomib, or vehicle. Cultures of human growth plate cartilage, chondrogenic- and cancer cell lines, and immunohistochemistry for detection of proapoptotic proteins were also used. Statistical significance was evaluated by two-sided Mann-Whitney U test or by parametric or nonparametric analysis of variance. Bortezomib efficiently blocked the proteasome and induced pronounced impairment of linear bone growth from day 0 to day 13 (0.09mm/day, 95% confidence interval [CI] = 0.07 to 0.11mm/day; vs 0.19mm/day, 95% CI = 0.15 to 0.23mm/day in vehicle; P < .001), an effect significantly prevented by the addition of HNG (0.15mm growth/day, 95% CI = 0.14 to 0.16mm/day; P < .001 vs bortezomib only; P = 0.03 vs vehicle). Bortezomib was highly toxic when added to cultures of human growth plate cartilage, with markedly increased apoptosis compared with control (P < .001). However, when combining with HNG, bortezomib-induced apoptosis was entirely prevented, as was Bax and PARP activation. Bortezomib delayed tumor growth, and HNG did not interfere with the anticancer effect when studied in human tumor xenografts or cell lines. HNG prevents bortezomib-induced bone growth impairment without interfering with bortezomib's desired anticancer effects.
    Journal of the National Cancer Institute 03/2014; 106(3). DOI:10.1093/jnci/djt459 · 12.58 Impact Factor
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    ABSTRACT: Plasmodium falciparum malaria is treated with 25 mg/kg of chloroquine (CQ) irrespective of age. Theoretically, CQ should be dosed according to body surface area (BSA). The effect of dosing CQ according to BSA has not been determined but doubling the dose per kg doubled the efficacy of CQ in children aged <15 years infected with P. falciparum carrying CQ resistance causing genes typical for Africa. The study aim was to determine the effect of age on CQ concentrations. Day 7 whole blood CQ concentrations were determined in 150 and 302 children treated with 25 and 50 mg/kg, respectively, in previously conducted clinical trials. CQ concentrations normalised for the dose taken in mg/kg of CQ decreased with decreasing age (p<0.001). CQ concentrations normalised for dose taken in mg/m(2) were unaffected by age. The median CQ concentration in children aged <2 years taking 50 mg/kg and in children aged 10-14 years taking 25 mg/kg were 825 (95% confidence interval [CI] 662-988) and 758 (95% CI 640-876) nmol/l, respectively (p = 0.67). The median CQ concentration in children aged 10-14 taking 50 mg/kg and children aged 0-2 taking 25 mg/kg were 1521 and 549 nmol/l. Adverse events were not age/concentration dependent. CQ is under-dosed in children and should ideally be dosed according to BSA. Children aged <2 years need approximately double the dose per kg to attain CQ concentrations found in children aged 10-14 years. Clinical trials assessing the efficacy of CQ in Africa are typically performed in children aged <5 years. Thus the efficacy of CQ is typically assessed in children in whom CQ is under dosed. Approximately 3 fold higher drug concentrations can probably be safely given to the youngest children. As CQ resistance is concentration dependent an alternative dosing of CQ may overcome resistance in Africa.
    PLoS ONE 01/2014; 9(1):e86801. DOI:10.1371/journal.pone.0086801 · 3.23 Impact Factor
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    Staffan Eksborg ·

  • Christina Egnell · Staffan Eksborg · Lena Grahnquist ·
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    ABSTRACT: Background: The aim of this study was to report on the clinical outcome and safety of jejunostomy tube feeding used in our clinical setting for more than 14 years. Material and methods: A retrospective study of all children who underwent a surgical catheter jejunostomy placement between July 1996 and March 2010 was conducted. Data were collected regarding the outcome and complications. Results: Thirty-three children (14 girls) were included. The median age at the time of primary surgery was 1.43 years (range, 0.15-17.7 years), and the median time of follow-up was 2.34 years (range, 0.27-12.6 years). Seventeen children were severely neurologically impaired (NI). Surgical insertion of a jejunostomy tube was performed due to 1 or more of the following indications: gastroesophageal reflux disease (GERD), failure to thrive, recurrent pneumonia, esophageal disease, or oral feeding difficulties. The effect of the indications showed a reduction in GERD and pneumonia. Feeding difficulties also decreased. Weaning was possible in 12 of 16 children without NI but in only 2 of 17 with NI. Major complications requiring surgical reoperation affected 8 children. No mortality was related to the jejunostomy feeding catheter. Conclusion: In selected cases, surgically placed jejunostomy tubes for feeding in children is an effective and safe method to overcome GERD, feeding difficulties, or recurrent pneumonia without major surgery.
    Journal of Parenteral and Enteral Nutrition 05/2013; 38(5). DOI:10.1177/0148607113489832 · 3.15 Impact Factor
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    ABSTRACT: Background: Drug-induced nausea and vomiting, both post-operatively and following chemotherapy, is often distressing for the patients. Our clinical impression is that certain patients are not prone to but instead protected against both post-operative and chemotherapy-induced nausea and vomiting (CINV). If support for this hypothesis could be generated, it might be easier to identify such patients as low-risk patients and judge all other patients as high-risk patients by default. Methods: All patients scheduled for breast cancer surgery at Danderyd Hospital, Stockholm, Sweden during 1 year (March 2003-March 2004) were asked to participate in this prospective, observational study. A number of women went on to receive adjuvant chemotherapy. Post-operatively, patients were assessed for 24 h with regard to the occurrence of post-operative nausea and vomiting (PONV). CINV was assessed for 5 days after start of chemotherapy. Results: A total of 275 women were included, 33% were classified as PONV and 67% as non-PONV. Sixty-one of the 275 women included were later subjected to adjuvant chemotherapy. In the non-PONV group, 95% of the patients did not experience CINV, whereas the association between PONV and subsequent CINV was only 38%. Conclusions: A substantially stronger interrelationship was found between non-PONV and non-CINV than between both PONV and CINV. This may suggest that certain patients, instead of being prone to nausea and vomiting, in fact in some way are protected against these unpleasant side effects.
    Acta Anaesthesiologica Scandinavica 01/2013; 57(6). DOI:10.1111/aas.12053 · 2.32 Impact Factor
  • S Lundeberg · N Stephanson · C-O Stiller · S Eksborg ·
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    ABSTRACT: 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. Fifteen full-term neonates (eight females) from 37 gestational weeks at birth and scheduled for elective surgery were included in the trial. Their median age was 3 days (range 1-18 days). Ketobemidone hydrochloride was administered as a single intravenous bolus dose, and ketobemidone concentrations were measured by liquid chromatography-mass spectrometry over 10 h. Pharmacokinetic parameters were calculated with standard compartmental methods. The median (range) values for ketobemidone clearance, apparent volume of distribution, volume of central compartment, distribution half-life and elimination half-life were 0.46 (0.23-0.84) l/h/kg, 4.64 (3.50-7.31) l/kg, 1.71 (0.16-3.47) l/kg, 2.85 (1.04-10.78) min and 7.26 (3.5-11.3) h. Compared with our previous study in children older than 1 year of age, the elimination of ketobemidone appeared to be slower in full-term neonates. Despite a low pharmacokinetic variability of ketobemidone as observed in the present neonatal patient population, we recommend individualizing the dose of ketobemidone based on observations of analgesic efficacy.
    Acta Anaesthesiologica Scandinavica 07/2012; 56(8):1026-31. DOI:10.1111/j.1399-6576.2012.02726.x · 2.32 Impact Factor
  • Peter Larsson · Staffan Eksborg · Per-Arne Lönnqvist ·
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    ABSTRACT: OBJECTIVES/AIM: To investigate whether nasal aerosol clonidine can reduce the onset time of preoperative sedation. Premedication is common in the pediatric population, but the optimal agent and administration route is still a matter of debate. Clonidine has many beneficial effects in the perioperative period. Clonidine nasal drops produce a similar sedative effect as after oral administration but do not reduce the onset time. Nasal aerosol administration of drugs is generally more effective than drops and an option to decrease the onset time of clonidine. Pediatric ASA status 1 and 2 patients were randomized to receive placebo (P), clonidine 3-4 μg kg(-1) (C4), or clonidine 7-8 μg kg(-1) (C7) as a nasal aerosol. Acceptance of administration, pre- and postoperative sedation, and adverse events were assessed. A total of 60 patients were enrolled with a median age of 3.5 years (range 0.7-6.9) and median weight of 14.8 kg (range 10-25). In the C7 group, 55% of the children were found adequately sedated at 30 min as compared to 32% in the C4 group (P = 0.1202). At 45 min, adequate sedation was seen in 65% of the patients in both C4 and C7 groups, which were both found to be significantly higher compared with the placebo control group (14%) (P-values = 0.0027 and 0.0013, respectively). The postoperative sedation profile did not differ between the three study groups. Clonidine administered as nasal aerosol (3-8 μg kg(-1)) was not found to achieve adequate preoperative sedation within 30 min of administration. Despite its sedative properties, no prolongation of postoperative sedation was noted compared with placebo.
    Pediatric Anesthesia 05/2012; 22(9):877-83. DOI:10.1111/j.1460-9592.2012.03877.x · 1.85 Impact Factor
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    Helen Nygren · Staffan Eksborg ·
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    ABSTRACT: Temozolomide (TMZ) is an alkylating agent with a broad spectrum of antitumor activity, including brain tumors in children. The oral use of TMZ is hampered by the lack of a suitable galenic formulation, since the capsules of TMZ (Temodal™) are large and difficult to swallow. A powder for preparation of a TMZ solution for intravenous administration (2.5 mg/mL) has recently been approved. A possibility to use this formulation for oral administration would facilitate TMZ administration. The aim of the present study was to investigate the stability of TMZ in solutions prepared from the commercially available powder for intravenous infusion. Solutions were prepared from the intravenous formulation by dissolving the powder in water. The degradation of TMZ was studied photometrically at 330 nm in two solutions, 2.5 mg/mL at room temperature (RT; 22°C) and 1.25 mg/mL at 5°C, prepared from the intravenous formulation. More than 90% of TMZ remained intact after storage for 9 days at RT (2.5 mg/mL) and 13 weeks at 5°C (1.25 mg/mL). The high stability of a TMZ solution prepared from the powder for infusion formulation makes it suitable for oral administration. Oral use of a TMZ solution facilitates administration of the drug to patients with difficulties to swallow capsules, and enables a more flexible and precise dosing.
    03/2012; 3(1):1-3. DOI:10.4103/2229-4708.97700

Publication Stats

4k Citations
748.81 Total Impact Points


  • 2000-2015
    • Karolinska Institutet
      • • Department of Women's and Children's Health
      • • Department of Medical Biochemistry and Biophysics
      • • Department of Oncology-Pathology
      Сольна, Stockholm, Sweden
  • 1980-2015
    • Karolinska University Hospital
      • • Department of Pediatric Anesthesiology and Intensive Care
      • • Clinical Pharmacology Trial Unit
      • • Department of Oncology
      • • Endocrinology Unit
      • • Department of Clinical Pharmacology
      Tukholma, Stockholm, Sweden
  • 2007
    • Uppsala University Hospital
      Uppsala, Uppsala, Sweden
  • 2001
    • University of Helsinki
      Helsinki, Uusimaa, Finland
  • 1994-1998
    • Capio S:t Görans sjukhus
      Tukholma, Stockholm, Sweden
  • 1996
    • Aarhus University Hospital
      • Department of Clinical Biochemistry
      Aarhus, Central Jutland, Denmark
  • 1990
    • Karlstad Central Hospital
      Karlstad, Värmland, Sweden
    • Odense University Hospital
      Odense, South Denmark, Denmark
  • 1989
    • Sahlgrenska University Hospital
      Goeteborg, Västra Götaland, Sweden