S Eksborg

Karolinska University Hospital, Tukholma, Stockholm, Sweden

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Publications (184)611.23 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Acta Anaesthesiologica Scandinavica 07/2014; · 2.36 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 and analgesia. 07/2014;
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    ABSTRACT: 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; · 4.24 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.
    CancerSpectrum Knowledge Environment 03/2014; · 14.07 Impact Factor
  • Source
    Staffan Eksborg
    Journal of Drug Assessment. 09/2013; 2.
  • 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; · 2.49 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; · 2.36 Impact Factor
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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. · 2.36 Impact Factor
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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. · 2.44 Impact Factor
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    Journal of Drug Assessment. 02/2012; 1.
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    Journal of Drug Assessment. 02/2012; 1.
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    ABSTRACT: Redistribution and secondary spread after the initial injection of local anaesthetics (LAs) are important factors that contribute to the final spread of caudal block in children. However, to date, these phenomena have yet not been studied in detail. Thus, the aim of this observational study was to define patterns of secondary spread and redistribution of a caudal block by means of real-time ultrasonography scanning and cutaneous testing. Ultrasound assessment of LA spread within the caudal-epidural space and epidural pressure was followed during 15 min after initial injection (1.5 ml kg(-1), ropivacaine 0.2%) in 16 infants. At 15 min post-injection, cutaneous testing was also performed to assess the cranial dermatomal level of the block (at end-tidal sevoflurane 2.5%). The median ultrasound-assessed cranial spread was Th10 and Th8 at 0 and 15 min, respectively, and the sensory level at 15 min was Th4. The caudal injection was initially found to compress the terminal part of the dural sac, later followed by a partial re-expansion as epidural pressure was returning towards pre-injection values. An intrasegmental redistribution from the dorsal to the ventral compartment of the epidural space was also observed. Two separate patterns of secondary spread of caudal block could be observed, being horizontal intrasegmental redistribution and longitudinal cranial spread. The observed bi-directional movement of cerebrospinal fluid (coined 'the CSF rebound mechanism') does explain a major part of the difference between the initial ultrasound-assessed cranial level and the final level determined by cutaneous testing.
    BJA British Journal of Anaesthesia 02/2012; 108(4):675-81. · 4.24 Impact Factor
  • 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.
    Pharmaceutical methods. 01/2012; 3(1):1-3.
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    ABSTRACT: Intermittent breathing of oxygen-enriched air, nitrox (1:1 air:oxygen, 60.5% O2), for attendants in multiplace hyperbaric chambers should enable treatment protocols (HOPAN - hyperbaric oxygen protocol attendants' nitrox) of up to 200 minutes at 2.8 atmospheres absolute (ATA), while retaining the option of a direct decompression and exit. HOPAN with cycles of 15 minutes of nitrox breathing followed by 10 minutes of chamber air for attendants were occasionally used from 2007-2009. HOPAN vs. LTP (local treatment protocols) were evaluated via an anonymous enquiry among attendants; patients' medical records were followed six months post-HBO2 treatment (HBO2T). 88 HOPANs, with 59 chamber attendants assisting 30 patients, were documented. HOPAN duration ranged from 55-167 minutes (median 140 minutes). 31/59 attendants answered the enquiry. Perceived comfort of each protocol (HOPAN vs. LTP) by attendants was reported as equal. Symptoms, both minor (parestesias) and severe (joint pain), were reported in connection with LTP, while only one occurrence (mild joint pain) was reported in connection with HOPAN. No complications were documented among the attendants or the patients. It is suggested that nitrox breathing for chamber attendants provide flexible HBO2T for patients at 2.8 ATA for up to 200 minutes within no-decompression limits, facilitating future studies of HBO2T dosage.
    Undersea & hyperbaric medicine: journal of the Undersea and Hyperbaric Medical Society, Inc 01/2012; 39(1):605-12. · 0.59 Impact Factor
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    ABSTRACT: The aim of the present study was to validate the Mosteller formula for the estimation of body surface area (BSA) in various childhood ages. Many physiological processes including drug metabolism correlate with values for BSA. In addition, dosing of many drugs, especially drugs with low therapeutic index, for example, anti-neoplastics, are based on estimated values of BSA. Published data from measured BSA in 268 children and infants (median age: 8 month; range: 0-18 years) were compared with BSA values estimated by the Mosteller formula. Correlation between estimated and measured BSA values was performed by the Spearman rank correlation. Bias and precision were evaluated as outlined by Sheiner and Beal. Measured and estimated BSA values were compared by the Eksborg's plot. Measured values of BSA and BSA values estimated by the Mosteller formula were closely correlated (r(s) = 0.973; p < 0.0001). The formula of Mosteller had with a precision of 9.38% and underestimated BSA by 4.06%. The quotients Estimated/Measured BSA were within the range 0.9-1.1 in 71.3% of the observations, but deviation up to 35% occurred. The Mosteller formula underestimates BSA in the paediatric population and must be used with precautions because of low precision, most pronounced in neonates and infants.
    Acta Paediatrica 12/2011; 101(5):540-4. · 1.97 Impact Factor
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    ABSTRACT: The anticancer agent cisplatin (cis-diamminedichloroplatinum(II), cis-[PtCl₂(NH₃)₂]) easily undergoes ligand-exchange reactions, resulting in mainly inactive Pt complexes. This paper presents a method for selective analysis of intact cisplatin in blood using LC and UV detection. Blood samples (hematocrit: 0.22-0.52) were spiked with cisplatin (final concentrations: 2.48 × 10⁻⁷ M-9.90 × 10⁻⁶ M) and subjected to centripetal ultrafiltration. The blood ultrafiltrate was separated (loop volume: 5 μl) with a porous graphitic carbon column and a mobile phase of HEPES-buffer (pH 9.3). Prior to UV detection (344 nm), the eluate was mixed with sodium N,N-diethyldithiocarbamate (DDTC) in a microwave field (115 °C) in order to improve the UV absorptivity. Cisplatin eluted as a Pt-DDTC complex after 11.8 min. The peak area was influenced primarily by the hematocrit, the DDTC concentration, and the temperature and residence time in the microwave cavity. The method was robust and sensitive provided preparing a fresh DDTC solution each day and, at the end of a day's run, destroying DDTC remaining in the system. It offers the main advantages of high selectivity, sensitivity, and robustness, minimal sample processing, and the possibility to use small sample volumes.
    Journal of pharmaceutical and biomedical analysis 08/2011; 56(1):126-30. · 2.45 Impact Factor
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    ABSTRACT: In children, the incidence of injection pain at i.v. anaesthetic induction with Etomidate-Lipuro is low when compared with propofol mixed with lidocaine (5%). However, the incidence of involuntary myoclonic movements (MM) after induction of anaesthesia is higher compared with propofol (85% vs. 15%). In adults, the incidence of MM is reported to be significantly reduced if a small priming dose is administered immediately before the main injection of etomidate. The aim of this prospective, randomized, double-blind, placebo-controlled clinical trial was to investigate if a small priming dose of etomidate effectively can reduce the incidence of MM also in children. Eighty ASA I-II children (1-15 yr) were randomized to receive either a small priming dose of etomidate (0.03 mg kg(-1)) or a lipid emulsion placebo. A standardized induction dose of etomidate (0.3 mg kg(-1)) was administered 60 s after the priming dose. The occurrence and severity (observational score 0-3) of MM was defined as the primary endpoint of the study and was recorded during a 2 min period after induction of anaesthesia. A post hoc analysis was performed regarding the incidence of MM with respect to age. No difference in the occurrence or severity of MM was found between the two study groups, the total incidence of MM being 73.8% (95% confidence interval: 62.7-83.0%). The incidence of MM (score > 0) was found to be statistically higher in the age group 5-10 yr compared with <5 yr; and >10 yr (P=0.0008 and 0.01730, respectively). The MM scores were highest in patients aged 5-10 yr (P=0.0021). Children in the age range of 5-10 yr appear to be especially prone to react with involuntary MM after i.v. induction of anaesthesia with etomidate. The use of a small, non-sedative, priming dose did not influence the incidence of involuntary MM after i.v. induction of anaesthesia with etomidate in children 1-15 yr of age.
    BJA British Journal of Anaesthesia 06/2011; 107(2):225-8. · 4.24 Impact Factor
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    ABSTRACT: Thiosulfate may reduce cisplatin-induced ototoxicity, most likely by relieving oxidative stress and by forming inactive platinum complexes. This study aimed to determine the concentration and protective effect of thiosulfate in the cochlea after application of a thiosulfate-containing high viscosity formulation of sodium hyaluronan (HYA gel) to the middle ear prior to i.v. injection of cisplatin in a guinea pig model. The release of thiosulfate (0.1 M) from HYA gel (0.5% w/w) was explored in vitro. Thiosulfate in the scala tympani perilymph of the cochlea 1 and 3 h after application of thiosulfate in HYA gel to the middle ear was quantified with HPLC and fluorescence detection. Thiosulfate in blood and CSF was also explored. The potential otoprotective effect was evaluated by hair cell count after treatment with thiosulfate in HYA gel applied to the middle ear 3 h prior to cisplatin injection (8 mg/kg b.w.). HYA did not impede the release of thiosulfate. Middle ear administration of thiosulfate in HYA gel gave high concentrations in the scala tympani perilymph while maintaining low levels in blood, and it protected against cisplatin-induced hair cell loss. HYA gel is an effective vehicle for administration of thiosulfate to the middle ear. Local application of a thiosulfate-containing HYA gel reduces the ototoxicity of cisplatin most likely without compromising its antineoplastic effect. This provides a minimally invasive protective treatment that can easily be repeated if necessary.
    Cancer Chemotherapy and Pharmacology 05/2011; 68(6):1547-56. · 2.80 Impact Factor
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    ABSTRACT: Oral clonidine is used as premedication in children. The bioavailability of clonidine given orally in adults is 75-100% but is unknown in children. Children (3-10 years) undergoing adenotonsillectomy were administered oral clonidine 4 mcg·kg(-1) mixed with apple fruit drink as premedication. Intravenous plasma was assayed for clonidine concentration at 5, 15, 30, 45 min and 1, 2, 4, 6, 12, 18 h after administration. Clonidine plasma concentrations were determined by liquid chromatography-mass spectroscopy, and pharmacokinetic parameters were calculated using nonlinear effects mixed-effects models. Current data were pooled with published time-concentration profiles from children (n = 49) administered intravenous clonidine to determine oral bioavailability. There were eight children studied (age 3-10 years, weight 10.5-36 kg). A two-compartment model with first-order absorption and elimination was used to describe time-concentration profiles. Population parameter estimates (CV%; 95% CI), standardized to a 70-kg person, were absorption half-life (Tabs), 0.45 (85.1; 0.221-0.884) h, absorption lag time (Tlag), 0.148 (91.2; 0.002-0.316) h, Clearance (CL) 17.9 (30.3; 16-20.3) l·h(-1) per 70 kg, between compartment clearance (Q) 121 (44.3; 80.1-165) l·h(-1) per 70 kg, central volume (V1) 81.2 (71.5; 60.7-105) l·70 kg(-1), peripheral volume of distribution (V2) 113 (33.9; 91-131) l·70 kg(-1). The oral bioavailability was 55.4% (CV 6.4%; 95% CI 0.469, 0.654). Clonidine administered with an apple fruit drink displays a variable and relatively slow absorption after oral administration (T(max) 1.04 h, C(max) 0.77 mcg·l(-1)). The oral bioavailability was 55.4%, which is less than reported in adults. Consequently, higher oral doses of clonidine (per kg) are required when this formulation is used to achieve concentrations similar to those reported in adults.
    Pediatric Anesthesia 03/2011; 21(3):335-40. · 2.44 Impact Factor
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    ABSTRACT: We have previously described an ultrasonography-guided technique to block the infrapatellar nerve that is associated with an extended duration of anaesthesia. The aim of the present study was to investigate the clinical usefulness of this new technique in patients undergoing arthroscopy-assisted anterior cruciate ligament repair. Using a prospective, double-blind and placebo-controlled study design, 64 patients were randomised to get an active infrapatellar nerve block (IPNB; 10 ml levobupivacaine 0.5%; n = 31) or a sham block with isotonic saline (n = 33) as a complement to a standardised anaesthetic and analgesic regimen. Pain was recorded hourly and the proportion of patients with a pain intensity of more than 3 (numeric rating scale 0-10) during 12-24 postoperative hours was chosen as the primary end-point of the study. Duration of the block, numbers of hours spent sleeping and other secondary parameters were also recorded. The proportion of patients with a pain score of higher than 3 at rest was significantly lower in patients receiving an IPNB during postoperative hours 16-24 (P = 0.0117) as well as on muscular activity during postoperative hours 16-24 (P = 0.0039). Median block duration was 23 h (95% confidence interval 19-24 h). A significantly larger proportion of patients were asleep during the time period 13-24 h after surgery in patients given active treatment as compared to sham block (P < 0.0269). Adjunct use of an ultrasound-guided block of the infrapatellar nerve is associated with improved pain relief and an increased number of sleep hours after arthroscopy-assisted anterior cruciate ligament repair.
    European Journal of Anaesthesiology 03/2011; 28(7):511-8. · 2.79 Impact Factor

Publication Stats

2k Citations
611.23 Total Impact Points

Institutions

  • 1978–2014
    • Karolinska University Hospital
      • • Department of Pediatric Anesthesiology and Intensive Care
      • • Department of Oncology
      • • Department of Clinical Pharmacology
      • • Department of Hematology
      Tukholma, Stockholm, Sweden
  • 1994–2009
    • Karolinska Institutet
      • • Institutionen för klinisk neurovetenskap
      • • Institutionen för mikrobiologi, tumör- och cellbiologi
      • • Institutionen för medicin, Huddinge
      • • Enheten för anestesi
      Solna, Stockholm, Sweden
  • 2007
    • Uppsala University Hospital
      • Department of Neurology
      Uppsala, Uppsala, Sweden
    • AstraZeneca
      Tukholma, Stockholm, Sweden
  • 2005
    • Lund University
      • Department of Occupational and Environmental Medicine
      Lund, Skane, Sweden
  • 1990
    • Karlstad Central Hospital
      Karlstad, Värmland, Sweden
    • Odense University Hospital
      Odense, South Denmark, Denmark
  • 1989
    • Sahlgrenska University Hospital
      Goeteborg, Västra Götaland, Sweden