Elliot J. Krane

All Publications

• Review of Ultrasound-Guided Procedures in the Management of Chronic Pain. Anesthesiology clinics Aggarwal, A. K., Ottestad, E., Pfaff, K. E., Huai-Yu Li, A., Xu, L., Derby, R., Hecht, D., Hah, J., Pritzlaff, S., Prabhakar, N., Krane, E., D'Souza, G., Hoydonckx, Y. 2023; 41 (2): 395-470

  Abstract

  This article summarizes clinical expert recommendations and findings for the application of ultrasound-guided procedures in chronic pain management. Data on analgesic outcomes and adverse effects were collected and analyzed and are reported in this narrative review. Ultrasound guidance offers opportunities for the treatment of pain, with focus in this article on greater occipital nerve, trigeminal nerves, sphenopalatine ganglion, stellate ganglion, suprascapular nerve, median nerve, radial nerve, ulnar nerve, transverse abdominal plane block, quadratus lumborum, rectus sheath, anterior cutaneous abdominal nerves, pectoralis and serratus plane, erector spinae plane, illioinguinal/iliohypogastric/genitofemoral nerve, lateral femoral cutaneous nerve, genicular nerve, and foot and ankle nerves.

  View details for DOI 10.1016/j.anclin.2023.02.003

  View details for PubMedID 37245950

• Signature for Pain Recovery IN Teens (SPRINT): protocol for a multisite prospective signature study in chronic musculoskeletal pain. BMJ open Simons, L., Moayedi, M., Coghill, R. C., Stinson, J., Angst, M. S., Aghaeepour, N., Gaudilliere, B., King, C. D., López-Solà, M., Hoeppli, M. E., Biggs, E., Ganio, E., Williams, S. E., Goldschneider, K. R., Campbell, F., Ruskin, D., Krane, E. J., Walker, S., Rush, G., Heirich, M. 2022; 12 (6): e061548

  Abstract

  Current treatments for chronic musculoskeletal (MSK) pain are suboptimal. Discovery of robust prognostic markers separating patients who recover from patients with persistent pain and disability is critical for developing patient-specific treatment strategies and conceiving novel approaches that benefit all patients. Given that chronic pain is a biopsychosocial process, this study aims to discover and validate a robust prognostic signature that measures across multiple dimensions in the same adolescent patient cohort with a computational analysis pipeline. This will facilitate risk stratification in adolescent patients with chronic MSK pain and more resourceful allocation of patients to costly and potentially burdensome multidisciplinary pain treatment approaches.Here we describe a multi-institutional effort to collect, curate and analyse a high dimensional data set including epidemiological, psychometric, quantitative sensory, brain imaging and biological information collected over the course of 12 months. The aim of this effort is to derive a multivariate model with strong prognostic power regarding the clinical course of adolescent MSK pain and function.The study complies with the National Institutes of Health policy on the use of a single internal review board (sIRB) for multisite research, with Cincinnati Children's Hospital Medical Center Review Board as the reviewing IRB. Stanford's IRB is a relying IRB within the sIRB. As foreign institutions, the University of Toronto and The Hospital for Sick Children (SickKids) are overseen by their respective ethics boards. All participants provide signed informed consent. We are committed to open-access publication, so that patients, clinicians and scientists have access to the study data and the signature(s) derived. After findings are published, we will upload a limited data set for sharing with other investigators on applicable repositories.NCT04285112.

  View details for DOI 10.1136/bmjopen-2022-061548

  View details for PubMedID 35676017

• International Association for the Study of Pain Presidential Task Force on Cannabis and Cannabinoid Analgesia: research agenda on the use of cannabinoids, cannabis, and cannabis-based medicines for pain management. Pain Haroutounian, S., Arendt-Nielsen, L., Belton, J., Blyth, F. M., Degenhardt, L., Di Forti, M., Eccleston, C., Finn, D. P., Finnerup, N. B., Fisher, E., Fogarty, A. E., Gilron, I., Hohmann, A. G., Kalso, E., Krane, E., Mohiuddin, M., Moore, R. A., Rowbotham, M., Soliman, N., Wallace, M., Zinboonyahgoon, N., Rice, A. S. 2021; 162 (Suppl 1): S117-S124

  Abstract

  ABSTRACT: The President of the International Association for the Study of Pain established a task force on cannabis and cannabinoid analgesia to systematically examine the evidence on (1) analgesic pharmacology of cannabinoids and preclinical evidence on their efficacy in animal models of injury-related or pathological persistent pain; (2) the clinical efficacy of cannabis, cannabinoids, and cannabis-based medicines for pain; (3) harms related to long-term use of cannabinoids; as well as (4) societal issues and policy implications related to the use of these compounds for pain management. Here, we summarize key knowledge gaps identified in the task force outputs and propose a research agenda for generating high-quality evidence on the topic. The systematic assessment of preclinical and clinical literature identified gaps in rigor of study design and reporting across the translational spectrum. We provide recommendations to improve the quality, rigor, transparency, and reproducibility of preclinical and clinical research on cannabis and cannabinoids for pain, as well as for the conduct of systematic reviews on the topic. Gaps related to comprehensive understanding of the endocannabinoid system and cannabinoid pharmacology, including pharmacokinetics and drug formulation aspects, are discussed. We outline key areas where high-quality clinical trials with cannabinoids are needed. Remaining important questions about long-term and short-term safety of cannabis and cannabinoids are emphasized. Finally, regulatory, societal, and policy challenges associated with medicinal and nonmedicinal use of cannabis are highlighted, with recommendations for improving patient safety and reducing societal harms in the context of pain management.

  View details for DOI 10.1097/j.pain.0000000000002266

  View details for PubMedID 34138827

• A systematic review and meta-analysis of cannabis-based medicines, cannabinoids and endocannabinoid system modulators tested for antinociceptive effects in animal models of injury-related or pathological persistent pain. Pain Soliman, N., Haroutounian, S., Hohmann, A. G., Krane, E., Liao, J., Macleod, M., Segelcke, D., Sena, C., Thomas, J., Vollert, J., Wever, K., Alaverdyan, H., Barakat, A., Barthlow, T., Harris Bozer, A. L., Davidson, A., Diaz-delCastillo, M., Dolgorukova, A., Ferdousi, M. I., Healy, C., Hong, S., Hopkins, M., James, A., Leake, H. B., Malewicz, N. M., Mansfield, M., Mardon, A. K., Mattimoe, D., McLoone, D. P., Noes-Holt, G., Pogatzki-Zahn, E. M., Power, E., Pradier, B., Romanos-Sirakis, E., Segelcke, A., Vinagre, R., Yanes, J. A., Zhang, J., Zhang, X. Y., Finn, D. P., Rice, A. S. 2021

  Abstract

  ABSTRACT: We report a systematic review and meta-analysis of studies which assessed the antinociceptive efficacy of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators on pain-associated behavioural outcomes in animal models of pathological or injury-related persistent pain. In April 2019, we systematically searched 3 online databases and used crowd science and machine learning to identify studies for inclusion. We calculated a standardised mean difference (SMD) effect size for each comparison and performed a random effects meta-analysis. We assessed the impact of study design characteristics and reporting of mitigations to reduce the risk of bias. We meta-analysed 374 studies in which 171 interventions were assessed for antinociceptive efficacy in rodent models of pathological or injury-related pain. Most experiments were conducted in male animals (86 %). Antinociceptive efficacy was most frequently measured by attenuation of hypersensitivity to evoked limb withdrawal. Selective CB1, CB2, non-selective cannabinoid receptor agonists (including delta-9-tetrahydrocannabinol; THC), and PPAR-alpha agonists (predominantly palmitoylethanolamide; PEA) significantly attenuated pain-associated behaviours in a broad range of inflammatory and neuropathic pain models. Fatty acid amide hydrolase (FAAH) inhibitors, monoacylglycerol lipase (MGL) inhibitors and cannabidiol (CBD) significantly attenuated pain-associated behaviours in neuropathic pain models but yielded mixed results in inflammatory pain models. The reporting of criteria to reduce the risk of bias was low, therefore the studies have an unclear risk of bias. The value of future studies could be enhanced by improving the reporting of methodological criteria, the clinical relevance of the models and behavioural assessments. Notwithstanding, the evidence supports the hypothesis of cannabinoid-induced analgesia.

  View details for DOI 10.1097/j.pain.0000000000002269

  View details for PubMedID 33729209

• Cannabinoids, the endocannabinoid system, and pain: a review of preclinical studies. Pain Finn, D. P., Haroutounian, S., Hohmann, A. G., Krane, E., Soliman, N., Rice, A. S. 2021

  Abstract

  ABSTRACT: This narrative review represents an output from the International Association for the Study of Pain's global task force on the use of cannabis, cannabinoids, and cannabis-based medicines (CBM) for pain management, informed by our companion systematic review and meta-analysis of preclinical studies in this area. Our aims in this review are: 1) to describe the value of studying cannabinoids and endogenous cannabinoid (endocannabinoid) system modulators in preclinical/animal models of pain; 2) to discuss both pain-related efficacy and additional pain-relevant effects (adverse and beneficial) of cannabinoids and endocannabinoid system modulators as they pertain to animal models of pathological or injury-related persistent pain; and 3) to identify important directions for future research. In service of these goals, this review a) provides an overview of the endocannabinoid system and the pharmacology of cannabinoids and endocannabinoid system modulators, with specific relevance to animal models of pathological or injury-related persistent pain; b) describes pharmacokinetics of cannabinoids in rodents and humans; and c) highlights differences and discrepancies between preclinical and clinical studies in this area. Preclinical (rodent) models have advanced our understanding of the underlying sites and mechanisms of action of cannabinoids and the endocannabinoid system in suppressing nociceptive signaling and behaviors. We conclude that substantial evidence from animal models supports the contention that cannabinoids and endocannabinoid system modulators hold considerable promise for analgesic drug development, although the challenge of translating this knowledge into clinically useful medicines is not to be underestimated.

  View details for DOI 10.1097/j.pain.0000000000002268

  View details for PubMedID 33729211

• Outcome in young adults who were diagnosed with complex regional pain syndrome in childhood and adolescence. Pain reports Wong, B. J., Yoon, I. A., Krane, E. J. 2020; 5 (6): e860

  Abstract

  Introduction: Complex regional pain syndrome (CRPS) is a neuropathic pain condition of unknown etiology. Little is known of long-term outcomes of young adults who were diagnosed with CRPS as children.Methods: In this study, surveys were mailed to adults who were treated for childhood CRPS at the Lucile Packard Children's Hospital between 1994 and 2018. Completed surveys were analyzed for pain symptoms. Health-related quality-of-life surveys, the Optum SF-8, were analyzed based on norm-based scoring.Results: This study had a 50% response rate. Patients were treated with physical and occupational therapy, peripheral or sympathetic nerve blocks, medication for neuropathic pain, and psychotherapy. Sixty-eight percent of the subjects reported pain. Each 1-year increase in the patient's age at the time of CRPS diagnosis increased the odds of having at least mild pain as an adult by 61% (P = 0.005). Most patients had slightly lower quality-of-life scores than the US population average in both the mental component score (43.4, 95%, confidence interval 3.4) and the physical component score (44.4, 95%, confidence interval 3.3).Conclusions: Young adults in our sample had long-lasting pain symptoms. More than two-thirds of adult patients reported some degree of pain, and these patients had a lower quality of life. Encouraging was that the majority did not have CRPS spreading to other areas, and their pain did not warrant further treatment. Understanding long-term outcomes may lead to risk stratification earlier in the disease to improve future quality of life.

  View details for DOI 10.1097/PR9.0000000000000860

  View details for PubMedID 33134754

• Cannabinoids, cannabis, and cannabis-based medicines for pain management: an overview of systematic reviews. Pain Moore, R. A., Fisher, E., Finn, D. P., Finnerup, N. B., Gilron, I., Haroutounian, S., Krane, E., Rice, A. S., Rowbotham, M., Wallace, M., Eccleston, C. 2020

  Abstract

  Cannabinoids, cannabis, and cannabis-based medicines (CBM) are increasingly used to manage pain, with limited understanding of their efficacy and safety. We assessed methodological quality, scope, and results of systematic reviews of randomised controlled trials of these treatments. Several search strategies sought self-declared systematic reviews. Methodological quality was assessed using both AMSTAR-2 and techniques important for bias reduction in pain studies. Of the 106 articles read, 57 were self-declared systematic reviews, most published since 2010. They included any type of cannabinoid, cannabis, or CBM, at any dose, however administered, in a broad range of pain conditions. No review examined the effects of a particular cannabinoid, at a particular dose, using a particular route of administration, for a particular pain condition, reporting a particular analgesic outcome. Confidence in the results in the systematic reviews using AMSTAR-2 definitions was critically low (41), low (8), moderate (6), or high (2). Few used criteria important for bias reduction in pain. Cochrane reviews typically provided higher confidence; all industry-conflicted reviews provided critically low confidence. Meta-analyses typically pooled widely disparate studies, and, where assessable, were subject to potential publication bias. Systematic reviews with positive or negative recommendation for use of cannabinoids, cannabis, or CBM in pain typically rated critically low or low (24/25 [96%] positive; 10/12 [83%] negative). Current reviews are mostly lacking in quality and cannot provide a basis for decision-making. A new high-quality systematic review of randomised controlled trials is needed to critically assess the clinical evidence for cannabinoids, cannabis, or CBM in pain.

  View details for DOI 10.1097/j.pain.0000000000001941

  View details for PubMedID 32804833

• Cannabinoids, cannabis, and cannabis-based medicine for pain management: a systematic review of randomised controlled trials. Pain Fisher, E., Moore, R. A., Fogarty, A. E., Finn, D. P., Finnerup, N. B., Gilron, I., Haroutounian, S., Krane, E., Rice, A. S., Rowbotham, M., Wallace, M., Eccleston, C. 2020

  Abstract

  Cannabinoids, cannabis, and cannabis-based medicines (CBMs) are increasingly used to manage pain, with limited understanding of their efficacy and safety. We summarised efficacy and adverse events (AEs) of these types of drugs for treating pain using randomised controlled trials: in people of any age, with any type of pain, and for any treatment duration. Primary outcomes were 30% and 50% reduction in pain intensity, and AEs. We assessed risk of bias of included studies, and the overall quality of evidence using GRADE. Studies of <7 and >7 days treatment duration were analysed separately. We included 36 studies (7217 participants) delivering cannabinoids (8 studies), cannabis (6 studies), and CBM (22 studies); all had high and/or uncertain risk of bias. Evidence of benefit was found for cannabis <7 days (risk difference 0.33, 95% confidence interval 0.20-0.46; 2 trials, 231 patients, very low-quality evidence) and nabiximols >7 days (risk difference 0.06, 95% confidence interval 0.01-0.12; 6 trials, 1484 patients, very low-quality evidence). No other beneficial effects were found for other types of cannabinoids, cannabis, or CBM in our primary analyses; 81% of subgroup analyses were negative. Cannabis, nabiximols, and delta-9-tetrahydrocannabinol had more AEs than control. Studies in this field have unclear or high risk of bias, and outcomes had GRADE rating of low- or very low-quality evidence. We have little confidence in the estimates of effect. The evidence neither supports nor refutes claims of efficacy and safety for cannabinoids, cannabis, or CBM in the management of pain.

  View details for DOI 10.1097/j.pain.0000000000001929

  View details for PubMedID 32804836

• Long-term Outcome of Complex Regional Pain Syndrome Diagnosed and Treated in Childhood and Adolescence Wong, B., Krane, E. J. LIPPINCOTT WILLIAMS & WILKINS. 2020: 608–9

  View details for Web of Science ID 000619264500292

• Societal issues and policy implications related to the use of cannabinoids, cannabis, and cannabis-based medicines for pain management. Pain Haroutounian, S. n., Gilron, I. n., Belton, J. n., Degenhardt, L. n., DiForti, M. n., Finn, D. P., Fogarty, A. n., Kalso, E. n., Krane, E. n., Moore, R. A., Rowbotham, M. n., Wallace, M. n., Rice, A. S. 2020

  View details for DOI 10.1097/j.pain.0000000000002001

  View details for PubMedID 33009248

• Team Approach: Complex Regional Pain Syndrome in Children and Adolescents. JBJS reviews Tileston, K. R., Griffin, A. n., Wagner, J. F., O'Day, M. N., Krane, E. J. 2020; 8 (4): e0174

  View details for DOI 10.2106/JBJS.RVW.19.00174

  View details for PubMedID 32304498

• Variation Between and Within Hospitals in Single Injection Caudal Local Anesthetic Dose: A Report From the Pediatric Regional Anesthesia Network. Anesthesia and analgesia Taenzer, A. H., Hoyt, M., Krane, E. J., Walker, B. J., Flack, S., Bosenberg, A., Sethna, N. F., Franklin, A. D., Polaner, D. M., PRAN investigators 2019

  Abstract

  BACKGROUND: Given that variation exists in health care utilization, expenditure, and medical practice, there is a paucity of data on variation within the practice of anesthesia. The Pediatric Regional Anesthesia Network (PRAN) data lend itself to explore whether different medical practice patterns exist and if there are nerve blocks with more local anesthetic dosing variation than others.The primary aim of this study was to quantify variation in single injection caudal block dosing, and the secondary aim was to explore possible causes for variation (eg, number of blocks performed versus geographic location).METHODS: We queried the PRAN database for single injection caudal blocks in children <1 year of age. Data were analyzed for local anesthetic dose, variation within and across institutions, and possible causes.RESULTS: Mean dose of bupivacaine equivalents per kilogram (BE·kg) among sites ranged from 1.39 to 2.22 with an interdecile range (IDR) containing the mid 80% of all doses ranging from 0.21 to 1.48. Mean dose (BE·kg) was associated with site, age, weight, and local anesthetic used (all P < .0001). Cohen's F effect size estimate was 10 times higher for site (0.65) than for age (0.05) or weight (0.02). Variation (IDR) was not related to number of blocks done at each site (P = .23). Mean volume per kilogram was 0.9± ± 0.2 (mean ± ±standard deviation) and was more strongly associated with site (Cohen's F 0.3) than age (0.04) or weight (0.07).CONCLUSIONS: Wide variation in caudal local anesthetic dosing and administered volume exists. This variation is independent of the number of cases performed at each center but rather is determined by study site (ie, variation between centers) with considerable additional variation within study centers, suggesting additional variability dependent on individual practitioners. While there are legitimate reasons to vary dosing, the current approach is inconsistent and not supported by strong evidence over giving a standardized dose.

  View details for DOI 10.1213/ANE.0000000000004447

  View details for PubMedID 31573994

• The Opioid Debate-PRO Opioids Have an Important Role in Pain Management in Children CLINICAL JOURNAL OF PAIN Krane, E. J. 2019; 35 (6): 468–72

  View details for DOI 10.1097/AJP.0000000000000700

  View details for Web of Science ID 000467737200003

• Design and Reporting Characteristics of Clinical Trials of Select Chronic and Recurrent Pediatric Pain Conditions: An Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks Systematic Review JOURNAL OF PAIN Connolly, M. R., Chaudari, J. Y., Yang, X., Ward, N., Kitt, R. A., Herrmann, R. S., Krane, E. J., LeBel, A. A., Smith, S. M., Walco, G. A., Weisman, S. J., Turk, D. C., Dworkin, R. H., Gewandter, J. S. 2019; 20 (4): 394–404

  View details for DOI 10.1016/j.jpain.2018.08.007

  View details for Web of Science ID 000462807000002

• Pharmacological interventions for chronic pain in children: an overview of systematic reviews. Pain Eccleston, C. n., Fisher, E. n., Cooper, T. E., Grégoire, M. C., Heathcote, L. C., Krane, E. n., Lord, S. M., Sethna, N. F., Anderson, A. K., Anderson, B. n., Clinch, J. n., Gray, A. L., Gold, J. I., Howard, R. F., Ljungman, G. n., Moore, R. A., Schechter, N. n., Wiffen, P. J., Wilkinson, N. M., Williams, D. G., Wood, C. n., van Tilburg, M. A., Zernikow, B. n. 2019; 160 (8): 1698–1707

  Abstract

  We know little about the safety or efficacy of pharmacological medicines for children and adolescents with chronic pain, despite their common use. Our aim was to conduct an overview review of systematic reviews of pharmacological interventions that purport to reduce pain in children with chronic noncancer pain (CNCP) or chronic cancer-related pain (CCRP). We searched the Cochrane Database of Systematic Reviews, Medline, EMBASE, and DARE for systematic reviews from inception to March 2018. We conducted reference and citation searches of included reviews. We included children (0-18 years of age) with CNCP or CCRP. We extracted the review characteristics and primary outcomes of ≥30% participant-reported pain relief and patient global impression of change. We sifted 704 abstracts and included 23 systematic reviews investigating children with CNCP or CCRP. Seven of those 23 reviews included 6 trials that involved children with CNCP. There were no randomised controlled trials in reviews relating to reducing pain in CCRP. We were unable to combine data in a meta-analysis. Overall, the quality of evidence was very low, and we have very little confidence in the effect estimates. The state of evidence of randomized controlled trials in this field is poor; we have no evidence from randomised controlled trials for pharmacological interventions in children with cancer-related pain, yet cannot deny individual children access to potential pain relief. Prospero ID: CRD42018086900.

  View details for DOI 10.1097/j.pain.0000000000001609

  View details for PubMedID 31335640

• Cannabinoids, cannabis, and cannabis-based medicine for pain management: a protocol for an overview of systematic reviews and a systematic review of randomised controlled trials. Pain reports Fisher, E. n., Eccleston, C. n., Degenhardt, L. n., Finn, D. P., Finnerup, N. B., Gilron, I. n., Haroutounian, S. n., Krane, E. n., Rice, A. S., Rowbotham, M. n., Wallace, M. n., Moore, R. A. 2019; 4 (3): e741

  Abstract

  Pain is an experience that affects many people worldwide and is associated with higher mortality and lower quality of life. Cannabinoid, cannabis, and cannabis-based medicines (CBMs) are thought to reduce pain, but a proliferation of different products has led to variability in trials, creating a challenge when determining the assessment of efficacy in systematic reviews. We will conduct 2 systematic reviews commissioned by the International Association for the Study of Pain Task Force on the use of cannabinoids, cannabis, and CBMs for pain management: first, an overview review of systematic reviews to summarise the evidence base and second, a systematic review of randomised controlled trials of cannabinoids, cannabis, and CBMs. In these reviews we will determine the harm and benefit of CBM from the current literature and will interpret the findings in light of the quality of evidence and reviews included. We will search online databases and registries in any language for systematic reviews and randomised controlled trials. We will include studies that evaluate any cannabinoid or CBM vs any control for people with acute and chronic pain. Our primary outcomes for both reviews are the number of participants achieving (1) a 30% and (2) 50% reduction in pain intensity, (3) moderate improvement, and (4) substantial improvement. A number of secondary outcome measures will also be included. We will assess risk of bias and quality of evidence. We will analyse data using fixed and random effect models, with separate comparators for cannabis and CBMs. Prospero ID (CRD42019124710; CRD42019124714).

  View details for DOI 10.1097/PR9.0000000000000741

  View details for PubMedID 31583356

  View details for PubMedCentralID PMC6749927

• A Case Report of Combined Ultrasound and Fluoroscopic-Guided Percutaneous Radiofrequency Lesioning of the Obturator and Femoral Articular Branches in the Treatment of Persistent Hip Pain in a Pediatric Patient PAIN PRACTICE Khan, J. S., Krane, E. J., Higgs, M., Pritzlaff, S., Hoffinger, S., Ottestad, E. 2019; 19 (1): 52–56

  View details for DOI 10.1111/papr.12724

  View details for Web of Science ID 000455105200005

• Pharmacological interventions for chronic pain in children: an overview of systematic reviews. Pain Eccleston, C. n., Fisher, E. n., Cooper, T. E., Grégoire, M. C., Heathcote, L. C., Krane, E. n., Lord, S. M., Sethna, N. F., Anderson, A. K., Anderson, B. n., Clinch, J. n., Gray, A. L., Gold, J. I., Howard, R. F., Ljungman, G. n., Moore, R. A., Schechter, N. n., Wiffen, P. J., Wilkinson, N. M., Williams, D. G., Wood, C. n., van Tilburg, M. A., Zernikow, B. n. 2019

  Abstract

  We know little about the safety or efficacy of pharmacological medicines for children and adolescents with chronic pain, despite their common use. Our aim was to conduct an overview review of systematic reviews of pharmacological interventions that purport to reduce pain in children with chronic non-cancer pain or chronic cancer-related pain. We searched the Cochrane Database of Systematic Reviews, Medline, EMBASE and DARE for systematic reviews from inception to March 2018. We conducted reference and citation searches of included reviews. We included children (0-18 years of age) with chronic non-cancer pain or chronic cancer-related pain. We extracted the review characteristics and primary outcomes of ≥30% participant-reported pain relief and patient global impression of change. We sifted 704 abstracts and included 23 systematic reviews investigating children with chronic non-cancer pain or chronic cancer-related pain. Seven of those 23 reviews included six trials that involved children with chronic non-cancer pain. There were no RCTs in reviews relating to reducing pain in chronic cancer-related pain. We were unable to combine data in a meta-analysis. Overall, the quality of evidence was very low and we have very little confidence in the effect estimates. The state of evidence of randomized controlled trials in this field is poor; we have no evidence from randomised controlled trials for pharmacological interventions in children with cancer-related pain, yet cannot deny individual children access to potential pain relief. Prospero ID: CRD42017081205. A video accompanying this abstract is available online as Supplemental Digital Content at http://links.lww.com/PAIN/A797.

  View details for DOI 10.1097/j.pain.0000000000001609

  View details for PubMedID 31107413

• Complications in Pediatric Regional Anesthesia An Analysis of More than 100,000 Blocks from the Pediatric Regional Anesthesia Network ANESTHESIOLOGY Walker, B. J., Long, J. B., Sathyamoorthy, M., Birstler, J., Wolf, C., Bosenberg, A. T., Flack, S. H., Krane, E. J., Sethna, N. F., Suresh, S., Taenzer, A. H., Polaner, D. M., Pediat Regional Anesthesia Network 2018; 129 (4): 721–32

  View details for DOI 10.1097/ALN.0000000000002372

  View details for Web of Science ID 000444808500015

• Design and Reporting Characteristics of Clinical Trials of Select Chronic and Recurrent Pediatric Pain Conditions: An Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks Systematic Review. The journal of pain : official journal of the American Pain Society Connolly, M. R., Chaudari, J. Y., Yang, X., Ward, N., Kitt, R. A., Herrmann, R. S., Krane, E. J., LeBel, A. A., Smith, S. M., Walco, G. A., Weisman, S. J., Turk, D. C., Dworkin, R. H., Gewandter, J. S. 2018

  Abstract

  Fewer randomized clinical trials (RCTs) are conducted for chronic or recurrent pain in pediatric populations compared with adult populations; thus, data to support treatment efficacy in children are limited. This article evaluates the design features and reporting practices of RCTs for chronic and recurrent pain that are likely unique to, or particularly important in, a pediatric population to promote improvements in the evidence base for pediatric pain treatments. Areas covered include outcome measure selection and reporting and reporting of adverse events and challenges to recruitment and retention. A search of PubMed and EMBASE identified primary publications describing RCTs of treatments for select chronic and recurrent pain conditions in children or adolescents published between 2000 and 2017. Only 49% of articles identified a primary outcome measure. The primary outcome measure assessed pain intensity in 38% of the trials, specifically measure by verbal rating scale (13%), faces pain scale (11%), visual analogue scale (9%), or numeric rating scale (5%). All of the CONSORT harms reporting recommendations were fulfilled by <50% of the articles. Discussions of recruitment challenges occurred in 64% of articles that enrolled <90% of their target sample. However, discussions regarding retention challenges only occurred in 14% of trials in which withdrawal rates were >10%. The goal of this article is to promote comprehensive reporting of pediatric pain RCTs to improve the design of future trials, facilitate conduction of systematic reviews and meta-analyses, and better inform clinical practice. PERSPECTIVE: This review of chronic and recurrent pediatric pain trials demonstrates inadequacies in the reporting quality of key features specifically important to pediatric populations. It provides recommendations that address these shortcomings to promote continued efforts toward improving the quality of the design and publication of future pediatric clinical pain trials.

  View details for PubMedID 30219729

• The National Opioid Epidemic and the Risk of Outpatient Opioids in Children PEDIATRICS Krane, E. J., Weisman, S. J., Walco, G. A. 2018; 142 (2)

  View details for DOI 10.1542/peds.2018-1623

  View details for Web of Science ID 000440459900057

• Complications in Pediatric Regional Anesthesia: An Analysis of More than 100,000 Blocks from the Pediatric Regional Anesthesia Network. Anesthesiology Walker, B. J., Long, J. B., Sathyamoorthy, M., Birstler, J., Wolf, C., Bosenberg, A. T., Flack, S. H., Krane, E. J., Sethna, N. F., Suresh, S., Taenzer, A. H., Polaner, D. M., Martin, L., Anderson, C., Sunder, R., Adams, T., Martin, L., Pankovich, M., Sawardekar, A., Birmingham, P., Marcelino, R., Ramarmurthi, R. J., Szmuk, P., Ungar, G. K., Lozano, S., Boretsky, K., Jain, R., Matuszczak, M., Petersen, T. R., Dillow, J., Power, R., Nguyen, K., Lee, B. H., Chan, L., Pineda, J., Hutchins, J., Mendoza, K., Spisak, K., Shah, A., DelPizzo, K., Dong, N., Yalamanchili, V., Venable, C., Williams, C. A., Chaudahari, R., Ohkawa, S., Usljebrka, H., Bhalla, T., Vanzillotta, P. P., Apiliogullari, S., Franklin, A. D., Ando, A., Pestieau, S. R., Wright, C., Rosenbloom, J., Anderson, T., Pediatric Regional Anesthesia Network Investigators 2018

  Abstract

  WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Complications in pediatric regional anesthesia are rare, so a large sample size is necessary to quantify risk. The Pediatric Regional Anesthesia Network contains data on more than 100,000 blocks administered at more than 20 children's hospitals. This study analyzed the risk of major complications associated with regional anesthesia in children.METHODS: This is a prospective, observational study of routine clinical practice. Data were collected on every regional block placed by an anesthesiologist at participating institutions and were uploaded to a secure database. The data were audited at multiple points for accuracy.RESULTS: There were no permanent neurologic deficits reported (95% CI, 0 to 0.4:10,000). The risk of transient neurologic deficit was 2.4:10,000 (95% CI, 1.6 to 3.6:10,000) and was not different between peripheral and neuraxial blocks. The risk of severe local anesthetic systemic toxicity was 0.76:10,000 (95% CI, 0.3 to 1.6:10,000); the majority of cases occurred in infants. There was one epidural abscess reported (0.76:10,000, 95% CI, 0 to 4.8:10,000). The incidence of cutaneous infections was 0.5% (53:10,000, 95% CI, 43 to 64:10,000). There were no hematomas associated with neuraxial catheters (95% CI, 0 to 3.5:10,000), but one epidural hematoma occurred with a paravertebral catheter. No additional risk was observed with placing blocks under general anesthesia. The most common adverse events were benign catheter-related failures (4%).CONCLUSIONS: The data from this study demonstrate a level of safety in pediatric regional anesthesia that is comparable to adult practice and confirms the safety of placing blocks under general anesthesia in children.

  View details for PubMedID 30074928

• The National Opioid Epidemic and the Risk of Outpatient Opioids in Children. Pediatrics Krane, E. J., Weisman, S. J., Walco, G. A. 2018

  View details for PubMedID 30012558

• A case report of combined ultrasound and fluoroscopic-guided percutaneous radiofrequency lesioning of the obturator and femoral articular branches in the treatment of persistent hip pain in a pediatric patient. Pain practice : the official journal of World Institute of Pain Khan, J. S., Krane, E. J., Higgs, M., Pritzlaff, S., Hoffinger, S., Ottestad, E. 2018

  Abstract

  Hip denervation comprising radiofrequency lesioning of the obturator and femoral articular branches is used in adults with refractory hip pain who are not surgical candidates. Persistent hip pain infrequently occurs in pediatric patients and there is limited data on the safety and efficacy of this procedure in a pediatric population. We provide a case report of a successful ultrasound and fluoroscopic-guided hip denervation procedure in an 11-year old female with persistent right hip pain after septic arthritis refractory to conservative and surgical management strategies. At an 18- week follow-up, hip denervation provided improvement in pain, mobility, and reduced opioid consumption by 20%. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/papr.12724

  View details for PubMedID 29896934

• Clinical trial designs and models for analgesic medications for acute pain in neonates, infants, toddlers, children, and adolescents: ACTTION recommendations PAIN Walco, G. A., Kopecky, E. A., Weisman, S. J., Stinson, J., Stevens, B., Desjardins, P. J., Berde, C. B., Krane, E. J., Anand, K. S., Yaster, M., Dampier, C. D., Dworkin, R. H., Gilron, I., Lynn, A. M., Maxwell, L. G., Raja, S., Schachtel, B., Turk, D. C. 2018; 159 (2): 193–205

  Abstract

  Clinical trials to test the safety and efficacy of analgesics across all pediatric age cohorts are needed to avoid inappropriate extrapolation of adult data to children. However, the selection of acute pain models and trial design attributes to maximize assay sensitivity, by pediatric age cohort, remains problematic. Acute pain models used for drug treatment trials in adults are not directly applicable to the pediatric age cohorts - neonates, infants, toddlers, children, and adolescents. Developmental maturation of metabolic enzymes in infants and children must be taken into consideration when designing trials to test analgesic treatments for acute pain. Assessment tools based on levels of cognitive maturation and behavioral repertoire must be selected as outcome measures. Models and designs of clinical trials of analgesic medications used in the treatment of acute pain in neonates, infants, toddlers, children, and adolescents were reviewed and discussed at an Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) Pediatric Pain Research Consortium consensus meeting. Based on extensive reviews and continuing discussions, the authors recommend a number of acute pain clinical trial models and design attributes that have the potential to improve the study of analgesic medications in pediatric populations. Recommendations are also provided regarding additional research needed to support the use of other acute pain models across pediatric age cohorts. (216 words).

  View details for PubMedID 29140927

• Management of a Ventral Cerebrospinal Fluid Leak With a Lumbar Transforaminal Epidural Blood Patch in a Child With Persistent Postdural Puncture Headache: A Case Report. Regional anesthesia and pain medicine D'souza, G., Seidel, F. G., Krane, E. J. 2017; 42 (2): 263-266

  Abstract

  Postdural puncture headache (PDPH) is an uncommon sequel of lumbar puncture in children. When conservative treatment with bed rest, hydration, and caffeine are ineffective, epidural blood patches are recommended and are generally effective. The purpose of this report was to highlight that when lumbar epidural blood patches fail to eliminate PDPH, diagnostic evaluation should be performed and alternative treatment sought.An unusual case is described of an 11-year-old boy with PDPH, which was successfully managed with a ventral (anterior) epidural blood patch and epidural saline infusion after headache and other symptoms failed to resolve after conservative treatment and conventionally performed blood patches.Ineffectiveness of conservative measures and epidural blood patches performed posteriorly to resolve PDPH should lead the physician both to question the diagnosis of PDPH by pursuing radiographic confirmation of a cerebral spinal fluid leak and, furthermore, identification of its location to best direct further therapy.

  View details for DOI 10.1097/AAP.0000000000000562

  View details for PubMedID 28178090

• Pediatric-Collaborative Health Outcomes Information Registry (Peds-CHOIR): a learning health system to guide pediatric pain research and treatment. Pain Bhandari, R. P., Feinstein, A. B., Huestis, S. E., Krane, E. J., Dunn, A. L., Cohen, L. L., Kao, M. C., Darnall, B. D., Mackey, S. C. 2016; 157 (9): 2033-2044

  Abstract

  The pediatric adaptation of the Collaborative Health Outcomes Information Registry (Peds-CHOIR) is a free, open-source, flexible learning health care system (LHS) that meets the call by the Institute of Medicine for the development of national registries to guide research and precision pain medicine. This report is a technical account of the first application of Peds-CHOIR with 3 aims: (1) to describe the design and implementation process of the LHS; (2) to highlight how the clinical system concurrently cultivates a research platform rich in breadth (eg, clinic characteristics) and depth (eg, unique patient- and caregiver-reporting patterns); and (3) to demonstrate the utility of capturing patient-caregiver dyad data in real time, with dynamic outcomes tracking that informs clinical decisions and delivery of treatments. Technical, financial, and systems-based considerations of Peds-CHOIR are discussed. Cross-sectional retrospective data from patients with chronic pain (N = 352; range, 8-17 years; mean, 13.9 years) and their caregivers are reported, including National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) domains (mobility, pain interference, fatigue, peer relations, anxiety, and depression) and the Pain Catastrophizing Scale. Consistent with the literature, analyses of initial visits revealed impairments across physical, psychological, and social domains. Patients and caregivers evidenced agreement in observable variables (mobility); however, caregivers consistently endorsed greater impairment regarding internal experiences (pain interference, fatigue, peer relations, anxiety, and depression) than patients' self-report. A platform like Peds-CHOIR highlights predictors of chronic pain outcomes on a group level and facilitates individually tailored treatment(s). Challenges of implementation and future directions are discussed.

  View details for DOI 10.1097/j.pain.0000000000000609

  View details for PubMedID 27280328

• Applying a Lifespan Developmental Perspective to Chronic Pain: Pediatrics to Geriatrics. journal of pain Walco, G. A., Krane, E. J., Schmader, K. E., Weiner, D. K. 2016; 17 (9): T108-17

  Abstract

  An ideal taxonomy of chronic pain would be applicable to people of all ages. Developmental sciences focus on lifespan developmental approaches, and view the trajectory of processes in the life course from birth to death. In this article we provide a review of lifespan developmental models, describe normal developmental processes that affect pain processing, and identify deviations from those processes that lead to stable individual differences of clinical interest, specifically the development of chronic pain syndromes. The goals of this review were 1) to unify what are currently separate purviews of "pediatric pain," "adult pain," and "geriatric pain," and 2) to generate models so that specific elements of the chronic pain taxonomy might include important developmental considerations.A lifespan developmental model is applied to the forthcoming Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks-American Pain Society Pain Taxonomy to ascertain the degree to which general "adult" descriptions apply to pediatric and geriatric populations, or if age- or development-related considerations need to be invoked.

  View details for DOI 10.1016/j.jpain.2015.11.003

  View details for PubMedID 27586828

• The European Society of Regional Anaesthesia and Pain Therapy and the American Society of Regional Anesthesia and Pain Medicine Joint Committee Practice Advisory on Controversial Topics in Pediatric Regional Anesthesia. Regional anesthesia and pain medicine Ivani, G., Suresh, S., Ecoffey, C., Bosenberg, A., Lonnqvist, P., Krane, E., Veyckemans, F., Polaner, D. M., Van de Velde, M., Neal, J. M. 2015; 40 (5): 526-532

  Abstract

  Some topics in the clinical management of regional anesthesia in children remain controversial. To evaluate and come to a consensus regarding some of these topics, The European Society of Regional Anaesthesia and Pain Therapy (ESRA) and the American Society of Regional Anesthesia and Pain Medicine (ASRA) developed a joint committee practice advisory on pediatric regional anesthesia (PRA).Representatives from both ASRA and ESRA comprised the joint committee practice advisory on PRA. Evidence-based recommendations were based on a systematic search of the literature. In cases where no literature was available, expert opinion was elicited. Experts selected controversial topics in PRA.The performance of PRA under general anesthesia or deep sedation is associated with acceptable safety and should be viewed as the standard of care (Evidence B2 and Evidence B3). Because of the difficulty interpreting a negative test dose, the use of test dosing should remain discretionary (Evidence B4). The use of either air-loss of resistance or saline-loss of resistance techniques is supported by expert opinion, but the literature supporting one technique over the other is sparse and controversial; when used appropriately, each technique may be safely used in children. There are no current evidence-based data that the use of RA increases the risk for acute compartment syndrome or delays its diagnosis in children.High-level evidence is not yet available for the topics evaluated, and most recommendations are based on Evidence B studies. The ESRA/ASRA recommendations intend to provide guidance for the safe practice of regional anesthesia in children.

  View details for DOI 10.1097/AAP.0000000000000280

  View details for PubMedID 26192549

• Paraplegia after epidural-general anesthesia in a Morquio patient with moderate thoracic spinal stenosis CANADIAN JOURNAL OF ANESTHESIA-JOURNAL CANADIEN D ANESTHESIE Drummond, J. C., Krane, E. J., Tomatsu, S., Theroux, M. C., Lee, R. R. 2015; 62 (1): 45-49

  Abstract

  We describe an instance in which complete paraplegia was evident immediately postoperatively after apparently uneventful lumbar epidural-general anesthesia in a patient with Morquio Type A syndrome (Morquio A) with moderate thoracic spinal stenosis.A 16-yr-old male with Morquio A received lumbar epidural-general anesthesia for bilateral distal femoral osteotomies. Preoperative imaging had revealed a stable cervical spine and moderate thoracic spinal stenosis with a mild degree of spinal cord compression. Systolic blood pressure (BP) was maintained within 20% of the pre-anesthetic baseline value. The patient sustained a severe thoracic spinal cord infarction. The epidural anesthetic contributed to considerable delay in the recognition of the diagnosis of paraplegia.This experience leads us to suggest that, in patients with Morquio A, it may be prudent to avoid the use of epidural anesthesia without very firm indication, to support BP at or near baseline levels in the presence of even moderate spinal stenosis, and to avoid flexion or extension of the spinal column in intraoperative positioning. If the spinal cord/column status is unknown or if the patient is known to have any degree of spinal stenosis, we suggest that the same rigorous BP support practices that are typically applied in other patients with severe spinal stenosis, especially stenosis with myelomalacia, should apply to patients with Morquio A and that spinal cord neurophysiological monitoring should be employed. In the event that cord imaging is not available, e.g., emergency procedures, it would be prudent to assume the presence of spinal stenosis.

  View details for DOI 10.1007/s12630-014-0247-1

  View details for Web of Science ID 000347680400008

  View details for PubMedID 25323122

  View details for PubMedCentralID PMC4288980

• Interscalene Brachial Plexus Blocks Under General Anesthesia in Children: Is This Safe Practice? A Report From the Pediatric Regional Anesthesia Network (PRAN) REGIONAL ANESTHESIA AND PAIN MEDICINE Taenzer, A., Walker, B. J., Bosenberg, A. T., Krane, E. J., Martin, L. D., Polaner, D. M., Wolf, C., Suresh, S. 2014; 39 (6): 502-505

  View details for DOI 10.1097/AAP.0000000000000166

  View details for Web of Science ID 000344933500010

• Asleep versus awake: does it matter?: Pediatric regional block complications by patient state: a report from the Pediatric Regional Anesthesia Network. Regional anesthesia and pain medicine Taenzer, A. H., Walker, B. J., Bosenberg, A. T., Martin, L., Suresh, S., Polaner, D. M., Wolf, C., Krane, E. J. 2014; 39 (4): 279-283

  Abstract

  The impact of the patient state at time of placement of regional blocks on the risk of complications is unknown. Current opinion is based almost entirely on case reports, despite considerable interest in the question. Analyzing more than 50,000 pediatric regional anesthesia blocks from an observational prospective database, we determined the rate of adverse events in relation to the patient's state at the time of block placement. Primary outcomes considered were postoperative neurologic symptoms (PONSs) and local anesthetic systemic toxicity (LAST). Secondary outcome was extended hospital stay due to a block complication.The Pediatric Regional Anesthesia Network is a multi-institutional research consortium that was created with an emphasis on rigorous, prospective, and complete data collection including a data validation and audit process. For the purpose of the analysis, blocks were divided in major groups by single injection versus continuous and by block location. Rates were determined in aggregate for these groups and classified further based on the patient's state (general anesthesia [GA] without neuromuscular blockade [NMB], GA with NMB, sedated, and awake) at the time of block placement.Postoperative neurological symptoms occurred at a rate of 0.93/1000 (confidence interval [CI], 0.7-1.2) under GA and 6.82/1000 (CI, 4.2-10.5) in sedated and awake patients. The only occurrence of PONSs lasting longer than 6 months (PONSs-L) was a small sensory deficit in a sedated patient (0.019/1000 [CI, 0-0.1] for all, 0.48/1000 [CI, 0.1-2.7] for sedated patients). There were no cases of paralysis. There were 5 cases of LAST or 0.09/1000 (CI, 0.03-0.21). The incidence of LAST in patients under GA (both with and without NMB) was 0.08/1000 (CI, 0.02-0.2) and 0.34/1000 (CI, 0-1.9) in awake/sedated patients. Extended hospital stays were described 18 times (0.33/1000 [CI, 0.2-0.53]). The rate for patients under GA without NMB was 0.29/1000 (CI, 0.13-0.48); GA with NMB, 0.29/1000 (CI, 0.06-0.84); sedated, 1.47/1000 (CI, 0.3-4.3); and awake, 1.15/1000 (CI, 0.02-6.4).The placement of regional anesthetic blocks in pediatric patients under GA is as safe as placement in sedated and awake children. Our results provide the first prospective evidence for the pediatric anesthesia community that the practice of placing blocks in anesthetized patients should be considered safe and should remain the prevailing standard of care. Prohibitive recommendations based on anecdote and case reports cannot be supported.

  View details for DOI 10.1097/AAP.0000000000000102

  View details for PubMedID 24918334

• The ACTTION-American Pain Society Pain Taxonomy (AAPT): An Evidence-Based and Multidimensional Approach to Classifying Chronic Pain Conditions JOURNAL OF PAIN Fillingim, R. B., Bruehl, S., Dworkin, R. H., Dworkin, S. F., Loeser, J. D., Turk, D. C., Widerstrom-Noga, E., Arnold, L., Bennett, R., Edwards, R. R., Freeman, R., Gewandter, J., Hertz, S., Hochberg, M., Krane, E., Mantyh, P. W., Markman, J., Neogi, T., Ohrbach, R., Paice, J. A., Porreca, F., Rappaport, B. A., Smith, S. M., Smith, T. J., Sullivan, M. D., Verne, G. N., Wasan, A. D., Wesselmann, U. 2014; 15 (3): 241-249

  Abstract

  Current approaches to classification of chronic pain conditions suffer from the absence of a systematically implemented and evidence-based taxonomy. Moreover, existing diagnostic approaches typically fail to incorporate available knowledge regarding the biopsychosocial mechanisms contributing to pain conditions. To address these gaps, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks (ACTTION) public-private partnership with the U.S. Food and Drug Administration and the American Pain Society (APS) have joined together to develop an evidence-based chronic pain classification system called the ACTTION-APS Pain Taxonomy. This paper describes the outcome of an ACTTION-APS consensus meeting, at which experts agreed on a structure for this new taxonomy of chronic pain conditions. Several major issues around which discussion revolved are presented and summarized, and the structure of the taxonomy is presented. ACTTION-APS Pain Taxonomy will include the following dimensions: 1) core diagnostic criteria; 2) common features; 3) common medical comorbidities; 4) neurobiological, psychosocial, and functional consequences; and 5) putative neurobiological and psychosocial mechanisms, risk factors, and protective factors. In coming months, expert working groups will apply this taxonomy to clusters of chronic pain conditions, thereby developing a set of diagnostic criteria that have been consistently and systematically implemented across nearly all common chronic pain conditions. It is anticipated that the availability of this evidence-based and mechanistic approach to pain classification will be of substantial benefit to chronic pain research and treatment.The ACTTION-APS Pain Taxonomy is an evidence-based chronic pain classification system designed to classify chronic pain along the following dimensions: 1) core diagnostic criteria; 2) common features; 3) common medical comorbidities; 4) neurobiological, psychosocial, and functional consequences; and 5) putative neurobiological and psychosocial mechanisms, risk factors, and protective factors.

  View details for DOI 10.1016/j.jpain.2014.01.004

  View details for PubMedID 24581634

• Chest CT in children: anesthesia and atelectasis. Pediatric radiology Newman, B., Krane, E. J., Gawande, R., Holmes, T. H., Robinson, T. E. 2014; 44 (2): 164-172

  Abstract

  There has been an increasing tendency for anesthesiologists to be responsible for providing sedation or anesthesia during chest CT imaging in young children. Anesthesia-related atelectasis noted on chest CT imaging has proven to be a common and troublesome problem, affecting image quality and diagnostic sensitivity.To evaluate the safety and effectiveness of a standardized anesthesia, lung recruitment, controlled-ventilation technique developed at our institution to prevent atelectasis for chest CT imaging in young children.Fifty-six chest CT scans were obtained in 42 children using a research-based intubation, lung recruitment and controlled-ventilation CT scanning protocol. These studies were compared with 70 non-protocolized chest CT scans under anesthesia taken from 18 of the same children, who were tested at different times, without the specific lung recruitment and controlled-ventilation technique. Two radiology readers scored all inspiratory chest CT scans for overall CT quality and atelectasis. Detailed cardiorespiratory parameters were evaluated at baseline, and during recruitment and inspiratory imaging on 21 controlled-ventilation cases and 8 control cases.Significant differences were noted between groups for both quality and atelectasis scores with optimal scoring demonstrated in the controlled-ventilation cases where 70% were rated very good to excellent quality scans compared with only 24% of non-protocol cases. There was no or minimal atelectasis in 48% of the controlled ventilation cases compared to 51% of non-protocol cases with segmental, multisegmental or lobar atelectasis present. No significant difference in cardiorespiratory parameters was found between controlled ventilation and other chest CT cases and no procedure-related adverse events occurred.Controlled-ventilation infant CT scanning under general anesthesia, utilizing intubation and recruitment maneuvers followed by chest CT scans, appears to be a safe and effective method to obtain reliable and reproducible high-quality, motion-free chest CT images in children.

  View details for DOI 10.1007/s00247-013-2800-4

  View details for PubMedID 24202432

• Neurological Complications Associated with Epidural Analgesia in Children: A Report of 4 Cases of Ambiguous Etiologies ANESTHESIA AND ANALGESIA Meyer, M. J., Krane, E. J., Goldschneider, K. R., Klein, N. J. 2012; 115 (6): 1365-1370

  Abstract

  The safety and utility of pediatric epidural analgesia is well established, but the risk of permanent neurological injury is unknown and largely must be extrapolated from adult literature. In this article we present a series of 4 cases of longterm or permanent neurologic complications associated with epidural analgesia. Possible mechanisms of injury and implications for practice are discussed.

  View details for DOI 10.1213/ANE.0b013e31826918b6

  View details for Web of Science ID 000311593800016

• Pediatric Regional Anesthesia Network (PRAN): A Multi-Institutional Study of the Use and Incidence of Complications of Pediatric Regional Anesthesia ANESTHESIA AND ANALGESIA Polaner, D. M., Taenzer, A. H., Walker, B. J., Bosenberg, A., Krane, E. J., Suresh, S., Wolf, C., Martin, L. D. 2012; 115 (6): 1353-1364

  Abstract

  Regional anesthesia is increasingly used in pediatric patients to provide postoperative analgesia and to supplement intraoperative anesthesia. The Pediatric Regional Anesthesia Network was formed to obtain highly audited data on practice patterns and complications and to facilitate collaborative research in regional anesthetic techniques in infants and children.We constructed a centralized database to collect detailed prospective data on all regional anesthetics performed by anesthesiologists at the participating centers. Data were uploaded via a secure Internet connection to a central server. Data were rigorously audited for accuracy and errors were corrected. All anesthetic records were scrutinized to ensure that every block that was performed was captured in the database. Intraoperative and postoperative complications were tracked until their resolution. Blocks were categorized by type and as single-injection or catheter (continuous) blocks.A total of 14,917 regional blocks, performed on 13,725 patients, were accrued from April 1, 2007 through March 31, 2010. There were no deaths or complications with sequelae lasting >3 months (95% CI 0-2:10,000). Single-injection blocks had fewer adverse events than continuous blocks, although the most frequent events (33% of all events) in the latter group were catheter-related problems. Ninety-five percent of blocks were placed while patients were under general anesthesia. Single-injection caudal blocks were the most frequently performed (40%), but peripheral nerve blocks were also frequently used (35%), possibly driven by the widespread use of ultrasound (83% of upper extremity and 69% of lower extremity blocks).Regional anesthesia in children as commonly performed in the United States has a very low rate of complications, comparable to that seen in the large multicenter European studies. Ultrasound may be increasing the use of peripheral nerve blocks. Multicenter collaborative networks such as the Pediatric Regional Anesthesia Network can facilitate the collection of detailed prospective data for research and quality improvement.

  View details for DOI 10.1213/ANE.0b013e31825d9f4b

  View details for Web of Science ID 000311593800015

  View details for PubMedID 22696610

• Pediatric Analgesic Clinical Trial Designs, Measures, and Extrapolation: Report of an FDA Scientific Workshop PEDIATRICS Berde, C. B., Walco, G. A., Krane, E. J., Anand, K. J., Aranda, J. V., Craig, K. D., Dampier, C. D., Finkel, J. C., Grabois, M., Johnston, C., Lantos, J., Lebel, A., Maxwell, L. G., McGrath, P., Oberlander, T. F., Schanberg, L. E., Stevens, B., Taddio, A., von Baeyer, C. L., Yaster, M., Zempsky, W. T. 2012; 129 (2): 354-364

  Abstract

  Analgesic trials pose unique scientific, ethical, and practical challenges in pediatrics. Participants in a scientific workshop sponsored by the US Food and Drug Administration developed consensus on aspects of pediatric analgesic clinical trial design. The standard parallel-placebo analgesic trial design commonly used for adults has ethical and practical difficulties in pediatrics, due to the likelihood of subjects experiencing pain for extended periods of time. Immediate-rescue designs using opioid-sparing, rather than pain scores, as a primary outcome measure have been successfully used in pediatric analgesic efficacy trials. These designs maintain some of the scientific benefits of blinding, with some ethical and practical advantages over traditional designs. Preferred outcome measures were recommended for each age group. Acute pain trials are feasible for children undergoing surgery. Pharmacodynamic responses to opioids, local anesthetics, acetaminophen, and nonsteroidal antiinflammatory drugs appear substantially mature by age 2 years. There is currently no clear evidence for analgesic efficacy of acetaminophen or nonsteroidal antiinflammatory drugs in neonates or infants younger than 3 months of age. Small sample designs, including cross-over trials and N of 1 trials, for particular pediatric chronic pain conditions and for studies of pain and irritability in pediatric palliative care should be considered. Pediatric analgesic trials can be improved by using innovative study designs and outcome measures specific for children. Multicenter consortia will help to facilitate adequately powered pediatric analgesic trials.

  View details for DOI 10.1542/peds.2010-3591

  View details for Web of Science ID 000300395100058

  View details for PubMedID 22250028

• Neuropathic Pain in Children: Special Considerations MAYO CLINIC PROCEEDINGS Walco, G. A., Dworkin, R. H., Krane, E. J., LeBel, A. A., Treede, R. 2010; 85 (3): S33-S41

  Abstract

  Neuropathic pain is relatively uncommon in children. Although some syndromes closely resemble those found in adults, the incidence and course of the condition can vary substantially in children, depending on developmental status and contextual factors. There are some neuropathic pain syndromes that are rare and relatively unique to the pediatric population. This article discusses the array of neuropathic pain conditions in children and available treatment strategies. Data are limited by small numbers and few randomized controlled trials. Research and clinical implications are discussed.

  View details for DOI 10.4065/mcp.2009.0647

  View details for Web of Science ID 000275807700004

  View details for PubMedID 20194147

  View details for PubMedCentralID PMC2844006

• Recommendations for the Pharmacological Management of Neuropathic Pain: An Overview and Literature Update MAYO CLINIC PROCEEDINGS Dworkin, R. H., O'Connor, A. B., Audette, J., Baron, R., Gourlay, G. K., Haanpaa, M. L., Kent, J. L., Krane, E. J., LeBel, A. A., Levy, R. M., Mackey, S. C., Mayer, J., Miaskowski, C., Raja, S. N., Rice, A. S., Schmader, K. E., Stacey, B., Stanos, S., Treede, R., Turk, D. C., Walco, G. A., Wells, C. D. 2010; 85 (3): S3-S14

  Abstract

  The Neuropathic Pain Special Interest Group of the International Association for the Study of Pain recently sponsored the development of evidence-based guidelines for the pharmacological treatment of neuropathic pain. Tricyclic antidepressants, dual reuptake inhibitors of serotonin and norepinephrine, calcium channel alpha(2)-delta ligands (ie, gabapentin and pregabalin), and topical lidocaine were recommended as first-line treatment options on the basis of the results of randomized clinical trials. Opioid analgesics and tramadol were recommended as second-line treatments that can be considered for first-line use in certain clinical circumstances. Results of several recent clinical trials have become available since the development of these guidelines. These studies have examined botulinum toxin, high-concentration capsaicin patch, lacosamide, selective serotonin reuptake inhibitors, and combination therapies in various neuropathic pain conditions. The increasing number of negative clinical trials of pharmacological treatments for neuropathic pain and ambiguities in the interpretation of these negative trials must also be considered in developing treatment guidelines. The objectives of the current article are to review the Neuropathic Pain Special Interest Group guidelines for the pharmacological management of neuropathic pain and to provide a brief overview of these recent studies.

  View details for DOI 10.4065/mcp.2009.0649

  View details for Web of Science ID 000275807700001

  View details for PubMedID 20194146

  View details for PubMedCentralID PMC2844007

• Patient-controlled analgesia: Proxy-controlled analgesia? ANESTHESIA AND ANALGESIA Krane, E. J. 2008; 107 (1): 15-17

  View details for DOI 10.1213/ane.0b013e31817532ae

  View details for Web of Science ID 000257097100006

  View details for PubMedID 18635462

• A comparison of the clinical utility of pain assessment tools for children with cognitive impairment ANESTHESIA AND ANALGESIA Voepel-Lewis, T., Malviya, S., Tait, A. R., Merkel, S., Foster, R., Krane, E. J. 2008; 106 (1): 72-78

  Abstract

  Difficulty assessing pain has been cited as one of the primary reasons for infrequent and inadequate assessment and analgesia for children with cognitive impairment (CI). Several behavioral observational pain tools have been shown to have good psychometric properties for pain assessment in this population; however, routine clinical use may depend largely on their pragmatic qualities. We designed this study to evaluate pragmatic attributes or clinical utility properties of three recently developed pain assessment tools for children with CI.A sample of clinicians from three medical centers were asked to review 15 videotaped observations of children with CI, recorded during their first three postoperative days during participation in a previous study. Participants scored pain using the revised-Face, Legs, Activity, Cry, Consolability (r-FLACC) tool (individualized for the child during the previous study) for five observations, the noncommunicative Non-Communicating Children's Pain Checklist-Postoperative Version (NCCPC-PV) for five, and the Nursing Assessment of Pain Intensity (NAPI) for five observations. After their review of all segments, participants completed the Clinical Utility Attributes Questionnaire (CUAQ) ranking three attributes of clinical utility; complexity, compatibility, and relative advantage.Five physicians and 15 nurses comprised the sample. There was excellent agreement between the coded pain scores (i.e., mild, moderate, severe pain) assigned using all tools and r-FLACC scores assigned by original observers (88%-98% exact agreement; kappa 0.71-0.96). The internal consistency or reliability of the CUAQ was supported by high alpha values for each of the subscales (alpha = 0.84-0.93). Subscale and total CUAQ scores were higher for the r-FLACC and NAPI compared with the NCCPC-PV. The r-FLACC had similar scores for complexity, but slightly higher scores for compatibility, relative advantage, and total utility compared with the NAPI.We found that clinicians rated the complexity, compatibility, relative advantage, and overall clinical utility higher for the r-FLACC and NAPI compared with the NCCPC-PV, suggesting that these tools may be more readily adopted into clinical practice.

  View details for DOI 10.1213/01.ane.0000287680.21212.d0

  View details for Web of Science ID 000251824300014

  View details for PubMedID 18165556

• A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy. I. Emergence and recovery profiles Annual Meeting of the American-College-of-Clinical-Pharmacy Davis, P. J., Galinkin, J., McGowan, F. X., Lynn, A. M., Yaster, M., Rabb, M. F., Krane, E. J., Kurth, C. D., Blum, R. H., Maxwell, L., Orr, R., Szmuk, P., Hechtman, D., Edwards, S., Henson, L. G. LIPPINCOTT WILLIAMS & WILKINS. 2001: 1380–86

  Abstract

  Pyloric stenosis is sometimes associated with hemodynamic instability and postoperative apnea. In this multicenter study we examined the hemodynamic response and recovery profile of remifentanil and compared it with that of halothane in infants undergoing pyloromyotomy. After atropine, propofol, and succinylcholine administration and tracheal intubation, patients were randomized (2:1 ratio) to receive either remifentanil with nitrous oxide and oxygen or halothane with nitrous oxide and oxygen as the maintenance anesthetic. Pre- and postoperative pneumograms were done and evaluated by an observer blinded to the study. Intraoperative hemodynamic data and postanesthesia care unit (PACU) discharge times, PACU recovery scores, pain medications, and adverse events (vomiting, bradycardia, dysrhythmia, and hypoxemia) were recorded by the study's research nurse. There were no significant differences in patient age or weight between the two groups. There were no significant differences in hemodynamic values between the two groups at the various intraoperative stress points. The extubation times, PACU discharge times, pain medications, and adverse events were similar for both groups. No patient anesthetized with remifentanil who had a normal preoperative pneumogram had an abnormal postoperative pneumogram, whereas three patients with a normal preoperative pneumogram who were anesthetized with halothane had abnormal pneumograms after.The use of ultra-short-acting opioids may be an appropriate technique for infants less than 2 mo old when tracheal extubation after surgery is anticipated.

  View details for Web of Science ID 000172364000005

  View details for PubMedID 11726411

• A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy. II. Perioperative breathing patterns in neonates and infants with pyloric stenosis Annual Meeting of the American-College-of-Clinical-Pharmacy Galinkin, J. L., Davis, P. J., McGowan, F. X., Lynn, A. M., Rabb, M. F., Yaster, M., Henson, L. G., Blum, R., Hechtman, D., Maxwell, L., Szmuk, P., Orr, R., Krane, E. J., Edwards, S., Kurth, C. D. LIPPINCOTT WILLIAMS & WILKINS. 2001: 1387–92

  Abstract

  Although former preterm birth infants are at risk for postoperative apnea after surgery, it is unclear whether the same is true of full-term birth infants. We evaluated the incidence of apnea in 60 full-term neonates and infants undergoing pyloromyotomy both before and after anesthesia. All subjects were randomized to a remifentanil- or halothane-based anesthetic. Apnea was defined by the presence of prolonged apnea (>15 s) or frequent brief apnea, as observed on the pneumocardiogram. Apnea occurred before surgery in 27% of subjects and after surgery in 16% of subjects, with no significant difference between subjects randomized to remifentanil or halothane anesthesia. This apnea was primarily central in origin, occurred throughout the recording epochs, and was associated with severe desaturation in some instances. Of the subjects with normal preoperative pneumocardiograms, new onset postoperative apnea occurred in 3 (23%) of 13 subjects who received halothane-based anesthetics versus 0 (0%) of 22 subjects who received remifentanil-based anesthetics (P = 0.04). Thus, postoperative apnea can follow anesthesia in otherwise healthy full-term infants after pyloromyotomy and is occasionally severe with desaturation. New-onset postoperative apnea was not seen with a remifentanil-based anesthetic.Abnormal breathing patterns can follow anesthesia in infants after surgical repair of pyloric stenosis. Occasionally, these patterns can be associated with desaturation. New-onset postoperative apnea was not seen with a remifentanil-based anesthetic.

  View details for Web of Science ID 000172364000006

  View details for PubMedID 11726412

• Outcomes after single injection caudal epidural versus continuous infusion epidural via caudal approach for postoperative analgesia in infants and children undergoing patent ductus arteriosus ligation PAEDIATRIC ANAESTHESIA Lin, Y. C., Sentivany-Collins, S. K., Peterson, K. L., Boltz, M. G., Krane, E. J. 1999; 9 (2): 139-143

  Abstract

  Adequate postoperative analgesia enhances deep breathing and minimizes respiratory complications after thoracotomy. This study compares postoperative outcomes after single injection caudal epidural vs continuous infusion epidural via caudal approach for postoperative analgesia in infants and children undergoing thoracotomy for patent ductus arteriosus (PDA) ligation. A retrospective chart review was performed for 27 children who had undergone PDA ligation. The children were divided into three groups. We compared patient demographics, surgical duration, anaesthesia duration, length of ICU stay, incidence of emesis requiring treatment, time required to establish regular oral intake, requirement for supplemental intravenous opioids during the first postoperative day, and length of hospital stay. For paediatric patients undergoing PDA ligation, postoperative analgesia with continuous infusion epidural via caudal approach produced shorter ICU stay, less occurrence of postoperative emesis, earlier oral intake, elimination of intravenous opioid supplementation, and shorter hospital stay compared with single injection caudal epidural techniques.

  View details for PubMedID 10189655

• The safety of epidurals placed under general anesthesia (editorial). Regional Anesthesia and Pain Medicine Krane, E.J., Dalens, B.J., Murat, I, Murrell, D. 1998
• SUBCLINICAL BRAIN-SWELLING IN CHILDREN DURING TREATMENT OF DIABETIC-KETOACIDOSIS NEW ENGLAND JOURNAL OF MEDICINE Krane, E. J., Rockoff, M. A., WALLMAN, J. K., Wolfsdorf, J. I. 1985; 312 (18): 1147-1151

  Abstract

  Clinically apparent cerebral edema is a rare and often fatal complication of diabetic ketoacidosis. To determine whether subclinical brain swelling occurs more commonly, we obtained cranial CT scans in six children with diabetic ketoacidosis treated with fluid resuscitation and continuous low-dose insulin therapy. Control scans were obtained before hospital discharge. Compared with the scans during convalescence, the early scans of all six children showed a narrowing of the brain's ventricular system, compatible with brain swelling. Average changes in diameter were 1.3 +/- 0.1 mm for the third ventricle and 3.7 +/- 0.8 mm for the lateral ventricles (P less than 0.01). In addition, a narrowing of the subarachnoid spaces was subjectively noted during a blind reading of the early scans. Although no single scan was overtly indicative of cerebral edema, the data suggest that subclinical brain swelling may be a common occurrence during treatment of diabetic ketoacidosis in children. Sequential CT scans of the brain may provide a means of evaluating modifications of standard therapy aimed at preventing cerebral edema.

  View details for Web of Science ID A1985AGA9500003

  View details for PubMedID 3920521

• Analgesic Drug Development for Children: A History of Shortcomings Until Now. Journal of pain research Dinh, A., Berger, A., Krane, E. 2021; 14: 867–70

  View details for DOI 10.2147/JPR.S291594

  View details for PubMedID 33833564

• Evaluating Telehealth Implementation in the Context of Pediatric Chronic Pain Treatment during COVID-19. Children (Basel, Switzerland) Richardson, P. A., Parker, D. M., Chavez, K., Birnie, K. A., Krane, E. J., Simons, L. E., Cunningham, N. R., Bhandari, R. P. 2021; 8 (9)

  Abstract

  Telehealth has emerged as a promising healthcare delivery modality due to its ability to ameliorate traditional access-level barriers to treatment. In response to the onset of the novel coronavirus (COVID-19) pandemic, multidisciplinary pain clinics either rapidly built telehealth infrastructure from the ground up or ramped up existing services. As the use of telehealth increases, it is critical to develop data collection frameworks that guide implementation. This applied review provides a theoretically-based approach to capitalize on existing data sources and collect novel data to inform virtually delivered care in the context of pediatric pain care. Reviewed multisource data are (1) healthcare administrative data; (2) electronic chart review; (3) clinical health registries; and (4) stakeholder feedback. Preliminary telehealth data from an interdisciplinary pediatric chronic pain management clinic (PPMC) serving youth ages 8-17 years are presented to illustrate how relevant implementation outcomes can be extracted from multisource data. Multiple implementation outcomes were assessed, including telehealth adoption rates, patient clinical symptoms, and mixed-method patient-report telehealth satisfaction. This manuscript provides an applied roadmap to leverage existing data sources and incorporate stakeholder feedback to guide the implementation of telehealth in pediatric chronic pain settings through and beyond COVID-19. Strengths and limitations of the modeled data collection approach are discussed within the broader context of implementation science.

  View details for DOI 10.3390/children8090764

  View details for PubMedID 34572195

• With Apologies to Lennon and McCartney, All We Need is Data Opioid Concerns in Pediatrics CLINICAL JOURNAL OF PAIN Krane, E. J., Walco, G. A. 2019; 35 (6): 461–62

  View details for DOI 10.1097/AJP.0000000000000699

  View details for Web of Science ID 000467737200001

• With Apologies to Lennon and McCartney, All We Need is Data: Opioid Concerns in Pediatrics. The Clinical journal of pain Krane, E. J., Walco, G. A. 2019

  View details for PubMedID 30985392

• The Opioid Debate-PRO: Opioids Have an Important Role in Pain Management in Children. The Clinical journal of pain Krane, E. J. 2019

  Abstract

  The increase in opioid-related deaths in the United States (and other countries) has prompted a national debate in medicine about the appropriateness of opioids for the treatment of acute and chronic pain, and specifically in children, if medical opioid use causes or increases the risk of opioid use disorder (OUD) later in life. Some in the medical community and in government advocate withholding opioids from children after an arbitrary number of days of treatment, regardless of diagnosis. Here, I argue that opioid experimentation and misuse is no more common in children and adolescents today than 2 or 3 decades ago, that there is no compelling evidence that appropriate medical use of opioids leads to OUD, and that the epidemic of inadequately treated pain in children remains the more compelling issue.

  View details for PubMedID 30985393

• Antiepileptic drugs for chronic non-cancer pain in children and adolescents COCHRANE DATABASE OF SYSTEMATIC REVIEWS Cooper, T. E., Wiffen, P. J., Heathcote, L. C., Clinch, J., Howard, R., Krane, E., Lord, S. M., Sethna, N., Schechter, N., Wood, C. 2017: CD012536

  Abstract

  Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization (WHO) guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past, pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as importantWe designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol) in order to review the evidence for children's pain utilising pharmacological interventions in children and adolescents.As the leading cause of morbidity in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (that is pain lasting three months or longer) can occur in the paediatric population in a variety of pathophysiological classifications (nociceptive, neuropathic, or idiopathic) relating to genetic conditions, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, and for other unknown reasons.Antiepileptic (anticonvulsant) drugs, which were originally developed to treat convulsions in people with epilepsy, have in recent years been used to provide pain relief in adults for many chronic painful conditions and are now recommended for the treatment of chronic pain in the WHO list of essential medicines. Known side effects of antiepileptic drugs range from sweating, headache, elevated temperature, nausea, and abdominal pain to more serious effects including mental or motor function impairment.To assess the analgesic efficacy and adverse events of antiepileptic drugs used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting.We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid, and Embase via Ovid from inception to 6 September 2016. We also searched the reference lists of retrieved studies and reviews as well as online clinical trial registries.Randomised controlled trials, with or without blinding, by any route, treating chronic non-cancer pain in children and adolescents, comparing any antiepileptic drug with placebo or an active comparator.Two review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and number needed to treat for one additional event, using standard methods if data were available. We assessed the evidence using GRADE and created two 'Summary of findings' tables.We included two studies with a total of 141 participants (aged 7 to 18 years) with chronic neuropathic pain, complex regional pain syndrome type 1 (CRPS-I), or fibromyalgia. One study investigated pregabalin versus placebo in participants with fibromyalgia (107 participants), and the other study investigated gabapentin versus amitriptyline in participants with CRPS-I or neuropathic pain (34 participants). We were unable to perform any quantitative analysis.Risk of bias for the two included studies varied, due to issues with randomisation (low to unclear risk), blinding of outcome assessors (low to unclear risk), reporting bias (low to unclear risk), the size of the study populations (high risk), and industry funding in the 'other' domain (low to unclear risk). We judged the remaining domains of sequence generation, blinding of participants and personnel, and attrition as low risk of bias. Primary outcomesOne study (gabapentin 900 mg/day versus amitriptyline 10 mg/day, 34 participants, for 6 weeks) did not report our primary outcomes (very low-quality evidence).The second study (pregabalin 75 to 450 mg/day versus placebo 75 to 450 mg/day, 107 participants, for 15 weeks) reported no significant change in pain scores for pain relief of 30% or greater between pregabalin 18/54 (33.3%), and placebo 16/51 (31.4%), P = 0.83 (very low-quality evidence). This study also reported Patient Global Impression of Change, with the percentage of participants feeling "much or very much improved" with pregabalin 53.1%, and placebo 29.5% (very low-quality evidence).We downgraded the evidence by three levels to very low for one of two reasons: due to the fact that there was no evidence to support or refute the use of the intervention, or that there were too few data and the number of events was too small to be meaningful. Secondary outcomesIn one small study, adverse events were uncommon: gabapentin 2 participants (2 adverse events); amitriptyline 1 participant (1 adverse event) (6-week trial). The second study reported a higher number of adverse events: pregabalin 38 participants (167 adverse events); placebo 34 participants (132 adverse events) (15-week trial) (very low-quality evidence).Withdrawals due to adverse events were infrequent in both studies: pregabalin (4 participants), placebo (4 participants), gabapentin (2 participants), and amitriptyline (1 participant) (very low-quality evidence).Serious adverse events were reported in both studies. One study reported only one serious adverse event (cholelithiasis and major depression resulting in hospitalisation in the pregabalin group) and the other study reported no serious adverse events (very low-quality evidence).There were few or no data for our remaining secondary outcomes (very low-quality evidence).We downgraded the evidence by three levels to very low due to too few data and the fact that the number of events was too small to be meaningful.This review identified only two small studies, with insufficient data for analysis.As we could undertake no meta-analysis, we were unable to comment about efficacy or harm from the use of antiepileptic drugs to treat chronic non-cancer pain in children and adolescents. Similarly, we could not comment on our remaining secondary outcomes: Carer Global Impression of Change; requirement for rescue analgesia; sleep duration and quality; acceptability of treatment; physical functioning; and quality of life.We know from adult randomised controlled trials that some antiepileptics, such as gabapentin and pregabalin, can be effective in certain chronic pain conditions.We found no evidence to support or refute the use of antiepileptic drugs to treat chronic non-cancer pain in children and adolescents.

  View details for DOI 10.1002/14651858.CD012536.pub2

  View details for Web of Science ID 000408828100004

  View details for PubMedID 28779491

• Opioids for chronic non-cancer pain in children and adolescents COCHRANE DATABASE OF SYSTEMATIC REVIEWS Cooper, T. E., Fisher, E., Gray, A. L., Krane, E., Sethna, N., van Tilburg, M. L., Zernikow, B., Wiffen, P. J. 2017: CD012538

  Abstract

  Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past, pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as importantWe designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol as priority areas) in order to review the evidence for children's pain utilising pharmacological interventions in children and adolescents.As the leading cause of morbidity in children and adolescents in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (lasting three months or longer) can arise in the paediatric population in a variety of pathophysiological classifications: nociceptive, neuropathic, idiopathic, visceral, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, and other unknown reasons.Opioids are used worldwide for the treatment of pain. They bind to opioid receptors in the central nervous system (mu, kappa, delta, and sigma) and can be agonists, antagonists, mixed agonist-antagonists, or partial agonists. Opioids are generally available in healthcare settings across most high-income countries, but access may be restricted in low- and middle-income countries. For example, opioids currently available in the UK include: buprenorphine, codeine, fentanyl, hydromorphone, methadone, morphine, oxycodone, and tramadol. Opioids are used in varying doses (generally based on body weight for paediatric patients) by means of parenteral, transmucosal, transdermal, or oral administration (immediate release or modified release). To achieve adequate pain relief in children using opioids, with an acceptable grade of adverse effects, the recommended method is a lower dose gradually titrated to effect in the child.To assess the analgesic efficacy and adverse events of opioids used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting.We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Library, MEDLINE via Ovid, and Embase via Ovid from inception to 6 September 2016. We also searched the reference lists of retrieved studies and reviews, and searched online clinical trial registries.Randomised controlled trials, with or without blinding, of any dose and any route, treating chronic non-cancer pain in children and adolescents, comparing opioids with placebo or an active comparator.Two review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and number needed to treat, using standard methods. We assessed GRADE (Grading of Recommendations Assessment, Development and Evaluation) and planned to create a 'Summary of findings' table.No studies were eligible for inclusion in this review. We rated the quality of the evidence as very low. We downgraded the quality of evidence by three levels due to the lack of data reported for any outcome.There was no evidence from randomised controlled trials to support or refute the use of opioids to treat chronic non-cancer pain in children and adolescents. We are unable to comment about efficacy or harm from the use of opioids to treat chronic non-cancer pain in children and adolescents.We know from adult randomised controlled trials that some opioids, such as morphine and codeine, can be effective in certain chronic pain conditions.This means that no conclusions could be made about efficacy or harm in the use of opioids to treat chronic non-cancer pain in children and adolescents.

  View details for DOI 10.1002/14651858.CD012538.pub2

  View details for Web of Science ID 000406831100032

  View details for PubMedID 28745394

• Prevention and Treatment of Pain in Children: Toward a Paradigm Shift OTOLARYNGOLOGY-HEAD AND NECK SURGERY Friedrichsdorf, S. J., Sidman, J., Krane, E. J. 2016; 154 (5): 804–5

  Abstract

  Rosenfeld et al in their recent article "Office Insertion of Tympanostomy Tubes without Anesthesia in Young Children" describe using a "papoose board for restraint" while performing a procedure resulting in severe pain for a significant number of children: a myringotomy and tube insertion. In 2016, it is inappropriate to perform elective painful procedures in children without treatment to avoid or minimize pain. We strongly disagree with the authors' conclusion "that office insertion of tubes in young children is a feasible alternative to general anesthesia for caregivers and clinicians who are comfortable with this choice."

  View details for PubMedID 27130944

• Two Virtual Reality Pilot Studies for the Treatment of Pediatric CRPS PAIN MEDICINE Won, A., Tataru, C. A., Cojocaru, C. M., Krane, E. J., Bailenson, J. N., Niswonger, S., Golianu, B. 2015; 16 (8): 1644–47

  View details for PubMedID 25930099

• Editorial Comment: Thoracic Paravertebral Blockade for the Management of Pain Associated with Cystic Fibrosis A & A CASE REPORTS Krane, E. J. 2015; 4 (3): 33

  View details for PubMedID 25642955

• Interscalene brachial plexus blocks under general anesthesia in children: is this safe practice?: A report from the Pediatric Regional Anesthesia Network (PRAN). Regional anesthesia and pain medicine Taenzer, A., Walker, B. J., Bosenberg, A. T., Krane, E. J., Martin, L. D., Polaner, D. M., Wolf, C., Suresh, S. 2014; 39 (6): 502-505

  Abstract

  A practice advisory on regional anesthesia in children in 2008, published in this journal, supported the placement of regional blocks in children under general anesthesia (GA). Interscalene brachial plexus (IS) blocks were specifically excluded, based on case reports (level 3 evidence) of injury, which occurred predominantly in heavily sedated or anesthetized adult patients. Apart from case reports, there is a paucity of data that explore the safety of IS blocks placed in patients under GA, and the level of evidence available on which to base recommendations is limited.Querying the database of the Pediatric Regional Anesthesia Network (PRAN), we report on the incidence of postoperative neurological symptoms, local anesthetic systemic toxicity, and other reported adverse events in children receiving IS blocks under GA or sedated.A total of 518 interscalene blocks were performed, 390 under GA and 123 with the patient sedated or awake (5 cases had missing status); 472 of these were single injection, and 46 involved the placement of infusion catheters. Eighty-eight percent of blocks were placed with ultrasound guidance, 7.7% with no location device, and 2.5% with a nerve stimulator. No local anesthetic systemic toxicity, postoperative neurological symptoms, cardiovascular complications, or dural puncture was reported in this cohort. There were 1 vascular puncture and 1 postoperative infection. These negative results are compatible with 0 to 7.7/1000 events for each of these complications for IS blocks placed under GA. There was no paralysis, motor block, or sensory deficit beyond the expected block duration time.Analyzing interscalene blocks in children placed under GA, we identified no serious adverse events. The upper limit of the confidence interval for these events is similar to that in awake or sedated adults receiving IS blocks. Based on these prospectively collected data, placement of IS blocks under GA in children is no less safe than placement in awake adults, calling into question the American Society of Regional Anesthesia and Pain Medicine advisory proscribing GA during IS block in pediatric patients.

  View details for DOI 10.1097/AAP.0000000000000166

  View details for PubMedID 25304482

• QUANTITATIVE CENTRAL AIRWAY MEASUREMENTS DO NOT DEMONSTRATE PROGRESSION IN BRONCHIECTSIS IN OLDER CHILDREN WITH MILD CF LUNG DISEASE Robinson, T., Ziyeh, T., Tu, C., Yilma, M., Krane, E., Newman, B. WILEY-BLACKWELL. 2014: 367

  View details for Web of Science ID 000342926000500

• Asleep Versus Awake: Does It Matter? Pediatric Regional Block Complications by Patient State: A Report From the Pediatric Regional Anesthesia Network REGIONAL ANESTHESIA AND PAIN MEDICINE Taenzer, A. H., Walker, B. J., Bosenberg, A. T., Martin, L., Suresh, S., Polaner, D. M., Wolf, C., Krane, E. J. 2014; 39 (4): 279-283

  Abstract

  The impact of the patient state at time of placement of regional blocks on the risk of complications is unknown. Current opinion is based almost entirely on case reports, despite considerable interest in the question. Analyzing more than 50,000 pediatric regional anesthesia blocks from an observational prospective database, we determined the rate of adverse events in relation to the patient's state at the time of block placement. Primary outcomes considered were postoperative neurologic symptoms (PONSs) and local anesthetic systemic toxicity (LAST). Secondary outcome was extended hospital stay due to a block complication.The Pediatric Regional Anesthesia Network is a multi-institutional research consortium that was created with an emphasis on rigorous, prospective, and complete data collection including a data validation and audit process. For the purpose of the analysis, blocks were divided in major groups by single injection versus continuous and by block location. Rates were determined in aggregate for these groups and classified further based on the patient's state (general anesthesia [GA] without neuromuscular blockade [NMB], GA with NMB, sedated, and awake) at the time of block placement.Postoperative neurological symptoms occurred at a rate of 0.93/1000 (confidence interval [CI], 0.7-1.2) under GA and 6.82/1000 (CI, 4.2-10.5) in sedated and awake patients. The only occurrence of PONSs lasting longer than 6 months (PONSs-L) was a small sensory deficit in a sedated patient (0.019/1000 [CI, 0-0.1] for all, 0.48/1000 [CI, 0.1-2.7] for sedated patients). There were no cases of paralysis. There were 5 cases of LAST or 0.09/1000 (CI, 0.03-0.21). The incidence of LAST in patients under GA (both with and without NMB) was 0.08/1000 (CI, 0.02-0.2) and 0.34/1000 (CI, 0-1.9) in awake/sedated patients. Extended hospital stays were described 18 times (0.33/1000 [CI, 0.2-0.53]). The rate for patients under GA without NMB was 0.29/1000 (CI, 0.13-0.48); GA with NMB, 0.29/1000 (CI, 0.06-0.84); sedated, 1.47/1000 (CI, 0.3-4.3); and awake, 1.15/1000 (CI, 0.02-6.4).The placement of regional anesthetic blocks in pediatric patients under GA is as safe as placement in sedated and awake children. Our results provide the first prospective evidence for the pediatric anesthesia community that the practice of placing blocks in anesthetized patients should be considered safe and should remain the prevailing standard of care. Prohibitive recommendations based on anecdote and case reports cannot be supported.

  View details for DOI 10.1097/AAP.0000000000000102

  View details for Web of Science ID 000338776000004

• The safety and effectiveness of continuous peripheral nerve blockade in children. Anesthesia and analgesia Krane, E. J., Polaner, D. 2014; 118 (3): 499-500

  View details for DOI 10.1213/ANE.0000000000000110

  View details for PubMedID 24557094

• INCREASED BRONCHIAL WALL THICKNESS (BWT) AND BRONCHIECTASIS (B) SCORES ARE STRONGLY ASSOCIATED WITH INCREASED QUANTITATIVE REGIONAL AIR TRAPPING IN YOUNG CHILDREN WITH EARLY CF LUNG DISEASE Robinson, T., Tu, C., Yilma, M., Prais, D., Goris, M., Krane, E., Holmes, T., Newman, B. WILEY-BLACKWELL. 2013: 354

  View details for Web of Science ID 000334387200487

• Brain uptake of Tc99m-HMPAO correlates with clinical response to the novel redox modulating agent EPI-743 in patients with mitochondrial disease MOLECULAR GENETICS AND METABOLISM Blankenberg, F. G., Kinsman, S. L., Cohen, B. H., Goris, M. L., Spicer, K. M., Perlman, S. L., Krane, E. J., Kheifets, V., Thoolen, M., Miller, G., Enns, G. M. 2012; 107 (4): 690-699

  Abstract

  While decreased ATP production and redox imbalance are central to mitochondrial disease pathogenesis, efforts to develop effective treatments have been hampered by the lack of imaging markers of oxidative stress. In this study we wished to determine if Tc99m-HMPAO, a SPECT imaging marker of cerebral blood flow and glutathione/protein thiol content, could be used to monitor the effect(s) of EPI-743, an oral redox modulating, para-benzoquinone based therapeutic for mitochondrial disease. We hypothesized that treatment changes in HMPAO uptake would be inversely proportional to changes in oxidative stress within the brain and directly correlate to clinical response to EPI-743 therapy. Twenty-two patients with mitochondrial disease were treated with EPI-743. Each underwent baseline and 3-month Tc99m-HMPAO SPECT scanning along with clinical/neurologic evaluations. Diseases treated were: Leigh syndrome (n=7), polymerase γ deficiency (n=5), MELAS (n=5), Friedreich ataxia (n=2), Kearns-Sayre syndrome, Pearson syndrome, and mtDNA depletion syndrome. Neuro-anatomic uptake analyses of HMPAO were performed with NeuroGam™ (Segami Corp.) statistical software and clinical response was assessed by the Newcastle Paediatric Mitochondrial Disease Scale or Newcastle Mitochondrial Disease Adult Scale depending on patient age. For all 22 patients there was a significant linear correlation between the change in cerebellar uptake of HMPAO and the improvement in Newcastle score (r=0.623, **p=0.00161). The MELAS subgroup showed a significant relationship of whole brain uptake (n=5, r=0.917, *p=0.028) to improvement in Newcastle score. We conclude that Tc99m-HMPAO SPECT scanning has promise as a general marker of the oxidative state of the brain and its response to redox modulating therapies. Further studies will be needed to confirm these findings in a more homogenous study population.

  View details for DOI 10.1016/j.ymgme.2012.09.023

  View details for Web of Science ID 000311816200010

  View details for PubMedID 23084792

• SAFETY AND FEASIBILITY OF CONTROLLED VENTILATION INFANT CT SCANNING USING RECRUITMENT AND SCAN ACQUISITION TECHNIQUES Robinson, T., Newman, B., Krane, E., Goris, M. WILEY-BLACKWELL. 2011: 351

  View details for Web of Science ID 000296071800462

• Non-pharmacological techniques for pain management in neonates SEMINARS IN PERINATOLOGY Golianu, B., Krane, E., Seybold, J., Almgren, C., Anand, K. J. 2007; 31 (5): 318-322

  Abstract

  Significant progress in understanding the physiology, clinical correlates, and consequences of neonatal pain have resulted in greater attention to pain management during neonatal intensive care. A number of nonpharmacological therapies have been investigated, including nonnutritive sucking, with and without sucrose use, swaddling or facilitated tucking, kangaroo care, music therapy, and multi-sensorial stimulation. Although the efficacy of these approaches is clearly evident, they cannot provide analgesia for moderate or severe pain in the neonate. Further, some of these therapies cannot be effectively applied to all populations of critically ill neonates. Acupuncture, an ancient practice in Chinese medicine, has gained increasing popularity for symptom control among adults and older children. Acupuncture may provide an effective nonpharmacological approach for the treatment of pain in neonates, even moderate or severe pain, and should be considered for inclusion in a graduated multidisciplinary algorithm for neonatal pain management.

  View details for DOI 10.1053/j.semperi.2007.07.007

  View details for PubMedID 17905187

• Tolerability of needlefree powder lidocaine delivery system in pediatric patients undergoing venipuncture or peripheral venous carmulation: The COMFORT-003 and-004 trials Scientific Assembly of the American-College-of-Emergency-Physicians (ACEP) Krane, E., Zempsky, W. T., Leong, M. MOSBY-ELSEVIER. 2007: S37–S38

  View details for Web of Science ID 000249535600115

• Efficacy of needlefree powder lidocalne delivery system in pediatric patients undergoing venipuncture or peripheral venous carmulation: The COMFORT-003 and-004 trials Scientific Assembly of the American-College-of-Emergency-Physicians (ACEP) Krane, E., Zempsky, W. T., Leong, M. MOSBY-ELSEVIER. 2007: S37–S37

  View details for Web of Science ID 000249535600113

• Single lung ventilation in children using a new paediatric bronchial blocker PAEDIATRIC ANAESTHESIA Hammer, G. B., Harrison, T. K., Vricella, L. A., Black, M. D., Krane, E. J. 2002; 12 (1): 69-72

  Abstract

  As video-assisted thoracoscopic surgery has become more common in paediatric patients, the use of single lung ventilation in children has also increased. Single lung ventilation in young children is performed by either advancing a tracheal tube into the mainstem bronchus opposite the side of surgery or by positioning a bronchial blocker into the mainstem bronchus on the operative side. Techniques for placing a variety of bronchial blockers outside the tracheal tube have been described. We describe a technique for placement of a new bronchial blocker through an indwelling tracheal tube using a multiport adaptor and a fibreoptic bronchoscope.

  View details for PubMedID 11849579

• Tunneled epidural catheters for prolonged analgesia in pediatric patients ANESTHESIA AND ANALGESIA Aram, L., Krane, E. J., Kozloski, L. J., Yaster, M. 2001; 92 (6): 1432-1438

  Abstract

  We conducted this retrospective study to document the efficacy and safety, and demonstrate the spectrum of indications for subcutaneously tunneled epidural catheters in the management of prolonged pain in pediatric patients. The charts of 25 patients with prolonged pain that was unresponsive to conventional opioid therapy (10: end stage malignancy, 8: extensive abdominal surgery, 7: trauma, etc.) and who received thoracic, lumbar, or caudal tunneled epidural catheters between 1995 and 1999 were reviewed for efficacy and catheter-related complications (infection or bleeding at the insertion site, toxicity related to local anesthetics, tachyphylaxis and respiratory depression). Tunneled epidural catheters were effective in providing extended analgesia in all subjects. In 14 patients with chronic pain, cumulative 48-h enteral and parenteral opioid requirements were reduced or eliminated after catheter insertion. Catheters remained in place for a median of 11 days (range, 4--240 days) until there was no further need for parenteral analgesia (n = 15), death because of the underlying disease (n = 6), accidental removal (n = 2), or possible infection (n = 2). No serious local or systemic complications (meningitis, epidural abscess, systemic infection, epidural hematoma, or spinal cord injury; seizures, local anesthetic toxicity) occurred related to this technique. Five patients were discharged from the hospital with the catheter for home analgesic therapy. The use of a percutaneously inserted, subcutaneously tunneled epidural catheter is safe, effective, and provides pain relief in situations in which conventional analgesic therapy either fails or is impractical. The technique is one that may be of great value to children suffering from pain.Children and adolescents with pain may safely have a spinal catheter placed for a period of time without undo risk of infection or other complications. Spinal catheters provide excellent pain relief, often eliminating the need for riskier medications for painful events such as wound cleansing and dressing changes.

  View details for PubMedID 11375820

• Anaesthesia for liver transplantation in children PAEDIATRIC ANAESTHESIA Hammer, G. B., Krane, E. J. 2001; 11 (1): 3-18

  View details for PubMedID 11123726

• Pediatric acute pain management PEDIATRIC CLINICS OF NORTH AMERICA Golianu, B., Krane, E. J., Galloway, K. S., Yaster, M. 2000; 47 (3): 559-?

  Abstract

  The past decade has brought about an explosion of knowledge about the physiology of nociception and many new techniques for pain relief, new analgesic drugs, and new applications of old analgesic drugs. These techniques include methods of opioid administration by transdermal and transmucosal absorption and the use of neuraxial analgesia for the management of pain in children. Interest in the use of regional anesthesia in children has been rekindled, and analgesic properties and pre-emptive analgesic properties of many agents not typically considered analgesics, such as clonidine and ketamine, have been recognized. Perhaps the greatest advance has been the paradigm shift in the recognition that pain not only exists in infants and children but also is a significant cause of morbidity and even mortality. Given the unprecedented interest in pain management in adults and children, physicians can now look forward to the development of new methods of drug delivery and of receptor-specific drugs that divorce analgesia from the untoward side effects of existing analgesics. Improvement in the quality of life of hospitalized children also will occur.

  View details for PubMedID 10835991

• Defining the anatomy of Freudian psychiatry ANESTHESIA AND ANALGESIA Krane, E. 2000; 90 (2): 499-499

  View details for Web of Science ID 000084989900053

  View details for PubMedID 10648349

• Spinal epidermoid tumors: Will a forgotten complication rise again? REGIONAL ANESTHESIA AND PAIN MEDICINE Krane, E. J. 1999; 24 (6): 494-496

  View details for Web of Science ID 000083847600002

  View details for PubMedID 10588550

• Venous access for pediatric liver transplantation ANESTHESIOLOGY Hammer, G. B., Krane, E. J. 1999; 91 (1): 322-322

  View details for Web of Science ID 000081188400051

  View details for PubMedID 10422964

• Combined regional and light general anesthesia: are the risks increased or minimized? Current opinion in anaesthesiology Boltz, M. G., Krane, E. J. 1999; 12 (3): 321-323

  Abstract

  Regional anesthesia during general anesthesia has become increasingly popular in recent years. Most pediatric anesthesiologists are proponents of this practice, and believe that surgical morbidity is reduced, but controversy remains regarding safety. Neuraxial anesthesia during general anesthesia is especially controversial. Unfortunately, outcome studies are lacking but the literature reflects an absence of reported serious morbidity or mortality.

  View details for PubMedID 17013331

• Thoracic epidurals: Reply to Hough REGIONAL ANESTHESIA AND PAIN MEDICINE Krane, E. J., Dalens, B. J., Murat, I., Murrell, D. 1999; 24 (3): 273-274

  View details for Web of Science ID 000080181000019

  View details for PubMedID 10338183

• The pediatric sedation unit: A mechanism for safe pediatric sedation PEDIATRICS Krane, E. J. 1999; 103 (1): 198-198

  View details for Web of Science ID 000078060900057

  View details for PubMedID 9988633

• The safety of epidurals placed during general anesthesia REGIONAL ANESTHESIA AND PAIN MEDICINE Krane, E. J., Dalens, B. J., Murat, I., Murrell, D. 1998; 23 (5): 433-438

  View details for Web of Science ID 000076109100001

  View details for PubMedID 9773693

• The safety of epidurals placed under general anaesthesia ANNALES FRANCAISES D ANESTHESIE ET DE REANIMATION Krane, E. J., Dalens, B., Murat, I., Murrell, D. 1998; 17 (7): 750-754

  View details for PubMedID 9786805

• Superior outcomes in pediatric renal transplantation 68th Annual Session of the Pacific-Coast-Surgical-Association Salvatierra, O., Alfrey, E., Tanney, D. C., Mak, R., Hammer, G. B., Krane, E. J., So, S. K., Lemley, K., Orlandi, P. D., Conley, S. B. AMER MEDICAL ASSOC. 1997: 842–47

  Abstract

  Nationally, results of renal transplantation in children, particularly in small children, are inferior to those obtained in adults.To determine factors important for success in renal transplantation in children.Results of 108 consecutive renal transplantations performed in patients aged 7 months to 18 years were reviewed and compared with those reported by the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS), the national registry.One-, 2-, and 3-year graft survival rates (+/-SE) were 99% +/- 1%, 95% +/- 3%, and 93% +/- 4%, respectively, for living donor grafts and 97% +/- 3%, 92% +/- 6%, and 92% +/- 6%, respectively, for cadaver grafts. Incidence of acute rejection was half that reported by NAPRTCS. There were no graft losses for technical reasons (19% in NAPRTCS). Twelve percent of patients were younger than 2 years (6% in NAPRTCS); 17% were 2 to 5 years old (16% in NAPRTCS). Most small children received an adult-sized kidney. Ninety-three percent of recipients weighing 15 kg or less received postoperative mechanical ventilation assistance to optimize fluid resuscitation and perfusion of adult-sized kidneys. Structural abnormalities of the urinary tract were present in 53.7% of the patients (48.5% in NAPRTCS; adults, 5.3%). Nephroureterectomy was required in 38 children; in 27 (71%) of them, it was performed at the time of transplant surgery.Excellent results can be obtained in pediatric renal transplantation by strict adherence to surgical detail, tight immunosuppressive management, aggressive fluid management in the small child, and careful integration of urologic and transplant surgery.

  View details for PubMedID 9267267

• The Pediatric Pain and Sedation Handbook. St. Louis, MO: Mosby-Yearbook, Inc. Krane, E., Yaster, M., Kaplan R., Coté, C., Lappe, D. 1997
• - The Pediatric Pain and Sedation Handbook Yaster, M., Krane, E., Kaplan R., Coté, C., Lappe, D. 1997
• Perioperative care of the neurosurgical pediatric patient INTERNATIONAL ANESTHESIOLOGY CLINICS Hammer, G. B., Krane, E. J. 1996; 34 (4): 55-71

  View details for PubMedID 8956064

• Respiratory depression after low-dose caudal morphine CANADIAN JOURNAL OF ANAESTHESIA-JOURNAL CANADIEN D ANESTHESIE Karl, H. W., Tyler, D. C., Krane, E. J. 1996; 43 (10): 1065-1067

  Abstract

  To report a case of respiratory depression after a small dose of caudal morphine administered to a 15-mo-old child.A 15 mo, 9.8 kg boy underwent ureteral reimplantation with general endotracheal anaesthesia and 10 ml bupivacaine 0.25% (2.5 mg.kg-1). Ninety minutes after the bupivacaine, 0.4 mg (1 mg.ml-1, 0.4 ml, 0.04 mg.kg-1) preservative-free morphine was injected after negative aspiration. Slightly more than two hours after caudal morphine, the patient became lethargic and developed decreases in oxygen saturation (to 62%) without change in heart rate or respiratory rate. Intravenous naloxone 0.1 mg (0.01 mg.kg-1) markedly improved his level of consciousness. Racemic epinephrine was administered for treatment of coincident stridor. The patient required 11 hr continuous naloxone infusion (0.001-0.002 mg.kg-1.hr-1) in the intensive care unit. He was discharged on the second postopertive day without further complication.Respiratory depression can occur in children greater than one year of age, even when small doses of caudal morphine are used. Decreased arterial oxygen saturation and lethargy are important heralds. A normal respiratory rate despite substantial hypoxaemia argues that pulse oximetry (without supplemental oxygen where possible) has a clear advantage over impedance pneumography for electronic monitoring.

  View details for Web of Science ID A1996VL88700016

  View details for PubMedID 8896861

• Continuous epidural anesthesia after ureteroneocystostomy in children JOURNAL OF UROLOGY Krane, E. J. 1996; 156 (2): 481-482

  View details for Web of Science ID A1996UX15200048

  View details for PubMedID 8683710

• The OOPS procedure (operation on placental support): In utero airway management of the fetus with prenatally diagnosed tracheal obstruction 27th Annual Meeting of the Canadian-Association-of-Paediatric-Surgeons Skarsgard, E. D., Chitkara, U., Krane, E. J., Riley, E. T., Halamek, L. P., Dedo, H. H. W B SAUNDERS CO. 1996: 826–28

  Abstract

  Tracheal obstruction of the newborn caused by cervical masses such as teratomas and cystic hygromas can result in a profound hypoxic insult and even death, owing to an inability to establish an adequate airway after birth. Prenatal sonographic diagnosis of these congenital anomalies permits (1) anticipation of an airway problem at the time of delivery and (2) formulation of an algorithm for airway management while oxygen delivery to the baby is maintained through the placental circulation. This is the report of a fetus in whom a large anterior cervical cystic hygroma was detected by prenatal ultrasonography. A multidisciplinary management team was assembled, and an algorithm for airway management was developed. Elective cesarean delivery of the fetal head and thorax, under conditions of uterine tocolysis, permitted a controlled evaluation of the airway and endotracheal intubation while oxygen supply to the infant was maintained through the placenta. The baby remained intubated, and 2 days later underwent subtotal excision of the cervical cystic hygroma. Pharmacological maintenance of the feto-placental circulation after hysterotomy is an invaluable adjunct to airway management of the neonate with prenatally diagnosed tracheal obstruction.

  View details for PubMedID 8783114

• Regional anesthesia and pain management in ambulatory pediatric patients Anes Clin N.A Krane, E.J., Lin, Y 1996; 14: 803-816
• Practice guidelines for cancer pain management: A report by the American Society of Anesthesiologists Task Force on Pain Management, Cancer Pain Section Anesthesiology Ferrante, F. Michael, Bedder, M.D., Caplan, R.A., Chang, H, Connis, R.T., Harrison, P., Jamison, R.N., Krane, E.J., Nedeljkovic, S., Patt, R., Portnoy, R.K. 1996; 84: 1243-57
• Diabetic ketoacidosis and cerebral edema. PedsCCM: The Pediatric Critical Care Website, http://PedsCCM.wustl.edu/FILE-CABINET/Metab/DKA-CEdema.html Krane, E. 1996
• Regional anesthesia and pain management in ambulatory pediatric patients. Anes Clin N.A. Krane, E.J., Lin, Y 1996: 803-816
• OUTCOMES AFTER SINGLE CAUDAL INJECTION VERSUS CONTINUOUS EPIDURAL INFUSION FOR POSTOPERATIVE ANALGESIA IN CHILDREN PATENT DUCTUS-ARTERIOSUS UNDERGOING LIGATION Lin, Y. C., SENTIVANY, S. K., Boltz, M. G., Krane, E. J. LIPPINCOTT WILLIAMS & WILKINS. 1995: A1142–A1142

  View details for Web of Science ID A1995RX68501142

• COMBINED EPIDURAL GENERAL-ANESTHESIA FOR THE REPAIR OF ATRIAL SEPTAL-DEFECTS IN CHILDREN RESULTS IN SHORTER ICU STAYS Frank, R. S., Boltz, M. G., SENTIVANY, S. K., Krane, E. J. LIPPINCOTT WILLIAMS & WILKINS. 1995: A1176–A1176

  View details for Web of Science ID A1995RX68501176

• SEDATION FOR PEDIATRIC PROCEDURES WESTERN JOURNAL OF MEDICINE Sectish, T. C., Krane, E. J. 1995; 162 (4): 357-358

  View details for Web of Science ID A1995QT56900012

  View details for PubMedID 7747506

• POSTOPERATIVE APNEA, BRADYCARDIA, AND OXYGEN DESATURATION IN FORMERLY PREMATURE-INFANTS - PROSPECTIVE COMPARISON OF SPINAL AND GENERAL-ANESTHESIA ANESTHESIA AND ANALGESIA Krane, E. J., Haberkern, C. M., Jacobson, L. E. 1995; 80 (1): 7-13

  Abstract

  Eighteen formerly premature infants scheduled for inguinal herniorrhaphy and who were less than 51 wk postconceptional age were assigned to either the general anesthesia group (GA: atropine, halothane, and nitrous oxide) or the spinal anesthesia group (SA: hyperbaric tetracaine). Twelve-hour, three-channel continuous recordings of respiratory rate (chest wall impedance), electrocardiogram (ECG), and hemoglobin O2 saturation (SpO2) were obtained preoperatively and after surgery. These were analyzed for short (11-15s) and long (> 15 s) apnea spells, periodic breathing, and episodes of hemoglobin oxygen desaturation and bradycardia. Infants in the GA group had lower postoperative minimum SpO2 (68.7% +/- 11.4%) and minimum heart rate (79 bpm +/- 19) than infants in the SA group (80.7% +/- 9.2%, and 109 bpm +/- 30, respectively; P < 0.05) and had lower postoperative minimum SpO2 and minimum heart rate than they had preoperatively (79.0% +/- 13.7%, and 93 bpm +/- 31, respectively; P < 0.05); pre- and postoperative studies in the SA group did not differ. There were no differences in the incidence of postoperative central apnea. We conclude that spinal anesthesia reduces postoperative hemoglobin oxygen desaturation and bradycardia in formerly premature infants undergoing inguinal herniorrhaphy.

  View details for Web of Science ID A1995PY27000003

  View details for PubMedID 7802303

• THE PREVALENCE OF PHANTOM SENSATION AND PAIN IN PEDIATRIC AMPUTEES JOURNAL OF PAIN AND SYMPTOM MANAGEMENT Krane, E. J., Heller, L. B. 1995; 10 (1): 21-29

  Abstract

  Phantom sensations and pain occur with an unknown frequency in children. We hypothesized that such experiences are common among children, and occur more often than is recognized by health-care personnel. Children and adolescents, ages 5-19 years, who had undergone limb amputation in the past 10 years, served as subjects for this retrospective study. Subjects were divided into three major groups depending upon the indication for amputation: congenital deformity (CD), trauma/infection (TI), and cancer (Ca). Surveys assessing phantom sensations and phantom pain were mailed to children and their parents/guardians. The incidence of phantom sensations was 100% in each group, and phantom pain occurred in the overwhelming majority. Both types of phantom phenomena began within days of surgery for almost all patients. Seventy-five percent of children and adolescents who had experienced phantom pain also had preoperative limb pain. At the time of the study, phantom pain had resolved in only 35% of the subjects. Phantom pain was documented in the medical records of only 40% of those answering positively to questions regarding phantom pain on the questionnaire. We conclude that phantom pain occurs commonly in children and adolescents. The association of preoperative pain in the diseased extremity and the later occurrence of phantom pain suggests that preoperative regional anesthesia may prevent phantom pain.

  View details for Web of Science ID A1995QL00700006

  View details for PubMedID 7714344

• INFLUENZA-B VIRUS-INFECTION IN PEDIATRIC SOLID-ORGAN TRANSPLANT RECIPIENTS PEDIATRICS Mauch, T. J., Bratton, S., Myers, T., Krane, E., GENTRY, S. R., Kashtan, C. E. 1994; 94 (2): 225-229

  Abstract

  Influenza B virus causes epidemic infection in normal children, but only one case of infection in an immunocompromised solid organ transplant (SOT) recipient has been reported. Characterization of the clinical course of influenza B virus infection in pediatric SOT recipients may increase the utilization of preventive and therapeutic interventions by pediatricians caring for these immunocompromised children.Retrospective chart review of patients whose respiratory viral cultures yielded influenza B from January 1989 through March 1992.Twelve pediatric SOT recipients with influenza B virus infection were identified. These included five renal, four hepatic, and three cardiac allograft recipients, ranging from 19 months to 17 years 9 months of age (median 6 years 2 months). The posttransplant interval ranged from 6 weeks to 4 years 6 months (average 26.7 months). No patient had been immunized against influenza. Exposure histories were documented for eight children; five of these occurred in the hospital.Clinical symptoms included fever (12/12), respiratory (11/12), or gastrointestinal complaints (8/12). Five patients had neurologic involvement; one died of uncal herniation. Ten children were hospitalized (median duration, 3 days; range, 2 to 79 days). Two patients (post-transplant interval, 3 to 8 months) required mechanical ventilation, and one of these received aerosolized ribavirin. Three children had concurrent allograft rejection.Influenza B infection is potentially life-threatening in pediatric SOT recipients. We recommend annual immunization of pediatric SOT recipients, their household contacts, and health care workers. Prospective studies are needed to evaluate the efficacy of influenza vaccination in pediatric SOT recipients.

  View details for Web of Science ID A1994NY95600016

  View details for PubMedID 8036078

• CLOSTRIDIUM-SEPTICUM INFECTIONS IN CHILDREN PEDIATRIC INFECTIOUS DISEASE JOURNAL Bratton, S. L., Krane, E. J., Park, J. R., BURCHETTE, S. 1992; 11 (7): 569-575

  View details for Web of Science ID A1992JC74600012

  View details for PubMedID 1528648

• POSTOPERATIVE PAIN MANAGEMENT IN CHILDREN MOUNT SINAI JOURNAL OF MEDICINE Haberkern, C. M., Tyler, D. C., Krane, E. J. 1991; 58 (3): 247-256

  Abstract

  Postoperative pain management in children is a topic that has been neglected in the past but is currently an active field of interest and effort. Clearly, the child's cognitive understanding of and emotional response to pain are different than an adult's, and these differences make pain assessment and control more difficult. Ongoing work to develop more accurate techniques of estimating pain intensity in children may have helpful results. The effects of untreated pain in children are similar to those in adults but may have more long-term consequences in children. In the past, postoperative pain treatment in children was often inadequate, but newer techniques, such as continuous infusion of opioids, patient-controlled analgesia, epidural administration of opioids, and regional analgesia, hold promise for improved care in the future.

  View details for Web of Science ID A1991FT90300010

  View details for PubMedID 1875963

• COMPARISON OF THE EFFECTS OF HALOTHANE ON SKINNED MYOCARDIAL FIBERS FROM NEWBORN AND ADULT-RABBIT .2. EFFECTS ON SARCOPLASMIC-RETICULUM ANESTHESIOLOGY Krane, E. J., Su, J. Y. 1989; 71 (1): 103-109

  Abstract

  The effect of halothane on Ca2+ uptake or release by the sarcoplasmic reticulum (SR) was compared in the newborn and adult rabbit myocardium. The sarcolemma of right ventricular myocardium was disrupted (skinned) by homogenization. Fiber bundles were dissected from the homogenate, mounted on tension transducers, and immersed sequentially in five solutions that loaded Ca2+ into the SR, then in solutions containing either 2 or 25 mM caffeine to release SR-stored Ca2+, resulting in transient tension development. Experimental solutions were saturated with halothane in N2 gas during Ca2+ uptake by SR, Ca2+ release by SR, or during both SR Ca2+ uptake and release. Halothane (0.5-1.7%) resulted in dose-dependent depression of SR Ca2+ uptake in both newborn and adult skinned fibers. Less tension transient depression resulted in newborn (35%) than adult skinned fibers (49.5%, P less than 0.05) with 0.5% halothane exposure during SR Ca2+ uptake. Similar depression resulted in newborn (53.7% and 73.4%) and adult fibers (65.2% and 77.9%) with 1.0% and 1.7% halothane. Halothane had little effect on SR Ca2+ release by 25 mM caffeine but enhanced submaximal SR Ca2+ release by 2 mM caffeine more in newborn than adult myocardium. Increased Ca2+ efflux from newborn SR may contribute to the greater sensitivity of intact newborn cardiac muscle to exposure to halothane.

  View details for Web of Science ID A1989AE74900024

  View details for PubMedID 2751121

• THE DOSE-RESPONSE OF CAUDAL MORPHINE IN CHILDREN ANESTHESIOLOGY Krane, E. J., Tyler, D. C., Jacobson, L. E. 1989; 71 (1): 48-52

  Abstract

  The authors compared the duration of analgesia and the frequency of side effects of three doses of caudal epidural morphine in children aged 1.2-7.9 yr. Caudal catheters were inserted in 32 children, randomly assigned to receive 0.033 mg.kg-1, 0.067 mg.kg-1, or 0.10 mg.kg-1 of preservative-free morphine for analgesia after major surgical procedures below the diaphragm. The first dose of caudal morphine was mixed with 0.25 ml.kg-1 of 1% lidocaine to confirm correct caudal catheter placement. By assessment of periodic pain scores and the time intervals between administration of caudal morphine and the recurrence of pain, the authors found that the mean (+/- SD) duration of analgesia was significantly longer after 0.10 mg.kg-1 (13.3 +/- 4.7 h) than after either 0.033 mg.kg-1 or 0.067 mg.kg-1 (10.0 +/- 3.3 and 10.4 +/- 4.2 h, respectively) (P less than 0.02). The frequency of vomiting, pruritus, and urinary retention was similar in each group. Vomiting was less common in patients who had nasogastric drainage than in patients who were fed soon after surgery (P less than 0.05). Delayed respiratory depression occurred in one child after 0.10 mg.kg-1 of caudal morphine. Caudal morphine, 0.033-0.10 mg.kg-1, provided prolonged analgesia in children. The authors recommend 0.033 mg.kg-1 of caudal morphine as an initial dose for children.

  View details for Web of Science ID A1989AE74900015

  View details for PubMedID 2751139

• EPIDURAL OPIOIDS IN CHILDREN JOURNAL OF PEDIATRIC SURGERY Tyler, D. C., Krane, E. J. 1989; 24 (5): 469-473

  Abstract

  Experience with spinal opioids in children is limited but is expanding. Anatomy, pharmacology, technique, and results are reviewed. Complications and side effects are described.

  View details for Web of Science ID A1989U468000013

  View details for PubMedID 2567780

• POSTOPERATIVE PAIN MANAGEMENT IN CHILDREN ANESTHESIOLOGY CLINICS OF NORTH AMERICA Tyler, D. C., Krane, E. J. 1989; 7 (1): 155-170

  View details for Web of Science ID A1989T172100010

• COMPARISON OF THE EFFECTS OF HALOTHANE ON SKINNED MYOCARDIAL FIBERS FROM NEWBORN AND ADULT-RABBIT .1. EFFECTS ON CONTRACTILE PROTEINS ANESTHESIOLOGY Krane, E. J., Su, J. Y. 1989; 70 (1): 76-81

  Abstract

  The effect of halothane on maximal and submaximal Ca2+-activated tension development of the contractile proteins of newborn and adult cardiac muscle from rabbits was determined. Right ventricular muscle was removed from newborn and adult rabbits, and the sarcolemma was disrupted (skinned) by homogenization. Fiber bundles were dissected from the homogenate and mounted on tension transducers. Fiber bundles were alternately immersed in relaxing solution [( Ca2+] less than 10(-9) M) and contracting solutions (various [Ca2+] from 10(-5.6) to 10(-3.8) M), which were saturated with 100% N2 alone or with three concentrations of halothane-N2 mixture. In the absence of halothane, newborn skinned myocardial fibers were slightly more sensitive to submaximal Ca2+ concentrations than were adult myocardial fibers. [Ca2+] required for 50% maximum tension were 10(-5.43) M and 10(-5.31) M, respectively (P less than 0.05). Halothane (1-3%) decreased the maximal Ca2+-activated tension (at [Ca2+] = 10(-3.8) M) similarly in adult and newborn myocardial fibers in a dose-dependent fashion. Tension was reduced by 5.9% for each 1% increase in halothane concentration. Halothane also decreased the sensitivity of adult myocardial skinned fibers to submaximal Ca2+ concentrations (10(-5.6) M to 10(-5.0) M) by shifting the Ca2+-tension response curve to the right. Only 3% halothane decreased the sensitivity of newborn myocardial skinned fibers to Ca2+. The authors conclude that halothane causes less depression of Ca2+ activation of the contractile proteins in newborn than adult rabbit myocardium and that this effect of halothane cannot account for greater negative inotropy of halothane in the newborn.

  View details for Web of Science ID A1989R703400016

  View details for PubMedID 2912319

• Anesthesiology: regional anesthesia in children. Western journal of medicine Krane, E. J., Tyler, D. C. 1988; 149 (1): 74-75

  Abstract

  The Scientific Board of the California Medical Association presents the following inventory of items of progress in anesthesiology. Each item, in the judgement of a panel of knowledge physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, research workers, or scholars to stay abreast of these items of progress in anesthesiology that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another.The items of progress listed below were selected by the Advisory Panel to the Section on Anesthesiology of the California Medical Association and the summaries were prepared under its direction.

  View details for PubMedID 18750437

• ARTERIAL THROMBOSIS CAUSING CEREBRAL EDEMA IN ASSOCIATION WITH DIABETIC-KETOACIDOSIS CRITICAL CARE MEDICINE Krane, E. J. 1988; 16 (1): 100-100

  View details for Web of Science ID A1988L890500021

  View details for PubMedID 3123137

• DELAYED RESPIRATORY DEPRESSION IN A CHILD AFTER CAUDAL EPIDURAL MORPHINE ANESTHESIA AND ANALGESIA Krane, E. J. 1988; 67 (1): 79-82

  View details for Web of Science ID A1988L510800017

  View details for PubMedID 3337350

• COMPARISON OF THE EFFECTS OF HALOTHANE ON NEWBORN AND ADULT-RABBIT MYOCARDIUM ANESTHESIA AND ANALGESIA Krane, E. J., Su, J. Y. 1987; 66 (12): 1240-1244

  Abstract

  The effect of halothane on myocardial contractility was studied in isolated right ventricular muscle preparations from newborn and adult rabbits. Right ventricular strips were mounted in oxygenated Krebs' solution and stimulated with supramaximal voltages at 1.0 Hz, while isometric force of contraction was continuously recorded. Halothane (0.4, 0.7, and 1.1%) caused a significant dose-dependent depression of both peak developed tension (42, 61, and 70%, respectively) and maximum rate of rise of isometric tension (40, 56, and 64%, respectively) of newborn myocardium. Newborn myocardial preparations exhibited approximately 20% greater depression of contractility than adult myocardium at each concentration studied (P less than 0.05), thus a parallel shift of the dose-response curves was observed. It was concluded that halothane exerts a potent depressant effect on newborn myocardium that is greater than that on adult myocardium. The depression effect of halothane on the newborn myocardium may contribute to its hypotensive effect in newborn infants.

  View details for Web of Science ID A1987L014100007

  View details for PubMedID 3688496

• DIABETIC-KETOACIDOSIS - BIOCHEMISTRY, PHYSIOLOGY, TREATMENT, AND PREVENTION PEDIATRIC CLINICS OF NORTH AMERICA Krane, E. J. 1987; 34 (4): 935-960

  Abstract

  Diabetic ketoacidosis (DKA) is the most common cause of death of juvenile-onset diabetics, and as such represents an important issue for pediatricians. In this article, the author reviews the endocrinology of insulin and the glucose counter-regulatory hormones, which are the basis for the development of DKA. The effects of hyperglycemia and acidosis upon organ physiology are detailed, and this serves as the foundation for subsequent discussion of the management of the patient with DKA. Finally, the author summarizes current strategies for prevention of DKA in patients with diabetes.

  View details for Web of Science ID A1987J442600009

  View details for PubMedID 3112717

• CAUDAL MORPHINE FOR POSTOPERATIVE ANALGESIA IN CHILDREN - A COMPARISON WITH CAUDAL BUPIVACAINE AND INTRAVENOUS MORPHINE ANESTHESIA AND ANALGESIA Krane, E. J., Jacobson, L. E., Lynn, A. M., Parrot, C., Tyler, D. C. 1987; 66 (7): 647-653

  Abstract

  We compared the efficacy, duration, and side effects of preservative-free morphine injected into the caudal space in children, with caudal bupivacaine and with intravenous morphine administration for relief of postoperative pain. Forty-six children, ages 1-16 yr, were randomly assigned to receive intravenous morphine (control group), caudal bupivacaine (0.25%, 1 ml/kg), or caudal morphine (0.5 mg/ml, 0.1 mg/kg). In half the patients given caudal morphine, the morphine was mixed with a dose of lidocaine adequate to produce sacral analgesia, to confirm correct caudal injection of the morphine. Caudal injections were performed at the end of surgery. Time until the first required postoperative intravenous morphine dose was recorded for each patient. The duration of analgesia was significantly greater with caudal morphine (median 12 hr, P less than 0.02) than with caudal bupivacaine (median 5 hr), and both were greater than with intravenous morphine in control patients (median 45 min). Urinary retention, pruritus, and nausea appeared with slightly greater frequency in the caudal morphine group, but no delayed respiratory depression occurred. Caudal morphine (0.5 mg/ml, 0.1 mg/kg) provided 8-24 hr of analgesia in children without a significantly greater incidence of side effects than caudal bupivacaine or intravenous morphine.

  View details for Web of Science ID A1987H953600012

  View details for PubMedID 3605674

• BRAIN-DEATH PEDIATRICS Morray, J. P., Krane, E. J., Lynn, A. M., Tyler, D. C. 1987; 79 (6): 1057-1057

  View details for Web of Science ID A1987H676900052

  View details for PubMedID 3588138

• PEDIATRIC NEUROANESTHESIA SEMINARS IN ANESTHESIA Krane, E. J., Rockoff, M. A. 1984; 3 (2): 117-126

  View details for Web of Science ID A1984SY45800005

• THYROID-HORMONE RELATIONSHIPS IN THE FETAL AND NEWBORN LAMB BIOLOGY OF THE NEONATE Mathur, H., BROWN, B. L., Krane, E. J., Thomas, A. L., Nathanielsz, P. W. 1980; 37 (3-4): 138-144

  Abstract

  Plasma thyroxine (T4) and reverse triiodothyronine (rT3) concentrations have been measured in chronically catheterised sheep fetuses during the last third of gestation. In some animals T4 and rT3 concentrations fell before delivery but there was no change in the t4/rT3 ratio. In several serially sampled fetuses a small rise in plasma triiodothyronine concentration has been demonstrated in the days preceding delivery. Infusion of cortisol to fetuses commencing at 130 days of gestation (term 147 days) with the simultaneous administration of progesterone to delay labour resulted in changes in T4 and rT3 concentrations which were similar to those normally seen at term. The nature of the changes in the peripheral metabolism of T4 around the time of birth are discussed.

  View details for Web of Science ID A1980JG74900002

  View details for PubMedID 7362852

• CONTINUOUS VARIABILITY OF FETAL PO2 IN THE CHRONICALLY CATHETERIZED FETAL SHEEP AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Jansen, C. A., Krane, E. J., Thomas, A. L., Beck, N. F., Lowe, K. C., Joyce, P., Parr, M., Nathanielsz, P. W. 1979; 134 (7): 776-783

  Abstract

  A method of continuous monitoring of fetal intravascular PO2 at various sites in the circulation in the chronically catheterized fetal sheep for up to 41 days (mean 11.1 days) has been compared with values obtained in blood samples measured extracorporeally in a standard blood gas analyzer. A double-blind comparison of the two methods showed that there was no bias between the two methods and correlation was 0.94. The stability of the electrodes was superior to that of a conventional blood gas analyzer. In every animal there was continuous variability of fetal vascular PO2. In the period from 105 to 126 days' gestation we noted the presence of slow increases in basal uterine tone that we have called "contractures". The frequency of these contractures was very regular at approximately one per hour. The frequency of these contracutres was very regular at approximately one per hour. There is a statistically significant related fall in fetal vascular PO2 in relation to these contractures. Well-coordinated uterine contractions during labor also produced a fall in fetal vascular PO2 that was related to the uterine activity.

  View details for Web of Science ID A1979HF58900011

  View details for PubMedID 463979

• Pituitary stalk-section and some of its effects on endocrine function in the fetal lamb. Quarterly journal of experimental physiology and cognate medical sciences Abel, M. H., Bass, F. G., Krane, E. J., Thomas, A. L., Liggins, G. C. 1978; 63 (3): 211-219

  Abstract

  A detailed description is given of a method to section the pituitary stalk of the fetal lamb after 105 days gestational age. The approach to the stalk is made through a window in the frontal bone. In order to prevent regeneration of the hypothalamo-pituitary connections a silicone plate is introduced through the probe used to fracture the stalk. The surgical outcome and viability of 11 pituitary stalk sectioned fetuses is described over periods of up to 23 days. The presence of pituitary infarction following stalk section was related to damage of the anterior hypophysial vesssels if the probe was deviated from the mid-line at any time in its course. The effect of this procedure on fetal plasma T4 and PRL concentrations and the initiation of premature labour by the continuous infusion of cortisol into the fetus is described.

  View details for PubMedID 250110

• ULTRASTRUCTURAL CHANGES IN PLACENTA OF EWE AFTER FETAL PITUITARY STALK SECTION QUARTERLY JOURNAL OF EXPERIMENTAL PHYSIOLOGY AND COGNATE MEDICAL SCIENCES STEVEN, D. H., Bass, F., JANSEN, C. J., Krane, E. J., Mallon, K., SAMUEL, C. A., Thomas, A. L., Nathanielsz, P. W. 1978; 63 (3): 221-?

  Abstract

  Binucleate cells are a normal component of the ovine chorionic epithelium, but are usually separated from the fetal-maternal interface by a thin layer of cytoplasm derived from the principal or uni-nucleate cells of the trophoblast. They are distinguished not only by two distinct and separate nuclei, but also by conspicuous membrane-bound cytoplasmic inclusions in the form of haloed droplets. After fetal pituitary stalk section binucleate cells move up to and participate in the formation of the fetal-maternal interface; furthermore they extend clear blunt-ended pseudopodia into the maternal epithelial syncytium. These activities do not appear to be supppressed by fetal infusion of cortisol or ACTH. The apparent motility of binucleate cells, together with the presence of haloed droplets within the maternal epithelial syncytium, suggests that after fetal pituitary stalk section binucleate cells invade the uterine syncytium, lose their limiting membranes and discharge their contents into the syncytial cytoplasm. Large molecules such as ovine placental lactogen may be transported from fetal to maternal tissues by this mechanism.

  View details for Web of Science ID A1978FK06500002

  View details for PubMedID 211539

• PITUITARY STALK-SECTION AND SOME OF ITS EFFECTS ON ENDOCRINE FUNCTION IN FETAL LAMB QUARTERLY JOURNAL OF EXPERIMENTAL PHYSIOLOGY AND COGNATE MEDICAL SCIENCES Nathanielsz, P. W., Abel, M. H., Bass, F. G., Krane, E. J., Thomas, A. L., Liggins, G. C. 1978; 63 (3): 211-?

  View details for Web of Science ID A1978FK06500001

• CHANGES IN FETAL THYROID AXIS AFTER INDUCTION OF PREMATURE PARTURITION BY LOW-DOSE CONTINUOUS INTRA-VASCULAR CORTISOL INFUSION TO FETAL SHEEP AT 130 DAYS OF GESTATION ENDOCRINOLOGY Thomas, A. L., Krane, E. J., Nathanielsz, P. W. 1978; 103 (1): 17-23

  Abstract

  The effect of cortisol infusion on plasma T4 and T3 concentrations has been investigated in the fetal lamb at 130-134 days of gestation. Infusion of cortisol at rates equivalent to one-third the quantity produced by the fetus at the time of parturition results in a significant fall in fetal plasma T4 concentration and a significant rise in fetal plasma T3 concentration. Delay in the initiation of labor as a result of progesterone administration to the ewe did not prevent the changes in the fetal thyroid axis. These modifications of thyroid function therefore appear to be caused by the infusion of cortisol rather than to be secondary to the induction of labor.

  View details for Web of Science ID A1978FE20300004

  View details for PubMedID 744069

• [An indwelling PO2 electrode used to monitor foetal vascular PO2 in the chronically catheterized foetal sheep [proceedings]. journal of physiology Jansen, C. A., Joyce, P., Krane, E. J., Nathanielsz, P. W., Thomas, A. L. 1977; 271 (2): 8P-9P

  View details for PubMedID 926014

• A method for the quantitative assessment of uterine activity in the pregnant sheep [proceedings]. journal of physiology Beck, N. F., Carter, M. C., Jansen, C. A., Joyce, P. L., Krane, E. J., Nathanielsz, P. W., Steer, P., Thomas, A. L. 1977; 271 (2): 9P-10P

  View details for PubMedID 926015

• The role and regulation of corticotropin in the fetal sheep. Ciba Foundation symposium Nathanielsz, P. W., JACK, P. M., Krane, E. J., Thomas, A. L., RATTER, S., Rees, L. H. 1977: 73-98

  View details for PubMedID 205399