Pain Management in Infants & Children with Serious Illness: From Myths, Morphine to Multimodal Analgesia

Transcription

1 Pain Management in Infants & Children with Serious Illness: From Myths, Morphine to Multimodal Analgesia Stefan J. Friedrichsdorf, MD, FAAP Medical Director, Department of Pain Medicine, Palliative Care & Integrative Medicine Children's Hospitals and Clinics of Minnesota, Minneapolis/St. Paul, MN Associate Professor of Pediatrics, University of Minnesota Medical School Minneapolis / St. Paul, Minnesota, USA Learning Objectives Critically review risks and safety of analgesic undertreatment versus over-treatment in pediatric patients receiving palliative care Evaluate assumptions about opioid use in children Discuss how multiple agents, interventions, rehabilitation, psychological and integrative ( nonpharmacologic ) therapies act synergistically for more effective pediatric pain control with fewer side effects than a single analgesic or modality

2 5-year old Marius: Procedural Pain Management Redningskvinder Channel Tv3 - (Episode 7, Season 4.) 2014 Don't have enough staff for pediatric pain control...? Funny, how there is always enough staff to restrain a child. Pediatric Analgesia in 1985 Papoose Boards

3 Pediatric Pain - Status Quo Under treatment of pain in children Parents expect pain to be relieved Forgeron PA, Finley GA, Arnaout M. Pediatric pain prevalence and parents' attitudes at a cancer hospital in Jordan. J Pain Symptom Manage. 2006; 31(5): Parents greatest distress: failing to protect their child from pain Tiedeman, M. (1997). Anxiety responses of parents during and after the hospitalisation of their 5 - to -11 year old children. Journal of Pediatric Nursing, 12(2), Melnyk BM. Intervention studies involving parents of hospitalized young children: an analysis of the past and future recommendations. J Pediatr Nurs Feb;15(1):4-13. Assumption: everything possible is done Anand s neonatal surgery studies Pediatric Pain - Status Quo USA: adults receive more than two - three times as many analgesic doses as children (with identical diagnoses) (1) Eland JM, Anderson JE: The experience of pain in children. In: Jacox A (ed). Pain: a source book for nurses and other health care professionals. Boston: Little Brown & C0; 1977: (2) Beyer JE, DeGood DE, Ashley LC, Russell GA. Patterns of postoperative analgesic use with adults and children following cardiac surgery. Pain Sep;17(1): (3) Schechter NL, Allen DA, Hanson K. Status of pediatric pain control: a comparison of hospital analgesic usage in children and adults. Pediatrics Jan;77(1):11-5. Compared to adults, pediatric patients receive fewer and/or incorrectly dosed analgesics in daily routine Ellis, J. A., O Connor, B. V., Cappelli, M., Goodman, J., Blouin, R., & Reid, C. W. (2002). Pain in hospitalized pediatric patients: How are we doing? Clinical Journal of Pain, 18, The younger children are, the less likely they receive appropriate analgesia Broome ME, Richtsmeier A, Maikler V, Alexander M. Pediatric pain practices: a national survey of health professionals. J Pain Symptom Manage May;11(5): ; Nikanne E, Kokki H, Tuovinen K. Postoperative pain after adenoidectomy in children. Br J Anaesth Jun;82(6): Wolfe J, Orellana L, Ullrich C et al Symptoms and Distress in Children with Advanced Cancer: Prospective Patient-Reported Outcomes from the PediQUEST Study, JCO 2015.

4 Pediatric Pain - Status Quo Pain in children s hospitals is common, under recognized and under treated Friedrichsdorf SJ, Postier AC, Eull D, Foster L, Weidner C, Campbell F: Pain outcomes in a US children s hospital: a prospective cross-sectional survey. Hospital Pediatrics (1):18-26 Kozlowski LJ, Kost-Byerly S, Colantuoni E, et al. Pain prevalence, intensity, assessment and management in a hospitalized pediatric population. Pain Manag Nurs. 2014;15(1): Taylor EM, et al. Pain in hospitalized children: A prospective cross-sectional survey of pain prevalence, intensity, assessment and management in a Canadian pediatric teaching hospital. Pain Res Manage ;1: Canada: 3,822 pediatric inpatients (32 units): Stevens BJ, Harrison D, Rashotte J, Yamada J, Abbott LK, Coburn G, et al. Pain assessment and intensity in hospitalized children in Canada. J Pain 2012 Sep;13(9): ; 33% moderate to severe pain 88% acute, 12% chronic pain USA Friedrichsdorf SJ, Postier AC, Eull D, Foster L, Weidner C, Campbell F: Pain outcomes in a US children s hospital: a prospective cross-sectional survey. Hospital Pediatrics (1): % of all children surveyed experienced moderate, 30% severe pain in previous 24 hours 12% reported having pain routinely before admission None of the 15 children with 1 severe pain score documented received consultation from Pain & Palliative Care Inappropriate Analgesia: Why Bother...? Children with persistent pain suffer more physical symptoms in adult life, more anxiety and more depression 1946 Medical Research Council and 1958 National Child Development Study Inadequate analgesia for initial procedures in children diminishes effect of adequate analgesia in subsequent procedures Weisman SJ, Bernstein B, Schechter NL: Consequences of inadequate analgesia during painful procedures in children. Arch Pediatr Adolesc Med :147-9 Higher morphine doses = less PTSD in months after major trauma Stoddard FJ, Jr., Sorrentino EA, Ceranoglu TA, Saxe G, Murphy JM, Drake JE, et al. Preliminary evidence for the effects of morphine on posttraumatic stress disorder symptoms in one- to four-year-olds with burns. J Burn Care Res Sep-Oct;30(5): Up to 25% of adults have fear of needles with most fears developing in childhood: avoidance of health care (including nonadherence with vaccination schedules Taddio A, Chambers CT, Halperin SA, et al. Inadequate pain management duringchildhood immunizations: the nerve of it. Clin Ther 2009;31(Suppl 2):S ) NICU: increased morbidity & mortality Anand KJ, Barton BA, McIntosh N, Lagercrantz H, Pelausa E, Young TE, et al. Analgesia and sedation in preterm neonates who require ventilatory support: results from the NOPAIN trial. Neonatal Outcome and Prolonged Analgesia in Neonates. Arch Pediatr Adolesc Med Apr;153(4):331-8 Outcomes Improved with PPC Involvement Parents of children with cancer report less distress from pain, dyspnea and anxiety at EOL Wolfe et al. J Clin Onc 2008 Children who received PPC/Oncology more likely to have fun (70% versus 45%) and to experience events that added meaning to life (89% versus 63%) Friedrichsdorf SJ et al. J Palliat Med 2015 Families who received PPC/Oncology report improved communication Kassam A, Skiadaresis J, Alexander S et al Differences in End-of-Life Communication for Children with Advanced Cancer who were Referred to a Palliative Care Team. Pediatr Blood Cancer, (8): p Children receiving PPC experience shorter hospitalizations and fewer emergency department visits Ananth, P., et al., Hospital Use in the Last Year of Life for Children With Life-Threatening Complex Chronic Conditions. Pediatrics, (5): p

5 Myths and Barriers to Using Opioids Case Scenario: You are taking care of a child with severe acute somatic nociceptive pain (e.g. cancer, sickle-cell crisis, major burn etc.). It crosses your mind to administer a strong opioid such as morphine or fentanyl. What would be the most common concerns you might hear from your colleagues or parents arguing against opioid use in this child? Common Opioid Assumptions Addiction chronic relapsing condition characterized by persistent, compulsive dependence on a behavior or substance despite adverse consequences Tolerance addiction Pseudo-addiction Over Sedation / Respiratory Depression Ileus / Constipation Medication Too strong Masking symptoms Abdominal Pain Ranji SR, Goldman LE, Simel DL, Shojania KG. Do opiates affect the clinical evaluation of patients with abdominal pain? JAMA 2006: 296: Opioids after major cranial surgery in children do NOT result in altered mental status nor respiratory depression Maxwell LG. PAIN MANAGEMENT FOLLOWING MAJOR INTRACRANIAL SURGERY IN PEDIATRIC PATIENTS: A PROSPECTIVE COHORT STUDY IN THREE ACADEMIC CHILDREN S HOSPITALS Pediatric Critical Care Medicine: May Volume 15 - Issue 4_suppl - p 77. Abstracts of the 7th World Congress on Pediatric Critical Care As always... Think first!(e.g. compartment syndrome?)... analgesia second... Safety of Analgesics Dr. Cox, I am worried about drug safety would it be okay not using analgesia for children in acute pain? Scrubs

6 Opioid Safety & Long-Term Outcome Studies in neonatal rats suggest potential adverse effects of opioids (changes in behavior and brain functioning) Handelmann GE, Dow-Edwards D. Modulation of brain development by morphine: effects on central motor systems and behavior. Peptides. 1985;6 Suppl 2: NEOPAIN multicenter trial: Detailed secondary analysis: Although morphine associated with hypotension among ventilated preterm neonates, it does NOT increase the risk of severe IVH, any IVH, or death Anand KJS, Lancet 2004;363: ; Richard W, Pediatrics 2005;115: Higher cumulative fentanyl dose in preterm infants correlated with higher incidence of cerebellar injury, lower cerebellar diameter: No correlation was detected between cumulative fentanyl dose and development at 2 years of age. McPherson, C., Haslam M, Pineda R, Rogers C, Neil JJ, Inder TE: Brain Injury and Development in Preterm Infants Exposed to Fentanyl. Ann Pharmacother, (12): p Long-Term Outcome Low-dose morphine analgesia received on NICU associated with early alterations in cerebral structure, short-term neurobehavioral problems; did not persist into childhood: at 7 years no detrimental impacts of morphine on neurobehavioral outcome observed Steinhorn R1, McPherson C2, Anderson PJ3, Neil J4, Doyle LW5, Inder T6. J Pediatr May;166(5): e4. doi: /j.jpeds Neonatal morphine exposure in very preterm infants-cerebral development and outcomes. Long-term outcome at 5-6 years among formerly preterm babies exposed to continuous morphine infusion: No adverse effect of morphine on intelligence, motor function, or behavior MacGregor R, Evans D, Sugden D, Gaussen T, Levene M. Outcome at 5-6 years of prematurely born children who received morphine as neonates. Archives of disease in childhood Fetal and neonatal edition Jul; 79(1):F40-3. Continuous morphine infusion of 10 mcg/kg/h during the neonatal period does not harm general functioning and may even have a positive influence on executive functions at 8 to 9 years. de Graaf, J., R. A. van Lingen, et al. (2013). "Does neonatal morphine use affect neuropsychological outcomes at 8 to 9 years of age?" Pain 154(3): Does analgesia improve outcome? Yes, in animal model (Suellen Walker, PhD, London) Walker SM, Fitzgerald M, Hathway GJ. Surgical injury in the neonatal rat alters the adult pattern of descending modulation from the rostroventral medulla. Anesthesiology. Jun 2015;122(6): Walker SM, Tochiki KK, Fitzgerald M. Hindpaw incision in early life increases the hyperalgesic response to repeat surgical injury: critical period and dependence on initial afferent activity. Pain. Dec ;147(1-3):

7 Declaration of Montreal (2010) Access to pain management is a fundamental human right Human right violation not to treat So, how do we treat the individual pain patient in front of us? Hmhh... Spoiler Alert: Crystal-clear answer on 3rd last slide! Multimodal Analgesia No Needless Pain: The Children s Comfort Promise

8 How Do We Manage Acute Pain in Children? WHO guidelines on the pharmacological treatment of persisting pain in children with medical illnesses (2012) Available online at: Dosing at regular intervals ( By the Clock ) Adapting treatment to the individual child ( With the Child ) Using the appropriate route of administration ( By the appropriate route) Using a two-step strategy ( By the Analgesic Ladder ) WHO Principle 1: Dosing at Regular Intervals PRN (pro re data = as needed ) PRN = Patient Receives Nothing When pain is constantly present, analgesics should be administered, while monitoring side-effects, at regular intervals By the clock and NOT as an as needed (or pro re nata PRN ) basis Regular scheduling ensures a steady blood level, reducing the peaks and troughs of PRN ( as needed ) dosing PRN (as needed) only: May take several hours & higher opioid doses to relieve pain Results in cycle of undermedication and pain, alternating with periods of overmedication and drug toxicity American Pain Society: Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain

9 Scheduling Analgesia It Is After 10, Give My Daughter The Pain Shot (Shirley Maclaine: Terms Of Endearment, 1983) WHO Principle 2: Adapting Treatment to the Individual Child Treatment should be tailored to the individual child and opioid analgesics should be titrated on an individual basis At analgesic dosing: no sedation expected The effective dose is what relieves the pain Different children may respond differently to same dose Effective dose must be adjusted to child s needs Dose of strong opioids: only the sky is the limit Assess response frequently Pain Scales Look for opioid-induced side effects and toxicity Regular (!) Pain Assessment One-dimensional selfreport scores Multi-dimensional rating scores

10 What are we measuring...? (1) Nociceptive Pain: arises from the activation of peripheral nerve endings (nociceptors) that respond to noxious stimulation Somatic (for example, muscles, joints) Chronic somatic pain typically well localized & often results from degenerative processes (such as arthritis) Visceral (internal organs) (2) Neuropathic Pain: resulting from injury to, or dysfunction of, the somatosensory system. Central pain: caused by a lesion or disease of the central somatosensory nervous system (3) Psycho-social-spiritualemotional Pain / Total Pain (4) Chronic Pain Pain beyond expected time of healing Pain in children with impaired communication Non-communicating Children s Pain Checklist - Revised (NCCPC-R); postoperative Version (NCCPC-PV) Breau LM, McGrath PJ, Camfield CS, Finley GA. Psychometric properties of the non-communicating children's pain checklist-revised. Pain 2002;99(1-2): Pediatric Pain Profile (PPP) Hunt A, Goldman A, Seers K, Crichton N, Mastroyannopoulou K, Moffat V, Oulton K, Brady M. Clinical validation of the paediatric pain profile. Dev Med Child Neurol 2004;46(1):9-18. r-flacc Malviya S, Voepel-Lewis T, Burke C, Merkel S, Tait AR. The revised FLACC observational pain tool: improved reliability and validity for pain assessment in children with cognitive impairment. Paediatr Anaesth 2006;16(3): WHO Principle 3: Route of Administration i.v. / s.c. nebulization? i.m. Analgesic Medications oral intranasal (MAD device) sublingual transmucosal transdermal suppository

11 WHO Principle 4: Using a Two-Step Strategy WHO Step 1 Mild Pain Ibuprofen and/or Acetaminophen (Paracetamol) Other NSAIDs? Cox-2 Inhibitor? Nociceptive Pathways & Primary Sites of Action of Analgesics Thalamus 2nd Neuron Aδ or C fiber Acetaminophen (Paracetamol) Injury NSAIDs Citius, Altius, Fortius...? Ibuprofen salts: fast-acting formulations Moore, R.A., et al., Faster, higher, stronger? Evidence for formulation and efficacy for ibuprofen in acute pain. Pain, (1): p Advil Film-Coated Tablets, contains 266 mg of ibuprofen sodium (equivalent to 200 mg of standard ibuprofen) Produced significantly better analgesia over 6h, fewer remedications than standard formulations 200-mg fast-acting ibuprofen (NNT 2.1; 95% confidence interval ) was as effective as 400 mg standard ibuprofen (NNT 2.4; 95% CI ), with faster onset of analgesia. More rapid absorption, faster initial pain reduction, good overall analgesia in more patients at the same dose, and probably longerlasting analgesia, but with no higher rate of patients reporting adverse events. However, earlier onset preferred in other pain condition, such as chronic nociceptive or neuropathic pain? Peloso, P.M., Faster, higher, stronger: to the gold medal podium? Pain, (1): p. 4-5.

12 WHO Principle 4: Using a Two-Step Strategy WHO Step 1 Mild Pain WHO Step 2 Moderate to Severe Pain Morphine Ibuprofen and/or Acetaminophen (Paracetamol) Other NSAIDs? Cox-2 Inhibitor? or fentanyl, hydromorphone, oxycodone, methadone (UK: diamorphine) Morphine Pharmacokinetics A principle of pharmacokinetics teaches us that unless the drug reaches the site of action, it cannot be expected to exert its dynamic effect. With morphine the situation is that when the drug dose not reach the PATIENT, what hope is there for pain relief? Ghooi, R.B. and S.R. Ghooi, A mother in pain. Lancet, (9140): p Nociceptive Pathways & Primary Sites of Action of Analgesics Thalamus Opioids Pre-synaptic nerve terminal i Neurotransmitter release Post-synaptic nerve terminal: hmembrane hyperpolarization 2nd Neuron => suppress neuronal excitability Aδ or C fiber Opioids Acetaminophen (Paracetamol) Injury NSAIDs

13 WHO Principle 4: Using a Two-Step Strategy WHO Step 1 Mild Pain Ibuprofen and/or Acetaminophen (Paracetamol) Other NSAIDs? Cox-2 Inhibitor? Intermediate Step? Tramadol Codeine Hydrocodone WHO Step 2 Moderate to Severe Pain Morphine or fentanyl, hydromorphone, oxycodone, methadone (UK: diamorphine) Multimodal (Opioid-sparing) Analgesia Non-Opioids Acetaminophen / Paracetamol NSAIDs Integrative Therapies Such as: Massage Distraction Deep Breathing Biofeedback Aromatherapy Hypnosis Opioids Tramadol ( weak ) Morphine ( strong ) 4 WHO- Principles By the clock Integrative Pain Management State of the art pain management in the 21st century demands that pharmacological management must be combined with supportive and integrative, nonpharmacological therapies to manage a child's pain. Physical methods (e.g. cuddle/hug, massage, comfort positioning, heat, cold, TENS) Cognitive behavioral techniques (e.g. guided imagery, hypnosis, abdominal breathing, distraction, biofeedback) Acupuncture, acupressure, aromatherapy

14 Integrative Pain & Symptom Management A Pediatrician s Top 10 Apps for Distraction & Pain Management NoNeedlessPain.org Stinson, J.N., et al., Construct validity and reliability of a real-time multidimensional smartphone app to assess pain in children and adolescents with cancer. Pain, (12): p Nociceptive Pathways & Primary Sites of Action of Analgesics Thalamus Periaqueductal grey (endorphins) Integrative (non-pharmacological) therapies Descending Inhibition + 2nd Neuron Descending pathways that modulate transmission of nociceptive signals originate in periaqueductal gray, locus coeruleus, anterior cingulate gyrus, amygdala & hypothalamus: are relayed through brainstem nuclei in the PEG and medulla to spinal cord. Inhibitory transmitters involved in these pathways incl. norepinephrine, 5-hydroxytryptamine, dopamine, & endogenous opioids. Aδ or C fiber Opioids Acetaminophen (Paracetamol) Injury NSAIDs Nociceptive Pathways & Primary Sites of Action of Analgesics CORTEX: Thalamus -Stress - Anxiety - Catastrophizing - Depression - perceived injustice - disturbed Sleep ON OFF 2nd Neuron Periaqueductal grey (endorphins) Integrative (non-pharmacological) therapies Aδ or C fiber Opioids Acetaminophen (Paracetamol) Injury NSAIDs

15 Multimodal (Opioid-sparing) Analgesia Friedrichsdorf S: 9th Annual Pediatric Pain Master Class, Minneapolis, MN, June 11-17, 2016 Non-Opioids Acetaminophen / Paracetamol NSAIDs Integrative Therapies Such as: Massage Distraction Deep Breathing Biofeedback Aromatherapy Hypnosis Opioids Such as: Tramadol ( weak ) Morphine ( strong ) 4 WHO- Principles By the clock Psychology CBT Rehabilitation Exercise, Physical Therapy Sleep Hygiene OT Spirituality Regional Anesthesia Neuraxial infusion Peripheral/Plexus Nerve block Neurolytic block Intrathecal port/pump Intraventricular opioids? Percutaneous cervical cordotomy? Adjuvants Such as: Alpha-Agonist Gabapentinoids TCA/Antidepressants NMDA-Antagonists Na-channel blockers Antispasmodics Benzodiazepines Corticosteroids Muscle relaxants Radiopharmaceuticals Bisphosphonates Cannabis San Diego, CA AAP Handout for parents "Despite relaxed regulations, marijuana harms developing brain": +html Updated AAP policy opposes marijuana use, citing potential harms, lack of research aapnews.aappublications.org/content/early/2015/01/26/ aapnews

16 Multimodal Analgesia Multimodal (opioid-sparing) analgesia: Multiple agents, interventions, rehabilitation, psychological and integrative therapies act synergistically for more effective pediatric pain control with fewer side effects than single analgesic or modality Multimodal = Awesome! 2016 Guidelines on the Management of Postoperative Pain Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council Tegethoff, M., et al., Comorbidity of Mental Disorders and Chronic Pain: Chronology of Onset in Adolescents of a National Representative Cohort. J Pain, (2): p (Adults): Multimodal analgesia therapy (versus PCA only) reduces length of hospitalization in patients undergoing surgery Michelson, J.D., R.A. Addante, and M.D. Charlson, Multimodal analgesia therapy reduces length of hospitalization in patients undergoing fusions of the ankle and hindfoot. Foot Ankle Int, (11): p Do you remember Marius...? How about a Plan B? LET Anesthesia Sitting upright Distraction Topical Anesthesia 3mL LET-gel: Lidocaine 4%- Epinephrine 0.18% -Tetracaine 0.5% Singer AJ, Stark MJ. Pretreatment of lacerations with lidocaine, epinephrine, and tetracaine at triage: a randomized double-blind trial. Acad Emerg Med Jul;7(7):

17 STEP 1: Topical Local Anesthetics STEP 2: Sucrose / Breastfeeding STEP 3: Positioning

18 STEP 4: Distraction Thanks to Patricia D. Scherrer MD Children's Hospitals and Clinics of Minnesota IV Access Under Nitrous Gas 22 months-old, Lidocaine 4% cream in place, needed IV for radiologic procedure, history of challenging IV access in the past

19 So, how do we treat the individual pain patient in front of us? Crystal clear answer: Σωκράτη Sōkrátēs; 470/ BC Pain Chronic Pain Psychological pain Mental Health Anxiety Nociceptive Pain Deconditined Neuropathic Pain Depression Social Pain Poor sleep hygiene School absenteeism Spiritual Pain Visceral Pain Racial Disparity Delirium Total Pain Withdrawal Conclusions Withholding evidence-based analgesia to children in pain is not only unethical, but causes immediate and long-term harm Patients/Parents do NOT have to choose between poor pain control or over sedation Potential risks in safety of analgesics are real, but manageable; cannot justify denying administration of pain medications to pediatric patients Opioids (outside end-of-life) usually short term only - contraindicated for chronic pain Use multimodal (opioid-sparing) analgesia: Multiple agents, interventions, rehabilitation, psychological and integrative therapies act synergistically for more effective pediatric pain control with fewer side effects than single analgesic or modality

20 Further Links The New York Times (June 28, 2016) Why Aren t We Managing Children s Pain? Covering Dr. Stefan Friedrichsdorf The New York Times (Dec 16, 2015) essay by Dr. Stefan Friedrichsdorf When a Baby Dies opinionator.blogs.nytimes.com/2015/12/16/when-a-baby-dies/?_r=1 Video: Kiran Stordalen and Horst Rechelbacher Pediatric Pain, Palliative and Integrative Medicine Clinic Tour Children s Comfort Promise: Doing everything possible to treat and prevent pain. Eliminating Needle Pain in children (Feb 2015) Staff video: Short Movie: Meet the Interdisciplinary Chronic Pain Clinic Team at Children s Minnesota: LittleStars TV Video: Tour of the Kiran Stordalen and Horst Rechelbacher Pediatric Pain, Palliative and Integrative Medicine Clinic at Children's Hospitals and Clinics of Minnesota and an overview of the three programs that are offered at Children's under this clinic. Short Movie: LittleStarsFilm 'Kali's Story - Beyond the NICU': This amazing pediatric palliative care short movie (7 min) features 8-year-old Kali's journey at Children's Hospitals and Clinics of Minnesota from NICU to today, receiving care by the Pain & Palliative & Integrative Medicine program while inpatient, in the clinic, and at home (Jan 22, 2015) Further Training 10th Annual Pediatric Pain Master Class Minneapolis, Minnesota, USA June 17-23, 2017 Education in Palliative & End-of-life Care [EPEC]: Become an EPEC-Pediatrics Trainer Montréal, Québec, Canada April 29-30, 2017 (Professional Development Workshop: 04/28/17) Contact: CIPPC@ChildrensMN.org Stefan J. Friedrichsdorf, MD, FAAP Medical Director, Department of Pain Medicine, Palliative Care & Integrative Medicine Associate Professor of Pediatrics, University of Minnesota Medical School Children's Hospitals and Clinics of Minnesota 2525 Chicago Ave S Minneapolis, MN USA phone fax stefan.friedrichsdorf@childrensmn.org Blog: