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Myron Yaster, MD
Richard J Traystman Professor
410-955-7610

myaster1@jhmi.edu

Pediatric Anesthesiology and Pain Management
  
 

Research Projects

Determining the Safety of Opioid Analgesic Therapy in Adult and Pediatric Craniotomy Patients


Adult and pediatric patients who undergo brain surgery (craniotomy) are often poorly treated for pain because it is considered unsafe and unnecessary.  We have recently shown that pain is common following this surgery.  However, we will be unable to change practice and improve the quality of patient care until we can demonstrate analgesic safety.  Thus, we are conducting 2 large (n = 350), prospective, randomized controlled clinical trials, powered to evaluate the safety of Patient Controlled Analgesia (PCA) compared to "as needed" nurse administered ( PRN)  opioid therapy as determined continuous respiratory rate monitoring in adults and children.

Specifically we will measure respiratory rate non-invasively using state of the art side stream capnography and impedance pneumography as well as pulse oximetry in acute pain post operative craniotomy patients being treated with opioids (e.g., morphine, hydromorphone, and fentanyl).  We will also be assessing opioid induced side effects such as somnolence, pruritus, nausea, vomiting, and bowel dysfunction.  We are also developing vigilance aids and interdevice and personnnel communication protocols to alert care givers to patient problems. Finally, we will be assessing the long term consequences of pain and therapy on quality of life and recovery.

In infants, children, and adolescents, using the same technology, we will evaluate the safety of surrogate PCA or PCA by proxy (the parent or nurse initiates the demand dose of drug) and the use of continuous background opioid infusions.  In this patient population we will be studying "all commers" and not be limited to craniotomy patients.  This will include pediatric patients with acute post operative pain, post traumatic pain, cancer and cancer therapy induced pain, and chronic pain.

Registered with clinical trials.gov


Determining the Fundamental Mechanisms Underlying the Develpment of Opioid Tolerance and Hyperalgesia

Opioids (e.g., morphine, hydromorphone, methadone, fentanyl, oxycodone, oxycontin) are the analgesics most commonly used to treat moderate to severe pain. Achieving clinical efficacy and tolerability is often hindered by opioid-induced side effects such as the development of tolerance, nausea, vomiting, somnolence and paradoxical hyperalgesia. Uncovering novel mechanisms that underlie these side effects may open the door for development of new drugs that prevent and/or treat them.

Mammalian target of rapamycin (mTOR), a serine-threonine protein kinase, controls translation of mRNA via phosphorylation of specific downstream effectors, such as the eukaryotic initiation factor 4E (eIF4E)-binding protein 1/2 (4E-BP1/2) and p70 ribosomal S6 protein kinase (p70S6K) and influences numerous physiologic and pathologic processes in the nervous system.  Some of these compounds are already available for human use.

In the laboratory we are using animal models to determine whether and how mTOR and its downstream effectors are activated in dorsal horn neurons during chronic morphine exposure and whether this activation contributes to the development and maintenance of morphine-induced analgesic tolerance and hyperalgesia.

Recent Publications




Monitto CL, Kost-Byerly S, White E, Lee CK, Rudek MA, Thompson C, Yaster M.  The optimal dose of prophylactic intravenous naloxone in ameliorating opioid-induced side effects in children receiving intravenous patient-controlled analgesia morphine for moderate to severe pain: A dose finding study.  Anesth Analg. 2011 Oct;113(4):834-42. Epub 2011 Sep 2.

Morad,A.; Winters,B.; Stevens,R.; White,E.; Weingart,J.; Yaster,M.; Gottschalk,A. The efficacy of intravenous patient-controlled analgesia after intracranial surgery of the posterior fossa: a prospective, randomized controlled trial. Anesth Analg 2012 114; 416-423



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. Pediatric analgesic clinical trial designs, measures, and extrapolation: report of an FDA scientific workshop. Pediatrics 2012; 129: 354-364





Morad AH, Winters BD, Yaster M, Stevens RD, White ED, Thompson RE, Weingart JD, Gottschalk A.  Efficacy of intravenous patient-controlled analgesia after supratentorial intracranial surgery: a prospective randomized controlled trial.  J Neurosurg. 2009; 111(2): 343-50.




Singh OV, Yaster M, Xu JT, GuanY, Guan X, Dharmarajan AM, Raja SN, Zeitlin PL, TaoYX.  Proteome of synaptosome-associated proteins in spinal cord dorsal horn after peripheral nerve injury.  Proteomics 2009; 9(5):1241-1253.


Making Pediatric Pain Management Safer and More Effective


Molecular MechanismsPediatric Patient CareRandomized Clnical Trial


The mission of the Division of Pediatric Anesthesia, Critical Care Medicine, and Pain Management of the Johns Hopkins University School of Medicine is to improve the health of the community and the world by setting the standard of excellence in patient care. Further, our goal is to educate medical students, graduate students, and postdoctoral fellows in accordance with the highest professional standards; to prepare them to practice patient-centered medicine of the highest standard; and to identify and answer fundamental questions in the mechanisms, prevention and treatment of disease, in health care delivery and in the basic sciences.

Organizationally, our clinical research group is primarily focused on the multi-modal management of acute medical and surgical pain in hospitalized patients. Although their pain may be acute in onset and the majority of patients are treated for < 5 days, for some, the duration of therapy may be of a much longer duration (> 2 weeks). Our research group provides expertise that is sought by industry, the United States Food and Drug Administration, and national and international colleagues in pediatric clinical trials involving pain and sedation management, quality and safety improvement, and cost effectiveness. We provide a full, broad range of functions that are flexibly matched to the needs of the project including everything from initial conceptualization, data collection, data storage, data management, data analysis, and publication.

Current research projects involve a multi-center trial studying the management of pediatric patients who underwent craniotomy for such conditions such as brain tumor, cranio-facial reconstruction, and chiari malformation to name a few. (We are enrolling 150 patients in 3 sites, Hopkins, Boston Children’s and Children’s Hospital of Philadelphia) In these patients, physicians and nurses are often reluctant to administer opioids, the analgesics most commonly prescribed for moderate to severe pain, because of a fear that opioids may interfere with the postoperative neurologic examination or worsen outcome. However, a growing body of published studies that we have performed in adult patients report that pain following intracranial surgery is in fact common, often intense, and under treated. Failure to adequately treat pain in other postoperative conditions is associated with poor outcome.

In this population as well as in others, we have been at the forefront of allowing patients to self administer opioids using patient controlled analgesia (PCA) devices. Further, we allow parents and nurses to use these devices (PNCA or surrogate PCA) in children who are either physically or mentally unable to use them. Although we have published our experience we have never demonstrated its safety. To do so we are currently studying the respiratory effects of PCA and PNCA using capnography, pulse oximetry, and impedance pneumography in both children and adults (we plan to enroll 400 patients). In this project we are also evaluating the cost and overall effectiveness of various respiratory monitoring devices and inter-device communication abilities.

For many patients, the side effects accompanying the treatment of pain such as nausea, vomiting, pruritus, constipation, and tolerance are worse than the pain itself. Finding solutions to treat or prevent opioid induced side effects is therefore of utmost importance. We recently completed a large dose finding study that demonstrated that low dose naloxone, 1 mcg/kg/hour significantly reduced the incidence of pruritus in patients being treated with IV PCA morphine. It was less effective for nausea and vomiting. Future studies will target this symptom as well constipation and tolerance.

Tolerance is increasingly becoming a serious problem in our hospitalized patients, particularly those who have had prolonged stays in the Pediatric Intensive Care Unit (PICU). For many reasons these patients require around the clock analgesia and deep sedation. Within a relatively short period of time (as little as 3 days) tolerance develops, necessitating ever increasing doses of drugs which become less and less effective. Realizing that better therapies are required to treat these problems, I have established a very promising and highly productive relationship with basic scientists working on acute and chronic pain in our Department. These basic scientists are internationally recognized pain researchers whose broad expertise in the neurophysiological, morphological, and molecular biology of this field. We have recently begun to investigate the role of mammalian target of rapamycin (mTOR), a serine-threonine protein kinase which controls translation of mRNA via phosphorylation of specific downstream effectors, in the development and maintenance of spinally mediated tolerance and hyperalgesia. Their preliminary results showed that mTOR and its downstream effectors p70S6K, and 4E-BP1 are highly activated via mu receptor/PI3K/Akt pathway in the dorsal horn during chronic opioid exposure and that blocking mTOR attenuated opioid-induced tolerance and hyperalgesia. This preliminary work was supported by the Jacob and Hilda Blaustain Pain Research Fund at the Johns Hopkins University and we applied for NIH funding.

 News and Events




Click the link below to hear Dr. Yaster's interview on "Ask the Experts."

May 2013: Pediatric Anesthesia and Pain; Neurotoxicity; New Drugs








History of Pediatric Anesthesia Project now underway
Christine Mai, Paul Firth, and Myron Yaster have launched a new history of pediatric anesthesia timeline in cooperation with the Journal of Paedatric Anaesthesia, the Society for Pediatric Anesthesia, and the Wood Library of Medicine.  These articles will be accompanied with video conversation.

The first pioneer featured is Dr George Gregory.  Upcoming figures include Drs. Jack Downes, Mark Rogers, and Fritz Berry
History of pediatric anesthesia timeline
The development of continuous positive airway pressure: an interview with Dr. George Gregory




50th CLINICAL CONFERENCE IN PEDIATRIC ANESTHESIOLOGY February 10 - 12, 2012
See lectures in presentation tab

  • Just say NO to N2O
  • Managing common side effects in opioid pain therapy
 



Pediatric Pharmaceutical Development Course:
December 7, 8 2011 Washington D.C.
See lectures in presentation tab

  • Pediatric Drug Development:  Anatomic and Physiologic Differences between Adults and Children
  • Pharmacovigilance: Safety Monitoring Issues: Vital Signs, Clinical Labs. Clinical Signs of Unwellness

 



Panel on Anesthesia for the Neonate:
Yesterday, Today and Tomorrow: Paralysis to Toxicity
1:30 - 3:00 PM
 
The Past -- George Gregory, MD
 
The Present -- Sol Soriano, MD and Myron Yaster, MD see lecture in presentation tab
 
The Future -- Mervyn Maze, MB, ChB


Original Publications:

1. Azizkhan RG, Dudgeon DL, Buck JR, Colombani PM, Yaster M, Nichols D, Civin C, Kramer SS, Haller JA, Jr: Life-threatening airway obstruction as a complication to the management of mediastinal masses in children. J Pediatr Surg 20:816-822, 1985

2. Yaster M, Simmons RS, Tolo VT, Pepple JM, Wetzel RC, Rogers MC: A comparison of nitroglycerin and nitroprusside for inducing hypotension in children: a double-blind study. Anesthesiology 65:175-179, 1986

3. Wetzel RC, Marsh BR, Yaster M, Casella JF: Anesthetic implications of protein C deficiency. Anesth Analg 65:982-984, 1986

4. Yaster M, Koehler RC, Traystman RJ: Effects of fentanyl on cerebral and peripheral hemodynamics in neonatal lambs. Anesthesiology 66:524-530, 1987

5. Yaster M: The dose response of fentanyl in neonatal anesthesia. Anesthesiology 66:433-435, 1987

6. Maxwell LG, Yaster M, Wetzel RC, Niebyl JR: The safety and efficacy of penile nerve block for newborn circumcision. Obstet Gynecol 70:415-419, 1987

7. Yaster M, Buck JR, Dudgeon DL, Manolio TA, Simmons RS, Zeller P, Haller JA: Hemodynamic effects of primary closure of omphalocele/gastroschisis in newborns. Anesthesiology 69:84-88, 1988

8. Yaster M, Koehler RC, Traystman RJ: Interaction of fentanyl and pentobarbital on cerebral and peripheral hemodynamics in newborn lambs. Anesthesiology 70:461-469, 1989

9. Yaster M, Scherer LR, Stone M, Maxwell LG, Schleien CL, Wetzel RC, Buck JR, Nichols DG, Colombani PM, Dudgeon DL, Haller JA: Determination of safe primary closure of congenital abdominal wall defects using intraoperative predictors. J Pediatr Surg 42:1217-1220, 1989

10. Yaster M, Nichols DG, Deshpande JK, Wetzel RC: Midazolam-fentanyl intravenous sedation in children. Case report of respiratory arrest. Pediatrics 86:463-467, 1990

11. Spear RM, Yaster M, Berkowitz ID, Maxwell LG, Bender KS, Naclerio R, Manolio TA, Nichols DG: Preinduction of anesthesia in children with rectally administered midazolam. Anesthesiology 71:670-674, 1991

12. Nichols DG, Yaster M, Lynn AM, Helfaer MA, Deshpande JK, Manson PN, Carson BS, Bezman M, Maxwell LG, Tobias JD, Grochow LB: Disposition and respiratory effects of intrathecal morphine in children. Anesthesiology 79:733-738, 1993

13. Yaster M, Tobin JR, Billett C, Casella JF, Dover G: Epidural analgesia in the management of vaso-occlusive sickle cell crisis. Pediatrics 93:310-315, 1994

14. Maxwell LG, Martin LD, Yaster M: Bupivacaine-induced cardiac toxicity in neonates--successful treatment with intravenous phenytoin. Anesthesiology 80:682-686, 1994

15. Yaster M, Sola JE, Pegoli WP, Paidas CN: The night after surgery: Postoperative management of the pediatric outpatient-surgical and anesthetic aspects. Pediatric Clinics of North America 41:199-220, 1994

16. Yaster M, Koehler RC, Traystman RJ: Interaction of fentanyl and nitrous oxide on peripheral and cerebral hemodynamics in newborn lambs. Anesthesiology 80:364-371, 1994

17. Lenox WC, Kost-Byerly S, Shipley R, Yaster M: Pediatric caudal epidural catheter sequestration: an unusual complication. Anesthesiology 83(5):1112-1114, 1995.

18. Greenberg RS, Maxwell LG, Zahurak M, Yaster M: Preanesthetic medication of children with midazolam using the Biojector jet injector. Anesthesiology 83: 264-269, 1995

19. Yaster, M., Kost-Byerly, S., Berde, C., and Billet, C. The management of opioid and benzodiazepine dependence in infants, children, and adolescents. Pediatrics 98(1):135-140, 1996.

20. Wong, D.F., Harris, J.C., Naidu, S., Yokoi, F., Marenco, S., Dannals, R.F., Ravert, H.T., Yaster, M., Evans, A., Rousset, O., Bryan, R.N., Gjedde, A., Kuhar, M.J., and Breese, G.R. Dopamine transporters are markedly reduced in Lesch-Nyhan disease in vivo. Proc.Natl.Acad.Sci.U.S.A. 93(11):5539-5543, 1996.

21. Fisher QA, Shaffner DH, Yaster M: Detection of intravascular injection of regional anaesthetics in children. Can J Anaesth 44(6):592-598, 1997.

22. Harris JC, Lee RR, Jinnah HA, Wong DF, Yaster M, Bryan RN: Craniocerebral magnetic resonance imaging measurement and findings in Lesch-Nyhan syndrome. Arch Neurol 55:547-553, 1998

23. Kost-Byerly S, Tobin JR, Greenberg RS, Billett C, Zahurak M, Yaster M: Bacterial colonization and infection rate of continuous epidural catheters in children. Anesth Analg 86:712-716, 1998

24. Rich JB, Yaster M, Brandt J: Anterograde and retrograde memory in children anesthetized with propofol. Journal of Clinical and Experimental Neuropsychology 21:535-546, 1999

25. Greenberg RS, Billett C, Zahurak M, Yaster M: Videotape increases parental knowledge about pediatric pain management. Anesth Analg 89:899-903, 1999

26. Monitto CL, Greenberg RS, Kost-Byerly S, Wetzel RC, Yaster M: The safety and efficacy of parent-/nurse-controlled analgesia in patients less than six years of age. Anesth.Analg. 91 (3):573-579, 2000.

27. Aram, L, Krane EJ, Kozlowski LJ, Yaster M: Tunneled epidural catheters for prolonged analgesia in pediatric patients. Anesth.Analg. 92 (6):1432-1438, 2001

28. Davis PJ, Galinkin J, McGowan FX, Lynn AM, Yaster M, Rabb MF, Krane EJ, Kurth CD, Blum RH, Maxwell L, Orr R, Szmuk P, Hechtman D, Edwards S, Henson LG: A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy. I. Emergence and recovery profiles. Anesth.Analg. 2001; 93: 1380-6

29. Galinkin JL, Davis PJ, McGowan FX, Lynn AM, Rabb MF, Yaster M, Henson LG, Blum R, Hechtman D, Maxwell L, Szmuk P, Orr R, Krane EJ, Edwards S, Kurth CD: 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. Anesth.Analg. 2001; 93: 1387-92

30. Villemagne PM, Naidu S, Villemagne VL, Yaster M, Wagner HN, Jr., Harris JC, Moser HW, Johnston MV, Dannals RF, Wong DF: Brain glucose metabolism in Rett Syndrome. Pediatr.Neurol. 2002; 27: 117-22

31. Liaw WJ, Zhang B, Tao F, Yaster M, Johns RA, Tao YX: Knockdown of spinal cord postsynaptic density protein-95 prevents the development of morphine tolerance in rats. Neuroscience 2004; 123: 11-5

32. Tao F, Liaw WJ, Zhang B, Yaster M, Rothstein JD, Johns RA, Tao YX: Evidence of neuronal excitatory amino acid carrier 1 expression in rat dorsal root ganglion neurons and their central terminals. Neuroscience 2004; 123: 1045-51

33. Schwengel DA, McGready J, Berenholtz SM, Kozlowski LJ, Nichols DG, and Yaster M: Peripherally inserted central catheters: a randomized, controlled, prospective trial in pediatric surgical patients. Anesth Analg 2004;99:1038-43

34. Maxwell LG, Kaufmann SC, Bitzer S, Jackson EV, Jr., McGready J, Kost-Byerly S, Kozlowski L, Rothman SK, Yaster M: The effects of a small-dose naloxone infusion on opioid-induced side effects and analgesia in children and adolescents treated with intravenous patient-controlled analgesia: a double-blind, prospective, randomized, controlled study. Anesth.Analg 2005; 100: 953-8

35. Gottschalk A, Berkow LC, Stevens RD, Mirski M, Thompson RE, White ED, Weingart JD, Long DM, Yaster M: Prospective evaluation of pain and analgesic use following major elective intracranial surgery. J.Neurosurg. 2007; 106: 210-6

36. Guan Y, Yaster M, Raja SN, Tao YX: Genetic knockout and pharmacologic inhibition of neuronal nitric oxide synthase attenuate nerve injury-induced mechanical hypersensitivity in mice. Mol Pain. 2007; 3: 29-34

37. Maher EN, Hansen SF, Heine M, Meers H, Yaster M, Hunt EA: Knowledge of procedural sedation and analgesia of emergency medicine physicians. Pediatr Emerg Care 2007; 23: 869-76

38. Berde CB, Yaster M, Meretoja O, McCann ME, Huledal G, Gustafsson U, Larsson LE: Stable plasma concentrations of unbound ropivacaine during postoperative epidural infusion for 24-72 hours in children. Eur J Anaesthesiol. 2008 May;25(5):410-7.

39. Kost-Byerly S, Jackson EV, Yaster M, Kozlowski LJ, Mathews RI, Gearhart JP: Perioperative anesthetic and analgesic management of newborn bladder exstrophy repair. J.Pediatr.Urol. 2008; 4: 280-5

40. Heitmiller ES, Nelson KL, Hunt EA, Schwartz JM, Yaster M, Shaffner DH: A survey of anesthesiologists' knowledge of American Heart Association Pediatric Advanced Life Support Resuscitation Guidelines. Resuscitation. 2008; 79: 499-505

41. Liaw WJ, Zhu XG, Yaster M, Johns RA, Gauda EB, Tao YX: Distinct expression of synaptic NR2A and NR2B in the central nervous system and impaired morphine tolerance and physical dependence in mice deficient in postsynaptic density-93 protein. Mol.Pain. 2008; 4:45

42. Hammer GB, Verghese ST, Drover DR, Yaster M, Tobin JR: Pharmacokinetics and pharmacodynamics of fenoldopam mesylate for blood pressure control in pediatric patients. BMC.Anesthesiol. 2008; 8:6.

43. Park JS, Yaster M, Guan X, Xu JT, Shih MH, Guan Y, Raja SN, Tao YX: Role of spinal cord alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in complete Freund's adjuvant-induced inflammatory pain. Mol Pain. 2008; 4:67.

44. Lee BH, Lehmann CU, Jackson EV, Kost-Byerly S, Rothman S, Kozlowski L, Miller MR, Pronovost PJ, Yaster M: Assessing controlled substance prescribing errors in a pediatric teaching hospital: an analysis of the safety of analgesic prescription practice in the transition from the hospital to home. J Pain. 2009;10:160-166.

45. Singh OV, Yaster M, Xu JT, Guan Y, Guan X, Dharmarajan AM, Raja SN, Zeitlin PL, Tao YX. Proteome of synaptosome-associated proteins in spinal cord dorsal horn after peripheral nerve injury. Proteomics. 2009 Mar;9(5):1241-53.

46. Morad AH, Winters BD, Yaster M, Stevens RD, White ED, Thompson RE, Weingart JD, Gottschalk A. Efficacy of intravenous patient-controlled analgesia after supratentorial intracranial surgery: a prospective randomized controlled trial. J Neurosurg. 2009; 111(2): 343-50.

47. Agthe AG, Kim GR, Mathias KB, Hendrix CW, Chavez-Valdez R, Jansson L, Lewis TR, Yaster M, Gauda EB: Clonidine as an adjunct therapy to opioids for neonatal abstinence syndrome: a randomized, controlled trial. Pediatrics. 2009; 123(5): e849-e856.

48. Nelson KL, Yaster M, Kost-Byerly S, Monitto CL. A national survey of American Pediatric Anesthesiologists: patient-controlled analgesia and other intravenous opioid therapies in pediatric acute pain management. Anesth Analg 2010; 110(3):754-760.

49. Singh OV, Yaster M, Xu JT, GuanY, Guan X, Dharmarajan AM, Raja SN, Zeitlin PL, TaoYX. Proteome of synaptosome-associated proteins in spinal cord dorsal horn after peripheral nerve injury. Proteomics 2009; 9(5):1241-1253.

50. Atianjoh FE, Yaster M, Zhao X, Takamiya K, Xia J, Gauda EB, Huganir RL, Tao YX. Spinal cord protein interacting with C kinase 1 is required for the maintenance of complete Freund's adjuvant-induced inflammatory pain but not for incision-induced post-operative pain. Pain 2010; 151(1):226-234.

51. Xu JT, Zhao X, Yaster M, Tao YX. Expression and distribution of mTOR, p70S6K, 4E-BP1, and their phosphorylated counterparts in rat dorsal root ganglion and spinal cord dorsal horn. Brain Res 2010; 1336:46-57. Epub;%2010 Apr 24.:46-57

52. Wang W, Petralia RS, Takamiya K, Xia J, Li YQ, Huganir RL, Tao YX, Yaster M. Preserved acute pain and impaired neuropathic pain in mice lacking protein interacting with C Kinase 1. Mol Pain 2011; 7(1):11.

53. Yaster M, Guan X, Petralia RS, Rothstein JD, Lu W, Tao YX. Effect of Inhibition of Spinal Cord Glutamate Transporters on Inflammatory Pain Induced by Formalin and Complete Freund's Adjuvant. Anesthesiology 2011; 114(2):412-423.

54. Yang CP, Veltri MA, Anton B, Yaster M, Berkowitz ID. Food and Drug Administration approval for medications used in the pediatric intensive care unit: A continuing conundrum. Pediatr Crit Care Med 2010.

55. Firth PG, McMillan KN, Haberkern CM, Yaster M, Bender MA, Goodwin SR. A survey of perioperative management of sickle cell disease in North America. Paediatr Anaesth 2011; 21(1):43-49.

56. Hayes M, Yaster M, Haythornthwaite JA, Riekert K, Nelson K, White E, Mogayzel P, Lechtzin N. Pain is a common problem affecting clinical outcomes in adults with cystic fibrosis. Chest 2011 June 9 (epub ahead of print)

57. Wang W, Atianjoh F, Gauda EB, Yaster M, Li Y, Tao YX. Increased expression of sodium channel subunit Nav1.1 in the injured dorsal root ganglion after peripheral nerve injury. Anat Rec (Hoboken). 2011 Aug;294(8):1406-11.

58. Monitto CL, Kost-Byerly S, White E, Lee CK, Rudek MA, Thompson C, Yaster M. The optimal dose of prophylactic intravenous naloxone in ameliorating opioid-induced side effects in children receiving intravenous patient-controlled analgesia morphine for moderate to severe pain: A dose finding study. Anesth Analg. 2011 Oct;113(4):834-42. Epub 2011 Sep 2.

Review Articles in Peer Reviewed Journals

1. Yaster M, Deshpande JK: Management of Pediatric pain - use of opioid analgesics. J Pediatr 113:421-429, 1988

2. Yaster M, Maxwell LG: Pediatric regional anesthesia - a review. Anesthesiology 70:324-338, 1989

3. Yaster M, Deshpande JK, Maxwell LG: The pharmacologic management of pain in children. Comprehensive Therapy 15:14-26, 1989

4. Yaster M, Maxwell LG, Nicholas E, Desphande JK: The management of acute pain in children with local anesthetics: A primer for the non-anesthesiologist. Comprehensive Therapy 17:27-35, 1991

5. Yaster M, Nicholas EJ, Maxwell LG: The use of opioids in pediatric anesthesia and in the management of childhood pain. Anesthesiology Clinics of North America, 9:745-762, 1991

6. Yaster M, Tobin JR, Fisher QA,Maxwell LG: Local anesthetics in the management of acute pain in children. J Pediatr 124: 165-176, 1994

7. Yaster M, Kost-Byerly S, Greenberg RS, Maxwell LG: The management of acute pain in the traumatized child. International Anesthesia Clinics 409-435, 1996

8. Yaster, M., Cohen, D., Monitto, C.L., Davis, P.J. The use of opioids in pediatric anesthesia and in the management of childhood pain. Am J Anesthesiol 23:182-189, 1996

9. Galloway KS, Yaster M: Pain and symptom control in terminally ill children. Pediatr Clin North Am 47:711-46, 2000

10. Golianu B, Krane EJ, Galloway KS, Yaster M: Pediatric acute pain management. Pediatr Clin North Am 47:559-87, 2000

11. Yaster M, Kost-Byerly S, Maxwell LG: The management of pain in sickle cell disease. Pediatr Clin North Am 47:699-710, 2000

12. Maxwell LG and Yaster M: Perioperative management issues in pediatric patients. Anesthesiol.Clin.North America. 18 (3):601-632, 2000.

13. Yaster M, Nichols DG: Pain management in the critically ill child. Indian J.Pediatr. 2001; 68: 749-69

14. Gottschalk A and Yaster M: Pain management after neruosurgery. Neurosurg Q 2007; 17: 64-73

15. Gottschalk A and Yaster M: Pain management after Craniotomy Part I. Contemporary Neurosurgery 2008; 30:(10)1-8

16. Gottschalk A and Yaster M: Pain management after Craniotomy Part II. Contemporary Neurosurgery 2008; 30:(11)1-8

17. Gottschalk A, Yaster M: The Perioperative Management of Pain from Intracranial Surgery. Neurocrit.Care. 2008

18. Galinkin JL, Demmer L, Yaster M. Review article: genetics for the pediatric anesthesiologist: a primer on congenital malformations, pharmacogenetics, and proteomics. Anesth Analg 2010; 111(5):1264-1274.

19. Yaster M. Multimodal analgesia in children. Eur J Anaesthesiol 2010; 27(10):851-857

Biography


Dr. Yaster graduated summa cum laude from Brooklyn College of the City University of New York and received his Medical Doctorate with honors in 1977 at the State University of New York’s Downstate Medical Center. After graduation, he completed residencies in pediatrics (1979, Universities of Pittsburgh) and anesthesiology (1981, University of Pennsylvania) and fellowships in pediatric anesthesia and pediatric critical care medicine (1982, Children’s Hospital of Philadelphia). Following his training he came to Johns Hopkins as an instructor and over an almost 30 year period has risen to the rank of Professor in the Departments of Anesthesiology/Critical Care Medicine and Pediatrics. He is board-certified in Pediatrics, Anesthesiology, and Pediatric Intensive Care.

In an ongoing series of clinical and laboratory experiments that started in the 1980s, Dr. Yaster has been at the forefront of studies that demonstrated that the newborn infant responds to pain. More importantly, he and his colleagues have proven that this pain can be prevented by the appropriate use of anesthetics (general and regional) and analgesic drugs. Clearly pain, anxiety, and discomfort (both physical and psychological) are not limited to the newborn and do not begin and end with the induction and conclusion of surgery and anesthesia. Dr. Yaster started the Pediatric Pain Service at Johns Hopkins and was until 2005 its clinical director. This program treats approximately 3,500 in- and out-patients a year and is considered by many to be among the best programs in the world. It sets the standard for practice nationally and internationally and has served as the source of extensive clinical and translational research as well as practice policy. He and his colleagues have published extensively in this area. His two textbooks, Pain in Infants, Children, and Adolescents and The Pediatric Pain Management and Sedation Handbook are considered the gold standard textbooks in the field. He has authored many original papers in this area as both the first author and as the senior author. In the later capacity he has been the mentor of many individuals within and outside of the department who have gone on to become leaders in the areas of Pediatric Anesthesiology and Pediatric Pain Management.

In 2004-2005, Dr. Yaster stepped down from his Directorship of the Pediatric Pain Service in order to return to the laboratory and learn molecular biologic techniques to find solutions to clinically vexing problems. He established a very promising and highly productive relationship with other basic scientists working on acute and chronic pain in our Department. These basic scientists are internationally recognized pain researchers whose broad expertise in the neurophysiological, morphological, and molecular biology of this field have allowed Dr. Yaster to make important translational contributions in the laboratory as well as in the clinical arena. While continuing to carry a full clinical work load he and his colleagues have published more than 10 basic science articles in peer-reviewed journals. Working as a co-investigator, principle investigator and senior author, he has demonstrated that post-synaptic density proteins (e.g., PSD-95, PSD-93) are critical to the assembly of the NMDA receptor/nitric oxide synthase signaling complex in the spinal cord. Additionally using combinations of gene knockdown and knockout technologies, Dr. Yaster has worked on projects implicating the post-synaptic density proteins in mediating NMDA receptor-dependent pain hypersensitivity in chronic inflammatory and neuropathic pain. This work represents cutting-edge neuroscience and has resulted in a successful patent application for using inhibition of these post-synaptic density proteins to prevent hyperalgesia.

A second highly innovative area of Dr. Yaster's work is his demonstration that spinal glutamate transporter inhibition relieves inflammatory pain through activation of inhibitory presynaptic group III metabotropic glutamate receptors. His lab group has also found that persistent peripheral inflammation can induce synaptic AMPA receptor trafficking in dorsal horn neurons. Inhibition of this trafficking reduces pain hypersensitivity in the maintenance period of chronic inflammatory pain.

Finally, as a clinician Dr. Yaster has been at the forefront of finding solutions to treat or prevent opioid induced side effects, such as nausea, vomiting, pruritus, and tolerance. In the laboratory, he and his colleagues are investigating the role of mammalian target of rapamycin (mTOR), a serine-threonine protein kinase which controls translation of mRNA via phosphorylation of specific downstream effectors in the development and maintenance of spinally mediated tolerance. Their preliminary results showing that mTOR and the phosphorylted downstream effectors p70S6K, and 4E-BP1 are highly expressed in the DRG and dorsal horn following opioid administration and found in very low concentrations under normal conditions are the basis for this grant and may provide an exciting new area of research and novel therapeutic drug development.

Projects on the Horizon

All of the projects listed below are either in the process of data collection or IRB review for future study.

The perioperative management of patients with tethered cord syndrome
We retrospectively determined basic patient and surgical demographics, intra-operative anesthetic and postoperative pain management, and the incidence and management of low pressure CSF leak (headache) in patients who underwent spinal cord untethering at the Johns Hopins Hospital. This data will be presented at the ASA 2012 annual meeting in Washington D.C.  We found that hospitalization is often prolonged and correlates to surgical preference for head of bed elevation and management of low pressure CSF leaks (headache). Future studies aimed at standardizing the perioperative care of these are warranted and underway. We are in the process of registering this trial with www.ClinicalTrials.gov .
ASA 2012 Tethered Cord Poster.pdf

Pain management of pediatric patients following skull based surgery (craniotomy, craniectomy, cranio-facial): A multi-institutional prospective cohort study
The purpose of this prospective, clinical observational trial is to assess the incidence of pain, methods of pain assessment (and by whom), prescribed analgesics, methods of analgesic delivery, and patient/parent satisfaction in pediatric patients undergoing cranial surgery at 3 major university children’s hospitals: The Charlotte Bloomberg Children's Center Johns Hopkins Hospital, The Children's Hospital of Philadelphia, University of Pennsylvania, and The Boston Children's Hospital, Harvard University.  The data from Johns Hopkins will be  presented at the the International Assembly for Pediatric Anesthesia as well as ASA 2012 annual meeting in Washington D.C.  The data from the other 2 institutions will be presented at the annual spring meeting of the Society for Pediatric Anesthsia 2013 Las Vegas, NV.  Future randomized controlled studies aimed at the perioperative care of these patients are warranted and being planned.  
SPA/ASA 2012 Craniotomy Poster.pdf

Endotracheal tube cuff and tube leak pressures.  Are we doing what we are supposed to be doing and does it make a difference? 
This prospective cohort study of adult, pediatric and pediatric private practice management will be performed by the residents and fellows of the Department of Anesthesiology/Critical Care Medicine as part of their  ACGME core competency of systems based practice improvement. Adult patients will be studied at the Johns Hopkins Hospital and pediatric patients will be studied at the Charlotte Bloomberg Children's Center Johns Hopkins Hospital and at All Children's Hospital in St Petersburg, FL.

Based on the results of this study we anticipate future studies instituting practice improvement plans utilizing the PressureEasy Pressure Controller device (Smiths Medical).  Performance improvement will utilize the Johns Hopkins Medicine simulation center and the electronic anesthesia record for data collection.

Patient Controlled Analgesia (PCA) and Parent/Nurse Controlled Analgesia (PNCA, or "PCA by proxy"):  Is hydromorphone REALLY better than morphine.  A double blind randomized controlled trial
Many practitioners believe that at equipotent doses hydromorphone produces fewer opioid induced side effects and more euphoria than morphine.  The purpose of our proposed study is to use a double blind randomized controlled trial design to finally settle this issue once and for all using data rather than belief.  We are in the process of submitting this study to the IRB and registering it with www.ClinicalTrials.gov .
 
 

 
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