Basic Scientific Research

Investigation of the Therapeutic Potential of Hypercapnic Acidosis in Acute Lung Injury

Objective

The objective of this work is to determine the therapeutic potential, mechanisms of action, and characterise the safety and efficacy, of hypercapnic acidosis in the setting of Acute Respiratory Distress Syndrome.

Collaborators:  Prof. P. McLoughlin, University College Dublin

Ongoing Laboratory Projects at University of Galway

  • Investigation of the effects of Hypercapnia and Acidosis in Acute Lung Injury induced by Systemic Sepsis
  • Investigation of the effects and mechanisms of action of hypercapnic acidosis in Acute Lung Injury induced by Ventilation induced Lung Injury
  • Investigation of the effects and mechanisms of action of hypercapnic acidosis on the repair process following in Acute Lung Injury

Recently Completed Laboratory Projects at University of Galway

  • Investigation of the effects and mechanisms of action of Hypercapnic Acidosis in Acute Lung Injury induced by early and established severe Pulmonary Sepsis
  • Investigation of the potential effects and mechanisms of hypercapnic acidosis in evolving and established systemic sepsis

Collaborative Laboratory Projects (with University College Dublin)

  • Investigation of the effect of buffering on the effects of Hypercapnia in sepsis Induced Lung Injury
  • Investigation of the effects and mechanisms of action of Hypercapnic Acidosis in Acute Lung Injury induced by Pulmonary Sepsis
  • Investigation of the effects and mechanisms of action of Hypercapnic Acidosis in Acute Lung Injury induced by Endotoxin

Selected Recent Publications

(1) Costello J, Higgins B, Contreras M, Ni Chonghaile M,  Hassett P, O’ Toole D, Laffey JG. Hypercapnic acidosis attenuates shock and lung injury in early and prolonged systemic sepsis. Critical Care Med 2009 (in press).

(2) Nichol A, O’ Croinin D, Howell K, Naughton F, O’Brien S, Boylan J, O’Connor CM, O’Toole D, Laffey JG, McLoughlin P. Infection induced lung injury is worsened following renal buffering of hypercapnic acidosis Critical Care Medicine 2009 (in press). (Note: Joint Publication with Conway Institute, UCD)

(3) Ni Chonghaile M, Higgins B, Costello J, Laffey JG. Hypercapnic Acidosis Attenuates Lung Injury Induced by Established Bacterial Pneumonia. Anesthesiology 2008; 109(5):837-848.

(4) Ni Chonghaile M, Higgins B, Costello J, Laffey JG. Hypercapnic acidosis attenuates the severity of severe pulmonary sepsis by a neutrophil independent mechanism. Critical Care Medicine 2008 Dec;36(12):3135-44.

(5) Kennedy M, Higgins B Laffey JG. Hypertonic Saline reduces inflammation and enhances the resolution of Oleic Acid induced Acute Lung Injury. BMC Pulmonary Medicine 2008 Jul 8;8(1):9. [PMID: 18611275]

(6) O'Croinin DF, Nichol AD, Hopkins N, Boylan J, O'Brien S, O'Connor C, Laffey JG, McLoughlin P. Sustained hypercapnic acidosis during pulmonary infection increases bacterial load and worsens lung injury* Crit Care Med. 2008 Jul;36(7):2128-35. PMID: 18552698 (Note: Joint Publication with Conway Institute, UCD)

(7) O' Croinin DF, Hopkins NO, Moore MM, Boylan JF, McLoughlin P, Laffey JG. Hypercapnic acidosis does not modulate the severity of bacterial pneumonia-induced lung injury. Crit Care Med. 2005 Nov;33(11):2606-2612 [PMID: 16276187]. (Note: Joint Publication with Conway Institute, UCD) 

Investigation of the therapeutic potential of Gene and Stem Cell Therapies in Acute Lung Injury

Objective

The objective of this work is to determine the therapeutic potential, mechanisms of action, and the safety and efficacy, of gene and stem cell therapies in the setting of Acute Respiratory Distress Syndrome. 

Principal Investigator: Prof. J. Laffey

Collaborators: Prof T. O'Brien, REMEDI, University of Galway and Prof F. Barry, REMEDI, University of Galway

Ongoing Laboratory Projects at University of Galway

  • Determination of the feasibility and therapeutic potential of somatic gene transfer in Acute Lung Injury
  • Investigation of efficacy of superoxide dismutase somatic gene transfer in Acute Lung Injury
  • Investigation of efficacy of gene therapy strategies to modulate the NF-ƒÛB pathway in Acute Lung Injury

Recent Publications

(1) MacLoughin R, Higgins B, Laffey JG, O¡¦Brien T. Optimised aerosol delivery in an in vitro model of a mechanically ventilated rodent. J Aerosol Med 2009 (in press).

Myocardial and Vascular Research

Objective

This research strand incorporates projects investigating the effects of sepsis on myocardial performance and on mitochondrial bioenergetics, determination of the effects and mechanisms of action of volatile anaesthetic agents in the Foeto-Placental Circulation, and determination of the effects and mechanisms of action of sidlenafil in the Foeto-Placental Circulation 

Principal Investigators:  Dr. Leo Kevin, Prof. John Laffey

Co- Investigator: Prof John Morrison, Dept of Obstetrics and Gynaecology, University of Galway.

Specific Laboratory Projects

  • Investigation the effects of sepsis on myocardial performance and on mitochondrial bioenergetics
  • Determination of the effects and mechanisms of action of Sildenafil in the Foeto-Placental Circulation
  • Investigation of the mechanisms underlying the vasodilatory effects of Sevoflurane in the Foeto-Placental Circulation

Recent Publications

(1) Maharaj C, Jarman J, Lynch T, Higgins B, O’ Toole D, Flynn N, Laffey JG. Effects and mechanisms of action of sildenafil citrate in human chorionic arteries. Reproductive Biology and Endocrinology 2009, 7 (1):34 (23 April 2009).

(2) Farragher R, Maharaj C, Higgins B, Crowe S, Burke P, Flynn N, Laffey JG. Sevoflurane and the fetal-placental circulation: Role of Nitric Oxide and Vasoactive Prostanoids. Anesthesia and Analgesia 2008 107: 171-177. 

Acute Perioperative Pain

Objective

This objective of research strand is to develop more effective and safer approaches to the provision of effective analgesia for acute pain, particularly acute postoperative pain. A major current focus is on the development and ongoing characterisation of the Transversus Abdominus Plane block, and determination of the utility of ultrasound as a means to enhance the efficacy and safety of regional blockade.

Principal Investigators:  Dr. John McDonnell and Prof. John Laffey

Research Fellow: Dr. Olivia Finnnerty

Co- Investigators: Prof Peter Dockery, Dept. of Anatomy, University of Galway and Dr David Finn, Dept. of Pharmacology, University of Galway.

Ongoing Clinical Projects

  • Characterization of the efficacy of the Transversus Abdominis Plane (TAP) block in children undergoing abdominal surgery
  • Comparison of the efficacy of the Paravertebral block versus Epidural blockade in adults undergoing nephrectomy
  • Characterization of the efficacy of the Transversus Abdominis Plane (TAP) block versus Epidural blockade in adults undergoing radical prostatectomy

Recently Completed Clinical Projects

  • Characterization of the efficacy of the Transversus Abdominis Plane (TAP) block in patients undergoing total abdominal hysterectomy
  • Anatomic and radiologic characterization of the Transversus Abdominis Plane (TAP) block
  • Characterization of a novel Transversus Abdominis Plane (TAP) block in patients undergoing abdominal laparotomy
  • Optimization of the dose of intrathecal morphine in patients undergoing total knee arthroplasty

Selected Recent Publications

1. Carney J, McDonnell JG, Ochana A, Bhinder R, Laffey JG. The Transversus Abdominis Plane Block provides effective postoperative analgesia in patients undergoing total abdominal hysterectomy. Anesthesia and Analgesia 2008 Dec;107(6):2056-60.

2. Hassett P, Ansari B, Gangamoorthy P, Kinirons B, Laffey JG. Determination of the efficacy and side-effect profile of lower doses of Intrathecal Morphine in Patients undergoing Total Knee Replacement. BMC Anesthesiology 2008, 8:5 (24 September 2008)

3. McDonnell JG, Curley G, Carney J, Benton A, Costello J, Maharaj C, Laffey JG. The analgesic efficacy of transversus abdominis plane block after cesarean section: a prospective randomized controlled trial. Anesthesia and Analgesia 2008 Jan;106(1):186-91 [PMID: 18165577]

4. McDonnell JG, O’Donnell B, Heffernan A, Power C, Laffey JG. Transversus Abdominus Plane (TAP) Block for Abdominal Surgery: Anatomic and Radiologic study. Reg Anes Pain Med 2007 Sep;32(5):399-404. [PMID: 17961838]

5. McDonnell JG, O'Donnell B, Curley G, Heffernan A, Power C, Laffey JG. The analgesic efficacy of transversus abdominis plane block after abdominal surgery: a prospective randomized controlled trial. Anesth Analg. 2007 Jan;104(1):193-7.  PMID: 17179269 [PubMed - in process].

6. Murphy PM, Stack D, Kinirons B, Laffey JG. Optimizing of the dose of Intrathecal Morphine in Older Patients undergoing Hip Arthroplasty. Anesthesia and Analgesia 2003 Dec; 97: 1709-1715.

Evaluation of Airway and Ventilation Devices

Objective

This objective of research programme is to evaluate novel medical devices of relevance to Anaesthesia and Intensive Care Medicine.  A major current focus is on the evaluation of novel laryngoscopes, in order to develop the evidence base supporting the use of these devices by different healthcare provider groups, from experienced anaesthetists to paramedics and novice users. A second focus is on the characterization of High Frequency Oscillation, in conjunction with colleagues in Biomedical Engineering at University of Galway.

Principal Investigators:  Prof. John Laffey and Dr. Brian Harte

Research Fellow: Dr. Anwar Malik

Collaborators: Dr. Mark Bruzzi, Dept of Bioengineering, University of Galway.

Ongoing Research Projects

  • Determination of the efficacy of the Pentax AWS laryngoscope device in patients at low risk for difficult intubation
  • Determination of the efficacy of the Pentax AWS laryngoscope device in patients at high risk for difficult intubation
  • Determination of the efficacy of the Truview laryngoscope device in patients undergoing cervical immobilization

Selected Completed Research Projects

  • Determination of the efficacy of the Truview laryngoscope device in patients at high risk for difficult intubation
  • Determination of the efficacy of novel laryngoscope devices for use by emergency medical personnel
  • Comparison of the Airtraq device to the Macintosh Laryngoscope for Tracheal Intubation

Selected Recent Publications

(1) Nasim S, Maharaj CH, Butt I, O’ Donnell J, Harte BH, Laffey JG. Comparison of the Pentax AWS® and Glidescope® laryngoscopes to the Macintosh laryngoscope for use by Advanced Paramedics in both easy and simulated difficult intubation. BMC Emerg Med 2009 (in press).

(2) Malik A, Ram, Churasia S, Maharaj CH, Harte BH, Laffey JG. Comparison of the Pentax AWS® and LMA Ctrach® laryngoscopes to the Macintosh laryngoscope in cervical spine immobilization. Br J Anaesth. 2009 May;102(5):654-61. Epub 2009 Mar 31

(3) Nasim S, Maharaj CH, Butt I, O’ Donnell J, Harte BH, Laffey JG. Comparison of the Airtraq® and Truview® laryngoscopes to the Macintosh laryngoscope for use by Advanced Paramedics in both easy and simulated difficult intubation. BMC Emerg Med 2009, 9:2.

(4) Malik MA, O’Donoghue C, Carney J, Maharaj CH, Harte BH, Laffey JG.  A comparison of the Glidescope®, the Pentax AWS® and the Truview® EVO2 to the Macintosh laryngoscope in experienced Anaesthetists – A manikin study. Br J Anaes 2009 102: 128-134.

(5) Heraty KB, Laffey JG, Quinlan HJ. Fluid dynamics of gas exchange in high frequency oscillatory ventilation: in vitro investigations in idealised and anatomically realistic airway bifurcation models. Annals of Biomedical Engineering 2008 Sep 11. [Epub ahead of print] PMID: 18785010 [PubMed - as supplied by publisher]

(6) Malik MA, Maharaj CH, Harte BH, Laffey JG.  A Comparison of Macintosh, Truview EV02â, Glidescope® and Airwayscope® Laryngoscopes in Patients with Cervical Spine Immobilization. Br J Anaesth. 2008 Nov;101(5):723-30. Epub 2008 Sep 9.

(7) Maharaj CH, Harte BH, Laffey JG. Evaluation of the Airtraq and Macintosh in Patients at increased risk for difficult tracheal intubation. Anesthesia 2008 Feb;63(2):182-8 [PMID: 18211450].

(8) Maharaj CH, McDonnell JG, Harte BH, Laffey JG. A comparison of the utility of direct and indirect laryngoscopes and the iLMA in novice users: A manikin study. Anaesthesia 2007 Nov;62(11):1161-6. PMID: 17924898

(9) Maharaj CH, Buckley E, Harte BH, Laffey JG. Endotracheal Intubation in Patients with Cervical Spine Immobilization: A Comparison of Macintosh and Airtraq Laryngoscopes. Anesthesiology. 2007 Jul;107(1):53-59. PMID: 17585215 [PubMed - as supplied by publisher]

(10) Maharaj CH, Higgins B, Harte BH, Laffey JG. Retention of tracheal intubation skills by novice personnel: A comparison of the Airtraq® and Macintosh laryngoscopes. Anaesthesia 2007 Mar;62(3):272-8. PMID: 17300305 [PubMed - in process].

(11) Maharaj CH, Ni Chonghaile M, Higgins BD, Harte BH, Laffey JG. Tracheal intubation by inexperienced medical residents using the Airtraq and Macintosh laryngoscopes-a manikin study. Am J Emerg Med. 2006 Nov;24(7):769-774. PMID: 17098095 [PubMed - as supplied by publisher].

(12) Maharaj CH, O’ Croinin D, Curley G, Harte BH, Laffey JG. Evaluation of ease of intubation with the Airtraq® or Macintosh laryngoscope in routine airway management: a randomized, controlled clinical trial. Anaesthesia 2006 Nov;61(11):1093-9.  PMID: 17042849 [PubMed - in process].

(13) Maharaj CH, Higgins B, Harte BH, Laffey JG. Learning and performance of tracheal intubation by novice personnel: a comparison of the Airtraq and Macintosh laryngoscope. Anaesthesia. 2006 Jul;61(7):671-7. PMID: 16792613 [PubMed - in process]

(14) Maharaj CH, Higgins B, Harte BH, Laffey JG. Evaluation of ease of intubation with the Airtraq® or Macintosh laryngoscope by anaesthetists in easy and simulated difficult laryngoscopy – A manikin study. Anaesthesia 2006 May;61(5):469-77. PMID: 16674623 [PubMed - indexed for MEDLINE]