Welcome in the research database

Cardio-pulmonary and cerebral dysfunctions

Over the last 10 years, our research team has mainly explored the following topics:
1) identification of the predictive risk factors of cardiopulmonary complications after major surgery (cohort studies);
2) implementation of peri-operative organ protective strategies (e.g., beta-blockers, epidural analgesia) and early treatment of acute lung oedema shortly after lung resection;
3) circulatory adaptive mechanisms to acute hypoxia, myocardial ischemia, anaemia and surgical stress;
4) pharmacological interactions between anaesthetic agents and methylene blue or neural blockade of the sympathetic nervous system (potentiation of general anaesthesia).
Cardio-pulmonary and cerebral dysfunctions have been thoroughly investigated by invasive hemodynamic monitoring, blood gas analysis (oxygenation indices, PaO2/FIO2), quantification of tissue biomarkers (Troponin-I, SP100), ECG and simplified EEG recordings as well as echocardiography and transcranial Doppler.
For the first time, we have demonstrated that moderate acute normovolemic hemodilution (ANH, hematocrit down to 27%) was well tolerated in patients with 3-vessels coronary disease and in those with severe aortic valvular stenosis : cardiac index increases by 20-25% as a result of facilitated venous return owing to lower blood viscosity whereas left ventricular afterload remains unchanged. Subsequently, we demonstrated in two RCTs including high-risk cardiac patients that moderate ANH was associated with less severe myocardial injuries, fewer arrhythmias as well as lower requirement for inotropes and vasopressor support. Likewise, we confirmed these beneficial effects of ANH in a rat model of transient coronary artery occlusion as evidence by smaller myocardial infarct size (-40%), better survival (83% vs 42% at 48 h). Interestingly, besides the improved rheological conditions, a delayed release of erythropoietine (EPO, 6-18h after ANH) might have contributed to these cardioprotective effects.
Experimental studies have unveiled the mechanisms of EPO-induced neuro- and cardio-protection involving different pathways (proliferation and differenciation of progenitor erythroid cells, inhibition of caspase activation, activation of JAK-2 kinase, activation of phosphatidyl-inositol-3 kinase and Akt phosporylation.
The infusion of Glucose-Insuline-Potassium (GIK) is another promising perioperative strategy to minimize myocardial ischemia-reperfusion injuries by acting at different key intra-cellular targets (activation of phospatidylinositol 3-kinase, hyperpolarisation of cardiomyocytes, increased glycogen content, utilization of glucides instead of FFA for energetic substrate synthesis, upregulation of the endothelial L-Arginine-NO pathway).
In 3 clinical RCTs, we will investigate the potential cardioprotective effects of beta-adrenergic blockers (emergency surgery), EPO and GIK solution (aortic valvular replacement, coronary artery bypass surgery). Neurocognitive disorders and nosocomial infections will also be evaluated in studies involving the administration EPO and GIK.

Group's publications

Impact of intraoperative lung-protective interventions in patients undergoing lung cancer surgery.
CRITICAL CARE
2009 vol. 13(2) pp. 41-41
LICKER M, DIAPER J, VILLIGER Y, SPILIOPOULOS A, LICKER V, ROBERT J, TSCHOPP J.-M.

The European Respiratory Society and European Society of Thoracic Surgeons clinical guidelines for evaluating fitness for radical treatment (surgery and chemoradiotherapy) in patients with lung cancer .
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY : OFFICIAL JOURNAL OF THE EUROPEAN ASSOCIATION FOR CARDIO-THORACIC SURGERY
2009 vol. 36(1) pp. 181-184
BRUNELLI A. AND AL.

ERS/ESTS clinical guidelines on fitness for radical therapy in lung cancer patients (surgery and chemo-radiotherapy).
EUROPEAN RESPIRATORY JOURNAL
2009 vol. 34(1) pp. 17-41
BRUNELLI A. AND AL.

Titrated sedation with propofol or midazolam for flexible bronchoscopy: a randomised trial.
EUROPEAN RESPIRATORY JOURNAL
2009 vol. 34(6) pp. 1277-1283
CLARK G, LICKER M, YOUNOSSIAN AB, SOCCAL PM, FREY J, ROCHAT T, DIAPER J, BRIDEVAUX PO, TSCHOPP JM

Effects of methylene blue on propofol requirement during anaesthesia induction and surgery.
ANAESTHESIA
2008 vol. 63(4) pp. 352-357
LICKER M, DIAPER J, ROBERT J, ELLENBERGER C

Adverse effects of methylene blue on the central nervous system.
ANESTHESIOLOGY
2008 vol. 108(4) pp. 684-692
VUTSKITS L, BRINER A, KLAUSER P, GASCON E, DAYER A, KISS JZ, MULLER D, LICKER MJ, MOREL D

Perioperative protective ventilatory strategies in patients without acute lung injuries.
ANESTHESIOLOGY
2008 vol. 108(2) pp. 335-336
LICKER M, DIAPER J, ELLENBERGER C

Impending paradoxical embolism. When and how to treat?
ANNALES DE CARDIOLOGIE ET D'ANGEIOLOGIE
2008 vol. 57(4) pp. 234-237
BONVINI RF, ROBERT-EBADI H, FONTANA P, FASSA A, MYERS P, LICKER M, BOEHLEN F, RIGHINI M

Aerosolized salbutamol accelerates the resolution of pulmonary edema after lung resection.
CHEST
2008 vol. 133(4) pp. 845-852
LICKER M, TSCHOPP JM, ROBERT J, FREY J, DIAPER J, ELLENBERGER C

Risk factors for methicillin-resistant Staphylococcus aureus surgical site infection.
INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY : THE OFFICIAL JOURNAL OF THE SOCIETY OF HOSPITAL EPIDEMIOLOGISTS OF AMERICA
2008 vol. 29(9) pp. 890-893
HARBARTH S, HUTTNER B, GERVAZ P, FANKHAUSER C, CHRAITI MARIE-NOELLE, SCHRENZEL J, LICKER M, PITTET D

Life-threatening pulmonary embolism associated with a thrombus straddling a patent foramen ovale: report of a case.
JOURNAL OF CARDIAC SURGERY
2008 vol. 23(4) pp. 376-378
MYERS PO, FASSA AA, PANOS A, LICKER M, BOUNAMEAUX H, ZENDER HO, KALANGOS A

Transoesophageal Doppler monitoring for fluid and hemodynamic treatment during lung surgery.
JOURNAL OF CLINICAL MONITORING AND COMPUTING
2008 vol. 22(5) pp. 367-374
DIAPER J, ELLENBERGER C, VILLIGER Y, ROBERT J, TSCHOPP JM, LICKER M

Perioperative beta-blockade: Still not enough for adequate cardioprotection!
ANESTHESIA AND ANALGESIA
2007 vol. 105 pp. 278-279
LICKER M, DIAPER J, ELLENBERGER C

Bispectral index and detection of acute brain injury during cardiac surgery
EUROPEAN JOURNAL OF ANAESTHESIOLOGY
2007 vol. 24 pp. 807-809
LICKER M, ELLENBERGER C, DIAPER J, PANOS A

Guided cerebral protection in cardiac surgery
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
2007 vol. 32 pp. 822-823
ELLENBERGER C, PANOS A, DIAPER J, LICKER M

Small size new silastic drains: life-threatening hypovolemic shock after thoracic surgery associated with a non-functioning chest tube
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
2007 vol. 31 pp. 566-568
CLARK G, LICKER M, BERTIN D, SPILIOPOULOS A

Cardioprotective effects of acute normovolemic hemodilution in patients with severe aortic stenosis undergoing valve replacement
TRANSFUSION
2007 vol. 47 pp. 341-350
LICKER M, SIERRA J, KALANGOS A, PANOS A, DIAPER J, ELLENBERGER C

Operative mortality and respiratory complications after lung resection for cancer: Impact of chronic obstructive pulmonary disease and time trends - Invited commentary
ANNALS OF THORACIC SURGERY
2006 vol. 81 pp. 1830-1838
LICKER MJ, WIDIKKER I, ROBERT J, FREY JG, SPILIOPOULOS A, ELLENBERGER C, SCHWEIZER A, TSCHOPP JM, ROCCO G

Rat or human-based blood therapy in acute myocardial infarction? Reply
CRITICAL CARE MEDICINE
2006 vol. 34 pp. 2026-2027
LICKER M, MOREL DR

Incidence, risk factors and prognosis of changes in serum creatinine early after aortic abdominal surgery
INTENSIVE CARE MEDICINE
2006 vol. 32 pp. 1808-1816
ELLENBERGER C, SCHWEIZER A, DIAPER J, KALANGOS A, MURITH N, KATCHATOURIAN G, PANOS A, LICKER M

Cardiovascular collapse due to massive pulmonary thromboembolism during orthotopic liver transplantation
JOURNAL OF CLINICAL ANESTHESIA
2006 vol. 18(5) pp. 367-371
ELLENBERGER CHRISTOPH, MENTHA GILLES, GIOSTRA EMILIANO, LICKER MARC

The impact of a cardioprotective protocol on the incidence of cardiac complications after aortic abdominal surgery
ANESTHESIA AND ANALGESIA
2002 vol. 95 pp. 1525-1533
LICKER M, KHATCHATOURIAN G, SCHWEIZER A, BEDNARKIEWICZ M, TASSAUX D, CHEVALLEY C

Absence of beneficial effect of acute normovolemic hemodilution combined with aprotinin on allogeneic blood transfusion requirements in cardiac surgery
ANESTHESIOLOGY
2002 vol. 96 pp. 276-282
HOHN L, SCHWEIZER A, LICKER M, MOREL DR

Risk factors for early mortality and major complications following pneumonectomy for non-small cell carcinoma of the lung
CHEST
2002 vol. 121 pp. 1890-1897
LICKER M, SPILIOPOULOS A, FREY JG, ROBERT J, HOHN L, DE PERROT M, TSCHOPP JM

Opening of a new postanesthesia care unit: Impact on critical care utilization and complications following major vascular and thoracic surgery
JOURNAL OF CLINICAL ANESTHESIA
2002 vol. 14 pp. 486-493
SCHWEIZER A, KHATCHATOURIAN G, HÖHN L, SPILIOPOULOS A, ROMAND JA, LICKER M

Research's domains




DATABASE-RESEARCH	GROUP OF CLINICAL PATIENT RESEARCH

Professor Marc LICKER	Head of group CV	Research subject	Members of the group


	Links about the group Prof. Marc LICKER HUG/ Dpt APSI Serv Anesthésiologie Rue Gabrielle-Perret-Gentil 4 1211 Genève 14 Suisse Marc-Joseph.Licker@hcuge.ch Tel.: +41 795 53 21 11 Comments Pages updated the 17.11.2015		Reseach's subject \| Group's publications \| Research's domains Cardio-pulmonary and cerebral dysfunctions Over the last 10 years, our research team has mainly explored the following topics: 1) identification of the predictive risk factors of cardiopulmonary complications after major surgery (cohort studies); 2) implementation of peri-operative organ protective strategies (e.g., beta-blockers, epidural analgesia) and early treatment of acute lung oedema shortly after lung resection; 3) circulatory adaptive mechanisms to acute hypoxia, myocardial ischemia, anaemia and surgical stress; 4) pharmacological interactions between anaesthetic agents and methylene blue or neural blockade of the sympathetic nervous system (potentiation of general anaesthesia). Cardio-pulmonary and cerebral dysfunctions have been thoroughly investigated by invasive hemodynamic monitoring, blood gas analysis (oxygenation indices, PaO2/FIO2), quantification of tissue biomarkers (Troponin-I, SP100), ECG and simplified EEG recordings as well as echocardiography and transcranial Doppler. For the first time, we have demonstrated that moderate acute normovolemic hemodilution (ANH, hematocrit down to 27%) was well tolerated in patients with 3-vessels coronary disease and in those with severe aortic valvular stenosis : cardiac index increases by 20-25% as a result of facilitated venous return owing to lower blood viscosity whereas left ventricular afterload remains unchanged. Subsequently, we demonstrated in two RCTs including high-risk cardiac patients that moderate ANH was associated with less severe myocardial injuries, fewer arrhythmias as well as lower requirement for inotropes and vasopressor support. Likewise, we confirmed these beneficial effects of ANH in a rat model of transient coronary artery occlusion as evidence by smaller myocardial infarct size (-40%), better survival (83% vs 42% at 48 h). Interestingly, besides the improved rheological conditions, a delayed release of erythropoietine (EPO, 6-18h after ANH) might have contributed to these cardioprotective effects. Experimental studies have unveiled the mechanisms of EPO-induced neuro- and cardio-protection involving different pathways (proliferation and differenciation of progenitor erythroid cells, inhibition of caspase activation, activation of JAK-2 kinase, activation of phosphatidyl-inositol-3 kinase and Akt phosporylation. The infusion of Glucose-Insuline-Potassium (GIK) is another promising perioperative strategy to minimize myocardial ischemia-reperfusion injuries by acting at different key intra-cellular targets (activation of phospatidylinositol 3-kinase, hyperpolarisation of cardiomyocytes, increased glycogen content, utilization of glucides instead of FFA for energetic substrate synthesis, upregulation of the endothelial L-Arginine-NO pathway). In 3 clinical RCTs, we will investigate the potential cardioprotective effects of beta-adrenergic blockers (emergency surgery), EPO and GIK solution (aortic valvular replacement, coronary artery bypass surgery). Neurocognitive disorders and nosocomial infections will also be evaluated in studies involving the administration EPO and GIK. Group's publications Impact of intraoperative lung-protective interventions in patients undergoing lung cancer surgery. CRITICAL CARE 2009 vol. 13(2) pp. 41-41 LICKER M, DIAPER J, VILLIGER Y, SPILIOPOULOS A, LICKER V, ROBERT J, TSCHOPP J.-M. The European Respiratory Society and European Society of Thoracic Surgeons clinical guidelines for evaluating fitness for radical treatment (surgery and chemoradiotherapy) in patients with lung cancer . EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY : OFFICIAL JOURNAL OF THE EUROPEAN ASSOCIATION FOR CARDIO-THORACIC SURGERY 2009 vol. 36(1) pp. 181-184 BRUNELLI A. AND AL. ERS/ESTS clinical guidelines on fitness for radical therapy in lung cancer patients (surgery and chemo-radiotherapy). EUROPEAN RESPIRATORY JOURNAL 2009 vol. 34(1) pp. 17-41 BRUNELLI A. AND AL. Titrated sedation with propofol or midazolam for flexible bronchoscopy: a randomised trial. EUROPEAN RESPIRATORY JOURNAL 2009 vol. 34(6) pp. 1277-1283 CLARK G, LICKER M, YOUNOSSIAN AB, SOCCAL PM, FREY J, ROCHAT T, DIAPER J, BRIDEVAUX PO, TSCHOPP JM Effects of methylene blue on propofol requirement during anaesthesia induction and surgery. ANAESTHESIA 2008 vol. 63(4) pp. 352-357 LICKER M, DIAPER J, ROBERT J, ELLENBERGER C Adverse effects of methylene blue on the central nervous system. ANESTHESIOLOGY 2008 vol. 108(4) pp. 684-692 VUTSKITS L, BRINER A, KLAUSER P, GASCON E, DAYER A, KISS JZ, MULLER D, LICKER MJ, MOREL D Perioperative protective ventilatory strategies in patients without acute lung injuries. ANESTHESIOLOGY 2008 vol. 108(2) pp. 335-336 LICKER M, DIAPER J, ELLENBERGER C Impending paradoxical embolism. When and how to treat? ANNALES DE CARDIOLOGIE ET D'ANGEIOLOGIE 2008 vol. 57(4) pp. 234-237 BONVINI RF, ROBERT-EBADI H, FONTANA P, FASSA A, MYERS P, LICKER M, BOEHLEN F, RIGHINI M Aerosolized salbutamol accelerates the resolution of pulmonary edema after lung resection. CHEST 2008 vol. 133(4) pp. 845-852 LICKER M, TSCHOPP JM, ROBERT J, FREY J, DIAPER J, ELLENBERGER C Risk factors for methicillin-resistant Staphylococcus aureus surgical site infection. INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY : THE OFFICIAL JOURNAL OF THE SOCIETY OF HOSPITAL EPIDEMIOLOGISTS OF AMERICA 2008 vol. 29(9) pp. 890-893 HARBARTH S, HUTTNER B, GERVAZ P, FANKHAUSER C, CHRAITI MARIE-NOELLE, SCHRENZEL J, LICKER M, PITTET D Life-threatening pulmonary embolism associated with a thrombus straddling a patent foramen ovale: report of a case. JOURNAL OF CARDIAC SURGERY 2008 vol. 23(4) pp. 376-378 MYERS PO, FASSA AA, PANOS A, LICKER M, BOUNAMEAUX H, ZENDER HO, KALANGOS A Transoesophageal Doppler monitoring for fluid and hemodynamic treatment during lung surgery. JOURNAL OF CLINICAL MONITORING AND COMPUTING 2008 vol. 22(5) pp. 367-374 DIAPER J, ELLENBERGER C, VILLIGER Y, ROBERT J, TSCHOPP JM, LICKER M Perioperative beta-blockade: Still not enough for adequate cardioprotection! ANESTHESIA AND ANALGESIA 2007 vol. 105 pp. 278-279 LICKER M, DIAPER J, ELLENBERGER C Bispectral index and detection of acute brain injury during cardiac surgery EUROPEAN JOURNAL OF ANAESTHESIOLOGY 2007 vol. 24 pp. 807-809 LICKER M, ELLENBERGER C, DIAPER J, PANOS A Guided cerebral protection in cardiac surgery EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY 2007 vol. 32 pp. 822-823 ELLENBERGER C, PANOS A, DIAPER J, LICKER M Small size new silastic drains: life-threatening hypovolemic shock after thoracic surgery associated with a non-functioning chest tube EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY 2007 vol. 31 pp. 566-568 CLARK G, LICKER M, BERTIN D, SPILIOPOULOS A Cardioprotective effects of acute normovolemic hemodilution in patients with severe aortic stenosis undergoing valve replacement TRANSFUSION 2007 vol. 47 pp. 341-350 LICKER M, SIERRA J, KALANGOS A, PANOS A, DIAPER J, ELLENBERGER C Operative mortality and respiratory complications after lung resection for cancer: Impact of chronic obstructive pulmonary disease and time trends - Invited commentary ANNALS OF THORACIC SURGERY 2006 vol. 81 pp. 1830-1838 LICKER MJ, WIDIKKER I, ROBERT J, FREY JG, SPILIOPOULOS A, ELLENBERGER C, SCHWEIZER A, TSCHOPP JM, ROCCO G Rat or human-based blood therapy in acute myocardial infarction? Reply CRITICAL CARE MEDICINE 2006 vol. 34 pp. 2026-2027 LICKER M, MOREL DR Incidence, risk factors and prognosis of changes in serum creatinine early after aortic abdominal surgery INTENSIVE CARE MEDICINE 2006 vol. 32 pp. 1808-1816 ELLENBERGER C, SCHWEIZER A, DIAPER J, KALANGOS A, MURITH N, KATCHATOURIAN G, PANOS A, LICKER M Cardiovascular collapse due to massive pulmonary thromboembolism during orthotopic liver transplantation JOURNAL OF CLINICAL ANESTHESIA 2006 vol. 18(5) pp. 367-371 ELLENBERGER CHRISTOPH, MENTHA GILLES, GIOSTRA EMILIANO, LICKER MARC The impact of a cardioprotective protocol on the incidence of cardiac complications after aortic abdominal surgery ANESTHESIA AND ANALGESIA 2002 vol. 95 pp. 1525-1533 LICKER M, KHATCHATOURIAN G, SCHWEIZER A, BEDNARKIEWICZ M, TASSAUX D, CHEVALLEY C Absence of beneficial effect of acute normovolemic hemodilution combined with aprotinin on allogeneic blood transfusion requirements in cardiac surgery ANESTHESIOLOGY 2002 vol. 96 pp. 276-282 HOHN L, SCHWEIZER A, LICKER M, MOREL DR Risk factors for early mortality and major complications following pneumonectomy for non-small cell carcinoma of the lung CHEST 2002 vol. 121 pp. 1890-1897 LICKER M, SPILIOPOULOS A, FREY JG, ROBERT J, HOHN L, DE PERROT M, TSCHOPP JM Opening of a new postanesthesia care unit: Impact on critical care utilization and complications following major vascular and thoracic surgery JOURNAL OF CLINICAL ANESTHESIA 2002 vol. 14 pp. 486-493 SCHWEIZER A, KHATCHATOURIAN G, HÖHN L, SPILIOPOULOS A, ROMAND JA, LICKER M Research's domains