Clinical trial NCT02065635: Effect of Type of General Anesthesia Maintenance on Exhaled Nitric Oxide and Eosinophil Blood Count
Official title: Investigation of Changes in the Levels of Exhaled NO and Eosinophil Blood Count in Patients Undergoing Thyroidectomy by Two Different Methods of General Anesthesia Maintenance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Anesthesia
Exhaled Nitric Oxide
Eosinophil Blood Count
Lead sponsor: Aretaieion University Hospital
Sponsor class: OTHER
First posted: 2014-02-19
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: * Nitric oxide (NO) is a free radical in gas state which plays an important role in a variety of processes relevant to respiratory physiology. It represents a means of detecting airway hyperresponsiveness and appears to have a strong correlation with the eosinophilic infiltration of the airway. Patients who suffered bronchospasm or laryngospasm intraoperatively or postoperatively showed higher levels of exhaled NO.
* Propofol modifies NO production by stimulating the constitutive synthesis of NO and by inhibiting the inducible production of NO. It seems to exert protective effects on acute lung injury (ALI) in experimental models and it can possibly reduce exhaled NO. There is also evidence that some intravenous anesthetic agents can influence chemotaxis of eosinophils in vitro.
* Variation of exhaled NO and eosinophils in surgical patients undergoing anesthesia has not been studied before. Therefore, the aim of this study will be to investigate the differential impact of maintenance of general anesthesia with propofol versus maintenance with sevoflurane on exhaled NO and eosinophil blood count.

Detailed description: * Nitric oxide (NO) is a free radical in gas state which plays an important role in a variety of processes relevant to respiratory physiology. NO is produced by several cellular types (epithelial, endothelial, neuronic, inflammatory cells) (Gaston B, et al, 1994), it represents a means of detecting airway hyperresponsiveness and appears to have a strong correlation with the eosinophilic infiltration of the airway (Warke TJ, et al, 2002). Patients who suffered bronchospasm or laryngospasm intraoperatively or postoperatively showed higher levels of exhaled NO (Saraiva-Romanholo BM, et al, 2009).
* Propofol modifies NO production by stimulating the constitutive synthesis of NO and by inhibiting the inducible production of NO (González-Correa JA, et al, 2008). It seems to exert protective effects on acute lung injury in experimental models (Chu CH, et al, 2007; Chen HJ, et al, 2008) and possibly reduces exhaled NO (Fijałkowska A, et al, 2012). There is also evidence that some intravenous anesthetic agents can influence chemotaxis of eosinophils in vitro (Krumholz W, et al, 1999)
* Variation of exhaled NO and eosinophils in surgical patients undergoing anesthesia has not been studied before. Therefore, the aim of this study will be to investigate the differential impact of maintenance of general anesthesia with propofol versus maintenance with sevoflurane on exhaled NO and eosinophil blood count.
* Patients with ASA score I-III who undergo thyroidectomy under general anaesthesia will participate in this study. Thyroidectomy has been chosen for the following reasons: a) there will be consistency in both the surgeon and the type of surgery and as a result manipulations and surgical stress will be similar for all patients and b) abdominal walls are not manipulated at all during thyroidectomy and therefore postoperative measurement of exhaled NO will be easier and painless for patients.
* Patients will be randomized to one of two groups: one group with general anesthesia maintenance based on an intravenous agent (propofol) and a second group with general anesthesia maintenance based on an inhalational agent (sevoflurane).
* When patients arrive in the operating room, standard monitoring will be applied and exhaled NO will be measured immediately before induction with the NObreath® device ( Antus B, et al, 2010, Pisi R, et al, 2010) and a blood sample will be taken for eosinophil count measurement.
* During the patients' stay in the PACU and when Aldrete score is ≥8, exhaled NO will be measured again and a second blood sample will be taken. Exhaled NO will be measured again 24 hours postoperatively.
* The clinical implications of this study lie in the fact that it may provide further information on the effects of anesthetics (intravenous and inhalational) on the physiology and pathophysiology of the respiratory system. In addition, new evidence may come to light about the relationship between intravenous and inhalational agents and NO production.

Eligibility criteria: Inclusion Criteria:

* adult patients, American Society of Anesthesiologists (ASA) distribution I-III, scheduled for thyroidectomy

Exclusion Criteria:

* patients with history of airway hyperreactivity (asthma, bronchitis)
* patients with history of allergy

Primary outcomes:
measure: change of exhaled nitric oxide from preoperative status to immediate postoperative status
timeFrame: preoperatively, immediately postoperatively
Secondary outcomes:
measure: change of exhaled nitric oxide from preoperative status to 24 hours postoperatively
timeFrame: preoperatively, 24 hours postoperatively
measure: change of eosinophil blood count from preoperative status to immediate postoperative status
timeFrame: preoperatively, immediately postoperatively
Other outcomes:
Locations:
city: Athens
country: Greece
facility: Aretaieion University Hospital
Study officials:
affiliation: Aretaieion University Hospital
name: Kassiani Theodoraki, PhD, DEAA
role: PRINCIPAL_INVESTIGATOR
affiliation: Aretaieion University Hospital
name: Artemis Vekrakou, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Aretaieion University Hospital
name: Eriphylli Argyra, PhD
role: STUDY_CHAIR
References:
citation: Gaston B, Drazen JM, Loscalzo J, Stamler JS. The biology of nitrogen oxides in the airways. Am J Respir Crit Care Med. 1994 Feb;149(2 Pt 1):538-51. doi: 10.1164/ajrccm.149.2.7508323.
citation: Warke TJ, Fitch PS, Brown V, Taylor R, Lyons JD, Ennis M, Shields MD. Exhaled nitric oxide correlates with airway eosinophils in childhood asthma. Thorax. 2002 May;57(5):383-7. doi: 10.1136/thorax.57.5.383.
citation: Saraiva-Romanholo BM, Machado FS, Almeida FM, Nunes Mdo P, Martins MA, Vieira JE. Non-asthmatic patients show increased exhaled nitric oxide concentrations. Clinics (Sao Paulo). 2009;64(1):5-10. doi: 10.1590/s1807-59322009000100002.
citation: Gonzalez-Correa JA, Cruz-Andreotti E, Arrebola MM, Lopez-Villodres JA, Jodar M, De La Cruz JP. Effects of propofol on the leukocyte nitric oxide pathway: in vitro and ex vivo studies in surgical patients. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jan;376(5):331-9. doi: 10.1007/s00210-007-0220-4. Epub 2007 Dec 7.
citation: Chu CH, David Liu D, Hsu YH, Lee KC, Chen HI. Propofol exerts protective effects on the acute lung injury induced by endotoxin in rats. Pulm Pharmacol Ther. 2007;20(5):503-12. doi: 10.1016/j.pupt.2006.03.006. Epub 2006 Apr 21.
citation: Chen HI, Hsieh NK, Kao SJ, Su CF. Protective effects of propofol on acute lung injury induced by oleic acid in conscious rats. Crit Care Med. 2008 Apr;36(4):1214-21. doi: 10.1097/CCM.0b013e31816a0607.
citation: Krumholz W, Abdulle O, Knecht J, Hempelmann G. Effects of i.v. anaesthetic agents on the chemotaxis of eosinophils in vitro. Br J Anaesth. 1999 Aug;83(2):333-5. doi: 10.1093/bja/83.2.333.
citation: Antus B, Horvath I, Barta I. Assessment of exhaled nitric oxide by a new hand-held device. Respir Med. 2010 Sep;104(9):1377-80. doi: 10.1016/j.rmed.2010.06.005. Epub 2010 Jul 2.
citation: Pisi R, Aiello M, Tzani P, Marangio E, Olivieri D, Chetta A. Measurement of fractional exhaled nitric oxide by a new portable device: comparison with the standard technique. J Asthma. 2010 Sep;47(7):805-9. doi: 10.3109/02770903.2010.485667.