Autonomic Nervous System Modulation During Laparoscopic Prostatectomy

Intervention Affecting Autonomic Nervous System Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01927380
• Other study ID #: CE#371/2013
• Status: Completed
• Phase: N/A
• First received: August 15, 2013
• Last updated: November 3, 2014
• Start date: August 2013
• Est. completion date: March 2014

Study information

• Verified date: November 2014
• Source: Ospedale L. Sacco – Polo Universitario
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to measure the variations of autonomic nervous system (ANS) modulation directed to the heart and vessels induced by pneumoperitoneum and steep trendelenburg position.

Description:

The association of pneumoperitoneum and steep trendelenburg position, commonly used during laparoscopic radical prostatectomy, leads to significant changes in hemodynamics. Many studies found modifications of cardiac output, stroke work index, arterial pressure, central vein pressure and wedge pressure. Moreover, there are reports of severe bradycardia and cardiac arrest following pneumoperitoneum in association with steep trendelenburg. A vagal hypertone (induced by the combination of these two factors) or sympathetic hypractivity (elicited by pneumoperitoneum) had been alternatively postulated to cause these hemodynamic changes. To date there are not sufficient physiologic evidences of modification of ANS activity during steep trendelenburg position in association with pneumoperitoneum.

ANS modulation is studied non invasively by means of heart rate variability and baroreflex sensitivity. Beat-to-beat intervals are computed detecting the QRS complex on the ECG and locating the R-apex using parabolic interpolation. The maximum arterial pressure within each R-to-R interval is taken as systolic arterial pressure (SAP). Sequences of 300 values are randomly selected inside each experimental condition. The power spectrum is estimated according to a univariate parametric approach fitting the series to an autoregressive model. Autoregressive spectral density is factorized into components each of them characterized by a central frequency. A spectral component is labeled as LF if its central frequency is between 0.04 and 0.15 Hz, while it is classified as HF if its central frequency is between 0.15 and 0.4 Hz. The HF power of R-to-R series is utilized as a marker of vagal modulation directed to the heart , while the LF power of SAP series is utilized as a marker of sympathetic modulation directed to vessels. The ratio of the LF power to the HF power assessed from R-to-R series is taken as an indicator simpatho-vagal balance directed to the heart. Baroreflex control in the low frequencies is computed as the square root of the ratio of LF(RR) to LF(SAP). Similarly baroreflex control in the high frequencies is defined as the square root of the ratio of HF(RR) to HF(SAP).

The optic nerve sheet's diameter is assessed echographically after induction of general anesthesia and at the end of the surgery.

Management of general anesthesia is standardized:

• induction with propofol 1.5-2 mg/kg, Remifentanil Target Controlled Infusion (TCI) Ce 4 ng/ml , neuromuscolar blockade with cisatracurium 0.2 mg/kg.

• Maintenance: Sevoflurane 0.6-1.5 MAC (State Entropy target: 40-60); Remifentanil TCI (range Ce 3-15 ng/ml) (Surgical Pleth Index target: 20-50).

• mechanical ventilation at respiratory rate ≥14 breats/min, with tidal volume adjusted to maintain end-tidal carbon dioxide at 32-38 mmHg, and Pplateu <32 cmH2O.

Sample size:

to detect a difference in LF/HF ratio of 0.8 with a SD of 1.7, a power of 0.80 and type I error of 0.05, 37 patients are needed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• males scheduled for elective laparoscopic prostatectomy

• sinus rhythm at ECG

• ectopic heart beats <5% of all heart beats

• american society of anesthesiologists status 1-3

Exclusion Criteria:

• autonomic dysfunction (documented or suspected)

• adrenal or thyroid dysfunction

• organ dysfunction secondary to diabetes (i.e. nephropathy, retinopathy, neuropathy)

• history of stroke, traumatic spinal injury, heart surgery or major vascular surgery

• intracranial hypertension (documented or suspected)

• hydrocephalus

• cardiac functional status =NYHA IIb

• non sinusal heart rhythm

• ectopic heart beats =5% of normal heart beats

• therapy with beta-blockers or beta2-agonists

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Intervention Affecting Autonomic Nervous System

Intervention

Other:
• steep trendelenburg position with pneumoperitoneum
ANS activity and baroreflex modulation is assessed at (i) baseline; (ii) after induction of general anesthesia; (iii) after steep trendelenburg position (head down at 25 degrees); (iv) after induction of pneumoperitoneum and (v) after removal of trendelenburg and pneumoperitoneum

Locations

Country	Name	City	State
Italy	Azienda Ospedaliera "Luigi Sacco" - Polo Universitario - University of Milan	Milan

Sponsors (1)

Lead Sponsor	Collaborator
Ospedale L. Sacco – Polo Universitario

Country where clinical trial is conducted

Italy, 

References & Publications (13)

Amini A, Kariman H, Arhami Dolatabadi A, Hatamabadi HR, Derakhshanfar H, Mansouri B, Safari S, Eqtesadi R. Use of the sonographic diameter of optic nerve sheath to estimate intracranial pressure. Am J Emerg Med. 2013 Jan;31(1):236-9. doi: 10.1016/j.ajem.2012.06.025. Epub 2012 Aug 31. — View Citation

Awad H, Santilli S, Ohr M, Roth A, Yan W, Fernandez S, Roth S, Patel V. The effects of steep trendelenburg positioning on intraocular pressure during robotic radical prostatectomy. Anesth Analg. 2009 Aug;109(2):473-8. doi: 10.1213/ane.0b013e3181a9098f. — View Citation

Crystal GJ, Salem MR. The Bainbridge and the "reverse" Bainbridge reflexes: history, physiology, and clinical relevance. Anesth Analg. 2012 Mar;114(3):520-32. doi: 10.1213/ANE.0b013e3182312e21. Epub 2011 Sep 29. Review. — View Citation

Falabella A, Moore-Jeffries E, Sullivan MJ, Nelson R, Lew M. Cardiac function during steep Trendelenburg position and CO2 pneumoperitoneum for robotic-assisted prostatectomy: a trans-oesophageal Doppler probe study. Int J Med Robot. 2007 Dec;3(4):312-5. doi: 10.1002/rcs.165. — View Citation

Ficarra V, Novara G, Artibani W, Cestari A, Galfano A, Graefen M, Guazzoni G, Guillonneau B, Menon M, Montorsi F, Patel V, Rassweiler J, Van Poppel H. Retropubic, laparoscopic, and robot-assisted radical prostatectomy: a systematic review and cumulative analysis of comparative studies. Eur Urol. 2009 May;55(5):1037-63. doi: 10.1016/j.eururo.2009.01.036. Epub 2009 Jan 25. Review. — View Citation

Haas S, Haese A, Goetz AE, Kubitz JC. Haemodynamics and cardiac function during robotic-assisted laparoscopic prostatectomy in steep Trendelenburg position. Int J Med Robot. 2011 Dec;7(4):408-13. doi: 10.1002/rcs.410. Epub 2011 Aug 3. — View Citation

Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation. 1996 Mar 1;93(5):1043-65. — View Citation

Lestar M, Gunnarsson L, Lagerstrand L, Wiklund P, Odeberg-Wernerman S. Hemodynamic perturbations during robot-assisted laparoscopic radical prostatectomy in 45° Trendelenburg position. Anesth Analg. 2011 Nov;113(5):1069-75. doi: 10.1213/ANE.0b013e3182075d1f. Epub 2011 Jan 13. — View Citation

Montano N, Ruscone TG, Porta A, Lombardi F, Pagani M, Malliani A. Power spectrum analysis of heart rate variability to assess the changes in sympathovagal balance during graded orthostatic tilt. Circulation. 1994 Oct;90(4):1826-31. — View Citation

Pagani M, Lombardi F, Guzzetti S, Rimoldi O, Furlan R, Pizzinelli P, Sandrone G, Malfatto G, Dell'Orto S, Piccaluga E, et al. Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog. Circ Res. 1986 Aug;59(2):178-93. — View Citation

Pagani M, Montano N, Porta A, Malliani A, Abboud FM, Birkett C, Somers VK. Relationship between spectral components of cardiovascular variabilities and direct measures of muscle sympathetic nerve activity in humans. Circulation. 1997 Mar 18;95(6):1441-8. — View Citation

Park EY, Koo BN, Min KT, Nam SH. The effect of pneumoperitoneum in the steep Trendelenburg position on cerebral oxygenation. Acta Anaesthesiol Scand. 2009 Aug;53(7):895-9. doi: 10.1111/j.1399-6576.2009.01991.x. Epub 2009 May 6. — View Citation

Ray CA. Interaction of the vestibular system and baroreflexes on sympathetic nerve activity in humans. Am J Physiol Heart Circ Physiol. 2000 Nov;279(5):H2399-404. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	to measure changes of the optic nerve sheet's diameter during steep trendelenburg and pneumoperitoneum		day of surgery	Yes
Primary	To measure the changes of ANS modulation directed to the heart and to the vessels, and the changes of baroreflex control induced by steep trendelenburg position and pneumoperitoneum		Day of surgery	No
Secondary	To measure the correlation between ANS changes and hemodynamics		day of surgery	No