Effect of Pneumoperitoneum and Steep Trendelenburg on Autonomic Nervous System

Autonomic Nervous System Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02315482
• Other study ID #: Prostate2
• Status: Completed
• Phase: N/A
• First received: November 24, 2014
• Last updated: June 23, 2015
• Start date: December 2014
• Est. completion date: June 2015

Study information

• Verified date: June 2015
• Source: Ospedale L. Sacco – Polo Universitario
• Contact: n/a
• Is FDA regulated: No
• Health authority: Etichs Comittee: Milan, Italy
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the different effects of pneumoperitoneum and steep trendelenburg position on autonomic nervous system modulation during laparoscopic prostatectomy

Description:

Laparoscopic radical prostatectomy is becoming a widely used surgical procedure because it carries some important advantages over open prostatectomy. This surgical technique requires positioning the patient at 25-40 degree head-down position (steep trendelenburg) for a prolonged time in association with pneumoperitoneum at 12-15 mmHg. The postural change from supine to head down position causes a hydrostatic fluid shift towards the head and the thorax, thus increasing venous return and stimulating the cardiopulmonary baroreceptors. 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 hyperactivity elicited by pneumoperitoneum insufflation have been alternatively advocated as a cause of such hemodynamic changes. However these speculations are little more than a narrative role because any evidence based demonstration is never been provided.

The aim of this study is to measure the variations of autonomic nervous system modulation induced by steep trendelenburg position at 25 degrees and pneumoperitoneum during laparoscopic radical prostatectomy.

Methods Patients are randomized into two groups. Group A: after induction of general anesthesia, in supine position a pneumoperitoneum is induced with carbon dioxide insufflation through a surgical inserted trocar into the abdominal cavity, then patients are positioned in steep trendelenburg at 25 degrees head down. Group B: after induction of general anesthesia, patients are positioned in steep trendelenburg position at 25 degrees head down, then a pneumoperitoneum is induced with carbon dioxide insufflation through a surgical inserted trocar into the abdominal cavity.

Autonomic nervous system modulation is assessed at four main time: (i) T1 baseline (before the induction of general anesthesia); (ii) T2, 5 min after the induction of general anesthesia, (iii) T3, pneumoperitoneum insufflation (Group A) or steep trendelenburg (Group B); (iv) T4, steep trendelenburg (Group A) or pneumoperitoneum insufflation (Group B).

Autonomic nervous system modulation is studied non invasively by means of heart rate variability (HRV) analysis through both linear and non linear methods. Beat-to-beat intervals are computed detecting the QRS complex on the electrocardiogram 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.

Linear HRV analysis 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 sympatho-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).

Non linear HRV analysis The symbolic analysis is conducted on the same sequences of 300 consecutive heart beats used for the autoregressive analysis. The whole range of the R-to-R interval into each series is uniformly divided in 6 slices (symbols) and pattern of 3 consecutive heart beat intervals are considered. Thus each sequence of 300 heart beats has its own R-to-R range and 298 consecutive triplets of symbols. The Shannon entropy of the distribution of the patterns is calculated to provide a quantification of the complexity of the pattern distribution. All triplets of symbols are grouped into 3 possible patterns of variation: (i) no variation (0V, all 3 symbols were equal), (ii) 1 variation (1V, 2 consequent symbols were equal and the remaining symbol was different), (iii) patterns with at least 2 variations (2V, all symbols were different from the previous one). Previously, the percentage of 0V patterns was found to increase (and 2V decrease) in response to sympathetic stimuli, whereas 2V patterns increased (and 0V decreased) in response to vagal stimuli.

Researcher who analyzes the HRV is blinded to the patient's group assignment.

Management of general anesthesia is standardized as follows:

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

Maintenance: Sevoflurane 0.6-1.5 minimum alveolar concentration (State Entropy target:

40-60); Remifentanil TCI (range Ce 3-15 ng/ml).

mechanical ventilation at respiratory rate ≥14 breaths/min, with tidal volume adjusted to maintain end-tidal carbon dioxide at 32-38 mmHg, and airway plateau pressure <32 cmH2O.

Sample size:

to detect a difference in mean HF(RR) between groups at the trendelenburg positioning of 40 msec^2 with a standard deviation of 50 msec^2 with a power of 0.80 and type I error of 0.05, 26 patients are needed for each group.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• males scheduled for elective laparoscopic prostatectomy

• sinus rhythm at electrocardiogram

• 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

• New York Heart Association cardiac functional status = IIb

• non sinusal heart rhythm

• ectopic heart beats =5% of normal heart beats

• therapy with beta-blockers or beta2-agonists

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Autonomic Nervous System
• Pneumoperitoneum

Intervention

Procedure:
• pneumoperitoneum insufflation and steep trendelenburg
the sequence of pneumoperitoneum insufflation and steep trendelenburg positioning is randomized

Locations

Country	Name	City	State
Italy	Luigi Sacco Hospital	Milan
Italy	Istituto Clinico Humanitas	Rozzano

Sponsors (6)

Lead Sponsor	Collaborator
Ospedale L. Sacco – Polo Universitario	Alberto Porta, Andrea Marchi, Ferdinando Raimondi, Stefano Guzzetti, Tommaso Fossali

Country where clinical trial is conducted

Italy, 

References & Publications (11)

Akselrod S, Gordon D, Ubel FA, Shannon DC, Berger AC, Cohen RJ. Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science. 1981 Jul 10;213(4504):220-2. — View Citation

Charkoudian N, Martin EA, Dinenno FA, Eisenach JH, Dietz NM, Joyner MJ. Influence of increased central venous pressure on baroreflex control of sympathetic activity in humans. Am J Physiol Heart Circ Physiol. 2004 Oct;287(4):H1658-62. Epub 2004 Jun 10. — View Citation

Deutschman CS, Harris AP, Fleisher LA. Changes in heart rate variability under propofol anesthesia: a possible explanation for propofol-induced bradycardia. Anesth Analg. 1994 Aug;79(2):373-7. — 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

Gainsburg DM, Wax D, Reich DL, Carlucci JR, Samadi DB. Intraoperative management of robotic-assisted versus open radical prostatectomy. JSLS. 2010 Jan-Mar;14(1):1-5. doi: 10.4293/108680810X12674612014266. — View Citation

Guzzetti S, Borroni E, Garbelli PE, Ceriani E, Della Bella P, Montano N, Cogliati C, Somers VK, Malliani A, Porta A. Symbolic dynamics of heart rate variability: a probe to investigate cardiac autonomic modulation. Circulation. 2005 Jul 26;112(4):465-70. Epub 2005 Jul 18. Erratum in: Circulation. 2005 Aug 30;112(9):e122. Mallani, Alberto [corrected to Malliani, Alberto]. — View Citation

Harrison MH, Rittenhouse D, Greenleaf JE. Effect of posture on arterial baroreflex control of heart rate in humans. Eur J Appl Physiol Occup Physiol. 1986;55(4):367-73. — 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

Hu JC, Gu X, Lipsitz SR, Barry MJ, D'Amico AV, Weinberg AC, Keating NL. Comparative effectiveness of minimally invasive vs open radical prostatectomy. JAMA. 2009 Oct 14;302(14):1557-64. doi: 10.1001/jama.2009.1451. — 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

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	changes of High Frequency and Low Frequency spectral heart rate power induced by pneumoperitoneum and steep trendelenburg	changes of autonomic nervous system activity independently elicited by (i) pneumoperitoneum and (ii) steep trendelenburg position. The High Frequency and Low Frequency spectral power of beat-to-beat heart intervals will be assessed with autoregressive analysis and expressed in msec^2	60 min	No
Secondary	changes of symbolic patterns induced by pneumoperitoneum and steep trendelenburg	changes of autonomic nervous system activity independently elicited by (i) pneumoperitoneum and (ii) steep trendelenburg position. The autonomic nervous activity will be analyzed by means of symbolic analysis of beat-to-beat heart intervals and expressed as percentage of triplets	60 min	No