Effect of Pneumoperitoneum and Steep Trendelenburg on Autonomic Nervous System

June 23, 2015 updated by: Riccardo Colombo, ASST Fatebenefratelli Sacco
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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Anticipated)

52

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milan, Italy, 20157
        • Luigi Sacco Hospital
      • Rozzano, Italy, 20089
        • Istituto Clinico Humanitas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group A
after induction of general anesthesia (i) a pneumoperitoneum is induced then (ii) patient is placed in steep trendelenburg position at 25 degrees head down
Procedure: pneumoperitoneum insufflation and steep trendelenburg
the sequence of pneumoperitoneum insufflation and steep trendelenburg positioning is randomized
Experimental: Group B
after induction of general anesthesia (i) the patient is placed in steep trendelenburg position at 25 degrees head down then (ii) a pneumoperitoneum is induced
Procedure: pneumoperitoneum insufflation and steep trendelenburg
the sequence of pneumoperitoneum insufflation and steep trendelenburg positioning is randomized

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
changes of High Frequency and Low Frequency spectral heart rate power induced by pneumoperitoneum and steep trendelenburg
Time Frame: 60 min
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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
changes of symbolic patterns induced by pneumoperitoneum and steep trendelenburg
Time Frame: 60 min
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ASST Fatebenefratelli Sacco

Collaborators

Andrea Marchi
Ferdinando Raimondi
Alberto Porta
Stefano Guzzetti
Tommaso Fossali

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2014

Primary Completion (Actual)

June 1, 2015

Study Completion (Actual)

June 1, 2015

Study Registration Dates

First Submitted

November 24, 2014

First Submitted That Met QC Criteria

December 8, 2014

First Posted (Estimate)

December 12, 2014

Study Record Updates

Last Update Posted (Estimate)

June 25, 2015

Last Update Submitted That Met QC Criteria

June 23, 2015

Last Verified

June 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Prostate2

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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