Effect of Pneumoperitoneum and Steep Trendelenburg on Autonomic Nervous System
Condition: Autonomic Nervous System
MeSH terms: Pneumoperitoneum
Study type: Interventional

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
    

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.
    

Intervention name(s): pneumoperitoneum insufflation and steep trendelenburg
Intervention type(s): Procedure
Intervention description(s): the sequence of pneumoperitoneum insufflation and steep trendelenburg positioning is randomized
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Primary purpose: Basic Science
Keywords: autonomic nervous system; heart rate variability; prostatectomy; steep trendelenburg; pneumoperitoneum; Intervention Affecting Autonomic Nervous System