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.

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.

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

Human males undergoing elective laparoscopic prostatectomy