QT interval and QT dispersion during the induction of anesthesia and tracheal intubation: a comparison of remifentanil and fentanyl.

BACKGROUND: The aim of this paper was to determine if there were any significant differences between the effects of fentanyl delivered as a bolus or remifentanil delivered as a continuous infusion on the QT interval and QT dispersion (QTD) during the induction of anesthesia and tracheal intubation. METHODS: This was a prospective, randomized and single blind study. A total of 50 ASA I-II patients scheduled to undergo elective minor abdominal surgery were divided into two groups. In the remifentanil group (N=25), patients received a continuous infusion (c.i.) of remifentanil (0.25 mcg/kg · min). In the fentanyl group (N=25), a bolus dose of fentanyl (2.0 mcg/kg) was administered. The QT interval, the difference between QTmax and QTmin (QTD), the heart rate-corrected QT (QTc) and the QT dispersion (QTcD) were calculated using a 12-lead computerized electrocardiogram (ECG). RESULTS: In both groups, there was no significant change in QT or QTc intervals during the study period. In the remifentanil group, a significant decrease in QTD and QTcD was observed during induction compared with baseline values (P<0.05). There was a significant increase in QTD at 1 min and in QTcD at 1 and 3 min after intubation in the fentanyl group (P<0.05). CONCLUSION: Both remifentanil and fentanyl did not prolong the QT interval. QTD decreased after the induction of anesthesia and did not increase after tracheal intubation in patients receiving c.i. remifentanil in comparison with fentanyl. Overall, remifentanil infusion may be the opioid-based treatment regimen of choice in patients at risk of dysrhythmias.

The effects of pneumoperitoneum and head-up position on heart rate variability and QT interval dispersion during laparoscopic cholecystectomy.

BACKGROUND: The aim of the study was to evaluate the effects of pneumoperitoneum and head-up position on autonomic cardiac function changes during inhalational or total intravenous anesthesia by using the analysis of QT dispersion and heart rate variability (HRV). METHODS: In this prospective, single-blind study, 30 patients scheduled for elective laparoscopic cholecystectomy were randomly divided in two groups: a sevoflurane-based inhalational anesthesia group (N=15) and an intravenous anesthesia group with propofol (N=15). Propofol 2.0 mg/kg-1 and cisatracurium 0.15 mg/kg-1 during induction of anesthesia and Remifentanil as titrated infusion for analgesia were used in both groups. Pneumoperitoneum was established at 12 mmHg with patients in the supine position. ECG was recorded before the induction of anesthesia; 1 and 3 min after pneumoperitoneum (supine position); 1 and 3 min after shifting the patient to a head-up position (HUP) of 60 degrees; after abdominal deflation; and after awakening. RR interval, QT interval, corrected QT interval (QTc), QT interval dispersion (QTD), corrected QT interval dispersion (QTcD), low-frequency power (LF), high-frequency power (HF) and LF/HF ratio were recorded. RESULTS: The LF/HF ratio increased significantly after 3 min HUP in the SEVO group (P<0.05). QTD and QTcD increased significantly at 3 min after abdominal insufflation and at 1 and 3 min after HUP in both groups (P<0.05). CONCLUSION: Statistically significant increases of QTD and QTcD occurred during pneumoperitoneum and HUP, regardless of the anesthetic techniques used. In patients receiving inhalational anesthesia, the LF/HF ratio increased significantly after HUP.

Remifentanil-TCI and propofol-TCI for conscious sedation during fibreoptic intubation in the acromegalic patient.

BACKGROUND AND OBJECTIVE: To evaluate the use of remifentanil-propofol administered as target-controlled infusion during awake fibreoptic intubation for anticipated difficult tracheal intubation in acromegalic patients. METHOD: In all, 20 consecutive acromegalic patients underwent elective endonasal endoscopic transsphenoidal pituitary surgery. After premedication with midazolam 0.03 mg kg(-1), initially a target-controlled infusion of remifentanil 1.0 ng mL(-1) and propofol 1.5 microg mL(-1) was started. The fibreoptic intubation was performed by the same physician experienced with the fibreoptic technique. During the fibreoptic procedure the target concentrations of remifentanil and propofol ranged between 1.0 and 5.0 ng mL(-1), and between 1.5 and 3.5 microg mL(-1), respectively. Changes in heart rate and mean arterial pressure were recorded during airway manipulation, during tracheal intubation, and at 1 and 3 min after. On the first postoperative day, patient recall and level of discomfort during fibreoptic intubation were evaluated. RESULTS: Endotracheal intubation was efficaciously and quickly secured in all patients. A significant increase in mean arterial pressure and heart rate was recorded only during tracheal intubation (P < 0.05). Oxygenation was sufficient and no bradypnea or apnoea was recorded. All patients later described their anaesthetic experience as satisfactory. During fibreoptic intubation, remifentanil (ng mL(-1)) and propofol (microg mL(-1)) mean effect-site concentrations were 3.2 +/- 0.3 and 2.0 +/- 1.0, respectively. CONCLUSION: Remifentanil and propofol target-controlled infusion provided satisfactory conscious sedation allowing for successful oral fibreoptic intubation in acromegalic patients with no recall.

Clinical comparison of remifentanil-sevoflurane vs. remifentanil-propofol for endoscopic endonasal transphenoidal surgery.

BACKGROUND: Endoscopic endonasal transphenoidal surgery has been recently proposed as a minimally invasive procedure for the treatment of pituitary adenomas. The main objective of the anaesthesiologist is to induce sufficient haemodynamic control together with rapid recovery at the end of surgery. The aim of this study was to examine recovery profile, surgical operative conditions and haemodynamic differences using remifentanil infusion with either propofol target controlled infusion system or sevoflurane. METHOD: Forty-four adult patients were enrolled in a prospective, randomized, single-blind, two-group study: Group P received propofol target controlled infusion system and remifentanil; Group S received sevoflurane and remifentanil for maintenance of anaesthesia. RESULTS: No statistically significant differences between the two groups with regards to the haemodynamic changes, operative conditions as assessed by a four-step bleeding score (0-3), were obtained. Recovery times were considerably shorter after remifentanil-sevoflurane in comparison with remifentanil-propofol target controlled infusion system group (7.4 vs. 12.8 min, P < 0.01). CONCLUSION: This study demonstrates that sevoflurane-remifentanil gives a faster recovery and equivalent intraoperative status compared with propofol target controlled infusion system with remifentanil for the endoscopic endonasal transphenoidal approach.

Non-invasive cardiac monitoring by aortic blood flow determination in patients undergoing hyperthermic intraperitoneal intraoperative chemotherapy.

AIM: The aim of this study was to evaluate the haemodynamic changes in patients undergoing cytoreductive surgery and intraperitoneal hyperthermic chemotherapy (IPHC) using an echo-Doppler device (Hemosonic 100). EXPERIMENTAL DESIGN: haemodynamic and cardiac function variables during IPHC, using a closed abdomen technique, were measured with the use of a non-invasive esophageal echo-Doppler monitor. SETTING: operating room in an oncologic surgery department in hospital. Fifteen patients, ASA II or III with age ranging from 59 to 66 years were successively studied. All patients were under general anaesthesia with sevoflurane, remifentanil as titrated infusion, and cisatracurium for muscle relaxation. The standard monitoring included ECG, capnometry, invasive measurement of blood pressure and central venous pressure, pulsoximetry, diuresis, esophageal and tympanic temperature. Haemodynamic changes evaluated by an echo-Doppler device were recorded at predetermined times. RESULTS: A significant reduction in stroke volume (SV) and aortic blood flow (ABF) values was recorded (P<0.05) during the abdominal cavity filling, followed by a significant increase in total systemic vascular resistance values (P<0.05). A significant increase in SV, ABF and left ventricular ejection time was recorded 90 min after the start of IPHC procedure (P<0.05) when the body temperature increased. Peak velocity and acceleration values increased significantly at the same time. CONCLUSIONS: These results suggest that the echo-Doppler device (Hemosonic 100) provided an easy-to-handle, non-invasive and reliable tool to monitor changes in cardiac parameters during IPHC.

Immediate postoperative pain management in patients undergoing major abdominal surgery after remifentanil-based anesthesia: sufentanil vs tramadol.

AIM: The transition from intraoperative analgesia to postoperative analgesia must be planned carefully after remifentanil-based anesthesia, due to the short duration of action of remifentanil. The aim of this study is to compare the efficacy and safety of 2 transition strategies using sufentanil or tramadol for early postoperative pain relief in patients who had major abdominal surgery under general anesthesia with remifentanil/sevoflurane. METHODS: Sixty patients participated in this double-blind, prospective study and were randomly assigned to either sufentanil (S) group or tramadol (T) group. Twenty minutes before the end of surgery the patients received either a bolus of 0.15 microg kg(-1) sufentanil (group S) or tramadol 100 mg (group T). Mean arterial pressure (MAP), heart rate (HR) and rate pressure product (RPP=systolic arterial pressure (SAP)xHR), analgesia by a verbal rating score (VRS) and sedation by a sedation score (SS) were evaluated at emergence from anesthesia. RESULTS: A statistically significant difference in HR between the 2 groups was recorded at extubation (78+/-13 in group S vs 86+/-24 in group T). A significant decrease of RPP values at extubation and 5 minutes later were found in group S in comparison with group T. VRS values were significantly lower in sufentanil group at 5 and 10 minutes after awakening. CONCLUSIONS: Sufentanil provided more effective transition analgesia in comparison with tramadol. The effects of remifentanil dissipated rapidly and analgesia with major opioids was required. A bolus dose of sufentanil 0.15 microg kg(-1) was efficacious in controlling the hemodynamic parameters at awakening from anesthesia. The lower HR values and, consequently the lower RPP values are of utmost importance especially in the aged cardiovascular risk patient.

Analgesic transition after remifentanil-based anesthesia in neurosurgery. A comparison of sufentanil and tramadol.

AIM: Transition from the end of remifentanil infusion and postoperative analgesia must be planned carefully owing to remifentanil's (R) rapid offset. Intraoperative morphine has been used for the transition to postoperative analgesia following remifentanil-based anesthesia. Sufentanil (S) is a very potent opioid with high micro-receptor affinity, a much wider therapeutic index and a lower fractional receptor occupancy. These pharmacological and dynamics features make sufentanil an interesting alternative to morphine for immediate postoperative analgesia. EXPERIMENTAL DESIGN: perspective, randomized, single blinded and comparative study. Institution: neurosurgical operating theatre at University. PATIENTS: 96 patients, aging from 25 to 67 years, ASA class I-III, undergoing neurosurgical operations, were studied. INTERVENTIONS AND MEASUREMENTS: the anesthetic management was: premedication: atropine 0.01 microg kg(-1) + remifentanil 0.20 microg kg(-1) min(-1); induction: propofol 2.0 microg kg(-1) + cisatracurium 0.15 microg kg(-1); maintenance: sevoflurane 0.8% + remifentanil (titrated infusion) cisatracurium. All patients received ketorolac 30 mg i.v. 1 hour before the end of surgery and ketorolac (60-90 mg) + tramadol (200-300 mg) by elastomeric pump; patients were divided into 2 groups: group T receiving tramadol 100 mg and group S receiving a bolus dose of sufentanil 0.10 microg kg(-1), 30 and 15 minutes before the end of surgery respectively. Recovery time, postoperative analgesia evaluated by VAS, cardiocirculatory parameters and side effects like nausea, vomiting, shivering, muscle rigidity, sedation and respiratory depression were recorded. RESULTS: VAS was significantly lower in Group S. Recovery time was shorter in Group T than in Group S (8.8 +/- 3.6 vs 11.6 +/- 4.6 min), no statistically significant differences between groups as regards nausea, vomiting and shivering. Short-lasting respiratory depression was detected in 3 cases in Group S. CONCLUSION: At the emergence much better control of the transition phase in patients treated with sufentanil: smooth recovery with better tolerability of the endotracheal tube; efficacious analgesia along with cardiocirculatory stability.

Remifentanil for intraoperative analgesia during the endoscopic surgical treatment of pituitary lesions.

AIM: The authors have evaluated remifentanil for intraoperative analgesia in endonasal endoscopic surgery for pituitary lesions. EXPERIMENTAL DESIGN: a perspective, randomized and comparative study between remifentanil and fentanyl for intraoperative analgesia was performed in an operating room of the neurosurgical department at University. Sixty patients of both sexes were studied and randomly divided into 2 groups. Patients were premedicated with fentanyl 0.15 microg.kg(-1) and atropine 0.01 microg.kg(-1) (group F) or with atro-pine and remifentanil 0.25 microg.kg(-1) min-1 (group R); induction was with propofol 2.0 microg.kg(-1) and maintenance with titrated infusion of propofol and for intraoperative analgesia, fentanyl as bolus injection of 1.0-1.5 microg.kg(-1) (group F) or a titrated infusion of remifentanil (group R). The following parameters were studied: MAP, HR, bleeding, awakening times, adverse effects and VAS. RESULTS: Much more stable hemodynamic parameters during surgery in patients treated with remifentanil; labetalol was administered in 10% of patients in group F; no significant differences as regards the adverse effects and VAS. Faster awakening time was obtained in the remifentanil group as compared with the fentanyl group. CONCLUSIONS: Remifentanil analgesia (mean dose of 0.37 microg.kg(-1).min-1) in patients undergoing endonasal endoscopic surgery of the sellar region provides a more efficacious cardiocirculatory control with reduced bleeding and faster psychosensorial recovery.

[Tracheal intubation in a case of idiopathic pulmonary fibrosis using remifentanil and propofol without muscle relaxants]. / Intubazione tracheale in un paziente con fibrosi polmonare idiopatica previa somministrazione di remifentanil e propofol senza l'uso di miorilassanti.

The anesthetic management of a 58 year-old-male suffering from idiopathic pulmonary fibrosis associated with a previous experience of altered dose-response relationship to muscle relaxants is reported. He underwent a gastroendoscopic surgical procedure. After intravenous atropine, remifentanil 3.0 microg kg(-1) was injected over 90 sec. Sixty seconds after the start of remifentanil bolus dose, propofol 2.0 mg kg(-1) was injected and intubation was performed 1 min after the administration of propofol. Anesthesia was maintained by N(2)O, oxygen, sevoflurane (0.5-0.8%) and remifentanil titrated infusion (mean dose of 0.15 mg kg(-1) min(-1)) under spontaneous respiration or assisted ventilation, if the patient was apnoic. The intubating conditions were good, a 30 per cent reduction in MAP was observed after propofol administration. The patient regained consciousness 5 minutes after the end of remifentanil administration and his trachea was extubated without any troubles. Recovery was uneventful without the need of long-term intensive therapy.

Rational use of opioids.

The role of analgesia and sedation in intensive care units (ICU) is ancillary to other intensive care strategies, nevertheless they permit that every other diagnostic and therapeutic procedure is safely performed by keeping the patient pain-free, anxiety-free and cooperative. Commonly used opioids in ICU include morphine, fentanyl, sufentanil and remifentanil. The choice among opioid drugs relies on their pharmacokinetics and their pharmacodynamic effects. Cardiovascular stability observed with fentanyl and sufentanil indicates their use in hemodynamically compromised patients. Short-acting remifentanil offers several advantages in patients requiring prolonged infusions. The organ-independent metabolism of this newer molecule may be valuable in patients with multiple organ failure. The main indications for opioid analgesia and sedation in ICU include: 1) Anxiety, pain and agitation: in turn, they can increase cardiac workload, myocardial oxygen consumption and rate of dysarrhythmias; 2) immediate postoperative period after major surgery; 3) short-term invasive procedures. Potential advantages offered by opioids in the ICU setting also include: a) Cardiac protection: in animal models, it has been observed that delta-opiate receptor stimulation confers a preconditioning-like protective effects against myocardial ischemia; b) Neuroprotection: recent studies suggest that mu- and kappa-opiate receptors are involved in ischemic preconditioning against seizures in the brain. During opioid therapy in the ICU, drug tolerance and withdrawal symptoms should be anticipated and the dose adjusted accordingly.

[Remifentanil in anesthesia and intensive care]. / Remifentanil: una realtà dall'anestesia alla terapia intensiva.

Remifentanil (R) is a novel short-acting mu-receptor opioid. R is in the same structural family as fentanyl and the other phenylpiperidines, but it differs from fentanyl because of its pharmacokinetic profile and its metabolism: R undergoes extrahepatic metabolism by blood and tissue nonspecific esterases. For these reasons the time required for decreases of any percentage plasmatic concentrations of R after termination of the infusion is independent of infusion duration. The pharmacokinetic profile of R is organ-independent and the dosing regimen must be regulated in elderly patients by reducing the bolus and infusion doses, and in obese subjects by calculating the intravenous dosages as a function of age and lean body mass. The placental transfer of R doesn't affect the newborn as recently described in literature but further and wider clinical experiences are needed for assessing the use of R in obstetric anesthesia. R causes either a reduction in the MAC of volatile anesthetics or a decrease in propofol requirements but it cannot be used as a sole anesthetic agent. R can be utilized to facilitate tracheal intubation without using muscle relaxants, to manage analgesia and sedation also in association with midazolam and/or propofol, furthermore as analgesic agent for monitored anesthesia care, for the critical patient in ICU and for the postoperative analgesia if a proper analgesic strategy had not been planned.

[Sufentanyl in balanced anesthesia for neurosurgery. Comparative study with fentanyl] . / Il sufentanil nell'anestesia bilanciata in neurochirurgia. Studio comparativo con il fentanyl.

BACKGROUND: The aim of this study was to evaluate the effects of sufentanil in comparison with those of fentanyl during balanced anesthesia in patients undergoing neurosurgery. EXPERIMENTAL DESIGN: prospective randomized study. SETTING: operating room in a neurosurgery University department. PATIENTS: 50 patients, ASA I and II with age ranging from 18 to 77 years were divided in two groups randomly. INTERVENTIONS: 25 patients received sufentanil as single bolus dose of 0.2 microgram/kg i.v. as premedication and supplemental bolus doses of 0.15 microgram/kg during the maintenance of anesthesia while the remainders received fentanyl 2.0 micrograms/kg as premedication and supplemental boluses of 1.5 micrograms/kg. All patients were induced with propofol 2.5 mg/kg, were intubated after cisatracurium 0.15 mg/kg for muscle relaxation, then were ventilated with sevoflurane and O2:N2O (1:1). MEASUREMENTS: heart rate, SAP, DAP and MAP were recorded at different times and ECG, ETCO2 and pulsoximetry were monitored continuously. Furthermore postoperative analgesia by VAS, recovery time and inspiratory concentrations of the volatile anesthetic were evaluated. Statistical analysis was carried out using ANOVA for repeated measures and Bonferroni "t"-test; a value of p < 0.05 was considered to be significant. RESULTS: Significant changes in MAP (at IOT and 1 and 2 min after IOT), in HR (at IOT) and in RPP (at IOT and 1, 2 and 3 min after IOT) were recorded in group F. Recovery time was shorter in group S than in group F and postoperative analgesia was more prolonged in group S. Inspiratory concentrations of volatile agent were lower in patients treated with sufentanil than in those treated with fentanyl. CONCLUSIONS: In patients treated with sufentanil a better cardiocirculatory stability was achieved with lower inspiratory concentrations of volatile agent and a well relaxed brain. Sufentanil can be considered a valid alternative to fentanyl as analgesic agent in balanced anesthesia for neurosurgery.

[The effects of remifentanil on hemodynamic response to intubation. A comparative study with fentanyl] . / Gli effetti del remifentanil sulla risposta emodinamica all'intubazione. Studio comparativo con il fentanyl.

BACKGROUND: The aim of this study was to evaluate the effects of remifentanil in comparison with those of fentanyl on the hemodynamic response to orotracheal intubation. EXPERIMENTAL DESIGN: prospective comparative and randomized study. SETTING: operating room in a neurosurgery department at University. PATIENTS: 50 patients, ASA I or II with age ranging from 32 to 64 years were divided in two groups randomly. INTERVENTIONS: 25 patients received fentanyl as single bolus dose of 2.0 micrograms/kg and atropine 0.01 mg/kg i.v. as premedication while the remainders received atropine 0.01 mg/kg i.v. and remifentanil 0.2 microgram/kg/min as infusion. All patients were induced with propofol 2.0 mg/kg and cisatracurium 0.15 mg/kg for muscle relaxation and were intubated 4 min after induction of anesthesia. MEASUREMENTS: Heart rate, SAP, DAP, MAP and RPP were recorded at different times: baseline, induction, intubation, 1, 2, 3 and 4 min after intubation; ECG and pulsoximetry were monitored continuously. Statistical analysis was carried out using ANOVA for repeated measures and Bonferroni t-test a value of p < 0.05 was considered to be significant. RESULTS: Significant increases in PAS were recorded, at intubation and at 1 min after in patients treated with fentanyl; in the remifentanil group significant decreases in SAP at induction and at 4 min after intubation were recorded. HR increased significantly at intubation and at 1, 2 and 3 min after in the fentanyl group. RPP showed a significant decrease at induction in the remifentanil group and significant increases at intubation and at 1, 2 and 3 min after in patients treated with fentanyl. CONCLUSION: In conclusion remifentanil was found to properly control the hemodynamic response to intubation in comparison with fentanyl.

Propofol in the anaesthetic management of percutaneous rhizolysis for trigeminal neuralgia.

BACKGROUND: To evaluate the efficacy of propofol as the sole anaesthetic agent for the anaesthetic management of the trigeminal rhizolysis. EXPERIMENTAL DESIGN: retrospective study. SETTING: operating room of the Neurosurgery Department at University. PATIENTS: 200 patients were studied, 115 males and 85 females, with mean age of 62.8 +/- 3.6 years, ASA status I, II or III and with various underlying medical problems. INTERVENTIONS: patients were premedicated with atropine 0.01 mg/kg i.v. 10 min before the induction of anaesthesia. The induction dose of P was titrated to the desired level in according to age and clinical conditions. After induction of anaesthesia the surgeon started the needle placement through the foramen ovale in the trigeminal cistern. MEASUREMENTS: during both procedures the mean dose of P, induction and recovery times, side effects and complications and quality of anaesthesia were assessed. Statistical analysis of the data was carried out using ANOVA for repeated measures and Bonferroni "t"-test and a value of p < 0.05 was considered to be significant. RESULTS: Anaesthesia was successfully induced after a mean dose of 1.9 mg/kg of P during PG and of 2.1 mg/kg during PR. A few side effects and short recovery time were recorded in all cases. P also provided an adequate cardiovascular stability during PG and PR. CONCLUSIONS: In conclusion, P can be considered suitable for this particular neurosurgical procedure requiring short period of anaesthesia and rapid recovery time in order to communicate with the neurosurgeon during the sensory testing.

Mivacurium in patients with intracranial pathology.

BACKGROUND: The aim of this study was to evaluate the effects of mivacurium on the cerebrospinal fluid pressure (CSFP) in patients requiring muscle relaxation to facilitate mechanical ventilation and on the intracranial pressure (ICP) in patients undergoing neurosurgery. EXPERIMENTAL DESIGN: prospective study. SETTING: ICU in a hospital and operating room in a neurosurgery department at University. PATIENTS: 12 patients, GCS 6-7, with a mean age of 62.6 +/- 6.2 were studied in ICU and 10 patients, ASA I-II, with a mean age of 58.6 +/- 6.4 were studied in the operating room. INTERVENTIONS: all patients received mivacurium as single bolus dose of 0.2 mg/kg i.v. MEASUREMENTS: Heart rate, SAP, DAP and MAP were recorded at different times. In ICU CSFP was measured via a catheter in lumbar subarachnoid space and in operating room ICP was measured via an intraventricular catheter. CPP was evaluated as the difference between MAP and ICP. Statistical analysis was carried out using ANOVA for repeated measures and Bonferroni "t"-test and a value of p < 0.05 was considered to be significant. RESULTS: Mivacurium was found not to influence or to increase ICP or CSFP. No significant changes in cardiocirculatory parameters were recorded in all patients. CONCLUSIONS: In conclusion, mivacurium can be considered a suitable and manageable neuromuscular blocking drug in the management of patients with intracranial pathology.

Hemodilution and revascularization for early treatment of stroke: an experimental trial.

A new experimental trial to investigate the usefulness of early therapeutic measures in case of acute I.V.D. has been performed, on the basis of a previous already reported experience. A combined treatment consisting of hemodilution and revascularization starting 16 hours after the onset of cerebral ischemia was tested. The study was performed in a population of 20 New Zealand male rabbits in which an acute cerebral ischemia was achieved by means of extracranial ligation of both common carotid artery and of one vertebral artery. The animals were divided into two groups. 1st group: no treatment; 2nd group: revascularization + hemodilution. Better results were observed in treated group considering either CBF rates or histological changes.

Beta-endorphin concentrations both in plasma and in cerebrospinal fluid in response to acute painful stimuli.

The beta-endorphin-like-immunoreactivity (beta-ELI) has been evaluated both in plasma and in cerebrospinal fluid (CSF) in 30 patients during trans-sphenoidal surgery. Blood and liquoral samples were collected in five conditions: (1) "reference", (2) "pain", (3) "analgesia", (4) "end", and (5) "24th hour". A significant rise of both plasma and liquoral beta-ELI levels (p less than 0.00001 and p less than 0.08, respectively) when compared to basal ones occurred following the painful stimulation due to the divarication of the nasal mucosa by speculum. A significant decrease (p less than 0.01) was noticed for plasma concentrations at the third sample followed by a new significant increase at the end of the operation, (p less than 0.05 when compared to the third sample and p less than 0.01 when compared to the reference sample). In CSF, beta-ELI levels decreased at the third sample (p less than 0.01 when compared to the painful levels) and at the end of surgery (p less than 0.01, p less than 0.01 and p less than 0.05 vs first, second and third samples, respectively). Twenty-four hours after surgery either plasma and liquoral beta-ELI levels decreased (p less than 0.05). The modifications of the opiatergic system after acute painful stimuli should be, hence, characterized by an early rise followed by a progressive decrease of beta-ELI concentrations. The increase of plasma beta-ELI levels, at the end of surgery, could be due to pituitary manipulation with massive release in the peripheral blood.