Sufentanil Sublingual Tablet System: from rationale of use to clinical practice.

The control of post-operative pain in Italy and other western countries is still suboptimal. In recent years, the Sufentanil Sublingual Tablet System (SSTS; Zalviso; AcelRx Pharmaceuticals, Redwood City, CA, USA), which is designed for patient-controlled analgesia (PCA), has entered clinical practice. SSTS enables patients to manage moderate-to-severe acute pain during the first 72 postoperative hours directly in the hospital setting. However, the role of SSTS within the current framework of options for the management of post-operative pain needs to be better established. This paper presents the position on the use of SSTS of a multidisciplinary group of Italian Experts and provides protocols for the use of this device.

Effect site concentrations of remifentanil maintaining cardiovascular homeostasis in response to surgical stimuli during bispectral index guided propofol anestesia in seriously obese patients.

AIM: The aim of this prospective study was to determine the effect site concentrations of remifentanil maintaining cardiovascular homeostasis in response to surgical stimuli during bispectral index (BIS) guided propofol anesthesia in seriously obese patients. METHODS: Twenty-two patients, female/male 15/7, ASA physical status II - III, aged 29-69 years, body mass index (BMI) 54.5+/-12, undergoing major open bariatric surgery, were enrolled to receive a propofol-remifentanil total intravenous anesthesia. All patients were intubated by using a flexible fiberoptic bronchoscopic technique facilitated by a target controlled effect site concentration of remifentanil set at 2.5 ng/mL. After endotracheal intubation, anesthesia was started with a target controlled infusion of propofol initially set at 6 microg/mL, then adjusted to maintain a BIS value between 40 and 50. The mean effect site concentration of remifentanil was recorded at different intervals time during surgery: skin incision-opening of peritoneum (T1), bowel resection (T2), cholecystojejunal anastomosis (T3), ileojejunal anastomosis (T4), closing of peritoneum (T5). RESULTS: The mean plasma concentrations of propofol required to maintain a BIS value between 40 and 50 were 4+/-0.55, 3.8+/-0.64, 3.8+/- 0.63, 3.8+/-0.65 and 3.8+/-0.63 microg/mL at T1, T2, T3, T4 and T5 interval time, respectively. The mean values of remifentanil target effect site concentration were 5.2+/-1.3, 7.7+/-1.7, 9.1+/-1.8, 9.7+/- 2.2 and 9.9+/-2.5 ng/mL at T1, T2, T3, T4 and T5 interval time. CONCLUSIONS: This study suggests that tolerance to remifentanil infusion is profound and develops very rapidly in morbidly obese patients submitted to open bariatric surgery during BIS guided propofol anesthesia. The administration of opiates during anesthesia based on target-controlled infusion should include corrections for the development of tolerance.

Acute Pain Service and multimodal therapy for postsurgical pain control: evaluation of protocol efficacy.

AIM: The institution of a postoperative Acute Pain Control Service is mandatory to improve the control of pain induced by surgical injury. Treatment of postoperative pain may be achieved using a combination of analgesic agents and techniques, reducing the incidence of side effects owing to the lower doses of the individual drugs. In 1997 we established an Acute Pain Service (APS) at the San Raffaele Hospital in Milan. The aim of this study was to assess the efficacy and safety of our APS both in terms of treatment protocols and organisational issues. METHODS: In this prospective observational study we included 592 patients undergoing abdominal, gynecological, or orthopedic surgery with severe expected pain. According to general guidelines on pain treatment, the patients were assigned to different treatment protocols based on the kind of operation. All protocols were based on the multimodal therapy, with the association of nonsteroidal anti-inflammatory drugs (NSAIDS), opioids and regional anesthesia techniques. During the first 48 h of the postoperative period we recorded vital signs, level of pain and occurrence of any side effect. RESULTS: Our analgesic protocols proved to be effective and safe (low incidence of side effects) for every surgery. The incidence of postoperative nausea and vomiting was higher in patients receiving patient-controlled morphine than that with continuous epidural or nerve block. After lower abdominal surgery, pain at movement at 24 h was significantly lower in the epidural group than in the Patient Control Analgesia group. Nausea and vomiting, numbness and paresthesias at the lower limbs were higher in gynecological patients. A larger percentage of orthopedic patients in the epidural group reported numbness and paresthesias at the lower limbs in comparison with patients receiving continuous peripheral nerve block. CONCLUSION: In agreement with previous literature, this study confirmed that a multimodal approach to pain treatment provides an adequate control of postoperative pain, minimizing side effects.

Spinal block or total intravenous anaesthesia with propofol and remifentanil for gynaecological outpatient procedures.

BACKGROUND AND OBJECTIVE: The aim of this prospective, randomized study was to compare the preparation and discharge times, the side-effects and patient satisfaction after gynaecological outpatient procedures performed using either spinal block or total intravenous anaesthesia with propofol and remifentanil. METHODS: With Ethics Committee approval and written informed consent, 40 healthy females scheduled for hysteroscopic ablation of endometrial neoplasm were randomly allocated to receive either a spinal block with bupivacaine 0.5% hyperbaric solution 10 mg (n = 20) or total intravenous anaesthesia with propofol and remifentanil (n = 20). Preparation and discharge times, as well as occurrence of untoward events and anaesthesia-related costs, were recorded. RESULTS: The median (range) preparation time was 7 (7-10) min with general anaesthesia, and 11 (7-21) min with spinal block (P = 0.00005). No differences in discharge time from the postanaesthesia care unit and incidence of hypotension or bradycardia, or both, were reported between the two groups. Hospital discharge times were 156 (101-345) min after general anaesthesia and 296 (195-720) min after spinal anaesthesia (P = 0.0005). Acceptance of the anaesthesia technique was better after general (100%) than after spinal anaesthesia (75%) (P = 0.04). No differences in total costs were reported between spinal block ([symbol: see text] 155 ([symbol: see text] 117-[symbol: see text] 224)) and propofol-remifentanil general anaesthesia ([symbol: see text] 143 ([symbol: see text] 124-[symbol: see text] 203) (P = 0.125)). CONCLUSIONS: Accurate titration of short-acting intravenous anaesthetic drugs such as propofol and remifentanil results in shorter preparation times and earlier home discharge after outpatient gynaecological procedures compared with spinal anaesthesia with hyperbaric bupivacaine 10 mg, with better patient acceptance and no increased costs.

Implementing sevoflurane anesthesia with small doses opioid for upper abdominal surgery. Postoperative respiratory function after either remifentanil or fentanyl.

BACKGROUND: The aim of this prospective, randomized study was to compare the effects on intraoperative cardiovascular homeostasis, recovery profile and postoperative oxygen saturation after sevoflurane anesthesia with small doses of either remifentanil or fentanyl in combination with postoperative epidural analgesia. METHODS: With Ethical Committee approval and written patient consent, 30 ASA physical status I-II patients scheduled for elective upper abdominal surgery were randomly allocated to receive sevoflurane general anesthesia implemented with small doses of either remifentanil (n = 15) or fentanyl (n = 15), followed by postoperative epidural analgesia. Remifentanil group patients received a 1 mg kg-1 bolus infused during a 60 sec period followed by a 0.15 mg kg-1 min-1 infusion; while patients of Fentanyl group were given a 3 mg kg-1 initial dose followed by 50 mg boluses as requested (according to the time to peak effect of the two drugs, the initial dose was given 5 min before induction in Fentanyl group, and 1 min before induction in Remifentanil group). Postoperatively, oxygen saturation was continuously recorded and stored on a computer during the first 12 h after surgery. SpO2 decrease < 90% for more than one minute was considered as a minor respiratory complication. RESULTS: The median sevoflurane's MAC-hour was 2.7 (1.4 - 4.9) in patients receiving remifentanil infusion and 4.1 (2.2 - 5.7) in those patients receiving fentanyl during surgery (P = 0.005). However, no differences in the recovery times were observed between the two groups. Similar pain relief was reported during coughing in the two studied groups at discharge from the recovery area and during the following study period. No major respiratory complication was observed throughout the study. Oxygen therapy was required in three patients of Fentanyl group only 20% (P = 0.22); however, 11 patients in the same group (73%) showed at least one minor respiratory complication (SpO2 < 90% for more than 1 min), with a median of 1 (range 0 - 12) episode per patient, compared with no episode in Remifentanil group (P = 0.0005). CONCLUSIONS: Implementing sevoflurane anesthesia with very small remifentanil infusion provides a safe and effective hemodynamic control reducing sevoflurane consumption during the procedure, and produces less respiratory effects postoperatively as compared with intermittent bolus administration of fentanyl.

Small doses of remifentanil or sufentanil for blunting cardiovascular changes induced by tracheal intubation: a double-blind comparison.

BACKGROUND AND OBJECTIVE: To compare the effects on cardiovascular changes induced by tracheal intubation when small doses of either remifentanil or sufentanil are used in the presence of midazolam. METHODS: Thirty normotensive, ASA physical status I-II patients, receiving general anaesthesia for major abdominal surgery, received an intravenous midazolam premedication (0.05 mg kg-1) 10 min before induction. They were randomly allocated to receive in a double-blind fashion an intravenous bolus of either (a) remifentanil given as a bolus dose 1 microgram kg-1 (n = 15), or else (b) sufentanil 0.1 microgram kg-1 infused over 60 s (n = 15). In each instance this loading dose was followed by a continuous intravenous infusion (0.1 microgram kg-1 min-1 or 0.01 microgram kg-1 min-1 of remifentanil or sufentanil, respectively). General anaesthesia was induced with propofol (2 mg kg-1), followed by atracurium besilate (0.5 mg kg-1) to facilitate tracheal intubation. Following intubation, the lungs were mechanically ventilated with a 60% nitrous oxide in oxygen mixture and a 1% inspired sevoflurane. RESULTS: Arterial pressure and heart rate were recorded before induction of anaesthesia (baseline), immediately before intubation, immediately after tracheal intubation and every minute for the first five minutes thereafter. No differences in systolic and diastolic arterial pressures were observed between the two groups. At the end of the study period, systolic and diastolic pressures slightly decreased from preinduction values in both groups. Four patients in the remifentanil group (26%) and five patients in sufentanil group (33%) showed at least one systolic pressure value < 90 mmHg during the study period (P = not significant); however, the observed decreases in systolic pressure were transient and did not require treatment. Heart rate values were not affected by tracheal intubation in either group. CONCLUSIONS: In healthy normotensive patients without cardiovascular disease the use of a relatively small dose of either remifentanil or sufentanil after standard midazolam premedication results in a similar and clinically acceptable effectiveness in blunting the cardiovascular changes induced by tracheal intubation.

[Systemic analgesia after peripheral block]. / Analgesia sistemica dopo il blocco periferico.

Over the past few years, increasing emphasis has been placed on the need to improve the management of acute pain. Despite a growing trend in acute pain management, many difficulties are still present for the treatment of postoperative pain. Loco-regional techniques together with an effective pain management should accelerate rehabilitation, decrease risk of postoperative complications and speed return to normal activities. A multimodal approach should be used for a reduction of pharmacological side effects, improving pain reduction. The association between NSAIDs and opioids permits reduction of full dose opioids with better pain relief and less side effects. If NSAIDs are contraindicated, acetaminophen is an alternative, though considered by someone to be an NSAID It's action is believed to result from inhibition of prostaglandin synthesis within the central nervous system. It doesn't cause gastrointestinal ulceration or bleeding, but we have to note that large amounts may lead to hepatic necrosis. Newer NSAIDs (COX-2 inhibitors), affect mainly COX-2, and appear to be associated with less adverse effect. Rofecoxib showed a reduction of morphine consuming after spinal fusion and has been admitted by FDA for the treatment of post operative pain. Newer methods of pain relief, as patient controlled analgesia (PCA), can provide excellent and safe pain relief. When high-tech options such as PCA are used, patients need a management by an anesthesiologist-based acute pain service (APS), allowing a better pain relief with less side effects compared to patients supervised by less experienced medical staff.

A comparison of remifentanil and sufentanil as adjuvants during sevoflurane anesthesia with epidural analgesia for upper abdominal surgery: effects on postoperative recovery and respiratory function.

UNLABELLED: We compared the recovery profile and postoperative SpO(2) after the administration of general anesthesia with either sevoflurane-remifentanil or sevoflurane-sufentanil in 30 healthy patients undergoing upper abdominal surgery. They were randomly allocated to receive general anesthesia with sevoflurane and small doses of either remifentanil (n = 15) or sufentanil (n = 15), followed by postoperative epidural analgesia. The median sevoflurane minimum alveolar anesthetic concentration-hour was 2.3 (1.2-6.3) in group Remifentanil and 2.6 (1.4-5.2) in group Sufentanil (P: = 0.39), while the median consumption of remifentanil was 1.3 mg (0.7-3.4 mg) and sufentanil 0.09 mg (0.05-0.6 mg). Tracheal extubation required 10 min (6-18 min) with remifentanil and 14 min (8-24 min) with sufentanil (P: = 0.05); however, no differences in time to discharge from the recovery area were reported (24 min [12-75 min] with remifentanil and 30 min [12-135 min] with sufentanil; P: = 0. 35). From the first to seventh hour after surgery, SpO(2) was decreased more in the sufentanil than in the remifentanil group (P: = 0.001), and seven patients in the sufentanil group showed at least one episode with SpO(2) < or = 90% for more than 1 min (P: = 0.006) (median: 1 episode; range: 0-17 episodes; P: = 0.003). When added to sevoflurane, remifentanil is as effective as sufentanil during the intraoperative period, but provides shorter time to tracheal extubation and fewer effects on postoperative SpO(2) in the first 7 h after surgery. IMPLICATIONS: In this double-blinded study, we evaluated the effects of adding small infusions of either remifentanil or sufentanil to sevoflurane in combination with postoperative epidural analgesia for upper abdominal surgery. We demonstrated that remifentanil is as effective as sufentanil during the intraoperative period, but that it provides shorter time to extubation and fewer effects on postoperative SpO(2) in the first 7 h after surgery.

Combined sciatic-femoral nerve block with 0.75% ropivacaine: effects of adding a systemically inactive dose of fentanyl.

To evaluate the effects of adding low-dose fentanyl to 0.75% ropivacaine during peripheral nerve blocks, 30 ASA physical status I-II patients undergoing hallux valgus repair under combined sciatic-femoral nerve block were randomly allocated in a double-blind fashion to receive nerve block placement with 30 mL of either 0.75% ropivacaine alone (group: ropivacaine, n = 15) or 0.75% ropivacaine plus fentanyl 1 microg kg(-1) (group: ropivacaine-fentanyl, n = 15). A blinded observer recorded haemodynamic variables and sedation, as well as the time required to achieve surgical block and the first request for analgesia. Readiness to surgery required 10 min (5-20 min) with 0.75% ropivacaine and 10 min (3-20 min) with the ropivacaine-fentanyl mixture. No differences in the degree of sedation, peripheral oxygen saturation, and haemodynamic variables were observed between the two groups. The degree of pain measured at first analgesic request, and the consumption of postoperative analgesics, was similar in the two groups, while the mean time from block placement to the first request for pain medication was 13.7 h (25-75th percentiles: 11.8-14.5 h) in the ropivacaine group and 13.9 h (25-75th percentiles: 10.5-14.5 h) in the ropivacaine-fentanyl group (P = not significant). We conclude that adding fentanyl 1 microg kg(-1) to 0.75% ropivacaine did not provide clinically relevant advantages in terms of onset time, quality and duration of combined sciatic-femoral nerve block in patients undergoing elective hallux valgus repair.

Interscalene brachial plexus anesthesia with either 0.5% ropivacaine or 0.5% bupivacaine.

BACKGROUND: To compare intra- and postoperative clinical properties of interscalene brachial plexus block performed with either 0.5% ropivacaine or 0.5% bupivacaine. EXPERIMENTAL DESIGN: prospective, randomized, double-blind study. SETTING: in patient at the University Hospital, Department of Orthopedic Surgery. PATIENTS: 30 ASA physical status I-II patients scheduled for elective shoulder surgery. INTERVENTIONS: interscalene brachial plexus block was performed using the multiple injection technique and a nerve stimulator by injecting 20 ml of either 0.5% ropivacaine (n = 15) or 0.5% bupivacaine (n = 15). Postoperative analgesia consisted of 100 mg intravenous ketoprofen, if required. A blind observer evaluated hemodynamic variables as well as sensory and motor blocks from the end of injection to achieve a surgical anesthesia (readiness for surgery: loss of pinprick sensation from C4 to C7 with the inability to elevate the operated limb against gravity). The time lasting from block placement to first requirement for postoperative pain medication was also recorded. RESULTS: No differences in anthropometric parameters and hemodynamic variables were observed throughout the study, and no signs of central nervous system (CNS) and cardiovascular toxicity, or other untoward events were reported in any patients. Readiness for surgery was obtained after 28 +/- 15 min with 0.5% bupivacaine and 22 +/- 8 min after 0.5% ropivacaine (p = NS). No differences in postoperative pain relief was observed between the two groups (11.1 +/- 5 hrs after 0.5% ropivacaine and 10.9 +/- 3.9 hrs after 0.5% bupivacaine, respectively). CONCLUSIONS: This study confirmed that 0.5% ropivacaine has clinical properties similar to those of 0.5% bupivacaine, when used for interscalene brachial plexus block, providing similarly long duration in postoperative pain relief. Compared with bupivacaine, ropivacaine has the further advantage of a lower potential for central nervous system and cardiovascular toxicity.

Patient supplemented epidural analgesia after major abdominal surgery with bupivacaine/fentanyl or ropivacaine/fentanyl.

PURPOSE: To compare analgesic efficacy and occurrence of motor block and other side effects during patient supplemented epidural analgesia (PSEA) with either ropivacaine/fentanyl or bupivacaine/fentanyl mixtures. METHODS: In a prospective, randomized, double-blind study, 32 ASAI-III patients undergoing major abdominal surgery received an epidural catheter at the T8- T10, followed by integrated general epidural anesthesia. Postoperative epidural analgesia was provided using a patient controlled pump with either ropivacaine 0.2%/2 microg x ml(-1) fentanyl (group Ropivacaine, n = 16) or bupivacaine 0.125%/2 microg x ml(-1) fentanyl (group Bupivacaine, n = 16) [background infusion 4-6 ml x hr(-1), 1.5 ml Incremental Doses and 20 min lock out]. Verbal pain rating score, number of incremental doses, consumption of epidural analgesic solution and rescue analgesics, sedation (four-point scale), and pulse oximetry were recorded by a blind observer for 48 hr after surgery. RESULTS: No differences in pain relief, motor block, degree of sedation, pulse oximetry and other side effects were observed between the two groups. The number of incremental doses and the volume of analgesic solution infused epidurally were higher in patients receiving the bupivacaine/fentanyl mixture (10 [0-52] I.D. and 236 [204-340] ml) than in patients receiving the ropivacaine/fentanyl solution (5 [0-50] I.D. and 208 [148-260] ml) (P = 0.03 and P = 0.05, respectively). CONCLUSION: Using a ropivacaine 0.2%/2 microg x ml(-1) fentanyl mixture for patient supplemented epidural analgesia after major abdominal surgery provided similar successful pain relief as bupivacaine 0.125%/2 microg x ml(-1) fentanyl, but patients receiving bupivacaine/fentanyl requested more supplemental.

Clinical comparison of either small doses of fentanyl or remifentanil for blunting cardiovascular changes induced by tracheal intubation.

BACKGROUND: To compare in a prospective, randomized study the effects on cardiovascular changes after tracheal intubation produced by small doses of either remifentanil or fentanyl. METHODS: With Ethical Committee approval, after intravenous midazolam premedication (0.05 mg.kg-1), 30 normotensive, ASA physical status I-II patients, without cardiovascular or respiratory diseases, and with a Mallampati score < 2, were randomly allocated to receive an intravenous bolus of either 3 micrograms.kg-1 fentanyl (n = 15) or 1 microgram.kg-1 remifentanil (n = 15) infused over 60 sec and followed by a 0.15 microgram.kg-1.min-1 continuous intravenous infusion. General anesthesia was then induced with propofol (2 mg.kg-1), followed by atracurium besilate (0.5 mg.kg-1) to facilitate tracheal intubation. Following intubation, the lungs were ventilated mechanically using a 60% nitrous oxide in oxygen mixture with a 1% inspired fraction of sevoflurane. Arterial blood pressure and heart rate were recorded before anesthesia induction (baseline), one minute after induction of anesthesia, immediately after tracheal intubation and every minute for the first five minutes after intubation. RESULTS: Systolic arterial blood pressure values were significantly higher in the Fentanyl than in the Remifentanil group patients from 2 to 5 min after tracheal intubation (p < 0.01), while no differences were observed between the two groups in either diastolic arterial blood pressure or heart rate values. Four patients in the Remifentanil group (26%) but only one patient in the Fentanyl group (7%) showed systolic blood pressure values < 90 mmHg during the study period (p = not significant); however, the observed decreases in systolic arterial blood pressure values were transient and did not require treatment for any subject. CONCLUSION: We conclude that in healthy normotensive patients, the control of cardiovascular responses to tracheal intubation obtained with a 1 microgram.kg-1 loading dose of remifentanil is more effective than that provided by a 3 micrograms.kg-1 bolus of fentanyl, with the advantage of no risks for postoperative respiratory depression.