Cardiac protection by volatile anesthetics in non-cardiac surgery? A meta-analysis of randomized controlled studies on clinically relevant endpoints.

INTRODUCTION: Volatile anesthetics improve post-ischemic recovery. A meta-analysis suggested that the cardioprotective properties of desflurane and sevoflurane could reduce mortality and cardiac morbidity in cardiac surgery. Recent American College of Cardiology / American Heart Association Guidelines recommended volatile anesthetic agents during non-cardiac surgery for the maintenance of general anesthesia in patients at risk for myocardial infarction but whether these cardioprotective properties exist in non-cardiac surgery settings is controversial. We therefore performed a meta-analysis of randomized studies to investigate this issue. METHODS: Two investigators independently searched PubMed. Inclusion criteria were random allocation to treatment, comparison of a total intravenous anesthesia regimen vs an anesthesia plan including desflurane or sevoflurane, performed on adult patients undergoing non-cardiac surgery. The primary endpoints were the incidence of perioperative myocardial infarction and death. RESULTS: A total of 6219 patients from 79 randomized trials were identified. No myocardial infarctions or deaths were reported in any of the studies we examined. CONCLUSIONS: This meta-analysis highlights a weakness in the literature and the results can be used to design future studies: the cardioprotective properties of desflurane and sevoflurane have never been studied in noncardiac surgery. No randomized study, among those which compared desflurane or sevoflurane to intravenous anesthetics, has addressed major outcomes such as myocardial infarction or mortality. Large, multicentre, randomized clinical trials including patients undergoing high-risk non-cardiac surgery and reporting clinically relevant outcomes such as myocardial infarction and mortality are needed.

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.

The effect of adding nitrous oxide on MAC of sevoflurane combined with two target-controlled concentrations of remifentanil in women.

BACKGROUND AND OBJECTIVE: The aim of this prospective, randomized, double-blind study was to determine the effects of adding nitrous oxide on sevoflurane requirement for blunting sympathetic responses after surgical incision combined with two different target-controlled concentrations of remifentanil (1 and 3 ng mL(-1)) in female. METHODS: 102 female patients, aged 20-50 yr, ASA I, undergoing general anaesthesia for elective abdominal surgery were enrolled and randomly allocated to receive sevoflurane anaesthesia alone (Group A, n=53), or with the addition of 60% nitrous oxide (Group N, n=49). Patients of both groups were further assigned to receive a target-controlled remifentanil infusion with an effect-site concentration of either 1 ng mL(-1) (Group N1, n=27; Group A1, n=30), or 3 ng mL(-1) (Group N3, n=22; Group A3, n=23). Sympathetic responses to surgical incision were determined after a 20-min period of stable end-tidal sevoflurane and target-controlled remifentanil concentrations. Predetermined end-tidal sevoflurane concentrations and minimum alveolar concentration (MAC) for each group were determined using an up-and-down sequential allocation technique. RESULTS: The MAC of sevoflurane was 3.96% (95% confidence interval, CI95: 3.69-4.23%) in Group A1 and 1.2% (CI95: 0.9-1.3%) in Group N1 (P < 0.01), while in Groups A3 and N3 the MAC of sevoflurane was 0.36% (CI95: 0.24-0.47%) and 0.18% (CI95: 0.1-0.3%), respectively (P < 0.05). CONCLUSION: Adding 60% nitrous oxide reduces the MAC of sevoflurane by 70% when using a remifentanil concentration of 1 ng mL(-1) and 50% when using a remifentanil concentration of 3 ng mL(-1).

0.2% ropivacaine with or without sufentanil for patient-controlled epidural analgesia after anterior cruciate ligament repair.

AIM: The aim of this prospective, randomized, double-blind study was to evaluate the effects of adding 0.5 microg/ml sufentanil to 0.2% ropivacaine for patient controlled epidural analgesia (PCEA) on the quality of postoperative pain control in patients undergoing anterior cruciate ligament (ACL) reconstruction. METHODS: Twenty ASA physical status I-II patients, scheduled to have elective ACL repair were studied. Combined spinal-epidural anesthesia was performed at the L3-L4 or L4-L5 interspace using a needle-through-needle technique. Spinal anesthesia was induced with 10 mg of 0.5% hyperbaric bupivacaine. Postoperative epidural analgesia was started at the end of surgery using a continuous epidural infusion of 0.2% ropivacaine alone (n=10) or 0.2% ropivacaine/0.5 mg mL(-1) sufentanil (n=10). The degree of pain was evaluated at 1, 8, 16, 24 and 48 hours after surgery; at the same observation times the degree of motor block, sedation, oxygen saturation, total consumption of PCEA solution and incremental doses given to the patient were also recorded. RESULTS: No differences in the quality of intraoperative anesthesia was observed, and in no case general anesthesia was required to complete surgery. Patients receiving the combination of ropivacaine and sufentanil showed lower levels of VAS from 16 hours after surgery as compared with ropivacaine group (P=0.02). However, no differences in the degree of pain were observed between the 2 groups during continuous passive mobilization. CONCLUSION: Adding 0.5 microg/ml sufentanil to 0.2% ropivacaine for patient controlled epidural analgesia improved pain control at rest but did not result in significant improvement of postoperative analgesia during continuous passive mobilization.

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.

Ropivacaine.

BACKGROUND: Ropivacaine is a relatively new long-acting local anesthetic. It is a pure S(-) isomer, with a high pKa and low lipid solubility. Because of its physical and chemical properties, ropivacaine produces a marked differential in sensory and motor blockades, with a toxic potential lower than other long-acting anesthetic solutions. The purpose of this paper was the evaluation of the literature concerning indications and advantages of ropivacaine for different regional anesthesia techniques. METHODS: We have evaluated results of prospective, randomized, controlled trials evaluating clinical use of ropivacaine for epidural anesthesia and analgesia, as well as spinal and peripheral nerve blocks. RESULTS: The literature clearly demonstrates both efficacy and safety of ropivacaine used for epidural anesthesia and analgesia as well as for upper and lower limb peripheral nerve blocks, both single-shot and continuous peripheral blocks. Although ropivacaine has not been registered yet for spinal anesthesia, various studies show its efficacy and safety also in this field. Because of its pharmacodynamic properties, intrathecal ropivacaine seems also interesting for outpatient procedures. CONCLUSIONS: Ropivacaine is a long-acting local anesthetic with a marked differential blockade between sensory and motor fibres, overall at the low concentrations used for postoperative analgesia. It probably has a slightly lower potency as compared with bupivacaine, but provides similar clinical efficacy in the different fields of regional anesthesia. Ropivacaine is less cardiotoxic and causes less central nervous system toxicity than bupivacaine, and this lower toxic potential has been reported not only with equivalent but also with equipotent concentrations and doses. For this reason, ropivacaine represents a useful alternative to bupivacaine for central and peripheral nerve blocks as well as for the management of postoperative pain relief.

[Levobupivacaine for peripheral blocks of the lower limb: a clinical comparison with bupivacaine and ropivacaine]. / Levobupivacaina per i blocchi periferici dell'arta inferiore: un confronto clinico con bupivacaina e ropivacaina.

BACKGROUND: The aim of this study was the comparison of clinical profile of sciatic nerve block performed with either 0,5% levobupivacaine, 0,5% bupivacaine, or 0,5% ropivacaine. METHODS: With ethical committee approval and written informed consent 45 ASA physical status I-II patients, undergoing elective hallux valgus repair received intravenous premedication with midazolam (0,05 mg/kg) followed by femoral nerve block with 15 ml of 2% mepivacaine. Then patients were randomly allocated to receive a sciatic nerve block with 20 ml of either 0,5% levobupivacaine (n=15), 0,5% bupivacaine (n=15), or 0,5% ropivacaine (n=15). An independent blind observer evaluated the onset time and duration of nerve block and postoperative analgesia. Postoperative analgesia consisted of 100 mg IV ketoprofen every 8 hours with the first administration at request. RESULTS: The onset time of sciatic nerve block was 15 (5-60) min with levobupivacaine, 30 (5-60) min with bupivacaine, and 15 (5-60) min with ropivacaine (P = NS). No differences in the quality of nerve block as well as in the nerve block resolution times were observed among the three groups. The duration of postoperative analgesia was 16 (8-24) hours with levobupivacaine, 14 (8-24) hours with bupivacaine, and 17 (8-24) hours with ropivacaine (P=NS). CONCLUSIONS: Using 0,5% levobupivacaine for sciatic nerve block results in similar clinical effects as those produced by using the same volume and concentration of either bupivacaine or ropivacaine.

[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.