Pharmacokinetics of levobupivacaine 0.5% after superficial or combined (deep and superficial) cervical plexus block in patients undergoing minimally invasive parathyroidectomy.

STUDY OBJECTIVE: To evaluate the pharmacokinetic profile of 0.35 mL/kg of 0.5% levobupivacaine during superficial and combined (deep and superficial) cervical plexus block (CPB) in patients undergoing minimally invasive parathyroidectomy. DESIGN: Prospective randomized study. SETTING: Operating theater of a university hospital. PATIENTS: 12 ASA physical status II and III patients (11 women and 1 man), scheduled for minimally invasive parathyroidectomy. INTERVENTIONS: Seven and 5 patients were randomly assigned to receive either superficial or combined CPB, respectively. The superficial CPB was performed with an injection of 0.35 mL/kg of 0.5% levobupivacaine subcutaneously along the posterior border of the sternocleidomastoid muscle and deeper on its medial surface. The combined CPB was initiated by the deep block at the C3 level vertebra by injecting 0.2 mL/kg of 0.5% levobupivacaine, followed by the superficial block with an injection of the remaining 0.15 mL/kg. After completion of the block, venous blood was sampled at the intervals of 5, 10, 15, 20, 30, 45, and 60 minutes. MEASUREMENTS AND MAIN RESULTS: Venous plasma concentrations were measured using gas chromatography-mass spectroscopy. Mean +/- SD of maximal concentrations of levobupivacaine was 0.58 +/- 0.41 mg/L in group superficial and 0.52 +/- 0.28 mg/L in group combined (P = 0.71). The median (range) time required to reach the maximal concentrations was 30 minutes (20-30 min) in group superficial and 20 minutes (15-30 min) in group combined (P = 0.45). The areas under the drug concentration/time curve (AUC(10-60)) were also similar in both groups. No signs of central nervous system or cardiovascular toxicity or other untoward events were observed in any patient. CONCLUSION: With the given dose regimen, levobupivacaine plasma concentrations were within safe ranges.

Systemic hemodynamic effects of sequential pneumatic compression of the lower limbs: a prospective study in healthy volunteers.

STUDY OBJECTIVE: To evaluate the effects on systemic hemodynamics of sequential pneumatic compression of the lower limbs in healthy volunteers. DESIGN: Prospective, self-controlled, volunteer study. SETTING: University teaching hospital. PATIENTS: 11 healthy volunteers, aged 25 +/- 1.3 years. INTERVENTIONS AND MEASUREMENTS: After volunteers underwent a 6-hour period of fasting and 15 minutes of rest in the supine position, baseline systemic hemodynamics were assessed using transthoracic electrical bioimpedance. Peripheral venous pressure was measured using a 16-gauge intravenous cannula inserted in the forearm and connected to a pressure monitor. Then sequential pneumatic compression of the lower limbs was activated for a 30-minute period, and systemic hemodynamic measurements were repeated. In each volunteer, measurements were repeated twice in two consecutive days, and average values were calculated for each volunteer. MAIN RESULTS: After activation of sequential pneumatic compression of the lower limbs, mean arterial blood pressure increased from 90 mmHg (79-107 mmHg) to 95 mmHg (79-129 mmHg) (P = 0.02), whereas heart rate decreased from 79 bpm (51-94 bpm) to 75 bpm (53-90 bpm) (P = 0.02). This was associated with a significant increase in peripheral vascular resistance index (from 545 [440-1066] to 613 [369-1280] dynes s cm(-5) m(-2) [P = 0.013]) and reduction in cardiac index (from 3.4 [2.7- 4.5] to 3.2 [2.5-4.0] L/min per m2 [P = 0.034]). CONCLUSIONS: The application of sequential pneumatic compression to the lower limbs is associated with minor increases in mean arterial blood pressure, with moderate reduction of cardiac output and heart rate.

Pharmacology, toxicology, and clinical use of new long acting local anesthetics, ropivacaine and levobupivacaine.

Levobupivacaine and ropivacaine, two new long-acting local anesthetics, have been developed as an alternative to bupivacaine, after the evidence of its severe toxicity. Both of these agents are pure left-isomers and, due to their three-dimensional structure, seem to have less toxic effects on the central nervous system and on the cardiovascular system. Many clinical studies have investigated their toxicology and clinical profiles: theoretically and experimentally, some differences have been observed, but the effects of these properties on clinical practice have not been shown. By examining randomised, controlled trials that have compared these three local agents, this review supports the evidence that both levobupivacaine and ropivacaine have a clinical profile similar to that of racemic bupivacaine, and that the minimal differences reported between the three anesthetics are mainly related to the slightly different anesthetic potency, with racemic bupivacaine > levobupivacaine > ropivacaine. However, the reduced toxic potential of the two pure left-isomers suggests their use in the clinical situations in which the risk of systemic toxicity related to either overdosing or unintended intravascular injection is high, such as during epidural or peripheral nerve blocks.

Preoperative administration of controlled-release oxycodone as a transition opioid for total intravenous anaesthesia in pain control after laparoscopic cholecystectomy.

BACKGROUND: The complexity of pain from laparoscopic cholecystectomy and the need for treating incident pain provide rationale for multipharmacological analgesia. We investigated the preoperative administration of controlled-release (CR) oxycodone as transition opioid from remifentanil infusion for pain after laparoscopic cholecystectomy. METHODS: Fifty consecutive patients undergoing laparoscopic cholecystectomy were randomly, double-blindly assigned to treatment group (n=25, CR oxycodone: 1 h before surgery and 12 h after the first administration) or to the control group (n=25, placebo: administered at the same intervals). General anaesthesia was maintained with propofol and remifentanil target-controlled infusions (TCIs). All patients received ketorolac 30 mg i.v. Tramadol i.v. was administered for patient-controlled analgesia (PCA) postoperatively. Numerical rating scale for pain at rest and at movement (NRSr and NRSi), tramadol consumption, times to readiness to surgery and awakening, times to modified Aldrete's and modified Post-Anesthetic Discharge Scoring System (PADSS)>9 and side effects were evaluated. RESULTS: All NRSr and NRSi and tramadol consumption were significantly lower in the treatment group. The oxycodone group showed higher modified Aldrete's scores at each time and reached a PADSS>9 faster. Side effects and postoperative nausea and vomiting episodes were comparable. CONCLUSIONS: We demonstrated the success of a multipharmacological treatment including opioid premedication with CR oxycodone used as transition opioid for TCI remifentanil infusion; the treatment group showed lower pain scores and rescue analgesic consumption, shorter time to discharge from recovery room and from surgical ward, and the same incidence of side effects, comparably to controls.

Spinal anesthesia: an evergreen technique.

Spinal anesthesia is a simple technique that provides a deep and fast surgical block through the injection of small doses of local anesthetic solution into the subarachnoid space. The purpose of this review is to provide an overview on recent developments on local anesthetic drugs, side effects, and special techniques of intrathecal anesthesia. Spinal anesthesia can be considered adequately safe, and severe complications are reasonably rare. The cardiovascular effects associated with sympathetic block are more frequent, but successfully treated with volume expansion and administration of vasoactive drugs. It is clear that the total dose of local anesthetic injected into the subarachnoid space is the most important determinant of both therapeutic and unwanted effects of spinal anesthesia. Several studies have also demonstrated the efficacy and safety of using small doses of long acting agents, such as bupivacaine or ropivacaine, to produce an adequately short spinal block in outpatients. Levopivacaine, the pure S(-)-enantiomer of racemic bupivacaine showed a lower risk of cardiovascular and central nervous system (CNS) toxicity than bupivacaine. In the last years we have assisted important changes in the health care organization, with most of the surgical procedures performed on outpatients or on elderly patients with concomitant diseases. This forced us to change the indications and clinical use of intrathecal anesthesia techniques, which have been modified according to the changing needs of surgery. The development of new drugs and special techniques for spinal anesthesia will further improve the clinical use of this old but evergreen technique.

72-hour epidural infusion of 0.125% levobupivacaine following total knee replacement: a prospective, randomized, controlled, multicenter evaluation.

BACKGROUND AND AIM OF THE WORK: To evaluate the efficacy in terms of pain relief and degree of motor impairment of a continuous epidural infusion of 0.125% levobupivacaine in patients undergoing total knee replacement surgery. METHODS: 186 patients receiving effective epidural analgesia with 0.125% levobupivacaine during the first 24 hours after surgery were randomly allocated to receive postoperative analgesia for the following 48 hours consisting in either a continued epidural infusion of 0.125% levobupivacaine (Levobupivacaine group, n = 96), or IV PCA morphine only (Morphine PCA group, n = 90). An independent observer recorded the average amount of morphine required per hour following randomisation, pain intensity, degree of motor blockade and occurrence of side effects. RESULTS: Median (range) hourly morphine consumption during the study period was 0.21 (0.00-4.65) mg/hr in the Levobupivacaine group and 0.43 (0.04-4.65) mg/hr in the Morphine PCA group (P = 0.005). The quality of pain relief was adequate (VAS < 30 mm) in both groups, but patients in the Levobupivacaine group showed lower VAS values during motion than patients in the Morphine PCA group (P = 0.001). No differences in the proportion of patients with clinically relevant motor block (Bromage's score > or = 1) were reported between the two groups. CONCLUSIONS: Continuing the epidural infusion of a concentration of levobupivacaine as low as 0.125% improves pain relief with a 50% reduction of hourly morphine consumption after total knee replacement even during the second and third postoperative days, and does not result in a gross impairment of motor function.

Comparison of parecoxib and proparacetamol in endoscopic nasal surgery patients.

PURPOSE: The aim of the study was to compare the efficacy of parecoxib for postoperative analgesia after endoscopic turbinate and sinus surgery with the prodrug of acetaminophen, proparacetamol. MATERIALS AND METHODS: Fifty American Society of Anesthesiology (ASA) physical status I-II patients, receiving functional endoscopic sinus surgery (FESS) and endoscopic turbinectomy, were investigated in a prospective, randomized, double-blind manner. After local infiltration with 1% mepivacaine, patients were randomly allocated to receive intravenous (i.v.) administration of either 40 mg of parecoxib (n=25) or 2 g of proparacetamol (n=25) 15 min before discontinuation of total i.v. anaesthesia with propofol and remifentanil. A blinded observer recorded the incidence and severity of pain at admission to the post anaesthesia care unit (PACU) at 10, 20, and 30 min after PACU admission, and every 1 h thereafter for the first 6 postoperative h. RESULTS: The area under the curve of VAS (AUC(VAS)) calculated during the study period was 669 (28-1901) cm x min in the proparacetamol group and 635 (26-1413) cm x min in the parecoxib group (p=0.34). Rescue morphine analgesia was required by 14 patients (56%) in the proparacetamol group and 12 patients (48%) in the parecoxib (p >or= 0.05), while mean morphine consumption was 5-3.5mg and 5-2.0 mg in the proparacetamol groups and parecoxib, respectively (p >or= 0.05). No differences in the incidence of side effects were recorded between the 2 groups. Patient satisfaction was similarly high in both groups, and all patients were uneventfully discharged 24 h after surgery. CONCLUSION: In patients undergoing endoscopic nasal surgery, prior infiltration with local anaesthetics, parecoxib administered before discontinuing general anaesthetic, is not superior to proparacetamol in treating early postoperative pain.

Effects of using the posterior or anterior approaches to the lumbar plexus on the minimum effective anesthetic concentration (MEAC) of mepivacaine required to block the femoral nerve: a prospective, randomized, up-and-down study.

BACKGROUND AND OBJECTIVES: To evaluate if psoas compartment block requires a larger concentration of mepivacaine to block the femoral nerve than does an anterior 3-in-1 femoral nerve block. METHODS: Forty eight patients undergoing anterior cruciate ligament repair were randomly allocated to receive an anterior 3-in-1 femoral block (femoral group, n = 24) or a posterior psoas compartment block (psoas group, n = 24) with 30 mL of mepivacaine. The concentration of the injected solution was varied for consecutive patients using an up-and-down staircase method (initial concentration: 1%; up-and-down steps: 0.1%). RESULTS: The minimum effective anesthetic concentration of mepivacaine blocking the femoral nerve in 50% of cases (ED(50)) was 1.06% +/- 0.31% (95% confidence interval [CI], 0.45%-1.68%) in the femoral group and 1.03% +/- 0.21% (95% CI, 0.6%-1.45%) in the psoas group (P = .83). The lateral femoral cutaneous and obturator nerves were blocked in 4 (16%) and 5 (20%) femoral group patients as compared with 20 (83%) and 19 (80%) psoas group patients (P = .005 and P = .0005, respectively). Intraoperative analgesic supplementation was required by 15 (60%) and 5 (20%) patients in the femoral and psoas groups, respectively (P = .01). CONCLUSIONS: Using a posterior psoas compartment approach to the lumbar plexus does not increase the minimum effective anesthetic concentration of mepivacaine required to block the femoral nerve as compared with the anterior 3-in-1 approach, and provides better quality of intraoperative anesthesia due to the more reliable block of the lateral femoral cutaneous and obturator nerves.

A prospective, randomized comparison between combined (deep and superficial) and superficial cervical plexus block with levobupivacaine for minimally invasive parathyroidectomy.

BACKGROUND: Minimally invasive parathyroidectomy (MIP) can be performed under cervical plexus block (CPB). Superficial CPB has been reported to be easier to perform with similar efficacy and less anesthesia-related complications than combined deep and superficial CPB. In this study, we compared the efficacy of superficial and combined (deep and superficial) CPB in patients undergoing MIP. METHODS: Forty-two patients with primary hyperparathyroidism due to a solitary adenoma were randomized to receive either a superficial (group superficial, n = 20) or a combined deep and superficial CPB (group combined, n = 22) using 0.35 mL/kg of 0.5% levobupivacaine. The primary end-point was the amount of supplemental fentanyl required to complete surgery. RESULTS: There were no differences in onset of block, pain scores during surgery, or time to first analgesic request between groups. Fentanyl consumption was similar in both groups, i.e., 50 (0-200) microg in group superficial and 50 (0-100) microg in group combined (P = 0.60). Six patients [1 in group superficial (5%) and 5 in group combined (22.7%)] were converted to general anesthesia for surgically required bilateral neck dissection (P = 0.18). General anesthesia for block failure was reported in three superficial (15%) and two combined group patients (9%) (P = 0.99). In group combined, only one patient (4.5%) showed diaphragmatic paresis after the block (P = 0.99). CONCLUSION: Superficial CPB is an alternative to combined block for MIP.

Forehead reflectance oximetry: a clinical comparison with conventional digit sensors during laparotomic and laparoscopic abdominal surgery.

OBJECTIVE: This study compared the performance of forehead reflectance and conventional pulse oximetry (SpO(2)) in mechanically ventilated, anesthetized patients undergoing major abdominal surgery with either laparoscopic or laparotomic techniques. METHODS: SpO(2) was continuously measured both with a forehead reflectance and a conventional digit sensor in 20 ASA physical status I-III, anesthetized patients undergoing either a laparotomic (group Laparotomy, n = 10) or laparoscopic (group Laparoscopy, n = 10) major abdominal surgery. SpO(2) values measured with the two sensors were continuously recorded at 10-second intervals during the entire procedure, and then analyzed for consistency. RESULTS: In group Laparotomy finger and forehead readings remained consistently similar during the study period; on the contrary, in group Laparoscopy forehead SpO(2) readings showed a much wider variability. The mean (95% Confidence Intervals) difference between finger and forehead SpO(2) readings was 2.0% (-1.3% to +6.0%) in group Laparotomy and 2.5% (-3.5% to +8.4%) in group Laparoscopy (p = 0.001); however, in group Laparoscopy the mean difference between digit and forehead SpO(2) values increased from 0.2% (CI(95): -2.1% to +2.5%) during the first hour to 4.5% (CI(95): -2.5% to +11-5%) in the second hour (p = 0.0005), and 3.1% (CI(95): -2.4% to + 8.6%) in the third hour of surgery (p = 0.0005). Clinically relevant desaturation (decrease of SpO(2) < 89% for > or =30 s) detected with the forehead sensor in the Laparoscopy group was significantly more frequent and longer lasting than with conventional digit sensor. No differences were observed in group Laparotomy. CONCLUSIONS: Forehead reflectance oximetry is as accurate as conventional digit based oximetry in mechanically ventilated patients undergoing laparotomic surgery in the supine position, but is significantly influenced by patient positioning and pneumoperitoneum during laparoscopic surgery.

Minimum effective anesthetic concentration (MEAC) for sciatic nerve block: subgluteus and popliteal approaches.

BACKGROUND: We tested the hypothesis that using a subgluteus approach to the sciatic nerve requires a lower concentration of mepivacaine to obtain complete anesthesia as compared with the popliteal approach. METHODS: With midazolam premedication (0.05 mg kg(-1) iv), 48 patients undergoing hallux valgus repair were randomly allocated to receive a sciatic nerve block using either a posterior popliteal (group Popliteal, n = 24) or subgluteus (group Subgluteus, n = 24) approach with 30 mL of local anesthetic injected after elicitation of plantar flexion of the foot with a current

A prospective, randomized comparison between ultrasound and nerve stimulation guidance for multiple injection axillary brachial plexus block.

BACKGROUND: This prospective, randomized, blinded study tested the hypothesis that ultrasound guidance can shorten the onset time of axillary brachial plexus block as compared with nerve stimulation guidance when using a multiple injection technique. METHODS: Sixty American Society of Anesthesiology physical status I-III patients receiving axillary brachial plexus block with 20 ml ropivacaine, 0.75%, using a multiple injection technique, were randomly allocated to receive either nerve stimulation (group NS, n = 30), or ultrasound guidance (group US, n = 30) for nerve location. A blinded observer recorded the onset of sensory and motor blocks, the need for general anesthesia (failed block) or greater than 100 microg fentanyl (insufficient block) to complete surgery, procedure-related pain, success rate, and patient satisfaction. RESULTS: The median (range) number of needle passes was 4 (3-8) in group US and 8 (5-13) in group NS (P = 0.002). The onset of sensory block was shorter in group US (14 +/- 6 min) than in group NS (18 +/- 6 min) (P = 0.01), whereas no differences were observed in onset of motor block (24 +/- 8 min in group US and 25 +/- 8 min in group NS; P = 0.33) and readiness to surgery (26 +/- 8 min in group US and 28 +/- 9 min in group NS; P = 0.48). No failed block was reported in either group. Insufficient block was observed in 1 patient (3%) of group US and 2 patients (6%) of group NS (P = 0.61). Procedure-related pain was reported in 6 patients (20%) of group US and 14 patients (48%) of group NS (P = 0.028); patient acceptance was similarly good in the two groups. CONCLUSION: Multiple injection axillary block with ultrasound guidance provided similar success rates and comparable incidence of complication as compared with nerve stimulation guidance.

Spinal anesthesia with lidocaine or preservative-free 2-chlorprocaine for outpatient knee arthroscopy: a prospective, randomized, double-blind comparison.

BACKGROUND: In this prospective, randomized, double-blind study we tested the hypothesis that 50 mg of 1% preservative-free 2-chloroprocaine would provide a faster resolution of spinal block than the same dose of 1% plain lidocaine. METHODS: After IV midazolam premedication (0.03 mg/kg), 30 ASA physical status I-II outpatients undergoing knee arthroscopy were randomly allocated to receive 50 mg of either 1% plain lidocaine (n = 15) or 1% preservative-free plain chloroprocaine (n = 15). A blinded observer recorded the evolution of sensory (loss of pinprick sensation) and motor (modified Bromage scale) block until complete regression, as well as times to unassisted ambulation and voiding. A telephone call follow-up was performed 24 h and 7 days after surgery. RESULTS: Two chloroprocaine patients (13%) and one lidocaine patient (7%) required fentanyl supplementation (100 microg IV) (P = 0.99) intraoperatively, but no patient required general anesthesia to complete surgery. Median (range) times for recovery of sensory and motor function, and unassisted ambulation were faster with 2-chloroprocaine [95 (68-170) min; 60 (45-120) min; and 103 (70-191) min] than lidocaine [120 (80-175) min; 100 (60-140) min; and 152 (100-185) min] (P = 0.019, P = 0.0005, and P = 0.003, respectively). No differences in first voiding were reported between chloroprocaine [180 (100-354) min] and lidocaine patients [190 (148-340) min] (P = 0.191). Transient neurological symptoms were reported in five lidocaine patients (33%) but no chloroprocaine patients (0%) (P = 0.042). CONCLUSION: Intrathecal injection of 50 mg of preservative-free 2-chloroprocaine 1% resulted in quicker recovery of sensory/motor function, and unassisted ambulation, and fewer incidences of transient neurologic symptoms than the same dose of 1% lidocaine.

Clinical complications, monitoring and management of perioperative mild hypothermia: anesthesiological features.

BACKGROUND AND AIM OF THE WORK: Perioperative hypothermia is a frequent occurrence and can lead to several complications, which adversely affect the patient's outcome, expecially in high risk patient. Nonetheless, central temperature is not frequently monitored in the clinical routine. The aim of this work is to make the point on complications, monitoring techniques, prevention and treatment of mild perioperative hypothermia. METHODS: We reviewed literature on cardiovascular, haemorragic, infectious, and other clinical consequences of mild intraoperative hypothermia, epidemiology and techniques, of temperature monitoring and efficacy of different approaches for the prevention and treatment of mild hypothermia. RESULTS: Cardiovascular, haemorragic and infectious complications are significantly more frequent in hypothermic than in normothermic patients. Elderly and high risk patients are more prone to develop perioperative hypotherma, and are more liable to hypothermia-related complications. The ideal monitoring site has to be chosen considering both the patients characteristics and surgical procedure. Once identified, hypothermia has to be treated and the most effective systems are represented by active forced-air skin warming system. Active prewarming during the preoperative period has been also demonstrated to be efficient in reducing the development of intraoperative hypothermia. Humidification and warming of inspired gases, and warming of intravenous fluids are useful techniques when used in a multimodal approach with active skin warming to maintain perioperative normothermia. CONCLUSIONS: All the patient undergoing surgery for more than 30 minutes should receive an accurate temperature monitoring and a correct management for the maintenance of normothermia. Reducing the incidence and severity of perioperative hypothermia has the potential for drastically reducing complication-related costs.

Transcutaneous monitoring of partial pressure of carbon dioxide in the elderly patient: a prospective, clinical comparison with end-tidal monitoring.

STUDY OBJECTIVE: To evaluate the accuracy and precision of estimation of partial pressure of carbon dioxide (Pa(CO2)) using end-tidal or transcutaneous CO2 (TcP(CO2)) measurements during mechanical ventilation in the elderly patient. DESIGN: A prospective, observational study was conducted. SETTINGS: The study was done in the anesthesia department of a university hospital. PATIENTS: Seventeen anesthetized, mechanically ventilated patients older than 60 years were studied. INTERVENTIONS AND MEASUREMENTS: During standard sevoflurane anesthesia, and after proper calibration and an equilibration time of 30 minutes with stable hemodynamic and respiratory variables, arterial (Pa(CO2)), end-tidal (Pet(CO2)), and transcutaneous (TcP(CO2)) CO2 partial pressures were determined. In each patient, 1 to 5 sample sets (Pa(CO2), Pet(CO2), and TcP(CO2)) were obtained. MAIN RESULTS: A total of 45 sample sets were obtained from the patients studied. The Pa(CO2) values ranged between 21 and 58 mm Hg. The Pa(CO2) - Pet(CO2) tension gradient was 6 +/- 5 mmHg (95% confidence interval, -3 to 16 mmHg), whereas the Pa(CO2) - TcP(CO2) tension gradient was 2 +/- 4 mmHg (95% confidence interval, -6 to 9 mmHg) (P = 0.0005). The absolute value of the difference between Pa(CO2) and Pet(CO2) was 3 mm Hg or less in 7 of 45 sample sets (15%), whereas the absolute value of the difference between Pa(CO2) and TcP(CO2) was 3 mm Hg or less in 21 of 45 sample sets (46%) (P = 0.003). Linear regression analysis for TcP(CO2) versus Pa(CO2) showed a slope of 0.84 (r(2) = 0.73), whereas the linear regression analysis for Pet(CO2) versus Pa(CO2) showed a slope of 0.54 (r(2) = 0.50). CONCLUSION: Transcutaneous monitoring of CO(2) partial pressure gives a more accurate estimation of arterial CO(2) partial pressure than does Pet(CO2) monitoring.

Synthesis and cytotoxic activity of polyamine analogues of camptothecin.

A number of derivatives of camptothecin with a polyamine chain linked to position 7 of camptothecin via an amino, imino, or oxyiminomethyl group were synthesized and tested for their biological activity. All compounds showed marked growth inhibitory activity against the H460 human lung carcinoma cell line. In particular, the iminomethyl derivatives where the amino groups of the chain were protected with Boc groups exhibited a high potency, with IC50 values of approximately 10(-8) M. The pattern of DNA cleavage in vitro and the persistence of the cleavable ternary complex drug-DNA-topoisomerase I observed with polyamine conjugates containing free amino groups support a contribution of specific drug interaction with DNA as a determinant of activity. Modeling of compound 7c in the complex with topoisomerase 1 and DNA is consistent with this hypothesis. The lack of a specific correlation between stabilization of the cleavable complex and growth inhibition likely reflects multiple factors including the cellular pharmacokinetic behavior related to the variable lipophilicity of the conjugate, and the nature and linkage of the polyamine moiety.

Early increases in cardiac troponin levels after major vascular surgery is associated with an increased frequency of delayed cardiac complications.

OBJECTIVE: To evaluate changes in cardiac troponin-I levels after major vascular surgery and their association with early and late postoperative cardiac complications. DESIGN: Prospective, observational investigation. SETTING: University teaching hospital. PATIENTS: 75 consecutive patients undergoing major vascular surgery. INTERVENTIONS: All patients received a standard sevoflurane-fentanyl anesthesia during the procedure. Blood levels of creatine kinase with MB subtype and cardiac troponin-I were assessed before surgery and then everyday for the first 3 days after surgery. At the same time, 12-lead electrocardiography was also performed, and occurrence of any cardiac adverse event was recorded. Patients were then followed up for 1 month after surgery. MEASUREMENT AND MAIN RESULTS: Troponin-I levels increased in 25 patients (33%) during the first 3 days after surgery; 9 of these patients (12%) had myocardial infarction. At univariate analysis, uncontrolled hypertension was the only risk factor for perioperative infarction (odds ratio, 16; (95% confidence interval, 3-74); however, multivariate logistic regression analysis failed to show statistically significant associations. Increases in troponin-I had a 100% sensitivity and 75% specificity in detecting myocardial ischemia with a 36% positive and 100% negative predictive values. Severe cardiac complication 1 month after surgery was reported in 5 patients (6.6%). The increase of cardiac troponin-I levels during the first 3 postoperative days was associated with an increased frequency of major cardiac complication at 1-month follow-up (P = 0.003), with a 100% sensitivity, 71% specificity, and 100% negative predictive value. CONCLUSIONS: Myocardial infarction after major noncardiac vascular surgery occurs in up to 12% of cases. Perioperative monitoring of troponin-I plasma levels may help to identify patients at increased risk for cardiac morbidity not only early after surgery but also during the first postoperative month.

Intrathecal 2-chloroprocaine for lower limb outpatient surgery: a prospective, randomized, double-blind, clinical evaluation.

We evaluated the dose-response relationship of 2-chloroprocaine for lower limb outpatient procedure in 45 ASA physical status I-II outpatients undergoing elective lower limb surgery under spinal anesthesia, with 30 mg (group Chlor-30, n = 15), 40 mg (group Chlor-40, n = 15), or 50 mg (group Chlor-50, n = 15) of 1% preservative free 2-chloroprocaine. Onset time was similar in the three groups. General anesthesia was never required to complete surgery. Intraoperative analgesic supplementation as a result of insufficient duration of spinal block was required in 5 patients of group Chlor-30 (35%) and 2 patients of group Chlor-40 (13%) (P = 0.014), with a median (range) time for supplementation request of 40 (30-60) min. Spinal block resolution and recovery of ambulation were faster in group Chlor-30 (60 [41-98] min and 85 [45-123] min) than in groups Chlor-40 (85 [46-141] min and 180 [72-281] min) and Chlor-50 (97 [60-169] min and 185 [90-355] min) (P = 0.001 and P = 0.003, respectively), with no differences in home discharge time (182 [120-267] min in group Chlor-30, 198 [123-271] min in group Chlor-40, and 203 [102-394] min in group Chlor-50; P = 0.155). No transient neurologic symptoms were reported at 24-h and 7-day follow-up. We conclude that although 40 and 50 mg of 2-chloroprocaine provide adequate spinal anesthesia for outpatient procedures lasting 45-60 min, 30 mg produces a spinal block of insufficient duration.