The analgesic efficiency of combined pregabalin and ketamine for total hip arthroplasty: a randomised, double-blind, controlled study.

Ketamine and pregabalin each provide postoperative analgesia, although the combination has yet to be evaluated. One hundred and forty-two patients undergoing total hip arthroplasty were randomly assigned to receive ketamine alone, pregabalin alone, ketamine and pregabalin combined, or placebo. Pain scores at rest and on movement, morphine consumption, side-effects, pressure pain thresholds and secondary hyperalgesia were evaluated. Mean (SD) total 48-h morphine use was reduced in patients given ketamine alone (52 (22) mg) and pregabalin alone (44 (20) mg) compared with placebo (77 (36) mg) p < 0.001. Morphine use was further reduced in patients given both ketamine and pregabalin (38 (19) mg) with an interaction between ketamine and pregabalin (ANOVA factorial; p = 0.028). Secondary hyperalgesia was reduced by ketamine. There were no differences between groups in pain scores after surgery, pressure pain thresholds or side-effects. The combination of pregabalin and ketamine has a small, beneficial clinical effect.

The comparative electrophysiologic and hemodynamic effects of a large dose of ropivacaine and bupivacaine in anesthetized and ventilated piglets.

UNLABELLED: Ropivacaine is less potent and less toxic than bupivacaine. We administered these two local anesthetics in a cardiac electrophysiologic model of sodium thiopental-anesthetized and ventilated piglets. After assessing the stability of the model, bupivacaine (4 mg/kg) and ropivacaine (6 mg/kg) were given IV in two groups (n = 7) of piglets. No alteration in biological variables was reported throughout the study. Bupivacaine and ropivacaine similarly decreased mean aortic pressure from 99 +/- 22 to 49 +/- 31 mm Hg and from 87 +/- 17 to 58 +/- 28 mm Hg, respectively, and decreased the peak of the first derivative of left ventricular pressure from 1979 +/- 95 to 689 +/- 482 mm Hg/s and from 1963 +/- 92 to 744 +/- 403 mm Hg/s, respectively. Left ventricular end-diastolic pressure was similarly increased from 6 +/- 5 to 9 +/- 5 mm Hg and from 6 +/- 4 to 12 +/- 4 mm Hg, respectively. Bupivacaine and ropivacaine similarly lengthened the cardiac cycle length (R-R; from 479 +/- 139 to 706 +/- 228 ms and from 451 +/- 87 to 666 +/- 194 ms, respectively), atria His (from 71 +/- 15 to 113 +/- 53 ms and from 64 +/- 6 to 86 +/- 10 ms, respectively), and QTc (QTc = QT x R-R(-0.5), Bazett formula; from 380 +/- 71 to 502 +/- 86 ms and from 361 +/- 33 to 440 +/- 56 ms, respectively) intervals. Bupivacaine altered to a greater extent the PQ (the onset of the P wave to the Q wave of the QRS complex) (from 97 +/- 20 to 211 +/- 60 ms versus from 91 +/- 8 to 145 +/- 38 ms, P < 0.05), QRS (from 58 +/- 3 to 149 +/- 34 ms versus from 60 +/- 5 to 101 +/- 17 ms, P < 0.05), and His ventricle interval (from 25 +/- 4 to 105 +/- 30 ms vs from 25 +/- 4 to 60 +/- 30 ms, P < 0.05) than ropivacaine. A 6 mg/kg ropivacaine dose induced similar hemodynamic alterations as 4 mg/kg bupivacaine. However, bupivacaine altered the variables of ventricular conduction (QRS and His ventricle) to a greater extent. IMPLICATIONS: A 6 mg/kg ropivacaine dose induced similar hemodynamic alterations as 4 mg/kg bupivacaine. However, bupivacaine altered the variables of ventricular conduction (QRS and His ventricle) to a greater extent.

A comparison of ropivacaine and bupivacaine for cervical plexus block.

UNLABELLED: We compared bupivacaine 0.5% and ropivacaine 0.75% for cervical plexus block (CB). Forty patients scheduled for carotid artery surgery were allocated randomly to undergo superficial and deep CB with 30 mL of one of the two anesthetic solutions. We evaluated the onset of anesthetic block; the requirement for supplementation during the surgery; the patients' satisfaction; postoperative pain on a visual analog scale at 1, 2, and 3 h; and the use of paracetamol as a rescue analgesic medication. Arterial blood was sampled immediately and 1, 3, 5, 10, 15, 30, 45, and 60 min after CB for measurements of bupivacaine or ropivacaine concentrations. Patients in both groups had equivalent onset of CB, local infiltration with lidocaine during surgery, and satisfaction scores. In the Bupivacaine group, visual analog scale scores were lower at 2 and 3 h, and the delay before paracetamol administration was prolonged. Observed peak concentrations were larger in the Ropivacaine group (4.25 [2.07-6.59 mg/L] vs 3.02 [0.98-5.82 mg/L]), but time to reach peak concentrations was comparable (5 [1-15 min] vs 5 [0-45 min] in the Ropivacaine and Bupivacaine groups, respectively). We conclude that ropivacaine has no advantage over bupivacaine for CB. IMPLICATIONS: Compared with bupivacaine (150 mg), a larger dose of ropivacaine (225 mg) produces comparable features of cervical plexus block but less postoperative analgesia and larger plasma concentrations. There is no reason to favor ropivacaine in such a case.

Relationship between clinical history, coagulation tests, and perioperative bleeding during tonsillectomies in pediatrics.

STUDY OBJECTIVE: To determine the value of clinical history and preoperative coagulation tests. DESIGN: Prospective, multicenter clinical investigation. SETTING: Twenty-four centers over a one-year period. PATIENTS: 1,706 children scheduled for tonsillectomy. In 1, 479 out of 1,706 children, studied age was ranged from 9 months to 15 years. Indications for surgery were tonsillar infection 54%, sleep apnea 33%, or both 13%. Surgical dissection was performed in 1, 284 cases (88%) and sluder technique in 172 cases (12%). MEASUREMENTS AND MAIN RESULTS: Clinical history of bleeding, preoperative coagulation tests, and perioperative bleeding were recorded. Clinical history of bleeding was positive in 13 patients; clinical history cannot predict abnormal coagulation tests. Coagulation tests were abnormal in 57 children (4%). Only 8 patients had disease-induced bleeding; five children had a preoperative correction of the deficiency in factor of coagulation or received desmopressin acetate prior to surgery in the case of von Willebrand's disease. Bleeding that occurred during the intraoperative period was assessed as abnormal by the surgeon in 101 children (7%) and during the postoperative period in 50 children (3%). Univariate analysis showed a relationship between intraoperative bleeding and age (p < 0.001), sluder technique (p < 0. 001), and abnormal preoperative coagulation tests (p < 0.05). Multivariate analysis showed the probability that bleeding was linked to the center where the surgery took place, the technique used, i.e., sluder technique, and the child's age, i.e., the older children. CONCLUSIONS: Preoperative assessment based on the history of bleeding cannot predict abnormal laboratory tests. Neither the history of bleeding or laboratory tests can predict postoperative bleeding.

Preemptive intravenous morphine-6-glucuronide is ineffective for postoperative pain relief.

BACKGROUND: Morphine-6-glucuronide (M-6-G), a major metabolite of morphine, is reported to be more potent than morphine when administered intrathecally; however, its efficiency remains under debate when administered intravenously. This study was designed to assess the analgesic efficiency of intravenous M-6-G for the treatment of acute postoperative pain. METHODS: After informed consent was obtained, 37 adults (American Society of Anesthesiologists physical status I-II) who were scheduled for elective open knee surgery were enrolled in the study. General anesthesia was induced with thiopental, alfentanil, and vecuronium and was maintained with a mixture of nitrous oxide/isoflurane and bolus doses of alfentanil. At skin closure, patients were randomized into three groups: (1) morphine group (n = 13), which received morphine 0.15 mg/kg; (2) M-6-G group (n = 12), which received M-6-G 0.1 mg/kg; and (3) placebo group (n = 12), which received saline. At the time of extubation, plasma concentration of morphine and M-6-G was measured. Postoperative analgesic efficiency was assessed by the cumulative dose of morphine delivered by patient-controlled analgesia. Opioid-related side effects were also evaluated. RESULTS: No difference was noted in patient characteristics and opioid-related side effects. Morphine requirements (mean +/- SD) during the first 24 h in the M-6-G group (41+/-9 mg) and the placebo group (49+/-8 mg) were significantly greater (P<0.05) compared with the morphine group (29+/-8 mg). CONCLUSION: A single intravenous bolus dose of M-6-G was found to be ineffective in the treatment of acute postoperative pain. This might be related to the low permeability of the blood-brain barrier for M-6-G.

Is lidocaine-prilocaine cream (EMLA) always useful for venous puncture in preoperative autologous blood donation?

PURPOSE: The goal of the present study was to evaluate in adults the benefit of the Eutectic Mixture of Local Anesthetics (EMLA) for preoperative autologous blood donation. METHODS: Twenty-six adult patients requiring three blood samples were studied. The pain of venipuncture was assessed by the patient using a 100 mm Visual Analogue Scale (VAS) and a four-category Verbal Rating Scale (VRS). The first puncture was performed without anaesthesia, as a "reference puncture". The second and third punctures were performed with EMLA and placebo in a double-blind cross-over randomization. For statistical analysis, the patients were allocated to two groups according to the VAS scores of the reference puncture: (Group 1) VASref < 20 mm; (Group 2) VASref > or = 20 mm. RESULTS: For the whole 26 patients, the VAS and the VRS pain scores were lower for EMLA puncture than for both the placebo and reference punctures (P < 0.05). Twenty patients had a VASref < 20 mm and six patients a VASref > or = 20 mm. In Group 1, there was no difference between EMLA and placebo for both the VAS and VRS scores. In contrast, in Group 2, the VAS score was lower for EMLA than for both the placebo and the reference punctures (respectively 11 +/- 7.1, 28.9 +/- 7.9, 29.1 +/- 6.4; P < 0.01); the VRS score was also lower for EMLA puncture than for placebo puncture (P < 0.05). CONCLUSION: In adults requiring repeated venous punctures, pain from cannulation may be evaluated at the first puncture with a Visual Analogue Scale, thus indicating or not the need for EMLA.

Effect of interpleural administration of bupivacaine or lidocaine on pain and morphine requirement after esophagectomy with thoracotomy: a randomized, double-blind and controlled study.

The purpose of the present study was to investigate the efficacy of interpleural (IP) analgesia with bupivacaine or lidocaine after esophageal surgery and to measure the plasma concentrations of bupivacaine and lidocaine after intermittent IP administrations. Two IP catheters were inserted percutaneously in the seventh intercostal space during operation. Patients in the bupivacaine group (Gr B) received 1 mg/kg of 0.5% bupivacaine with epinephrine 1:200000 in 20 mL of saline 0.9%, patients in the lidocaine group (Gr L) received 3 mg/kg of 2% lidocaine with epinephrine in 20 mL of saline 0.9%, and patients in the placebo group (Gr P) received 20 mL of saline 0.9% every 4 h during 2 days. Pain was assessed by visual analog scale (VAS) every 4 h at rest (VASR), after a deep breath or cough (VASC), at the thoracotomy (VAST), and at the laparotomy (VASL). Morphine consumption using a patient-controlled analgesia (PCA) device was recorded. There was no significant difference in the mean VASR, VASC, and VASL scores among the three groups. VAST scores were significantly lower in Gr B at 12, 16, 28, and 32 h when compared with Gr P and Gr L (P < 0.05). There was no statistical difference in mean VAST between Gr L and Gr P. Total consumption of morphine was lower in Gr B than in Gr P and Gr L (41.2 +/- 13 mg vs 66.1 +/- 21 mg in Gr P (P < 0.02) and 75.5 +/- 27 mg in Gr L (P < 0.01)), but were similar in Gr L when compared with Gr P.(ABSTRACT TRUNCATED AT 250 WORDS)

Interpleural infusion of 2% lidocaine with 1:200,000 epinephrine for postthoracotomy analgesia.

The value of intrapleural analgesia after thoracotomy is still controversial. We investigated the pharmacokinetics of interpleural analgesia in 14 patients with and without thoracic drainage (Groups TD+ and TD-, respectively) to determine the safety of the technique. The infusion led to a high steady-state concentration (Css) of 5.91 +/- 2.46 mg/mL in Group TD-. We then performed a placebo-controlled double-blind study on 16 patients to evaluate the analgesic effects of an interpleural infusion of 2% lidocaine using intravenous patient-controlled analgesia (PCA) with morphine and a visual analog scale score (VAS). In both studies an initial bolus of 3 mg/kg of 2% lidocaine was followed by an infusion of 1 mg.kg-1.h-1 for 48 h. The VAS score was slightly reduced after the bolus (6.6 +/- 1.0 vs 8.7 +/- 0.3; P < 0.05 vs the placebo group) but the cumulative doses of morphine were similar in both groups. There was a slight, but not sustained, improvement in pulmonary function test. In conclusion, interpleural analgesia by continuous infusion of lidocaine is poor after thoracotomy and may lead to blood levels in the toxic range.

[Respiratory response to carbon dioxide after brachial plexus block with fentanyl and lidocaine]. / Réponse ventilatoire au dioxyde de carbonue après bloc axillaire avec fentanyl et lidocaïne.

Respiratory parameters, ventilatory response to carbon dioxide and quality of anaesthesia were studied in patients undergoing upper limb surgery under axillary blockade. Thirteen patients were randomly assigned to two groups, group A (n = 6), who were given 35 ml of 1.5% lidocaine with 1 in 200,000 of adrenaline, and group B (n = 7), who received 1 microgram.kg-1 of fentanyl with the same dose of lidocaine. Quality of the sympathetic, sensory and motor blocks were tested at 15 min (T1) and 45 min (T2) after the injection (T0). The other parameters measured at these three times, both with the patient in a half-sitting position breathing room air, and after a rebreathing test with CO2 through Read's circuit, were respiratory rate (FR), tidal volume (VT), minute ventilation (VE), and PetCO2. Fentanyl provided a better sensory and motor blockade at T1, without any difference in sympathetic blockade. The quality of the blocks was similar in both groups at T2. There were no significant differences in the respiratory parameters between the two groups. Moreover, there was no untoward effect due to fentanyl (nausea, pruritus). It is concluded that 1 microgram.kg-1 fentanyl added to a local anaesthetic solution may be useful, at least during the first hour of an axillary block, without any respiratory side-effects.

Effects of age on plasma protein binding of sufentanil.

The plasma protein binding of sufentanil has been studied in newborns, infants (0.5 +/- 0.3 yr), children (6.8 +/- 3.0 yr), and adults (39.5 +/- 9.0 yr). Binding of sufentanil was determined in vitro by equilibrium dialysis, and radioactive tritiated sufentanil was used for the determination of drug concentrations in plasma and buffer. The free fraction of sufentanil was significantly higher in the newborn (19.5 +/- 2.7%; P less than 0.01) than in the other age groups. The free fraction was also significantly higher in infants (11.5 +/- 3.2%; P less than 0.01) than in children (8.1 +/- 1.4%) or in adults (7.8 +/- 1.5%) but did not differ significantly between children and adults. The free fraction of sufentanil was strongly correlated with the alpha 1-acid glycoprotein plasma concentration (r = -0.73; P less than 0.001) whereas it was weakly correlated with albumin plasma concentration (r = -0.35; P less than 0.05). These data suggest that the lower concentration of alpha 1-acid glycoprotein in newborns and infants probably accounts for the decrease in protein binding of sufentanil in these age groups when compared with that in older children or adults. The increased free fraction in the neonate might contribute to the enhanced effects of lipophilic opioids in the neonate.

Efficacy of an epidural test dose in children anesthetized with halothane.

The effect of an intravenous (iv) injection of lidocaine with epinephrine was studied to determine if such a test dose would cause a reliably detectable increase in heart rate and systemic blood pressure in children anesthetized with halothane and nitrous oxide. The effect of the injection of atropine before the test dose on these parameters was also determined. Sixty-five children 1 month to 11 yr of age and weighing 3.9-35 kg were studied. The children were assigned to one of four groups, each of which was anesthetized with 1% halothane and 50% nitrous oxide. Group 1 (n = 20) received 10 micrograms/kg atropine followed 5 min later by an iv dose of 0.1 ml/kg 1% lidocaine with 1/200,000 epinephrine (0.5 micrograms/kg) to simulate an intravascularly administered epidural test dose. Group 2 (n = 21) was identical to group 1 but did not receive atropine prior to the simulated intravascular test dose. Groups 3 (n = 12) and 4 (n = 11) were identical to groups 1 and 2, but the simulated intravascular test dose did not contain epinephrine: group 3 received atropine prior to the test dose and group 4 did not. The simulated intravascular test dose increased heart rate in group 1 (with atropine) at each time period from 15 to 120 s, but only at 45 and 60 s in group 2 (without atropine). Following the iv test dose, 6 of 21 children in group 2 had an increase in heart rate of less than 10 beats/min, while only one child in group 1 had an increase in heart rate of less than 10 beats/min. Intravenous test doses that did not contain epinephrine (groups 3 and 4) had no effect on heart rate or blood pressure. Atropine, 10 micrograms/kg, improves the reliability of an epidural test dose in children anesthetized with halothane and nitrous oxide but does not ensure total reliability in detecting an intravascular injection.