Randomized controlled trial of patient-controlled epidural analgesia after orthopaedic surgery with sufentanil and ropivacaine 0.165% or levobupivacaine 0.125%

BACKGROUND: Ropivacaine, and to a lesser extent also levobupivacaine, is commonly used for postoperative epidural analgesia. Despite ED50 data suggesting a potency difference between these drugs, clinically they can be difficult to distinguish. As a consequence, it is unclear which concentration of each drug to use when comparing them for long-term analgesia. METHODS: One hundred patients undergoing total hip or knee replacement were selected to participate in a double-blind randomized study comparing ropivacaine 0.165% with levobupivacaine 0.125% to which was added sufentanil 1 microg ml(-1) for postoperative analgesia by the epidural route. Patient-controlled epidural analgesia (PCEA) was offered for 48 h. After the first 24 h, the basal infusion was omitted. RESULTS: Pain scores both at rest and on mobilization were similar between both groups. The volume of local anaesthetic solution consumed during the first 48 h after surgery was 25% higher in those patients receiving ropivacaine (P=0.02). Patients receiving ropivacaine made a mean (SD) of 38.5 (16) PCEA demands in the first 48 h after surgery compared with 28 (13) in the levobupivacaine group (P=0.04). CONCLUSIONS: Both local anaesthetics provided effective postoperative analgesia but, even in a 25% weaker concentration, a small volume of levobupivacaine and opiate substance was consumed. These differences may be explained by a potency difference or by the duration of action of levobupivacaine.     

Pre-incisional epidural ropivacaine, sufentanil, clonidine, and (S)+-ketamine does not provide pre-emptive analgesia in patients undergoing major pancreatic surgery

BACKGROUND: The concept of pre-emptive analgesia remains controversial. This prospective, randomized, and double-blind study compared epidural administration of ropivacaine 2 mg ml(-1), sufentanil 0.5 microg ml(-1), clonidine 3 microg ml(-1), and S(+)-ketamine 0.25 mg ml(-1) (study solution) given before incision with the same combination started at the end of the operation. METHODS: After testing the stability of the solution using high performance liquid chromatography (HPLC) and examining 12 patients for possible side-effects in comparison with the epidural infusion of ropivacaine 2 mg ml(-1) and sufentanil 0.5 microg ml(-1), 30 patients undergoing major pancreatic surgery were recruited into the study. Before induction of anaesthesia, an epidural catheter was inserted (TH6-8). Patients in Group 1 received a bolus of 8 ml followed by a continuous infusion (8 ml h(-1)) of the study solution before induction of anaesthesia. In Group 2, patients received the same volume of saline before operation, the study solution was started at the end of surgery. After operation, the infusion was maintained for at least 96 h using a patient-controlled epidural analgesia (PCEA) pump in both groups. Patients were evaluated up to the seventh postoperative day for pain and side-effects. RESULTS: Visual analogue scale (VAS) values at rest were as follows: G1 vs G2: 24 h, 19 (sd 23) vs 6 (13); 48 h, 4 (10) vs 11 (21); and 72 h, 12 (22) vs 13 (21). VAS values during coughing and mobilization were also comparable. Total volume of epidural infusion was 904 (114) ml in G1 vs 892 (154) ml in G2. The incidence of side-effects (nausea, vomiting, and motor block) was low and not different between the groups. CONCLUSIONS: Pre-incisional epidural analgesic infusion did not provide pre-emptive analgesia compared with administration started at the end of surgery, but both groups had low pain scores.     

Spinal anaesthesia with articaine 5% vs bupivacaine 0.5% for day-case lower limb surgery: a double-blind randomized clinical trial

BACKGROUND: A local anaesthetic with fast onset and short reliable duration of anaesthesia may be preferable for out-patient lower limb surgery. Articaine is believed to act faster and to have a shorter duration of action than bupivacaine, but there are no conclusive data available. The purpose of this study was to compare articaine and bupivacaine for day-case lower limb surgery. METHODS: Eighty patients planned for day-case lower limb surgery enrolled in this study. Patients were randomized to receive hyperbaric articaine 80 mg or plain bupivacaine 15 mg intrathecally. Primary outcome variable was recovery time from motor block. Secondary outcomes were: onset of sensory and motor block, maximum spread of sensory block, time to micturition, discharge from the hospital, and complications. RESULTS: The groups were comparable for the medians and the range of the maximum blocks after 30 min. Median time to complete regression of motor block was 101 min (range 80-129) for articaine compared with 307 min (range 225-350) for bupivacaine (P<0.0005). First spontaneous micturition occurred after 257 min (210-293) in the articaine group and after 350 min (304-370) in the bupivacaine group (P<0.0005). In the articaine and bupivacaine groups, patients were discharged after 300 min (273-347) and 380 min (332-431), respectively (P<0.0005). There was no significant difference in the occurrence of complications between the groups. CONCLUSIONS: Spinal anaesthesia with 80 mg of hyperbaric articaine has a shorter duration than a spinal anaesthesia with 15 mg of plain bupivacaine in lower limb surgery of approximately 1 h duration.     

Lung injury following thoracic aortic occlusion: comparison of sevoflurane and propofol anaesthesia

Background: Halogenated anaesthetics have been shown to reduce ischaemia–reperfusion injuries in various organs due to pre- and post-conditioning mechanisms. We compared volatile and total intravenous anaesthesia with regard to their effect on remote pulmonary injury after thoracic aortic occlusion and reperfusion.
Methods: Eighteen pigs were randomized after sternotomy and laparotomy (fentanyl–midazolam anaesthesia) to receive either sevoflurane or propofol in an investigator-blinded fashion. Ninety minutes of thoracic aortic occlusion was induced by a balloon catheter. During reperfusion, a goal-directed resuscitation protocol was performed. After 120 min of reperfusion, the anaesthetic regimen was changed to fentanyl–midazolam again for another 180 min. The oxygenation index and intra-pulmonary shunt fractions were calculated. After 5 h of reperfusion, a bronchoalveolar lavage was performed. The total protein content and lactate dehydrogenase activity were measured in epithelial lining fluid (ELF). Alveolar macrophage oxidative burst was analysed. The wet to dry ratio was calculated and tissue injury was graded using a semi-quantitative score. Ten animals ( n =5 for each anaesthetic) without aortic occlusion served as time controls.
Results: The oxygenation index decreased and the intra-pulmonary shunt fraction increased significantly in both occlusion groups. There were no significant differences between sevoflurane and propofol with respect to the oxygenation index, ELF composition, morphologic lung damage, wet to dry ratio and alveolar macrophage burst activity. Differences were, however, seen in terms of systemic haemodynamic stability, where catecholamine requirements were less pronounced with sevoflurane.
Conclusion: We conclude that the severity of remote lung injury was not different between sevoflurane and propofol anaesthesia in this porcine model of severe lower-body ischaemia and reperfusion injury.     

Sevoflurane-induced cardioprotection depends on PKC-alpha activation via production of reactive oxygen species

BACKGROUND: We previously demonstrated the involvement of the Ca2+-independent protein kinase C-delta (PKC-delta) isoform in sevoflurane-induced cardioprotection against ischaemia and reperfusion (I/R) injury. Since sevoflurane is known to modulate myocardial Ca2+-handling directly, in this study we investigated the role of the Ca2+-dependent PKC-alpha isoform in sevoflurane-induced cardioprotective signalling in relation to reactive oxygen species (ROS), adenosine triphosphate-sensitive mitochondrial K+ (mitoK+(ATP)) channels, and PKC-delta. METHODS: Preconditioned (15 min 3.8 vol% sevoflurane) isolated rat right ventricular trabeculae were subjected to I/R, consisting of 40 min superfusion with hypoxic, glucose-free buffer, followed by normoxic glucose-containing buffer for 60 min. After reperfusion, contractile recovery was expressed as percentage of force development before I/R. The role of PKC-alpha, ROS, mitoK+(ATP) channels, and PKC-delta was established using the following pharmacological inhibitors: Go6976 (GO; 50 nM), n-(2-mercaptopropionyl)-glycine (MPG; 300 microM), 5-hydroxydecanoic acid sodium (5HD; 100 microM), and rottlerin (ROT; 1 microM). RESULTS: Preconditioning of trabeculae with sevoflurane improved contractile recovery after I/R [65 (3)% (I/R + SEVO) vs 47 (3)% (I/R); n = 8; P < 0.05]. This cardioprotective effect was attenuated in trabeculae treated with GO [42 (4)% (I/R + SEVO + GO); P > 0.05 vs (I/R)]. In sevoflurane-treated trabeculae, PKC-alpha translocated towards mitochondria, as shown by immunofluorescent co-localization analysis. GO and MPG, but not 5HD or ROT, abolished this translocation. CONCLUSIONS: Sevoflurane improves post-ischaemic contractile recovery via activation of PKC-alpha. ROS production, but not opening of mitoK+(ATP) channels, precedes PKC-alpha translocation towards mitochondria. This study shows the involvement of Ca2+-dependent PKC-alpha in addition to the well-established role of Ca2+-independent PKC isoforms in sevoflurane-induced cardioprotection.     

Sevoflurane preconditioning at 1 MAC only provides limited protection in patients undergoing coronary artery bypass surgery: a randomized bi-centre trial

BACKGROUND: Volatile agents can mimic ischaemic preconditioning leading to a decrease in myocardial infarct size. The present study investigated if a 15 min sevoflurane administration before cardiopulmonary bypass (CPB) has a cardioprotective effect in patients undergoing coronary surgery. METHODS: Seventy-two patients were randomized in two centres. The intervention group (S) received 1 MAC sevoflurane administrated via the ventilator for 15 min followed by a 15 min washout before CPB, the control group did not. The primary outcome was the postoperative troponin Ic peak. A biopsy of the atrium was taken during canulation for enzyme dosages. Results are expressed as mean (SD). RESULTS: Neither troponin Ic nor tissular enzyme measurement exhibited any difference between the groups: peak of troponin Ic was 4.4 (5.6) in S group vs 5.2 (6.6) ng ml(-1) in control group (ns). Intratissular ecto-5'-nucleotidase activity was 7.1 (4.3) vs 8.5 (11.9), protein kinase C activity was 27.1 (15.7) vs 29.2 (28.7), tyrosine kinase activity was 101 (54.1) vs 98.5 (63.3), and P38 MAPKinase activity was 131.1 (76.1) vs 127.1 (86.8) nmol mg protein(-1) min(-1) in S group and control group, respectively (ns). However there were fewer patients with low postoperative cardiac index in S group (11% in S vs 35% in control group, P < 0.05) when considering the per protocol population. In S group, 25% of patients required an inotropic support during the postoperative period, vs 36% of patients in control group (ns). CONCLUSIONS: This study did not show a significant preconditioning signal after 15 min of sevoflurane administration. The 15 min duration might be too short or the concentration of sevoflurane too low to induce cardioprotection detected by troponin I levels.     

Randomized, double-blind comparison of patient-controlled epidural infusion vs nurse-administered epidural infusion for postoperative analgesia in patients undergoing colonic resection

BACKGROUND: There is little published evidence of the analgesic efficacyof patient-controlled epidural analgesia (PCEA) for postoperativepain relief. The aim of this study was to compare the analgesicefficacy of epidural infusion of bupivacaine 0.125% and fentanyl4 µg ml^–1 administered by either PCEAwith a background infusion or nurse-administered continuousepidural infusion (CEI) after major intra-abdominal surgery. METHODS: In a double-blind, randomized clinical trial, 205 adult patientsundergoing colonic resection by laparotomy received either PCEAor CEI. Pain scores were recorded via a four-point verbal ratingscale at 1, 2, 3, 4, 8, 12, 24, 48, and 72 h after surgery.The administration of epidural top-ups and systemic analgesiaover the same period was also recorded, and patient satisfactionquestionnaires completed. RESULTS: The median area under the curve of pain against time was significantlylower in the PCEA group (2 vs 24, P<0.001) as were mediansummary pain scores on movement (0.67 vs 1.33, P<0.001).Significantly fewer patients in the PCEA group received oneor more epidural top-ups (13 vs 36%, P = 0.0002) or any systemicanalgesics (41 vs 63%, P = 0.0021). Patients in the PCEA groupwere significantly more likely to be very satisfied than inthe CEI group (76 vs 43%, P<0.0001). CONCLUSIONS: PCEA provides greater analgesic efficacy than CEI for postoperativeanalgesia after major intra-abdominal surgery, and a decreasedrequirement for physician or nurse intervention.     

Reduction of pain during induction with target-controlled propofol and remifentanil

BACKGROUND: Pain on injection of propofol is unpleasant. We hypothesized that propofol infusion pain might be prevented by infusing remifentanil before starting the propofol infusion in a clinical setting where target-controlled infusions (TCI) of both drugs were used. A prospective, randomized, double-blind, placebo-controlled trial was performed to determine the effect-site concentration (Ce) of remifentanil to prevent the pain without producing complications. METHODS: A total of 128 patients undergoing general surgery were randomly allocated to receive normal saline (control) or remifentanil to a target Ce of 2 ng ml(-1) (R2), 4 ng ml(-1) (R4), or 6 ng ml(-1) (R6) administered via TCI. After the target Ce was achieved, the infusion of propofol was started. Remifentanil-related complications were assessed during the remifentanil infusion, and pain caused by propofol was evaluated using a four-point scale during the propofol infusion. RESULTS: The incidence of pain was significantly lower in Groups R4 and R6 than in the control and R2 groups (12/32 and 6/31 vs 26/31 and 25/32, respectively, P<0.001). Pain was less severe in Groups R4 and R6 than in the control and R2 groups (P<0.001). However, both incidence and severity of pain were not different between Groups R4 and R6. No significant complications were observed during the study. CONCLUSIONS: During induction of anaesthesia with TCI of propofol and remifentanil, a significant reduction in propofol infusion pain was achieved without significant complications by prior administration of remifentanil at a target Ce of 4 ng ml(-1).     

Narcotrend-assisted propofol/remifentanil anaesthesia vs clinical practice: does it make a difference?

BACKGROUND: The Narcotrend is a computer-based EEG monitor designed to measure the depth of anaesthesia. The aim of the present study is to test the hypothesis that the intraoperative level of anaesthetic depth differs if decision-making is guided by Narcotrend monitoring or not. METHODS: Forty-eight patients undergoing elective surgery were randomized to receive a Narcotrend-controlled propofol/remifentanil anaesthetic regimen or standard clinical practice. In the EEG group, anaesthesia was adjusted to achieve a Narcotrend level of D2-E0, which is recommended for moderate to deep anaesthetic depth for surgery. EEG values were recorded continuously every 20 s in both groups. Depending on data distribution, group comparisons of the EEG parameters, propofol plasma concentration, and recovery characteristics were performed by analysis of variance for repeated measurements or non-parametric statistics. RESULTS: About 62 (sd 29)% of the Narcotrend values were within the target level in the EEG group during maintenance of anaesthesia; this was true for 64 (26)% of the data in the non-EEG group. The variance of the Narcotrend data was significantly lower in the EEG group compared with the non-EEG group [median: 0.4 (range: 3.5) vs 0.6 (2.5); P = 0.048]. There was no difference in propofol or remifentanil dosage, propofol plasma concentrations, and time for extubation. Ten minutes after extubation, visual analogue scores for nausea indicated a lower incidence in the Narcotrend group [7 (15) vs 24 (34); P = 0.005]. CONCLUSIONS: Guidance of anaesthesia with the Narcotrend-monitor leads to fewer deviations from a defined target than clinical assessment of anaesthetic depth only. This results in lower scores of nausea in the immediate period after anaesthesia.     

Midlatency auditory evoked potentials in children: effect of age and general anaesthesia

BACKGROUND: Midlatency auditory evoked potentials (MLAEP) are a promising tool for monitoring suppression of sensory processing during anaesthesia and might help to avoid awareness. MLAEP in children are different to those in adults and the exact changes during general anaesthesia are unknown. METHODS: In 49 children of age between 2 and 12 yr, MLAEP were recorded before anaesthesia, during tracheal intubation, at steady-state balanced anaesthesia, and after extubation. RESULTS: MLAEP were recordable in all children in the awake (premedicated) state with latencies but not amplitudes dependent on children's age. MLAEP latencies significantly increased during tracheal intubation and steady-state anaesthesia. Changes in amplitudes were inconsistent. All MLAEP variables returned to near baseline values after extubation. CONCLUSIONS: The results of this study imply that MLAEP can successfully be recorded during anaesthesia in children above the age of 2 yr. Further studies are necessary before MLAEP might be applicable for monitoring purposes in paediatric anaesthesia.