Can regional anaesthesia for lymph-node dissection improve the prognosis in malignant melanoma?

BACKGROUND: Optimized anaesthetic management might improve the outcome after cancer surgery. A retrospective analysis was performed to assess the association between spinal anaesthesia (SpA) or general anaesthesia (GA) and survival in patients undergoing surgery for malignant melanoma (MM). METHODS: Records for 275 patients who required SpA or GA for inguinal lymph-node dissection after primary MM in the lower extremity between 1998 and 2005 were reviewed. The follow-up ended in 2009. Survival was calculated as days from surgery to the date of death or last patient contact. The primary endpoint was mortality during a 10 yr observation period. RESULTS: Of 273 patients included, 52 received SpA and 221 GA, either as balanced anaesthesia (sevoflurane/sufentanil, n=118) or as total i.v. anaesthesia (propofol/remifentanil, n=103). The mean follow-up period was 52.2 (sd 35.69) months after operation. Significant effects on cumulative survival were observed for gender, ASA status, tumour size, and type of surgery (P=0.000). After matched-pairs adjustment, no differences in these variables were found between patients with SpA and GA. A trend towards a better cumulative survival rate for patients with SpA was demonstrated [mean survival (months), SpA: 95.9, 95% confidence interval (CI), 81.2-110.5; GA: 70.4, 95% CI, 53.6-87.1; P=0.087]. Further analysis comparing SpA with the subgroup of balanced volatile GA confirmed this trend [mean survival (months), SpA: 95.9, 95% CI, 81.2-110.5; volatile balanced anaesthesia: 68.5, 95% CI, 49.6-87.5, P=0.081]. CONCLUSIONS: These data suggest an association between anaesthetic technique and cancer outcome in MM patients after lymph-node dissection. Prospective controlled trials on this topic are warranted.

[PATHOS study on postoperative pain management in Europe: French data]. / Enquête européenne sur la prise en charge de la douleur et de l'analgésie postopératoires (PATHOS) : les résultats français.

INTRODUCTION: Relief of postoperative pain is a major topic of public health and has been repeatedly shown to be inadequate. STUDY DESIGN: A questionnaire survey performed in seven European countries (postoperative analgesic therapy observational survey) in 746 health structures--which perform more than 80% of the total number of surgical procedures of each country--has demonstrated significant improvement when compared with previous surveys, particularly regarding increased use of multimodal analgesia and regular administration of analgesic drugs. The present study describes specific results for the 178 French health care institutions surveyed and 345 questionnaires collected. Preoperative patient information is given on a regular basis for 84% of respondents. RESULTS: Multimodal analgesia is used after major surgery in 87% of cases and prescribed on a regular basis for 84% of respondents. Written protocols are available in 36% of responding institutions. Pain scores are measured several times a day in 65% of institutions. An acute pain service (or any other structure with a similar aim) is found in 52% of institutions. Regular on-site training courses on pain control are delivered to 30% of anaesthesiologists, to 6% of surgeons, to 57% of recovery-room nurses and to 63% of ward nurses. Overall, the study suggests an improvement of current practices but also highlights remaining insufficiencies. CONCLUSION: Important efforts remain to be done, particularly in the field of initial and continuous education of all healthcare categories as this is believed to be the only real way to obtain long-term results.

[Organisation of postoperative acute pain therapy in Germany compared to other European nations - results of a postoperative analgetic therapy observational survey (PATHOS)]. / Organisation der postoperativen Schmerztherapie Deutschlands im europäischen Vergleich - Ergebnisse einer europaweiten Umfrage (PATHOS).

BACKGROUND: From 2004 to 2005, a survey concerning the structure and organisation of postoperative acute pain therapy (APT) was conducted in 1358 hospitals from 7 EU states. METHODS: Anaesthesiologists, general and abdominal surgeons, orthopaedic / trauma surgeons, gynaecologists and ENT specialists were interviewed concerning: Education of medical and non-medical employees, patient information, protocols for acute pain therapy and methods of pain assessment. RESULTS: 1558 questionnaires from 746 hospitals were returned, among them 516 questionnaires from Germany where surgeons were more often responsible for acute pain therapy (50 vs. 36 %, p < 0.05). A budget for APT existed in only 8 % of German hospitals (vs. 22 % of hospitals in other nations, p < 0.05). German surgeons were more often responsible for the APT education of nurses on the general ward (58 vs. 20 %, p < 0.05). Patient information about APT was more often presented in Germany in selected cases (45 vs. 23 %, p < 0.05), APT protocols were developed more often (42 vs. 30 %, p < 0.05) and the influence of APT on morbidity and mortality was judged to be higher by German physicians (p < 0.05 each) as compared to other nations. Nevertheless, postoperative pain was not assessed at all in 53 % of all German hospitals, and only in 25 % of the hospitals of other nations (p < 0.05). CONCLUSION: Further initiatives to improve postoperative acute pain therapy are urgently needed in all nations under evaluation. National measures in Germany have to take into account the specific problems identified in this large survey and should focus on the interests and needs of German surgeons.

A multicentre trial comparing different concentrations of ropivacaine plus sufentanil with bupivacaine plus sufentanil for patient-controlled epidural analgesia in labour.

BACKGROUND AND OBJECTIVE: To determine the optimal concentration of ropivacaine for bolus-only patient-controlled epidural labour analgesia, three different doses of ropivacaine were evaluated in comparison with bupivacaine in a double-blinded multicentre study. METHODS: Four hundred-and-fifty labouring parturients at term in three different academic institutions were randomized to four groups receiving bupivacaine 0.125% with sufentanil 0.75 microg mL(-1), ropivacaine 0.125% or 0.175% with sufentanil 0.75 microg mL(-1), or ropivacaine 0.2%. After an initial bolus of 10 mL of the study solution, and once visual analogue scores (VAS) were below 30 mm, patient-controlled epidural analgesia was initiated with a bolus of 4 mL, a lockout interval of 15 min and without a background infusion. Variables studied were the quality of analgesia, incidence of side-effects, the degree of motor blockade, and the mode of delivery. RESULTS: Bupivacaine 0.125% and ropivacaine 0.125% with sufentanil proved equally effective in providing labour analgesia without a difference in local anaesthetic consumption (48.6 +/- 23 mg bupivacaine vs. 52.1 +/- 38 mg ropivacaine), motor blockade or mode of delivery. Ropivacaine 0.175% plus sufentanil enhanced the quality of analgesia of the initial loading dose, whereas ropivacaine 0.2% without sufentanil increased the consumption of local anaesthetics (80.2 +/- 34 mg; P < 0.05) and the degree of motor blockade. CONCLUSION: Despite recent studies indicating that bupivacaine and ropivacaine may not be equipotent, both local anaesthetics provided equi-effective analgesia at equal doses without a difference in side-effects.

Adsorption of sufentanil to epidural filters and catheters.

BACKGROUND AND OBJECTIVE: Stable drug concentrations must be administered to provide adequate patient-controlled epidural analgesia. This study investigated the stability of sufentanil after the epidural delivery system had been flushed with solutions containing the drug. METHODS: Sufentanil citrate, 5 microg mL(-1) was injected through an epidural catheter system into a glass container. The concentrations of the drug leaving the system, in 1 mL aliquots (1-5 mL) were measured using high-performance liquid chromatography. In the same manner, sufentanil samples were analysed after flushing the filter, as well as after priming the filter and catheter. RESULTS: ANOVA for repeated measurements demonstrated that sufentanil concentrations remained constant as long as the catheter had been adequately flushed. However, the concentration of sufentanil in the solution exiting the filter was reduced significantly. Hardly any sufentanil could be detected (0.09 +/- 0.01 microg mL(-1), P < 0.001) in the first 1 mL aliquot (probe) leaving the filter. Altogether, 3 mL sufentanil solution was needed to pass through the filter before the baseline values were restored (P > 0.05). The greatest decrease occurred when the whole epidural delivery apparatus (catheter and filter) was primed; to regain baseline values, as much as 4 mL solution was needed to flush the system. CONCLUSIONS: Sufentanil citrate is adsorbed by the materials used to manufacture systems (catheters, filters) used in epidural anaesthesia. Hence, the epidural catheter system should be primed with sufentanil before connecting it to the patient so as to deliver reliable concentrations.

Stability of a sufentanil-ropivacaine mixture in a glass and a PVC reservoir.

BACKGROUND AND OBJECTIVE: Drug mixtures containing sufentanil may be unstable owing to absorption into the drug reservoirs of patient-controlled epidural analgesia systems that contain polyvinylchloride. The stability of sufentanil in a mixture of ropivacaine 0.2% in a 750 mL reservoir was therefore investigated. METHODS: During simulated epidural infusions of 5 mLh(-1) at 25 degrees C, sufentanil concentrations were measured for 96 h. Samples were taken from the reservoir and from the end of the epidural catheter under the following conditions: into glass or polyvinylchloride reservoirs containing ropivacaine 0.2% with sufentanil 1, 0.75 or 0.5 microg mL(-1); and into polyvinylchloride reservoirs with ropivacaine 0.2% and sufentanil 1 microg mL(-1) which were stored for 4 weeks at 8 degrees C. RESULTS: The different solutions remained stable over the observation period of 96 h. Using the same solutions, independent samples' ANOVA showed no difference in the sufentanil concentrations between the glass and polyvinylchloride reservoirs, or between the polyvinylchloride reservoirs when stored for 4 weeks. Correlations between the concentrations at the different measurement times were extremely high for the reservoir (r(min) = 0.98, r(max) = 1.00) and the catheter end (rmin = 0.86, r(max) = 1.00). CONCLUSIONS: Sufentanil citrate at 0.5-1.0 microg mL(-1) in an admixture of ropivacaine 0.29 for 5 days, which is the usual period for postoperative epidural analgesia, remains stable in a polyvinylchloride reservoir. There is no change in the drug concentration even if the reservoir is stored for 4 weeks at 8 degrees C.

[Efficacy of oncologic surgery. Does anesthesia influence the postoperative outcome?]. / Effizienz der onkologischen Chirurgie. Hat die Anästhesie einen Einfluss auf das postoperative Ergebnis?

Major surgical interventions in tumour surgery are still associated with perioperative cardiopulmonary, infectious, thromboembolic, cerebral, and gastrointestinal complications. There are different prophylactic and therapeutic possibilities to anticipate or counteract these perioperative complications. The most important, including beta blockers and alpha-2-agonists for patients at coronary risk, preoperative optimisation of oxygen transport in high risk surgical patients and the concept of multimodal perioperative therapy (analgesia, early mobilisation, early enteral nutrition, and others) combined with high perioperative inspiratory oxygen concentration and maintenance of normothermia to reduce wound infection and cardiac complications are described in this paper.

Multimodal perioperative management--combining thoracic epidural analgesia, forced mobilization, and oral nutrition--reduces hormonal and metabolic stress and improves convalescence after major urologic surgery.

We sought in this prospective study to use a multimodal approach to reduce stress and improve recovery in patients undergoing major surgery. During an initial study period, 30 patients were randomly allocated to receive general anesthesia (GA; Group 1) or a combination of GA and intraoperative thoracic epidural analgesia (TEA; Group 2) when undergoing radical cystectomy. Parenteral nutrition was provided for 5 days after surgery. During the second period, 15 patients were treated with a multimodal approach (Group 3) consisting of intraoperative GA and TEA, postoperative patient-controlled TEA, early oral nutrition, and enforced mobilization. Data for plasma and urine catecholamines, plasma cortisol, the nitrogen balance, the postoperative inflammatory nutrition index, pain relief, fatigue, sleep, overnight recovery, recovery of bowel function, and mobilization were recorded up to the fifth postoperative day. Plasma concentrations of catecholamines and cortisol were comparable in all patients, but those in Group 3 had lower levels of urinary catecholamine excretion. Protein intake was more effective with parenteral nutrition. Nitrogen balances were less negative, and the postoperative inflammatory nutrition index score increased significantly in the traditional groups but not in Group 3. Multimodally treated patients reported less fatigue and better overnight recovery. Along with improved pain relief, recovery of bowel function, and ambulation, there were no differences in the postoperative complication rates among the three groups. The multimodal approach reduced stress and improved metabolism and recovery after radical cystectomy.

Acute pain management: analysis, implications and consequences after prospective experience with 6349 surgical patients.

An acute pain service (APS) was set up to improve pain management after operation. We attempted to reduce the length of stay in the intensive care unit (ICU) of patients undergoing major surgery and to improve their homeostasis and rehabilitation using a multimodal approach (pain relief, stress reduction, early extubation). Patient-controlled epidural analgesia (PCEA) was a keystone of this approach. If PCEA was not applicable, patients received patient-controlled intravenous analgesia (PCIA) instead. Brachial plexus blockade (BPB) was used for surgery of the upper limbs. A computer based documentation system was used to help evaluate prospectively (a) the quality of analgesia, (b) adverse effects and risks of the special pain management techniques, and (c) cost-effectiveness. Patients receiving PCEA (n = 5.602) received a patient-titrated continuous infusion into the epidural space of either bupivacaine 0.175% or ropivacaine 0.2%, with 1 microg sufentanil mL(-1) added, followed by patient-controlled boluses of 2 mL (lockout time 20 min). For patients receiving PCIA (n = 634) an initial bolus of 7.5-15 mg piritramide was given, and the subsequent bolus was 2 mg (lockout time 10 min). A continuous infusion of bupivacaine 0.25% was administered to patients receiving BPB (n = 113). The dose was titrated to a dynamic visual analogue scale (VAS) scores < 40. The mean treatment periods were: BPB = 4.33 days, PCEA = 5.6 days, PCIA = 5.0 days. In the case of PCEA, the quality of pain relief, vigilance and satisfaction were superior compared with the PCIA method, which resulted in greater sedation and nausea. Although personal supervision was higher for the PCEA-treated patients, cost analysis revealed final savings of Euro 91,620 for the year 1998 obviating the need for an ICU stay totalling 433 days. Provided that PCEA is part of a fast-track protocol employing early tracheal extubation and optimal perioperative management, the associated initial higher costs will be recouped by the benefits to patients of better pain relief after surgery and fewer days subsequently spent in the ITU.

What concentration of sufentanil should be combined with ropivacaine 0.2% wt/vol for postoperative patient-controlled epidural analgesia?

UNLABELLED: In this randomized double-blinded study, we sought to determine an optimal dose-combination of sufentanil with ropivacaine 0.2% wt/vol as postoperative epidural analgesics. One hundred twenty patients undergoing major abdominal surgery under general and thoracic epidural anesthesia (T9-11) were assigned to groups receiving patient-controlled epidural analgesia with ropivacaine 0.2% wt/vol (R), ropivacaine 0.2% wt/vol + sufentanil 0.5 microg/mL (R+S0.5), 0. 75 microg/mL (R+S0.75), 1.0 microg/mL (R+S1). A visual analog score of less than 40 was considered effective, and all side effects were recorded. In randomized subgroups (10 patients per group), plasma pharmacokinetic data were obtained for both epidural drugs. Four patients in Group R and two in Group R+S0.5 were excluded because of inadequate analgesia. The drug infusion rates (range of means: 5.4-5. 9 mL/h) were similar in all patients. Analgesia was superior for sufentanil 0.75 microg/mL with no further enhancement by the larger sufentanil concentration of 1 microg/mL. Sufentanil plasma levels were within the range of the minimal effective concentrations (highest in R+S1), and there was no covariation between plasma levels and pain relief. Free ropivacaine plasma concentrations remained stable for 96 h. No severe side effects were detected, although pruritus correlated with an increasing dose of sufentanil. We conclude that the combination of ropivacaine 0.2% wt/vol and 0.75 microg/mL sufentanil provided the best analgesia with the fewest side effects of the three combinations tested. IMPLICATIONS: Sufentanil is added to epidural infusions of ropivacaine 0.2% wt/vol to improve the effectiveness of postoperative pain management. Regarding the risk of side effects, however, it is still unclear what concentration of sufentanil should be added to the local anesthetic. For postoperative thoracic epidural analgesia after major abdominal surgery, the combination of ropivacaine 0.2% wt/vol and 0.75 microg/mL sufentanil resulted in an appropriate cost:benefit ratio between good analgesia and side effects.

Experimental arthritis in the rat does not alter the analgesic potency of intrathecal or intraarticular morphine.

UNLABELLED: To explore further the role of inflammatory processing on peripheral opioid pharmacology, we examined whether the potency of intraarticular (i.a.) or intrathecal (i.t) morphine in tests of thermal and mechanical nociception changed during the induction of experimental arthritis in the rat. Thermal nociception by i.t. morphine (3, 10, and 50 micrograms) or i.a. morphine (100, 1000, and 3000 micrograms) was assessed by means of a modified Hargreaves box ever) 28 h. Mechanical antinociception was determined for the largest applied doses of morphine using von Frey hairs. Morphine produced dose-dependent thermal antinociception after i.t. or i.a. administration: a 50% increase in maximum antinociceptive thermal response (50% effective dose) was produced by i.t. doses of 9.7 micrograms at the start and 9.1 micrograms at the end of this 28-h observational interval, whereas after i.a. administration, 50% effective dose values were 553 micrograms at the start and 660 micrograms at the end. The largest applied dose of either i.t. or i.a. morphine produced mechanical antinociception. On Day 1, the antinociceptive effect for mechanical nociception (expressed as the area under the curve of the percentage of maximal possible effect values at 0.5, 1, 2, and 4 h) was 68% for i.t. morphine 50 micrograms and 53% for i.a. morphine 3000 micrograms. Neither result differed from the corresponding area under the curve values on Day 2. Naloxone administered either i.t. or i.a. abolished the antinociceptive action of morphine given at the same site. We conclude that, although morphine has a peripheral analgesic site of action in a rat arthritis model, its potency for both i.a. and i.t. routes of administration does not change during the onset of arthritis. IMPLICATIONS: In this animal study, we showed that the administration of morphine modulates thermal and mechanical antinociception at central and peripheral sites in inflammatory pain.

Epidural analgesia with local anesthetics after abdominal surgery: earlier motor recovery with 0.2% ropivacaine than 0.175% bupivacaine.

UNLABELLED: The aim of this prospective, randomized, double-blinded study was to compare pain relief, side effects, and ability to ambulate during epidural anesthesia with ropivacaine 0.2% plus sufentanil versus bupivacaine 0.175% plus sufentanil after major gastrointestinal surgery. Epidural catheters were inserted at T8-11, and 30 microg of sufentanil with 15 mL of ropivacaine 0.75% (Group 1, n = 42) or bupivacaine 0.5% (Group 2, n = 44) was injected. General anesthesia was induced, a continuous epidural infusion (5 mL/h) was then begun with 1 microg/mL sufentanil plus ropivacaine 0.2% (Group 1) or bupivacaine 0.175% (Group 2). Postoperatively, the infusion rate was adjusted to individual requirements. Patients were also able to receive additional 2-mL bolus doses every 20 min. Demographic data (except for gender and height), analgesia, drug dosage, and side-effects, including motor blockade (Bromage score), were similar in both groups, but mobilization recovered more quickly in Group 1. Gender, age, ASA physical status, duration of surgery, and intraoperative blood loss had no effect on mobilization. We conclude that epidural analgesia is effective and safe with both regimens. There is not necessarily a correlation between the Bromage score and the desired outcome of mobilization. The ability to walk postoperatively is hastened if ropivacaine is used instead of bupivacaine. IMPLICATIONS: Regarding pain relief and side effects, epidural analgesia with ropivacaine 0.2% and sufentanil 1 microg/mL yields pain scores and pain intensity comparable to those for the well evaluated combination of bupivacaine 0.175% and sufentanil 1 microg/mL. However, earlier recovery of the ability to walk unassisted in patients receiving the combination of ropivacaine and sufentanil may result in their earlier rehabilitation.

Central and peripheral analgesia mediated by the acetylcholinesterase-inhibitor neostigmine in the rat inflamed knee joint model.

UNLABELLED: Intrinsic cholinergic inhibitory pathways present a key modulating system in pain perception. The use of intrathecal (i.t.) acetylcholinesterase-inhibitors, such as neostigmine, result in analgesia in both preclinical and clinical models. However, whether i.t. neostigmine suppresses tonic persistent pain or has peripheral sites of antinociceptive action has not been determined. Thus, we studied central (i.t.) and peripheral (intraarticular; i.a.) neostigmine in a rat inflamed knee joint model. Inhibition of thermal and mechanical hyperalgesia was assessed over 28 h using a modified Hargreaves box and von Frey hairs, respectively. I.t. neostigmine resulted in a dose-dependent thermal analgesia (50% of maximal effective dose [ED50] 0-4 h: 6.6 microg, 24-28 h: 9.4 microg) and mechanical analgesia (ED50 0-4 h: 3.5 microg, 24-28 h: 4.3 microg). I.t. atropine reversed analgesia by i.t. neostigmine. I.a. neostigmine also resulted in an i.a. atropine reversible dose-dependent increase of thermal analgesia, although it did not exceed 60% of a maximal possible analgesic effect with the largest applied dose (ED50 0-4 h: 76.2 microg, 24-28 h: 140.1 microg). Partial suppression of mechanical hyperalgesia was observed after i.a. neostigmine. We conclude that centrally administered neostigmine modulates thermal and mechanical antinociception in this animal model of inflammatory pain. These data suggest a peripheral site of muscarinic antinociception. IMPLICATIONS: This animal study shows that administration of the acetylcholinesterase-inhibitor neostigmine results in enhanced levels of the endogenous neurotransmitter acetylcholine, which seems to act as one of a group of analgesia-modulating compounds at central and peripheral sites in inflammatory pain.