The constraints on day-case total knee arthroplasty: the fastest fast track.

Total knee arthroplasty (TKA) is a major orthopaedic intervention. The length of a patient's stay has been progressively reduced with the introduction of enhanced recovery protocols: day-case surgery has become the ultimate challenge. This narrative review shows the potential limitations of day-case TKA. These constraints may be social, linked to patient's comorbidities, or due to surgery-related adverse events (e.g. pain, post-operative nausea and vomiting, etc.). Using patient stratification, tailored surgical techniques and multimodal opioid-sparing analgesia, day-case TKA might be achievable in a limited group of patients. The younger, male patient without comorbidities and with an excellent social network around him might be a candidate. Demographic changes, effective recovery programmes and less invasive surgical techniques such as unicondylar knee arthroplasty, may increase the size of the group of potential day-case patients. The cost reduction achieved by day-case TKA needs to be balanced against any increase in morbidity and mortality and the cost of advanced follow-up at a distance with new technology. These factors need to be evaluated before adopting this ultimate 'fast-track' approach.

Pain after total knee arthroplasty: a narrative review focusing on the stratification of patients at risk for persistent pain.

The patient with a painful arthritic knee awaiting total knee arthroplasty (TKA) requires a multidisciplinary approach. Optimal control of acute post-operative pain and the prevention of chronic persistent pain remains a challenge. The aim of this paper is to evaluate whether stratification of patients can help identify those who are at particular risk for severe acute or chronic pain. Intense acute post-operative pain, which is itself a risk factor for chronic pain, is more common in younger, obese female patients and those suffering from central pain sensitisation. Pre-operative pain, in the knee or elsewhere in the body, predisposes to central sensitisation. Pain due to osteoarthritis of the knee may also trigger neuropathic pain and may be associated with chronic medication like opioids, leading to a state of nociceptive sensitisation called 'opioid-induced hyperalgesia'. Finally, genetic and personality related risk factors may also put patients at a higher risk for the development of chronic pain. Those identified as at risk for chronic pain would benefit from specific peri-operative management including reduction in opioid intake pre-operatively, the peri-operative use of antihyperalgesic drugs such as ketamine and gabapentinoids, and a close post-operative follow-up in a dedicated chronic pain clinic.

Continuous regional anesthesia and inflammation: a new target.

Inflammation can be defined as the host response when confronted with an aggression. The purpose of the inflammatory reaction is the defense of the host for re-establishing the baseline homeostasis of the organism. Compared to the neuroendocrine changes associated to the stress response to injury, the inflammatory reaction is the major determinant of patient's recovery in the perioperative period. Perioperative inflammation is involved in the occurrence of various postoperative adverse outcomes other than only acute pain. By consequence, perioperative strategies which limit or control the inflammatory response might have beneficial effects on patient's recovery. The present review summarizes the current knowledges on the interactions between some of these strategies, specifically regional anesthesia (RA) techniques, and inflammation in the context of perioperative medicine. Regional anesthesia through its components i.e. local anesthetics and analgesic adjuvants like alpha-2 adrenergic agonists (clonidine, dexmedetomidine) modulates the inflammatory response consecutive to tissue injury by various mechanisms, at different levels. While experimental studies have shown that RA techniques modulate both local and systemic inflammatory reactions, in contrast, clinical findings are inconsistent as actual RA techniques fail to impact major patients' outcomes beyond immediate postoperative analgesia. The discrepancy between experimental findings and clinical observations asks questions and argues for a different view of perioperative inflammatory processes, in other words for an individualized management of the patients. Future developments of tools to quantify inflammatory and immune profile of patients might certainly lead to exciting findings and to major improvements in perioperative medicine.

[Postoperative pain trajectories to identify risk of chronic postsurgical pain in living donors for liver transplantation]. / Identification du risque de douleur chronique après hépatectomie pour don de foie par les trajectoires de douleur.

OBJECTIVES: To assess pain trajectories in predicting risk of chronic postoperative pain (CPP) after liver resection for living donor transplantation. STUDY DESIGN: Retrospective analysis of patients undergoing liver resection for living donor transplantation during 3years. PATIENTS AND METHODS: After recording perioperative data, patients presenting CPP at 3months were separated from patients without postsurgical pain problem in order to build a pain trajectory for liver donor patients without CPP. Postoperative course of liver donors with CPP was then compared to that standard pain trajectory. RESULTS: Sixty-five patients (30 females, 35 males) were included. Epidural analgesia was used in 66%; others received autocontrolled analgesia by morphine. Severe acute pain was expressed by 11% and 37% at rest and movement respectively on the first day. Chronic pain involved six patients without any link with gender or type of analgesia. Analysis of pain trajectories shown that these patients presented either higher initial pain at day 1 or positive slopes with worsening of pain. CONCLUSION: Acute postoperative pain is a risk factor of developing CPP. Identification of those people by pain trajectories can be useful to treat them early.

Abnormal sensations evoked over the chest and persistent peri-incisional chest pain after cardiac surgery.

Risk factors for developing Persistent peri-incisional Chest Pain (PCP) after sternotomy are multiple. We examined whether hypoesthesia, hyperalgesia or dysesthesia, evoked in the postoperative period might be associated with PCP after sternotomy. One hundred patients undergoing a sternotomy were evaluated on day 5. Peri-incisional sensory testing was performed using von Frey filament. Presence and severity of PCP were assessed at 2 and 6 months. PCP was present in 29% and 15% of patients respectively at 2 and 6 months. Hyperalgesia on day 5 was present in 43% of patients with PCP at 6 months compared to 15% without PCP. Hypoesthesia was present in 57% of patients with PCP at 6 months compared to 22% without PCP. There was no significant difference in the incidence of dysesthesia. On day 5, hyperalgesia was correlated with a risk to develop PCP at 6 months. Among sensory abnormalities, the presence of hyperalgesia is associated with PCP at 6 months postoperatively.

Patient-controlled intravenous analgesia as an alternative to epidural analgesia during labor: questioning the use of the short-acting opioid remifentanil. Survey in the French part of Belgium (Wallonia and Brussels).

Childbirth ranks among the most intense experiences of acute pain. Neuraxial analgesia (i.e. epidural or combined spinal-epidural technique) is the most effective way to relieve that pain but it is contraindicated or impossible to perform for some parturients. We designed a survey of the current use of analgesic alternatives to epidural analgesia (EA) for labor pain, specifically the use of opioid patient-controlled intravenous analgesia (PCIA), in the French part of Belgium (Wallonia and Brussels). A questionnaire was mailed to the departmental chair of the hospitals with an obstetric unit, both in university and non-university centers (total of 53 centers). The questionnaire evaluated the availability of EA, the alternatives used when EA was contraindicated, the use of opioid-based PCIA for labor analgesia as well as opioid preference and doses, and finally the reasons for not using opioid PCIA. The response rate was 67.5% (36 centers). Among the responding hospitals, EA was available for 68% (range 25-85%) of labors and deliveries. When EA was not available or contraindicated, a parenteral opioid (piritramide, tramadol or pethidine) was proposed in 19% (7/36) of the centers, Entonox in 11% (4/36), a pudendal block by obstetricians in 28% (10/36) and non-pharmacologic alternatives (i.e. hypnosis, sophrology, baths and massages) in 19% (7/36). In 28% (10/36) of the centers however, no analgesic alternative was proposed. Opioid PCIA was employed in 36% (13/36) of the centers and for an additional 11% (4/36) only in case of intrauterine death. Remifentanil was the first choice (76.5% of the PCIA), followed by sufentanil (23.5%). Other opioids (piritramide, morphine, fentanyl) and ketamine were also administered by PCIA. Forty-five percents of the centers reported never using opioid PCIA by either lack of knowledge (7%), fear of maternal or fetal side effects (48%) and unability to provide a correct supervision of the parturient during PCIA use (48%), opposition from the pediatricians or obstetricians (17%) or because they considered the technique as ineffective to relieve labor pain (17%). In conclusion, the survey demonstrated that, when EA is contraindicated, systemic opioid administered by PCIA is used in almost half of the centers (47%) and that remifentanil is the first choice, particularly when a live birth is expected.

The use of intraoperative epidural or spinal analgesia modulates postoperative hyperalgesia and reduces residual pain after major abdominal surgery.

INTRODUCTION: The use of intraoperative multimodal analgesia has clearly improved postoperative pain control, mortality and morbidity after major surgical procedures. However, very few clinical trials have studied the longterm impact of intraoperative epidural or spinal analgesia on chronic postsurgical pain (CPSP) development. Even less studies have evaluated the modulatory effect of intraoperative neuraxial analgesia on objective changes (i.e. mechanical hyperalgesia) reflecting central sensitization. METHODS: The present work compares general anesthesia alone (GA group) versus general anesthesia combined to either intraoperative epidural analgesia (EPID group: combination of bupicavaine, sufentanil and clonidine 1 microg/kg) or spinal analgesia (IT group: either bupivacaine or clonidine 300 microg) on the development of secondary mechanical hyperalgesia and the incidence of CPSP after major abdominal surgery. Data analyzed in the present work involve adult patients undergoing surgical resection of rectal adenocarcinoma who participated in three previously published randomized trials. RESULTS: Intraoperative epidural and particularly spinal analgesia reduced both incidence (p < 0.05 between GA alone and spinal analgesia) and extent (area) of secondary mechanical hyperalgesia surrounding the wound at 48h and 72 h after surgery. The use of intraoperative epidural and spinal analgesia also reduced CPSP incidence. Postoperative area of mechanical hyperalgesia seems positively correlated with the incidence CPSP. CONCLUSION: An effective intraoperative neuraxial block of nociceptive inputs from the wound using multimodal analgesia--specifically when involving spinal analgesics and antihyperalgesic drugs--contributes to prevent central sensitization and hence reduces CPSP after major abdominal procedures.

Questioning the cardiocirculatory excitatory effects of opioids under volatile anaesthesia.

BACKGROUND: Opioid-induced hyperalgesia has been demonstrated in awake animals. We observed an increased haemodynamic reactivity in response to noxious stimuli in rats under sevoflurane anaesthesia treated with a very low dose of sufentanil. The aim of this investigation was to determine whether the two phenomena share a common origin: an opioid-induced excitatory reaction. To address this, we administered several drugs with proven efficacy in opioid hyperalgesia to rats presenting with haemodynamic hyper-reactivity. METHODS: The MACbar of sevoflurane was measured in controls and in animals treated with sufentanil 0.005 micro g kg(-1) min(-1) before and after administration of i.v. (0.25, 0.5 mg kg(-1)) and intrathecal (i.t.) (250 micro g) ketamine, i.v. (0.5, 1 mg kg(-1)) and i.t. (30 micro g) MK-801(NMDA antagonist), i.v. (0.1, 0.5 mg kg(-1)) naloxone, i.v. (10 mg kg(-1)) and i.t. (50, 100 micro g) ketorolac or i.t. (100, 150 micro g) meloxicam (COX-2 inhibitor). RESULTS: Sufentanil 0.005 micro g kg(-1) min(-1) significantly increased MACbar (3.2 (sd 0.3) versus 1.9 (0.3) vol%). With the exception of naloxone, all drugs displayed a significant MACbar-sparing effect (>50%) in controls. Naloxone completely prevented haemodynamic hyperactivity. Two patterns of reaction were recorded for the other drugs: either hyper-reactivity was suppressed and the MACbar-sparing effect was maintained (i.t. ketamine, i.t. MK-801, i.t. ketorolac [100 micro g], i.t. meloxicam [150 micro g]) or hyper-reactivity was blocked but MACbar-sparing effect was lost (i.v. ketamine [0.5 mg kg(-1)], i.v. MK-801 [0.5, 1 mg kg(-1)], i.v. ketorolac [10 micro g kg(-1)], i.t. ketorolac [50 micro g], i.t. meloxicam [100 micro g]). CONCLUSIONS: We have demonstrated that low-dose sufentanil-induced haemodynamic hyper-reactivity is an excitatory micro -opiate-related phenomenon. This effect is reversed by drugs effective in treating opiate-induced hyperalgesia.

Perioperative administration of the alpha2-adrenoceptor agonist clonidine at the site of nerve injury reduces the development of mechanical hypersensitivity and modulates local cytokine expression.

The development of chronic pain after surgery is not rare. Nerve injury from complete or partial nerve section during surgery leads to macrophage recruitment and release of pro-inflammatory cytokines, leading in turn to sensitization. Macrophages also express alpha2-adrenoceptors, and we previously demonstrated a prolonged reduction in hypersensitivity following peri-neural injection of the alpha2-adrenoceptor agonist, clonidine, in rats with chronic nerve injury. The current study tested whether peri-neural clonidine at the time of injury could also prevent development of hypersensitivity. Rats underwent partial ligation of one sciatic nerve, and peri-neural saline, clonidine or a combination of clonidine and the alpha2A-adrenceptor-preferring antagonist, BRL44408, were administered before wound closure and, in some animals, also 24 and 48 h later. The single clonidine injection reduced hypersensitivity for only 5 h, whereas repeated injection for three days reduced hypersensitivity for 28 days. Peri-neural clonidine reduced the increase in tissue content of the proinflammatory cytokines IL-1beta and particularly TNFalpha in sciatic nerve, DRG and spinal cord while increasing concentrations of the anti-inflammatory cytokine TGF-beta1. Clonidine's effects on behavior and TNFalpha content were blocked by BRL44408. We conclude that peri-neural administration of clonidine at the site and time of injury reduces the degree of hypersensitivity in part by altering the balance of pro- and anti-inflammatory cytokines through activation of alpha2A-adrenoceptors. These results support testing of whether clonidine, as an adjuvant in continuous peripheral nerve blocks in settings of known major nerve injury, such as limb amputation, might prevent the development of chronic pain.

Acute toxicity of local anesthetic ropivacaine and mepivacaine during a combined lumbar plexus and sciatic block for hip surgery.

Hip fracture is a common pathology in elderly patients. Intercurrent diseases, mainly cardiac and respiratory, often result in significant morbidity and mortality. Anesthesia for hip fracture can be provided by general or regional techniques. The combination of a lumbar plexus and posterior sciatic nerve block represents an alternative to neuraxial technique of anaesthesia such as spinal anesthesia (4, 6). We report a case of acute toxicity resulting in the injection of local anesthetics Ropivacaine and Mepivacaine in elderly patient. An elderly woman was scheduled for surgical repair of a fractured femur neck by dynamic hip screw synthesis. Anesthesia was realized by peripheral nerve bi-block (lumbar plexus and posterior sciatic block) (7). The patient experienced seizures and dysrhythmias twenty minutes after block completion and injection of the anesthetic solution [Ropivacaine 0.75%, administered for lumbar plexus block performed via the posterior approach (WINNIE) and Mepivacaine 1.5%, administered for posterior sciatic nerve block (LABAT)]. Cardiopulmonary resuscitation was successful. All signs of toxicity disappeared after injection of midazolam and atropine, intubation and 100% oxygen ventilation. We decided to proceed with surgery. The postoperative course was uncomplicated and made a full recovery.

Intrathecal ropivacaine and clonidine for ambulatory knee arthroscopy: a dose-response study.

BACKGROUND: The aim of this study was to evaluate the association of a small dose of intrathecal ropivacaine with small doses of intrathecal clonidine for ambulatory surgery. METHODS: One hundred twenty patients, classified as American Society of Anesthesiologists physical status I and scheduled for knee arthroscopy, were studied. Patients were randomly assigned to receive 4 ml of one of the following double-blinded isobaric intrathecal solutions: 8 mg of ropivacaine (group 1; n =30); 8 mg ropivacaine plus 15 microg clonidine (group 2; n =30); 8 mg ropivacaine plus 45 microg clonidine (group 3; n =30); and 8 mg ropivacaine plus 75 microg clonidine (group 4; n =30). The level and duration of sensory anesthesia were recorded, along with the intensity and duration of motor block. Patient and surgeon were interviewed to evaluate the quality of anesthesia. RESULTS: Intrathecal ropivacaine (8 mg alone) produced short sensory anesthesia and motor blockade (132 +/- 38 min and 110 +/- 35 min; mean +/- SD). However, the quality of anesthesia was significantly lower than in any other group (P < 0.05). Ropivacaine (8 mg) plus 75 microg clonidine produced significantly longer sensory and motor anesthesia (195 +/- 40 min and 164 +/- 38 min; P < 0.05). However, this was associated with systemic effects, such as sedation and reduction of arterial blood pressure. Ropivacaine (8 mg) plus 15 microg clonidine did not prolong sensory or motor blockade, afforded high quality anesthesia, and was not associated with detectable systemic effects. CONCLUSION: Small-dose intrathecal clonidine (15 microg) plus 8 mg intrathecal ropivacaine produces adequate and short-lasting anesthesia for knee arthroscopy.

Patient-controlled intravenous analgesia using remifentanil in the parturient.

PURPOSE: To show the use of the short acting opioid remifentanil for labour analgesia when epidural analgesia is considered to be contraindicated. CLINICAL FEATURES: After Ethics Committee approval and informed consent, six patients (36-40 wk gestation), in whom epidural analgesia was considered contraindicated (women refusing regional analgesia, presenting with coagulation or platelet abnormalities or sepsis) benefited from patient-controlled intravenous analgesia (PCIA) with remifentanil. The Abbott Lifecare patient-controlled analgesia (PCA) pump with remifentanil 50 microg x ml(-1) was set to deliver remifentanil continuous background infusion of 0.05 microg x kg(-1) x min(-1) and 25 microg boluses with a five minutes lockout period. The PCIA was started when the parturients experienced regular painful contractions (cervical dilatation of at least 4 cm) and stopped just before delivery (cervix fully dilated). Maternal monitoring included non-invasive blood pressure measurements, heart rate, percutaneous arterial oxyhemoglobin saturation and respiratory rate. Percutaneous fetal heart rate was continuously monitored. All patients remained alert or sleepy but easily arousable and were satisfied with their analgesia. No particular side effects have been noticed. Apgar scores were between 6 and 10. CONCLUSION: Remifentanil PCIA combining low continuous background infusion and small bolus doses is an alternative when epidural analgesia in labour is contraindicated. Under careful anesthesia monitoring, the technique seems to be safe for both mother and baby, at least when delivery occurs at or near the normal term of pregnancy.

The comparative toxicity of ropivacaine and bupivacaine at equipotent doses in rats.

We compared the toxicity of systemic local anesthetics bupivacaine and ropivacaine administered at equivalent and equipotent doses. In the first experiments, 18 male Wistar rats were anesthetized with thiopental and maintained under positive controlled ventilation. Electrocardiogram, electroencephalogram, and invasive arterial blood pressure were continuously recorded. The animals were randomly assigned to receive 3 mg x kg(-1) x min(-1) bupivacaine, 3 mg x kg(-1) x min(-1) ropivacaine IV (equivalent group), or 4.5 mg x kg(-1) x min(-1) ropivacaine (equipotent group). The timing of the occurrence of local anesthetic-induced toxic events (defined as the first QRS modification, dysrhythmia, seizures, moderate and severe bradycardia and hypotension, final systole) was recorded and the dose calculated. Eighteen additional rats, treated according to the same protocol were killed at the time of moderate, severe, and final hypotension for blood sampling and plasma bupivacaine and ropivacaine concentration measurement. In a third experiment, 15 awake rats (5 per group) received IV bupivacaine or ropivacaine (same infusion as in the first experiments) until seizure. At this moment, rats were allowed to recover from local anesthetic intoxication. In the first experiment, except for the first QRS modification, all the other toxic manifestations occurred at significantly larger doses (P<0.05) in the two ropivacaine groups in comparison to the bupivacaine group. In awake rats, all the animals intoxicated by ropivacaine easily recovered. In the bupivacaine group, two animals required cardiopulmonary resuscitation before any seizure activity could be detected, and only three rats survived. We conclude that, in the model used, ropivacaine, even at an equipotent dose, is less toxic than bupivacaine.

Ornipressin (Por 8): An efficient alternative to counteract hypotension during combined general/epidural anesthesia.

UNLABELLED: We sought to evaluate the efficacy and side effect profile of a small dose of ornipressin, a vasopressin agonist specific for the V1 receptor, administered to reverse the hypotension associated with combined general/epidural anesthesia. A total of 60 patients undergoing intestinal surgery were studied. After the induction of anesthesia, 7-8 mL of bupivacaine 0.5% with 2 microg/kg clonidine and 0.05 microg/kg sufentanil after an infusion of 5 mL of bupivacaine 0.06% with 0.5 microg x kg(-1) x h(-1) clonidine and 0.1 microg/h of sufentanil were administered by an epidural catheter placed at T7-8 vertebral interspace. When 20% reduction of baseline arterial blood pressure developed, patients were randomly assigned to receive, in a double-blinded design, dopamine started at 2 microg x kg(-1) x min(-1), norepinephrine started at 0.04 microg x kg(-1) x min(-1), or ornipressin started at 1 IU/h. Fifteen patients presenting without hypotension were used as control subjects. Beside routine monitoring, S-T segment analysis, arterial lactacidemia, and gastric tonometry were performed. Ornipressin restored arterial blood pressure after 8 +/- 2 vs 7 +/- 3 min in the norepinephrine group and 11 +/- 3 min in the dopamine group (P < 0.05). This effect was achieved with 2 IU/h of ornipressin in most of the patients (11 of 15). Ornipressin did not induce any modification of the S-T segment; however, it significantly increased intracellular gastric PCO(2) (P < 0.05), indicating splanchnic vasoconstriction. IMPLICATIONS: In the population studied, small-dose ornipressin was effective to restore arterial blood pressure without causing major ischemic side effects.

Antinociceptive and hemodynamic effects of a novel alpha2-adrenergic agonist, MPV-2426, in sheep.

BACKGROUND: alpha2-Adrenergic agonists produce analgesia primarily by a spinal action and hypotension and bradycardia by actions at several sites. Clonidine is approved for epidural use in the treatment of neuropathic pain, but its wider application is limited by hemodynamic side effects. This study determined the antinociceptive and hemodynamic effects of a novel alpha2-adrenergic agonist, MPV-2426, in sheep. METHODS: Forty sheep of mixed Western breeds with indwelling catheters were studied. In separate studies, antinociception to a mechanical stimulus, hemodynamic effects, arterial blood gas tensions, cerebrospinal fluid pharmacokinetics, and spinal cord blood flow was determined after epidural, intrathecal, and intravenous injection of MPV-2426. RESULTS: MPV-2426 produced antinociception with greater potency intrathecally (ED50 = 49 microg) than epidurally (ED50 = 202 microg), whereas intravenous administration had no effect. Intrathecal injection, in doses up to three times the ED95, failed to decrease systemic or central arterial blood pressures or heart rate, whereas larger doses, regardless of route, increased systemic arterial pressure. Bioavailability in cerebrospinal fluid was 7% after epidural administration and 0.17% after intravenous administration. Intrathecal MPV-2426, in an ED95 dose and three times this dose, produced a dose-independent reduction in thoracic and lumbar spinal cord blood flow. CONCLUSIONS: MPV-2426 shares many characteristics of other alpha2-adrenergic agonists examined in sheep, but differs from clonidine and dexmedetomidine by lack of antinociception and minimal reduction in oxygen partial pressure after large intravenous and epidural injections. No hemodynamic depression was observed after intrathecal injection at antinociceptive doses. These results suggest this compound may be an effective spinal analgesic in humans with less hypotension than clonidine, although its relative potency to cause sedation was not tested in this study.

Sex differences in cholinergic analgesia II: differing mechanisms in two models of allodynia.

BACKGROUND: Cholinergic agents reduce allodynia after nerve injury in animals and may be useful in the treatment of neuropathic pain. Intrathecally administered neostigmine and neuronal nicotinic agonists are more potent in female than in male rats against acute thermal noxious stimuli. The purpose of this study was to determine whether there is also a sex difference in the antiallodynic effects of intrathecal cholinomimetic agents in two models of allodynia and to test their pharmacologic mechanisms. METHODS: Male and female rats with indwelling intrathecal catheters received injections of neostigmine, bethanechol (muscarinic agonist), RJR-2403 (neuronal nicotinic agonist) alone or with atropine (muscarinic antagonist), mecamylamine (nicotinic antagonist), phentolamine (alpha-adrenergic antagonist), or saline control. The effect of these agents was determined on mechanical allodynia produced by either intraplantar injection of capsaicin or ligation of spinal nerves. RESULTS: Neostigmine and RJR-2403 but not bethanechol were more potent in female than in male rats in reducing allodynia after nerve injury, and antagonist studies were also consistent with a nicotinic component to explain this sex difference. Phentolamine did not reverse neostigmine's effect. In contrast, for capsaicin-induced allodynia, neostigmine plus mecamylamine but not neostigmine or RJR-2403 was more potent in female than in male rats. CONCLUSIONS: These data demonstrate a sex difference of intrathecal neostigmine after nerve injury-induced allodynia similar to that observed in normal animals that received acute noxious thermal stimulation. However, this sex difference is not universal to all pain models because it was not present after intradermal capsaicin injection, nor is its interaction with spinal noradrenergic mechanisms consistent in all models.

Adult liver transplantation: UCL experience.

OBJECTIVE: To evaluate the impact of standardized operative and peri-operative care on the outcome of liver transplantation in a single center series of 395 adult patients. METHOD AND MATERIAL: Between February 1984 and December 31, 1998, 451 orthotopic liver transplantations were performed in 395 adult patients (> or = 15 years) at the University Hospitals St-Luc in Brussels. Morbidity and mortality of the periods 1984-1990 (Gr I--174 pat.) and 1991-1998 were compared (Gr II--221 pat.). During the second period anti-infectious chemotherapy and perioperative care were standardized and surgical technique changed from classical orthotopic liver transplantation with recipients' vena cava resection (and use of veno-venous bypass) towards liver implantation with preservation of the vena cava (without use of bypass). Immunosuppression was cyclosporine based from 1984 up to 1996 and tacrolimus based during the years 1997 and 1998. Immunosuppression was alleviated during the second period due to change from quadruple to triple and even double therapy and due to the introduction of low steroid dosing and of steroid withdrawal, once stable graft function was obtained. Indications for liver grafting were chronic liver disease (284 pat--71.9%), hepatobiliary tumor (52 pat--13.2%), acute liver failure (40 pat--10.1%) and metabolic disease (19 pat--4.8%). Regrafting was necessary because of graft dysfunction (21 pat), technical failure (12 pat), immunological failure (18 pat) and recurrent viral allograft disease (5 pat); three of these patients were regrafted at another institution. Follow-up was complete for all patients with a minimum of 9 months. RESULTS: Actuarial 1, 5 and 10 years survival rates for the whole group were 77.9%, 65.7% and 58.3%. These survival rates were respectively 77.3%, 69.7%, 62.5% and 73.2%, 59.6% 51.4% for benign chronic liver disease and acute liver failure; those for malignant liver disease were 80.6%, 44.3% and 36.7%. Early (< 3 months) and late (> 3 months) posttransplant mortalities were. 14.4% (57 pat) and 21.2% (84 pat). Early mortality lowered from 20% in Gr I to 9.4% in Gr II (p < 0.02); this was due to a significant reduction during the second period of bacterial (99/174 pat.--56.9% vs 82/221 pat.--37.1%), fungal (14 pat.--8% vs 7 pat.--3.2%) and viral (87 pat.--50% vs 49 pat.--22.2%) infections (p < 0.05) as well as of perioperative bleeding (92 pat.--52.9% vs 39 pat.--17.6%--p < 0.001). Late mortality remained almost identical throughout the two periods as lethal outcome was mainly caused by recurrent allograft diseases, cardiovascular and tumor problems. Morbidity in these series was important considering that almost, half of the patients had a technical complication, mostly related to bleeding (131 pat--33.2%) and biliary problems (66 pat--16.7%). Retransplantation index was 1.1 (54 pat.--14%). Early retransplantation mortality was 24%; it lowered, although not yet significantly, during the second period (8/25 pat.--32% vs. 5/29 pat.--17.2%). CONCLUSION: Despite a marked improvement of results, liver transplantation remains a major medical and surgical undertaking. Standardization of operative and perioperative care, less haemorraghic surgery and less aggressive immunosuppression are the keys for further improvement.

Epidural clonidine or bupivacaine as the sole analgesic agent during and after abdominal surgery: a comparative study.

BACKGROUND: The rationale of this study was to compare high-dose epidural clonidine with a more commonly used agent, such as bupivacaine. This was performed to give a more objective idea of the relative analgesic potency of epidural clonidine. METHODS: Sixty patients undergoing intestinal surgery during propofol anesthesia were studied. At induction, the patients received epidurally a dose of 10 micrograms/kg [corrected] clonidine in 7 ml saline followed by an infusion of 6 micrograms [corrected] x kg(-1) x h(-1) (7 ml/h) (group 1, n = 20), a dose of 7 ml bupivacaine, 0.5%, followed by 7 ml/h bupivacaine, 0.25% (group 2, n = 20), or a dose of 7 ml bupivacaine, 0.25%, followed by 7 ml/h bupivacaine, 0.125% (group 3, n = 20). Intraoperatively, increases in arterial blood pressure or heart rate not responding to propofol (0.5 mg/kg) were treated with intravenous alfentanil (0.05 mg/kg). Additional doses of propofol were given to maintain an adequate bispectral index. The epidural infusions were maintained for 12 h. In cases of subjective visual analogue pain scores up to 5 cm at rest or up to 8 cm during coughing, the patients were given access to a patient-controlled analgesia device. RESULTS: During anesthesia, patients in group 1 required less propofol than those in groups 2 and 3 (78 [36-142] mg vs. 229 [184-252] mg and 362 [295-458] mg; P < 0.05) and less alfentanil than patients in group 3 (0 [0-0] mg vs. 11 [6-20] mg; P < 0.05). Analgesia lasted 380 min (range, 180-645 min) in group 1 versus 30 min (range, 25-40 min) in group 2 and 22 min (range, 12.5-42 min) in group 3 (P < 0.05). There was no suggestion of a hemodynamic difference among the three groups except for heart rates that were significantly reduced in patients in group 1. Sedation scores were significantly higher in this group during the first 2 h postoperatively. CONCLUSION: Our results show that high doses of epidural clonidine potentiate general anesthetics and provide more efficient postoperative analgesia than the two bupivacaine dosage regimens investigated.