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PURPOSE OF REVIEW: The management of postoperative pain after cesarean section slightly differs from that of the general surgical population, specifically women need to recover quickly to take care of their newborn baby. Optimal pain management is imperative for the success of immediate-term and long-term rehabilitation and this principle applies to obstetric patients. There is growing evidence that perioperative pain management has consequences extending well beyond the immediate recovery period. Unrelieved postoperative pain is a striking risk factor for the development of residual pain. RECENT FINDINGS: A recent study has highlighted that chronic pain may be a significant clinical problem after cesarean section. Among the risk factors, recalls of severe acute postoperative pain led to the reconsideration of postoperative pain management after cesarean delivery. Current published data agree that drug combinations, that is, multimodal or balanced analgesia, are mandatory to achieve satisfactory and effective pain relief with reduced side effects. SUMMARY: The use of balanced analgesia has significantly improved acute pain management after cesarean section. Future studies should extend their investigations beyond the first 48 h and consider the long-term effects of different analgesic regimens, that is, those that alter the development of residual pain. [ABSTRACT FROM AUTHOR]

PURPOSE OF REVIEW: The management of postoperative pain after cesarean section slightly differs from that of the general surgical population, specifically women need to recover quickly to take care of their newborn baby. Optimal pain management is imperative for the success of immediate-term and long-term rehabilitation and this principle applies to obstetric patients. There is growing evidence that perioperative pain management has consequences extending well beyond the immediate recovery period. Unrelieved postoperative pain is a striking risk factor for the development of residual pain.RECENT FINDINGS: A recent study has highlighted that chronic pain may be a significant clinical problem after cesarean section. Among the risk factors, recalls of severe acute postoperative pain led to the reconsideration of postoperative pain management after cesarean delivery. Current published data agree that drug combinations, that is, multimodal or balanced analgesia, are mandatory to achieve satisfactory and effective pain relief with reduced side effects.SUMMARY: The use of balanced analgesia has significantly improved acute pain management after cesarean section. Future studies should extend their investigations beyond the first 48 h and consider the long-term effects of different analgesic regimens, that is, those that alter the development of residual pain. [ABSTRACT FROM AUTHOR]

Purpose of Review: The acute inflammatory reaction induced by tissue trauma causes pain but also promotes recovery. Recovery is highly variable among peoples. Effective acute pain (AP) management is very important but remains suboptimal what could affect long term outcomes. The review questions the impact of either failure or effectiveness of AP treatments and the choice of analgesic drugs on different long-term outcomes after tissue trauma., Recent Findings: Pain control during mobilization is mandatory to reduce the risk of complications which exacerbate and prolong the inflammatory response to trauma, impairing physical recovery. Common analgesic treatments show considerable variability in effectiveness among peoples what argues for an urgent need to develop personalized AP management, that is, finding better responders to common analgesics and targeting challenging patients for more invasive procedures. Optimal multimodal analgesia to spare opioids administration remains a priority as opioids may enhance neuroinflammation, which underlies pain persistence and precipitates neurocognitive decline in frail patients. Finally, recent findings demonstrate that AP treatments which modulate nociceptive and inflammatory pain should be used with caution as drugs which inhibit inflammation like nonsteroidal antiinflammatory drugs and corticoids might interfere with natural recovery processes., Summary: Effective and safe AP management is of far greater importance than previously realized. Evidence of suboptimal AP management in many patients and recent reports pointing out the impact of current treatments on long term outcomes argue for further research in the field., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Chronic post-surgical pain (CPSP) prevalence has not changed over the past decades what questions the efficacy of preventive strategies. Regional analgesia is used to control acute pain, but preventive effect on CPSP remains debated. Failures and future application of regional analgesia to prevent transition from acute to chronic pain will be discussed., Recent Findings: After thoracotomy, perioperative regional analgesia does not seem to prevent CPSP. After breast cancer surgery, paravertebral block might prevent CPSP intensity and impact on daily life up to 12 months, particularly in high catastrophizing patients. In knee arthroplasty, perioperative regional analgesia or preoperative genicular nerve neuroablation do not prevent CPSP, although current studies present several bias. The protective role of effective regional analgesia and early pain relief in trauma patients deserves further studies., Summary: Regional analgesia failure to prevent CPSP development should prompt us to reconsider its perioperative utilization. Patients' stratification, for example high-pain responders, might help to target those who will most benefit of regional analgesia. The impact of regional analgesia on secondary pain-related outcomes such as intensity and neuropathic character despite no difference on CPSP incidence requires more studies. Finally, the preventive effect of regional analgesia targeted interventions on CPSP in patients suffering from severe subacute pain deserves to be assessed., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: The International Classification of Diseases-11 (ICD-11) chronic pain classification includes about 100 chronic pain diagnoses on different diagnostic levels. Each of these diagnoses requires specific operationalized diagnostic criteria to be present. The classification comprises more than 200 diagnostic criteria. The aim of the Classification Algorithm for Chronic Pain in ICD-11 (CAL-CP) is to facilitate the use of the classification by guiding users through these diagnostic criteria. The diagnostic criteria were ordered hierarchically and visualized in accordance with the standards defined by the Society for Medical Decision Making Committee on Standardization of Clinical Algorithms. The resulting linear decision tree underwent several rounds of iterative checks and feedback by its developers, as well as other pain experts. A preliminary pilot evaluation was conducted in the context of an ecological implementation field study of the classification itself. The resulting algorithm consists of a linear decision tree, an introduction form, and an appendix. The initial decision trunk can be used as a standalone algorithm in primary care. Each diagnostic criterion is represented in a decision box. The user needs to decide for each criterion whether it is present or not, and then follow the respective yes or no arrows to arrive at the corresponding ICD-11 diagnosis. The results of the pilot evaluation showed good clinical utility of the algorithm. The CAL-CP can contribute to reliable diagnoses by structuring a way through the classification and by increasing adherence to the criteria. Future studies need to evaluate its utility further and analyze its impact on the accuracy of the assigned diagnoses., (Copyright © 2021 International Association for the Study of Pain.)

Chronic pain is a major source of suffering. It interferes with daily functioning and often is accompanied by distress. Yet, in the International Classification of Diseases, chronic pain diagnoses are not represented systematically. The lack of appropriate codes renders accurate epidemiological investigations difficult and impedes health policy decisions regarding chronic pain such as adequate financing of access to multimodal pain management. In cooperation with the WHO, an IASP Working Group has developed a classification system that is applicable in a wide range of contexts, including pain medicine, primary care, and low-resource environments. Chronic pain is defined as pain that persists or recurs for more than 3 months. In chronic pain syndromes, pain can be the sole or a leading complaint and requires special treatment and care. In conditions such as fibromyalgia or nonspecific low-back pain, chronic pain may be conceived as a disease in its own right; in our proposal, we call this subgroup "chronic primary pain." In 6 other subgroups, pain is secondary to an underlying disease: chronic cancer-related pain, chronic neuropathic pain, chronic secondary visceral pain, chronic posttraumatic and postsurgical pain, chronic secondary headache and orofacial pain, and chronic secondary musculoskeletal pain. These conditions are summarized as "chronic secondary pain" where pain may at least initially be conceived as a symptom. Implementation of these codes in the upcoming 11th edition of International Classification of Diseases will lead to improved classification and diagnostic coding, thereby advancing the recognition of chronic pain as a health condition in its own right.

The upcoming 11th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD) of the World Health Organization (WHO) offers a unique opportunity to improve the representation of painful disorders. For this purpose, the International Association for the Study of Pain (IASP) has convened an interdisciplinary task force of pain specialists. Here, we present the case for a reclassification of nervous system lesions or diseases associated with persistent or recurrent pain for ≥3 months. The new classification lists the most common conditions of peripheral neuropathic pain: trigeminal neuralgia, peripheral nerve injury, painful polyneuropathy, postherpetic neuralgia, and painful radiculopathy. Conditions of central neuropathic pain include pain caused by spinal cord or brain injury, poststroke pain, and pain associated with multiple sclerosis. Diseases not explicitly mentioned in the classification are captured in residual categories of ICD-11. Conditions of chronic neuropathic pain are either insufficiently defined or missing in the current version of the ICD, despite their prevalence and clinical importance. We provide the short definitions of diagnostic entities for which we submitted more detailed content models to the WHO. Definitions and content models were established in collaboration with the Classification Committee of the IASP's Neuropathic Pain Special Interest Group (NeuPSIG). Up to 10% of the general population experience neuropathic pain. The majority of these patients do not receive satisfactory relief with existing treatments. A precise classification of chronic neuropathic pain in ICD-11 is necessary to document this public health need and the therapeutic challenges related to chronic neuropathic pain.

Chronic pain after tissue trauma is frequent and may have a lasting impact on the functioning and quality of life of the affected person. Despite this, chronic postsurgical and posttraumatic pain is underrecognised and, consequently, undertreated. It is not represented in the current International Classification of Diseases (ICD-10). This article describes the new classification of chronic postsurgical and posttraumatic pain for ICD-11. Chronic postsurgical or posttraumatic pain is defined as chronic pain that develops or increases in intensity after a surgical procedure or a tissue injury and persists beyond the healing process, ie, at least 3 months after the surgery or tissue trauma. In the classification, it is distinguished between tissue trauma arising from a controlled procedure in the delivery of health care (surgery) and forms of uncontrolled accidental damage (other traumas). In both sections, the most frequent conditions are included. This provides diagnostic codes for chronic pain conditions that persist after the initial tissue trauma has healed and that require specific treatment and management. It is expected that the representation of chronic postsurgical and posttraumatic pain in ICD-11 furthers identification, diagnosis, and treatment of these pain states. Even more importantly, it will make the diagnosis of chronic posttraumatic or postsurgical pain statistically visible and, it is hoped, stimulate research into these pain syndromes.

Purpose of Review: Regional anesthesia is popular in ambulatory setting allowing safe and fast recovery. The problem of 'rebound pain', that is very severe pain when peripheral nerve block (PNB) wears off represents a clinically relevant problem and a cause of increased healthcare resource utilization. This review tries to make the point on a not so rare, unwanted and often neglected side effect of PNB., Recent Findings: The major finding is the lack of large prospective studies. Incidence of rebound pain is unknown but could reach 40% of patients at PNB resolution. To date, pathophysiological mechanisms remain debated: mechanical and chemical (proinflammatory effect of local anesthetics) nerve insult caused by PNB in predisposed patients (with severe preoperative pain, younger patients). Effective preventive strategies also are missing (e.g. role of analgesic adjuvants in PNB). Long-term consequences in term of functional recovery and persistent pain have not been demonstrated. Interview of patients has underlined the need of information and education about PNB and postoperative analgesia., Summary: Patients' report of excruciating pain and major distress when PNB wears off questions the quality of current anesthesia practice in ambulatory setting. Rebound pain unanswered questions are challenging in the area of perioperative medicine.

Purpose of Review: In the past two decades, opioids have been prescribed increasingly for the treatment of various chronic pain conditions and during the perioperative period. Perioperative opioid administration is associated with well known adverse effects and recently to long-term use and poor surgical outcomes. In this context, the anesthesiologists have to face their responsibilities. The review discusses the neurophysiological basis of opioid-free anesthesia (OFA), the rational supporting its use in perioperative medicine as well as barriers and future challenges in the field., Recent Findings: OFA has gained in popularity as a way to enhance early recovery and to spare opioids for the postoperative period. Whether it is possible to deliver safe and stable anesthesia without intraoperative opioids to many patients undergoing various surgical procedures, OFA still raises questions. Accurate monitoring to measure intraoperative nociception and guide the use of adjuvants are not available. There is a need for the development of procedure-specific strategies as well as indications and contraindications to the technique. Finally, objective assessment of OFA use on patient outcomes should be recorded in large multicenter studies., Summary: OFA stands as a new paradigm, which questions anesthesiology practice and might help to rationalize perioperative opioids use.

Purpose of Review: Cesarean section is the most common surgical procedure performed in the world. Postoperative pain management remains a challenge, particularly in a context of enhanced recovery after surgery. Several barriers related to the specific condition of 'postpartum recovery' may prevent application of effective analgesia in this population. The present review focuses on novel approaches of cesarean section postoperative pain assessment, beyond pain-rating intensity, including objective patient-centered recovery parameters. Predictive tools currently available to target patients at high risk of acute and chronic pain are also examined., Recent Findings: Postoperative pain after cesarean section is more severe than reported in the majority of randomized control trials. Pain seriously interferes with early and also late functional recovery, although Enhanced Recovery after Surgery (ERAS) programmes are being promoted. Pain-rating scores can differ from scores of physical comfort and physical independence, which are priorities for postpartum patients. Further, the value of subjective pain intensity rating to adapt analgesic prescription is misleading and may promote opioid over-prescription. Available tools to predict at-risk patients for severe pain after cesarean section are not easy to use in daily clinical practice and have, at best, moderate predictive value., Summary: Patient and healthcare provider education on reported pain and well tolerated analgesic use is the key to improve postpartum pain management after cesarean section.

Purpose of Review: Although childbirth is considered a natural event, some deliveries may necessitate instrumentation or surgical intervention. In contrast with trauma or surgery, persistent pain after delivery has received little attention until recently, despite the large number of individuals potentially at risk., Recent Findings: Excluding pre-existing pain or pain that developed during pregnancy, prospective studies show a surprisingly low prevalence of persistent pain after childbirth, much lower than the prevalence reported in retrospective studies and that of persistent postsurgical pain in a general population for similar procedures. The nature of persistent pain itself remains poorly characterized; the chronic pain following caesarean delivery appears to be predominantly neuropathic, but the intensity is generally lower than usually reported for other types of chronic neuropathic pain. Finally, the type of delivery and the degree of tissue trauma do not seem to impact the risk of developing persistent pain. It is unclear whether individual factors place specific women at a risk for persistent pain. Experimental study suggests that protective mechanisms against the development of neuropathic pain may be active during the puerperium, but whether these mechanisms exist following human childbirth remains unknown., Summary: Some recent findings on the development of persistent pain after childbirth are intriguing and might open the way to interesting perspectives for the treatment of persistent pain caused by trauma or surgery.

Background: Chronic pain after surgery occurs in 10-40% of individuals, including 5-20% of women after cesarean delivery in previous reports. Pain and depression 2 months after childbirth are independently associated with more severe acute post-delivery pain. Here we examine other predictors of pain at 2 months and determine the incidence of pain at 6 and 12 months after childbirth., Methods: Following Institutional Review Board approval, 1228 women were interviewed within 36 h of delivery. Of these, 937 (76%) were successfully contacted by telephone at 2 months, and, if they had pain, at 6 and 12 months after delivery. The primary outcome measure was presence of pain which began at the time of delivery. We also generated a model of severity of acute post-delivery pain and 2 month pain and depression., Results: Pain which began at the time of delivery was remarkably rare 6 and 12 months later (1.8% and 0.3% [upper 95% confidence limit, 1.2%], respectively). Past history of pain and degree of tissue damage at delivery accounted for 7.0% and 16.7%, respectively, of one aspect in the variability in acute post-delivery pain. Neither of these factors was associated with incidence of pain 2 months later., Conclusions: Using a definition of new onset pain from delivery, we show a remarkably low incidence of pain 1 yr after childbirth, including those with surgical delivery. Additionally, degree of tissue trauma and history of chronic pain, risk factors for pain 2 months after other surgery, were unimportant to pain 2 months after cesarean or vaginal delivery.

Purpose of Review: The persistence of pain after surgical procedure or trauma has become a major focus of interest and its prevention now represents a challenge as an indicator of quality of healthcare. The only way to develop effective strategies to prevent the development of chronic pain is to better understand the mechanisms involved in the progression from acute to chronic pain, with the aim to target high-risk patients and to adapt perioperative management., Recent Findings: Several important risk factors involved in chronic pain development after tissue injury have been identified, underlining how much the phenomenon is complex and multifaceted. Recent studies have highlighted some important points on which to focus, mainly during the acute and subacute postinjury periods. These studies promote a more dynamic approach related to a better evaluation of acute pain resolution using individualized pain trajectories, the assessment of endogenous pain-modulatory processes and individual's psychological flexibility when facing physical threat and pain., Summary: A dynamic view of both physiological and psychological response of an individual after injury (trauma, surgery) should improve our ability to target predisposed patients who might develop persistent pain. We should then be more able to provide those patients with the most appropriate preventive management.

Cesarean delivery rates continue to increase, and surgery is associated with chronic pain, often co-existing with depression. Also, acute pain in the days after surgery is a strong predictor of chronic pain. Here we tested if mode of delivery or acute pain played a role in persistent pain and depression after childbirth. In this multicenter, prospective, longitudinal cohort study, 1288 women hospitalized for cesarean or vaginal delivery were enrolled. Data were obtained from patient interviews and medical record review within 36 h postpartum, then via telephone interviews 8 weeks later to assess persistent pain and postpartum depressive symptoms. The impact of delivery mode on acute postpartum pain, persistent pain and depressive symptoms and their interrelationships was assessed using regression analysis with propensity adjustment. The prevalence of severe acute pain within 36 h postpartum was 10.9%, while persistent pain and depression at 8 weeks postpartum were 9.8% and 11.2%, respectively. Severity of acute postpartum pain, but not mode of delivery, was independently related to the risk of persistent postpartum pain and depression. Women with severe acute postpartum pain had a 2.5-fold increased risk of persistent pain and a 3.0-fold increased risk of postpartum depression compared to those with mild postpartum pain. In summary, cesarean delivery does not increase the risk of persistent pain and postpartum depression. In contrast, the severity of the acute pain response to childbirth predicts persistent morbidity, suggesting the need to more carefully address pain treatment in the days following childbirth.

Purpose of Review: Incisional pain remains underevaluated and undermanaged while evidence is growing that perioperative treatments strongly influence patients' outcome. The present review examines the recent developments in mechanisms underlying perioperative pain and questions current understanding of incisional pain features observed in patients., Recent Findings: Experimental models of incisional pain have highlighted specific mechanisms underlying perioperative pain plasticity, i.e. sensitization of sensory processing, clinically expressed by the development of hyperalgesia. In patients, however, the long-term impact of sensory system sensitization, e.g. development of residual pain, as well as the effects of perioperative pain management on sensitization, are still poorly understood, partly because most of the trials assess only the subjective experience of pain (by evaluation of either pain intensity or analgesic needs) instead of directly measuring objective changes (i.e. hyperalgesia) with quantitative sensory testing., Summary: Experimental studies and recent clinical trials using objective measures of sensory processing sensitization induced by surgical incision have shown the importance of hyperalgesia in perioperative pain. Effective perioperative block of nociceptive inputs from the wound as well as use of antihyperalgesic and analgesic drugs in combination seem the best way to control postoperative pain and specifically to prevent central sensitization.

Background: As a broader definition of preemptive analgesia, preventive analgesia aims to prevent the sensitization of central nervous system, hence the development of pathologic pain after tissular injury. To demonstrate benefits from preventive treatment, objective measurement of postoperative pain such as wound hyperalgesia and persistent pain should be evaluated. The current study assessed the role and timing of epidural analgesia in this context., Methods: In a randomized, double-blinded trial, 85 patients scheduled to undergo neoplastic colonic resection were included. All the patients received a thoracic epidural catheter, systemic ketamine at a antihyperalgesic dose, and general anesthesia. Continuous infusion of analgesics belonging to the same class was administered by either intravenous or epidural route before incision until 72 h after surgery. Patients were allocated to four groups to receive intraoperative intravenous lidocaine-sufentanil-clonidine or epidural bupivacaine-sufentanil-clonidine followed postoperatively by either intravenous (lidocaine-morphine-clonidine) or epidural (bupivacaine-sufentanil-clonidine) patient-controlled analgesia. Postoperative pain scores (visual analog scale), analgesic consumption, wound area of punctuate hyperalgesia, residual pain, and analgesics needed from 2 weeks until 12 months were recorded., Results: Analgesic requirements, visual analog scale scores, and area of hyperalgesia were significantly higher in the intravenous treatment group (intravenous-intravenous), and more patients reported residual pain from 2 weeks until 1 yr (28%). Although postoperative pain measurements did not differ, postoperative epidural treatment (intravenous-epidural) was less effective to prevent residual pain at 1 yr (11%; P = 0.2 with intravenous-intravenous group) than intraoperative one (epidural-epidural and epidural-intravenous groups) (0%; P = 0.01 with intravenous-intravenous group)., Conclusion: Combined with an antihyperalgesic dose of ketamine, intraoperative epidural analgesia provides effective preventive analgesia after major digestive surgery.

Unlabelled: In this study, we investigated the antihyperalgesic effect of clonidine after surgery. Sixty patients undergoing right colic resection were studied. Patients were randomized to receive prior to general anesthesia a 2-mL intrathecal (IT) injection of 300 microg of clonidine or saline, or 10 mg of bupivacaine. General anesthesia was achieved using a target concentration propofol infusion and monitored using bispectral index. Postoperative analgesia was provided by morphine IV given through a patient-controlled analgesia device. Postoperative analgesia was assessed by morphine requirements and visual analog scale pain scores at rest, cough, and movement during the first 72 h. Mechanical hyperalgesia was measured by von Frey filaments. Patients were questioned regarding residual pain at 2 wk,1, 6, and 12 mo. The patient-controlled analgesia morphine requirements were significantly smaller in the IT clonidine group (31.5 +/- 12 versus 91 +/- 25.5 and 43 +/- 15 mg, respectively, in groups clonidine, saline, and bupivacaine: P < 0.05 at 72 postoperative hours). The area of hyperalgesia at 72 h was 3 +/- 5 cm(2) in the clonidine group versus 90 +/- 30 and 35 +/- 20 cm(2) in the saline and bupivacaine groups (P < 0.05). At 6 mo, fewer patients in the clonidine group experienced residual pain than in the saline group (0 of 20 versus 6 of 20, P < 0.05). We conclude that both intraoperative spinal clonidine and bupivacaine improve immediate postoperative analgesia. IT clonidine was, however, more potent than IT bupivacaine to reduce postoperative secondary hyperalgesia., Implications: Spinal clonidine contributes to the reduction of secondary hyperalgesia in patients recovering from abdominal surgery.

Unlabelled: We intended to evaluate the reliability of the minimum anesthetic alveolar concentration (MAC)-sparing effect as an objective measure of the antinociceptive properties of a drug. For this purpose, we tested different variables and analyzed the significance of the results obtained. In a first set of experiments, we studied rats under mechanical ventilation and sevoflurane anesthesia. Outcome variables such as gross purposeful movements consecutive to tail clamping, paw withdrawal consecutive to increasing pressure, and cardio-circulatory reactivity (MACBAR) after these stimuli were recorded. In a second set of experiment, sevoflurane-anesthetized rats under spontaneous breathing conditions were used. Thermal stimuli were compared with pressure. The MAC-sparing effect of several doses of sufentanil and clonidine was evaluated in both anesthetized and awake rodents. When considering the stimulus applied, larger concentrations of sevoflurane were required to suppress reactivity after tail clamp than after paw pressure or radiant heat (1.81 +/- 0.28 versus 1.45 +/- 0.22 and 1.53 +/- 0.26; P < 0.05). For the two first stimuli, no significant differences were noted between the concentrations that suppress motor or cardio-circulatory reactions. All doses of sufentanil tested significantly reduced (P < 0.05) the different MAC values except the smallest one (0.005 micro g x kg(-1) x min(-1)) that significantly increased MACBAR in ventilated animals and both MAC and MACBAR in spontaneously breathing rodents (P < 0.05). Clonidine, at its optimal dose (10 micro g/kg), significantly reduced both MAC and MACBAR to the same degree. In awake animals submitted to radiant heat or pressure challenge, none of the clonidine doses nor sufentanil doses (0.005 and 0.07) were active. In conclusion, the MAC-sparing effect provides several reliable and quantifiable variables that allow comparison between different analgesic substances. However, the observations made are not simply the result of antinociceptive effects of the tested drugs but rather that of complex interactions between these drugs and a halogenated vapor., Implications: The MAC-sparing effect provides several variables that allow comparison between different analgesic substances. However, the observations made are not simply the result of the antinociceptive effects of the tested drugs but rather the result of complex interactions between these drugs and a halogenated vapor.

Unlabelled: Spinal neostigmine produces analgesia without respiratory depression or hypotension but provokes major gastrointestinal side effects. Epidural injection of this drug, however, appears to induce analgesia devoid of such side effects. In this study, we evaluated the effect of a bolus of epidural neostigmine on the duration and magnitude of analgesia in early labor and assessed its eventual sparing effect on subsequent local anesthetic requirements. Epidural neostigmine methylsulfate (maximal dose 4 microg/kg) was added to 10 mL of ropivacaine 0.1%, with and without sufentanil 10 microg, to initiate analgesia. Twenty minutes after injection, pain score, sensory level, and motor block were assessed. Time until request for supplemental epidural medication was also recorded. Patient-controlled epidural analgesia with ropivacaine 0.1% was used for epidural supplementation. Maternal and fetal side effects were closely recorded. Neostigmine (4 microg/kg), when added to ropivacaine 10 mg, provided equivalent analgesia to ropivacaine 20 mg but was less effective than sufentanil 10 microg for the initiation of labor epidural analgesia. Further, neostigmine did not modify the subsequent patient-controlled epidural analgesia local anesthetic requirements during labor. No hemodynamic instability, additional motor block, or bothersome side effects were recorded., Implications: The combination of epidural neostigmine (4 microg/kg) with the local anesthetic ropivacaine, with or without sufentanil, does not significantly enhance neuraxial analgesia during labor. Such a dose, however, has no bothersome side effects.

Unlabelled: We evaluated the central or spinal mechanism involved in the MACbar-sparing effect of systemic clonidine by using intrathecal alpha-adrenergic antagonist administration. The minimum alveolar concentration of sevoflurane that blocks cardiovascular response to a noxious stimulus (MACbar(sevo)) was determined in rats after treatment with IV saline, IV clonidine 10 micro g/kg, intrathecal (IT) or IV phentolamine 50 micro g, IT or IV yohimbine 200 micro g, IT or IV prazosin 30 micro g, or the combination of IV clonidine and the different IT or IV alpha-adrenergic antagonists. In the studied model, the MACbar(sevo) of saline-treated controls was 2.10 +/- 0.8. After clonidine administration, it decreased to 1.07 +/- 0.4. The IT administration of phentolamine and yohimbine did not modify the MACbar(sevo) of naïve rats, whereas in IV clonidine-treated animals, it totally suppressed the MAC-sparing effect of this drug (phentolamine) or even significantly increased (yohimbine) the MACbar(sevo) (2.78 +/- 1) when compared with controls (P < 0.05). IT prazosin alone significantly reduced the MACbar(sevo) (0.35 +/- 0.3; P< 0.05) and suppressed any hemodynamic reaction when combined with IV clonidine. The IV administration of the different alpha-adrenergic antagonists had no significant effect on the MACbar(sevo) of controls or IV clonidine-treated animals. These results argue for a spinal mechanism of action involved in the MACbar-sparing effect of systemic clonidine. Moreover, the spinally administered alpha-antagonists displayed different effects in rats under sevoflurane anesthesia than those reported in awake animals., Implications: Using intrathecal alpha-adrenergic antagonist administration, we demonstrated that a spinal mechanism is involved in the MACbar-sparing effect of systemic clonidine in rats.

We investigated whether intraoperative 'subanesthetic doses' of ketamine have a postoperative anti-hyperalgesic and an analgesic effect and which is the preferential route of administration, either systemic (intravenous, i.v.) or epidural. One hundred patients scheduled for rectal adenocarcinoma surgery under combined epidural/general anesthesia were included. Before skin incision all the patients received an epidural bolus followed by an infusion of continuous bupivacaine/sufentanil/clonidine mixture. They were randomly assigned to receive no ketamine (group 1), i.v. ketamine at the bolus dose of 0.25 mg/kg followed by an infusion of 0.125 mg/kg per h (group 2), 0.5 mg/kg and 0.25 mg/kg per h (group 3), epidural ketamine 0.25 mg/kg and 0.125 mg/kg per h (group 4), or 0.5 mg/kg and 0.25 mg/kg per h (group 5). All i.v. and epidural analgesics were stopped at the end of surgery and patients were connected to an i.v. morphine patient-controlled analgesia (PCA) device. Short-term postoperative analgesia (72 h) was assessed by pain visual analog scale scores at rest, cough, and movements as well as by PCA requirements. Wound mechanical hyperalgesia was evaluated and residual pain was assessed by asking the patients at 2 weeks, and 1, 6, and 12 months. The area of hyperalgesia and morphine PCA requirements were significantly reduced in group 3. These patients reported significantly less residual pain until the sixth postoperative month. These observations support the theory that subanesthetic doses of i.v. ketamine (0.5 mg/kg bolus followed by 0.25 mg/kg per h) given during anesthesia reduce wound hyperalgesia and are a useful adjuvant in perioperative balanced analgesia. Moreover, they show that the systemic route clearly is the preferential route.

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.

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.

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.

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.

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.

Introduction: Pain resulting from a usually nonpainful stimulus (allodynia) is a common characteristic of neuropathic pain. Among animal models of allodynia, tight ligature of lumbar spinal nerves has been of special interest because it has been reported to be relieved by sympathectomy. The purpose of this study was to determine whether spinal analgesic agents, which have opposite effects on sympathetic nervous system activity (clonidine decreases it and neostigmine increases it), have differing efficacy in this model., Methods: Male Sprague-Dawley rats were anesthetized, and the left L5 and L6 spinal nerves were ligated. At least 2 weeks later, a lumbar intrathecal or jugular intravenous catheter was inserted. Withdrawal threshold to mechanical stimulation of the hind paw was determined by application of von Frey filaments before surgery; after surgery; after intrathecal injection of clonidine, neostigmine, or their combination; after intravenous injection of phentolamine or guanethidine; and after surgical sympathectomy., Results: Spinal nerve ligation reduced withdrawal threshold ipsilateral to the lesion. This allodynia was relieved by clonidine (50% block of allodynia at 20+/-1.2 microg and neostigmine (50% block of allodynia at 2+/-0.1 microg, and they interacted synergistically to block allodynia. Neither chemical nor surgical sympathectomy altered allodynia., Discussion: These results disagree with previous observations that mechanical allodynia in this animal model depends on sympathetic nervous system activity. Therefore, intrathecally administered analgesic agents, one that reduces sympathetic outflow from the spinal cord (clonidine) and one that increases it (neostigmine), were similarly effective in this model.