Pain management after elective craniotomy: A systematic review with procedure-specific postoperative pain management (PROSPECT) recommendations.

BACKGROUND: Pain after craniotomy can be intense and its management is often suboptimal. OBJECTIVES: We aimed to evaluate the available literature and develop recommendations for optimal pain management after craniotomy. DESIGN: A systematic review using procedure-specific postoperative pain management (PROSPECT) methodology was undertaken. DATA SOURCES: Randomised controlled trials and systematic reviews published in English from 1 January 2010 to 30 June 2021 assessing pain after craniotomy using analgesic, anaesthetic or surgical interventions were identified from MEDLINE, Embase and Cochrane Databases. ELIGIBILITY CRITERIA: Each randomised controlled trial (RCT) and systematic review was critically evaluated and included only if met the PROSPECT requirements. Included studies were evaluated for clinically relevant differences in pain scores, use of nonopioid analgesics, such as paracetamol and NSAIDs, and current clinical relevance. RESULTS: Out of 126 eligible studies identified, 53 RCTs and seven systematic review or meta-analyses met the inclusion criteria. Pre-operative and intra-operative interventions that improved postoperative pain were paracetamol, NSAIDs, intravenous dexmedetomidine infusion, regional analgesia techniques, including incision-site infiltration, scalp nerve block and acupuncture. Limited evidence was found for flupirtine, intra-operative magnesium sulphate infusion, intra-operative lidocaine infusion, infiltration adjuvants (hyaluronidase, dexamethasone and α-adrenergic agonist added to local anaesthetic solution). No evidence was found for metamizole, postoperative subcutaneous sumatriptan, pre-operative oral vitamin D, bilateral maxillary block or superficial cervical plexus block. CONCLUSIONS: The analgesic regimen for craniotomy should include paracetamol, NSAIDs, intravenous dexmedetomidine infusion and a regional analgesic technique (either incision-site infiltration or scalp nerve block), with opioids as rescue analgesics. Further RCTs are required to confirm the influence of the recommended analgesic regimen on postoperative pain relief.

Pain management after total knee arthroplasty: PROcedure SPEcific Postoperative Pain ManagemenT recommendations.

BACKGROUND: The PROSPECT (PROcedure SPEcific Postoperative Pain ManagemenT) Working Group is a global collaboration of surgeons and anaesthesiologists formulating procedure-specific recommendations for pain management after common operations. Total knee arthroplasty (TKA) is associated with significant postoperative pain that is difficult to treat. Nevertheless, pain control is essential for rehabilitation and to enhance recovery. OBJECTIVE: To evaluate the available literature and develop recommendations for optimal pain management after unilateral primary TKA. DESIGN: A narrative review based on published systematic reviews, using modified PROSPECT methodology. DATA SOURCES: A literature search was performed in EMBASE, MEDLINE, PubMed and Cochrane Databases, between January 2014 and December 2020, for systematic reviews and meta-analyses evaluating analgesic interventions for pain management in patients undergoing TKA. ELIGIBILITY CRITERIA: Each randomised controlled trial (RCT) included in the selected systematic reviews was critically evaluated and included only if met the PROSPECT requirements. Included studies were evaluated for clinically relevant differences in pain scores, use of nonopioid analgesics, such as paracetamol and nonsteroidal anti-inflammatory drugs and current clinical relevance. RESULTS: A total of 151 systematic reviews were analysed, 106 RCTs met PROSPECT criteria. Paracetamol and nonsteroidal anti-inflammatory or cyclo-oxygenase-2-specific inhibitors are recommended. This should be combined with a single shot adductor canal block and peri-articular local infiltration analgesia together with a single intra-operative dose of intravenous dexamethasone. Intrathecal morphine (100 µg) may be considered in hospitalised patients only in rare situations when both adductor canal block and local infiltration analgesia are not possible. Opioids should be reserved as rescue analgesics in the postoperative period. Analgesic interventions that could not be recommended were also identified. CONCLUSION: The present review identified an optimal analgesic regimen for unilateral primary TKA. Future studies to evaluate enhanced recovery programs and specific challenging patient groups are needed.

Pain trajectories identify patients at risk of persistent pain after knee arthroplasty: an observational study.

BACKGROUND: Persistent postsurgical pain is a major source of dissatisfaction after knee arthroplasty. Postoperative pain trajectories allow a dynamic view of pain resolution after surgery and might help to identify patients at risk for persistent pain. QUESTIONS/PURPOSES: In this prospective observational study, we examined the relationship between postoperative pain trajectories and persistent pain, specifically neuropathic pain, at 3 months after knee arthroplasty. METHODS: Over a 1-year period, all patients undergoing elective unilateral knee arthroplasty for osteoarthritis by one surgeon were invited to participate in the study, provided they had not had prior knee surgery and their American Society of Anesthesiologists grade was 3 or lower; 128 patients fulfilled these criteria. Patients filled in a diary questioning postoperative pain at rest and during mobilization and maximal pain from Day 1 until Day 8 after surgery. At 3 months, the patients were questioned concerning the presence of persistent pain and its nature and intensity using the Douleur Neuropathique 4 [Neuropathic Pain 4] and Brief Pain Inventory questionnaires. At 3 months, 112 of the 128 patients (87%) were successfully contacted. RESULTS: At 3 months, 47 of the 112 (42%) patients were totally pain free and 65 (58%) reported persistent pain at the surgical site. Among the latter, 12 patients (11%) presented with a neuropathic component and more severe persistent pain. Pain trajectories highlighted higher acute pain scores for maximal pain (from Day 1 until Day 8) and for pain at mobilization (from Day 3 until Day 8) in patients with neuropathic persistent pain (p < 0.05 at all time points compared with the no persistent pain group). CONCLUSIONS: Postoperative pain trajectories constructed from patient's pain diary suggest that a subgroup of patients who will present with higher pain at 3 months after knee arthroplasty might be identified early in the postoperative period and might benefit from preventative treatment. LEVEL OF EVIDENCE: Level III, diagnostic study. See Instructions for Authors for a complete description of levels of evidence.

Evaluation of pregabalin as an adjuvant to patient-controlled epidural analgesia during late termination of pregnancy.

INTRODUCTION: Late termination of pregnancy combines psychological distress with severe physical pain. The present study evaluated the benefit of adding oral pregabalin to epidural analgesia during this procedure. METHODS: Healthy women were randomly allocated to receive either oral pregabalin 150 mg/12 h or prazepam 10 mg/12 h at the induction of the late termination of pregnancy procedure. When they felt abdominal pain (numerical rating scale ranging from 0 [no pain] to 100 [worst pain possible]), patient-controlled epidural analgesia was activated and set to deliver ropivacaine 0.1% with sufentanil 0.25 µg/ml, 5 ml/h with a bolus dose of 5 ml/30 min. Rescue analgesia was available as needed by administration of 10 ml ropivacaine 0.1% (pain score less than 60/100) or 0.2% (at least 60/100). The primary outcome was the consumption of epidural analgesics. RESULTS: Forty-eight patients participated in the study. Demographic and obstetric data were similar. Pregabalin reduced total ropivacaine consumption 11.3 ± 3.2 mg/h (mean ± SD) versus 15.1 ± 4.9 mg/h in the prazepam group (P = 0.005), an effect related to a decrease in the need for rescue analgesia. In the pregabalin group, fewer women asked for rescue dose (75 vs. 96%; P = 0.048), and the number of rescue doses per patient was reduced (1 [0-2] vs. 2 [1-3]); median [interquartile range], P = 0.005), particularly the need for ropivacaine 0.2%. DISCUSSION: This is the first study considering the use of pregabalin for labor pain associated with late termination of pregnancy, showing that pregabalin 150 mg/12 h is a helpful adjuvant to epidural analgesia. Modulation of both visceral sensitization and affective component of pain may contribute to the benefits observed.

An evaluation of the postoperative antihyperalgesic and analgesic effects of intrathecal clonidine administered during elective cesarean delivery.

BACKGROUND: Intrathecal clonidine improves intraoperative anesthesia and postoperative analgesia after cesarean delivery. Clonidine also possesses antihyperalgesic properties. Hyperalgesia contributes to postoperative pain and may be associated with increased risk of chronic pain after surgery. In this study, we evaluated the postoperative antihyperalgesic effect of intrathecal clonidine after caesarean delivery. METHODS: Ninety-six parturients undergoing elective cesarean delivery were randomly assigned to receive intrathecal bupivacaine-sufentanil (BS group), bupivacaine-sufentanil-clonidine 75 microg (BSC group), or bupivacaine-clonidine 150 microg (BC group). The primary outcome was the extent and the incidence of periincisional punctate mechanical hyperalgesia as assessed by response to application of a von Frey filament at 24 and 48 h after cesarean delivery. Postoperative morphine requirements and pain scores, as well as residual pain at 1, 3, and 6 mo, were also assessed. RESULTS: The BC group had a significantly reduced area of periincisional hyperalgesia at 48 h (median, 25th-75th percentiles): 1.0 (1.0 - 3.3) cm(2) vs 9.5 (5.0-14.0) cm(2) in the BS group vs 5.0 (2.5-12.3) cm(2) in the BSC group (P = 0.02 with the BS group). The incidence of hyperalgesia at 48 h was also lower in the BC group: 16% vs 41% in the BS group vs 34% in the BSC group (P = 0.03 with BS group). Postoperative morphine consumption, pain scores, and incidence and intensity of residual pain did not differ among groups. CONCLUSIONS: Intrathecal clonidine 150 mug combined with bupivacaine had a postoperative antihyperalgesic effect expressed as a significant reduction in the extent and incidence of periincisional punctate mechanical hyperalgesia at 48 h after elective cesarean delivery compared with intrathecal bupivacaine-sufentanil and intrathecal clonidine 75 mug-bupivacaine-sufentanil.

Postoperative analgesic effects of continuous wound infiltration with diclofenac after elective cesarean delivery.

BACKGROUND: Postoperative pain mostly results from sensitization of afferent fibers at injury sites driving central sensitization. Recently, peripheral processes have gained attention as mechanisms of hyperalgesia, and prostaglandins are among highly sensitizing agents. To date, perioperative administration of a single local dose of nonsteroidal antiinflammatory drugs has shown inconclusive efficacy. Rather than a single bolus, the current study evaluates the postoperative analgesic effect of diclofenac continuous intrawound infusion after elective cesarean delivery. METHODS: Ninety-two parturients were randomly allocated to receive a 48-h continuous intrawound infusion with 240 ml containing 300 mg diclofenac, 0.2% ropivacaine, or saline. In the ropivacaine and saline groups, patients also received 75 mg intravenous diclofenac every 12 h for 48 h. Postoperative evaluation included intravenous morphine consumption by patient-controlled analgesia and visual analog pain scores. Punctate mechanical hyperalgesia surrounding the wound and presence of residual pain after 1 and 6 months were also assessed. RESULTS: Continuous diclofenac infusion significantly reduced postoperative morphine consumption (18 mg; 95% confidence interval, 12.7-22.2) in comparison with saline infusion and systemic diclofenac (38 mg; 95% confidence interval, 28.8-43.7) (P=0.0009) without unique adverse effects. Postoperative analgesia produced by local diclofenac infusion was as effective as local ropivacaine infusion with systemic diclofenac. CONCLUSIONS: After elective cesarean delivery, continuous intrawound infusion of diclofenac demonstrates a greater opioid-sparing effect and better postoperative analgesia than the same dose administered as an intermittent intravenous bolus.

The clinical role of NMDA receptor antagonists for the treatment of postoperative pain.

Recent advances in the understanding of postoperative pain have demonstrated its association with sensitization of the central nervous system (CNS) which clinically elicits pain hypersensitivity. N-methyl-D-aspartate (NMDA) receptors play a major role in synaptic plasticity and are specifically implicated in CNS facilitation of pain processing. Therefore, NMDA receptor antagonists, and specifically ketamine commonly used in clinical practice, have been implicated in perioperative pain management. At subanesthetic (i.e. low) doses, ketamine exerts a specific NMDA blockade and hence modulates central sensitization induced both by the incision and tissue damage and by perioperative analgesics such as opioids. However, the mechanisms underlying ketamine anti-hyperalgesic effect are not totally understood, and neither is the relationship between central sensitization and the risk of developing residual pain after surgery. This chapter examines the role of low doses of ketamine as an adjuvant drug in current perioperative pain management and questions the anti-hyperalgesic mechanisms involved.

The effect of a lidocaine test dose on analgesia and mobility after an epidural combination of neostigmine and sufentanil in early labor.

We previously demonstrated the effectiveness of epidural sufentanil and the cholinesterase inhibitor, neostigmine, to initiate selective labor analgesia. Because the traditional lidocaine plus epinephrine test dose (TD) may alter the effect of subsequent epidural drugs, we undertook this investigation to evaluate the impact of a lidocaine TD on analgesia from a combination of epidural neostigmine plus sufentanil administered in early labor. Eighty healthy parturients were randomly allocated to two groups to receive a 3 mL-TD, either lidocaine 2%-epinephrine (1:200,000) or saline-epinephrine (1:200,000), followed 3 min later by epidural neostigmine 500 microg plus sufentanil 10 microg. Pain scores were recorded for 30 min after injection, as was the time elapsed from initial bolus until request for supplemental analgesia. Thirty minutes after injection, adequacy of motor function was evaluated by the parturient's ability to sit, stand up, bend her knees, and walk. Lidocaine TD hastened the onset (5 min vs 15 min) and increased duration (122 +/- 53 min vs 98 +/- 54 min; P = 0.02) of analgesia from epidural neostigmine plus sufentanil bolus. In contrast, the TD did not significantly impair the ability to sit, stand up, or bend the knees. The ability to ambulate, however, was reduced (57% vs 82%; P = 0.04). In conclusion, a traditional lidocaine TD significantly enhances the analgesic effect from the epidural neostigmine plus sufentanil combination, but affects ambulation in early labor.

Epidural administration of neostigmine and clonidine to induce labor analgesia: evaluation of efficacy and local anesthetic-sparing effect.

BACKGROUND: Epidural clonidine produces analgesia without motor impairment, and is associated with a local anesthetic-sparing effect during labor. The authors have recently demonstrated that epidural neostigmine initiates selective labor analgesia devoid of adverse effects. Both drugs possess common analgesic mechanisms mediated through spinal acetylcholine release. This study evaluates their epidural combination in parturients. METHODS: At the beginning of labor, parturients were randomly allocated to one of five groups to receive one of the following after a test dose: 150 microg epidural clonidine, 750 microg neostigmine, or 75 microg clonidine combined with 250, 500, or 750 microg neostigmine. A pain score (visual analog scale, 0-100) was recorded before administration and at regular intervals until request for a supplemental injection. Subsequent analgesia was provided by continuous epidural infusion of ropivacaine. RESULTS: Parturients did not differ regarding demographic data and initial pain score. Clonidine 150 microg , neostigmine 750 microg , and 75 microg clonidine plus 250 microg neostigmine produced ineffective and short-lasting effects. Clonidine 75 microg plus 500 microg neostigmine and 75 microg clonidine plus 750 microg neostigmine presented comparable durations of 90 +/- 32 and 108 +/- 38 min (mean +/- SD), respectively, and final analgesic efficacies, with 72.2% and 84%, respectively, of the parturients reporting a visual analog scale score of less than 30 out of 100 after 30 min. Ropivacaine use was significantly reduced in all clonidine groups (average, 9.5 mg/h) in comparison with neostigmine alone (17 +/- 3 mg/h). No adverse effects were observed for 75 mug clonidine combined with any dose of neostigmine while maternal sedation (20%) and hypotension (33%) occurred with 150 microg clonidine alone. CONCLUSIONS: Epidural clonidine, 75 microg , with 750 microg neostigmine is an effective combination to initiate selective labor analgesia without adverse effects. Clonidine use further reduces local anesthetic consumption throughout the course of labor.

Epidural neostigmine combined with sufentanil provides balanced and selective analgesia in early labor.

BACKGROUND: This study evaluated the efficacy of an epidural single dose of neostigmine combined with sufentanil to provide selective and balanced analgesia at the beginning of labor. METHODS: After informed consent, 125 healthy parturients were randomly allocated to receive, after a test dose, a single injection of either epidural sufentanil 20 micrograms (minimal analgesic dose) or 10 micrograms or a combination of sufentanil 10 micrograms with neostigmine 250, 500, or 750 micrograms in a total volume of 12 ml. Pain scores were recorded at regular intervals to determine onset and duration of analgesia. Maternal and fetal vital parameters as well as side effects were closely monitored. RESULTS: Parturients did not differ concerning demographic data. Epidural neostigmine 500 micrograms with sufentanil 10 micrograms produced effective analgesia (visual analog scale <30 mm within 10 min in 72% parturients and within 15 min in 85% parturients; average duration of 119 min, confidence interval 96-142 min) that was as effective as epidural sufentanil 20 micrograms. Epidural combination with neostigmine 250 micrograms was ineffective, whereas 750 micrograms did not produce higher effect than 500 micrograms. No motor block was recorded. Maternal and fetal vital parameters remained stable during labor. CONCLUSIONS: Epidural combination of neostigmine 500 micrograms (e.g., 6-7 micrograms/kg) with sufentanil 10 micrograms provides similar duration of analgesia as epidural sufentanil 20 micrograms and allows effective and selective analgesia devoid of side effects in the first stage of labor.

Perineural alpha(2A)-adrenoceptor activation inhibits spinal cord neuroplasticity and tactile allodynia after nerve injury.

BACKGROUND: Nerve injury in animals increases alpha(2)-adrenoceptor expression in dorsal root ganglion cells and results in novel excitatory responses to their activation, perhaps leading to the phenomenon of sympathetically maintained pain. In contrast to this notion, peripheral alpha(2)-adrenoceptor stimulation fails to induce pain in patients with chronic pain. We hypothesized that alpha(2) adrenoceptors at the site of nerve injury play an inhibitory, not excitatory role. METHODS: Partial sciatic nerve ligation was performed on rats, resulting in a reduction in withdrawal threshold to tactile stimulation. Animals received perineural injection at the injury site of clonidine, saline, or clonidine plus an alpha(2)-adrenergic antagonist, and withdrawal threshold was monitored. Immunohistochemistry was performed on the sciatic nerve ipsi- and contralateral to injury and on the spinal cord. RESULTS: Clonidine reduced this hypersensitivity in a dose-dependent manner, and this was blocked by an alpha(2A)-preferring antagonist. Perineural clonidine injection had a slow onset (days) and prolonged duration (weeks). Systemic or intrathecal clonidine, or transient neural blockade with ropivacaine, had short lasting or no effect on hypersensitivity. alpha(2A)-adrenoceptor immunostaining was increased near the site of peripheral nerve injury, both in neurons and in immune cells (macrophages and T lymphocytes). Phosphorylated cAMP response element binding protein (pCREB) in lumbar spinal cord was increased ipsilateral to nerve injury, and this was reduced 1 week after perineural clonidine injection. CONCLUSIONS: These data suggest that peripheral alpha(2) adrenoceptors are concentrated at the site of peripheral nerve injury, and their activation receptors produce long-lasting reductions in abnormal spinal cord gene activation and mechanical hypersensitivity.