Epidural and intrathecal analgesia for cancer pain

The three-step analgesic ladder approach developed by the World Health Organization works well in treating the vast majority (70–90%) of patients suffering from pain related to cancer. In those patients who do not get pain relief by this three-step approach, intraspinal agents can be a fourth step in managing pain of malignant origin. Although morphine is the only opioid approved by the US Food and Drug Administration for intraspinal use, many different opioid analgesics are used intraspinally, including hydromorphone, fentanyl, sufentanil, meperidine and methadone in the treatment of cancer pain. Many non-opioid agents have also been used intraspinally either alone or in combination with opioids in the treatment of intractable cancer pain. This chapter summarizes the clinical use of these agents with some practical points.     

Current and developing methods of patient-controlled analgesia

Moderate-to-severe acute postoperative pain is commonly controlled with opioids administered via programmable intravenous (IV) patient-controlled analgesia (PCA) infusion pumps. Intravenously administered opioids provide effective relief of postoperative pain, and IV PCA enables patients to control their level of analgesia, which has advantages over nurse-administered approaches, including more satisfied patients and improved pain relief. Unfortunately, commonly used opioid analgesics can cause significant adverse effects. Furthermore, IV PCA has drawbacks, such as device programming errors, system errors, medication errors, limitations in patient mobility, and potential for IV tubing kinks, clogging, and transmission of infection. The IV route of administration is also characterized by a rapid, high peak in analgesic drug concentration followed by rapidly decreasing concentrations. Consequently, respiratory depression, excessive sedation, and inadequate pain control can occur. Furthermore, the technical assembly of an infusion pump is often complex and time-consuming. PCA modalities that incorporate superior opioid analgesics, such as sufentanil, and novel noninvasive routes of administration offer great promise for enhancing the patient and caregiver experience with the use of postoperative PCA.     

阿片类药物依赖患者的术后镇痛

背景 阿片类药物是术后镇痛的主要药物,但长期使用阿片类药物的患者因对阿片类药物产生耐受而难以得到较理想的临床术后镇痛效果.目的 讨论如何采用不同的镇痛技术和药物来更好地为这些患者提供良好镇痛.内容 介绍阿片类药物依赖的流行病学及术后镇痛特点,如何对阿片类药物依赖规范合理使用阿片类药物及辅助类镇痛药物,麻醉医生擅长的神经...     

Basal heat pain thresholds predict opioid analgesia in patients with postherpetic neuralgia

BACKGROUND: A variety of analgesics have been studied in the treatment of postherpetic neuralgia, with several medications demonstrating some degree of efficacy. However, existing trials have documented large individual differences in treatment responses, and it is important to identify patient characteristics that predict the analgesic effectiveness of particular interventions. Several animal studies have indicated that reduced basal nociceptive sensitivity, in the form of relatively high heat pain thresholds, is associated with greater opioid analgesia, but this finding has not been applied to human studies of opioid treatment for chronic pain. METHODS: Using data from a previously published crossover trial of opioids and tricyclics in postherpetic neuralgia, the authors evaluated baseline thermal pain thresholds, assessed at a body site contralateral to the affected area, as a predictor of treatment responses. RESULTS: During opioid treatment, a greater reduction in pain and higher ratings of pain relief were observed in patients with relatively higher heat pain thresholds at baseline. Baseline pain thresholds did not predict responses to tricyclics or placebo. Interestingly, other individual-difference variables such as age and baseline pain intensity also significantly predicted opioid responses (i.e., higher baseline pain and younger age were related to greater opioid-associated pain reduction, with nearly 20% of the variance in opioid analgesia explained by these two factors). CONCLUSIONS: These findings, which will require replication, suggest that pretreatment assessment of heat pain sensitivity might prove useful in identifying those patients most likely to respond to opioids.     

Systemic adjunct analgesics for cesarean delivery: a narrative review

It is critical to adequately treat postoperative cesarean delivery pain. The use of parenteral or neuraxial opioids has been a mainstay, but opioids have side effects that can be troubling and the opioid crisis in the United States has highlighted the necessity to utilize analgesics other than opioids. Other analgesic options include neuraxial analgesics, nerve blocks such as the transversus abdominis plane block, and non-opioid parenteral and oral medications. The goal of this article is to review non-opioid systemic analgesic adjuncts following cesarean delivery, focusing on their efficacy and side effects as well as their impact on reduction of opioid requirements after surgery.     

Analgesia in labour: inhalational and parenteral

Inhalational analgesia and parenteral opioids are the most widely used analgesics for labour pain because of their availability, simplicity of administration, and cost. However, their analgesic efficacy is limited compared with regional analgesia. Nitrous oxide in oxygen (Entonox) provides moderate pain relief and is safe for use in labour. Low-dose isoflurane (e.g. 0.25%) with Entonox gives superior pain relief compared with Entonox alone. The more recently introduced inhalational agent, sevoflurane, at a concentration of 0.8% also seems to provide superior pain relief compared with Entonox. Sedation scores tend to be increased with inhalational analgesia. Pethidine is the most widely used opioid for labour despite its side effects and lack of analgesia. Diamorphine is being increasingly used in the UK. There is no good evidence to distinguish analgesic efficacy amongst the standard parenteral opioids and opioid partial agonists and antagonists. Fentanyl patient-controlled analgesia (PCA), with a bolus dose of 20 μg and lockout of 5 minutes, seems to be efficacious but accumulates over time. Close maternal, fetal and neonatal monitoring is required. Parenteral remifentanil PCA, at a dose of 0.25–0.5μg/kg with a lockout time of 1–2 minutes, has a rapid onset and offset without accumulative effects, which makes it ideal for use in labour with improved analgesic efficacy. However, more sophisticated modes of drug delivery and careful titration and monitoring of the parturient are required when sevoflurane and remifentanil are used.     

Opioid therapy in chronic non-malignant pain

In long-term treatment opioids seem to have only minimal side-effects compared with other analgesics and co-analgesics.Nevertheless, some risks have to be considered. While immunosuppression, neurotoxicity, teratogenity, tolerance and addiction are clinically not relevant or very rare, cognitive impairment, sedation and obstipation may have a clinical impact.However, these symptoms can usually be managed by adjuvant medication and patient education.Treatment of non-malignant pain with opioids can only be considered on an individual basis. Scientific evidence for general treatment with opioids, treatment of specific pain syndromes or treatment with certain opioids is not available. In conclusion, only recommendations regarding opioid treatment for certain chronic pain syndromes can be made. In only a minority of patients can a long-term analgesic effect be expected.Therefore, careful evaluation of alternative options of pain management is necessary before opioid therapy is started.With standardized documentation responders may be distinguished from non-responders.For clinical practice of long-term opioid therapy in non-malignant pain a specialized knowledge in pain management is a prerequisite.Future studies with more sophisticated methodology will be necessary to advocate more precise guidelines.However, the therapeutic recommendations from the DGSS consensus conference allow a safer,well structured and validated use of opioids for chronic non-malignant pain.     

Weak opioids--an educational substitute for morphine?

The World Health Organization guidelines suggest the use of weak opioids on the second step of the analgesic ladder for cancer pain relief. Weak opioids are important substitutes for low doses of morphine, although their analgesic efficacy is lower than that of non-opioid or strong opioid analgesics. The use of weak opioids has great educational impact and has helped spread the use of the guidelines. Furthermore, weak opioids are more freely available and are expected to have a better side-effect profile. Controlled long-term studies are required for confirmation.     

Treatment of severe low back pain with opioids during pregnancy in a patient with incomplete tetraplegia

We report a case of severe low back pain during pregnancy in a woman with incomplete tetraplegia due to viral myelitis. The pain was interpreted as a radiculopathy in the presence of multiple herniated discs. Surgical intervention was not indicated and physiotherapy failed; therefore, a symptomatic drug treatment with oral analgesics was initiated. To minimise the total daily opioid dosage and the potential risk of a neonatal withdrawal syndrome due to opioids, the route of administration was changed from oral to epidural. Adequate pain relief was maintained with this regimen until caesarean section was necessary. The neonatal withdrawal symptoms after delivery were mild. Residual pain slowly diminished after delivery and the patient was able to discontinue opioid therapy. The aetiology of low back pain remains unclear and may be multifactorial.     

Use of intravenous ketorolac in the neonate and premature babies

BACKGROUND: Ketorolac is a powerful nonsteroidal anti-inflammatory drug widely used for pain control in children and adults. The aim of this study was to evaluate its safety and analgesic efficacy in the neonate. METHODS: Ketorolac was used in a group of 18 spontaneously breathing neonates presenting with chronic lung disease, for the control of postsurgical pain and pain from invasive procedures. Pain scores (Neonatal Infant Pain Scale) were assessed before and after i.v. administration of 1 mg.kg(-1) of ketorolac. RESULTS: Total pain control was achieved in 94.4% of the neonates. None of the neonates had haematological, renal or hepatic changes prior to treatment, and these complications did not occur after treatment. No neonate had systemic haemorrhage or bleeding from injection and blood withdrawal sites. CONCLUSIONS: Ketorolac could represent an efficacious analgesic alternative to opioids, particularly in neonates. It would avoid the side-effects associated with opioid analgesics, especially respiratory depression.     

Postoperative Analgesia in Morbid Obesity

Morbidly obese patients due to high incidence of obstructive sleep apnea (OSA) are predisposed to opioid induced airway obstruction and thus frontline high ceiling analgesics (opioids) have concerns based on safety in their liberal use. Although surgical techniques over the last two decades have seen a paradigm shift from open to laparoscopic procedures for morbidly obese patients; optimally titrated yet safe analgesic management still remains a challenge. The present review sums up the analgesic options available for management of morbidly obese patients undergoing surgery. We highlight the utility of multimodal approach for analgesia with combinations of agents to decrease opioids requirements. Pre-emptive analgesia may be additionally used to improve the efficacy of postoperative pain relief while allowing further reductions in opioid requirements.     

Patient-controlled analgesia]

Patient controlled analgesia (PCA) is a drug delivery system aimed to control acute pain using negative feedback technology in a closed loop system in which the patient plays an active role. It overcomes the inadequacies of traditional analgesic protocols due to marked differences in pharmacokinetic and dynamy of analgesis between patients. Moreover, doctors and nurses frequently underprescribe opioids in patients with severe pain for fear of dangerous side-effects. A safe and effective delivery of these drugs on patient demand can be achieved using various delivery systems, modes and dosing parameters. Most devices provide both demand dosing, where a constant predetermined dose is self administered, and constant rate infusion plus demand dosing, where the minimum administration rate is determined by the doctor, but can be supplemented by patient demand. Morphine sulphate remains the drug most commonly used in PCA therapy, but meperidine hydrochloride, alfentanil, nalbuphine and buprenorphine are also sometimes administered. The doctor determines the incremental dose per demand, the lockout interval, and the maximum dose per time unit, possibly also the loading dose and the minimum dose rate when a continuous flow is used. PCA provides improved analgesia, which is immediate and independent of nurse availability. This technique decreases opioid requirements, and the required total amounts are lowered. PCA gives patients both behavioural and decisional control. They can titrate the analgesic dose in such a way as to balance pain relief with the degree of side-effects, the patient is willing to tolerate. Patients often choose less than the available total dose of analgesic. The risks consists in the usual opioid side-effects, mainly respiratory depression. These may be due to mechanical problems, machine failure, or user incidents (misprogramming, or miscalculation of doses). Standards help to ensure consistent care and avoid errors that can occur even with handwritten orders. The principles of demand analgesia are now being investigated using other agents, such as local anaesthetics, and other routes of administration, mainly epidural injection. In most patients, even in children, PCA can replace intramuscular injections, which are the standard route for opioid administration. Today PCA and spinal opioids are the two main methods of analgesia for postoperative pain management.     

神经病理性疼痛中阿片类药物的应用

阿片类药物作为一种较为有效的药物用来治疗重度疼痛以及包括神经病理性疼痛在内的慢性疼痛.然而在神经病理性疼痛中,阿片类药物的疗效存在争议.长期持续的运用阿片类药物容易产生耐受的现象,表现为需要增加药物剂量来维持疼痛的缓解程度.但最近的几个研究都表明阿片类药物在神经病理痛中的应用是有效的.现就神经病理性疼痛中阿片类药物的耐受及应用发展作一阐述.     

阿片类药物依赖患者的术后镇痛

背景 阿片类药物是术后镇痛的主要药物,但长期使用阿片类药物的患者因对阿片类药物产生耐受而难以得到较理想的临床术后镇痛效果.目的 讨论如何采用不同的镇痛技术和药物来更好地为这些患者提供良好镇痛.内容 介绍阿片类药物依赖的流行病学及术后镇痛特点,如何对阿片类药物依赖规范合理使用阿片类药物及辅助类镇痛药物,麻醉医生擅长的神经阻滞技术在该类患者应有独特的地位.趋向 在阿片类药物依赖患者,通过使用阿片类药物、局麻药和辅助性镇痛药,将不同作用机制的药物或方法联合使用,发挥药物的相加或协同作用的平衡镇痛及多模式镇痛将是术后镇痛技术的主要发展方向.     

Ketamine in perioperative analgesia for knee surgeries: Review of evidence from randomized controlled trials

Successful perioperative analgesia for knee surgeries results in improved patient satisfaction and promotes successful rehabilitation. However, effective perioperative pain control is commonly a challenging task for knee surgeries. Such surgical procedures as total knee replacement or knee arthroscopy may be accompanied by severe postoperative pain. As opioids and nonsteroidal anti-inflammatory drugs are commonly used, the side effects of these types of medicines are quite common as well, especially in patients with chronic pain, as they are commonly dissatisfied with regular analgesia. Patients with chronic pain tend to have lower tolerance to pain, and be dependent and tolerant to opioids. These patients typically require higher doses of analgesics, which further negatively affect patients’ safety and the overall perioperative experience. Multimodal perioperative analgesia helps to spare opioids and promote successful rehabilitation. Ketamine is a noncompetitive N-Methyl-d-aspartate (NMDA) receptor antagonist that has been used for multimodal perioperative analgesia as an adjunct to opioids and nonsteroidal anti-inflammatory drugs. Despite the significant number of papers evaluating the role of ketamine in perioperative analgesia, the feasibility of ketamine for perioperative pain control in knee surgeries remains a subject of debate. There are only a limited number of high-quality studies on the topic. We used a systematic approach to evaluate randomized controlled trials with perioperative ketamine used for knee surgeries. The majority of the studies confirmed that the utilization of ketamine in perioperative analgesia was associated with lower pain scores, reduced opioid use, improved knee joint mobility, and an increase in patient tolerance for physical therapy and rehabilitation. The techniques for ketamine administration and dosing varied significantly, which may explain the inconsistencies between the reports. In addition, some of the studies, even those of high quality, used nitrous oxide in both the study and control groups. Nitrous oxide has NMDA receptor antagonist properties, as does ketamine. None of the studies reported whether patients were taking methadone, dextromethorphan, memantine, or magnesium sulfate, which are NMDA receptor antagonists too. The concomitant use of NMDA receptor antagonists, other than ketamine, may have interfered with the realization of analgesic effects of ketamine. Although it is largely accepted that NMDA receptor antagonism at the spinal level explains most of the analgesic effects of ketamine, it also interacts at other multiple receptors centrally, including, cholinergic receptors, nicotinic and muscarinic, adrenergic, central NMDA, and non-NMDA glutamate receptors. These influences may potentially explain why patients treated with other NMDA receptor antagonists had improved with ketamine as well. Ketamine also interacts with opioid receptors at supraspinal sites, where it produces supraspinal antinociception. Some of the studies did not report whether the participants were opioid naïve or opioid dependent. That might be an important determinant of the analgesic effect because opioid dependent patients are shown to benefit from the ketamine significantly. None of the examined randomized controlled trials assessed the effects of ketamine on opioid dependent patients. The variability between the outcomes of ketamine utilization for perioperative analgesia for knee surgeries might be, at least partially, explained by these findings.     

Opioids in cancer and chronic non-cancer pain therapy – indications and controversies

Indications for strong opioids for cancer-related pain as well as for chronic non-cancer pain are that non-opioid drugs, and other less risky therapies, fail and that the pain is opioid-sensitive. The WHO analgesic ladder principle continues to serve as an excellent educational tool in the efforts by WHO in collaboration with the World Federation of Societies of Anaesthesiologists (WFSA) and The International Association for the Study of Pain (IASP) to increase knowledge of pharmacological pain therapy and increase availability of essential opioid analgesics world-wide. Opioids differ in pharmacodynamics and pharmacokinetics, and patients have different pharmacogenetics and pain mechanisms. Sequential trials of the increasing numbers of available opioid drugs are therefore appropriate when oral morphine fails. Controversies continue concerning diagnosis and handling of opioid-insensitive pain in cancer and chronic non-cancer pain, opioid-induced neurotoxicities, risks of tolerance, addiction, pseudo-addiction, and methods for improving effectiveness and decreasing adverse effects of long-term opioid therapy, treating breakthrough pain with immediate release oral and transmucosal opioids. Consensus guidelines have recently been developed in the Nordic countries concerning the ethical practice of palliative sedation when opioids and other pain-relieving therapies fail in patients soon to die. Guidelines for long-term treatment with strong opioids of chronic non-cancer-related pain are also being developed in the Nordic countries, where very diverging traditions for the usage of such therapy still exist.