Stephan A. Schug

Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: results from overview of randomised trials

Abstract Objectives: To obtain reliable estimates of the effects of neuraxial blockade with epidural or spinal anaesthesia on postoperative morbidity and mortality. Design: Systematic review of all trials with randomisation to intraoperative neuraxial blockade or not. Studies: 141 trials including 9559 patients for which data were available before 1 January 1997. Trials were eligible irrespective of their primary aims, concomitant use of general anaesthesia, publication status, or language. Trials were identified by extensive search methods, and substantial amounts of data were obtained or confirmed by correspondence with trialists. Main outcome measures: All cause mortality, deep vein thrombosis, pulmonary embolism, myocardial infarction, transfusion requirements, pneumonia, other infections, respiratory depression, and renal failure. Results: Overall mortality was reduced by about a third in patients allocated to neuraxial blockade (103 deaths/4871 patients versus 144/4688 patients, odds ratio=0.70, 95% confidence interval 0.54 to 0.90, P=0.006). Neuraxial blockade reduced the odds of deep vein thrombosis by 44%, pulmonary embolism by 55%, transfusion requirements by 50%, pneumonia by 39%, and respiratory depression by 59% (all P<0.001). There were also reductions in myocardial infarction and renal failure. Although there was limited power to assess subgroup effects, the proportional reductions in mortality did not clearly differ by surgical group, type of blockade (epidural or spinal), or in those trials in which neuraxial blockade was combined with general anaesthesia compared with trials in which neuraxial blockade was used alone. Conclusions: Neuraxial blockade reduces postoperative mortality and other serious complications. The size of some of these benefits remains uncertain, and further research is required to determine whether these effects are due solely to benefits of neuraxial blockade or partly to avoidance of general anaesthesia. Nevertheless, these findings support more widespread use of neuraxial blockade.

A Systematic Review of Randomized Trials Evaluating Regional Techniques for Postthoracotomy Analgesia

BACKGROUND:Thoracotomy induces severe postoperative pain and impairment of pulmonary function, and therefore regional analgesia has been intensively studied in this procedure. Thoracic epidural analgesia is commonly considered the “gold standard” in this setting; however, evaluation of the evidence is needed to assess the comparative benefits of alternative techniques, guide clinical practice and identify areas requiring further research. METHODS:In this systematic review of randomized trials we evaluated thoracic epidural, paravertebral, intrathecal, intercostal, and interpleural analgesic techniques, compared to each other and to systemic opioid analgesia, in adult thoracotomy. Postoperative pain, analgesic use, and complications were analyzed. RESULTS:Continuous paravertebral block was as effective as thoracic epidural analgesia with local anesthetic (LA) but was associated with a reduced incidence of hypotension. Paravertebral block reduced the incidence of pulmonary complications compared with systemic analgesia, whereas thoracic epidural analgesia did not. Thoracic epidural analgesia was superior to intrathecal and intercostal techniques, although these were superior to systemic analgesia; interpleural analgesia was inadequate. CONCLUSIONS:Either thoracic epidural analgesia with LA plus opioid or continuous paravertebral block with LA can be recommended. Where these techniques are not possible, or are contraindicated, intrathecal opioid or intercostal nerve block are recommended despite insufficient duration of analgesia, which requires the use of supplementary systemic analgesia. Quantitative meta-analyses were limited by heterogeneity in study design, and subject numbers were small. Further well designed studies are required to investigate the optimum components of the epidural solution and to rigorously evaluate the risks/benefits of continuous infusion paravertebral and intercostal techniques compared with thoracic epidural analgesia.

A classification of chronic pain for ICD-11

Chronic pain has been recognized as pain that persists past normal healing time5 and hence lacks the acute warning function of physiological nociception.35 Usually pain is regarded as chronic when it lasts or recurs for more than 3 to 6 months.29 Chronic pain is a frequent condition, affecting an estimated 20% of people worldwide6,13,14,18 and accounting for 15% to 20% of physician visits.25,28 Chronic pain should receive greater attention as a global health priority because adequate pain treatment is a human right, and it is the duty of any health care system to provide it.4,13 The current version of the International Classification of Diseases (ICD) of the World Health Organization (WHO) includes some diagnostic codes for chronic pain conditions, but these diagnoses do not reflect the actual epidemiology of chronic pain, nor are they categorized in a systematic manner. The ICD is the preeminent tool for coding diagnoses and documenting investigations or therapeutic measures within the health care systems of many countries. In addition, ICD codes are commonly used to report target diseases and comorbidities of participants in clinical research. Consequently, the current lack of adequate coding in the ICD makes the acquisition of accurate epidemiological data related to chronic pain difficult, prevents adequate billing for health care expenses related to pain treatment, and hinders the development and implementation of new therapies.10,11,16,23,27,31,37 Responding to these shortcomings, the International Association for the Study of Pain (IASP) contacted the WHO and established a Task Force for the Classification of Chronic Pain. The IASP Task Force, which comprises pain experts from across the globe,19 has developed a new and pragmatic classification of chronic pain for the upcoming 11th revision of the ICD. The goal is to create a classification system that is applicable in primary care and in clinical settings for specialized pain management. A major challenge in this process was finding a rational principle of classification that suits the different types of chronic pain and fits into the general ICD-11 framework. Pain categories are variably defined based on the perceived location (headache), etiology (cancer pain), or the primarily affected anatomical system (neuropathic pain). Some diagnoses of pain defy these classification principles (fibromyalgia). This problem is not unique to the classification of pain, but exists throughout the ICD. The IASP Task Force decided to give first priority to pain etiology, followed by underlying pathophysiological mechanisms, and finally the body site. Developing this multilayered classification was greatly facilitated by a novel principle of assigning diagnostic codes in ICD-11, termed “multiple parenting.” Multiple parenting allows the same diagnosis to be subsumed under more than 1 category (for a glossary of ICD terms refer to Table ​Table1).1). Each diagnosis retains 1 category as primary parent, but is cross-referenced to other categories that function as secondary parents. Table 1 Glossary of ICD-11 terms. The new ICD category for “Chronic Pain” comprises the most common clinically relevant disorders. These disorders were divided into 7 groups (Fig. ​(Fig.1):1): (1) chronic primary pain, (2) chronic cancer pain, (3) chronic posttraumatic and postsurgical pain, (4) chronic neuropathic pain, (5) chronic headache and orofacial pain, (6) chronic visceral pain, and (7) chronic musculoskeletal pain. Experts assigned to each group are responsible for the definition of diagnostic criteria and the selection of the diagnoses to be included under these subcategories of chronic pain. Thanks to Bedirhan Ustun and Robert Jakob of the WHO, these pain diagnoses are now integrated in the beta version of ICD-11 (http://id.who.int/icd/entity/1581976053). The Task Force is generating content models for single entities to describe their clinical characteristics. After peer review overseen by the WHO Steering Committee,39 the classification of chronic pain will be voted into action by the World Health Assembly in 2017. Figure 1 Organizational chart of Task Force, IASP, and WHO interactions. The IASP Task Force was created by the IASP council and its scope defined in direct consultation of the chairs (R.D.T. and W.R.) with WHO representatives in 2012. The Task Force reports to ... 2. Classification of chronic pain Chronic pain was defined as persistent or recurrent pain lasting longer than 3 months. This definition according to pain duration has the advantage that it is clear and operationalized. Optional specifiers for each diagnosis record evidence of psychosocial factors and the severity of the pain. Pain severity can be graded based on pain intensity, pain-related distress, and functional impairment. 2.1. Chronic primary pain Chronic primary pain is pain in 1 or more anatomic regions that persists or recurs for longer than 3 months and is associated with significant emotional distress or significant functional disability (interference with activities of daily life and participation in social roles) and that cannot be better explained by another chronic pain condition. This is a new phenomenological definition, created because the etiology is unknown for many forms of chronic pain. Common conditions such as, eg, back pain that is neither identified as musculoskeletal or neuropathic pain, chronic widespread pain, fibromyalgia, and irritable bowel syndrome will be found in this section and biological findings contributing to the pain problem may or may not be present. The term “primary pain” was chosen in close liaison with the ICD-11 revision committee, who felt this was the most widely acceptable term, in particular, from a nonspecialist perspective.

A procedure-specific systematic review and consensus recommendations for postoperative analgesia following total knee arthroplasty

The PROSPECT Working Group, a collaboration of anaesthetists and surgeons, conducts systematic reviews of postoperative pain management for different surgical procedures (http://www.postoppain.org). Evidence‐based consensus recommendations for the effective management of postoperative pain are then developed from these systematic reviews, incorporating clinical practice observations, and transferable evidence from other relevant procedures. We present the results of a systematic review of pain and other outcomes following analgesic, anaesthetic and surgical interventions for total knee arthroplasty (TKA). The evidence from this review supports the use of general anaesthesia combined with a femoral nerve block for surgery and postoperative analgesia, or alternatively spinal anaesthesia with local anaesthetic plus spinal morphine. The primary technique, together with cooling and compression techniques, should be supplemented with paracetamol and conventional non‐steroidal anti‐inflammatory drugs or COX‐2‐selective inhibitors, plus intravenous strong opioids (high‐intensity pain) or weak opioids (moderate‐ to low‐intensity pain).

Impact of Epidural Analgesia on Mortality and Morbidity After Surgery Systematic Review and Meta-analysis of Randomized Controlled Trials

Objective:To quantify benefit and harm of epidural analgesia, compared with systemic opioid analgesia, in adults having surgery under general anesthesia. Background:It remains controversial whether adding epidural analgesia to general anesthesia decreases postoperative morbidity and mortality. Methods:We searched CENTRAL, EMBASE, PubMed, CINAHL, and BIOSIS till July 2012. We included randomized controlled trials comparing epidural analgesia (with local anesthetics, lasting for ≥24 hours postoperatively) with systemic analgesia in adults having surgery under general anesthesia, and reporting on mortality or any morbidity endpoint. Results:A total of 125 trials (9044 patients, 4525 received epidural analgesia) were eligible. In 10 trials (2201 patients; 87 deaths), reporting on mortality as a primary or secondary endpoint, the risk of death was decreased with epidural analgesia (3.1% vs 4.9%; odds ratio, 0.60; 95% confidence interval, 0.39–0.93). Epidural analgesia significantly decreased the risk of atrial fibrillation, supraventricular tachycardia, deep vein thrombosis, respiratory depression, atelectasis, pneumonia, ileus, and postoperative nausea and vomiting, and also improved recovery of bowel function, but significantly increased the risk of arterial hypotension, pruritus, urinary retention, and motor blockade. Technical failures occurred in 6.1% of patients. Conclusions:In adults having surgery under general anesthesia, concomitant epidural analgesia reduces postoperative mortality and improves a multitude of cardiovascular, respiratory, and gastrointestinal morbidity endpoints compared with patients receiving systemic analgesia. Because adverse effects and technical failures cannot be ruled out, individual risk–benefit analyses and professional care are recommended.

A long-term survey of morphine in cancer pain patients

We surveyed 550 cancer patients who experienced pain and were treated with morphine for a total of 22,525 treatment days. Sufficient pain relief was achieved during more than 80% of this time using an average oral morphine dose of 82.4 mg--significantly lower than other studies. The use of this low dose, which was possible due to the concomitant administration of nonopioids and specific coanalgesics in most patients, resulted in a low incidence of side effects. Constipation and nausea/vomiting were the most common of these side effects. Physical dependence posed no practical problem in discontinuation of morphine treatment. Long-term opioid intake and development of tolerance did not appear to be linked; an increase in morphine dosage was most often explained by progression of the terminal disease. Addiction was a negligible problem, with only one observed case.

The safety and utilization of patient-controlled analgesia

Between December 1989 and March 1996, more than 6000 patients were treated with patient-controlled analgesia (PCA) at Auckland Hospital. The overall incidence of potentially life-threatening complications was low (0.28%). A small number (276) received PCA with a background opioid infusion. This technique was associated with a higher incidence of such complications (1.08%, P < 0.05). To further characterize the safety and utilization of PCA, a subgroup of 300 patients was analyzed. The average duration of PCA was 76.4 +/- 39.2 hr. The peak morphine consumption was highest on the day of operation (45.4 +/- 37.0 mg) and rapidly declined over the next 3 postoperative days (40.6 +/- 39.0, 33.3 +/- 26.2, and 27.8 +/- 36.6 mg, respectively). The ratio of drug demands to deliveries decreased from 1.76 on the morning of the first postoperative day to 1.17 on the evening of the third. The percentage of patients with inadequate analgesia (pain score > or = 3/10) and an inability to comply with physiotherapy (Bruggemann comfort score < or = 2/10) was high on the first postoperative day (42% and 18%, respectively). Men used significantly more morphine than women (141.7 +/- 123.6 versus 102.7 +/- 111.2 mg, P < 0.0001) and general surgical patients used more morphine than urology and orthopedic patients (152.6 +/- 136.9 versus 96.0 +/- 84.2 and 83.7 +/- 97.9 mg, P < 0.0001). There was no association between morphine consumption and age (r = -0.216). Of the 6% of patients who experienced hypoxemia and 2% who experienced respiratory depression, virtually all had one of three risk factors: bolus dose greater than 1 mg morphine, age greater than 65 years, or intra-abdominal surgery. The most common side effects were nausea and sedation. The incidence of nausea was highest on day 1 (28%) and decreased over the next 2 days (14.3% and 4.7%, respectively). A similar pattern was observed with sedation (incidence over the first 3 days: 28%, 9.3%, and 3.3%, respectively). Overall patient satisfaction scores were high (8.3/10 +/- 1.9). We conclude that the risk of serious complications with PCA is very low, but worrying degrees of hypoxemia and bradypnea do occur. We suggest prescribing regimens that may reduce complications and identify patients at high risk.

Adverse Effects of Systemic Opioid Analgesics

SummaryAdverse effects of opioids are multiple. They are most often receptor-mediated and inseparable from their desired effects. The most severe mishaps with opioids are related to their respiratory depressant effect, which is widely influenced by factors such as pain, previous opioid experience and awareness. Other relevant central nervous system effects of opioids include cough suppression, nausea and vomiting, rigidity, pruritus and miosis.The cardiovascular adverse effects of opioids are mainly related to histamine release and differ widely between agonists and agonist-antagonists. Gastrointestinal effects such as constipation, reflux and spasms of the bile duct are well described. Adverse effects on endocrine, immunological and haematological functions are possible, while allergic reactions are extremely rare.The adverse effects of long term use are overestimated. Systemic toxicity is negligible and development of tolerance is minimal while treating pain. In the clinical setting of pain control, addiction and withdrawal do not pose significant problems. Nevertheless, the possible effects of opioids on the unborn child should always be considered.Overall, opioids show a good record of safety. Their use should not be unduly limited by unfounded fears of adverse effects, but these effects should be avoided by anticipation and prevention.

Underutilisation of Opioids in Elderly Patients with Chronic Pain - Approaches to correcting the problem

The impact of poorly managed chronic pain on the quality of life of elderly patients and the problems related to its management are widely acknowledged. Underutilisation of opioids is a major component of poor pain management in this group of patients, despite good evidence for the effectiveness of opioids and published guidelines directing their usage.Reasons for this underutilisation are, among others, poor assessment of pain in this age group; fear of polypharmacy and opiophobia; and avoidance of opioids because of concerns about tolerance, physical dependence, addiction and adverse effects.This review suggests approaches to overcome these barriers to opioid usage, such as regular pain assessments, education to overcome opiophobia, rational prescribing, utilisation of less conventional opioids and non-oral routes of administration, avoidance of inappropriate opioids, opioid rotation, and education about managing or preventing adverse effects, the reasons why opioid therapy may be unsuccessful, and the effects of psychological factors on the pain experience.This more rational and knowledge-based approach to the use of opioids in the management of chronic pain in the elderly population should correct the current problems with underprescribing in this age group.

Treatment principles for the use of opioids in pain of nonmalignant origin

SummaryInadequately treated acute and chronic pain remains a major cause of suffering, in spite of enormous advances in pharmacology and technology. Opioids provide a powerful, versatile, widely available means of managing this pain, but their use is too often restrained by ignorance and mistaken fears of addiction.The management of postoperative pain (perhaps the most common form of acute pain) is traditionally attempted with fixed dosages of analgesics by relatively unpredictable routes (e.g. oral, rectal and intramuscular). Intravenous opioid infusions (an improvement) risk respiratory depression and require close monitoring and titration. Patient-controlled analgesia (PCA), by contrast, permits the most efficacious medication (pure opioid agonist) by the optimal route (intravenous) under direct control of the patient, and provides high levels of satisfaction and safety. Ideally, any opioid use should be integrated with a wide spectrum of other analgesic modalities in an anaesthesiology-based ‘acute pain service’.The use of opioids for chronic pain of nonmalignant origin remains controversial. There is a perceived conflict between patients’ interests and those of society. However, problems (such as tolerance, physical dependence, addiction and chronic toxicity), anticipated from experience with animal experiments and pain-free abusers, seldom cause difficulties when opioids are used appropriately to treat pain (so-called’ dual pharmacology’).With sensible guidelines, and in the context of a multidisciplinary pain clinic, opioids may provide the only hope of relief to many sufferers of chronic pain.