PROSPECT guideline for total hip arthroplasty: a systematic review and procedure-specific postoperative pain management recommendations.

The aim of this systematic review was to develop recommendations for the management of postoperative pain after primary elective total hip arthroplasty, updating the previous procedure-specific postoperative pain management (PROSPECT) guidelines published in 2005 and updated in July 2010. Randomised controlled trials and meta-analyses published between July 2010 and December 2019 assessing postoperative pain using analgesic, anaesthetic, surgical or other interventions were identified from MEDLINE, Embase and Cochrane databases. Five hundred and twenty studies were initially identified, of which 108 randomised trials and 21 meta-analyses met the inclusion criteria. Peri-operative interventions that improved postoperative pain include: paracetamol; cyclo-oxygenase-2-selective inhibitors; non-steroidal anti-inflammatory drugs; and intravenous dexamethasone. In addition, peripheral nerve blocks (femoral nerve block; lumbar plexus block; fascia iliaca block), single-shot local infiltration analgesia, intrathecal morphine and epidural analgesia also improved pain. Limited or inconsistent evidence was found for all other approaches evaluated. Surgical and anaesthetic techniques appear to have a minor impact on postoperative pain, and thus their choice should be based on criteria other than pain. In summary, the analgesic regimen for total hip arthroplasty should include pre-operative or intra-operative paracetamol and cyclo-oxygenase-2-selective inhibitors or non-steroidal anti-inflammatory drugs, continued postoperatively with opioids used as rescue analgesics. In addition, intra-operative intravenous dexamethasone 8-10 mg is recommended. Regional analgesic techniques such as fascia iliaca block or local infiltration analgesia are recommended, especially if there are contra-indications to basic analgesics and/or in patients with high expected postoperative pain. Epidural analgesia, femoral nerve block, lumbar plexus block and gabapentinoid administration are not recommended as the adverse effects outweigh the benefits. Although intrathecal morphine 0.1 mg can be used, the PROSPECT group emphasises the risks and side-effects associated with its use and provides evidence that adequate analgesia may be achieved with basic analgesics and regional techniques without intrathecal morphine.

Regional anaesthesia in patients with diabetes.

Diabetes is the most common metabolic condition worldwide and about 20% of surgical patients will have this condition. It is a major risk-factor for worse outcomes after surgery including mortality; infective and non-infective complications; and increased length of stay. However, diabetes is a modifiable risk-factor, and programs to improve medical management have the potential to reduce peri-operative complications and the risk of harm. Regional anaesthesia has well-documented benefits in promoting the restoration of function but there are legitimate concerns that the incidence of complications of regional anaesthesia in patients with diabetes is higher. The aim of this review is to explore in detail the various potential advantages and disadvantages of regional anaesthesia in patients with diabetes. This, in turn, will allow practitioners to undertake more informed shared decision-making and potentially modify their anaesthetic technique for patients with diabetes.

Ultrasound guided supra-inguinal Fascia Iliaca Compartment Blocks in hip fracture patients: An alternative technique.

INTRODUCTION: In the Emergency Department, regional anesthesia is increasingly used in elderly patients with hip fractures. An example is a Fascia Iliaca Compartment Block (FICB). Traditionally, this block is administered below the inguinal ligament. There is no Emergency Department data regarding effectivity of an alternative, more cranial approach above the inguinal ligament. The objective was to determine analgesic effects of an ultrasound-guided supra-inguinal FICB in hip fracture patients in the Emergency Department. METHODS: This case series included all Emergency Department hip fracture patients who were treated with a supra-inguinal FICB during a period of 10 months. All data were recorded prospectively. Primary study outcome was decrease in Numerical Rating Scale (NRS) pain scores 60 min after the FICB. Secondary outcomes included the proportion of patients achieving 1.5 NRS points decrease at 60 min; NRS differences at 30 and 120 min compared to baseline; need for additional analgesia and occurrence of adverse events. RESULTS: A total of 22 patients were included in the study. At 60 min median NRS pain scores decreased from 6.0 to 3.0 (p < 0.001). Of all patients, a total of 59% achieved a decrease in 1.5 NRS points after 60 min. Median pain scores at 30 and 120 min were 4.0 (Interquartile Range (IQR) 2.0-5.0) and 2.5 (IQR 0.8-3.0). Seven patients (31.8%) required additional opioid analgesia after the FICB. No adverse events were recorded. CONCLUSION: An ultrasound-guided supra-inguinal FICB decreases NRS pain scores in hip fracture patients both clinically relevant and statistically significantly after 60 min. CLINICAL TRIAL REGISTRATION: The study was registered in the ISRCTN database (ISRCTN74920258).

Haematoma and abscess after neuraxial anaesthesia: a review of 647 cases.

Although rare, spinal haematoma and abscess after central neuraxial blocks may cause severe permanent neurological injury. Optimal treatment and outcome remain unclear. In order to identify possible predisposing patient characteristics and describe the ensuing clinical course, we searched Medline, Embase, and the Cochrane Library for reports of spinal haematomas and abscesses associated with central neuraxial blocks. Extracted data included patient characteristics, symptoms, treatment, and outcome. We analysed 409 reports, including 647 patients (387 patients with spinal haematoma and 260 patients with spinal abscess). Spinal haematoma and abscess occurred predominantly after epidural anaesthesia (58% and 83%, respectively). Neurological recovery was correlated with the severity of initial neurological deficit. When decompression of spinal haematoma was delayed for >12 h after clinical diagnosis, neurological outcome was worse compared with earlier decompression (odds ratio 4.5, 95% confidence interval 2.1-9.9, P<0.001, n=163). After spinal haematoma, 47% of published patients had full recovery, 28% had partial recovery, and in 25% no recovery was observed. Good outcome after conservative management was observed in patients with mild symptoms or with spontaneous recovery during the diagnostic and therapeutic workup. After spinal abscess, 68% of reported patients recovered fully, 21% showed partial recovery, and no recovery was reported in 11%. Persistent neurological symptoms after spinal haematoma and abscess are common and correlate with the severity of initial neurological deficit. Neurological outcome seems worse when decompressive surgery of haematoma is delayed. Notwithstanding the considerable risk of selection bias and publication bias, conservative management may be feasible in patients with mild symptoms or spontaneous recovery.

Systematic review of the systemic concentrations of local anaesthetic after transversus abdominis plane block and rectus sheath block.

BACKGROUND.: Safe and efficacious modalities of perioperative analgesia are essential for enhanced recovery after surgery. Truncal nerve blocks are one potential adjunct for analgesia of the abdominal wall, and in recent years their popularity has increased. Transversus abdominis plane block (TAPB) and rectus sheath block (RSB) have been shown to reduce morphine consumption and improve pain relief after abdominal surgery. These blocks typically require large volumes of local anaesthetic (LA). We aimed to synthesize studies evaluating systemic concentrations of LA after perioperative TAP and RSB to enhance our understanding of systemic LA absorption and the risk of systemic toxicity. METHODS.: An independent literature review was performed in accordance with the methods outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. An electronic search of four databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and PubMed) was conducted. Primary articles measuring systemic concentrations of LA after single-shot bolus TAPB or RSB were included. RESULTS.: Fifteen studies met the inclusion criteria. Rapid systemic LA absorption was observed in all studies. Of a total of 381 patients, mean peak concentrations of LA exceeded toxic thresholds in 33 patients, of whom three reported mild adverse effects. The addition of epinephrine reduced systemic absorption of LA. No instances of seizure or cardiac instability were observed. CONCLUSIONS.: Local anaesthetic in TAPB and RSB can lead to detectable systemic concentrations that exceed commonly accepted thresholds of LA systemic toxicity. Our study highlights that these techniques are relatively safe with regard to LA systemic toxicity.

Diabetic neuropathy increases stimulation threshold during popliteal sciatic nerve block.

BACKGROUND: Peripheral nerve stimulation is commonly used for nerve localization in regional anaesthesia, but recommended stimulation currents of 0.3-0.5 mA do not reliably produce motor activity in the absence of intraneural needle placement. As this may be particularly true in patients with diabetic neuropathy, we examined the stimulation threshold in patients with and without diabetes. METHODS: Preoperative evaluation included a neurological exam and electroneurography. During ultrasound-guided popliteal sciatic nerve block, we measured the current required to produce motor activity for the tibial and common peroneal nerve in diabetic and non-diabetic patients. Proximity to the nerve was evaluated post-hoc using ultrasound imaging. RESULTS: Average stimulation currents did not differ between diabetic (n=55) and non-diabetic patients (n=52). Although the planned number of patients was not reached, the power goal for the mean stimulation current was met. Subjects with diminished pressure perception showed increased thresholds for the common peroneal nerve (median 1.30 vs. 0.57 mA in subjects with normal perception, P=0.042), as did subjects with decreased pain sensation (1.60 vs. 0.50 mA in subjects with normal sensation, P=0.038). Slowed ulnar nerve conduction velocity predicted elevated mean stimulation current (r=-0.35, P=0.002). Finally, 15 diabetic patients required more than 0.5 mA to evoke a motor response, despite intraneural needle placement (n=4), or required currents ≥2 mA despite needle-nerve contact, vs three such patients (1 intraneural, 2 with ≥2 mA) among non-diabetic patients (P=0.003). CONCLUSIONS: These findings suggest that stimulation thresholds of 0.3-0.5 mA may not reliably determine close needle-nerve contact during popliteal sciatic nerve block, particularly in patients with diabetic neuropathy. CLINICAL TRIAL REGISTRATION: NCT01488474.

Neurophysiological effects of needle trauma and intraneural injection in a porcine model: a pilot study.

BACKGROUND: Neurophysiological data are lacking in the research of nerve injury during regional anaesthesia. The aim of this pilot study was to establish a large animal model in order to test the hypothesis that needle trauma alone or in combination with intraneural injection would result in measurable nerve injury. METHODS: The experimental set-up was elaborated in four pre-test animals. In the remaining animals (n = 11), 22 sciatic nerves were randomly assigned to one of four groups: needle trauma (n = 5) generated by ultrasound-guided forced needle advancement; intraneural injection of 2.5 ml saline (n = 6); intraneural injection of 5 ml saline (n = 6); extraneural injection of 5 ml saline (n = 5) as control group. Compound muscle action potential (CMAP) amplitudes as well as latencies were taken as outcome parameter and monitored over 180 min. Sonographic assessments were performed simultaneously. RESULTS: Following needle trauma and intraneural injection, CMAP amplitudes declined significantly over 180 min (P < 0.001). The control group showed no electrophysiological alterations. At 60 min, decreases in amplitude were significant after needle trauma (P = 0.04) and intraneural injection of 2.5 ml (P = 0.045), and highly significant after injection of 5 ml (P = 0.006) when compared to controls. Sustained nerve swelling was observed after intraneural injection, but not after needle trauma and perineural injection. CONCLUSIONS: Isolated mechanical trauma caused by forced needle advancement alone or in combination with intraneural injection of saline was followed by a significant decline in CMAP amplitudes indicating conduction block due to disruption of myelin or axon loss (pseudo-conduction block).

Epigenetics in the perioperative period.

The perioperative period is characterized by profound changes in the body's homoeostatic processes. This review seeks to address whether epigenetic mechanisms may influence an individual's reaction to surgery and anaesthesia. Evidence from animal and human studies suggests that epigenetic mechanisms can explain many facets of susceptibility to acute and chronic pain, making them potential therapeutic targets. Modern pain management is still based upon opiates, and both the developmental expression of opioid receptors and opioid-induced hyperalgesia have been linked to epigenetic mechanisms. In general, opiates seem to increase global DNA methylation levels. This is in contrast to local anaesthetics, which have been ascribed a global demethylating effect. Even though no direct investigations have been carried out, the potential influence of epigenetics on the inflammatory response that follows surgery seems a promising area for research. There is a considerable body of evidence that supports the involvement of epigenetics in the complex process of wound healing. Epigenetics is an important emerging research topic in perioperative medicine, with a huge potential to positively influence patient outcome.

Effects of early and late diabetic neuropathy on sciatic nerve block duration and neurotoxicity in Zucker diabetic fatty rats.

BACKGROUND: The neuropathy of type II diabetes mellitus (DM) is increasing in prevalence worldwide. We aimed to test the hypothesis that in a rodent model of type II DM, neuropathy would lead to increased neurotoxicity and block duration after lidocaine-induced sciatic nerve block when compared with control animals. METHODS: Experiments were carried out in Zucker diabetic fatty rats aged 10 weeks (early diabetic) or 18 weeks (late diabetic, with or without insulin 3 units per day), and age-matched healthy controls. Left sciatic nerve block was performed using 0.2 ml lidocaine 2%. Nerve conduction velocity (NCV) and F-wave latency were used to quantify nerve function before, and 1 week after nerve block, after which sciatic nerves were used for neurohistopathology. RESULTS: Early diabetic animals did not show increased signs of nerve dysfunction after nerve block. In late diabetic animals without insulin vs control animals, NCV was 34.8 (5.0) vs 41.1 (4.1) ms s(-1) (P<0.01), and F-wave latency was 7.7 (0.5) vs 7.0 (0.2) ms (P<0.01), respectively. Motor nerve block duration was prolonged in late diabetic animals, but neurotoxicity was not. Late diabetic animals receiving insulin showed intermediate results. CONCLUSIONS: In a rodent type II DM model, nerves have increased sensitivity for short-acting local anaesthetics without adjuvants in vivo, as evidenced by prolonged block duration. This sensitivity appears to increase with the progression of neuropathy. Our results do not support the hypothesis that neuropathy due to type II DM increases the risk of nerve injury after nerve block.

Lidocaine and ropivacaine, but not bupivacaine, demethylate deoxyribonucleic acid in breast cancer cells in vitro.

BACKGROUND: Lidocaine demethylates deoxyribonucleic acid (DNA) in breast cancer cells. This modification of epigenetic information may be of therapeutic relevance in the perioperative period, because a decrease in methylation can reactivate tumour suppressor genes and inhibit tumour growth. The objectives of this study were to determine the effect of two amide local anaesthetics, ropivacaine and bupivacaine, on methylation in two breast cancer cell lines and to detect whether the combination of lidocaine with the chemotherapy agent 5-aza-2'-deoxycytidine (DAC) would result in additive demethylating effects. METHODS: Breast cancer cell lines BT-20 [oestrogen receptor (ER)-negative] and MCF-7 (ER-positive) were incubated with lidocaine, bupivacaine, and ropivacaine to assess demethylating properties. Then, we tested varying concentrations of lidocaine and DAC to assess whether their demethylating effects were additive. Cell numbers and global methylation status were analysed. RESULTS: Lidocaine decreased methylation in BT-20 and MCF-7 cells, ropivacaine decreased methylation in BT-20 cells, and bupivacaine had no demethylating effect. When combined, lidocaine and DAC had additive demethylating effects. CONCLUSIONS: At clinically relevant doses, lidocaine and ropivacaine exert demethylating effects on specific breast cancer cell lines, but bupivacaine does not. The demethylating effects of lidocaine and DAC are indeed additive.

Outcome after regional anesthesia: weighing risks and benefits.

Regional anesthesia has become a widely used method to provide intraoperative anesthesia, and postoperative analgesia. This review seeks to address the question whether patient outcomes are improved to an extent that justifies using regional anesthesia as a routine method. During the past decade, a very critical appraisal of risks and benefits of regional anesthetic procedures has taken place. In general, the indications for epidural blockade have decreased, and are limited to individual high-risk patients, major upper abdominal and major vascular surgery, and thoracotomy. We review the changing role of central and peripheral regional anesthesia in the perioperative management of total knee arthroplasty. Immediate perioperative outcome after knee arthroplasty concerning function and pain is improved, and rehabilitation facilitated, by peripheral nerve blockade, but this does not translate into superior functional outcome one year later. A substantial share of the beneficial effects of regional anesthesia on the immune system, hemostasis, pain, and the duration of ileus can be duplicated using intravenous administration of local anesthetics. In general, the use of regional anesthesia should always be preceded by a weighing of potential risks and proven benefits. Regional anesthesia continues to play a major role in perioperative medicine, but its role keeps getting more defined and less non-committal.

Time-dependent modulation of muscarinic m1/m3 receptor signalling by local anaesthetics.

BACKGROUND: Signalling of several G-protein-coupled receptors of the Gq/11 family is time-dependently inhibited by local anaesthetics (LAs). Since LA-induced modulation of muscarinic m1 and m3 receptor function may explain their beneficial effects in clinical practice, such as decreased postoperative cognitive dysfunction or less bronchoconstriction, we studied how prolonged exposure affects muscarinic signalling (Wang D, Wu X, Li J, Xiao F, Liu X, Meng M. The effect of lidocaine on early postoperative cognitive dysfunction after coronary artery bypass surgery. Anesth Analg 2002; 95: 1134-41; Groeben H, Silvanus MT, Beste M, Peters J. Combined lidocaine and salbutamol inhalation for airway anesthesia markedly protects against reflex bronchoconstriction. Chest 2000; 118: 509-15). METHODS: A two-electrode voltage clamp was used to assess the effects of lidocaine or its permanently charged analogue QX314 on recombinantly expressed m1 and m3 receptors in Xenopus oocytes. Antisense knock-down of functional Gαq-protein and inhibition of protein kinase C (PKC) served to define mechanisms and sites of action. RESULTS: Lidocaine affected muscarinic signalling in a biphasic way: an initial decrease in methylcholine bromide-elicited m1 and m3 responses after 30 min, followed by a significant increase in muscarinic responses after 8 h. Intracellularly injected QX314 time-dependently inhibited muscarinic signalling, but had no effect in Gαq-depleted oocytes. PKC-antagonism enhanced m1 and m3 signalling, but completely abolished the LA-induced increase in muscarinic responses, unmasking an underlying time-dependent inhibition of m1 and m3 responses after 8 h. CONCLUSIONS: Lidocaine modulates muscarinic m1 and m3 receptors in a time- and Gαq-dependent manner, but this is masked by enhanced PKC activity. The biphasic time course may be due to interactions of LAs with an extracellular receptor domain, modulated by PKC activity. Prolonged exposure to LAs may not benefit pulmonary function, but may positively affect postoperative cognitive function.

Management of the patient with diabetic peripheral neuropathy presenting for peripheral regional anesthesia: a European survey and review of literature.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a frequent complication of longstanding diabetes mellitus. There is no evidence-based consensus whether neuropathic patients undergoing peripheral regional anesthesia are at increased risk of neurologic damage. It is unknown whether these controversial results have been incorporated into clinical practice. We conducted a survey to test the hypothesis that the majority of respondents would consider DPN a potential risk factor for nerve damage in regional anesthesia, and would adapt their technique when performing regional anesthesia. In parallel, we sought to summarize the current knowledge-base regarding regional anesthesia and DPN. METHODS: We therefore performed 1) a literature search to review current literature and 2) an online computer-based survey among members of the European Society of Regional Anesthesia and Pain Therapy (ESRA). RESULTS: The overall response rate was 19% (584 responders/3107 invitations). About a quarter of participants would avoid regional anesthesia in patients with diabetic neuropathy, and 59% of respondents would counsel patients with diabetic neuropathy about increased risk of regional anesthesia. When techniques were modified, most participants would decrease or omit epinephrine, while fewer respondents would decrease dose of local anesthetic or perform other adjustments. More than 80% agreed with the statement that nerve blocks could be performed safely in diabetic neuropathic patients. CONCLUSION: In conclusion, we report the results of the first survey analyzing attitudes and standards of care among European anesthesiologists with regards to regional anesthesia in DPN. While literature is divided on the question whether pre-existing diabetic neuropathy is a risk factor for new neurological deficit after regional anesthesia, most of the responders of this survey take measures to reduce risks, counsel patients on a possible greater risk of neurologic complications, but only a minority of responders would avoid peripheral regional anesthesia altogether.

Failed epidural: causes and management.

Failed epidural anaesthesia or analgesia is more frequent than generally recognized. We review the factors known to influence the success rate of epidural anaesthesia. Reasons for an inadequate epidural block include incorrect primary placement, secondary migration of a catheter after correct placement, and suboptimal dosing of local anaesthetic drugs. For catheter placement, the loss of resistance using saline has become the most widely used method. Patient positioning, the use of a midline or paramedian approach, and the method used for catheter fixation can all influence the success rate. When using equipotent doses, the difference in clinical effect between bupivacaine and the newer isoforms levobupivacaine and ropivacaine appears minimal. With continuous infusion, dose is the primary determinant of epidural anaesthesia quality, with volume and concentration playing a lesser role. Addition of adjuvants, especially opioids and epinephrine, may substantially increase the success rate of epidural analgesia. Adjuvant opioids may have a spinal or supraspinal action. The use of patient-controlled epidural analgesia with background infusion appears to be the best method for postoperative analgesia.

Lidocaine time- and dose-dependently demethylates deoxyribonucleic acid in breast cancer cell lines in vitro.

BACKGROUND: Anaesthetic management of cancer surgery may influence tumour recurrence. The modulation of gene expression by methylation of deoxyribonucleic acid (DNA) (epigenetics) is increasingly recognized as a major hallmark of cancer. Next to direct effects of local anaesthetics upon tumour cells, the ester-type local anaesthetic, procaine, has been shown to affect methylation status in several tumour cell lines, promoting the reactivation of tumour suppressor genes. We sought to determine whether the prototype amide-type local anaesthetic, lidocaine, influences the survival and epigenetic status of oestrogen receptor (ER)-positive and -negative breast cancer cell lines in vitro. METHODS: Breast cancer cell lines BT-20 (ER-negative) and MCF-7 (ER-positive) were incubated with lidocaine and procaine as the reference substance. We performed cell count and determined apoptosis using TUNEL stain. Further, we assessed global methylation status, and methylation of three known tumour suppressor genes (RASSF1A, MYOD1, and GSTP1) using the MethyLight assay and real-time quantitative polymerase chain reaction, respectively. RESULTS: Baseline methylation was 100-fold higher in BT-20 cells. Here, we observed a dose-dependent decrease in DNA methylation in response to lidocaine (1, 0.01, and 0.01 mM) after 72 h (P<0.001, <0.001, and 0.004, respectively). The corresponding changes were smaller in MCF-7 cells. Global methylation status was profoundly influenced, but the methylation and mRNA expression status of three tumour suppressor genes was unchanged. CONCLUSIONS: Our findings suggest that demethylating tumour-suppressive effects of anaesthetic interventions may only be detectable in specific types of cancer due to differential methylation profiles. In conclusion, at clinically relevant concentrations, lidocaine demethylates DNA of breast cancer cell lines in vitro.

Pulmonary effects of bupivacaine, ropivacaine, and levobupivacaine in parturients undergoing spinal anaesthesia for elective caesarean delivery: a randomised controlled study.

BACKGROUND: Spinal anaesthesia is the method of choice for elective caesarean delivery, but has been reported to worsen dynamic pulmonary function when using bupivacaine. Similar investigations are lacking for ropivacaine and levobupivacaine. We have therefore compared the pulmonary effects of intrathecal bupivacaine, ropivacaine and levobupivacaine used for caesarean delivery. METHODS: Forced vital capacity, forced expiratory volume in the first second, and peak expiratory flow rate were measured in 48 parturients before and after onset of spinal anaesthesia using either 0.5% bupivacaine 10 mg, 1% ropivacaine 20 mg, or 0.5% levobupivacaine 10 mg. Apgar scores and umbilical arterial pH were recorded. RESULTS: The final level of sensory blockade was not different between groups. Forced vital capacity was significantly decreased with bupivacaine (3.6+/-0.5 L to 3.5+/-0.4 L, P<0.05) and ropivacaine (3.2+/-0.4 L to 3.1+/-0.5 L, P<0.05), but not with levobupivacaine (3.6+/-0.5 L to 3.4+/-0.6 L). Forced expiratory volume during the first second was not decreased in any group. Peak expiratory flow rate was significantly decreased with ropivacaine (5.5+/-1.5 L/s to 5.0+/-1.1 L/s, P<0.05) and levobupivacaine (from 6.0+/-1.1 L/s to 5.2+/-0.9 L/s, P<0.01). Neonatal vital parameters did not differ between the three groups. CONCLUSIONS: Decreases in maternal pulmonary function tests were similar following spinal anaesthesia with bupivacaine, ropivacaine, or levobupivacaine for caesarean delivery. The clinical maternal and neonatal effects of these alterations appeared negligible.

An evidence-based update on nonsteroidal anti-inflammatory drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including both traditional nonselective NSAIDs and the selective cyclooxygenase (COX)-2 inhibitors, are widely used for their anti-inflammatory and analgesic effects. NSAIDs are a necessary choice in pain management because of the integrated role of the COX pathway in the generation of inflammation and in the biochemical recognition of pain. This group of drugs has recently come under scrutiny because of recent focus in the literature on the various adverse effects that can occur when applying NSAIDs. This review will provide an educational update on the current evidence of the efficacy and adverse effects of NSAIDs. It aims to answer the following questions: (1) are there clinically important differences in the efficacy and safety between the different NSAIDs, (2) if there are differences, which are the ones that are more effective and associated with fewer adverse effects, and (3) which are the effective therapeutic approaches that could reduce the adverse effects of NSAIDs. Finally, an algorithm is proposed which delineates a general decision-making tree to select the most appropriate analgesic for an individual patient based on the evidence reviewed.