1Acute Pain Management Unit, York District Hospital, York YO3 7HE, UK. 2Section of Anaesthetics, Department of Pharmacology, University of Auckland, PO Box 92019, Auckland, New Zealand*Corresponding author: The Old Barn, Main Street, Shipton, York YO30 1AA, UK
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Keywords: literature review
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
This review considers the efficacy and safety of epidural analgesia in patients recovering from major surgery and is based on a computerized search of the literature from 1976 to 2000 (EMBASE/Medline). The final section will deal with the organizational issues which need to be considered to maximize efficacy and safety and is based on the authors joint experience of supervising acute pain services (APS) in New Zealand and the UK; these services have been responsible for pain relief in over 20 000 patients nursed on general postoperative wards.
![]() |
Efficacy |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The ideal epidural analgesic technique for major surgery would provide effective pain relief with minimal side effects and high levels of patient satisfaction. It would also obtund central sensitization and pain-induced organ dysfunction, leading to improved outcome. This topic is covered in the accompanying review in this issue on postoperative pain relief and surgical outcome83. It is self-evident that the primary measure of efficacy of any analgesic regimen is pain relief. However, pain is a complex, subjective experience which has proved difficult to measure in a reproducible way. Early studies of postoperative analgesia relied on measurement of pain scores at rest and surrogate measures, such as respiratory spirometry. Reliance on measuring pain scores at rest resulted in failure to identify those techniques which allowed patients to mobilize and cough effectively, i.e. techniques that provided dynamic pain relief.42 Total dynamic pain relief, i.e. complete absence of pain on moving and coughing after major upper abdominal surgery, can be produced in the intensive care environment by the use of large doses of opioid and LA drugs. This is an unrealistic aspiration for a ward-based analgesic technique, as high doses of these drugs are associated with an unacceptable incidence of hypotension and respiratory depression. A more realistic approach is to measure pain on movement or coughing and to aim for a patient who can mobilize, take deep breaths and cough effectively and who scores 3 or less out of 10 on a visual analogue or numerical rating scale measured on movement.133 Although many studies have used spirometric assessment as an outcome measure, a recent meta-analysis cast doubt on the validity of using these techniques as a surrogate measure of the efficacy of epidural analgesia.9
The difficulty with interpreting the available data on efficacy is that epidural analgesia is not a single entity but can be provided by a number of pharmacological agents administered into different levels of the epidural space before or after surgical incisions for a wide variety of operations. In this section of the review we consider the evidence from randomized controlled trials (RCTs) in which dynamic pain relief was an outcome measure, in order to assess the factors which modify the effectiveness of epidural analgesia such as the choice of drugs, the site of epidural insertion in relation to the surgical incision and the timing and method of drug delivery.
Choice of drug
Local anaesthetic
Epidural LA drugs administered alone have never become widely used for routine postoperative analgesia because of the significant failure rate resulting from regression of the sensory block110 and the unacceptable incidence of motor blockade and hypotension. In a study of patients undergoing thoracic surgery, despite the infusion of bupivacaine 37.550 mg h1 via a thoracic epidural, 30% of patients required opioid supplementation for inadequate analgesia and 80% had significant hypotension.33 Similar results were also found when bupivacaine 2445 mg h1 or ropivacaine 1030 mg h1 was infused epidurally after upper131 141 and lower53 108 abdominal surgery. In an opioid-free postoperative analgesic regimen, infusion rates of bupivacaine 1012.5 mg h1 supplemented by systemic non-steroidal anti-inflammatory drugs were found to be ineffective in lower abdominal surgery.25
Opioids
The use of epidural analgesia for pain relief was revolutionized by the use of epidural opioids after the discovery of opioid receptors in the dorsal horn of the spinal cord. Opioids have both presynaptic and postsynaptic effects in the dorsal horn and affect the modulation of nociceptive input but do not cause motor or sympathetic blockade.
Despite the initial enthusiasm for epidural opioids, with their promise of profound, long-lasting analgesia with minimal side-effects, there is still considerable debate about their place in postoperative pain management.29 44
Opioid-based techniques have been used widely in the USA and Australia and are usually based on bolus administration of drugs such as morphine, diamorphine and pethidine or the continuous infusion of lipophilic opioids such as fentanyl or sufentanil.
Although bolus epidural opioids may produce longer-lasting analgesia with smaller doses than intermittent i.m. opioids,29 there is less convincing evidence that they improve the quality of analgesia when the technique is compared to i.v. patient-controlled anaesthesia (PCA).60
The RCTs of continuous infusions of lipophilic opioids compared with i.v. or patient-controlled i.v. opioids in which pain on coughing or movement was assessed are shown in Table 1.
|
On the basis of the available studies, the benefits of administering lipophilic opioids alone by the epidural route appear to be marginal, or unproven in the case of upper abdominal surgery, and in many situations will not outweigh the risks of the more invasive route of administration.
Opioidlocal anaesthetic combinations
Epidural infusions of LAopioid combinations are the most commonly used epidural technique in the UK34 and Australia,35 being used by 97% of anaesthetists who use the technique. Their use is based on the clinical observation that the combination of LA and opioid drugs limits the regression of the sensory block seen with LAs alone65 and improves the quality of dynamic pain relief.42 However, there are major regional and national differences in the choice of opioid and LA drugs used for postoperative epidural analgesia. In a UK survey, 40% of anaesthetic departments used diamorphine and 51% used fentanyl in combination with LA drugs.129
The RCTs comparing LAopioid combinations and LA or opioids alone with dynamic pain relief as an outcome measure are shown in Table 2.
|
However, in a within-patient crossover study, Torda and colleagues could not demonstrate any difference in efficacy between bolus doses of fentanyl 50 µg, bupivacaine 50 mg or a mixture of both.157 Similarly, Mahon and colleagues were unable to demonstrate any improvement in efficacy by adding 0.10.2% bupivacaine to fentanyl 10 µg ml1 after the first 2 h after thoracotomy.103
Epidural analgesia with LAopioid combinations has been shown to be significantly better than i.v. PCA morphine in providing dynamic pain relief after major abdominal surgery18 97 104 113 (Table 3).
|
The optimal dose of the LA component of the epidural mixture is becoming clearer. In two postoperative studies in which pain relief on movement37 52 was not significantly better in the combination group, the concentration of bupivacaine used was 0.1% or less and it was delivered as patient-controlled epidural anaesthesia (PCEA) without a background infusion. A dose of 412 mg h1 of bupivacaine, when combined with morphine 50 µg ml1,42 diamorphine 80 µg ml1,101 fentanyl 10 µg ml1,119 sufentanil 1 µg ml1,168 and administered via a thoracic epidural catheter, has been shown to provide effective dynamic pain relief. The addition of opioid, therefore, significantly reduces the hourly requirement of bupivacaine from 2545 mg h1 when used alone.33 108 131
In a recent study, in which a direct search procedure was used to determine the optimal combinations of thoracic epidural bupivacaine and fentanyl after major abdominal surgery, the two most effective regimens were bupivacaine 8 mg h1 and fentanyl 30 µg h1 or bupivacaine 13 mg h1 and fentanyl 25 µg h1; both infused at 9 ml h1.40
Although the doses of LA are small, it is likely that the newer LA drugs, levobupivacaine and ropivacaine, will be used increasingly because of their improved safety margin and, in the case of ropivacaine, the potential advantage of less motor blockade. Although this latter advantage appears to be relevant at the higher concentrations used for intraoperative analgesia, the differences between the drugs are less marked at the dilute concentrations used for postoperative analgesia. In a study after major abdominal surgery, 0.2% ropivacaine was not significantly different, in terms of analgesia or motor blockade, from 0.125% bupivacaine when both were combined with fentanyl 2 µg ml1.14
Site of insertion
A meta-analysis of studies comparing the thoracic or lumbar approaches to the epidural space for opioids alone failed to demonstrate any significant improvement in analgesia when the thoracic approach was used.9
There are no RCTs comparing LAopioid combinations administered via the thoracic and lumbar approaches. Nevertheless, the use of the thoracic rather than the lumbar approach to the epidural space has been one of the major changes in anaesthetic practice over the last 20 yr and has been used in the majority of studies that have demonstrated improved dynamic pain relief.39 42 95 97 101 104 113 115 119 145 146 168 This technique has a number of potential benefits when used for the administration of LAopioid mixtures. The thoracic approach facilitates the incision-congruent administration of lipophilic opioids in small doses and minimizes motor and sympathetic blockade of the lower limbs. Although initially seen as a disadvantage because of the attendant hypotension, the importance of a controllable degree of sympathetic blockade in the attenuation of the adverse adrenergic effects on the cardiovascular and gastrointestinal systems is now being realized.128
Pre- or post-incisional epidural analgesia
In order to see a pre-emptive effect with an analgesic intervention, it is necessary to provide good analgesia with inhibition of central sensitization extending into the postoperative period.169 This may explain the lack of pre-emptive effect when an epidural is given before or after surgical incision and analgesia is provided in the postoperative period by i.v. PCA morphine51 126 (Table 4).
|
Method of drug delivery
Bolus versus infusion
postoperative epidural analgesia is usually administered via a continuous infusion to maintain a level of analgesia and to minimize the cardiovascular and respiratory effects of bolus doses of LA and opioid respectively. Intermittent bolus dosing of LA alone has been shown to minimize block regression and marginally improve analgesia compared with a continuous infusion of the same hourly dose in patients undergoing lower abdominal surgery.48 However, there was no difference in pain scores on coughing between the two groups, and this technique has not been studied in patients receiving epidural LAopioid combinations for upper abdominal surgery.
PCEA with or without a background infusion
Allowing patients to have control of their analgesia has become an important principle in acute pain management. Although the role and optimal regimen of PCEA after major surgery have not yet been fully clarified, the technique has the practical safety advantage of permitting bolus doses which do not require to be mixed on the ward. The importance of a background infusion when using an LAopioid combination was emphasized in a recent study in patients recovering from gastrectomy when PCEA alone was shown to be less effective in reducing pain on coughing than PCEA with a background infusion.86
Choice of adjuvants
In addition to LA agents and opioids, a number of agents have been used as adjuvants to improve the efficacy of epidural analgesia. These include ketamine [antagonist of NMDA (N-methyl-D-aspartate)], midazolam [agonist of GABA (-aminobutyric acid)], clonidine (
2 agonist) and adrenaline.
The results of RCTs of adjuvant agents added to LAopioid combinations are shown in Table 5.
|
The addition or removal of adrenaline to a low-dose epidural mixture of bupivacaine and fentanyl has been investigated by Niemi and Breivik in a double-blind crossover study after major surgery.116 The use of epinephrine was associated with minimal regression of the sensory block, markedly improved pain relief on coughing and reduced serum fentanyl concentrations. Despite concerns about the safety of adding vasoconstrictors to epidural mixtures, Breivik and colleagues have used this triple-component epidural mixture in over 6000 patients with apparent safety.20
![]() |
Safety |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Incidence of serious neurological complications due to epidural analgesia
Because of the rarity of permanent neurological damage resulting from epidural analgesia, it is difficult to estimate its incidence. In a combined series of more than 50 000 epidural anaesthetics, only three patients suffered permanent leg weakness (0.006%).80 A retrospective study of 170 000 epidural anaesthetics in Finland over 10 yr and of the resulting claims for compensation revealed nine serious complications (0.005%): one case of paraparesis, one case of permanent cauda equina syndrome, one case of peroneal nerve paresis, one case of neurological deficit, two bacterial infections, two acute toxic reactions related to the anaesthetic solutions and one overdose of epidural opioid.6 However, the incidence may be underestimated by such retrospective reviews. A prospective French study, involving 30 413 epidurals inserted over a 5-month period, revealed an incidence of severe complications of 0.04%: three cardiac arrests, four convulsions and six neurological injuries.8 Although Giebler and colleagues found no permanent neurological deficit in a study of 4185 epidurals, the upper limit of his 95% confidence interval gives a predicted maximal risk for permanent neurological complications of 0.07%.59 Dahlgren and Tornebrandt similarly reported an incidence of persistent neurological deficit of 0.03% after 9232 epidurals;43 this is 10 times the risk given by Kane80 and by Aromaa and colleagues.6
However, on many occasions the association between epidural anaesthesia/analgesia and serious neurological sequelae is only a temporal one and might be inappropriately suspected to be causal, as described in various case reports.16 94 100 106 132
Adverse events due to the insertion of needle and catheter
Dural puncture
Dural puncture occurs in 0.321.23% of epidural placements59 138 155 172 and can result in the development of a postdural puncture headache. Rarely, subdural haematoma that can result in neurological deterioration has been described after dural puncture58 75; its incidence may be less with loss of resistance to saline than to air.46 81 130 There is also a risk of pneumocephalus if air is used,7 105 which can result in serious complications.93 127 150 The use of saline may again help to reduce the incidence of this and other complications that have been associated with the use of air, notably spinal cord and nerve root compression and venous air embolism.76 78 134 148 In addition, accidental pleural puncture during epidural catheter insertion has been described,57 175 as has haemothorax.74
Direct trauma
Direct trauma to the spinal cord or peripheral nerves due to the needle or catheter is extremely rare, but has been reported. Epidural catheterization is most frequently performed in the awake patient to avoid this risk of neurological damage. This problem, which was highlighted in a recent case report,22 is still being debated.54 In support of epidural insertion in the anaesthetized patient, a recent study involving the placement of cerebrospinal fluid drainage needles and catheters in 530 anaesthetized patients undergoing neurosurgery reported no cases of nerve injury in the immediate postoperative period or within 1 yr of surgery.63
Transient neuropathy
Transient neuropathy with eventual full recovery occurs more commonly but is still relatively infrequent; a recent large prospective multicentre series involving 30 413 epidural anaesthetics reported five cases of radiculopathy (0.016%), over 50% recovering completely within 3 months.8 This incidence is similar to previously published large studies on transient neuropathy: 4 out of 17 439 patients (0.023%)155 and 0.013% from a retrospective study of 1 304 214 epidurals.172 Other much smaller studies report an incidence of 0.240.56%.59 138 A recent paediatric study found an incidence of up to 3%, but this involved small numbers of patients.121 After certain operations, such as tibial fracture fixation, epidural analgesia has been implicated in a higher incidence of neurological complications.73 However, a retrospective study demonstrated no significant association between the development of peroneal nerve palsy after total knee replacement and the use of postoperative epidural analgesia66.
Adverse events due to the presence of an indwelling catheter in the epidural space
Spinal haematoma
Puncture of epidural vessels during catheter placement occurs during 312% of attempts.143 However, the subsequent development of a spinal haematoma causing neurological damage is a rare complication. If not detected and treated early, it results in irreversible paraplegia. The incidence of clinically apparent epidural haematoma is unknown, as any study attempting to quantify it would have to involve an enormous number of patients. However, its occurrence does seem to be increasing, possibly as a result of increased use of regional anaesthesia in combination with altered coagulation [in particular low-molecular weight heparin (LMWH)] or of better reporting of the complication.
The risk of developing a spinal haematoma can be quantified only by either studying large numbers of routine or at-risk patients or collecting case reports of spinal haematoma after epidural blockade. The reported incidence varies greatly between studies. Vandermeulen and colleagues combined 18 studies involving 200 000 patients who received epidural analgesia and found no incidence of epidural haematoma.161 In a review including 13 case series that involved >850 000 epidurals, there were only three cases of haematoma (0.0004%).152 At the other extreme, three cases of epidural haematoma were reported after 9232 (0.03%) epidural insertions;43 an even higher incidence, of two cases out of 1014 (0.2%) insertions, has also been reported.144 On the basis of all available information, Tryba has given the best estimate for the risk of a spinal haematoma after epidural analgesia to be 1:150 000 at the upper 95% confidence interval.158
Examination of case reports of spinal haematoma has revealed potential risk factors, notably haemostatic abnormalities and/or anticoagulation, in particular the timing of catheter insertion and removal in relation to the administration of anticoagulants. In 61 cases of spinal haematoma associated with epidural/spinal anaesthesia, 42 (68%) of them had evidence of haemostatic abnormality: 30 had received heparin and 12 had evidence of coagulopathy or were treated with antiplatelet agents, thrombolytics or anticoagulants.161 Forty-six of these had undergone epidural anaesthesia, 32 with the use of an epidural catheter. In nearly 50% of these 32 patients, the spinal haematoma occurred immediately after removal of the catheter, nine being removed when heparin concentrations were therapeutic. This demonstrates that development of a haematoma is not just related to insertion but also (of equal importance) to removal of the epidural catheter. Overall, 87% of epidural haematomas were related to some haemostatic abnormality or procedure difficulty. Literature concerning obstetric patients revealed 17 cases of haematoma after epidural catheter insertions, of which 14 (82%) had a bleeding diathesis.135
However, three studies involving over 5000 systemically anticoagulated patients and one study of 805 patients taking antiplatelet medication who received central neuraxial blockade described no cases of spinal haematoma.10 70 117 123 Furthermore, four studies, involving intraoperative high-dose heparin during cardiac surgery in 776 adult patients and 234 paediatric patients who received central neuraxial blockade, failed to demonstrate any spinal haematoma formation, provided there were no other risk factors.102 121 136 160
The situation has changed dramatically with the introduction of LMWH as routine thromboembolic prophylaxis. A subsequent surge of epidural haematomas has ignited a very complex debate.67 For detailed current recommendations, the reader is directed to a recent review by Horlocker and Wedel.69 This review can be summarized as follows.
Oral anticoagulation. Catheter placement/removal should not be performed in fully anticoagulated patients. Epidural insertion is relatively safe, if low-dose warfarin (35 mg day1) is started after catheter insertion (192 patients).71 An international normalized ratio (INR) of <1.4 at the time of catheter removal resulted in no case of spinal haematoma (459 patients).170
Intravenous and subcutaneous standard heparin. Systemic heparinization is safe for vascular surgery, if administered 60 min after catheter placement if coagulation is closely monitored and if the catheter is removed when circulating heparin concentrations are low.123 Low-dose subcutaneous heparin in combination with epidural analgesia is safethere were only three cases of spinal haematoma in the literature and none in a review of more than 5000 patients.143
LMWH. At least 40 cases of spinal haematoma have been reported in the USA with neuraxial anaesthesia under LMWH prophylaxis.68 These were probably related to intraoperative or early postoperative administration, a twice-daily dosing schedule and concomitant antiplatelet therapy in the USA, as the European experience, with adherence to strict guidelines, is quite different. The worst incidence of spinal haematoma has been estimated at 1 in 3100 cases with continuous epidural analgesia under LMWH cover in the USA.140 New recommendations follow the European guidelines, recommending 24-hourly dosing and a 12-h interval between LMWH injection and insertion or removal of the catheter.
Antiplatelet medications. It is relatively safe to insert an epidural whilst the patient is receiving antiplatelet medication; this is supported by several large studies involving obstetric and surgical patients.5 72 No increased incidence of bloody tap was observed during epidural insertion in 1000 patients on antiplatelet medication, suggesting no difference in traumatic needle/catheter placement.70
Infection
Infection can be introduced into the epidural space from an exogenous source via contaminated equipment or drugs, or from an endogenous source, leading to bacteraemia, which seeds to the insertion site. Alternatively, the catheter can act as a wick through which infection tracks down from the entry site on the skin to the epidural space. Infection can result in meningitis (if the dura is breached) or epidural abscess formation, resulting in cord compression. It has been demonstrated that the spread of streptococci from the anaesthetists buccal mucosa can cause epidural infections.139 However, facemasks have not been shown to reduce the incidence of neuraxial infections.
Serious neuraxial infections after epidural anaesthesia have been reported as being rare. A review of 50 000 epidural anaesthetics did not show a single epidural or intrathecal infection80 and, more recently, Dahlgren and Tornebrandt reported no cases of epidural abscess out of 9232 epidural insertions.43 However, more recent, smaller studies cite the incidence as being closer to 1:10 000. A prospective Danish study, involving 17 372 epidural catheters, reported the incidence of epidural abscess to be 1:1930 (0.05%),163 other studies giving similar figures of 2:13 000 and 2:2000.84 133 The findings of the Danish study suggest that patients with epidural abscess had a longer mean catheterization time than the population mean, the majority of such patients were immunocompromised by one or more complicating diseases (malignancy, diabetes, multiple trauma, chronic obstructive respiratory disease) and perioperative anticoagulant therapy was involved in most cases.163 There were no reports of abscess formation in patients with catheters in situ for 2 days or less. Predominance of immunocompromised patients has also been found in previous studies.47 82 The risk of persistent neurological deficit from an epidural abscess is almost 50%, which may be explained by the long period from diagnosis of an epidural abscess to intervention;163 this outcome has not improved since the period 19471974.85
Epidural analgesia in patients with known systemic or localized infection remains controversial. Many anaesthetists have considered sepsis to be a relative contraindication for epidural anaesthesia. It is generally recommended that epidural catheterization should not be performed in patients with untreated bacteraemia, unless there is an overwhelming reason to do so.69 Jakobsen and colleagues, in a retrospective study of 69 patients with localized skin infections who underwent repeated epidural catheterization, reported no signs or symptoms of neuraxial infection.77 However, another study reported three neuraxial infections related to epidural catheterization in patients with localized infections.43 Small numbers in the studies make it difficult to provide recommendations.
Any patient with local or systemic infection is potentially at risk of developing neuraxial infection; extreme vigilance must be maintained in the monitoring and detection of epidural infection. There should be careful selection of patients currently responding to antibiotic treatment of their sepsis for which epidural analgesia is proposed. Also, the potential unproven risk of neuraxial infection after intraoperative transient bacteraemia during an obstetric or urological procedure should be considered. However, short-term catheterization in these patients is probably safe.69
Catheter migration
After initial placement of the epidural catheter in the epidural space, the tip of the catheter can move intrathecally. Similarly, i.v. migration can occur. Both must be considered before any bolus dose is administered via the epidural catheter by careful aspiration; a test dose of LA containing epinephrine can also provide evidence of i.v. migration by producing a transient tachycardia. These techniques, and the use of low-dose LAopioid infusions, may help to prevent dramatic complications, such as total spinal anaesthesia with possible neurotoxicity90 and seizures.15 107 147 Unintentional subdural catheter placement or migration can also lead to a high block requiring intubation.27
The incidence of intrathecal migration has been reported as 0.150.18%125 142 a similar figure of 0.18% has been reported for intravenous migration.125
Adverse events related to epidural drug administration
Drug errors
Most commonly, LAs, opioids and/or clonidine are infused into the epidural space to provide postoperative analgesia. All these drugs carry the potential for serious adverse effects. In addition, occasionally drug errors occur whereby the wrong drug is administered via the epidural catheter, sometimes resulting in tragic consequences. The incidence of such cases remains unclear as there are very few case reportsglucose,167 antibiotics,88 thiopentone,26 55 potassium chloride89 92 149 (resulting in paraplegia) and total parenteral nutrition120 have all been inadvertently injected. The use of pharmacy-prepared or commercially prepared solutions, extreme care with labelling of epidural catheters and drugs, checking procedures and the use of dedicated pumps should help avoid these problems.
Respiratory depression
The side-effect of most concern with epidural opioids is respiratory depression. Because of the hydrophilic nature of some opioids, such as morphine, there is an increased tendency for the drug to remain in the CNS, particularly the cerebrospinal fluid, resulting in possible cephalad spread and delayed respiratory depression.
There is an abundance of literature devoted to neuraxial opioids and the incidence of respiratory depression. One Swedish review, encompassing 15 departments of anaesthesia, estimated an incidence of 0.250.4%, the major risk factors being age over 70 yr and additional administration of opioids by other routes.64 A Canadian questionnaire, involving 56 teaching hospitals, cited an estimated incidence of 0.13%.176 Although the choice of opioid is important, fentanyl or diamorphine being more lipophilic and less likely to cause delayed respiratory depression, the dose of drug given by continuous infusion is also important. To emphasize this point, there has been a case report describing three patients who developed severe respiratory depression during an epidural infusion containing bupivacaine and fentanyl 2025 µg ml1.164
The actual, not estimated, incidence of respiratory depression has been reported in numerous studies involving data collection from an APS. The number of patients studied varies between 1014 and 1 304 214, with a reported incidence of 0.241.6%,24 56 125 133 144 154 172 often associated with sedation.91 144 The higher figures are more representative of the incidence using epidural morphine infusion. However, with the administration of epidural morphine <200 µg h1 the risk of respiratory depression is probably no higher than with other epidural opioids.21 Using a PCEA containing fentanyl and LA, the incidence is reported as 0.3%.96
The quoted incidence of respiratory depression when epidural analgesia is supervised by an APS is no higher than the incidence of respiratory depression seen with other forms of opioid analgesia.19 Regular monitoring of respiratory rate and, more importantly, the level of consciousness appears to be adequate to detect respiratory depression, and is indicated for up to 12 h after a bolus injection of morphine and for the entire duration of a continuous infusion.
Hypotension
Accompanying the sensory and motor block of epidural LAs are the sympatholytic effects due to blockade of the sympathetic chain; this results in hypotension. If the block height reaches the cardiac outflow between T1 and T5, there may be a marked hypotensive and bradycardic response, particularly in the presence of hypovolaemia. The degree of hypotension depends on the actual dose, lower concentrations of LA causing less effect on blood pressure. Unopposed parasympathetically mediated bronchoconstriction has also been proposed as the cause of a case of severe bronchospasm during epidural anaesthesia.162
Combining the results of three studies involving nearly 9000 patients, the incidence of hypotension during epidural infusion of LA is 0.73% depending on the concentration used (0.06250.25% bupivacaine) and the criteria for hypotension.45 133 159 Use of a PCEA gave a 6.8% incidence of hypotension.96
The routine use of epidural clonidine up to 900 µg as boluses of 100 µg is likely to produce significant haemodynamic depression and sedation.50 17 114 When infused at 20 µg h1 with bupivacaine and fentanyl, it was shown to improve analgesia at rest and during coughing but, again, was associated with significant haemodynamic changes.118
CNS toxicity
The incidence of CNS toxicity, notably convulsions, as a result of high plasma concentrations of free LA, was reported to be 0.010.12% for bupivacaine when 16 87023 and 40 010155epidural blocks were assessed There was a higher incidence of 0.3 per 1000 with lidocaine.23 Cerebral irritation after doses as low as 30 mg h1 has been described,49 but this is still considerably higher than the optimal dose of bupivacaine recommended by Curatolo and colleagues for LAopioid combination.40 A case of ropivacaine-induced seizure has been described after epidural anaesthesia.1
Motor blockade
Excessive lower limb motor blockade with controlled infusion of epidural LAs is uncommon, occurring in only in 3.0% of cases using low concentrations of bupivacaine.144 If motor blockade does occur, it may result in the development of pressure areas on the heels32 122 151 and deep venous thrombosis.166 Persistent motor blockade of one or both lower limbs in a patient receiving a low dose combination LAopioid thoracic epidural should always be treated with suspicion. Stopping the epidural infusion normally results in neurological improvement within 2 h. If this does not occur, consideration should be given to excluding a spinal haematoma or abscess. Ropivacaine may produce less motor blockade compared with an equianalgesic dose of bupivacaine,174 especially if used in low concentrations (0.1%) with fentanyl (2 µg ml1).98 Epidural blockade has been blamed in occasional case reports for masking the symptoms of compartment syndrome,112 153 156 although there have also been cases which have been diagnosed successfully during epidural blockade.12 111
![]() |
Organizational issues |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The major factors to be considered in the safe and effective management of ward-based epidural analgesia are shown in Table 6.
|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
2 Aguilar JL, Cubells C, Rincon R, Preciado MJ, Valldeperas I, Vidal F. Pre-emptive analgesia following epidural 0.5% bupivacaine. In thoracotomy. Reg Anesth 1994; 19: 72
3 Allaire PH, Messick JMJ, Oesterling JE, et al. A prospective randomized comparison of epidural infusion of fentanyl and intravenous administration of morphine by patient-controlled analgesia after radical retropubic prostatectomy. Mayo Clin Proc 1992; 67: 10311041[ISI][Medline]
4 Andersen G, Rasmussen H, Rosenstock C, et al. Postoperative pain control by epidural analgesia after transabdominal surgery. Efficacy and problems encountered in daily routine. Acta Anaesthesiol Scand 2000; 44: 296301[ISI][Medline]
5 Anonymous. CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women. CLASP (Collaborative Low-dose Aspirin Study in Pregnancy) Collaborative Group. Lancet 1994; 343: 61929[ISI][Medline]
6 Aromaa U, Lahdensuu M, Cozanitis DA. Severe complications associated with epidural and spinal anaesthesias in Finland 19871993. A study based on patient insurance claims. Acta Anaesthesiol Scand 1997; 41: 44552[ISI][Medline]
7 Ash KM, Cannon JE, Biehl DR. Pneumocephalus following attempted epidural anaesthesia. Can J Anaesth 1991; 38: 7724[Abstract]
8 Auroy Y, Narchi P, Messiah A, Litt L, Rouvier B, Samii K. Serious complications related to regional anesthesia: results of a prospective survey in France. Anesthesiology 1997; 87: 47986[ISI][Medline]
9 Ballantyne JC, Carr DB, deFerranti S, et al. The comparative effects of postoperative analgesic therapies on pulmonary outcome: cumulative meta-analyses of randomized, controlled trials. Anesth Analg 1998; 86: 598612[Abstract]
10 Baron HC, LaRaja RD, Rossi G, Atkinson D. Continuous epidural analgesia in the heparinized vascular surgical patient: a retrospective review of 912 patients. J Vasc Surg 1987; 6: 1446[ISI][Medline]
11 Baxter AD, Laganiere S, Samson B, Stewart J, Hull K, Goernert L. A comparison of lumbar epidural and intravenous fentanyl infusions for post-thoracotomy analgesia. Can J Anaesth 1994; 41: 18491[Abstract]
12 Beerle BJ, Rose RJ. Lower extremity compartment syndrome from prolonged lithotomy position not masked by epidural bupivacaine and fentanyl. Reg Anesth 1993; 18: 18990[ISI][Medline]
13 Benzon HT, Wong HY, Belavic JA, et al. A randomized double-blind comparison of epidural fentanyl infusion versus patient-controlled analgesia with morphine for postthoracotomy pain. Anesth Analg 1993; 76: 316322[Abstract]
14 Berti M, Fanelli G, Casati A, et al. Patient supplemented epidural analgesia after major abdominal surgery with bupivacaine/fentanyl or ropivacaine/fentanyl. Can J Anaesth 2000; 47: 2732
15 Bhate H. Cerebral seizures during peridural anaesthesia (systemic reaction following bupivacaine 0.75%). Reg Anaesth 1983; 6: 668[Medline]
16 Bhuiyan MS, Mallick A, Parsloe M. Post-thoracotomy paraplegia coincident with epidural anaesthesia. Anaesthesia 1998; 53: 583586[ISI][Medline]
17 Bonnet F, Boico O, Rostaing S, et al. Postoperative analgesia with extradural clonidine. Br J Anaesth 1989; 63: 4659[Abstract]
18 Boylan JF, Katz J, Kavanagh BP, et al. Epidural bupivacainemorphine analgesia versus patient-controlled analgesia following abdominal aortic surgery: analgesic, respiratory, and myocardial effects. Anesthesiology 1998; 89: 58593[ISI][Medline]
19 Breivik H. Safe perioperative spinal and epidural analgesia: Importance of drug combinations segmental site of injection, training and monitoring. Acta Anaesthesiol Scand 1995; 39: 86971[ISI][Medline]
20 Breivik H, Hogstrom H, Niemi G, et al. Safe and effective postoperative pain relief: Introduction and continuous quality-improvement of comprehensive postoperative pain management programmes. Baillières Clin Anaesthesiol 1995; 9: 42360[ISI]
21 Breivik H, Niemi G, Haugtomt H, Hogstrom H. Optimal epidural analgesia: Importance of drug combinations and correct segmental site of injection. Baillières Clin Anaesthesiol 1995; 9: 493512
22 Bromage PR, Benumof JL. Paraplegia following intracord injection during attempted epidural anesthesia under general anesthesia. Reg Anesth Pain Med 1998; 23: 1047[ISI][Medline]
23 Brown DL, Ransom DM, Hall JA, Leicht CH, Schroeder DR, Offord KP. Regional anesthesia and local anesthetic-induced systemic toxicity: seizure frequency and accompanying cardiovascular changes. Anesth Analg 1995; 81: 3218[Abstract]
24 Burstal R, Wegener F, Hayes C, Lantry G. Epidural analgesia: prospective audit of 1062 patients. Anaesth Intens Care 1998; 26: 16572[ISI][Medline]
25 Callesen T, Schouenborg L, Nielsen D, Guldager H, Kehlet H. Combined epiduralspinal opioid-free anaesthesia and analgesia for hysterectomy. Br J Anaesth 1999; 82: 8815
26 Cay DL. Accidental epidural thiopentone. Anaesth Intens Care 1984; 12: 613[ISI][Medline]
27 Chauhan S, Gaur A, Tripathi M, Kaushik S. Unintentional combined epidural and subdural block. Case report. Reg Anesth 1995; 20: 24951[ISI][Medline]
28 Chauvin M, Hongnat JM, Mourgeon E, Lebrault C, Bellenfant F, Alfonsi P. Equivalence of postoperative analgesia with patient-controlled intravenous or epidural alfentanil. Anesth Analg 1993; 76: 12518[Abstract]
29 Cheam EW, Morgan M. The superiority of epidural opioids for postoperative analgesiafact or fallacy? Anaesthesia 1994; 49: 101921[ISI][Medline]
30 Chia Y-Y, Liu K, Liu Y-C, Chang H-C, Wong C-S. Adding ketamine in a multimodal patient-controlled epidural regimen reduces postoperative pain and analgesic consumption. Anesth Analg 1998; 86: 12459[Abstract]
31 Clinical Standards Advisory Group. Services for patients with pain. London: United Kingdom Stationery Office, 1999
32 Cohen S, Amar D, Pantuck CB, Pantuck EJ, Weissman AB. Adverse effects of epidural 0.03% bupivacaine during analgesia after cesarean section. Anesth Analg 1992; 75: 7536[Abstract]
33 Conacher ID, Paes ML, Jacobson L, Phillips PD, Heaviside DW. Epidural analgesia following thoracic surgery. A review of two years experience. Anaesthesia 1983; 38: 54651[ISI][Medline]
34 Cook TM, Eaton JM, Goodwin AP. Epidural analgesia following upper abdominal surgery: United Kingdom practice. Acta Anaesthesiol Scand 1997; 41: 1824[ISI][Medline]
35 Cook TM, Riley RH. Analgesia following thoracotomy: a survey of Australian practice. Anaesth Intens Care 1997; 25: 5204[ISI][Medline]
36 Cooper DW, Ryall DM, Desira WR. Extradural fentanyl for postoperative analgesia: predominant spinal or systemic action? Br J Anaesth 1995; 74: 1847
37 Cooper DW, Ryall DM, McHardy FE, Lindsay SL, Eldabe SS. Patient-controlled extradural analgesia with bupivacaine, fentanyl, or a mixture of both, after Caesarean section. Br J Anaesth 1996; 76: 6115
38 Cooper DW, Saleh U, Taylor M, et al. Patient-controlled analgesia: epidural fentanyl and i.v. morphine compared after caesarean section. Br J Anaesth 1999; 82: 366370
39 Crews JC, Hord AH, Denson DD, Schatzman C. A comparison of the analgesic efficacy of 0.25% levobupivacaine combined with 0.005% morphine, 0.25% levobupivacaine alone, or 0.005% morphine alone for the management of postoperative pain in patients undergoing major abdominal surgery. Anesth Analg 1999; 89: 15049
40 Curatolo M, Schnider TW, Petersen-Felix S, et al. A direct search procedure to optimize combinations of epidural bupivacaine, fentanyl, and clonidine for postoperative analgesia. Anesthesiology 2000; 92: 32537[ISI][Medline]
41 Dahl JB, Hansen BL, Hjortso NC, Erichsen CJ, Moiniche S, Kehlet H. Influence of timing on the effect of continuous extradural analgesia with bupivacaine and morphine after major abdominal surgery. Br J Anaesth 1992; 69: 48[Abstract]
42 Dahl JB, Rosenberg J, Hansen BL, Hjortso NC, Kehlet H. Differential analgesic effects of low-dose epidural morphine and morphinebupivacaine at rest and during mobilization after major abdominal surgery. Anesth Analg 1992; 74: 3625[Abstract]
43 Dahlgren N, Tornebrandt K. Neurological complications after anaesthesia. A follow-up of 18,000 spinal and epidural anaesthetics performed over three years. Acta Anaesthesiol Scand 1995; 39: 87280[ISI][Medline]
44 De Leon-Casasola OA, Lema MJ. Postoperative epidural opioid analgesia: what are the choices?. Anesth Analg 1996; 83: 86775[Abstract]
45 De Leon-Casasola OA, Parker B, Lema MJ, Harrison P, Massey J. Postoperative epidural bupivacainemorphine therapy. Experience with 4,227 surgical cancer patients. Anesthesiology 1994; 81: 36875[ISI][Medline]
46 Diemunsch P, Balabaud VP, Petiau C, et al. Bilateral subdural hematoma following epidural anesthesia. Can J Anaesth 1998; 45: 32831[Abstract]
47 Du Pen SL, Peterson DG, Williams A, Bogosian AJ. Infection during chronic epidural catheterization: diagnosis and treatment. Anesthesiology 1990; 73: 9059[ISI][Medline]
48 Duncan LA, Fried MJ, Lee A, Wildsmith JA. Comparison of continuous and intermittent administration of extradural bupivacaine for analgesia after lower abdominal surgery. Br J Anaesth 1998; 80: 710[ISI][Medline]
49 Dunne NM, Kox WJ. Neurological complications following the use of continuous extradural analgesia with bupivacaine. Br J Anaesth 1991; 66: 6179[Abstract]
50 Eisenach JC, Lysak SZ, Viscomi CM. Epidural clonidine analgesia following surgery: Phase I. Anesthesiology 1989; 71: 6406[ISI][Medline]
51 Espinet A, Henderson DJ, Faccenda KA, Morrison LMM. Does pre-incisional thoracic extradural block combined with diclofenac reduce postoperative pain after abdominal hysterectomy. Br J Anaesth 1996; 76: 20913
52 Etches RC, Gammer T-L, Cornish R. Patient-controlled epidural analgesia after thoracotomy: A comparison of meperidine with and without bupivacaine. Anesth Analg 1996; 83: 816[Abstract]
53 Etches RC, Writer WD, Ansley D, et al. Continuous epidural ropivacaine 0.2% for analgesia after lower abdominal surgery. Anesth Analg 1997; 84: 78490[Abstract]
54 Fischer HB. Regional anaesthesiabefore or after general anaesthesia? Anaesthesia 1998; 53: 7279[ISI][Medline]
55 Forestner JE, Raj PP. Inadvertent epidural injection of thiopental: a case report. Anesth Analg 1975; 54: 4067[ISI][Medline]
56 Fuller JG, McMorland GH, Douglas MJ, Palmer L. Epidural morphine for analgesia after caesarean section: a report of 4880 patients. Can J Anaesth 1990; 37: 63640[Abstract]
57 Furuya A, Matsukawa T, Ozaki M, Kumazawa T. Interpleural misplacement of an epidural catheter. J Clin Anesth 1998; 10: 4256[ISI][Medline]
58 Garcia-Sanchez MJ, Prieto-Cuellar M, Sanchez-Carrion JM, Galdo-Abadin JR, Martin-Linares JM, Horcajadas-Almansa A. Chronic subdural hematoma secondary to an accidental dural puncture during lumbar epidural anesthesia. Rev Esp Anestesiol Reanim 1996; 43: 3279[Medline]
59 Giebler RM, Scherer RU, Peters J. Incidence of neurologic complications related to thoracic epidural catheterization. Anesthesiology 1997; 86: 5563[ISI][Medline]
60 Gopinathan C, Sockalingham I, Fung MA, Peat S, Hanna MH. A comparative study of patient-controlled epidural diamorphine, subcutaneous diamorphine and an epidural diamorphine/bupivacaine combination for postoperative pain. Eur J Anaesthesiol 2000; 17: 18996[ISI][Medline]
61 Gottschalk A, Smith DS, Jobes DR, et al. Preemptive epidural analgesia and recovery from radical prostatectomy: a randomized controlled trial. J Am Med Assoc 1998; 279: 107682
62 Gourlay GK, Lowalski SR, Plummer JL, Cousins MJ, Armstrong PJ. Fentanyl blood concentration analgesia response relationship in the treatment of postoperative pain. Anesth Analg 1988; 67: 3278
63 Grady RE, Horlocker TT, Brown RD, Maxson PM, Schroeder DR. Neurologic complications after placement of cerebrospinal fluid drainage catheters and needles in anesthetized patients: implications for regional anesthesia. Mayo Perioperative Outcomes Group. Anesth Analg 1999; 88: 38892
64 Gustafsson LL, Schildt B, Jacobsen K. Adverse effects of extradural and intrathecal opiates: report of a nationwide survey in Sweden. Br J Anaesth 1982; 54: 47986[Abstract]
65 Hjortso NC, Lund C, Mogensen T, Bigler D, Kehlet H. Epidural morphine improves pain relief and maintains sensory analgesia during continuous epidural bupivacaine after abdominal surgery. Anesth Analg 1986; 65: 10336[Abstract]
66 Horlocker TT, Cabanela ME, Wedel DJ. Does postoperative epidural analgesia increase the risk of peroneal nerve palsy after total knee arthroplasty? Anesth Analg 1994; 79: 495500[Abstract]
67 Horlocker TT, Wedel DJ. Neuraxial block and low-molecular-weight heparin: balancing perioperative analgesia and thromboprophylaxis. Reg Anesth Pain Med 1998a; 23: 16477
68 Horlocker TT, Wedel DJ. Spinal and epidural blockade and perioperative low molecular weight heparin: smooth sailing on the Titanic. Anesth Analg 1998b; 86: 11536[ISI][Medline]
69 Horlocker TT, Wedel DJ. Neurologic complications of spinal and epidural anesthesia. Reg Anesth Pain Med 2000; 25: 8398[ISI]
70 Horlocker TT, Wedel DJ, Offord KP. Does preoperative antiplatelet therapy increase the risk of hemorrhagic complications associated with regional anesthesia? Anesth Analg 1990; 70: 6314[Abstract]
71 Horlocker TT, Wedel DJ, Schlichting JL. Postoperative epidural analgesia and oral anticoagulant therapy. Anesth Analg 1994; 79: 8993[Abstract]
72 Horlocker TT, Wedel DJ, Schroeder DR, et al. Preoperative antiplatelet therapy does not increase the risk of spinal hematoma associated with regional anesthesia. Anesth Analg 1995; 80: 3039[Abstract]
73 Iaquinto JM, Pienkowski D, Thornsberry R, Grant S, Stevens DB. Increased neurologic complications associated with postoperative epidural analgesia after tibial fracture fixation. Am J Orthop 1997; 26: 6048
74 Iida Y, Kashimoto S, Matsukawa T, Kumazawa T. A hemothorax after thoracic epidural anesthesia. J Clin Anesth 1994; 6: 5057[ISI][Medline]
75 Jack TM. Post-partum intracranial subdural haematoma. A possible complication of epidural analgesia. Anaesthesia 1979; 34: 17680[ISI][Medline]
76 Jackson KE, Rauck RL. Suspected venous air embolism during epidural anesthesia. Anesthesiology 1991; 74: 1901[ISI][Medline]
77 Jakobsen KB, Christensen MK, Carlsson PS. Extradural anaesthesia for repeated surgical treatment in the presence of infection. Br J Anaesth 1995; 75: 53640
78 Jennings AL, Rothwell MP, Naysmith A. Epidural complications and a case of malignant meningitis. Palliative Med 1997; 11: 4836[ISI][Medline]
79 Kampe S, Weigand C, Kaufmann J, Klimek M, Konig DP, Lynch J. Postoperative analgesia with no motor block by continuous epidural infusion of ropivacaine 0.1% and sufentanil after total hip replacement. Anesth Analg 1999; 89: 3958
80 Kane RE. Neurologic deficits following epidural or spinal anesthesia. Anesth Analg 1981; 60: 15061[ISI][Medline]
81 Katz Y, Markovits R, Rosenberg B. Pneumoencephalus after inadvertent intrathecal air injection during epidural block. Anesthesiology 1990; 73: 12779[ISI][Medline]
82 Kee WD, Jones MR, Thomas P, Worth RJ. Extradural abscess complicating extradural anaesthesia for caesarean section. Br J Anaesth 1992; 69: 64752[Abstract]
83 Kehlet H, Holte K. Effect of postoperative analgesia on surgical outcome. Br J Anaesth 2001; 87: 6272.
84 Kindler C, Seeberger M, Siegemund M, Schneider M. Extradural abscess complicating lumbar extradural anaesthesia and analgesia in an obstetric patient. Acta Anaesthesiol Scand 1996; 40: 85861[ISI][Medline]
85 Kindler CH, Seeberger MD, Staender SE. Epidural abscess complicating epidural anesthesia and analgesia. An analysis of the literature. Acta Anaesthesiol Scand 1998; 42: 61420[ISI][Medline]
86 Komatsu H, Matsumoto S, Mitsuhata H, Abe K, Toriyabe S. Comparison of patient-controlled epidural analgesia with and without background infusion after gastrectomy. Anesth Analg 1998; 87: 90710[Abstract]
87 Kopacz DJ, Sharrock NE, Allen HW. A comparison of levobupivacaine 0.125%, fentanyl 4 µg/ml, or their combination for patient-controlled epidural analgesia after major orthopedic surgery. Anesth Analg 1999; 89: 1497503
88 Kopacz DJ, Slover RB. Accidental epidural cephazolin injection: safeguards for patient-controlled analgesia. Anesthesiology 1990; 72: 9447[ISI][Medline]
89 Kulka PJ, Stratesteffen I, Grunewald R, Wiebalck A. Inadvertent potassium chloride infusion in an epidural catheter. Anaesthesist 1999; 48: 8969[ISI][Medline]
90 Lee DS, Bui T, Ferrarese J, Richardson PK. Cauda equina syndrome after incidental total spinal anesthesia with 2% lidocaine. J Clin Anesth 1998; 10: 669[ISI][Medline]
91 Leith S, Wheatley RG, Jackson IJ, Madej TH, Hunter D. Extradural infusion analgesia for postoperative pain relief. Br J Anaesth 1994; 73: 5528[Abstract]
92 Lin D, Becker K, Shapiro HM. Neurologic changes following epidural injection of potassium chloride and diazepam: a case report with laboratory correlations. Anesthesiology 1986; 65: 2102[ISI][Medline]
93 Lin HY, Wu HS, Peng TH, et al. Pneumocephalus and respiratory depression after accidental dural puncture during epidural analgesiaa case report. Acta Anaesthesiol Sin 1997; 35: 11923[Medline]
94 Linz SM, Charbonnet C, Mikhail MS, et al. Spinal artery syndrome masked by postoperative epidural analgesia. Can J Anaesth 1997; 44: 117881[Abstract]
95 Liu S, Angel JM, Owens BD, Carpenter RL, Isabel L. Effects of epidural bupivacaine after thoracotomy. Reg Anesth 1995; 20: 30310[ISI][Medline]
96 Liu SS, Allen HW, Olsson GL. Patient-controlled epidural analgesia with bupivacaine and fentanyl on hospital wards: prospective experience with 1,030 surgical patients. Anesthesiology 1998; 88: 68895[ISI][Medline]
97 Liu SS, Carpenter RL, Mackey DC, et al. Effects of perioperative analgesic technique on rate of recovery after colon surgery. Anesthesiology 1995; 83: 757765[ISI][Medline]
98 Liu SS, Moore JM, Luo AM, Trautman WJ, Carpenter RL. Comparison of three solutions of ropivacaine/fentanyl for postoperative patient-controlled epidural analgesia. Anesthesiology 1999; 90: 72733[ISI][Medline]
99 Loper KA, Ready LB, Downey M, et al. Epidural and intravenous fentanyl infusions are clinically equivalent after knee surgery. Anesth Analg 1990; 70: 725[Abstract]
100 Lovstad RZ, Steen PA, Forsman M. Paraplegia after thoracotomynot caused by the epidural catheter. Acta Anaesthesiol Scand 1999; 43: 2302[ISI][Medline]
101 Lowson SM, Alexander JI, Black AMS, Bambridge AD. Epidural diamorphine infusions with and without 0.167% bupivacaine for postoperative analgesia. Eur J Anaesthesiol 1994; 11: 34552[ISI][Medline]
102 Maeda M, Kosaka Y, Kushizaki H, Yamamori Y, Hashimoto K, Saito Y. Safety of continuous epidural anesthesia during heart surgerychange of coagulation-fibrinolysis under heparinization. Masui Jpn J Anesthiol 1999; 48: 72330
103 Mahon SV, Berry PD, Jackson M, Russell GN, Pennefather SH. Thoracic epidural infusions for post-thoracotomy pain: a comparison of fentanyl-bupivacaine mixtures vs. fentanyl alone. Anaesthesia 1999; 54: 6416[ISI][Medline]
104 Mann C, Pouzeratte Y, Boccara G, et al. Comparison of intravenous or epidural patient-controlled analgesia in the elderly after major abdominal surgery. Anesthesiology 2000; 92: 43341[ISI][Medline]
105 Mateo E, Lopez-Alarcon MD, Moliner S, et al. Epidural and subarachnoidal pneumocephalus after epidural technique. Eur J Anaesthesiol 1999; 16: 4137[ISI][Medline]
106 Matsuura JA, Makhoul RG, Posner MP, Smith J, Litwack RS. Intradural herniation of a thoracic disc causing paraplegia coincident with epidural anesthesia. Anesth Analg 1997; 84: 9223[ISI][Medline]
107 Miguel R, Barlow I, Morrell M, Scharf J, Sanusi D, Fu E. A prospective, randomized, double-blind comparison of epidural and intravenous sufentanil infusions. Anesthesiology 1994; 81: 34652[ISI][Medline]
108 Mitchell RWD, Scott DB, Holmquist E, Lamont M. Continuous extradural infusion of 0.125% bupivacaine for pain relief after lower abdominal surgery. Br J Anaesth 1988; 60: 8513[Abstract]
109 Mogensen T, Eliasen K, Ejlersen E, Vegger P, Nielsen IK, Kehlet H. Epidural clonidine enhances postoperative analgesia from a combined low-dose epidural bupivacaine and morphine regimen. Anesth Analg 1992; 75: 60710[Abstract]
110 Mogensen T, Hjortso N-C, Bigler D, Lund C, Kehlet H. Unpredictability of regression of analgesia during the continuous postoperative extradural infusion of bupivacaine. Br J Anaesth 1988; 60: 5159[Abstract]
111 Montgomery CJ, Ready LB. Epidural opioid analgesia does not obscure diagnosis of compartment syndrome resulting from prolonged lithotomy position. Anesthesiology 1991; 75: 5413[ISI][Medline]
112 Morrow BC, Mawhinney IN, Elliott JR. Tibial compartment syndrome complicating closed femoral nailing: diagnosis delayed by an epidural analgesic techniquecase report. J Trauma-Inj Infect Crit Care 1994; 37: 8678
113 Motamed C, Spencer A, Farhat F, Bourgain JL, Lasser P, Jayr C. Postoperative hypoxaemia: Continuous extradural infusion of bupivacaine and morphine vs patient-controlled analgesia with intravenous morphine. Br J Anaesth 1998; 80: 742747
114 Motsch J, Graber E, Ludwig K. Addition of clonidine enhances postoperative analgesia from epidural morphine: a double-blind study. Anesthesiology 1990; 73: 10671073[ISI][Medline]
115 Mourisse J, Hasenbos MA, Gielen MJ, Moll JE, Cromheecke GJ. Epidural bupivacaine, sufentanil or the combination for post-thoracotomy pain. Acta Anaesthesiol Scand 1992; 36: 7074[ISI][Medline]
116 Niemi G, Breivik H. Adrenaline markedly improves thoracic epidural analgesia produced by a low-dose infusion of bupivacaine, fentanyl and adrenaline after major surgery. A randomised, double-blind, cross-over study with and without adrenaline. Acta Anaesthesiol Scand 1998; 42: 897909[ISI][Medline]
117 Odoom JA, Sih IL. Epidural analgesia and anticoagulant therapy. Experience with one thousand cases of continuous epidurals. Anaesthesia 1983; 38: 2549[ISI][Medline]
118 Paech MJ, Pavy TJ, Orlikowski CE, Lim W, Evans SF. Postoperative epidural infusion: a randomized, double-blind, dose-finding trial of clonidine in combination with bupivacaine and fentanyl. Anesth Analg 1997; 84: 13238[Abstract]
119 Paech MJ, Westmore MD. Postoperative epidural fentanyl infusionis the addition of 0.1% bupivacaine of benefit? Anaesth Intens Care 1994; 22: 914[ISI][Medline]
120 Patel PC, Sharif AM, Farnando PU. Accidental infusion of total parenteral nutrition solution through an epidural catheter. Anaesthesia 1984; 39: 3834[Medline]
121 Peterson KL, DeCampli WM, Pike NA, Robbins RC, Reitz BA. A report of two hundred twenty cases of regional anesthesia in pediatric cardiac surgery. Anesth Analg 2000; 90: 10149
122 Punt CD, van Neer PA, de Lange S. Pressure sores as a possible complication of epidural analgesia. Anesth Analg 1991; 73: 6579[ISI][Medline]
123 Rao TL, El-Etr AA. Anticoagulation following placement of epidural and subarachnoid catheters: an evaluation of neurologic sequelae. Anesthesiology 1981; 55: 61820[ISI][Medline]
124 Ready LB. Acute pain: lessons learned from 25,000 patients. Reg Anesth Pain Med 1999; 24: 499505[ISI]
125 Ready LB, Loper KA, Nessly M, Wild L. Postoperative epidural morphine is safe on surgical wards. Anesthesiology 1991; 75: 4526[ISI][Medline]
126 Richards JT, Read JR, Chambers WA. Epidural anaesthesia as a method of pre-emptive analgesia for abdominal hysterectomy. Anaesthesia 1998; 53: 2968[ISI][Medline]
127 Rodrigo P, Garcia JM, Ailagas J. General convulsive crisis related to pneumocephalus after inadvertent dural puncture in an obstetric patient. Rev Esp Anestesiol Reanim 1997; 44: 2479[Medline]
128 Rolf N, Van Aken H. Physiology and pathophysiology of thoracic sympathetic blockade. Thoracic Epidural Anaesthesia. Baillières Clin Anaesthesiol 1999; 13: 17
129 Romer HC, Russell GN. A survey of the practice of thoracic epidural analgesia in the United Kingdom. Anaesthesia 1998; 53: 101622[ISI][Medline]
130 Rosenow F, Huber M, Scheidt W, Heiss WD. Neurological cause of late postpartum seizures. Arch Gynecol Obstet 1991; 248: 1515[ISI][Medline]
131 Ross RA, Clarke JE, Armitage EN. Postoperative pain prevention by continuous epidural infusion. A study of the clinical effects and the plasma concentrations obtained. Anaesthesia 1980; 35: 6638[ISI][Medline]
132 Rutter SV, Jeevananthan V, Souter R, Cowen MJ. Shared spinal cord scenario: paraplegia following abdominal aortic surgery under combined general and epidural anaesthesia. Eur J Anaesthesiol 1999; 16: 6469[ISI][Medline]
133 Rygnestad T, Borchgrevink PC, Eide E. Postoperative epidural infusion of morphine and bupivacaine is safe on surgical wards. Organisation of the treatment, effects and side-effects in 2000 consecutive patients. Acta Anaesthesiol Scand 1997; 41: 86876[ISI][Medline]
134 Saberski LR, Kondamuri S, Osinubi OY. Identification of the epidural space: is loss of resistance to air a safe technique? A review of the complications related to the use of air. Reg Anesth 1997; 22: 315[ISI][Medline]
135 Sage DJ. Epidurals, spinals and bleeding disorders in pregnancy: a review. Anaesth Intens Care 1990; 18: 31926[ISI][Medline]
136 Sanchez R, Nygard E. Epidural anesthesia in cardiac surgery: is there an increased risk? J Cardiothorac Vasc Anesth 1998; 12: 1703[ISI][Medline]
137 Sandler AN, Stringer D, Panos L, et al. A randomized, double-blind comparison of lumbar epidural and intravenous fentanyl infusions for postthoracotomy pain relief: analgesic, pharmacokinetic, and respiratory effects. Anesthesiology 1992; 77: 62634[ISI][Medline]
138 Scherer R, Schmutzler M, Giebler R, Erhard J, Stocker L, Kox WJ. Complications related to thoracic epidural analgesia: a prospective study in 1071 surgical patients. Acta Anaesthesiol Scand 1993; 37: 3704[ISI][Medline]
139 Schneeberger PM, Janssen M, Voss A. Alpha-hemolytic streptococci: a major pathogen of iatrogenic meningitis following lumbar puncture. Case reports and a review of the literature. Infection 1996; 24: 2933[ISI][Medline]
140 Schroeder DR. Statistics: detecting a rare adverse drug reaction using spontaneous reports. Reg Anesth Pain Med 1998; 23: 1839[ISI]
141 Schug SA, Scott DA, Payne J, Mooney PH, Hagglof B. Postoperative analgesia by continuous extradural infusion of ropivacaine after upper abdominal surgery. Br J Anaesth 1996; 76: 48791
142 Schug SA, Torrie JJ. Safety assessment of postoperative pain management by an acute pain service. Pain 1993; 55: 38791[ISI][Medline]
143 Schwander D, Bachmann F. Heparin and spinal or epidural anesthesia: decision analysis. Ann Fr Anesth Reanim 1991; 10: 28496[ISI][Medline]
144 Scott DA, Beilby DS, McClymont C. Postoperative analgesia using epidural infusions of fentanyl with bupivacaine. A prospective analysis of 1,014 patients. Anesthesiology 1995; 83: 72737[ISI][Medline]
145 Scott DA, Blake D, Buckland M, et al. A comparison of epidural ropivacaine infusion alone and in combination with 1, 2, and 4 µg/mL fentanyl for seventy-two h of postoperative analgesia after major abdominal surgery. Anesth Analg 1999; 88: 85764
146 Scott NB, Mogensen T, Bigler D, Lund C, Kehlet H. Continuous thoracic extradural 0.5% bupivacaine with or without morphine: effect on quality of blockade, lung function and the surgical stress response. Br J Anaesth 1989; 62: 2537[Abstract]
147 Seeling W, Heinrich H. Unexpected intravenous penetration of an epidural catheter. Reg Anaesth 1984; 7: 1379[Medline]
148 Sethna NF, Berde CB. Venous air embolism during identification of the epidural space in children. Anesth Analg 1993; 76: 9257[ISI][Medline]
149 Shanker KB, Palkar NV, Nishkala R. Paraplegia following epidural potassium chloride. Anaesthesia 1985; 40: 457[ISI][Medline]
150 Sherer DM, Onyeije CI, Yun E. Pneumocephalus following inadvertent intrathecal puncture during epidural anesthesia: a case report and review of the literature. J Maternal-Fetal Med 1999; 8: 13840[Medline]
151 Smet IG, Vercauteren MP, De Jongh RF, Vundelinckx GJ, Heylen RJ. Pressure sores as a complication of patient-controlled epidural analgesia after cesarean delivery. Case report. Reg Anesth 1996; 21: 33841[ISI][Medline]
152 Stafford-Smith M. Impaired haemostasis and regional anaesthesia. Can J Anaesth 1996; 43: 12941[Abstract]
153 Strecker WB, Wood MB, Bieber EJ. Compartment syndrome masked by epidural anesthesia for postoperative pain. Report of a case. J Bone Joint Surg Am Vol 1986; 68: 14478[Medline]
154 Stuart-Taylor ME, Billingham IS, Barrett RF, Church JJ. Extradural diamorphine for postoperative analgesia: audit of a nurse-administered service to 800 patients in a district general hospital. Br J Anaesth 1992; 68: 42932[Abstract]
155 Tanaka K, Watanabe R, Harada T, Dan K. Extensive application of epidural anesthesia and analgesia in a university hospital: incidence of complications related to technique. Reg Anesth 1993; 18: 348[ISI][Medline]
156 Tang WM, Chiu KY. Silent compartment syndrome complicating total knee arthroplasty: continuous epidural anesthesia masked the pain. J Arthroplasty 2000; 15: 2413[ISI][Medline]
157 Torda TA, Hann P, Mills G, De Leon G, Penman D. Comparison of extradural fentanyl, bupivacaine and two fentanylbupivacaine mixtures for pain relief after abdominal surgery. Br J Anaesth 1995; 74: 3540
158 Tryba M. Epidural regional anesthesia and low molecular heparin: Pro. Anasthesiol Intensivmed Notfallmed Schmerzther 1993; 28: 17981[Medline]
159 Tsui SL, Irwin MG, Wong CM, et al. An audit of the safety of an acute pain service. Anaesthesia 1997; 52: 10427[ISI][Medline]
160 Turfrey DJ, Ray DA, Sutcliffe NP, Ramayya P, Kenny GN, Scott NB. Thoracic epidural anaesthesia for coronary artery bypass graft surgery. Effects on postoperative complications. Anaesthesia 1997; 52: 10905[ISI][Medline]
161 Vandermeulen EP, Van Aken H, Vermylen J. Anticoagulants and spinal-epidural anesthesia. Anesth Analg 1994; 79: 116577[ISI][Medline]
162 Wang CY, Ong GS. Severe bronchospasm during epidural anaesthesia. Anaesthesia 1993; 48: 5145[ISI][Medline]
163 Wang LP, Hauerberg J, Schmidt JF. Incidence of spinal epidural abscess after epidural analgesia: a national 1-year survey. Anesthesiology 1999; 91: 192836[ISI][Medline]
164 Weightman WM. Respiratory arrest during epidural infusion of bupivacaine and fentanyl. Anaesth Intens Care 1991; 19: 2824[ISI][Medline]
165 Welchew EA. The optimum concentration for epidural fentanyl. A randomised, double-blind comparison with and without 1: 200 000 adrenaline. Anaesthesia 1983; 38: 103741[Abstract]
166 Wheatley RG, Madej TH, Jackson IJB, Hunter D. The first years experience of an acute pain service. Br J Anaesth 1991; 67: 3539[Abstract]
167 Whiteley MH, Laurito CE. Neurologic symptoms after accidental administration of epidural glucose. Anesth Analg 1997; 84: 2167[ISI][Medline]
168 Wiebalck A, Brodner G, Van Aken H. The effects of adding sufentanil to bupivacaine for postoperative patient-controlled epidural analgesia. Anesth Analg 1997; 85: 1249[Abstract]
169 Woolf CJ, Chong M-S. Preemptive analgesiatreating postoperative pain by preventing the establishment of central sensitization. Anesth Analg 1993; 77: 36279[ISI][Medline]
170 Wu CL, Perkins FM. Oral anticoagulant prophylaxis and epidural catheter removal. Reg Anesth 1996; 21: 51724[ISI][Medline]
171 Wu CT, Yeh CC, Yu JC, et al. Pre-incisional epidural ketamine, morphine and bupivacaine combined with epidural and general anaesthesia provides pre-emptive analgesia for upper abdominal surgery. Acta Anaesthesiol Scand 2000; 44: 638[ISI][Medline]
172 Xie R, Liu YP. Survey of the use of epidural analgesia in China. Chin Med J 1991; 104: 5105[ISI][Medline]
173 Yaksh TL. Epidural ketamine: a useful, mechanistically novel adjuvant for epidural morphine? Reg Anesth 1996; 21: 50813[ISI][Medline]
174 Zaric D, Nydahl PA, Philipson L, Samuelsson L, Heierson A, Axelsson K. The effect of continuous lumbar epidural infusion of ropivacaine (0.1%, 0.2%, and 0.3%) and 0.25% bupivacaine on sensory and motor block in volunteers: a double-blind study. Reg Anesth 1996; 21: 1425[ISI][Medline]
175 Zaugg M, Stoehr S, Weder W, Zollinger A. Accidental pleural puncture by a thoracic epidural catheter. Anaesthesia 1998; 53: 6971
176 Zimmermann DL, Stewart J. Postoperative pain management and acute pain service activity in Canada. Can J Anaesth 1993; 40: 56875[Abstract]