Safety Steps for Epidural Injection of Local Anesthetics

Epidural postoperative analgesia is a popular technique that may improve patient comfort and outcome while reducing hospital costs [1,2]. However, significant risks accompany the injection of local anesthetic into the epidural space, including unintentional subdural, subarachnoid, and intravenous (IV) drug injection. Despite years of use, controversy still surrounds the appropriate steps to ensure the safe initiation of epidural anesthesia. Risks Associated with Epidural Blockade Subdural Injection Subdural injection is the least common misadventure. The subdural space is difficult to enter deliberately, because the arachnoid is closely adherent to the overlying dura in most patients. Entry into this space may not be recognized because cerebral spinal fluid will not flow freely, either spontaneously or with aspiration. Injection of the local anesthetic solution into this small space produces a high level of sensory and motor anesthesia, but with a slower onset than a subarachnoid injection. Subdural anesthesia resembles epidural anesthesia in its speed of onset, although the duration is usually shorter. This clinical picture is suggestive, but definitive confirmation can only be obtained by injection of radiocontrast dye [3-7]. A retrospective review of a pain clinic experience reports an incidence of 0.82% subdural injections, based on a clinical picture of unexpected high "epidural" anesthesia [8], but this report may overestimate the true frequency because of the patient population and the criteria used. Despite several case reports of subdural injection, it seems to be a relatively rare occurrence, as it is not mentioned as a complication of epidural techniques in large series. Intrathecal Injection Accidental dural puncture ("wet tap") is a more common complication. The reported frequency varies between 0.61% and 10.9% (Table 1) [9-16]. Because it is usually readily recognized, a "total spinal" from unintentional injection is relatively rare. Subarachnoid placement is less frequent but more difficult to appreciate when it occurs as a result of migration of the tip of the epidural catheter, during either initial insertion [17] or the course of ongoing epidural therapy, with an incidence reported between 0.26% [11] and 0.6% [16].Table 1: Incidence of Dural Puncture and Total Spinal During Epidural AnesthesiaIntravascular Injection The most significant hazard of epidural blockade is unrecognized unintentional intravascular injection. This is more likely with epidural anesthesia than with other regional techniques because of the number of venous plexuses in the epidural space, and it may be at least partially related to the relatively low pressure existing in these veins. This low pressure, usually equated to intrathoracic pressure, may produce neither a spontaneous flow of blood from a punctured vein nor a positive flow with aspiration; the veins collapse when further negative pressure is applied. Vessel entry can occur on initial insertion of the epidural needle or on insertion of the catheter, or, again, because of migration of the catheter tip at any time during ongoing epidural therapy [18,19]. The frequency of vessel entry ranges from 0.2% to 11% (Table 2) [9,10,13,20-27]. Although the typical frequency seems to be in the range of 2%, vessel entry may occur more often in obstetrical patients [7%-8.5% incidence [28,29]] and in situations in which the epidural catheter is inserted before injection of the local anesthetic [up to 9% incidence [21,30]].Table 2: Frequency of Intravascular Injection with Epidural AnesthesiaIntravascular placement presents significant patient risks for two reasons. First, vessel entry is sometimes difficult to diagnose. Second, bolus injection of large volumes of local anesthetic can rapidly produce toxic drug concentrations. Seizures, respiratory arrest, and, with bupivacaine especially, cardiac arrest and death [31,32] can follow. Reports of bupivacaine-induced cardiac arrest in 1979 stimulated the current interest in test procedures to detect IV placement. Before this time, recommendations regarding safety steps were vague [33,34] and nonspecific [35,36]. Since 1979, there has been extensive interest in developing a simple and reliable method of detecting incorrect, especially intravascular, placement of an epidural needle or catheter. Desirable Properties of Ideal Test The ideal epidural "test" should be safe, simple to use, and incorporate readily available materials and monitoring devices. It must also reliably provide for detection of both intravascular and subarachnoid placement of drug and do so within a short time with minimal patient cooperation. It should have a highly sensitive and specific end point. It should be applicable under multiple situations, including the extremes of age and the presence of concomitant medications, including general anesthetics. Last, it should be safe so as to represent no additional risk to the patient when producing a positive result. Multiple regimens for testing epidural needles and catheters have been suggested, although none are ideal. Recommendations include aspiration, incremental injection, and the injection of markers of intravascular placement such as local anesthetics, epinephrine, air, ephedrine, isoproterenol, succinylcholine, and fentanyl. Critical Review of Current Components of Suggested Tests Aspiration Aspiration of the needle or catheter often allows the identification of subarachnoid and intravascular placement, but there are multiple reports of intravascular injection after negative aspiration [16,20,25] (Table 2). The ability of aspiration to detect intravascular catheter location may depend on the type of epidural catheter used. Aspiration has failed to detect intravascular placement when catheters with a single end-hole are used [25,37]. Some claim that aspiration always detects IV placement of multiholed catheters [38,39]. Systematic clinical trials have not addressed this issue. Aspiration is a useful first step but cannot be relied on as the sole test. Incremental Injection Incremental injection is the mainstay of safe regional anesthesia practice. Theoretically, if small injections are used, the patient will report subjective symptoms before blood local anesthetic concentration reaches the threshold for seizures [25,40]. Even if subjective symptoms are not reported, the use of increments might reduce the peak blood levels obtained before the first signs of seizure activity. Although this recommendation is a logical and appropriate safety step, the efficacy of incremental injection as a true test dose has not been substantiated in a large clinical series. One report of obstetrical patients included 12 of 51 women who received relatively large doses of local anesthetic without any systemic symptoms (the other 39 had seizures), despite subsequent aspiration of blood from the catheter [25], implying that incremental injection will not detect all intravascular injections. Local Anesthetic Test Injections Subarachnoid Injection. A 3-mL local anesthetic test dose is traditionally used to detect subarachnoid injection. Abraham et al. [20] reported that the onset of sensory anesthesia in the S2 dermatome occurs within 2 min when 3 mL of 1.5% hyperbaric lidocaine is injected in the subarachnoid space at the second lumbar level. In contrast, at least 3 min will pass before epidural injection will produce sensory changes, first seen in the L2 distribution. Subarachnoid isobaric bupivacaine has also been studied, but the variability of spread and the delay in onset with doses of 8-15 mg make this an inadequate test [41-46]. The perception of warmth in the feet has been suggested as a potential sign of subarachnoid injection but is not a reliable indicator [47]. If subarachnoid injection of a hyperbaric lidocaine test solution is suspected, a minimum of 2 min should pass before testing for sensory changes in the sacral area. With bupivacaine, a longer delay and a high index of suspicion, seeking multiple signs and symptoms that suggest intrathecal drug injection, are needed. There are risks associated with subarachnoid injection of test doses. In laboring women, significant hypotension and midthoracic (or higher) levels of sensory blockade can follow an intrathecal injection of 3 mL 1.5% lidocaine with 1:200,000 epinephrine [11]. Spinal anesthesia requiring intubation and ventilation has been reported after 3 mL 1.5% lidocaine (45 mg) [48], 2.5 mL 2% 2-chloroprocaine (50 mg) [49], and 3.0 mL 0.5% bupivacaine (15 mg) [42]. Intravascular Injection. Assessing for symptoms of central nervous system irritability produced by subtoxic doses of local anesthetic has also been recommended as an indicator of unintentional intravascular injection [35,36,50-52]. Symptoms include tinnitus, perioral tingling, metallic taste, dizziness, sedation, change in hearing, and multiple other subjective symptoms. Patients are often asked whether they can identify any of these signs after the injection of the standard 3-mL test dose. Unfortunately, there are several limitations of this practice. The amount of local anesthetic required to produce these symptoms is unclear but is probably greater than the total milligram dose usually contained in the standard 3-mL initial test. Lidocaine or chloroprocaine 100 mg [51] or 1 mg/kg [52] or 25 mg of bupivacaine [53] produces subjective symptoms in the unmedicated patient. This requires a minimum of a 5-mL volume (of 2% lidocaine or 0.5% bupivacaine) [40,44]. Preliminary data suggest that the dose of ropivacaine required to produce symptoms is 25% greater than that of bupivacaine [54]. A smaller test dose (to exclude subarachnoid placement) should precede the larger dose designed to identify intravascular placement. Unfortunately, local anesthetics do not produce symptoms in all clinical situations. Laboring women may not report dizziness, tinnitus, or metallic taste after chloroprocaine [51]. Premedication with sedatives such as the benzodiazepines may reduce the sensitivity of this test. Mulroy and colleagues [53] reported that 40% of patients premedicated with midazolam and fentanyl were unable to detect the presence of intravascular doses of chloroprocaine or bupivacaine that were otherwise easily appreciated by unmedicated volunteers. Although there are no large prospective series that quantify the efficacy of this test, it seems that local anesthetics might be an effective indicator of intravascular injection if used in appropriate doses and in unpremedicated patients. Epinephrine Epinephrine is the most extensively studied marker of IV injection (Table 3). Moore and Batra [55] initially reported the use of 15 micro g of epinephrine with local anesthetic in a series of 175 surgical patients. They observed an average increase in heart rate from 79 bpm to 110 bpm within 60 s of injection of the epinephrine test dose. The tachycardia resolved within 60 s. Subsequent studies have established that for unmedicated surgical patients, an increase of heart rate of 20 bpm and an increase of systolic blood pressure (SBP) of 15 mm Hg are sensitive indicators of intravascular injection [56]. Although no large prospective study of the efficacy of the epinephrine test dose has been published, it has become widely used since 1981.Table 3: Summary of Prospective Studies of Efficacy of Epinephrine Epidural Test Doses for Detection of Intravascular InjectionLimitations of Epinephrine. Although the epinephrine test dose meets the desired criteria of simplicity, use of available materials, easy monitoring, and clear end points, both patient conditions and concomitant medications limit its usefulness or require modification of the criteria for a positive test (Table 4).Table 4: Use of Epinephrine Test DosesAcute and chronic use of selective or nonselective beta adrenergic blocking agents reduce the pulse rate changes after epinephrine [56,57]. Although beta blockade attenuates the heart rate changes produced by IV epinephrine, an increase of systolic blood pressure of 15 mm Hg within 2 min is a reliable indicator of intravascular injection in the presence of beta blockade [56]. Studies of other cardiac medications, such as calcium channel blockers or antiarrhythmics, have not been reported. At 1-minimum alveolar anesthetic concentration (MAC) levels in children and adults, halothane [58] and isoflurane [59-61] attenuate the intrinsic hemodynamic variability and interfere with the tachycardic response to epinephrine. As a result, the magnitude of positive hemodynamic criteria should be adjusted in patients receiving potent inhaled anesthetics. During anesthesia with 1 MAC volatile anesthetics, an increase in heart rate of >8 bpm or of SBP >13 mm Hg is an appropriate indicator of intravascular injection of epinephrine. Regional anesthesia alone (in the form of spinal or epidural blockade) does not interfere with the heart rate response, but it can attenuate the increase in SBP from IV injection of epinephrine [62,63]. A high (T5) epidural combined with general anesthesia attenuates both the heart rate and the blood pressure response to an epinephrine test [62]. The chronotropic response to beta-adrenergic stimulation declines progressively with increasing age. Five times the dose of isoproterenol is required to produce a 25-bpm increase in heart rate at age 70 yr as at age 20 yr [64]. This same phenomenon occurs with epinephrine. The original report of Moore and Batra [55] did not include patients over the age of 60 yr. The question is unanswered whether the epinephrine test dose is adequate in the elderly. Two elderly patients have failed to respond to the epinephrine-containing test doses [65]. Shoenwald and colleagues [66] have shown a decrease in sensitivity of the epinephrine test dose in a group of vascular surgery patients (average age 67 yr), in whom a threshold of a 9-bpm increase in heart rate had to be used as a positive criterion. Guinard et al. [67] have shown a progressive decline with age in the heart rate increase in response to a (nonstandard) 10-micro g injection of epinephrine. In their series of 33 patients, the only false-negative 15-micro g test occurred in one patient over the age of 60 yr. These data suggest caution in interpretation of the epinephrine test dose in the elderly. controversy surrounds the use of epinephrine-containing test doses in Although the epinephrine test dose has been recommended in several the response to epinephrine in the and there is the safety of intravascular epinephrine in the and the patient. of Epinephrine in a sensitivity to and require times as isoproterenol to a 25-bpm increase in heart rate as patients patients, the average heart rate by only bpm after IV injection of the standard 15-micro g dose of epinephrine and the average response is a tachycardia by Some women only a the other women with have a increase in and are more sensitive than to the chronotropic of isoproterenol and other with the use of epinephrine in is the presence of heart rate changes during often a significant tachycardia with between an increase in heart rate by IV epinephrine and an increase by pain is than 25% of laboring women have heart rate of at least 20 bpm during the of epidural analgesia without injection of an epinephrine test dose the epinephrine test dose between may limit this In can so often that one injection within 60 s of the test dose injection. 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The in heart rate and blood pressure associated with the IV injection of epinephrine and a of patients to or cardiac The original report by Moore and Batra [55] included patients who changes in during the time of the test dose injections, including one case of the other there have been no reports in the anesthesia of patients an outcome from a positive epinephrine test dose. this may the use of test doses and the on incremental injection in patients who are to be at significant risk of if an epinephrine-containing test dose were injected Test Doses In of the limitations of epinephrine, especially in several other markers of intravascular injection have been recommended and In and reported that mL an effective marker of intravascular injection the heart rate over the changes in heart by small of IV are readily The test is easy to in the is of heart rate changes, and has no In a series of patients, it sensitive rate and specific rate 2%, for intravascular injection It has been effective in a case report and there are no reports of with this test. The safety of the injection test in clinical has to be IV of has been reported in obstetrical with rare which that test are A greater is that the may not be readily available in and this may limit the of the test to the obstetrical isoproterenol, has also been as a potential to epinephrine, especially in and children receiving general anesthesia in whom micro or a total dose of 3 micro g will produce a heart rate increase of 20 bpm (Table In a series of obstetrical patients, IV isoproterenol produced a reliable increase in the heart rate In it does not blood flow There are limitations to the potential use of isoproterenol in the First, its safety on intravascular injection in the has not been Second, sensitivity to this drug may be in there are no data the safety of epidural or subarachnoid injection of Summary of Prospective Studies of Epidural Test Doses for Detection of Intravascular that blood pressure but that the changes not be from et al. required a of the change in heart rate frequency to detect the presence of the intravascular This and of make it that will a as an IV has been as a potential marker of unrecognized intravascular injection and has the that it is to the spinal and has no on blood laboring women, identify the of injection or of 100 micro g fentanyl but patients report and after epidural fentanyl Some do not report any symptoms after IV fentanyl may be useful in producing under general anesthesia (in the of other when epinephrine may not be reliable but its limitations in the patient are Efficacy and of Despite extensive of the risks of epidural anesthesia, there a small but risk of misadventure. subdural and subarachnoid injections will although to testing and appropriate seems to make rare with these two IV insertion of a needle or catheter also seems The risk varies between 0.2% and with a frequency in and with insertion of epidural In to the relatively rate of subdural and subarachnoid injections with epidural anesthesia, there seems to have been a decline in the frequency of systemic toxic with this technique since Although several studies reported high of intravascular injection (Table reports of large series of patients with epidural techniques for postoperative analgesia to a single case of systemic toxic as a complication of epidural insertion In surgical use of et al. reported an incidence of of systemic toxic in in a hospital with the use of aspiration and local anesthetics without epinephrine as a test dose before injection. In a series of with epinephrine-containing test and colleagues 2 patients who systemic toxic to local anesthetics. et al. reported patients who systemic symptoms of local anesthetic no associated with epidural injections during the trials of ropivacaine in patients. In obstetrical et al. reported decrease in to regional since with the frequency of related to local anesthetic in the yr on data from the from the for These data do not any the in the of although et that the decline in systemic is related to a to of local anesthetics, smaller initial and the use of than They reported a decrease in the frequency of systemic from 0.6% to when changes were in in their A review of the reports of to the also an decline in the frequency of systemic toxic and 33 systemic toxic and to bupivacaine were reported, in to and from to total local anesthetic in that Unfortunately, the of these data is they are and do not the true incidence or the of the frequency of these If there has been a decline in the true frequency of systemic toxic it is unclear whether this is an of this the use of incremental injection, the of epinephrine-containing test the use of and smaller total doses of local anesthetic in or other no one for this and no single has by single safety step or test no sensitive or should be as adequate or Recommendations In of the the appropriate at this Subdural injection is a but difficult to complication of epidural anesthesia. and a high index of for the of the signs of subdural anesthesia will Subarachnoid injection is a more but usually more readily recognized, It can occur despite negative aspiration. A local anesthetic test dose 3 mL of solution a milligram dose of local anesthetic to produce a onset of subarachnoid is before the injection of a larger bolus of epidural anesthetic Intravascular placement of an epidural needle or catheter an with epidural anesthesia. the frequency of systemic toxic to local anesthetics seems to have been by the use of multiple safety steps in this including the use of aspiration; incremental injection of local epinephrine-containing test doses in appropriate patients, with appropriate monitoring rate SBP with and modification of the criteria to the clinical (Table test doses anesthetic injections unmedicated when and the minimal required concentration and dose of local single safety step has been shown to be reliable in systemic toxic A of steps associated with on the of the the most effective safety in epidural anesthesia. The their to and for review of the and to the for the