Regional Anesthesia in Children (1996)

Regional anesthesia has been used increasingly for postoperative analgesia in infants and children over the past 15 years. With the introduction of any treatment to new populations, safety concerns are prominent. The French-Language Society of Pediatric Anesthesiologists (ADARPEF), as reported in this issue of Anesthesia & Analgesia, examined the safety of pediatric regional anesthesia in a prospective, uncontrolled, multicenter study [1]. Why Is Safety a Particular Concern with Pediatric Regional Anesthesia? 1. Most children coming for surgery and anesthesia are healthy and tolerate systemic opioids with moderate pain scores, frequent annoying side effects, and a good, but not perfect, safety margin. In order to recommend regional anesthesia for healthy children, the therapeutic ratio must be extremely high and the technique must offer additional advantages to warrant exposing these children to any additional risks. 2. In most circumstances, lack of cooperation requires that children be asleep or heavily sedated for needle or catheter placement; thus, the signs of effective or ineffective placement, intravascular placement, or subarachnoid placement are much more indirect. General anesthetics may reduce the sensitivity of epinephrine as a test dose. 3. While the dose of local anesthetics that can produce cardiovascular or central nervous system toxicity scales directly with body size, the effective dose to block an individual nerve is only weakly dependent on body size. This geometric factor reduces the therapeutic ratio for local anesthetic blockade in smaller subjects compared with larger ones [2,3]. How Safe Is Regional Anesthesia in Children? The primary conclusion of the ADARPEF study was that regional anesthesia in children is generally safe. Among a total of 24,409 cases involving regional anesthesia, there were only 23 reported critical incidents, and none resulted in death or neurologic sequelae. The authors' conclusion of a comparatively low overall risk seems valid, although it is possible that particular subgroups and techniques may be associated with greater risk than others. The authors confirmed the predictions of Desparmet and coworkers [4,5] and of Perillo et al. [6] in our group that test dosing is an imperfect marker for intravascular injection. Several cases of intravascular injection were apparently preceded by uneventful test doses. Problems related to the low predictive value of test dosing have been outlined recently by Toledano et al. [7]. Fortunately, all episodes were managed without sequelae. These findings support the view that dosing of local anesthetics for major conduction blockade should be fractionated and continuous electrocardiographic monitoring should be used to detect signs in addition to tachycardia, including bradycardia, changes in QRS morphology, and ventricular ectopy. In an otherwise excellent pattern of care, two episodes of systemic toxicity were due to very excessive dosing: bupivacaine 3.75 mg/kg along with lidocaine 7.5 mg/kg. This dosing may have been based on a common misconception worth denouncing: simultaneous administration of maximum permissable doses of two local anesthetics is not safe. Clinicians should assume that the toxicities of pairs of local anesthetics are roughly additive. Thus, the composite local anesthetic dosing reported in these two cases is excessive by nearly threefold. Similarly, an episode of hypoventilation was associated with an epidural morphine dose of 100 micro g/kg, which is widely considered to be excessive. The authors conclude that complications of central blockade "are rare and minor as they occur most often in the operating room and are readily managed by experienced anesthesiologists with resuscitative equipment at hand." Their conclusion may not apply as directly to American pediatric centers, which make greater use of continuous epidural opioid infusions in nonintensive care settings. Among the 38 institutions in the French study, 30 used continuous epidural catheter infusions, but in only 13 of 38 centers were patients cared for in non-intensive care unit/nonpostanesthesia care unit settings. Overall, continuous epidural infusions were used for only 4% of patients receiving regional anesthesia (9.4% x 43%). In addition, among all the patients receiving epidural analgesia, via either infusion or single shot, only 5% received opioids. It is plausible that in other populations in which continuous epidural techniques are used more freely on postoperative wards, and particularly in which opioids are used more freely, a greater percentage of complications and critical incidents might occur outside of the operating rooms. Roughly half of all complications are ascribed to wrong equipment, although the correct equipment remains a matter of some debate, and more details would be helpful to confirm or reject these assertions. Which Are Preferable, Peripheral Blocks or Central Blocks? The second major conclusion of the authors of the ADARPEF study is that peripheral nerve blocks should be used more widely, and that, where appropriate, they should be used to substitute for central blocks. The authors may well be correct, and one of the study's authors, Dr. Dalens, has done pioneering work to develop techniques for peripheral nerve blockade in children [8-10]. Nevertheless, these broad assertions remain unproven for several reasons: 1. Assignment of patients was by the practitioner's preference, not by a randomized protocol designed to test a specific hypothesis comparing the two techniques. Thus, selection bias could confound which patients receive which technique. In many hospitals, for example, peripheral blocks are used more for minor procedures and central blocks, particularly involving continuous epidural catheters, are reserved for major procedures. 2. A balanced comparison of central and peripheral nerve blockade (or any other method of analgesia) must evaluate not just safety but efficacy (i.e., pain scores, patient satisfaction, impact of analgesic technique on recovery and postoperative complications), side effects, costs, and charges. The current study does not evaluate efficacy or other outcome variables. Consider by analogy a hypothetical study of 24,000 children after major surgery comparing standard recommended doses of acetaminophen to standard recommended doses of morphine. In the acetaminophen group, the median pain score was 9 of a possible 10, and in the morphine group, the median pain score was 4 out of 10. Suppose that acetaminophen generated fewer nonlethal critical incidents than morphine, e.g., 0 vs 10 episodes of mild hypoventilation, and suppose further that all the morphine-associated hypoventilation episodes were recognized and managed without sequelae. It would be erroneous to conclude from this hypothetical study that, based on the differing incidence of critical incidents, children undergoing major surgery should receive acetaminophen instead of morphine as their primary analgesic, since acetaminophen alone would be quite inadequate for analgesia. In a similar fashion, proper comparison of peripheral blocks to central blocks must include factors in addition to safety. Single-shot caudal blockade with bupivacaine has been compared with either wound infiltration, ilioinguinal/iliohypogastric blockade, or penile blockade in at least 14 controlled studies. A few studies favored caudal blockade, a few favored peripheral blocks or infiltration, and most found no difference in analgesia and small differences in side effects [11-13]. Other studies found that either peripheral or central regional techniques are superior to placebo, acetaminophen, and fixed doses of systemic opioids for hernia repairs and circumcision with regard to either analgesia, side effects, or both. Meta-analysis is made difficult by the differences in study design, doses, and end points (pain scores versus requirements for supplemental analgesics). Potential Limitations of Peripheral Blockade 1. Wound infiltration [14] and peripheral blocks are most effective for minor inguinal or extremity procedures, where near-complete blockade of afferent impulses is feasible. For major upper abdominal or thoracic procedures, unlike more peripheral or minor procedures, peripheral blocks provide some analgesia and reduction in opioid requirements, but they cannot adequately interrupt all the necessary afferent pathways and often require very large doses of local anesthetics [15]. For major abdominal surgery, the most impressive studies of effects of analgesic technique on postoperative outcome in adults have required epidural local anesthetics as a component of a regimen that combines multimodal analgesic therapy with aggressive approaches to postoperative mobilization and early introduction of enteral nutrition [16-18]. 2. Many adult series on brachial plexus blockade include a few cases of paresthesias, some lasting for weeks postoperatively. With blocks performed while patients are asleep, there may be a greater potential for intraneural injection of larger volumes of local anesthetics, and it is somewhat surprising that no cases of prolonged paresthesias were reported. Techniques that do not require close proximity of needles to nerves, such as fascia iliaca blockade, have a theoretical advantage in this regard. Since detailed sensory and motor examinations were not conducted, and since younger children may be unable to report paresthesias, it is possible that a mild peripheral nerve injury could have been missed in the ADARPEF study. 3. The short duration of peripheral blocks limits their effectiveness for adults and children in many settings. For example, single-shot intercostal blockade provides good, but incomplete, analgesia of the chest wall after thoracotomy, but of less than six hours' duration in most cases. Since pain after thoracotomy remains intense for several days, repeated injections are required in order to use intercostal blockade as the primary analgesic technique. Adults might grudgingly tolerate repeated percutaneous injections in multiple intercostal nerves; most children would not. It is noteworthy that intercostal blocks accounted for only 0.2% of the regional anesthetics in the current series. 5. Duration of peripheral blockade appears shorter in children than in adults. In an infant and adult rat model of sciatic nerve blockade, block duration is proportional to absolute dose, not dose per body weight. When dosed proportional to body weight, infant rats have shorter duration of blockade than older rats [2,3]. Continuous catheter techniques for peripheral and plexus blocks are available, but in many locations in the body it is difficult to maintain catheter positions during routine patient movements. Theoretical Advantages of Peripheral Nerve Blockade 1. Effects can be targeted to the affected source of pain directly. The studies of Dalens et al. on extremity blocks are noteworthy in this regard. For example, patients with femur fractures or femur osteotomies experience excellent analgesia from a fascia iliaca block, as with epidural analgesia, but, unlike with epidural analgesia, with fascia iliaca blockade patients maintain full sensory and motor function in the contralateral leg, urinary function, and lower leg protective function in the affected leg. 2. Dangers associated with inadvertent dural puncture and subarachnoid injection are greatly diminished relative to epidural blockade. 3. If opioid dosing can be diminished, opioid side effects, such as sedation, respiratory depression, itching, and urinary retention, may occur less frequently. 4. Continuous peripheral block techniques can extend block duration. In adults, continuous blockade of a plexus or nerve sheath has been used extensively. Continuous femoral blockade may improve outcome in major knee procedures. Pediatric studies of continuous peripheral blockade are limited but show some promise. J. Mehler and coworkers (personal communication) found reduced analgesic requirements and accelerated tracheal extubation using continuous intercostal (not interpleural) blockade in infants undergoing coarctation repairs and ductus arteriosus ligations. 5. Longer duration local anesthetics may become available. The short duration of peripheral nerve blocks may be overcome by sustained-release local anesthetic delivery systems, such as one recently developed here [19]. Biodegradable polyester-bupivacaine microspheres produced three to seven-day block of sciatic nerves in rats with a very wide margin of safety from systemic toxicity. Scale-up from rats to sheep (roughly 100-fold heavier organisms, similar in size to children and adults) has confirmed the safety of this approach; preliminary studies have found five to 10-day blockade of intercostal nerves via percutaneous and open-chest approaches with very safe plasma concentrations (C. Draeger and C. Berde, unpublished observations). Although these studies are preliminary, the implications of these or other types of long-duration local anesthetics for pediatric peripheral nerve blockade are apparent. Conclusion Despite the concerns outlined above, the authors have performed a useful service in prospectively assessing safety of regional anesthesia in a large group of children. Future controlled outcome studies should weigh safety against efficacy in specific populations. The article in this issue of Anesthesia & Analgesia helps identify additional questions to be answered and areas where current techniques and drugs fall short of the ideal care for children [1].