True allergic reactions to local anesthetics are, thankfully, rare. The full spectrum of allergic signs and symptoms ranging from skin irritation to anaphylaxis are indeed possible, though reports are scarce [4, 5]. The likelihood of an allergic reaction is higher with local anesthetics belonging to the amino-ester class. Reactions to preservatives (e.g., methylparaben, metabisulfite) are also possible [6].

Preventing a de novo allergic reaction is not possible. One must, however, ensure that a detailed history is taken from the patient and parents detailing previous exposures to local anesthetics (e.g., dentist’s appointments, emergency room visits) and that the chart is reviewed for documented allergies. When a family history of an allergic reaction to a local anesthetic is provided, the anesthetist should fully characterize the incident, including the offending agent and the consequence thereof. A positive family history does not preclude the use of a particular agent but should increase the level of vigilance in monitoring for a possible adverse event.

One can, however, prevent a mild local reaction from transforming into an anaphylactic reaction with careful monitoring and early intervention. As the majority of blocks are performed in the deeply sedated or anesthetized child, careful monitoring of the site of injection is required for early recognition of local reactions. Continuous cardiopulmonary monitoring is required during the initial stages of a block, and particular attention should be made to ventilator pressures (in the ventilated child), as bronchospasm can occur prior to hemodynamic alterations.

The management of an allergic reaction should be tailored to the presentation. For mild local reactions (e.g., pruritus, erythema), an antihistamine is often sufficient in children who cannot tolerate the symptoms. When the symptoms remain mild but become systemic (e.g., nausea, vomiting), then one should consider the addition of a corticosteroid to systemic and complete (i.e., H1 and H2 receptors) antihistamine blockade. Finally, true anaphylaxis (e.g., hypotension, bronchospasm) should be managed as per Pediatric Advanced Life Support guidelines with maintenance of a patent airway, supplemental oxygenation, and cardiovascular support, bearing in mind that anaphylaxis requires epinephrine (0.01 mg/kg s.c. or i.m.) for successful treatment.

As with allergic reactions, severe systemic toxic reactions to local anesthetics are so exceedingly rare that quantification of the risks of such a reaction is virtually impossible. In three studies that attempted quantification, each with an excess of 20,000 patients, the occurrence of such events was estimated at less than 0.05 % [7–9]. The specific presentations included in this category include cardiovascular disturbances (both electrical and hemodynamic) as well as neural insults (seizures and neurotoxicity).

The pattern of systemic toxic reactions is no different in children than it is in adults, but the presentation can be vastly different. One of the major reasons for this is that when a child is heavily sedated or anesthetized, initial irritability and seizures will not be evident when performing initial blocks. The first signs may in fact be dysrhythmias, hypotension, or even cardiac arrest. The ability to detect inadvertent intravascular injection of local anesthetics is also altered in the pediatric population. Resting heart rates in neonates and infants are so high that a bolus dose of a local anesthetic with epinephrine does not increase the heart rate to a reliably detectable level [10, 11]. Some advocate for vagolysis with atropine prior to injection of epinephrine containing local anesthetic to increase the sensitivity of intravascular injection, while others advocate for the use of isoproterenol [12, 13]. Monitoring T wave height may also provide an early warning system for a systemic toxic reaction (Fig. 8.2). Indeed, detecting an increase in impedance with a nerve stimulator following an injection of D5W prior to the administration of a local anesthetic can be used to rule out intravascular injection [14, 15]. At the very least, one must carefully aspirate prior to the injection of a local anesthetic and repeat the aspiration after any change in needle position.

In any event, it is important for the clinician to recognize the early CNS indicators of inadvertent intravascular injection, as they may occur during continuous anesthetic infusion via peripheral or epidural catheters (Table 8.3).

The toxicity to the nervous system from local anesthetics comes in two forms: CNS toxicity (seizures) and local neural toxicity. Fortunately, the incidence of each remains rare. In two large studies, the incidence of seizures or convulsions following any regional anesthesia in infants and children was estimated at 0.01–0.05 % [9]. Case reports, however, are present in the literature. In one of the first accounts of the use of a caudal block in children with lidocaine, convulsions were reported in two children [16]. Seizures caused by bupivacaine have been also reported in association with continuous infusions [17, 18] and after a top up [19].

The management of seizures induced by local anesthetics remains unclear. There has been a case report of the successful halting of a bupivacaine-induced seizure with a dose of phenytoin [20]. Since the incidence is so low, it is difficult to devise standardized management recommendations. One must always be guided by basic resuscitation principles (i.e., circulation, airway, breathing). The particular agent used to halt seizure activity will be guided by local practice patterns and personal comfort – there is no conclusive evidence for the use of phenytoin compared to benzodiazepines. There are early reports that the use of lipid emulsions may halt seizure activity in an adult patient [21], although this has not yet been reported in the pediatric population. This treatment modality has the advantage of possibly aborting the syndrome of local anesthetic systemic toxicity and preventing the development of life-threatening cardiovascular consequences. Nevertheless, insufficient evidence exists for this method to be uniformly recommended.

Local anesthetics are also directly toxic to neural structures and can result in an irreversible blockade if used at high enough concentrations [22]. Reports suggestive of direct local anesthetic toxicity are difficult to tease out of the literature, and neurological injuries reported are more likely due to direct injury by needles or ischemia from embolized air as a result of a loss of resistance technique. Some have suggested that the young pediatric patient may, theoretically, be at a higher risk for neural toxicity as myelination is not complete until at least two years of age. In children, there is always the possibility that our ability to detect neural injury is lower since we must rely solely on clinical exams and parental history for detection. Furthermore, the plasticity of the nervous system is so great in these patients that the insult may be fully recovered before it was ever detected. Regardless, long-term morbidity is not evident from direct toxicity from local anesthetics.

Cardiovascular toxicity of local anesthetics is the final step in the presentation of local anesthetic toxicity and, as such, is one of the rarest manifestations. In a prospective study performed by Giaufre et al. [9] of over 24,000 infants and children, only four dysrhythmias (0.017 %) were reported, which is within the same order of magnitude reported by a previous retrospective study [23].

Local anesthetics exert their effect by blocking sodium channels. A portion of this block is a use-dependent block – the faster the sodium channels cycle through open, closed, and inactivated conformations, the higher the probability that they will be blocked by the anesthetic. It is this same mechanism that contributes to the dysrhythmias induced by local anesthetics. In case reports, the predominant pattern of presentation of cardiac toxicity in infants and children is ST-segment elevation followed by elevation of T waves and subsequent bradycardia and ventricular dysrhythmias [11, 24, 25]. Complete cardiovascular collapse follows [26].

The initial steps to managing a patient in which local anesthetic systemic toxicity is suspected are no different than any other resuscitation. Airway, respiratory, and cardiovascular support as outlined by Pediatric Advanced Life Support should be followed. A helpful mnemonic, SAVED (Stop injection, Airway, Ventilation, Evaluate circulation, Drugs; Fig. 8.3), was published in the adult literature and is also relevant in the pediatric population [27]. Once the patient’s airway is appropriately controlled and the respiratory status has been optimized, the next step is management of the cardiovascular toxicity. As the child presenting with cardiovascular toxicity is often bradycardic and hypotensive, appropriate support in the form of fluid boluses (10–20 mL/kg of an isotonic crystalloid), epinephrine (0.01 mg/kg), and chest compressions should be provided.

One of the more novel methods of treating cardiovascular toxicity is the use of a lipid emulsion such as Intralipid® (see Chap.​ 7). Recent studies demonstrate improved hemodynamics and survival in animal models of bupivacaine toxicity with the administration of intravenous lipid emulsion [28, 29]. There are two proposed mechanisms of action. One is that the lipid emulsions function to remove local anesthetic molecules from binding sites responsible for cardiovascular depression [30], effectively acting as a “sink” for the anesthetic drug. Evidence also exists that lipid emulsions act by reversing the local anesthetic inhibition on myocardial fatty acid oxidation [31]. By doing this, they restore myocardial adenosine triphosphate supplies, allowing the cardiomyocytes to regain normal electrical and mechanical function. In the adult population, the use of lipid emulsions has been reported to treat local anesthetic-induced cardiac arrest due to bupivacaine, levobupivacaine, ropivacaine, and mepivacaine [32–34]. The use of lipid emulsions in pediatrics has only recently been reported. The first report of the use of lipid emulsions in a pediatric patient was in a 13-year-old girl by Ludot et al. [35]. Fifteen minutes after placing a posterior lumbar plexus block with lidocaine and ropivacaine under general anesthesia, a wide, complex tachycardia was noted and attributed to the use of local anesthetics. A 20 % lipid emulsion was administered at a dose of 3 mL/kg resulting in the restoration of normal hemodynamic parameters and a normalization of the electrocardiogram. Since then, Shah et al. [36] have reported the successful use of a 20 % lipid emulsion at a dose of 2 mL/kg to reverse hypotension and tachycardia attributed to the use of bupivacaine, which was not responsive to two doses of epinephrine (0.02 mg/kg) in a 40-day-old male infant. Currently, the upper limit of safe dosing is unclear, and whether ideal dosing varies among neonates, infants, and children is still unclear. Moreover, whether doses need to be adjusted in those with comorbidities has also not been elucidated. At this time, the recommended dosing for Intralipid® 20 % is a bolus of 1.5 mL/kg i.v. over 1 min, followed by infusion of 0.25 mL/kg/min. Compressions should be maintained to circulate the lipid. Bolus doses can be administered every 3–5 min to a total of 3 mL/kg. Lipid emulsions should be administered (during resuscitation) to patients in cardiac arrest due to local anesthetic toxicity and perhaps even preemptively to those exhibiting neurologic toxicity.

Serious adverse events resulting from the use of local anesthetics remain quite rare. Management guidelines are as scarce as the case reports which support them. That being said, when faced with a case of local anesthetic systemic toxicity or an allergic reaction, the consequences are dire and are true anesthetic emergencies. Basic principles in the management of adverse events from local anesthetics include [37]:

In a prospective study of over 24,000 patients, not one permanent peripheral neural injury was reported as a result of needle penetration [9]. In an adult population, Auroy et al. [39] reported an incidence of permanent nerve injury caused by peripheral nerve blocks to be about 0.02 %, and this finding has been validated in a smaller, more recent study [40]. Assuming that the incidence is similar in the pediatric population, one would have expected that perhaps five to ten pediatric patients in large safety studies would have experienced permanent neural injury, but this has not been the case. There are several possible reasons for this. Perhaps our ability to detect neural injury is diminished in the young child, as history may prove less reliable and is not available in the infant or neonate. In the adult patient, neural injury is almost always accompanied with paresthesia or pain upon injection of local anesthetic, which raises suspicion of intraneural injection and neural trauma. This reporting is not possible in the sedated or anesthetized child and is perhaps unreliable in the immature child; as a result, we do not go looking for transient or permanent neural injuries. In the adult patient, however, there is insubstantial evidence that performing nerve blocks in awake patients results in less neural injury than performing them in anesthetized patients [41]. It is also possible that the child’s immature nervous system is able to adapt to a neural insult and recover function before it is detectable.

Our ability to prevent peripheral neural trauma may account for the low incidence. Needle selection is one particular method of prevention (Table 8.4). Common sense dictates that damage caused by a small-gauge needle is less than that caused by a larger-gauge one. The recommendation for the use of blunt needles in regional anesthesia was made by Selander et al. [42] in 1977. It was thought that blunt needles were less likely to penetrate neural structures and that resultant intraneural injections would be less likely. Although there are no clinical trials supporting recommendations as to what type of needle is best for regional anesthesia procedures in any age range, small-gauge, short, blunt needles are recommended if possible. The likelihood of neural damage can also be decreased with low injection pressures. Even if the needle is placed within the nerve sheath, the majority of trauma may be related to the pressure of injection. Rapid, high-pressure injections should be avoided. A practical way to do this is to aspirate air above the injectate in a syringe and to monitor the volume of the air during injection using a compressed air injection technique (CAIT) (Chap.​ 1, Fig. 1.​9). Injection pressure should be decreased if the volume of air decreases to less than half of its original volume [43]. Finally, one would assume that one of the primary modalities of preventing neural injury would be to use either nerve stimulation or ultrasound to rule out intraneural injection. While we recommend the use of both of these technologies (as described elsewhere in this book), it remains difficult to prove that they in fact decrease intraneural injection and neural trauma from needles [37, 44]. Neural damage as a result of peripheral nerve blocks is rare, and as such, demonstrating the safest approach will prove difficult.

As discussed in Chap.​ 2, recent literature has suggested that by measuring differences in electrical impedance of tissues, it may be possible to distinguish between extraneural and intraneural injection during administration of peripheral nerve blocks. This difference in impedance is thought to relate to the different tissue compositions and water contents of extraneural and intraneural tissue. However, further research is needed to determine whether this technique can be utilized in peripheral nerve blocks in humans as a method to avoid intraneural injection.

Regardless of the safety record of needles with respect to the peripheral nerve, when neurological sequelae are present in a child who has undergone a regional anesthesia procedure, it is the duty of the anesthesiologist to rule out iatrogenic neural injury. Neural symptoms can include motor, sensory, and autonomic dysfunction in a specific neural territory. When these symptoms are found, other causes must be considered. Patient positioning, surgical trauma, and tourniquet application are all possible causes and must be considered. Neural injury caused by the needle may not necessarily be due to laceration, but rather to high-pressure injections which may cause mechanical destruction of the neural fascicular architecture, damage, and subsequent scarring [45]. As indicated previously in this chapter, the substance being injected is also a potential source of injury.

Thus, when a neurologic injury is suspected, a thorough history must be taken, a complete physical examination must be performed and documented, and all stages of the operative period scrutinized. Consultation should be sought with neurological specialists to determine the best and quickest way to achieve a diagnosis. During this time, disclosure to the patient and parents must be timely and thorough. Oftentimes, imaging in the form of an MRI is the primary modality of diagnosis. The anesthesiologist, neurologist, neurosurgeon, and radiologist must work as a team to arrive at a diagnosis before permanent injury occurs. Electrodiagnostic techniques (such as nerve conduction studies, electromyography and evoked potentials) can also be useful under the guidance of a neurologist. Experience from the adult population suggests that should a neurological deficit persist at the time of discharge, most will resolve in 4–6 weeks, and the majority (>99 %) are resolved within one year. The paucity of reports from the pediatric literature suggests that permanent peripheral nerve injury is almost unheard of.

Spinal cord injury following a peripheral or neuraxial block is a feared complication. In the adult literature, there are multiple examples of permanent spinal cord injuries following peripheral nerve blocks [46–48]. There are, however, no such case reports in the pediatric literature. In the 2010 ADARPEF study, complications from over 30,000 regional anesthesia procedures were reported over a 1-year period, and not one permanent spinal cord injury was reported [8]. This is in contrast to the reporting of one permanent neurological deficit in a 3-month-old child in a study following over 10,000 epidurals over a 5-year period [49].

Prevention of needle trauma to the spinal cord is critical. In adults, most cases of permanent neuraxial injury involve deviations from recommended practice. As such, when deviating from the standard practice, the anesthetist should consider it carefully and document the justification for doing so. One of the key ways of preventing neuraxial injury is to increase the distance of the needle from the spinal cord by performing a peripheral block. There are already reports [8] of a large shift away from neuraxial techniques in favor of peripheral blocks in pediatric regional anesthesia. One particular institution reported a decrease in the use of neuraxial anesthesia in pediatric patients from 97 to 24.9 % of cases over the past 17 years [50]. Although placement of epidurals in anesthetized adults remains controversial [41, 51–53], it seems quite clear that this practice is the accepted – and safe – standard in the pediatric population. The reason for this disparity remains unclear.

Knowing the position of the needle tip at all times is key to the prevention of spinal cord injury. This begins with a well-studied technique and a detailed understanding of the anatomy involved for performance of a particular block. Even with technological aids, placing needles without the prerequisite knowledge is tempting fate. Although difficult to prove from the literature, techniques involving nerve stimulation and ultrasound for monitoring needle tip placement are useful tools. As described in other chapters, both techniques can be used for a variety of peripheral and neuraxial procedures and have the potential to decrease the likelihood of a devastating spinal cord injury.

Should it occur, there is no specific treatment for primary needle damage to the spinal cord. When suspected, the initial step in the management of spinal cord injury is the recognition and identification of neural dysfunction. It is important to rule out acute and reversible causes of spinal cord injury (Fig. 8.4). This includes nerve compression from hematomas, as they must be identified and dealt with early (within 6–8 h) to avoid the development of permanent paraplegia or quadriplegia. All causes of neural injury must be investigated, including surgical causes (ligation of spinal cord vessels during abdominal or thoracic surgery, injury to the femoral nerve during pelvic surgery, injury to the lateral cutaneous nerve of the thigh during retraction near the inguinal ligament, and fibular head pressure causing neurapraxia of the lateral popliteal nerve), patient positioning, preexisting conditions, and the regional anesthesia procedure. As with peripheral nerve injuries, neurology and radiology specialists must be consulted immediately and a team approach used to arrive at the correct diagnosis. Each of these specialties has a very useful body of knowledge when dealing with these situations. An emergent MRI is often used to arrive at the correct diagnosis, and management is often guided by the consultant neurologist and neurosurgeon.

Regional techniques involving needles moving towards the lung, particularly the supraclavicular approach, involve the risk of pneumothorax. The risk of pneumothorax in the pediatric population is difficult to quantify, and it is even difficult to glean from the adult literature, with some studies reporting incidences in the range of 5 % and others quoting positive radiologic evidence in up to 25 % of patients [54, 55]. Other approaches to the brachial plexus are often sought for this very reason. With the advent of ultrasound, there is renewed interest in the supraclavicular block. In a series [56] of 40 children (>5 years old), 40 ultrasound-guided supraclavicular blocks were placed without a clinically significant pneumothorax, and Pande et al. [57] reported the successful use of ultrasound in performing nearly 200 supraclavicular blocks without incidence of pneumothorax. These studies are too small to detect the true incidence but provide evidence that the practice of supraclavicular blocks is being revisited with some success.