Portal de Periódicos da CAPES

General principles of regional anaesthesia in children

2019; Elsevier BV; Volume: 19; Issue: 10 Linguagem: Inglês

10.1016/j.bjae.2019.06.003

2058-5357

F. Merella, N. Canchi-Murali, Valeria Mossetti,

Cardiac, Anesthesia and Surgical Outcomes

Learning objectivesBy reading this article, you should be able to:•Explain the benefits of ultrasound-guided regional anaesthesia in children.•Discuss the main physiological and anatomical differences between adults and children.•Demonstrate knowledge of appropriate local anaesthetic agents and adjuncts, their doses in children, and measures to prevent systemic toxicity.•Recognise the controversies in regional anaesthesia and the current recommendations.Key points•Regional anaesthesia in children has many well-documented benefits.•Advances in ultrasound technology have enabled practitioners to perform regional blocks in children with greater accuracy.•Central neuraxial blocks have been progressively replaced by peripheral nerve blocks.•Large retrospective studies and data from a prospective registry suggest that regional anaesthesia is a viable and safe option for postoperative pain relief in children. By reading this article, you should be able to:•Explain the benefits of ultrasound-guided regional anaesthesia in children.•Discuss the main physiological and anatomical differences between adults and children.•Demonstrate knowledge of appropriate local anaesthetic agents and adjuncts, their doses in children, and measures to prevent systemic toxicity.•Recognise the controversies in regional anaesthesia and the current recommendations. •Regional anaesthesia in children has many well-documented benefits.•Advances in ultrasound technology have enabled practitioners to perform regional blocks in children with greater accuracy.•Central neuraxial blocks have been progressively replaced by peripheral nerve blocks.•Large retrospective studies and data from a prospective registry suggest that regional anaesthesia is a viable and safe option for postoperative pain relief in children. Regional anaesthesia (RA) in children has gained acceptance worldwide over the past few decades, and many factors have contributed to the rapid growth in its use. There is good evidence that RA provides good-quality postoperative pain relief.1Suresh S. Schaldenbrand K. Wallis B. et al.Regional anaesthesia to improve pain outcomes in paediatric surgical patients: a qualitative systematic review of randomized controlled trials.Br J Anaesth. 2014; 113: 375-390Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar, 2Liu Y. Seipel C. Lopez M.E. et al.A retrospective study of multimodal analgesic treatment after laparoscopic appendectomy in children.Paediatr Anaesth. 2013; 23: 1187-1192PubMed Google Scholar, 3Chiono J. Raux O. Briguier S. et al.Bilateral suprazygomatic maxillary nerve block for cleft palate repair in children: a prospective, randomized, double-blind study versus placebo.Anesthesiology. 2014; 120: 1362-1369Crossref PubMed Scopus (46) Google Scholar, 4Richman M. Liu S.S. Courpas G. et al.Does continuous peripheral nerve block superior pain control to opioids? A meta-analysis.Anesth Analg. 2006; 102: 248-257Crossref PubMed Scopus (491) Google Scholar, 5Splinter W.M. Thomson M.E. Somatic paravertebral block decreases opioid requirements in children undergoing appendectomy.Can J Anesth. 2010; 57: 206-210Crossref PubMed Scopus (19) Google Scholar In addition, advances in ultrasound (US) technology have influenced the practice of RA in paediatric practice. The benefits of RA in children include: (i) reduced opioid consumption; (ii) reduced incidence of postoperative nausea and vomiting; (iii) reduced postoperative pain scores; and (iv) reduced incidence of respiratory complications.6Bosenberg A. Regional anaesthesia in children: an update.South Afr J Anaesth Analg. 2013; 19: 282-288Crossref Scopus (7) Google Scholar The prevalence of persistent postoperative pain in children after major surgery remains high.7Mossetti V. Boretsky K. Astuto M. et al.Persistent pain following common outpatient surgeries in children: a multicenter study in Italy.Paediatr Anaesth. 2018; 28: 231-236Crossref PubMed Scopus (17) Google Scholar RA is being increasingly used as part of multimodal analgesic regimens, and has proved to be a valid alternative to conventional opioid-based strategies. The drive to reduce the duration of hospital stay and the increased proportion of surgery performed as day-case procedure in higher income countries, has led to an increased use and diversification of RA techniques, as these techniques improve postoperative pain relief and enable early discharge after surgery. Single-shot or catheter techniques, such as paravertebral, transversus abdominis plane, and ilioinguinal and iliohypogastric blocks, are increasingly being offered as part of multimodal analgesic regimens for thoracic and abdominal procedures, although they are still under-utilised.8Willschke H. Bösenberg A. Marhofer P. et al.Ultrasonographic-guided ilioinguinal/iliohypogastric nerve block in rediatric anesthesia: what is the optimal volume?.Anesth Analg. 2006; 102: 1680-1684Crossref PubMed Scopus (140) Google Scholar, 9Boretsky K.R. Regional anesthesia in pediatrics: marching forward.Curr Opin Anaesthesiol. 2014; 27: 556-560Crossref PubMed Scopus (14) Google Scholar, 10Hall Burton D.M. Boretsky K.R. A comparison of paravertebral nerve block catheters and thoracic epidural catheters for postoperative analgesia following the Nuss procedure for pectus excavatum repair.Paediatr Anaesth. 2014; 24: 516-520Crossref PubMed Scopus (77) Google Scholar Serious adverse events after RA in children are rare. The first and second French-Language Society of Paediatric Anaesthesiologists audits (Association des Anesthésistes Réanimateurs Pédiatriques d'Expression Française [ADARPEF]) reported a rate of complications at 0.12% (95% confidence interval [CI]: 0.09–0.17).11Giaufre E. Dalens B. Gombert A. Epidemiology and morbidity of regional anesthesia in children: a one-year prospective survey of the French-Language Society of Pediatric Anesthesiologists.Anesth Analg. 1996; 83: 904-912Crossref PubMed Google Scholar, 12Ecoffey C. Lacroix F. Giaufré E. et al.Epidemiology and morbidity of regional anesthesia in children: a follow-up one-year prospective survey of the French-Language Society of Paediatric Anaesthesiologists (ADARPEF).Paediatr Anaesth. 2010; 20: 1061-1069Crossref PubMed Scopus (238) Google Scholar Subsequent data from the Pediatric Regional Anesthesia Network (PRAN) registry of more than 100,000 nerve blocks confirmed similar findings.13Walker B.J. Long J. Madhankumar S. et al.Complications in pediatric regional anesthesia: an analysis of more than 100,000 blocks from the Pediatric Regional Anaesthesia Network.Anesthesiology. 2018; 129: 721-732Crossref PubMed Scopus (127) Google Scholar Transient neurological deficit was recorded in only 25 cases (2.4 in 10,000 [95% CI: 1.6–3.6 in 10,000]), but none resulted in permanent sequelae. The most common adverse events were catheter malfunctions, such as displacement, occlusion, and disconnection, which occurred in 4% of cases. Another analysis of neuraxial techniques, which included 18,650 caudal blocks, showed an incidence of complications of 1.9% (95% CI: 1.7–2.1), with a peak in children younger than 6 months.14Suresh S. Long J. Birmingham P. et al.Are caudal blocks for pain control safe in children? An analysis of 18,650 caudal blocks from the Pediatric Regional Anesthesia Network (PRAN) database.Anesth Analg. 2015; 120: 151-156Crossref PubMed Scopus (99) Google Scholar Similar findings were reported from the UK National Paediatric Epidural Audit, which showed only a few serious adverse events, including two epidural abscesses, one case of meningism, one post-dural puncture headache, and five cases of severe neuropathy/radiculopathy, which resolved over a period of 4–10 months.15Llewellyn N. Moriarty A. The national pediatric epidural audit.Paediatr Anaesth. 2007; 17: 520-533Crossref PubMed Scopus (203) Google Scholar A single case of cauda equina syndrome in a 4-month-old child was the only persistent neurological deficit reported in 10,633 neuraxial blocks. In a more recent single-centre prospective study, Vicchio and colleagues found similar results.16Vicchio N. Mossetti V. Ivani G. Evaluation of 18279 blocks in a pediatric hospital.Anesth Pain Med. 2015; 5e22897Crossref PubMed Scopus (4) Google Scholar Although neuraxial complications can be potentially devastating, their incidence is extremely low; some cases are potentially preventable, whilst in others the aetiology is unclear.17Meyer M.J. Krane E. Goldschneider K.R. et al.Neurological complications associated with epidural analgesia in children: a report of 4 cases of ambiguous etiologies.Anesth Analg. 2012; 115: 1365-1370Crossref PubMed Scopus (67) Google Scholar, 18Wong G.K. Arab A.A. Chew S. et al.Major complications related to epidural analgesia in children: a 15-year audit of 3,152 epidurals.Can J Anesth. 2013; 60: 355-363Crossref PubMed Scopus (35) Google Scholar In addition, the risk of infection from continuous epidural infusion is low, and its main risk factor is the duration of catheter placement.18Wong G.K. Arab A.A. Chew S. et al.Major complications related to epidural analgesia in children: a 15-year audit of 3,152 epidurals.Can J Anesth. 2013; 60: 355-363Crossref PubMed Scopus (35) Google Scholar Regional anaesthesia has a protective effect in reducing surgical stress and the minimum alveolar concentration of volatile anaesthetic agents.6Bosenberg A. Regional anaesthesia in children: an update.South Afr J Anaesth Analg. 2013; 19: 282-288Crossref Scopus (7) Google Scholar Another potential advantage is the option that certain surgical procedures may be performed using neuraxial anaesthesia in neonates and infants breathing spontaneously with minimal airway instrumentation. When appropriate, peripheral nerve blocks (PNBs) should be offered as an alternative to neuraxial anaesthesia.12Ecoffey C. Lacroix F. Giaufré E. et al.Epidemiology and morbidity of regional anesthesia in children: a follow-up one-year prospective survey of the French-Language Society of Paediatric Anaesthesiologists (ADARPEF).Paediatr Anaesth. 2010; 20: 1061-1069Crossref PubMed Scopus (238) Google Scholar, 13Walker B.J. Long J. Madhankumar S. et al.Complications in pediatric regional anesthesia: an analysis of more than 100,000 blocks from the Pediatric Regional Anaesthesia Network.Anesthesiology. 2018; 129: 721-732Crossref PubMed Scopus (127) Google Scholar Kapral and colleagues published the first report of the use of US imaging in RA in 1994.19Kapral S. Krafft P. Eibenberger K. et al.Ultrasound-guided supraclavicular approach for regional anesthesia of the brachial plexus.Anesth Analg. 1994; 78: 507-513Crossref PubMed Scopus (300) Google Scholar A few years later, its first application in RA practice in children was reported.20Marhofer P. Sitzwohl C. Greher M. et al.Ultrasound guidance for infraclavicular brachial plexus anaesthesia in children.Anaesthesia. 2004; 59: 642-646Crossref PubMed Scopus (224) Google Scholar Since then, the use of US in the performance of RA in children has increased rapidly. Ultrasonography is a valuable aid in visualising anatomical structures, such as sacral dimples or hairy birthmarks in young children. Such features could arouse suspicions of underlying spinal dysraphism or bony defects, both of which are deemed contraindications to neuraxial techniques. US has also enabled anaesthetists to assess the degree of angulation of the spinal processes for epidural anaesthesia, guiding clinicians in optimising the angle of insertion of the Tuohy needle. Historically, high volumes of local anaesthetic (LA) have been used to compensate for imprecise needle placement during landmark-based regional blocks, potentially exposing children to the risk of LA toxicity. US imaging permits a careful evaluation of anatomical targets, visualisation of anatomical variations and of vital structures surrounding the nerves, and distribution of LA around the nerve or plexus. Advances in US technology have improved accuracy and clarity in identifying structures and fascial planes, allowing newer techniques to be developed (transversus abdominis plane, quadratus lumborum, pectoralis, and serratus anterior blocks). In children with skeletal or connective tissue disorders, such as epidermolysis bullosa and syndactyly, the responses to a peripheral nerve stimulator (PNS) can be unreliable and the muscle contractions elicited by these stimuli could be harmful to the fragile tissues. US-guided nerve blocks in such cases prevent the need for the use of a PNS and reduce the potential for tissue damage.20Marhofer P. Sitzwohl C. Greher M. et al.Ultrasound guidance for infraclavicular brachial plexus anaesthesia in children.Anaesthesia. 2004; 59: 642-646Crossref PubMed Scopus (224) Google Scholar Studies in adults and children demonstrate that US-guided regional block increases precision and success rate, enables a faster onset of block, and reduces the amount of LA injected.9Boretsky K.R. Regional anesthesia in pediatrics: marching forward.Curr Opin Anaesthesiol. 2014; 27: 556-560Crossref PubMed Scopus (14) Google Scholar, 21Marhofer P. Harrop-Griffiths W. Kettner S.C. et al.Fifteen years of ultrasound guidance in regional anaesthesia: part 1.Br J Anaesth. 2010; 104: 538-546Abstract Full Text Full Text PDF PubMed Scopus (164) Google Scholar On a transverse-axis view, peripheral nerves can appear as small circles of a few millimetres in diameter, with little interposing adipose tissue or muscle septa. The appearance of nerves can vary from hypo- to hyperechoic, depending on their diameter and the frequency and angle of the US beam. Whilst it is important to stress that every nerve has its own particular US appearance, as a general rule, more central, compact structures like plexuses tend to generate hypoechoic pictures, whilst moving peripherally towards their terminal branches, nerves often appear hyperechoic, because of the presence of large subepineural and interfascicular connective tissues. As nerves and plexuses are often located close to vital structures, such as the spinal cord, pleura (Fig. 1a), major blood vessels, and peritoneum, high-frequency US probes (10–15 MHz) are recommended in children, with an active transducer surface length between 25 and 30 mm. The in-plane (IP) technique, maintaining the needle path along the transducer long axis, Fig. 1(b), is the technique of choice in children, as it permits continuous visualisation of needle tip and its entire length during performance of the block. Lack of training in US-guided RA is believed to be one of the factors limiting its uptake in paediatric practice. Adequate integrated training in US imaging and needling techniques is vital for the safe performance and increased appropriate use of RA in children.21Marhofer P. Harrop-Griffiths W. Kettner S.C. et al.Fifteen years of ultrasound guidance in regional anaesthesia: part 1.Br J Anaesth. 2010; 104: 538-546Abstract Full Text Full Text PDF PubMed Scopus (164) Google Scholar Local anaesthetics are weak bases classified as amide or ester, depending on the intermediate chain between their hydrophobic and hydrophilic domains. Free fractions of both ester and amide LAs bind to the voltage-dependent Na+ channel, preventing depolarisation of the cell membrane, which ultimately blocks the nerve conduction for afferent pain signals and efferent motor transmission. Esters are rapidly metabolised by plasma pseudocholinesterase in adults and young children (including neonates), whilst amides require hepatic biotransformation by cytochrome P450 enzymes, whose function is still immature at birth. Compared to esters, amide LAs produce a lower incidence of allergic reactions, greater lipid solubility and potency, prolonged duration of action, and a greater stability to hydrolysis. Hence, in current paediatric practice, the only ester LA used in practice is tetracaine, which is indicated for spinal anaesthesia in neonates, infants, and young children. Lidocaine is the oldest, safest, and most popular amide LA, but has a short duration of action. The newer S-enantiomers, levobupivacaine and ropivacaine, introduced in the early 2000s, are considered the drugs of choice for RA in children. Both drugs have a prolonged action with better cardiac and neurotoxicity profiles compared with the respective racemic preparations. In addition, ropivacaine has differential neural block properties, with an increased motor-sparing effect. In 2018, the European Society of Regional Anaesthesia & Pain Therapy (ESRA) and the American Society of Regional Anesthesia and Pain Medicine (ASRA) joint committee published evidence-based recommendations, harmonising the choice, dosage of LA, and adjuvant use for RA in children (Table 1).22Suresh S. Ecoffey C. Bosenberg A. et al.The European society of regional anaesthesia and pain therapy/American society of regional anesthesia and pain medicine recommendations on local anesthetics and adjuvants dosage in pediatric regional anesthesia.Reg Anesth Pain Med. 2018; 43: 211-216PubMed Google ScholarTable 1ASRA/ESRA recommendations for a single-injection LA dose for neuraxial nerve block and PNB in childrenNerve blockDrug and concentrationDose (ml kg−1)Spinal anaesthesiaTetracaine 0.5%0.5–1(Child 15 kg) hyper-isobaric bupivacaine 0.5%0.3CaudalRopivacaine 0.2% or levobupivacaine 0.25%0.5–1.2Upper limbBupivacaine, levobupivacaine 0.25%, or ropivacaine 0.2%0.5–1.5Lower limbBupivacaine, levobupivacaine 0.25%, or ropivacaine 0.2%0.5–1.5Fascial plane blocksBupivacaine 25% or ropivacaine 0.2%0.2–0.75 Open table in a new tab Neonates and infants differ from older children and adults in anatomical, physiological, and pharmacokinetic characteristics. Whilst appreciation of smaller and more superficial structures is a critical step, anatomical differences in the spine must also be considered before performing neuraxial blocks (Table 2).Table 2Key anatomical and physiological differences between adults and young childrenCharacteristicsClinical implicationsAnatomicalNerves, vessels, and tendons are smaller; very superficial; with less adipose tissues; and lie close togetherPotential risk of injury to nerve and structures around nerves; US imaging improves accuracy of needle placementThe endoneurium has less connective tissueNerves have shorter diameter with incomplete myelin sheath. Complete myelination may take several yearsEarly onset of both sensory and motor blocks with a risk of prolonged motor block, even with lower concentrations of LANeonates:The dural sac ends at S3–S4 (S2 in adults)The intercristal line is at L5-S1 (L4–L5 in older children and adults)Spinal cord terminates at L3 (L1 in adults)Caution must be taken whilst advancing needle during caudal anaesthesia to avoid dural punctureSpinal anaesthesia should be performed below L4PhysiologicalResults of high cardiac output: (i) Increased systemic absorption of LA(ii) Relatively high proportion of cardiac sodium gated channels are in an open state, with a high affinity to LAIncreased risk of cardiac toxicityHepatic metabolism of LA is not fully functional until 9 months of age.There is reduced concentration of α1-acid glycoprotein until 1 yr of ageRisk of drug accumulation after repeated doses of LA or during continuous infusionLumbar ortho-sympathetic component is poorly represented in childrenChildren are less prone to hypotension after neuraxial block Open table in a new tab Infants have an increased cardiac output and immature hepatic function (in both synthetic and clearance pathways), which can result in increased systemic absorption and accumulation of LA. The accumulation of LA potentially increases the risk of LA systemic toxicity (LAST), especially with repeated bolus doses or a continuous infusion (Table 2). Local anaesthetic systemic toxicity is a very rare, but potentially fatal event in children, with an estimated incidence of 0.76–1.6:10,000; the majority of cases occur in infants.12Ecoffey C. Lacroix F. Giaufré E. et al.Epidemiology and morbidity of regional anesthesia in children: a follow-up one-year prospective survey of the French-Language Society of Paediatric Anaesthesiologists (ADARPEF).Paediatr Anaesth. 2010; 20: 1061-1069Crossref PubMed Scopus (238) Google Scholar, 13Walker B.J. Long J. Madhankumar S. et al.Complications in pediatric regional anesthesia: an analysis of more than 100,000 blocks from the Pediatric Regional Anaesthesia Network.Anesthesiology. 2018; 129: 721-732Crossref PubMed Scopus (127) Google Scholar, 23Polaner D. Taenzer A. Walker B.J. et al.Pediatric Regional Anesthesia Network (PRAN): a multi-institutional study of the use and incidence of complications of pediatric regional anesthesia.Anesth Analg. 2012; 115: 1353-1364Crossref PubMed Scopus (267) Google Scholar In the second ADARPEF study, LAST resulted in one case of convulsions, whilst the UK epidural audit reported only two respiratory arrests and one seizure.12Ecoffey C. Lacroix F. Giaufré E. et al.Epidemiology and morbidity of regional anesthesia in children: a follow-up one-year prospective survey of the French-Language Society of Paediatric Anaesthesiologists (ADARPEF).Paediatr Anaesth. 2010; 20: 1061-1069Crossref PubMed Scopus (238) Google Scholar The current PRAN registry reported seven events, five of which in infants (0.76 in 10,000 [95% CI: 0.3–1.6 in 10,000]).13Walker B.J. Long J. Madhankumar S. et al.Complications in pediatric regional anesthesia: an analysis of more than 100,000 blocks from the Pediatric Regional Anaesthesia Network.Anesthesiology. 2018; 129: 721-732Crossref PubMed Scopus (127) Google Scholar Only three cases (two cardiac arrests and one seizure) required rescue treatment with an intra-lipid. Measures suggested to minimise the risk of LAST include a high level of vigilance; continuous monitoring of vital signs (including ECG); strict compliance with recommended LA doses; and gentle aspiration followed by slow and fractionated injection of LA, avoiding excessive pressure. Conditions that could enhance toxicity, such as hypoxaemia, acidaemia, and hypercarbia, should also be avoided. The maximum safe doses for ropivacaine and levobupivacaine should follow those doses suggested for bupivacaine (Table 1). Early recognition of toxicity is paramount. However, as the majority of children are either anaesthetised or heavily sedated, the detection of CNS symptoms can be challenging. Cardiovascular toxicity can occur without any preceding CNS symptoms. Lipid resuscitation therapy (LRT) in the form of intralipid 20% has shown encouraging results both in animal models and human studies. The latest research results suggest that LRT could work through a multimodal mechanism, which comprises the ability to remove drugs from the brain and myocardium, and redistribute them to muscle and liver, enhancing detoxification. Lipid rescue also improves myocardial performance through its lipid substrates.24Fettiplace M.R. Weinberg G. The mechanisms underlying lipid resuscitation therapy.Reg Anesth Pain Med. 2018; 43: 138-149Crossref PubMed Scopus (66) Google Scholar Ten of the eleven documented cases of LAST in children have been successfully treated with LRT.25Lönnqvist P.A. Ecoffey C. Bosenberg A. et al.The European Society of Regional Anesthesia and Pain Therapy and the American Society of Regional Anesthesia and Pain Medicine joint committee practice advisory on controversial topics in pediatric regional anesthesia I and II: what do they tell us?.Curr Opin Anaesthesiol. 2017; 30: 613-620Crossref PubMed Scopus (28) Google Scholar The Society for Pediatric Anesthesia (SPA) and the ESRA/ASRA joint committee have recently proposed a management guideline for LAST in paediatrics, adapted from the latest adult ASRA guidelines, limiting the maximum cumulative amount of LRT to 10 ml kg−1 (Box 1).25Lönnqvist P.A. Ecoffey C. Bosenberg A. et al.The European Society of Regional Anesthesia and Pain Therapy and the American Society of Regional Anesthesia and Pain Medicine joint committee practice advisory on controversial topics in pediatric regional anesthesia I and II: what do they tell us?.Curr Opin Anaesthesiol. 2017; 30: 613-620Crossref PubMed Scopus (28) Google Scholar, 26Society for Pediatric AnesthesiaPedi crisis checklist 2018.https://www.pedsanesthesia.org/wp-content/uploads/2018/11/SPAPediCrisisChecklistsNov2018.pdfDate accessed: November , 2018Google ScholarManagement of local anaesthetic toxicity in children: SPA guidelines.•Stop injecting the local anaesthetic and call for help.•Confirm or establish adequate IV access.•Maintain the airway and give 100% oxygen. Consider tracheal intubation and optimize lung ventilation.•If seizures occur give a benzodiazepine, such as midazolam 0.05–0.1 mg kg−1 min−1 i.v., while assessing cardiovascular status throughout.•Treat hypotension with small epinephrine dose (max 1 mcg kg−1).•Avoid propofol, vasopressin, calcium channel blockers and beta blockers.•Administer intravenous intralipid as an initial bolus injection of 20% lipid emulsion 1.5 ml kg−1 over a min.•Start an infusion of 20% lipid emulsion at 0.25 ml kg−1 min−1.•Increase the infusion to 0.5 ml kg−1 min−1 if cardiovascular stability is not restored.•Repeat bolus every 3–5 min up to 4.5 ml kg−1 as total dose until circulation is restored.•The total dose should not exceed 10ml kg−1.•Recognize arrhythmias and or cardiac arrest: cardiopulmonary resuscitation (CPR)/pediatric advanced life support (PALS)/advanced paediatric life support (APLS) guidelines.•Continue chest compressions (lipid must circulate). May need prolonged compressions.•Consider alerting nearest cardiopulmonary bypass/ECMO centre and ICU if no return to spontaneous circulation after 6 min.•Monitor and correct acidosis, hypercarbia and hyperkalemia. •Stop injecting the local anaesthetic and call for help.•Confirm or establish adequate IV access.•Maintain the airway and give 100% oxygen. Consider tracheal intubation and optimize lung ventilation.•If seizures occur give a benzodiazepine, such as midazolam 0.05–0.1 mg kg−1 min−1 i.v., while assessing cardiovascular status throughout.•Treat hypotension with small epinephrine dose (max 1 mcg kg−1).•Avoid propofol, vasopressin, calcium channel blockers and beta blockers.•Administer intravenous intralipid as an initial bolus injection of 20% lipid emulsion 1.5 ml kg−1 over a min.•Start an infusion of 20% lipid emulsion at 0.25 ml kg−1 min−1.•Increase the infusion to 0.5 ml kg−1 min−1 if cardiovascular stability is not restored.•Repeat bolus every 3–5 min up to 4.5 ml kg−1 as total dose until circulation is restored.•The total dose should not exceed 10ml kg−1.•Recognize arrhythmias and or cardiac arrest: cardiopulmonary resuscitation (CPR)/pediatric advanced life support (PALS)/advanced paediatric life support (APLS) guidelines.•Continue chest compressions (lipid must circulate). May need prolonged compressions.•Consider alerting nearest cardiopulmonary bypass/ECMO centre and ICU if no return to spontaneous circulation after 6 min.•Monitor and correct acidosis, hypercarbia and hyperkalemia. The analgesic effect of a single-shot PNB does not generally extend over 12 h, requiring a plan for supplemental analgesia in the extended postoperative period. The use of adjuncts has been advocated for PNB in children and can provide the following advantages: (i) early onset of block; (ii) enables the use of diluted LA, especially in neonates and young infants, reducing the total dose of LA; (iii) potential reduction in the incidence of LAST; (iv) prolonged duration of block (at least a 50% increase over LA alone); and (v) reduced use of opioids, with concomitant reduction in adverse effects. In neuraxial block, the ESRA/ASRA joint committee has suggested that the use of either preservative-free morphine (10–20 μg kg−1) or clonidine (1–2 μg kg−1) through intrathecal injection improves the quality analgesia and the duration of blocks. The intrathecal injection of racemic ketamine is not recommended in neonates and infants because of concerns over potential neurotoxic effects. It should be used with caution and only in older children at a dose not exceeding 0.5 μg kg−1. Dexamethasone is not recommended in the absence of any evidence from paediatric studies to support its use. In the context of PNBs, findings from a recent meta-analysis on α2-adrenoceptor agonists, clonidine and dexmedetomidine, showed an improvement in postoperative analgesia compared with plain LA.27Lundblad M. Trifa M. Kaabachi O. et al.Alpha-2 adrenoceptor agonists as adjuncts to peripheral nerve blocks in children: a meta-Analysis.Paediatr Anaesth. 2016; 26: 232-238Crossref PubMed Scopus (30) Google Scholar In absence of more data on toxicity, the minimum effective dose is generally recommended. Currently, there is no evidence to recommend other additives (such as midazolam, neostigmine, magnesium, buprenorphine, and tramadol), and their use in children should be considered only in the context of clinical trials. Several aspects of paediatric RA have generated debate amongst experts. Recent recommendations released by the ESRA/ASRA joint committee on some of these critical topics aim to provide clarification and guidance on safe practice in children.28Ivani G. Suresh S. Ecoffey et al.The European society of regional anaesthesia and pain therapy and the American society of regional anesthesia and pain medicine joint committee practice advisory on controversial topics in pediatric regional anesthesia.Reg Anesth Pain Med. 2015; 40: 526-532Crossref PubMed Scopus (58) Google Scholar The following sections provide a summary of recommendations on asleep compared with awake analgesia, compartment syndrome, the value of a test dose, and saline compared with loss-of-resistance techniques. RA has been successfully described in awake children for short duration of surgery. Potential advantages of awake RA include early detection of symptoms of LAST, reduced risk of intra-neural injection, permanent nerve damage and of complications associated with general anaesthesia (GA), including opioid-related adverse effects. However, in paediatric patients, awake RA may not always be practical and may be associated with an increased risk of failure or potential harm. Causative factors include high levels of patient anxiety, uncontrolled movements during the performance of a block, and difficulty in assessing the intensity of painful stimuli reported by young patients. The late ADARPEF study reported an incidence of postoperative neurological symptoms of 0.17% in 29,870 blocks performed under GA. LAST occurred in only one awake patient.12Ecoffey C. Lacroix F. Giaufré E. et al.Epidemiology and morbidity of regional anesthesia in children: a follow-up one-year prospective survey of the French-Language Society of Paediatric Anaesthesiologists (ADARPEF).Paediatr Anaesth. 2010; 20: 1061-1069Crossref PubMed Scopus (238) Google Scholar In The current PRAN study, the risk of neurological complications or severe LAST was 2.2 in 10,000 (95% CI: 1.5–3.4) for nerve blocks performed under GA, and 15.2 in 10,000 (95% CI: 7.8–28.4) for blocks placed in sedated or awake patients.13Walker B.J. Long J. Madhankumar S. et al.Complications in pediatric regional anesthesia: an analysis of more than 100,000 blocks from the Pediatric Regional Anaesthesia Network.Anesthesiology. 2018; 129: 721-732Crossref PubMed Scopus (127) Google Scholar Such risk remained higher (odds ratio: 2.93; 95% CI: 1.34–5.52; p 30 mmHg is considered critical and should prompt immediate intervention. Continuous epidural or perineural catheter LA, and single-shot LA, have all been blamed for masking early signs of ACS. However, only a few case reports of ACS in paediatrics have been published, and none of them showed a convincing link between RA and delayed diagnosis of ACS, which suggests that sudden pain in previously comfortable patients treated with RA should raise suspicion of ACS. The ESRA/ASRA committee reported that common symptoms of ACS of both upper and lower limbs were (i) increasing pain with increasing analgesic requirement, and (ii) swelling. Conversely, (i) pain remote from the site of surgery, (ii) paraesthesia not ascribed to the analgesic technique, and (iii) pain on passive movement of the limb were more-reliable signs of impending lower-limb ischaemia. The board concluded that there is no convincing evidence that RA complicates the diagnosis of ACS, provided patients are adequately monitored and assessed in the perioperative period. The current best practice guidelines are suggested as follows:(i)Concentration of LA for a single shot in peripheral and neuraxial blocks: bupivacaine, levobupivacaine, or ropivacaine 0.1–0.25%; these are less likely to mask ischaemic pain or to produce muscle weakness.(ii)Dose for continuous infusion: bupivacaine, levobupivacaine, or ropivacaine 0.1% as the maximum permitted concentration.(iii)For high-risk surgery for ACS, when a sciatic nerve catheter is indicated, a restriction in LA volume and concentration is advisable.(iv)Cautious use of LA adjuvants is recommended, as they could enhance the duration and density of the block.(v)High-risk patients should be adequately reviewed by the acute pain services to allow the detection of potential, early ACS signs and symptoms.(vi)If ACS is suspected, measurement of compartment pressure should be performed urgently. Adding adrenaline (epinephrine) (2–5 μg kg−1) to LA to detect accidental intravascular injection in children is controversial. GA and deep sedation are both confounding factors for a correct interpretation of an increase in HR. In addition, false-negative results might be caused by incomplete i.v. administration of the test dose and, although the absence of T-wave changes might be reassuring, it does not entirely exclude intravascular injection. Given the intrinsic challenge in interpreting a negative response, the use of a test dose should remain discretionary. If a test dose is used, the LA solution should be injected slowly, in fractioned boluses (0.1–0.2 ml kg−1), with intermittent aspiration and under ECG monitoring. Finally, a test dose should be interpreted as positive, if T wave or HR modification happens within 30–90 s after its injection. Given the paucity of studies supporting either technique, when used appropriately and when also minimising the injected volume, both techniques have an acceptable level of safety in both infants and children, but in neonates and infants, the cumulative volume of injected air should be limited to 1 ml. A growing body of literature has dispelled concerns about the safety of RA under GA or deep sedation in paediatric practice. Training in the acquisition of US imaging and needling skills, knowledge of paediatric anatomy and physiology, and familiarity with the latest guidelines are key elements to the successful and safe practice of RA in children.