**3. Commonly used Adjuvants to local anaesthetics in clinical practice**

Local anaesthetics added to the number of anaesthetic techniques to accommodate various patient groups depending on the type of surgery and patient's functional status. Amide local anaesthetics (LA) are the most widely used in modern clinical anaesthetic practice. However, Anaesthesiologists still awaits development of an ideal LA with longer duration of action, bet‐ ter nerve fibre selectivity, a lesser degree of motor blockade and lower incidences of systemic toxicity. In this quest, multiple adjuvants have been used in clinical practice with varying results. This section aims to discuss the adjuvants to LA for nerve blocks, spinal anaesthesia, caudals and epidural anaesthesia. The actual techniques and complications are beyond the scope of this chapter.

#### **3.1. Adjuvants to local anaesthetics (LA)**

#### **1. Opioids**

Low concentration of local anaesthetics causes vasoconstriction, and higher concentration causes vasodilation with the exception of cocaine, which consistently produces vasoconstric‐

The management of cardiovascular toxicity is based on sound understanding and imple‐ mentation of the basic principle of cardiopulmonary resuscitation [25]. The steps for effective

prevent hypercarbia, and acidosis which potentiate the CNS toxicity of local anaesthetics [20]. Ensure the patency of airway: if the patency of the airway is compromised or patient is un‐ able to maintain the airway, securing the airway endotracheal tube and subsequent ventila‐

• Suppress seizures with the use of benzodiazepines or induction of a full general anaesthesia. • In case of a cardiovascular collapse, effective chest compression as per the advanced car‐ diac life support (ACLS) guideline should commence. Clinicians need to be aware that CPR in a setting of local anaesthetics cardiac toxicity will require prolonged effort and dosage adjustment (limit epinephrine bolus doses to <1 mcg/kg which is far less than in a classic

• Avoid vasopressin, calcium channel blockers, beta blockers or local anaesthetic in the man‐

• Twenty per cent of intralipid should be used without delay along with the initial resuscita‐ tive measures as per the practice guidelines of the American Society of Regional Anaesthe‐

• Recommended upper limit: approximately 10 mL/kg lipid emulsion over the first 30 min.

This is a complication associated with a specific local anaesthetic, namely prilocaine. Prilocaine is metabolised in the liver, and o‐toluidine is produced as a by‐product of this metabolism. O‐toluidine is a strong oxidant that oxidises haemoglobin to methaemoglobin. Severe meth‐

aemoglobinemia can be treated effectively with an infusion of methylene blue [21].

• A bolus of 1.5 mL/kg IV for 1 min followed by an infusion of 0.25 mL/kg/min.

• Double the infusion rate to 0.5 mL/kg/min if blood pressure remains low. • Continue infusion for at least 10 min after attaining circulatory stability.

• Repeat bolus once or twice for persistent cardiovascular collapse.

to prevent hypoxaemia, ventilate the patient to

tion regardless of the concentration [21].

14 Current Topics in Anesthesiology

*2.2.3. Management of local anaesthetic toxicity*

• Stop injection or infusion of the agent.

tion is recommended.

CPR protocol).

sia (ASRA) [25].

**2.3. Methaemoglobinemia**

agement of cardiac arrhythmia.

• Call for help and start basic life support.

• Airway management: administer 100% O<sup>2</sup>

management of CNS toxicity of local anaesthetics include:

The use of neuraxial opioids in human subjects dates back to 1979 [26, 27]. Since then, they have been proven to provide effective and prolonged analgesia [28]. In addition, this synergy allows for decreased LA doses with the hope to reduce the incidence of hypotension for simi‐ lar pain relief. Combining LA with intrathecal morphine has been shown to prolong analgesic effect after lower limb arthroplasty and spinal anaesthesia [29–31]. Epidural opioids also pro‐ vide similar analgesic benefit although only limited to 6 h following joint arthroplasty [32]. These benefits have to be balanced against a high incidence of side effects including respira‐ tory depression (which may be delayed up to several hours post‐administration), nausea, vomiting and urinary retention [33]. The evidence for analgesic benefit of using opioids in brachial plexus blocks over systemic administration is scanty [34].

**Fentanyl** has a more rapid onset and shorter duration of action in comparison with more hydrophilic opioids such as morphine when administered neuraxially. The recommended intrathecal dose is 10–25 μg, and the epidural loading dose is 50–100 μg. It does not prolong motor block thus allowing for early ambulation. The duration of action is 2–4 h, and the risk of respiratory depression is very low and of short duration.

**Morphine**: a hydrophilic drug less readily absorbed in the spinal cord resulting in slower onset but prolonged duration of analgesia, and as it moves cephalad via CSF, the analgesia spreads over more dermatomes. However, this late cephalad spread increases the potential for brainstem binding and delayed respiratory depression although very rare in clinical prac‐ tice. The recommended dose is 50–300 μg intrathecal and 2–5 mg epidural loading dose. The risk of side effects increases exponentially with the increase in the dose.

**Diamorphine**: a diacetylated analogue of morphine with a potency of approximately 1.5–2 times that of morphine resulting in a faster onset and slightly shorter duration of action. The intrathecal dose is 300–400 μg, and epidural loading dose is 2–3 mg.

**Sufentanil**: an intrathecal dose is 2.5–10 μg, and epidural loading dose is 10–50 μg. It is an extremely potent opioid with a faster onset of action. Its use in clinical practice is limited by its short duration of action and high side effect profile.

#### **2. Alpha‐2 adrenoceptor agonists**

**Clonidine**: intrathecal use of clonidine as an adjunct to local anaesthetics prolongs the dura‐ tion of sensory blockade by approximately 1 h [35]. However, the duration of motor block‐ ade is increased, and the incidence of hypotension is also high. The recommended dose for intrathecal use is in the range of 15–150 μg with the incidence of adverse effects (bradycardia, sedation, hypotension) increasing with doses above 150 μg. In paediatric anaesthesia, the use of clonidine (1 mg/kg) for caudal blocks doubles the duration of analgesia when compared to LA alone, but causes sedation. Further research is needed to examine the benefits of using clonidine for peripheral nerve and plexus blocks [36].

**Dexmedetomidine** is a highly selective alpha‐2 adrenoceptor agonist. There is some evidence to suggest a clinical benefit to use of dexmedetomidine with LA for intravenous regional anaesthesia [37].

**Adrenaline** has direct and indirect actions as an adjuvant. It acts directly on α‐2 adrenocep‐ tors in the substantia gelatinosa of the dorsal horn of the spinal cord resulting in presynaptic inhibition of transmitter release from C and Aδ fibres. Indirectly, it causes local vasculature constriction thus prolonging the duration of action of the LA. Adrenaline used as an adjunct to thoracic epidural infusions improves the quality of analgesia [38, 39]. There are conflicting reports regarding the use of adrenaline in lumbar epidurals.

#### **3.** *N***‐methyl‐d‐aspartate receptor antagonists**

**Ketamine**: preservative‐free ketamine injected into the caudal epidural space for children at a dose of 0.5 mg/kg has been shown to extend analgesia time by several hours. The opponents of ketamine cite increased the risk of psychotomimetic side effects, but the use of benzodiaz‐ epine premedication prior to block reduces the risk of these side effects.

**Magnesium**: intrathecal or epidural magnesium has been used with variable results. It may prolong LA/opioid block in women in labour at a dose of 50 mg, but a very high dose of mag‐ nesium has been reported to produce transient neurological toxicity.

#### **4. Other adjuvants**

Other adjuvants like midazolam and neostigmine have been suggested to improve the quality of analgesia. However, the high incidence of significant side effects far outweighs the small improvement in analgesia.
