Pain relief
Edited by Anthony Brown
22.1 General pain management
Daniel M Fatovich
Introduction
Pain is defined by the International Association for the Study of Pain as: ‘An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage’ [1]. Acute pain is defined as: ‘Pain of recent onset and probable limited duration. It usually has an identifiable temporal and causal relationship to injury or disease’ [2]. However, once a patient presents for medical care, severe acute pain has ceased to serve a useful purpose. Whereas in some conditions the nature and progression of the pain may be helpful in making the diagnosis of the underlying pathology, too great a reliance has been placed upon this feature, thereby allowing the patient to suffer needlessly for prolonged periods [2,3].
When severe pain is inadequately relieved it produces pathophysiological and abnormal psychological reactions that often lead to complications. This is important as acute pain is the most common presenting complaint to an emergency department (ED) [4] and its management forms part of the daily practice of emergency medicine. It should be considered poor patient care not to treat pain while attempting to arrive at a diagnosis. There can be no greater gift to one’s neighbour than to practise, teach and discover more effective methods to relieve pain and suffering [2,3]. Unfortunately, the management of acute pain is often not a specific component of medical training.
Physiology
Pain is one of the most complex aspects of an already intricate nervous system [2]. A number of theories have been developed to explain the physiology of pain, but none is proven or complete.
‘Gate Control Theory’
In 1965, the Melzack–Wall ‘Gate Control Theory’ emphasized mechanisms in the central nervous system that control the perception of a noxious stimulus and thus integrated afferent, upstream processes with downstream modulation from the brain [5]. However, this theory did not incorporate long-term changes in the central nervous system to the noxious input and to other external factors that impinge upon the individual [5].
Nociceptor function
Most pain originates when specific nerve endings (nociceptors) are stimulated, producing nerve impulses that are transmitted to the brain. Nociception is the detection of tissue damage by specialized transducers [5]. It is now recognized that nociceptor function is altered by the ‘inflammatory soup’ that characterizes a region of tissue injury [5]. The final pain experience is subject to a complex series of facilitatory and inhibitory events that precede pain awareness, such as past experience, anxiety or expectation [6].
There are two types of nociceptors [7]:
Once transduced into electrical stimuli, conduction of neuronal action potentials is dependent on voltage-gated sodium channels [2]. A number of chemicals are involved in the transmission of pain to the ascending pathways in the spinothalamic tract. These include substance P and calcitonin gene-related peptide, but many others have been identified [2,8,9]. Opioid receptors are present in the dorsal horn and it is thought that encephalins (endogenous opioid peptides) are neurotransmitters in the inhibitory interneurons [7].
Phospholipids released from damaged cell membranes trigger a cascade of reactions, culminating in the production of prostaglandins that sensitize nociceptors to other inflammatory mediators, such as histamine, serotonin and bradykinin [7].
The threshold for the perception of a painful stimulus is similar in everyone and may be lowered by certain chemicals, such as the mediators of inflammation. The discrete cognitive processes and pathways involved in the interpretation of painful stimuli remain a mystery. The cognitive and emotional reactions to a given painful stimulus are variable among individuals and may be affected by culture, personality, past experiences and underlying emotional state [2,5,10]. In addition, intense and ongoing stimuli further increase the excitability of dorsal horn neurons, leading to central sensitization [2]. With increased excitability of central nociceptive neurons, the threshold for activation is reduced and pain can occur in response to low intensity, previously non-painful stimuli known as allodynia [2]. Pain is a complex, multidimensional, subjective phenomenon [10].
Assessment of pain and pain scales
There is no truly objective measurement of pain. Doctors use a variety of methods for determining how much pain a patient feels. These include the nature of the illness or injury, the patient’s appearance and behaviour and physiological concomitants. None of these is reliable.
Pain scales have been developed because there are no accurate physiological or clinical signs to measure pain objectively. Three scales have become popular tools to quantify pain intensity [11,12]: the visual analogue scale (VAS), the numeric rating scale and the verbal rating scale.
Visual analogue scale
The VAS usually consists of a 100-mm line with one end indicating ‘no pain’ and the other end indicating the ‘worst pain imaginable’. The patient simply indicates a point on the line that best indicates the amount of pain experienced. The minimum clinically significant change in patient pain severity measured with a 100-mm visual analogue scale is 13 mm [13]. Studies of pain experience that report less than a 13 mm change in pain severity, although statistically significant, may have no clinical importance [13].
Numeric rating scale
The patient is asked in the numeric rating scale to choose a number from a range (usually 0–10) that best describes the amount of pain experienced, with zero being ‘no pain’ and 10 being the ‘worst pain imaginable’. This has been used for cardiac ischaemia pain and is also useful in illiterate patients.
Verbal rating scale
The verbal rating scale simply asks a patient to choose a phrase that best describes the pain, usually ‘mild’, ‘moderate’ or ‘severe’.
The use of pain scales has been restricted predominantly to research, where experimental pain is not associated with the strong emotional component of acute pain. In the clinical setting, anxiety, sleep disruption and illness burden are present [9]. It is difficult to use a unidimensional pain scale to measure a multidimensional process. Using pain intensity alone will often fail to capture the many other qualities of pain and the overall pain experience. The best illustration of this problem is that the same pain stimulus can be applied to two different people with dramatically different pain scores and analgesic requirements [14]. At best, the use of pain scales is an indirect reflection of ‘real’ pain, with patient self-reporting still being the most reliable indicator of the existence and intensity of pain [15].
Nevertheless, pain scales are simple and easy to use. They are now routine in many EDs, often being a standard part of the triage process, which leads to substantially faster provision of initial analgesia [4] (see Vazirani J, Knott JC in Further reading).
General principles
Patients in pain should receive timely, effective and appropriate analgesia, titrated according to response [2]. Therefore, essentially there is no role for the intramuscular route for parenteral analgesia, which simply delays the onset of analgesia. The following points should be stressed:
Specific agents
Opioids
The term ‘opioid’ refers to all naturally occurring and synthetic drugs producing morphine-like effects. Morphine is the standard opioid agonist against which others are judged [16]. These drugs are the most powerful agents available in the treatment of acute pain. A number of specific opioid receptors have been identified.
Opioid receptor effects
Opiods are responsible for a variety of effects, including analgesia, euphoria, respiratory depression and miosis (μ receptor); cough suppression and sedation (Κ); dysphoria and hallucinations (σ); nausea and vomiting, and pruritus (δ) [7]. Opioids act on injured tissue to reduce inflammation in the dorsal horn to impede transmission of nociception and supraspinally to activate inhibitory pathways that descend to the spinal segment [9].
Unfortunately, many doctors use opioids inappropriately as there are particular concerns regarding the risks of respiratory depression and inducing iatrogenic addiction. Less than 1% of patients who receive opioids for pain develop respiratory depression [17]. Tolerance to this side effect develops simultaneously with tolerance to the analgesic effect. If the opioid dose is increased so that at least half the pain is relieved, the chance of respiratory depression is small. Further, naloxone will reverse the effects of opioids. In relation to fears of addiction, large studies have shown that inducing this following opioid analgesia use is exceedingly rare [18].
Use of intravenous opiods
From a clinical practice point of view, many patients who require intravenous opioid will also require admission to hospital, as there will be ongoing opioid requirements that can only be administered in hospital. There have been occasions where patients have received opioid analgesia that has relieved their pain and they have then been discharged without a final diagnosis. This is an unacceptable practice. A patient may present with abdominal pain with vomiting and, for instance, a provisional diagnosis of gastroenteritis is made. After opioid analgesia is given the patient may feel better and be discharged. A diagnosis, such as appendicitis or bowel obstruction, has not been excluded.
It is therefore necessary for patients to have an appropriate diagnostic evaluation to confirm a benign cause and to reassess the patient after the opioid effects have waned. For patients in whom the final diagnosis is certain, such as in anterior shoulder dislocation, discharge is appropriate after a suitable period of observation until the patient is deemed clinically fit for discharge. This is a different scenario from that described previously, as it is a single system problem in which there is no doubt about the diagnosis. In summary, pain that is considered severe enough to warrant intravenous opioid analgesia requires a high index of suspicion for significant pathology.
Side effects
All potent opioid analgesics have the potential to depress the level of consciousness, protective reflexes and vital functions. It is mandatory that these are closely monitored during and after administration [7]. Specific side effects include:
respiratory depression: rare<1%
nausea and vomiting: nausea occurs in approximately 40% and vomiting in 15% [7]
hypotension: opioids may provoke histamine release
spasm of the sphincter of Oddi, therefore patients with biliary colic may initially experience more pain. There is no good evidence to suggest that pethidine has any clinically significant advantage at equi-analgesic doses over other opioids for biliary or renal colic [16]
Routes of administration
Opioids may be administered by many routes, including oral, subcutaneous, intramuscular, intravenous, epidural, nebulized, intrapleural, intranasal, intra-articular and transdermal. All may have a role in a specific clinical situation [4]. There is a good rationale for the use of the intravenous route in moderate-to-severe pain [4] and titration of intravenous opioids remains the standard of care for acute severe pain.
Opioid analgesics
Morphine
The standard intravenous morphine dose is 0.1–0.2 mg/kg or more with a duration of action of 2–3 h. This should be initiated as a loading dose of opioid to provide rapid initial pain relief aiming for an optimal balance between effective pain relief and minimal side effects. This means tailoring the approach to each individual patient. Thus, a young fit healthy man with renal colic may require an initial bolus of 0.1 mg/kg morphine, followed by further increments of 0.05 mg/kg. Conversely, a frail elderly patient may only tolerate 1.0–2.5 mg morphine total to begin with. There may also be considerable inter-individual variation in response to analgesia. Procedural pain may require higher-dose opioid analgesia, which has been found to be well tolerated and safe [19]. Appropriate monitoring and resuscitation equipment should be available to maximize safety.
Rapid pain relief and titration to effect are obvious advantages. Intramuscular administration results in unreliable and variable absorption and older routine practices, such as prescribing ‘5–10 mg morphine IM’, take no account of an individual’s requirements [7].
Pethidine
Pethidine should be used with caution in patients with renal failure, as there is increased risk of central nervous system toxicity due to the toxic metabolite, norpethidine. Norpethidine causes tremor, twitching, agitation and convulsions [16]. Also pethidine is contraindicated in patients receiving monoamine oxidase (MAO) inhibitors, as they interfere with pethidine metabolism, increasing the likelihood of toxicity [20]. Finally, pethidine may trigger the serotonin syndrome if used concomitantly with selective serotonin reuptake inhibitors (SSRIs).
Pethidine has approximately one-eighth the potency of morphine and causes the same degree of bronchospasm and increased biliary pressure as morphine [2]. Its use has now declined and it should continue to be discouraged in favour of other opioids [2].
Fentanyl
Allergic reactions are extremely rare with opioids. Fentanyl does not release histamine, making it ideal for treating patients with reactive airways disease. There are advantages in using fentanyl for brief procedures in the ED because of its short half-life. The intravenous dose of fentanyl is 1–2 μg/kg or more with a duration of action of 30–60 min. High doses of fentanyl may produce muscular rigidity, which may be so severe as to make ventilation difficult, but which responds to naloxone or muscle relaxants. Intranasal fentanyl is an effective analgesic in the ED and in the pre-hospital setting [2].
Oral opioids
Oral opioids tend to be underused in the ED, but are effective for all levels of pain and are associated with improved patient satisfaction. Their side effect profile may be better than paracetamol/codeine combinations. Oxycodone (immediate release) reaches peak levels at 45 min to 1 h but the dose should be reduced and dosing interval increased in the elderly and in those with hepatic or renal dysfunction. The main contraindication is acute respiratory depression. The initial dose is 5–10 mg. However, it is important to be aware that the increased prescribing of oral opioids is associated with increased deaths. Oxycodone/ naloxone combinations are now available.
Codeine
Codeine is the most commonly used oral opioid prodrug. Unfortunately, up to 6–10% of the Caucasian population, 2% of Asians, and 1% of Arabs have poorly functional cytochrome P450 2D6 (CYP2D6), which may render codeine largely ineffective for analgesia in these patients, although some analgesic efficacy may occur via alternate cytochrome P450 pathways.
Prescribed alone in doses as high as 120 mg, codeine has been demonstrated to be no more effective than placebo in both the adult and geriatric populations, while causing increasing gastrointestinal side effects, such as nausea, vomiting and constipation, with increasing doses [4]. It is frequently given in combination with paracetamol or aspirin.
Tramadol
Tramadol is a new opioid, with novel non-opioid properties [21]. Its efficacy lies between codeine and morphine. It has a relative lack of serious side effects, such as respiratory depression, and the potential for abuse and psychological dependence is low [21]. However, other side effects, such as nausea, vomiting, dizziness and somnolence, may be troublesome and there is a risk of seizures [21,22]. Thus, it should be avoided or used with caution in patients who are taking drugs that reduce the seizure threshold, such as tricyclic antidepressants and SSRIs. Also the concomitant administration of tramadol with monoamine oxidase inhibitors, or within 2 weeks of their withdrawal, is contraindicated [21].
The role of tramadol in emergency medicine is ill defined. One review concluded that tramadol does not offer any particular benefits over existing analgesics for the majority of emergency pain relief situations [22], with oral doses having equivalent analgesic effects in mild-to-moderate severity acute pain compared with currently available analgesics [22]. Intravenous tramadol is less effective than intravenous morphine [22].
However, tramadol may be useful in certain situations: [22]
Non-opioid analgesics
Simple analgesics
Non-steroidal anti-inflammatory drugs
Non-steroidal anti-inflammatory drugs are either non-selective cyclo-oxygenase (COX) inhibitors or selective inhibitors of COX-2 (COX-2 inhibitors). NSAIDs are effective analgesic agents for moderate pain, specifically when there is associated inflammation [4]. As with opioids, there are multiple routes of administration available. Unfortunately, their use in acute severe pain is limited by the length of onset time of 20–30 min. There is no clear superiority of one agent over another.
There is up to a 30% incidence of upper gastrointestinal bleeding when NSAIDs are used for over 1–2 weeks. The risk of bleeding in the elderly for short (3–5 days) acute therapy appears to be minimal [4]. NSAID use in pregnancy (especially late) is not recommended. Ibuprofen is considered the NSAID of choice in lactation.
NSAIDs have a spectrum of analgesic, anti-inflammatory and antipyretic effects and are effective analgesics in a variety of pain states [2]. Unfortunately, significant contraindications and adverse effects limit the use of NSAIDs, many of these being regulated by COX-1 [2]. NSAIDs are useful analgesic adjuncts and hence NSAIDs are therefore integral components of multimodal analgesia [2]. NSAID side effects are more common with long-term use. The main concerns are renal impairment, interference with platelet function, peptic ulceration and bronchospasm in individuals who have aspirin-exacerbated respiratory disease [2]. In general, the risk and severity of NSAID-associated side effects is increased in elderly people [2].
Caution is therefore needed in the elderly and in patients with renal disease, hypertension and heart failure, or with asthma. NSAIDs reduce renal cortical blood flow and may induce renal impairment, especially when used in patients already on diuretics. In patients with asthma, 2–20% are aspirin sensitive and there is a 50–100% cross-sensitivity with NSAIDs.
Ketorolac is a parenteral NSAID that is equipotent to opioids, with ketorolac and morphine equivalent in reducing pain. There is a benefit favouring ketorolac in terms of side effects when ketorolac is titrated intravenously for isolated limb injuries [23,24]. However, the utility of ketorolac in acute pain is limited due to a prolonged onset of action and a significant number of patients (25%) who exhibit little or no response [25]. There is also benefit to using ketorolac for acute renal colic [23,26]. A combination of morphine and ketorolac offered pain relief superior to either drug alone and was associated with a decreased requirement for rescue analgesia in patients with renal colic [27]. Rectal NSAIDs (e.g. indomethacin 100 mg) are an effective alternative to parenteral NSAIDs in the treatment of renal colic.
Paracetamol
Paracetamol is an effective analgesic for acute pain [2] and has useful antipyretic activity [28]. The addition of an NSAID further improves efficacy [2]. Paracetamol inhibits prostaglandin synthetase in the hypothalamus, prevents release of spinal prostaglandin and inhibits inducible nitric oxide synthesis in macrophages [28].
Indications for paracetamol include mild pain, particularly of soft tissue and musculoskeletal origin, mild procedural pain, supplementation of opioids in the management of more severe pain allowing a reduction in opioid dosage and as an alternative to aspirin [28]. Paracetamol has no gastrointestinal side effects of note and may be prescribed safely in patients with peptic ulcer disease or gastritis [4]. Aspirin has the risk of gastrointestinal side effects, such as ulceration and bleeding. It also has an antiplatelet effect which lasts for the life of the platelet.
Paracetamol is rapidly absorbed with a peak concentration reached in 30–90 min [28]. The recommended adult dose is 1 g every 4–6 h to a generally accepted maximum of 4 g per day [28]. Paracetamol has a low adverse event profile and is an excellent analgesic, especially when used in adequate dose. Parenteral paracetamol is now available and may have additional utility, e.g. in the vomiting patient. Chronic use of paracetamol alone does not seem to cause analgesic nephropathy [28]. It can be used safely in alcoholics and patients with liver metastases [28,29].
Combination drugs
Non-opioid agents, e.g. paracetamol, NSAIDs and paracetamol/codeine combinations, are all useful analgesics for mild-to-moderate pain. A systematic review found that paracetamol–codeine combinations in single dose studies produce a slightly increased analgesic effect (5%) compared with paracetamol alone [30]. However, none of the studies reviewed were based in the ED. In multidosage, paracetamol–codeine preparations have significantly increased side effects [30]. However, other reports state that the combination of paracetamol 1000 mg plus codeine 60 mg has a number needed to treat of 2.2 [2]. NSAIDs have a higher rate of serious adverse effects.
Other analgesic agents
Nitrous oxide
Nitrous oxide is an inhalational analgesic and sedative which, in a 50% mixture with oxygen (Entonox), has equivalent potency to 10 mg morphine in an adult [7]. The Entonox delivery system uses a preferential inhalational demand arrangement for self-administration, which requires an airtight fit between the mask/mouthpiece and face. As the patient holds the mask/mouthpiece, their grip will relax if drowsiness occurs, the airtight seal will be lost and the gas flow stops, thereby avoiding overdosage.
This system requires a degree of patient involvement and cooperation and is useful for patients who have difficult intravenous access or are needle-phobic. Patients who are elderly, young, confused or uncooperative will not find the technique effective. Nitrous oxide increases the volume of a pneumothorax or any other gas-filled cavity, so is contraindicated in patients with pneumothorax or pneumoperitoneum.
Ketamine
Ketamine is an N-methyl-D-aspartate (NMDA) antagonist. It is a unique anaesthetic that induces a state of dissociation between the cortical and limbic systems to produce a state of dissociative anaesthesia, with analgesia, amnesia, mild sedation and immobilization. It does not impair protective airway reflexes and random or purposeful movements are frequently observed in patients after administration. Side effects include hypersalivation, vomiting, emergence reactions, nightmares, laryngospasm, hypertension, tachycardia and increased intracranial pressure [31,32].
There are many potential contraindications to ketamine use including upper or lower respiratory infection, procedures involving the posterior pharynx, cystic fibrosis, age younger than 3 months, head injury, increased intracranial pressure, acute glaucoma or globe penetration, uncontrolled hypertension, congestive cardiac failure, arterial aneurysm, acute intermittent porphyria and thyrotoxicosis [32]. Despite this, ketamine is used increasingly in the EDs as part of procedural sedation (see Chapter 22.3). It is also an effective analgesic at sub-dissociative doses especially for opioid resistant pain, e.g. 0.2–0.3 mg/kg bolus plus infusion at 0.2 mg/kg/h.
Pain relief in pregnancy
Non-pharmacological treatment options should be considered where possible for pain management in pregnancy, because most drugs cross the placenta [2]. Use of medications for pain in pregnancy should be guided by published recommendations [2]. Paracetamol is regarded as the analgesic of choice [2]. NSAIDs are used with caution in the last trimester of pregnancy and should be avoided after the 32nd week [2]. The use of NSAIDs is associated with increased risk of miscarriage [2]. Overall, the use of opioids to treat pain in pregnancy appears safe [2].
Non-pharmacological therapies
Although pain perception involves neuroanatomical processes, the other interrelated component of pain reaction is psychophysiological. The use of non-pharmacological techniques is therefore important. These include empathy, a compassionate approach, a calm manner and reassurance. Immobilization of fractures with splinting is effective, as is the application of ice to a wound. Other techniques, such as hypnosis, transcutaneous nerve stimulation, acupuncture and manipulation, have not been widely studied in the ED setting.
Special pain situations and non-analgesic agents
This chapter has focused on specific analgesic agents, but there are many miscellaneous agents that are effective in providing disease-specific analgesia.
glyceryl trinitrate and β-blockers for acute cardiac ischaemia pain
antiviral agents for herpes zoster
oxygen therapy for cluster headache
In addition, adjuvant therapy with anxiolytics, such as midazolam, contributes to pain relief. Obtaining a definitive diagnosis allows directed therapy that contributes to pain relief. If specific treatments appear to be ineffective, then the diagnosis should be reconsidered.
Acute neuropathic pain
Acute neuropathic pain is an important issue in the ED. This may be due to conditions such as sciatica and cervical radiculopathy. In addition to agents, such as the antidepressants (e.g. nortriptylline) or anticonvulsants (e.g. carbamazepine), another option includes the use of antihyperalgesic drugs, such as gabapentin 100–300 mg per dose, repeated as necessary, titrating up to a maximum of 3600 mg per day over time. The main side effects are dizziness, somnolence and ataxia. However, there have been no ED studies of gabapentin or pregabalin and there is wide variability of response.
Chronic pain
Chronic pain ‘commonly persists beyond the time of healing of an injury and frequently there may not be any clearly identifiable cause’ [2]. Patients with chronic pain attend the ED with exacerbations of their chronic pain and are often taking multimodal therapies prescribed by a pain specialist. The main difference between acute and chronic pain is that, in chronic pain, central sensitization is the main underlying pathophysiology [33]. It is important to avoid a judgemental attitude to these patients as there is a risk of overlooking serious pathology.
Antihyperalgesic drugs in the setting of chronic pain, especially ketamine, are of particular value in those with poor opioid responsiveness [2]. Other antihyperalgesics may be useful for neuropathic pain, such as gabapentin and pregabalin.
Another issue with chronic pain is to be aware of adjuvant therapies for decreasing the likelihood of chronic pain developing. For example, early management of acute zoster infection may reduce the incidence of post-herpetic neuralgia [2]. Aciclovir given within 72 h of onset of the rash accelerates the resolution of pain and reduces the risk of post-herpetic neuralgia [2]. Amitriptyline 25 mg daily in patients over 60 years for 90 days, started at the onset of acute zoster, reduces pain prevalence at 6 months post-zoster infection [34].
Acute abdomen
Traditionally, it was held that pain relief masks the clinical signs of pathology in the acute abdomen. Evidence from randomized controlled trials clearly shows that the early administration of opioids in patients with an acute abdomen does not reduce the detection rate of serious pathology and may actually facilitate the diagnosis. Thus, titrated opioid analgesia should never be withheld, certainly not pending surgical review. The effect of analgesia on physical signs cannot be used as a diagnostic test [35–37].
Likely developments over the next 5–10 years
22.2 Local anaesthesia
Anthony Brown and Tor NO Ercleve
Local anaesthesia
Local anaesthetic infiltration and nerve blocks should be used for patients presenting to the emergency department (ED) with pain, either to supplement other analgesia or for definitive pain relief. Nerve blocks are most appropriate when the pain is localized, as in certain fractures and wounds to a digit, or within a peripheral nerve distribution region. Local anaesthesia may also be used topically, particularly in children, and prior to arterial blood gas puncture and insertion of large intravenous cannulae where, contrary to popular perception, it does not increase the likelihood of failure [1,2].
Pharmacology
Local anaesthetic agents are all weak organic bases that inactivate intracellular fast sodium channels, temporarily blocking membrane depolarization and preventing nerve impulse transmission. All are vasodilators with the exception of ropivacaine and cocaine, hence the use of adrenaline to prolong their duration of activity and to improve safety by delaying absorption and/or by administering lower effective doses.
Amino ester and amino amide local anaesthetics
Local anaesthetic agents containing an ester bond between the intermediate chain and lipophilic aromatic end (amino esters) include cocaine, procaine and amethocaine. They are poorly protein bound and undergo hydrolysis by plasma pseudocholinesterase to para-amino benzoic acid. Amide-type agents containing an amide bond between the intermediate chain and aromatic end (amino amides) include lignocaine, prilocaine, bupivacaine and ropivacaine, are highly protein bound, much more stable and undergo hepatic metabolism.
Local anaesthetics are available in single or multidose vials, with or without dilute adrenaline at 1:200 000 (containing 5 μg adrenaline per millilitre) to prolong their duration of action. Antioxidants, such as sodium bisulphite or metabisulphite, are added to adrenaline-containing solutions and preservative, such as methylparaben, to multidose vials and are implicated in some apparent allergic reactions to the local anaesthetic. True allergy to local anaesthetics is extremely rare when verified by progressive challenge testing and is usually to the amino esters [3].
The duration of action of local anaesthetics is related to the degree of protein binding, vasoactivity, concentration and possibly pH, although the addition of adrenaline is the most practical way to prolong their effect. Table 22.2.1 gives standard maximum safe doses and duration of action of commonly used agents. Solutions containing adrenaline should not be injected near end arteries, such as in the fingers, toes, nose or penis, even though this well-established dogma is surprisingly not supported by the literature. Normal blood flow is restored to the digit within 60–90 min of inadvertent injection of local anaesthesia with adrenaline (epinephrine) at standard commercial dilutions, without any evidence of harm [4].
Table 22.2.1
Maximum recommended safe dose and duration of action of common local anaesthetics
| Drug | Dose (mg/kg)* | Duration (h) |
| Lignocaine | 3 | 0.5–1 |
| Lignocaine with adrenaline | 7 | 2–5 |
| Bupivacaine | 2 | 2–4 |
| Prilocaine | 6 | 0.5–1.5 |
Adverse effects
Systemic toxicity
Systemic toxicity occurs after unrecognized rapid intravenous injection or by exceeding the recommended safe maximum dose. Symptoms and signs of toxicity are related to plasma drug levels and progress from circumoral tingling, dizziness, tinnitus and visual disturbance to muscular twitching, confusion, convulsions, coma and apnoea. Cardiovascular effects are also seen with high plasma levels, including bradycardia, hypotension and cardiovascular collapse ultimately with ventricular fibrillation or asystole, which are all exacerbated by associated hypoxia. See Table 22.2.2 for the features of local anaesthetic toxicity related to increasing plasma levels.
Table 22.2.2
Features of systemic local anaesthetic toxicity (in order of increasing plasma levels)
Circumoral tingling
Dizziness
Tinnitus
Visual disturbance
Muscular twitching
Confusion
Convulsions
Coma
Apnoea
Cardiovascular collapse (highest plasma levels)
The management of systemic toxicity includes immediate cessation of the drug, summoning help, airway maintenance, supplemental oxygen and incremental doses of an intravenous benzodiazepine, such as midazolam 0.05–0.1 mg/kg, for seizures. Major reactions may require endotracheal intubation, fluids and cautious use of vasopressors and inotropes, as high doses can impede resuscitation in toxic cardiomyopathy. Refractory arrhythmias with cardiovascular collapse from local anaesthetic systemic toxicity (LAST) may respond best to intravenous 20% lipid emulsion 1.5 mL/kg bolus followed by 0.25 mL/kg/min for roughly 10 min following recovery of vital signs [5].
