Toxicity (LAST): Recognition And Treatment (Intralipid)

Foundations and mechanisms

Definition and epidemiology

Local anaesthetic systemic toxicity (LAST) is a dose-dependent, potentially fatal syndrome caused by excessive plasma and tissue concentrations of local anaesthetic, producing predominantly central nervous system and cardiovascular toxicity. It may follow inadvertent intravascular injection, rapid systemic absorption from vascular tissue planes, excessive total dose, or impaired clearance. Contemporary registry data suggest an incidence of approximately 0.03–0.27 per 1000 peripheral nerve blocks, higher with neuraxial and highly vascular blocks, and lower with ultrasound guidance, incremental injection and adrenaline markers.

LAST is most classically associated with bupivacaine, but all amide and ester local anaesthetics can cause toxicity. Severe cardiovascular collapse may occur without preceding seizures, particularly after high-dose fascial plane blocks, neuraxial injections, or in patients under general anaesthesia or deep sedation.

Determinants of systemic toxicity

Systemic toxicity reflects the relationship between absorbed dose, peak arterial concentration, protein binding, tissue distribution and intrinsic drug toxicity. Local anaesthetics are weak bases; the un-ionised fraction crosses lipid membranes, whereas the ionised fraction binds voltage-gated sodium channels. Acidosis, hypercarbia and hypoxia increase toxicity by increasing free drug delivery to the heart and brain and by potentiating sodium-channel blockade.

Factor	Effect on LAST risk	Exam-relevant point
Vascularity of injection site	Higher peak plasma concentration	Intercostal > caudal/epidural > brachial plexus > sciatic/subcutaneous absorption
Protein binding	Only unbound drug is pharmacologically active	Reduced α1-acid glycoprotein in neonates, pregnancy, liver disease and critical illness increases free fraction
Acidosis and hypercarbia	Increase CNS and myocardial toxicity	Enhance ion trapping intracellularly and reduce resuscitation success
Cardiac disease	Reduced reserve and impaired conduction	Bupivacaine particularly dangerous in conduction disease, low-output states and severe ventricular dysfunction
Pregnancy	Increased sensitivity and free fraction	Lower epidural dose requirement; increased neuraxial spread and vascularity

Molecular mechanisms of toxicity

The principal target is the voltage-gated sodium channel. Local anaesthetics bind preferentially to open and inactivated channel states from the intracellular side, producing use-dependent blockade. In nerves this is therapeutic; in brain and myocardium it is toxic. Potent, highly lipid-soluble agents dissociate slowly from cardiac sodium channels. Bupivacaine has slow unbinding kinetics and strong affinity for inactivated myocardial sodium channels, causing QRS widening, conduction block and malignant ventricular arrhythmias. Ropivacaine and levobupivacaine are less cardiotoxic because they are less lipophilic and, for levobupivacaine/ropivacaine, avoid the more cardiotoxic racemic profile of bupivacaine.

LAST is not purely sodium-channel toxicity. Local anaesthetics also inhibit calcium channels, potassium channels, mitochondrial oxidative phosphorylation and fatty-acid transport. Myocardial depression is therefore multifactorial: reduced phase 0 depolarisation, impaired excitation–contraction coupling, reduced ATP generation and impaired β-adrenergic responsiveness. Bupivacaine also interferes with mitochondrial carnitine-acylcarnitine translocase, reducing fatty-acid utilisation in the myocardium.

Clinical staging and concentration-response pattern

The traditional progression is early CNS excitation followed by CNS depression and then cardiovascular collapse, but this sequence is unreliable. Early symptoms include circumoral paraesthesia, metallic taste, tinnitus, agitation and dizziness. As inhibitory cortical pathways are blocked, seizures occur. With increasing concentrations, global neuronal depression produces coma and respiratory arrest. Cardiovascular manifestations range from hypertension and tachycardia during CNS excitation to bradycardia, hypotension, PR/QRS/QT prolongation, ventricular tachycardia, ventricular fibrillation and asystole.

Phase	Dominant mechanism	Typical features
Prodromal CNS toxicity	Preferential blockade of inhibitory cortical pathways	Perioral numbness, tinnitus, metallic taste, visual disturbance, agitation
Seizure phase	Cortical excitation and impaired inhibitory neurotransmission	Generalised tonic-clonic seizure, metabolic acidosis, hyperkalaemia, hypoxia if untreated
CNS depression	Global neuronal sodium-channel blockade	Coma, respiratory depression or apnoea
Cardiovascular toxicity	Myocardial sodium/calcium/potassium-channel blockade and mitochondrial dysfunction	Hypotension, bradyarrhythmia, QRS widening, ventricular arrhythmia, cardiac arrest

Core pharmacological numbers

Drug	Approximate maximum dose without adrenaline	With adrenaline	Key toxicity characteristic
Lidocaine	3 mg kg-1	7 mg kg-1	Less cardiotoxic; CNS toxicity usually precedes cardiovascular collapse
Bupivacaine	2 mg kg-1	2–3 mg kg-1	High cardiotoxicity; slow dissociation from cardiac sodium channels
Levobupivacaine	2 mg kg-1	2–3 mg kg-1	Less cardiotoxic than racemic bupivacaine
Ropivacaine	3 mg kg-1	3–4 mg kg-1	Lower lipid solubility; greater sensory-motor separation
Prilocaine	6 mg kg-1	8 mg kg-1	Methaemoglobinaemia risk, especially >600 mg in adults

These maximum doses are pragmatic safety limits rather than true toxicity thresholds; plasma concentrations correlate imperfectly with toxicity because arterial peaks, protein binding and patient susceptibility vary. Bupivacaine plasma concentrations causing early CNS symptoms are often cited around 2–4 micrograms ml^-1, with severe cardiovascular toxicity more likely at higher levels, but sudden intravascular injection may cause collapse before venous sampling is informative.

Lipid emulsion: mechanistic foundation

20% lipid emulsion is the specific antidotal therapy for severe LAST. It contains long-chain triglycerides, commonly soya oil with egg phospholipid emulsifier and glycerol, providing a lipid phase that modifies local anaesthetic distribution. The dominant model is the lipid sink/shuttle: lipophilic drug partitions into the intravascular lipid phase, reducing free aqueous plasma concentration and facilitating redistribution away from heart and brain to liver and muscle. Additional mechanisms include improved myocardial fatty-acid substrate availability, partial reversal of mitochondrial fatty-acid transport inhibition, and direct inotropic effects. Its benefit is greatest for highly lipid-soluble agents such as bupivacaine, although it is recommended for severe toxicity from any local anaesthetic.

Clinical assessment and investigations

Clinical presentation: recognise a toxidrome, not a single sign

Local anaesthetic systemic toxicity (LAST) is a clinical diagnosis based on temporal association with local anaesthetic administration and evolving neurological and/or cardiovascular toxicity. It most commonly follows unintended intravascular injection, excessive total dose, rapid absorption from vascular tissue planes, or impaired clearance. Presentation may be immediate, typically within seconds to minutes of injection, or delayed after high-volume fascial plane blocks, wound infiltration catheters, topical mucosal use, or continuous infusions. Registry data suggest approximately 50% of cases declare within 1 minute and 75% within 5 minutes after injection, but delayed presentations beyond 30–60 minutes are well described.

The classical sequence is circumoral numbness, metallic taste, tinnitus, agitation, tremor, seizure, then coma, followed by cardiovascular toxicity. However, this sequence is absent in many anaesthetised, sedated, obstetric, paediatric, or critically ill patients. Cardiovascular collapse may be the first manifestation, particularly with potent, highly protein-bound long-acting agents such as bupivacaine.

Domain	Early features	Severe features	Mechanistic interpretation
CNS	Perioral paraesthesia, tongue numbness, metallic taste, tinnitus, dizziness, visual disturbance, dysarthria, agitation	Generalised tonic-clonic seizure, coma, respiratory arrest	Preferential blockade of inhibitory cortical interneurones precedes global neuronal depression; acidosis and hypercarbia increase unbound drug and cerebral delivery
Cardiovascular	Hypertension, tachycardia, palpitations; later bradycardia or hypotension	PR/QRS prolongation, ventricular ectopy, VT/VF, pulseless electrical activity, asystole	Fast sodium-channel blockade, impaired calcium handling, mitochondrial dysfunction, reduced myocardial contractility; bupivacaine shows use-dependent binding and slow dissociation
Atypical	Isolated confusion, drowsiness, nausea, panic, syncope-like episode	Sudden cardiovascular collapse without prodrome	More likely under general anaesthesia, sedation, pregnancy, extremes of age, or beta-blockade

Differential diagnosis

LAST should be assumed until excluded when neurological excitation or cardiovascular instability occurs after regional anaesthesia. The differential is broad and often time-critical; several alternatives may coexist, especially hypoxia, hypercarbia, acidosis, and electrolyte disturbance, which also worsen LAST.

Differential	Clues favouring diagnosis	Key discriminating tests
High neuraxial block / total spinal	Recent spinal/epidural dosing; ascending sensory/motor block, profound sympathectomy, apnoea with preserved consciousness initially	Block level, haemodynamics, response to vasopressors and ventilation
Vasovagal episode	Needle stimulus, pallor, sweating, bradycardia; rapid recovery supine	ECG, blood pressure trend; absence of CNS prodrome or arrhythmia
Anaphylaxis	Hypotension with bronchospasm, urticaria, angioedema; exposure to antibiotic, chlorhexidine, latex	Serum tryptase at 1–2 h and baseline; clinical pattern
Intravascular adrenaline	Immediate tachycardia, hypertension, tremor after test dose	Transient haemodynamic surge; no progressive seizure/coma
Hypoglycaemia, hypoxia, hypercarbia	Altered consciousness or seizure independent of block timing	Capillary glucose, pulse oximetry, capnography, arterial/venous blood gas
Methemoglobinaemia	Cyanosis unresponsive to oxygen, chocolate-brown blood; classically prilocaine, benzocaine, EMLA excess	Co-oximetry metHb; pulse oximetry often fixed around 85%
Primary cardiac event	Ischaemic symptoms, risk factors, non-temporal relation	12-lead ECG, troponin series, echocardiography

Investigations and interpretation

Investigations must not delay treatment or lipid rescue when there is seizure, malignant arrhythmia, severe hypotension, or rapid progression after local anaesthetic exposure. Initial assessment is structured as ABCDE with continuous ECG, non-invasive or invasive blood pressure, pulse oximetry, capnography if ventilated, and immediate capillary glucose. Secure venous access and document the exact agent, concentration, volume, route, timing, use of adrenaline, patient weight, pregnancy status, hepatic/cardiac disease, and concurrent sodium-channel-blocking drugs.

• ECG: look for PR prolongation, QRS widening, QT changes, ventricular ectopy, VT/VF, bradyarrhythmia or PEA. A QRS duration >120 ms indicates clinically significant sodium-channel blockade; >160 ms is associated with increased risk of ventricular arrhythmia in sodium-channel poisoning, though no LAST-specific threshold is validated.
• Blood gas: assess pH, PaCO₂, PaO₂, lactate, potassium and ionised calcium. Acidaemia, hypercarbia and hypoxia increase free local anaesthetic fraction and potentiate cardiotoxicity. Aim to identify reversible precipitants rather than to “confirm” LAST.
• Electrolytes: potassium, magnesium, calcium and sodium abnormalities may precipitate seizures or arrhythmias and should be corrected. Hypokalaemia may follow adrenaline-containing solutions; hyperkalaemia may follow severe acidosis or arrest.
• Local anaesthetic plasma concentration: not useful acutely. Samples may support later confirmation but require specialist toxicology assays, are affected by redistribution and lipid emulsion, and correlate imperfectly with toxicity because the unbound arterial concentration at target tissue is most relevant.
• Co-oximetry: mandatory if cyanosis or unexpectedly low saturation follows prilocaine, benzocaine or large topical anaesthetic exposure. MetHb >10% causes cyanosis; >20–30% is usually symptomatic and generally warrants treatment if clinically significant.
• Other tests: FBC, U&E, LFTs, coagulation, troponin, pregnancy test where relevant, and chest radiography/echocardiography if pulmonary oedema, aspiration, myocardial dysfunction or alternative shock states are suspected.

Toxic concentration thresholds

Published thresholds are approximate total venous plasma concentrations; toxicity depends on protein binding, pH, PaCO₂, cardiac output, pregnancy, age, hepatic blood flow and site vascularity. Therefore, normal concentrations do not exclude LAST and elevated concentrations alone do not mandate treatment in an asymptomatic patient.

Agent	Approximate CNS toxicity threshold	Approximate severe cardiovascular toxicity threshold
Lidocaine	>5 microgram/mL; seizures often >10 microgram/mL	Usually >20–25 microgram/mL
Bupivacaine	Approximately 2–4 microgram/mL	Approximately >4 microgram/mL; collapse may occur at relatively low concentrations if acidaemic or hypoxic
Ropivacaine	Similar or slightly higher than bupivacaine on total concentration basis	Less cardiotoxic than bupivacaine, but serious arrhythmia and arrest still occur
Prilocaine	Systemic toxicity possible at high dose	Methemoglobinaemia is the characteristic dose-limiting toxicity, especially with large doses or infants

The practical diagnostic threshold is therefore clinical: any unexplained seizure, altered consciousness, conduction disturbance, ventricular arrhythmia, severe bradycardia, hypotension or arrest occurring in temporal proximity to local anaesthetic administration should trigger the LAST pathway and preparation for lipid emulsion therapy.

Management, pharmacology and procedures

Immediate management: treat early and interrupt progression

LAST is a time-critical poisoning syndrome: management must begin on suspicion, without waiting for cardiovascular collapse or plasma local anaesthetic concentrations. The priorities are cessation of local anaesthetic delivery, prevention of secondary exacerbating physiology, seizure control, lipid emulsion therapy and modified advanced life support. Hypoxia, hypercarbia and acidosis markedly increase the free fraction of local anaesthetic, reduce protein binding, and potentiate sodium-channel blockade; meticulous airway management is therefore a pharmacological intervention as well as supportive care.

1. Stop injection immediately; disconnect or clamp infusion pumps/catheters. Preserve syringes, ampoules and infusion devices for dose reconstruction.
2. Call for help: senior anaesthetist, resuscitation team, perfusion/ECMO team if available. Retrieve the LAST/lipid rescue kit.
3. ABCDE resuscitation: 100% oxygen, secure airway early if reduced consciousness, recurrent seizures or cardiovascular instability. Aim normoxia, normocapnia and correction of acidosis.
4. Establish/maintain IV access, attach defibrillator, invasive arterial monitoring if feasible, and obtain ECG, glucose, arterial blood gas, electrolytes and lactate without delaying treatment.
5. Treat seizures promptly with benzodiazepines; avoid large propofol doses in cardiovascular instability.
6. Administer 20% intravenous lipid emulsion for significant CNS toxicity, arrhythmia, hypotension or cardiac arrest.

Drug therapy and modified resuscitation

Intervention	Recommended approach	Exam-relevant cautions
20% lipid emulsion	Bolus 1.5 mL/kg IV over 1–3 min, then infusion 0.25 mL/kg/min (15 mL/kg/h). Repeat bolus up to two further times for persistent cardiovascular collapse; increase infusion to 0.5 mL/kg/min if instability persists.	Maximum commonly recommended cumulative dose 12 mL/kg. For adults >70 kg, ASRA cognitive aid uses pragmatic bolus 100 mL and infusion 200–250 mL over 15–20 min. Use lean body weight where obesity makes total body weight implausible.
Seizure control	Midazolam 0.05–0.1 mg/kg IV titrated, diazepam 0.1–0.2 mg/kg IV, or lorazepam 0.05–0.1 mg/kg IV.	Avoid worsening acidosis from prolonged convulsions. Propofol may be used in small titrated doses if haemodynamically stable, but large induction doses are undesirable in evolving myocardial depression.
Vasopressors	Use small-dose adrenaline; ASRA recommends boluses not exceeding 1 microgram/kg.	High-dose adrenaline may impair lipid resuscitation, increase afterload, provoke arrhythmias and worsen lactate/acidosis. Avoid vasopressin.
Arrhythmias	Follow modified ALS; defibrillate VF/pulseless VT. Amiodarone is preferred for refractory ventricular arrhythmias.	Avoid lidocaine and procainamide. Avoid calcium-channel blockers and beta-blockers, which may exacerbate conduction block and myocardial depression.
Cardiac arrest	High-quality CPR, early lipid, prolonged resuscitation. Consider extracorporeal CPR/cardiopulmonary bypass for refractory arrest.	Recovery may occur after prolonged CPR because redistribution and lipid-mediated clearance take time; do not abandon resuscitation prematurely.

Pharmacology of lipid rescue

The standard preparation is 20% intravenous lipid emulsion, typically soybean oil triglyceride emulsified with egg phospholipid and glycerol, providing approximately 2 kcal/mL. Its benefit in LAST is not explained solely by a passive “lipid sink”. Current models include a lipid shuttle effect: expansion of the intravascular lipid phase extracts highly lipophilic local anaesthetic from brain and myocardium and redistributes it to liver, skeletal muscle and adipose tissue. Bupivacaine and ropivacaine, with high lipid solubility and strong protein/tissue binding, are particularly amenable to this mechanism. Additional proposed effects include improved myocardial fatty-acid substrate delivery, reversal of bupivacaine-induced inhibition of mitochondrial fatty-acid transport, augmentation of intracellular calcium handling and favourable inotropy.

Evidence is necessarily dominated by animal studies, volunteer pharmacokinetic studies, case series and registry data rather than randomised trials in cardiac arrest. Nevertheless, consistent survival after otherwise refractory bupivacaine-induced cardiovascular collapse led to incorporation into AAGBI/Association of Anaesthetists and ASRA guidance. In an emergency, egg or soya allergy is not considered an absolute contraindication; the risk of untreated LAST is substantially greater.

Procedural and post-crisis management

Once stabilised, continue lipid infusion for at least 10 min after haemodynamic stability, while respecting the maximum cumulative dose. Remove or clearly label local anaesthetic infusions; regional catheters should not be restarted until senior review and dose reconciliation. Search for contributing causes: inadvertent intravascular injection, excessive cumulative dose, reduced clearance, pregnancy, extremes of age, cardiac disease, hepatic impairment, acidosis, hypoalbuminaemia and interacting drugs.

Observation must reflect severity because recurrence can occur after initial improvement, particularly with long-acting agents or continuous infusions. ASRA recommends monitoring for at least 2 h after isolated, rapidly resolving CNS symptoms and at least 4–6 h after cardiovascular instability; many institutions admit significant LAST cases to a high-dependency or intensive care environment for 12–24 h. Continue ECG monitoring, serial neurological assessment, glucose, electrolytes and acid-base evaluation. Plasma local anaesthetic concentrations may assist later interpretation but are rarely available rapidly and should not guide acute therapy.

Complications of lipid therapy are uncommon at rescue doses but include hypertriglyceridaemia, pancreatitis, fat overload syndrome, acute lung injury, interference with laboratory assays and extracorporeal circuit issues. Document the event meticulously, disclose to the patient, report through institutional critical incident systems, and provide clear future anaesthetic advice including implicated agent, estimated dose, timing, manifestations and response to lipid rescue.

Exam controversies and advanced synthesis

Guidelines: what examiners expect versus what the evidence proves

Modern management of local anaesthetic systemic toxicity (LAST) is driven primarily by consensus algorithms rather than high-grade human trial evidence. The key sources are the Association of Anaesthetists lipid rescue guidance and the ASRA LAST checklist, which emphasise early recognition, stopping injection, calling for help, seizure control, modified advanced life support and early 20% lipid emulsion. A viva trap is to present lipid as a proven antidote from randomised human trials: it is not. The evidence base comprises animal models, pharmacokinetic modelling, registries and case reports, with ethically impossible randomisation in severe human LAST.

Intervention	Recommended approach	Exam controversy / pitfall
20% lipid emulsion	Bolus 1.5 ml kg-1 over 1 min; infusion 0.25 ml kg-1 min-1. Repeat bolus for persistent instability; increase infusion to 0.5 ml kg-1 min-1. Approximate upper limit 10–12 ml kg-1 in first 30 min.	Do not delay lipid until arrest if severe CNS toxicity is evolving or cardiovascular signs appear. Do not confuse with propofol lipid: propofol is not lipid rescue and may worsen myocardial depression.
Adrenaline	Use smaller doses than standard ALS; suggested boluses <1 microgram kg-1.	Large adrenaline doses may impair lipid resuscitation, increase arrhythmogenicity and worsen pulmonary/systemic vasoconstriction.
Antiarrhythmics	Amiodarone is preferred for refractory ventricular arrhythmias.	Avoid lidocaine and procainamide: both add sodium-channel blockade.
Vasopressin, calcium-channel blockers, beta-blockers	Generally avoided in LAST algorithms.	May aggravate refractory myocardial depression and impair resuscitation.

Mechanistic synthesis: why lipid works, and why it sometimes fails

The simplistic “lipid sink” model is insufficient for postgraduate answers. Lipid emulsion probably acts through several mechanisms: sequestration of lipophilic local anaesthetic in an expanded intravascular lipid phase; redistribution from heart and brain to liver and skeletal muscle; augmentation of myocardial fatty-acid substrate delivery; and direct modulation of intracellular signalling and calcium handling. The effect is most plausible for highly lipophilic, highly protein-bound agents such as bupivacaine and levobupivacaine; it is less predictable for less lipophilic drugs. Severe acidosis, hypoxia and hypercarbia worsen sodium-channel blockade by increasing the ionised fraction and reducing protein binding; therefore ventilation and perfusion are not supportive details but central therapy.

Landmark evidence and its limitations

Weinberg’s animal work in the late 1990s and early 2000s demonstrated successful resuscitation from bupivacaine-induced cardiovascular collapse using lipid emulsion, forming the biological basis for clinical adoption. Early human reports, including cases of refractory bupivacaine or ropivacaine toxicity recovering after lipid administration, drove rapid guideline incorporation. However, publication bias is substantial: successful rescues are more likely to be reported than failures. Registry data suggest benefit but cannot reliably separate lipid effect from ventilation, seizure control, chest compressions, adrenaline dose reduction and spontaneous redistribution. Thus, the correct exam phrase is: lipid is recommended early in serious LAST despite low-level clinical evidence because the condition is rare, rapidly fatal and biologically plausible treatment has favourable risk-benefit balance.

Recognition controversies: not all LAST is immediate or dramatic

Classic teaching describes circumoral numbness, tinnitus, metallic taste, agitation, seizures, then coma and cardiovascular collapse. Examiners increasingly test atypical presentations. Ultrasound-guided peripheral nerve blockade has reduced but not abolished intravascular injection; LAST may be delayed by 20–60 minutes, especially after fascial plane blocks or large-volume infiltration. Cardiovascular presentation without preceding CNS symptoms is more likely under general anaesthesia, deep sedation, pregnancy, extremes of age and beta-blockade. Reported incidence varies by technique and ascertainment, but serious LAST after peripheral nerve block is commonly quoted around 0.3–1.8 per 1000 blocks, with lower rates in contemporary ultrasound-guided practice.

Maximum dose tables: useful but dangerous

“Maximum safe dose” is an exam favourite and a clinical trap. Toxicity depends on site vascularity, total dose, concentration, speed of injection, patient physiology and protein binding, not simply mg kg^-1. Adrenaline reduces peak plasma concentration by vasoconstriction and is a marker of intravascular injection, but it is not absolute protection. High-risk states include pregnancy, low cardiac output, hepatic impairment, severe acidosis, hypoxia, frailty, low alpha-1-acid glycoprotein and extremes of age. Fascial plane blocks, although perceived as superficial, may require large volumes and can generate clinically important systemic absorption.

Viva-level differentials and integration

Scenario	Alternative diagnosis	Discriminating features
Collapse after neuraxial or regional anaesthesia	High spinal	Profound sympathetic block, bradycardia, hypotension, respiratory insufficiency; no prodromal tinnitus or seizures unless hypoxic.
Hypotension, bronchospasm, rash	Anaphylaxis	Temporal relation to antibiotic, chlorhexidine, latex; raised mast-cell tryptase; lipid not definitive therapy.
Seizure after block	Hypoglycaemia, epilepsy, hypoxia, intrathecal opioid/local anaesthetic error	Check glucose, oxygenation, drug route and dose; treat seizure while preparing lipid if LAST plausible.
Cyanosis refractory to oxygen after prilocaine/benzocaine	Methaemoglobinaemia	Saturation gap, chocolate blood, co-oximetry; treat with methylene blue 1–2 mg kg-1 unless contraindicated.

Practical pitfalls that lose marks

• Continuing to inject local anaesthetic after early neurological symptoms.
• Using standard high-dose adrenaline during LAST arrest without modification.
• Choosing lidocaine for ventricular arrhythmia caused by local anaesthetic toxicity.
• Assuming lipid replaces high-quality CPR, oxygenation, seizure control and correction of acidosis.
• Stopping monitoring too early: observe at least 2 hours after isolated CNS symptoms and at least 4–6 hours after cardiovascular instability or lipid treatment.
• Failing to notify, document, report and restock a readily accessible LAST rescue kit.