33.3 Vasoconstrictors, Maximum Doses and Systemic Toxicity

Vasoconstrictors in Dental Anaesthesia

Vasoconstrictors are included in dental local anaesthetic solutions to counteract the intrinsic vasodilatory actions of local anaesthetic bases (especially lidocaine and procaine). They provide four major clinical benefits:

1. Prolonged Duration: Constriction of local arterioles delays vascular clearance, maintaining the drug around nerve fibres.
2. Enhanced Pulpal Depth: Increases the concentration of anaesthetic molecules reaching the inner core fibres of the nerve trunk.
3. Reduced Peak Plasma Concentrations: Slower systemic absorption lowers the risk of systemic toxicity (LAST).
4. Surgical Haemostasis: Decreases intraoperative haemorrhage in the surgical field.

Adrenaline (Epinephrine) Receptor Pharmacology

Adrenaline is an endogenous catecholamine that acts as a potent, non-selective agonist across adrenergic receptor subtypes:

                               Adrenaline (Epinephrine)
                                          │
             ┌────────────────────────────┼────────────────────────────┐
             ▼                            ▼                            ▼
     Alpha-1 (α1) Receptors       Beta-1 (β1) Receptors        Beta-2 (β2) Receptors
  - Submucosal vasoconstriction  - Positive inotropy (force)  - Skeletal arteriolar dilation
  - Local surgical haemostasis   - Positive chronotropy (rate)- Bronchodilation
  - Reduced systemic uptake      - Increased cardiac output   - Lowers diastolic BP
                                 - Elevated myocardial MVO2

Maximum Safe Dosage Guidelines

1. Adrenaline Thresholds:

   • Healthy Adult Patient: Maximum recommended dose is 0.2 mg (200 micrograms) per appointment.
     • For 1:80,000 adrenaline ($12.5\text{ mcg/mL}$), 0.2 mg corresponds to $16.0\text{ mL}$, or 7.2 UK cartridges (2.2 mL). In practice, this is rounded to a safe maximum of 7 to 8 cartridges.
     • For 1:100,000 adrenaline ($10.0\text{ mcg/mL}$), 0.2 mg corresponds to $20.0\text{ mL}$, or 9 UK cartridges (2.2 mL).
   • Cardiovascular Patient (ASA III/IV, Ischaemic Heart Disease, Uncontrolled Arrhythmia): Maximum recommended dose is restricted to 0.04 mg (40 micrograms).
     • For 1:80,000 adrenaline, 0.04 mg corresponds to $3.2\text{ mL}$, representing 1.45 cartridges (strictly capped at maximum 1.5 to 2 cartridges).

2. Local Anaesthetic Base Dosage Limits:

   • Lidocaine (with adrenaline): The figure taught for UK dental practice is 4.4 mg/kg of body weight, up to an absolute ceiling of 300 mg in adults. Note that maximum-dose figures for lidocaine differ between sources — the BNF and the manufacturer's summary of product characteristics support a higher ceiling of 7 mg/kg up to 500 mg — so quote the conservative dental figure and calculate from body weight. In a healthy adult the adrenaline limit is reached first in any case.
   • Articaine (with adrenaline): Maximum safe dose is 7.0 mg/kg of body weight, up to an absolute ceiling of 500 mg in adults.
   • Mepivacaine plain: Maximum safe dose is 4.4 mg/kg, up to an absolute ceiling of 400 mg.
   • Prilocaine (with felypressin): Maximum safe dose is 6.0 mg/kg, up to an absolute ceiling of 400 mg.

Step-by-Step Clinical Calculation Examples

[!NOTE] Worked Example 1: 70 kg Healthy Adult (2% Lidocaine with 1:80,000 Adrenaline)

1. Calculate base limit: $70\text{ kg} \times 4.4\text{ mg/kg} = 308\text{ mg}$, which is capped by the 300 mg adult ceiling.
2. Determine drug content per cartridge: A 2.2 mL cartridge of 2% lidocaine contains $20\text{ mg/mL} \times 2.2\text{ mL} = 44\text{ mg}$.
3. Calculate maximum cartridges based on lidocaine: $300\text{ mg} \div 44\text{ mg/cartridge} = 6.8\text{ cartridges}$, so 6 whole cartridges.
4. Check adrenaline limit: 6 cartridges contain $6 \times 27.5\text{ mcg} = 165\text{ mcg} = 0.165\text{ mg}$, safely below the 0.2 mg (200 mcg) healthy-adult threshold.
5. Safe Clinical Limit: 6 cartridges on the conservative dental figure; the adrenaline ceiling of 0.2 mg would permit at most 7.

[!WARNING] Worked Example 2: 20 kg Child (2% Lidocaine with 1:80,000 Adrenaline)

1. Calculate base limit: $20\text{ kg} \times 4.4\text{ mg/kg} = 88\text{ mg}$.
2. Determine cartridges: $88\text{ mg} \div 44\text{ mg/cartridge} = 2.0\text{ cartridges}$.
3. Check adrenaline: $2 \times 27.5\text{ mcg} = 55\text{ mcg} = 0.055\text{ mg}$ (well below childhood systemic threshold).
4. Safe Clinical Limit: Exactly 2 cartridges (4.4 mL). A third cartridge would give 132 mg, or 6.6 mg/kg, exceeding the recommended maximum for this child and moving the dose towards the range in which systemic toxicity becomes a real risk.

Local Anaesthetic Systemic Toxicity (LAST)

Local Anaesthetic Systemic Toxicity (LAST) is a life-threatening adverse event triggered by an excessive plasma concentration of free local anaesthetic. It most commonly results from inadvertent direct intravascular injection due to failure to aspirate in two planes, or from exceeding maximum weight-adjusted dosage limits.

Pathophysiological Cascade

Local anaesthetic bases are lipophilic and rapidly cross the blood-brain barrier. In the central nervous system, they initially block inhibitory cortical interneurons (GABAergic pathways), releasing unopposed excitatory pathways. As plasma levels continue to climb, both inhibitory and excitatory pathways are suppressed, producing generalized central nervous system depression. Concurrently, high plasma concentrations block cardiac sodium channels ($Na_v 1.5$), uncoupling cardiac excitation-contraction and precipitating lethal conduction blocks and refractory arrhythmias.

                                  Plasma LA Concentration Rising
                                                │
                 ┌──────────────────────────────┴──────────────────────────────┐
                 ▼                                                             ▼
     Central Nervous System (CNS)                               Cardiovascular System (CVS)
  1. Initial Cortical Excitation:                            1. Electrophysiological Depression:
     - Circumoral / perioral numbness                           - PR interval prolongation
     - Metallic taste in mouth                                  - QRS widening
     - Tinnitus and auditory distortion                         - Sinus bradycardia & heart blocks
     - Agitation, restlessness, slurred speech
                 │                                                             │
                 ▼                                                             ▼
  2. Severe Excitation:                                      2. Contractile Depression:
     - Muscle twitching and fasciculations                      - Profound peripheral vasodilation
     - Generalized tonic-clonic seizures                        - Severe hypotension
                 │                                                             │
                 ▼                                                             ▼
  3. CNS Depression:                                         3. Cardiovascular Collapse:
     - Loss of consciousness, coma                              - Ventricular arrhythmias (VF/pVT)
     - Respiratory depression & arrest                          - Asystolic cardiac arrest

Emergency Management Protocol for LAST

1. Immediate Cessation & Airway Support:
   • Cease injection immediately and summon emergency assistance (call 999).
   • Administer 100% high-flow oxygen via a non-rebreather reservoir mask (15 L/min). Hyperventilation prevents respiratory acidosis; acidosis increases the free ionized fraction of local anaesthetics and exacerbates CNS toxicity.
2. Seizure Management:
   • Terminate tonic-clonic convulsions promptly to prevent metabolic acidosis. Administer Buccal Midazolam 10 mg (or IV Midazolam 2–5 mg if venous access is established).
3. Advanced Resuscitation & Intravenous Lipid Emulsion Therapy:
   • If cardiovascular compromise or cardiac arrest develops, initiate high-quality chest compressions immediately.
   • Specific Antidote: Intravenous 20% Lipid Emulsion (Intralipid):
     • Mechanism ("Lipid Sink"): The circulating lipid droplets establish a separate intravascular hydrophobic phase that sequesters lipophilic local anaesthetic molecules away from cardiac myocytes and brain tissue, restoring sodium channel conductances.
     • Administration Regimen: Administer an initial IV bolus of 1.5 mL/kg of 20% Intralipid over 1 minute (~100 mL for a 70 kg adult), followed immediately by a continuous IV infusion of 0.25 mL/kg/min. If cardiovascular stability is not restored, the bolus can be repeated up to two times at 5-minute intervals, and the infusion rate increased to 0.5 mL/kg/min.
   • Resuscitation Modifications: In LAST-induced cardiac arrest, reduce individual adrenaline boluses during CPR to $<1\text{ mcg/kg}$ (avoid large 1 mg boluses which worsen arrhythmias), and avoid vasopressin, calcium channel blockers, and beta-blockers.