2019A Question 08
20mL of 1% ropivacaine is inadvertently administered intravenously over 15 seconds to a 60 year old, 60kg woman. Describe the potential complications and mechanisms of these. Do not discuss treatment.
Examiner Report
60.2% of candidates achieved a pass in this question.
To score a pass in this question candidates needed to recognise that what has occurred represents a significant overdose, that it is life threatening, to list the likely clinical symptoms, and explain their mechanisms both within the organ systems involved and within the excitable cells on which ropivacaine acts.
It was very commonly stated that the maximum safe dose was 3mg/kg and this this dose of 200mg in a 60kg woman exceeded this dose by 20mg and would therefore cause toxicity. This is a fundamental misunderstanding as this “maximum” of 3mg/kg would not apply to direct intravenous injection, which would cause the heart and CNS to be exposed within one arm-brain time to a plasma concentration of ropivacaine far beyond that required to cause life threatening side effects.
The CNS effects were generally well described but within the cardiovascular system many candidates simply stated that arrhythmias and cardiovascular collapse would occur without providing an adequate description of the full range of cardiovascular effects. The mechanism by which ropivacaine causes these several effects on the heart and circulation were poorly understood. A common deficit among the lower scoring answers was a lack of sufficient detail in regard to the molecular mechanism of toxicity of local anaesthetics.
Many candidates with an obvious appreciation of the severity of the situation did not discuss the mechanisms (including the cellular mechanism) of ropivacaine action and therefore lost marks that were likely within their grasp. Furthermore, some wasted time with discussion of treatment, which the question explicitly stated should not be discussed.
Model Answer
Structure:
- Ropivacaine pharmacology
- Calculations
- CNS
- CVS
Ropivacaine Pharmacology
| Property | Detail |
|---|---|
| Class | Amide local anaesthetic |
| Target | - Voltage-dependent Na+ channel (VDNaC) - (Less active at VDKC, VDCaC) |
| Entry | - From ICF: Unionised form diffuses into axoplasm, ionised form enters active receptor - From ECF: Ionised form enters active receptor (less common) |
| Binding | - Rate ∝ time spent in active state ∝ Rate of cycling ∝ Nerve activity - Affinity ∝ Inactive > Resting > Activated |
| Effect | - ↓ Rate of cycling → No action potential propagation - Initial: Incomplete blockade, tonic - Repeated stimulation: Complete blockade, phasic - No change to resting potential |
| Toxic Thresholds | - Subcut dose: 3mg.kg-1 - Plasma concentration: 4μg/mL - CC:CNS ratio 5:1 (c.f. lignocaine 7:1); hence ‘warning shot’ is late |
Calculations
| Property | Detail |
|---|---|
| Amount given | - 10mg/mL x 20mL = 200mg |
| Cardiac output | - 70mL.kg-1.min-1 x 60kg = 4200mL - In 15 seconds: 1050mL |
| Estimated plasma concentration | - 200mg/4200mL ≈ 50μg/mL - Way above toxic threshold of 4μg/mL |
| Consequences | - Coma and cardiac arrest almost certain - Rx intralipid - Likely prolonged CPR +/- CPB; long duration of action, t1/2β 120 mins |
CNS Toxicity
| Factor | Detail |
|---|---|
| Mechanism | - Inhibition of neuronal VDNaC - Highly lipid soluble (300x procaine), easy passage across BBB |
| Effects | - Initial excitatory effects - Inhibition of inhibitory interneurons - Peri-oral tingling, tinnitus, vertigo, slurred speech, inattention, twitching, seizures - Then inhibitory effects - Inhibition of excitatory interneurons and others - Coma, apnoea |
CVS Toxicity
| Factor | Detail |
|---|---|
| Mechanism | - Inhibition of cardiac VDNaC (very high affinity) - Inhibition of VDKC and VDCC (lower affinity) - ?↓ cAMP |
| Effects | - Second phase: Myocardial depression, ↓ MAP - Terminal phase: Peripheral vasodilatation, ↓↓ MAP, arrhythmia, arrest |
| ECG | - “As if being pulled apart” ↑ QTC, ↑ QRS duration - Arrhythmias: Sinus bradycardia, AV block, ventricular tachyarrhythmia, asystole |