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PH2.1-5 | Autonomic and Peripheral Pharmacology — PBL Case

CLINICAL SETTING

Vikram, a 22-year-old state-level wrestler, is brought to the emergency department of a district hospital in Kolhapur at 8 pm on a Saturday. He competed in a tournament that afternoon and received a 'strain injection' from a local sports trainer before the bout — reportedly a muscle relaxant to help with a prior back injury. Thirty minutes later during the match, Vikram collapsed on the mat. Bystanders report he had a brief period of generalised stiffening followed by complete limpness. He is now breathing but shallow, apnoeic periods lasting 20–30 seconds, and is only responding to pain. His team-mate (also a wrestler) who received the same injection is asymptomatic and sitting in the waiting room. Vikram's wife, visibly distressed, says he 'never touched drugs' but shows the injection vial she recovered from the trainer — it is unlabelled.

Trigger 1: First Presentation and Stabilisation

Vitals: HR 58/min regular, BP 98/64 mmHg, SpO2 78% on room air, RR 6/min with visible accessory muscle use. Pupils: bilaterally mid-dilated and sluggishly reactive. GCS 8 (E2V2M4). No SLUDGE features (no excessive salivation, no diaphoresis, no miosis). Chest auscultation: bilateral wheeze with reduced air entry. On closer inspection of the recovered vial label fragment, the senior resident can make out '...curonium'. The anaesthesiology registrar is called urgently.

DISCUSSION POINTS

  • Based on the clinical picture — generalised flaccidity, apnoea, absent secretory features, and the vial label fragment — what is the most likely pharmacological cause of Vikram's condition?
  • Why is the team-mate asymptomatic? What pharmacological concept explains why two people receiving the same dose of a neuromuscular blocking drug can have very different clinical responses?
  • What is the first priority in this patient? What physiological parameter drives the immediate management decision, and which drugs and equipment should be prepared immediately?
Click to reveal Trigger 2: Definitive Reversal and Haemodynamic Instability (discuss previous trigger first!)

Trigger 2: Definitive Reversal and Haemodynamic Instability

The patient is mask-ventilated and intubated. Peripheral nerve stimulator (train-of-four) shows 0/4 twitches. Blood pressure has dropped further to 72/48 mmHg. The anaesthesiology registrar asks the team: 'What can we give to reverse this? Can we give neostigmine?' A neurology consult is called to assess whether there is an underlying NMJ disease. Blood sample is sent for plasma cholinesterase activity (returns at 28% of normal). Meanwhile, the 'curonium' partial label and the onset time (~30 minutes from injection to collapse, then still profoundly paralysed 45 minutes later) are discussed.

DISCUSSION POINTS

  • Neostigmine is proposed for reversal. What receptor mechanism does it use? Under what conditions (train-of-four count) is it safe to use neostigmine for reversal, and why is it contraindicated when TOF is 0/4? What is the specific risk?
  • Given the very prolonged paralysis and low plasma cholinesterase activity, reconstruct what likely happened. Was this a depolarising or non-depolarising agent? What pharmacokinetic or pharmacogenomic feature explains the prolonged duration in Vikram specifically?
  • Sugammadex is mentioned as an alternative reversal agent. How does it work? Which NMBD class and which specific agents can it reverse? What dose is appropriate for deep block (TOF 0/4)?
Click to reveal Trigger 3: Recovery and Perioperative Planning for the Next Procedure (discuss previous trigger first!)

Trigger 3: Recovery and Perioperative Planning for the Next Procedure

After 16 mg/kg sugammadex IV, TOF count returns to 4/4 with sustained tetany within 3 minutes. Vikram is successfully extubated. SpO2 normalises to 99% on 4L O2. HR is now 90/min and BP 106/72 mmHg. He is alert and recalls 'a sharp pain in his shoulder then everything went dark.' Urine toxicology is pending. The consultant nephrologist on call notes Vikram has an undiagnosed creatinine of 3.2 mg/dL (chronic from a childhood infection). He will need an elective tendon repair under general anaesthesia in 4 weeks. The question of NMBD choice for that future procedure is now being discussed. Additionally, the local sports trainer is arrested. Investigation reveals the vial contained succinylcholine sourced illicitly. The low plasma cholinesterase activity in Vikram explains his prolonged Phase 2 block.

DISCUSSION POINTS

  • For Vikram's future elective surgery (renal impairment, creatinine 3.2 mg/dL), which non-depolarising NMBD would you recommend for the anaesthetist, and why? Specifically address the elimination pathway and why it matters in his case.
  • Given that the true agent was succinylcholine and Vikram has low plasma cholinesterase, explain the sequence: initial fasciculations → prolonged flaccid paralysis (Phase 2 block) → why sugammadex worked (or did not, in theory). Is this consistent with what was observed?
  • Draft a one-paragraph 'pharmacological safety briefing' for the surgical and nursing team that will perform the elective procedure in 4 weeks. Include: (a) which drugs to prepare, (b) which to avoid, and (c) what emergency reversal must be immediately available at the bedside.

Group Task Assignments

Group 1: Receptor pharmacology of neuromuscular blocking drugs

  • Describe the mechanism of depolarising vs non-depolarising NMBDs at the NMJ
  • Explain Phase 1 and Phase 2 block of succinylcholine with the clinical features of each
  • Tabulate onset, duration, and elimination route for succinylcholine, vecuronium, atracurium, rocuronium, and pancuronium

Competencies: PH2.4

Group 2: Reversal agents — mechanism and clinical decision rules

  • Explain how neostigmine reverses non-depolarising block and why it cannot reverse depolarising block
  • Describe the mechanism of sugammadex and which NMBDs it reverses
  • State the train-of-four count thresholds for safe use of neostigmine vs sugammadex reversal

Competencies: PH2.4, PH2.2

Group 3: Plasma cholinesterase — pharmacogenomics and drug safety

  • Describe the normal role of plasma (pseudo)cholinesterase in drug metabolism
  • List drugs metabolised by plasma cholinesterase and the clinical implications of deficiency
  • Explain the Dibucaine number test for cholinesterase variants and its clinical interpretation

Competencies: PH2.4

Group 4: NMBD choice in organ failure — pharmacokinetic adaptation

  • Compare elimination pathways for the five major NMBDs in renal and hepatic failure
  • Explain Hofmann elimination (atracurium/cisatracurium) — why it is organ-independent
  • Recommend an NMBD regimen for a patient with combined renal and hepatic failure and justify the choice

Competencies: PH2.4

Group 5: Malignant hyperthermia and anaesthetic triggers — safety briefing

  • List the known triggers for malignant hyperthermia (NMBD and anaesthetic agents)
  • Explain why succinylcholine is an MH trigger and which NMBDs are safe in MH-susceptible patients
  • Outline the pharmacological management of an acute MH crisis (dantrolene — mechanism, dose)

Competencies: PH2.4

Learning Issues

Research these questions and bring your findings to the discussion.

  1. [PH2.4] Describe the classification, pharmacokinetics, pharmacodynamics, and adverse effects of neuromuscular blocking drugs, including the conditions under which each is preferred or contraindicated.
  2. [PH2.4] Explain the pharmacological basis for reversal of neuromuscular blockade, the role of train-of-four monitoring, and the clinical rules governing the safe use of neostigmine and sugammadex.
  3. [PH2.2] How does neostigmine inhibit acetylcholinesterase, and why must a muscarinic antagonist (glycopyrrolate or atropine) be co-administered? What are the implications if co-administration is omitted?