Muscle Relaxants: Appropriate Dosing and Monitoring

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Muscle RelaxantsAppropriate Dosing and
Monitoring

• Case Reports and SimulationsAnesthesia Grand
  RoundsJuly 8, 2002

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Acknowledgment

• Rupp SM, Castagnoli KP, Fisher DM, Pancuronium
  and vecuronium pharmacokinetics and
  pharmacodynamics in younger and elderly adults.
  Anesthesiology 1987 6745-9.

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Case 1

• 60 kg, 50 year old cachectic woman with large
  pelvic mass
• Induced with 5 mg vecuronium
• At 60 minutes, twitch 1 out of 4, and the
  surgeon reports the abdominal wall is tight.
• In response, an additional 5 mg of vecuronium was
  given.
• Case ends at 90 minutes, patient cant be
  extubated until about 150 minutes

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Case 1 Simulation
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Case 1 Alternatives
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4
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2
1
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Case 1 Conclusions

• This patient was unusually sensitive to
  vecuronium, as the expected recovery at 60
  minutes would be 4 twitches out of 4, not 1.
  Increased sensitivity may be from
• Pharmacokinetics Hepatic clearance may be
  decreased by underlying illness (particularly
  cholestasis)
• Pharmacodynamics Most commonly a drug
  interaction (e.g., inhalational anesthetics,
  aminoglycosides, quinidine, magnesium).

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Case 1 Conclusions

• The dose of 5 mg at 60 minutes did not
  appreciably accelerate the onset of relaxation.
• A dose of 1 mg would have provided adequate
  relaxation for 20-30 minutes.
• There is almost never a need to redose with more
  than 1 mg of vecuronium in an adult.

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Case 1 Conclusions

• Monitoring NMB at the wrist, as was done in this
  case, can overestimate the amount of block. In
  other words, it is not uncommon for a patient
  with NMB monitored at the wrist to have more
  abdominal muscle tone than the twitch monitor
  suggests.
• Monitoring NMB on the face can underestimate the
  amount of block. In other words, if the patient
  has only 1 twitch on the face, it is very
  unlikely that there is any appreciably abdominal
  muscle tone.

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Case 1 Conclusions

• If a vecuronium infusion had been used, the dose
  (to quote the package insert, emphasis added)
  would be
• After an intubating dose of 80-100 µg/kg, a
  continuous infusion of 1 µg/kg/min can be
  initiated approximately20-40 min later. Infusion
  of Norcuron (vecuronium bromide) for Injection
  should be initiated only after early evidence of
  spontaneous recovery from the bolus dose. The
  infusion of Norcuron (vecuronium bromide) for
  Injection should be individualized for each
  patient. The rate of administration should be
  adjusted according to the patient's twitch
  response as determined by peripheral nerve
  stimulation. An initial rate of 1 µg/kg/min is
  recommended, with the rate of the infusion
  adjusted thereafter to maintain a 90 suppression
  of twitch response. Average infusion rates may
  range from 0.8 to 1.2 µg/kg/min.

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Case 1 Conclusions

• To adjust an infusion for the inhalational
  anesthetic (again quoting the package insert,
  emphasis added)
• Inhalation anesthetics, particularly enflurane
  and isoflurane may enhance the neuromuscular
  blocking action of nondepolarizing muscle
  relaxants. In the presence of steady-state
  concentrations of enflurane or isoflurane, it may
  be necessary to reduce the rate of infusion 25-60
  percent, 45-60 min after the intubating dose.
  Under halothane anesthesia it may not be
  necessary to reduce the rate of infusion.

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Case 1 Conclusions

• The patient was not hurt, because reversal and
  extubation was delayed until adequate reversal
  could be assured.
• An overdose of muscle relaxant cannot be
  pharmacologically reversed.
• Waiting for the drug to be eliminated to the
  point that reversal is possible is the only
  correct response to an overdose of muscle
  relaxant.
• (assuming you dont want the embarrassment of
  setting up a ventilator in the recovery room)

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Case 2

• Patient was undergoing removal of a screw from
  the ankle.
• Patient received 7 mg of vecuronium with
  induction of anesthesia
• At 30 minutes, the resident felt the twitch was
  returning, and gave 3 mg of vecuronium.
• Surgery was completed 10 minutes later.
• Patients relaxation could not be reversed until
  30 minutes after the end of surgery.

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Case 2
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Case 2 Where you were headed
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Case 2 Conclusions

• The patient did not need relaxation for the
  surgery to proceed.
• The anesthesiologist did not adequately
  communicate with the surgeon
• The surgeon was perfectly happy with the state of
  relaxation of the patient.
• The anesthesiologist was unaware that the case
  was nearly finished when additional relaxation
  was given.

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Case 2 Conclusions

• Even if additional relaxation had been indicated,
  there was no need to give more than 1 mg.
• As before there is almost never a reason to give
  more than 1 mg of vecuronium as a follow-up dose.
• If you are confident that the case has at least
  another hour to proceed, and are monitoring
  relaxation, then perhaps 2-3 mg can be justified.
• Over time, you get a bigger effect, and a more
  prolonged effect, from each top-up dose of
  relaxant, reflecting accumulation of drug in the
  body.

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Case 3

• A neurosurgical patient needed a rapid sequence
  induction of anesthesia, while keeping the ICP
  low.
• Relaxation was provided with rocuronium, 0.6
  mg/kg.
• 1 minute after induction, intubation was
  performed.
• Intubation was followed by severe coughing and
  bucking on the endotracheal tube, and a dangerous
  increase in ICP.
• Questions
• Was the dose of rocuronium adequate?
• Was 1 minute adequate?
• Should the twitch have been monitored on
  induction?

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Case 3 Rocuronium Onset

• Amazingly, nobody seems to have published an
  integrated PK/PD model for rocuronium

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Case 3 Rocuronium Onset

• 0.6 mg/kg in 1 minute, with propofol, was judged
  adequate only 32 of time.
• Tan CH, Onisong MK, Chiu WK. Anaesthesia 2002
  57223-6
• 0.6 mg/kg at 1 minute 50 blockade, peak effect
  is at 141 seconds.
• Zhou TJ, White PF, Chiu JW, Joshi GP, Dullye KK,
  Duffy LL, Tongier WK. Br J Anaesth 2000 85246-50
• 0.6, 0.9, and 1.2 mg/kg, N108. Intubation
  conditions at 60 seconds OK for all but 2
  patients, both in the 0.6 mg/kg group
• Schultz P, Ibsen M, Ostergaard D, Skovgaard LT.
  Acta Anaesthesiol Scand 2001 45612-7

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Case 3Rocuronium Package Insert Info
Dose (mg/kg) Onset (range) Peak (range) Duration
(range) 0.45 (n50) 1.3 (0.8-6.2) 3.0
(1.3-8.2) 22 (12-31) 0.6 (n142) 1.0
(0.4-6.0) 1.8 (0.6-13.0) 31 (15-85) 0.9
(n20) 1.1 (0.3-3.8) 1.4 (0.8-6.2) 58 (27-111)
1.2 (n18) 0.7 (0.4-1.7) 1.0 (0.6-4.7) 67
(38-160)
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Case 3 Conclusions

• The dose was too small to reliably assure
  relaxation within 1 minute
• Under the circumstances, the combination of a
  marginal dose and the lack of a monitor of effect
  created a dangerous situation for the patient.

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Case 3 Conclusions

• Dr. Saidman would argue that a larger dose and
  monitoring of onset would be the appropriate
  conclusion to prevent this from happening in
  future cases.
• Dr. Shafer would accept the increased dose (i.e.,
  1.0 mg/kg) alone, in combination with a full 60
  seconds of delay, as an appropriate conclusion to
  prevent this from happening in future cases.

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Rocuronium Infusions

• If you are going to use an infusion, be sure you
  have a good reason to pick rocuronium over
  vecuronium, which is about ¼ as expensive.
• Personally, I cant think of one
• The package guideline states
• Infusion at an initial rate of 10 to 12
  mcg/kg/min should be initiated only after early
  evidence of spontaneous recovery from an
  intubating dose. Due to rapid redistribution and
  the associated rapid spontaneous recovery,
  initiation of the infusion after substantial
  return of neuromuscular function (more than 10
  of control T 1 ), may necessitate additional
  bolus doses to maintain adequate block for
  surgery. Upon reaching the desired level of
  neuromuscular block, the infusion of ZEMURON
  must be individualized for each patient. The rate
  of administration should be adjusted according to
  the patient's twitch response as monitored with
  the use of a peripheral nerve stimulator. In
  clinical trials, infusion rates have ranged from
  4 to 16 mcg/kg/min. In the presence of
  steady-state concentrations of enflurane or
  isoflurane, it may be necessary to reduce the
  rate of infusion by 30 to 50, at 45 to 60
  minutes after the intubating dose.

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Two Classes of Relaxants

• Benzylisoquinolones curare, metocurine,
  atracurium
• Steroids pancuronium, vecuronium, rocuronium
• Within class additive interaction
• Between classes STRONGLY synergistic interaction.

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STANPUMP

• Can be used for simulations of vecuronium,
  pancuronium, atracurium, and rocuronium.
• I was incorrect earlier when I said that PK/PD
  models for rocuronium hadnt been published. They
  are published, and I added them to STANPUMP years
  ago).
• Source code and executable file can be downloaded
  from our departmental website
• http//anesthesia.stanford.edu/pkpd/Target20Contr
  ol20Drug20Delivery/STANPUMP/Forms/AllItems.htm