Neurosurgery notes/Procedures/Cranial procedures/Functional cranial procedures/Spasm/ITB underdosing or withdrawal

ITB underdosing or withdrawal

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Spasm

Due to

  • Under dose
  • Withdrawal
  • Blockage
  • Wrong drug concentration during refilling

Clinical features

  • Present within a few to 48 hours
  • Differential diagnosis
    • Sepsis/meningitis,
    • Neuroleptic malignant syndrome,
    • Autonomic dysreflexia,
    • Serotonin syndrome,
    • Malignant hyperthermia.
  • Symptoms
    • A spectrum of signs and symptoms with a variable degree of intensity
    • The severity of ITB withdrawal syndrome is not consistently related with dosing levels.
    • Return of patient’s “baseline” degree of hypertonia
      • Most common symptom
    • Baclofen withdrawal syndrome spectrum
        • Mild
        Moderate
        Severe
        Increase in tone
        Return of pathological tone
        Severe increase in tone
        Pruitus w/o rash
        Altered mental state
        Stupor and coma
        Irritability
        Mild Dysphoria
        Rhabdomyolysis
        ㅤ
        Elevated CK level
        Elevated CK level
        ㅤ
        Hypotension
        Seizure
        ㅤ
        Paresthesia
        ㅤ
        ㅤ
        Fever
        ㅤ
      • Many of these signs and symptoms are nonspecific and thus their presence should not solely be attributed to ITB underdosing.

Treatment

  • In the case of emergent withdrawal, medical treatment of the patient should be undertaken prior to or in parallel with the diagnostic workup described earlier (Fig. 2).
  • Manage in HDU
    • Potential for multiorgan system failure in severe cases
  • Definitive therapy of acute, severe ITB withdrawal requires restoration of ITB delivery.
    • If catheter disruption is detected, surgical revision or replacement of the catheter is warranted. Similarly, if low battery condition is discovered, then pump replacement should be undertaken.
    • While catheter replacement is usually fairly straightforward from a surgical standpoint, medical management of the patient following replacement can be challenging.
      • In cases of suspected catheter malfunction, the pump rate should be reduced significantly following revision.
    • Postoperative monitoring in an inpatient setting is appropriate for at least 24 hours and will insure that over- or underdosing is not apparent.
  • Temporizing treatments
      • Bolus administration (single or multiple) via LP.
      • The dose administered and the frequency of dosing during these interventions is dependent on
        • Severity of withdrawal
        • Previous ITB dosing levels
        • Time elapsed from the onset of symptoms
        • Responses to prior bolus doses.
      • It is at least reasonable to consider using the same dose as used during the initial trial if not higher.
      • The panel did not achieve consensus as to whether a lumbar puncture bolus could confirm or exclude tolerance.
      Lumbar drain infusion
      • If the ITB system is not functioning, consider continuous infusion with an indwelling lumbar intrathecal catheter and an external infusion pump.
        • The use of such devices is not approved by the Food and Drug Administration.
        • This approach should be maintained until the system is surgically corrected.
        • A potential advantage of continuous infusion through an externalized pump and catheter is that it may mimic the function of the indwelling pump.
        • The indwelling pump should be programmed to run at minimum rate, and the external pump set either to deliver bolus doses at the physician’s discretion, subject to the patient’s tolerance, every two to four hours. Patients should be monitored as the drug effect is cumulative and peak effect may not be seen until four hours after administration.
      • A challenging issue is the dosing of the patient’s ITB upon resumption of permanent delivery.
        • The medical literature and the consensus group had varied opinions on this issue.
        • If the withdrawal/underdosing is of relatively short duration, then restarting with the prior dosing schedule is a reasonable option.
        • If the underdosing has been present for a longer duration (days to weeks), then the ITB dose should be restarted at a reduced level.
          • Some panellists recommended restarting at a percentage of the baseline dosing (30% and 50% were the most common levels suggested), while other clinicians recommended resumption of ITB delivery as if the patient was pump-native (e.g., 100 mcg/day).
      Oral baclofen
      • If intrathecal exposure cannot be achieved promptly, then oral medications should be used as a temporizing measure.
      • Oral or enteral baclofen is the agent of choice but it should not be relied upon to halt the progression of ITB withdrawal.
      • It is important to emphasize that there is no uniform oral-to-intrathecal baclofen ratio.
      • Panel members described patients who were poorly tolerant of relatively low oral baclofen doses despite safely experiencing high ITB dosing.
      • A reasonable starting regimen would be 10–20 mg every six hours with the recognition that wide variability of tolerability and effectiveness can be demonstrated by a given patient.
      • Oral baclofen has several pharmacologic limitations
        • Variable oral absorption
        • Short duration of action
        • Slow onset of action
        • Delayed time to peak effect
        • Erratic renal elimination
        • Poor blood-brain barrier penetration.
      • Given these shortcomings, oral baclofen is of imperfect utility in severe underdosing and early in the evolution of withdrawal syndrome.
      • Multiple, small doses of oral baclofen may be required to adequately manage underdosing.
      • Intravenous (IV) baclofen is not commercially available.
      Other medications that can be adjunctively utilized
      • Benzodiazepines
        • Advantage
          • Can be given IV
          • Can be given via continuous infusion
          • As prophylactic agent for seizures
            • Which can be observed during underdosing/withdrawal ITB.
        • Pharmacodynamics
          • Activate presynaptic GABA type a receptors, circumventing the problem of resistance to oral baclofen due to downregulation in GABA type b receptors in patients with a long history of baclofen use.
        • IV infusion require monitoring due to concerns over respiratory and cardiovascular depression.
        • Benzodiazepines can mitigate symptoms of ITB withdrawal, thereby controlling spasticity, rigidity, and hyperthermia.
        • Types
          • Diazepam
            • Most commonly used
          • Lorazepam
          • Midazolam
      • Cyproheptadine
        • A serotonin agonist
        • Is an adjunct treatment for symptoms associated with acute ITB withdrawal.
        • Off-label
        • Administration of this medication has been observed to improve symptoms of spastic hypertonia, fever, and pruritus
        • Dosage
          • 2–4 mg every six hours with the possibility of increasing dosing amounts or frequency based on patient response.
      • Other medications
        • Have been reported in the published literature as useful in ITB withdrawal management, but the cases may represent loss of ITB drug effects rather than the more serious withdrawal syndrome.
        • Thus, some patients may have recovered despite the administration of nonspecific or potentially ineffective (against ITB withdrawal) sedative and muscle-relaxant drugs, or other therapies that included propofol, dantrolene, tizanidine, phenytoin derivatives, bromocriptine, diphenhydramine (Benadryl), and neuromuscular blocking agents.