January 2008 MH Case of the Month

Topic:  Postoperative Recurrent Fever, Hallucinations, and Agitation in a Child with Spastic Quadriplegia

The hotline consultant was paged by 1-800-MH-HYPER at 3 a.m.  He was very surprised to learn that the call originated from the medical center where he works.  A pediatric resident working in the ICU desired assistance managing the following patient:

A 13-year-old male with spastic quadriplegia was ventilator-dependent following a car accident at age 2.  Six days before the hotline call, selective dorsal rhizotomy (cutting  nerve roots in the lower back using EMG (electromyography) guidance) was performed for relief of severe spasticity.  The intraoperative and immediate postoperative course was uneventful. Hallucinations, temperature elevation and agitation were noted more than 48 hours postoperatively. 

Questions

1) The onset of temperature elevation more than 48 hours postoperatively is most likely delayed-onset anesthetic-induced malignant hyperthermia.

       a)  true

       b)  false

The child was treated with one dose of haloperidol (Haldol).  CK (Creatine Kinase) elevation (350) and trace myoglobinuria were noted on postoperative day 3. Psychiatry evaluated the patient, and suggested a diagnosis of NMS (Neuroleptic Malignant Syndrome.)

2) Agitation is a typical finding in NMS.

       a)  true

       b)  false

The consulting psychiatrist recommended dantrolene 1mg/kg iv, which was  given on postoperative day 3, then 1 mg/kg iv q 8 hours starting again on postoperative day 5 for recurrent temperature elevation and tachycardia.  No additional haldol was given; lorazepam (Ativan) was given for control of agitation.

3) Other causes of agitation and hyperthermia could include which of the following:

a)      pneumonia

b)      urosepsis

c)      central nervous system infection

d)      hyperthyroidism

e)      baclofen withdrawal syndrome

f)        ALL of the above

There was no evidence of pneumonia, urinary infection, or meningitis.  Psychiatry  recommended stopping lorazepam. The MH Hotline was called because of recurrent temperature to 42.5° C and heart rate >160 despite dantrolene, Tylenol and ibuprofen.  End-tidal CO₂<30 mm. Some diarrhea was noted. ABG @0300 showed BE -11.     No seizures or myoclonus were observed.

Hotline Consultant’s Response and Subsequent Course:

      The consultant asked if this could be baclofen withdrawal syndrome.  Review of the preoperative history revealed that the patient was, in fact, on preoperative baclofen 30 mg q 6 hours per gastrostomy tube, as well as tizanidine (an a2-agonist) and dantrolene. Baclofen was not continued postoperatively. Patient had been treated with Robaxin (methocarbamol) postoperatively. 

    The consultant recommended that baclofen be restarted as soon as possible, and that the treating physicians consider re-instituting benzodiazepine treatment as well.  The hotline consultant commented that higher doses of iv dantrolene could be given until one observed the desired effect (e.g. reduced muscle tone and temperature) of restarting  baclofen, along with surface cooling and cool iv fluids.

     Literature search suggested potential benefit of enteral cyproheptadine (an oral anti-histamine with serotonin (5-HT2A) antagonism) as adjunctive treatment.  There was also a report of benefit with propofol sedation until baclofen effect was re-established.

    The consultant communicated his evaluation with the attending neurosurgeon and Pediatric ICU attending.  The consultant also reassured the patient’s family that the patient did NOT have anesthetic-induced malignant hyperthermia.

    The patient’s hyperthermia, agitation, and metabolic acidosis resolved within 12 hours of restarting enteral baclofen.

Answers:

1)      False

2)      False

3)      f (ALL of the above)

Narrative:  The key to rapidly determining the cause of the patient’s recurrent hyperthermia and agitation was the consultant’s awareness that the patient was almost certainly taking baclofen preoperatively for treatment of spasticity.  Anesthetic-induced malignant hyperthermia will occur intraoperatively or within the first hour following emergence from general anesthesia.  While neuroleptic malignant syndrome can occur following haloperidol administration, NMS is characterized by lethargy (e.g obtunded, mute or catatonic), not agitation.  The patient was at risk for infection; this was excluded by appropriate investigation.

Baclofen is a GABA_B (gamma-aminobutyric acid) agonist. Baclofen withdrawal syndrome is usually associated with an interruption of intrathecal baclofen delivery.  Clinical findings may include hallucinations, agitation, delusions, hyperthermia, tachycardia, blood pressure instability, increased spasticity, muscle rigidity and seizures.

Severe cases may result in rhabdomyolysis, disseminated intravascular coagulation (DIC), multi-organ failure, and death. 

The hotline case demonstrates that baclofen withdrawal syndrome may also occur after abrupt discontinuation of high doses of oral (or per G-tube) baclofen.  The case further demonstrates that treatment with dantrolene alone does not relieve the delirium or hyperthermia caused by baclofen withdrawal. 

When baclofen withdrawal syndrome is suspected, one should promptly seek appropriate medical consultation by the patient’s neurologist, neurosurgeon, or physiatrist (a specialist in Physical Medicine and Rehabilitation.)

References:

1)      For information about NMS: www.nmsis.org website

      2)   Coffey, RJ et al, “Abrupt withdrawal from intrathecal baclofen: recognition and management of a potentially life-threatening syndrome.” Arch Phys Med Rehabil.           2002 Jun;83(6):735-41.

Erratum in:

Arch Phys Med Rehabil 2002 Oct;83(10):1479.

4)      Leo, RJ et al, “Delirium Associated with Baclofen Withdrawal: A Review of    Common Presentations and Management Strategies.” Psychosomatics 46:503-507, December 2005.

5)      Ackland, G et al, “Low-dose Propofol Infusion for Controlling Acute Hyperspasticity after Withdrawal of Intrathecal Baclofen Therapy.” Anesthesiology. 103(3):663-665, September 2005.

6)      Meythaler, J et al, “Cyproheptadine for intrathecal baclofen withdrawal.” Archives of Physical Medicine and Rehabilitation, Volume 84, Issue 5, Pages 638-642.

Harvey K. Rosenbaum, M.D.

         Clinical Professor of Anesthesiology

                    David Geffen School of Medicine at UCLA