Neuroleptic Malignant Syndrome Flashcards
what is NMS
life threatening idiosyncratic reaction to DOPAMINE ANTAGONISTS (most commonly antipsychotics but not always just antipsychotics)
what are the characteristic features of NMS
fever
altered mental status
muscle rigidity
autonomic dysfunction
what is the hypothesized underlying mechanism of NMS
excessive dopamine receptor blockade
what is the incidence of NMS
0.01-0.02% among those treated with antipsychotics
how soon does NMS develop after drug initiation
most develop within first 24 hours of drug initiation
may be within first week
virtually all cases are within first 30 days
what is the fatality rate of NMS
10-20% when UNrecognized
what is the mean recovery time after drug discontinuation
7-10 days
most people recover within 1 week and nearly all within 30 days
residual neurological signs may persist for weeks after the acute hyper metabolic symptoms resolve
do people tend to have recurrences of NMS?
people generally do NOT experience a recurrence of NMS when re-challenged with an antipsychotic
but theoretically there is a risk
list risk factors for NMS
agitation
exhaustion
dehydration
iron deficiency
parenteral administration of drug
rapid titration
higher total drug doses (though most cases occur within the dose range)
what types of antipsychotics present greater risk of NMS
higher potency are higher risk
what other types of drugs, other than antipsychotics, could cause NMS
ANY dopamine antagonist–> i.e metoclopramide or prochloperazine
can also see it in those with parkinsons disease if there is withdrawal of L-dopa or dopamine agonist therapy, dose reductions or a switch from one dopamine agonist to another
how are NMS and catatonia related
NMS related to malignant catatonia–> NMS being iatrogenic form of malignant catatonia
is there consensus or diagnostic criteria for NMS
no–> there was proposed criteria by a “2011 international consensus study of NMS diagnostic criteria”
what is a mnemonic to remember the clinical and lab findings of NMS
FEVERR
Fever
Encephalopathy (confusion, mental status changes)
Vital sign instability (tachycardia, tachypnea, and/or labile BP)
Enzyme elevation (creatinine phosphokinase increase due to rhabdo)
Rhabdomyolysis (caused by muscle rigidity)
Rigidity (generalized lead pipe muscle rigidity)
what feature distinguishes NMS from other toxidromes like serotonin syndrome and anticholinergic toxicity
muscle rigidity often leading to rhabdo
what are the 8 proposed diagnostic criteria mentioned previously
- recent dopamine agonist withdrawal or dopamine antagonist exposure (within last 72 hours)
- hyperthermia (above 38 on at least two oral measurements)
- rigidity (lead pipe)
- mental status alteration (reduced or fluctuating LOC)
- CK elevation
- sympathetic nervous system lability (defined by at least two of: BP elevation 25% or more above baseline; BP fluctuation of 20mmHg systolic change within 24 hours; diaphoresis; urinary incontinence)
- hypermetabolism (HR increase 25% or more above baseline AND respiratory rate increase of 50% or more above baseline)
- negative workup for infectious, toxic, metabolic or neurologic causes
what amount of CK elevation is expected in NMS
at least 4x upper limit of normal
what features do you look for in terms of assessing sympathetic nervous system instability when assessing for NMS
defined by at least two of:
BP ELEVATION 25% or more above baseline
BP FLUCTUATION of 20mmHg systolic change within 24 hours
diaphoresis (often profuse)
urinary incontinence
what features do you look for in terms of assessing hypermetabolism when assessing for NMS
HR increase of 25% or more above baseline
RR increase of 50% or more above baseline
what other neuro signs can be present with NMS
tremors
trismus
dysarthria
dysphagia
akinesia
sialorrhea
myoclonus
what might you see on EEG for NMS
generalized slowing
what might you see on blood work for someone with NMS
leukocytosis
metabolic acidosis
hypoxia
decreased serum iron concentrations
elevations in serum muscle enzymes and catecholamines
does NMS show up on CSF analysis or neuroimaging studies
no–> these are generally unremarkable in NMS
how do you make the diagnosis of NMS
diagnosis of exclusion
must exclude other infectious, toxic, metabolic and neuropsychiatric conditions i.e status epilepticus
ddx of NMS
serotonin syndrome
parkinsonian hyperthermia syndrome (usually following ubrupt discontinuation of dopamine agonists)
alcohol or sedative withdrawal
malignant hyperthermia (during anesthesia)
hyperthermia associated with abuse of stimulants and hallucinogens
atropine poisoning
malignant catatonia
CNS infection
inflammatory or autoimmine conditions
status epilepticus
structural cortical lesions
systemic conditions i.e pheo, thyrotoxicosis, tetanus, heat stroke
what is the first think you should do once you suspect NMS
stop all dopamine antagonists
what is the treatment of NMS
supportive care
includes:
fluid replacement
–> aggressive hydration often required especially if highly elevated CPK levels threaten to damage kidneys
supporting cardiac, lung and renal function
–>consider bicarbonate loading to prevent renal failure
temperature reduction
trend and monitor WBC, CK, temp, serum iron, liver transaminases
what pharmacologic options are there to treat NMS
bromocriptine–> pro dopaminergic and pro-serotonergic agent
amantadine
dantrolene –> muscle relaxant that inhibits calcium release from the sarcoplasmic reticulum
(bromocriptine and dantrolene are most common)
*for more severe cases
what is the classic triad of NMS
fever
muscle rigidity
altered mental status
*there is a lot of heterogeneity in presentation
does the muscle rigidity seen in NMS tend to respond to antiparkinsonian agents
no
how serious is NMS
considered neurological emergency
why might you consider empiric pharmacotherapy for NMS with bromocriptine and/or dantrolene
may SHORTEN the course of the syndrome and possibly REDUCE MORTALITY when used alone or in combo
why is bromocriptine given in NMS
to reverse the hypodopaminergic state
admin orally or by NG
what is the dosing of bromocriptine for NMS
2.5 mg 2-3x daily
increasing doses by 2.5 mg every 24 hours until response or until max dose of 45mg/day reached
generally continued for at least 10 days for NMS related to oral neuroleptics and 2-3 weeks for depot neuroleptics
dosing of dantrolene
can be admin IV statting with 1-2.5mg/kg bolus followed by 1mg/kg every 6 hours up to max dose of 10mg/kg/day
what risks are there with dantrolene
hepatotoxicity (so stop once patient is improving)
what is dantrolene
muscle relaxant (blocks calcium release from sarcoplasmic reticulum)
what other pharmacologic agents other than bromocriptine/amantadine and dantrolene can be used to manage NMS
benzos
carbamazepine
clonidine
if standard care is not helping, what other treatment can u use for NMS
ECT
