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Neuroleptic Malignant SyndromeSerotonin syndromeMalignant HyperthermiaEpidemiologyOccurs in 0.5-3% patients on drugs (rare); 50% recurrence rate if re-challenged; 5-30% mortality; M:F 2:1; diagnosis of exclusion10% mortality rate70% mortality untreated7% mortality with trtPatho-physiologyDopamine blockade in basal ganglia and hypothalamus hyperthermia due to sustained muscle contraction (EPSE) or elevated T set point; also incr Ca release from SRIncr 5-HTGenetic abnormality of L-type Ca channel in SR incr intracellular Ca and muscle contraction; autosomal dominantCausesOccurs after starting / incr dose / adding 2nd drug, within 2/52 (in 2/3); may occur after months; after IV meds (esp haloperidol); idiosyncratic reaction, not toxicityPatient factors: young, male, agitated, organic brain disease, dehydration, malnutrition, PMH NMSDrug factors: high potency (eg. Haloperidol), high dose, rapid incr in dose, depot medsTypical/aytpical antipsychotics (haloperidol, chlorprom, olanzapine, quetiapine, risperidone)Antiemetics (chlorpromazine, maxalon, stemetil)AntihistaminesCauses of EPSE: MAOI +/- TCA, SSRI, SNRI, Lithium, amphetamine, cocaine, MDMAUsually due to >1 drugSertraline (most common)SSRIsOther antidepressants: Li (incr post-synaptic 5-HT stimulation), moclobemide and other MAOI, citalopram, St John’s wort, TCA, SSNRIIllicit drugs: LSD, cocaine, amphetamines, EAnalgesia: Pethidine, fentanyl, tramadol, sumatriptanChlorpheniramineAntiParkinsons: L dopa, bromocriptineInhalational anaesthetic (halothane, sevoflurane, desflurane, isoflurane)Depolarising muscle relaxants (sux)Others (ketamine, phenothiazines, MAOI)AssessmentHx: onset over hrs - 3/7Fever (>38 in >90%; ETT indications as per SS)----------------------------------------------------------------------------------------------------------------------------------------------------------------------Muscle rigidity (Parkinsonian in >90%, leadpipe)-----------------------------------------------------------------------------------------------------------------------------------------------------------------------NM: tremor, incontinence; decr reflexes-----------------------------------------------------------------------------------------------------------------------------------------------------------------------Autonomic instability: incr HR / RR / BP, sweating but pallor, mydriasis or normal pupils; normal BS’s-----------------------------------------------------------------------------------------------------------------------------------------------------------------------Altered LOC (may be dysphagia, aphonia, dysarthria, staring, bradykinesia)----------------------------------------------------------------------------------------------------------------------------------------------------------------------- RS/CV failure, ARF, MOF, DVT, NCPO, PE, pneumonia, seizures, rhabdo, dehydrationEPSE:Early reversible (hrs-days): with high potency1) Dystonic reaction: oculogyric crisis (esp eye, tongue, facial, neck muscles); normal LOC; no muscle rigidity between spasms; 1-5/7 after starting trt (50% 2/7, 95% 5/7); esp in young males, cocaine, hyperventilation, hypoCa2) Akathesia: restlessness; onset 5-60/7Late reversible (days-wks): with low potency1) Parkinsonism: akinesia, cogwheel rigidity, resting tremor, shuffling gait, masked facies, drooling; onset 5-30/72) NMSIrreversible (mths-yrs):1) Tardive dyskinesiaOnset over hrs (faster than NMS; 60% within 6hrs); resolves over hrs (24-48hrs if severe)Fever (milder than in NMS)---------------------------------------------------------------------Muscle rigidity (esp legs; occurs late)-------------------------------------------------------NM hyperactivity: akathesia, hyperreflexia, clonus (esp legs; ocular – distinguishable from nystagmus as no fast component); repetitive rotation of head with neck in mod extension; myoclonic jerks; seizures----------------------------------------------------------------------Autonomic hyperactivity: incr HR / RR / BP, sweating, mydriasis, hyperactive bowel sounds, diarrhoea--------------------------------------------------------Altered LOC: agitation, confusion, change in behaviour / cognition--------------------------------------------------------------------- metabolic acidosis, rhabdo (rare), ARF, seizures, DICOnset over mins –hrsHx: FHFever: >38.8-------------------------------------------------------Muscle rigidity: generalised rigidity, trismus-------------------------------------------NM changes: decr reflexes-------------------------------------------Autonomic changes: Incr HR / BP / RR, normal pupils; ileus; sweaty and mottled-------------------------------------------Altered LOC: agitation------------------------------------------------------- resp acidosis (incr ETCO2) and metabolic acidosis; rhabdoInvestigationBloods: WCC up to 30; CK >1000; incr LFTs; incr K / phos / Ur / Cr / plt; myoglobinuria; ARF; metabolic acidosis; incr CrRhabdo rareCK >20,000, myoglobin in urine, K >6; incr phos; muscle biopsy; ARFMngStop cause; aggressive supportive care; cooling; IVF; trt rhabdo; can use ECT in severe NMS refractory to medical trtAvoid: sux (use roc)Bromocriptine: 2.5mg PO TDS incr to max 5mg Q4h; dopamine agonist; in mod/severe casesDantrolene: 1mg/kg IV load 1mg/kg QID IV; controversial; in severe casesFor dystonic reaction:Benztropine: 1-2mg IV rpt at 15mins if needed discharge on 2mg TDS PO for 1-2/7Diphenhydramine: 1-2mg/kg IV (max 50mg) 25-50mg TDS POBenzo’s25% ETT rate (do if coma, recurrent seizures, incr T >39.5, severe rigidity); benzos; barbs and paralysis if severe; GTN or nitroprusside for HTN; observe at least 8hrsCyproheptadine: 8mg PO 4mg PO Q4h; 5-HT receptor antagonistChlorprothixine: IM alternative to aboveChlorpromazine 50-100mg IV 50-100mg Q6hor olanzapine 5mg PODantrolene: 1mg/kg IV load 1mg/kg QID IV or rpt to 10mg/kg max in 24hrs ................
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