Toxic syndromes

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Toxic Syndromes Theodoros Aslanidis

Drug-induced Hepatic Failure : 

Drug-induced Hepatic Failure Definitions of Liver failure Tray (1970) Fulminant hepatic failure: encephalopathy within 8 weeks of onset of symptoms with no preexisting liver disease Bernuau (1986) Fulminant hepatic failure: encephalopathy within 2 weeks of onset of jaundice Subfulminant hepatic failure: encephalopathy within 2-12 weeks of onset of jaundice Gimson (1986) Late –onset hepatic failure: encephalopathy within 8-25 weeks of onset of symptoms O’Grady (1993) Hyperacute liver failure: encephalopathy within 7 days of onset of jaundice Acute liver failure: encephalopathy within 8-28 days of onset of jaundice Subacute liver failure :encephalopathy within 5-12 weeks of onset of jaundice

Etiology of Fulminant Hepatic Failure : 

Etiology of Fulminant Hepatic Failure Infections (0.4%) HAV (0.35% of infected patients with mortality of  40%) HBV (1% of infected patients with 17-47% survival rate) HCV HDV (in pregnant women with HDV-FHF 40% mortality) (HDV inf. has been implicated with 30% HBV-related FHF ) Herpesviruses (HSV/CMV/VZV/EBV in immunosuppressed) Coxiella burnetti Plasmodium falciparum Bacillus cereus Parvodirus B19 Mycobacterium tuberculosis (disseminated TBC) Yellow fiver virus Amebic abscesses

Etiology of Fulminant Hepatic Failure : 

Etiology of Fulminant Hepatic Failure Toxins / Chemicals Cyclopeptide mushrooms Amanita phalloides A. verna A. virosa A.tenuifolia A. brunnescens A. bisporigera Galerina venetata G. autumnalis G. marginata Lepiota helveola L. vosserandii Sea anemone sting Herbals Kava Chaparral Gentian Scutellaria Germander Alchemilla Senna Shark cartilage Carbon tetrachloride Aflatoxin Halogenated hydrocarbons Toluene 3-chloroethylene 4-chloroethylene Chloroform Phosphorus Ethanol

Etiology of Fulminant Hepatic Failure : 

Etiology of Fulminant Hepatic Failure Vascular Budd- Chiary Syndrome Vascular Occlusive disease (chemotherapy- or bone marrow transplant related) Heatstroke (21% mortality in case of FHF) Chronic Heart Failure Ischemia AMI,PE, Tamponade, Intraoperative hypotension ,etc. Malignant infiltration (carcinoid syndrome) Amyloisosis Gram –negative sepsis Others Reye’s syndrome Acute fatty liver of pregnancy Wilsnon ‘s disease HELLP Sdr Post-OLT

Etiology of Fulminant Hepatic Failure : 

Etiology of Fulminant Hepatic Failure Drugs Acetaminophen (20% of cases) Rimfampicin Amiodarone Tetracyclines Carbon tetrachloride MAO inhibitors Gold Tricyclic antidepressants Halothane Erythromicin Isoniasid Clarythromycin Ketoconazole Zidovudine Methyldopa Drugs of abuse: NSAIDS (1.7/100.000 prescriptions) Cocaine Phenytoin Phenycyclidine Sulfonamides “Ectsasy” (3,4-methylenedioxymethamphetamine)

Diagnosis and Complications : 

Diagnosis and Complications Coagulopathy (PT,PTT,fV levels-prognostic significance) Encephalopathy

Diagnosis and Complications : 

Diagnosis and Complications Cerebral edema Sings of increased ICP in FHF

Diagnosis and Complications : 

Diagnosis and Complications Factors that increase ICP

Diagnosis and Complications : 

Diagnosis and Complications Cardiovascular Arrythmias( ST,AV blocks) ST segment and T wave changes Cardiac arrest Decreased SVR (resembling septic sock) Renal failure Renal impairment in up to 75% of patients with FHF Hepatorenal syndrome (Cr >1.55 mg/dl,Nau <10 meq/lt, volume challenge negative,bland urinary sediment) Oliguric RF= poorer prognosis Pulmonary Derangements Pulmonary edema up to 30%,a-v shunting, periph. capillary blockage from cellular debris,

Diagnosis and Complications : 

GI bleeding Infections Hyponatremia Hypokalemia Hypophosphatemia Hypomagnesemia Hypocalcemia Acid-base desordes lactic acidosis-poor prognosis Hypoglycemia (in up to 40%) Diagnostic test/monitoring Glu/2h ABG/6h Electrolytes,CBC/8h Coagulation parameters/ 12h Liver profil/24h BUN,creatinine/24h Toxicol.,virology,autoimmune pannel Abdominal U/S and CXR ICP on stage III-IV encephalopathy Diagnosis and Complications

Treatment goals : 

Treatment goals At ICU setting ,preferably at a liver transplant center. Blood products for correction of coagulopathy only in a bleeding patient. Lactulose 30ml x 4 p.os(Levin) Metronidazole 250-500 mg/8h on grade 4 encephalopathy. Aminopenicillins 2-4gr/d Vancomycin 1-2 gr/d ICP goal <20 mmHg: Mannitol 0.5-1gr/kg in boluses till Posm 310-325 mOsm/Kg) Sedatives in the lowest possible dose. Propofol may be used. Dexamethasone ,hyperventilation ineffective. Renal failure: treatment is centered on prevention GI bleeding:80mg PPI bolus and 8 mh/h c.i.v and endoscopic therapy Glucose goal>65 mg/dl

Treatment goals : 

Low-protein diet in grade 1 to 2 encephalopathy. Enteral low-protein tube feeding should be considered early for the rest.(gastrostomy) Control of infections Specific antidotes: N-acetylcysteine regimens for Acetaminophen- e.g (dose tot-300mg/kg) 150 mg/kg c.i.v. over 15min , followed by 50mg/kg c.i.v over 4h , and then 100mg/kg c.i.v over 20h Sillibilin for Amanita poisoning: ( 5 mg/kg c.i.v. over 2h)x4 /d ….. Treatment goals

Prognosis : 

Prognosis 10% of patients with FHF undergo an OLT. Post-OLT survival rate is 55-75%. In general ,OLT is recommended if patient’s survival rate is <20%. Absolute CONTRAINDICATIONS to OLT: Severe cardiac or pulmonary diasease Severe PAH (SPAP>60mmHg) ARDS HIV inf/AIDS Sepsis Extrahepatic malignancy Portal and mesenteric thrombosis Active alcochol or drug use Severe psychological disordes Inability to understand /cooperate.

Prognosis : 

Prognosis King’s College Criteria for OLT Acetaminophen Non-acetaminophen Toxicity toxixity Ph<7.3 (irrespective of PT >35 sec or INR>7.7 Other factors OR ANY OF 3 of: OR ALL 3 of: Age<10 or >40 yrs Grade III-IV encephalop. Bil >17 mg/dl PT>100 sec INR>4.0 Cr >3.4mg/dl Time from jaundice to encelopathy >7d Unfavorable etiology (Wilson,NonA-nonBH,etc)

Toxin-induced Renal failure : 

Toxin-induced Renal failure Definitions Acute renal failure is commonly established as an increase in serum creatinine greater than 0.5gr/dl (44μmol/lt) over baseline or a reduction in calculated creatinine clearance of 50% or more. It can be : nonoliguric (>400ml/d) and also : prerenal failure oliguric (100-400 ml/d) intrarenal failure anuric (<100ml/d) postrenal failure.

Etiology of renal failure : 

Etiology of renal failure Major causes of prerenal acute renal failure

Etiology of renal failure : 

Etiology of renal failure Major causes of intrarenal acute renal failure

Pharmacologic agents that cause acute renal failure : 

Pharmacologic agents that cause acute renal failure

Inhaled or cutaneously absorbed nephrotoxins : 

Inhaled or cutaneously absorbed nephrotoxins

Chemicals/Toxins/Foods/Plants causing Renal Failure : 

Chemicals/Toxins/Foods/Plants causing Renal Failure

Diagnosis : 

Diagnosis Evaluation of patient’s history( exposure to nephrotoxins, previous volume status, medications) Physical examination (for e.g .edema ,palpable purpura, ascites….) Renal U/S, renal biopsy Urinary indices

Complications : 

Complications Hyperkalemia Hypermagnesemia Hyperphosphatemia Hypernatremia Hypocalcemia Hyponatremia Metabolic acidosis Symptomatic uremia: anemia, bleeding diathesis, malnutrition, mental status changes, nausea/vomiting, pericarditis Volume overload/ pulmonary edema

Treatment strategies : 

Treatment strategies Reversal of the underlying cause of ARF: For prerenal azotemia: stop nephrotoxic drug, in volume depletion volume resuscitation (crystalloids, colloids in certain setting-liver disease, bleeding diathesis) For intrarenal ARF: renal replacement therapy early Conversion of an anuric ARF to an oliguric :via 100-200 mg furosemide or 10-40mg/h c.i.v. furosemide Mannitol 12.5-25 gr in addition to NaHCO3 and volume replacement to treat ARF from rhabdomyolysis. 6h trial of Dopamine(05-2.5μg/kg/min) may be tried. Thiazide diuretic 30 to 60 min before loop diuretic may improve urine output. Correction of electrolytes and metabolic anomalies.

Extracorporeal removal of toxic substances : 

Extracorporeal removal of toxic substances Clinical consideration for Hemodialysis or Hemoperfusion in Poisoning

Drugs that can be removed by hemodialysis or hemoperfusion : 

Drugs that can be removed by hemodialysis or hemoperfusion

Choise of Hemodialysis or Hemoperfusion for certain drugs : 

Choise of Hemodialysis or Hemoperfusion for certain drugs

Criteria for starting Continuous renal replacement (CVVH) therapy in the ICU : 

Criteria for starting Continuous renal replacement (CVVH) therapy in the ICU 1.Oliguria (<200 ml/12h) 2.Anuria (<50ml/12h) 3. Acidemia (pH<7.10 ) due to metabolic acidosis 4. Hyperkalemia (K>6.5 mmol/lt) 5.Clinical signs of uremia 6. Na>160 mmol/lt or Na<1150= mmol/lt 7.Hyperpyrexia(t>39.5°C) noncontrolable 8.Deterioration despite supportive therapy 9. Coagulopathy and danger of PE/ARDS

R.I.F.L.E. scale of ARF : 

R.I.F.L.E. scale of ARF GFR Diuresis/h Risk Cr x 1.5 , ↓ GFR 25% <0.5ml/kg/h for 6h Injury Cr x2, ↓GFR 50% <0.5ml/kg/h for 12h Failure Cr x3 or >4mg/dl <0.3 ml/kg/h for 24h or ↑>0.5mg/dl, ↓GFR 75% or anuria for 12h Loss ARF > 4weeks ESKD (end stage kidney disease) CRF >3 mnths ADQI workgroup 2004

Alterations in Consciousness : 

Alterations in Consciousness Definitions Lethargy: inability to maintain wakeful state without external stimulation Stupor: arousability only in response to noxious stimul Delirium(= acute cortical-subcortical neuronal encephalopathy) fluctuating condition with confusion, irritability, disorientation that develops within hoursor days Coma: unresponsiveness to any stimulus.

Cellular targets and potentially neurotoxic agents : 

Cellular targets and potentially neurotoxic agents

Toxic causes of Delirium : 

Toxic causes of Delirium

Toxic causes of delirium : 

Toxic causes of delirium

Drugs and toxins causing Miosis : 

Drugs and toxins causing Miosis

Drugs and toxins causing Mydriasis : 

Drugs and toxins causing Mydriasis

Toxicants causing Mydriasis : 

Toxicants causing Mydriasis

Agents causing Cranial Nerve Palsies : 

Agents causing Cranial Nerve Palsies

Drugs that cause Cyclic coma : 

Drugs that cause Cyclic coma Barbiturates Carbamazepine Glutethimide Meprobamate Ethchlorvynol

Agents used to reverse coma or encephalopathy of toxic etiology : 

Agents used to reverse coma or encephalopathy of toxic etiology Treatment

Reversal agents -dose : 

Reversal agents -dose Naloxone : 0.4-0.2 mg i.v. starting dose (0.01 mg/kg in pediatric patient) wide LD50:EC50 - 4 mg/kg i.v has been given without side effects in case of opioid dependency : 0.1-0.2 mg starting dose onset:1-2 min T1/2 : 60-90 min. Nalmefene : 0.5-1.0 mg/70kg BW i.v. and if needed, after 2-5 min, another 1mg /70kg BW i.v. Effect plateau -1.5mg/70kg BW i.v. clinical response:5 min T1/2 : 11 h. Naltrexone : 50mg p.o /d T1/2:10h Duration effect:24h Flumazenil : 0.2 mg over 30 sec, second dose of 0.3mg may be given, and then 0.5mg doses at interval of 1 min till 3 mg. children -0.01mg/kg i.v. 0.25-1mg/h c.i.v. may be used after loading dose. onset :1-2 min duration of action (!) :0.7-1.3h

Reversal agents -dose : 

Pyridoxime : max initial dose up to 70 mg/kg at a rate of 0.5 gr/min adults T1/2 : 20d (!) Gram-for-gram dosing p.os strategy for isoniazid poisoning Side Effect: Peripheral sensory neuropathy!(e.g. in 2g/kg for 3d) Amyl nitrite: should be inhaled for 30 sec out of each min. The pearl should be replaced with fresh every 2-4 min. Sodium nitrite : vial 3% sol 10ml.Usual adult dose 300mg i.v over at least 5 min diluted to 50-100ml N/S. Pediatric dose 0.12-0.33 ml/kg to max of 300mg (10ml).(NB to Hg values!) Thiosulfate : 12.5gr i.v. over 10 min (NB to Hg values!). Repeat if needed. Methylene blue : 0.3-2mg/kg i.v. and repeat dose ,if needed. Reversal agents -dose

Use of Flumazenil : 

Use of Flumazenil

Agents with Anticholinergic effects : 

Agents with Anticholinergic effects

Prognosis : 

Prognosis Poor prognostic signs

Toxin-induced seizures : 

Toxin-induced seizures Definitions Toxicant – induced convulsion meet clinical and mechanistic definitions for status epilepticus Status epilepticus : a condition of prolonged or recurrent seizure activity without interictal awaking for 5 to 30 min. Subtle or nonconvulsive or subclinical status epilepticus: ongoing electrical seizure activity shown by EEG with or without subtle muscle twitches or tonic eye deviation. Mortality rate for subclinical SE is up to 65% vs 27% in cases of overt SE!

Proconvulsant agents – Classification by source and use : 

Proconvulsant agents – Classification by source and use

Mechanism of action of proconvulsant drugs and toxins : 

Mechanism of action of proconvulsant drugs and toxins

Differential Diagnosis of Toxin-induced Seizures : 

Differential Diagnosis of Toxin-induced Seizures

Treatment highlights : 

Treatment highlights Delay in termination of SE is associated with a marked decline in responsiveness to subsequent anticonvulsant treatment. Initial anticonvulsant therapy is different than in an non-toxin-induced SE! - Medications that cause neuronal hyperpolarization via increases in Clinflux (or Kefflux) and that increase neuroinhibitory tone or reduce neuroexcitatory tone by supressing NMDA-glu-Na and Ca influx are first-choise therapy. - Phenobarbital is second-line therapy, and phenytoin is considered third-line therapy. Preferred route :i.v. Drugs: Diazepam 0.15-0.25mg/kg i.v. adults and 0.1-1mg/kg i.v in children at a rate no faster than 5mg/min. Rectal-gel 0.5mg/kg to 20 mg. Lorazepam 0.05-0.2mg/kg i.v. at a rate of 2mg/min to a total 8mg. Side effect: Propylene glycole –induced hyperomsolality, anion gap metabolic acidosis , hyperlactatemia.

Treatment highlights : 

Phenobarbital :at 20 mg/kg c.i.v. at a rate of 50-75mg/kg. (=needs about 20-30min for appropriate loading dose) Pyridoxime :for isoniazid seizures- gram-for-gram strategy or 5 gr incremental boluses. REFRACTORY STATUS EPILEPTICUS Phenobarbital :load 20mg/kg c.i.v. and then 5-10mg/kg c.i.v. Pentobarbital: load 10-15mg/kg c.i.v. over an 1h and then 0.5-1mg/kg c.i.v. Midazolam : load 0.2mg/kg slow i.v. and then 0.75-10 μgr/kg/min c.i.v. Propofol : load 1-2 mg/kg and then 2-10 mg/kg /h c.i.v. Treatment highlights

Cardiac conduction and Rate Disturbances : 

Cardiac conduction and Rate Disturbances

Fast Sodium Channel Inhibition : 

Fast Sodium Channel Inhibition

Selected cause of acquired Long QT Syndrome : 

Selected cause of acquired Long QT Syndrome

Differential diagnosis of drug/toxin –induced tachyarrhythmias : 

Differential diagnosis of drug/toxin –induced tachyarrhythmias

Thioridazine toxicity : 

Thioridazine toxicity

TCA toxicity : 

TCA toxicity

Cocaine toxicity : 

Cocaine toxicity

Digitalis toxicity : 

Digitalis toxicity

Anticholinergic Syndrome : 

Anticholinergic agents antagonize the effects of Ach by competitively blocking its binding to Ach-R sites . Ach-Receptors: Nicotinic (N) –primarily on the autonomic ganglion and neuromuscular plates. 12 types: α2 to α9 and β2 to β9.Ionotropic –R (Na and Ca) whose activation rapid depolarization and excitation. Muscarinic (M)- postganglionic PS, autonomic ganglions, adrenal medulla Anticholinergic Syndrome Anticholinergic Syndrome

Anticholinergic Drugs and Natural Substances : 

Anticholinergic Drugs and Natural Substances

Belladonna alkaloids : 

Belladonna alkaloids

Clinical sings : 

Clinical sings

Differential diagnosis : 

Differential diagnosis

Treatment : 

Treatment Most cases are not life threatening. Delayed gastric emptying and drug absorption are major concerns.GI decontamination may be useful for a longer time after ingestion. Significant agitation is usually treated with either an antichilinesterase or a sedating agent. Not by physical restraint (Rhabdomyolysis!) For hyperthermia rapid cooling ,ice packs on axilla, ice water irrigation and dantrolene. Treatment of seizures with BZP or other than physostigmine. For Rhabdomyolysis i.v. fluids, mannitol and NaHCO3 Physostigmine: 0.5 to 1mg i.v /i.m. with an i.v. rate of max 1mg/min. NO more than 2mg q. 5min.!Pediatric dose:0.02 mg/kg i.v/i.m. May be repeated in 10 min.Onset-2min. T1/2 15-20min Specific treatment if needed.

Cholinergic Syndromes : 

Cholinergic Syndromes Anatomy ,physiology and Pharmacology of the Autonomic Nervous System

Cholinergic toxicologic syndromes : 

Cholinergic toxicologic syndromes

Examples of compounds that potentially cause toxic effects in cholinergic mechanisms : 

Examples of compounds that potentially cause toxic effects in cholinergic mechanisms

Differential Diagnosis of Cholinergic syndrome : 

Differential Diagnosis of Cholinergic syndrome

Treatment : 

Treatment Depends on the severity and the poisoning agent. Nicotinic effects on skeletal muscle are treated symptomatically. CNS agitation secondary to muscarinic effects may respond to atropine, but sedative agents such as diazepam, may be required for convulsions. Atropine is the mainstay treatment of muscarinic symptoms. Case-by-case assessment is necessary.

Acute manifestations of Organophosphorus Insecticide Poisoning : 

Acute manifestations of Organophosphorus Insecticide Poisoning

Cardiac manifestations of Organophosphorus Insecticide Poisoning : 

Cardiac manifestations of Organophosphorus Insecticide Poisoning

Assessment of severity and management of severe organophosphorus insecticide poisoning : 

Assessment of severity and management of severe organophosphorus insecticide poisoning Grade 0 Suggestive history but no features of intoxication present Grade 1 Patient is alert and awake and has increased secretions ,fasciculation + Grade 2 Patient is drowsy and has severe bronchorrhea, fasciculations +++, crackles/wheezes on auscultation, SBP<90 mmHg Grade 3 Patient is comatose and has all the features of intoxication. Increased FiO2 but no mechanical ventilation. Grade 4 Patient is comatose and has all the features of intoxication. PaO2<60 mmHg despite FiO2>40%,PaCO2 >45mmHg, Mechanical ventilation required.

Nerve Agent Poisoning : 

Nerve Agent Poisoning

Nerve Agent Poisoning : 

Nerve Agent Poisoning

Nerve Agent Poisoning : 

Nerve Agent Poisoning

Nerve Agent Poisoning : 

Nerve Agent Poisoning

Specific treatment in cholinergic syndromes : 

Specific treatment in cholinergic syndromes Atropine: 2mg i.v. adults (0.02-0.1mg/kg i.v. children) for organophosphorus inicticides poisoning. 2-10mg i.v. in nerve gas poisoning. In severe cases up to 100mg have been reported. T1/2:2.6-4.3h Oximes Pralidoxime: 30mg/kg i.v. q 4-6h and then 10mg/kg/h c.i.v. Obidoxime :4mg/kg i.v. and then 0.5mg/kg/h c.i.v. or 2mg/kg i.v. q 4h

Serotonin syndrome : 

Serotonin syndrome

Serotonin Receptors : 

Serotonin Receptors

Clinical presentation of serotonin syndrome : 

Clinical presentation of serotonin syndrome

Criteria for diagnosis of serotonin syndrome : 

Criteria for diagnosis of serotonin syndrome Documented expose to one or more serotoninergic agents Exclusions of other causes Presence of three or more symptoms consistent with diagnosis No recent addiction or dosage increase of antipsychotic medications No recent discontinuation of dopamine agonists* Rapid improvement with antiserotoninergic medications*

Treatment : 

Treatment Usually about 25% of cases needs ICU admission. Most of the patients show improvement within the first 24h. The pharmacokinetics of the most serotoninergic agents is such that C14 is not benefit in repeated doses. Lithium is the only serotoninergic agent that extracorporeal removal may be indicated. For hypothermia: Benzodiazepines, nondepolarizing agents, and Dantrolene THERE ARE NO TRUE ANTIDOTES FOR SEROTONIN SYNDROME. Chlorpromazine 50mg i.m. q6h up to 4 doses Cyproheptadine (non specific 5HT1A,2 )0.5mg/kg/d. 4-8mg q.1-4hup to 32mg/d(12mg in children) Methysergide, propranolol has also been used.

Malignant Hyperthermia : 

Malignant Hyperthermia Synonyms: Anesthesia-related myodystrophy, Rhabdomyolysis of anesthesia Incidence: <7% in the developed countries 1:200.000 exposure to anesthesia is fulminant MH (adults) 1:8500 exposures to anesthesia (children) M/F ratio: 68/32 1: 5000 exposure of anesthesia-cases diagnosis is uncertain 80% mortality if dantrolene is not used on time,5-10% with its use. susceptibility to MH (Quebec):1 in 200 MH mutations (France): 1 in 2000 Description: MH is a clinical syndrome that occurs during anesthesia, producing rapidly increasing temperature( 0.5-1°C/min) and extreme acidosis. The effects results from loss of control of Cai .

Malignant hyperthermia triggers : 

Malignant hyperthermia triggers Succinylcholine All potent inhalational anesthetics halothane, desflurane, enflurane, isoflurane, sevoflurane, ethers,metoxyflurane,cyclopropane,fluroxene * In 80% of cases 2 or more trigger-agents was given simultaneously, while in 50% of the patients with M.H. was discovered previous contact with the agent without any symptoms. * If 2 or more agent are combined they aggravate the clinical outcome, Safe agents N2O,all intravenous anesthetic , all local anesthetics, nondepolarizing muscle relaxants, opiods, anxiolytics and benzodiazepines, reversal agents, butyrophenones, mixed opioid agents

Genetics of M.H. : 

Genetics of M.H. *Although it has low penetration in humans, the inheritance appear to has autosomal dominant character. *Genes in chromosomes 1,3,7,17 and 19 has been related to M.H. * Key role plays the ryanodine receptor, who takes part in the molecular events of the excitation –contraction coupling. It has 3 isoforms: skeletal-RYR1(19q13.1) , cardiac-RYR2(1q42.1-q43) and brain – RYR3(15q14-q15) RYR1 interact with many other molecules : calmodulin, triadin, calsequestrin, α1s-DHPR, FKBP12, Homer proteins,etc. * Mutations(>30) in RYR1 occur in at least 50% of susceptible subjects, although genetic HETEROGENITY exists.(e.g the gene CACNL1A3 encoding α1s-DHPR )

Pathophysiology of M.H. : 

Pathophysiology of M.H. A trigger-agents results the sudden and vast release of Ca+2 The muscles fibers contract and lead to “dyscampsia” A hyper metabolic tendance appear (augmentted demand for O2,production of heat and CO2 ) followed by anaerobic metabolism. Production of lactic acid leads to acidosis. Destruction of cells membranes and hyperkaliaemia. Increased cateholamines Increased C.O Increased Minute Ventilation

Signs and Symptoms : 

Signs and Symptoms Tachycardia Hypercarbia Rigidity Hypertension Hyperthermia (2O/h to 43oC) Complication *Cerebral edema *D.I.C. *Renal Failure *Hepatic Failure *Cardiac arrhytmias

Differential diagnosis : 

Differential diagnosis -Amphetamine toxicity -Anticholinergic sdr -Brain injury -Cocaine toxicity -Heatstroke -Hypoxic encephalopaathy -Sepsis -Serotonin sdr - Iatrogenic hyperthermia -Pheochromocytoma -Meningitis -Thyrotoxicosis -Intracranial bleeding -Neuroleptic malignant sdr -Salicylate taxocity -Sympathomimetic sdr -Lethal catatonia Laboratory findings K K+,Na+,PO3-,Mg+2,CPK (++) Myoglobinuria

Therapy protocol : 

Therapy protocol

Locate the candidates for triggering M.H. : 

Locate the candidates for triggering M.H. Duchene’s Dystrophia Becker’s Dystrophia King - Denborough Sdr Myotonia Neuroleptic malignant sdr Myopathies Caffeine/contracture test -Sensitivity 93%, with false positive 15% -Muscle tissue in solution of halothane and caffeine independently, measure of power of contraction

Neuroleptic malignant Sdr : 

Neuroleptic malignant Sdr

Criteria for diagnosis : 

Criteria for diagnosis

Differential diagnosis : 

Differential diagnosis

Therapy plan : 

Therapy plan Immediate withdraw of neuroleptic Empirical antibiotic administration Rehydration up to 1 ml/kg/h to avoid ARF Dantrolene for NMS-hyperthermia and rigidity (2.5mg/kg q 6h duration up to 5-10d after symptoms resolve) Bromocriptine 20 mg x 4 p.os with duration 2 – 56d Amantadine 100-200mg x 2 p.os Benzodiazepines: diazepam (01-02 mg/kg i.v) or lorazepam (0.05-0.1mg/kg i.v) q 10-30 min Phenobarbital 5- 10mg/kg i.v. Supportive care in ICU setting