Specific considerations Flashcards
Discuss coma in the poisoned patient
Describes an altered mental status where the patient cannot be roused.
Can be due to
- direct toxic effect on the CNS
- secondary effect of poisoning on the CNS (hypoxaemia, hypoglycaemia, hyopnatraemia, hypotension, seizure or cerebral oedeam.
Toxic agents usually act on the CNS in a global and symmetrical fashio and any focal or unilateral neurological sign is highly suggestive of an alternative cause.
Discuss management of coma in the poisoned patient
Establishment of airway and adequate ventilation is the immediate priority irrespective of the aetiology oc coma. If comatose most patient will require RSI and ETT the excpetion being those with rapidly reversible causes of coma such as hypoglycaemia or opiate toxicity
If requiring intubation and ventilation it is necessary to be aware of required respiratory rate. Many poisoning will results in metabolic or respiratory acidosis and if hyperventilation is not maintained acute acidosis, clinical deterioation and possibly death.
List complications of coma in patient who have been poisoned
1) pulmonary aspiration
2) rhabdo
3) Acute renal failure
4) compartment syndromes
5) pressure areas
6) hypoxic brain injury
Discuss investigation in a comatose patient who has been possibly poisoned
-ECG, paracetamol, BGL –> all tox patients
ABG
- anion gap, lactate
- osmolar gap
Specific drug levels
-carbamezepine, ehtanol, ethyolen glycol, methanol, salicylattes, valproic acid
Discuss agents that cause coma in poisoning that require specific intervention
1) Carbamezepine
- -HD
- - Multi dose activated chracoal
2) isoniazid
- b6
3) opiods
- naloxone
4) organophosphate
- pralidoxime
- atropine
5) phenobarb
- MDAC
- HD
6) salicylates ( severe only)
- HD
7) sulfonylureas
- dextrose
- octreotide
8) Toxic alcohols ( ethylene glycol, methanol)
- Ethanol/fomepizole
- HD
9) Valproic acid
- HD
Discuss toxic seizures
Usually generalised and self limiting - easily controlled with benzo
Most common causes in australia
- venlafaxine, bupropion, tramadol and amphetamines
- common in multiple withdrawal syndromes
In certain poisoning the presence of seizure activity is a herald of grave prognosis if management is not appropriate and rapid. ( chloroquine, propanolol, salicylates, theophylline, TCA)
Discuss management of toxic seizures
- ABC
- check BGL if low correct
- Benzo
- Barbituate as second line
- pyridoxine as third line especially if isonizide poisoning is considered
Define delirium
1) disturbance in attention ( reduced ability to direct, focus, sustain and shift attention) and awareness
2) change in cognition that is not better accounted for by a pre-existing, established or evolving dementia
3) The disturbance develops over a short period ( usually hours to days) and tends to fluctuate throughout the course of the day
4) There is evidence from the history exam or lab finding that the disturbance is caused by a direct physiological conequency of a general medical condition, intoxicating substance, medication use or more than one cause
List common toxicological causes of agitation and delirium
Alcohol Anticholinergic syndrome Antidepressants Atypical antipsychotics Baclofen Benzo and other sedative hypnotic agents cannabis Hallucinogenic agents Neuroleptic malignant syndrome Nicotine Salicylates serotonin syndrome sympathomimetic syndrome synthetic cannabinoids synthetic cathinones theophylline withdrawals syndromes
Discuss agents or syndromes associated with delirium or agitaiton that require specific therapy
Anticholinergic agents – physostigmine
Neuroleptic malignant syndrome - bromocriptine
salicylates – urinary alkinisation, HD
Serotonin syndrome – crypoheptadine, paralysis and I&V
Theophylline - MDA, HD
Discuss serotonin syndrome
Serotonin syndrome is the clinical manifestation of excessive stimulation of serotonin receptors in the CNS
occurs when there is excess serotonin secondary to
- inhibition of serotonin metabolism (MOA)
- prevontion of uptake ( SSRI)
- serotonin release or increase intake of serotonin precursors
Hunter Serotonin toxicity criteria
1) spontaneous clonus
2) inducible clonus and agitation or diaphoresis
3) occular clonus and agitation or diaphoresis
4) tremor and hyper-reflexia
5) hypertonic and ocular or inducible clonus
Discuss clinical features of serotonin syndrome
Mental status change
- apprehension
- anxiety
- agitation, psychomotor acceleration and delirium
- confusion
Autonomic
- diarrhoea
- flushing
- hypertension
- hyperthemia
- mydriasis
- sweating
- tachycardia
Neuromuscular excitation
- rigidity
- hypereflexia
- clonus (esp ocular and ankle)
- increased tone
- tremor
Syndrome will usually resolve within 12 hours up to 24-48 hour in severe cases
Discuss clinical setting in serotonin syndrome may develop
- At the introduction or increase of a single serotonergic agent
- change in therapy from one to another without adequate intervening washout period
- Drug interaction between two serotonergic agents
- INteraction between serotenergic drug and an illicit drug or herbal preparation
- Deliberate self poisoning with serotonergic agents
Discuss management of serotonin syndrome
ABC
Indication for I&V with paralysis include - coma, recurrent seizures, hyperthemia greater than 39.5 or severe rigidity compromising ventilation
If mild to moderate. Can consider cyproheptadine – first gen antihistamine with anticholinergic, antiserotonergic and LA properties. Initial dose is 8mg can be given orally or via NG – airway needs to be uncompromised. TDS dosing
Can consider the use of olanzapine specifically if agitation is a significant issue.
If severe will need to be intubated
Discuss anticholinergic syndrome and its clinical features
Arises due to competitive inhibition of central and peripheral ach muscarinic receptors
Clinical features can be divided into central and peripheral Central -Agitated delirium -- -fluctuating mental state ---confyusion ---restlessness ---hallucinations ---picking at objects in the air ---disruptive behaviour -Tremor -mycoclonus -coma -seizures
Peripheral
- tachycardia
- mydriasis
- dry mouth and skin
- hyperthermia
- urinary retention, consptiation
- flusing
Once established it is difficult to predict the duration of the syndrome – can last up to 5 days
Discuss complications of untreated anticholinerigic syndrome
Aspiration Dehydration Renal failure Rhabdomyolisis INjury to themselves
Discuss management of anticholinergic syndrome
RESUS
- ABCD
- Attention to BSL, seizures and hyperthemia
Fluid balance – benifit from IDC to titrate fluid to UO
- Treat agitation with benzo (diaz agent of choice due to duration of action)
Can use physostigmine a centrally acting acetylcholinesterase inhibtor
Discuss cholinergic syndrome and clinical features of the same
Caused by an increase in acetylcholine activity at central and peripheral receptors. Usually seen secondary to organophosphate or carbamate pesticides.
Also seen with chemical warfare nerve agents (sarin), agents used to treat dementia (donepezil, galantamine, rivastigmine, tacrine) and those used in the treatment of myasthenia gravis ( edrophonium, neostigmine, physostigmine, pyridostigmine)
Clinical features include Central -agitation, -respiratory depression -coma -confusion -lethargy -seizures
Neuromuscular
- fasciculations
- muscle weakness
Parasympathetic
- abdominal cramping
- bradycardia
- bronchoconstriction
- bronchorrhoea
- diahorrea
- lacrimation
- miosis
- salivation
- urinary incontinence
- vomiting
Sympathetic nicotinic effects
- hypertension
- mydraisis
- sweating
- tachycardia
Death with cholinergic syndrome is typically due to respiratory failure secondary to excessive respiratory secretion and resp muscle weakness
Discuss management of cholinergic syndrome
Decontamination – care with use of sophisticated PPE
Resus
- ABC
- early attention to control of pulmonary secretion and administration of o2 is the key to survival
- Attention to bsl, temperature and seizures
ADminister atropine if there are any objective signs of muscarinic excess. Praladoxamine is indicated in organophosphate poisoning
Discuss neuroleptic malignant syndrome
Rare but potentially lethal syndrome complicating the use of neuroleptic medications. Aetiology is not clear but a central defieicny of dopaminergic neurotransmission appear pivotal
Clinical features CNS - confusion -delirium - stupor - coma
Autonomic instability
- Hyperthemia
- tachycardia
- hypertension
- respiratory irregularities
- cardiac dysrhythmias
Lab findings - Neuromuscular -Lead pip rigidity - Generalised bradykinesia -Mutism and staring -dysarthria -dystonia and abnormal postures -abnromal involuntarty movements -incontinence
Onset of NMS typically occurs over 24-72 hours and recovery may take many days to months
Discuss criteria for the diagnosis of NMS
- Recent exposure to dopamine antagonist or dopamine agonist withdrawal
- Hyperthermia
- Rigidity
- Mental status alteration
- CK elevation (at last 4 times upper limit)
- Sympathetic nervous system lability defined as at least 2 of the following
- – BP >25% above baseline
- – BP fluctuation (>20mmhg diastolic change or >25mmHg systolic change within 24 hours)
- – Diaphoresis
- – Urinary incontinence
- tachycardia plus tachypnoea
- -ve workup for other cause
Discuss risk factors for NMS
- High dose of neuroleptic agent
- increase dose of neuroleptic agent
- large magnitude dosage increase
- parenteral adminstration
- Simulataneous use of 2 or more agents
- use of halo or depot fluphenazine
- young age
- male sex
- psychiatric co-morbidity
- genetic factors
- pre-exisiting brain disorders
- dehydration
- high CK levels during episodes of psychosis not associated with NMS
Discuss complciations of NMS
Resp faiure
dehydration
renal failure
MOF
-VTE
Residual catatonia and parkinsonian symptoms
Recurrance after rechallenge with an atnipsychotic agent may occur in 30-50% of patients who suffer NMS
Discuss management of NMS
Resus
- ABCD
- attention to BSL, temp and seizsures
HTN may intiially be treated with parentral vasodilators such as GTN or sodium nitroprusside.
Bromocriptine a dopamine agonist can be given in severe to moderate cases dosing at 2.5mg TDS increasing to 5mg q4hrlys – autonomic instability and fever usually resolve within 24 hours of commencing bromocriptine but neuromuscular changes and delirium cna take longer to resolve – if used should have a 1-2 week taper
Dantrolene is indicated if there is severe muscle rigidity and fevere – IV 2-3mg/kg/day up to a total dose of 10mg/kg/day. Dantrolene inhibiting Ca2+ ions release from sarcoplasmic reticulum stores by antagonizing ryanodine receptors reducing excitation contraction coupling
ECT has been reported to improve fever sweating and consciousness level in some patient. Indicated for severe NMS refractory to supportive care and antidote treatment. NMS that is difficult to differentiate from acute lethal catatonia, treatment of residual catatonic symptoms after NMS
Discuss the osmolar gap
Assists in the diagnosis of toxic alcohols
Osmolality is measured by an osmmometer in a lab
Osmolarity is calculated from a formula that represents the soluts which under normal circumstances represnet nearly all of the osmolality of the sample =2xNA + (urea and glucose)
The osmolar gap is the difference between the measured osmolality and calculated osmolarity
A normal osmolar gap is <10
- an elevated osmolar gap suggest the presence of high concentration of unmeasured osmotically active compounds
- a number of non-toxicological conditions also cause an elevated osmolar gap
- a normal osmolar gap does not exlude potentionaly life threatening tox alchol ingestion
- — small concentration of toxic alcohols not detected by this surrogate measure may still cause significant intoxications
- – late in the course the parent compounds are already metabolised to non-osmotically active compounds
List exogenous agents associated with elevated osmolar gap
- Acetone
- Ethanol
- Ethylene glycol
- Glycerol ‘
- Glycine
- isopropyl alcohol
- mannitol
- methanol
- propylene glycol
Discuss non tox conditions that are associated with elevated osmolar gap
- Alcoholic ketoacidosis
- CKD
- DKA
- Hyperlipidaemia
- Hyperptoreniaemia
- Massive hypermagnesaemia
- Severe lactic acidosis
- shock
- trauma and burns
Discuss pregnancy induced phsyiological changes that affect drug PK and PD
1) absorption - delayed gastric emptying and intestinal transit time slow drug absorption and may prolong the period where decontamination is of potential benifit
2) Distribution - increased blood volume (45-50%) increases volume of distribution and potentially decreease plasma levels; dilution of plasma proteins increases free drug levels
3) elimination: hepatic enzyme systems are altered by ciruclating hormones; renal blood flow and GFR incrase
Discuss management of poisoning in pregnancy and lactation
Most drugs cross the placenta via diffusion and maternal blood levels are the most significant indication of foetal exposure
On a practical level management remains unchanged. Greater ciruclating volumes, increased RR and tachycardia seen normally in pregnancy can mask signs of hypovolaemia and respiratory compromise
List agents who pose a greater risk to the foetus than the mother
CO Methaemoglobin incuding agents -nitrates and their derivatives -sulfonamides -dapsone -pnehacetin -LA such as prilocaine -anticonvulsants ( phenytoin, sodium valproate) Lead salicylates
Discuss estimation of drug ingestion by children
1) the time of ingestion is assumed to be the latest possible time
2) assume all missing or unaccounted agents have been ingested
3) do not attempt to account for spillage
4) if more than one child assume each child has ingested all the unaccounted agents
List pharmaceutical with the potential for severe toxicity if 1-2 tabs are ingested by a 10kg toddles
Amphetamines
Baclofen (25mg)
Calcium chnnel blockers
- Diltiazem CD 180,240 or 360mg
- Verapamil SR 160,180 or 240mg
Carbamezapine - 400mg
Chloroquine - 155mg
Clozapine 100-200mg
Dextropropoxyphene 100mg
Opioids
- oxycodone
- hydromorphone
- morphine
Propanolol 160mg
Sulfonylureas
-gliclazide
Theophylline SR 200-250-300
TCA
Venlafxine
Discuss management of a toddle who has ingested unidentified tablets
1) admit for a minimum of 12hour period
- IV access can be deffered until evidence of poisoning occur
- BSL
- monitor GCS
- If any alteration in GCS cardiac monitoring
- discharge patient only in daylight hours
Discuss RSI DEAD
Supportive care and IX unchanged
Decontamination rarely indicated - if charcoal is indicated mix with icecream to make more palatable
Enhanced elimination is again rarely indicated
Discuss physiological change in PK and PD in the elderly
PK - delayed gastrointestinal absorption, decreased protein binding and reduced hepatic metablic function and GFR result in impaired elimination
Acute renal failure secondary to intercurrent medical problems or prescribed medications commonly leads to poisoning syndromes in the elderly such as chronic lithium or dig toxicity
PD changes are a result of drug actions on pbhysiologically impaired organs- this is particulalry evident with CVS, resp and CNS depressants
