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Toxicology Cases: Tom Heaps Consultant Acute Physician

The document describes three clinical toxicology cases involving drug overdoses and their presentations, diagnoses, treatments, and outcomes. The first case involves cannabis hyperemesis syndrome from long-term cannabis use. The second case involves serotonin syndrome caused by a drug interaction between an SSRI and antibiotic. The third case involves a mixed overdose of amitriptyline and benzodiazepines requiring intensive care treatment including sodium bicarbonate, glucagon, and intravenous fat emulsion.

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129 views

Toxicology Cases: Tom Heaps Consultant Acute Physician

The document describes three clinical toxicology cases involving drug overdoses and their presentations, diagnoses, treatments, and outcomes. The first case involves cannabis hyperemesis syndrome from long-term cannabis use. The second case involves serotonin syndrome caused by a drug interaction between an SSRI and antibiotic. The third case involves a mixed overdose of amitriptyline and benzodiazepines requiring intensive care treatment including sodium bicarbonate, glucagon, and intravenous fat emulsion.

Uploaded by

drusmansaleem
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© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as PPT, PDF, TXT or read online on Scribd
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Toxicology Cases

Tom Heaps
Consultant Acute Physician
Case 1
Nothing A Hot Bath Won’t Cure…
Case Presentation
• 29-year-old male, history of alcohol dependence

• alcohol intake reduced to 28 units per week for last year

• 3d history of intractable vomiting

• 4th admission in last 4/12 with similar symptoms

• symptoms usually resolved after 2-3 days as inpatient

• OGD after 2nd admission mild gastritis

• taking regular omeprazole 40mg OD


Case Progression
• transferred to AMU
• observations all normal
• FBC, U&E, LFT, CRP, amylase NAD
• well groomed and clean!
• OEx mild epigastric tenderness only
• AMU nurse concerned that he was spending an excessive
amount of time in the bathroom
• 3 baths since arriving on AMU 24h earlier
What was the single question I
asked him to reach a diagnosis?
Do you regularly use cannabis?
• admitted to regular cannabis use for last 4y
• daily use since cutting down alcohol intake

• cyclical episodes of severe nausea/vomiting for last 6/12


• having a hot bath or shower was the only thing which
provided temporary relief from his symptoms

DIAGNOSIS = CANNABIS HYPEREMESIS SYNDROME (CHS)


CHS: Diagnostic Criteria (Simonetto et al. 2012)
Essential for Diagnosis
• long-term cannabis use, usually 1-5y (32% <1y)

Major Features
• at least weekly cannabis use (daily in 59%)
• cyclical episodes of severe nausea and vomiting (>7/y in 70%)
• epigastric or periumbilical abdominal pain (86%)
• temporary relief of symptoms with hot baths/showers (91%)
• resolution of symptoms with cessation of cannabis use
CHS: Diagnostic Criteria (Simonetto et al. 2012)
Other supporting features
• weight loss >5kg

• morning predominance of symptoms

• normal bowel habit

• autonomic symptoms e.g. diaphoresis, flushing, polydipsia

• negative laboratory, radiological and endoscopic tests


Pathophysiology of CHS
• speculative and paradoxical
• cannabinoids usually antiemetic e.g. nabilone (CNS CB1 receptors)
• downregulation of CB1 receptors in brainstem emetic area?
• delayed gastric emptying (enteric CB1 receptors)?
• disturbance of hippocampal-hypothalamic-pituitary axis?
• toxic accumulation of lipophilic THC in fat stores?
• toxicity of other substances used in preparation of marijuana?
Compulsive Bathing Behaviour
• mean of 5 baths/d (5h bathing time/d) in one case series

• mechanisms of relief again speculative

• increase in body temperature


– may counteract hypothalamic autonomic and thermoregulatory
dysfunction seen with chronic cannabis use

• diversion of blood to peripheries


– may counteract cannabinoid receptor-mediated splanchnic dilatation
(cutaneous steal syndrome)
Complications of CHS
• profound weight loss

• dehydration

• pneumomediastinum

• oesophagitis

• scalding secondary to compulsive bathing behaviour


Treatment of CHS
• IV fluids and electrolyte replacement often required

• PPIs and antiemetics generally ineffective

• cessation of cannabis use is definitive treatment

• symptoms resolve within 2-3d in vast majority

• recurrence common within several weeks of relapse even if


prolonged period of abstinence
Case 2
Confused or just deliriously happy?
Case Presentation
• 82-year-old female, PMHx COPD, HTN, depression
• DHx seretide, tiotropium, ramipril 2.5mg, bendroflumethiazide 2.5mg,
citalopram 20mg (no recent changes to medications)
• allergic to penicillin
• presents to ED with increasing SOB and productive cough
• vitals stable, AMTS 10/10
• Na 132, CRP 26, WCC 11.9, CXR unremarkable
• treated for AECOPD (antibiotics, nebs, steroids)
• transferred to AMU
Case Progression
• 48h post-admission
• GCS 13/15, delirious +++
• sweating, T 38.9°C, HR 112, BP 137/68, SpO2 95% OA
• CT head NAD
• repeat bloods unremarkable (CK 337)
• dilated pupils
• increased tone and generalized rigidity
• hyperreflexia, bilateral extensor plantars, ankle clonus
Diagnosis?
• serotonin syndrome

Mechanism?
• reduced metabolism of citalopram due to
introduction of p450 inhibitor (clarithromycin)
Causes of Serotonin Syndrome
1. intentional overdose with serotonergic drugs

2. initiating or increasing dose of a serotonergic drug

3. co-prescription of multiple drugs with serotonergic actions


(often accidentally)

4. introduction of drugs which inhibit CYP450 enzymes in


patients already taking SSRIs

Onset of symptoms usually within 24h (often <6h)


Drugs with Serotonergic Action
• SSRIs • tramadol
• SNRIs • fentanyl
• MAOIs • sibutramine
• TCAs esp. clomipramine • linezolid
• trazodone • carbamazepine
• lithium
• metoclopramide
• amphetamines
• triptans
• MDMA (ecstasy)
• St. John’s wort
• cocaine
Drugs with potential to increase SSRI toxicity
CYP2D6 inhibitors CYP3A4 inhibitors
• amiodarone • macrolides
• terbinafine • fluconazole
• chlorphenamine • verapamil
• cimetidine • ciprofloxacin
• metoclopramide • metronidazole
• antipsychotics • antiretrovirals
• cocaine • grapefruit juice
Diagnostic Features of Serotonin Syndrome
1. altered mental status
agitation, confusion, disorientation, delirium
hallucinations
drowsiness, coma

2. neuromuscular hyperactivity
profound shivering, tremor, teeth grinding
hypertonia, hyperreflexia, bilateral Babinski
spontaneous or inducible clonus, ocular clonus, myoclonus

3. autonomic instability
tachycardia, hypertension or hypotension
flushing, sweating
diarrhoea and vomiting
Other Features of Serotonin Syndrome
• leucocytosis
• elevated CK
• transaminitis
• metabolic acidosis
• DIC
• AKI secondary to rhabdomyolysis
• ARDS
• seizures
• malignant hyperthermia
• fulminant hepatic failure
Management of Serotonin Syndrome
• stop all offending drugs
• fluid and electrolyte replacement
• IV sodium bicarbonate for persistent acidosis
• IV benzodiazepines
• 5HT2A antagonists (cyproheptadine, chlorpromazine, olanzapine)
• IV labetalol/GTN or noradrenaline for hyper/hypotension
• conventional cooling measures (paracetamol ineffective)
• ice bath, IV dantrolene, paralysis/intubation for hyperpyrexia
• rapid improvement within 24-48h is the rule
Case 3
A sink to save the sinking patient!
Case Presentation
• 60-year-old female with history of bipolar depression
• found ‘unconscious’ at home (daughter spoke to her 4h prior)
• suicide note and empty packet of amitriptyline (28 x 50mg)
• also takes temazepam and lithium
• HR 130, BP 96/44, GCS 8, BM 5.9, RR 24
• warm peripheries, dilated pupils
• increased tone and hyperreflexia bilaterally with extensor plantars
• ECG sinus tachycardia
• ABG (FiO2 0.4) pH 7.31, pO2 19.6, pCO2 3.5, BE -5.1, lactate 1.9
Which of the following receptors do TCAs act on?
• acetylcholine
• histamine
• GABA
• cardiac sodium channels
• cardiac delayed rectifier potassium channels (I kr)
• noradrenaline
• serotonin
• α-adrenergic
TCAs are ‘dirty drugs’
• anticholinergic: tachycardia, confusion, pyrexia, dry skin, dilated pupils,
urinary retention and ileus
• α1-adrenergic blockade: vasodilatation and hypotension
• histamine: confusion, hallucinations and drowsiness
• GABA: drowsiness, ataxia, divergent squint, nystagmus
• cardiac sodium and Ikr channel blockade : sinus tachycardia, PR/QRS/QTc
prolongation, RBBB, AVB
• serotonin: features of serotonin syndrome especially if coningestion of
other serotonergic drugs
• other effects: increased tone, hyperreflexia, seizures, metabolic acidosis,
hypothermia, rhabdomyolysis, ARDS
True or False?
in view of her low GCS and airway risk, our patient should be given a
trial of IV flumazenil to reverse any CNS sedative effects of temazepam
which she may have coingested

FALSE

flumazenil is rarely indicated in benzodiazepine overdose and in the


case of mixed overdose (especially with TCAs) it is contraindicated due
to risk of precipitating seizures/SE
Which of the following is an indication for
IV sodium bicarbonate administration in
the context of TCA OD?

•metabolic acidosis
•hypotension despite fluid resuscitation
•cardiac arrhythmia
•QRS prolongation >120ms
Answer:
• all of these are indications for administration of IV sodium bicarbonate in
TCA poisoning

• give 50ml 8.4% or 333ml 1.26% NaHCO3 aiming for arterial pH of 7.5-7.55

• increased pH favours neutral form of tricyclic drug reducing receptor


binding

• sodium load increases extracellular [Na+] attenuating blockade of rapid


sodium channels
How should arrhythmias and seizures after
TCA overdose be treated?
Arrhythmias Seizures

CORRECT HYPOXAEMIA, ELECTROLYTE DISTURBANCES AND ACIDOSIS


IV Magnesium IV Benzodiazepines
IV Lignocaine

CONTRAINDICATED CONTRAINDICATED
Class 1a e.g. quinidine IV Phenytoin
Class 1c e.g. flecainide
Case Progression
• GCS dropped to 3 after a seizure, intubated by ITU
• IV bicarbonate administered until pH 7.48
• 3l of crystalloid given for falling BP
• BP 67/35, oligoanuric
• started on noradrenaline and adrenaline infusions
• BP still only 79/44
• 10mg IV glucagon given with minimal effect
• episode of VT which responded to single shock
• remained peri-arrest
What rescue treatment did we give?
• IV fat emulsion (20% Intralipid®) 90ml bolus (1.5mg/kg) followed by 30ml/min
(0.5ml/kg/min) until 500ml total given

• rapid sustained improvement in BP and urine output

• adrenaline discontinued and noradrenaline weaned down

• no further arrhythmias

• discharged from ITU 48h later


IV Fat Emulsion (20% Intralipid®)
• previously used as an antidote for local anaesthetic toxicity

• growing body of evidence for use in overdose with other drugs


– tricyclics
– lipophilic calcium channel blockers e.g. diltiazem, verapamil
– lipophilic β-blockers e.g. propanolol, metoprolol, carvedilol, labetalol
– antipsychotics

• mechanism of action uncertain


– ‘lipid sink’ reducing free active drug concentrations
– modulation of intracellular metabolism by free fatty acids
– direct activation of myocardial Ca2+ channels
Key Learning Points
1. remember to ask about cannabis use in recurrent
attenders with cyclical vomiting (especially if unusually
clean!)

2. serotonin syndrome may affect all ages and can be


caused by introduction of CYP450 inhibitors in patients
on SSRIs

3. when running out of options in TCA/CCB/BB poisoning,


consider grabbing the fat!

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