Iron Overdose

Iron overdose is common, but it is infrequent that it causes severe problems. I have seen it frequently in children, who take their parents well woman tablets, or similar.

Background
When thinking about iron, the first thing that must be done is to convert the amount of iron taken, to the amount of elemental iron ingested. This varies considerably between different types of iron tablets, depending on the type of ferrous or ferric salt:

  ferrous sulfate (dried) — divide dose by 3.3
  ferrous sulfate (heptahydrate) — divide dose by 5
  ferrous gluconate — divide dose by 9
  ferrous fumarate — divide dose by 3
  ferric chloride — divide dose by 3.5
  ferrous chloride — divide dose by 4

You can then risk stratify, by the amount of elemental iron they have ingested:
  <20mg/kg –– asymptomatic
  20-60mg/kg –– GI symptoms only
  60-120mg/kg –– potential for systemic toxicity
  >120mg/kg –– potentially lethal

Peak serum iron levels occur 4-6 hours following iron ingestion, then levels fall due to intracellular shift. Levels do not clearly correlate with clinical toxicity, but > 90 micromol/L (500 mcg/dL) is generally considered predictive of systemic toxicity (equivalent to >60mg/kg)

Pathophysiology
Local Effects - corrosive injury to the GI mucosa (vomiting, diarrhoea, haematemeis, melaena) . Can lead to gastric strictures.

Systemic Effects - cellular toxin, targeting the cardiovascular syndrome. Severe lactic acidosis from hypoperfusion due to volume loss, vasodilation and negative inotropic effects.


Clinical Symptoms


Investigations
Blood gas - can look like DKA. Anion gap metabolic acidosis.
BMs - can be hyperglycaemic
AXR
LFTs, Coags — hepatic failure
U&E — renal failure
Iron levels

Management
**Not adsorbed by activated charcoal**
Whole bowel irrigation for ingestion >60mg/kg
Surgical or endoscopy removal if >120mg/kg or WBI not feasible

Desferroxamine Chelation:
    level >90 micromol/L at 4-6 hours post-ingestion
    evidence of systemic toxicity
    shock
    metabolic acidosis
    altered mental status

Chelates free irons that can be renally excreted. Ferrioxamine is then excreted unchanged in the urine which classically, not reliably, turns a vin rose colour.

15 mg/kg/h, reduced if hypotension occurs, may be titrated up to 40mg/kg/h in severe toxicity
cardiac monitoring is mandatory. Can cause hypersensitivity, ARDS, toxic retinopathy or yersinia sepsis. Can be stopped when the patient is stable and serum iron is <60micromol/L - usually 56 hours.

References
http://learning.bmj.com/learning/modules/elucidat/57067260702df.html?moduleId=10055999&status=LIVE&action=start&_flowId=ELU&sessionTimeoutInMin=90&locale=en_GB&shouldStartAtQuestionSection=false

https://www.aliem.com/2014/management-iron-toxicity/
http://lifeinthefastlane.com/ccc/iron-overdose/
http://lifeinthefastlane.com/toxicology-conundrum-034/
https://wikem.org/wiki/Iron_toxicity
http://lifeinthefastlane.com/tox-library/antidote/desferrioxamine/
http://www.foamem.com/2014/08/06/management-of-iron-toxicity/
http://adc.bmj.com/content/87/5/400.full 
http://lifeinthefastlane.com/cicm-saq-2009-2-q18/ 

Methaemoglobin

Pathogenesis
- Oxidisation of the haem of haemoglobin by free radicals or things like hydrogen peroxide and nitric oxide. 
- Shifts O2 dissociation curve to the left. 

Causes
- Hereditary / Congenital: Hb and NADH-MetHb reductase deficiency
- Acquired: 
  *   Medications eg. Amyl nitrite, Benzocaine, Dapsone, Lidocaine, Nitroglycerin, Nitroprusside, Phenacetin, Phenazopyridine, Prilocaine, Quinones, Sulfonamides (eg. sulfamethoxazole). Chloroquine. 
  *   Chemical agents eg. Aniline dye derivatives (shoe dyes, inks) Butyl nitrite, Chlorobenzene, Nitrate-containing foods, Isobutyl nitrite, Naphthalene, Nitrophenol, Nitrous gases, Silver nitrate, and Trinitrotoluene. Sodium nitrite - used in food preservation. 

Signs & Symptoms
- chocolate brown discoloration of the blood. 
- SaO2 readings go crazy 

0-10% - Features unlikely

10-30%- Mild effects 
Blue-grey ‘apparent’ central cyanosis, fatigue, dizziness, headaches

30-50% - Moderate effects – weakness, tachypnoea, tachycardia

50-70% - Severe effects 
stupor, coma, convulsions, respiratory depression, cardiac arrhythmias, acidosis

> 70% - Potentially fatal

Treatment
<20% - nothing
20 - 30% - oxygen therapy 
>30% - methylene blue
            1-2 mg/kg IV over 5 minutes - 1% (10mg/ml solution) 
            repeat up to 7 mg/kg 
SpO2 normally dives as you give the methylene blue. 
Recheck levels after an hour 

Interesting Note
Hydrogen sulfide poisoning is similar to cyanide poisoning and can be treated by inducing metHb. 

References
http://stemlynsblog.org/feeling-blue-at-st-emlyns/
http://www.rcemlearning.co.uk/modules/papa-smurf-has-a-seizure/
http://emergencymedicineireland.com/2011/07/why-methaemoglobinaemia-is-a-good-thing/
http://emergencymedicineireland.com/2011/07/why-methaemoglobinaemia-is-a-bad-thing/

Carbon Monoxide

I thought I knew about Carbon Monoxide poisoning, and then I went to an (R)CEM day - and learnt a whole lot more about it.

Numbers
4,000 attend ED with CO
200 hospitalised

50 die each year

Pathophysiology

CO binds to haemoglobin with an affinity of approximately 220 times that of oxygen. CO shifts the oxygen dissociation curve to the left. It also binds to myoglobin and mitochondrial cytochrome oxidase, impairing ATP production. Somehow it also binds to platelets so that nitric oxide gets released.

CO binds to fetal haemoglobin and shifts the already left-shifted fetal oxyhaemoglobin dissociation curve further to the left. The half-life of CO in the fetus is longer than in the Mum.

CO is produced continuously in the body as a by-product of haem breakdown. This leads to a normal baseline COHb concentration of about 0.5%. In pregnancy and haemolytic anaemias this can rise towards 5%. 

Animal research – dogs given COHb 65-70%. They died.

2/3 of blood removed, and replaced with already poisoned blood - they were fine. They were then injected with CO, and were also fine. 

- Cigarette smoking leads to COHb concentrations of up to about 12% in heavy smokers 

Non-smokers living away from urban areas have carboxyhaemoglobin concentrations of between 0.4% and 1.0%. 

In an urban or industrial setting, concentrations of up to 5% may be considered normal.

- Methylene chloride (dichloromethane), which is found in some paint strippers and sprays. Once in the liver, is converted to carbon monoxide. Methylene chloride is stored in body tissues and released gradually.

- Electric fires, fires, wood burning stoves, barbeques, shesha pipes gas - anything. 

Clinical Presentation

With prolonged exposure her symptoms could lead to hypotension, seizures, cerebral oedema, metabolic acidosis and respiratory failure.

4.3% of 1758 patients presenting to 4 EDs had raised COHb levels

Unsuspected positive cases 3.5%: 

COPD 7.5% 

Headache 6.3%

Flu-like 4.3% 

Chest pain 3.3% 

Seizures 2.1% 

More Severe Symptoms:

The appearance of intoxication or a personality change

Impaired mini mental-state examination

Vertigo and ataxia

Breathlessness and tachycardia

Chest pain (due to angina or myocardial infarction)

Loss of consciousness 

Seizure or multiple seizures

Abnormal neurological signs including blindness, deafness, and extrapyramidal effects. 

High risk features include chest pain, history of unconsciousness, any continuing neurological symptoms or signs (especially cerebellar features) and pregnancy due to the effects on the foetus

Chronic Presentation

Chronic fatigue

Emotional distress

Memory deficits

Difficulty concentrating

Sleep disturbances

Vertigo 

Neuropathy

Paraesthesias

Recurrent infection

Polycythaemia

Abdominal pain

Diarrhoea

Clinical Assessment

Neuro exam: including tests of coordination and balance, MMSE, short term memory for chronic.

Cherry red skin is only seen in severe poisoning, with levels >20.

Investigations

CO reading taken from a breath analyzer - lactose intolerant patients have raised H2 in their expired breath which can interfere with the readings. 

Venous blood should be taken into anti-coagulant and sent to the laboratory. 

Treatment

Administration of oxygen speeds the elimination of CO from the body. Without therapy, the elimination half life of CO is 4-6 hours. Administration of high flow oxygen by a tight fitting mask at normal atmospheric pressure reduces half life to approximately 76 mins. 

Get your NIV out – you just need the seal and the flow rates of O2 high enough to maintain 100% oxygen. Even manually holding a BVM over them with a good seal does the job.

There is debate about the added value provided by hyperbaric oxygen. A COHb concentration of >20% should be an indication to consider hyperbaric oxygen especially if has any other symptoms:

Loss of consciousness at any stage

Neurological signs other than headache

Myocardial ischaemia/arrhythmia diagnosed by ECG

The patient is pregnant

If metabolic acidosis persists despite correction of hypoxia and adequate fluid resuscitation consider correction with intravenous sodium bicarbonate.

I wrote a powerpoint presentation on this - ages ago - feel free to use and adjust... 

References

http://www.enlightenme.org/the-curriculum-zone/node/11057

http://www.enlightenme.org/learning-zone/its-been-gas 

http://www.enlightenme.org/learning-zone/heating-it%E2%80%99s-not-just-bills-giving-you-headache%E2%80%A6 

http://learning.bmj.com/learning/module-intro/acute-carbon-monoxide-poisoning-diagnosis-management.html?moduleId=10011945&searchTerm=%E2%80%9Ccarbon%20monoxide%E2%80%9D&page=1&locale=en_GB

http://emergencymedicineireland.com/2012/10/smoke-without-fire/?ut

Toxbase

Cyanide

There was a chemical incident declared once because the pre-hospital team could smell almonds- they thought cyanide could be involved. Turns out someone had been baking... 

Cyanide is released by the incomplete combustion of nitrogen-containing materials, and metabolised from amygdalin. Amygdalin can be found in the pits of many fruits, such as apricots and papayas and raw nuts.

Cyanide is a colourless gas with a bitter almond smell, detectable by only 40% of people.

http://www.christem.com/storage/cyanide%20mechanism

CN blocks cellular respiration by blocking the cytochromes. Affected cells convert to anaerobic metabolism, and a lactic acidosis results. The CNS and the heart are most sensitive.

Symptoms

#fcem #toxicology #FOAMed #revision Features of cyanide toxicity. pic.twitter.com/1UYxjDrIPI
— Kirsty Challen (@KirstyChallen) July 15, 2014

Symptoms after exposure to high vapor concentrations may include the following:
Transient hyperpnea and hypertension 15 seconds after inhalation
Loss of consciousness in 30 seconds
Respiratory arrest in 3-5 minutes
Bradycardia, hypotension, and cardiac arrest within 5-8 minutes of exposure

Symptoms after exposure to lower vapor concentrations or after ingestion or liquid exposure may include the following:
Feelings of apprehension or anxiety
Vertigo
Nausea, with or without vomiting
Muscular trembling
Loss of consciousness
Headache
Dyspnea

Patients exposed to cyanogen chloride experience severe eye and mucous membrane irritation.Low-dose exposure results in rhinorrhea, bronchorrhea, and lacrimation. Inhalational exposure results in dyspnea, cough, and chest discomfort. Onset of symptoms after exposure to nitriles (acetonitrile and/or propionitrile) may be significantly delayed.

Physical findings of cyanide exposure are generally nonspecific. They classically have cherry red skin.

Laboratory Investigations
- Normal arterial oxygen tension, high venous oxygen tension = decreased AV difference (<10%)
- High anion gap metabolic acidosis
- Raised lactate

Antidotes

#REBELReview 67 Cyanide Toxicity Treatment http://t.co/Fo3oz5PIN2 #FOAMed #FOAMtox #MedEd #ABIM #EMBoardReview #USMLE pic.twitter.com/j6FlhcmlKs
— Salim R. Rezaie (@srrezaie) June 1, 2014

To accompany episode # 1.. a fabulous #FOAMed visual representation of the mech of action of cyanide antidotes http://t.co/RxRCsTmnci
— FOAMcast (@FOAMpodcast) May 24, 2014

Minimal symptoms that resolve spontaneously need observation only.

Other Factors
- Oxygen
- Consider sodium bicarbonate if severe lactic acidosis
- Treat haemodynamic instability and cerebral oedema

@Lmellick video on smoke inhalation injury https://t.co/SbhSGXZWZX #FOAMed
— Jasmin Hamzic (@jasmin_hamzic) January 11, 2015

#EMSqoD A:Cyanide can be the toxic agent in smoke. http://t.co/r2Hu7eFs & http://t.co/Tt439mpi So use cyanokit, 50% increase in ROSC #FOAMed
— Dr. Howie Mell (@DrHowieMell) January 4, 2013

Cyanide poisoning: key facts #FOAMed #Toxicology #FCEM pic.twitter.com/LYGWeNf451
— Natalie May (@_NMay) July 9, 2013

References
http://blog.clinicalmonster.com/2015/02/em-ccm-carbon-monoxide-and-cyanide-poisoning/
https://umem.org/educational_pearls/2675/
http://www.enlightenme.org/knowledge-bank/cempaedia/industrial-chemical-incidents