aka Toxicology Conundrum 008
It’s Christmas, and you’re called by a doctor who has recently arrived in Australia from the UK. He is in North Queensland looking after a 23 year-old female swimmer who doesn’t look at all well…
An “old nurse” (who only works when no one else wants to…) mentioned something that sounds like “ROO-CANDY”, started pouring vinegar over the patient, and then told the doctor he should “stop being a drongo and give her some pethidine!” (that’s meperidine to you Yanks!). Eventually, the doctor worked out that this condition was some kind of marine envenoming and decided to call you for help.
On further questioning you get this information:
The woman, a tourist from the United States, was swimming in shallow water within the boundaries of a stinger net when she felt a mild sting on her right calf and arm. After 10 minutes she had moderate back pain and then had a shower. She then developed severe aching in her back, abdomen, and limbs. She felt so weak she sat on the floor and couldn’t stand. A surf life-saver noticed her distress when she started vomiting. She was taken to the local hospital and an hour later in the emergency department she was writhing in pain, profusely diaphoretic (covered in sweat!), with a blood pressure of 170/100 mmHg and a heart rate of 110/min.
Before tackling the questions watch the video to see why some people would rather have a lethal Chironex sting than Irukandji Syndrome – at least you’d die quickly…
1. What is the diagnosis? How did you make this diagnosis?
This is a clinical diagnosis, there are no confirmatory laboratory investigations available.
Key features include:
- Recent contact with seawater
- A relatively innocuous initial sting
- A delayed systemic syndrome that progresses over minutes-to-hours, characterized by pain in multiple regions distant to the sting site and other symptoms such as nausea and vomiting, and restlessness. Features of a “catecholamine excess” state, such as tachycardia and hypertension, are common.
2. Would you suggest pethidine (meperidine) for analgesia? What about other opioid drugs?
Any opioid drug will have an analgesic effect in Irukandji syndrome
However, potential problems with pethidine include:
- stimulation of histamine release
- tachycardia and myocardial depression – additive to the cardiotoxicity in Iriukandji syndrome (? direct from Irukandji venom and ? indirect due to excessive catecholamine release)
- accumulation of the neurotoxic metabolite norpethidine (normeperidine) when high doses are required – seizures may occur
- potential drug interactions – e.g. serotonin syndrome if the patient is on other serotonergic medications.
- anticholinergic-like side-effects – e.g. dry mouth.
Fentanyl is my opioid of choice for Irukandji syndrome for a number of reasons:
- rapid onset
- can be rapidly titrated
- preserves cardiac stability and blunts stress-related hormonal changes at higher doses
- rarely elicits histamine release
- no toxic metabolites
- Interestingly, both pethidine and fentanyl appear to have sodium channel blockade effects. This may be relevant because a putative Irukandji toxin from C. barnesi was shown to be a sodium channel activator in animal models. Also Barnes himself felt that the effects of pethidine were somehow “specific” in that less pethidine than he expected was needed to gain (temporary) relief from the excruciating pain (based on his own experience as a self-inflicted victim of Irukandji Syndrome!). Anecdotal experience in Cairns suggests that less opioid analgeisa may be required if promethazine is also given, perhaps because of promethazine’s additive sodium channel blocking effects.
3. Is covering the patient with vinegar a good idea?
Yes — but only the sting sites!
Vinegar is known to be of benefit for Chironex fleckeri stings – it irreversibly inactivates nematocyst firing. Also vinegar appears to inhibit Carukia barnesi nematocysts in vitro. Based on this knowledge, vinegar application to possible sting sites in Irukandji syndrome is recommended. The vinegar should be poured over the site continuously for 30 seconds.
- Repeated applications of vinegar are not required – I know of patients still getting “vinegar wraps” applied many hours after a sting! It is not known when it is too late to apply vinegar and, apart from the smell, vinegar doesn’t cause any harm.
- Vinegar should be applied for even a minor sting if it occurred while swimming in sea water where Irukandji syndrome has been reported – sometimes the initial sting is so minor that the victim doesn’t suspect a jellyfish sting.
- Don’t use methylated spirits, methanol or ethanol – they all cause a massive discharge of nematocysts in cubozoans (box jellies)!
- Don’t do this:
4. What is the risk assessment for a patient with this condition? Is it lethal?
Experience from North Queensland, Western Australia, and the Northern Territory all suggest that Irukandji syndrome is usually a self-limiting, but often very distressing, illness. However in a small percentage of cases there is a risk of life-threatening cardiovascular complications. These include uncontrolled hypertension, transient cardiomyopathy, and acute pulmonary edema.
Irukandji syndrome can kill.
Two fatalities – both tourists – were attributed to Irukandji syndrome in 2002. In each case the cause of death was intracranial hemorrhage, and both patients were hypertensive prior to death. One of the deaths was a 58 year-old man on warfarin with an INR of 4.9, but the other was a healthy 44 year-old male. The identification of the jellyfish species responsible for these deaths has been a source of considerable controversy.
5. Describe your management plan.
- Prehospital care —
Apply generous volumes of vinegar to all visible sting sites to inactivate all undischarged nematocysts (sting cells)
Do not apply a pressure immobilisation bandage (PIB)
Transport all patients with pain refractory to first‑aid, or systemic symptoms to a medical facility – this is a potentially life‑threatening emergency
- Resuscitation, supportive care and monitoring —
Potential early life‑threats that require immediate intervention include:
- Severe hypertension
- Pulmonary oedema
Administer IV fentanyl (0.5-1.0 microgram/kg/dose) repeated every 10 minutes until appropriate analgesia is achieved. Large doses may be required (e.g. 200-300 microgram). Note: If fentanyl is not available, give morphine 0.1 mg/kg IV in titrated doses
Treat nausea with IV promethazine (25 mg; 0.5 mg/kg in children)
Control hypertension refractory to opioid analgesia with an intravenous infusion of glyceryl trinitrate (50 mg in 100 mL starting at 6 mL/minute; 1-4 microgram/kg/minute in children) titrated to achieve a systolic blood pressure <160 mmHg
Manage pain refractory to opioids with IV magnesium (0.2 mmol/kg up to 10 mmol in adults) administered over 5-15 minutes. Seek expert advice.
- Investigations — will be required if the patient has pain or hypertension refractory to opioids:
ECG (arrhythmia, ischemic changes, conduction blocks)
Chest radiograph (acute pulmonary edema)
FBC, UEC, troponin, CK
- Decontamination, enhanced elimination, and antidotes — nil
- Disposition —
This patient has severe pain requiring opioid analgesia. She may be discharged when pain-free and well for 6 hours.
Cardiovascular complications may necessitate admission to HDU/ ICU level care.
6. How did the patient get stung if she was swimming inside a stinger net?
The stinger nets are designed to keep out the larger multi-tentacled box jellyfish Chironex fleckeri. Small jellyfish like Carukia barnesi, which can cause Irukandji Syndrome, can penetrate the net.
As a result most cases of Irukandji Syndrome in North Queensland result from stings inside stinger nets that are close to the shore.
- Irukandji Syndrome
- Murray L, Daly FFS, Little M, and Cadogan M. Chapter 5.11 Irukandji Syndrome; in Toxicology Handbook, Elsevier Australia, 2007. [Google Book Preview]
- Barnes JH. Cause and effect in Irukandji stingings. Med J Aust 1964;i:897-904.
- Fenner PJ, Hadok JC. Fatal envenomation by jellyfsh causing Irukandji syndrome. Med J Aust 2002;177:362-3. [fulltext]
- Hartwick R, Callanan V, Williamson J. Disarming the box-jellyfsh: nematocyst inhibition in Chironex feckeri. Med J Aust 1980;1:15-20. [abstract]
- Huynh TT, Seymour J, Pereira P, Mulcahy R, Cullen P, Carrette T, Little M. Severity of Irukandji syndrome and nematocyst identifcation from skin scrapings. Med J Aust 2003;178:38-41. [fulltext]
- Little M, Mulcahy RF. A year’s experience of Irukandji envenomation in far north Queensland. Med J Aust 1998;169:638-41. [fulltext]
- Macrokanis CJ, Hall NL, Mein JK. Irukandji syndrome in northern Western Australia: an emerging health problem. Med J Aust 2004;181:699-702. [fulltext]
- Nickson CP, Waugh EB, Jacups S, Currie B. Irukandji syndrome case series from Australia’s tropical Northern Territory. Ann Emerg Med. 2009 Sep;54(3):395-403. Epub 2009 May 5. PMID: 19409658 [fulltext pdf].
- Tibballs J, Li R, Tibballs HA, Gershwin LA, Winkel KD. Australian carybdeid jellyfish causing “Irukandji syndrome”. Toxicon. 2012 May;59(6):617-25. Epub 2012 Feb 14. PubMed PMID: 22361384.
- Winkel, K. D., J. Tibballs, et al. (2005). Cardiovascular actions of the venom from the Irukandji (Carukia barnesi) jellyfish: effects in human, rat and guinea-pig tissues in vitro and in pigs in vitro. Clin Exp Pharmacol Physiol 32(9): 777-88. [abstract]