The dreaded Chironex fleckeri, responsible for some of the worst stings in the world. Does new research change everything we thought we knew about how to treat stings? Experts don't think so. Photo by Dr. Robert Hartwick When you're stung by a box jellyfish, you know it almost immediately. These somewhat squarish shaped cnidarians are armed to the bell with some of the most painful venom in the world. Long tentacles are packed with millions of stinging cells, called nematocysts, each with its own microscopic, needle-like harpoon-tipped tubule waiting to plunge into your flesh and inject the animal's intense venom. The pain is not only debilitating, it can also be deadly. More than 60 deaths from box jelly stings have been reported in the last forty years. Being stung is an awful experience. The best course of action is to remove any tentacles quickly to ensure that nematocysts that haven't fired don't get the chance to add their venom to the sting, and then treat for pain. Luckily enough, scientists discovered early on that vinegar (~5% acetic acid solution) irreversibly prevents nematocysts from firing, allowing people to rinse off tentacles without causing more trauma (which is also how the folk remedy of peeing on a sting originated, though vinegar is more effective and far less gross). For this reason, vinegar has been the go-to emergency response to box jelly stings for more than twenty years. It is currently the primary recommended treatment by the Australian Resuscitation Council, the American Heart Association and the American Red Cross. “Now (we’re saying) don’t do what we’ve been telling you to do for the last 30 years," Jamie Seymour, associate professor at James Cook University, told reporters at The Australian. Seymour's sudden change of heart is the result of new research published by him with colleagues from the Cairns Hospital, including lead author Philippa Welfare. Other news sites have been quick to cover the story which originated in a press release from James Cook University, warning that "vinegar on jellyfish sting can be deadly" and that "Queensland researchers have discovered the cure can kill." Not so fast, guys. The team used an in vitro model of stinging—a membrane attached inside a sterile cylinder—to discharge and collect venom from box jelly tentacles. The tentacles were placed on the rinsed membrane and electrically shocked with a six volt DC battery to stimulate discharge. The resultant 'venom' was then collected from the underside of the membrane using saline washes. Then the tentacles were treated with acetic acid (vinegar), and the underside washed again to determine what, if any venom was discharged during vinegar treatment. All the washes were evaporated and tested for venom activity against human heart cells. The results were unexpected: while the vinegar did prevent undischarged nematocysts from firing, it appeared to make those that had fired excrete even more venom. The scientists reported that vinegar caused a ~70% (+/- 32%) increase in venom discharge. "What we found was that by using vinegar, what you're effectively doing is increasing the venom load in the victim,” Seymour explained. These findings were supported, the authors say, by a survey of sting patients which found that those who received vinegar treatment required more pain medication. In addition to making stings worse, Seymour said that vinegar treatment distracts emergency responders from the most important part of sting treatment—monitoring vitals and ensuring the victim doesn't stop breathing. This new study, published in the brand-new journal Diving and Hyperbaric Medicine, has instantly garnered a lot of attention in Australia, with many calling for an immediate change of protocol. "I've been getting a steady stream of requests today from big organizations looking to change their policies in a hurry in response to today's media," said Lisa Gershwin, Director of the Australian Marine Stinger Advisory Services. But she and other scientists aren't convinced that the new findings are enough to call for a complete 180. Angel Yanagihara, jellyfish venom expert and research professor at the University of Hawaii, was immediately skeptical of the study. "I find the paper questionable on many levels, from the methodology to the conclusions." Yanagihara's first issue with the study is the membrane model using electric shock to stimulate venom discharge. "The extrapolation of this modest increase in recovery from an amniotic membrane model to live complex skin is not obvious," she said. Gershwin echoed her concerns. "Electrocuted tentacles in a lab environment don't have a parallel in the real world," she explained. "They offer no evidence, nor is there any from anywhere else, that this [model] bears any relationship to an actual sting event. Specifically, it seems reasonably likely (though unconfirmed) that the electrocution itself causes incomplete discharge, resulting in more venom to be discharged later. If this is the case, then the research is scientifically interesting but not applicable to the real world." Yanagihara also points out that the venom obtained is relatively weak compared to other research on box jellies. Her lab and others have isolated venom that over a thousand times more potent. "The fact that the activity of the recovered venom cytolytic activity is on the order of 10 mg/ml suggests that this is a very poor preparation." But moreover, Yanagihara is concerned that the results are not as cut and dry as they appear. There was no control solution applied to compare with vinegar after the electrical stimulation, thus it's unclear if using anything else would be better to remove tentacles. But more importantly, she says, the research didn't wholly ensure that the additional venom extracted by vinegar came from the tentacles' nematocysts, rather than venom stuck in or on the membrane after the initial sting. Vinegar could be causing changes to the membrane that release venom trapped within it, says Yanagihara, or is simply better than saline at bringing venom into solution and thus recovers more venom from the membrane surface than the saline wash. These alternative explanations were not accounted for because the researchers didn't test both sides of the membrane or use a control, says Yanagihara, and the difference is not inconsequential. Instead of being worse than we thought, vinegar could be an even better treatment than we realized. "In vivo vinegar could potentially assist in the extraction of venom from the upper layers of skin." But perhaps the greatest concern these scientists have is with the way the study is being represented in the media. "The paper clearly acknowledges and confirms that vinegar inhibits discharge of undischarged nematocysts," says Gershwin. "This subtle but utterly important distinction was lost in the media flurry." Yanagihara said it is "critical that the public understand" that in the paper, the authors state:
Previous research has shown that application of weak (3–10%) acetic acid for 30 seconds to C. fleckeri tentacles does not trigger discharge of nematocysts, and that nematocyst discharge from undischarged nematocysts is irreversibly inhibited... This action is not refuted by this study.
During most stings, surprisingly few of the tentacle's attack cells are actually triggered—less than 20% in most cases. The entire reason for vinegar treatment is to safely remove tentacles without causing more cells to fire, thus preventing further envenomation. Even if vinegar causes slightly more venom to come from the cells that have discharged, the additional venom load pales in comparison with the amount that could be injected by the rest of the tentacles if vinegar isn't used. "Despite acknowledging that vinegar does neutralize unfired nematocysts, Dr Seymour is prioritizing the 5-10% that may or may not further discharge, as more dangerous than the other 80-90% that we know will discharge,” said Gershwin. "Mathematically, this doesn't add up." According to Gershwin: "Preventing half of 10 or 20% but ignoring the other 80-90% to discharge is simply irresponsible.” Yet another expert on venom and envenomations, Director of the Australian Venom Research Unit Kenneth Winkel, said the study was "poorly controlled," and has "unknown relevance to the treatment of human box jellyfish stings." "They have created headlines from a very incomplete study— obviously this needs assessment in a more clinically realistic model." Winkel, too, expressed concern about the media attention, saying that the conclusions from the paper have been "way overstated," and "clearly already led to a state of public confusion." The official response from the Australian Resuscitation Council is that this new study "does not provide a convincing argument to alter our advice to dowse the tentacles on the skin of a victim in order to prevent further envenomation." They, too, cite flaws in methodology. "Unfortunately the design of the study, conducted on a membrane, was not designed to show... whether it is better to apply vinegar and prevent additional stinging from undischarged stinging cells (the majority) or whether it is better to not apply vinegar and so not promote further release of venom from stinging cells already discharged," reads a statement provided to me by an ARC representative. "Members of the ARC believe the study, although useful, does not provide a clear answer to this dilemma in an experimental design which mimics a real-life situation. Until such evidence becomes available, the ARC believes that the overall benefit to a stung victim is still to apply vinegar." That's not to say that Welfare and Seymour's study is completely invalid. Gershwin and Yanagihara both found the results fascinating, and think they're worthy of further attention. "The research is intriguing from a scientific point of view, because it is both a novel approach to an interesting question and it begs for more research to better understand what if any applicability it has to the real world," said Gershwin. "But intriguing research doesn't mean that it's a done deal and grist for a policy change. It's a question, not a conclusion.” Yanagihara stated that she plans to examine the parameters in her lab, replicating the study using a Hawaiian box jelly species, but also including some of the controls she felt were lacking in the original research. This is exactly how science is supposed to work—observations prompt hypotheses, which can then be tested with increased rigor. Preliminary findings aren't meant to cause complete changes in established policy, especially without detailed examination.
A signpost at a beach in Australia warning of box jellyfish. Image by Wikipedia user TydeNet The media has overstepped yet again in its science reporting, and in this case, the consequences could be severe. Box jelly stings are a rising problem in Australia and other areas, as jellyfish abundances have been increasing in recent years and more and more people are flocking to the beach. Emergency responders need to be confident that their treatments are backed by solid science, and that they are doing everything they can to mitigate the impacts of these potentially deadly species. Already, overzealous reporting has caused many to panic, and regulatory bodies are being inundated with calls to update their treatment policies. But those policies have not only been in place for decades, they're there for a damned good reason, and have saved many lives. Saying that "the cure can kill" is not just clear hyperbole, its outright misinterpretation of the study. In no way did the researchers test whether vinegar increases the likelihood of death, and they didn't test whether any other methods of removing tentacles are safer or more effective. To change treatment policy based on the findings would be premature at best, and disastrous at worst. Despite what you might have read, the best thing to do if you are stung by a box jellyfish remains unchanged. Seek medical attention as soon as possible. If vinegar is available, douse the sting site for 30 seconds or more to remove any remaining tentacles and nematocysts, and try to stay calm. If you're helping someone who is stung, help them remove the tentacles and pay close attention to their breathing, performing CPR if necessary. Once the tentacles have been removed, steps can be taken to reduce pain. Immersion in hot water appears to be the best method to reduce the intensity and duration of pain after any stray tentacles have been removed*, while ice packs** and topical and oral pain medications may help take the edge off. As awful and scary as a sting might be, it's important to remember that the vast majority of victims survive stings, and the odds of survival are almost 100% if the victim makes it through the first five to ten minutes.
Citation: Welfare P., Little M., Pereira P. & Seymour J. (2014). An in-vitro examination of the effect of vinegar on discharged nematocysts of Chironex fleckeri. Diving and hyperbaric medicine : the journal of the South Pacific Underwater Medicine Society, 44 (1) 30-34. PMID: 24687483
*There is some debate between experts on the efficacy of hot water immersion, though reviews (e.g. Atkinson et al. 2006) have suggested it can help in a variety of stings, including those by box jellies. However, there is concern that it can cause remaining undischarged nematocysts to fire and inject venom as well as dilate capillaries, allowing the venom to move more quickly through the body (see Cegolon et al. 2013). Some have also noted that the temperatures required to inactivate venom and the difficulty in obtaining hot water on-site when a sting occurs may limit its usefulness. The one thing both sides of this debate agree on is that the removal of tentacles, especially with a vinegar rinse (though seawater or manual removal will do in a pinch) is still the best first step in treating box jelly stings.
[UPDATE] **Ice packs have been shown to help alleviate pain in the case of stings by several species, but only act as temporary relief and may cause problems by discharging remaining nematocysts or masking symptoms when receiving professional care. They will not replace vinegar washing or aid in decreasing the venom load, and are not recommended for Hawaiian box jelly stings in particular.
