The first patient was a 42-year-old man, classified as ASA I, meaning a completely healthy individual with no systemic disease, scheduled for an inguinal hernia repair. Six months earlier he had been stung on the forearm by a wasp. An experienced anesthesiologist performed spinal anesthesia at the L3–L4 interspace of the lumbar spine using a 25-gauge Quincke needle, the workhorse of neuraxial techniques. Free and continuous flow of cerebrospinal fluid confirmed that the needle tip sat correctly within the thecal sac, the membrane-enclosed space containing the fluid that bathes the spinal cord and nerve roots. The team then injected 3 milliliters of 0.5 percent hyperbaric bupivacaine — a total of 15 milligrams — a dose routinely sufficient for lower abdominal surgery. The injection met no resistance, and cerebrospinal fluid continued to flow throughout, ruling out displacement of the needle. Barbotage, the repeated aspiration and reinjection sometimes used to confirm placement, was not performed.

Ten minutes later, the patient should have been profoundly anesthetized. Instead, pinprick and cold sensation testing demonstrated no sensory blockade at any dermatome level, and the modified Bromage scale, the standard measure of lower-limb motor block, remained at Grade 0, indicating full strength and movement in both legs. The team repeated the procedure at a different interspace, L2–L3, using the same technique and the same anesthetic solution. The result was identical: no sensory change, no motor weakness, nothing. With two failed attempts and no explanation, the clinicians converted to general anesthesia, which proceeded uneventfully. Postoperative evaluation, including allergy testing, was entirely normal, and no technical error could be identified on review.

The second case followed a strikingly similar script. A 35-year-old healthy man, also ASA I, presented for knee arthroscopy. Five months before surgery he had been stung on the chest by a wasp. Spinal anesthesia was again performed at L3–L4 with a 25-gauge Quincke needle, and free cerebrospinal fluid flow was confirmed before the injection of 2.5 milliliters of 0.5 percent hyperbaric bupivacaine, equivalent to 12.5 milligrams. The injection was smooth, with continuous fluid return confirming correct needle positioning throughout. After ten minutes the patient retained full sensory and motor function. A second attempt at L2–L3 with the same drug and technique again produced no blockade whatsoever. Pinprick and cold testing showed no reduction in sensation at any level, and the Bromage score stayed at Grade 0. He too was converted to general anesthesia and recovered without complications.

The authors of the report, led by Ammir Abuzahra and colleagues, emphasize that the pattern shared by these two cases is what makes them remarkable. Typical causes of failed spinal anesthesia — needle misplacement, inadequate dosing, obesity, spinal pathology — were absent in both patients. Both blocks were performed by experienced anesthesiologists with correct technique and appropriate drug doses, and both patients were fully cooperative. Under ideal conditions, the incidence of total spinal anesthetic failure is very low. The complete absence of both sensory and motor blockade, rather than a patchy or insufficient block, suggested that something fundamental had prevented the local anesthetic from acting on neural tissue at all. The decision to repeat the block with the same agent reflected standard clinical practice, since a first failure can usually be attributed to subtle technical error, but the repeated negative result, combined with the normal appearance of cerebrospinal fluid in every pass, made a purely technical explanation unlikely.

The hypothesis the authors put forward is provocative: that prior wasp envenomation may have altered the patients’ neuronal responsiveness to spinal local anesthetics. They are careful to label this as speculative, and with only two cases no causal inference is possible. But there is genuine biological plausibility buried in wasp venom chemistry. Wasp venoms contain multiple biologically active peptides, among them the pompilidotoxins, a class of neurotoxins that act directly on voltage-gated sodium channels — the same molecular gates that bupivacaine blocks to produce anesthesia. Experimental studies have shown that alpha-pompilidotoxin slows the inactivation of sodium currents, prolonging the influx of sodium ions into neurons and thereby changing how nerve cells fire. Because bupivacaine exerts its anesthetic effect principally by plugging these very channels, an interaction between venom-induced channel changes and the drug’s mechanism is, at least in theory, conceivable.

A second possible mechanism involves inflammation. Wasp venom also contains mastoparan peptides, which can activate mast cells and trigger the release of histamine, as demonstrated in experimental cell models. In theory, inflammatory mediators could alter neural excitability or the responsiveness of nerve membranes to local anesthetics. Delayed immune-mediated neurologic complications after wasp stings have been described in the medical literature, showing that venom effects are not always confined to the minutes after the sting. However, the authors note that no published evidence currently establishes sustained inflammatory changes within the neuraxis — the spinal canal and its contents — after a remote sting, and neither patient underwent biomarker testing or neurophysiological studies that might have detected such changes. The mechanism remains an open question rather than a demonstrated pathway.

The report builds on an earlier and equally curious observation. A case-control study published in the Indian Journal of Anaesthesia by Panditrao and colleagues reported delayed or incomplete spinal blockade with intrathecal bupivacaine among patients with histories of scorpion stings, and proposed venom-related alterations in anesthetic responsiveness as a possible explanation. The new wasp cases echo that finding across a different venomous species, though the authors stress that the scorpion study does not establish that the same phenomenon occurs after wasp stings. Reduced effectiveness of local anesthetics has also been reported in some patients with connective tissue disorders such as Ehlers–Danlos syndrome Type III, indicating that altered anesthetic responsiveness, while poorly understood, is not without precedent. Neither of the current patients had any connective tissue disorder, and both had normal postoperative allergy testing.

The limitations of the report are considerable, and the authors lay them out candidly. Two cases might be coincidental; many people are stung by wasps every year and receive spinal anesthesia without any difficulty. The temporal pattern — failure occurring months after the sting — argues against an acute allergic reaction, since neither patient showed any perioperative allergic signs, but it also means any lasting change would have to persist far longer than venom components themselves remain in the body. The team lacked laboratory evidence such as inflammatory biomarker measurements, serum antibody testing, or nerve-excitability studies that could have supported a venom-related mechanism. Neither patient developed signs of local anesthetic systemic toxicity, though that does not independently exclude problems related to drug preparation, storage, or distribution. Subtle differences in technique or interspace level cannot be entirely excluded, but the repeated failure at two different spinal levels makes a technical cause improbable.

For now, the authors present these observations as hypothesis-generating rather than practice-changing. No anesthesiologist should refuse a spinal block to a patient with an old wasp sting on the basis of two case reports. But the known neuroactive properties of wasp venom — sodium-channel modification by pompilidotoxins and mast-cell activation by mastoparan — provide enough biological plausibility to justify closer attention. The authors call for larger observational studies, pharmacological testing, and mechanistic investigations before any clinical relationship can be established, along with additional case reports from other centers. If the association holds up, it would suggest that a sting’s effects can echo through the nervous system in ways nobody expected, and that the humble wasp still holds chemical secrets relevant to the operating room. Until then, the two men who lay awake and unnumbed on their operating tables remain a medical mystery — and a reminder that even the most routine procedures in medicine can occasionally defy every textbook expectation.

Subject of Research: Spinal anesthesia failure following wasp envenomation

Article Title: Spinal Anesthesia Failure Following Wasp Envenomation: A Case Series of Two Patients

Article References: Abuzahra, A., Maraqah, M., Atawneh, S., Qawasmi, R., Rabaee, M., Sweity, S., Ewidat, O., Riyad, N., & Mujahed, A. (2026). Spinal Anesthesia Failure Following Wasp Envenomation: A Case Series of Two Patients. Clinical Case Reports, 14(10), Article e73637. https://doi.org/10.1002/ccr3.73637

Image Credits: AI Generated

DOI: 10.1002/ccr3.73637

Keywords: spinal anesthesia, wasp venom, bupivacaine, pompilidotoxin, mastoparan, voltage-gated sodium channels, anesthesia failure, envenomation, neurotoxicity, case series, local anesthetics, mast cells

Against this backdrop, a research team from the ICMR National Institute of Traditional Medicine in Belagavi, working with colleagues at KLE College of Pharmacy, has turned to a plant with deep roots in traditional medicine. Plumbago zeylanica, known in Ayurvedic practice as chitraka, has long been used across the Indian subcontinent for wound healing and inflammatory conditions, and folk accounts have credited it with value against snakebite. The new study, published in the journal 3 Biotech, set out to test whether those traditional claims could survive rigorous modern scrutiny, using a hydromethanolic extract of the plant’s aerial parts against cobra venom in a combined program of laboratory assays, animal experiments and computational modeling.

The in vitro results were striking in their breadth. The extract, abbreviated PZE by the researchers, inhibited phospholipase A2 activity in a dose-dependent fashion, with inhibition ranging from roughly 13 percent at lower concentrations to more than 53 percent at the highest dose tested. Because phospholipase A2 is a principal driver of venom-induced hemolysis, the team also examined its effect on red blood cell destruction and found that the extract reduced PLA2-mediated hemolysis by 46.2 percent. These are not trivial numbers for a crude plant extract, and they suggest that compounds within the aerial parts of the plant can interfere directly with one of the most destructive enzymatic families in elapid venom.

The enzyme-inhibitory profile extended well beyond phospholipase A2. PZE suppressed venom acetylcholinesterase activity by 58.12 percent, an effect with direct relevance to the neurotoxic component of cobra envenomation, since acetylcholinesterase breaks down the neurotransmitter that carries signals from nerve to muscle. Protease activity, which contributes to tissue degradation and hemorrhage, was inhibited by 81.94 percent, the strongest effect recorded in the enzymatic panel. A fluorometric assay also indicated apparent inhibition of collagenase, an enzyme that attacks the collagen scaffolding of connective tissue. Perhaps most tellingly, the extract preserved the alpha chain of fibrinogen, the blood protein that venoms frequently fragment to disrupt clotting, indicating protection of a key substrate at the heart of venom-induced coagulopathy.

Translating these findings into living systems, the researchers challenged mice with twice the lethal dose of cobra venom and treated them orally with the extract at 100 and 200 milligrams per kilogram of body weight. Untreated animals succumbed rapidly, but the treated groups survived significantly longer, with mean survival times of 16 hours 23 minutes and 19 hours 42 minutes at the low and high doses respectively. For comparison, the commercial antisnake venom serum, administered as the current standard of care, provided complete protection for the full 24-hour observation period. The plant extract did not outperform antivenom, and the authors are explicit on this point, but the demonstration that an orally delivered plant preparation can meaningfully extend survival against a supralethal venom challenge is a meaningful proof of concept for an adjunctive therapy that could be administered early, even before a patient reaches a clinic.

The in vivo work also probed the inflammatory and tissue-level consequences of envenomation. At a sublethal challenge of half the lethal dose, venom did not produce significant alterations in the measured serum biomarkers and biochemical parameters, but treatment with the extract reduced venom-associated elevations in interleukin-6 and tumor necrosis factor-alpha, two central cytokines of the inflammatory response, as well as the brain and cardiac isoforms of creatine kinase, enzymes whose release signals damage to neural and muscle tissue. Histopathological examination told a consistent story: venom produced dilatation of the central vein, vascular congestion and mild lymphocytic infiltration in the liver, along with vascular congestion and tubular hemorrhage in the kidney, and the extract markedly ameliorated all of these changes. The pattern suggests that PZE acts not only on venom enzymes themselves but also on the downstream inflammatory storm that venom triggers in host tissues.

To understand which molecular targets might underlie these effects, the team employed network pharmacology, a computational approach that maps the interactions between the phytochemicals in the extract and the host proteins involved in disease pathways. The analysis identified multiple host targets connected through inflammatory, immune and neuronal signaling networks, providing a systems-level rationale for why a crude extract containing many different compounds could produce such broad protective effects. This multitarget character is precisely what conventional single-molecule drug development struggles to achieve against a venom that is itself a complex cocktail of toxins, and it mirrors the logic by which polyvalent antivenoms work, albeit through entirely different molecular means.

The computational arm of the study went further, using molecular docking and molecular dynamics simulations to examine how individual constituents of the extract interact with venom enzymes at atomic resolution. Two flavonoid compounds, 6-C-fucosylluteolin and 6-C-galactosylluteolin, emerged as the most interesting candidates. Docking placed both molecules within the catalytic sites of acetylcholinesterase and phospholipase A2, and the molecular dynamics simulations demonstrated that these interactions remained stable over the simulated timescales, indicating that the binding is not a fleeting artifact but a physically plausible mode of enzyme inhibition. While docking and simulation cannot by themselves prove activity in a patient, they provide a mechanistic scaffold that connects the observed biochemical inhibition to specific compounds that can now be isolated, tested and potentially optimized.

The authors position PZE not as a replacement for antivenom but as a candidate adjunctive phytotherapeutic intervention for the early management of snakebite envenomation, to be used alongside conventional therapy. The logic is compelling. Antivenom must be administered in a clinical setting, is expensive, carries a risk of adverse reactions including anaphylaxis, and is often unavailable in the rural areas where bites occur. A plant-derived oral preparation that could blunt local tissue destruction and dampen inflammation during the critical window before antivenom is given would address a genuine gap in the treatment pathway, particularly in South Asia, where the socioeconomic burden of snakebite is enormous and where traditional plant remedies already occupy a trusted place in first-response practice.

Considerable work remains before any such therapy could reach patients. The active constituents need to be fully characterized and standardized, dose-response relationships and safety margins must be established in accordance with internationally recognized toxicology guidelines, and the protective effects demonstrated here in mice must be validated against the biogeographical variation that is known to exist in cobra venom across India, a variation that already challenges the efficacy of existing antivenoms. Clinical efficacy, drug interactions and the pharmacokinetics of the relevant flavonoids in envenomated patients all remain open questions. Nevertheless, the study represents a rigorous, multi-level validation of a traditional remedy, combining classical enzyme assays, survival studies, histopathology, cytokine profiling, network pharmacology and molecular simulation into a single coherent case. In doing so, it transforms an ethnobotanical claim from folklore into a testable hypothesis, and it adds Plumbago zeylanica to the short but growing list of medicinal plants whose anti-venom potential has survived contact with modern experimental science.

Subject of Research: Evaluation of Plumbago zeylanica aerial part extract as a multitarget adjunctive therapy against Naja naja snake venom

Article Title: Anti-envenomation potential of Plumbago zeylanica aerial part extract against Naja naja: experimental validation and mechanistic insights

Article References: Anti-envenomation potential of Plumbago zeylanica aerial part extract against Naja naja: experimental validation and mechanistic insights. (n.d.). https://doi.org/10.1007/s13205-026-05067-5

Image Credits: AI Generated

DOI: 10.1007/s13205-026-05067-5

Keywords: snakebite, Naja naja, Plumbago zeylanica, antivenom, phospholipase A2, acetylcholinesterase, network pharmacology, molecular docking, phytotherapy, envenomation, flavonoids, traditional medicine