| Cannabis
has long occupied an unusual position in medicine and culture. For
centuries it has been associated with relief—of pain, anxiety,
nausea, and loss of appetite. In modern clinical practice, cannabinoids
are frequently invoked as antiemetics, particularly in
chemotherapy-induced nausea and vomiting. Yet over the past two
decades, an unsettling paradox has emerged: in a subset of chronic
users, cannabis appears to provoke the very symptoms it is known to
suppress. Cannabinoid Hyperemesis Syndrome (CHS) is the name given to
this contradiction, and its increasing prevalence reflects both
changing patterns of cannabis use and the evolving potency of the
substance itself. CHS is characterized by recurrent episodes of severe nausea, vomiting, and abdominal pain in the setting of chronic cannabis exposure. Patients are often young, otherwise healthy, and deeply familiar with emergency departments long before a diagnosis is made. What distinguishes CHS from other causes of cyclic vomiting is not a laboratory test or imaging finding, but a constellation of behaviors, histories, and responses that only become coherent when cannabis use is examined honestly and longitudinally. The syndrome often unfolds in phases. In the prodromal period, patients experience early-morning nausea, vague epigastric discomfort, and a growing fear of vomiting. Appetite may decline, but cannabis use frequently increases, driven by the belief that it will alleviate symptoms. This phase can persist for months or years, often unnoticed or misattributed to anxiety, gastritis, or functional gastrointestinal disorders. Over time, however, the illness progresses into a hyperemetic phase marked by relentless vomiting, abdominal pain, dehydration, electrolyte disturbances, and repeated hospital visits. Vomiting may occur dozens of times per day, leading to acute kidney injury, metabolic derangements, and profound physical exhaustion. One of the most striking features of CHS is the compulsive use of hot showers or baths for symptomatic relief. Patients often describe standing under scalding water for prolonged periods, sometimes multiple times a day, as the only intervention that provides even transient comfort. This behavior is so characteristic that its presence strongly supports the diagnosis, yet it is frequently overlooked or dismissed as incidental. The relief appears to be mediated through cutaneous heat activation rather than psychological comfort, suggesting a neurophysiologic mechanism rather than a learned coping strategy. The pathophysiology of CHS remains incompletely understood, but several converging mechanisms have been proposed. Chronic exposure to delta-9-tetrahydrocannabinol (THC) appears to alter cannabinoid receptor signaling, particularly at the CB1 receptor, which plays a central role in gastrointestinal motility, visceral sensation, and emesis control. With sustained stimulation, these receptors may become dysregulated or desensitized, leading to a paradoxical proemetic effect. THC also interacts with dopamine and serotonin pathways, both of which are intimately involved in nausea and vomiting. Over time, these interactions may shift from inhibitory to excitatory, especially in susceptible individuals. Another important pathway involves the transient receptor potential vanilloid 1 (TRPV1) receptor, commonly known as the capsaicin receptor. TRPV1 is activated by heat and capsaicin and plays a role in pain perception and autonomic regulation. Chronic cannabis use appears to overstimulate TRPV1 receptors centrally while impairing their peripheral modulation, leading to splanchnic vasodilation, nausea, and abdominal pain. External heat or topical capsaicin may temporarily restore balance by activating peripheral TRPV1 receptors, explaining both the compulsive hot bathing behavior and the emerging role of capsaicin cream as a therapeutic adjunct. Clinically, CHS presents a diagnostic challenge because it closely resembles cyclic vomiting syndrome (CVS), a disorder of gut–brain interaction that predates the recognition of CHS by more than a century. Both conditions feature episodic vomiting with symptom-free intervals, abdominal pain, and significant morbidity. The key distinction lies in the temporal relationship between cannabis use and symptom onset, as well as the resolution of symptoms with sustained abstinence. Unfortunately, this distinction is often blurred because patients with CVS may use cannabis to self-medicate, and patients with CHS frequently deny or underreport use, either due to stigma or genuine disbelief that cannabis could be the cause. Laboratory and imaging studies in CHS are typically nonspecific. Mild leukocytosis, hypokalemia, metabolic alkalosis, and elevated creatinine from dehydration are common but not diagnostic. Imaging studies are often normal and rarely change management, yet they are frequently repeated as clinicians search for structural explanations. The absence of definitive tests contributes to diagnostic delay and unnecessary healthcare utilization, reinforcing patient frustration and clinician uncertainty. Acute management of CHS focuses on supportive care. Intravenous fluids are essential to correct dehydration and electrolyte abnormalities. Traditional antiemetics such as ondansetron or promethazine may provide partial relief but are often ineffective. Dopamine antagonists, particularly those that act centrally, have demonstrated greater efficacy in controlling symptoms, though they require careful monitoring due to potential cardiac and extrapyramidal side effects. Benzodiazepines may be helpful in select cases, especially when anxiety exacerbates symptoms, but they do not address the underlying mechanism. Topical capsaicin applied to the abdomen has emerged as a low-cost, low-risk intervention that can reduce nausea and vomiting by exploiting TRPV1-mediated pathways. Despite these measures, the only definitive treatment for CHS is complete cessation of cannabis use. Symptom resolution typically occurs within days to weeks of abstinence, though residual nausea may persist as THC is slowly released from adipose tissue. Relapse is common if cannabis use resumes, often with a shorter latency and more severe symptoms. This pattern underscores the importance of recognizing CHS not only as a gastrointestinal disorder but also as a condition intertwined with substance use behavior, mental health, and social context. The chronic phase of management therefore extends beyond the emergency department or hospital ward. Patients require education that reframes cannabis not as a remedy but as a trigger. This conversation is often difficult, particularly in an era when cannabis is widely perceived as benign or therapeutic. Many patients express disbelief, anger, or grief when confronted with the diagnosis, especially if cannabis has played a central role in their identity, coping strategies, or social environment. Addressing comorbid anxiety, depression, and substance use disorder is critical to sustained recovery, as these conditions frequently drive continued use despite clear consequences. CHS is not a benign syndrome. Repeated episodes of severe vomiting can lead to esophageal injury, aspiration, acute renal failure, and life-threatening electrolyte disturbances. Prolonged QT intervals, particularly in the context of antiemetic use, increase the risk of malignant arrhythmias. The economic burden is substantial, driven by repeated emergency visits, hospitalizations, diagnostic testing, and lost productivity. Yet despite its growing prevalence, CHS remains underrecognized, underdiagnosed, and often misunderstood. The increasing legalization and commercialization of cannabis have altered both the frequency and intensity of exposure. Modern cannabis products often contain significantly higher concentrations of THC than those used in prior decades, and new delivery systems allow for rapid, repeated dosing. These changes may partially explain why CHS is being identified more frequently and at younger ages. At the same time, cultural narratives surrounding cannabis as a natural or harmless substance may delay recognition of its adverse effects, both by patients and clinicians. Understanding CHS requires abandoning simple binaries of "good" or "bad" drugs and embracing a more nuanced view of dose, duration, individual susceptibility, and neurobiology. Cannabis can be both antiemetic and emetogenic, therapeutic and toxic, depending on context. CHS occupies the uncomfortable space where these contradictions converge, reminding clinicians that physiology does not always conform to expectation or intention. As awareness grows, earlier recognition of CHS offers the possibility of reducing harm, avoiding unnecessary testing, and guiding patients toward effective treatment. Doing so requires careful listening, nonjudgmental inquiry into substance use, and a willingness to question assumptions—both the patient's and the clinician's. In this sense, CHS is not only a medical syndrome but also a lesson in clinical humility: a reminder that even familiar remedies can betray us when used without limits, and that relief, like illness, often carries a history we must learn to read. References: 1- Lonsdale H, Wilsey MJ: Paediatric cannabinoid hyperemesis. Current Opinion in Pediatrics. 34(5):510–515, 2022 2- Geraci E, Cake C, Mulieri KM, Fenn NE 3rd: Comparison of antiemetics in the management of pediatric cannabinoid hyperemesis syndrome. Journal of Pediatric Pharmacology and Therapeutics. 28(3):222–227, 2023 3- Shah M, Jergel A, George RP, Jenkins E, Bashaw H: Distinguishing clinical features of cannabinoid hyperemesis syndrome and cyclic vomiting syndrome: A retrospective cohort study. The Journal of Pediatrics. 271:114054, 2024 4- Ibia IE, Toce MS: Cannabis hyperemesis syndrome in children: A review of epidemiology, pathology, diagnosis, and treatment. Pediatric Emergency Care. 41(5):397–405, 2025 5- Meyer J, Burns MM: Current recommendations in the diagnosis and management of cannabinoid hyperemesis syndrome. Current Opinion in Pediatrics. 37(3):240–243, 2025 6- Yacob D: Cyclic vomiting syndrome and cannabinoid hyperemesis syndrome: Their intersection and joint existence. Gastroenterology Clinics of North America. 54(3):557–568, 2025 |
| Acute
appendicitis remains one of the most common surgical emergencies
worldwide, traditionally managed by appendectomy as definitive therapy.
For more than a century, early surgical removal of the appendix was
justified by the belief that appendicitis represents a progressive
disease that inevitably leads to perforation if left untreated.
However, advances in diagnostic imaging, antimicrobial therapy, and a
growing body of clinical evidence have challenged this paradigm, giving
rise to renewed interest in non-operative management using antibiotics
alone, particularly in cases of uncomplicated appendicitis. The conceptual shift underlying non-operative management is rooted in the recognition that appendicitis may not represent a single disease process. Instead, it appears to encompass a spectrum ranging from mild, self-limited inflammation to severe gangrenous or perforated disease. This distinction has profound implications for treatment strategies. Uncomplicated appendicitis, characterized by localized inflammation without perforation, abscess, or phlegmon, has emerged as a potential target for conservative treatment. The increasing use of high-resolution ultrasound and computed tomography has improved diagnostic accuracy, enabling clinicians to more reliably identify patients who may be suitable for non-operative approaches. Across adult and pediatric populations, antibiotic-first strategies have demonstrated high rates of initial clinical success. Most patients experience symptom resolution during the index admission without the need for urgent surgery. These findings suggest that, in selected patients, acute appendicitis can be effectively controlled with antimicrobial therapy, avoiding the immediate risks associated with anesthesia and surgery. Moreover, the observation that many patients do not experience disease progression despite delayed or absent surgical intervention has further weakened the long-held assumption that appendicitis is uniformly progressive. Despite these encouraging early outcomes, the long-term durability of non-operative management remains a central concern. Recurrence of appendicitis or failure of antibiotic therapy requiring appendectomy is consistently reported during follow-up, particularly within the first year. While a substantial proportion of patients avoid surgery altogether, cumulative failure rates increase over time, resulting in a significant minority ultimately undergoing appendectomy. This pattern underscores an important distinction between short-term treatment success and definitive cure. From a clinical perspective, non-operative management may be best understood not as a replacement for surgery, but as an alternative initial strategy that defers or potentially avoids operative intervention. Complication profiles associated with non-operative and operative management differ in nature rather than magnitude. Appendectomy, even when performed laparoscopically, carries risks related to anesthesia, surgical site infection, postoperative pain, and, in rare cases, more serious adverse events. However, contemporary surgical techniques have markedly reduced morbidity, and appendectomy remains one of the safest emergency operations performed in both adults and children. In contrast, non-operative management avoids surgical risks but introduces others, including antibiotic-related adverse effects, increased rates of unplanned healthcare visits, and the psychological burden associated with recurrence risk. Importantly, available evidence suggests that delayed appendectomy following failed non-operative treatment does not result in a substantially higher rate of severe complications when appropriate monitoring and timely intervention are ensured. Length of hospital stay has been widely examined as a comparative outcome between treatment strategies. Contrary to the perception that conservative management necessarily shortens hospitalization, antibiotic-based treatment often requires prolonged observation and intravenous therapy, leading to longer initial hospital stays than early appendectomy. Surgical management, particularly when minimally invasive, offers predictable postoperative recovery and discharge timelines. Nevertheless, some patients treated non-operatively may resume normal activities sooner and require less postoperative analgesia, highlighting that hospital length of stay alone does not fully capture functional recovery. The presence of an appendicolith has emerged as a critical predictor of non-operative treatment failure. Patients with appendicoliths consistently demonstrate higher rates of recurrence, complications, and subsequent appendectomy when managed with antibiotics alone. This finding supports the hypothesis that luminal obstruction plays a key role in disease persistence and progression in a subset of patients. As a result, many contemporary protocols exclude patients with appendicoliths from non-operative management, emphasizing the importance of careful patient selection based on imaging findings. In pediatric populations, the debate surrounding non-operative management is particularly nuanced. Children generally tolerate appendectomy well, with low complication rates and excellent long-term outcomes. At the same time, avoidance of surgery may be appealing to families seeking to minimize procedural intervention, postoperative pain, or school absence. Evidence in children demonstrates that non-operative management is safe in the short term, with no increase in mortality or severe morbidity. However, non-inferiority to appendectomy has not been consistently demonstrated when long-term failure rates are considered. A substantial proportion of children initially treated with antibiotics ultimately require appendectomy, raising questions about the overall effectiveness of conservative management in this population. Quality of life considerations further complicate treatment decisions. Patients managed non-operatively often report less pain and reduced use of analgesics in the early phase, as well as faster return to daily activities. Conversely, the uncertainty associated with recurrence risk and the need for ongoing vigilance may negatively impact long-term quality of life for some patients and families. Appendectomy, while associated with short-term postoperative discomfort, offers definitive resolution and eliminates the risk of recurrence. These contrasting experiences highlight the importance of incorporating patient and family preferences into shared decision-making processes. From a healthcare system perspective, non-operative management offers both potential benefits and challenges. Reduced operative volume may alleviate surgical workload and resource utilization, particularly in settings with limited operating room availability. However, increased rates of emergency department visits, readmissions, and delayed surgery may offset these advantages. Economic analyses remain heterogeneous, reflecting differences in healthcare delivery models, antibiotic protocols, and follow-up practices. Taken together, current evidence supports non-operative management as a safe and feasible option for carefully selected patients with uncomplicated appendicitis, particularly in the absence of appendicoliths and when reliable follow-up can be ensured. Nonetheless, appendectomy remains the most definitive treatment, with the highest likelihood of permanent resolution and predictable outcomes. Rather than framing these strategies as competing approaches, contemporary practice increasingly recognizes them as complementary options within a patient-centered framework. Future research should focus on refining selection criteria, identifying biomarkers predictive of sustained response to antibiotics, and standardizing treatment protocols. Long-term outcome data extending beyond one year are essential to better define true treatment effectiveness. Additionally, greater emphasis on patient-reported outcomes will enhance understanding of how different management strategies impact quality of life. In conclusion, non-operative management represents a significant evolution in the treatment of acute appendicitis. While it challenges long-standing surgical dogma, its role is best defined as an individualized option rather than a universal substitute for appendectomy. Ongoing evidence continues to shape a more nuanced, personalized approach to appendicitis care, balancing efficacy, safety, patient preference, and healthcare system considerations. References: 1- Jumah S, Wester T: Non-operative management of acute appendicitis in children. Pediatric Surgery International. 39(1):11, 2022 2- Zagales I, Sauder M, Selvakumar S, Spardy J, Santos RG, Cruz J, Bilski T, Elkbuli A: Comparing outcomes of appendectomy versus non-operative antibiotic therapy for acute appendicitis: A systematic review and meta-analysis of randomized clinical trials. The American Surgeon. 89(6):2644–2655, 2023 3- Decker E, Ndzi A, Kenny S, Harwood R: Systematic review and meta-analysis to compare the short- and long-term outcomes of non-operative management with early operative management of simple appendicitis in children after the COVID-19 pandemic. Journal of Pediatric Surgery. 59(6):1050–1057, 2024 4- Adams SE, Perera MRS, Fung S, Maxton J, Karpelowsky J: Non-operative management of uncomplicated appendicitis in children: A randomized, controlled, non-inferiority study evaluating safety and efficacy. ANZ Journal of Surgery. 94(9):1569–1577, 2024 5- St Peter SD, Noel-MacDonnell JR, Hall NJ, Eaton S, Suominen JS, Wester T, Svensson JF, Almström M, Muenks EP, Beaudin M, Piché N, Brindle M, MacRobie A, Keijzer R, Engstrand Lilja H, Kassa AM, Jancelewicz T, Butter A, Davidson J, Skarsgard E, Te-Lu Y, Nah S, Willan AR, Pierro A: Appendicectomy versus antibiotics for acute uncomplicated appendicitis in children: An open-label, international, multicentre, randomised, non-inferiority trial. The Lancet. 405:233–240, 2025 6- Brucchi F, Filisetti C, Luconi E, Fugazzola P, Cattaneo D, Ansaloni L, Zuccotti G, Ferraro S, Danelli P, Pelizzo G: Non-operative management of uncomplicated appendicitis in children, why not? A meta-analysis of randomized controlled trials. World Journal of Emergency Surgery. 20:25, 2025 |
| Pediatric
crotalid snakebites represent a distinct but well-characterized subset
of venomous injuries in the United States, accounting for a substantial
proportion of snakebite-related morbidity in children. Crotalid snakes,
which include rattlesnakes, copperheads, and cottonmouths, are
responsible for the vast majority of venomous snake envenomation
nationwide. Although children differ physiologically from adults,
accumulated evidence indicates that the clinical course, systemic
toxicity, and outcomes of pediatric crotalid envenomation closely
parallel those observed in adults, with important nuances related to
venom effects, laboratory abnormalities, and patterns of care . Envenomation typically results from defensive bites and most often involves the extremities. Lower extremity bites predominate overall, particularly in younger children, whereas upper extremity bites are more common in older children and adolescents, reflecting behavioral and environmental exposure patterns. Local manifestations are nearly universal and include pain, edema, erythema, and ecchymosis, which may progress proximally from the bite site. Tissue necrosis and blistering occur less frequently and, when present, are often associated with delayed presentation or more severe envenomation. Importantly, after adjusting for bite location, the likelihood of necrosis does not differ substantially between pediatric and adult patients, underscoring that venom dose and composition rather than patient size are key determinants of local tissue injury . Systemic toxicity is a defining concern in crotalid envenomation and is primarily hematologic in nature. Venom-induced coagulopathy, hypofibrinogenemia, and thrombocytopenia result from consumption and degradation of clotting factors mediated by venom metalloproteinases and other enzymes. Pediatric patients demonstrate early hematologic abnormalities at rates comparable to or slightly higher than adults, particularly with respect to hypofibrinogenemia and prolonged coagulation parameters during the initial phase of care. However, late or recurrent hematologic toxicity, which may occur after apparent initial control, develops at similar frequencies in children and adults and rarely leads to clinically significant bleeding when appropriately monitored and treated . Geographic and climatic factors influence the epidemiology and severity of pediatric snakebites. Children bitten in semi-arid regions are more likely to encounter rattlesnakes, present earlier to care, and require higher levels of monitoring and antivenom administration compared with those in subtropical regions, where copperhead bites are more common. These regional differences translate into longer hospital stays, increased intensive care utilization, and higher antivenom dosing in high-risk environments, despite similar rates of laboratory abnormalities and overall survival . Notably, mortality from pediatric crotalid envenomation remains exceedingly rare in modern series. Antivenom therapy is the cornerstone of treatment for moderate to severe envenomation and is administered based on clinical progression rather than patient age or weight. Ovine-derived Crotalidae polyvalent immune Fab has become the most widely used antivenom and has demonstrated a favorable safety profile in children. Acute hypersensitivity reactions, historically a major concern with older whole IgG antivenoms, are uncommon with Fab-based products. Large pediatric cohorts have reported no acute hypersensitivity reactions during or shortly after infusion, even among patients requiring intensive care and relatively high cumulative doses. Delayed complications such as recurrent coagulopathy may occur but are not directly attributable to allergic mechanisms and instead reflect the pharmacokinetics of venom and antivenom interactions . Despite its efficacy, antivenom use varies widely, particularly in copperhead envenomation, which is often milder and may be self-limited. Younger age, upper extremity bites, progression of local tissue effects across major joints, and the presence of comorbidities have all been associated with increased likelihood of antivenom administration. These practice variations highlight ongoing controversy regarding optimal thresholds for treatment and emphasize the need for standardized, evidence-based decision tools to balance benefits, risks, and resource utilization . In response to variability in care, pediatric-specific management strategies have been developed to better align treatment intensity with clinical severity. The Pediatric Crotalid Envenomation Score integrates physical examination findings and basic coagulation laboratory values to stratify patients into severity tiers that guide admission level and antivenom dosing. Implementation of such structured guidelines has been associated with significant reductions in intensive care admissions and ICU length of stay, without increases in hospital length of stay, readmissions, or adverse outcomes. Importantly, these protocols preserve excellent clinical results while conserving critical resources and reducing unnecessary exposure to antivenom in children with mild envenomation . Overall outcomes in pediatric crotalid snakebites are favorable when modern supportive care, timely antivenom administration, and appropriate monitoring are employed. Surgical intervention is rarely required and is typically limited to selected cases involving compartment syndrome or significant tissue compromise. Long-term functional impairment is uncommon, and most children recover fully with minimal residual effects. The growing body of pediatric-focused evidence reinforces that children should not be managed more aggressively solely because of age or size; rather, they should be treated according to objective clinical and laboratory indicators of venom effect. In summary, pediatric crotalid snakebites produce a spectrum of local and systemic effects that closely resemble those seen in adults. Early hematologic abnormalities may be more prominent in children, but overall severity, late toxicity, and outcomes are similar across age groups. Antivenom therapy is safe and effective in pediatric patients, with a very low incidence of hypersensitivity reactions. Regional differences in snake species and exposure patterns influence resource utilization, underscoring the importance of context-specific preparedness. The adoption of pediatric-specific severity scoring systems and treatment guidelines represents an important advance, enabling high-quality, efficient care while maintaining excellent outcomes for children affected by crotalid envenomation. References: 1- Levine M, Ruha AM, Wolk B, Caravati M, Brent J, Campleman S, Wax P; ToxIC North American Snakebite Study Group: When It Comes to Snakebites, Kids Are Little Adults: a Comparison of Adults and Children with Rattlesnake Bites. J Med Toxicol. 16(4):444–451, 2020 2- Chotai PN, Watlington J, Lewis S, Pyo T, Abdelgawad AA, Huang EY: Pediatric Snakebites: Comparing Patients in Two Geographic Locations in the United States. J Surg Res. 265:297–302, 2021 3- Corbett B, Otter J, Masom CP, Clark RF: Prevalence of Acute Hypersensitivity Reactions in Pediatric Patients Receiving Crotalidae Polyvalent Immune Fab. J Med Toxicol. 17(1):48–50, 2021 4- Ramirez-Cueva F, Larsen A, Knowlton E, Baab K, Rainey Kiehl R, Hendrix A, Condren M, Woslager M: Predictors of FabAV use in copperhead envenomation. Clin Toxicol (Phila). 60(5):609–614, 2022 5-Malek AJ, Criscitiello AA, Nes EK, Regner JL, Zamin SA, Wills HE, Little DC, Stagg HW: Development of the pediatric Crotalid envenomation score guideline and its influence on resource utilization. J Pediatr Surg. 61(1):162549, 2026 |
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