Alkali Toxicity

Etiology

Caustic substances can inflict damage on any surface they come into contact with, affecting both their functionality and histological composition if ingested. Substances with a pH greater than 7 are considered alkaline, and those exceeding a pH of 11 require special attention due to potential human exposure. Certain household cleaning products include potent alkalis capable of inducing liquefactive necrosis. The corrosive effects of alkali substances intensify as pH levels rise and persist until the alkali is neutralized.[2] This chemical pathway can significantly damage human tissue, especially within the esophagus. 

Many household or industrial products contain chemicals with caustic properties. Common alkaline substances include bleach, sodium hydroxide, potassium hydroxide, ammonia, and dishwashing detergents.[3] Bleach is the most common household alkali with a pH level of 11, typically available as a 3% to 6% sodium hypochlorite solution. Household caustics usually have lower concentrations, resulting in a reduced likelihood of causing severe injuries. In contrast, industrial-strength bleach contains higher concentrations of sodium hypochlorite and a higher pH level, thereby increasing the potential for significant tissue damage.

Epidemiology

In developed countries, there are reduced morbidity and mortality rates associated with caustic ingestion, primarily due to stricter product regulations and increased public education about alkaline products. However, exposure to caustic substances remains a persistent issue in underdeveloped nations.[2] Similar to other toxic exposure cases, caustic ingestion can be categorized as intentional, unintentional, or incidental.

Intentional exposures frequently occur in the context of suicide attempts and primarily impact adolescents and adults. Such incidents are often associated with severe injuries. Unintentional exposures typically involve young children who ingest caustic substances out of curiosity, but these incidents generally do not lead to serious harm. Incidental exposures most frequently occur in occupational or industrial settings, posing a potential risk of significant injury.[4] 

Developed countries have implemented more effective measures to prevent exposure to caustic substances. These measures include using childproof containers, regulations on highly corrosive substances, improved access to emergency care, better nutrition status, and enhanced follow-up protocols. Despite these efforts, caustic substances still account for many poison control center calls and emergency department visits. In 2019, the American Association of Poison Control Centers reported over 180,000 exposures to household cleaners. Most of these cases involved pediatric patients, with over 97,000 incidents involving exposure to a single substance.[5] Improved access to care often leads to favorable outcomes associated with these exposures.

The challenges related to caustic substance exposure are more pronounced in underdeveloped nations. Factors such as the absence of regulations, delays in accessing care, malnutrition, and cultural-specific tendencies toward using caustic agents during suicide attempts contribute to higher morbidity and mortality rates.[4]

Pathophysiology

Several physiological characteristics influence the extent of damage resulting from alkali ingestion. These factors include the pH of the substance, the duration of contact with the affected surface, the quantity or volume ingested, and the titratable alkali reserve (TAR).[4][6] 

The TAR is the amount of acid required to neutralize an alkaline substance to a pH of 8.0. Although evidence suggests that the TAR may better predict tissue injury, this value is often unavailable in emergencies.[6] The formulation of the alkaline substance can also influence the extent of damage. Alkaline products are available in various forms, including solid, granule, gel, liquid, or gas. Liquid and gaseous forms can spread further within the gastrointestinal (GI) and airway tracts, thereby increasing the potential for more extensive injury. Solid alkali materials, such as sodium hydroxide, lye, or caustic soda, are more commonly associated with oropharyngeal and proximal esophageal injury due to their tendency to adhere to the tissue surfaces they come in contact with. However, their adhesive nature can also prolong the contact time, thereby increasing the risk of more profound tissue damage.[7]

The pH of the substance determines the type of damage caused by caustic ingestion. Acids, with a pH of less than 7.0, induce coagulative necrosis, leading to the formation of an eschar, which may restrict the extent of tissue damage.[8] In contrast, alkalis, with a pH of more than 7, induce liquefactive necrosis. Alkalis with a pH exceeding 11 are more likely to result in severe injuries. Although direct contact with a caustic substance is the primary mechanism of damage, interactions with other acids can produce toxic byproducts. For instance, when bleach encounters an acid, such as hydrochloric acid, it can produce chlorine gas in the stomach.[9] Inhalation of chlorine gas can cause respiratory irritation and related complications.[10]

Recent evidence suggests that tissue damage from caustic ingestion is not exclusively attributed to the chemical burn caused by direct contact with the caustic substance. Evidence indicates that the formation of reactive oxygen species and subsequent lipid peroxidation also plays a role in the initial injury and the potential development of strictures in cases of esophageal damage.[11]

In ocular exposure to caustic substances, direct contact with the caustic can result in corneal injury, potentially leading to corneal scarring and blindness, even when prompt treatment is administered.[12] Moreover, additional damage to the retina can occur, resulting in further visual impairments. This damage is thought to be partly induced by the upregulation of tumor necrosis factor-alpha (TNF-α) and the inflammatory response triggered by the initial alkali burn.[13][14]

Button batteries present a unique type of exposure as they cause alkali damage, but the damage is not due to the battery's contents. When a button battery becomes lodged in the trachea or esophagus, it triggers localized water electrolysis, forming hydroxide anions. This process, in turn, results in a localized alkaline burn and liquefactive necrosis in the surrounding tissues.[15][16]

Histopathology

When a body surface is exposed to an alkali substance, hydroxide ions penetrate the tissue, leading to protein denaturation and lipid saponification. Thrombosis of microvasculature also occurs during this process, leading to further tissue necrosis and deep tissue injury. When a caustic substance comes into contact with tissue, it causes eosinophilic necrosis, swelling, and hemorrhagic congestion. In the days following the exposure, mucosal sloughing becomes evident. Subsequently, granulation tissue forms, which will cover ulcers with fibrinous tissue.[17]

History and Physical

Obtaining a comprehensive history of a patient with suspected caustic exposure is crucial. This should include details about the alkali substance, the quantity or amount ingested, and the circumstances surrounding the exposure. Determining whether the exposure was intentional or accidental is essential. In cases of intentional exposure, additional inquiries should be made to determine whether any coingestions or additional substances were involved.

Patients who have ingested alkali substances can exhibit various symptoms, whereas those who have ingested benign substances or in smaller quantities will often remain asymptomatic. However, individuals with more significant ingestions often experience symptoms, including abdominal pain, nausea, vomiting, hematemesis, bloody stools, dysphagia, odynophagia, and chest pain. If there has been pulmonary exposure, individuals may experience shortness of breath.

During a physical examination, these patients may exhibit signs of tachycardia or tachypnea, as well as drooling, stridor, oropharyngeal burns, and edema. Abdominal tenderness can also be a common finding.[7][18] Furthermore, specific physical findings associated with caustic ingestion may include dribble burns, which are streaks of burns on the chest and face. Occasionally, the presence of subcutaneous emphysema, characterized by a crepitus sensation upon chest palpation, may indicate mediastinal injury.

Dermal exposures to alkali substances typically result in erythema and localized pain, accompanied by edema in the affected area. The skin may appear inflamed and irritated, and patients may report discomfort or tenderness at the exposure site. In contrast, patients with ocular exposures frequently complain of pain and visual disturbances, ranging from blurry vision to complete blindness.

Evaluation

The primary approach to evaluating patients with alkali ingestion involves determining the necessity of performing esophagogastroduodenoscopy (EGD). EGD is considered the gold standard for evaluating the extent of injury and predicting the risk of esophageal stricture formation.[19] EGD should be performed between 12 to 24 hours of alkali ingestion, as the risk of iatrogenic perforation is lowest during this time.[20] However, reports suggest that EGD can be safely performed up to 96 hours after alkali ingestion.[21][22]

During EGD, the assessment of the esophagus in cases of alkali ingestion is typically performed using the Zargar classification system (see Table 1. Zargar Classification System).[21][23] The only contraindication to EGD is clinical or radiological evidence of a perforated viscus.

 Table 1. The Zargar Classification System

Laboratory studies are crucial in guiding patient care when evaluating individuals who have ingested alkali substances. Complete blood count, basic metabolic panel, hepatic function tests, coagulation profile, type and screen, lactate, and venous blood gas analyses will likely help in directing management decisions. These tests may show significant leukocytosis, anemia, renal and hepatic failure, coagulopathy, lactic acidosis, and severe metabolic acidosis. In cases where coingestions with substances such as acetaminophen, salicylate, or ethanol are suspected, specific levels of these substances should be measured if there is clinical suspicion.

An electrocardiogram (ECG) assists in assessing potential cardiac ischemia and may aid in identifying electrolyte imbalances, such as hyperkalemia.

Radiological studies can help identify patients with a perforated viscus [9] and assist in assessing the extent of tissue damage. An upright chest radiograph can detect the presence of air under the diaphragm, indicating a perforated viscus and ingested button batteries.

Computed tomography (CT) studies may be valuable in providing a more comprehensive characterization of the extent of tissue damage and can aid in predicting esophageal stricture formation. Obtaining a CT scan from the neck down to the pelvis with and without intravenous contrast is recommended for a more thorough evaluation.[24]

Although there are several proposed grading scales for alkali-related injuries, notably, they have not been validated.[25][26] Combining CT and EGD evaluations may help decrease the likelihood of unnecessary surgical interventions in patients with confirmed high-grade EGD findings. Identifying patients with full-thickness necrosis on a CT scan through this combined approach can aid in determining the appropriate course of management.[25][27][28]

Practitioners should conduct litmus testing to assess the pH of alkali before irrigating burns, particularly in cases related to a battery explosion, such as electronic cigarette batteries.[10] 

Ocular burns should lead to a consultation with ophthalmology, and damage is classified based on the Roper-Hall classification.[29]

Table 2. The Roper-Hall Classification

Treatment / Management

The primary focus of treatment when initially evaluating a patient after a caustic ingestion is to assess the airway, recognize and manage circulatory shock, and achieve stabilization. Signs suggestive of airway compromise and severe esophageal injuries, such as stridor, drooling, and vomiting, should not be overlooked.[30] Patients experiencing respiratory distress or airway compromise require immediate intervention with endotracheal intubation.

Airway Protection

After caustic ingestion, managing the airway can be challenging due to oropharyngeal edema, friable tissue, and potential bleeding. Therefore, assessing the airway with a fiberoptic device is advisable when possible. Blind nasotracheal intubation should be avoided. Techniques such as laryngeal mask airways, combination tubes, retrograde intubation, and bougies are relatively contraindicated due to the risk of perforation. In cases where endotracheal intubation or ventilation is not feasible, the physician should be prepared to perform a surgical airway to establish a secure airway and ensure proper ventilation for the patient.[31](A1)

Decontamination

Decontamination is a vital step in the management of alkali exposures and caustic exposures in general. To ensure safety, healthcare providers should wear protective gowns, gloves, and masks with face shields when treating patients with suspected caustic exposures. In cases of ocular and dermal exposures, immediate and thorough irrigation with water is essential. Copious irrigation helps dilute and remove the caustic agent from the affected area, reducing its potential for further damage.[2] Furthermore, any soiled clothing should be promptly removed from the affected area.(B3)

There is limited evidence to support the routine use of dilution with water or other liquids in the management of caustic ingestions, and it is generally not recommended due to the risk of inducing emesis. This can further damage the esophagus, obscure endoscopic evaluation, and potentially increase luminal pressure, which may lead to perforation in cases of severe injury.[32] However, dilution with water or other liquids may be considered immediately after caustic ingestion.(B3)

GI decontamination methods, including activated charcoal or whole bowel irrigation, are typically contraindicated in cases of caustic ingestion. Caustic substances are not well adsorbed by activated charcoal, and there is a high risk of vomiting and aspiration, which can exacerbate tissue injury.[7] Notably, it is no longer recommended to induce vomiting using syrup of ipecac for any type of ingestion, including caustic ones.[33](B3)

Fluid Resuscitation

Fluid resuscitation may be necessary for patients presenting with hemodynamic compromise following caustic ingestion. If a patient exhibits significant signs of hemorrhage, such as hematemesis, and is hemodynamically unstable, transfusion of uncross-matched blood may be indicated. In cases of refractory shock and for accurate blood pressure monitoring, central venous access may be necessary. 

Nasogastric Tube Placement

The placement of a nasogastric tube (NG tube) in cases of caustic ingestion continues to be debated and controversial. The rationale behind NG tube placement is to maintain the patency of the esophageal lumen and potentially reduce the risk of stricture formation.[34] However, there is no definitive consensus on the routine use of NG tube placement in all cases of caustic ingestion.(B2)

There is consensus that NG tube placement should be performed under direct visualization with endoscope assistance, ideally in an endoscopy suite rather than in the emergency department.[35][36](B3)

Endoscopy

Prompt endoscopy is necessary to grade the extent of a caustic injury in symptomatic patients. If radiographic studies reveal an ingested button battery located in the esophagus or trachea, immediate endoscopy is warranted to facilitate its removal.[2] (B3)

Viscus Perforation

Signs suggestive of hollow viscus perforation, such as mediastinal or intraperitoneal free air on imaging studies or clinical findings of a peritonitic abdomen, necessitate emergent surgical consultation. Surgical exploration should also be a consideration in the setting of shock, ingestion of more than 150 mL of a caustic substance, respiratory distress, and persistent lactic acidosis.[37]

Ocular Burns

Ocular burns require immediate ophthalmologic consultation. Due to the delicate nature of the eye and the potential for severe damage, prompt assessment and management of the condition by an ophthalmologist are essential.

Steroid Use

Managing caustic ingestions with steroids is controversial due to limited current evidence supporting its routine use.[38][39] However, in cases where patients present with airway compromise, dexamethasone may be considered as a treatment option. Dexamethasone can help reduce airway inflammation and edema, thereby improving respiratory symptoms in patients when administered at a recommended dose of 0.6 mg/kg, with a maximum of 10 mg.(B2)

Alkali Toxicity Grading and Care Levels

All patients with symptomatic ingestions should be admitted to a monitored setting. The specific management approach and level of care required depend on the severity of the injury, as determined by the grading system.

• Grade 1 injuries: Patients with grade 1 injuries, which typically involve superficial damage or mucosal inflammation, may be considered for discharge once they can tolerate oral intake and show signs of clinical improvement.
• Grade 2a injuries: Patients with grade 2a injuries, characterized by superficial ulceration or erosion without significant stricture, require observation for injury progression and symptomatic treatment. These patients can be started on a soft diet and monitored closely for signs of worsening.
• Grades 2b and 3 injuries: Patients with grades 2b and 3 injuries, which involve deeper ulceration, necrosis, or strictures, require intensive care management and should be admitted to the ICU for close monitoring, enteral or parenteral nutrition, symptomatic treatment, and consideration of surgical consultation. These patients are at high risk of developing immediate complications following caustic ingestion and are more likely to develop strictures in the future.

Differential Diagnosis

The management approach is more easily determined in the setting of known caustic ingestion. Therefore, identifying the ingested substance, determining the quantity consumed, assessing the duration of exposure, and noting the physical form of the substance, including solid or liquid, are crucial aspects to consider in cases of caustic substance ingestion. Differentiation between acid and alkali exposures is of lower clinical significance.

The management principles for caustic exposures are generally similar regardless of whether the substance is an acid or alkali. Exceptions to this include mercuric chloride and zinc chloride, which are acids with significant systemic toxicity. More targeted and specific management approaches may be necessary in cases involving these particular acid ingestions.

In intentional ingestions, maintaining a high index of suspicion for coingestions is of paramount importance.[40]

Other potential differential diagnoses include asthma or chronic obstructive pulmonary disease (COPD) exacerbation, acute coronary syndrome, pneumothorax, intraabdominal pathologies such as appendicitis or cholecystitis, gastroenteritis, intoxication, diabetic or alcoholic ketoacidosis, and sepsis.

Prognosis

In cases of caustic burns, the prognosis and the risk of developing strictures are determined by the extent of the esophageal injury. Grade 1 and fewer grade 2a burns usually have a favorable prognosis, with the recovery of esophageal function typically occurring over time. The risk of stricture formation in these cases is generally low.

However, grades 2b and 3 burns can form dense scar tissue, which increases the risk of stricture formation. Strictures necessitate long-term management, typically involving regular dilations, stents to maintain esophageal patency, and occasionally, surgical intervention.[41]

When assessing the prognosis in patients, it is crucial to consider several factors, including grade 3 esophageal injuries, systemic complications related to caustic ingestion, and an age of 65 or older, all of which are associated with a poorer prognosis.[42] 

Ocular exposures to caustic substances are typically associated with a poor prognosis, and many patients may develop blindness.[13] Several potential treatment options are available to address chronic complications and improve visual outcomes in affected patients. These treatments may include limbal stem cell transplantation, keratoplasty, and keratoprosthesis.[29]

Complications

Ingesting alkali substances may lead to the formation of esophageal strictures, which can cause symptoms such as odynophagia and dysphagia. If left untreated, these strictures can lead to subsequent malnutrition.

Squamous cell carcinoma of the esophagus is a complication of grade 3 esophageal caustic injuries.[43][44] This complication can occur decades after the initial caustic exposure. Notably, this complication can arise decades after the initial caustic exposure. However, routine screening for esophageal cancer in patients with prior caustic injuries is generally not recommended.[45] 

In cases where strictures become refractory to conservative management and significantly affect the patient's quality of life, reconstructive surgery may be necessary. Total removal of the esophagus, also known as esophagectomy, is recommended as a potential surgical option for these patients. This procedure allows for reconstruction and relief from the strictures.[20]