Background

A medical disorder known as acalculous cholecystitis is characterized by gallbladder inflammation when gallstones are not present. The liver produces bile, a digestive fluid, which is stored in the gallbladder, a small organ underneath the liver. Gallstones are solid particles that accumulate in the gallbladder and are frequently the cause of cholecystitis. However, acalculous cholecystitis occurs when there are no gallstones present. 

The exact cause of acalculous cholecystitis is not always clear, but it is often associated with underlying medical conditions or factors that affect the normal functioning of the gallbladder. Some common causes and risk factors for acalculous cholecystitis include: 

• Critical Illness or Trauma: This condition is frequently observed in critically ill patients, especially those who have undergone major surgery, severe trauma, or burns. The stress and inflammation associated with such conditions can affect the gallbladder’s function. 
• Sepsis: Sepsis, a serious illness that can harm several organs in the body, can lead to complications such acalculous cholecystitis. Infections can lead to inflammation of the gallbladder. 
• Ischemia: Insufficient blood supply to the gallbladder, known as ischemia, can contribute to acalculous cholecystitis. Conditions such as cardiovascular disease or shock may compromise blood flow to the gallbladder. 
• Immunosuppression: Individuals undergoing chemotherapy or those with HIV/AIDS may have a higher chance of getting acalculous cholecystitis due to compromised immune systems. 
• Fasting or Total Parenteral Nutrition (TPN): Prolonged periods of fasting or receiving nutrition intravenously (TPN) without oral intake can lead to gallbladder stasis, increasing the risk of inflammation. 
• Organ Transplantation: Patients who have undergone solid organ transplantation, particularly liver transplantation, may be susceptible to acalculous cholecystitis. 

Epidemiology

• Hospitalized Patients: Acalculous cholecystitis is often encountered in hospitalized patients, particularly those in critical care settings. It is more prevalent in individuals who are critically ill due to conditions such as severe infections, trauma, or major surgeries. 
• Critical Illness and Surgery: The incidence of acalculous cholecystitis is higher in individuals who are critically ill or have undergone major surgery. Trauma, burns, and other critical conditions can contribute to the development of this form of cholecystitis. 
• ICU Patients: The syndrome is commonly seen in patients hospitalized in intensive care units (ICUs), where risk factors such as organ failure and sepsis are more common, and the severity of underlying diseases makes the condition more common there. 
• Sepsis: A significant proportion of acalculous cholecystitis cases is associated with sepsis, a condition where the body’s response to infection can lead to widespread inflammation and organ dysfunction. 
• Immunocompromised Patients: Acalculous cholecystitis is more common in people whose immune systems are weakened, such as those with AIDS or HIV or those receiving immunosuppressive care. 
• Elderly Population: Acalculous cholecystitis may occur more frequently in the elderly population, especially those with multiple comorbidities. Organ dysfunction and a higher risk of serious diseases are frequently linked to ageing. 
• Organ Transplant Recipients: Patients who have undergone solid organ transplantation, particularly liver transplantation, may be susceptible to acalculous cholecystitis as a complication of the transplant process. 
• Gender and Ethnicity: There is no significant gender or ethnic predilection for acalculous cholecystitis. People of all genders and ethnicities may be affected. 

Anatomy

Pathophysiology

Ischemia and Reduced Blood Flow: 

• Critical illness, trauma, or major surgeries can lead to decreased blood flow to the gallbladder, a condition known as ischemia. Insufficient blood supply can result from systemic hypoperfusion, shock, or vascular complications. 
• Ischemia can lead to tissue damage and impaired function of the gallbladder, contributing to inflammation. 

Disturbed Bile Flow: 

• The regular flow of bile can be disrupted by illnesses like sepsis or systemic inflammation. This disruption can result in stasis of bile within the gallbladder. 
• Stagnant bile can become concentrated and contribute to the formation of sludge, which may further obstruct the gallbladder’s ducts. 

Infection and Inflammatory Response: 

• Acalculous cholecystitis is often associated with systemic infections, such as sepsis. Gallbladder-affecting inflammatory mediators can be released as a result of infections. 
• Inflammatory cells infiltrate the gallbladder wall, causing swelling, edema, and damage to the tissue. This inflammatory response contributes to the symptoms of cholecystitis. 

Gallbladder Wall Distension: 

• Stasis of bile and inflammation can lead to distension of the gallbladder wall. The gallbladder may become enlarged and sensitive to touch. 
• Distension can further compromise blood flow to the gallbladder, worsening ischemia and inflammation. 

Impaired Contractility: 

• Inflammatory processes and the accumulation of sludge or debris within the gallbladder can impair its contractility. Reduced contractility can lead to poor emptying of bile, exacerbating the inflammatory response. 

Immunosuppression:   

• Individuals with immune system weakness, such as those on immunosuppressive medicine or living with HIV/AIDS, may be more vulnerable to infections that might lead to acalculous cholecystitis. 

Etiology

• Critical Illness: Patients who are critically ill, especially those admitted to intensive care units, are at an increased risk of developing acalculous cholecystitis. Conditions such as severe infections, trauma, or major surgeries can contribute to the development of this form of cholecystitis. 
• Sepsis and Systemic Infections: Sepsis is a significant contributor to acalculous cholecystitis. The release of inflammatory mediators during sepsis can affect the gallbladder and lead to inflammation. 
• Ischemia and Reduced Blood Flow: Conditions that result in reduced blood flow to the gallbladder, such as shock, vascular compromise, or systemic hypoperfusion, can lead to ischemia. Ischemia contributes to tissue damage and inflammation in the gallbladder. 
• Immunosuppression: Individuals on immunosuppressive medication or those with HIV/AIDS may be more vulnerable to infections that might damage the gallbladder and cause acalculous cholecystitis, among other impaired immune system conditions. 
• Trauma and Burns: Trauma and severe burns can contribute to the development of acalculous cholecystitis. The stress response and inflammation associated with these conditions can affect gallbladder function. 
• Organ Transplantation: Individuals who have undergone solid organ transplantation, particularly liver transplantation, may be at an increased risk of acalculous cholecystitis as a complication of the transplant process. 
• Total Parenteral Nutrition (TPN): Prolonged use of total parenteral nutrition (TPN), a method of delivering nutrients intravenously without concurrent oral intake, can lead to gallbladder stasis and contribute to the development of cholecystitis. 
• Hemodynamic Instability: Conditions causing hemodynamic instability, such as severe heart failure or shock, can compromise blood flow to the gallbladder, leading to ischemia and inflammation. 
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Genetics

Prognostic Factors

• Underlying Health Status: The overall health and comorbidities of the patient play a crucial role in the prognosis. 
• Severity of the Underlying Illness: Acalculous cholecystitis often occurs in the setting of severe infections, trauma, or major surgeries. The severity of the underlying condition can impact the prognosis, with more critical illnesses leading to a potentially poorer outcome. 
• Timeliness of Diagnosis and Treatment: Better results have been linked to early detection and the timely start of the right treatment. Delayed diagnosis and intervention can lead to the progression of inflammation, complications, and an increased risk of mortality. 
• Presence of Complications: The development of complications, such as gangrene or perforation of the gallbladder, is a negative prognostic factor. Complications can lead to more severe consequences and may necessitate more aggressive interventions. 
• Age of the Patient: The prognosis may be affected by advanced age and may be linked to an increased risk of complications. Critical illness-related stress may be harder for elderly people to handle. 
• Organ Failure: The occurrence of multi-organ failure or dysfunction can significantly impact the prognosis. The involvement of other organs may complicate the management of acalculous cholecystitis. 

Clinical History

Age Group: 

Elderly Individuals (65 years and older): 

• Elderly patients may present with atypical or subtle symptoms. 

• Common symptoms include abdominal pain, tenderness, and fever, but these may be less pronounced. 

Younger Adults: 

• Younger adults may present with more classic symptoms of cholecystitis, such as tenderness, nausea, and vomiting. 
• The acuity of presentation can vary, but it is often associated with critical illness or underlying conditions. 

Physical Examination

Abdominal Examination: 

Right Upper Quadrant (RUQ) Abdominal Pain and Tenderness: 

• Patients typically experience pain and tenderness in the right upper quadrant of the abdomen. Palpation in this area may elicit discomfort or pain. 
• Murphy’s sign, characterized by pain or an abrupt halt in inspiration during palpation of the right subcostal area, may be positive. However, this sign can be less reliable in acalculous cholecystitis compared to calculous cholecystitis. 

Guarding and Rigidity: 

• Guarding (involuntary tensing of the abdominal muscles) and rigidity may be present, especially in severe cases or when complications such as perforation are suspected. 

Rebound Tenderness: 

• Rebound tenderness, or increased pain upon the sudden release of pressure after palpation, may be assessed cautiously. 

Systemic Signs of Inflammation: 

• Fever: Patients with acalculous cholecystitis may present with fever, indicating an inflammatory response. 
• Tachycardia: Increased heart rate (tachycardia) may be present, reflecting the systemic effects of inflammation. 
• Hypotension: In severe cases, hypotension may be a sign of hemodynamic instability, often associated with sepsis or systemic inflammation. 

General Appearance: 

• Ill-Appearing or Critically Ill: Patients with acalculous cholecystitis, especially in the context of critical illness, may appear ill or critically ill. 

Respiratory Examination: 

• Shallow or Guarded Breathing: Respiratory examination may reveal shallow or guarded breathing, especially if the patient is trying to minimize movement due to abdominal pain. 

Skin Examination: 

• Jaundice: Jaundice may be present in cases where acalculous cholecystitis is associated with underlying liver dysfunction. 

Age group

Associated comorbidity

Critically Ill Patients: 

• It is frequently seen in critically ill patients in intensive care units (ICUs). 
• Associated conditions may include severe infections, sepsis, trauma, major surgeries, or burns. 
• The stress and inflammatory response from critical illness contribute to gallbladder inflammation. 

Immunocompromised Individuals: 

• Patients with HIV/AIDS or undergoing immunosuppressive therapy, may be more susceptible to infections leading to acalculous cholecystitis. 

Post-Operative Cases: 

• Individuals who have undergone major surgeries, especially those involving the gastrointestinal or vascular systems, may develop acalculous cholecystitis postoperatively. 

Total Parenteral Nutrition (TPN) Use: 

• Prolonged use of total parenteral nutrition (TPN) without concurrent oral intake is a risk factor for acalculous cholecystitis. 

Associated activity

Acuity of presentation

Acute Presentation: 

• Acalculous cholecystitis often presents acutely, with sudden-onset symptoms such as severe abdominal pain, tenderness, fever, and signs of systemic inflammation. 
• Patients may appear critically ill, especially in the context of severe infections or trauma. 

Subacute Presentation: 

• In some cases, the symptoms may develop more gradually, and the presentation may be subacute. 
• Subacute cases may still involve significant inflammation and complications, but the onset of symptoms may be less abrupt. 

Chronic Presentation: 

• Chronic acalculous cholecystitis is less common but can occur, particularly in individuals with ongoing underlying conditions leading to gallbladder dysfunction. 
• Chronic cases may have less intense symptoms but can still result in complications over time. 

Differential Diagnoses

• Cholangitis: It is a medical condition characterized by inflammation of the bile ducts. The inflammation is often a result of an obstruction in the common bile duct, which can be caused by factors such as gallstones, bacterial infections ascending from the duodenum, or tumors in the bile ducts. Clinical presentation typically includes Charcot’s triad, consisting of fever, jaundice, and right upper quadrant pain.  
• Acute Cholecystitis: It is characterized by inflammation of the gallbladder, often associated with the blockage of the cystic duct, typically by gallstones. This condition can also result from ischemia or infection of the gallbladder wall. Clinical presentation includes severe right upper quadrant abdominal pain, fever, nausea, vomiting, and positive Murphy’s sign (tenderness and a pause in inspiration during palpation of the right upper quadrant). 
• Pancreatitis: It is the inflammation of the pancreas, and various factors, including gallstones, alcohol consumption, trauma, and infections can cause it. Clinical presentation often includes severe abdominal pain that may radiate to the back, along with nausea and vomiting. 
• Hepatitis: It refers to inflammation of the liver, and it can have multiple causes, including viral infections (hepatitis A, B, C, etc.), alcohol consumption, autoimmune conditions, and certain medications. Clinical presentation includes jaundice, fatigue, nausea, abdominal pain, and elevated liver enzymes.

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Medical Management: 

• Fluid Resuscitation: Intravenous (IV) fluid resuscitation is initiated to maintain hydration and support hemodynamic stability, especially in critically ill patients. 
• Antibiotics: Broad-spectrum antibiotics are typically administered to cover a range of potential pathogens causing inflammation. Common choices include third-generation cephalosporins, quinolones, or piperacillin-tazobactam. Adjustments to the antibiotic regimen may be made based on culture results and the patient’s response to treatment. 
• Percutaneous Cholecystostomy Tube (PTC) Placement: In critically ill or high-risk patients who are not suitable candidates for immediate surgery, percutaneous cholecystostomy tube placement may be considered.PTC allows for drainage of infected bile, reducing gallbladder distension and inflammation. 

Surgical Intervention: 

Cholecystectomy: 

• Definitive treatment often involves the removal of the gallbladder (cholecystectomy). 

• In stable patients, laparoscopic cholecystectomy is the preferred approach. However, open cholecystectomy may be necessary in more severe cases or if laparoscopic surgery is contraindicated. 
• Early cholecystectomy is generally recommended once the patient’s clinical condition has stabilized. 

Supportive Care: 

• Pain Management: Analgesics may be administered for pain relief. 
• Nutritional Support: Nutritional support is essential, especially in patients with prolonged fasting or those unable to tolerate oral intake. Enteral or parenteral nutrition may be considered. 

Monitoring and Follow-up: 

• Clinical Monitoring: Continuous monitoring of vital signs, laboratory parameters, and clinical status is essential. Serial imaging studies may be performed to assess the response to treatment and to detect any complications. 

Management of Complications: 

• Complications such as Perforation or Gangrene: If complications like gallbladder perforation or gangrene are present, the management approach may need to be more aggressive. Surgical exploration and intervention may be required to address complications. 

Underlying Condition Management: 

• Treatment of Underlying Causes: If acalculous cholecystitis is secondary to a specific underlying condition (e.g., sepsis, trauma), addressing the primary cause is crucial for a comprehensive treatment approach. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

use-of-a-non-pharmacological-approach-for-treating-acalculous-cholecystitis

• Low-Fat Diet: A low-fat diet can help reduce the workload on the gallbladder, as fats stimulate the release of bile. This may ease symptoms and prevent exacerbation of inflammation. 
• Increased Fluid Intake: Staying well-hydrated can help prevent complications and promote overall digestive health. 
• Enteral Nutrition: In severe cases, especially when the patient is unable to tolerate oral intake, enteral nutrition through a feeding tube may be considered. This can help provide essential nutrients without putting additional stress on the digestive system. 
• Heat Therapy: Applying heat to the affected area can help alleviate pain and discomfort associated with acalculous cholecystitis. 
• Early Ambulation: Encouraging early ambulation or gentle physical activity can promote digestion and prevent complications associated with immobility. 
• Close Clinical Observation: Regular monitoring of vital signs and clinical symptoms is essential. Observation may include regular ultrasound imaging to assess gallbladder inflammation and response to treatment. 

• Percutaneous Cholecystostomy: In some cases, a non-surgical intervention such as percutaneous cholecystostomy may be performed. This involves draining fluid from the gallbladder using a catheter inserted through the skin, which can relieve symptoms and inflammation. 
• Stress Reduction Techniques: Since stress can exacerbate symptoms, techniques such as mindfulness, relaxation exercises, and counselling may be beneficial. 

Role of analgesics in the treatment of acalculous cholecystitis

Analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, may be prescribed to manage the pain associated with acalculous cholecystitis. NSAIDs, such as diclofenac, can help reduce inflammation and provide pain relief. However, caution should be exercised in patients with renal or gastrointestinal issues. 

NSAIDs not only provide pain relief but also have anti-inflammatory properties. By reducing inflammation, these medications can contribute to the overall management of cholecystitis. In cases where the pain is severe or not well-controlled with NSAIDs, opioid analgesics may be considered.

These medications, such as morphine or oxycodone, act on the central nervous system to provide more potent pain relief. 

The choice of analgesic may vary based on the patient’s factors, such as the severity of pain, overall health, and potential contraindications or side effects of specific medications. 

use-of-intervention-with-a-procedure-in-treating-acalculous-cholecystitis

Cholecystostomy Tube Placement: 

Indication: Cholecystostomy tube placement is often considered in cases of acalculous cholecystitis where there is significant inflammation or infection or when the patient is not a suitable candidate for immediate surgery. 

Objective: The primary goal of placing a cholecystostomy tube is to drain the infected or inflamed contents of the gallbladder, relieving pressure and allowing for improved clinical outcomes. 

Procedure: 

• Percutaneous Approach: The cholecystostomy tube is usually placed percutaneously, meaning through the skin. This is often done under imaging guidance, such as an ultrasound or CT scan, to position the tube accurately. 
• Local Anesthesia: Local anaesthetic is usually used to numb the region before the tube is implanted. 

Drainage: Once the tube is in place, it allows for the continuous drainage of bile and infected material from the gallbladder into an external drainage bag. 

Monitoring: The patient is closely monitored for improvements in clinical symptoms, such as a reduction in pain and signs of infection. 

Considerations for Cholecystostomy Tube Placement: 

• Critically Ill Patients: This intervention is often considered in critically ill patients who may not be able to undergo surgery immediately or who have a high surgical risk. 

• Failed Conservative Management: If conservative measures such as antibiotics and supportive care do not lead to improvement, or if the patient’s condition is worsening, a cholecystostomy tube may be considered. 
• Bridge to Surgery: In some cases, cholecystostomy tube placement serves as a temporary measure, providing relief until the patient is stable enough for a definitive surgical procedure, such as cholecystectomy (surgical removal of the gallbladder). 
• Complications: Although generally considered safe, cholecystostomy tube placement carries some risks, including infection, bleeding, or injury to surrounding structures. Close monitoring and appropriate management of any complications are essential. 

use-of-phases-in-managing-acalculous-cholecystitis

Managing acalculous cholecystitis often involves different phases of care, including initial assessment, acute intervention, and long-term management. 

Initial Assessment: 

• Clinical Evaluation: Assess the patient’s clinical presentation, including symptoms such as fever, abdominal pain in the right upper quadrant, and signs of systemic illness. 
• Diagnostic Imaging: Use imaging studies, such as ultrasound, to confirm the diagnosis and assess the severity of inflammation in the gallbladder. 
• Laboratory Tests: Perform blood tests, including complete blood count (CBC) and liver function tests, to evaluate for signs of infection and liver involvement. 

Acute Intervention Phase: 

• Supportive Care: Initiate supportive care measures, such as nil per os (NPO) to rest the gallbladder and intravenous (IV) fluids for hydration. 
• Pain Management: Administer analgesics, such as nonsteroidal anti-inflammatory drugs (NSAIDs) or opioids, to alleviate pain. 
• Antibiotics: Start broad-spectrum antibiotics to address bacterial infection, a common complication of acalculous cholecystitis. 
• Cholecystostomy Tube Placement: Consider the placement of a cholecystostomy tube to drain the gallbladder contents, especially in critically ill patients or those with contraindications to surgery. 
• Monitoring: Regularly monitor the patient’s clinical response, vital signs, and laboratory parameters. 

Transition to Definitive Management: 

• Surgical Consultation: If the patient is stable, consult with a surgeon to determine the appropriateness and timing of a surgical intervention, such as cholecystectomy. 
• Further Imaging: Obtain additional imaging studies if necessary to assess the extent of inflammation and any complications. 

Definitive Management Phase: 

• Cholecystectomy: Perform surgical removal of the gallbladder (cholecystectomy), which is the definitive treatment for acalculous cholecystitis in many cases. 
• Laparoscopic Approach: Whenever feasible, a laparoscopic cholecystectomy may be preferred for its minimally invasive nature and faster recovery. 
• Open Surgery: In some cases, an open cholecystectomy may be necessary, especially in the presence of severe inflammation or complications. 

Postoperative Care and Follow-Up: 

• Recovery: Provide postoperative care, including pain management, monitoring for complications, and resumption of oral intake. 
• Follow-Up Imaging: Perform follow-up imaging studies to ensure the resolution of inflammation and rule out any residual or recurrent issues. 
• Addressing Underlying Causes: If acalculous cholecystitis is associated with an underlying medical condition (e.g., critical illness, trauma), address and manage the underlying cause. 

Long-Term Management: 

• Lifestyle Modifications: Guide dietary modifications, especially if the patient experiences post-cholecystectomy syndrome. 
• Monitoring for Complications: Regularly monitor for any long-term complications, such as bile duct issues, and address them as needed. 

Medication

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References

Acalculous Cholecystitis:ncbi.nlm.nih