IVIG For Major Surgery-Associated Secondary Immunosuppression

After major surgical procedures like organ transplantation or open-heart surgery, your body goes through a lot more than what you see on the outside. The physical stress of the procedures can weaken your immune system, which is also known as major surgery-associated secondary immunosuppression or surgery-induced secondary immunosuppression. 

Secondary immunosuppression after major surgery also raises the risks of serious complications like pneumonia, bloodstream infection (sepsis), or delayed wound healing in many patients. Globulin miễn dịch tiêm tĩnh mạch (IVIG) is sometimes used as an adjunct therapy to support the immune system during this vulnerable period. 

Read on to learn what surgery-related immunosuppression is, what recent studies show, how IVIG may help, and who may benefit from this treatment.

Major Surgery-Associated Secondary Immunosuppression: Overview

Major surgery-associated secondary immunosuppression occurs as a consequence of an external factor (such as surgery and the physical stress it creates), not by a disease or primary immune defect that the patient may already have. 

Generally, when a person undergoes major surgery such as heart surgery, organ surgery, trauma repair, or a major abdominal operation, their body experiences drastic immunological changes. 

The immune system reacts in two stages: the hyperinflammation phase and the compensatory anti-inflammatory phase (CARS). 

In the hyperinflammation phase, which begins within a few hours after surgery, the body activates a strong inflammatory response to manage the tissue injury. Levels of inflammatory molecules (such as TNF-α, IL-1β, and IL-6) rise, immune cells rush to the injury site, and swelling occurs as part of the healing process. 

After this initial surge, the body shifts into the CARS phase to calm the inflammation caused by elevated cytokines and heightened immune activity. However, sometimes, this “calming response” becomes so strong that it results in immunosuppression. This leads to:

• Reduced immune cell activity (e.g., T cells, B cells & natural killer cells) 
• Reduced antibody levels (IgG and IgM)
• Imbalanced protective cytokine levels
• Impaired neutrophil and macrophage function

These changes typically last from several days to several weeks, depending on the surgery type and patient condition.

Clinical Consequences of Surgery-Induced Immunosuppression

Many post-operative patients, especially those who are older and critically ill, become vulnerable to serious complications due to low immune strength (secondary immunosuppression). Some of the reported clinical complications include: 

• Hạ gammaglobulin máu (low level of circulating antibodies)
• Post-operative infections (such as pneumonia, wound infection, sepsis, or septic shock)
• Severe systemic inflammatory response syndrome (SIRS)
• Slower recovery and longer ICU or hospital stays

Ví dụ, một học found that infants who underwent heart surgery with cardiopulmonary bypass experienced a sharp drop in their IgG levels (reduced to less than half of baseline within 24 hours). More than half of the children (about 53%) developed post-operative hạ gammaglobulin máu (low IgG). This shows how significantly surgery can weaken their immune defenses.

Tương tự như vậy, một prospective study of 60 patients undergoing abdominal surgery found that patients who had emergency surgery developed systemic inflammatory response syndrome (SIRS) after the surgery. The higher SIRS scores were associated with a slower recovery process and longer hospital stays. 

IVIG and Secondary Immunosuppression After Surgery: What Research Says

There is currently no strong, high-quality data that directly examines the use of IVIG for major surgery-associated secondary immunosuppression. However, several related studies have reported the promising effects of IVIG in managing post-operative complications that may be caused by secondary immunosuppression.  

Ví dụ, một single-center, prospective, double-blind, randomized study reported that when an intravenous immunoglobulin A- and immunoglobulin M-enriched solution was administered immediately after cardiac surgery, it significantly reduced the incidence of post-operative infections in patients.

Similarly, an ICU-based retrospective study found that IVIG use in ICU septic patients significantly reduced in-hospital mortality and improved laboratory biomarkers (e.g., CRP, albumin) over time. 

Also, a recent systematic review and meta-analysis showed that IVIG, particularly IgM-enriched IVIG, is effective in both adult and neonatal sepsis and reduces sepsis mortality. 

These findings collectively indicate that IVIG may help mitigate post-surgical complications that may be induced by immunosuppression. However, more clinical studies and in-depth trials are required to evaluate the benefits of IVIG in secondary immunosuppression after surgery. 

Understanding the Role of IVIG in Surgery-Induced Immunosuppression

As already mentioned above, IVIG shows promise in selected post-operative situations, especially when a patient has severe infection (sepsis/septic shock) due to immunosuppression. Here are several ways in which IVIG can help reduce surgery-induced immunosuppression. 

1. Restores Antibody Levels and Clears Pathogens

It has been found that patients with complex procedures like heart surgery with cardiopulmonary bypass often develop hypogammaglobulinemia (a sharp drop in IgG/IgM levels due to blood loss, catabolism, or capillary leakage). 

Since IVIG is essentially a concentrated pool of kháng thể from thousands of donors, administering IVIG can restore antibody levels. These antibodies then fight pathogens that might cause post-operative secondary infections.

2. Modulates Immune Cell Function

Major surgery impairs immune cells, including T cells, B cells, and monocytes, and reduces their ability to respond to infections. IVIG contains antibodies that interact with immune cells to enhance their function:

• Boosting phagocytosis (how immune cells “eat” bacteria)
• Supporting T-cell responses
• Regulating inflammatory pathways

3. Reduces Risk of Post-operative Infections

By restoring antibodies and supporting immune cell function, IVIG may reduce susceptibility to common post-operative infections, such as pneumonia, surgical site infections, or bloodstream infections.

Ví dụ, một nghiên cứu hồi cứu of adult patients undergoing orthotopic liver transplantation (OLT) who received an IVIG enriched in IgM (rather than a standard IgG-only formulation) had a significantly lower rate of new bacterial or fungal infections in the first 30 days after transplant and better 90-day survival. 

Some studies suggest that patients receiving IVIG show faster normalization of inflammatory markers, indicating improved immune response, even though evidence is limited.

4. Has Potential Anti-Inflammatory Effects

Surgery triggers a two-phase immune response: hyperinflammation (immediately after surgery) followed by immunosuppression. This sudden drop in immune strength also increases the risk of infection. 

IVIG, which has anti-inflammatory properties, can help balance the immune response, prevent excessive inflammation, and support defense against pathogens.

Even though IVIG has these theoretical benefits, current clinical evidence is limited. IVIG is usually reserved for high-risk patients, especially those with documented antibody deficiency, transplant recipients, and patients with severe infections or sepsis risk post-surgery. 

Who Might Be Considered for IVIG?

IVIG is not routinely used for all surgical patients. Instead, it is generally reserved for selected high-risk individuals based on their clinical status, lab findings, and infection risk. Patients who may be considered include:

• Solid organ or heart/lung/liver transplant recipients with hypogammaglobulinemia or recurrent/severe infections
• Post-operative patients with documented low immunoglobulin levels (e.g., low IgG) and a high risk of serious infection
• Critically ill patients with sepsis or septic shock in whom immune dysfunction or low antibody levels are suspected
• Infants or other vulnerable patients after complex procedures (such as cardiac surgery with cardiopulmonary bypass) who develop significant antibody loss

The decision to use IVIG is always individualized and made by the treating specialist team, taking into account potential benefits, risks, and alternative therapies.

Risks, Limitations, and Cost

Like any blood-derived product, IVIG carries potential risks and is not appropriate for everyone. Possible tác dụng phụ include infusion reactions (such as headache, fever, or chills), fluid overload, and, more rarely, serious complications like kidney injury or blood clots in patients who are already at risk.

In addition, the current evidence for IVIG use specifically in surgery-associated secondary immunosuppression is limited and based largely on small or heterogeneous studies, so clear treatment guidelines are still evolving. IVIG is also an expensive therapy and may not be covered or approved for all indications, which means its use is typically reserved for patients in whom the expected benefit justifies the cost and potential risks.

Dòng cuối cùng

Major surgeries can temporarily weaken the immune system, leading to secondary immunosuppression, which increases the risk of infections and delays recovery. IVIG may help boost immunity, but data on its use specifically for surgery-associated secondary immunosuppression are limited. 

Few studies, however, suggest a potential role of IVIG in post-operative complications and indicate that it may be considered in high-risk patients, such as transplant recipients or those with antibody deficiencies or septic shock.