Introduction

Sepsis is a medical emergency which occurs when the body's immune response to infection is disrupted leading to systemic inflammation. On a global scale, it is a leading cause of illness and mortality. Sepsis is thought to kill over 11 million people every year, or 19.7% of all fatalities worldwide, and affects over 49 million people annually.¹ Sepsis is very deadly and can result in numerous organ failures and tissue damage having the respiratory system being one of the most impacted. A serious and frequent complication in sepsis patients is acute respiratory failure (ARF) which often manifests as acute respiratory distress syndrome (ARDS). This condition considerably worsens the prognosis of sepsis. 

This article will explore the pathophysiology, clinical presentation, complications, and management of acute respiratory failure as a complication of sepsis. Understanding these concepts is vital for clinicians to diagnose and treat patients more quickly and effectively.

Pathophysiology of sepsis-induced acute respiratory failure

The onset of ARDS is linked to acute respiratory failure in sepsis. The hallmarks of ARDS include diffuse alveolar damage, increased permeability of respiratory epithelial and vascular endothelial cells, vascular damage and inflammation resulting in pulmonary edema and compromised gas exchange.² There are numerous important pathways that help explain the pathophysiology of acute respiratory failure in sepsis.

Systemic Inflammatory Response Syndrome (SIRS) in Sepsis

In the pathophysiology of sepsis, the lungs are the most affected organ. The cascade of events caused on the lungs lead to acute respiratory failure. Systemic inflammatory response syndrome (SIRS) is caused by a dysregulated immunological response to infection resulting in systemic inflammation. This disruption of the innate immune response to infection is the major characteristic of sepsis.² 

Pro-inflammatory cytokines like tumour necrosis factor-alpha (TNF-α), interleukins (IL-1, IL-6), and chemokines are released during this process, aggravating endothelial dysfunction and increasing vascular permeability, which leads to extensive tissue damage and organ dysfunction, including lung dysfunction. The pulmonary system is most severely affected by SIRS. Protein-rich fluid builds up in the interstitial and alveolar gaps due to endothelial injury and inflammation. This causes acute alveolar injury, leading to pulmonary edema, decreased exchange of oxygen, thereby putting the patient at the risk of acute respiratory failure.² 

Impact of Sepsis on lung function

People with sepsis experience lung damage and can result in acute respiratory injury (ARI) and ARDS which are characterised by the lungs inability to remove carbon dioxide and oxygenate the blood, respectively causing hypercapnia and hypoxemia, accumulation of fluid in the alveoli, pulmonary fibrosis, and the release of inflammatory factors.³ 

Sepsis-induced multiple organ dysfunction

The event of sepsis often results in the failure of multiple organs of the body. Sepsis when progresses to septic shock manifests reduced perfusion resulting in decreased blood flow and oxygen delivery to vital organs of which the lung is part of. Often, dysfunction of a single organ is rare due to the interconnectivity of the organs. As a result, multi-organ damage occurs.⁴

Oxidative stress and hyperinflammatory response

During inflammation, there is a release of cytokines that causes cell permeability leading to the formation of reactive oxygen species (ROS). In the human body, there should always be a balance between the production of ROS and the protective antioxidant neutralising mechanism. When there is no equilibrium between these two events, oxidative stress occurs. The overproduced ROS induces oxidative stress on many organs including the kidney, liver and lung, leading to their damage.⁴

What are the risk factors for acute respiratory failure in sepsis?

There are possible risk factors that predispose a septic patient to acute respiratory failure. They include;

Pulmonary infections

Pulmonary infections affect the lungs directly, thereby predisposing the patient to respiratory complications.⁵

Lactic acidosis

Increase in the production of lactic acid in the blood results lactic acidosis. There is an inadequate distribution of oxygen to the vital organs and this contributes to the incidence of acute respiratory failure in sepsis.⁵

Smoking

Smokers who are diagnosed with sepsis are at higher risk of developing acute respiratory failure.⁶

Scoring system

Acute physiology, age and chronic health evaluation (APACHE) score and sequential organ failure assessment (SOFA) score are factors used to determine the seriousness of disease including sepsis. Patients with high APACHE and SOFA scores are at higher risk of developing acute respiratory failure in sepsis, than those with lower scores.^5,6 

Pancreatitis 

Patients with an inflamed pancreas who are diagnosed with sepsis are at risk of developing respiratory complications.^{2, 5}

Other risk factors of acute respiratory failure in sepsis include;

• Extreme abdominal pain (acute abdomen)
• Delay in fluid resuscitation⁷

Clinical manifestations of sepsis induced acute respiratory failure

A variety of respiratory symptoms are commonly observed in patients with sepsis-related acute respiratory failure. These includes;

Dyspnea 

Dyspnea, which is the shortness of breath is presented by patients with sepsis induced acute respiratory failure due to low arterial oxygen partial pressure (PaO2 in mmHG) to fractional inspired oxygen (FiO2).²

Hypoxemia 

Hypoxemia is when you have insufficient levels of oxygen in your blood. You may present with hypoxia if you have sepsis-related acute respiratory failure. In severe cases of hypoxemia, death may occur.² 

Pulmonary edema

Another sign of sepsis-related acute respiratory failure is pulmonary edema.²

Tachypnea

Tachypnea is a fast shallow breathing resulting from shortage of oxygen or excess of carbon dioxide in the body. It is a characteristic of sepsis-induced acute respiratory failure.⁸

What are the diagnoses of acute respiratory failure in sepsis?

The diagnosis of acute respiratory failure in sepsis involves a combination of clinical findings, tests and imaging. Among the diagnostic approaches include:

The release of inflammatory cytokines during septic shock keeps patients at a high risk of developing acute respiratory failure.⁵

Arterial blood gas (ABG) analysis

Arterial blood gas analysis is used in the diagnosis of patients with sepsis. This test measures the acid-base level of the blood, the amount of carbon dioxide and oxygen in the blood as well as lactate level. Due to the high cost of the analysis and lack of trained professionals, low and middle income countries, and many countries may not afford the test.⁹ 

Chest x-ray

Chest x-ray is done to observe the extent of lung damage. It is used to check for pulmonary edema caused by respiratory failure due to sepsis.¹⁰ 

Computed tomography (CT) scan 

CT scan is also used in the diagnosis of acute respiratory failure. A CT scan shows the extent to which the lung is damaged due to reduced lung capacity.¹¹ 

Lung ultrasound

Lung ultrasound can also be used to diagnose acute respiratory failure. This procedure uses the degree of lung aeration to determine the severity of respiratory failure.¹¹

Can acute respiratory failure in sepsis be managed and treated?

The management and treatment of acute respiratory failure in sepsis involve a multifaceted approach. They include:

Ventilatory support

Ventilation support of the lungs is done in order to open collapsed alveoli to improve oxygenation.¹²

Oxygenation

Optimal oxygenation is done to prevent hypoxia in patients who have developed ARF due to sepsis. Care must to taken to avoid the risk of hyperoxia (high oxygen level in the blood) during oxygenation, which can expose the lung to injury.¹²

Fluid management therapy

Giving too much liquids might make pulmonary edema worse. To prevent the lungs from becoming overloaded, fluid balance has to be regularly checked. This will prevent the risk of pulmonary edema and also improve oxygenation.¹²

Antimicrobial therapy

The use of antibiotics like macrolides or quinolones is recommended for the treatment of respiratory infection that may be associated with ARF.¹²

Use of corticosteroids 

The use of corticosteroids like intravenous dexamethasone may be required to reduce excessive inflammatory response.¹²

FAQ’s

How does sepsis damage the lungs?

The coagulation system is triggered in sepsis, vascular endothelial cell damage results in thrombosis and fibrin deposition, and anticoagulant system malfunction exacerbates lung injury and dysfunction. In the course of lung damage, platelets play a vital role.

Can asthma cause sepsis?

Asthma is linked to a lower risk of Sepsis and sepsis-related death.

What type of respiratory failure is associated with sepsis?

Acute respiratory distress syndrome (ARDS) is a devastating complication of severe sepsis. Sepsis and ARDS have similar underlying mechanisms, characterised by inflammation and endothelial dysfunction.

Summary

Sepsis-induced acute respiratory failure (ARF) often presents as acute respiratory distress syndrome (ARDS). Sepsis, a leading cause of global mortality, triggers systemic inflammation, particularly impacting the respiratory system. ARF in sepsis occurs due to diffuse alveolar damage, increased vascular permeability, and pulmonary inflammation, leading to impaired oxygen exchange and pulmonary edema.

Key risk factors for ARF in sepsis include pulmonary infections, lactic acidosis, smoking, high APACHE and SOFA scores, and septic shock. Patients with sepsis-induced ARF may manifest clinical symptoms like dyspnea, hypoxemia, pulmonary edema, and tachypnea. Diagnosis of this condition typically involves arterial blood gas analysis, chest X-ray, CT scan, and lung ultrasound.

Management and treatment include ventilatory support, optimal oxygenation, careful fluid management, antimicrobial therapy, and corticosteroids to reduce inflammation.