Multiorgan Dysfunction Case File

Multiorgan Dysfunction Case File

Eugene C. Toy, MD, Manuel Suarez, MD, FACCP, Terrence H. Liu, MD, MPH

Case 33

A 63-year-old man underwent a surgical appendectomy and colostomy formation for a ruptured appendicitis with abscess and devitalized cecum. At the time of the operation, he was noted to have necrosis and perforation of the cecum with fecal  peritonitis. On postoperative day 8, the patient remains on the ventilator with PAO2/FIO2 = 260. Over the past 48 hours, he has developed worsening oliguria with urine output of <300 mL over the past 18 hours. The patient is becoming visibly jaundiced.  ACT scan of the abdomen reveals no intrahepatic ductal  dilatation, moderate amount of postoperative inflammatory changes throughout the peritoneal  cavity, and no signs of active intrabdominal infections.

⯈What is the most likely diagnosis?

⯈What are the causes of the patient's current condition?

⯈How would you monitor and quantify the patient's organ dysfunction?

⯈What are your therapeutic strategies and goals for this patient?

ANSWER TO CASE

Multiorgan Dysfunction

Summary: This is a 63-year-man who had an operation for a ruptured appendicitis, and his course was complicated by colonic perforation and fecal peritonitis. The patient is now developing organ dysfunction despite adequate source control. He is showing signs of pulmonary dysfunction with compromised oxygenation (P/F ratio = 260). In addition, h e has new-onset compromised renal and hepatic functions a s seen by his decreased urine output and visible jaundice. There is no evidence of continued intra-abdominal pathology. 

• Causes of the patient's current condition: The patient's initial peritonitis and subsequent inflammatory response has resulted in organ dysfunction in multiple systems. 
• Monitoring and quantifying the organ dysfunction: Continuous monitoring of his organ functions via standard measures (urine output, MAP, oxygen saturation, etc) is mandatory, and the level of dysfunction is quantified using the multiple organ dysfunction scale. 
• Therapeutic strategies and goals for this patient: The therapy for multiple organ dysfunction is mainly supportive, addressing each organ system that is injured. The underlying cause should be treated. Mechanical support may be necessary, such as ventilatory support for pulmonary failure and hemodialysis for renal failure.

ANALYSIS

Objectives

1. To learn to identify, quantify, and manage multiple organ dysfunctions associated with critical illnesses.
2. To learn the factors that may contribute to the development of multiple organ dysfunction syndrome (MODS).
3. To learn the supportive care for patients with MODS.

Considerations

This patient presented with a single identifiable cause for his illness-appendicitis, cecal perforation with fecal peritonitis. His illness has not resolved with the removal of his diseased colon, irrigation of the peritoneal cavity, and antibiotic administration. Instead, despite appropriate treatment of his peritonitis, his overall status is continuing to deteriorate. His pulmonary function has declined with a P/F ratio that is indicative of acute lung injury. Likewise, he has acute kidney injury demonstrated by his progressive oliguria. His hepatic function has also deteriorated as evidenced by his visible jaundice. These organs become dysfunctional days following the inciting event and continue despite the resolution of his initial illness. These are indicative of secondary MODS.

Approach To:

Multiple Organ Dysfunction Syndrome

DEFINITIONS

MULTIPLE ORGAN DYSFUNCTION SYNDROME: The continued dysfunction of two or more organ systems that occurs as a result of a disruption in homeostasis. The organ dysfunction may continue despite the resolution of the initial event.

SYSTEMIC INFLAMMATORY RESPONSE SYNDROME: Occurs when 2 of the following are present:

1 . Body temperature <36°C or > 38°C

2. Heart rate >90 beats/minute

3 . Respiratory rate >20 breaths/minute

4. White blood cell count <4000 cells/mm³ or > 12,000 cells/mm³ or the presence of > 10% immature neutrophils (band forms)

ACUTE KIDNEY INJURY (AKI): AKI was formerly referred to as acute renal failure (ARF). AKI is defined by a rapid decline in renal function (<48 hours). The decrease in renal function is determined using urine output and/or serum creatinine levels. An absolute increase in serum creatinine of >0.3 mg/dL or a percentage increase in serum creatinine of >50% is indicative of AKI . Also, a reduction in urine output, defined as <0.5 mL/kg/h for more than 6 hours is also AKI .

ACUTE LUNG INJURY/ACUTE RESPIRATORY DISTRESS SYNDROME: Hypoxemic respiratory failure, of which the most severe form is acute respiratory distress syndrome (ARDS). Acute lung injury is defined as a P/F ratio of 200 to 300. ARDS is hypoxemic failure with a P/F ratio of <200, bilateral fluffy infiltrates on chest x-ray, and no evidence of congestive heart failure.

P/F RATIO: (PAO2/FIO2 ) X 100. This is used to identify the degree of pulmonary failure.

CLINICAL APPROACH

MODS is a clinical syndrome that has its origins in the ICU. MODS did not exist prior to the ability to keep patients alive who would have otherwise died from their disease processes. Once the ICU care began to evolve and became successful at sustaining patients after life-threatening illnesses, we began to see patients develop remote organ dysfunction despite resolution of their initial insults. Patients who develop MODS have increased length of ICU stays and a 20-fold increase in mortality rate when compared to those patients without MODS.

Pathophysiology

There are multiple factors that may contribute to the development of MODS. Originally, it was thought that MODS only occurred in patients who had severe sepsis. Although sepsis is responsible for almost three-fourths of MODS cases, any clinical scenario that leads t o significant inflammation o r host injury responses can cascade into MODS. The beginning of MODS starts with the normal, appropriate physiologic response to a single inciting event, such as pneumonia, pancreatitis, or a gunshot wound to the abdomen. This initial insult activates macrophages, which in turn release pro-inflammatory mediators, as well activate coagulation factors. The pro-inflammatory mediators interact with white blood cells resulting in their recruitment and activation. The inflammatory mediators also cause microvascular thromboses, apoptosis derangements, and increased capillary permeability. The procoagulant effects act in conjunction with the previously activated coagulation system, and serves to act as a local protective mechanism against injury. Once the original injury is treated, the inflammatory mediators and coagulation factors return to normal and healing is achieved.

However, occasionally, despite the resolution of the inciting event, the normal physiologic response acts as a positive feedback loop, leading to overamplification of the immune response. The activation of the white blood cells can also release pro- inflammatory mediators that activate more monocytes/macrophages, which in turn releases additional pro-inflammatory mediators. This continued inflammation and coagulation cause cellular damage, which in turn activates more inflammatory mediators. More cellular damage occurs with subsequent organ failure. Once this initial organ system fails, inflammatory mediators continue to be released, acting on other organ systems, until there is multiorgan dysfunction.

Once patients have been treated for their original injury and continue to have clinical deterioration, MODS should be considered as the diagnosis. Although the pulmonary system is often noted to be the first organ system to fail, there is no standard progression of organ failure. The degree of organ dysfunction is often graded by the multiple organ dysfunction syndrome score (see Table 33-1). There is no single therapy for MODS and the treatment is largely supportive. The goal of therapy is to decrease the continued cellular injury in each organ so that the positive feedback loop can be interrupted with an aim toward return of normal homeostasis.

The best treatment of MODS is to identify the patients at greatest risk for MODS and begin preemptive therapy to limit its progression. This is best accomplished by optimizing cardiac and pulmonary performance early in the disease process,

Data from: Marshall JC, Cook DJ, Christou NV, et al. Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Grit Care Med. 1995 Oct;23(10):1638-1652.

providing early and adequate nutritional support, giving appropriate antibiotics to decrease the risk of resistant "super" infections, and minimizing the use of blood transfusions.

The identification of organ failure in patients with MODS necessitates continuous monitoring and supportive therapy for that organ. Increased vigilance should also be used to monitor and detect new organ failure during treatment. Mortality in the ICU is related to the number of organs and the severity of organ injury. Prognosis depends on the MOD score (Table 33-2 ).

The pulmonary system is frequently the earliest organ system to fail. Patients who develop MODS are often already intubated and are unable to be weaned off the ventilator despite treatment of their original illness. Acute lung injury (ALI) is an umbrella term for hypoxemic respiratory failure. The most severe form of ALI is ARDS. In acute lung injury, there is a failure of normal gas exchange. The inflammation affects oxygen uptake more than carbon dioxide elimination. This occurs early because of atelectasis and intravascular thrombosis. As the inflammatory process progresses, there is an increase in capillary permeability, leading to increase in alveolar fluid that increases the distance for oxygen diffusion to occur.

Identification of a P/F ratio of <300 indicates that the patient has acute lung injury. A P/F ratio of <200 is a risk factor for having ARDS. The definition of ARDS is having a P/F ratio <200 with bilateral fluffy infiltrates without evidence of congestive heart failure. Once acute lung injury or ARDS is diagnosed, lung-protective ventilation should be initiated. The goal for treatment of these patients is to continue to provide adequate oxygenation without further damage to the alveoli. This is best accomplished with low tidal volumes, increased positive end expiratory pressure (PEEP), and limiting peak plateau pressures. This lung-protective ventilation strategy decreases the incidence of volutrauma and barotrauma, and also decreases the levels of inflammatory mediators.

The biggest risk factor for developing MODS is circulatory failure within the first 24 hours of admission. This is why early management of resuscitation is extremely important in critically ill patients. The cause of circulatory failure during MODS is multifactorial. During the initial phase of inflammation, TNF and reactive oxygen species inhibit cardiac contractility. Additionally, the early cytokines released result in increased vascular permeability and vasodilation. This combination results in loss of effective preload, contractility, and afterload. The treatment for circulatory failure is fluid resuscitation. However, this treatment may contribute to the worsening of the system, as the fluids administered may not stay intravascular because of the increased vascular permeability. This contributes to the increase in organ failure and the cycle continues. The use of pressors is advocated only once it is determined that the intravascular volume has been repleted. Likewise, the blood and blood products can be used to increase intravascular volume, but are associated with complications. The injudicious use of vasopressors and blood transfusions is known to increase morbidity and mortality. The use of ScVO2 (central venous oxygen saturation obtained via central venous catheter) , lactate, and base excess can help guide the initial resuscitation. The ScVO2 reflects the upper body/head extraction of oxygen and is usually higher than the mixed venous O2 in situations of shock.

Acute kidney injury (AKI), formerly referred to as acute renal failure (ARF) is a decline in renal function as determined by either a rise in serum creatinine levels or a decrease in urine output. Serum creatinine levels that increase by 0.3 mg/dL or by 50% from baseline is AKI. Urine output that is <0.5 mL/kg/h for more than 6 hours is also AKI. In MODS, the causes of AKI are both intrinsic and pre-renal. Early in the course of MODS, hypotension can lead to early AKI, while examples of late causes are nephrotoxic drugs and contrast-induced nephropathy. Hypoxemia can lead to cellular destruction and altered renal function. Renal replacement therapy (dialysis) may be necessary to support a patient with MODS and AKI.

Patients with MODS can develop hepatic dysfunction as identified by cholestasis and jaundice. Bilirubin levels are used to determine the severity of dysfunction on the MODS-scoring system. The elevation of bilirubin is most likely a result of leakage of bile from hepatic canaliculi that have been damaged by cytotoxins and inflammatory mediators. The elevation of acute-phase reactants, such as C-reactive protein and α1 antitrypsin, is common during the inflammatory stages of MODS. The hepatic dysfunction identified in MODS is usually not life threatening. There is no specific supportive therapy aimed directly at the liver, so continued support of the other systems is all that is necessary.

CLINICAL CASE CORRELATION

• See also Case 1 (Early Awareness of Critical Illness), Case 3 (Scoring Systems and Patient Prognosis), Case 22 (Acute Liver Failure), and Case 23 (Acute Kidney Injury).

COMPREHENSION QUESTIONS

33.1  A 63 -year-old, otherwise healthy man is admitted to the ICU with sepsis and right lower lobe pneumonia. He is started on broad-spectrum antibiotics and is being mechanically ventilated. The ventilator settings are assist-control ventilation, tidal volume of 9 mL/kg, oxygen concentration of 60%, and a PEEP of 8. Two days later, his chest x-ray shows bilateral fluffy infiltrates and a PAO2/FIO2 ratio of 195 . His oxygen saturations are 85%. The best treatment for this patient is:

A. Increase the tidal volume on the ventilator.

B. Decrease the amount of PEEP.

C. Add additional antibiotic coverage.

D. Increase the PEEP and decrease the tidal volume.

E. Perform bronchoscopy to rule out atypical pneumonia.

33.2  A 35-year-old man with a history of chronic alcohol abuse is admitted with severe pancreatitis that does not appear to be necrotic on CT scan. He is admitted to the ICU with respiratory failure and low urine output. His bilirubin is 3.8 mg/dL. He has no history of cholelithiasis and ultrasound shows normal ductal anatomy. The most likely cause of his multiorgan failure is:

A. Release of pancreatic enzymes into the circulation, degrading level of serum proteins

B. Infection of the pancreas

C. Blockage of the biliary system

D. Malnutrition from chronic alcoholism

E. Release of inflammatory cytokines from monocytes

33.3  A 21-year-old man sustained a gunshot wound to the abdomen. He had multiple small bowel enterotomies repaired and a short segment of bowel was resected. After 36 hours, he remains intubated and develops increasing white blood cell count, tachycardia, and fevers. Which of the following statements is most accurate regarding the patient's possible diagnosis of MODS?

A. This patient likely has MODS based the fever and elevated white cell count

B. This patient likely has MODS based on bowel system injury

C. This patient does not likely have MODS without more evidence of organ system injury

D. This patient does not likely have MODS because of his young age

33.4 The best treatment for MODS is:

A. Preventative

B. Large volume resuscitation

C. Dialysis

D. Lung protective ventilation

E. Enteral nutrition

ANSWERS TO QUESTIONS

33.1  D. This patient is hypoxic and has a diagnosis of ARDS. The essentials of treating ARDS revolve around decreasing the incidence of both volutrauma and barotrauma. The goal is to decrease the tidal volume, increase the PEEP, and maintain adequate oxygenation. Permissive hypercapnia is allowed as long as the pH does not fall below 7.2. The low oxygen saturations in this patient should be treated by decreasing his tidal volume and increasing the PEEP using the ARDS net protocol strategy for lung protective ventilation. Atypical pneumonias are mostly encountered in immunocompromised hosts; therefore, not a likely diagnosis in this otherwise healthy man.

33.2  E. While the other mechanisms may be the instituting and contributing factors, the systemic inflammatory response is secondary to the release of cytokines from monocytes that have been activated. Under normal circumstances, the cytokine release decreases as the patient's inciting pathology improves. Occasionally, the inflammatory cascade does not subside and becomes a positive feedback loop. This is the beginning of MODS.

33.3  C. Increasing WBC, fever, and tachycardia in this patient can represent a number of possible complications. Given the circumstances of his injury, missed intra-abdominal injury and intra-abdominal infections are distinct possibilities. Similarly, this patient who is a trauma victim and who recently underwent emergency laparotomy for intraabdominal injuries is at risk for the development of pneumonia. The timing of these symptoms do not fit the typical picture of MODS, which generally occurs days to weeks following the initial insult. Additionally, there is currently no evidence of acute kidney injury or hepatic injury or pulmonary injury.

33.4  A. The best treatment for MODS is supportive and prevention. Resuscitation, dialysis, enteral nutrition, and lung protective ventilation are all treatment or supportive modalities used when treating a patient with MODS. However, identifying which patients are at risk for developing MODS and instituting early and appropriate care before MODS starts is the best treatment. Once MODS occurs, supportive care through the above modalities is often necessary.

References

Barie PS, Hydo LJ , Pieracci FM, Shou J , Eachempati SR. Multiple organ dysfunction syndrome in critical surgical illness. Surg Infect (Larchmt). 2009 Oct; l 0 ( 5 ) :369-3 7 7. 

Dewar D , Moore FA, Moore EE, Balogh Z. Postinjury multiple organ failure. Injury . 2009 Sep;40 ( 9 ) : 9 1 2-928. 

Mizock BA. The multiple organ dysfunction syndrome. Dis Mon. 2009 Aug; 5 5 ( 8 ) :476-526.

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