Occult Sepsis in Traumatic Injuries

Author: Brit Long, MD (@long_brit, EM staff physician at SAUSHEC, USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Jennifer Robertson, MD, MSEd

It is 7pm, and several trauma patients are already being treated in the emergency department (ED). This includes one male patient who was transported to the ED by emergency medical services (EMS) from the site of a bad motor vehicle crash (MVC). He required orotracheal intubation, two units each of packed red blood cells (PRBC), two units of fresh frozen plasma (FFP), and a right-sided chest tube. Unfortunately, he also had a positive FAST (Focused Assessment with Sonography for Trauma) with continued hypotension. Thus, the patient was transported to the operating room (OR) for definitive repair of his injuries.

Suddenly, the radio alerts again. EMS is bringing in another patient who was the driver in a head-on collision. The 54-year-old male patient is tachycardic, has a blood pressure (BP of 92/54 mm Hg, an oxygen saturation of 92% on 2 liters (L) nasal cannula (NC) oxygen (O2), and a respiratory rate (RR) of 22 breaths/minute (min).  The patient arrives in the ED with repeat vital signs (VS) showing a BP 110/56 after one L of normal saline (NS), a heart rate (HR) 101, RR 22/min, and an O2 saturation of 94% on 2L NC. He is protecting his airway, has a Glasgow Coma Scale (GCS) of 12, has symmetric rise and fall of his chest with equal breath sounds, and has warm skin with palpable distal pulses. His rapid glucose level (D-stick) is 192, and his FAST with lung windows (E-FAST) is negative for acute injury.  The cardiac window demonstrates hyperkinesis. A nurse shouts out that his temperature is 101° Fahrenheit (F). The patient’s venous blood gas (VBG) demonstrates normal electrolytes but an abnormal lactic acid of 4.2 and a base excess of (-) 10.

Two large peripheral intravenous lines are placed and the patient is put on supplemental O2 by facemask. However, the patient remains febrile, tachycardic and tachypneic. His mental status is also not appropriate. Is something else going on with this patient?

Trauma

Emergency physicians are well acquainted with trauma. Trauma is the predominant cause of mortality in patients ages 1 year to 44 years, and it is the third leading cause of death overall. The major causes of death include head injury, chest injury, and vascular injury. Interestingly, 90% of patients survive the initial trauma, but ongoing morbidity occurs due to traumatic brain injuries, chronic pain, and/or extremity injuries.^1,2

However, despite the obvious causes of morbidity from trauma, some trauma patients may also be septic. Obviously we are drawn to the initial stabilization with Airway-Breathing-Circulation-Disability-Exposure-FAST-Glucose.  Unfortunately, many patients with trauma also demonstrate SIRS (systemic inflammatory response) criteria, which creates a diagnostic challenge. What steps can be taken in order to prevent missing sepsis in trauma?

SIRS and Sepsis

SIRS and sepsis are common clinical entities, but there are distinct differences because there must be infection for sepsis to occur, while SIRS can occur without an underlying infection.

The definition of SIRS includes: HR > 90 beats per minute (bpm), RR > 20/min or arterial carbon dioxide tension (PaCO2) < 32 mmHg, temperature < 36^oCelcius (C) or > 38^oC, and a white blood cell (WBC) count < 4 x 10⁹ cells/L or > 12 x 10⁹ cells/L or > 10% bands. Two or more of these equals SIRS, and two or more with a source of infection equals sepsis.^1,2 Unfortunately these criteria are non-specific, and the criteria alone do not provide a diagnosis or predict outcome.^3,4 As you can see, traumatic injury often meets SIRS criteria. The updated Sepsis 3.0 definition will be discussed later in the post.

The diagnostic challenge is present because sepsis is defined using SIRS criteria, but it is not always initially known which patients are simply SIRS without infection, while others have actual sepsis.  This post will evaluate two aspects of sepsis in trauma: sepsis with initial trauma and sepsis after multiple trauma.

Together, sepsis and trauma are deadly. Patients with acute trauma are often in extremis, and many will meet SIRS criteria. However, a source of infection is necessary to diagnose true sepsis and this can be difficult due to other clinical findings. For example, an infiltrate on chest x-ray could be lobar pneumonia or a pulmonary contusion. Sepsis hinges on suspected infection and unfortunately, is a subjective diagnosis.

Emergency physicians train and work to develop excellent clinical gestalt and be masters of resuscitation. The clinician at the bedside is the best diagnostic test available.  In the setting of acute trauma, there are several steps that can be followed in order to reduce the risk of missing sepsis.

1. First, work to stabilize the patient and take care of Airway-Breathing-Circulation-Disability-Exposure-FAST/Fetus-Glucose (D-stick). Obtain laboratory and radiographic studies as indicated, but also try to determine what could be missed before automatically sending the patient to the computed tomography (CT) scanner.
2. Do your best to obtain an accurate history. What was the cause of the trauma? If a patient, especially an elderly patient, was in a MVC, did he or she lose consciousness? Was there an arrhythmia? Was the patient weak from hypotension in the setting of a pneumonia (PNA) or urinary tract infection (UTI)? Try to understand why the trauma occurred and if there were any other issues before the trauma, such as symptoms concerning for infection such as dysuria, cough or fever. If a patient is not cooperative or is confused or intubated, try to obtain a collateral history from the patient’s family and/or from EMS.

3. Next, ensure a complete examination is done. Never forget to look over every nook and cranny in the trauma patient (primary survey = exposure) and complete a thorough secondary examination, including the feet, back, and perianal regions. You may uncover cellulitis, necrotizing fasciitis, or even a head/ears/nose/throat (HEENT) infection. Does the patient have stigmata of drug use and new murmur (or better yet, ultrasound (US) evidence of vegetation on cardiac views)? Are there any other clinical findings consistent with endocarditis, pneumonia, a UTI, or meningitis? Also, beware of the altered patient with negative imaging. New-onset delirium can be a marker of infection, especially in older patients.⁵

4. Carefully scrutinize VS of the patient. We commonly consider a systolic BP (SBP) < 90 mmHg as hypotensive. However, this may be an extremely abnormal blood pressure compared to a patient’s baseline. An older male may have a baseline BP of 170/100. In the setting of trauma, a drop of 30mmHg to a SBP of 140 mmHg is abnormal and a marker of disease.⁵ Pay close attention to the patient’s temperature. Any fever requires an explanation. Trauma may slightly elevate a baseline temperature, but any reading over 100.4 requires explanation and evaluation. Tachypnea is an early marker of infection in the elderly (one of the first).^5,6 A trauma patient with abnormal VS, especially tachypnea and fever, in the setting of normal imaging, requires further evaluation and consideration of sepsis.

Older patients present an even greater challenge in trauma.^5,6 Many of these patients will be on a beta-blocker or other hypertensive medications. Unfortunately, if you resuscitate just based on VS alone, half of trauma patients will not receive proper resuscitation. The relationship of cardiac output and blood pressure is reliable for diagnosing shock only with almost 50% of total blood loss.⁷

5. Use your ultrasound. Almost every trauma patient receives an E-FAST exam. Pay close attention to the cardiac window (hyperkinesis), and consider looking at the lungs for findings consistent with pneumonia (consolidation, shred sign, bronchograms). Hypotension and loss of intravascular volume can be due to bleeding from trauma or third-spacing in sepsis. A view of the inferior vena cava (IVC) will show respiratory variation in the setting of hypovolemia/third spacing from trauma or sepsis.

6. Use biomarkers carefully. Lactic acid and base excess are commonly used tests in resuscitation, especially in trauma. Abnormal lactic acid and base excess levels speak to hypoperfusion, which is associated with increased morbidity and mortality. These markers reflect metabolic derangement at the cellular level and will often elevate before clinically apparent end organ damage or decompensation occurs. Base excess (BE) more negative than -6 mmol/L and a lactic acid greater than 2.0 are consistent with shock, or occult shock in those patients with normal VS.^8-14 If these tests are abnormal in the setting of trauma, but your other evaluations including imaging and labs are normal, strongly consider other diagnoses. Both tests are markers of end organ damage and hypoperfusion, and if abnormal, some pathology is present.

One very informative article about occult infection in sepsis found that in those trauma patients with infection, close to 70% did not normalize their lactate levels after initial resuscitation. Injury severity score and occult hypoperfusion were both predictive of infection. Thus, patients with lactic acid levels or other markers of hypoperfusion that do not normalize with trauma resuscitation warrant evaluation for infection.¹⁵

Other biomarkers for sepsis include procalcitonin (PCT) and C-reactive protein (CRP). PCT, in particular, has shown strong correlation with sepsis, though this has not been specifically evaluated in patients with trauma.^16-21

7. Can the new Sepsis 3.0 definition assist you? Both the new and older definitions of sepsis are subjective. The new definition of sepsis includes an acute increase of ≥ 2 SOFA (sepsis related organ failure assessment) points in a patient with unexplained organ dysfunction PLUS documented or suspected infection. However, every critical patient in an ED usually has some organ dysfunction.²²

And just for reference, the qSOFA (quick Sepsis Related Organ Failure Assessment)   score uses SBP < 100, altered mental status, or a RR > 22. Please see http://www.emdocs.net/8419-2/, http://www.jamasepsis.com, http://rebelem.com/sepsis-3-0/, http://foamcast.org/2016/02/21/sepsis-redefined/, http://stemlynsblog.org/sepsis-16/, and http://emcrit.org/pulmcrit/problems-sepsis-3-definition/ for further thoughts on Sepsis 3.0.

Sepsis 3.0 is a marker for severity of disease and should not be used for screening of sepsis. However, the new definition may have some utility in trauma, as it can act as a trigger for providers to consider sepsis. A patient with qSOFA ≥ 2 or organ dysfunction has risk of greater mortality. The following algorithm is from the new Sepsis 3.0 definition and literature.²²

Sepsis 3.0 Clinical pathway from http://www.jamasepsis.com

8. This final step is looking at the overall clinical picture. Emergency physicians are masters of resuscitation. If anything is abnormal from the history, vital signs, exam, laboratory findings, or other studies, consider sepsis. The clinician must take into account the entire clinical picture including the history, physical exam, US, biomarkers, and vital signs. We rely on our clinical gestalt every day and with every patient. If something does not seem right with the clinical picture, consider any missing pieces and consider sepsis.

Sepsis after Multiple Trauma

Sepsis is a challenging complication after trauma. One study evaluated the incidence of sepsis in trauma over four periods, finding 14.8% in 1993-1996, 12.5% in 1997-2000, 9.4% in 2001-2004, and 9.7% in 2005-2008.  Unfortunately, in this study, patients with sepsis had mortality rates of 16.2%, 21.5%, 22.0%, and 18.2% respectively.

Post-traumatic sepsis is associated with male gender, existing co-morbidities, high injury severity score (ISS), greater number of injuries, the number of units of RBCs transfused, the number of operative procedures, and laparotomy.²³

Another study found the existence of co-morbidities, male gender, lower admission GCS, and higher injury severity scores (ISS) to be associated an increased risk of sepsis. Compared to mild injury, moderate injury (ISS 15-29) had a 6-fold increased incidence of sepsis, while severe injury (ISS ≥ 30) had a 16-fold increased incidence of sepsis.  Thus, the sicker the patient, the higher risk of sepsis.²⁴

Why would older age and co-morbidities predict sepsis? These patients have decreased cardiopulmonary function, poor nutrition, increased bleeding risk, and decreased immune function (decreased/dysfunctional antibodies, T cells, macrophages).^23,24

One 2014 review demonstrated that the combination of risk factors and abnormal PCT and/or lactate should raise the suspicion for sepsis in trauma. Again, older age and presence of co-morbidities also increase risk of sepsis.²⁵ The value of these from the 2014 study are listed below. ²⁵ Providers may balk at the article’s preference for biomarkers. However, this study is important in that it provides important risk factors for the development of sepsis in trauma patients.

Biomarkers from He Jin, Zheng Liu, Ya Xiao, Xia Fan, Jun Yan, Huaping Liang. Ji H, Liu Z, Xiao Y, et al. Prediction of sepsis in trauma patients. July 2014;2(3):106-113.

So what do you do?

Sepsis and Trauma patients may both demonstrate positive SIRS criteria. The qSOFA score may also be positive in these patients, which raises questions regarding the use of Sepsis 3.0 to differentiate sepsis and trauma.

The best tools for diagnosis likely include the use of history, vital signs, physical examination, ultrasound, laboratory markers, and clinical gestalt.

 One recent review article published in 2015 compares the classic approaches to resuscitation in trauma and sepsis patients.²⁶

Management priorities in trauma from Frankel HL, Magee GA, Ivatury RR. Why is sepsis resuscitation not more like trauma resuscitation? Should it be? J Trauma Acute Care Surg 2015 Oct; 79 (4): 669-77.

This diagram reflects the primary strategies for trauma management: (1) fix the problem (often bleeding source), (2) provide fluids (usually blood products), and (3) utilize appropriate tests and monitoring. The authors advocate that sepsis should be cared for similar to trauma, with targeted source control and minimizing “collateral damage,” including over-resuscitation.²⁶

The initial management strategy of the patient in extremis for trauma and sepsis is similar. Resuscitate first and ask questions later. As discussed above, go through Airway, Breathing, Circulation, Disability/D-stick, Exposure, E-FAST exam/fetus (is the female patient pregnant?). Obtain IV access, attach monitors, and be prepared to provide supplemental O₂.

Finally, when diagnosing sepsis, a potential source needs to be found. The LUCCASSS pneumonic is helpful toward assisting in a search for the source: source: lung (pneumonia), urine (cystitis/pyelonephritis), cardiac (endocarditis), CNS (meningitis, encephalitis), abdominal (abscess, cholecystitis), spine (osteomyelitis, abscess), skin (cellulitis, IV line/PICC infection), and septic arthritis.  Fortunately, an accurate history, physical examination, and appropriate laboratory tests and imaging can usually pinpoint the source of sepsis, but a systematic approach should be followed. Look for biomarkers that are not improving, and evaluate for hypotension, altered mental status, and RR ≥ 22/min. These are markers for mortality and should trigger consideration of sepsis.

References/Further Reading:

1. Bonnie RJ, Fulco CE, Liverman CT (eds); Committee on Injury Prevention and Control, Division of Health Promotion and Disease Prevention, Institute of Medicine. Reducing the Burden of Injury: Advancing Prevention and Treatment. Washington, DC: National Academy Press, 1999.
2. American College of Surgeons, Committee on Trauma: Resources for Optimal Care of the Injured Patient: 1999. Chicago, American College of Surgeons, 1998.

3. Elixhauser A, Friedman B, Stranges E. Septicemia in U.S. Hospitals, 2009. Agency for Healthcare Research and Quality, Rockville, MD. http://www.hcup-us.ahrq.gov/reports/statbriefs/sb122.pdf

4. Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013;41:580–637.

5. Caterino JM. Evaluation and management of geriatric infections in the emergency department. Emerg Med Clin N Am 2008;26:319-343.

6. Khoujah D, Shen C. Systemic infections in the elderly patients. Critical Decisions April 2013.
7. Wo CC, Shoemaker WC, Appel PL, Bishop MH, Kram HB, Hardin E. Unreliability of blood pressure and heart rate to evaluate cardiac output in emergency resuscitation and critical illness. Crit Care Med 1993 Feb;21(2):218-23.
8. Ziglar MK. Application of base deficit in resuscitation of trauma patients. Int J Trauma Nurs. 2000 Jul-Sep;6(3):81-4.
9. Porter JM, Ivatury RR. In search of the optimal end points of resuscitation in trauma patients: a review. J Trauma. 1998 May;44(5):908-14.
10. Paladino L, Sinert R, Wallace D, Anderson T, Yadav K, Zehtabchi S.The utility of base deficit and arterial lactate in differentiating major from minor injury in trauma patients with normal vital signs. Resuscitation. 2008 Jun;77(3):363-8.
11. Singer AJ, Taylor M, Domingo A, Ghazipura S, Khorasonchi A, Thode HC Jr, Shapiro NI. Diagnostic characteristics of a clinical screening tool in combination with measuring bedside lactate level in emergency department patients with suspected sepsis. Acad Emerg Med. 2014 Aug;21(8):853-7.
12. Nguyen H, Rivers E, Knoblich B, et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med. 2004; 32:1637–42.
13. Arnold RC, Shapiro NI, Jones AE, et al. Multi-center study of early lactate clearance as a determinant of survival in patients with presumed sepsis. Shock. 2009;32:36–9.
14. .Jansen TC, van Bommel J, Schoonderbeek FJ, et al. Early lactate-guided therapy in intensive care unit patients a multicenter, open-label, randomized controlled trial. Am J Respir Crit Care Med. 2010;182:752–61.
15. Ciriello V, Gudipati S, Stavrou PZ, Kanakaris NK, Bellamy MC, Giannoudis PV. Biomarkers predicting sepsis in polytrauma patients: Current evidence. Injury. 2013 Dec;44(12):1680-92.
16. Schuetz P, Aujesky D, Mueller C, and Mueller B. Biomarker-guided personalised emergency medicine for all – hope for another hype? Swiss Med Wkly. 2015;145:w14079.
17. Wacker C, Prkno A, Brunkhorst FM, et al. Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infect Dis. 2013;13:426-435.
18. Schuetz P, Briel M, Mueller B. Clinical outcomes associated with procalcitonin algorithms to guide antibiotic therapy in respiratory tract infections. JAMA. 2013;309(7):717–8.
19. Schuetz P, Chiappa V, Briel M, Greenwald JL. Procalcitonin algorithms for antibiotic therapy decisions: a systematic review of randomized controlled trials and recommendations for clinical algorithms. Arch Intern Med. 2011;171(15):1322–31.
20. Schuetz P, Muller B, Christ-Crain M, Stolz D, Tamm M, Bouadma L, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2012; 9: CD007498.
21. Freund Y, Delerme S, Goulet H, et al. Serum lactate and procalcitonin measurements in emergency room for the diagnosis and risk-stratification of patients with suspected infection. Biomarkers. 2012;17:590-596.
22. Singer M et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315(8): 801 – 810.
23. Wafaisade A, Lefering R, Bouillon B, et al. Epidemiology and Risk Factors of Sepsis after Multiple Trauma. Crit Care Med. 2011;39(4):621-628.
24. Osborn TM, Tracy JK, Dunne JR, Pasquale M, Napolitano LM. Epidemiology of sepsis in patients with traumatic injury. Crit Care Med. 2004 Nov;32(11):2234-40.
25. He Jin, Zheng Liu, Ya Xiao, Xia Fan, Jun Yan, Huaping Liang. Jin H, Liu Z, Xiao Y, et al. Prediction of sepsis in trauma patients. July 2014;2(3):106-113.
26. Frankel HL, Magee GA, Ivatury RR.Why is sepsis resuscitation not more like trauma resuscitation? Should it be? J Trauma Acute Care Surg. 2015 Oct;79(4):669-77.