Sepsis and Trauma

Educational Objectives

The purpose of this program is to improve the management of sepsis and trauma. After hearing and assimilating this program, the clinician will be better able to:

1.   Recognize and manage systemic inflammatory response syndrome, severe sepsis, and septic shock.

2.   Discuss and implement guidelines from the Surviving Sepsis campaign.

3.   List predictors of mortality in anesthetic management of trauma patients.

4.   Explain the principles of damage control resuscitation.

5.   Describe conventional and alternative markers for shock.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of in­terest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the faculty and planning committee reported nothing to disclose. In their lectures, Drs. Johansen and Lin discuss the off-label or investigational use of therapies, products, or devices.

Acknowledgements

Dr. Dhillon spoke at Anesthesiology Update 2009, held November 14, 2009, in Los Angeles, CA, and sponsored by the Da­vid Geffen School of Medicine at the University of California, Los Angeles. Dr. Johansen was recorded at New Horizons in Anesthesiology, held September 6-11, 2009, in Vail, CO, and sponsored by the Emory University School of Medicine, At­lanta, GA. Dr. Lin spoke at Critical Care Medicine and Trauma, held May 28-30, 2009, in San Francisco, CA, and spon­sored by the University of California, San Francisco, School of Medicine. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

Anesthesia for the Septic Patient

Anahat K. Dhillon, MD, Assistant Clinical Professor, Department of Anesthesiology, David Geffen School of Medicine, University of California, Los Angeles

Definitions: systemic inflammatory response syndrome (SIRS)  —>2 criteria including hypothermia or hyperthermia, tachycardia, tachypnea, respiratory distress, leukocytosis, and leukopenia; sepsis  —  SIRS plus documented or high possibility of infectious source; definition vague despite multiple attempts at clarification; other criteria  —  elevated lactate, central venous O₂ saturation (S_CVO₂), or procalcitonin

Severe sepsis: sepsis with organ dysfunction or evidence of hypoperfusion, such as oliguria or coagulopathy

Septic shock: sepsis plus hypotension despite adequate fluid resuscitation

Multiorgan dysfunction syndrome: sepsis associated with failure of multiple organs requiring intervention such as mechanical ventilation or renal replacement therapy; most serious septic syndrome

Incidence: cases due to gram-positive organisms and fungi increasing (due to antibiotic overuse); mortality due to septic shock seen in intensive care unit (ICU) ranges from 40% to 60%; >200,000 deaths per year (similar to rates due to myocardial infarction)

Pathophysiology: bacteria release endotoxins and toxic- shock proteins, which cause cellular inflammation or injury; initial response generally proinflammatory, followed by anti-inflammatory response; imbalance in responses exac­erbates sepsis; proinflammatory response  —  mediated by tumor necrosis factor (TNF)-a; contributes to leaky ves­sels characteristic of sepsis; anti-inflammatory response  —mediated by interleukin (IL)-10; causes apoptosis, which leads to further cellular injury; much research now aimed at modulating body’s responses to infection; coag­ulation cascade  —  action of coagulation factors decreases, which leads to microthrombosis and further apoptosis, cellular ischemia, and injury; genetic polymorphisms may contribute to susceptibility; every organ system affected

Surviving Sepsis Campaign: started in 2001 to define sepsis and develop treatment guidelines (available at www.survivingsepsis.org); most recent update in 2008

Diagnosis: obtain blood cultures and imaging studies in emergency department (ED) or ICU to determine etiology

Antibiotics: administer within first hour, even before diagnosis; source control  —  early surgical resolution of under­lying cause (eg, cholecystitis, appendicitis)

Guidelines: associated with documented decrease in mortality; hemodynamic support (resuscitation)  —  begin im­mediately when patient hypotensive and septic, or if lactate level elevated (should decrease anti-inflamma­tory/proinflammatory pathway imbalance); goals set by Surviving Sepsis Campaign include central venous pressure (CVP) of 8 to 12 mm Hg; mean arterial pressure (MAP) >65 mm Hg; urine output >0.5 mg/kg per hour; central venous O₂ saturation (S_CVO₂) >70%; supportive therapy  —  deep venous thrombosis (DVT) pro­phylaxis; pulmonary protection and ventilation; nutritional support

Early goal-directed therapy: start during first 6 hr of sepsis; administer antibiotics; use crystalloid to get CVP to desired level; start vasopressors if MAP <65 mm Hg; if S_CVO₂ <70%, administer red blood cells to maintain he­matocrit >30%; begin inotrope if S_CVO₂ still low

Pressors: norepinephrine and dopamine used classically in sepsis management; in small studies, dopamine associ­ated with slightly higher risk for mortality (either agent probably acceptable); vasopressin  —  deficient in all septic patients; however, combining low doses (0.01 to 0.03 µg/min) with norepinephrine in severely septic pa­tients conferred no survival benefit, compared to norepinephrine alone; in speaker’s opinion, norepinephrine pressor of choice; use of inotropes  —  global biventricular dilation occurs in 25% to 40% of all septic patients; usually presents 24 to 48 hr after onset of sepsis

Cardiac problems: patients also have significant diastolic dysfunction; of patients with low ejection fraction (EF), nearly 1 in 6 have EF <30%; pathophysiology of cardiac dysfunction  —  inflammation leads to apoptosis; mechanisms not related to O₂ supply and demand; almost always reversible within 7 to 10 days; patients re­cover 100% of cardiac function; if patient still hypotensive while on norepinephrine, with high CVP or low S_CVO₂, consider pulmonary artery catheterization or echocardiography to determine whether dobutamine indi­cated

Troponin I as guide to cardiac function: alternative to invasive procedures; in study of 45 patients with septic shock, 78% had left ventricular (LV) dysfunction as indicated by elevated troponin I; on echocardiography, LV dysfunction seen in 78% of patients with troponin levels ³0.4 ng/mL vs only 9% of patients with troponin readings <0.4 ng/mL; suggests combination of elevated troponin and high CVP indicative of significant car­diac dysfunction; troponin also promising as prognosticator (the higher the troponin level, the greater the need for pressors and risk for mortality)

Fluids: recent findings suggest no difference in mortality with use of albumin vs saline; trend toward higher mortal­ity among septic patients who received saline; choice mainly depends on institution’s preference; however, saline associated with higher rates of postoperative edema, wound infection, and pulmonary edema

Starch: in rat studies, decreases sepsis-associated inflammation and improves microcirculation; however, also asso­ciated with hyperoncotic syndrome, leading to renal failure and nephrotic-like lesions in proximal tubules; can result in renal insufficiency and failure, requiring renal replacement therapy (rarely permanent); as septic patients have renal artery constriction and hypovolemia before surgery and ICU admission, speaker recommends avoid­ing starch

Etomidate: single doses decrease cortisol levels in healthy patients; etomidate possibly associated with higher mor­tality among septic patients due to decreased response to corticosteroids; speaker advises against use in septic pa­tients

Update on Trauma Anesthesia

Jay W. Johansen, MD, PhD, Associate Professor, Clinical Anesthesiology, Emory University School of Medi­cine, Atlanta, GA

Priorities in trauma management: ventilation, oxygenation, and hemorrhage control; restore tissue perfusion to vi­tal organs; treatment of posttraumatic hypercoagulable state; predictors of mortality  —  severe coagulopathy, need for emergency thoracotomy, transfusion of >10 U blood, and age; cardiac arrest and closed-chest massage also associated with high risk for death; damage control resuscitation — defer definitive treatment until after resusci­tation and salvage; use advanced trauma life support (ATLS), with rapid assessment and testing to identify treat­ment priorities; prehospital low-volume resuscitation may improve survival; warming “crucially important”; reverse acidosis; restore physiologic hemodynamics; reassess constantly to detect problems that may have been overlooked

Vasopressin: should be used earlier and more frequently; consider administration to replace endogenous hormone; may be especially helpful with traumatic brain injuries (instead of norepinephrine); early use associated with im­proved survival of cardiac arrest due to ventricular fibrillation

Preoperative evaluation: look for pneumothorax; blunt trauma more complex than isolated penetrating trauma; con­sider other issues possibly affecting patient (eg, drug or alcohol intoxication, psychiatric history); altered mental status common; ultrasonography and spiral computed tomography (CT) helpful; assess volume resuscitation; es­tablish large-bore intravenous (IV) access

Airway management: assess for difficult airway early; no documented case in which securing airway first harmed patient

Monitoring: speaker does not recommend Swan-Ganz catheter; transesophageal echocardiography (TEE) gaining acceptance (shows pericardial and some pleural effusions)

Induction of anesthesia: regional anesthesia rarely applicable to trauma; general anesthesia with rapid-sequence in­duction most common; choice of drugs less important than dose; choice depends on assessment of status, ei­ther 1) normovolemic; 2) compensated, but with loss of »25% of blood volume; or 3) loss of >25% of blood volume (volume replacement indicated; must locate source of bleeding); maintenance anesthesia — whatever patient can tolerate

Ominous signs: sudden loss of CO₂; flat bispectral index despite stable appearance (ie, brain not being perfused); important to prevent physiologic collapse (before acidosis [pH <7.2] or hypothermia [temperature <34^O C]) de­velop

End points: not well established; stabilize blood pressure and heart rate; discuss with surgeon best time to reassess patient; anesthesiologist should try to distinguish between salvageable and unsalvageable situations; treatment of hypothermia (rewarming) essential; transfuse early and aggressively

Factor VII: can treat dilutional coagulopathy, but inappropriate use relatively common; good guidelines unavail­able; discuss indications and dose with surgeon

Recovery: deferred problems may move into postanesthesia care unit (PACU); monitor patients to determine need for more surgery, or to identify previously overlooked problems

Resuscitation Endpoints

Eric Y. Lin, MD, Assistant Clinical Professor of Anesthesia and Critical Care Medicine, University of Califor­nia, San Francisco, School of Medicine

End points: in speaker’s opinion, overemphasis on numbers diverts attention from most important end point (correct­ing cause of shock within few hours)

Pathogenesis of shock: imbalance in O₂ delivery and consumption due to injury, which leads to cell hypoxia, cell death, organ damage, and organ dysfunction; eventually causes multiple organ failure and death

Primary goals: to stop injury; resuscitate patient while shock still reversible; achieve survival without organ failure

Principles of resuscitation: golden hour  —  proper treatment within first hour of trauma makes difference between life and death; ATLS, prehospital protocols, and regional trauma systems have decreased prehospital times and mortality rates; retrospective evidence shows longer delays in hemorrhage control result in decreased survival; institutional efforts to shorten time before surgery also improve survival; mortality from cardiogenic shock 70% to 90% in early 1990s; several subsequent studies showed that revascularization within £6 hr associated with sig­nificant decreases in mortality; cardiology guidelines now call for revascularization within 18 hr of onset of car­diogenic shock, and door-to-balloon time <90 min; septic shock  —  every additional hour without antimicrobial therapy increases mortality by 8%; treatment within 4 hr of admission reduces mortality and length of stay; fail­ure to treat primary cause of injury associated with increased morbidity and mortality; most important end point  —  control of source of injury; begin hemorrhage control, revascularization, and antibiotic administration as quickly as possible

Timing of resuscitation: in 1994 study, fluid resuscitation delayed until arrival at operating room associated with better survival before operative control of hemorrhage; suggests resuscitation should be secondary to treating un­derlying cause of injury

Predictors of survival: aerobic metabolism; organ recovery; markers of normal perfusion and organ function current targets of resuscitation

Markers of shock: tachycardia, tachypnea, hypotension, decreased urine output, and diminished mentation; blood pressure targets arbitrary; data on best blood pressure targets for any type of shock limited; conclusion  —traditional markers inadequate; vital signs neither sensitive nor specific for shock; compensated shock com­mon; use of normal blood pressure, heart rate, or urine output as targets misses many cases of persistent hypo­perfusion; trauma patients in shock have average systolic blood pressure >100 mm Hg, yet shock usually defined as systolic blood pressure <90 mm Hg

Alternative markers: serum lactate  —  produced when patient shifts from aerobic to anaerobic metabolism; in one study, normalization of lactate levels within 24 hr associated with 100% survival; normalization within 24 to 48 hr associated with 78% survival; persistence of abnormal lactate levels for >48 hr associated with »14% survival; base deficit  —  correlated with increased mortality, multiorgan failure, and longer ICU stays; benefit of correcting questionable for medical-surgical patients who may not have deficit at baseline; relationship be­tween base deficit and morbidity and mortality persists even with alcohol intoxication, which increases abso­lute base deficit level; optimizing preload  —patients have different pressure-volume curves; right-sided pressures may not reflect left-sided pressures; only 50% of patients with circulatory failure and low CVP re­spond to fluid challenge; O₂ delivery  —  no proven decrease in mortality with supernormal indices, but study results mixed; venous oximetry  —  measures balance between systemic O₂ delivery and consumption; S_CVO₂ fairly accurate predictor

Lessons: early intervention more important than any measured end point; look beyond hypotension and tachycardia to markers such as serum lactate, base deficit, and S_CVO₂; correct primary cause of shock within hours (aim for 1 hr); achieving objective goals within 6 hr will likely improve outcomes; no single end point proven better than any other; use preload and O₂ balance as markers, in addition to blood pressure; avoid efforts that may delay correction of primary cause of trauma; minimize complications, perhaps by avoiding unnecessary use of invasive monitors and shifting to restrictive fluid strategies within 12 to 24 hr

Suggested Reading

Abernathy JH 3rd, Reeves ST: Airway catastrophes. Curr Opin Anaesthesiol 23:41, 2010; Annane D et al: Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Lancet 370:676, 2007; Bickell WH et al: Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. N Engl J Med 331:1105, 1994; Durthaler JM et al: Managing severe sepsis: a national survey of current practices. Am J Health Syst Pharm 66:45, 2009; Haas T et al: Successful resuscitation of a traumatic cardiac arrest victim in hemorrhagic shock with vasopressin: a case report and brief review of the literature. J Trauma 57:177, 2004; Hochman JS et al: Early revascularization in acute myocardial infarction complicated by cardiogenic shock. N Engl J Med 341:625, 1999; Levy MM et al: The Surviving Sepsis Campaign: Results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med 2009 Dec 23 [Epub ahead of print]; Morrell MR et al: The management of severe sepsis and septic shock. Infect Dis Clin North Am 23:485, 2009; Rivers E et al: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345:1368, 2001; Russel JA: The current management of septic shock. Minerva Med 99:431, 2008; Salah N et al: Air­way injury during emergency transcutaneous airway access: a comparison at cricothyroid and tracheal sites. Anesth Analg 109:1901, 2009.