The most award winning
healthcare information source.
TRUSTED FOR FOUR DECADES.
Authors: Kenneth Butler, DO, FACEP, Assistant Professor of Surgery, Division of Emergency Medicine, Department of Surgery, University of Maryland School of Medicine, Baltimore; and Michael Winters, MD, Division of Emergency Medicine, Department of Surgery, University of Maryland School of Medicine, Baltimore.
Peer Reviewers: Richard Salluzzo, MD, FACEP, Chief Executive Officer and Chief Medical Officer, Conemaugh Health System, Johnstown, PA; and O. John Ma, MD, Associate Professor, University of Missouri—Kansas City School of Medicine; Vice Chair, Research Director, Department of Emergency Medicine, Truman Medical Center, Kansas City, MO.
As the number of visits to emergency departments (EDs) continues to rise steadily across the nation, emergency physicians (EPs) are confronted with the task of caring for a seemingly endless stream of patients. Contributing to the challenge of treating an increasing number of patients is the proportionate increase in the number of those who present in shock. Treating the patient in shock can be challenging, for nearly all require rapid assessment simultaneously with multiple treatment interventions. Once proper ED stabilization has been achieved, these patients require prompt transport to the intensive care unit (ICU) or the operating room (OR) for continued care. Unfortunately, as evidenced by recent literature, timely transport to the ICU or the OR has become progressively problematic. As a result of the escalating epidemic of hospital and ICU congestion, critically ill patients often remain in the ED for exceedingly long times.1 During these initial hours of shock and resuscitation, the detrimental effects of inadequate oxygen delivery begin to take hold. If not detected and treated promptly, the disastrous sequence of events that stems from prolonged cellular hypoxia ultimately will overwhelm the patient. Therefore, given a potentially prolonged stay in the ED, it is essential that the EP not only initiate appropriate resuscitation measures, but also remain vigilant for evidence of continued cellular ischemia.
Within the past several years, clinical researchers have shown that ED detection and treatment of patients in shock significantly can influence outcome. One study demonstrated that early and aggressive ED treatment of patients in septic shock resulted in a significant reduction in mortality.2 Although additional clinical trials are needed to support this study, it suggests that the EP may have the greatest impact on patient survival.
To improve patient survival, the EP must be knowledgeable about current concepts and controversies in the management of patients in shock. No longer can one simply rely on the presence of traditional clinical markers of shock to make the diagnosis. New and innovative monitoring techniques, as well as continually evolving treatment algorithms, are at the forefront of shock research. This article will educate and update the EP on current and future trends in the management of patients in shock. Equipped with this information, the EP more effectively can identify patients in shock, administer the latest evidence-based treatment, and ultimately improve patient outcome.—The Editor
The Basic Principle of Shock
Simply stated, shock is the transition from illness to death.3 Ever since the English surgeon Guthrie coined the term in 1815, scientists and clinicians have sought to accurately define shock. One of the earliest definitions can be traced to the late 1800s, when Warren described shock as "a momentary pause in the act of death."4 Shortly thereafter, Gross published his belief that shock was "a rude unhinging of the machinery of life."5 Since then, numerous concepts and observations have been published in an attempt to capture the fundamental principle of shock. It was not until the 1940s, however, that the principle of irreversible cellular dysfunction first was put forth.6 This proposal led researchers to focus on the harmful effects of cellular hypoxia and the disastrous cascade of events that results from disruption of cellular homeostasis. Based on the past several decades of shock research, the current understanding of the basic principle of shock can be summarized as follows: shock is the inability of the circulatory system to deliver sufficient oxygen and other vital nutrients to meet the normal or increased metabolic demands of the patient.
The causes of shock are myriad. In many cases, the exact cause of shock does not become evident until after the patient has left the ED. Therefore, it seems impractical and unnecessary for the EP to memorize a lengthy list of sources. Rather, the busy EP should focus on recognizing broad categories of causes. One historic classification system segregates the causes into hemorrhagic, cardiogenic, vasogenic, and neurogenic.3 Another commonly used system divides the etiologies of shock into hypovolemic, cardiogenic, distributive, and obstructive.7 Perhaps the simplest system, and the one easiest to recall at the bedside of an acutely ill patient, is represented by the mnemonic SHOCK. (See Table 1.) For the purposes of this discussion, the etiologies of shock are categorized into hemorrhagic, septic, cardiogenic, neurogenic, and anaphylactic.
The true incidence of shock is unknown. Some authors estimate that more than 1 million patients in shock present to EDs each year.7 Given the inconsistency of the traditional markers of shock, its frequently subtle presentation, and the fact that some patients die before reaching medical attention, the true incidence of shock is likely to be much higher. Shock can afflict males and females of every age, race, and socioeconomic class. Not surprisingly, hemorrhagic/traumatic shock is more prevalent among persons between the ages of 1 and 44, while septic shock is more prevalent among persons older than 55.8 Recent literature indicates that the incidence of septic shock is increasing, paralleling the continued growth of the elderly population.12 Epidemiologic data regarding cardiogenic shock continue to be imprecise. Current estimates place the incidence of cardiogenic shock complicating acute myocardial infarction at 6-8%.9 Since anaphylaxis is not a reportable disease, data regarding its incidence are scarce. The current estimate of the international annual incidence of fatal anaphylaxis is 154 per 1 million.10 To date, no reliable data have been published regarding the incidence of neurogenic shock.
Regardless of the etiology, several fundamental pathophysiologic mechanisms are universal in regard to shock. To gain a more thorough understanding of shock pathophysiology, it is helpful to organize these mechanisms into the following categories: the autonomic response to shock, the effects of cellular hypoxia, and the role of inflammatory mediators. Although described below as separate entities, it is crucial to appreciate that all of the following effects act in concert.
Autonomic Response. The initial insult that leads to the development of shock is a decrease in oxygen delivery (DO2) to the tissues. DO2 is the product of the total arterial oxygen content and the cardiac output (CO). To counteract the decrease in oxygen delivery, the initial compensatory response is an increase in cardiac output. This is accomplished through the release of epinephrine and norepinephrine from the sympathetic nervous system. These cardiopulmonary catecholamines increase heart rate and contractility in an attempt to increase DO2. Additional effects of epinephrine and norepinephrine include increased minute ventilation and increased peripheral vasomotor tone.7 As the decrease in DO2 continues, blood is shunted away from the skin, kidneys, muscles, and splanchnic beds.8 With the decrease in effective arterial circulating volume, the kidneys release renin, activating the renin-angiotensin-aldosterone axis. Additional vasoactive substances released into the systemic circulation during this initial phase of shock include dopamine, cortisol, glucagon, growth hormone, and anti-diuretic hormone (ADH). The net effect of the autonomic response to shock is to preserve oxygen and nutrient delivery to the most critical organs: the brain and heart.
Cellular Hypoxia. As stated above, shock begins when there is an imbalance between tissue oxygen delivery and oxygen demand, as measured by tissue oxygen consumption (VO2). VO2 is the difference between oxygen delivered and that returning from the tissues.7 Under normal physiologic conditions, cells extract approximately 25% of available oxygen. Hence, venous blood that returns to the heart from the periphery is normally 70-75% saturated.8 This relatively constant fraction of oxygen extraction allows tissues to aerobically synthesize a sufficient quantity of high-energy phosphate bonds (i.e., adenosine triphosphate [ATP]) to maintain cellular homeostasis. When the increase in CO is insufficient to restore adequate oxygen delivery, cells begin to extract a higher percentage of available oxygen from the bloodstream. If the underlying etiology is not corrected, the discrepancy between oxygen delivery and consumption will continue to widen, creating an oxygen debt. Eventually, the limit of increased oxygen extraction is reached, resulting in cellular hypoxia.
As cellular hypoxia worsens and available ATP stores are depleted, cells convert to anaerobic metabolism in an attempt to maintain homeostasis. Anaerobic metabolism produces only one-eighteenth of the energy that aerobic metabolism produces.8 As a result, ion-pump disruption occurs, causing damaging influxes of calcium, sodium, and water. Lysosomal enzymes are released, leading to the denaturation of DNA, RNA, and phosphate esters.9 Lactate accumulation from continued anaerobic metabolism results in both intracellular and extracellular acidosis. This acidosis, along with its unfavorable effects on the myocardium, renders cells less responsive to the autonomic changes discussed above. Furthermore, cellular hypoxia causes the buildup of large amounts of xanthine oxidase.8 Increased amounts of this enzyme result in the formation of superoxide free radicals, which produce further DNA damage, protein denaturation, and lipid peroxidation.8 Ultimately, the breakdown in cellular metabolism and the accumulation of free radicals culminate in cell death.
Inflammatory Mediators. Although the adaptive responses of the autonomic system may be beneficial initially, ongoing shock creates an uneven distribution of blood flow, resulting in distinct areas of tissue hypoxia. As evidenced above, the effects of tissue hypoxia on cellular function can be catastrophic. Eventually, hypoxic cells of the vascular endothelium activate tissue macrophages and leukocytes, leading to the production of numerous harmful inflammatory mediators.7 Mediators that have been implicated in shock include tumor necrosis factor, interleukins 1 and 2, eicosanoids, interferon gamma, and platelet activating factor. With resuscitation, the hypoxic vascular beds are reperfused, resulting in the delivery of these mediators to the systemic circulation. It is this washout of inflammatory mediators that leads to the development of the systemic inflammatory response syndrome (SIRS). SIRS is defined as the presence of two or more of the following: temperature greater than 38° C or less than 36° C, respiratory rate greater than 24 breaths/minute, heart rate greater than 90 beats/minute, and a white blood cell count greater than 12,000 cells/microliter or less than 4000 cells/microliter. As SIRS progresses, multi-organ dysfunction (MODS) develops, resulting in acute renal failure, cardiac failure, adult respiratory distress syndrome, gut dysfunction, and immunosuppression.6
History. No single historical feature is diagnostic of shock. Unfortunately, in only a few patients will the diagnosis of shock be evident within the first several minutes of the encounter (e.g., in those with hemorrhage from multisystem trauma). More often, patients in shock will present with nonspecific complaints that easily can mislead even the seasoned EP. Some patients may report nothing more than generalized lethargy or fatigue.9 Others may arrive by ambulance, arrive in the custody of law enforcement, or may be brought by family members for evaluation of bizarre behavior. Additional nonspecific complaints may include subjective fevers, nausea, vomiting, diarrhea, or low back pain (ruptured abdominal aortic aneurysm). Pertinent aspects of the medical history include any history of cardiovascular, pulmonary, renal, neurologic, or immunosuppressive conditions. However, the absence of any previously known medical condition does not exclude the possibility of cardiogenic, hypovolemic, or septic shock.
A recent medication list is imperative and may suggest the possibility of toxicity from either accidental or intentional ingestion. Any new medications should raise suspicion for possible adverse reactions, toxicity, or anaphylaxis. In addition to prescribed medications, the EP should question the patient regarding use of illicit substances.
For patients who arrive at the ED with a depressed mental status, information obtained from emergency medical personnel, family, or bystanders can be invaluable. Once again, no single historical feature is diagnostic of shock. Although the presence of any of the above complaints or conditions is helpful, the EP cannot diagnose or exclude shock without additional objective information.
Physical Examination. No single vital sign abnormality is diagnostic of shock. Traditionally, shock has been diagnosed based on the presence of abnormal vital signs. Hypotension, tachycardia, tachypnea, hypoxia, decreased urine output, peripheral hypothermia, and altered mental status have been the hallmark clinical indicators of shock. Unfortunately, there is an abundance of data demonstrating that these findings are imprecise and often subjective. Furthermore, they represent the secondary effects of circulatory failure, not the principle pathophysiologic problem.10 Due to compensatory mechanisms, the effects of age, or the use of certain medications, a large percentage of patients in shock will present with a normal blood pressure and heart rate. Thus, normal vital signs cannot be used to exclude the presence of shock. In fact, waiting for hypotension and tachycardia to develop to make the diagnosis invariably will increase patient mortality.8 Some clinicians, in an attempt to improve the reliability of vital signs, incorporate orthostatic blood pressure measurements and calculation of the shock index (heart rate/systolic blood pressure) into their armamentarium. Regrettably, these also have been shown to be inconsistent indicators of shock.
No single physical exam finding is diagnostic of shock. Notwithstanding, a complete physical examination must be performed with the patient fully exposed. Essential components of the physical exam include examination of the skin, the appearance of the jugular veins, auscultation of the heart and lungs, examination of the abdomen, and a complete neurologic exam. Any signs of trauma, infection, or the presence of a characteristic odor (i.e., alcohol or ketones) can provide additional clues. Similar to the above discussion regarding vital signs, physical exam findings have been shown to be imprecise and often are observer-dependent. Therefore, even in the presence of normal vital signs and an unremarkable physical exam, the diagnosis of shock still must be considered.
Laboratory Data. No single laboratory value is diagnostic of shock. Nonetheless, a variety of laboratory data can provide the EP with invaluable information when confronted with a critically ill patient. A complete blood count may demonstrate an elevated, or even low, white blood cell (WBC) count, suggesting the possibility of sepsis. A manual differential of the WBC count should be ordered. The presence of greater than 10% bands, even in the face of a normal WBC count, suggests the presence of an infection. Serial hemoglobin or hematocrit levels are crucial when managing the patient suspected of suffering from hemorrhagic shock. A basic electrolyte panel will not only provide information about the patient’s renal function, but also may indicate the presence of an acid-base disturbance. An elevated anion gap suggests either continued anaerobic metabolism or the presence of an ingested toxin. Additional labs that may be useful depending on the patient’s presentation include an arterial blood gas; cardiac enzymes, including troponins; urinalysis; coagulation profile; toxicologic screens; hepatic enzymes; and a urine pregnancy test. In patients with hemorrhagic or hypovolemic shock, blood transfusions may be required. Therefore, some authors argue that the most important laboratory test to order in the critically ill patient is a blood type and screen.8
Electrocardiogram (ECG). An ECG should be obtained in every patient with suspected shock. Any abnormality consistent with myocardial ischemia or infarction suggests the possibility of cardiogenic shock. Although obtained primarily to detect the occurrence of an acute coronary syndrome, the ECG also can provide the EP with insightful clues to the presence of alternative diagnoses. Detection of right heart strain, as evidenced by right axis deviation, incomplete or complete right bundle-branch block, or the characteristic S1Q3T3 pattern suggests the possibility of pulmonary embolism. The diagnosis of cardiac tamponade is implied by the findings of low-voltage QRS complexes and electrical alternans. The presence of U waves can indicate profound electrolyte disturbances such as hypokalemia or central nervous system abnormalities such as subarachnoid hemorrhage. In addition to the above findings, the EP also should examine the ECG for characteristic signs of drug toxicity (i.e., digoxin or tricyclic antidepressants).
Radiographic evaluation of the patient in shock usually begins with the portable chest film. In most cases, it can be obtained quickly and can diagnose, or at least suggest, the etiology of shock. A widened mediastinum in the patient with chest pain or recent trauma indicates aortic dissection. Similarly, a new pleural effusion in the patient with chest pain suggests aortic dissection, pulmonary embolism, or esophageal rupture. The finding of a water-bottle-shaped cardiac silhouette implies pericardial effusion and the possibility of cardiac tamponade. In a patient with acute abdominal pain, detection of free air confirms a hollow viscus perforation. Additional diagnoses that can be made by chest film include congestive heart failure, pneumonia, and pneumothorax. Of note, tension pneumothorax never should be diagnosed by chest film. It must be detected during the primary survey and decompressed long before the radiology technician can arrive at the bedside.
Although a chest film eventually is obtained on every patient in shock, there often can be many unforeseen delays. An imaging modality that quickly is gaining popularity in the ED is ultrasonography. By virtue of its design and versatility, ultrasound is safe and can be performed on any patient in the ED. Furthermore, it allows the EP to confirm a clinical suspicion virtually within seconds of considering a diagnosis.
The usefulness of ultrasonography in the evaluation of blunt abdominal trauma is well documented.32 Patients with blunt abdominal trauma who are hypotensive and have intraperitoneal fluid on ultrasound should be taken immediately to the OR. In addition to the focused abdominal survey performed on the trauma patient, ultrasound can provide invaluable information regarding other abdominal catastrophes. In the geriatric patient with hypotension, visualizing the abdominal aorta and measuring its diameter is crucial. Furthermore, in any elderly or immunocompromised patient who presents in shock with right upper quadrant abdominal pain, ultrasound can be used to detect the presence of emphysematous cholecystitis or ascending cholangitis. Ultrasonography is essential in the evaluation of the female patient with abdominal pain and a positive pregnancy test. The presence of a complex adnexal mass and free fluid in the cul-de-sac on pelvic ultrasound makes the diagnosis of ectopic pregnancy more likely.
In addition to identifying abdominal emergencies, ultrasonography can be used to evaluate the patient for the presence of other life-threatening etiologies of shock. In patients who are hypotensive and have evidence of right heart failure despite a normal lung exam, identification of a pericardial effusion can be lifesaving. In patients with suspected pulmonary embolism, demonstration of a deep venous thrombosis in the lower extremities clinches the diagnosis. Finally, ultrasound can be used to secure central venous access in those patients for whom peripheral access is unobtainable. As more EPs receive formal training, ultrasound undoubtedly will become an integral component in the evaluation and management of the critically ill.
Additional radiologic studies performed on critically ill patients include computed tomography (CT), magnetic resonance imaging (MRI), and angiography. Many patients with equivocal results from physical exam and/or chest film require further imaging. If the patient is hemodynamically stable, CT is the modality most often chosen. In fact, CT has become the preferred imaging method for the evaluation of pulmonary embolism, aortic dissection, pulmonary parenchymal abnormalities, and intra-abdominal pathology. Due to the prolonged imaging time and relative inaccessibility of the patient during imaging, MRI almost never is obtained during the early management of the critically ill patient. Angiography of the patient in shock usually is reserved for those in hemorrhagic shock secondary to trauma, when localization and embolization of bleeding vessels is required.
When managing the patient in shock, the primary objective is to restore normal aerobic metabolism. To accomplish this goal, the EP should focus on optimizing oxygen delivery to the tissues. This may require the initiation of mechanical ventilation to improve arterial oxygen saturation, transfusion of blood to improve oxygen-carrying capacity, administration of intravenous fluids to improve left ventricular filling and cardiac output, or administration of vasopressor agents to augment or even maintain hemodynamic parameters. These, along with many other aspects of treating the critically ill, are addressed in the subsequent sections.
Initial Approach. As previously stated, the etiology of shock may not be evident during the initial primary and secondary surveys. Therefore, it is crucial that the EP follow a systematic approach to all critically ill patients until further data can be obtained to direct disease-specific therapy.
For any patient who passes through the doors of the ED, the initial evaluation begins with assessment of the airway. For those with obvious clinical signs of shock (i.e., unstable vital signs, cardiopulmonary arrest, severely depressed mental status), airway control is best established through endotracheal intubation. Many of the drugs used to facilitate intubation may further exacerbate cardiovascular instability. For this reason, some authors suggest that, because of their minimal effects on the myocardium and vasculature, etomidate and ketamine be used as first-line agents in the critically ill.3 Of the patients who have a more subtle presentation, many will not require immediate intubation. Notwithstanding, the EP always should anticipate the need for airway control and have the necessary equipment at the bedside. For patients not initially intubated, frequent re-assessment of the airway is essential.
Following confirmation of airway patency, the EP must evaluate the adequacy of ventilation. This often is a challenging task. Frequently, the EP must rely on arterial blood gas analysis when making decisions regarding the need for assisted ventilation. Continued hypoxia and worsening hypercapnia are indications to initiate mechanical ventilatory support. The respiratory muscles are avid consumers of oxygen and can produce large quantities of lactic acid.7 In fact, strenuous accessory muscle use can increase consumption anywhere from 50% to 100%, leading to a decrease in cerebral blood flow by as much as 50%.3 Thus, the tachypneic patient in shock ultimately may require mechanical ventilation as respiratory muscles fatigue, hypercapnia increases, and acidosis worsens. Advantages to mechanical ventilation include improved oxygen delivery to the alveoli, correction of hypercapnia, and, most importantly, a decrease in oxygen consumption by the respiratory muscles.
After ensuring proper airway control and assessing adequacy of ventilations, the EP must focus on verifying circulatory stability. Similar to the evaluation of breathing, determining sufficient circulatory stability can be problematic. As demonstrated above, relying on normal values for blood pressure and heart rate can be misleading. Patients in shock from hemorrhage or hypovolemia demonstrate profound vasoconstriction, providing inaccurate blood pressure readings. Conversely, patients in septic shock have warm extremities, leading to the false assumption of adequate perfusion. Nevertheless, initial assessment of the circulation should include the establishment of adequate intravenous (IV) access. Two large-bore peripheral IV lines are preferred, especially in cases of trauma. However, if these cannot be established, a central venous line should be placed. If a central line is required, cannulation of either the internal jugular or subclavian vein is preferred. Standard practice dictates the use of crystalloid fluid as the initial resuscitative fluid in the hypotensive patient. However, recent literature questions not only the choice of fluid, but also the timing of its administration. The subject of fluid resuscitation is addressed in the section on the treatment of hemorrhagic shock.
Patient Monitoring. Traditional ED monitoring of the acutely ill patient begins with use of a cardiac monitor and continuous pulse oximetry. In the majority of patients, a Foley catheter should be placed so that the EP accurately can follow urine output. Serial blood pressure measurements usually are obtained every 2-5 minutes.3 Arterial blood pressure readings obtained by cuff sphygmomanometry tend to underestimate true arterial pressures. Therefore, a radial arterial line should be placed in patients who have inconsistent, or persistently low, cuff pressures. An arterial line also is indicated when the EP is initiating, and titrating, vasopressor agents. Unfortunately, these traditional methods of monitoring the critically ill patient, while necessary, have been shown to be insensitive and inconsistent indicators of hypoperfusion and ongoing shock.11 Thus, the EP must rely on other adjuncts when attempting to assess the adequacy of resuscitation and restoration of normal tissue perfusion.
Pulmonary Artery (PA) Catheter. The PA catheter (Swan-Ganz catheter) long has been considered the gold standard for differentiating between the various categories of shock. Information obtained from the PA catheter includes the pulmonary capillary wedge pressure (PCWP), pulmonary artery pressure (PAP), right ventricular and central venous pressures (CVP), mixed venous oxygen saturation (SmvO2), cardiac output (CO), and calculation of the systemic vascular resistance (SVR). By determining the PCWP, CVP, CO, and SVR, one can determine if a patient has hypovolemic, septic, or cardiogenic shock. Equally as important as these values is the SmvO2. As oxygen delivery to the tissues decreases, cells begin to extract a larger percentage of available oxygen, resulting in a lower SmvO2. Hence, an SmvO2 less than 70-75% indicates ongoing hypoperfusion and the need to continue aggressive resuscitation. The PA catheter is inserted through a 7-French catheter placed in the internal jugular or subclavian veins. Complications of placing a PA catheter include cardiac perforation with subsequent tamponade, atrial and ventricular arrhythmias, and pulmonary artery rupture. Given these potentially disastrous complications, combined with prolonged time required to insert the device, placement of a PA catheter in the busy ED usually is not feasible or routinely recommended.
Central Venous Oxygen Saturation (ScvO2). As discussed above, patients may have ongoing tissue hypoxia despite a normal blood pressure, pulse, oxygen saturation, mental status, and urine output. One way to detect ongoing cellular hypoxia is to measure SmvO2. However, placement of a PA catheter and measurement of SmvO2 are not performed routinely in the ED. What can be measured in the ED is the ScvO2. This usually is obtained through a central line placed in either the internal jugular or subclavian vein. Numerous studies have demonstrated that ScvO2 correlates well with SmvO2 in shock states.12 Therefore, serial measurements of ScvO2 can provide the EP with objective evidence of the effectiveness of resuscitation, as well as aid in determining the need for additional interventions.
Central Venous Pressure (CVP). Monitoring CVP can be helpful in the volume-depleted patient who initially presents with low CVP.8 Unfortunately, this seems to be the only scenario in which serial CVP measurements are useful. A normal, or even elevated, initial CVP can be misleading. In the acutely ill patient, several conditions falsely will elevate the CVP (e.g., cardiac tamponade, pulmonary embolism, and right ventricular infarction). Therefore, the EP should not mistakenly infer a normal volume status based on a normal, or elevated, CVP.
Lactate. Another laboratory value that can be useful in monitoring the critically ill patient is the arterial (or venous) lactate level. As mentioned previously, cells convert to anaerobic metabolism if the body’s compensatory mechanisms fail to deliver enough oxygen to maintain aerobic metabolism. The predominant by-product of anaerobic metabolism is lactic acid. Persistently elevated blood lactate levels (> 4 mM) can signify continued cellular hypoxia. In fact, the severity of lactic acidosis correlates with the oxygen debt and, ultimately, with patient survival.8 Several studies demonstrate mortality in excess of 50% for those with persistently elevated levels.13 It is important for the EP to realize that a single lactate level has no value in predicting morbidity or mortality. Rather, the trend in serial measurements provides the most valuable prognostic information.
Additional Monitoring Methods. New methods to monitor the acutely ill patient continue to be put forth in an attempt to find the holy grail for detecting shock. Most have been studied for several years and continue to be the focus of new research endeavors, yet few have been implemented in the everyday management of the critically ill. Nonetheless, the EP should be familiar with emerging concepts that soon may complement, or even replace, existing monitoring modalities.
One modality that has practical application in the ED is the measurement of end-tidal carbon dioxide (etCO2). During shock (or any low-flow state), etCO2 frequently is low. This reflects the impaired venous return of metabolic by-products caused directly by the global decrease in perfusion. As resuscitation proceeds, previously hypoxic regions regain adequate perfusion, resulting in a return of CO2 to the central circulation. Hence, etCO2 increases. By following continuous etCO2 measurements, the EP can make educated inferences regarding the overall success of resuscitation. With the appropriate equipment, etCO2 can be measured and monitored from an endotracheal tube, face mask, or nasal cannula.
Using the same principle of detecting changes in the partial pressure of CO2 (pCO2), sublingual capnometry recently has emerged as a promising method of monitoring the acutely ill. Infrared biosensors placed under the tongue detect changes in pCO2. Although it currently is used only in research protocols, sublingual capnometry has shown excellent correlation compared with the above-mentioned methods of monitoring patients in shock.14
Gastric tonometry and transcutaneous oxygen monitoring were introduced more than 20 years ago. During early stages of shock, compensatory vasoconstriction preferentially shunts blood away from the splanchnic circulation, the skin, and skeletal muscle. Not only are these vascular beds the first to demonstrate reduced blood flow, they are the last to regain normal perfusion when resuscitation has been successful. Therefore, one conceivably could identify shock at earlier stages, or identify ongoing subclinical shock, by following the respective changes in the gastric mucosal pH and tissue oxygen tension. An unfortunate problem with both of these methods is that normal and critically abnormal values have not been established.15 Furthermore, the optimal site for monitoring tissue oxygen tension continues to be debated. Thus, gastric tonometry and transcutaneous oxygen monitoring remain investigational and primarily are limited to academic research centers.
A final adjunct useful in assessing overall tissue perfusion is optical spectroscopy. This method allows the EP to directly measure the oxygen saturation of the retinal vein. Numerous studies8 have demonstrated good correlation with the SmvO2 obtained by PA catheter. As is true for most of the above-mentioned new monitoring methods, it is not readily available in most EDs.
The Geriatric Patient
The geriatric patient in shock deserves special attention. Elderly patients have decreased physiologic reserves, an increased incidence of shock, and a greater mortality rate compared to younger patients. The older patient is more likely to have preexisting organ dysfunction. In addition, the elderly are more likely to be taking medications that alter the physiologic response to decreased oxygen delivery. The presentation of shock in the elderly may take the form of an alteration in mental status, syncope, or unresponsiveness. Management of the geriatric patient in shock can be challenging, especially in the patient with cardiovascular disease. The EP undoubtedly will have to rely on many of the monitoring methods discussed above to effectively treat the elderly patient in shock.
Cause-Specific Management and Current Controversies
Hemorrhagic Shock. In patients suffering from traumatic shock, the cornerstone of treatment rests in getting the patient to the OR as expeditiously as possible. Except for rare occurrences, patients usually are not taken directly from the ambulance bay into the OR. Rather, patients are triaged to a designated resuscitation area, where they are evaluated and resuscitation is initiated. During the past several years, a multitude of questions has been raised regarding proper resuscitation of the patient in traumatic shock. Although many of these questions continue to be investigated, recent literature has provided the EP with invaluable information.
Perhaps the most widely debated topic regarding the trauma patient is fluid resuscitation. Since 1918, when the administration of intravenous fluids was reported to improve outcome in patients with hemorrhagic shock,16 debate has raged over not only the proper timing, but also the type of fluid administered. Traditional teaching during the past 40 years has been to infuse large volumes of isotonic fluid as quickly as possible. Recent literature, however, questions this dogmatic approach. In fact, data from numerous recent animal trials and one human clinical trial suggest that mortality rates may be higher among patients resuscitated using the traditional method.17 Current literature suggests that patients with traumatic shock who have the potential for ongoing hemorrhage be resuscitated to modest degrees of hypotension until repair of the culprit vessel is accomplished. Unfortunately, there are no published clinical guidelines that define a target blood pressure. Most authorities in trauma management suggest resuscitating this select group of patients to a systolic blood pressure of 70 mmHg. This value, however, is based on ongoing research and must be validated by randomized, prospective trials.
In addition to the timing and amount of fluid resuscitation, there is as much debate over the type of fluid used. EPs are familiar with the long-standing debate over crystalloid vs. colloid fluids. A recent evidence-based review of studies comparing crystalloid and colloid fluids concluded there was no overall difference in mortality, except in the subgroup analysis pertaining to traumatic injury.18 Trauma patients appeared to have a slightly increased relative risk of death when resuscitated with colloid fluids. Based on this association, a higher cost, relatively short half-life, and the risk of disease transmission, colloid fluids are not recommended routinely in the care of patients with traumatic shock. Although crystalloid fluids frequently are administered, recent data indicate they may not be as benign as was once thought. Isotonic crystalloid resuscitation increases neutrophil activation and adhesion following hemorrhage.19 Neutrophils may play an important role in the release of the inflammatory mediators implicated in the pathogenesis of shock. Further research is required to determine the clinical significance of this discovery.
It is well known that blood is the ideal isotonic resuscitative fluid. Conventional wisdom teaches that when a patient in hemorrhagic shock remains hypotensive despite two liters of crystalloid fluid, blood transfusion should be initiated. Unfortunately, there are recognized risks associated with receiving large quantities of transfused packed red blood cells. Because of the potential complications associated with blood transfusion, other modalities of fluid replacement are being investigated. In fact, millions of dollars of research funds have been spent in an attempt to find an acceptable blood substitute. One modality of interest is hemoglobin-based oxygen carriers (HBOC). Currently, there are four HBOCs undergoing clinical investigation.20 Clinical application has been limited, however, secondary to documented toxic effects on the cardiovascular system, kidney, gastrointestinal system, and the coagulation cascade. Research continues on the use of these products.
Along with research into blood substitutes, there also has been renewed interest in hypertonic saline as a possible resuscitative fluid. The use of hypertonic saline traditionally has been reserved for the treatment of life-threatening hyponatremia or in patients with traumatic brain injury.11 In patients with traumatic shock, hypertonic saline has the theoretical benefit of increasing intravascular volume with smaller quantities of fluid.11,16,21 Current literature proposes that the combination of hypertonic saline and dextran may be useful in situations where larger quantities of fluid may be harmful (e.g., elderly patients with impaired cardiac function). Additional randomized, prospective trials are required before this combination can be added to the treatment regimen for patients with hemorrhagic shock.
One final controversy in the treatment of patients in hemorrhagic shock is the addition of antioxidants and/or free radical scavengers to resuscitative fluids. Hemorrhagic shock impairs antioxidant defense mechanisms and increases free radical production.22 As discussed in detail above, free radical formation plays a key role in the pathogenesis of shock and subsequent MODS. To date, the results of studies involving superoxide dismutase, N-acetylcysteine, ascorbic acid, vitamin E, and even deferoxamine have been published.23 Preliminary data imply that the inflammatory response to shock is somewhat mitigated by the addition of an antioxidant to the resuscitation fluid.19 Given the small number of patients enrolled in the above studies, additional trials clearly are needed to determine clinical significance.
Septic Shock. More than 380,000 patients are admitted through EDs each year with the diagnosis of severe sepsis or septic shock.12 (See Figure.) Sepsis is the most common cause of hypotension requiring emergent care.24 The initial insult leading to septic shock is the formation of an infectious nidus. The goal of treatment is to eradicate the area of infection through the administration of intravenous antibiotics and/or surgical drainage. Antibiotic selection in the ED usually is empiric. Selection should be based on the suspected site of infection, the suspected organism, whether the organism was acquired in the community or hospital, and on host factors such as the degree of immunodeficiency. Furthermore, the EP should consider local resistance patterns when choosing among the plethora of antibiotics. Table 2 provides general guidelines for empiric antibiotic treatment based on the source of sepsis and the potential pathogens.
Resuscitation of the hypotensive septic patient begins with the administration of intravenous fluids. A systematic review of the clinical trials comparing crystalloid and colloid fluids demonstrated no difference in mortality, pulmonary edema, or length of stay.18 However, given the potential complications and cost of colloid fluid (see above), isotonic crystalloid fluid is the resuscitative fluid of choice. In a large percentage of patients, hypotension will persist despite the administration of large volumes of isotonic fluid. These patients require vasopressor therapy. The vasopressor agent of choice heavily has been debated during the past several years. Traditional teaching recommended dopamine as the first-line vasopressor agent for septic patients. This recommendation, however, was based solely on expert opinion, not the results of well-designed, randomized, controlled trials.25 More recently, norepinephrine has gained favor as the vasopressor agent of choice in septic shock. Once thought to have deleterious effects on end-organ perfusion, norepinephrine has been shown to achieve more reliable, rapid, and effective blood pressure control than dopamine.26 Added benefits of norepinephrine include improved splanchnic flow, and improved renal flow with subsequent increases in urine output.24 In addition to single vasopressor agents, numerous combinations of agents have been studied. To date, the combination of dobutamine with either norepinephrine or epinephrine appears to have the most promising results. Randomized, controlled trials are required to confirm any superior benefit.
Aside from the debate over vasopressor agents, there is ongoing controversy about the use of steroids in septic shock. It is known that a large percentage of patients with confirmed septic shock have a relative state of adrenal insufficiency. Therefore, will the physiologic replacement of steroids have any effect on mortality? The most recent data indicate that a short course of treatment with low-dose hydrocortisone and fludrocortisone reduces the risk of death in septic patients with relative adrenal insufficiency.27 Unfortunately, the results of this study are mainly applicable to septic patients who remain vasopressor dependent. Thus, the administration of steroids is not considered until several days into the ICU course. Routine ED administration of steroids to patients in septic shock cannot be recommended. Further research will elucidate the role of steroids in the treatment of sepsis.
Finally, an exciting area of research in sepsis involves antagonizing the deleterious effects of cytokines. As previously mentioned, cytokines have a large role in the pathogenesis of sepsis and septic shock. In general, cytokines can be divided into a pro-inflammatory arm and an anti-inflammatory arm. The two most well-known pro-inflammatory cytokines are TNF-alpha and IL-1. The most recognized anti-inflammatory cytokine is IL-10. These cytokines, as well as many others, interact in a complex network in which they influence each other’s production and activity.
In 1987, a monoclonal antibody to TNF was reported to protect baboons against lethal gram-negative bacteremia.33 Since then, there has been an explosion of research pertaining to the immunotherapy of sepsis. To date, there have been trials examining the effects of endotoxin monoclonal antibodies, glucocorticoids, ibuprofen, TNF-alpha antibodies, soluble TNF receptors, IL-1 receptor antagonists, platelet activating factor antagonists, granulocyte colony stimulating factor, intravenous immunoglobulins, antithrombin III, and activated protein C. Unfortunately, many of the earlier studies did not demonstrate marked improvement in patient mortality. Notwithstanding, Marshall, combining all studies of monoclonal antibodies against TNF, found an absolute risk reduction of 3.5%34 Additional trials have demonstrated similar results to this composite reduction in mortality.35 Recently, therapy with recombinant human activated protein C has received much attention in the medical literature. This stems from the study by Bernard et al, in which the authors found a 19.4% reduction in the relative risk of death in patients with severe sepsis.36 Although the immunotherapy of sepsis still is investigational and not immediately applicable to the ED, it is likely to be at the forefront of the battle against sepsis in the coming years. Thus, EPs should be familiar with its principles.
Cardiogenic Shock. The most common cause of cardiogenic shock is acute myocardial infarction (AMI). For shock to occur after an AMI, at least 40% of the myocardium must be involved. Shock occurs as a complication in 5-10% of patients with AMI.28 Despite important advances in the care of the patient with AMI (i.e., aspirin, beta-blockers, angiotensin-converting enzyme inhibitors, thrombolytics, percutaneous transluminal coronary angioplasty [PTCA], and intra-aortic balloon pump counterpulsation), the mortality rate from cardiogenic shock remains high.
Like other etiologies of shock, initial management of the patient in cardiogenic shock begins with fluid resuscitation. For reasons discussed above, isotonic crystalloid fluid is the initial fluid of choice. When administering fluids to patients with profound left ventricular failure, frequent re-assessment is necessary to detect the presence of pulmonary edema. Most patients with cardiogenic shock have existing coronary artery disease and/or left ventricular dysfunction. Often these patients are on medications such as nitrates, beta-blockers, and angiotensin converting enzyme inhibitors. These medications should be withheld until the patient’s hemodynamic status improves.
For patients who remain hypotensive despite fluid therapy, or who develop pulmonary edema, vasopressor support is required. Current recommendations for vasopressor therapy are based on the systolic blood pressure. For systolic blood pressures greater than 80 mmHg, dobutamine is the agent of choice.29 Dobutamine improves contractility and increases cardiac output. It also can exacerbate hypotension and precipitate arrhythmias. For systolic blood pressures of 70-80 mmHg, dopamine is the recommended vasopressor.29 When blood pressure is below 70 mmHg, norepinephrine is the agent of choice. The phosphodiesterase inhibitors, amrinone and milrinone, have been studied extensively. They may be used in combination with one of the above agents but are not recommended as single-line therapy.
The cornerstone of therapy for the patient in cardiogenic shock is the re-establishment of perfusion to ischemic myocardium. To accomplish this, three treatment modalities are available: thrombolytics, PTCA, and coronary artery bypass grafting (CABG). The introduction of thrombolytic therapy greatly has advanced the care of the patient with AMI. Unfortunately, the benefits of lytic therapy are less clear once cardiogenic shock has developed. In fact, no clinical trial has demonstrated reduced mortality when thrombolytics are administered to patients in shock.9 Reasons for this decreased efficacy are unclear and continue to be investigated.
Given the relative inefficacy of lytics, the remaining modalities are PTCA and CABG. When appropriate facilities are available, PTCA is superior to the use of lytics alone in patients presenting with AMI. Unfortunately, there is a paucity of data regarding the use of PTCA in patients with cardiogenic shock. To date, just one randomized, controlled, prospective trial has assessed the efficacy of these revascularization strategies in the setting of shock. The results of this ongoing trial continue to be debated. Preliminary conclusions support the use of PTCA in patients presenting with cardiogenic shock. Indications for CABG include left main disease and severe three-vessel disease.
For EPs working in facilities without the resources to perform PTCA or CABG, intra-aortic balloon pump counterpulsation (IABCP) can be helpful. Essentially, IABCP reduces systolic afterload and augments coronary perfusion during diastole.9 Regrettably, the use of IABCP has not been shown to reduce mortality. It does appear, however, that IABCP is helpful in stabilizing patients while the EP arranges for transfer to a tertiary care facility.
Neurogenic Shock. The most common cause of neurogenic shock is trauma to the spinal cord. For lesions above T1, sympathetic tone is lost, producing hypotension and bradycardia, the hallmarks of neurogenic shock. The goal of therapy is to maintain adequate perfusion pressure to prevent further ischemic injury to the spinal cord, brain, heart, and kidneys. Atropine usually is given in the acute setting to combat unopposed vagal tone. Frequently, vasopressor support is required. Unfortunately, there is no consensus or evidence-based medicine to recommend the ideal vasopressor.24 Furthermore, the optimal target mean arterial pressure has not been defined. Older texts have recommended the use of phenylephrine or ephedrine. Recent literature suggests dopamine as the vasopressor of choice in neurogenic shock.24 Dopamine not only increases peripheral vascular resistance, it also has chronotropic effects that increase heart rate.
Anaphylactic Shock. The presentation of patients with anaphylaxis can be dramatic. Intense bronchospasm, laryngeal edema, cardiac arrhythmias, hypotension, urticaria, and altered mental status are a few of the manifestations of anaphylaxis. Treatment is aimed at reversing the effects of the various mediators that are released when the patient is re-exposed to an antigen. Although debate continues about the ideal dose, epinephrine is the drug of choice in the treatment of anaphylactic shock. Its beta-1 and beta-2 stimulating effects reverse bronchoconstriction and increase cardiac contractility and heart rate. Additional medications given in anaphylaxis include steroids, antihistamines (both H1 and H2 blockers), and intravenous fluids. Table 3 lists the common medications used in anaphylaxis. Unlike the treatment of shock of other etiologies, in the treatment of anaphylactic, shock fluids are considered adjunctive therapy.
As hospitals combat the growing problem of overcrowding, EPs are confronted with the daunting task of caring for critically ill patients for longer periods of time. The EP no longer can resuscitate a hypotensive patient and expeditiously transport him either to the ICU or OR. In fact, EPs can expect to care for critically ill patients long after the "golden hour"30,31 has elapsed. Therefore, it is imperative that the EP resist the temptation to rely on the presence, or absence, of traditional clinical markers of shock. Rather, the EP must use objective information obtained from current monitoring methods to determine which patients require further resuscitation. By identifying patients who continue to exhibit evidence of ongoing cellular hypoxia, the EP can continue aggressive treatment and ultimately improve patient survival.
1. Osborn TM, Scalea TM. A call for critical care training of emergency physicians. Ann Emerg Med 2002;39:562-563.
2. Rivers EP, Nguyen HB, Havstad S, et al. Early goal directed therapy in the treatment of the systemic inflammatory response syndrome (SIRS): An outcome evaluation of emergency department intervention [abstract]. Acad Emerg Med 2000;7:427.
3. Kline JA. Shock. In: Marx JA et al, eds. Rosen’s Emergency Medicine: Concepts and Clinical Practice, 5th ed. St. Louis: Mosby; 2002:33-47.
4. Warren JC. Surgical Pathology and Therapeutics. Philadelphia, 1895.
5. Gross SD. Systems of Surgery. Quoted by Mann FC. Bulletin of the Johns Hopkins Hospital. 1914;25:205-212.
6. Dutton RP. Shock and trauma anesthesia. Anesthesiol Clin North Am 1999;17:83-95.
7. Rivers EP, Rady MY, Bilkovski R. Approach to the patient in shock. In: Tintinalli. Emergency Medicine: A Comprehensive Study Guide, 5th ed. McGraw Hill: New York; 2000;3:215-222.
8. McNutt S, Denninghoff KR, Terndrup T. Shock: Rapid recognition and appropriate ED intervention. Emergency Medicine Practice 2000;2:1-24.
9. Hollenberg SM. Cardiogenic shock. Crit Care Clin 2001;17:391-410.
10. Kemp SF. Current concepts in pathophysiology, diagnosis, and management of anaphylaxis. Immunol Allergy Clin North Am 2001;21:611-634.
11. Orlinksky M, Shoemaker W, Reis ED, et al. Current controversies in shock and resuscitation. Surg Clin North Am 2001;81:1217-1262.
12. Rivers E. Sepsis: From the ED to ICU: The importance of early intervention. Michigan Emergency Medicine Assembly, July 2002.
13. Auden J, Bernstein WK, Khastgir T, et al. The use and clinical importance of a substrate-specific electrode for rapid determination of blood lactate concentrations. JAMA 1994;272:1678-1685.
14. Marik PE. Sublingual capnometry: A clinical validation study. Chest 2001; 120:923-927.
15. Waxman K. Monitoring in shock: Stomach or muscle? Crit Care Med 1999;27:2047-2048.
16. Pryor JP, Pryor RJ, Stafford PW. Initial phase of trauma management and fluid resuscitation. Trauma Reports 2002;3:1-12.
17. Stern SA. Low-volume fluid resuscitation for presumed hemorrhagic shock: Helpful or harmful? Curr Opin Crit Care 2001;7:422-430.
18. Choi PT, Yip G, Quinonex LG, et al. Crystalloid vs. colloids in fluid resuscitation: A systematic review. Crit Care Med 1999;27:200-210.
19. Waxman K. Are resuscitation fluids harmful? Crit Care Med 2000; 28:264-265.
20. Ketcham EM, Carirns CB. Hemoglobin-based oxygen carriers: Development and clinical potential. Ann Emerg Med 1999;33:326-337.
21. McCunn M, Karlin A. Nonblood fluid resuscitation: More questions than answers. Anesthesiol Clin North Am 1999;17:107-123.
22. Dietch EA. Shock resuscitation: Is the glass half-empty or half-full? Crit Care Med 2000;28:2665-2666.
23. Porter JM, Ivatury RR, Azimuddin K, et al. Antioxidant therapy in the prevention of organ dysfunction syndrome and infectious complications after trauma: Early results of a prospective randomized study. Am Surg 1999;65: 478-483.
24. Khalif S, DeBlieux PM. Vasopressors in emergency medicine. Accessed at www.emedhome.com, February 2003.
25. Nasraway SA. Norepinephrine: No more "leave ’em dead"? Crit Care Med 2000;28:3096-3097.
26. Martin C, Papazian L, Perrin G, et al. Norepinephrine or dopamine for the treatment of hyperdynamic septic shock? Chest 1993;103:1826-1831.
27. Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002;288:862-871.
28. Goldberg RJ, Gore JM, Alpert JS, et al. Cardiogenic shock after acute myocardial infarction: Incidence and mortality from a community-wide perspective, 1975-1988. N Engl J Med 1991;325:1117-1122.
29. Hollenberg SM, Kavinsky CJ, Parrillo JE. Cardiogenic shock. Ann Intern Med 1999;131:47-59.
30. Cowley RA. Maryland's EMS system: Built to serve. Traumagram: Newsletter of the American Trauma Society 1978;4:4-7.
31. Taylor B. Close encounters of the Cowley kind: An exclusive journal interview with R Adams Cowley, MD, Director of the Maryland Institute for Emergency Medical Services, State of Maryland. Maryland State Medical Journal 1978;27:35-49.
32. Brown MA, Casola G, Sirlin CB, et al. Blunt abdominal trauma: Screening ultrasound in 2693 patients. Radiology 2001;218:352-358.
33. Tracey KJ, Fong Y, Hesse DG, et al. Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteremia. Nature 1987:330; 662-664.
34. Marshall JC. Clinical trials of mediator-directed therapy in sepsis: What have we learned? Intensive Care Med 2000;26:S75-S83.
35. Reinhart K, Menges T, Gardlund B, et al. Randomized, placebo-controlled trial of the anti-tumor necrosis factor antibody fragment afelimomab in hyperinflammatory response during severe sepsis: The RAMSES study. Crit Care Med 2001;29:765-769.
36. Bernard GR. LaRosa SP, Laterre PF, et al. The efficacy and safety of recombinant human activated protein C for the treatment of patients with severe sepsis. N Engl J Med 2001:344:699-709.