Changing paradigms in surgical resuscitation

Yvette Fouche, MD; Robert Sikorski, MD; Richard P. Dutton, MD, MBA
Patients undergoing emergency surgery typically require resuscitation, either because they are hemorrhaging or because they are experiencing signicant internal uid shifts. Intravascular hypovolemia is common at the time of anesthesia induction and can lead to hemodynamic collapse if not promptly treated. Central pressure monitoring is associated with technical complications and does not improve outcomes in this population. Newer modalities are in use, but they lack validation. Fluid resuscitation is different in bleeding and septic patients. In the former group, it is advisable to maintain a deliberately low blood pressure to facilitate clot formation and stabilization. If massive transfusion is anticipated, blood products should be administered from the outset to prevent the coagulopathy of trauma. Early use of plasma in a ratio approaching 1:1 with red blood cells (RBCs) has been associated with improved outcomes. In septic patients, early uid loading is recommended. The concept of goal-directed resuscitation is based on continuing resuscitation until venous oxygen saturation is normalized. In either bleeding or septic patients, however, the most important goal remains surgical control of the source of pathology, and nothing should be allowed to delay transfer to the operating room. We review the current literature and recommendations for the resuscitation of patients coming for emergency surgery procedures. (Crit Care Med 2010; 38[Suppl.]: S411S420) KEY WORDS: resuscitation; emergency; trauma; deliberate hypotension; transfusion; vasopressin; stroke volume variation; plasma; colloid; monitoring

he principal difference between anesthesia and resuscitation for elective surgical cases and anesthesia and resuscitation for emergency cases is the common presence of shock in the latter group of patients. Shock is a physiologic state characterized by a systemic reduction in tissue perfusion below that necessary to meet the metabolic needs of tissues and organs. Hypoperfusion results in oxygen debt, occurring as oxygen delivery becomes unable to meet metabolic requirements. Hypoperfusion is a timedependent emergency (1). The American College of Surgeons categorizes shock by cause into four classes: distributive, obstructive, cardiogenic, and hemorrhagic. Hemorrhage is the most common cause of shock after injury, and a frequent cause of shock in nontrauma emergency cases. The Advanced Trauma Life Support curriculum of the American College of Surgeons further classies hemorrhagic shock into four

From the Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD; and R Adams Cowley Shock Trauma Center, University of Maryland Medical System, Baltimore, MD. Dr. Sikorski has held consultancies and received honoraria from Edwards Lifesciences. Drs. Fouche and Dutton have not disclosed any potential conicts of interest. For information regarding this article, E-mail: r.dutton@asahq.org Copyright 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/CCM.0b013e3181ec5bdf

classes, with class 4 being the most severe, based on signs and symptoms, amount of blood loss, and the type of uid replacement (2). Hemorrhagic shock is a severe lifethreatening emergency affecting all organ systems of the body. Uncontrolled hemorrhagic shock initially leads to hypotension (decrease in mean arterial pressure [MAP]) due to an acute decrease in cardiac output. The intrinsic response to hemorrhagic shock is an increase in heart rate in an attempt to preserve cardiac output. In most cases, tachycardia is the earliest measurable circulatory sign of shock. The release of endogenous catecholamines increases peripheral vascular resistance, which in turn increases diastolic blood pressure and reduces pulse pressure but does little to increase organ perfusion. Other hormones with vasoactive properties are released into the circulation during shock, including histamine, bradykinin, endorphins, and a cascade of prostanoids and other cytokines (3). These substances have profound effects on the microcirculation and vascular permeability leading to microcirculatory dysfunction. Microcirculatory dysfunction is characterized by contraction or disappearance of arterioles with cessation of blood ow. Arterial hemorrhage is controlled intrinsically by formation of extraluminal clot, a process that occurs during hypotension (4).

In large elective cases, hemorrhage and third-space uid shifts may necessitate the administration of uid and even blood products, but it is possible to anticipate these needs and the patient seldom reaches a state of tissue hypoperfusion. In emergency surgery, on the other hand, bleeding or infection has often resulted in a substantial total body decit of uid at the time of presentation to the operating room (OR). Failure to recognize and address this decit can result in immediate cardiovascular collapse with induction of anesthesia and will contribute to a wide variety of poor outcomes, including coagulopathy, sepsis, myocardial ischemia, stroke, and organ system failure. Successful anesthetic management of the emergency general surgery patient depends as much as anything on successful uid resuscitation. This article will present current recommendations for monitoring volume status during emergency surgery and for administration of uids, blood products, and pressors. The role of deliberate hypotension will be explored, as well as early therapies to prevent the coagulopathy of trauma and shock. We will begin with a discussion of diagnostic modalities.

Monitoring and assessment of volume status

The traditional approach to the measurement of intravascular uid volume has come under scrutiny during the past
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few decades. The gold standard methods, such as central venous pressure monitoring and pulmonary artery catheter (PAC) monitoring (5), have seen a decline in routine clinical use. There exists a very poor relationship between central venous pressure and blood volume, and recent data (6) suggested that neither absolute central venous pressure nor change in central venous pressure over time reliably predict the hemodynamic response to a uid challenge. There still exist certain clinical scenarios, such as acute air embolus (multiorice catheter), acute pulmonary embolus, and right ventricle infarction, where central venous monitoring may have a role. Furthermore, a recent study (7) showed that central venous catheter management, utilizing an explicit management protocol, led to fewer complications than PAC management in the treatment of acute lung injury, as well as an increase in intensive care unit-free days. Pulmonary artery catheterization has been the mainstay of hemodynamic monitoring throughout the past four decades, but it is becoming increasingly controversial (8). An international consensus conference (9) was held to develop recommendations for hemodynamic monitoring and implications for management of patients with shock. Evidence-based recommendations were developed after conferring with experts and reviewing the pertinent literature, by a jury of 11 persons representing ve critical care societies. The jury recommended against the routine use of the PAC in shock and against the use of static preload measurements alone to predict uid responsiveness. The use of the PAC in critically ill patients with a high severity of illness and acute coronary syndrome may provide a decrease in the mortality rate but further randomized trials are needed (10, 11). Over the past decade, there has been a temporal improvement in survival at ARDSnet centers for acute lung injury/ acute respiratory distress syndrome not only because of the use of lower tidal volume ventilation and conservative uid therapy but also with advancements in critical care; however, the use of the PAC has not been implicated in this survival (1215). In one recent retrospective study, trauma patients managed with PAC were more severely injured and had a high mortality rate. However, severely injured patients (Injury Severity Score, 2575) who arrived in severe shock (base decit of 11), and older patients (age,
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6191 yrs) had an associated survival benet when managed with the PAC (16). Addition of continuous mixed venous oxygen monitoring to central venous pressure measurement has shown a benet in the Emergency Department and intensive care unit management of patients in septic shock (17). Decreased venous saturation is an indirect indicator of poor tissue perfusion and the need for resuscitation. Use of venous or tissue oximetry during emergency general surgery or acute trauma cases has not gained a large following, however, because the dynamic response of these systems is felt to be too slow to guide therapy during active hemorrhage. Other minimally invasive technologies which have been used recently to determine uid volume status include echocardiography, transesophageal Doppler, and arterial pressure-based cardiac output systems. The arterial pressure-based cardiac output technologies also allow for assessment of volume responsiveness. The use of echocardiography, both transthoracic and transesophageal, has gained popularity in the assessment of ventricular function (both systolic and diastolic) and volume status in the critically ill patient. Left ventricular function, assessment of global wall motion, and ventricular lling by transthoracic echocardiography can be utilized by the nonechocardiographer in the critical care setting. Basic parasternal, apical, and subxyphoid views can be obtained in the majority of patients to assess real-time hemodynamics. These skills can be acquired through specialized training under the guidance of an experienced echocardiographer or in a critical care training program with an emphasis on echocardiographic assessment. Transesophageal echocardiography displays the left ventricle with superior denition to transthoracic echocardiography. It is difcult, however, to view the apex in a nonforeshortened manner with transesophageal echocardiography making, transthoracic echocardiography superior for apical views of the left ventricle. Basic left ventricular volume assessment and wall motion in transesophageal echocardiography are done in the transgastric midpapillary short-axis view. This view is easy to obtain and subjectively can give the necessary information for basic hemodynamic assessment and guidance. Doppler echocardiography can also be used in the assessment of both right and left ventricular systolic function. The use

of Doppler requires both experience and acceptable viewing angles for accuracy of measurement. Cardiac output measurements can be obtained, using velocity time integrals in the right and left ventricular outow tracts utilizing pulse wave and continuous wave Doppler. Mitral inow measurements, with the pulse wave sample gate placed at the tips of the mitral leaets, will allow assessment of diastolic function and diastolic hemodynamics (18, 19). It must be remembered, however, that left ventricular loading conditions, heart rate, and left atrial and ventricular interactions inuence mitral inow patterns. Pulmonary capillary wedge pressure can be estimated, using color M-mode Doppler imaging and Doppler tissue imaging. However, estimating pulmonary artery occlusion pressure by this method in critically ill patients with circulatory shock and acute lung injury may not be accurate enough to adjust therapy (20). Because of the dependence on expensive technology and operator experience, echocardiography both transthoracic and transesophageal remains an excellent diagnostic tool but a poor monitoring device. Esophageal Doppler monitoring measures blood ow velocity in the descending aorta by way of an ultrasound transducer at the tip of a exible probe. The probe must be placed so that the transducer faces the aorta and an aortic velocity signal is obtained. The estimation of stroke volume with this method relies on the measurement of stroke distance in the descending aorta (velocity time integral), which is then converted into systemic stroke volume via algorithms that vary slightly between manufacturers (21). Esophageal Doppler has been shown to be a clinically useful alternative to thermodilution in determination of cardiac output (2224) but suffers the common problem of noninvasive monitors in that the algorithms have been developed and much of the clinical validation studies performed in relatively healthy and normal patients. Algorithms used to derive familiar metrics, such as cardiac output and stroke volume, may be awed in patients with the extreme physiology of severe shock or exsanguinating hemorrhage. Most clinicians are now familiar with the concept of a goal-directed approach for volume resuscitation and the treatment of early sepsis (17). There are many new technologies available to guide uid resuscitation with a more dynamic apCrit Care Med 2010 Vol. 38, No. 9 (Suppl.)

proach, rather than the use of the historical static parameters. Determining where the patient lies on their individual Starling curve, during the resuscitation process, may be more important than the uid type being administered (25). Arterial pressure waveform systems function on the relationship between pulse pressure and stroke volume. Systolic pressure variation, the difference between maximum and minimum systolic pressure during one mechanical breath, has been shown to predict uid responsiveness to volume loading. Concepts, such as pulse pressure variation and stroke volume variation in ventilated patients, have been extensively reviewed in the literature and found to be reliable predictors of volume responsiveness. Arterial-based systems in clinical use today include the PiCCO (Phillips, Andover, MA), pulseCO (LiDCO, Ltd., Lake Villa, IL), and the FloTrac/ Vigileo (Edwards Lifesciences, Irvine, CA). The systems are all minimally invasive. Some require calibration, such as the LiDCO plus which utilizes lithium dilution and a specialized lithium sensor; however, the LiDCO rapid does not require calibration and can be used with a standard arterial catheter. This system utilizes a validated pulseCO algorithm, as well as pulse power analysis. The PiCCO system uses continuous pulse contour analysis but also requires a femoral arterial thermodiluton catheter. Any standard central venous catheter may be used for the transpulmonary thermodilution. Transpulmonary cardiac output and intrathoracic blood volume may be obtained with this system. Calculation of extravascular lung water using this device has been described elsewhere but is not available in the United States. These features make this system relatively more invasive than the others. The FloTrac system (Edwards Lifesciences) requires a special transducer, which is attached to the existing arterial catheter. The FloTrac transducer samples at a higher sampling rate than the intraoperative monitoring systems currently in use (100 Hz vs. 15 40 Hz). This system does not require calibration and calculates ow parameters every 20 secs. The need for calibration is overcome by automatic vascular tone adjustments averaged over 1 min. All of the aforementioned systems calculate, through various methods, dynamic parameters, such as stroke volume variation, pulse pressure variation, stroke
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Figure 1. Receiver operator characteristics of various measures of vascular status. AUC, area under the curve; SVV, stroke volume variation; PPV, pulse pressure variation; CVP, central venous pressure; PCWP, pulmonary capillary wedge pressure; GEDVI, global end-diastolic volume index; LVEDAI, left ventricular end-diastolic area index. Reprinted with permission from Hofer et al (26).

volume, stroke volume index, cardiac output, and cardiac index. Stroke volume variation and pulse pressure variation are more reliable indicators of volume responsiveness than central venous pressure, pulmonary artery occlusion pressure, left ventricular end-diastolic volume index, and global end-diastolic volume index, as shown in Figure 1. Stroke volume variation and pulse pressure variation have limitations in clinical use. They can be affected by alterations in ventilatory settings, chest wall compliance, and dysrhythmias, as well as by pharmacologically induced changes in ventricular and aortic compliance (26). In summary, no one monitor or system has been shown to improve outcome by itself. Direct examination of cardiac lling and function is possible, using echocardiography, but not useful as an ongoing monitor except over very short periods of time. Use of minimally invasive technologies for following trends has largely replaced traditional central venous pressure and pulmonary artery catheter-based techniques, but the newer technologies suffer from a lack of supportive evidence, especially in highly complex patients. Increasing clinical experience and evidence-based practice along with the introduction of new technologies may prove to inuence outcome in a positive manner now and in the future.

Fluid administration: Quantity and rate

Many emergency surgery and trauma patients are hypotensive at the time of presentation to the OR. This may be due to hemorrhage (e.g., trauma, peptic ulcer disease), dehydration (e.g., bowel obstruction), cardiac dysfunction (e.g., patients with coronary artery disease), loss of vasomotor tone (e.g., sepsis, spinal cord injury), or even mechanical issues, such as tension pneumothorax or pericardial tamponade. In most cases, blood pressure will be improved by intravenous uid administration. This is usually the rst line of therapy in hypotensive patients, especially those about to undergo induction of anesthesia. When providing this initial bolus, however, the anesthesiologist must not lose sight of the larger picture. Hypotension is easily temporized, but rarely cured, by administration of uids. Temporary reversal of hypotension should not be mistaken for reversal of sepsis or resolution of hemorrhage. Figure 2 shows the relationship between the functional capacity of the vascular system and the volume of uid which lls it. This ratio, along with the pumping power of the heart, determines the blood pressure. The dotted diagonal line in the gure represents the isobaric state and shows that a patient with hemorrhage compensated by vasoconstriction (e.g., 4 L of blood in a 4-L space)
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Figure 2. Relationship between blood volume and the capacity of the vascular system. A normal patient with a normal blood pressure has about 5 L of blood circulating in a 5-L vasculature. Bleeding decreases blood volume, but compensatory vasoconstriction restores blood pressure. The dotted line represents the isobaric state of preserved blood pressure in various states of shock.

can have a blood pressure similar to that of a normal control (5 L in a 5-L space). This explains why blood pressure alone is not a good indicator of shock state, because the bleeding, vasoconstricted patient may be suffering from signicant occult hypoperfusion at the tissue level. In young patients especially, blood loss up to 40% of the normal circulating volume can occur before the limits of compensation are reached and catastrophic vascular collapse occurs. The goals of resuscitation include restoring circulatory volume via uid resuscitation, restoring the microcirculation, preventing clot disruptionthereby preventing rebleedingand maintaining adequate perfusion pressure to the brain and other vital organs. Fluid administration is clearly benecial to the patient who has lost blood but is not actively bleeding (e.g., an isolated femur fracture, a duodenal ulcer which has spontaneously coagulated). This patient may have been hypotensive acutely but will more likely be normotensive (but hypoperfused) at the time of treatment, due to the compensatory vasoconstriction described above. In this case, a uid bolus will produce an immediate increase in blood pressure by the Frank-Starling law: Increased pressure n the right side of the heart means increased myocardial wall tension, which results in increased force of contraction. Over ensuing heartbeats, the blood pressure will return to
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normal as the vascular system relaxes. Tissue perfusion is improved. In the patient who is still actively bleeding or who has formed only fragile early clots, a uid bolus may be deleterious. Blood pressure will still increase acutely, for the reasons just described. The rise in pressure for a given volume of uid may be more pronounced than in a normal patient, because the bolus represents a larger increase in volume relative to a smaller (i.e., vasoconstricted) vasculature. This rise in pressure will increase bleeding from open vessels and will wash off fragile early clots (4). Secondary negative effects include dilution of the clotting system and progressive hypothermia if uids are not carefully warmed before administration. The overall effect will be a rise in pressure followed by a second drop as bleeding accelerates. If this motivates further uid administration, a vicious cycle is created that leads rapidly to exsanguination and vascular collapse. This is the transient responder described in the Advanced Trauma Life Support curriculum and represents a surgical emergency (2). Effective treatment consists of denitive anatomical source control (surgery or anesthesia) facilitated by tolerance of hypotension until hemostasis is achieved. The timing of crystalloid uid resuscitation with respect to intrinsic hemostasis has been studied in animal models. Hirshberg et al (27) studied this in adult

human models. The model was designed to simulate hemorrhagic shock in an urban trauma context. The model demonstrated that an injured patient with a fast initial bleeding rate of 1.0 L/min (representing a major vascular injury), bleeds for 5.5 mins until intrinsic hemostasis occurs. An injured patient with a slower initial bleeding rate of 0.1 L/min bleeds for 24 mins before hemostasis occurs. Thus, at approximately 15 mins from injury (a realistic time frame for a paramedic to arrive in an urban scenario), both the faster and slower bleeders will be hypotensive (MAP 60 mm Hg). However, the former will already be in the self-resuscitation phase with a gradual increase in MAP after bleeding has stopped, whereas the latter will still have ongoing blood loss. Based on this and other experimental data, intrinsic hemostasis is both a ow-dependent process and a time-dependent process. Extraluminal clot formation is triggered by hypotension (MAP 60 mm Hg) and lasts 10 mins, which is the mean normal value of whole blood clotting (27). Therefore, the rate of uid administration during resuscitation may affect the stability of immature clots. Slow bleeders will take longer to become hypotensive and a rapid bolus will inhibit a further drop in MAP, therefore delaying the process of clot formation. If a rapid bolus is given in the face of an immature or vulnerable clot, then rebleeding can occur. Fast bleeders will become hypotensive sooner and initiate the clot formation process sooner. Although Sondeen et al (28) have shown a single reproducible threshold for rebleeding in a pig aortotomy model, their results do not explain why trauma patients do not invariably rebleed when their pressure returns to normal. This may be due to stabilization of clot over time orin clinical practiceto surgical or angiographic hemostasis. When crystalloids are given after the onset of intrinsic hemostasis, rebleeding occurs when the combined effect of intravenous uids and transcapillary rell on MAP exceeds the rebleeding threshold, a linear timedependent function that operates at MAP of between 50 and 100 mm Hg. Hirshberg et al (27) demonstrated that, with higher initial bleeding rates (0.4 L/min), only volumes in excess of 2 L, given at rates over 0.2 L/min, will trigger rebleeding. Animal models have shown that the risk of death in uncontrolled hemorrhage seems to be related to the severity of hemorrhage. In severe hemorrhage, uid
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resuscitation reduces the risk of death, but in less severe hemorrhage, the risk of death is increased. Aggressive uid resuscitation increases hydrostatic pressure and leads to destabilization of premature clot, leading to increased blood loss and diluting the oxygen-carrying capacity of blood. This suggests that the risks and benets of uid resuscitation are nely balanced. Animal studies showed a benet to small-volume, hypotensive resuscitation in reducing the risk of death. A systematic review of animal studies by Mapstone et al (29) suggested that using a lower than normal blood pressure as a guide to uid resuscitation consistently reduces the risk of death, regardless of the severity of injury. Laboratory evidence showing the benet of controlled hypotensive resuscitation for hemorrhagic shock came from a wide variety of animal studies performed in the 1980s and 1990s. Studies (30) performed in rat, swine, sheep, and dog models of uncontrolled hemorrhage all demonstrated that, although some uids were required to avoid hemodynamic collapse, attempts to normalize blood pressure in the face of ongoing hemorrhage were counterproductive. Rebleeding and total blood loss were consistently increased, and survival was reduced. The most elegant of these models directly demonstrated increased rebleeding from an abdominal aortic injury in swine, and decreased total blood ow and tissue perfusion, despite the administration of signicantly larger volumes of uid (31). These laboratory studies prompted investigation of uid-limited resuscitation in human trauma victims. A landmark article (32) published in 1994 described deliberate restriction of presurgical uids in a population of hypotensive patients with penetrating torso trauma and demonstrated a signicant reduction in mortality in this high-risk group. This work was conrmed, in part, by a retrospective review (33) of trauma patients resuscitated with a rapid infusion system, and a later prospective study (34) of a similar population, which titrated uid therapy to either normal or low blood pressure (MAP 80 mm Hg vs. 60 mm Hg). The overall effect of these studies was to greatly reduce the quantity and rate of initial uid administration in trauma patients treated at major centers, with increased emphasis on rapid diagnosis and anatomical resolution of ongoing bleeding. The equivocal results achieved in the later study suggest that animal models do
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not reect the complexity of multiple injuries or comorbidities in humans. The Advanced Trauma Life Support guidelines, reecting this more recent thinking, now emphasize control of bleeding rst with more cautious early uid resuscitation (2). Not all patients presenting for emergency surgery are bleeding, however, and perioperative uid administration strategy must be adjusted accordingly. In the patient with early or impending sepsis, third-space loss of intravascular uid may lead to dehydration, whereas endotoxin-mediated vasodilation can produce a substantial mismatch of vascular volume with vascular capacity (Fig. 2). The patient with a perforated viscus organ and peritonitis will typically present to the OR hypotensive from a combination of three mechanisms: loss of uid from the bloodstream to the extravascular or intraluminal space; inappropriate dilation of the vasculature; and decreased myocardial power from the negative inotropic effects of endotoxin. In contrast to hemorrhagic shock, however, tissue perfusion is often better preserved in the septic, hypotensive patient because the initial compensation for hypotension is a high-ow, low-pressure state that preserves oxygen delivery. Fluid administration is benecial to these patients in the short term, and improved outcomes have been shown with goal-directed therapy that more rapidly restores intravascular volume during early efforts at source control (17). Although a signicant proportion of the administered uid will exit the bloodstream over time, due to inammation-mediated increases in vascular permeability, the early support of intravascular volume will facilitate organ system perfusion during initial resuscitation. Fluid administration in the septic patient is, thus, a reverse image of the hemorrhaging patient, with more value early than late. A nal note on the rate and quantity of uid administration concerns the interaction with anesthesia. Most anesthetic agents are direct vasodilators and negative inotropes. All of them, even safe agents, such as etomidate or ketamine, have potent indirect negative effects through reduction of circulating catecholamine levels in patients who are in pain or otherwise physiologically stresssed (35). Administration of anesthetics must be approached cautiously in emergency surgery patients, with induction doses reduced by 50% to 90% and

maintenance doses started at low levels and only titrated upward if the patient is tolerant. A series of laboratory studies have shown that hemorrhagic shock itself changes cerebral responsiveness to intravenous anesthetics. An induction dose of propofol as little as one tenth of normal has been shown to produce equivalent reductions in cerebral electrical activity when administered to an animal in shock, even after adjustment for a reduced circulating blood volume (36). Although indicated surgical therapy and source control of either hemorrhage or a septic focus should not be delayed to pursue resuscitation, bolus administration of uid at the time of anesthetic induction may help to prevent catastrophic vascular collapse. In the hemorrhaging patient, this bolus therapy should be carefully monitored and balanced against the administration of anesthetics to preserve a state of controlled hypotension.

Fluid administration: Crystalloids

Fluid resuscitation typically begins with isotonic crystalloid solutions, such as normal saline and lactated Ringers solution. These solutions have the advantage of being inexpensive, plentiful, and easy to administer. For patients who are hypovolemic (rather than hemorrhaging), isotonic crystalloids may be all the uid that is required. These solutions do not linger long in the bloodstream, with rapid equilibration of administered volume across the interstitial and intravascular compartments and relatively rapid transit into the cells. Patients with normal renal function can tolerate relatively large amounts of administered crystalloid solution without harm and will maintain normal blood chemistry. The use of large volumes of normal saline may be deleterious because this uid is actually slightly hypertonic and can predispose the patient to hyperchloremic metabolic acidosis. Lactated Ringers solution does not share this problem but has theoretical concerns of its own related to the potential for immune modulation. Several theoretical articles have been published on this point, but the likely clinical impact is small relative to the larger concern with crystalloids: what they are not. Crystalloid uids do not clot or carry oxygen and are therefore of limited (and potentially negative) value in resuscitation of hemorrhaging patients.
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Fluid administration: Hypertonic saline

Although the traditional approach to uid resuscitation in nonbleeding emergency surgery patients is the infusion of isotonic crystalloids, a newer and evolving modality is small-volume resuscitation (SVR) using rapid infusion of a small volume of a hypertonic solution. Hypertonic solutions (i.e., 3% NaCl) act like magnets, drawing uid from tissues into the bloodstream, and thereby rapidly increasing circulating volume. SVR is recommended by the Committee on Fluid Resuscitation for Combat Casualties (37). SVR has been extensively analyzed (38) and is currently approved for use in several countries, including Europe (39). SVR is currently not part of the Advanced Trauma Life Support guidelines (2). When crystalloid is infused, it undergoes an exponential departure from the intravascular space with a half-life of only17 mins, yielding an eventual distribution of intravascular to interstitial uid of between 1:3 and 1:10. This is why one must infuse a much larger volume of crystalloids than the perceived blood loss to stabilize MAP in operative hemorrhage. In trauma patients this could jeopardize vulnerable early clot formation. There are also other potential complications with large-volume resuscitation, such as pulmonary edema (resulting in hypoxemia and circulatory insufciency), increase in total body water, hypoalbuminemia resulting in systemic edema, coagulopathy, abdominal compartment syndrome, cardiac dysfunction, gastrointestinal ileus, and bowel anastomotic complications. When hypertonic solutions are infused, they undergo a longer exponential decay from the vascular space, yielding a distribution of intravascular to interstitial uid of 1:1.5. SVR is not a denitive therapy and must be followed by conventional therapy once the patient has been resuscitated and source control achieved. Hypertonic solutions have also been noted to improve microvascular ow, control intracranial pressure, and stabilize arterial pressure and cardiac output, with no deleterious effects on immune function or coagulation. However, meta-analysis of clinical studies shows no signicant improvement in survival with the use of hypertonic solutions for resuscitation in hemorrhagic shock, perhaps again due to the heterogeneity of emergency surgery patients and the multiple confounding variables which apply (40).
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Fluid administration: Colloids

The use of colloid solutions, which tend to remain in the intravascular compartment due to their protein content, has also been advocated for treatment of uncontrolled hemorrhage. These solutions are referred to in the literature as hyperosmotic-hyperoncotic solutions. Hyperviscous solutions may also play a role in controlling cerebral blood ow (41). It is theorized that a hyperoncotic/ hyperviscous combination during the initial uid resuscitation of emergency surgery patients will both improve MAP and preserve the microcirculation with a minimum volume of infused uid (42). Hyperviscous combined with hyperoncotic solutions may also reduce the amount of oncotic load to the kidneys. Further studies are needed in this area. Several colloid solutions are commercially available, including albumin, hydroxyl ethyl starch, and dextran. Colloids have been shown in several studies to improve microvascular perfusion. It had been suggested that colloids may have anti-inammatory properties, but this nding is controversial and has not been conrmed by larger studies. Furthermore, colloid solutions are more expensive, may bind serum ionized calcium, decrease circulating immunoglobulins, and can lead to coagulopathy in doses of 30 mL/kg. Furthermore, some hyperoncotic solutions have been associated with renal tubular dysfunction. Again, meta-analysis of clinical studies (43) showed no signicant improvement in survival with the use of colloid solutions. In addition to restoring circulating volume and increasing MAP, it is important to restore the microcirculation. This, in turn, can restore tissue perfusion and prevent the end-organ damage, which results from shock. Microvascular blood ow is regulated by MAP and blood viscosity. Arteriolar blood vessels dilate when MAP decreases, thereby increasing blood ow to tissue beds. The cerebral and splanchnic vasculatures have especially sensitive microcirculations. Several small animal studies (44) demonstrated arteriolar dilation with increased blood viscosity. However, large animal studies (45) with hyperviscous solutions alone do not demonstrate improved tissue oxygenation or oxygen utilization. When a hyperviscous solution is used alone, it results in an expanded blood volume compartment and the need for larger total uid volume to ll the vascular space.

Dextran is the commercially available hyperviscous solution in the United States. Dextran is commonly used by microsurgeons to decrease vascular thrombosis. Because dextran is a complex branched glucan (polysaccharide made of many glucose molecules), it can be used to increase plasma viscosity. The side effects of dextran are few, but very serious. They include anaphylaxis, volume overload, pulmonary edema, or platelet dysfunction. An uncommon but signicant complication of the dextran osmotic effect is acute renal failure. Pathogenesis of this complication is not clear. Some suggest that dextran is directly toxic to the tubules and glomeruli,whereas others suggested intraluminal hyperviscosity results in indirect damage (45).

Fluid administration: Blood products

Knowledge of the underlying pathophysiology is essential for determination of the best choice of resuscitative uid. Emergency surgical patients who are not hemorrhaging should be managed initially with infusion of isotonic crystalloid or colloids to replete the intravascular space. Patients who are bleeding should receive blood. Although the evils of transfusion have been well described, there is little doubt that increased exposure to blood products increases the long-term risk of inammatory complications; there is also a substantial short-term benet to transfusion. Administration of blood products to a hemorrhaging patient restores oxygencarrying capacity and supports the coagulation system, both of which are essential to survival. The clinical decision, therefore, is one of weighing the relative risks and benets of the individual situation. Monitoring data can be of assistance, by indicating the degree of hypoperfusion and, thus, the speed at which resuscitation needs to proceed; laboratory data can indicate the patients baseline hemoglobin concentration, platelet count, and clotting factor activity. In real time, however, laboratory data may lag behind the clinical situation. The fastest measure of blood composition to turn aroundthe hemoglobinis not a good indicator of the depth of hemorrhage, because it expresses a concentration of red cells, which will not change in a patient who is losing whole blood. Hemoglobin and hematocrit only fall later, when crystalloid uid infusion or recruitCrit Care Med 2010 Vol. 38, No. 9 (Suppl.)

ment of extravascular uid restores the circulating blood volume. The most common measures of coagulation activity prothrombin time and partial thromboplastin timemay take so long to return values from the laboratory that the clinical situation has changed by the time the results are known. The experienced clinician must be willing to initiate transfusion therapy empirically, based on the patients degree of distress, an understanding of the underlying pathophysiology, and the likely time required for anatomical control. Red blood cells (RBCs) are traditionally the rst blood products administered. RBCs carry oxygen and, thus, help to reverse shock caused by anemia. In previously healthy patients, the threshold hemoglobin value at which lactic acid begins to accumulate during acute hemorrhage (indicating cellular hypoperfusion) is about 6 g/day (46). Values lower than this can be tolerated in chronic situations arising over time, because the patient can compensate physiologically. The effects of vasoconstriction, on the other hand, will exacerbate the effects of anemia and produce more rapid deterioration in physiology. Care should also be taken with patients with underlying chronic diseases; they may have both a lower baseline hematocrit and a greater sensitivity to the effects of hypoperfusion. A single unit of RBC administered to a euvolemic patient should raise the hemoglobin concentration by about 1 g/dL. The emergency surgery patient is seldom euvolemic so this understanding is of little value clinically. In practice, each unit of RBC should be administered like a dose of medication. There should be a specic purpose in the transfusion, and the effects once given should be carefully assessed before proceeding with the next unit. Cross-matching and delivery of blood to the bedside will typically take at least an hour from the time a sample is delivered to the blood bank. Delivery of RBCs to patients who already have crossmatched blood in the blood bank, or transfusion of type-specic but not crossmatched blood, can happen more quickly but typically still requires at least half an hour of logistic time. Major trauma centers, therefore, maintain a supply of type O (universal donor) RBC on hand for rapid delivery to patients with exsanguinating hemorrhage (47). This practice has been closely examined in both civilian and military experience and found to
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be safe and efcacious (48). Type O transfusion is continued until typespecic and then cross-matched units are available; with modern leukoreduction techniques, the clinician can switch to units of the patients own blood type as soon as they are available, with little fear that they will react with the previously administered type O blood (47). Greater controversy exists regarding the early and empirical use of plasma in emergency surgery patients. Retrospective data gathered from both military and civilian trauma centers suggested that, in patients with severe, ongoing hemorrhage, survival is improved when plasma is administered early and in a ratio of 1:1 with RBCs (49). Physiologically, this makes sense: The patient is losing whole blood which contains both plasma and RBCs, so replacement in equal proportions is a best guess until the situation stabilizes and laboratory data become available. Use of 1:1 transfusion, with minimal infusion of asanguineous uids, also overcomes the effects of dilution and storage loss in the infused blood products. Recent publications in the trauma literature have emphasized that tissue hypoperfusionshock by itself is an important contributor to the onset of coagulopathy, further reinforcing the potential benet of early replacement of clotting factors in unstable patients (50). Unfortunately, plasma transfusion is also the most common cause of transfusionrelated acute lung injury and has been linked even more than RBCs to negative long-term outcomes. Although more than a dozen retrospective studies have shown improved survival in massively transfused patients associated with increased ratios of plasma to RBCs, there is a strong confounding of these data by survival bias (51). Because most systems, both military and civilian, are able to deliver RBCs more rapidly to the bedside than plasma, there is a tendency for the RBCs to be infused rst. In very unstable situations, this creates the possibility that the patient will die before the ratio can be increased, regardless of the intentions of the providers. In studies that have attempted to control for survival bias, the very strong associations between plasma/RBC ratio and outcome are noticeably reduced. Determination of the actual benet of 1:1 transfusion will await the completion of prospective studies now underway. In the meantime, most major trauma centers have sought

mechanisms for delivering plasma more readily to the bedside, including the use of prethawed plasma, universal donor (type AB) plasma, liquid plasma, and creation of a massive transfusion protocol that delivers quantities of RBCs and plasma to the emergency department or OR in predened ratios (52). Timely transfusion of platelets may be even more important for prevention of coagulopathy in emergency surgery patients than administration of plasma. Based on the theoretical data presented above, many trauma centers now transfuse packs of platelets at the same whole blood 1:1:1 ratio. As with plasma, there is some evidence that this improves early outcomes in rapidly hemorrhaging patients (53). There is less evidence available about the risks of early platelet transfusion. For emergency surgery cases in general, the need for early or empirical transfusion of blood products vs. resuscitation with crystalloid will depend on the anesthesiologists assessment of the cause of the patients instability, baseline laboratory studies, early returns from clinical monitors, and the anticipated surgical course. Aggressive transfusion is more appropriate in surgeries with a higher potential for intraoperative blood loss (e.g., control of a ruptured abdominal aortic aneurysm) than in those with a more predictably controlled course (e.g., drainage of a musculoskeletal abscess cavity). As with many aspects of anesthesia, the experienced clinician must anticipate potential hazards to the patient and should emphasize staying out of trouble (preventing coagulopathy) over getting out of trouble (attempting to restore clotting function when it has been lost).

Adjuvant therapies for resuscitation

Vasoactive drugs have been used in the treatment of shock for 40 yrs (54) Vasoactive drug therapy is used to manipulate blood ow and restore tissue perfusion. These agents are subdivided based on their predominant pathway of activity into vasopressors and inotropes. Vasopressors modulate vasoconstriction and thereby increase blood pressure, whereas inotropes increase cardiac performance and thereby improve cardiac output. Vasopressor and inotropic agents function primarily through stimulation of adrenergic receptors or through the induction of intracellular process that mimics symS417

pathetic end points. Uncontrolled hemorrhage results in an intrinsic release of catecholamines, mainly vasopressin. Vasopressins primary role is to regulate the bodys retention of water. It also raises the blood pressure by inducing moderate vasoconstriction. If hemorrhage is prolonged, it can result in depletion of vasopressin, leading to refractory hypotension/shock. Therefore, neuroendocrine manipulation may be necessary to treat shock. Vasopressin is chosen because it may be more potent than other vasopressors or catecholamines when shock and acidosis are profound. Vasopressin has been shown to improve neurologic outcome for those patients in severe shock by improving cerebral perfusion pressure (55). Vasopressin also results in less bleeding below the diaphragm and more perfusion above the diaphragm. However, all is not rosy with vasopressin. Vasopressin is associated with indiscriminant vasoconstriction, which contributes to microcirculatory dysfunction. Splanchnic perfusion is particularly at risk. One study in septic shock (56) suggested that dobutamine (an inotrope) may compensate for the deleterious hemodynamic and metabolic effects of vasopressin in the splanchnic region. Dobutamine may also be effective in hemorrhagic shock in maintaining splanchnic perfusion. Vasopressin use is also associated with problems, such as negative cardiac inotropy, right ventricular failure, or even myocardial ischemia. Sperry et al (57) compared early vasopressin use with early crystalloid resuscitation. When confounding factors were controlled for, patients who received early crystalloid resuscitation (rst 12 hrs) were statistically more likely to survive than those patients who received early vasopressin therapy. Other studies (58) have shown an increase in mortality when vasopressors (levophed, phenylephrine, dopamine, and vasopressin) were used in the rst 1224 hrs (early phase) of hemorrhagic shock. The untoward effects of vasopressin are usually dose related, and it is recommended that the lowest possible dose be used. Thus, it is important to make an attempt to restore circulating volume before instituting vasopressin. In those patients who remain hypotensive despite aggressive uid resuscitation, early judicial use of vasopressin or another vasopressor or inotrope should be considered. Pathologic maldistribution of blood ow is hard to measure using hemodynamic criteria alone, alS418

though there is some evidence that stroke volume variation is a reliable indicator of preload status in the face of hypovolemia and use of a vasopressor.

End points of resuscitation

The ultimate end point of any resuscitation is an awake, functional, hemodynamically stable patient. This target becomes obvious in the later stages of resuscitation, after successful surgical source control of hemorrhage, infection, or the mechanical cause of the emergent procedure. At this stage, the clinician can strive for normality in vital signs, laboratory measures, and organ system function. Many of the new resuscitation monitors listed earlier are useful in this phase, and they achieve consistent results in demonstrating completion of resuscitation when used over several hours in the intensive care unit. In particular, optimization of mixed venous oxygen saturation, peripheral tissue oxygenation, or cardiac outputas indicated by new less invasive monitoring modalities have all been associated with good long-term results, whereas failure to achieve these values is associated with an increased prevalence of organ system failure and death. Two decades ago, there was considerable enthusiasm for the concept of supranormal resuscitation, because of the observation that patients who achieved supranormal values of oxygen delivery had better outcomes (30). Various attempts to force patients into a supranormal state postoperatively have yielded mixed results, leading to the current theory that patients should be given enough uids to maximize cardiac output and oxygen delivery (35). Attempting to push them beyond this point with inotropic agents is not likely to be successful. More complex are the goals of early resuscitation, before denitive surgical control of the underlying pathology. Striving for normal vital signs or laboratory measures during this phase may aggravate the underlying pathology, leading to increased hemorrhage, uid overload, or an increased inammatory state. Because the causes of emergency surgery are varied, the early end points of resuscitation are varied as well. Furthermore, absolute numeric targets are not appropriate in a highly heterogeneous population of patients. Instead, the clinician must assess the patients age, comorbidities, underlying disease, and degree of

instability. There must be some understanding of how quickly the patient is deteriorating, and how quickly he/she is likely to get better after surgery. Finally, the clinician must assess the impact of the surgery itself in terms of pain, tissue injury, and additional blood loss. Although the setting of emergency surgery does not lend itself to absolute goals, there are some basic principles that can be applied depending on the underlying pathology. For patients who are bleeding, whose greatest risk is exsanguination, the rst principle is to get the patient to denitive care. It is almost always more appropriate to move to the OR and get the surgery started than to wait for additional monitoring, laboratory studies, or crossmatched blood. Fluids should be administered to prevent hemodynamic collapse, but moderate hypotension should be tolerated. If a massive transfusion is anticipated, it is appropriate to begin transfusion at once, using a balanced mix of RBCs, plasma, and platelets until hemostasis is achieved and laboratory studies can be obtained. If possible, it is desirable to get the patient deeply anesthetized. This facilitates the reversal of vasoconstriction and, combined with gentle uid loading, restores tissue oxygen delivery. Frequent assessment of arterial blood gas values is important both to determine the degree of acidosis (and thus, the course of resuscitation) and the level of ionized calcium. Rapid transfusion of banked blood will induce citrate intoxication, a rapid fall in ionized calcium that can have a profound negative inotropic effect. Replacement of calcium is an important adjuvant therapy during rapid massive transfusion. Once surgical hemostasis is achieved, the rate of uid administration can be slowed, blood composition and clotting function can be assessed, and resuscitation can be completed in a datadriven fashion. For emergency surgery patients who are not bleeding, the greatest risk is usually septic shock. Source control is important in this situation as well, although administration of antibiotics and generous uid therapy can temporize or mitigate the situation while awaiting the OR. During the period before denitive drainage of the nidus of infection, it is reasonable to apply the concept of goal-directed resuscitation and administer uids aggressively to improve vital signs and tissue oxygen delivery. Guidance by use of mixed venous oximetry has shown the
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best results to date, but it is possible that other monitors could ll this role as well. Transfusion should be withheld without laboratory evidence of anemia or coagulopathy, as the inammatory effects of blood transplant may add to the potential for organ system failure. Pressor or inotropic agents are more likely to be needed as a second-line therapy in septic patients than in those who are hemorrhaging but should generally not be started until after an adequate trial of uid loading. The most specic agent to use will depend on the clinicians assessment of the relative need for increased vascular tone or increased cardiac inotropy and will vary with the specics of the patient and situation. Once the patients clinical situation stabilizes, therapies should be withdrawn in the reverse order of their application. Chemical agents should be titrated off rst, then uid administration decreased. At that point, the goals of resuscitation and additional indicated therapies should be clear.

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CONCLUSION
In summary, resuscitation of the emergency surgery patient depends on correctly identifying the underlying pathophysiology, expediting surgical control, and supporting organ system perfusion. Fluid administration is the mainstay of resuscitation but must be approached in a reasoned fashion. No perfect monitor exists to indicate the patients degree of shock or vasoconstriction, although continuous assessment of stroke volume variation offers promise. In actively hemorrhaging patients, there is evidence to suggest that attempting to normalize blood pressure will increase mortality. SVR shows promise, although the ideal hyperoncotic uid has not yet been established. In hemorrhaging patients, the timing and rate of uid administration play a critical role in hemostasis. Early use of blood products, especially plasma, may help to prevent the onset of coagulopathy. For refractory hypotension in the face of aggressive uid resuscitation, judicial use of a vasopressor, especially vasopressin, is indicated. Vasopressin in combination with an inotrope,which lowers systemic vascular resistance, may mitigate some of the microcirculatory vasoconstriction seen with vasopressin alone.

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