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Clinical Practice Guideline: Endpoints of Resuscitation

2004; Lippincott Williams & Wilkins; Volume: 57; Issue: 4 Linguagem: Inglês

10.1097/01.ta.0000133577.25793.e5

1529-8809

Samuel A. Tisherman, Philip S. Barie, Faran Bokhari, John Bonadies, Brian J. Daley, Lawrence N. Diebel, Soumitra R. Eachempati, Stanley Kurek, Fred A. Luchette, Juan Carlos Puyana, Martin A. Schreiber, Ronald Simón,

Hemodynamic Monitoring and Therapy

STATEMENT OF THE PROBLEM Severely injured trauma victims are at high risk of development of the multiple organ dysfunction syndrome (MODS) or death. To maximize chances for survival, treatment priorities must focus on resuscitation from shock (defined as inadequate tissue oxygenation to meet tissue O2 requirements), including appropriate fluid resuscitation and rapid hemostasis. Inadequate tissue oxygenation leads to anaerobic metabolism and resultant tissue acidosis. The depth and duration of shock leads to a cumulative oxygen debt.1 Resuscitation is complete when the oxygen debt has been repaid, tissue acidosis eliminated, and normal aerobic metabolism restored in all tissue beds. Many patients may appear to be adequately resuscitated based on normalization of vital signs, but have occult hypoperfusion and ongoing tissue acidosis (compensated shock), which may lead to organ dysfunction and death. Use of the endpoints discussed in this guideline may allow early detection and reversal of this state, with the potential to decrease morbidity and mortality from trauma. Without doubt, resuscitation from hemorrhagic shock is impossible without hemostasis. Fluid resuscitation strategies before obtaining hemostasis in patients with uncontrolled hemorrhage, usually victims of penetrating trauma, remain controversial. Withholding fluid resuscitation may lead to death from exsanguination, whereas aggressive fluid resuscitation may disrupt the clot and lead to more bleeding. "Limited," "hypotensive," and/or "delayed" fluid resuscitation may be beneficial, but clinical trials have yielded conflicting results.2,3 This clinical practice guideline will focus on resuscitation after achieving hemostasis and will not address the issue of uncontrolled hemorrhage further. Use of the traditional markers of successful resuscitation, including restoration of normal blood pressure, heart rate, and urine output, remain the standard of care per the Advanced Trauma Life Support Course.4 When these parameters remain abnormal, i.e., uncompensated shock, the need for additional resuscitation is clear. After normalization of these parameters, up to 85% of severely injured trauma victims still have evidence of inadequate tissue oxygenation based on findings of an ongoing metabolic acidosis or evidence of gastric mucosal ischemia.5,6 This condition has been described as compensated shock. Recognition of this state and its rapid reversal are critical to minimize risk of MODS or death. Consequently, better markers of adequate resuscitation for severely injured trauma victims are needed. This guideline committee sought to evaluate the current state of the literature regarding use of potential markers and related goals of resuscitation, focusing on those that have been tested in human trauma victims. This manuscript is part of an ongoing process of guideline development that includes periodic (every 3–4 years) review of the topic and the recommendations in light of new data. The goal is for these guidelines to assist clinicians in assuring adequate resuscitation of trauma patients, ultimately improving patient outcomes. Goals of the Guideline To demonstrate that the proposed endpoints are useful for stratifying the patients' severity of physiologic derangement. To demonstrate that the proposed endpoints are useful for predicting risk of development of MODS or death. To determine the endpoints for resuscitation that would predict survival without organ system dysfunction if a defined level is achieved within a certain time frame. To improve patient survival and morbidity (organ system dysfunction) by use of appropriate resuscitation endpoints. Information regarding risk of death could lead to consideration of limiting therapy that may be futile. In trauma victims who have not suffered a cardiac arrest or who do not have injuries that are incompatible with life, there is little literature on determining medical futility. Consequently, this guideline does not make any recommendations regarding when to limit therapy. Proposed Endpoints The proposed endpoints of resuscitation fall into 2 categories: global and regional. The global O2 delivery issue has been examined by studies of supranormal O2 delivery and studies of the utility of mixed venous O2 saturation. Other global hemodynamic parameters that have been explored include right ventricular end-diastolic volume, left-ventricular stroke work index, and left-ventricular power output. Similarly, global acid-base status has been explored using base deficit and lactate levels. On the regional level, compensated shock disproportionately decreases blood flow to the splanchnic and other tissue beds to maintain cerebral and coronary blood flow. Examination of gut-related parameters may be useful as a marker of the severity of shock and may also demonstrate the pathophysiologic connection between gut ischemia and later MODS. Gastric ischemia can be monitored using gastric tonometry. Intramucosal pH (pHi) or the gap between intramucosal and arterial pco2 can be utilized. Skeletal muscle and subcutaneous tissue blood flow is similarly decreased during shock. Tissue po2, pco2, and pH can be monitored using near infrared spectroscopy or tissue electrodes. From a clinical perspective, in addition to direct clinical utility, other issues to consider for potential resuscitation endpoints include: general availability, cost, speed, invasiveness, and risk. PROCESS The process utilized by this committee was developed by the Practice Management Guidelines Committee of the Eastern Association for the Surgery of Trauma (www.east.org). The committee agreed upon the potential endpoints to be considered. Literature for review included: human, trauma patients, and some attempted connection between the proposed endpoint and patient outcome (morbidity, survival, etc), not just process variables. Some non-trauma studies of critically ill patients were also included, particularly if the parameter seemed promising in other surgical patients. Similarly, some non-human studies of promising techniques are discussed, though these were not included in the main review or recommendations. Medline and EMBASE were searched from 1980 to 2001. Articles were distributed among committee members for formal review. Each article was entered into a review data sheet that summarized the main conclusions of the study and identified any deficiencies in the study. Furthermore, reviewers classified each reference by the methodology established by the Agency for Health Care Policy and Research of the U.S. Department of Health and Human Services as follows: Class I: prospective, randomized, double-blinded study; Class II: prospective, randomized, nonblinded trial; Class III: retrospective series, meta-analysis. An evidentiary table (Table 1) was constructed using the 74 references that were identified: Class I, 12 references; Class II, 38 references; and Class III, 24 references. Recommendations were made on the basis of the studies included in this table. Level I recommendations, usually based on class I data, were meant to be convincingly justifiable on scientific evidence alone. Level II recommendations, usually supported by class I and II data, were to be reasonably justifiable by available scientific evidence and strongly supported by expert opinion. Level III recommendations, usually based on Class II and III data, were to be made when adequate scientific evidence is lacking, but the recommendation is widely supported by available data and expert opinion.Table 1: Endpoints of ResuscitationTable 1: Continued)Table 1: Continued)Table 1: Continued)RECOMMENDATIONS Recommendations Regarding Stratifying Physiologic Derangement Although the original goal of this guideline was to determine separate recommendations regarding the four goals listed in Section I, the literature on 1) stratifying patients' severity of physiologic derangements, 2) risk of MODS and death, and 3) predicting survival if certain values of the parameters are achieved, generally combines these issues. Consequently, the following recommendations refer to the first three goals of this guideline in aggregate. Recommendations related to goal 4, improving patient survival and morbidity, are presented separately. Level I Standard hemodynamic parameters do not adequately quantify the degree of physiologic derangement in trauma patients. The initial base deficit, lactate level, or gastric pHi should be used to stratify patients with regard to the need for ongoing fluid resuscitation, including packed red blood cells and other blood products, and the risks of MODS and death. Oxygen delivery parameters should be observed since the ability of a patient to attain supranormal correlates with an improved chance for survival relative to patients who cannot achieve these parameters. Level II The time to normalization of base deficit, lactate, and pHi is predictive of survival. Observation of at least one of these parameters should be used clinically for prognostication. Persistently high base deficit or low pHi (or worsening of these parameters) may be an early indicator of complications, e.g., ongoing hemorrhage or abdominal compartment syndrome. These findings should prompt rapid reassessment of the patient. The effects of ethanol intoxication, seizures, sepsis, a hyperchloremic metabolic acidosis, or a pre-existing metabolic acidosis, as well as administration of sodium bicarbonate, on base deficit levels should be considered when using this parameter as an endpoint of resuscitation. Level III Right ventricular end diastolic volume index (RVEDVI) measurement may be utilized as a better indicator of adequate volume resuscitation (preload) than central venous pressure or pulmonary capillary wedge pressure (PCWP). Measurements of tissue (subcutaneous or muscle) O2 and/or CO2 levels may be used to identify patients who require additional resuscitation and are at an increased risk for MODS and death. Serum bicarbonate levels may be substituted for base deficit levels. Recommendations Regarding Improved Patient Outcomes Level I There are insufficient data to formulate a Level I recommendation. Level II During resuscitation, O2 delivery should be increased to normalize base deficit, lactate, or pHi during the first 24 hours. The optimal algorithms for fluid resuscitation, blood product replacement, and the use of inotropes and/or vasopressors have not been determined. SCIENTIFIC FOUNDATION Oxygen Delivery Shoemaker et al.,7,8 reviewed the hemodynamic profiles of high-risk surgical patients who survived versus those who did not. They found that survivors had significantly higher O2 delivery and cardiac index (CI) values than nonsurvivors. The values in the survivors included: CI (≥4.5 L/min/m2), O2 delivery (≥600 mL/min/m2), and O2 consumption (≥170 mL/min/m2). In a prospective study of high-risk surgical patients, using these parameters as goals for resuscitation resulted in decreased complications, length of stay, and hospital costs.9 This group then recommended adding to the "ABCs" of resuscitation: "D" for increased delivery of O2 and "E" for ensuring extraction and utilization of O2 by tissues.10 In severely injured patients, this group similarly found that attaining supranormal hemodynamic parameters improved survival and decreased the frequency of organ failures.11 They then prospectively tested the hypothesis that using the values of survivors as goals for resuscitation rather than the values for these parameters found in normal, non-injured patients would improve survival. Fleming et al.,12 randomized trauma patients to be resuscitated to the supranormal values above versus standard hemodynamic variables. The supranormal group had fewer organ failures and shorter hospital stays, particularly when the values were attained within 24 hours of injury. Mortality was slightly better at p = 0.08. In a randomized trial in victims of severe trauma, Bishop et al.,13 found that resuscitating to supranormal values of cardiac index, O2 delivery, and O2 consumption, compared with normal vital signs, urine output, and central venous pressure, decreased the risk of MODS and death. Oxygen delivery was augmented by volume loading, followed, if necessary, by dobutamine infusion and blood transfusions up to hemoglobin of 14 gm/dL. Others have tried to duplicate these findings with limited success. Moore et al.,14 utilized a resuscitation protocol aimed at maximizing O2 delivery. Patients who did not reach the established goals within 12 hours were at increased risk for developing MODS. Durham et al.,15 found that resuscitation of critically ill patients to the O2 delivery and/or consumption parameters defined by Shoemaker did not improve the rate of MODS or death compared with conventional parameters. Patients in both groups had similar goals for preload based on PCWP or RVEDV and hemoglobin concentration. Patients who did not attain the supranormal O2 delivery values were at high risk of developing MODS, regardless of group assignment. In trauma patients, Velmahos et al.,16 found that early optimization of O2 delivery parameters did not improve outcome. In this study, 40% of the control patients achieved these parameters spontaneously compared with 70% of the protocol patients. None of the patients who attained these parameters died, compared with 30% of those who did not, regardless of group assignment. In these studies, attaining these parameters seemed to be more predictive of survival than useful as a goal of resuscitation, particularly if fluid resuscitation was adequate. The means used to attain the O2 delivery goals may be an important issue that has not been adequately explored. In the original studies by the Shoemaker group, the protocol consisted of volume loading with crystalloids and blood, followed by enhancement of cardiac output with dobutamine.7,8 In a heterogeneous group of medical and surgical critically ill patients, Hayes et al.,17 found that use of dobutamine to help augment O2 delivery may actually have increased mortality. In contrast, Boyd et al.,18 found that, after fluid resuscitation, increasing O2 delivery with dopexamine in high-risk surgical patients improved mortality and rate of complications. The optimal O2 delivery goal has recently been questioned. McKinley et al.,19 using a bedside computerized decision support tool, found that there was no difference in outcome between groups resuscitated to an O2 delivery goal of 600 mL/min/m2 versus 500 mL/min/m2. The latter group required less fluid for resuscitation. Outcome was not compared with other endpoints, however. Several methodological issues regarding these studies should be noted. First, these studies cannot be totally blinded. Second, patients in the control groups often attain the same physiologic endpoints as those in the treatment groups. Third, control of other aspects of management is variable. Fourth, entrance criteria vary from one study to another. Heyland et al.,20 reviewed the evidence for supraphysiologic goals for O2 delivery in surgical patients and found no overall benefit. There was a suggestion of benefit if the goals were achieved preoperatively. More recently, Kern and Shoemaker21 reviewed all randomized clinical trials of hemodynamic optimization in high-risk patients, both medical and surgical. They grouped the studies by the timing of intervention (before or after the onset of organ dysfunction) and mortality in the control group. They found improved overall mortality with supranormal O2 delivery goals only in the studies with interventions initiated before the onset of organ failure and mortality of >20% in the control group. Thus, it seems that optimization of hemodynamic variables should be initiated as early as possible during resuscitation. The greatest benefit seems to be in the sickest groups of patients. In summary, patients who achieve supranormal oxygen delivery goals have a better chance of survival than those who do not achieve these goals. There is no convincing evidence that attempting to attain these goals directly improves survival. The best algorithm for attaining the goals is yet to be determined. Mixed Venous Oxygen Saturation Use of mixed venous O2 saturation (SvO2) levels should reflect the adequacy of O2 delivery to tissues in relation to global tissue O2 demands. In a general population of critically ill patients, Gattinoni et al.,22 resuscitated patients to a normal CI (2.5–3.5 L/min/m2), supranormal CI (>4.5 L/min/m2), or normal SvO2 (≥70%). There were no differences in mortality or MODS. There are few specific data on the use of mixed venous oxygen saturation in trauma victims. Additional Invasive Hemodynamic Monitoring Parameters Occult cardiac dysfunction and systemic hypoperfusion may occur in many trauma patients. To explore this question, Scalea et al.,23 instituted a protocol of early invasive hemodynamic monitoring of high-risk geriatric blunt trauma victims. They found that monitoring identified occult shock early and may have helped to prevent MODS and death. These investigators5 even found that young victims of penetrating trauma often had evidence of hypoperfusion. They utilized a protocol of volume resuscitation, inotropes, and blood transfusions to increase O2 delivery until lactate concentration normalized and O2 consumption was no longer flow dependent. Patients who did not normalize lactate or reach their hemodynamic goals by 24 hours were at high risk of dying. Recognizing that fluid resuscitation is the primary treatment for trauma patients in hemorrhagic shock, indicators of adequate intravascular volume, i.e., optimized preload, are needed. Central venous and pulmonary capillary wedge pressures are useful, but have limitations in critically ill patients due to changes in ventricular compliance (edema, ischemia, or contusion) and intrathoracic pressure (mechanical ventilation). The group at Bowman Gray School of Medicine has explored the use of several parameters that can be measured or calculated using a pulmonary artery catheter. In the face of potentially variable ventricular compliance and intrathoracic pressure, measurement of RVEDVI may more accurately reflect left ventricular preload than CVP or PCWP. This value can be determined using a right ventricular ejection fraction/oximetry volumetric catheter. Cheatham et al.,24 demonstrated that CI correlates better with RVEDVI than PCWP at up to very high levels of positive end-expiratory pressure. This same group25 examined 79 consecutive critically ill trauma patients. Patients with splanchnic hypoperfusion as defined by low gastric mucosal pH (pHi) had a high risk of developing MODS and death. These patients also had lower RVEDVI than those with normal pHi. PCWP, CI, O2 delivery index, and O2 consumption index did not correlate with pHi. Chang et al.,26 examined hemodynamic parameters in patients with normal versus low pHi after severe trauma. Normalized pHi and high RVEDVI were strongly associated with better outcomes. Recently, Kincaid et al.,27 suggested that the optimal RVEDVI for each patient could be calculated based on measurements of ventricular compliance. Chang et al.,28 compared the hemodynamic variables left ventricular stroke work index (LVSWI=stroke index × mean arterial pressure × 0.0144) and left ventricular power output (LVP=cardiac index × [mean arterial pressure-central venous pressure]), which encompass blood pressure and flow, with the standard, purely flow-derived, hemodynamic and O2 transport variables (CI, O2 delivery index, O2 consumption index) as predictors of outcome in critically-ill trauma patients. The only variables that significantly correlated with lactate clearance and survival were heart rate, LVSWI and LVP. Using the ventricular pressure-volume relationships, they found that survivors also had better ventricular-arterial coupling, as determined by a lower ratio of afterload (aortic input impedance) to contractility (ventricular end-systolic elastance). They then prospectively resuscitated patients with the goal of achieving the survivors' level of LVP (>320 mm Hg × L/min/m2).29 This group of patients (n = 20) was compared with a group of patients from a previous prospective study (n = 39). The patients resuscitated to the LVP goal normalized their base deficit sooner and had a lower risk of developing organ system failure. The difference in survival did not reach statistical significance. In a separate study, these investigators30 found that improved ventricular-arterial coupling during resuscitation was associated with improved myocardial efficiency (ratio of stroke work to total myocardial energy output as measured via the pressure-volume loop) and decreased base deficit. In summary, novel hemodynamic parameters that can be calculated by measurements obtained from the pulmonary artery catheter can be predictive of increased chances for survival. The utility of these parameters to directly improve survival is yet to be determined. Arterial Base Deficit Inadequate tissue O2 delivery leads to anaerobic metabolism. The degree of anaerobiosis is proportional to the depth and severity of hemorrhagic shock, which should be reflected in the base deficit and lactate level. Arterial pH is not as useful since the body's compensatory mechanisms attempt to maintain a normal pH.31 A recent study by Eachempati et al.,32 suggests that serum bicarbonate concentrations, which may be more readily available than arterial blood gases, correlate very well with base deficit values. Because it is rapidly available, the base deficit has been extensively studied. Davis et al.,33 retrospectively found that higher base deficit was associated with lower blood pressure on admission and greater fluid requirements. They stratified patients' level of illness as mild (base deficit 2–5 mmol/L), moderate (base deficit 6–14 mmol/L), or severe (base deficit >14 mmol/L). Two-thirds of patients with an increasing base deficit had ongoing blood loss. Rutherford et al.,34 added that base deficit correlated with mortality and enhanced the predictive value of the TRISS methodology.35 Falcone et al.,36 further found a good correlation between base deficit and blood product requirements, although they did not find base deficit to independently correlate with mortality. Sauaia et al.,37 found that base deficit, lactate, and transfusion requirements were predictive of the development of multiple organ failure. Age and injury severity score (ISS) were also important variables. The importance of a normal base deficit may vary with different patient populations. Davis et al.,38 found that a base deficit of ≥6 mmol/L is a marker of severe injury in all patients, but a normal base deficit was associated with an ISS of >16 in patients older than 55 years more often than in younger patients. Base deficit changes over time may add to the utility of this parameter. Davis et al.,31 found that changes in base deficit over time were more predictive of survival than pH levels. Kincaid et al.,39 further found that, among trauma patients who normalized their lactate levels, those that had persistently high base deficit had greater risk of MODS and death than patients with normal base deficit. These patients also demonstrated impaired O2 utilization, as evidenced by lower O2 consumption and O2 utilization coefficient. Rixen et al.,40 similarly found that an increase in base deficit between arrival at the hospital and admission to the intensive care unit identified trauma patients with hemodynamic instability, high transfusion requirements, metabolic and coagulation abnormalities, and an increased risk of death. Using a multivariate analysis, Siegel et al.,41 found that base deficit and initial 24 hour blood transfusion requirements were independently predictive of mortality. Lactate levels and injury severity scores were not. The combination of Glasgow Coma Scale and base deficit produced the best predictive model. In victims of penetrating trauma, Eachempati et al.,42 found that the worst base deficit in the first 24 hours, blood pressure on admission, and estimated blood loss were predictive of mortality by univariate analysis. Only base deficit remained predictive by multivariate analysis. To determine preoperative factors that could predict outcome in the most severely injured patients, Krishna et al.,43 retrospectively examined 40 patients with multivisceral trauma (ISS >35) who required urgent operations for hemorrhage. Using base deficit, core temperature, and ISS, they could predict outcome with 92.5% accuracy. Severe hypothermia ( 12 mmol/L), and a combination (temperature 5 mmol/L) were strong predictors of death. Elevated base deficit is not only predictive of mortality, but of complications, such as the need for blood transfusions and organ failure, particularly the acute respiratory distress syndrome (ARDS). Davis et al.,44 found that admission base deficit correlated with need for blood transfusion (72% if base deficit ≥6 mmol/L versus 18% if base deficit 8 mmol/L corresponded with a 25% mortality risk. This was corroborated by Randolph et al.50 In addition to anaerobic metabolism, base deficit levels may be increased by a number of factors. Alcohol intoxication can worsen base deficit for similar levels of injury severity and hemodynamics after trauma. Dunham et al.,51 suggest that a base deficit of ≥4.1 mmol/L should be concerning in intoxicated patients, whereas a base deficit of 1.1 is concerning in non-intoxicated patients. Davis et al.,52 on the other hand, found no difference in length of stay regardless of alcohol level. A base deficit of ≥6 mmol/L was still predictive of a significant injury and need for blood transfusion. Using an even larger database (15,179 patients), Dunne et al.,53 found that, although 21% of patients had ingested alcohol and 7% had used other drugs, admission lactate and base deficit remained as significant independent predictors of outcome. Development of a hyperchloremic metabolic acidosis from resuscitation with normal saline or lactated Ringer's solution can increase base deficit independent of injury severity.54 Acidosis secondary to hyperchloremia is associated with a lower mortality than that from other causes, particularly anaerobic metabolism. Eachempati et al.,32 have shown that serum bicarbonate levels, which may be more readily available from some labs, correlate well with base deficits. Administration of sodium bicarbonate will at least transiently improve base deficit and bicarbonate levels and confound their use as endpoints for resuscitation. There is little role for sodium bicarbonate in the treatment of hemorrhagic shock. Pre-existing metabolic acidosis (e.g., renal failure), sepsis, and seizure activity can also alter base deficit levels. Initial base deficit levels and time to normalization of these levels correlate well with need for transfusion and risk of MODS and death. Persistently high or worsening base deficit levels may be an early indicator of complications, e.g., ongoing hemorrhage or the abdominal compartment syndrome. There are currently no data to suggest that using base deficit as an endpoint for resuscitation improves survival. Arterial Lactate Vincent et al.,55 showed that not only were initial lactate levels important, but the response of the lactate level to an intervention, such as fluid resuscitation, would add predictive value in patients with noncardiogenic circulatory shock. Abramson et al.,56 studied patients who had severe trauma and were resuscitated to supranormal values of O2 transport.8 They found that the time needed to normalize serum lactate levels was an important prognostic factor for survival. All patients who had normalized lactate levels at 24 hours survived; those patients who normalized their levels between 24 and 48 hours had a 25% mortality rate; those that did not normalize by 48 hours had an 86% mortality rate. McNelis et al.,57 found a similar trend in post-operative surgical patients admitted to the ICU. Manikas et al.,58 further found that initial and peak lactate levels, as well as the duration of hyperlactatemia, correlated with the development of MODS after trauma. In theory, the severity of metabolic acidosis secondary to tissue hypoperfusion should be similarly reflected in lactate levels and anion gap or base deficit. In 52 critically ill trauma patients, Mikulasch