Clinical Practice Guideline: Endpoints of Resuscitation

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 lactate level, or gastric be to patients with to the need for ongoing fluid resuscitation, including blood and other blood and the of MODS and death. delivery parameters be the of a patient to supranormal with an for survival to patients who these Level II The time to normalization of base and is of of at of these parameters be for high base deficit or of these may be an early of ongoing hemorrhage or findings rapid of the The of a metabolic or a metabolic as as of on base deficit be when using this parameter as an endpoint of Level III ventricular may be utilized as a better of adequate resuscitation venous or of tissue or O2 and/or may be to patients who additional resuscitation and are at an risk for MODS and death. may be for base deficit levels. Recommendations Regarding Level I are data to a Level I Level II resuscitation, O2 delivery be to base or during the first 24 The for fluid resuscitation, blood and the use of and/or have not been the hemodynamic of surgical patients who those who that O2 delivery and cardiac values The values in the included: O2 delivery and O2 In a study of surgical patients, using these parameters as goals for resuscitation in decreased of and This to the of for delivery of O2 and for and of O2 by In severely injured patients, this similarly that supranormal hemodynamic parameters survival and decreased the of organ tested the that using the values of as goals for resuscitation the values for these parameters in patients would improve trauma patients to be resuscitated to the supranormal values standard hemodynamic variables. The supranormal organ and particularly when the values were within 24 of was better at In a in victims of trauma, that to supranormal values of cardiac index, O2 and O2 with normal vital signs, urine output, and venous pressure, decreased the risk of MODS and death. delivery was by if by and blood up to of have to these findings with utilized a resuscitation at O2 who not the established goals within 12 were at risk for MODS. that resuscitation of critically ill patients to the O2 delivery and/or parameters defined by not improve the of MODS or death with in goals for based on or and who not the supranormal O2 delivery values were at high risk of of In trauma patients, that early of O2 delivery parameters not improve In this of the patients achieved these parameters with of the patients. of the patients who these parameters with of those who of In these these parameters seemed to be more of survival useful as a goal of resuscitation, particularly if fluid resuscitation was The to the O2 delivery goals may be an issue that has not been adequately In the original studies by the the of with and by of cardiac with In a of medical and surgical critically ill patients, that use of to O2 delivery may have In after fluid resuscitation, O2 delivery with in surgical patients mortality and of The O2 delivery goal has been using a that there was in outcome between resuscitated to an O2 delivery goal of The fluid for was not with other issues regarding these studies be these studies be patients in the the physiologic endpoints as those in the treatment of other of is from study to the evidence for goals for O2 delivery in surgical patients and was a of if the goals were achieved and all clinical trials of hemodynamic in patients, medical and the studies by the of or after the of organ dysfunction) and mortality in the mortality with supranormal O2 delivery goals in the studies with before the of organ and mortality of in the that of hemodynamic be as early as during The to be in the of patients. In patients who supranormal oxygen delivery goals have a better of survival those who do not these is evidence that to these goals The for the goals is to be Use of mixed venous O2 the of O2 delivery to in to global tissue O2 In a general of critically ill patients, resuscitated patients to a normal supranormal or normal were in mortality or MODS. are data on the use of mixed venous oxygen in trauma victims. cardiac dysfunction and hypoperfusion may in trauma patients. To this a of early hemodynamic of trauma victims. that identified occult shock early and may have to MODS and death. that victims of penetrating trauma evidence of utilized a of resuscitation, and blood to O2 delivery lactate and O2 was flow who not lactate or hemodynamic goals by 24 were at high risk of that fluid resuscitation is the treatment for trauma patients in hemorrhagic shock, of adequate volume, i.e., are needed. venous and are but have in critically ill patients to in ventricular or and The at of has explored the use of parameters that can be or using a In the of ventricular and pressure, of may more ventricular or This can be using a right ventricular that better with at up to high of This examined critically ill trauma patients. with splanchnic hypoperfusion as defined by gastric mucosal pH (pHi) a high risk of MODS and death. patients also those with normal O2 delivery index, and O2 not with examined hemodynamic parameters in patients with normal after trauma. and high were strongly with better outcomes. that the for each patient could be based on of ventricular the hemodynamic ventricular stroke work arterial and ventricular power arterial venous which blood and with the hemodynamic and O2 O2 delivery index, O2 as of outcome in trauma patients. The that with lactate and survival were heart rate, and the ventricular that also better as by a of to resuscitated patients with the goal of achieving the level of This of patients was with a of patients from a study The patients resuscitated to the goal base deficit and a risk of organ system The in survival not In a separate these that during resuscitation was with of stroke work to as the and decreased base In hemodynamic parameters that can be by from the can be of chances for The utility of these parameters to improve survival is to be Inadequate tissue O2 delivery leads to anaerobic The degree of is to the depth and severity of hemorrhagic shock, which be in the base deficit and lactate pH is not as useful the to maintain a normal study by that which may be more available arterial blood with base deficit is the base deficit has been that base deficit was with blood on and fluid patients’ level of as deficit deficit or deficit of patients with an base deficit ongoing blood that base deficit with mortality and the of the a between base deficit and blood not base deficit to with that base and were of the development of multiple organ and severity were also variables. The of a normal base deficit may with patient that a base deficit of is a marker of in all patients, but a normal base deficit was with an of in patients more in patients. deficit time may to the utility of this that in base deficit time were more of survival pH levels. among trauma patients who lactate those that high base deficit risk of MODS and death patients with normal base patients also O2 as by O2 and O2 similarly that an in base deficit between at the and to the care identified trauma patients with hemodynamic high metabolic and and an risk of death. a that base deficit and initial 24 blood were of and severity were The of and base deficit the In victims of penetrating trauma, that the base deficit in the first 24 blood on and blood were of mortality by base deficit by To determine that could predict outcome in the severely injured patients, examined patients with trauma who for base and could predict outcome with metabolic acidosis deficit and a and base deficit were of death. base deficit is not of but of as the need for blood and organ particularly the syndrome that base deficit with need for blood if base deficit if base deficit of and the development of and MODS. that the initial base deficit was in patients who developed with those who and that high lactate and base deficit during the first 24 of were with high and the development of within the first of that base deficit values with that are in the between severity of shock and later development of MODS and death. patients who for injuries to would determine which patients were at the risk of hemodynamic and need for blood that base deficit and lactate with whereas mixed venous O2 all studies of base deficit have on that base deficit could also severity and risk of mortality in patients. base deficit with blood pressure, and trauma deficit with a mortality risk. This was by In addition to anaerobic base deficit may be by a of can base deficit for of severity and after trauma. that a base deficit of be in patients, whereas a base deficit of is in patients. on the other in of of base deficit of was still of a and need for blood an of patients and other lactate and base deficit as of of a metabolic acidosis from resuscitation with normal or can base deficit of to is with a mortality that from other particularly anaerobic have that which may be more available from some with base of will at improve base deficit and and use as endpoints for is little for in the treatment of hemorrhagic shock. metabolic acidosis and can also base deficit levels. base deficit and time to normalization of these with need for and risk of MODS and death. high or base deficit may be an early of ongoing hemorrhage or the are data to that using base deficit as an endpoint for resuscitation that not were initial lactate but the of the lactate level to an as fluid resuscitation, would in patients with shock. patients who trauma and were resuscitated to supranormal values of O2 that the time to lactate was an for patients who lactate at 24 those patients who between 24 and a mortality those that not by an mortality a in surgical patients to the that initial and lactate as as the duration of with the development of MODS after trauma. In the severity of metabolic acidosis to tissue hypoperfusion be similarly in lactate and gap or base In critically ill trauma patients, that lactate were in in were not for gap or base between these were The of patients was and the lactate were to In the initial lactate level and time to normalization of lactate with risk of MODS and death. survival using lactate as an endpoint for resuscitation has not been cardiac and/or of blood flow can lead to This can lead to an in the between arterial and as by trauma patients who and decreased as with This study that study of in trauma patients is Gastric The has been the of the blood flow to the and is at the of other and In detection of ischemia to these would allow of patients who additional resuscitation vital Use of gastric is based on the that tissue ischemia leads to an in tissue pco2 and decrease in tissue and the pco2 in gastric with that in the gastric gastric to be is to gastric and gastric to a is into the The is with and is to into the for a of The pco2 in the is are also Intramucosal pH (pHi) can be based on the The between pco2 and arterial pco2 pco2 or with the degree of gastric In a of surgical patients, that with with a mortality of whereas those with all that with development of MODS and mortality in critically ill patients, particularly if the for that was a better of mortality in a general arterial base and lactate levels. O2 and O2 were not between and In that markers of metabolic acidosis deficit and with base deficit of a and a of predicting of In medical and surgical patients, to O2 parameters in and and O2 but O2 O2 and lactate and mixed venous and mixed venous patients who values In a separate critically ill patients to standard treatment a that included O2 or O2 if the decreased or the was between if the initial was but the survival in those patients with normal In resuscitated patients in a general using a to maintain arterial blood urine blood and arterial O2 uncompensated acidosis was were to standard therapy or to additional fluid resuscitation and/or to were between in or of In trauma patients, trauma patients who or of these developed and 2 with normal between initial and shock, or physiologic and II similarly that was a of MODS and deficit and mixed venous O2 were also with 24 the that was between patients who developed MODS and those who not was patients who developed MODS values for and for the gastric gap were explored by using a of trauma patients. The to predict MODS and death was with and gap of Some have that the gap is a better of gut which is a that may be by arterial as an endpoint for resuscitation was with supranormal O2 delivery of and a O2 of in a prospective, study of trauma patients by The resuscitation included with and blood if with using goals were achieved in all patients. to or O2 was The parameter that between was in achieving goals was more of organ system and death achieving the O2 The gap between gastric mucosal and arterial was similarly In the or was an early of of pco2 be in The using a is An in which the is with and the is after a of time is also by the and could the within the by O2 or using a for are that the and with each other in but in during hemorrhagic shock and resuscitation in The values were the The using the does not with the on the utility of a of that could pco2 in the An new to determine regional during shock is the use of pco2 that pco2 with lactate of shock, and survival in a of ill patients. and pco2 to blood flow during hemorrhagic shock in were between pco2 values and blood flow. In victims of penetrating trauma, that pco2 was in patients with ongoing bleeding. studies in are in In gastric can data that can be to predict risk of MODS and death. of or pco2 gap as endpoints for resuscitation in as at achieving supranormal O2 Tissue and of O2 and may also be of death in critically ill patients based on the of gastric tonometry. utilized an into subcutaneous to first that this as as a standard and in that the subcutaneous decreased during hemorrhagic shock and with The values not to ongoing in trauma patients, that still subcutaneous adequate resuscitation by standard clinical subcutaneous in patients surgical using a in the that subcutaneous values were in the and pco2 in critically ill trauma patients. who pco2 and of time with pco2 values patients who pco2 values for this by muscle a before and after an O2 was that patients who were adequately resuscitated would with an in tissue O2 would not be Tissue would not if flow O2 is and all additional during trauma trauma and In trauma patients in the care to the O2 with evidence of flow a to that patients who surgical were In data that and muscle and pco2 may be to predict risk of death from trauma. of muscle by a for of resuscitation in of tissue In hemorrhagic shock, that gastric tissue O2 with a decreased with blood flow. The of flow with in the was not as In human of that cerebral and muscle O2 by decreased in to blood The oxygenation also decreased O2 of in tissue during resuscitation in trauma patients. that with O2 base and This was better that with gastric mucosal pco2 and pco2 the of tissue po2, pco2, and hemorrhagic shock, in that each pH during shock and Gastric mucosal pco2, and pco2 gap were not as data that of tissue po2, pco2, and pH of particularly the may better of and better endpoints for that of a into muscle could also be useful for the severity of hemorrhagic shock, as as the of resuscitation, in that and pco2 during shock and resuscitation, whereas pH but not to The pH with blood pH and in muscle from ongoing and resuscitation blood In addition to tissue can regarding tissue O2 are to O2 that of trauma patients who developed multiple organ of these whereas 2 of patients who not multiple organ In studies that of tissue po2, pco2, and pH has potential for predicting risk of MODS and death after trauma. Examination all the in as as data from and to determine the of resuscitation, not the of a examined the of to hypoperfusion by of patients’ The described the patients’ as or with patients with those with and and lactate levels. resuscitation from hemorrhagic shock, normalization of standard clinical parameters as blood pressure, heart rate, and urine are not adequate to survival without organ system parameters including hemodynamic acid-base gastric and regional of tissue O2 and have been Many can be useful for predicting risk of organ and death. use of these parameters as endpoints for resuscitation have to in of patient outcomes. to use of these endpoints on standard clinical The parameter to use as an endpoint for resuscitation would be to and clinical trials parameters as endpoints for resuscitation are but these are to of of and and need for of resuscitation In to a standard of care may more that use of at parameter has The appropriate endpoints are is to do that the patient is adequately which and/or are for achieving the the be early in of to of trauma patients. The for the i.e., a endpoint that for all trauma patients, may be acid-base parameters may not work in patients with acid-base that are or patients, and heart may be and use of that work with may be these will to the in the of studies be to the of patients that will be to complete the studies in a and to utility of the a of patient and