The Golden Hour and the Silver Day: Detection and Correction of Occult Hypoperfusion within 24 Hours Improves Outcome from Major Trauma

Abstract

Background 

The significance of occult hypoperfusion (OH) in the development of respiratory complications (RC), multiple system organ failure (MSOF), and death, and the effect of rapid identification and correction of OH in the severely injured trauma patient was investigated.

Methods 

A pilot retrospective study and the analysis of a prospective protocol to correct OH were performed. Pilot study: all trauma patients admitted to our Level I trauma center between February and December of 1995, who survived greater than 48 hours, had an Injury Severity Score greater than or equal to 20, and intensive care unit stays greater than 48 hours were evaluated. Prospective study: patients admitted between January 1, 1996, and April 30, 1997, who survived greater than 24 hours, with Injury Severity Score greater than or equal to 20, and who were hemodynamically stable (systolic blood pressure greater than 100, pulse rate less than 120, and urine output greater than 1 mL/kg per hour) were included. Serum lactic acid (LA) levels were measured at arrival and at proscribed intervals. In the pilot study, initial LA levels were examined in relation to outcome and complications. In the prospective study, patients with two consecutive LA levels greater than 2.5 mmol/L underwent invasive monitoring and vigorous resuscitation to correct their lactic acidosis.

Results 

Among the 31 patients studied in the pilot study, there were 4 deaths, 6 cases of MSOF, and 13 patients with RC. Lactic acidosis and poor cardiac performance, as evidenced by low cardiac index (CI) with normal filling pressures, were seen in all cases of MSOF and RC, as well as in all deaths. From these results, the prospective study was performed. Eighty-five intensive care unit patients met criteria for inclusion in the study. Six additional patients were excluded because of severe, untreatable intracranial hypertension at admission to the intensive care unit. Fifty-eight of these patients had OH in the first 24 hours. Forty-four patients corrected their OH within 24 hours with vigorous resuscitation. There were no deaths, three cases of MSOF, and 10 cases of RC in those patients who corrected OH within 24 hours. Persistent OH (>24 hours) was seen in 14 patients, despite resuscitative efforts, 43% of whom died. MSOF and RC were present in 36% and 50% of cases, respectively (p< 0.05).

Conclusion 

Initial lactic acidosis is associated with lower cardiac performance and higher morbidity and mortality. Persistent OH is associated with higher rates of RC, MSOF, and death after severe trauma. Early identification and aggressive resuscitation aimed at correcting continued elevation in serum lactate improves survival and reduces complications in severely injured trauma patients.

Traumatic injury remains the leading cause of death and disability in the first four decades of life. Excluding head injury, the most frequent cause of death after trauma is multiple system organ failure (MSOF). In addition, severely injured trauma patients have a high incidence of respiratory complications (RC), leading to increased intensive care unit (ICU) and hospital stays. Recent studies have highlighted the importance of early rapid hemodynamic stabilization and the early correction of organ perfusion in the prevention of organ failure and death. ^1–4

Inadequate organ perfusion often ensues after severe traumatic injury. Ischemic injury and tissue hypoxia develop. The diminished oxygen supply is accompanied by an increase in serum lactic acid (LA) levels, reflecting anaerobic metabolism in response to the oxygen debt. ^5–7 A clear correlation between blood lactate levels and the development of circulatory septic shock has been reported repeatedly. ^5,6,8,9 Several reports have studied the correlation between the severity of injury and serum LA levels. ^10–13 The relationship between serum lactate concentrations in trauma patients and the development of MSOF and adult respiratory distress syndrome rarely has been investigated. ¹⁴

We sought to study the significance of lactic acidosis in predicting morbidity and mortality from severe trauma. It was hypothesized that significant elevation of the serum lactate level at arrival correlates with an increased incidence of death, MSOF, and RC after severe trauma. From this initial study, we investigated the impact of early detection and correction of occult hypoperfusion (OH) on outcome, development of MSOF, and incidence of RC in severely injured trauma patients. The first hypothesis was that elevation of serum lactate levels, in the absence of clinical signs of shock, correlates with an increased incidence of death, MSOF, and RC after severe trauma. The second hypothesis was that early identification and correction of OH improves survival and decreases the incidence of MSOF and RC that follows severe trauma.

MATERIALS AND METHODS

The University of Virginia Health Sciences Center is a Level I trauma center serving the population of central Virginia. It operates a helicopter and fixed-wing transport service and provides medical control for local emergency medical services agencies. All major adult trauma patients are admitted to the trauma service, which manages in-patient ICU and floor care. The trauma registry at The University of Virginia is managed by a full-time registered nurse. All admissions with diagnoses related to injury are initially abstracted by the registrar and followed until discharge in conjunction with the Medical Records Department, which ensures that all injured patients admitted to the hospital are included in the registry.

Pilot Study

The charts of all adult trauma patients admitted to the institution between February and December of 1995 were reviewed. Patients who survived greater than 48 hours, had an Injury Severity Score (ISS) equal to or greater than 20, and who stayed in the ICU longer than 48 hours met the criteria for inclusion in the study. Age, mechanism of injury, ISS, Glasgow Coma Scale (GCS) score, and revised trauma score (RTS) were determined on admission. The ISS was calculated by scoring the severity of injury in all major body systems (head and neck, chest, abdomen, extremities, externals) on a scale of 1 to 6 and then summing the squares of the scores for the three most severely injured systems. ¹⁵ The RTS was calculated from a weighted sum of the coded values for the GCS score, systolic blood pressure, and respiratory rate. ^16,17 Probability of survival (Ps) was calculated by using the equation Ps = 1/(1+e^−b), where e = 2.7183 (base of Napierian logarithms), and b = b_o + b₁ (RTS) + b₂ (ISS) +b₃ (A), where b_o, b₁, b₂, and b₃ are weights derived from study data and A = 1 (age > 54 years) and A = 0 (age < 54 years). ¹⁷ Serum LA levels and other routine laboratory tests were obtained on admission in the emergency department and at 6-hour intervals until the values returned to within normal limits or until death. In general, patients with persistently elevated LA underwent Swan-Ganz catheter placement. However, before January 1, 1996, the timing and aggressiveness of resuscitation was not well regimented. The normal value for serum LA is below 2.2 mmol/L in our laboratory. Cardiac index (CI) was calculated by dividing the cardiac output, which was measured by using the thermal dilution technique, by the body surface area. During this period, some patients underwent resuscitation directed at correcting lactic acidemia. This was erratic and consistent in each patient.

Prospective Study

A prospective management protocol was analyzed. This examination entailed a retrospective cohort study of this prospective management protocol. No randomization took place. Adult trauma patients admitted to The University of Virginia between January 1, 1996, and April 30, 1997, were studied. Patients who survived greater than 24 hours, had an ISS equal to or greater than 20, and who were hemodynamically stable (systolic blood pressure greater than 100, pulse rate less than 120, and urine output greater than 1 mL/kg per hour) met the criteria for inclusion in the study. Age, mechanism of injury, ISS, GCS score, and RTS were determined on admission.

A regimented protocol for correction of OH was instituted concurrent with the initiation of this study. Serum LA levels were obtained on admission and at proscribed intervals until the values returned to within the normal range or until death. Patients whose initial LA was greater than 2.5 mmol/L, who showed signs of inadequate perfusion, or both, underwent pulmonary artery catheterization. Correct placement of the Swan-Ganz catheter was confirmed by the pattern of tracing during placement and verified by chest radiograph. Pulmonary capillary wedge pressures were obtained at regular intervals along with cardiac indices. Correction of lactic acidosis (LA < 2.5 mmol/L) with fluid resuscitation, pressors, or both, defined the end point of resuscitative therapy. The resuscitative algorithm is shown in Figure 1.

FIG 1: Resuscitation strategy. LA, lactic acid;PCWP, pulmonary capillary wedge pressure.

The presence of MSOF was assessed during the ICU period. MSOF was defined by Moore’s criteria. Individual organ failure is defined as dysfunction grade of 2 or more. Multiple system organ failure is defined as the sum of the concurrent individual organ dysfunction grades, after 48 hours of admission, greater than or equal to 4. Adult respiratory distress syndrome scores are derived from the following equation: adult respiratory distress syndrome score = A + B + C + D + E, in a clinical setting for which pulmonary capillary wedge pressures is less than or equal to 18; where A = chest radiograph findings, ranging from normal (0) to diffuse severe airspace consolidation (4); B = hypoxemia (PaO₂/FIO₂), ranging from 250 or greater (0) to less than 80 (4); C = minute ventilation (L/min), ranging from less than 11 (0) to greater than 20 (4); D = positive end-expiratory pressure (cm H₂O), ranging from less than 6 (0) to greater than 17 (4); and E = static compliance (mL/cm H₂O), ranging from greater than 50 (0) to less than 20 (4). ¹⁸ Respiratory complications included pneumonia, empyema, and respiratory insufficiency requiring tracheostomy in the absence of coma. Pneumonia was defined as the presence of fever, leukocytosis, and radiographic evidence of a new or expanding infiltrate and sputum cultures exhibiting a predominant organism. The diagnosis of empyema was established by the presence of a thoracentesis, which produced exudative material with or without bacteria seen on Gram’s stain. Data analysis was performed by using the Student’s t test for continuous variables and chi-square analysis for categorical variables. A p value of < 0.05 was considered to be significant.

Variables are expressed as mean ± SDM. Statistical analysis was performed by using the Instat program (GraphPad software). The Student’s t test was used for comparison between groups, and analysis of variance was used for comparison of more than two groups. To analyze differences in outcome and categorical variables the χ² test was used.

RESULTS

Pilot Study

A total of 1,349 adult trauma evaluations were conducted between February and December of 1995. These evaluations resulted in 390 admissions to the trauma service. Thirty-one patients met inclusion criteria (survival > 48 hours, ISS ≥ 20, and ICU stays > 48 hours). There were 4 deaths, 6 cases of MSOF, and 13 cases of RC. Table 1 shows the distribution by mechanism of injury. Motor vehicle crashes (MVC) represented the most frequent mechanism of injury, totaling 23 cases (74%). Crush injuries and falls made up the remainder of the patients with blunt injuries. Although gunshot wounds (GSW) constituted 100% of the penetrating injuries, they represented only 10% of the patients in this study. MVC had the highest mean ISS of 35.45 and lowest mean p of 0.69. Crush injuries, falls, and GSW had comparable mean ISS and p values, as shown in Table 2. Surgical intervention was necessary in all GSW, in 42% of the MVC, and in 25% of the crush injuries.

Table 1: Pilot study: mechanism of injury

Table 2: Pilot study: mean values (ranges) of ISS and Ps by mechanism of injury

Elevated LA levels in patients injured by blunt mechanisms (MVC, crush injuries, and falls) resulted in poor clinical outcomes, as manifested by either MSOF, RC, or death. There was no association between elevated initial LA levels and poor outcome in patients who sustained GSW (Table 3).

Table 3: Pilot study: correlation of mean values (± SD) of LA, CI, and PCWP with death, MSOF, and RC^a

Patient outcomes were also evaluated. Groups were stratified according to survival, MSOF, and RC. All deaths were due to overwhelming MSOF. There was no statistically significant difference in age or ISS, as shown in Table 3. Patients who died, and/or suffered from MSOF or RC, had significantly higher initial LA levels and lower CI, as depicted in Table 3 and Figures 2–4. When patients were assessed individually, elevated LA levels and low CI were always present in cases of death, MSOF, and RC.

FIG 2: Correlation of mean lactic acid (LA), pulmonary capillary wedge pressure (PCWP), and cardiac index (CI) with survival. Filled bars, died;hatched bars, survived. Asterisks indicate p< 0.05.

FIG 3: Correlation of mean lactic acid (LA), pulmonary capillary wedge pressure (PCWP), and cardiac index (CI) with RC. Filled bars, RC;hatched bars, no RC. Asterisks indicate p< 0.05.

FIG 4: Correlation of mean lactic acid (LA), pulmonary capillary wedge pressure (PCWP), and cardiac index (CI) with MSOF. Filled bars, MSOF;hatched bars, no MSOF. Asterisks indicate p< 0.05.

Prospective Study

Four hundred ninety-two patients were admitted to the trauma service during the study period. There were 196 ICU admissions, of which 85 met the criteria for inclusion in the study. Six patients were excluded due to severe, untreatable intracranial hypertension from severe head injury on admission to the ICU, leaving 79 patients suitable for analysis. The demographics of the patients in the study are shown in Table 4. This table demonstrates that the W score for the entire group was +6.32, indicating overall survival greater than that predicted by the TRISS method.

Table 4: Demographics of prospective study group^a

Analysis was carried out with respect to the amount of time required to correct OH, according to the treatment protocol and its effect on complications and outcome. Patients were separated into five groups: group 1, no evidence of OH; group 2, OH present on admission, but corrected by 6 hours; group 3, OH present at 6 hours after admission, but corrected by 12 hours; group 4, OH present 12 hours after admission, but corrected by 24 hours; and group 5, OH present at 24 hours after admission. Patient data for each group are shown in Table 5.

Table 5: Prospective study: patient data for each group^a

Twenty-one patients never exhibited OH. There were no deaths or complications in this group. Fifty-eight patients exhibited OH as evidenced by lactic acidosis (LA > 2.5 mmol/L) in the first 24 hours after admission. Of these patients, 19 corrected OH (by achieving a LA ≤ 2.5 mmol/L) within 6 hours. All of these patients received therapy directed at improving perfusion, which included fluid boluses or blood administration to bring their hematocrits to 30%. Seven patients had Swan-Ganz catheters placed; only three patients required pressor agents. There were no deaths or incidences of MSOF in this group. There were three cases of RC.

Eleven patients with initial evidence of OH corrected their LA by 12 hours after admission. Three patients required Swan-Ganz catheters and pressors, the remainder corrected with fluid administration, blood administration, or both. In this group, there were no deaths or MSOF; one patient had significant RC. Fourteen patients required up to 24 hours to correct OH, 9 patients required Swan-Ganz catheters to guide fluid management, and 4 patients required pressors. There were three cases of MSOF and six patients with significant RC, but 100% survival in this group (Fig. 5).

FIG 5: Morbidity and survival versus time to correct occult hypoperfusion. Filled bars, survival;hatched bars, RC;dotted bars, MSOF.

Fourteen patients did not correct their LA by 24 hours. In this group, there were 8 deaths (43%), 6 cases of MSOF (36%), and 7 patients with RC (50%). The mortality rate in this group was significantly higher than all other groups. The incidence of MSOF and RC was significantly higher than in the 0- to 6-hour and 7- to 12-hour correction groups (Table 6). There were no significant differences between any of the groups with respect to age, ISS, RTS, or GCS score. In addition, there were no significant differences among groups 2 to 5 with respect to delay between admission and Swan-Ganz placement, or injury and Swan-Ganz placement in those patients who were catheterized (Table 7).

Table 6: Prospective study: comparison of outcome and complications among groups

Table 7: Prospective study: comparison of time for injury/admission to Swan-Ganz placement^a

DISCUSSION

These studies demonstrate the direct correlation of duration of OH to outcome, the development of MSOF, and the increased incidence of RC in severely injured trauma patients. The hypothesis that continued elevation of serum lactate correlates with an increased incidence of death, MSOF, and RC after severe blunt trauma was supported. The data support our second hypothesis that early detection and rapid correction of LA improves survival and decreases the incidence of MSOF and RC after severe trauma.

Several aspects of this study require clarification. The prospective study examined the institution of a management protocol. Before that time, we had a policy of resuscitating patients until LA was normal, but this policy was not observed closely and was not audited. After January 1, 1996, and the completion of the pilot study, we made a special effort to educate nursing and resident staff as to the importance of rapid, aggressive resuscitation from OH. We also audited patients on a weekly basis to determine why LA could not be corrected and to determine what logistical problems stood in the way of our resuscitation protocol. The data were collected prospectively, but the groups for analysis were not chosen until after the study period had elapsed. Thus, the significance of the 24-hour time point in resuscitation was not apparent until after the patient data were analyzed. We attempted to correct hypoperfusion as rapidly as possible in all patients during the prospective study period. The exclusion criteria were chosen for several reasons. First, because the mortality rate was so low on the trauma service for patients with ISS less than 20 (<1%), it was believed that inclusion of this group would not provide any useful data for analysis. The four deaths in patients with ISS less than 20 were due to severe medical problems in patients over age 75 years (stroke, intra-cranial hemorrhage, myocardial infarction leading to a MVC). Patients who died in less than 24 hours were also excluded. All of these patients died either of massive head injury or hypotension that could not be corrected. Because the majority of these patients were in clinical shock (not OH), we were not interested in studying this group. The patients in this group without signs of clinical shock died of massive head injuries.

Our hypothesis states that patients without signs of clinical shock (hypotension, tachycardia, oliguria) can still be hypoperfused at the cellular level and are at risk for complications if this hypoperfusion is not rapidly corrected. Therefore, those patients who reached the ICU with signs of clinical shock (systolic blood pressure < 100 mm Hg, pulse rate > 120, urine output < 1 mL/kg per hour) were similarly excluded from analysis. We do not believe measurement of LA is necessary to guide therapy in these patients because their hypoperfusion is not “occult.”

As in other studies, MVC were the principal blunt mechanism by which patients were injured, accounting for 90% of the blunt trauma patients in this study. The overall mortality of 7% is comparable to that of other studies. ^19–21 All deaths were due to overwhelming MSOF secondary to blunt mechanisms of injury. Stratification of the cohort according to duration of OH demonstrated that all deaths occurred in the subgroup of patients whose LA levels remained elevated at and beyond 24 hours.

Injury severity score was not predictive of outcome or the development of MSOF or RC. This observation is in contrast to some other reports, ^14,20 but is in accordance with a recent study by Moore et al. ² In the present study, we have shown that initial serum LA levels are predictive of poor outcome, especially in patients with low CI measurements. The correlation of serial lactate levels and the development of MSOF confirm the findings in penetrating trauma patients reported by Abramson et al. ²² Roumen et al. ¹⁴ reported that blood lactate levels on days 2, 3, and 4 can predict the development of MSOF. The additional finding that persistent lactic acidemia at 24 hours correlates with a poor clinical outcome extends these previously reported observations. Lactic acidosis is an indicator of the oxygen debt that signifies OH. Aggressive resuscitation and the treatment of poor cardiac performance are necessary to attempt to treat OH.

It has been shown that hemorrhage activates leukocyte-endothelial adhesion, leading to sequestration and activation of neutrophils in the lung and other organs. ²³ Acute lung injury is thought to result from activation of neutrophils within the lung parenchyma. ²⁴ The activated neutrophils release activated substances that increase endothelial permeability leading to tissue edema and increased distance for oxygen diffusion. These observations suggest that the development of tissue hypoxia after injury is largely responsible for subsequent MSOF and RC. Respiratory complications were noted in 50% of trauma patients with persistent OH at 24 hours. A 36% incidence of MSOF was seen in this same group of patients. The relationship between duration of OH and the development of MSOF and RC rarely has been investigated.

In the prospective study, not all patients with OH received Swan-Ganz catheters. The results of the pilot study demonstrated that patients with major trauma and increased LA have significantly lower CI than those who present with normal LA. However, because of logistical problems (long emergency department stays, delays in radiology, orthopedic procedures, angiography, etc.) we were not always able to place invasive monitoring in patients who may have benefited from this in the first 24 hours after admission. Had we been able to place these catheters anywhere in the hospital, the data obtained may have focused our resuscitation efforts and improved outcome. Since review of this study, we have instituted training and policies that allow placement of invasive monitoring in the radiology suite and in the emergency department. Further efforts are required to indoctrinate our anesthesia colleagues to the benefits of this resuscitation strategy, because many patients are under their care during the “Silver Day.”

Therefore, this study has shown that persistent OH after the first 24 hours of resuscitation is strongly associated with increased morbidity and mortality after severe trauma. In addition, we have shown that early identification and treatment of OH directly impacts on patient survival and patient morbidity. These findings support the idea of a posttraumatic therapeutic window of 24 hours (the Silver Day), which if used efficaciously may dramatically influence the outcome of severely injured trauma patients.

Acknowledgments

The authors thank Mrs. Avis T. Brent for her editorial assistance in the preparation of this manuscript.