Esophageal Doppler-guided fluid management decreases blood lactate levels in multiple-trauma patients: a randomized controlled trial

cc5703 CCJ Research Esophageal Doppler-guided fluid management decreases blood lactate levels in multiple-trauma patients: a randomized controlled trial Chytra Ivan chytra@fnplzen.cz Pradl Richard pradl@fnplzen.cz Bosman Roman bosman@fnplzen.cz Pelnář Petr pelnar@fnplzen.cz Kasal Eduard kasal@fnplzen.cz Židková Alexandra zidkova@fnplzen.cz

Department of Anesthesia and Intensive Care Medicine, University Hospital, Alej svobody 80, Plzeň 30460, Czech Republic

Critical Care 1364-8535 2007 11 1 R24 http://ccforum.com/content/11/1/R24 17313691 10.1186/cc5703 23 10 2006 30 11 2006 8 1 2007 22 2 2007 22 2 2007 2007 Chytra et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Introduction

Esophageal Doppler was confirmed as a useful non-invasive tool for management of fluid replacement in elective surgery. The aim of this study was to assess the effect of early optimization of intravascular volume using esophageal Doppler on blood lactate levels and organ dysfunction development in comparison with standard hemodynamic management in multiple-trauma patients.

Methods

This was a randomized controlled trial. Multiple-trauma patients with blood loss of more than 2,000 ml admitted to the intensive care unit (ICU) were randomly assigned to the protocol group with esophageal Doppler monitoring and to the control group. Fluid resuscitation in the Doppler group was guided for the first 12 hours of ICU stay according to the protocol based on data obtained by esophageal Doppler, whereas control patients were managed conventionally. Blood lactate levels and organ dysfunction during ICU stay were evaluated.

Results

Eighty patients were randomly assigned to Doppler and 82 patients to control treatment. The Doppler group received more intravenous colloid during the first 12 hours of ICU stay (1,667 ± 426 ml versus 682 ± 322 ml; p < 0.0001), and blood lactate levels in the Doppler group were lower after 12 and 24 hours of treatment than in the control group (2.92 ± 0.54 mmol/l versus 3.23 ± 0.54 mmol/l [p = 0.0003] and 1.99 ± 0.44 mmol/l versus 2.37 ± 0.58 mmol/l [p < 0.0001], respectively). No difference in organ dysfunction between the groups was found. Fewer patients in the Doppler group developed infectious complications (15 [18.8%] versus 28 [34.1%]; relative risk = 0.5491; 95% confidence interval = 0.3180 to 0.9482; p = 0.032). ICU stay in the Doppler group was reduced from a median of 8.5 days (interquartile range [IQR] 6 to16) to 7 days (IQR 6 to 11) (p = 0.031), and hospital stay was decreased from a median of 17.5 days (IQR 11 to 29) to 14 days (IQR 8.25 to 21) (p = 0.045). No significant difference in ICU and hospital mortalities between the groups was found.

Conclusion

Introduction

Post-traumatic hemorrhage in multiple-trauma patients leads to hypovolemia, in which blood flow and consequently oxygen delivery to the tissues are decreased. Reduction of oxygen delivery and oxygen consumption to below a critical level produces ischemic metabolic insufficiency followed by increased generation of lactate 1234. Blood lactate levels are closely related to outcome in critically ill trauma patients 456789, and failure of serum lactate levels to reach normal values within a specific time during critical illness could be even more closely related to survival than the initial level 101112131415. According to a systematic Medicine/Cochrane Library literature search, blood lactate level was shown to predict outcome in almost 3,000 multiple-trauma patients 4.

Fluid resuscitation of trauma patients has traditionally been guided by the normalization of vital signs such as blood pressure, heart rate, and urine output. However, blood pressure and heart rate remain relatively unchanged despite reduced blood flow to certain tissues and hence they are insensitive indicators of hypovolemia and hypoperfusion 14161718. Occult hypoperfusion, defined as elevated blood lactate levels without signs of clinical shock, was associated with increased morbidity and mortality, and early correction is likely to improve the outcome 781019.

The esophageal Doppler is a non-invasive technique for monitoring cardiac function in intensive care unit (ICU) patients. The technique and clinical use were first described in 1971 20, subsequently refined by Singer and colleagues in 1989 21, and recently have been successfully approved for optimizing fluid management perioperatively and in intensive care patients 2223242526272829. Unfortunately, the Doppler probe is not readily tolerated by conscious patients, restricting its use to patients who are sedated and ventilated. To our knowledge, no prospective study has been performed to assess the efficacy of the esophageal Doppler for optimization of fluid management in multiple-trauma patients in the immediate postoperative period.

The aim of this study was to examine the effect of esophageal Doppler-guided fluid management during the first 12 hours after ICU admission on blood lactate levels, organ dysfunction development, infectious complications, and length of ICU and hospital stays in comparison with standard hemodynamic management in multiple-trauma patients.

Materials and methods

This was a randomized, controlled, single-center study conducted in the interdisciplinary ICU of a university teaching hospital. The study was approved by the Local Research Ethics Committee of University Hospital in Plzeň (Czech Republic). Because the protocol was approved and regarded as part of the routine practice and (due to the emergency clause) informed consent by the patients or the family was not required, an independent physician was designated to give the consent. However, subjects were informed at discharge that they had participated in this clinical study.

Participants

Ventilated patients with multiple trauma and estimated blood loss of more than 2,000 ml admitted to the interdisciplinary ICU of our university teaching hospital from 2003 to 2005 were considered for inclusion in this study. We excluded patients younger than 18 years old, patients with traumatic brain injury requiring treatment of intracranial hypertension, and those with relative contraindications to the use of the esophageal Doppler probe, such as orofacial and esophageal injury or other known oropharyngeal and esophageal disease.

Protocol

Primary outcome measures were blood lactate levels after 12 and 24 hours after ICU admission and organ dysfunction development during ICU stay. Secondary outcome measures were duration of ICU and hospital stays and the incidence of infectious complications during ICU stay.

Patients meeting inclusion criteria were randomly assigned to the protocol group (Doppler) or the control group according to the assigned admission number generated by the admission office of the university hospital (even: Doppler group, odd: control group). Randomization of the patients was performed by a member of the research team at the time of ICU admission. Data were analyzed on an intention-to-treat basis and included all patients who were randomly assigned (Figure 1).

Figure 1

Flow of participants through the trial

Flow of participants through the trial. ICU, intensive care unit.

Patients with multiple trauma were initially examined and treated in the emergency department of the university teaching hospital and after urgent surgery were admitted to the ICU. The amount of blood loss in the pre-study period was estimated by an emergency department physician and by an anesthesiologist taking care of the screened patient. Neither of them was a member of the research team. At the time of ICU admission and during the first 12 hours of ICU stay, all patients were mechanically ventilated (pressure-controlled ventilation) and received adequate continuous analgosedation (fentanyl + midazolam) to keep the Ramsay Scale score between 4 and 5 30.

All patients were managed to maintain hemoglobin oxygen saturation (measured using pulse oximetry) above 95%, mean arterial pressure (MAP) above 65 mm Hg, heart rate below 100 bpm, urine output above 1 ml/kg per hour, temperature at 37°C, and hemoglobin above 85 g/l. Anemia and coagulation disorders in all patients were treated by administration of erythrocytes, platelets, and fresh frozen plasma (FFP) according to clinical and laboratory results. All patients received basic crystalloid infusion of 1.5 ml/kg per hour (Hartman's solution; B. Braun Melsungen AG, Melsungen, Germany). When necessary, norepinephrine was added to keep MAP above 65 mm Hg. Further plasma volume replacement in the Doppler and control groups was managed by colloid solutions administration of gelatine and hydroxyethylstarch in a 1:1 ratio (Gelofusine^®; B. Braun Melsungen AG, and Voluven^®; Fresenius Kabi AG, Bad Homburg, Germany). Fluid management in the control group was guided using the abovementioned routine cardiovascular monitoring and central venous pressure (CVP) measurement in order to keep CVP between 12 and 15 mm Hg.

In the Doppler-guided fluid replacement group, the esophageal 7-mm probe was placed into the lower esophagus through the mouth or nose to a depth of 35 to 40 cm from the dental row within 30 minutes after ICU admission. The probe was rotated as needed to obtain the best Doppler signal of blood flow in the midstream of the descending aorta. Correct placement was assumed when reproducible, sharply defined waveforms appeared on the screen of the monitor and crisp sound was heard through the loudspeaker. The algorithm for fluid replacement during the first 12 hours after ICU admission in the Doppler group was similar to that used by Sinclair and colleagues 23 (Figure 2). Corrected flow time (FTc) of less than 0.35 seconds was considered an indication of possible hypovolemia. Patients were given an initial bolus of colloid (250 ml) in a five minute period. If the stroke volume (SV) was either maintained or increased after the fluid challenge and FTc remained below 0.35 seconds, the bolus of colloid was repeated. If the FTc exceeded 0.35 seconds and the SV rose by more than 10%, the fluid challenge was repeated. If the FTc exceeded 0.35 seconds and SV was unchanged or rose by less than 10%, no further fluid was given until the FTc dropped below 0.35 seconds or SV fell by 10%. If the FTc rose above 0.40 seconds, no further fluid was given until the FTc dropped below 0.35 seconds or SV fell by 10%. Esophageal Doppler monitoring measurements were obtained using the Hemosonic 100 device (Arrow International, Inc., Reading, PA, USA), which enables continuous measurement of descending thoracic aorta blood velocity (Doppler transducer) and of aortic diameter (M-mode echo transducer). The technical details and relative merits of this technique have been reviewed elsewhere 3132. In the workplace where the study was implemented, the esophageal Doppler for hemodynamic monitoring has been used routinely for several years and all members of the research team were experienced in its use, and therefore measurement was performed by any of the clinical study investigators. This fluid protocol started immediately after probe placement and continued for 12 hours until the esophageal probe was removed. Following fluid management in both groups was guided in the same way as in the control group.

Figure 2

Fluid management algorithm in the Doppler group

Fluid management algorithm in the Doppler group. FTc, corrected flow time; ICU, intensive care unit; SV, stroke volume.

Assessments

The following parameters were monitored during the study period: electrocardiograph, pulse oximetry, invasive arterial pressure, CVP, urine output, and (in the Doppler group) SV and FTc. Acute Physiology and Chronic Health Evaluation II (APACHE II) score and Injury Severity Score (ISS) were calculated after admission to the ICU. Sequential Organ Failure Assessment (SOFA) score was calculated daily, and the values at the time of ICU admission and the highest SOFA during ICU stay were assessed. MAP and CVP were evaluated at baseline and at the end of the 12-hour study period. Blood lactate levels were assessed at baseline and 12 and 24 hours after ICU admission. The normal value of blood lactate in our laboratory is less than 2.4 mmol/l. Rate and dose of norepinephrine, volume of administered crystalloids and colloids, and blood and FFP during the first 12 hours of the study period were assessed. Length of ICU and hospital stays, ICU and hospital mortalities, and incidence of infectious complications during ICU stay were evaluated. Diagnosis of infectious complications was established by non-research staff in accordance with predefined criteria 33. Patients were followed up to hospital discharge.

Statistical analysis

For the measure of primary outcome with reference to previous studies and our pilot data 13153435, we calculated a study size of 75 patients in each group to demonstrate the decrease of blood lactate levels by 0.6 mmol/l per 24 hours (standard deviation [SD] ± 1.3) in the Doppler group in comparison with the control group. For the measure of secondary outcome with reference to previous data 25, we calculated a sample size of 160 patients (80 in each group) by postulating a reduction in mean ICU stay from nine days in the control group to seven days in the protocol group (SD ± 4.5). Sample sizes were calculated for two-tailed tests allowing for a type I error of 5% and a type II error of 20%. The Kolmogorov-Smirnov test was used to check for normal distribution of data. Continuous normally distributed data were tested with the t test, and not normally distributed data were tested with the Mann-Whitney U test. Categorical data were tested with the Fisher exact test. Data are presented as means (SDs) where normally distributed and as medians (interquartile ranges) where not normally distributed. Relative risk is presented with 95% confidence intervals (CIs). A p value of less than 0.05 was considered statistically significant. Analysis was performed with MedCalc^®version 7.1.0.0 (Frank Schoonjans, MedCalc Software, Broekstraat 52, 9030 Mariakerke, Belgium).

Results

A total of 162 patients were recruited between January 2004 and December 2005 (Figure 1). Eighty patients were randomly assigned to the Doppler group, and 82 patients to the control group. The groups were well matched for age, gender, SOFA score at the time of ICU admission, APACHE II score and ISS, and the type of injuries (Table 1). There were no differences between the Doppler and control groups in MAP, CVP, blood lactate level, and frequency and dose of norepinephrine administration at baseline (that is, at the time of ICU admission) (Table 2). After the 12-hour study period, blood lactate in Doppler group patients was lower (2.92 ± 0.54 mmol/l versus 3.23 ± 0.56 mmol/l; p = 0.0003) as were the dose of norepinephrine (0.093 ± 0.035 μg/kg per minute versus 0.169 ± 0.068 μg/kg per minute; p = 0.0009) and the rate of norepinephrine (18 patients [23%] versus 33 patients [40%]; relative risk = 0.56, 95% CI = 0.34 to 0.91; p = 0.018). We found no difference between the Doppler and control groups in MAP, but CVP in the Doppler group was higher (13.7 ± 1.8 mm Hg versus 12.1 ± 2.4 mm Hg; p < 0.0001). Patients in the Doppler group received a greater volume of colloid solutions (1,667 ± 426 ml versus 682 ± 322 ml; p < 0.0001) but similar volumes of blood, FFP, and crystalloid solution (Table 3). The difference of lactate level between the Doppler and control groups changed little after 24 hours of ICU stay (1.99 ± 0.44 mmol/l versus 2.37 ± 0.59 mmol/l; p < 0.0001). During ICU stay, no difference between the Doppler and control groups in the highest SOFA score was found (10 [7 to 12.75] versus 11 [7 to 14]; p = 0.17), but in the Doppler group fewer patients developed infectious complications (15 patients [18.8%] versus 28 patients [34.1%]; relative risk = 0.5491, 95% CI = 0.3180 to 0.9482; p = 0.032) (Table 4). The reduction of complications was associated with a reduction of median duration of ICU stay (7 days [6 to 11] versus 8.5 days [6 to 16]; p = 0.031) as well as with a reduction of median duration of hospital stay (14 days [8.25 to 21] versus 17.5 days [11 to 29]; p = 0.045) (Table 4). There was no significant difference in ICU and hospital mortalities (11 patients [13.8%] versus 16 patients [19.5%] [p = 0.40] and 13 patients [16.3%] versus 18 patients [22%] [p = 0.43], respectively) (Table 4). There were no complications related to esophageal Doppler ultrasonography.

Table 1

Baseline characteristics of patients in the Doppler and control groups

Characteristics

Doppler group

Control group

Number in group

Age in years

33 (26–57)

40 (26–50)

Male

73 (91%)

70 (85%)

APACHE II

20 (16–21)

18 (12–23)

Injury Severity Score

38.5 ± 10.5

36.4 ± 11.8

SOFA score at ICU admission

8 (7–10)

8 (6–11)

Type of injury

Chest

42 (52%)

50 (61%)

Abdomen

52 (65%)

48 (58%)

Spine

24 (30%)

21 (26%)

Pelvis

36 (45%)

43 (52%)

Extremities

76 (95%)

76 (93%)

Values are presented as absolute (percentage) or mean ± standard deviation or median (interquartile range). APACHE II, Acute Physiology and Chronic Health Evaluation II; ICU, intensive care unit; SOFA, Sequential Organ Failure Assessment.

Table 2

Baseline parameters and therapeutic interventions

Parameters

Doppler group (n = 80)

Control group (n = 82)

Mean arterial pressure (mm Hg)

65 (60–71)

65 (55–75)

0.71

Central venous pressure (mm Hg)

7.1 ± 2.1

6.8 ± 2.1

0.34

Lactate (mmol/l)

4.2 (3.2–5.2)

3.9 (3.0–4.7)

0.08

Intervention

Norepinephrine (patients)

58 (73%)

57 (70%)

0.73

Norepinephrine (μg/kg per minute)

0.23 (0.14–0.60)

0.21 (0.12–0.41)

0.25

Values are presented as absolute (percentage) or mean ± standard deviation or median (interquartile range).

Table 3

Therapeutic interventions and changes in parameters during the 12-hour study period

Parameters

Doppler group (n = 80)

Control group (n = 82)

Mean arterial pressure (mm Hg)

78 ± 6.5

79 ± 9.5

0.76

Central venous pressure (mm Hg)

13.7 ± 1.8

12.1 ± 2.4

< 0.0001

Lactate (mmol/l)

2.92 ± 0.54

3.23 ± 0.54

0.0003

Intervention

Colloid (ml)

1,667 ± 426

682 ± 322

< 0.0001

Crystalloid (ml)

1,293 ± 300

1,334 ± 320

0.38

Blood (ml)

814 ± 228

833 ± 340

0.67

Fresh frozen plasma (ml)

742 (566–949)

750 (562–1,108)

0.69

Norepinephrine (patients)

18 (23%)

33 (40%)

0.018

Norepinephrine (μg/kg per minute)

0.093 ± 0.035

0.169 ± 0.068

0.0009

Values are presented as absolute (percentage) or mean ± standard deviation or median (interquartile range).

Table 4

Summary of outcomes after the 12-hour intervention period

Parameters

Doppler group (n = 80)

Control group (n = 82)

Lactate after 24 hours of ICU stay (mmol/l)

1.99 ± 0.44

2.37 ± 0.59

< 0.0001

The highest SOFA during ICU stay

10 (7–12.75)

11 (7–14)

0.17

Infectious complication

Pneumonia

0.09

Central venous catheter

1.00

Abdominal

0.68

Urinary tract

1.00

Wound

0.44

Total infectious complications

0.033

Patients with infectious complications

15 (18.8%)

28 (34.1%)

0.032

Length of ICU stay in days

7 (6–11)

8.5 (6–16)

0.031

Length of hospital stay in days

14 (8.25–21)

17.5 (11–29)

0.045

ICU mortality

11 (13.8%)

16 (19.5%)

0.40

Hospital mortality

13 (16.3%)

18 (22%)

0.43

Values are presented as absolute (percentage) or mean ± standard deviation or median (interquartile range). ICU, intensive care unit; SOFA, Sequential Organ Failure Assessment.

Discussion

Esophageal Doppler-guided fluid management in multiple-trauma patients decreased blood lactate levels, lowered the incidence of infectious complications, and reduced the length of ICU and hospital stays. Occult tissue hypoperfusion in trauma patients is relatively common and cannot be diagnosed and eliminated using traditional markers and resuscitation endpoints (blood pressure, heart rate, and urine output). Scalea and colleagues 16 found that up to 80% of critically ill patients who are normotensive and have adequate urine output may remain in a state of compensated shock. One of most commonly used markers in assessing occult tissue hypoperfusion in trauma patients is blood lactate. Several studies have shown that normalization of blood lactate levels within 24 hours of admission in hemodynamically stable trauma patients was associated with improved survival, less frequent infection rate, and organ dysfunction development 78101112. Persistent elevated lactate levels 24 hours after admission significantly correlated with mortality 13. Limited prospective data are available, but these indicate that rapid normalization of increased blood lactate levels is an important therapeutic goal in critically ill patients 19. Adequate fluid resuscitation to increase cardiac output has been found to improve tissue oxygen delivery in patients with tissue hypoxia and remains the mainstay of therapy in these circumstances 36. Esophageal Doppler flowmetry used to maximize intraoperative SV by repeated fluid challenges was associated with improved outcome and reductions in length of hospital stay after cardiac, orthopedic, or abdominal surgery 2223242528. Our data are in agreement with other studies 192636 and support the statement that some beneficial effects might still be achieved from optimization of circulatory status in the immediate postoperative period.

Although decreased blood lactate levels in Doppler group patients during the first 12 and 24 hours of ICU stay indicate improved tissue perfusion and oxygenation, surprisingly we did not prove a significant difference between the Doppler and control groups in organ failure development during ICU stay. Presumably, the difference in tissue oxygen delivery in both groups was not significant enough to induce organ-function changes measurable by SOFA score. With reference to the 'golden hour' and the 'silver day' of trauma resuscitation 1037, a partial explanation for this finding can be that despite the higher blood lactate levels in control group patients, oxygen delivery in both groups was sufficient to achieve normal lactate levels within 24 hours of ICU stay. However, other factors that could help to explain the uniformity in levels of organ dysfunction and mortality between the protocol and control groups (that is, amount of time elapsed between the injury and emergency department admission, duration of surgery, and amount of blood transfused before ICU admission) were not analyzed.

A relationship between the rapid normalization of blood lactate level and the lower rate of infectious complications in trauma patients was clearly demonstrated 781036. The blood lactate level in the control group after 12 and 24 hours of study was higher than in the Doppler group, and even though the blood lactate level after 24 hours of ICU stay in both groups reached the normal range, more patients in the control group developed infectious complications during ICU stay. Clinical studies support the notion that adequate fluid resuscitation may improve tissue oxygen tension and decrease the rate of complications 2238. Other studies have demonstrated that inadequate tissue perfusion measured with gastric tonometry is associated with adverse perioperative outcome 3940. Possibly, better tissue oxygenation results in improved tissue healing and decreased infection rate.

The use of esophageal Doppler for hemodynamic optimization based on administering fluids to achieve maximal left ventricular SV was associated with important reductions of ICU or hospital stay 2223242526. In the present study, esophageal Doppler-guided fluid management was associated with a 1.5-day median reduction in ICU stay and a 3.5-day median decrease in hospital stay. This suggests that optimization of circulatory status may also have financial implications and reduce the cost of care for multiple-trauma patients.

In a meta-analysis of hemodynamic optimization studies, Poeze and coworkers 41 showed that the use of strategies to optimize the hemodynamic condition perioperatively and during trauma significantly reduced mortality. In the present study, there was no statistical difference in ICU and hospital mortalities between the groups, and the study was not powered to show any difference in mortality. This would have required more than 700 patients.

There are some potential weaknesses in the design of our trial. It was of relatively small size, was not blinded, and was conducted in only one center. All patients in the control group received intravenous resuscitation guided by CVP measurement in order to keep CVP between 12 and 15 mmHg. However, because no reliable correlation between intravascular volume and absolute CVP measurement has been established, rather than apply an absolute target for CVP, dynamic changes of CVP to fluid challenge would likely provide a more reliable guide to fluid requirements 2436. Recruitment of patients was possible only when a member of the research team was available to administer the 12-hour study protocol. During the trial period, 539 multiple-trauma patients were admitted to the ICU and mortality was 22.4% (including deaths within 24 hours after ICU admission).

The application of the 12-hour study protocol in the Doppler group was time-consuming and would not have been feasible without the close cooperation of the nursing staff. The continuous presence of a clinician at bedside for a 12-hour period is not realistic and thus the fluid challenge according to the Doppler-guided protocol was given partly by trained nursing staff. Whenever the quality of the Doppler signal was altered (due mostly to a change of probe position resulting from nurse or patient movement), a member of the research team was called and the probe was restored to the proper position. In spite of adequate sedation, it was difficult to keep the Doppler probe in the right position for 12 hours without frequent adjustments. We suppose that the use of other relatively non-invasive devices that measure SV and cardiac output (for example, cardiac output measurement using partial carbon dioxide rebreathing, thoracic impedance, and technologies using arterial pressure waveform analysis) may be less demanding for postoperative fluid and hemodynamic optimization. Moreover, these methods do not require deep sedation, can be used for longer periods, and do not discriminate patients who are not suitable for esophageal Doppler monitoring.

Conclusion

Optimization of intravascular volume using esophageal Doppler in multiple-trauma patients is associated with a decrease of blood lactate levels, a lower incidence of infectious complications, and a reduced duration of ICU and hospital stays. A large multicenter study should be performed to validate these findings and to demonstrate an effect on mortality.

Key messages

• Optimization of intravascular volume using esophageal Doppler in multiple-trauma patients decreases blood lactate levels.

• Fluid resuscitation in multiple-trauma patients guided by esophageal Doppler is associated with a lower incidence of infectious complications and reduces ICU and hospital stays.

Abbreviations

APACHE II = Acute Physiology and Chronic Health Evaluation II; CI = confidence interval; CVP = central venous pressure; FFP = fresh frozen plasma; FTc = flow time corrected; ICU = intensive care unit; ISS = Injury Severity Score; MAP = mean arterial pressure; SD = standard deviation; SOFA = Sequential Organ Failure Assessment; SV = stroke volume.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

IC and RP were responsible for study design and data analysis. All authors were responsible for administering the protocol, were involved in drafting the manuscript and approved the final version, and have full access to the data and take full responsibility for the integrity of the data.

Acknowledgements

The study was supported by a research grant (IGA MZ CR ND/7712-3) and by the Czech Ministry of Education (project MSM0021620819).

Physiology of blood flow and oxygen utilization by peripheral tissue in circulatory shock Rackow EC Weil MH Clin Chem 1990 36 1544 1546 2387064 Shock American College of Surgeons Advanced Trauma Life Support Manual Chicago, IL 6 Correlation of serial blood lactate levels to organ failure and mortality after trauma Manikis P Jankowski S Zhang H Kahn RJ Vincent JL Am J Emerg Med 1995 13 619 622 10.1016/0735-6757(95)90043-8 7575797 Bench-to-bedside review: oxygen debt and its metabolic correlates as quantifiers of the severity of hemorrhagic and post-traumatic shock Rixen D Siegel JH Crit Care 2005 9 441 453 1297598 16277731 10.1186/cc3526 Pattern of organ failure following severe trauma Regel G Grotz M Weltner T Sturm JA Tscherne H World J Surg 1996 20 422 429 10.1007/s002689900067 8662130 Multiple organ failure can be predicted as early as 12 hours after injury Sauaia A Moore FA Moore EE Norris JM Lezotte DC Hamman RF J Trauma 1998 45 291 301 9715186 Persistent occult hypoperfusion is associated with a significant increase in infection rate and mortality in major trauma patients Claridge JA Crabtree TD Pelletier SJ Butler K Sawyer RG Young JS J Trauma 2000 48 8 14 10647559 Occult hypoperfusion is associated with increased morbidity in patients undergoing early femur fracture fixation Crowl AC Young JS Kahler DM Claridge JA Chrzanowski DS Pomphrey M J Trauma 2000 48 260 267 10697084 Relationship between injury severity and lactate levels in severely injured patients Cerovic O Golubovic V Spec-Marn A Kremzar B Vidmar G Intensive Care Med 2003 29 1300 1305 10.1007/s00134-003-1753-8 12904861 The golden hour and the silver day: detection and correction of occult hypoperfusion within 24 hours improves outcome from major trauma Blow O Magliore L Claridge JA Butler K Young JS J Trauma 1999 47 964 969 10568731 Prolonged lactate clearance is associated with increased mortality in the surgical intensive care unit McNelis J Marini CP Jurkiewicz A Szomstein S Simms HH Ritter G Nathan IM Am J Surg 2001 182 481 485 10.1016/S0002-9610(01)00755-3 11754855 Lactate clearance and survival following injury Abramson D Scalea TM Hitchcock R Trooskin SZ Henry SM Greenspan J J Trauma 1993 35 584 588 8411283 Serum lactate and base deficit as predictors of mortality and morbidity Husain FA Martin MJ Mullenix PS Steele SR Elliott DC Am J Surg 2003 185 485 491 10.1016/S0002-9610(03)00044-8 12727572 Occult hypoperfusion is associated with increased mortality in hemodynamically stable, high-risk, surgical patients Meregalli A Oliveira RP Friedman G Crit Care 2004 8 R60 65 10.1186/cc2423 15025779 420024 Base excess and lactate as prognostic indicators for patients admitted to intensive care Smith I Kumar P Molloy S Rhodes A Newman PJ Grounds RM Bennett ED Intensive Care Med 2001 27 74 83 10.1007/s001340051352 11280677 Resuscitation of multiple trauma and head injury: role of crystalloid fluids and inotropes Scalea TM Maltz S Yelon J Trooskin SZ Duncan AO Sclafani SJ Crit Care Med 1994 22 1610 1615 7924373 Hemodynamic responses to shock in young trauma patients: need for invasive monitoring Abou-Khalil B Scalea TM Trooskin SZ Henry SM Hitchcock R Crit Care Med 1994 22 633 639 10.1097/00003246-199404000-00020 8143473 Unreliability of blood pressure and heart rate to evaluate cardiac output in emergency resuscitation and critical illness Wo CC Shoemaker WC Appel PL Bishop MH Kram HB Hardin E Crit Care Med 1993 21 218 223 10.1097/00003246-199302000-00012 8428472 A prospective, randomized study of goal-oriented hemodynamic therapy in cardiac surgical patients Polonen P Ruokonen E Hippelainen M Poyhonen M Takala J Anesth Analg 2000 90 1052 1059 10.1097/00000539-200005000-00010 10781452 Non-surgical assessment of cardiac function Side CD Gosling RG Nature 1971 232 335 336 10.1038/232335a0 5094838 Continuous hemodynamic monitoring by esophageal Doppler Singer M Clarke J Bennett ED Crit Care Med 1989 17 447 452 2651004 Perioperative plasma volume expansion reduces the incidence of gut mucosal hypoperfusion during cardiac surgery Mythen MG Webb AR Arch Surg 1995 130 423 429 7535996 Intraoperative intravascular volume optimisation and length of hospital stay after repair of proximal femoral fracture: randomised controlled trial Sinclair S James S Singer M BMJ 1997 315 909 912 9361539 Randomized controlled trial to investigate influence of the fluid challenge on duration of hospital stay and perioperative morbidity in patients with hip fractures Venn R Steele A Richardson P Poloniecki J Grounds M Newman P Br J Anaesth 2002 88 65 71 10.1093/bja/88.1.65 11881887 Goal-directed intraoperative fluid administration reduces length of hospital stay after major surgery Gan TJ Soppitt A Maroof M el-Moalem H Robertson KM Moretti E Dwane P Glass PS Anesthesiology 2002 97 820 826 10.1097/00000542-200210000-00012 12357146 Randomised controlled trial assessing the impact of a nurse delivered, flow monitored protocol for optimisation of circulatory status after cardiac surgery McKendry M McGloin H Saberi D Caudwell L Brady AR Singer M BMJ 2004 329 258 261 498021 15242867 10.1136/bmj.38156.767118.7C Noninvasive optimization of left ventricular filling using esophageal Doppler Singer M Bennet ED Crit Care Med 1991 19 1132 1137 1884612 Intraoperative oesophageal Doppler guided fluid management shortens postoperative hospital stay after major bowel surgery Wakeling HG McFall MR Jenkins CS Woods WG Miles WF Barclay GR Fleming SC Br J Anaesth 2005 95 634 642 10.1093/bja/aei223 16155038 Randomised controlled trial investigating the influence of intravenous fluid titration using oesophageal Doppler monitoring during bowel surgery Conway DH Mayall R Abdul-Latif MS Gilligan S Tackaberry C Anaesthesia 2002 57 845 849 10.1046/j.1365-2044.2002.02708.x 12190747 Instruments for monitoring intensive care unit sedation Carrasco G Crit Care 2000 4 217 225 150039 11094504 10.1186/cc697 Minimally invasive hemodynamic monitoring for the intensivist: current and emerging technology Chaney JC Derdak S Crit Care Med 2002 30 2338 2345 10.1097/00003246-200210000-00025 12394965 Utility of esophageal Doppler as a minimally invasive hemodynamic monitor: a review Laupland KB Bands CJ Can J Anaesth 2002 49 393 401 11927480 CDC definitions for nosocomial infections Garner JS Jarvis WR Emori TG Horan TC Hughes JM Am J Infect Control 1988 16 128 140 10.1016/0196-6553(88)90053-3 2841893 Early hemodynamic optimization in multiple trauma patients by transesophageal Doppler Pradl R Chytra I Kasal E Bosman R Židková A Intensive Care Med 2004 30 s130 Optimization of intravascular volume in multiple trauma patients using esophageal Doppler – preliminary results Chytra I Pradl R Bosman R Pelnář P Kasal E Židková A Anest Intenziv Med 2006 17 156 163 Early goal-directed therapy after major surgery reduces complications and duration of hospital stay. A randomised, controlled trial [ISRCTN38797445] Pearse R Dawson D Fawcett J Rhodes A Grounds M Bennet D Crit Care 2005 9 R687 693 10.1186/cc3887 16356219 1414018 Increased blood lactate levels: an important warning signal in surgical practice Bakker J de Lima AP Crit Care 2004 8 96 98 420048 15025766 10.1186/cc2841 Supplemental perioperative fluid administration increases tissue oxygen pressure Arkilic CF Taguchi A Sharma N Ratnaraj J Sessler DI Read TE Fleshman JW Kurz A Surgery 2003 133 49 55 10.1067/msy.2003.80 12563237 The use of a postoperative morbidity survey to evaluate patients with prolonged hospitalization after routine, moderate-risk, elective surgery Bennett-Guerrero E Welsby I Dunn TJ Young LR Wahl TA Diers TL Phillips-Bute BG Newman MF Mythen MG Anesth Analg 1999 89 514 519 10.1097/00000539-199908000-00050 10439777 Can gastric intramucosal pH (pHi) predict outcome of paediatric cardiac surgery? Bichel T Kalangos A Rouge JC Paediatr Anaesth 1999 9 129 134 10.1046/j.1460-9592.1999.9220324.x 10189653 Meta-analysis of hemodynamic optimization: relationship to methodological quality Poeze M Greve JW Ramsay G Crit Care 2005 9 R771 779 10.1186/cc3902 16356226 1414050