BJA Advance Access published online on May 28, 2008
British Journal of Anaesthesia, doi:10.1093/bja/aen126
Influence of systolic-pressure-variation-guided intraoperative fluid management on organ function and oxygen transport
1 Department of Anaesthesiology and Intensive Care Medicine
2 Department of Anaesthesiology and Intensive Care Medicine, Hospital Worms, Worms, Germany
3 Department of Informatics, Friedrich-Schiller-University of Jena, Jena, Germany
4 Department of Anaesthesiology and Intensive Care Medicine, University Witten/Herdecke, Medical Center Cologne-Merheim, Ostmerheimerstr. 200, D-51109 Cologne, Germany
* Corresponding author. E-mail: sakkas{at}kliniken-koeln.de
Accepted for publication March 9, 2008.
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Abstract |
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Background: Dynamic variables, for example, systolic pressure variation (SPV), are superior to filling pressures for assessing fluid responsiveness. We analysed the effects of SPV-guided intraoperative fluid management on organ function and perfusion when compared with routine care.
Methods: Eighty patients (44 female and 36 male) undergoing elective major abdominal surgery were randomly assigned to a control group [n=40, mean age 66 (SD 10), range 40–84 yr] or SPV group [n=40, age 61 (16), range 26–100 yr] in which intraoperative fluid management was guided by SPV (trigger: SPV>10%). Central venous O2 saturation (ScvO2), lactate and bilirubin, creatinine, indocyanine green plasma disappearance rate (ICG-PDR), and gastric mucosal CO2 tension were measured after induction of anaesthesia, after 3, 6, 12, and 24 h.
Results: Patient characteristics, duration of surgery [5.8 (2.5) vs 5.4 (2.5) h], and infusion volumes (median 4865 vs 4330 ml) were comparable between the groups. At 3 and 6 h, SPV (P=0.04, P=0.01) and 
down (P=0.005, P=0.01) were significantly higher in the control group. Oxygen transport and organ function were comparable: baseline and 24 h values for ICG-PDR: 28.5 (7.9) and 22.7 (7.8) vs 23.9 (6.9) and 26.1 (5.9)% min–1, 77.7 (6.6) and 72.6 (5.5) vs 79.3 (7.1) and 72.8 (6.7)% for ScvO2 and 1.0 (0.4) and 1.2 (0.6) vs 0.9 (0.2) and 1.3 (0.5) mmol litre–1 for lactate. Length of mechanical ventilation, ICU stay, and mortality were comparable.
Conclusions: In comparison with routine care, intraoperative SPV-guided treatment was associated with slightly increased fluid adminstration whereas organ perfusion and function was similar.
Keywords: arterial pressure, measurement; complications, multiple organ dysfunction syndrome; fluid, balance; heart, myocardial function; monitoring, intraoperative; surgery, abdominal
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Introduction |
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Major abdominal surgery is associated with a risk of hypovolaemia which may cause organ dysfunction, increased postoperative morbidity, and death.1 2 Goal-directed fluid management during the intraoperative period has been found to be associated with improved outcome and reduction in hospital stay in patients undergoing cardiac and major orthopaedic surgery.3–5 The hepato-splanchnic tract is considered to be an early warning system (‘canary of the body’) and plays an important role in the development of sepsis and multiple organ failure.6 As a consequence, optimization and maintenance of hepato-splanchnic blood flow is considered to be of major clinical relevance. Mythen and Webb3 demonstrated a reduction in the incidence of gastrointestinal mucosal hypoperfusion and major complications in patients who received plasma volume optimization. However, it is still a matter of debate which indicator of cardiac preload should be clinically used for optimizing cardiac preload, and central venous pressure (CVP) is widely used during major abdominal surgery. However, CVP as a static preload variable has its limitations7 and systolic pressure variation (SPV)8 as marker of fluid responsiveness has been shown to be superior to cardiac filling pressures.9 10 Gan and colleagues11 reported that intraoperative optimization of volume status by an oesophageal Doppler-based algorithm positively influenced postoperative morbidity and mortality. Most recently, and with respect to assessment of fluid responsiveness by dynamic variables, Lopes and colleagues12 reported that monitoring and minimizing pulse pressure variation (PPV) by volume loading during high-risk surgery improves postoperative outcome and decreases length of hospital stay. In this study, we studied whether goal-directed intraoperative fluid management using SPV as an infusion trigger in patients undergoing major abdominal surgery would maintain stability of global and hepato-splanchnic perfusion thereby leading to a reduction in postoperative ICU length of stay and mortality.
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Methods |
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The study had approval from the institutional ethics board and written informed patient consent was obtained. Between September 2002 and March 2003, we enrolled 80 patients, American Society of Anesthesiologists (ASA) class I–III. All patients were undergoing elective major abdominal general or gynaecologic surgery with bowel resection and an anticipated blood loss of >500 ml. Exclusion criteria were: age <18 yr, emergency surgery, coagulopathy, renal and hepatic dysfunction, hyperthyroidism (because indocyanine green used in this study contains iodine), and cardiac rhythm other than sinus rhythm. All patients received midazolam p.o. (3.75–7.5 mg) on the evening before and before anaesthesia. All patients underwent central venous (triple lumen catheter, Certofix Trio, Braun Melsungen, Germany) and arterial catheterization (A. radialis, 20 G, BD Medical Systems, Swindon, UK) after induction of anaesthesia. Since no arterial thermistor catheter was used, no transpulmonary thermodilution cardiac output was obtained. We decided not to place such a catheter, since it is not standard care in our department for those patients. CVP was monitored continuously using a patient monitor system (Datex AS3TM, Datex-Ohmeda, Helsinki, Finland). The arterial pressure curve was analysed continuously for the SPV by transferring the raw data (50 Hz) from the PiCCOplusTM monitor (version 6.0 non-US, Pulsion Medical Systems AG, Munich, Germany) by a serial interface to a personal computer.
Stroke volume variation (SVV) was obtained on-line from the PiCCOplusTM system after manual calibration with an arbitrary cardiac output of 5 litre min–1 in all patients. We considered this strategy adequate since SVV relies on changes in stroke volume and represents the variation (as a percentage) of the beat-to-beat pulse contour-derived stroke volume averaged during 30 s. Determination of SPV was carried out real-time by using the software called LIQUO v 0.89f (developed in association with Stefan Schenke, Department of Informatics, Friedrich-Schiller-University of Jena). The components of SPV (down and up) were calculated every 15 min. During the measurements, ventilator settings and dosages of vasoactive drugs remained unchanged. Over a short period of apnoea (8 s) followed by three to five respiratory cycles, the components of the SPV were automatically resolved by the computer using a reference systolic arterial blood pressure at end-expiration. The validity of the LIQUO software has been confirmed before by manual calculations based on the raw arterial pressure data. At 1 h time intervals, the accuracy of SPV estimation was confirmed by using the freeze function of the Datex monitor system and manually derived in a blinded fashion by one investigator who was not a member of the clinical anaesthesia team.
For induction of anaesthesia, patients received sufentanil (0.3 µg kg–1) and propofol (2–3 mg kg–1). Intubation of the trachea was facilitated with succinylcholine and rocuronium (0.6 mg kg–1) and neuromuscular block was maintained throughout surgery. Anaesthesia was maintained by sevoflurane (1 MAC) in O2 and air in a 1:2 ratio (Datex AS3TM, Datex-Ohmeda). Additional sufentanil, up to 0.3 µg kg–1, was given as individually required. Ventilation was adjusted to maintain arterial carbon dioxide partial pressure at 4.7–5.3 kPa, and temperature was maintained at >35°C throughout surgery. In all patients, end-expiratory pressure (PEEP) was kept at a level of 5 cm H2O, the I:E ratio was 1:1, and tidal volume was set at 8 ml kg–1.
If an epidural catheter was placed before operation for postoperative pain management, a 3 ml test dose consisting of lidocaine 1.5% with 1:200 000 epinephrine was administered. Subsequent epidural local anaesthetic drugs were started at the end of surgery. Postoperative analgesia was provided by either epidural (ropivacaine 0.125% and fentanyl 0.001%) or patient-controlled analgesia with pirinitramide. Anaesthesia was maintained at a constant level as judged by standard clinical criteria. All cardiovascular variables and urinary flow were monitored and recorded during anaesthesia. Types and volumes of all fluids administered intraoperatively (including but not limited to colloid and crystalloid solutions, blood, and blood products) were recorded, as were the volumes and doses of any drugs given during anaesthesia. For infusion management, a crystalloid solution (E153, Serumwerk Bernburg AG, Bernburg, Germany) (Na+ 140 mmol litre–1, K+ 5 mmol litre–1, Ca2+ 2.5 mmol litre–1, Mg2+ 1.5 mmol litre–1, Cl– 103 mmol litre–1, and acetate 50 mmol litre–1) and 6% hydroxyethylstarch, 130/0.4, VoluvenTM, Fresenius, Bad Homburg, Germany, were used. The choice of fluid was made by the anaesthesiologist. When considered necessary, norepinephrine (the only ‘vasopressor’ used in our department) was administered to maintain mean arterial pressure >70 mm Hg.
Before surgery, patients were randomized into either the protocol (SPV) or control (CON) groups using sealed envelopes. SPV and SVV data were visible to the anaesthesia team for patients in the SPV group whereas the team were blinded to these data for patients in the control group. Recording of SPV and SVV was finished at the end of surgery. In the SPV group, fluid treatment was guided by SPV which was kept <10%. The control group received usual care.
The protocol called for the administration of blood products (red blood cells, platelets, and fresh frozen plasma) when clinically indicated and supported by laboratory evidence of a haematocrit <23% or abnormal coagulation (platelet count <100 000 litre–1, prothrombin time >1.5 times control, or activated partial thromboplastin time >1.5 times control).
The objectives of our study were to analyse the effects on SPV-guided treatment on oxygen transport and regional perfusion. Samples for determination of central venous oxygen saturation (ScvO2), serum lactate, bilirubin, and creatinine were taken after induction of anaesthesia, after 3, 6, 12, 18, and 24 h. As an indicator of hepato-splanchnic blood flow, we measured the indocyanine green plasma disappearance rate (ICG-PDR).13 We have previously shown that ICG-PDR, which is a marker of hepatic blood flow and function, can be obtained reliably non-invasively by a transcutaneous system in critically ill patients.14 ICG-PDR was measured by a finger clip system (LiMONTM, Pulsion Medical Systems, Munich, Germany). For each measurement, 0.5 mg kg–1 ICG (Pulsion Medical Systems) was injected into a central vein. Gastric mucosal PCO2 tension was measured continuously by a gas tonometric catheter which was advanced into the stomach immediately after induction of anaesthesia (Tonometrics catheter, Tono-14F, Datex-Ohmeda).15 As a measure of gastric mucosal perfusion, we calculated the difference between gastric mucosal and end-tidal CO2 tension (‘PCO2-gap’). During the measurement, ventilator settings and dosages of vasoactive drugs remained unchanged. The ScvO2, ICG-PDR, and PCO2-gap were not available to the clinical team.
After operation, all patients were transferred to the ICU while mechanically ventilated and extubated when they fulfilled standard clinical criteria. Length of ICU and hospital stay and outcome were recorded.
Statistical analysis
Patient characteristic data are presented as median and range. Groups were compared using 
2 and Wilcoxon tests. Organ function variables, variables of global O2 transport, and vasoactive drug support were compared by one-way ANOVA on ranks for repeated measurements with an all pairwise comparison method (Student–Newman–Keuls procedure). P<0.05 was considered statistically significant. For the statistical analysis, SigmaStat for WindowsTM (version 1.0) was used.
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Results |
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Patient characteristics are summarized in Table 1. Both groups were comparable with regard to most variables. Patients in the SPV-guided group tended to receive more fluid. Duration of mechanical ventilation, length of ICU and hospital stay, and mortality were comparable between both groups. One patient in the control group had severe bleeding complications, required operative revision, and developed multiple organ failure from which the patient finally died after several weeks. In contrast, all patients in the SPV group were discharged from the ICU alive. No patient developed arrhythmias and nobody experienced adverse events after ICG injections.
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Heart rate significantly varied but not between corresponding time points whereas arterial blood pressure during operation was comparable throughout between groups (Table 2). However, at 3 and 6 h after induction of anaesthesia, there was a significant increase in SPV (P=0.04 and P=0.01) and
down (P=0.005 and P=0.01) in the control group, suggesting hypovolaemia at these time points when compared with the SPV group. Variables of oxygen transport and organ function at the corresponding time points were not different between both groups (Table 3). Baseline and 24 h values for ICG-PDR: 28.5 (7.9) and 22.7 (7.8) vs 23.9 (6.9) and 26.1 (5.9)% min–1 (Fig. 1), 77.7 (6.6) and 72.6 (5.5) vs 79.3 (7.1) and 72.8 (6.7) % for ScvO2 and 1.0 (0.4) and 1.2 (0.6) vs 0.9 (0.2) and 1.3 (0.5) mmol litre–1 for lactate. Furthermore, bilirubin and creatinine significantly increased after 24 h in both groups. Finally, norepinephrine requirements transiently increased at 3 h in both groups.
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Discussion |
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In this study, we found that intraoperative SPV-guided therapy was associated with slightly increased fluid administration whereas organ perfusion was not different when compared with routine care. In detail, global O2 transport and organ function and perfusion were comparable between both groups.
In general, previous studies that compared different managements for i.v. fluid administration demonstrated no difference in the endpoints if there is not enough difference in the amount of fluid administered between the groups. Our study is in line and confirms these results insofar as our groups were also not significantly different. However, in other studies, average differences of only 565,11 650,16 or 625 ml,17 for example, did improve the results in the goal-directed groups. Notably, volume differences are in the same range as ours (535 ml more fluid in the SPV group). For instance, Gan and colleagues11 reported that intraoperative plasma volume expansion guided by oesophageal Doppler led to an earlier return of bowel function, lower incidence of postoperative nausea and vomiting, and decrease in length of postoperative hospital stay. In this study, significantly more colloid was infused in the protocol group. Conway and colleagues16 found that fluid titration using oesophageal Doppler during bowel surgery can improve haemodynamic parameters (i.e. cardiac output) and may reduce critical care admissions after operation. In cardiac surgical patients, McKendry and colleagues17 reported fewer postoperative complications, a significantly lower usage of intensive care beds and a shorter duration of hospital stay in the protocol group. Wakeling and colleagues18 reported that intraoperative oesophageal Doppler-guided fluid management was associated with a reduction in gut dysfunction, overall morbidity, and postoperative hospital stay. Patients in the protocol group received significantly more colloids (median 2000 vs 1500 ml), but the range of colloid given in the treatment group was large, that is, 500–5000 ml. Oesophageal Doppler which requires practice for adequate use19 was used in all these previous studies. To explain the differences between the abovementioned results and our findings, one may speculate that SPV is not sensitive enough to guide the administration of fluid. It is not clear if full PiCCOTM technology would have been a more sensitive marker. By using transpulmonary thermodilution-derived variables (global end-diastolic volume, extravascular lung water) for guiding fluid treatment, Goepfert and colleagues20 recently reported less use of vasoactives (norepinephrine and epinephrine) and potentially earlier readiness for discharge from the ICU in cardiac surgical patients.
In general, SPV and PPV both have a higher specificity and sensitivity for prediction of a positive reaction (increase in cardiac output by fluid challenge) when compared with cardiac filling pressures. In a small randomized trial, Lopes and colleagues12 found that monitoring and minimizing PPV by volume loading during high-risk surgery improved postoperative outcome, decreased duration of mechanical ventilation, and the length of stay in hospital. The PPV group received more fluids and transiently had lower serum lactate values. In our study, we did not assess PPV but SVV which has been shown to be correlated with SPV.21
Flow autoregulation in the splanchnic bed maintains the perfusion constant, despite variations in circulating volume.22 In anaesthetized pigs,22 effects of low (3 ml kg–1 h–1), medium (7 ml kg–1 h–1) or high (20 ml kg–1 h–1) fluid volumes were compared. The three volume regimens tested did not have different effects on tissue oxygen pressure in the gut, suggesting efficient autoregulation of intestinal blood flow in healthy subjects undergoing uncomplicated abdominal surgery.
ScvO2 which in abdominal surgical patients shows significant fluctuations in the immediate postoperative period that are not always associated with changes in oxygen delivery, suggesting that oxygen consumption is also an important determinant of ScvO2.23 Reductions in ScvO2 were found to be independently associated with postoperative complications: ScvO2 was 63.4 (10.4)% in patients with complications vs 67.1 (7.7) % in patients without complications.23 Noteworthy, we found a significant decrease in ScvO2 between baseline and 24 h which was not different between the groups whereas values after 24 h were higher than those reported by Pearse and colleagues.23 Finally, patients in the control group transiently required slightly more norepinephrine (3 h), but this seemed not to have negatively influenced global and regional perfusion.
Our study suffers from several limitations. Since all patients studied routinely only underwent peripheral arterial cannulation and no extended haemodynamic monitoring, no cardiac output values are available in this study. Furthermore, the number of patients in this single centre study was intended to study effects on global and regional variables and does not allow us to draw conclusions with respect to ‘hard’ criteria such as length of ICU or hospital stay or even mortality. Finally, we studied relatively healthy patients as is clear from the normal ScvO2, PCO2-gap,24 and lactate levels. Probably, results may be different in more severely ill patients in whom transient hypovolaemia may have more impact on organ dysfunction and length of ICU stay.
In conclusion, SPV-guided treatment was associated with slightly more intraoperative fluid whereas organ perfusion and function was similar when compared with routine care.
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Footnotes |
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This work was presented in part at the Annual Meeting of the European Society of Intensive Care Medicine (ESICM), Berlin, 2004, and the International Congress of Intensive Care and Emergency Medicine (ISICM), Brussels, 2005. 
Declaration of interest. Dr S.G.S. has received honoraria from and is a member of the Medical Advisory Board of Pulsion Medical Systems AG, Munich, Germany.
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