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Anesth Analg 2001;93:405-409
© 2001 International Anesthesia Research Society

CRITICAL CARE AND TRAUMA

Colloids Versus Crystalloids and Tissue Oxygen Tension in Patients Undergoing Major Abdominal Surgery

Katrin Lang, MD, Joachim Boldt, MD, Stefan Suttner, MD, and Günther Haisch, MD

Department of Anesthesiology and Intensive Care Medicine, Klinikum der Stadt Ludwigshafen, Ludwigshafen, Germany

Address correspondence and reprint requests to Prof. Dr. med. Joachim Boldt, Department of Anesthesiology and Intensive Care Medicine, Klinikum der Stadt Ludwigshafen, Bremserstr. 79, D-67063 Ludwigshafen, Germany. Address e-mail to BoldtJ @gmx.net.


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
The effects of intravascular volume replacement regimens on tissue oxygen tension (ptiO2) are not definitely known. Forty-two consecutive patients scheduled for elective major abdominal surgery were prospectively randomized to receive either 6% hydroxyethyl starch (HES) (mean molecular weight 130 kd, degree of substitution 0.4, n = 21) or lactated Ringer’s solution (RL, n = 21) for intravascular volume replacement. Fluids were administered perioperatively and continued for 24 h on the intensive care unit to keep central venous pressure between 8 and 12 mm Hg. The ptiO2 was measured continuously in the left deltoid muscle by using microsensoric implantable partial pressure of oxygen catheters after the induction of anesthesia (baseline, T0), 60 min (T1) and 120 min thereafter (T2), at the end of surgery (T3), and on the morning of the first postoperative day on the intensive care unit (T4). HES 130/0.4 2920 ± 360 mL and 11,740 ± 2,630 mL of RL were given to the patients within the study period. Systemic hemodynamics and oxygenation (PaO2, PaCO2) did not differ significantly between the two volume groups throughout the study. From similar baseline values, ptiO2 increased significantly in the HES-treated patients (a maximum of 59% at T4), whereas it decreased in the RL group (a maximum of -23% at T4, P < 0.05). The largest differences of ptiO2 were measured on the morning of the first postoperative day. We conclude that intravascular volume replacement with 6% HES 130/0.4 improved tissue oxygenation during and after major surgical procedures compared with a crystalloid-based volume replacement strategy. Improved microperfusion and less endothelial swelling may be responsible for the increase in ptiO2 in the HES 130/0.4-treated patients.

IMPLICATIONS: In patients undergoing major abdominal surgery, a colloid-based (with hydroxyethyl starch [HES] 130/0.4) and a crystalloid-based (with lactated Ringer’s solution [RL]) volume replacement regimen was compared regarding tissue oxygen tension (ptiO2) measured continuously by microsensoric implantable catheters. The ptiO2 increased in the HES-treated (+59%) but decreased in the RL-treated (-23%) patients. Improved microcirculation may be the mechanism for the better ptiO2 in the HES group.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
An adequate intravascular volume replacement is essential in the management of patients undergoing major surgery. Hypovolemia may initiate complex pathophysiologic processes that may result in an inadequate tissue perfusion and decreased tissue oxygen supply (1). Different intravascular volume replacement regimens have been proposed for providing hemodynamic stability in this situation, including blood and its components (e.g., human albumin), synthetic colloidals (dextrans, gelatins, hydroxyethyl starch [HES]), or crystalloids (e.g., lactated Ringer’s solution [RL]) (2,3). Various modifications of approved HES have different molecular weights (MWs) (450 kd, 200–260 kd, and 70 kd) and degrees of substitution (DSs) (0.7, 0.62, and 0.5). Recently a new HES with an intermediate MW (130 kd) and a very low DS (0.4) has been developed. This HES specification has already been approved in several countries for treating hypovolemia. It is supposed to have convincing advantages in pharmacokinetics and pharmacodynamics and may be the safest synthetic colloid. Waitzinger et al. (4) found no clinically relevant plasma accumulation and related side effects after single-dose infusion in healthy volunteers. In an animal study with rats, Bepperling et al. (5) demonstrated a significantly lower tissue storage with HES 130/0.4 than with conventional HES preparations. Finally, HES 130/0.4 is assumed to have less effect on coagulation compared with HES preparations with higher MWs and higher DSs (6).

The hypovolemic patient is at risk of experiencing tissue hypoperfusion with subsequent development of (multiple) organ failure (7). The effects of different intravascular volume replacement strategies on microcirculation and tissue oxygenation in humans have not been clarified. Monitoring of systemic variables of oxygen metabolism (e.g., oxygen delivery, volume of oxygen consumption) fails to identify which solution is most suitable for avoiding tissue oxygenation deficits. New monitoring devices enable us to measure tissue oxygen tension (ptiO2) and tension in body fluids and organs directly and continuously. The ptiO2 corresponds to oxygen availability on a cellular level and estimates tissue oxygenation and microcirculation (8). The aim of our study was to compare the effects of a crystalloid-based volume replacement strategy with a colloid-based regimen by using HES 130/0.4 on ptiO2 in patients undergoing major abdominal surgery.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
Forty-two consecutive patients scheduled for major abdominal surgery were enrolled in the study. The study protocol was approved by the local ethics committee of the hospital, and written, informed consent was obtained from the patients. Exclusion criteria included a hemoglobin (Hgb) of <10 g/dL, compensated or decompensated myocardial insufficiency, decreased renal function (serum creatinine >2.0 mg/dL), severe pulmonary disease (chronic obstructive lung disease, PaO2 <70 mm Hg), liver dysfunction (aspartate aminotransferase >40 U/L, alanine aminotransferase >40 U/L), abnormal coagulation tests (platelet count <100/nL, activated partial thromboplastin time >70 s, fibrinogen <2 g/dL, antithrombin III <40%), and known allergic reactions to starch preparations.

The patients were randomly assigned to one of two volume groups by use of a closed-envelope system. In the HES group (n = 21), patients received 6% HES 130/0.4 (MW 130 kd, DS 0.4; Fresenius AG, Bad Homburg, Germany). RL was additionally given to compensate insensible water loss (sweating, gastric tubes) or drug mixing (e.g., antibiotics). In the Crystalloid group (Control group, n = 21), volume replacement was performed exclusively with RL. In all patients, 500 mL/h of RL was administered routinely during the time of surgery. Packed red blood cells were administered when Hgb was <8 g/dL. Volume was given to keep central venous pressure (CVP) between 8 and 12 mm Hg throughout the study period. The specific volume replacement regimen was started after the induction of anesthesia and continued during the following 24 h on the intensive care unit (ICU).

General anesthesia was induced with thiopental, fentanyl, and rocuronium for muscular relaxation in doses adapted for the patient’s need. Maintenance of anesthesia was performed with fentanyl, rocuronium, and desflurane. Mechanical ventilation was performed in all patients to keep arterial oxygen saturation >95% and end-expiratory CO2 between 35 and 40 mm Hg. Mean arterial blood pressure (MAP) was kept between 60 and 80 mm Hg by administering volume (when CVP was <8 mm Hg), by reducing the depth of anesthesia (when CVP was >12 mm Hg), or by adding dopamine (when both volume administration and reducing depth of anesthesia were not effective). A rewarming cover blanket system and fluid warmers were used to guarantee normothermia during surgery. After surgery, all patients were transported to the ICU. Mechanical ventilation was continued when necessary until the patient was ready for tracheal extubation (stable hemodynamics, sufficient spontaneous breathing, warmed up to 36°C). Perioperative management was performed by anesthesiologists who were not involved in the study and who were blinded to the grouping.

In all patients, standard monitoring included central venous catheterization and arterial cannulation. Hemodynamic monitoring consisted of measuring MAP, heart rate, and CVP. Esophageal temperature was also measured continuously.

A LICOX CMPTM monitoring device (GMS, Mielkendorf, Germany) and a flexible minimally invasive microsensoric partial pressure of oxygen (pO2) catheter (RevoxodeTM; GMS) were used to measure ptiO2. The catheter tip includes small electrochemical (polarographic) probes for oxygen tension measurement. A precalibrated, sterile, microsensoric pO2 catheter was inserted into the left deltoid muscle after the induction of anesthesia. The catheter was placed percutaneously via a 20-gauge cannula to stabilize the IM position of the polarographic tip. To avoid tissue damage that might influence the oxygen measurement, and to guarantee a stable position of the catheter tip, the cannula was fixed with sterile bandages to the skin. The ptiO2 attained stable baseline values within 20 min after placement of the catheter probe. Measurements were interrupted (by disconnecting the cable from the LICOX CMP monitor) only for transporting the patient to the ICU.

Data were documented after the induction of anesthesia (baseline, T0), 60 min (during surgery, T1) and 120 min thereafter (during surgery, T2), at the end of surgery (T3), and on the morning of the first postoperative day (POD) on the ICU (T4).

Before the start of the study, the number of patients required in each group was determined with a power analysis according to data obtained from an earlier study on the effects of a HES with low MW (6% HES, MW 40 kd) on tissue oxygenation (9). On the basis of these data, we assumed that the minimum difference we wished to detect was a 40% increase in skeletal muscle ptiO2 after the administration of HES 130/0.4. We estimated that the SD of skeletal muscle ptiO2 values would be up to 15 mm Hg. The {alpha} error was set at 0.05 (two-sided), and type II error was at 0.2. On the basis of these assumptions, 21 patients per group were required. A PC-based statistical program was used for statistical analysis (Syststat 7.0 for Windows; SPSS, Chicago, IL). Data are shown as mean ± SD. Normal distribution of the data was assessed with the Kolmogorov-Smirnov test. Continuous, normally distributed data were compared by using paired and unpaired Student’s t-tests or analysis of variance for repeated measures. The Bonferroni correction was applied when multiple comparisons were made. Continuous, nonnormally distributed data were compared with the Wilcoxon test. Binomial data were compared with {chi}2 analysis and Fisher’s exact test when appropriate. P values <0.05 were considered significant.


   Results
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 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
There were no significant differences between the groups with regard to biometric data, type of surgery, duration of surgery or anesthesia, and outcome (Table 1). Use of dopamine also did not differ between the two groups throughout the study.


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  		Table 1. Demographic and Perioperative Data
 
MAP, heart rate, and CVP did not differ between the groups at any time (Table 2). Hgb, PaO2, fraction of inspired oxygen (FIO2), and PaCO2 were also without significant differences between the two volume groups within the study period (Table 2). Esophageal temperature was also comparable in both groups (Table 2).


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  		Table 2. Hemodynamics and Laboratory Data
 
In the RL group, 11,740 ± 2,630 mL of RL was infused until the end of the study period, whereas 3050 ± 440 mL of RL and 2920 ± 360 of HES 130/0.4 was administered in the HES group (Table 3). Blood loss and use of allogeneic blood products (packed red blood cells, fresh frozen plasma) did not differ between the groups. Urine output was significantly larger in the Crystalloid group than in the HES-treated patients (Table 3).


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  		Table 3. Volume Input and Output (Cumulative)
 
To eliminate differences of ptiO2 at baseline (before treatment) and because no normal range of ptiO2 is defined, percentages of change in ptiO2 from baseline values (T0) were calculated (Fig. 1). The ptiO2 increased significantly in the HES-treated patients (a maximum of 59% at T4), whereas it decreased significantly in the RL-treated group (a maximum of -23% at T4). The highest differences between the two groups were seen on the morning of the first POD (T4).



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  		Figure 1. Differences (in percentage from baseline) of tissue oxygen tension (ptiO2) in the two volume groups. Data are presented as mean ± SD. T0 = baseline (before volume administration and before surgery); T1 = 60 min thereafter (during surgery); T3 = 120 min after T1 (during surgery); T3 = at the end of surgery; T4 = on the morning of the first postoperative day on the intensive care unit. +P < 0.05 compared with baseline data; *P < 0.05 compared with the other volume group. HES = hydroxyethyl starch (molecular weight, 130 kd; degrees of substitution, 0.4); RL = lactated Ringer’s solution.

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
There is still controversy concerning the "ideal" intravascular volume replacement regimen. Fluid administration should not only stabilize macrohemodynamics, but also have beneficial effects on microcirculation and tissue oxygenation. Our primary goal was to investigate the effects of a colloid-based versus a crystalloid-based intravascular volume replacement regimen on tissue oxygenation in patients undergoing major abdominal surgery. The major result was a significant increase of ptiO2 during the perioperative period in the HES-treated group and a significant decrease of ptiO2 in the RL-treated patients.

There may be several reasons for the differences in tissue oxygenation in the two groups, including differences in systemic circulation and oxygenation as well as differences in the use of vasoactive substances. However, neither MAP nor PaO2/FIO2 nor PaCO2 nor the use of dopamine showed significant differences between the two groups throughout the study period. Another reason for the decrease of ptiO2 in the Crystalloid group may be that crystalloids are mostly distributed in the interstitium, resulting in (endothelial) tissue swelling (10). A decreased interstitial colloid oncotic pressure may result in tissue and endothelial edema, resulting in decreased capillary perfusion and subsequently in reduced ptiO2. By using in vivo microscopy and surface pO2 electrodes in RL hemodiluted animals, tissue perfusion and tissue pO2 decreased significantly, although systemic hemodynamics were kept stable (11). In an animal (hemorrhage) experiment, Wang et al. (12) assessed the quality of fluid resuscitation by laser Doppler flowmetry. They concluded that RL did not restore microvascular perfusion sufficiently in this situation, most likely because of a progressive formation of tissue edema. Although experimental findings cannot be extrapolated to clinical studies, our study confirmed this assumption. The largest differences in ptiO2 between the groups were found on the morning of the first POD after the administration of approximately 12 L of RL.

The effects of HES on tissue edema formation and capillary dysfunction seem less extensive than with crystalloids (13). Comparing a HES solution with narrow-range MW and crystalloid solutions in neonatal cardiopulmonary bypass, Yeh et al. (14) found a significant reduction of tissue edema and capillary permeability in the HES group compared with the crystalloid treated subjects. In an animal model, Zikria et al. (15) demonstrated that the degrees of tissue edema and capillary leakage depend on the molecular mass distribution and DS of the HES solution used.

In cardiac surgery patients, cutaneous microcirculatory flow measured by laser Doppler flowmetry increased in patients who had been treated with HES 200/0.5 (16). The HES solution administered in our study had a MW of 130 kd and a DS of 0.4. The lower DS is responsible for a fast elimination rate of the substance and lower tissue edema than with conventional higher MW (MW 450 kd) HES with a high DS (0.7) (e.g., hetastarch). Although we did not measure the effects of HES 130/0.4 on endothelial integrity, we assume that increased ptiO2 levels were most likely caused by improved microcirculation. In an animal model of sepsis, a larger capillary luminal area with less endothelial swelling and less parenchymal injury was found with colloids (HES [pentastarch]) than with RL (17). Monitoring of tissue oxygenation in humans is much more difficult than in experimental models. Cardiac index, oxygen delivery, and volume of oxygen consumption are of only limited value when assessing tissue oxygenation. Polarographic microelectrodes for direct monitoring of tissue oxygenation have been described in experimental settings. In a canine model, Standl et al. (18) investigated the effects of complete blood exchange with polymerized bovine Hgb on skeletal muscle oxygen tension and hemodynamic changes. The ptiO2 was measured with polarographic needle probes. In a swine model, Manley et al. (19) used similar electrodes for the monitoring of brain tissue oxygenation during hemorrhagic shock and resuscitation. In clinical studies, polarographic microelectrodes were used in patients with severe head injury and septic syndrome (20). Boeckstegers et al. (21) investigated oxygen availability in skeletal muscle in 67 ICU patients by intermittent and continuous measurements of ptiO2 with pO2 catheters. The ptiO2 increased markedly in septic patients compared with control subjects, who showed only limited infection and no cardiogenic shock. Patients with severe sepsis showed the highest ptiO2. Decreased oxygen consumption on the cellular level secondary to the release of inflammatory cytokines was assumed to be responsible for this result. However, no definite correlation between tissue oxygenation and outcome has been documented.

One objection to the results of this study may be that we measured ptiO2 only in skeletal muscle and not in other organs. This area may not be representative for oxygenation in tissues of more life-threatening organs (e.g., brain, heart, kidneys). We selected this area because the pO2 catheter could be fixed effectively, and thus artifacts during the measurement were avoided.

We conclude that intravascular volume replacement by using HES 130/0.4 in patients undergoing major abdominal surgery showed improved tissue oxygenation compared with a crystalloid-based volume replacement strategy with RL. The improved ptiO2 seems to be most likely caused by improved microcirculation. Whether this is of benefit to decrease postoperative complications such as organ dysfunction, infections, or impaired wound healing has to be elucidated in further studies.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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Accepted for publication April 10, 2001.




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D. M. Moskowitz, S. I. Perelman, K. M. Cousineau, J. J. Klein, A. Shander, E. J. Margolis, S. A. Katz, H. L. Bennett, N. E. Lebowitz, and M. A. Ergin
Multidisciplinary management of a Jehovah's Witness patient for the removal of a renal cell carcinoma extending into the right atrium: [La prise en charge multidisciplinaire d'un patient Temoin de Jehovah pour le retrait d'un hypernephrome s'etendant dans l'oreillette droite]
Can J Anesth, April 1, 2002; 49(4): 402 - 408.
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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press