But what was lost has to be replaced. The human body, which is more than half water, needs fluid to maintain balance. It is a balance that keeps the organs well nourished--with oxygen and other elements--and normal pressure within blood vessels.

    In normal circumstances, an adult human will have five to six liters of blood circulating--about seven to eight percent of total body weight. If 10 to 20 percent of this blood volume is lost, the body's system goes into shock.

    How can this lost fluid be replaced then if blood transfusion is too risky?

    In a recent lecture on fluid thereapy,1 pharmacologist Hrishikesh Kulkarni offered alternative. Kulkarni is consultant at Fresenius Kabi, a European leader in infusion and nutrition therapy.

THE REPLACEMENTS

    There are methods to replace intravenously fluids and electrolytes lost from trauma or surgery. Either a crystalloid or colloid solution can be used to add volume to blood plasma.

• Crystalloids--low-molecular-weight ions (salts), dissolved in water, with or without glucose. Lactated Ringer's solution is the most used clinically. It contains potassium, calcium, sodium, chloride, and lactate.

• Colloids--high-molecular-weight proteins or glucose polymers. Examples are albumin, dextran, and hestastarch.

    However, even as the first attempt at fluid resuscitation (when physicians in the 1600s tried to transfuse dogs with wine) must have stunned witnesses, the use---or rather the selection--of these alternative fluids created its own share of controversy.

STAYING POWER

    Though crystalloids are the least expensive and most readily available of the fluids, it stays in circulation relatively briefly. An hour after infusion, about three-fourths have already moved out from capillary blood into the fluid between tissue cells, which can be as much as 250 ml per minute. "This is because the composition of fluid in the vascular space and extracellular fluid is identical," explained Kulkarni.

    Three to four times the volume of blood lost is therefore required to restore blood volume and normal blood flow throughout the body.

    In contrast, colloids are capable of dwelling within the intravascular space (inside blood vessels) for three to six hours. They cannot freely cross the capillary membrane, which allows them to hold and pull water in the blood, keeping blood volume high enough for normal pressure.

    "Extracellular fluid stays more or less the same, but it is the vascular space that expands," Kulkarni pointed out.

    Only a 1:1 ratio for blood lost is required in the use of colloids, which greatly lessens the risk of excess fluid accumulating in tissues. "Extracellular fluid expansion only contributes to edema and impaired oxygenation of the tissue," observed Kulkarni.

    "We need them (crystalloids) as maintenance fluids but, in overdosage, they can produce some bad effects," he commented. "Lactated Ringer's solution, in large amounts can produce hyponatremia and alkalosis."

    Crystalloids are also less effective than colloids at producing a plasma colloid oncotic pressure, a force that makes plasma swell and adds to blood volume. Crystalloids reduce it, in fact, by thinning the proteins still in the blood.

    The efficiency of colloids at maintaining volume, particularly of hydroxyethyl starch (HES), is notable. "The volume goes up, it stays up, and comes down." He pointed out that this plateau is absent in the volume effect of the other plasma expanders, which is usually characterized by a peak (Figure 1).

PEARLS V. CRYSTALS

    In the early 1990s, Kulkarni said, the benefits of colloids above crystalloids seemed established. Of course, this favor did not carry on to present clinical practice. What went wrong?

    Studies were undertaken to see if the patients' chances to survive improved when resuscitated with colloids compared with other fluid resuscitation methods. When a Cochrane group analyzed the results of 24 randomized trials in 1998,2 the reviewers concluded that colloids do not reduce mortality, and may even increase it in some cases. Outside of randomized controlled trials, they do not recommend its continued use.

    On the other hand, a 2001 metaanalysis--of 55 randomized trials by Wilkes and Navickis3--showed that colloids did not significantly affect mortality. Its findings supported the SAFEty of colloids.

    Without this improved survival, why favor colloids when the less expensive crystalloids could be just as effective at managing blood-volume deficiencies when given in sufficient amounts, the proponents of crystalloids argued?

SAFE AS IN SAFE

    With data from SAFE study4 having just come out, concerns about the SAFEty of colloids should be put to rest.

    SAFE is Saline v. Albumin Fluid Evaluation. Undertaken by the Australian and New Zealand Intensive Care Society, it randomized 6,997 intensive-care patients to either four-percent albumin or normal saline (0.9 percent solution) for all resuscitations.

    SAFE showed that, clinically, albumin and saline are equivalent and equally SAFE. Only in those with traumatic brain injury were more deaths reported for the albumin group.

    With his own study done at Saiwani Hospital in Hyderabad, India, Kulkarni addressed the question of increased cost of colloid use.5

    His study involved high-risk-surgery patients. They were given either lactated Ringer's solution alone or both it and HES. In terms of hemodynamics, volume management was more efficient in the group given crystalloid and colloid. Vascular resistance came out also better in the second group.

    Kulkarni related that when his group realized the mortality for the colloid/crystalloid group was only 19 percent compared with the 47 percent of the crystalloid only group, they had to stop the study for ethical reasons.

    Regarding cost, said: "Use of colloids did not contribute to an increased hospital cost or hospital stay, and that led to a lot of cost-saving."

    But "not all colloids are equal," Kulkarni stressed.

    He said that there is more to fluid therapy than hemodynamics and tissue oxygenation. "What about capillary leak?" he proposed. It has to be examined, he advised.

    A colloid that is too rapidly infused could expand plasma volume too well, overloading the vascular system and spilling out. In large amounts, this spillage could cause a water-pulling force strong enough to further interfere with the volume and pressure in intravascular space. Hypotension would again follow or be aggravated. And when there is sepsis and capillary leak together, Kulkarni said albumin would not help.

    Evidence points to albumin as the colloid more likely to contribute to capillary leak, Kulkarni explained. Data from studies by Dietrich (2003) and Nohe et al. (1999) confirmed this.

    When Dietrich compared endothelial function after infusion with colloids, he found that "the expression of adhesion molecules [was] being expressed to a greater extent" when the endothelial cells were treated with albumin. While Nohe's study had similar findings, reported Kulkarni.

    Other studies comparing HES and crystalloids also found the starch to be superior in hemodynamics and preserving capillary function and integrity.6

SMALL, LARGE, AND TOUGH

    Why this hemodynamic balance? The median molecular weight (MW) and molecular structure of colloids are important to how they work inside the body, explained Kulkarni.

    HES is a starch derived from corn. To make it more resistant to degradation and, therefore, extend its duration of action within the vascular system, portions of the glucose units are substituted with hydroxyethyl groups. Then to make it appropriate as a plasma volume expander, the resulting material is hydrolyzed.

    The HES approved in the United States is hetastarch 0.7 (i.e., seven out of 10 glucose units are hydroxyethylated.), while in other countries, pentastarch 0.5 (5 out of 10) is already available.

    Molecular units are made up of molecules that are big and some that are small, Kulkarni described. According to him, this heterogeneity allows quick elimination of excess volume through diuresis-of molecules with MW <50-but allows sufficient intravascular dwelling time for volume goals to be achieved.

    The relatively big molecular units of HES pentastarch, at 200 kilodaltons, are then broken down by the enzyme amylase in the blood.

    Kulkarni also noted how suitable HES is to treat hypotension. "For therapy to control hypotension by using volume, we have to give therapy that sustains the hemodynamic effect for four to six hours."

    What about interference with clothing? He said that all colloids do, but starches are evolving toward better safetty and optimal efficacy.

    Combined data from six studies on the effect of HES on coagulation showed that the interference is decreasing.7

    For the "prevention of and treatment of shock due to surgery, spinal anesthesia, trauma, sepsis, bone, and even gynecological bleeding like placenta previa or dysfunctional uterine bleeding," Kulkarni maintained that HES is effective.

    HES is distributed in the Philippines (at six percent and 10 percent in isotonic sodium chloride solution) as HAES-steril by Zuellig Pharma Corporation. Michelle Ciriacruz

References

1. 11th postgraduate course in obstetrics and gynecology of Our Lady of Lourdes Hospital, Cardinal Santos Medical Center, The Medical City, San Juan Medical Center, and Dr. Victor R. Potenciano Medical Center, 3 June 2004.

2. British Medical Journal, 1998

3. Annals of Internal Medicine, 2001

4. New England Journal of Medicine, 2004

5. Presented June 13, 2003 at the first NATA North American Symposium, San Francisco

6. Hoffman et al, Anesthesiology 2002. Boldt et al, Internal Care Medicine 2003. Lang et al, Canadian Journal of Anesthesia 2003

7. Haisch 2001, Boldt 2000, Entholzner 2000, Treib 1997, G. Huet 2000, Langeron 2001