Third-space fluid

Therapy with leucovorin/5-FU must not be initiated or continued in patients who have symptoms of Gl toxicity of any severity, until those symptoms have completely resolved. Patients with diarrhea must be monitored with particular care until the diarrhea has resolved, as rapid clinical deterioration leading to death can occur. Methotrexate concentrations Monitoring of the serum methotrexate concentration is essential in determining the optimal dose and duration of treatment with leucovorin. Delayed methotrexate excretion may be caused by a third space fluid accumulation, renal insufficiency, or inadequate hydration. Under such circumstances, higher doses of leucovorin or prolonged administration may be indicated. Doses higher than those recommended for oral use must be given IV. 

OHSS is characterized by cystic ovarian enlargement, increased capillary permeability, and third space fluid accumulation (that is in an extracellular compartment that is not in equilibrium with either the extracellular or intracellular fluid, for example the bowel lumen, subcutaneous tissues, retroperitoneal space, or peritoneal cavity). Risk factors include a previous history of OHSS, age under 30 years (probably because more follicles are available), and polycystic ovary syndrome. Non-pregnant patients usually recover within 14 days with supportive treatment. The severe form (with ascites or pleural effusion and hemoconcentration) occurs in 1-10% of patients (64,65). In critical cases, hypoxemia, renal insufficiency, thromboembolism, and rarely death can occur (66). 

Although the basic pathophysiology is similar for the various causes of hypovolemic shock, there are unique considerations relative to each. For example, whereas isolated head injuries associated with trauma typically do not result in substantial blood loss or shock, pelvic fractures may sequester several liters of blood as hematoma formation. Patients with traumatic or thermal injuries, as well as postoperative patients, may have substantial fluid accumulation in sites where it cannot be readily transferred back into blood vessels (i.e., third-spaced fluid) for maintaining pressure. With these types of injuries, prompt control of compressible bleeding sources with rapid patient transfer to the hospital for definitive treatment may preclude the cascade of events leading to shock. Indeed, with trauma patients, a scoop and run approach is used in most urban hospitals that places a priority on rapid transport to a hospital. ... 

If peritonitis continues untreated, the patient may experience hypovolemic shock from third-space fluid loss into the peritoneum, bowel wall, and lumen. This may be accompanied by sepsis because the inflamed peritoneum absorbs bacteria and toxins into mesenteric blood vessels and lymph nodes, initiating production of inflammatory... 

Methotrexate distributes readily into third space fluids (ascites, pleural effusions), prolonging exposure and increasing toxicity. May be contraindication for use. 

The transcellular fluid includes the viscous components of the peritoneum, pleural space, and pericardium, as well as the cerebrospinal fluid, joint space fluid, and the gastrointestinal (GI) digestive juices. Although the transcellular fluid normally accounts for about 1% of TBW, this amount can increase significantly during various illnesses favoring fluid collection in one of these spaces (e.g., pleural effusions or ascites in the peritoneum). The accumulation of fluid in the transcellular space is often referred to as third spacing. To review the calculations of the body fluid compartments in a representative patient, see Patient Encounter 1. 

The fluid and protein shift into the abdomen (called third-spacing) may be so dramatic that circulating blood volume is decreased, which causes decreased cardiac output and hypovolemic shock. Accompanying fever, vomiting, or diarrhea may worsen the fluid imbalance. A reflex sympathetic response, manifested by sweating, tachycardia, and vasoconstriction, may be evident. With an inflamed peritoneum, bacteria and endotoxins are absorbed easily into the bloodstream (translocation), and this may result in septic shock. Other foreign substances present in the peritoneal cavity potentiate peritonitis, notably feces, dead tissues, barium, mucus, bile, and blood. 

When bacteria become dispersed throughout the peritoneum, the inflammatory process involves the majority of the peritoneal lining. Fluid and protein shift into the abdomen (called third spacing ) may decrease circulating blood volume and cause shock. 

Pleural effusions or ascites In patients with significant third space accumulations, evacuate the fluid before treatment and monitor plasma methotrexate levels. Psoriasis lesions Lesions of psoriasis may be aggravated by concomitant exposure to ultraviolet radiation. Radiation dermatitis and sunburn may be recalled by the use of methotrexate. 

A wide range of aldesleukin-induced adverse effects is associated with the capillary leak syndrome, which is characterized by an increase in vascular permeability with subsequent leakage of fluids and proteins into the extravascular space (4). This results in a third-space clinical syndrome, generalized or peripheral edema, weight gain, cardiovascular and pulmonary comphcations with hypotension, pericardial, and pleural effusions, ascites, oliguria, and prerenal azotemia. Symptoms usually resolve in a few days after aldesleukin withdrawal. Studies on the mechanism have raised a number of hypotheses, such as damage to the endothehal cells, release of secondary cytokines, and activation of the complement cascade (15). 

Proper attention to plasma expansion must be continued into the intraoperative and postoperative periods. A number of neurohormonal changes take place that affect urine output, and patients may have substantial third-spacing of fluid depending on the operation and the preexisting condition of the patient. Furthermore, postoperative patients are prone to hyponatremia from renal generation of electrolyte-free water and from antidiuretic hormone release. As in acute resuscitation, the administration of hypotonic solutions in the perioperative period does not prevent the decrease in extracellular volume that often occurs. Therefore, although excess fluid administration is to be avoided in the perioperative setting, isotonic crystalloid solutions should be used when fluids are indicated to prevent intravascular depletion and circulatory insufficiency. 

Third-spacing—The shift of fluid and protein into the peritoneal cavity and bowel wall lumen that occurs as a result of peritonitis. 

At 10 days to 5 weeks, 50-100% of personnel will develop pathogenic and opportunistic infections, bleeding, fever, loss of appetite, GI ulcerations, bloody diarrhea, severe fluid and electrolyte shifts, third space losses, capillary leak, hypotension... 

HYPOTENSION WITH TACHYCARDIA Fluid loss or third spacing... 

Cardiovascular effects. In severe cases, extensive tissue third spacing of fluids combined with fluid loss from gastroenteritis may lead to hypotension, tachycardia, shock, and death. Metabolic acidosis and rhabdomyoly-sis may be present. After a delay of 1-6 days, there may be a second phase of congestive cardiomyopathy, cardiogenic or noncardiogenic pulmonary edema, and isolated or recurrent cardiac arrhythmias. Prolongation of the QT interval may be associated with torsade de pointes ventricular arrhythmia. 

The apparent volume of distribution is 8-111/m. Fluorouracil readily penetrates the extracellular space, including the cerebrospinal fluid and third spaces, such as ascites and pleural effusions. More than 80% of the dose is broken down by dihydropyrimidine dehydrogenase in the liver and less than 10% is excreted unchanged in the urine [72, 73 ]. 

The terms space time and space velocity are antiques of petroleum refining, but have some utility in this example. The space time is defined as F/2, , which is what t would be if the fluid remained at its inlet density. The space time in a tubular reactor with constant cross section is [L/m, ]. The space velocity is the inverse of the space time. The mean residence time, F, is VpjiQp) where p is the average density and pQ is a constant (because the mass flow is constant) that can be evaluated at any point in the reactor. The mean residence time ranges from the space time to two-thirds the space time in a gas-phase tubular reactor when the gas obeys the ideal gas law. 

O Total body water (TBW) is approximately 50% of lean body weight in the normal female and 60% of lean body weight in males. TBW is comprised of the intracellular fluid (two-thirds of TBW) and the extracellular fluid (one-third of TBW). The extracellular fluid is made up of two major fluid subcompartments the interstitial space and the intravascular space. 

The extracellular fluid (ECF) is the fluid outside the cell and is rich in sodium, chloride, and bicarbonate. O The ECF is approximately one-third of TBW (14 L in a 70-kg man or 12 Lin a 70-kg woman) and is subdivided into two compartments the interstitial fluid and the intravascular fluid. The interstitial fluid (also known as lymphatic fluid) represents the fluid occupying the spaces between cells, and is about 25% of TBW (10.5 L in a 70-kg man or 8.8 L in a 70-kg woman). The intravascular fluid (also known as plasma) represents the fluid within the blood vessels and is about 8% of TBW (3.4 L in a 70-kg man or 2.8 L in a 70-kg woman). The ECF is approximately one-third of TBW or 14 L in a 70-kg male. Because the exact percentages are cumbersome to recall, many clinicians accept that the ECF represents roughly 20% of body weight (regardless of gender) with 15% in the interstitial space and 5% in the intravascular space.6 Note that serum electrolytes are routinely measured from the ECF. 

Cerebrospinal fluid is produced in chambers within the brain called ventricles. Two lateral ventricles and a midline third ventricle are contained within the cerebrum, while the fourth ventricle exists within the brain stem. CSF is produced by the choroid plexus in the lateral and third ventricles. It flows out through the ventricles by a series of aqueducts and into subarachnoid space. CSF supports the brain and spinal cord, ab-... 

A third example is as follows. Initially a crystal has a uniform 8 0. Then the crystal is in contact with a fluid with a higher 8 0. Ignore the dissolution of the crystal in the fluid (e.g., the fluid is already saturated with the crystal). Then would diffuse into the crystal. Because fluid is a large reservoir and mass transport in the fluid is rapid, 8 0 at the crystal surface would be maintained constant. Hence, this is again a half-space diffusion problem with uniform initial concentration and constant surface concentration. The evolution of 8 0 with time is shown in Figure l-8b. 

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