Resuscitation of the Injured Patient: The Three Phases of Treatment

Symposium on Trauma

Resuscitation of the Injured Patient: The Three Phases of Treatment

Charles E. Lucas, M.D.*

When I push fluids, he becomes overloaded; when I restrict fluids, he becomes oliguric. A SURGICAL RESIDENT

The objective of this article is to provide a simplistic and rational approach to the treatment of hypovolemic shock in the injured patient. This approach or philosophy of therapy is based upon sequential pathophysiologic or dynamic homeostatic changes which are an integral part of the body's defense and recuperative mechanisms. In view of the numerous and widely diverse viewpoints concerning resuscitation, it is apparent that while the material presented herein reflects data collected from many clinical and experimental studies, the ultimate interpretation of the pathophysiologic changes must reflect author bias. Such bias in turn reflects the author's observation of patient response to several different therapeutic regimens for hypovolemic shock administered over the past 9 years on the Emergency Surgical Service at Detroit General Hospital.

THE THREE PHASES OF TREATMENT Although each of the many homeostatic responses to hypovolemic shock evolves from minute to minute in a gradual pattern, the clinical recognition and therapeutic responses to these changes can be separated into three categories or phases of treatment. The therapeutic problems and challenges arising within each phase are distinct as are the complications and potential causes of death. Phase I represents the period of active bleeding; it begins at the time of injury and terminates ':'Professor of Surgery, Wayne State University School of Medicine, and Chief, Emergency Surgical Service, Detroit General Hospital, Detroit, Michigan Supported by the Detroit General Hospital Research Corporation, Detroit, Michigan.

Surgical Clinics of North America- VoL 57, No.1, February 1977

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Table 1.

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Phases of Treatment

PHASE

I:

Active Bleeding Begins with injury, ends at conclusion of operation.

PHASE

II:

Extravascular Fluid Sequestration Begins after operation, ends at point of maximal weight gain.

PHASE

III:

Extravascular Fluid Mobilization Begins at point of maximal weight gain, ends at time of maximal weight loss.

at the conclusion of operation which controls bleeding (Table 1). Phase II represents the period of extravascular fluid sequestration; it begins at the conclusion of operation and ends at the time of maximal weight gain. Phase III represents the period of fluid mobilization; it begins at the point of maximal weight gain and ends at the time of maximal weight loss. After Phase III, the patient begins the anabolic state which continues beyond discharge until the patient returns to his previous weight unless other complications supervene.

PHASE I: RESPONSE AND TREATMENT The physiologic responses to blood loss in the injured patient occur rapidly and vary with the degree of blood loss. The immediate responses are: (1) contraction of the vascular compartment to maintain circulatory pressure with perfusion of core organs and (2) refilling of the vascular volume by way of extravascular fluid, primarily interstitial fluid. Both catecholamine discharge and endocrine release of antidiuretic hormone, aldosterone, and cortical steroids cause increased peripheral vascular resistance with a marked fall in flow to the muscles, extremities, gut, liver, spleen, and kidneys in order to preserve flow to' the heart, lungs, and brain. Early vascular refilling occurs primarily from the interstitial fluid space; later vascular refilling in patients with slower but more prolonged hemorrhage reflects intracellular fluid movement through the interstitial fluid space. The physiologic response accommodates the underlying insult. The normal blood volume in a 70 kg adult is about 5 L divided into 2 L of red blood cell mass and 3 L of plasma (Table 2). An acute reduction of 10 to 20 per cent or 500 to 1000 ml is well tolerated as the release of catecholamines produces protective contraction of the blood volume. Such vasoconstriction allows the peripheral resistance to double from a normal of 16 resistance units (RU) to a maximum of 32 RU while maintaining mean arterial pressure (MAP). The cardiac output, however, falls 50 per cent from a pre bleed level of 5 L per min to a new level of 2.5 L per min. This level of mild to moderate hypovolemia is well tolerated in that both MAP and cellular perfusion are maintained; the sequelae of cellular ischemia are not seen. A severe acute blood loss of over 30 per cent or more than 1500 ml surpasses the body's

,

.j

J

I I

I I

I

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RESUSCITATION OF THE INJURED PATIENT

Table 2.

Normal Body Water Distribution':'

~

IF-llL

E C F - 14 L __________

I

~Arterial-1L

PV-3L___________

BV-5L~

TBW-42L 70 kg male

'icF-28L~

/ RBCV-2L

~

Venous-3.5L Capillary-0.5L

~Muscle, organ, etc.-26L

"'TBW = ECF = IF = PV =

Total body weight Extracellular fluid Interstitial fluid Plasma volume

ICF = Intracellular fluid RBCV = Red blood cell volume BV = Blood volume

compensatory ability to contract the vascular compartment and to maintain MAP. As a result, hypotension and poor cellular perfusion ensue (Table 3). Hypotension, therefore, reflects severe hypovolemic shock. Shortly following the onset of severe hypovolemic shock, the normal ECF of 14 L falls and remains decreased throughout Phase I. This reflects refilling of the vascular compartment by way of the interstitial fluid space, and has been confirmed both experimentally and clinically using radioactive sulfate and inulin to measure extracellular fluid space (ECF). Concomitant with this decrease in ECF there is also a fall in skeletal muscle membrane potential which has important therapeutic considerations in the postoperative period. The factor responsible for this fall in skeletal muscle membrane potential correlates directly with the severity and duration of shock and may be under hormonal control in that this response can be crosscirculated from a shocked dog to a nonshocked dog. The prime therapeutic objectives during Phase I are to stop external bleeding, identify internal bleeding, restore blood volume as monitored by blood pressure, pulse, pulse pressure, and urine output, and prepare for operative intervention to correct organ injuries. These multiple objectives run concurrent and require a highly coordinated effort Table 3.

Acute Response to Severe Blood Loss (Phase IY

1. Selection vasoconstriction - catecholamine release

A. Hypoperfusion to skin, muscles, gut, limbs, and kidneys B. Maintained perfusion to heart, lungs, and brain 2. Water conservation-antidiuretic hormone release 3. Sodium conservation - adrenal cortical release 4. Vascular refilling A. Rapid IF to PV movement B. Slow ICF to IF to PV movement "In the absence of cellular ischemia.

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for implementation based upon a systematized but flexible order of priorities. Correction of the blood volume deficit is best achieved by the rapid infusion of 2 L of balanced electrolyte solution (BES) such as lactated Ringer's solution (Table 4). This regimen will restore blood volume in patients with a mild hemorrhage of 10 per cent blood volume, assuming that no further bleeding is present. Restoration of volume deficit may also be achieved by this regimen in patients with a moderate hemorrhage of 20 per cent of blood volume if all bleeding has ceased. Severe hypovolemia or moderate hypovolemia with continued bleeding, however, will not respond completely to the infusion of 2 L of balanced electrolyte solution; fresh whole blood when typed and cross-matched must be added to achieve and maintain normal volume and vital signs. With severe or continued hemorrhage, whole blood is needed to maintain vital signs and restore the hemoglobin level to 12 gm per cent to provide both adequate oxygen carrying capacity and an adequate reserve against additional blood loss. Further BES is then infused to maintain vital signs and urine ouput. Most patients with severe shock or moderate shock with continued bleeding will respond to this regimen; there is usually no need to give blood which has not been typed and crossmatched. Patients with severe blood loss of 30 per cent of blood volume and continued bleeding, or moribund patients presenting with extreme hypovolemia will not survive during the 45 minutes required for typing and crossmatching of blood. Such patients require whole blood replacement sooner, and for this reason, type-specific blood is given as soon as it is available, usually within 10 to 15 minutes. The most severely injured and hypovolemic patient presenting in an agonal state requires the combined administration of BES plus low titer, type 0 blood upon arrival. The morbidity of low titer type 0 blood infusion is minimal, whereas death may result from a 10 to 15 minute delay in transfusion. The above objectives are best accomplished by the rapid placement of at least two intravenous lines with large bore catheters. One of these should also function as a central venous pressure (CVP) monitor and can be easily inserted by way of a basilic vein cutdown or percutaneous subclavian puncture. Intracaths and angiocaths prevent subcutaneous

Table 4.

Therapeutic Regimen for Phase I

1. Control external bleeding

2. Identify internal bleeding 3. Restore blood volume~two or three intravenous routes A. Balanced electrolyte solution~2 liters per 15 to 30 minutes B. Whole blood~ideally typed and crossmatched (40 min) ~ type specific if still hypovolemic (15 min) ~ low titer type 0 if agonal 4. Objective ~ maintain Hg at 12 gm per cent, restore normal blood pressure, pulse, pulse pressure and urine volume 5. Supplement every fourth transfusion~ 1 unit plasma, 1 ampule sodium bicarbonate (44.3 mEq), 1 ampule calcium chloride (10 gm)

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extravasation when rapid intravenous infusion is vital. The addition of a Swan-Ganz catheter to measure pulmonary artery pressure (PAP) or pulmonary artery wedge pressure (P AWP) and the use of a radial artery catheter to measure MAP may provide assistance in the postoperative period, but are not needed in Phase I when correction of hypovolemia and hypotension carries the greatest priority. Such correction is best achieved by monitoring cuff pressure, pulse, and urine output, regardless of the PAP, P AWP, or MAP. Whole blood and BES should be supplemented with one unit of fresh frozen plasma, one ampule of sodium bicarbonate (44.3 mEq) and one ampule of calcium chloride (10 gm) for every 4 units of blood. This provides replacement for coagulation factors "washed out" by the acute blood loss and helps restore inotropic action of the heart by the calcium supplementation. Indwelling Foley catheter drainage of the urinary bladder facilitates close monitoring of urine output which is a vital yardstick of volume restoration. If possible, the bladder catheter should be inserted after a urine specimen has been obtained so as to prevent confusion caused by "traumatic" microhematuria due to the catheter placement. Oliguria in Phase I is invariably a reflection of hypovolemia and indicates the continued need for volume expansion. Diuretics at this point are hazardous. Induced diuresis interferes with this most valuable monitor of adequate hydration and, if effective, makes the hypovolemic state worse. Both osmotic and loop diuretics, therefore, should be avoided at this time and attention should be directed to volume expansion. After blood pressure and pulse have been restored prior to or during operation, 2 additional liters of BES should be added to complete restoration of blood volume. Only if this regimen fails to induce urine flow should a diuretic be added. This circumstance is rare.

Colloid Use The greatest controversy concerning treatment in Phase I deals with the use of colloid such as albumin, dextran, or starch versus crystalloid. Shires and co-workers demonstrated the superiority of crystalloid solution several years ago, and no studies since have shown their conclusions to be in error. Using a modified Wiggers shock preparation, they demonstrated a 70 per cent survival rate in animals replaced with shed blood plus BES, a 30 per cent survival with replacement of shed blood plus plasma, and only a 20 per cent survival following replacement of shed blood alone. Early administration of human serum albumin either as a 5 per cent solution or as an intravenous bolus has been proposed as a means of decreasing the amount of BES required to maintain vital signs and urine output during Phase I. This recommendation is based upon its oncotic effect and, therefore, its purported ability to mobilize fluid from the interstitial space into the vascular space. Such a reversal in fluid movement would theoretically decrease the subsequent problems ·of post-traumatic pulmonary insufficiency. Our own data belie these theoretical merits of albumin; patients receiving the larger amounts of albumin during Phase I gained the most weight, voided the least urine, and had the most florid respiratory insufficiency postoperatively. These observations were made retrospectively in patients receiv-

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ing during Phase I a minimum of eight transfusions in addition to BES to maintain vital signs. Currently, a prospective randomized evaluation of albumin effectiveness is underway in similar patients. Thus far, it appears that albumin will not prevent third space expansion, leaves the vascular space rapidly, and may lead to renal failure. Until more controlled data are available, one should rely on fresh frozen plasma and whole blood to provide adequate colloid replacement during Phase I, whereas BES should be relied upon to replenish both the depleted blood volume and interstitial fluid space volume. Dextran, like albumin, provides a temporary increase in plasma volume and in theory should protect vital viscera against "sludging" and ischemia from hypoperfusion. Its value is questionable, however, in that it carries the undesirable risk of anaphylactoid reaction which may be lethal and interferes with subsequent crossmatching of blood during the course of therapy. Both of these complications have occurred in our patients and the use of dextran has, therefore, been abandoned in the emergency room since its theoretical value appears to be outweighed by its detrimental effects. We have had no experience with polyethylene starch in the early resuscitation of hypovolemic injured patients, but its role as a valuable adjunct to resuscitation has never been clearly established. Our current policy for resuscitation is to begin with BES, in the form of lactated Ringer's solution. Most hypotensive injured patients respond within 15 to 30 minutes to 2000 ml of BES; lack of response is an indication for type-specific whole blood replacement which can be available within 10 minutes. It is very unusual for a patient to require whole blood during the initial 10 minutes of therapy; when this does occur in agonal patients, low titer type 0 blood is administered since the threat of death outweighs potential morbidity from mismatch. In addition to BES and whole blood replacement, massive transfusions are supplemented with 1 unit of fresh frozen plasma, 1 ampule of calcium chloride, and 1 ampule of sodium bicarbonate for every four transfusions.

PHASE II: RESPONSE AND TREATMENT Phase II begins when control of bleeding has been achieved as marked by the end of operation and ends at the time of maximum weight gain; it is the period of extravascular fluid sequestration (Table Table 5.

Phase II-Fluid Sequestration

~ a

ICF

~"OVerlOad" to lungs

H 20

ECF \

Sodium pump poisoning

N~

-

L

Tubular insufficiency Confusion

PV------->HYPovolemia------->Shock)

~o--

Loop diuretics

Na~H20 L

oss

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5). The average time for Phase II is 40 hours. Shires and co-workers demonstrated that this extravascular flux is associated with membrane depolarization of skeletal muscles resulting in a reduction in the ECF space. This reduction results from the movement of ECF into the intracellular fluid space (lCF) along with sodium and chloride. The intracellular sodium level increases from 9 mEq per L to 18 to 20 mEq per L; the intracellular chloride concentration increases from 3.5 mEq per L to approximately 10 mEq per L. This movement is apparently the result of cellular hypoperfusion or ischemia resulting in disruption of the sodium pump. Membrane depolarization may persist for a number of days and is reflected in man by an increase in total body weight by as much as 20 kg in patients surviving severe shock, requiring as much as 40 units of blood during resuscitation. Recovery of cell membrane function in turn is associated with reverse flux from the ICF space to the ECF space during Phase III. Other authors have suggested that salt and water become sequestered onto the acellular component, collagen, or within "extracellular" mitochondria, both of which equilibrate slowly with radioactive sulfate or inulin which are used to measure ECF. Regardless of site of fluid sequestration and later mobilization, the clinical implications are the same. This extravascular expansion resembles that seen in the burn patient with the prime difference being the mechanism of injury which is heat in the burned patient. The volume of extravascular expansion, therefore, is a function of the degree of cellular ischemia and therefore correlates best with the duration and severity of shock causing impaired cellular oxygenation. Clinically, early Phase II is recognized by decreased MAP, tachycardia, decreased pulse pressure, oliguria, and cold clammy skin whenever the intravenous fluids are given at standard maintenance rate; rapid infusion in contrast results in weight gain, elevated CVP, increased PAP, and respiratory insufficiency. This paradox during Phase II, therefore, has attracted the greatest attention and controversy in the therapy of severely injured hypovolemic patients. The administration of crystalloid solution on the basis of dynamically changing vital signs invariably results in significant weight gain.This weight gain reflects extravascular fluid sequestration which is obligatory; fluid restriction, induced diuresis, and colloid administration at this time cannot prevent this expansion without producing concomitant hypovolemia. The most effective way of maintaining organ perfusion during Phase II is to maintain the hemoglobin level at 12 gm per cent and infuse sufficient BES to maintain vital signs. During the late 1960's, the associated rise in CVP led to a compromise on volume replacement accepting a low normal blood pressure and low normal urine flow rate as adequate end points of resuscitation. This was done to protect the lungs. Inulin space measurements during this period showed a contracted ECF, whereas urine volume, sodium clearance, osmolar clearance, and glomerular filtration rates were well below normal. Since that time, a more aggressive fluid regimen has demonstrated that this reduction in ECF space can be corrected iLl most patients by appropriate replacement with BES as judged by blood pressure, pulse pressure, pulse, and urine output. Furthermore, once this is achieved, sodium clearance, osmolar clearance, and

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glomerular filtration rate return to normal. It is now clear that the kidneys reflect the degree of hydration best; when the sodium clearance, osmolar clearance, and creatinine clearance are decreased, adequate hydration has almost certainly not been achieved regardless of CVP, PAP, or PAWP. Intravenous albumin, during Phase I or Phase II, may also affect renal function. Carey and co-workers noted that military casualties receiving albumin required nearly twice as much blood, put out only half as much urine and did not have significantly higher total protein or serum albumin levels compared to patients who did not receive albumin. Siegel and co-workers observed "tubular dysfunction" in baboons resuscitated from shock with albumin-in-saline solutions compared to saline diuresis. Together, the above factors may prolong the renal insult seen with hypovolemic shock and thereby delay fluid mobilization, which in turn makes the post-traumatic respiratory insufficiency syndrome worse. The clinical difficulty consequent to providing adequate blood and BES to maintain cardiovascular and renal function is that the respiratory status frequently worsens from "fluid overload" as reflected by a rising CVP and PAWP. Unfortunately, "fluid overload" has bad therapeutic implications since fluid restriction at this time is followed by oliguria and leads to acute renal failure which usually results in death despite hemodialysis. The advocates of fluid restriction during Phase II ascribe death in such patients to multiple end-organ failure not related to the acute renal failure since adequate levels of creatinine and blood urea nitrogen were maintained by frequent dialysis; it is more likely that multiple end-organ failure reflects the deficiency in circulatory volume which leads to the acute oliguric renal failure. Therapeutic efforts during Phase II, therefore, must be directed at simultaneously (1) maintaining effective myocardial performance, (2) supporting the lungs, and (3) perfusing the kidneys.

Myocardial Performance Various shock models have shown decreased myocardial contractility subsequent to severe hypovolemic shock. The substance responsible for this has been labeled myocardial depressant factor (MDF), although much controversy exists about its chemical makeup. MDF can be crosscirculated from a shock animal to a nons hock animal; MDF or some similar factor appears to be operative in hypovolemic man. Myocardial performance in patients with a rising CVP or P AWP during late Phase II, therefore, is best supported by digitalization and calcium chloride administration. OccaSionally, massive steroids may be helpful and rarely an infusion of a low dose of levarteronol and phentolamine or dopamine is required in patients with severe respiratory failure who have a low cardiac ouptut. Isoproterenol is rarely indicated in such patients because most have concomitant tachycardia which is likely to convert to ventricular arrhythmia if isoproterenol is added. Respiratory Insufficiency The post-traumatic respiratory insufficiency syndrome reaches its

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peak near the end of Phase II. Many etiologic agents have been incriminated including fat emboli, platelet emboli, perfusion of the lungs with vasoactive products of peripheral ischemic metabolism, diffuse particulate emboli related to massive transfusions, aspiration of gastric contents, and pulmonary ischemia during the period of hypovolemia and hypotension. The controversy about which of the above factors are more important will persist for many years; the temporal sequence of this syndrome which becomes worse near the end of Phase II suggests that the combination of pulmonary ischemia, acute hypervolemia from mobilization of previously sequestered fluid, and inadequate diuresis due to renal insufficiency are responsible. The role of fat emboli, platelet emboli, and particulate emboli seems less critical, otherwise the posttraumatic respiratory insufficiency syndrome would be most severe shortly after insult rather than 48 to 72 hours later, as is normally seen. Regardless of etiology, the pathophysiologic changes appear to be similar and consist of early breakdown of pulmonary capillary membrane permeability resulting in interstitial edema. More extensive changes in permeability permit a further movement of fluid from the interstitial space into the alveolar space; this fluid contains protein which coalesces and forms a hyaline membrane. This process is associated with diffuse microatelectasis. It is recognized clinically by varying degrees of hypoxia and can be quantitated by measurements of physiologic shunting in the lungs or alveolar-arterial oxygen difference. Since the underlying pathophysiologic derangement is diffuse microatelectasis, the lungs should be supported with continuous positive pressure breathing (CPPB) on a volume cycled ventilator using relatively high tidal volumes (10 to 12 ml per kg body wt), positive end expiratory pressure (PEEP) at 5 to 8 cm H 2 0, and increased Fi O 2 to achieve an arterial P0 2 of at least 60 mm Hg. Although higher levels of CPPB and PEEP are probably beneficial for the treatment of diffuse microatelectasis, these cause increased intrathoracic pressure and may impair cardiac output, thereby decreasing oxygen delivery. For this reason, when larger levels of CBBP and PEEP are used, cardiac output determinations must be made to be sure that overall oxygen delivery and consumption are not decreased. A frequent sequel to high tidal volume and PEEP is increased inspiratory pressure required to expand lungs which have a significant decrease in pulmonary compliance. High inspiratory pressures under such circumstances have been associated with a much greater incidence of sudden tension pneumothorax, which is frequently fatal. It is currently recommended that all patients with persistent inspiratory pressures greater than 40 cm H 2 0 be treated with prophylactic bilateral chest tubes to prevent this potentially fatal complication. A beneficial result of bilateral closed thoracostomy tube drainage in such patients is the serendipitous removal of 300 to 500 ml of unsuspected serous fluid from both chest cavities. These tubes are then left in place until the inspiratory pressure has decreased to less than 35 cm H 2 0 as the post-traumatic pulmonary insufficiency syndrome improves and pulmonary compliance returns to normal. The addition of albumin as an intravenous bolus to mobilize extravascular pulmonary water in this phase has not been helpful. La-

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belled albumin leaks out of the vascular space fairly rapidly during Phase II and can even be measured in the tracheal secretions. It has been postulated that this extravascular albumin leak may cause a reverse oncotic effect making the respiratory insufficiency syndrome worse. Further clinical studies along these lines are needed. Renal Support Since the appearance of respiratory insufficiency during Phase II prompts the reduction in the rate of intravenous infusion, oliguria is a frequent coexisting problem. Diuretics under such circumstances have been widely recommended but should not be used in a hypovolemic or hypotensive patient regardless of weight gain. The powerful loop diuretics such as furosemide or ethacrynic acid will produce polyuria despite relative hypovolemia and thereby promote further hypovolemia. Since this sequence of events has all too frequently led to renal shutdown followed by death despite dialysis, it is recommended that diuretics be restricted to patients who have a high-normal or elevated blood pressure. The kidneys in most of these patients are functioning well during Phase II and will regulate water, sodium, and osmoles provided blood pressure is maintained with adequate volume replacement.

PHASE III: RESPONSE AND TREATMENT

Phase III is the period of fluid mobilization. It is associated with cellular recovery in animals as reflected by a normalization of membrane potential and a re-establishment of a normal sodium pump. This produces a rapid, sometimes massive cellular efflux causing an acute expansion of the interstitial space and plasma volume. This massive intravascular and interstitial fluid space expansion is well tolerated by most patients who respond with marked diuresis and natriuresis for the ensuing 24 to 48 hours when the bulk of previously sequestered fluid has been mobilized. The plasma volume and interstitial fluid space volume then return to normal. Clinically, this period of hypervolemia is reflected by an increase in pulse pressure and blood pressure which plateaus at a new high-normal level. Cardiac output is also increased. Respiratory and renal function in patients having this response remain stable or improve throughout Phase III. Some patients, unfortunately, do not tolerate this rapid intravascular flux and develop acute hypervolemia with hypertension, worse respiratory failure, central nervous sytem edema with confusion, and sometimes nonoliguric renal failure. This cardiovascular intolerance was thought to be due to inadequate diuresis of the rapid vascular influx. This hypothesis has some support in that impaired or decreased glomerular filtration rate and renal plasma flow have been documented in patients having the worst problems with hypertension and respiratory insufficiency. This is distinctly abnormal since the kidneys should normally respond to hypervolemia and increased cardiac output with an increase in glomerular filtration rate and renal plasma flow. The amount of sodium, osmolar and water clearance at the height of this hypervolemic and hypertensive state, however, are

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elevated compared to patients without hypertension, suggesting that the kidneys are responding appropriately. Possibly, the natriuretic and diuretic response in these hypervolemic patients should be even greater; such a speculative hypothesis falls within the unknown category of "biologic relativity." Interstitial Fluid Space Compliance One of the functions of the interstitial fluid space is to buffer against sudden changes in plasma volume with which the interstitial fluid space is in dynamic equilibrium. In this capacity the interstitial fluid space contracts in response to fluid deprivation as might occur in the human stranded in the desert and expands in response to fluid abundance such as likely occurs when the camel "refuels." This expansion occurs with little change in interstitial fluid space pressure because of a high interstitial space volume. Under normal circumstances, the interstitial fluid space volume is elevated in early Phase III while the kidneys accommodate the acute hypervolemia of rapid mobilization. Such patients do not develop excessive hypervolemia, hypertension, or severe respiratory failure. Recent data show that the interstitial fluid space dynamics are distinctly different in patients with the "fluid overload syndrome" and respiratory failure. As might be expected, patients who actually develop hypertension with respiratory failure have higher plasma volumes than comparable patients who do not develop hypertension. In contrast, the total ECF volume is significantly smaller in patients with the "fluid overload" syndrome. Specifically, the interstitial fluid space volume in patients with the greatest hypervolemia and respiratory insufficiency is significantly decreased compared to similar patients without the post-traumatic respiratory insufficiency syndrome. Furthermore, since the patients with hypertension and respiratory failure also have the greatest weight gain, it appears that they must also have a residual increase in ICF at this time. In essence, then, the controversial syndrome of acute hypervolemia and respiratory failure seen at the onset of Phase III appears to be due more to fluid maldistribution rather than fluid overload. A reduction in interstitial fluid space compliance drives fluid into the plasma volume and impedes the reflux of previously sequestered intracellular fluid. The result is severe progressive hypervolemia with all its morbid sequelae and a decreased buffering effect by the interstitial fluid space on the plasma volume. This latter effect decreases the margin of safety between hypervolemia with hypertension and hypotension; this explains the many episodes of hypovolemic shock precipitated in such patients by the administration of normal dosages of furosemide during the hypervolemic hypertensive phase. It further explains why some patients, namely those with normal interstitial fluid space dynamics, have an excellent clinical response to loop diuretics. The Renal Factor Floyer and Lucas, in a series of experiments on rats, have produced hypertension by fluid administration combined with unilateral nephrectomy and contralateral renal artery narrowing. These hypervolemic,

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hypertensive rats have increased urine output, sodium clearance and osmolar clearance, but decreased interstitial fluid space volume and compliance. Furthermore, the factor causing reduced interstitial fluid space compliance is transferable to crossperfused rats with normal kidneys. These authors have postulated that a hormone normally released by the renal medulla controls interstitial fluid space compliance and becomes ineffective from the renal insult received by these animals. It is interesting, therefore, that those patients who have acute hypervolemia with hypertension also have decreased interstitial fluid space volume and presumably decreased compliance coincidental to significant derangements in renal function as reflected by increased renal vascular resistance and decreased renal plasma flow and glomerular. filtration rate. None of these observed effects was related to catecholamines, renin release, or adrenocortical release, all of which are normal during this period. Possibly, the previous episode of hypotension produced renal medullary ischemia leading to a decreased release of such a hormone which controls interstitial fluid space compliance. This would explain the combination of inordinate hypervolemia with hypertension, contracted interstitial fluid volume, expanded total body water, and diminished renal plasma flow seen in selected patients during Phase III. Such a hypothesis is speculative. Treatment

The therapeutic response to this rapid vascular influx centers on keeping the patient as normovolemic and normotensive as possible. Unfortunately, there is no exact endpoint of maximal obligatory third-space expansion followed by intravascular flux. It appears, however, that patients reach a new steady state near the end of Phase II when only small volumes of fluid are required to maintain vital signs and urine output. Once reverse fluid flux occurs, an increase in pulse pressure and a new plateau in systolic blood pressure becomes evident. This can be recognized by the new plateau which typically levels near 140/90 mm Hg after having been "stable" at a much lower range for 24 to 36 hours. This is a warning that the period of massive intravascular flux is beginning and the clinical response must be appropriate. Loop diuretics should be given at this time to keep the blood pressure from exceeding 160/100 mm Hg as the fluid flux continues. Unfortunately, this "new plateau" is frequently overlooked for a period of time with the result that the full-blown picture of hypervolemia with hypertension becomes manifest. Once the full-blown picture of hypervolemia with respiratory failure, hematuria with or without nonoliguric renal failure, and cerebral edema with confusion becomes established, induced diuresis is urgently needed. Occasionally, one must give 40 mg of furosemide every 30 minutes to bring the blood pressure below 150/100 mm Hg and keep it there throughout this period of rapid autoinfusion. An interesting complication of this furosemide regimen is hypovolemia and hypotension. This reflects the fact that the patients with acute hypervolemia tend to have a narrow margin of safety between "overload" and hypovolemia. The danger of acute hypovolemia and hypotension with this furosemide regimen, therefore, necessitates close bedside monitoring.

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This narrow margin of safety reflects the contracted interstitial fluid volume, which normally serves as a buffer against both hypervolemia and hypovolemia. Besides exogenous diuretics during this period, all crystalloid and colloid infusion must cease and, if the hypertension and hypervolemia persists, systemic vasodilators such as chlorpromazine should be added to temporarily increase vascular capacitance until the kidneys are able to effectively reduce the overload. The post-traumatic respiratory insufficiency syndrome will dramatically improve as the fluid is mobilized but CPPB and PEEP should be maintained until the Fp2 can be reduced below 40 per cent and still maintain an arterial P0 2 of 60 to 70 mm Hg. Once the kidneys have excreted this excess load, the interstitial fluid space and the ICF will normalize and the hypertension will disappear. Renal function, after the acute hypervolemia has passed, is usually normal. Once the patient has completely mobilized the excess fluid, he will rapidly enter into the convalescent period. The critical problems of total resuscitation will then have been successfully overcome.

REFERENCES 1. Antonenko, D. R: Ultrastructural changes in skeletal muscle during early hemorrhagic shock: A morphologic and steriologic analysis. University of Alberta, Ph.D. Thesis, May 1976. 2. Barger, A. C., and Herd, J. A.: The renal circulation. N. Eng. J. Med., 284:482-490, 1971. 3. Bradley, V. E., Shier, M. R, Lucas, C. E., et al.: Renal response to furosemide in critically ill patients. Surg. Forum, 25 :23-24, 1974. 4. Carey, L. C., Lowery, B. D., and Cloutier, C. P.: Hemorrhagic shock. Curro Probl. Surg., 31-32, 1971. 5. Davidman, M., Alexander, E., Lalone, R, et al.: Nephron function during volume expan· sion in the rat. Am. J. Physiol., 223:188,1972. 6. Floyer, M. A.: Renal control of interstitial space compliance: A physiological mechanism which may playa part in the etiology of hypertension. Clin. Neph., 4: 152-156, 1975. 7. Hayes, D. F., Werner, M. H., Rosenberg, I. K., et al.: Effects of traumatic hypovolemic shock on renal function. J. Surg. Res., 16:490-497,1974. 8. Ledgerwood, A. M., and Lucas, C. E.: Postresuscitation hypertension: Etiology, morbidity and treatment. Arch. Surg., 108:531-538, 1974. 9. London, R E., and Burton, J. R: Post-traumatic renal failure in military personnel in Southeast Asia. Am. J. Med., 53:137-147,1972. 10. Lucas, C. E.: The renal response to acute injury in sepsis. SURG. CLIN. N. AM., 56:953975,1976. 11. Lucas, J., and Floyer, M. A.: Renal control of the compliance of the interstitial space: A factor in the etiology of renoprival hypertension. Clin. ScL, 44:379,1974. 12. Lucas, J., and Floyer, M. A.: Changes in body fluid distribution and interstitial tissue compliance during the development or reversal of experimental or renal hypertension in the rat. Clin. ScL, 47:1,1974. 13. Shier, M. R, Bradley, V. E., Ledgerwood, A. M., et al.: Renal function and the postresuscitative hypertension syndrome. Surg. Forum, 23:56,1975. 14. Shires, T., Cunningham, J. N., Barke, C. R F., et al.: Alterations in cellular membrane function during hemorrhagic shock. Ann. Surg., 176:288,1972. 15. Siegel, D. C., Cochin, A., Geocaris, T., et al.: Effects of saline and colloid resuscitation on renal function. Ann. Surg., 177:51,1973. 16. Starling, E. H.: On the absorption of fluids from the connective tissue spaces. J. Physiol., 19:312-326, 1895-189& Department of Surgery Wayne State University School of Medicine 540 E. Canfield Street Detroit, Michigan 48201