General Approach to Therapy

Securing an adequate airway and ventilation is imperative in hypovolemic shock patients consistent with the airway, breathing, and circulation (ABCs) of life support. Any compromise in ventilation will only accentuate the tissue hypoxia occurring secondary to inadequate perfusion. Thus, tracheal intubation and mechanical ventilation may be needed (Fig. 13-4). IV access is also essential for administration of IV fluids and medications. IV access can be accomplished through the placement of peripheral IV lines or catheterization with central venous lines if rapid or large volumes of re-suscitative fluids are indicated. While primarily facilitating fluid administration, the IV lines provide access for blood samples for obtaining appropriate laboratory tests. Placement of an arterial catheter is advantageous to allow for accurate and continual monitoring of BP, as well as arterial blood gas (ABG) sampling. A bladder catheter should be inserted for ongoing monitoring of urine output. Baseline laboratory tests that should be done immediately include: complete blood cell counts with differentials, serum chemistry profile, liver enzymes, prothrombin and partial thromboplastin times, and serum lactate. A urinalysis and an ABG should also be obtained and ongoing ECG monitoring should be performed. In addition to restoring circulating blood volume, it is necessary to prevent further losses from the vascular space. This is especially true with hemorrhagic hypovolemic shock where identifying the bleeding site and achievement of hemostasis are critical in the successful resuscitation of the patient. This frequently involves surgical treatment of hemorrhages.

ADULT : Admrnsier 1000-2000 mLdO 9 normal taime or lactaied R mger't PEDIATRIC Admn«W 20 mLAg 0« 09 normal ulne or lactated Ringer"» (An anernaive r adult or peaa»ic patten» « S rrOVg Ot hetatUrch )




Oeck Hg i <7 (<70gL or 4 34 mrrolL) Trantlute 2 unci (10-20 mlAg) Type O nogatwe PR8Ct Provide emerge« hemorrhage control

Go »^»J


Oetain tuskyy Ootan IV kc«u lor «wOdoMxy Ottam food 5or laboratory Bladder catheWiMtxn ECG monrtonng

Upa^it herr»dyndm»ca»y ixwiaWe» (S8P <90 mm Hg; PAOP <14-18 mm Kg; CVP <l0-15cmMj0 .»ava.iat*})

ADULT A0r*n«tler 1000-2000 rr*.o109 normal

Mine or bcttMd R^Q^l. PEDIATRIC: Admr^wr 20 mlAg ol 09 normal seine or LKtattd Ringer's (An aflema&ve n adjit or pediatric patent» * 5 mlAg o< 6N hetattareti)

Evidence Ol corot-'a'of myocA'dai ochema?

Bepn doparrmo 10 mogrVgyn« or norepinephrine 2 mcg'nvn intert PA catheier or CVP c«9»oflor lor monitoring i not yot

Monitor normaliaton 0»

organ function. »9*1 stress ulcer prophjlax anMhromboK map* t no evidence olongong Weeding

FIGURE 13-4. Treatment algorithm for the management of moderate to severe hypovolemia. (CVP, central venous pressure; MAP, mean arterial pressure; PA, pulmonary artery; PAOP, pulmonary artery occlusion pressure; PRBCs, packed red blood cells; SBP, systolic blood pressure.)

Upon stabilization, placement of a pulmonary artery (PA) catheter may be indicated based on the need for more extensive cardiovascular monitoring than is available from noninvasive measurements such as vital signs, cardiac rhythm, and urine output.9,10 Key measured parameters that can be obtained from a PA catheter are the pulmonary artery occlusion pressure (PAOP), which is a measure of preload, and CO. From these values and simultaneous measurement of HR and BP, one can calculate the left ventricular SV and SVR.10 Placement of a PA catheter should be reserved for patients at high risk of death due to the severity of shock or pre-existing medical conditions such as heart failure.11 Use of PA catheters in broad populations of critically ill patients is somewhat controversial because clinical trials have not shown consistent benefits with their use.12-14 However, critically ill patients with a high severity of illness may have improved outcomes from PA catheter placement. It is not clear why this was seen, but it could be that more severely ill patients have less physiologic reserve and less "room for error" and benefit from the therapeutic decisions that come from detailed PA catheter data.15 An alternative to the PA catheter is placement of a central venous catheter that typically resides in the superior vena cava to monitor central venous pressure (CVP). While central venous catheters are less expensive and more readily placed, they are not particularly accurate in monitoring effective fluid resuscitation. 0

Fluid Therapy

^^ Three major therapeutic options are available to clinicians for restoring circulating blood volume: crystalloids (electrolyte-based solutions), colloids (large-molecular-weight solutions), and blood products. Blood products are used only in instances involving hemorrhage (or severe preexisting anemia), thus leaving crystalloids and colloids as the mainstay of therapy in all types of hypovolemic shock, along with adjunctive vasopressor support. The aggressiveness of fluid resuscitation (rate and volume) will be dictated by the severity of the hypovolemic shock and the underlying cause. Warming of all fluids to 37°C (98.6°F) prior to administration is an important consideration to prevent hypothermia, arrhythmias, and coagulopathy, as they will have a negative impact on the success of the resuscitation effort.16


Conventional, "balanced" crystalloids are fluids with (a) electrolyte composition that approximates plasma, such as lactated Ringer's (LR), or (b) a total calculated osmolality similar to that of plasma (280 to 295 mOsm/kg), such as 0.9% sodium chloride (also known as normal saline [NS] or 0.9% NaCl) ( ).17 Thus, convention al crystalloids will distribute in normal proportions throughout the extracellular fluid space upon administration. In other words, expansion of the intravascular space will only increase by roughly 200 to 250 mL for every liter of isotonic crystalloid fluid administered.5 Hypertonie crystalloid solutions such as 3% NaCl or 7.5% NaCl have osmolalities substantially higher than plasma. The effect observed with these fluids is a relatively larger volume expansion of the intravascular space. By comparison to conventional crystalloids, administration of 250 mL of 7.5% sodium chloride will result in an intravascular space increase of 500 mL.5 This increase is a result of the fluid administered as well as osmotic drawing of intracellular fluid into the intravascular and interstitial spaces. This occurs because the hypertonic saline increases the osmolality of the intravascular and interstitial fluid compared to the intracellular fluid. Hypertonic saline also has the potential for decreasing the inflammatory response.18 Despite these theoretical advantages, data are lacking demonstrating superiority of hypertonic crystalloid solutions compared with isotonic solutions.19 Crystalloids are generally advocated as the initial resuscitation fluid in hypovolemic shock because of their availability, low cost, and equivalent outcomes compared with colloids.9 A reasonable initial volume of an isotonic crystalloid (0.9% NaCl or LR) in adult patients is 1,000 to 2,000 mL (about 2 to 4 pints) administered over the first hour of therapy. Ongoing external or internal bleeding will require more aggressive fluid resuscitation.

In the absence of ongoing blood loss, administration of2,000 to 4,000 mL (about

4 to 8 pints) of isotonic crystalloid will normally re-establish baseline vital signs in adult hypovolemic shock patients.20 Selected populations, such as burn patients, may require more aggressive fluid resuscitation, while other patient subsets such as those with cardiogenic shock or heart failure may warrant less aggressive fluid administra-

tion to avoid over-resuscitation. In hemorrhagic shock patients, approximately three to four times the shed blood volume of isotonic crystalloids is needed for effective resuscitation.20,21

Side effects from crystalloids primarily involve fluid overload and electrolyte dis-

turbances of sodium, potassium, and chloride. Dilution of coagulation factors can also occur resulting in a dilutional coagulopathy.5 Two clinically significant reasons LR is different from NS is that LR contains potassium and has a lower sodium con tent (130 versus 154 mEq/L or mmol/L). Thus, LR has a greater potential than NS to cause hyponatremia and/or hyperkalemia. Alternatively, NS can cause hypernatremia and hypokalemia. Nevertheless, there is no clear cut advantage when comparing NS and LR.


Understanding the effects of colloid administration on circulating blood volume necessitates a review of those physiologic forces that determine fluid movement between


capillaries and the interstitial space throughout the circulation (Fig. 13-5). Relative hydrostatic pressure between the capillary lumen and the interstitial space is one of the major determinants of net fluid flow into or out of the circulation. The other major determinant is the relative colloid osmotic pressure between the two spaces. Administration of exogenous colloids results in an increase in the intravascular colloid osmotic pressure. The effects of colloids on intravascular volume are a consequence of their relatively large molecular size (greater than 30 kilodaltons [kDa]), limiting their passage across the capillary membrane in large amounts. Alternatively stated, colloids can be thought of as "sponges" drawing fluid into the intravascular space from the interstitial space. In the case of isosmotic colloids (5% albumin, 6% hetastarch, and dextran products), initial expansion of the intravascular space is essentially 65% to 75% of the volume of colloid administered accounting for some "leakage" of the colloid from the intravascular space.5 Thus, in contrast to isotonic crystalloid solutions that distribute throughout the extracellular fluid space, the volume of isooncot-ic colloids administered remains relatively confined to the intravascular space. In the case of hyperoncotic solutions such as 25% albumin, fluid is pulled from the interstitial space into the vasculature resulting in an increase in the intravascular volume that is much greater than the original volume of the 25% albumin that was administered. While theoretically attractive, hyperoncotic solutions should not be used for hypovolemic shock since the expansion of the intravascular space is at the expense of depletion of the interstitial space. Exogenous colloids available in the United States include 5% albumin, 25% albumin, 5% plasma protein fraction (PPF), 6% hetastarch, 10% pentastarch, 10% dextran 40, 6% dextran 70, and 6% dextran 75 (Table 13-3). The first three products are derived from pooled human plasma. Hetastarch and penta-starch are semisynthetic hydroxyethyl starches derived from amylopectin. The dextran products are semisynthetic glucose polymers that vary in terms of the average molecular weight of the polymers. Superiority of one colloid solution over another has not

been clearly established.

Table 13-3 Composition of Common Resuscitation Fluids



K M g





:-nLc| L"


(niEn.'L)' (mEq/Lf-1





(rnOi in i'kij^

0.9% Had




309 1










Laciafsd Ringefi






Hit«ur<h (He* tend)


Ï 0.9



ni.'tjistjrthi e i^jL



Hetastarth IHespan}



Hetaitarch 6 gM





1 ifl

Kynanaich 10 g/dL



516 AKjuflfin



Allxirriiri 5 ^/JL (WEJ/Ü




Alhnriiii 1 75 gM (Î50g/L)


5% FW




Plasma |M»iri5

Detfran -ft) Dftfljan A? Demran ii lit IM

154 154

1M V>i i gKiL (50cyL)(SB% ■albumint tertian 10 g/dL (jvg. TOlKUlar weight 10 kL'ji OiMlrinfi (jiiVUl (a^cf. molecular wit'iqhr 70 kDu) Oefliini grVdL (jvq. molecular weight /S kl J.s)

avg.. avc-caof; Ca, calcium.: CI, cWoiide; K, potaiilum; kDa, kHodalton; Vo. magnesujirç Ni. i( f'W, pJaiiitt pioiein traction.

"fm values, mtq/1 = mrroVL e.g.. nrtfcq/l Na = 15J1 mirv.ii/L.

aFtn lhsie valuer mF-q/1 x lb mnnoL'l ; eg, D.ifmfq/l Mg îïjÛ mmatl. Mg.

'For thuvahit1. nïOimVkg = dniwsl/kg. eg. iûàmûim/tg = 30ä «Ynat/kg.

From Ref. 17

FIGURE 13-5 Operative forces at the capillary membrane tend to move fluid either outward or inward through the capillary membrane. In hypovolemic shock, one therapeutic strategy is the admin-

istration of colloids that can sustain and/or draw fluid from the interstitial space by increasing the plasma colloid osmotic pressure. (From Guyton AC, Hall JE. Textbook of Medical Physiology. 8th ed. Philadelphia: Saunders; 1991: 174, with permission.)

For years within the critical care literature a controversy known as the "colloid versus crystalloid debate" raged over the relative merits of the two types of resuscitation fluids. At the center of the debate was what the goal of fluid resuscitation in shock should be: immediate expansion of the intravascular space with colloids versus expansion of the entire extracellular fluid space with crystalloids. A randomized controlled study involving 6,997 critically ill patients (Saline versus Albumin Fluid Evaluation

[SAFE] study) demonstrated no difference in mortality between patients receiving sa-25

line versus albumin. Largely in response to the SAFE trial, the FDA issued a notice to health care providers in May 2005 declaring albumin safe for use in most critically ill patients.26 Burn, traumatic brain injury, and septic shock patients were excluded from the SAFE trial; however, based on previous data there do not appear to be a clear-cut overall advantage for either crystalloids or colloids in these patient groups.26

Thus, while the debate is not fully resolved, most clinicians today prefer using crys-

21 27

talloids based on their availability and inexpensive cost compared with colloids. '

Generally, the major adverse effects associated with colloids are fluid overload, dilutional coagulopathy, and anaphylactoid/anaphylactic reactions.28,29 Although derived from pooled human plasma, there is no risk of disease transmission from commercially available albumin or PPF products since they are heated and sterilized by ultrafiltration prior to distribution.28 Because of direct effects on the coagulation system with the hydroxyethyl starch and dextran products, they should be used cautiously in hemorrhagic shock patients. This is another reason why crystalloids may be preferred in hemorrhagic shock. Furthermore, hetastarch can result in an increase in amylase not associated with pancreatitis. As such, the adverse-effect profiles of the various fluid types should also be considered when selecting a resuscitation fluid.

Blood Products

Blood products are indicated in hypovolemic shock patients who have sustained blood losses from hemorrhage exceeding 1,500 mL. This, in fact, is the only setting in which freshly procured whole blood is administered. In virtually all other settings, blood products are given as the individual components of whole blood units, such as packed red blood cells (PRBCs), fresh frozen plasma (FFP), platelets, cryoprecipitate,

and concentrated coagulation factors. This includes ongoing resuscitation of hem-orrhagic shock, when PRBCs can be transfused to increase oxygen-carrying capacity in concert with crystalloid solutions to increase blood volume. In patients with documented coagulopathies, FFP for global replacement of lost or diluted clotting factors, or platelets for patients with severe thrombocytopenia (less than 20 x 10/mm or 20 x 10 L]) should be administered.31 Type O negative blood or "universal donor blood" is given in emergent cases of hemorrhagic shock. Thereafter, blood that has been typed and cross-matched with the recipient's blood is given. The traditional threshold for PRBC transfusion in hypovolemic shock has been a serum hemoglobin of less than 10 g/dL (100 g/L or 6.2 mmol/L) and hematocrit less than 30%. However, a more restrictive transfusion threshold of 7 g/dL (70 g/L or 4.34 mmol/L) appears to be safe for critically ill patients after they have received appropriate fluid resuscitation and have no

signs of ongoing bleeding. Traditional risks from allogeneic blood product administration include hemolytic and nonhemolytic transfusion reactions and transmission of bloodborne infections in contaminated blood. However, recent large studies have also shown that transfusions are associated with higher mortality, possibly because of ad-

verse immune and inflammatory effects. Based on limitations of homologous blood donations, intraoperative salvage techniques can be employed in patients with massive hemorrhage in an effort to conserve blood.6,32,33

Due to blood shortages and associated risks with transfusions, there are ongoing research efforts concerning the development of red blood cell substitutes as a possible therapy alternative. Products that have reached clinical trials include perfluorocarbon emulsions and hemoglobin-based oxygen carriers (HBOCs).34 These blood products have several advantages over PRBCs including greater availability (because donors aren't needed), increased shelf-life, absence of infectious risks, and no need for crossmatching. As such, red blood cell substitutes have the potential to serve as temporizing measures in hypovolemic shock patients until conventional red blood cell transfusions can be administered or in instances in which availability of donated PRBCs is extremely limited. Nonetheless, lack of adequate efficacy data and additional side effects associated with each of the respective red blood cell substitutes have precluded their approval in the United States at present.34

Research also continues into the use of recombinant activated factor VII (rFVIIa) as an adjunctive agent to treat uncontrolled hemorrhage. Initial experiences with rFVIIa show that it can decrease transfusions, though large studies have not been

performed. A major unresolved issue surrounding the use of rFVIIa is its safety where the risk of thromboembolic events in patients receiving this agent off-label was recently highlighted.36 The optimal dose of rFVIIa in nonhemophilic patients is also unknown. This latter issue is particularly important in light of the high acquisi tion costs for rFVIIa, and ultimately, pharmacoeconomic analyses of rFVIIa will be needed.

Pharmacologic Therapy Vasopressor Therapy

Vasopressor is the term used to describe any pharmacologic agent that can induce arterial vasoconstriction through stimulation of the ai-adrenergic receptors. While replenishment of intravascular volume is undoubtedly the cornerstone of hypovolemic shock therapy, use of vasopressors may be warranted as a temporary measure in patients with profound hypotension or evidence of organ dysfunction in the early stages of shock.2. Typically, vasopressors are used concurrently with fluid administration. Table 13-4 is a list of those vasopressors used in the management of hypovolemic shock. Dopamine or norepinephrine may be preferred over epinephrine because epinephrine has an increased potential for causing cardiac arrhythmias and impaired ab-

dominal organ (splanchnic) circulation. In cases involving concurrent heart failure, an inotropic agent such as dobutamine may be needed, in addition to the use of a vasopressor.

Vasopressors are almost exclusively administered as continuous infusions because of their very short duration of action and the need for close titration of their dose-related effects. Starting doses should be at the lower end of the dosing range followed by rapid titration upward if needed to maintain adequate BP. Monitoring of end-organ function such as adequate urine output should also be used to monitor therapy. Once BP is restored, vasopressors should be weaned and discontinued as soon as possible to avoid any untoward events. The most significant systemic adverse events associated with vasopressors are excessive vasoconstriction resulting in decreased organ perfusion and potential to induce arrhythmias (Table 13-4). Central venous catheters should be used to minimize the risk of local tissue necrosis that can occur with extravasation of peripheral IV catheters.

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