Page 841 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

572 PART 5: Infectious Disorders

Hetastarch and Gelatin: Hetastarch (HES) and gelatin solutions are syn- patients with septic shock, particularly those unresponsive to crystalloid
thetic colloids. HES solutions come in differing concentrations with fluid resuscitation. However, additional trials are needed in this area
various molecular weights and hydroxyethyl groups. Although effective as as well in order to delineate the optimal use for this fluid and the cost
resuscitative agents, HES solutions are known to induce a coagulopathy effectiveness of this choice.
through effects on von Willebrand factor and factor VIII, potentially
shown to increase the risk of AKI in patients with severe sepsis and septic ■ HEMODYNAMIC MANAGEMENT
increasing the risk of bleeding. Recently, HES solutions have been
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shock. This was suggested in an early study and convincingly shown in Vasopressors: Despite fluid resuscitation, there are occasions when
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the large VISEP trial where HES use caused a dose-dependent increase vasopressor therapy is required to sustain life. Below a certain MAP,
in kidney injury and need for renal replacement therapy. Gelatin-based autoregulation of pressure in vascular beds can be lost and perfu-
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colloid solutions are available in Europe and have similarly been associ- sion becomes linearly dependent on pressure. 134,135 Currently, a
ated with coagulation defects, which may be less significant than with MAP greater than or equal to 65 mm Hg has been recommended to
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HES. Because of these data, HES is not recommended as an intravenous maintain perfusion pressure. Titration of norepinephrine to this
colloid. The most common adverse effect of either colloid is an allergic pressure has been shown to preserve tissue perfusion in a small study
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response, which may include anaphylaxis. 128 of 10 patients, and increasing vasopressor dose to a higher MAP of
85 mm Hg does not significantly affect metabolic parameters or renal
Albumin: Albumin is a natural protein colloid and is the most frequently function. 135,136 However, the baseline blood pressure of the individual
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prescribed colloid in the United States. Studies comparing albumin involved should also be considered. Individuals with chronic systemic
to crystalloid administration in sepsis have found that time to reach arterial hypertension might require higher arterial pressures to main-
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resuscitation targets is reduced by more than one-third with isooncotic tain tissue perfusion and reduce acute kidney injury, and those with
albumin. 125,132 Whether albumin exerts beneficial effects through other diseases associated with relative hypotension (eg, chronic hepatic fail-
biological mechanisms, being the most abundant extracellular anti- ure) may appropriately be managed with a lower goal MAP. Therefore,
oxidant, inhibiting oxidative stress and adhesion molecule expression care providers must always supplement arterial pressure with other
or altering vascular permeability remains to be seen. From a clinical measures of global tissue perfusion, such as Scv O 2 , tissue oximetry,
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perspective, most applicable is the recent review specifically comparing blood lactate levels, delayed capillary refill, and urine output. 91,135
albumin and crystalloids in 1977 patients with sepsis where the use of Over the years, there has been a long-standing debate regarding the
albumin was associated with lower mortality. In support of this meta- optimal vasopressor choice in septic shock. Although these discussions
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analysis is the subset of patients enrolled into the large saline versus are intellectually stimulating, it is important to remember that each cate-
albumin fluid evaluation (SAFE) study conducted in Australia and cholamine agent has variable receptor-mediated effects and thus distinct
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New Zealand. The SAFE clinical trial compared isooncotic albumin clinical situations may require different vasopressors (Table 64-4). For
with isotonic crystalloid in patients needing fluid resuscitation. Overall example, norepinephrine has potent α-adrenergic and less β-adrenergic
there was no difference in clinical outcomes by fluid type. In a post hoc effects, while dopamine’s receptor effects are dose dependent. Some
analysis of the subset of 1218 sepsis patients who received albumin, after studies suggest that norepinephrine or dopamine may have some advan-
adjusting for important predictors of death, there was a significantly tages over the other vasopressors and recent guidelines recommend
lower mortality for those treated with albumin (adjusted odds ratio 0.71; either norepinephrine or dopamine as first choice vasopressor agent to
p = 0.03). In a multicenter, open-label trial, 1,818 patients with severe correct hypotension in septic shock. Norepinephrine is a more potent
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sepsis were randomized to receive either 20% albumin and crystalloid vasoconstrictor than dopamine and may be more effective in treating
solution or crystalloid solution alone. There were no differences in hypotension in septic shock patients. In the randomized trial compar-
either 28 or 90-day mortality rates between the two groups. 224 ing these vasopressors, 32 patients were compared in the ability of
In summary, HES solutions should be avoided in patients with severe dopamine and norepinephrine to reverse hemodynamic derangements
sepsis and septic shock until additional prospective trials can confirm associated with septic shock. A greater number of patients were suc-
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the risks and demonstrate a clinical benefit to their use. Albumin, cessfully treated with norepinephrine, including those patients who did
particularly in its isooncotic formulation (4% or 5%), may be used in not respond to dopamine. Subsequently, in a larger observational study

TABLE 64-4 Vasopressors and Inotropes
Drug α1 β1 β2 DA Other
Epinephrine +++++ ++++ +++ NA
Norepinephrine +++++ +++ ++ NA
Phenylephrine +++++ 0 0 NA
Dopamine
0.5-2 0 + + ++++
3-10 + +++ + ++
10-20 ++++ ++++ ++ ++
Dobutamine 0/+ +++++ +++ 0
Isoproterenol 0 +++++ +++++ 0
Vasopressin NA NA NA NA V1
Milrinone NA NA NA NA PDI
Levosimendan NA NA NA NA Partial PDI and calcium sensitizer
PDI, phosphodiesterase inhibitor; V1, vasopressin-1.

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