Fluid Resuscitation State of the Science for Treating Combat Casualties and Civilian Injuries (1999) / Chapter Skim
Currently Skimming:
4 Novel Approaches to Treatment of Shock
4 Novel Approaches to Treatment of Shock
Pages 79-96
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 79... ...
However, a variety of research observations and potential novel therapeutics hold promise as additives to some basic resuscitation solutions. Those novel therapeutics that emerge from preclinical testing might be tested as additives to the basic resuscitation fluid in a stepwise, controlled fashion in appropriate animal models and subsequent human studies.
|
From page 80... ...
Shock syndrome may predispose the individual to other major comorbidities such as acute respiratory distress syndrome, sepsis, systemic inflmnmatory response syndrome, and multiple-organ dysfunction syndrome (MODS)
|
From page 81... ...
This was due in part to contradictory results in clinical trials and in part to an incomplete understanding about how these drugs deliver 02, the mechanisms of their side effects, and the fundamental mechanisms in shock, hemorrhage, and the control of blood flow. Currently the only formulation licensed as a red blood cell replacement is the veterinary product Oxyglobin (Biopure Corp., Cambridge, Mass.)
|
From page 82... ...
Surprisingly few experimental data concerning iron chelation during resuscitation are published, considering that recognition of a connection between iron, free radicals, and tissue damage in hemorrhagic shock goes back almost 30 years (Hedlund and Hallaway, 1991~. Polynitroxylation of biomacromolecules (albumin, starch, or hemoglobin)
|
From page 83... ...
The ability of Perfluorocarbons to replace red blood cells as temporary O2 carriers was demonstrated more than 30 years ago (Geyer et al., 1968~. Perfluorocarbons exchange O2 by simple diffusion; O2-carrying capacity is directly proportional to the partial pressure of O2 in arterial blood.
|
From page 84... ...
For example, crocetin, a carotenoid compound derived from the fruit of Gardenia jaminoides Ellis, a Chinese medicinal herb, has been investigated for its protective action in quenching free radicals. However, the compound has also been demonstrated to increase O2 diffusivity, and it has been observed to increase the level of O2 consumption and the rate of survival in a rat hemorrhagic model (Gainer et al., 1993~.
|
From page 85... ...
supply. Agents like cyclosporin and FK506 inhibit opening of a high-conductance pore in the mitochondrial inner membrane, preventing necrotic cell death after restoration of the pH following reperfusion, an injury that is not mediated through oxygen free radicals.
|
From page 86... ...
However, the availability of scavengers of excess nitric oxide or inhibitors of iNOS provides opportunities for experimental approaches that may modulate the inflammatory response and ameliorate end-organ damage in hemorrhagic shock. Therapies for Reperfusion-l\lediated Free-Radical Damage Although free radicals remain difficult to measure in living tissue because of their short half-lives, multiple strategies to the scavenging or neutralization of radicals have provided indirect evidence of increased free-radical production after resuscitation from shock.
|
From page 87... ...
NAcetylcysteine improved the survival rate, reduced the time of ventilatory support, and improved the oxygenation index (partial arterial pressure O2/fraction of inspired 02~; in addition, no adverse effects were observed dig Nacetylcysteine treatment. N-Acetylcysteine has also been shown to provide significant protection in a number of models, including ischemia reperfusion and hemorrhagic shock (Demir and Inal-Erden, 1998; Fan et al., 19984.
|
From page 88... ...
Although the number of publications implicating iron chelation in shock resuscitation-related injury is extensive, the concept of adding an iron chelator at the time of fluid resuscitation to reduce injury and to attenuate numerous aspects of the postshock inflammatory response has proven to be exceptionally attractive. DFO administered with fluid for resuscitation from hemorrhagic shock significantly improved cellular function (Sanan et al., 1989)
|
From page 89... ...
Of particular concern is generation of the highly toxic compound peroxynitrite, which is formed by the interaction of nitric oxide and the superoxide radical. Both pharmacologic approaches and iNOS-knockout animals have confirmed that nitric oxide and peroxynitrite play significant roles in cellular injury and organ dysfunction after fluid resuscitation from hemorrhagic shock.
|
From page 90... ...
(Harbrecht, 1998~. Although compelling evidence implicates iNOS in the proinflammatory response initiated by fluid resuscitation from hemorrhagic shock, a primary concem regarding nitric oxide blockade is secondary alterations in vascular compensatory mechanisms.
|
From page 91... ...
has not been resolved; in addition, questions regarding oxygen delivery by the resuscitation regimen and dose-response relationships have not been examined. The polynitroxyl human serum albumin produced by covalently labeling human serum albumin with 40 molar equivalents of the nitroxide 4acetamido-2,2,6,6-tetramethylpiperidine-1-oxyl has been studied extensively with animal models of ischemic reperfusion, stroke, and hemorrhagic shock, and clinical trials are scheduled for 2000 (C.J.
|
From page 92... ...
Perhaps antioxidants or nitric oxide scavengers that are given prophylactically or as a component of a first resuscitation fluid might lead to an oral medication or fluid additive to ameliorate neural cell injury after trauma. TOLERANCE Perhaps the most interesting, possibly the most promising, and certainly the most challenging approach might be to render the soldier globally less vulnerable to the effects of hemorrhagic shock, either prophylactically or at some point
|
From page 93... ...
Because organ toxicity following hemorrhagic shock results from a complex of interrelated mechanisms that lead to death, it is unlikely that a single drug, vitamin, electrolyte, or other agent would be able to alter organ toxicity significantly. Some markedly altered physiologic states offer protection to cells and organs.
|
From page 94... ...
94 FLUID RESUSCITATION models and subsequently in clinical trials. Combinations of several therapeutic agents should also be investigated.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.