Titrated hypertonic/hyperoncotic solution for hypotensive fluid resuscitation during uncontrolled hemorrhagic shock in rats

ArticleinResuscitation 65(1):87-95 · April 2005with5 Reads
DOI: 10.1016/j.resuscitation.2004.10.012 · Source: PubMed
Abstract
In volume- or pressure-controlled hemorrhagic shock (HS) a bolus intravenous infusion of hypertonic/hyperoncotic solution (HHS) proved beneficial compared to isotonic crystalloid solutions. During uncontrolled HS in animals, however, HHS by bolus increased blood pressure unpredictably, and increased blood loss and mortality. We hypothesized that a titrated i.v. infusion of HHS, compared to titrated lactated Ringer's solution (LR), for hypotensive fluid resuscitation during uncontrolled HS reduces fluid requirement, does not increase blood loss, and improves survival. We used our three-phased uncontrolled HS outcome model in rats. HS phase I began with blood withdrawal of 3 ml/100g over 15 min, followed by tail amputation. Then, hydroxyethyl starch 10% in NaCl 7.2% was given i.v. to the HHS group (n=10) and LR to the control group (n=10), both titrated to prevent mean arterial pressure (MAP) from falling below 40 mmHg during HS time 20-90 min. At HS 90 min, resuscitation phase II of 180 min began with hemostasis, return of all the blood initially shed, plus fluids i.v. as needed to maintain normotension (MAP>or=70 mmHg). Liver dysoxia was monitored as increase in liver surface pCO2 during phases I and II. Observation phase III was to 72 h. During HS, preventing a decrease in MAP below 40 mmHg required HHS 4.9+/-0.6 ml/kg (all data mean+/-S.E.M.), compared to LR 62.2+/-16.6 ml/kg (P<0.001), with no group difference in MAP. Uncontrolled blood loss during HS from the tail stump was 13.3+/-1.9 ml/kg with HHS infusion, versus 12.6+/-2.5 ml/kg with LR infusion (P=0.73). Serum sodium concentrations were moderately elevated at the end of HS in the HHS group (149+/-3 mmol/l) versus the LR group (139+/-1 mmol/l) (P=0.001), and remained elevated throughout. Liver pCO2 increased during HS in both groups equally (P<0.001 versus baseline), and tended to return to baseline levels at the end of HS. Blood gas and lactate values throughout did not differ between groups. During HS, 2 of 10 rats in the HHS group versus 0 of 10 in the LR group died (P=0.47). There was no difference between HHS and LR groups in survival rates to 72 h (3 of 10 in the HHS group versus 2 of 10 in the LR group) (P=1.0). Survival times, by life table analysis, were not different (P=0.75). In prolonged uncontrolled HS, a titrated i.v. infusion of HHS can maintain controlled hypotension with only one-tenth of the volume of LR required, without increasing blood loss. This titrated HHS strategy may not increase the chance of long-term survival.
    • "The main sources of FR are represented by mitochondria, xanthine oxidase, nicotinamide adenine dinucleotide phosphate NAD(P)H oxidase, as well as a number of endothelial factors [9, 10]. Fluid therapy can be achieved by administering blood products and substitutes, crystalloid solutions (low molecular weight molecules able to cross the semi-permeable membranes) or colloidal solutions (high molecular weight molecules, unable to cross the semipermeable membrane)111213. Most clinical studies are inconsistent regarding the use of solutions for volume replacement in hemorrhagic shock resuscitation. "
    [Show abstract] [Hide abstract] ABSTRACT: Nowadays, fluid resuscitation of multiple trauma patients is still a challenging therapy. Existing therapies for volume replacement in severe haemorrhagic shock can lead to adverse reactions that may be fatal for the patient. Patients presenting with multiple trauma often develop hemorrhagic shock, which triggers a series of metabolic, physiological and cellular dysfunction. These disorders combined, lead to complications that significantly decrease survival rate in this subset of patients. Volume and electrolyte resuscitation is challenging due to many factors that overlap. Poor management can lead to post-resuscitation systemic inflammation causing multiple organ failure and ultimately death. In literature, there is no exact formula for this purpose, and opinions are divided. This paper presents a review of modern techniques and current studies regarding the management of fluid resuscitation in trauma patients with hemorrhagic shock. According to the literature and from clinical experience, all aspects regarding post-resuscitation period need to be considered. Also, for every case in particular, emergency therapy management needs to be rigorously respected considering all physiological, biochemical and biological parameters.
    Full-text · Article · Feb 2016
    • "[8,9] Moreover, HTS is thought to decrease lung tissue damage and pulmonary inflammation, and increase cellular protection in animal models of UHS. [10,11] Studies of rats, dogs, swine, and pigs showed the relative efficacy of HTS fluid compared to normal saline (NS) for treating UHS.121314151617 Studies in the literature have proven the benefits of HTS in cases of brain and cord trauma.181920 "
    [Show abstract] [Hide abstract] ABSTRACT: To evaluate the effects of various fluids on uncontrolled hemorrhagic shock (UHS). Controversy exists over the appropriate doses and types of fluids for best treating UHS. This study evaluated the effects of hypertonic saline (HTS), normal saline (NS), and no fluid resuscitation (NFR) on UHS. Thirty goats were anesthetized and underwent right leg ablation. The animals were randomly assigned to equal NFR, HTS, and NS groups. The following features of UHS were analyzed: hemoglobin, heart rate, blood loss, mean arterial pressure, bleeding time, and pH. Animals were sacrificed two hours after ablation. All of the goats who received HTS died within 60 minutes. Four goats in the NS group and one goat in the NFR group died within 120 minutes. The NFR group had significantly higher hemoglobin values than the NS and HTS groups at the end of the trial. Blood loss in the HTS group was greater than in the other two groups (p<0.05). The NS group had higher blood loss than the NFR group (p<0.05). Mean arterial pressure in the HTS group decreased sharply toward zero within the first 60 minutes. In the NFR and NS groups, mean arterial pressure was higher than in the HTS group (p<0.05), and remained constant at 60mmHg after 35 minutes. The NFR group had higher pH values compared to the other two groups (p<0.05). Our study demonstrated that HTS is not suitable for treating UHS when compared to NFR and NS. Goats treated with NFR had superior values for all UHS features, including hemoglobin, pH, blood pressure, and bleeding time, compared to those treated with HTS and NS. Pre-hospital field treatment with NS or HTS may worsen the condition until surgical repair is accomplished.
    Full-text · Article · Nov 2013
    • "Complement inhibition may interfere with the coagulation cascade (Horstick, et al., 2001; Tassani P, et al., 2001). It is also known that colloidal and starch fluids may also cause dilutional coagulopathy (Kentnera, et al., 2005; Vollmar and Menger, 2004). The increased mortality associated with the administration of high dose of DAF and Hextend may be caused by the induction of severe coagulopathy. "
    [Show abstract] [Hide abstract] ABSTRACT: The current wars in Iraq and Afghanistan have resulted in the highest rates of combat casualties experienced by the U.S. military since the Vietnam conflict, and hemorrhage has been indentified as the principal cause of death among potentially salvageable patients. Hemorrhagic blood loss or resuscitation following hemorrhage leads to complement activation, which in turn, plays a key role in the pathogenesis of subsequent shock, tissue inflammation and multiple organ failure. The current study used a porcine model of controlled hemorrhage to determine the effects of early bolus injection of a complement inhibitor, decay-accelerating factor (DAF), administered 20 minutes after the onset of hemorrhagic shock. We report that hemorrhaged animals if untreated die 100 minutes before the procedure endpoint, whereas animals treated with DAF alone or in combination with resuscitation fluids displayed increased survival when compared to controls. Administration of DAF (5 and 25micrometers/kg) reduces the volume of Hextend required 60 minutes after achieving target blood pressure by approximately 56.9 and 62%, respectively. Furthermore, DAFtreated pigs showed improvement of hemodynamic and metabolic parameters and reduced injury in several organs including the lungs and the intestine. In summary, our data demonstrate that administration of DAF within 20 minutes of hemorrhagic shock may reduce mortality and morbidity of severely injured soldiers. Furthermore, its effect in reducing or eliminating the need for resuscitation fluids should reflect in great logistical and operational improvement during far-forward medical support missions.
    Full-text · Article · Dec 2008 · Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma & emergency surgery: TJTES
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