where resuscitation with HES led to a significant increase in acute renal failure compared with crystalloids ( 34.9 % vs 22.8 %) and an increased need for renal replacement therapy . 9 This finding was confirmed in a 2013 meta-analysis of 38 clinical trials in critically ill patients which showed HES was associated with a 27 % increased risk of renal failure , a 32 % greater need for renal replacement therapy and a 51 % increased risk of mortality compared with crystalloids , albumin and gelatin . 10
Conversely , an international survey based on data collected in 2007 revealed how colloids were the preferred resuscitation fluid and used more frequently than crystalloids ( 48 % vs 33 %) and that starch was used more often than albumin ( 44 % vs 30 %). 11 Nevertheless and possibly in light of the various analyses demonstrating greater harm from HES , this pattern of use was significantly reversed by 2014 , with a greater use of crystalloids ( 84.3 % vs 27.1 %) compared with colloids , although albumin appeared to be the dominant colloid in use compared with HES ( 79.7 % vs 8.8 %). 12
In the Scandinavian Starch for Severe Sepsis / Septic Shock ( 6S ) study , a large , randomized trial in 804 patients with sepsis , the tetrastarch HES 130 / 0.4 was compared with Ringer ’ s acetate . Use of HES 130 / 0.42 was associated with a higher 90-day mortality ( 51 % vs 43 %), a greater need for renal replacement therapy ( 22 % vs 16 %) and severe bleeding . 13 Similarly , in the Crystalloid versus Hydroxyethyl Starch Trial ( CHEST ), 142 HES 130 / 0.4 was evaluated in 7000 intensive care unit patients compared to saline . While there were no mortality differences , patients given HES 130 / 0.4 had a significantly increased need for renal replacement therapy ( RRT ; 7 % vs 5.8 %, p = 0.04 ). In a 2013 Cochrane review examining the effect of different HES on kidney function , the authors identified 42 trials with 11,399 patients . The results showed at 31 % increased need for RRT ( relative risk , RR = 1.31 , 95 % CI 1.16 – 1.49 ) and a 14 % ( RR = 1.14 , 95 % CI 1.01 – 1.30 ) increased risk of acute kidney injury . The authors concluded that the current evidence suggests that all HES products increase the risk of RRT and acute kidney injury . 15 A similar conclusion , i . e ., that HES is associated with an increased risk of requiring RRT has also been reached in other meta-analyses . 16 , 17 Finally , despite the concerns over adverse effects from HES , the results of the Colloids versus Crystalloids for the resuscitation of the critically ill ( CRISTAL ) trial in 2013 , suggested no difference between colloids and crystalloids . This randomized trial in 2612 intensive care patients with hypovolemic shock compared colloids ( dextrans , HES , albumin ) with crystalloids ( saline or Ringer ’ s acetate ). Mortality did not differ at day 28 ; however , patients treated with colloids had more days free of vasopressor therapy and mechanical ventilation at day 7 and day 28 and had a lower mortality at 90 days ( 30.7 % in the colloids group versus 34.2 % in the crystalloids group ). No differences in the incidence of organ failure or renal replacement therapy were detected between the two groups . 18
Finally , while a review of the use of tetrastarch in the perioperative setting identified no adverse safety signals , 19 this was subsequently criticised 20 because the study was commissioned by a tetrastarch manufacturer and did not make reference to relevant studies that identified harm .
Gelatin The hydrolysis of either bovine or porcine collagen results in the formation of gelatin . The products are now modified by urea cross-linking or succinylation .
Evidence for the safety of gelatin for volume resuscitation is limited . One review in 2012 included 40 randomized trials with a combined total of 3275 patients although the authors concluded that the safety and efficacy of gelatin cannot be reliably assessed in some settings for which it is currently used . 21 Nevertheless , a review of the benefits and risks of the perioperative use of gelatin as a plasma expander concluded that it is associated with a lower risk of renal failure compared with starches but that there are no mortality advantages over crystalloids or albumin . 22 However , a more recent review concluded that gelatin is associated with an increased risk of mortality , acute kidney injury and anaphylaxis and the authors cautioned against its use given cheaper and safer alternatives . 23 In fact , gelatins are not used in the US because of their short duration of action as well as the relatively high incidence of anaphylaxis . 24
In summary , it is clear from several high-quality trials and meta-analyses in critically ill patients that treatment with albumin has advantages over tetrastarches which themselves cause impairment of renal function and hemostasias and may even increase mortality . Given the limited evidence-base to support gelatins , the use of these products should be avoided .
Crystalloids Crystalloids are isotonic solutions of low molecular weight salts or sugars that can pass between the intravascular and interstitial compartments . They are the most widely utilized IV solutions in hospitals for fluid and electrolyte maintenance and replacement with most surgical in-patients and many medical patients receiving at least one intravenous crystalloid infusion during their hospital admission . The first reported use of the crystalloid normal saline was during the cholera pandemic that swept across Europe during the early 19th century . 25 While crystalloids might be perceived to be innocuous , low-risk intravenous solutions , a study of hospital doctors indicated that physicians ’ fluid management knowledge is low due , in part , to poor training . 26
Table 1 ( see page 6 ) shows the composition of some of the commonly used crystalloid fluids . 1 , 27 Other formulations of both Hartmann ’ s and Ringer ’ s lactate solutions are available , which contain lactate as a bicarbonate precursor . 1 Some crystalloid solutions are available with additional potassium , so that maintenance or replacement of potassium can be achieved via the one infusion . 1
The value of crystalloids as both replacement and maintenance fluids has been confirmed in metaanalyses and systematic reviews in both septic and critically ill patients . 7 , 10
In a study by Semler et al in 2018 , among critically ill adults , the use of balanced crystalloids ( lactated Ringer ’ s solution or Plasma-Lyte A ) for intravenous fluid administration resulted in a lower rate of the composite outcome of death from any cause , new renal-replacement therapy , or persistent renal dysfunction than the use of saline . 28
In the SALT-ED study in non-critically ill patients in the emergency room , there was no difference in hospital-free days between treatment with balanced crystalloids and treatment with saline . 29
Nevertheless , there are some potential disadvantages from using crystalloids and in particular when the sodium concentration is close to that of intravascular fluid ( 140mmol / l ), there
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