MS
Generic name
Commercial products
0.7
Hetastarch
Hespan®, Plasmasteril®, Hextend®
0.6
Hexastarch
Elohes®
0.5
Pentastarch
HAES-Steril®, Pentaspan®, Hemohes®
0.4
Tetrastarch
Voluven®, Venofundin®, Tetraspan®
There has been considerable criticism of HES recently in the light of three “pragmatic” critical care trials in which HES solutions were associated with harm, notably renal complications. The first of these studies used a hyperoncotic 10 % HES in doses well in excess of those recommended by the manufacturer and showed a dose-related incidence of renal injury [84]. The second study (CHEST) was powered to detect a mortality difference between HES and saline and found no difference in mortality over nearly 7000 subjects. Although the HES group received more renal replacement therapy (RRT), the RIFLE criteria favoured the HES [85]. The third (6S) study found an increased incidence of RRT in septic patients in the HES 130/0.42 (potato starch) group together with an increased 90-day mortality [86]. None of these studies enrolled patients prior to initial resuscitation and are not pertinent to the consideration of trauma resuscitation. By contrast another intensive care study published recently in which colloid was compared to crystalloid for initial resuscitation found a similar mortality signal to that of the 6S study, but on this occasion in favour of colloid, with the predominant colloid being HES 130/0.4 [87].
The first study to demonstrate a survival benefit associated with the use of colloids in trauma was published recently. In this retrospective study of 1714 patients admitted to a level 1 trauma centre, the authors examined the outcomes in patients who did, or did not, receive a colloid (Hextend®) as part of the resuscitation strategy. Compared to the crystalloid-only standard of care treatment, the overall mortality analysed by univariate analysis was significantly lower in the colloid-treated patients (5.2 % vs. 8.9 %, p = 0.0035). The results were slightly better when limited to patients with penetrating trauma (p = 0.0016) and also when only severely injured patients with Injury Severity Scores (ISS) >26 were considered (p = 0.0014). More starch-treated patients survived to reach intensive care and more blood and blood products were used in this group. However, coagulation measures (prothrombin time and partial thromboplastin time) were not different between the groups. Urine output and renal function were similar between the groups, but there were more early deaths in the standard of care group, which introduces the possibility of selection bias. Controlling for early deaths with multivariate analysis showed similar trends, but the data no longer reached statistical significance [88].
The first randomised, double-blind, controlled trial of crystalloid (0.9 % saline) versus isotonic colloid (HES 130/0.4 in saline) in trauma resuscitation has recently been published (FIRST trial). In this study of 109 patients, blunt and penetrating trauma were randomised separately. In the penetrating trauma group (n = 67), lactate clearance was faster over the first 4 h of resuscitation and lactate and acid base balance were significantly better in the HES group on Day 1. The HES group had a zero incidence of renal injury (RIFLE criteria) compared to 17 % in patients treated with saline p = 0.019). This difference persisted even after allowance for the early deaths in both groups. Maximum SOFA scores were significantly lower in the HES group. The ratio of colloid: crystalloid in the first 24 h was approximately 1:1.5, resulting in a reduction of 2.5 L of study fluid in the HES group. The use of blood and blood products was similar, with a non-significant trend to lower product use in the penetrating HES group. The blunt trauma analysis was severely hampered by the fact that patients in the blunt HES group were much more severely injured (median injury severity score 29.5 vs. 18; P < 0.01). There was no significant difference in the use of study fluid between groups and the HES group required significantly more blood and blood products. Outcomes were similar in both blunt trauma groups in terms of renal function and organ recovery, with no differences in mortality despite substantially higher ISS in the blunt HES group [89].
In a retrospective analysis of penetrating trauma patients in whom the principles of damage control surgery and resuscitation were applied, outcomes were analysed by the volumes of fluid received in addition to the DCR fluids: RBCs, FFP and platelets. In the study of 307 patients, 43 % received <129 mL of crystalloid prior to surgery, while the comparator group received an average of 2757 mL in the emergency department. During subsequent intraoperative management, the restricted fluid group received significantly less crystalloid (3152 mL vs. 8931 mL) together with non-significantly higher volumes of PRBCs, FFP and platelets. The restricted fluid group had significantly lower overall mortality (OR 0.69; 95 % CI 0.37–0.91) [90]. A subsequent matched case–control study from the same group examined the influence of asanguineous fluids used in support of the DCR strategy in patients requiring ≥4 units PRBCs. In this study, mortality was significantly lower in patients who received low volumes (median 1.0 L) of colloid (Hextend®) than those who received crystalloid (median 3.6 L), and the mortality was directly related to the volumes of crystalloid administered. These authors concluded that DCR principles coupled with low-volume, primarily colloid, resuscitation improved survival in these patients [91].
The appropriate use of HES in surgery and trauma resuscitation has recently been reviewed [92].
12.2.7 Neurotrauma
As has been alluded to above, the issue of neuro trauma remains poorly resolved. In the prehospital phase, it is generally accepted that, in the absence of active bleeding, more aggressive resuscitation may be appropriate than in other forms of trauma. Where there is a conflict of interests in a bleeding patient who also has suffered neurological injury, the situation is much less clear, but most authorities would recommend a higher arterial pressure (SBP >100 mmHg) in the prehospital phase [37]. Once the patient is in hospital, similar principles apply, with damage control resuscitation being appropriate inpatients requiring massive transfusion. Aggressive management including resuscitation with blood products and hyperosmolar therapy in gunshot wounds of the brain was associated with significant improval in survival in a recent report [93]. In less seriously bleeding patients, fluid resuscitation should probably be minimised and there is an argument in favour of hypertonic solutions, although these have not been shown to be beneficial. On the basis of subgroup analysis of the SAFE study [76] albumin was suggested to be associated with a worse outcome in head injured patients, probably on the basis of increased intracranial pressure [94]. However, the albumin used in this study was substantially hypo-osmolar with an osmolality of around 260 mosm/L [65] quite sufficient to account for worse intracranial pressures in the albumin group. Other studies of the use of HES or albumin in head injured patients have not demonstrated similar increases in intracranial pressure [95]. A retrospective study of 93 patients with severe traumatic brain injury investigated the impact of a resuscitation protocol that incorporated the use of albumin. These authors reported an early achievement of negative fluid balance in these patients with well maintained plasma albumin concentrations. Over the first 10 days for which the patients were studied, colloids constituted 40–60 % of the total fluids given daily and fluid balance was assisted by the use of furosemide. Mortality at 28 days and 18 months was 11 % and 14 % respectively. The authors contrast this with the SAFE study. In the Scandinavian study, [96] mortality in the study group was substantially lower than that in the SAFE study, but these comparisons should be viewed with caution as the resuscitation strategies, particularly the management of intracranial pressure may well have been different between the study groups. However, a reappraisal of the use of albumin in brain injury has recently been advocated [97].
12.2.8 Burns
Fluid resuscitation formulas, such as the Parkland formula, have found wide application around the world and form the basis for calculation of fluid resuscitation regimes in burnt patients. There have been a number of recent papers examining the use of fluids in patients suffering burns, emphasising that most patients end up receiving crystalloids well in excess of the calculated needs. This fluid overload has been called “fluid creep” and associated with worsening of burn oedema, conversion of superficial into deep burns, and compartment syndromes [98].
A recent review of this topic commented that, while crystalloid fluid has been the mainstay of resuscitation for the better part of four decades, there has been a progressive but as yet unexplained recent trend toward provision of resuscitation volumes well in excess of those predicted by the formula. This increased fluid load has been associated with numerous oedema-related complications. This review emphasizes that, in burns involving >25 % body surface area capillary, capillary permeability is increased, not only in the damaged tissue, but also in non-burnt areas. It was proposed that correction of fluid creep will likely revolve around several strategies, which may include tighter control of titration, re-emergence of colloids and hypertonic salt solutions, and possibly the use of adjunctive markers of resuscitation other than urinary output [99]. In a subsequent retrospective review, the same author concluded that this trend had not improved and that, over an 8-year period, higher than recommended urine output had been attained as a result of increased crystalloid administration [100].
In one publication, the role of hyperoncotic 10 % HES 200/0.5, was examined in a pilot trial of 30 patients. Although the numbers are small, the study was abandoned as the hyperoncotic starch was associated with an apparent increased incidence of fatal outcome [101]. These data underline the view that there is virtually no place for hyperoncotic colloids as acute resuscitation solutions. However, a number of other studies and reviews suggest that the role of colloids in the resuscitation of patients suffering burns is being re-examined.
Another review concluded that starch colloids may limit burn oedema by ameliorating capillary leak and that improved endpoints for resuscitation may help to minimize the problems of over-resuscitation [98]. A further retrospective review examined the effect of adding albumin to the resuscitation fluid strategy on fluid input/output (I/O) ratios. The administration of albumin rapidly reduced hourly fluid requirements, restored normal I/O ratios and ameliorated fluid creep [102]. A study in paediatric burns confirmed these findings showing that the use of albumin restored a normal I/O ratio in paediatric patients, adding further weight to the inclusion of colloid in burns resuscitation strategies [103].
12.3 Conclusions
In recent years there has been a marked shift in the concepts governing trauma resuscitation, with modern views startlingly resembling the initial findings in the First World War. In patients with severe trauma requiring massive transfusions (<10 % of all trauma patients) aggressive damage-control resuscitation and surgery carries the prospect of reducing mortality particularly amongst battle casualties with penetrating injuries. In the civilian population, these data are less conclusive, but the principles are probably still valid. Prehospital resuscitation now focuses on minimal fluid interventions with low volumes of crystalloid as the first line fluid approach. Once the patient reaches hospital, more aggressive fluid resuscitation strategies may be appropriate. In patients requiring less than massive transfusion, substantial portions of the resuscitation volume should be administered with clear fluids. No more than 2–3 L of such fluid should be given as crystalloid, preferably as a balanced crystalloid that is isotonic with plasma. The use of colloids in penetrating trauma seems to be beneficial, but there is insufficient data at present in blunt trauma and burns to make soundly-based recommendations.
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