Correspondence

Saline or Albumin for Fluid Resuscitation in Traumatic Brain Injury

N Engl J Med 2007; 357:2634-2636December 20, 2007

Article

To the Editor:

The Saline versus Albumin Fluid Evaluation (SAFE) study investigators (Aug. 30 issue)1 report that in their post hoc follow-up study of patients from the SAFE study who had traumatic brain injury (the SAFE–TBI study), resuscitation with 4% albumin resulted in higher mortality at 2 years than resuscitation with saline. This requires careful consideration to avoid overinterpretation. The main SAFE study investigated two types of resuscitation fluids during the first 28 days of intensive care in a large and heterogeneous collective, with patients who had traumatic brain injury representing only a small subgroup.2 Therefore, several shortcomings limit a direct transfer of the findings to the clinical treatment of traumatic brain injury. First, the authors themselves acknowledge the possibility that the findings represent a “chance subgroup finding.”1 Second, there may be better options than saline or albumin for the treatment of a decreased circulatory state in patients with traumatic brain injury.3,4 Third, randomization forestalled individualized fluid therapy in the albumin group.5 Patients who do not have substantial blood losses should not generally require the substitution of iso-oncotic colloid for crystalloids. Rather, patients with ongoing urinary output and insensible perspiration, representing colloid-free extracellular losses, primarily require crystalloid-fluid replacement.

Matthias Jacob, M.D.
Daniel Chappell, M.D.
Ludwig-Maximilians University Munich, 80336 Munich, Germany
matthias.jacob@med.uni-muenchen.de

Dr. Jacob reports receiving an unrestricted research grant from ZLB Behring and lecture fees from B. Braun and Fresenius Kabi. No other potential conflict of interest relevant to this letter was reported.

5 References

1. 1

   The SAFE Study Investigators. Saline or albumin for fluid resuscitation in patients with traumatic brain injury. N Engl J Med 2007;357:874-884
   Full Text | Web of Science | Medline

2. 2

   The SAFE Study Investigators. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 2004;350:2247-2256
   Full Text | Web of Science | Medline

3. 3

   Diringer MN, Axelrod Y. Hemodynamic manipulation in the neuro-intensive care unit: cerebral perfusion pressure therapy in head injury and hemodynamic augmentation for cerebral vasospasm. Curr Opin Crit Care 2007;13:156-162
   CrossRef | Web of Science | Medline

4. 4

   Stubbe HD, Greiner C, Westphal M, et al. Cerebral response to norepinephrine compared with fluid resuscitation in ovine traumatic brain injury and systemic inflammation. Crit Care Med 2006;34:2651-2657
   CrossRef | Web of Science | Medline

5. 5

   Jacob M, Chappell D, Rehm M. Clinical update: perioperative fluid management. Lancet 2007;369:1984-1986
   CrossRef | Web of Science | Medline

To the Editor:

The SAFE study investigators report that patients with traumatic brain injury who received 4% albumin for fluid resuscitation had a lower survival rate at 24 months of follow-up than those who received saline. A colloid-based fluid strategy, including albumin infusion, induces coagulation abnormalities, possibly owing to dilution of the coagulation factors.1,2 In our experience, in a neurology intensive care unit, when colloids are administered at large doses, it is sometimes necessary to correct the coagulation abnormalities. Coagulation abnormalities in patients with severe traumatic brain injury are associated with a worse outcome and deserve prompt correction.3 In patients enrolled in the SAFE–TBI study who were assigned to albumin infusion, the concentration of serum albumin was significantly higher than in those assigned to saline infusion (see Table 2 of the article), thus possibly leading to dilution of coagulation factors and to coagulation abnormalities. We wonder whether there were significant differences in the coagulation patterns between the two treatment groups, especially in the first days after enrollment.

Federico Bilotta, M.D., Ph.D.
Giovanni Rosa, M.D.
University of Rome La Sapienza, 00161 Rome, Italy
bilotta@tiscali.it

3 References

1. 1

   Falk JL, Rackow EC, Astiz ME, Weil MH. Effects of hetastarch and albumin on coagulation in patients with septic shock. J Clin Pharmacol 1988;28:412-415
   Web of Science | Medline

2. 2

   Rackow EC, Mecher C, Astiz ME, Griffel M, Falk JL, Weil MH. Effects of pentastarch and albumin infusion on cardiorespiratory function and coagulation in patients with severe sepsis and systemic hypoperfusion. Crit Care Med 1989;17:394-398
   CrossRef | Web of Science | Medline

3. 3

   Schirmer-Mikalsen K, Vik A, Gisvold SE, Skandsen T, Hynne H, Klepstad P. Severe head injury: control of physiological variables, organ failure and complications in the intensive care unit. Acta Anaesthesiol Scand 2007;51:1194-1201
   Web of Science | Medline

Author/Editor Response

We concur with Jacob and Chappell that the interpretation of our results requires careful consideration, primarily because our study was conducted as a subgroup analysis of the SAFE study.1 However, given the equivalence of injury severity at baseline in the saline group and the albumin group, the similar resuscitation end points achieved under double-blind conditions, and the significant difference in long-term mortality between the two study groups, a reevaluation of purported crystalloid-specific and colloid-specific effects is warranted. Considering the additional cost of albumin, we recommend that saline be used preferentially in patients with traumatic brain injury until fluid strategies with other crystalloids or synthetic colloids have been evaluated under the same rigorous conditions applied in our study.

We concur with Bilotta and Rosa that dilutional coagulopathy may be a potential biologic mechanism for the increased mortality associated with the use of albumin in patients with traumatic brain injury. Patients who received albumin had increased requirements for transfusion of packed red cells in the first 2 days after randomization in the main SAFE study and on the second day in the SAFE–TBI study.

Ultimately, the selection of resuscitation fluid for patients with traumatic brain injury will depend on the attending clinician's preference and experience, the cost and availability of specific fluids, and the interpretation of published evidence, to which our study adds new data.

John A. Myburgh, M.D., Ph.D.
D. James Cooper, M.D.
Simon Finfer, M.D.
Australian and New Zealand Intensive Care Society, Melbourne 3000, Australia
j.myburgh@unsw.edu.au

for the SAFE Study Investigators

1 References

1. 1

   The SAFE Study Investigators. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 2004;350:2247-2256
   Full Text | Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   B. Nohé, A. Ploppa, V. Schmidt, K. Unertl. (2011) Volumentherapie in der Intensivmedizin. Der Anaesthesist 60:5, 457-473
   CrossRef

2. 2

   Ann G. Bailey, Peggy P. McNaull, Edmund Jooste, Jay B. Tuchman. (2010) Perioperative Crystalloid and Colloid Fluid Management in Children: Where Are We and How Did We Get Here?. Anesthesia & Analgesia 110:2, 375-390
   CrossRef

3. 3

   Daniel Chappell, Matthias Jacob, Klaus Hofmann-Kiefer, Peter Conzen, Markus Rehm. (2008) A Rational Approach to Perioperative Fluid Management. Anesthesiology 109:4, 723-740
   CrossRef