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Increasing hematocrit above 28% during early resuscitative phase is not associated with decreased mortality following severe traumatic brain injury

  • Clinical Article
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Abstract

Background

To prevent iatrogenic damage, transfusions of red blood cells should be avoided. For this, specific and reliable transfusion triggers must be defined. To date, the optimal hematocrit during the initial operating room (OR) phase is still unclear in patients with severe traumatic brain injury (TBI). We hypothesized that hematocrit values exceeding 28%, the local hematocrit target reached by the end of the initial OR phase, resulted in more complications, increased mortality, and impaired recovery compared to patients in whom hematocrit levels did not exceed 28%.

Methods

Impact of hematocrit (independent variable) reached by the end of the OR phase on mortality and morbidity determined by the extended Glasgow outcome scale (eGOS; dependent variables) was investigated retrospectively in 139 TBI patients. In addition, multiple logistic regression analysis was performed to identify additional important variables.

Findings

Following severe TBI, mortality and morbidity were neither aggravated by hematocrit above 28% reached by the end of the OR phase nor worsened by the required transfusions. Upon multiple logistic regression analysis, eGOS was significantly influenced by the highest intracranial pressure and the lowest cerebral perfusion pressure values during the initial OR phase.

Conclusions

Based on this retrospective observational analysis, increasing hematocrit above 28% during the initial OR phase following severe TBI was not associated with improved or worsened outcome. This questions the need for aggressive transfusion management. Prospective analysis is required to determine the lowest acceptable hematocrit value during the OR phase which neither increases mortality nor impairs recovery. For this, a larger caseload and early monitoring of cerebral metabolism and oxygenation are indispensable.

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Abbreviations

CPP:

Cerebral perfusion pressure

FFP:

Fresh frozen plasma

ICP:

Intracranial pressure

ICU:

Intensive care unit

RBC:

Red blood cells

TBI:

Traumatic brain injury

References

  1. Carlson AP, Schermer CR, Lu SW (2006) Retrospective evaluation of anemia and transfusion in traumatic brain injury. J Trauma 61:567–571

    Article  PubMed  Google Scholar 

  2. Cherry T, Steciuk M, Reddy VV, Marques MB (2008) Transfusion-related acute lung injury: past, present, and future. Am J Clin Pathol 129:287–297

    Article  PubMed  Google Scholar 

  3. Corwin HL, Gettinger A, Pearl RG, Fink MP, Levy MM, Abraham E, MacIntyre NR, Shabot MM, Duh MS, Shapiro MJ (2004) The CRIT Study: anemia and blood transfusion in the critically ill—current clinical practice in the United States. Crit Care Med 32:39–52

    Article  PubMed  Google Scholar 

  4. Duchesne JC, Hunt JP, Wahl G, Marr AB, Wang YZ, Weintraub SE, Wright MJ, McSwain NE Jr (2008) Review of current blood transfusions strategies in a mature level I trauma center: were we wrong for the last 60 years? J Trauma 65:272–276

    Article  PubMed  Google Scholar 

  5. Ekelund A, Reinstrup P, Ryding E, Andersson AM, Molund T, Kristiansson KA, Romner B, Brandt L, Säveland H (2002) Effects of iso- and hypervolemic hemodilution on regional cerebral blood flow and oxygen delivery for patients with vasospasm after aneurysmal subarachnoid hemorrhage. Acta Neurochir (Wien) 144:703–712

    Article  CAS  Google Scholar 

  6. Frietsch T, Lenz C, Kuschinsky W, Waschke KE (2004) Effects of chronic isovolaemic haemodilution on regional cerebral blood flow in conscious rats. Eur J Anaesthesiol 21:53–59

    CAS  PubMed  Google Scholar 

  7. Ge YL, Lv R, Zhou W, Ma XX, Zhong TD, Duan ML (2007) Brain damage following severe acute normovolemic hemodilution in combination with controlled hypotension in rats. Acta Anaesthesiol Scand 51:1331–1337

    Article  CAS  PubMed  Google Scholar 

  8. George ME, Skarda DE, Watts CR, Pham HD, Beilman GJ (2008) Aggressive red blood cell transfusion: no association with improved outcomes for victims of isolated traumatic brain injury. Neurocrit Care 8:337–343

    Article  PubMed  Google Scholar 

  9. Gonzalez AM, Yazici I, Kusza K, Siemionow M (2007) Effects of fresh versus banked blood transfusions on microcirculatory hemodynamics and tissue oxygenation in the rat cremaster model. Surgery 141:630–639

    Article  PubMed  Google Scholar 

  10. Habib RH, Zacharias A, Schwann TA, Riordan CJ, Durham SJ, Shah A (2003) Adverse effects of low hematocrit during cardiopulmonary bypass in the adult: should current practice be changed? J Thorac Cardiovasc Surg 125:1438–1450

    Article  PubMed  Google Scholar 

  11. Han SH, Ham BM, Oh YS, Bahk JH, Ro YJ, Do SH, Park YS (2004) The effect of acute normovolemic haemodilution on cerebral oxygenation. Int J Clin Pract 58:903–906

    Article  CAS  PubMed  Google Scholar 

  12. Hare GM, Mazer CD, Hutchison JS, McLaren AT, Liu E, Rassouli A, Ai J, Shaye RE, Lockwood JA, Hawkins CE, Sikich N, To K, Baker AJ (2007) Severe hemodilutional anemia increases cerebral tissue injury following acute neurotrauma. J Appl Physiol 103:1021–1029

    Article  PubMed  Google Scholar 

  13. Hébert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, Tweeddale M, Schweitzer I, Yetisir E (1999) A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med 340:409–417

    Article  PubMed  Google Scholar 

  14. Klein HG, Spahn DR, Carson JL (2007) Red blood cell transfusion in clinical practice. Lancet 370:415–426

    Article  PubMed  Google Scholar 

  15. Kroppenstedt SN, Thomale UW, Griebenow M, Sakowitz OW, Schaser KD, Mayr PS, Unterberg AW, Stover JF (2003) Effects of early and late intravenous norepinephrine infusion on cerebral perfusion, microcirculation, brain-tissue oxygenation, and edema formation in brain-injured rats. Crit Care Med 31:2211–2221

    Article  CAS  PubMed  Google Scholar 

  16. Leal-Noval SR, Muñoz-Gómez M, Arellano-Orden V, Marín-Caballos A, Amaya-Villar R, Marín A, Puppo-Moreno A, Ferrándiz-Millón C, Flores-Cordero JM, Murillo-Cabezas F (2008) Impact of age of transfused blood on cerebral oxygenation in male patients with severe traumatic brain injury. Crit Care Med 36:1290–1296

    Article  PubMed  Google Scholar 

  17. Leal-Noval SR, Múñoz-Gómez M, Murillo-Cabezas F (2008) Optimal hemoglobin concentration in patients with subarachnoid hemorrhage, acute ischemic stroke and traumatic brain injury. Curr Opin Crit Care 14:156–162

    Article  PubMed  Google Scholar 

  18. Leal-Noval SR, Rincón-Ferrari MD, Marin-Niebla A, Cayuela A, Arellano-Orden V, Marín-Caballos A, Amaya-Villar R, Ferrándiz-Millón C, Murillo-Cabeza F (2006) Transfusion of erythrocyte concentrates produces a variable increment on cerebral oxygenation in patients with severe traumatic brain injury: a preliminary study. Intensive Care Med 32:1733–1740

    Article  CAS  PubMed  Google Scholar 

  19. Madjdpour C, Spahn DR, Weiskopf RB (2006) Anemia and perioperative red blood cell transfusion: a matter of tolerance. Crit Care Med 34(5 Suppl):S102–S108

    Article  PubMed  Google Scholar 

  20. Marik PE, Corwin HL (2008) Efficacy of red blood cell transfusion in the critically ill: a systematic review of the literature. Crit Care Med 36:2667–2674

    Article  PubMed  Google Scholar 

  21. McHugh GS, Engel DC, Butcher I, Steyerberg EW, Lu J, Mushkudiani N, Hernández AV, Marmarou A, Maas AI, Murray GD (2007) Prognostic value of secondary insults in traumatic brain injury: results from the IMPACT study. J Neurotrauma 24:287–293

    Article  PubMed  Google Scholar 

  22. McIntyre LA, Fergusson DA, Hutchison JS, Pagliarello G, Marshall JC, Yetisir E, Hare GM, Hébert PC (2006) Effect of a liberal versus restrictive transfusion strategy on mortality in patients with moderate to severe head injury. Neurocrit Care 5:4–9

    Article  PubMed  Google Scholar 

  23. McIntyre LA, Hebert PC (2006) Can we safely restrict transfusion in trauma patients? Curr Opin Crit Care 12:575–583

    Article  PubMed  Google Scholar 

  24. McIntyre L, Hebert PC, Wells G, Fergusson D, Marshall J, Yetisir E, Blajchman MJ, Canadian Critical Care Trials Group (2004) Is a restrictive transfusion strategy safe for resuscitated and critically ill trauma patients? J Trauma 57:563–568

    Article  PubMed  Google Scholar 

  25. Meier R, Béchir M, Ludwig S, Sommerfeld J, Keel M, Steiger P, Stocker R, Stover JF (2008) Differential temporal profile of lowered blood glucose levels (3.5 to 6.5 mmol/l versus 5 to 8 mmol/l) in patients with severe traumatic brain injury. Crit Care 12:R98

    Article  PubMed  Google Scholar 

  26. Meixensberger J, Kunze E, Barcsay E, Vaeth A, Roosen K (2001) Clinical cerebral microdialysis: brain metabolism and brain tissue oxygenation after acute brain injury. Neurol Res 23:801–806

    Article  CAS  PubMed  Google Scholar 

  27. Meixensberger J, Renner C, Simanowski R, Schmidtke A, Dings J, Roosen K (2004) Influence of cerebral oxygenation following severe head injury on neuropsychological testing. Neurol Res 26:414–417

    Article  CAS  PubMed  Google Scholar 

  28. Rosenthal G, Hemphill JC, Sorani M, Martin C, Morabito D, Meeker M, Wang V, Manley GT (2008) The role of lung function in brain tissue oxygenation following traumatic brain injury. J Neurosurg 108:59–65

    Article  PubMed  Google Scholar 

  29. Sarrafzadeh AS, Kiening KL, Callsen TA, Unterberg AW (2003) Metabolic changes during impending and manifest cerebral hypoxia in traumatic brain injury. Br J Neurosurg 17:340–346

    Article  CAS  PubMed  Google Scholar 

  30. Smith MJ, Stiefel MF, Magge S, Frangos S, Bloom S, Gracias V, Le Roux PD (2005) Packed red blood cell transfusion increases local cerebral oxygenation. Crit Care Med 33:1104–1108

    Article  PubMed  Google Scholar 

  31. Thomale UW, Bender M, Casalis P, Rupprecht S, Griebenow M, Neumann K, Woiciechowsky C, Unterberg AW, Stover JF (2007) Tacrolimus depresses local immune cell infiltration but fails to reduce cortical contusion volume in brain-injured rats. Immunobiology 212:567–576

    Article  CAS  PubMed  Google Scholar 

  32. Thomale UW, Kroppenstedt SN, Beyer TF, Schaser KD, Unterberg AW, Stover JF (2002) Temporal profile of cortical perfusion and microcirculation after controlled cortical impact injury in rats. J Neurotrauma 19:403–413

    Article  PubMed  Google Scholar 

  33. Tinmouth A, Fergusson D, Yee IC, Hébert PC, ABLE Investigators; Canadian Critical Care Trials Group (2006) Clinical consequences of red cell storage in the critically ill. Transfusion 46:2014–2027

    Article  PubMed  Google Scholar 

  34. Tomiyama Y, Brian JE Jr, Todd MM (2000) Plasma viscosity and cerebral blood flow. Am J Physiol Heart Circ Physiol 279:H1949–H1954

    CAS  PubMed  Google Scholar 

  35. Tomiyama Y, Jansen K, Brian JE Jr, Todd MM (1999) Hemodilution, cerebral O2 delivery, and cerebral blood flow: a study using hyperbaric oxygenation. Am J Physiol 276:H1190–H1196

    CAS  PubMed  Google Scholar 

  36. Treggiari MM, Schutz N, Yanez ND, Romand JA (2007) Role of intracranial pressure values and patterns in predicting outcome in traumatic brain injury: a systematic review. Neurocrit Care 6:104–112

    Article  PubMed  Google Scholar 

  37. Tsai AG, Cabrales P, Intaglietta M (2004) Microvascular perfusion upon exchange transfusion with stored red blood cells in normovolemic anemic conditions. Transfusion 44:1626–1634

    Article  PubMed  Google Scholar 

  38. Tschuor C, Asmis LM, Lenzlinger PM, Tanner M, Härter L, Keel M, Stocker R, Stover JF (2008) In vitro norepinephrine significantly activates isolated platelets from healthy volunteers and critically ill patients following severe traumatic brain injury. Crit Care 12:R80

    Article  PubMed  Google Scholar 

  39. Van Beek JG, Mushkudiani NA, Steyerberg EW, Butcher I, McHugh GS, Lu J, Marmarou A, Murray GD, Maas AI (2007) Prognostic value of admission laboratory parameters in traumatic brain injury: results from the IMPACT study. J Neurotrauma 24:315–328

    Article  PubMed  Google Scholar 

  40. van Bommel J, Trouwborst A, Schwarte L, Siegemund M, Ince C, Henny ChP (2002) Intestinal and cerebral oxygenation during severe isovolemic hemodilution and subsequent hyperoxic ventilation in a pig model. Anesthesiology 97:660–670

    Article  PubMed  Google Scholar 

  41. Vincent JL, Baron JF, Reinhart K, Gattinoni L, Thijs L, Webb A, Meier-Hellmann A, Nollet G, Peres-Bota D, ABC (Anemia and Blood Transfusion in Critical Care) Investigators (2002) Anemia and blood transfusion in critically ill patients. JAMA 288:1499–1507

    Article  PubMed  Google Scholar 

  42. Weinberg JA, McGwin G Jr, Griffin RL, Huynh VQ, Cherry SA 3rd, Marques MB, Reiff DA, Kerby JD, Rue LW 3rd (2008) Age of transfused blood: an independent predictor of mortality despite universal leukoreduction. J Trauma 65:279–282

    Article  PubMed  Google Scholar 

  43. Weiskopf RB, Feiner J, Hopf H, Lieberman J, Finlay HE, Quah C, Kramer JH, Bostrom A, Toy P (2006) Fresh blood and aged stored blood are equally efficacious in immediately reversing anemia-induced brain oxygenation deficits in humans. Anesthesiology 104:911–920

    Article  PubMed  Google Scholar 

  44. Weiskopf RB, Kramer JH, Viele M, Neumann M, Feiner JR, Watson JJ, Hopf HW, Toy P (2000) Acute severe isovolemic anemia impairs cognitive function and memory in humans. Anesthesiology 92:1646–1652

    Article  CAS  PubMed  Google Scholar 

  45. Weiskopf RB, Toy P, Hopf HW, Feiner J, Finlay HE, Takahashi M, Bostrom A, Songster C, Aminoff MJ (2005) Acute isovolemic anemia impairs central processing as determined by P300 latency. Clin Neurophysiol 116:1028–1032

    Article  PubMed  Google Scholar 

  46. Zauner A, Daugherty WP, Bullock MR, Warner DS (2002) Brain oxygenation and energy metabolism: part I-biological function and pathophysiology. Neurosurgery 51:289–301

    Article  PubMed  Google Scholar 

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Acknowledgements

The help of the ER and ICU nursing staff in collecting clinical data is gratefully acknowledged.

Conflict of interest

None.

Funding

This study was supported in part by grants from the SUVA funds to JFS and RS.

Author information

Authors and Affiliations

  1. Surgical Intensive Care Medicine, University Hospital Zürich, Raemistrasse 100, 8091, Zürich, Switzerland

    Carole Flückiger, Markus Béchir, Silke Ludwig, Jutta Sommerfeld, Silvia R. Cottini, Reto Stocker & John F. Stover

  2. Institute of Anesthesiology, University Hospital Zürich, Zürich, Switzerland

    Mirko Brenni

  3. Division of Trauma Surgery, University Hospital Zürich, Zürich, Switzerland

    Marius Keel

Authors
  1. Carole Flückiger
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  2. Markus Béchir
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  3. Mirko Brenni
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  4. Silke Ludwig
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  6. Silvia R. Cottini
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Corresponding author

Correspondence to John F. Stover.

Additional information

This paper addresses pertinent questions related with the acute, presumably cranial and extracranial, surgical management of traumatic brain injury (TBI) patients. How tolerable is the blood loss, due to traumatic loss or bleeding during surgical procedures, either in terms of blood volume or hemoglobin levels, without jeopardizing brain oxygen supply and, consequently, outcome? In addition, which objectives should be aimed for if the patient should be transfused?

The study design is very similar to the design of Clifton hypothermia trial, as it divides TBI patients in two predefined clusters based on the initial hematocrit level, using a hematocrit 28% as a cut-off. Further exploring the similitude between these two studies, it also evaluates the impact of blood transfusion or abstention of transfusion, in both cohorts of patients.

This study accrues a significant number of patients, and the statistical analysis is very robust, which altogether confers a considerable power to the conclusions. As shown by previous research, it demonstrates that substrate delivery, including oxygen, may not be the main problem in TBI pathophysiology, reason why increasing hematocrit, and thus oxygen-carrying capacity, is not necessarily associated with a decrease in morbidity and mortality.

In normal physiological conditions, the maximal capacity of oxygen transport and unload to the brain is achieved at a hemoglobin level around 10 mg/dl. In head-injured patients, this axiom is probably questionable because the injury itself carries changes in patterns of oxygen delivery and consumption, as well as cerebral microcirculation. Many of these patients are either on increased inspired fraction of oxygen or under the effect of drugs, as mannitol, that have favorable rheological properties, or are sedated to improve the flow/metabolism mismatch. Furthermore, the occurrence of extracranial injuries that often requires surgical repair adds to secondary brain lesions due to a higher incidence of hypoxia and hypotension in these patients.

I suppose that some interesting conclusions can be drawn from this study:

– It is better for head-injured patients if a blood transfusion is not needed.

– Raising the hematocrit is not a technical problem, but it does not translate into an increased outcome, probably because patients that need a transfusion are those with higher incidence of hypoxia and hypotension due to extracranial injuries or higher surgical blood loss. The importance of the severity of primary injuries is expressed in deceased patients with low hematocrit that fail to increase hematocrit with transfusion.

– As shown in the prolific Fig. 3, mortality tends to be higher in patients with low (28%) or in patients with higher (>36%) initial hematocrit levels, as well as mortality is independent of blood transfusion.

– The survival probability of non-transfused patient with <28% hematocrit by the end of the OR phase is similar to those transfused patients with >28% hematocrit, thus outshining the effect of transfusion on raising the hematocrit.

Oscar Alves

Porto, Portugal

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Flückiger, C., Béchir, M., Brenni, M. et al. Increasing hematocrit above 28% during early resuscitative phase is not associated with decreased mortality following severe traumatic brain injury. Acta Neurochir 152, 627–636 (2010). https://doi.org/10.1007/s00701-009-0579-8

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