Pro/Con Debate: Use of Albumin in Craniotomies

Educational Objectives

The goal of this program is to improve fluid management in neurosurgery. After hearing and assimilating this program, the clinician will be better able to:

1. Compare and contrast the use of albumin or saline for resuscitation.
2. Select fluids for resuscitation in patients with intracranial pathology.

Summary

Arguments Against the Use of Albumin in Craniotomies

Albumin: administered to maintain intravascular oncotic pressure (OP) and OP relative to the subendothelial glycocalyx space (SGS); the maintenance of pressure restores intravascular volume by drawing fluid into the intravascular space (IVS); albumin is used in an attempt to provide better volume expansion compared with crystalloids, which have a faster redistribution into the SGS

Blood-brain barrier (BBB): the shift of volume in and out of the brain in the event of a breach in the BBB caused by, eg, traumatic brain injury (TBI), craniotomy, glioma with vasogenic edema, is driven by the osmotic gradient and the hydrostatic gradient; OP that is dependent on levels of albumin or protein is minor in comparison with the overall osmotic pressure; administering high dose albumin does not draw the volume out of the brain

Fluid resuscitation for TBI: the saline vs albumin fluid evaluation (SAFE) study found no difference in mortality, organ failure, incidence requiring renal replacement therapy, and length of stay in the intensive care unit (ICU) or hospital between patients who received 0.9% normal saline or 4% albumin for fluid resuscitation in the ICU; an analysis of the data showed that patients with severe TBI receiving albumin had increased mortality within the first 28 days and had a lower incidence of a favorable outcome at 24 mo (SAFE study investigators, 2007)

Intracranial pressure (ICP) monitoring: a subgroup analysis of the patients from the TBI SAFE study (Cooper et al, 2013) found that in patients with severe TBI who received albumin, ICP was higher in the first 7 days, and requirements for sedatives, vasopressors, and analgesics were higher

Exogenous albumin: whether a small volume of albumin causes better volume expansion than crystalloid (at a 1:4 or 1:3 ratio) is disputed; exogenous albumin has a shorter half-life than crystalloid; extravasation of albumin is expedited out of the IVS in patients with a disrupted glycocalyx layer (the half-life of albumin may be 4 or 8 hr in patients with sepsis or on peritoneal dialysis); half-life decreases in patients undergoing major surgery with severe hemorrhage; clinical studies have found that the volume expansion with albumin is less than previously believed (crystalloid to colloid ratio of 1:1.3 or 1:1.5)

Neuroprotective benefits: high-dose albumin improved neurological outcomes in experimental studies in rat models; patients with lower levels of albumin (poorer physiological state) at baseline are more likely to have poor outcomes with neurological injury; prospective randomized studies do not show neuroprotective benefits; administering high-dose albumin to patients with stroke (ischemic stroke or subarachnoid hemorrhage [SAH]) results in higher mortality associated with cardiopulmonary compromise (eg, congestive heart failure); hyper-oncotic albumin may help to maintain plasma OP and improves microcirculation; clinical evidence for the benefits of albumin is lacking

Evidence for harm: experimental data show that albumin administration increased BBB permeability and exacerbated cerebral edema in rat models; albumin may worsen the breach in the BBB that occurs in patients with brain injury or vasogenic edema-associated brain tumor; albumin may enter into the parenchyma, exert OP, and draw fluids into the brain, which worsens the edema

Coagulopathy: albumin may induce coagulopathy; albumin administration is associated with reduced clot firmness and clot formation time; albumin may reduce activation of platelets through the release of inflammatory mediators; patients undergoing cardiac bypass surgery have increased bleeding and transfusion requirements when albumin is used to prime the bypass pump compared with crystalloid

Taylor et al (2021): albumin for fluid resuscitation is expensive when compared with other fluids

Oddo et al (2018): the European Society of Intensive Care Medicine (ESICM) recommends against the use of albumin as the resuscitation fluid in patients in neurointensive critical care with ischemic stroke, TBI, or SAH

Arguments for the Use of Albumin in Craniotomies

TBI: studies have shown that albumin helps to restore a damaged glycocalyx; the authors in the SAFE trial stated that the mortality difference between the albumin group and the saline group in patients with TBI should be interpreted with caution; patients with TBI accounted for 7% of study participants; the excess number of deaths in the albumin group was minimal compared with the size of the study; the all-cause 28-day mortality is not the most appropriate outcome measure for measuring treatment effects in patients with TBI

Intravenous (IV) fluids: the electrolyte content and osmolarity of IV fluids are criteria for deciding which fluid to administer or avoid; plasma osmotic pressure must be maintained in patients undergoing neurosurgery; the osmotic gradient drives water across the BBB into the cerebral tissue; cerebral edema increases which causes ICP to increase; hypotonic fluids should be avoided in patients with intracranial pathology; patients with TBI in the SAFE trial were administered a hypotonic solution of 4% albumin; the hypotonic fluid given to patients randomized to the albumin group may have been the cause of worse outcomes

Fluid tonicity: studies by Iguchi et al (2018) on sheep models found no change in ICP with normal saline or isotonic albumin; ICP was increased with hypotonic albumin

Neuroprotective effects: Belayev et al (2002) found that rats who received moderate doses of albumin had improved neurologic function, decreased infarct volume, and decreased brain swelling; albumin may have antioxidative properties and hemodilution effects which improves microcirculatory flow; neuroprotective effects of albumin were observed in some patients in the albumin in SAH (ALISAH) trial by Suarez et al (2012)

Cerebral edema: large volumes of crystalloid may cause fluid shifts into brain parenchyma leading to cerebral edema and worsening ICP; the OP exerted by albumin is a small part of the osmotic gradient between the brain and the plasma; albumin does not exert enough OP to cause cerebral edema

Jungner et al (2010): demonstrated that rats with brain injury receiving 20 ml/kg of albumin had reduced brain edema than rats that received 50 or 90 ml/kg of crystalloid

Coagulopathies: may occur if excessively large doses of albumin are administered; most studies comparing different fluids do not show any change in blood loss; appropriate doses of albumin do not change coagulation profile, blood loss, and transfusion requirements; administration of albumin is does not cause adverse associated with the renal system

Conclusion: fluid resuscitation with crystalloids in place of albumin in the operating room (OR) may cause clinical complications (eg, delay in stopping vasopressors, edema in the prone position); time in the OR and length of stay in the ICU may increase; the type of fluid for resuscitation depends on the patient and the clinical scenario

Readings

Cooper DJ, Myburgh J, Heritier S, et al. Albumin resuscitation for traumatic brain injury: is intracranial hypertension the cause of increased mortality? J Neurotrauma. 2013;30(7):512-518. doi:10.1089/neu.2012.2573; Iguchi N, Kosaka J, Bertolini J, et al. Differential effects of isotonic and hypotonic 4% albumin solution on intracranial pressure and renal perfusion and function. Crit Care Resusc. 2018;20(1):48-53; Ma HK, Bebawy JF. Albumin use in brain-injured and neurosurgical patients: Concepts, indications, and controversies. J Neurosurg Anesthesiol. 2021;33(4):293-299. doi:10.1097/ANA.0000000000000674; Mikhael B, Steele DJR, Fenves AZ. In defense of normal saline: Our perspective. Clin J Am Soc Nephrol. 2022;17(4):588-590. doi:10.2215/CJN.10400821; Milford EM, Reade MC. Resuscitation fluid choices to preserve the endothelial glycocalyx. Crit Care. 2019;23(1):77. Published 2019 Mar 9. doi:10.1186/s13054-019-2369-x; Oddo M, Poole D, Helbok R, et al. Fluid therapy in neurointensive care patients: ESICM consensus and clinical practice recommendations. Intensive Care Med. 2018;44(4):449-463. doi:10.1007/s00134-018-5086-z; Paar M, Rossmann C, Nusshold C, et al. Anticoagulant action of low, physiologic, and high albumin levels in whole blood. PLoS One. 2017;12(8):e0182997. Published 2017 Aug 11. doi:10.1371/journal.pone.0182997.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Bebawy, Dr. Ma, and Dr. Uejima were recorded at TASCON 2023, held on October 13, 2023, in San Francisco, CA, and presented by the Trauma Anesthesiology Society. For information on upcoming CME activities from this presenter, please visit tashq.org. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.00 CE contact hours.

Lecture ID:

AN660801

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.