The relationship of fluid balance and sodium administration to cerebral edema formation and intracranial pressure in a porcine model of brain injury

Ramming, Scott; Shackford, SR; Zhuang, Jian; Schmoker, JD

doi:10.1016/0300-9572(95)99676-2

Cited by 4 publications

(6 citation statements)

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“…Volume-limiting approaches have been shown to be neuroprotec-tive with reduced brain edema. 6,7,28 Also, ICP was highest in the LR-treated group (also consistent with our prior work); however, in this study we showed a strong correlation of lower %-brain water in the injured hemisphere to higher PNPH doses. ICP may be greatly underestimated in our model given the presence of a craniotomy.…”

Section: Discussionsupporting

confidence: 92%

“…However, large volumes of these fluids are typically required for adequate resuscitation, which has been shown to contribute to increased brain edema-potentially exacerbating brain injury. [5][6][7] Additionally, they have been shown to have other deleterious extracranial effects, including increased duration of mechanical ventilation and mortality. 8,9 In addition, in combat casualty cases, a resuscitation fluid of the smallest volume and weight would be highly desirable for the military medic.…”

Section: Introductionmentioning

confidence: 99%

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Polynitroxylated Pegylated Hemoglobin—A Novel, Small Volume Therapeutic for Traumatic Brain Injury Resuscitation: Comparison to Whole Blood and Dose Response Evaluation

BrockmanErik

JacksonTravis

Edward

et al. 2017

Journal of Neurotrauma

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Resuscitation with polynitroxylated pegylated hemoglobin (PNPH), a pegylated bovine hemoglobin decorated with nitroxides, eliminated the need for fluid administration, reduced intracranial pressure (ICP) and brain edema, and produced neuroprotection in vitro and in vivo versus Lactated Ringer's solution (LR) in experimental traumatic brain injury (TBI) plus hemorrhagic shock (HS). We hypothesized that resuscitation with PNPH would improve acute physiology versus whole blood after TBI+HS and would be safe and effective across a wide dosage range. Anesthetized mice underwent controlled cortical impact and severe HS to mean arterial pressure (MAP) of 25-27 mm Hg for 35 min, then were resuscitated with PNPH, autologous whole blood, or LR. Markers of acute physiology, including mean arterial blood pressure (MAP), heart rate (HR), blood gases/chemistries, and brain oxygenation (PbtO), were monitored for 90 min on room air followed by 15 min on 100% oxygen. In a second experiment, the protocol was repeated, except mice were resuscitated with PNPH with doses between 2 and 100 mL/kg. ICP and 24 h %-brain water were evaluated. PNPH-resuscitated mice had higher MAP and lower HR post-resuscitation versus blood or LR (p < 0.01). PNPH-resuscitated mice, versus those resuscitated with blood or LR, also had higher pH and lower serum potassium (p < 0.05). Blood-resuscitated mice, however, had higher PbtO versus those resuscitated with LR and PNPH, although PNPH had higher PbtO versus LR (p < 0.05). PNPH was well tolerated across the dosing range and dramatically reduced fluid requirements in all doses-even 2 or 5 mL/kg (p < 0.001). ICP was significantly lower in PNPH-treated mice for most doses tested versus in LR-treated mice, although %-brain water did not differ between groups. Resuscitation with PNPH, versus resuscitation with LR or blood, improved MAP, HR, and ICP, reduced acidosis and hyperkalemia, and was well tolerated and effective across a wide dosing range, supporting ongoing pre-clinical development of PNPH for TBI resuscitation.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Polynitroxylated Pegylated Hemoglobin—A Novel, Small Volume Therapeutic for Traumatic Brain Injury Resuscitation: Comparison to Whole Blood and Dose Response Evaluation

BrockmanErik

JacksonTravis

Edward

et al. 2017

Journal of Neurotrauma

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“…Large resuscitation volumes can exacerbate cerebral edema and fail to restore oxygen delivery. 12 Furthermore, volume-limiting resuscitation strategies with hypertonic or colloidal-based solutions, or even a combination of fluid and vasopressors 35 have been shown to have potential central nervous system protective effects, with reduced ICP and brain edema as well as improved CPP. These findings parallel our observations, as we noted significantly reduced ICP and %BW with PNPH vs. LR resuscitation, along with improved CPP.…”

Section: Discussionmentioning

confidence: 99%

“…Traditional resuscitation fluids for TBI patients include lactated Ringer’s (LR) or normal saline for civilians or the colloid Hextend (Hex) for military personnel; however, large volumes of these fluids are often required, potentially increasing brain edema and raising intracranial pressure (ICP). 12 In prior models of TBI + HS, the use of hypertonic or colloid-based resuscitation reduced fluid requirements, brain edema, and ICP. 13,14 Clinical trials, however, failed to show benefit from resuscitation with hypertonic fluids or albumin.…”

Section: Introductionmentioning

confidence: 99%

Polynitroxylated-Pegylated Hemoglobin Attenuates Fluid Requirements and Brain Edema in Combined Traumatic Brain Injury Plus Hemorrhagic Shock in Mice

Brockman

Bayır

Blasiole

et al. 2013

J Cereb Blood Flow Metab

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Polynitroxylated-pegylated hemoglobin (PNPH), a bovine hemoglobin decorated with nitroxide and polyethylene glycol moieties, showed neuroprotection vs. lactated Ringer's (LR) in experimental traumatic brain injury plus hemorrhagic shock (TBI þ HS). Hypothesis: Resuscitation with PNPH will reduce intracranial pressure (ICP) and brain edema and improve cerebral perfusion pressure (CPP) vs. LR in experimental TBI þ HS. C57/BL6 mice (n ¼ 20) underwent controlled cortical impact followed by severe HS to mean arterial pressure (MAP) of 25 to 27 mm Hg for 35 minutes. Mice (n ¼ 10/group) were then resuscitated with a 20 mL/kg bolus of 4% PNPH or LR followed by 10 mL/kg boluses targeting MAP470 mm Hg for 90 minutes. Shed blood was then reinfused. Intracranial pressure was monitored. Mice were killed and %brain water (%BW) was measured (wet/dry weight). Mice resuscitated with PNPH vs. LR required less fluid (26.0 ± 0.0 vs. 167.0 ± 10.7 mL/kg, Po0.001) and had a higher MAP (79.4 ± 0.40 vs. 59.7 ± 0.83 mm Hg, Po0.001). The PNPH-treated mice required only 20 mL/kg while LR-resuscitated mice required multiple boluses. The PNPH-treated mice had a lower peak ICP (14.5±0.97 vs. 19.7±1.12 mm Hg, P ¼ 0.002), higher CPP during resuscitation (69.2 ± 0.46 vs. 45.5 ± 0.68 mm Hg, Po0.001), and lower %BW vs. LR (80.3 ± 0.12 vs. 80.9 ± 0.12%, P ¼ 0.003). After TBI þ HS, resuscitation with PNPH lowers fluid requirements, improves ICP and CPP, and reduces brain edema vs. LR, supporting its development. Keywords: blood substitute; cerebral edema; hemoglobin blood oxygen carrier; intracranial pressure; nitroxide; resuscitation INTRODUCTION Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in civilian and military settings and is often accompanied by secondary insults such as hemorrhage. Optimum resuscitation is critical given the severe consequences of hemorrhagic shock (HS) after TBI. Early hypotension is a strong clinical predictor of mortality after TBI, doubling mortality rates with a reduction in systolic blood pressure of as small as 10 mm Hg. 1 In blast polytrauma victims in Operation Iraqi Freedom, sustained hypotension was associated with 100% mortality. 2 Ischemia as a consequence of hypotension greatly worsens outcomes in TBI models. 3 Hypotension leads to impaired energy metabolism, 4 reduced neuroprotective gene expression, 5 and increased neuronal death. 6-8 After TBI, cerebral blood flow (CBF) can also be reduced. 9 Animal models of TBI have revealed impaired autoregulation, exacerbating ischemic injury. 10 At autopsy, most TBI patients show evidence of cerebral ischemia, 11 implicating hypoperfusion in secondary injury after TBI. Journal of Cerebral BloodOptimized resuscitation of TBI patients is critical given the consequences of hypotension, and multiple fluids have been studied. Traditional resuscitation fluids for TBI patients include

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“…Both 3% HTS and 20% mannitol had been investigated, either in humans or animals, for their physical effects on brain dehydration. 10,11 Both agents were evidenced to be effective in reducing brain bulk as showed by Min Li et al 12 and Wu et al, 6 but which is more effective ?. Sakellaidis et al 13 found no statistically significant difference using 20% mannitol and 15% HTS regarding ICP reduction, while Battison et al, 14 Wu et al 6 and others showed that HTS was superior to Mannitol 20%.…”

Section: Discussionmentioning

confidence: 99%

\"Balanced hyperosmolar therapy\" using 3% hypertonic saline - 20% mannitol versus an equiosmolar volume of either 3% hypertonic saline or mannitol 20% in supratentorial tumor resection: A new approach to achieve hemodynamic stability

Elkafrawy¹,

Khames²,

Kandeel³

2021

IJCA

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Both 3% hypertonic saline (3% HTS) and 20% mannitol were proven to be effective in relaxing the brain during supratentorial surgeries. This work aimed to study the effect of consecutive use of both drugs on the brain relaxation score and hemodynamic status during such surgeries.Ninety patients scheduled for supratentorial brain surgeries included in this prospective, randomized and double-blind study. Patients were allocated in three groups; HTS group (n=30) received 3 ml/kg 3% NaCl infusion over 30 minutes, HTS/M group (n=30) received mannitol 20% (1.4 ml/kg) as an infusion over 15 minute followed by 1.5 ml/kg 3% NaCl infused over 15 minutes and M group (n=30) received 3.2 ml/kg mannitol 20% infusion over 30 minutes. Brain relaxation was estimated. MAP and serum Na level were recorded at baseline and then at 30, 90 and 150 min. Total fluid intake, total urine output and operative time were recorded. Fluid intake and urine output were the highest with 20% mannitol (p ˂ 0.001). HTS/M and HTS groups showed no significance when satisfactory and fairly brain relaxation scores were added (p=0.862). MAP and CVP were near to baseline in HTS/M group at 30 and 90 min, while at 150 min no significant difference between groups. Serum hyperosmolarity was noticed in all groups at all check points but maximally with HTS group at 30 min (321.1 mOsm/L). Balanced hyperosmolar therapy using 3% HTS and 20% mannitol consecutively resulted in a satisfactory brain relaxation and allowed more hemodynamic stability.

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The relationship of fluid balance and sodium administration to cerebral edema formation and intracranial pressure in a porcine model of brain injury

Cited by 4 publications

References 0 publications

Polynitroxylated Pegylated Hemoglobin—A Novel, Small Volume Therapeutic for Traumatic Brain Injury Resuscitation: Comparison to Whole Blood and Dose Response Evaluation

Polynitroxylated Pegylated Hemoglobin—A Novel, Small Volume Therapeutic for Traumatic Brain Injury Resuscitation: Comparison to Whole Blood and Dose Response Evaluation

Polynitroxylated-Pegylated Hemoglobin Attenuates Fluid Requirements and Brain Edema in Combined Traumatic Brain Injury Plus Hemorrhagic Shock in Mice

\"Balanced hyperosmolar therapy\" using 3% hypertonic saline - 20% mannitol versus an equiosmolar volume of either 3% hypertonic saline or mannitol 20% in supratentorial tumor resection: A new approach to achieve hemodynamic stability

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