Mechanisms and implications of hypoalbuminemia in head-injured patients

1988 ◽  
Vol 69 (3) ◽  
pp. 386-392 ◽  
Author(s):  
Craig J. McClain ◽  
Bernhard Hennig ◽  
Linda G. Ott ◽  
Simeon Goldblum ◽  
A. Byron Young
Keyword(s):  
Endothelial Cell ◽  
Acute Phase ◽  
Nutritional Support ◽  
Cell Injury ◽  
Acute Phase Proteins ◽  
Interleukin 1 ◽  
Endothelial Permeability ◽  
Content Type ◽  
Head Injured ◽  
Injured Patients

✓ Severely head-injured patients are hypermetabolic/hypercatabolic and exhibit many aspects of the postinjury acute-phase response. These patients have hypoalbuminemia, hypozincemia, hypoferremia, hypercupria, fever, and increased synthesis of acute-phase proteins such as ceruloplasmin and higher C-reactive protein levels. It has been suggested that increased interleukin-1 (IL-1) in the ventricular fluid may be responsible, at least in part, for these metabolic abnormalities. In the present study, serum albumin levels were evaluated throughout an 18-day study period in 62 head-injured patients receiving aggressive nutritional support. Hypoalbuminemia (mean ± standard error of the mean 3.10 ± 0.2 gm/dl; normal value 3.5 to 5 gm/dl) was observed upon hospital admission; these albumin levels continued to decrease until 2 weeks postinjury, despite aggressive nutritional support. This hypoalbuminemia may be mediated via altered endothelial permeability properties due to endothelial cell dysfunction caused by cytokines such as IL-1. Transendothelial movement of albumin was assayed using a pulmonary artery endothelial cell culture system. Both a crude macrophage supernatant derived from a murine P388D cell line having IL-1 activity (mIL-1) and human recombinant IL-1 (rIL-1) were tested. The amount of albumin transferred was time- and concentration-dependent, with maximal transfer at 24 hours and 20 U of mIL-1 per 0.5 ml of culture medium. Endothelial permeability changes observed after incubation with mIL-1 were confirmed using rIL-1. Compared to control cultures, 20 U of rIL-1 and 20 U of mIL-1 increased albumin transfer across endothelial monolayers 205% and 459%, respectively. These findings suggest that the mechanism of hypoalbuminemia seen after severe head trauma can be explained in part by IL-1-induced endothelial cell injury, resulting in enhanced endothelial permeability to albumin.

Verbal learning deficits following severe head injury: heterogeneity in recovery over 1 year

1991 ◽  
Vol 75 (Supplement) ◽  
pp. S50-S58 ◽  
Author(s):  
Ronald M. Ruff ◽  
David Young ◽  
Theresa Gautille ◽  
Lawrence F. Marshall ◽  
Jeff Barth ◽  
...  
Keyword(s):  
Memory Performance ◽  
Verbal Learning ◽  
Data Bank ◽  
Learning Deficits ◽  
Content Type ◽  
Recovery Curve ◽  
Recovery Curves ◽  
Head Injured ◽  
Injured Patients ◽  
Case Basis

✓ A total of 40 severely head-injured patients were selected from the Traumatic Coma Data Bank, supported by the National Institute of Neurological Disorders and Stroke, to analyze the recovery of verbal learning across baseline and 6- and 12-month evaluations postinjury. During the initial 6 months, the group demonstrated marked recovery, followed by an absence of improvement over the latter part of the year. Analysis of this recovery curve on a case by case basis revealed three recovery subtypes: namely, a flat curve, a peak-drop curve, or an improvement curve. These three subtypes proved to have concurrent validity when compared with another memory test. Adding 19 new patients to the sample cross-validated the subtypes. However, the memory performance of the 59 patients was dissociated from other neuropsychological tests which showed recovery at more equivalent rates across the subtypes. Analysis of the demographic and neurological characteristics disclosed that the group with a peak-drop recovery curve was less well educated and the group with a flat curve demonstrated a trend toward higher levels of hypoxia. Moreover, the three subgroups were rated by their relatives to have equivalent levels of depression at baseline and at 6 months, but only the improved subgroup demonstrated reduced depression at 1 year. The clinical relevancy of these differential recovery curves is discussed.

scholarly journals Comparison of host endothelial, epithelial and inflammatory response in ICU patients with and without COVID-19: a prospective observational cohort study

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Pavan K. Bhatraju ◽  
Eric D. Morrell ◽  
Leila Zelnick ◽  
Neha A. Sathe ◽  
Xin-Ya Chai ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Epithelial Cell ◽  
Acute Phase ◽  
Cell Injury ◽  
Acute Phase Proteins ◽  
Invasive Mechanical Ventilation ◽  
Icu Patients ◽  
Icu Admission ◽  
Amyloid A ◽  
Epithelial Cell Injury

Abstract Background Analyses of blood biomarkers involved in the host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection can reveal distinct biological pathways and inform development and testing of therapeutics for COVID-19. Our objective was to evaluate host endothelial, epithelial and inflammatory biomarkers in COVID-19. Methods We prospectively enrolled 171 ICU patients, including 78 (46%) patients positive and 93 (54%) negative for SARS-CoV-2 infection from April to September, 2020. We compared 22 plasma biomarkers in blood collected within 24 h and 3 days after ICU admission. Results In critically ill COVID-19 and non-COVID-19 patients, the most common ICU admission diagnoses were respiratory failure or pneumonia, followed by sepsis and other diagnoses. Similar proportions of patients in both groups received invasive mechanical ventilation at the time of study enrollment. COVID-19 and non-COVID-19 patients had similar rates of acute respiratory distress syndrome, severe acute kidney injury, and in-hospital mortality. While concentrations of interleukin 6 and 8 were not different between groups, markers of epithelial cell injury (soluble receptor for advanced glycation end products, sRAGE) and acute phase proteins (serum amyloid A, SAA) were significantly higher in COVID-19 compared to non-COVID-19, adjusting for demographics and APACHE III scores. In contrast, angiopoietin 2:1 (Ang-2:1 ratio) and soluble tumor necrosis factor receptor 1 (sTNFR-1), markers of endothelial dysfunction and inflammation, were significantly lower in COVID-19 (p < 0.002). Ang-2:1 ratio and SAA were associated with mortality only in non-COVID-19 patients. Conclusions These studies demonstrate that, unlike other well-studied causes of critical illness, endothelial dysfunction may not be characteristic of severe COVID-19 early after ICU admission. Pathways resulting in elaboration of acute phase proteins and inducing epithelial cell injury may be promising targets for therapeutics in COVID-19.

scholarly journals Immunization with Pneumococcal Polysaccharide Serotype 3 and Lipopolysaccharide Modulates Lung and Liver Inflammation during a Virulent Streptococcus pneumoniae Infection in Mice

2013 ◽  
Vol 20 (5) ◽  
pp. 639-650 ◽  
Author(s):  
Katherine H. Restori ◽  
Mary J. Kennett ◽  
A. Catharine Ross
Keyword(s):  
Gene Expression ◽  
Streptococcus Pneumoniae ◽  
Acute Phase ◽  
Acute Phase Proteins ◽  
Expression Profiles ◽  
Cytokine Gene Expression ◽  
Dependent Manner ◽  
Pneumonia Severity ◽  
Content Type ◽  
Amyloid A

ABSTRACTVaccination reduces morbidity and mortality from pneumonia, but its effect on the tissue-level response to infection is still poorly understood. We evaluated pneumonia disease progression, acute-phase response, and lung gene expression profiles in mice inoculated intranasally with virulent Gram-positiveStreptococcus pneumoniaeserotype 3 (ST 3) with and without prior immunization with pneumococcal polysaccharide ST 3 (PPS3) or after coimmunization with PPS3 and a low dose of lipopolysaccharide (PPS3+LPS). Pneumonia severity was assessed in the acute phase at 5, 12, 24 and 48 h postinoculation (p.i.) and in the resolution phase at 7 days p.i. Primary PPS3-specific antibody production was upregulated, and IgM binding to pneumococci increased in PPS3-immunized mice. Immunizations with PPS3 or PPS3+LPS decreased bacterial recovery in the lung and blood at 24 and 48 h and increased survival. Microarray analysis of whole-lung RNA revealed significant changes in the acute-phase protein serum amyloid A (SAA) levels between noninfected and infected mice, and these changes were attenuated by immunization. SAA transcripts were higher in the liver and lungs of infected controls, and SAA protein was elevated in serum but decreased in PPS3-immunized mice. Thus, during a virulent pneumonia infection, prior immunization with PPS3 in an IgM-dependent manner as well as immunization with PPS3+LPS attenuated pneumonia severity and promoted resolution of infection, concomitant with significant regulation of cytokine gene expression levels in the lungs and acute-phase proteins in the lungs, liver, and serum.

Contribution of CSF and vascular factors to elevation of ICP in severely head-injured patients

1987 ◽  
Vol 66 (6) ◽  
pp. 883-890 ◽  
Author(s):  
Anthony Marmarou ◽  
Angelo L. Maset ◽  
John D. Ward ◽  
Sung Choi ◽  
Danny Brooks ◽  
...  
Keyword(s):  
Severe Head Injury ◽  
Ventricular Catheter ◽  
Outflow Resistance ◽  
Content Type ◽  
Relative Contribution ◽  
Temporal Course ◽  
Head Injured ◽  
Predominant Factor ◽  
Injured Patients ◽  
Fine Print

✓ The authors studied the relative contribution of cerebrospinal fluid (CSF) and vascular parameters to the level of intracranial pressure (ICP) in 34 severely head-injured patients with a Glasgow Coma Scale score of less than 8. This was accomplished by first characterizing the temporal course of CSF formation and outflow resistance during the 5-day period postinjury. The CSF formation and outflow resistance were obtained from pressure responses to bolus addition and removal of fluid from an indwelling ventricular catheter. The vascular contribution to the level of ICP was assessed by withdrawing fluid at its rate of formation and observing the resultant change in equilibrium ICP level. It was found that, with the exception of patients with subarachnoid hemorrhage, CSF parameters accounted for approximately one-third of the ICP rise after severe head injury, and that a vascular mechanism may be the predominant factor in elevation of ICP.

Outcome from head injury related to patient' age

1988 ◽  
Vol 68 (3) ◽  
pp. 409-416 ◽  
Author(s):  
Thomas G. Luerssen ◽  
Melville R. Klauber ◽  
Lawrence F. Marshall
Keyword(s):  
Mortality Rate ◽  
Pediatric Population ◽  
Adult Population ◽  
Content Type ◽  
Head Injured ◽  
Injured Patients ◽  
Age Range ◽  
Relationship Of ◽  
The Relationship ◽  
Pupillary Reactivity

✓ A series of 8814 head-injured patients admitted to 41 hospitals in three separate metropolitan areas were prospectively studied. Of these, 1906 patients (21.6%) were 14 years of age or less. This “pediatric population” was compared to the remaining “adult population” for mechanism of injury, admission Glasgow Coma Scale score, motor score, blood pressure, pupillary reactivity, the presence of associated injuries, and the presence of subdural or epidural hematoma. The relationship of each of these factors was then correlated with posttraumatic mortality. Except for patients found to have subdural hematoma and those who were profoundly hypotensive, the pediatric patients exhibited a significantly lower mortality rate compared to the adults, thus confirming this generally held view. This study indicates that age itself, even within the pediatric age range, is a major independent factor affecting the mortality rate in head-injured patients.

Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial

1991 ◽  
Vol 75 (5) ◽  
pp. 731-739 ◽  
Author(s):  
J. Paul Muizelaar ◽  
Anthony Marmarou ◽  
John D. Ward ◽  
Hermes A. Kontos ◽  
Sung C. Choi ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Control Group ◽  
Content Type ◽  
Cerebral Vasoconstriction ◽  
Number Of Patients ◽  
Severity Of Injury ◽  
Head Injured ◽  
Injured Patients ◽  
To Receive

✓ There is still controversy over whether or not patients should be hyperventilated after traumatic brain injury, and a randomized trial has never been conducted. The theoretical advantages of hyperventilation are cerebral vasoconstriction for intracranial pressure (ICP) control and reversal of brain and cerebrospinal fluid (CSF) acidosis. Possible disadvantages include cerebral vasoconstriction to such an extent that cerebral ischemia ensues, and only a short-lived effect on CSF pH with a loss of HCO3− buffer from CSF. The latter disadvantage might be overcome by the addition of the buffer tromethamine (THAM), which has shown some promise in experimental and clinical use. Accordingly, a trial was performed with patients randomly assigned to receive normal ventilation (PaCO2 35 ± 2 mm Hg (mean ± standard deviation): control group), hyperventilation (PaCO2 25 ± 2 mm Hg: HV group), or hyperventilation plus THAM (PaCO2 25 ± 2 mm Hg: HV + THAM group). Stratification into subgroups of patients with motor scores of 1–3 and 4–5 took place. Outcome was assessed according to the Glasgow Outcome Scale at 3, 6, and 12 months. There were 41 patients in the control group, 36 in the HV group, and 36 in the HV + THAM group. The mean Glasgow Coma Scale score for each group was 5.7 ± 1.7, 5.6 ± 1.7, and 5.9 ± 1.7, respectively; this score and other indicators of severity of injury were not significantly different. A 100% follow-up review was obtained. At 3 and 6 months after injury the number of patients with a favorable outcome (good or moderately disabled) was significantly (p < 0.05) lower in the hyperventilated patients than in the control and HV + THAM groups. This occurred only in patients with a motor score of 4–5. At 12 months posttrauma this difference was not significant (p = 0.13). Biochemical data indicated that hyperventilation could not sustain alkalinization in the CSF, although THAM could. Accordingly, cerebral blood flow (CBF) was lower in the HV + THAM group than in the control and HV groups, but neither CBF nor arteriovenous difference of oxygen data indicated the occurrence of cerebral ischemia in any of the three groups. Although mean ICP could be kept well below 25 mm Hg in all three groups, the course of ICP was most stable in the HV + THAM group. It is concluded that prophylactic hyperventilation is deleterious in head-injured patients with motor scores of 4–5. When sustained hyperventilation becomes necessary for ICP control, its deleterious effect may be overcome by the addition of THAM.

Impairment of helper T-cell function and lymphokineactivated killer cytotoxicity following severe head injury

1991 ◽  
Vol 75 (5) ◽  
pp. 766-773 ◽  
Author(s):  
Keith B. Quattrocchi ◽  
Edmund H. Frank ◽  
Claramae H. Miller ◽  
Asim Amin ◽  
Bernardo W. Issel ◽  
...  
Keyword(s):  
T Cell ◽  
Head Injury ◽  
Severe Head Injury ◽  
Cell Cytotoxicity ◽  
Content Type ◽  
Lak Cell ◽  
Head Injured ◽  
Injured Patients ◽  
Fine Print

✓ Infection is a major complication of severe head injury, occurring in 50% to 75% of patients who survive to hospitalization. Previous investigations of immune activity following head injury have demonstrated suppression of helper T-cell activation. In this study, the in vitro production of interferon-gamma (INF-γ), interleukin-1 (IL-1), and interleukin-2 (IL-2) was determined in 25 head-injured patients following incubation of peripheral blood lymphocytes (PBL's) with the lymphocyte mitogen phytohemagglutinin (PHA). In order to elucidate the functional status of cellular cytotoxicity, lymphokine-activated killer (LAK) cell cytotoxicity assays were performed both prior to and following incubation of PBL's with IL-2 in five patients with severe head injury. The production of INF-γ and IL-2 by PHA-stimulated PBL's was maximally depressed within 24 hours of injury (p < 0.001 for INF-γ, p = 0.035 for IL-2) and partially normalized within 21 days of injury. There was no change in the production of IL-1. When comparing the in vitro LAK cell cytotoxicity of PBL's from head-injured patients and normal subjects, there was a significant depression in LAK cell cytotoxicity both prior to (p = 0.010) and following (p < 0.001) incubation of PBL's with IL-2. The results of this study indicate that IL-2 and INF-γ production, normally required for inducing cell-mediated immunity, is suppressed following severe head injury. The failure of IL-2 to enhance LAK cell cytotoxicity suggests that factors other than decreased IL-2 production, such as inhibitory soluble mediators or suppressor lymphocytes, may be responsible for the reduction in cellular immune activity following severe head injury. These findings may have significant implications in designing clinical studies aimed at reducing the incidence of infection following severe head injury.

The metabolic response to severe head injury

1984 ◽  
Vol 60 (4) ◽  
pp. 687-696 ◽  
Author(s):  
Guy L. Clifton ◽  
Claudia S. Robertson ◽  
Robert G. Grossman ◽  
Susan Hodge ◽  
Richard Foltz ◽  
...  
Keyword(s):  
Body Surface ◽  
Nitrogen Balance ◽  
Metabolic Response ◽  
The Body ◽  
Nitrogen Excretion ◽  
Content Type ◽  
Head Injured ◽  
The Mean ◽  
Metabolic Expenditure ◽  
Injured Patients

✓ Caloric expenditure and nitrogen balance were measured in 14 steroid-treated comatose head-injured patients acutely and up to 28 days after injury. During this period patients were fed with a continuous enteral infusion of a formula containing 2 Kcal/cc and 10 gm nitrogen/liter. Indirect calorimetry was carried out for 102 patient-days. The mean resting metabolic expenditure (RME) for nonsedated nonparalyzed patients was 138% ± 37% of that expected for an uninjured resting person of equivalent age, sex, and body surface area. Nitrogen excretion was measured for 135 patient-days. The mean excretion was 20.2 ± 6.4 gm/day. The mean protein caloric contribution was 23.9% ± 6.7% and was greater than 25% for six patients, compared to normal values of 10% to 15%. Despite hyperalimentation, positive nitrogen balance for any 3-day period was achieved in only seven patients, and required replacement of 161% to 240% of RME with enterally administered formula. Head-injured patients had a metabolic response similar to that reported for patients with burns of 20% to 40% of the body surface.

Prediction tree for severely head-injured patients

1991 ◽  
Vol 75 (2) ◽  
pp. 251-255 ◽  
Author(s):  
Sung C. Choi ◽  
Jan P. Muizelaar ◽  
Thomas Y. Barnes ◽  
Anthony Marmarou ◽  
Danny M. Brooks ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Predictive Accuracy ◽  
Head Injuries ◽  
Pupillary Response ◽  
Prognostic Indicators ◽  
Critical Threshold ◽  
Content Type ◽  
Intermediate Outcomes ◽  
Head Injured ◽  
Injured Patients

✓ Prediction tree techniques are employed in the analysis of data from 555 patients admitted to the Medical College of Virginia hospitals with severe head injuries. Twenty-three prognostic indicators are examined to predict the distribution of 12-month outcomes among the five Glasgow Outcome Scale categories. A tree diagram, illustrating the prognostic pattern, provides critical threshold levels that split the patients into subgroups with varying degrees of risk. It is a visually useful way to look at the prognosis of head-injured patients. In previous analyses addressing this prediction problem, the same set of prognostic factors (age, motor score, and pupillary response) was used for all patients. These approaches might be considered inflexible because more informative prediction may be achieved by somewhat different combinations of factors for different patients. Tree analysis reveals that the pattern of important prognostic factors differs among various patient subgroups, although the three previously mentioned factors are still of primary importance. For example, it is noted that information concerning intracerebral lesions is useful in predicting outcome for certain patients. The overall predictive accuracy of the tree technique for these data is 77.7%, which is somewhat higher than that obtained via standard prediction methods. The predictive accuracy is highest among patients who have a good recovery or die; it is lower for patients having intermediate outcomes.

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