The Metabolism of an Exogenous Lipid Source during Septic Shock in the Puppy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142302/1/jpen0652.pd

Combined fluid and corticosteroid therapy in septic shock in puppies

The optimal treatment of septic shock remains controversial. In order to evaluate the efficacy of fluid resuscitation and corticosteroid administration, the following experimental study was undertaken. Forty-five puppies (1.6–5.4 kg) were randomly divided into 9 groups generated by combining 3 different fluid regimens and 3 different timings for steroid administration. Arterial, venous, and pulmonary artery catheterization allowed continuous hemodynamic and metabolic monitoring. Septic shock was achieved by a slow bolus infusion of 10 9 /kg Escherichia coli organisms. Methylprednisolone (30 mg/kg) was administered either 30 min before bacterial infusion, at the time of shock, or 30 min after shock. When cardiac output dropped to less than 50% of control values, 1 of the 3 following fluid resuscitation regimens was begun: 5% albumin in lactated Ringer's (LR) at 35% of the estimated blood volume (EBV), LR at 105% EBV, or 5% albumin in LR at 105% EBV. When all the groups were combined, early steroid treatment was more effective than delayed therapy, yielding respective survival rates of 47% and 7% at 180 min. Similarly, the large-volume resuscitation groups achieved a 43% survival rate compared to 13% for the smaller fluid protocols. Neither early steroid therapy nor large volume fluid therapy was shown by itself to increase survival, however. Despite steroid pretreatment, none of the puppies given the lower-volume infusion survived. Also, despite large-volume fluid resuscitation, there were no survivors when this was combined with steroid treatment that was delayed 30 min. Only by combining early steroid administration with large-volume fluid therapy was a markedly increased survival rate achieved: 60% with simultaneous steroid treatment, and 70% with steroid pretreatment. A definite increase in animal survival has, therefore, been shown in the acute period of severe septic shock using a combination of high-volume fluid resuscitation and the early administration of steroids. Le meilleur traitement du choc septique prête encore à controverse. Pour le déterminer, une étude expérimentale a été entreprise de manière à apprécier l'efficacité de la compensation liquidienne et celle des corticoïdes. Pour ce faire, 45 chiots (1,6–5,4 kg) furent randomisés en 9 groupes en combinant l'administration de 3 types de liquide et celles des stéroïdes à 3 moments différents. Le cathétérisme artériel, veineux et celui de l'artère pulmonaire permirent l'étude continue de l'hémodynamique et des métabolismes. Le choc septique fut provoqué par l'injection lente d'un bolus constitué de 10 9 /kg d'E. Coli. Le méthylprednisolone (30 mg/kg) fut employé 30 minutes avant l'injection, au moment du choc ou encore après le choc. Dès que le débit sanguin fut réduit de la moitié, la réanimation par apport liquidien fut assurée suivant 3 protocoles différents: injection de solution de Ringer enrichi de 5% d'albumine (35% du volume sanguin ou 105% du volume sanguin), solution de Ringer pur (105% du volume sanguin). Les résultats furent les suivants: l'administration précoce des stéroïdes fut plus efficace que l'administration tardive, se traduisant par un taux respectif de survie de 47% dans le premier cas et de 7% dans la seconde éventualité. De façon identique, l'injection importante de liquide se solda par un taux de survie de 43% alors que celui de l'injection limitée ne dépassa pas 7%. Cependant, ni la corticothérapie précoce, ni la compensation liquidienne importante n'augmenta par elle-même la survie. Aucun des chiots qui furent soumis à la corticothérapie précoce mais ne reçurent que peu de liquide ne survécut. Il en fut de même lorsque le chiot reçut un apport liquidien important et fut soumis à la corticothérapie tardive. C'est seulement en combinant la corticothérapie précoce et un apport liquidien important que le taux de survie fut amélioré: 70% quand la corticothérapie fut entreprise avant le choc, 60% lorsque les stéroïdes furent injectés au moment ou le choc fut provoqué. Le choc est susceptible d'être jugulé seulement par l'administration précoce de corticoïdes et par un apport liquidien important; telle est la conclusion des auteurs. El tratamiento óptimo del shock séptico sigue siendo motivo de controversia. Con el objeto de evaluar la eficacia de la resucitación con líquido y la administración de corticoesteroides, se acometío el siguiente estudio experimental. Cuarenta y cinco cachorros (1.6–5.4 kg) fueron divididos al azar en 9 grupos generados por la combinación de 3 diferentes regímenes de líquidos y 3 diferentes programas para la administración de esteroides. El cateterismo arterial, venoso y de arteria pulmonar permitió la monitoría continua hemodinámica y metabólica. El shock séptico fue inducido mediante la infusión lenta de un bolo de 10 9 /kg de microorganismos E. coli . Se administró metilprednisolona (30 mg/kg) 30 minutos antes de la infusión bacteriana, o en el momento del shock, o 30 minutos después del shock. Una vez que el débito cardiaco hubo descendido a menos del 50% de los valores de control, uno de tres regímenes de resucitación fue iniciado: albúmina al 5% en lactato de Ringer (LR) a razón de 35% del volumen sanguíneo estimado (VSE), LR a razón de 105% VSE, o albúmina al 5% en LR a razón de 105% VSE.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41312/1/268_2005_Article_BF01655350.pd

Modification of the serum bromide assay for the measurement of extracellular fluid volume in small subjects

Serum bromide has been used in the past to measure extracellular fluid volume in infants. In this report, a modification and refinement of a previously described spectrophotometric assay suitable for determining bromide levels in blood is presented. The assay involves sample deproteinization with perchloric acid followed by spectrophotometric analysis of the complexes formed by the reaction between sodium bromide and gold chloride. Linear standard curves were obtained by diluting 1:2 with pooled serum at the following bromide concentrations: 10, 20, 30 and 40 mg%. Intra- and interassay variation using this technique was extremely small (n = 6, correlation coefficient, 0.995, and n = 5, correlation coefficient, 0.988, respectively). For toxicological analysis, a linear standard curve was derived from sodium bromide standards at the following concentrations: 40, 60, 80, and 100 mg%. The reproducibility and reliability of this assay have been excellent and the correlaton with neutron activation analysis was excellent. The assay is easily adapted for the analysis of large numbers of samples, is easy to perform, and requires only small sample volumes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23820/1/0000059.pd

Interleukin-6 changes tight junction permeability and intracellular phospholipid content in a human enterocyte cell culture model

Proinflammatory cytokines and secretory phospholipase A 2 (sPLA 2 ) are elevated in patients with inflammatory bowel disease (IBD). We previously reported that the proinflammatory cytokine IL-6 increased the expression of sPLA 2 (a hydrolyzer of phosphatidylcholine) and decreased membrane integrity in an intestinal epithelial cell culture model. To determine the physiological effects of the IL-6 mediated increase in sPLA 2 on decreased epithelial layer integrity, we investigated alterations of intracellular/secretory phospholipid (PL) composition in a cell culture model. In addition, since other PLs may also mediate epithelial membrane activity, we investigated the effect of IL-6 on PL activity in a Caco-2 enterocyte culture model. Caco-2 cells were incubated for 72 h with IL-6 or media alone (control). Both media and cell lysate were analyzed for PL composition using thin-layer chromatography. The PL composition in the media did not show any differences between the two groups ( p >0.1). Total intracellular PL contents were also unchanged; however, IL-6 led to significant changes in PL composition including an increase in phosphatidylethanolamine (PE) and sphingomyelin (SM) and a decrease in phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) ( p <0.05). Both PE and SM are known as inflammatory signaling factors involved in human IBD. Our study suggests that the decreased membrane integrity seen with IL-6 application may occur via intracellular PL alterations, rather than through the direct effects of sPLA 2 .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47156/1/383_2003_Article_1003.pd

CT appearance of the spleen following conservative management of traumatic injury

Objective: To describe the long-term changes in the traumatized spleen following conservative management in pediatric patients. Methods: Between 1991 and 1997, 92 children were imaged with splenic trauma. The study population includes the 25 boys and 11 girls with follow-up computed tomography (CT) imaging at our institution. The follow-up CT studies were evaluated to determine the evolution of splenic injury. Results: On initial CT there were 6 grade I, 12 grade II, 9 grade III, and 9 grade IV–V splenic injuries. In follow-up 11 spleens were normal (30 %), including at least one in each grade of severity of injury. Splenic abnormalities were identified on follow-up in 25 children. These findings comprised clefts in 8 children, small cysts in 4, and devascularized segments involving less than 1 cm 3 in 6, 1–2 cm 3 in 2, and 2–4 cm 3 in 5 children. Conclusions: All grades of splenic injury can resolve completely on subsequent CT imaging. In this series 30 % of patients had a normal follow-up CT. The most common persistent abnormalities included clefts and devascularized areas less than 4 cm 3 .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42349/1/10140-6-3-157_90060157.pd

The effect of hypoxia on permeability and bacterial translocation in Caco-2 adult and I-407 fetal enterocyte cell culture models

Hypoxia has been implicated in the breakdown of the intestinal epithelial barrier in animals, leading to bacterial translocation (BT); however, the mechanism of this hypoxic insult is unknown. To determine the effects of hypoxic injury in vitro on epithelial membrane integrity, transepithelial electrical resistance (TEER), mannitol permeability (Ma-Pm), and BT were measured in both an adult (Caco-2) and fetal (I-407) intestinal epithelial cell culture model. Caco-2 adult and I-407 fetal epithelial cell monolayers were treated with or without bacteria (1×10 7 Escherichia coli. C-25), and then incubated under either normoxic (5% CO 2 in room air) or hypoxic (5% CO 2 and 95% N 2 ) conditions at 37°C for 6 h. Hypoxia caused a 10% increase in Ma-Pm in the I-407 fetal cell model independent of the bacterial challenge. In contrast, a bacterial challenge in the Caco-2 adult model caused a 485% increase in Ma-Pm independent of hypoxia. Neither hypoxia, nor C-25 bacteria, for 6 h caused BT in either cell culture model. In the adult cell culture model, bacteria appear to mediate changes in epithelial barrier function, with hypoxia having no effect. On the other hand, hypoxia is the major factor in the loss of epithelial barrier function in fetal epithelium, but has no effect on adult epithelium. The data suggest that the breakdown of barrier function caused by a hypoxic insult is the primary stimulus for subsequent BT in neonates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47155/1/383_2003_Article_1002.pd

Bacterial translocation in the newborn rabbit: effect of age on frequency of translocation

Sepsis is a significant cause of morbidity and mortality in neonates, and in a significant number of cases no predisposing factors can be identified. We hypothesize that bacterial translocation (BT) may be the etiology of neonatal sepsis when no source is identified. Mesenteric lymph nodes (MLN), spleen (SPL), and liver (LIV) were harvested from 36 rabbit pups ranging in age from 4 to 24 days and divided into three groups based on their age: group I, 4–6 days; group II, 13–15 days; and group III, 22–24 days. Tissues from each organ were homogenized and placed in both aerobic and anaerobic environments. After 48 h the number of colony-forming units/g tissue was identified. The total percentage of positive growth was significantly higher in group I for MLN (33%) and LIV (23%) when compared to groups II and III (<4% for both groups). Gram-negative growth (as selected by MacConkey [MC] media) was significantly higher in all tissue specimens from group I (MLN + 35%, SPL = 20%, LIV = 25%) compared to groups II and III (0% growth in all MC plates, P <0.01). These data support the hypothesis that spontaneous BT occurs with significant frequency in the neonate.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47149/1/383_2004_Article_BF00171174.pd

Trauma scores, accident deformity codes, and car restraints in children

The importance and effectiveness of the appropriate use of automobile restraints by young children has been emphasized in several studies. Once the child has entered the emergency care system, however, restraint use may not be the best predictor of injury severity. This study was undertaken to investigate the relationship of restraint status to morbidity and mortality in children examined in a hospital emergency facility following involvment in a motor vehicle crash (MVC). The emergency room charts of 101 children under 18 years of age, who were victims of MVCs, were reviewed and the following trauma scores were calculated: Glascow Coma Scale, Pediatric Trauma Score, Revised Trauma Score, Injury Severity Score, and Maximum Abbreviated Injury Score. In addition, the Traffic Accident Damage (TAD) score, an estimate of crash severity determined by the police at the accident scene, was recorded. The patients were age stratified as follows: 0 to 4 years (n = 24), 5 to 11 years (n = 29), and 12 to 17 years (n = 48). Fifty patients were appropriately restrained at the time of the crash. There was a significant correlation between mean trauma scores and mean TAD codes (P P &gt; .05) across all age groups, and these children were grouped together as "unrestrained" in further analyses. In the 0 to 4 age group, there were no significant differences in mean trauma scores between restrained and improperly restrained or unrestrained children in contrast to the 5 to 11 and the 12 to 17 age groups. There were no significant difference between the distribution of restrained and unrestrained victims with regard to mean TAD scores (P = .5224) in the 0 to 4 age group. This study demonstrates a close correlation between mean trauma scores and vehicle deformity in all age groups, and shows that mean trauma scores appear to be independent of restraint use for the 0 to 4-year-old age subset. Therefore, a police-assigned crash severity score, such as the TAD, may be useful in the initial traige of pediatric trauma victims to an appropriate hospital or trauma center.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31099/1/0000777.pd

Extracellular fluid and total body water changes in neonates undergoing extracorporeal membrane oxygenation

After being placed on extracorporeal life support (ECLS), newborn patients typically weight 5% to 30% more than their birthweight. Recovery and eventual decannulation from ECLS is associated with a return to baseline weight or birthweight values after a pronounced diuresis. It has been assumed that the increases in weight in these patients are due to increases in extracellular fluid (ECF) and total body water (TBW). This study was undertaken to prove or disprove this hypothesis. ECF space was measured using the compound sodium bromide and TBW was determined with the use of deuterium oxide (nonradioactive heavy water). Fluid compartment measurements were made prior to the institution of ECLS, immediately after placement on bypass, approximately every other day while on bypass, and a final measurement was made once the patient was off bypass. Sodium bromide concentration was analyzed by high-pressure liquid chromatography, and deuterium oxide concentration was measured by the falling drop method. Eight newborns with respiratory failure were placed on either venoarterial (4 patients) or venovenous (4 patients) ECLS for an average of 106 hours (range, 71 to 219 hours). Pre-ECLS TBW was high in the neonates (87% of total body weight v the normal of 75% to 80%). Mean values for each fluid compartment were corrected for the additional volume of the bypass circuit when the patient was on bypass. ECF increased immediately after the institution of ECLS; however, both ECF and TBW decreased during the bypass run, and post-ECLS levels of ECF and TBW were similar to those found prior to ECLS. Body weight increased significantly at the onset of ECLS and returned to near pre-ECLS (birthweight) levels at the conclusion of bypass. We conclude that neonates with respiratory distress, once placed on ECLS, have increased body weight, ECF, and TBW, which decrease during the course of ECLS, and reach baseline levels. These decreases in weight, ECF, and TBW appear to be associated with lung recovery.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30366/1/0000768.pd

Increased respiratory symptoms following surgery in children exposed to environmental tobacco smoke

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75635/1/j.1460-9592.2003.01100.x.pd