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Improved hemodynamics with a novel chest compression device during treatment of inhospital cardiac arrest

129 pages
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Ajouté le : 01 janvier 2003
Lecture(s) : 8
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Critical Care Volume 7 Suppl 2, 2003 23rd International Symposium on Intensive Care and Emergency Medicine Brussels, Belgium, 18–21 March 2003
Published online: 3 March 2003 This article is online at http://ccforum.com/supplements/7/S2 © 2003 BioMed Central Ltd (Print ISSN 13648535; Online ISSN 1466609X)
P1 Endocrinedysfunction in the immediate period following traumatic brain injury I Dimopoulou, S Tsagarakis, G Assithianakis, M Christoforaki, M Theodorakopoulou, A Kouyialis, S Korfias, N Thalassinos, C Roussos Department of Critical Care Medicine and Department of Endocrinology, Evangelismos Hospital, Athens, Greece Critical Care2003,7(Suppl 2):P001 (DOI 10.1186/cc1890) Studies on head injuryinduced pituitary dysfunction are limited inserum fT4 level was associated with a normal or low TSH. Hypogo number and conflicting results have been reported. To further clarifynadism was considered when T (males) or E2 (women) were below this issue, 29 consecutive patients (24 males), with severe (nthe local reference ranges, in the presence of normal PRL levels.= 21) or moderate (nhead trauma, having a mean age of= 8)Severe or partial GH deficiencies were defined as a peak GH 37 ± 17 yearswere investigated in the immediate posttraumabelow 3µg/l or between 3 and 5µg/l, respectively, after stimulation period. All patients required mechanical ventilatory support forwith GHRH. Twentyone subnormal responses were found in 15 of 8–55 days and were enrolled in the study within a few days beforethe 29patients (52%) tested; seven (24%) had hypogonadism, ICU discharge. Basal hormonal assessment included measurementseven (24%) had cortisol hyporesponsiveness, five (17%) had of cortisol, corticotropin, free thyroxine (fT4), thyrotropin (TSH),hypothyroidism, and two patients (7%) had partial GH deficiency. testosterone (T) in men, estradiol (E2) in women, prolactin (PRL), and growth hormone (GH). Cortisol and GH levels were measuredThese preliminary results suggest that a certain degree of hypo also after stimulation with 100µg human corticotropin releasingpituitarism occurs in more than 50% of patients with moderate or hormone (hCRH) and 100µg growth hormone releasing hormonesevere head injury in the immediate posttrauma period, with cortisol (GHRH), respectively. Cortisol hyporesponsiveness was considhyporesponsiveness and hypogonadism being most common. Further ered when peak cortisol concentration was less than 20µstudies are required to elucidate the pathogenesis of these abnorg/dl fol lowing hCRH. TSH deficiency was diagnosed when a subnormalmalities and to investigate whether they affect longterm morbidity. P2 Cortisolreserve in head trauma victims: evaluation with the lowdose (1µg) corticotropin (ACTH) stimulation test I Dimopoulou, A Kouyialis, S Tsagarakis, M Theodorakopoulou, G Assithianakis, M Christoforaki, N Thalassinos, C Roussos Department of Critical Care Medicine and Department of Endocrinology, Evangelismos Hospital, Athens, Greece Critical Care2003,7(Suppl 2):P002 (DOI 10.1186/cc1891) To investigate cortisol reserve in head trauma, 35consecutive 49± 27 pg/ml,19.7 ± 5.5µg/dl and 23.6± 6.7µg/dl, respectively. patients (30men) with a mean age of 36± 16 yearswere studiedSix of the 35 patients (17%) failed the LDST. Nonresponders were 5–60 days after physical injury. Patients were enrolled in the studysimilar to responders with regard to age, gender, and severity of within a few days before ICU discharge. First, a morning bloodhead injury. However, nonresponders more frequently required sample was obtained to measure baseline cortisol, and ACTHvasopressors (6/6 vs 14/29,P= 0.02)and for a longer time inter plasma levels. Subsequently, 1µg synthetic ACTH was injectedval (median, 293 hours vs 24 hours,P= 0.01)to maintain haemo intravenously and, 30 min later, a second blood sample was drawndynamic stability compared with responders to the LDST. to determine stimulated plasma cortisol. Patients having stimulated cortisol levels below 18µg/dl were defined as nonresponders toIn conclusion, adrenal cortisol secretion following dynamic stimula the lowdose stimulation test (LDST). Mean (±SD) values fortion is deficient in a subset of head injury patients; this condition is ACTH, baseline, and stimulated cortisol concentrations wereassociated with vasopressor dependency. P3 Steroidhormone synthesis is impaired in patients with severe sepsis M Angstwurm, A Rashidi Kia, J Schopohl, R Gaertner Medical Intensive Care Unit, Medizinische Klinik, Ziemssenstraße 1, 80336 Munich, Germany Critical Care2003,7(Suppl 2):P003 (DOI 10.1186/cc1892) In patients with severe illness, adrenal insufficiency is often susWe analyzed the synthesis of different steroid hormones within pected and treatment with hydrocortisone has been shown tothe adrenal in severely ill patients in a prospective study using decrease mortality. However, the pathophysiology of an adrenalthe established high dose stimulation test with synthetic failure is only partially understood.cosyntropin.S1
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Using commercially available essays, the steroid hormones proges terone, cortisole, testosterone, dehydroepiandrostenedione (DHEAS) and 17βminestradiol were determined before, and 30and 60 after stimulation with cosyntropin. Patients were characterized by scoring systems (APACHEII, SAPSII, MOD score). The underly ing admission diagnosis grouped patients in septic, cardiogenic shock or control.
Sixtyfive patients (22in cardiogenic and 43in septic shock, five and nine women, mean age 58 years, APACHE score of 20) were compared with 34 control patients (17 cancer patients, 10 healthy, four pulmonary emphysema and three other).
At baseline, septic and cardiogenic patients showed similar cortisol levels (21and 21µg/dl), higher than control (15µg/dl,P< 0.05). Progesterone was increased fourfold (P< 0.001)in septic (1.2 ng/ml)and cardiogenic shock (1.1ng/ml) compared with control (0.3ng/ml). Men with sepsis had the highestβestradiol levels. Baseline cortisol levels were only slightly higher in intensive care patients compared with control. There were no clear correla tions between steroid hormones and scoring systems or laboratory signs of infections like CRP, PCT, leukocyte or platelet counts.
After stimulation with cosyntropin, testosterone, 17βestradiol and DHEAS remained constant, whereas progesterone increased (P< 0.001)in all groups of patients without significant difference between groups. In control or cardiogenic patients cosyntropin stimulation leads to significantly increasing values of cortisol –12 (Pand= 2.15 × 10Pin patients with sepsis the= 0.04); increase of cortisol (Pwas blunted, however. This decrease> 0.1) in cortisol stimulation was independent of the use of sedatives or mechanical ventilation. In cardiogenic patients the increase in corti sol levels after stimulation was similar to control patients (7µg/dl) and was not influenced by increasing dosage of catecholamines; in septic patients the cortisol increase was significantly lower (P< 0.01)with high catecholamines (2µg/dl) than with low cate cholamines (7µg/dl).
At baseline, patients at the intensive care unit had higher proges terone levels than normal. Septic patients showed diminished response to cosyntropin stimulation regarding cortisol levels despite a normal increase of progesterone. This points to an impairment of cortisol synthesis.
P4 Determinationof functional states during sepsisinduced activation of the hypothalamic–pituitary–adrenal (HPA) axis using measurement of ACTH, cortisol, dehydroepiandrosteronesulfate (DHEAS) and dehydroepiandrosterone (DHEA) 1,2 13 12 1 C Marx, M Wendt, S Petros, L Engelmann, M Weise, G Höffken 1 23 Internal Medicine I/ Medical ICU, University Hospital Carl Gustav Carus, Fetscherstraße 74, 01307 Dresden;Medical ICU, University of Leipzig, Germany Critical Care2003,7(Suppl 2):P004 (DOI 10.1186/cc1893) IntroductionActivation of the HPA axis occurs in order to controlinflammation or exhaustion and hyperinflammation, respectively: potentially deleterious effects of systemic inflammation duringsuppression of inflammation by glucocorticoids or development of sepsis. Practically, it is difficult to determine different states of HPArelative adrenal insufficiency by adrenal exhaustion resulting in rela activation since a differing dynamics and individual risk have to betive hyperinflammation. IV)Recovery or insufficiency, respectively: considered. normalisationof cytokine levels and regeneration of the adrenal driven by normalisation of ACTH. Reconstitution of physiologic MethodsACTHdriven regulation or relative adrenal insufficiency with poorRecently, we examined levels of cortisol, DHEAS, DHEA as well as ACTH in 30patients with severe sepsis (15survivors, prognosis,respectively. 15 nonsurvivors)and correlated the time course during early and late sepsis to the clinical course and inflammatory markers [1].DiscussionThe HPA axis reflects the individual prognostic risk of Here, we demonstrate and describe different states of HPA activathe patient. The clinical course rarely enables the detection of all tion in characteristic surviving (n= 3)and nonsurviving (nseptic timedependentstates of HPA response. For individual diagnostic= 3) patients of this study by use of hormone and inflammatory profiles.benefit of hormone measurements in septic patients, rapid avail ability of hormone levels is necessary. ResultsFour functional states of HPA response with prognostic relevance could be differentiated. I)Activation: infection, systemicReference inflammation and activation of the HPA axis; high cytokine levels 1. MarxC,et al.:Adrenocortical hormones in survivors and non lead to release of ACTH and cortisol. II) Immunogenic stimulation: survivors of severe sepsis: diverse time course of dehy high cytokine levels maintain cortisol release whereas ACTH is droepiandrosterone, dehydroepiandrosteronesulfate, and suppressed by high glucocorticoid levels. III)Suppression ofcortisol.Crit Care Med2003, in press.
P5 Doestransient hyperglycaemia affect cerebral energy metabolism in patients with severe brain trauma? CH Nordström, P DiazParejo, N Ståhl, W Xu, P Reinstrup, U Ungerstedt Department of Clinical Neuroscience, Lund University Hospital, S22185 Lund, Sweden Critical Care2003,7(Suppl 2):P005 (DOI 10.1186/cc1894) ObjectiveTo study whether transient hyperglycaemia adverselyInterventionsAll patients were treated according to neurosurgical affects cerebral energy metabolism in patients with severe trauintensive care routine including monitoring of intracranial pressure. matic brain lesions.One microdialysis catheter was inserted via a burr hole frontally to that used for the intraventricular catheter (‘better’ position). In S2DesignProspective, nonrandomised study.patients with focal lesions one or more catheters were inserted into
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the cerebral cortex surrounding an evacuated focal contusion orglycerol or lactate/pyruvate ratio. During pronounced hypergly underlying an evacuated haematoma (‘worse’ position). The perfucaemia lactate concentration increased. A pronounced cerebral sion rate was 0.3µor lacticacidosis and a moderate increase in interstitial glycerol conl/min and samples were taken every 30 60 min.The levels of glucose, pyruvate, lactate, glutamate, andcentration indicating cell membrane degradation was observed in a glycerol were analysed and displayed bedside.single patient with pronounced, longlasting hyperglycaemia. Measurements and main resultsIn 108 patients, 18 episodes ofConclusionsCerebral energy metabolism was affected by tran moderate (12–15mmol/l) and six episodes of pronouncedsient hyperglycaemia only at blood glucose concentration above (> 15 mmol/l)hyperglycaemia occurred. Moderate hyperglycaemia15 mmol/las shown by a moderate increase in interstitial lactate did not change intracerebral levels of lactate, pyruvate, glutamate,level. P6 Hyperglycemiaat admission to ICU is independently associated with increased serum levels of IL6 and reducedex vivo TNFalpha production 1 12 11 13 31 HE Wasmuth, F Lammert, J Graf, EA Purucker, A Koch, C Gartung, D Kunz, AM Gressner, S Matern 1 23 Department of Medicine III andDepartment of Medicine I, andInstitute of Clinical Chemistry and Pathobiochemistry, University Hospital Aachen, Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany Critical Care2003,7(Suppl 2):P006 (DOI 10.1186/cc1895) BackgroundHyperglycemia has been shown to be an independentResultsOverall mortality within the study period was 20.1%. Patients risk factor of mortality in patients with stroke and myocardial infarcwith hyperglycemia had an increased risk of mortality in the ICU com tion. Furthermore, strict control of hyperglycemia reduces mortalitypared with patients with normoglycemia at admission (29.3% vs and rates of infectious complications in surgical ICU patients. The15.2%; OR= 2.3,P= 0.03).Sepsis according to Bone criteria was aim of the present study was to investigate immunological changesequally distributed between groups (14.3% vs 10.7%;PAt> 0.05). in medical patients in relation to blood glucose at admission to ICU.logistic regression analysis, higher serum levels of IL6, a reduced ex vivoproduction of TNFalpha, and a history of diabetes were inde Patients and methodsOverall, 189 consecutive medical ICUpendently associated with hyperglycemia at admission to ICU patients were enrolled. At admission, blood glucose and serum(P= 0.007,P< 0.001,P= 0.002,respectively), while IL8, IL10, TNF levels of IL6, IL8, IL10, and TNFalpha were measured. Furtheralpha, monocyte HLADR expression and the SAPS II score were not more, monocyte HLADR expression andex vivoTNFalpha proassociated with increased blood glucose levels (allP> 0.05). duction in whole blood after stimulation with LPS were determined. In all patients, SAPSII score was calculated for day of admissionConclusionsIndependent of SAPSII score and underlying to ICU. Hyperglycemia was defined as a venous blood glucosedisease, hyperglycemia at admission to ICU is associated with > 126 mg/dlin fasting and >200 mg/dlin nonfasting individuals.immunological changes that are frequently observed in critically ill Frequencies in contingency tables were calculated with Fisher’spatients (‘immunoparalysis’). Particularly, a reducedex vivoproduc exact test. Logistic regression was used with hyperglycemia as thetion of TNFalpha might contribute to the increased risk for infec dependent variable and immune parameters, SAPS II score, andtious complications and death in patients with acute and chronic history of diabetes as covariates.hyperglycemia. P7 Influenceof insulin clearance to glucose tolerance in acutely ill severe patients: analysis with glucose clamp method by means of artificial pancreas 1 21 11 1 M Hoshino, Y Haraguchi, M Sakai, I Mizushima, Y Morita, M Kobayashi 1 Department of Intensive and Critical Care Medicine, Tokyo Police Hospital, Fujimi 21041, Chiyodaku, 1028161 Tokyo, Japan; 2 Tokyo Disaster Medical Center, Tokyo, Japan Critical Care2003,7(Suppl 2):P007 (DOI 10.1186/cc1896) PurposeAcutely ill patients often have glucose intolerance (GI),blood glucose level of 80mg/dl and Insulin Infusion Rate (IIR) of which is one of the factors preventing appropriate nutritional1.12 and 3.36mU/kg per min. I1/I3 and M1/M3 indicate the blood support. However, mechanisms of GI are not clearly understood.insulin level (µ: M value (mg/kg perU/ml) and glucose disposal rate Among the factors that influence GI, insulin sensitivity (IS) andmin), when IIR is 1.12/3.36mU/kg per min, respectively (normal insulin clearance (IC) are considered to be the important factors,value of M1: 5–10mg/kg per min). M1/I1: (M1/I1× 1000)was cal because insulin is one of the most important factors which controlculated as the parameter of IS (normal value of M1/I1: more than glucose metabolism and insulin therapy is usually performed for50 mg/lper kg per min perµU). IC was calculated from the follow patients with GI. We investigated glucose tolerance in terms of ISing formula: IC= (3.36–1.12) × 1000/(I3–I1)(normal value of IC: and IC in acutely ill severe patients by the glucose clamp method10–15 ml/kgper min). Glucose tolerance was analyzed in terms of (GC) by means of a bedsidetype artificial pancreas (STG22:M1, IS (M1/I1), and IC. NIKKISO Corporation, Tokyo, Japan). Results1) The proportion of the patients who had M1 levels less MethodThirtyone patients (27 patients had sepsis) in whomthan 5mg/kg per min (GI), IS (M1/I1) less than 50mg/l per kg per blood glucose levels were controlled by means of the artificial panmin perµU (insulin resistance), and IC more than 15ml/kg per min creas were investigated. First measurement of GC was performed(increased IC) were 66% (29/44), 27% (12/44), and 61% in acute condition or within 3days after admission for all the(27/44), respectively. 2) Among the patients with GI (nonly= 29), patients, and second measurement was done 1 week after the first38% (11/29) of the patients had insulin resistance. Sixtytwo measurement for 13patients. GC was performed with clampedpercent (18/29) of the patients with GI had normal IS, and 83% ofS3
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them (15/18) had increased IC (mean± SDof IC, I1: 22 ± 3.8 ml/kgper min, 38.3± 9.5µU/ml,nthe3) Among= 15). patients with normal glucose tolerance (n93% (14/15) of= 15), them had normal IS. However, one patient had both insulin resis tance (M1/I1= 43.5 mg/lper kg per min perµU) and decreased IC (IC = 3.9 ml/kgper min, I1= 131µU/ml).
Interpretation and conclusionswas the important factor1) IC that influenced the glucose tolerance in acutely ill severe patients, although the mechanisms of the change of IC was unclear. 2) Suffi cient insulin administration was considered to be necessary from the aspect of metabolic and nutritional control for those patients with increased IC.
P8 Boneturnover in prolonged critical illness: effect of vitamin D P Vanhove, D Van Roosbroeck, P Wouters, L De Pourcq, R Bouillon, G Van den Berghe Department of Intensive Care & LEGENDO, Leuven University Hospital, Herestraat 49, 3000 Leuven, Belgium Critical Care2003,7(Suppl 2):P008 (DOI 10.1186/cc1897) IntroductionIn prolonged critical illness, substantially increasedterminal of propeptide typeI collagen, serum and urinary collagen bone resorption and osteoblast dysfunction have been reported incrosslinks (βCTX, PYD and DPD) as well as IL6, TNFαand OPG the face of low 25hydroxy vitaminD [25(OH)D] concentrations.were several fold elevated. sRANKL was undetectable. The current prospective, randomized, controlled study investigates the impact of increased daily vitamin D supplement during intensiveThe high dose increased circulating 25(OH)D (P <0.05) but care on the time course of bone turnover and its major regulatorsnormal levels were not reached and low 1,25(OH) D levels not 2 such as cytokines and calciotropic hormones.altered. High dose vitaminD slightly increased osteocalcin and decreased carboxy terminal propeptide typeI collagen (P <0.05). Methodsalkaline phosphatase and collagen crosslinksof Bonespecific10 daysCritically ill patients, assumed to require > intensive care, were compared with healthy matched controls andmarkedly increased with time in both groups (P <0.01). Elevated randomly allocated to a daily vitaminD supplement of eitherCRP and IL6 decreased significantly with time and more so in the ± 200 IU(low dose) or ±500 IU(high dose). Of the 33patients highdose group (PTNF< 0.05).αand IL1 remained unaltered. included, 22remained in ICU for >10 days and were analyzed.Except for a mirroring ofβCTX rise by a decrease in OPG, circulat Urine from 24hour collections and blood was sampled daily foring cytokines were unrelated to the progressively aggravating bone characterization of vitamin D status, bone turnover and inflammation.resorption.
ResultsThe 12 patients who received the high dose vitamin D and 10 patients who received the low dose were comparable at base line. At intensive care admission, serum concentrations of 25(OH)D, 1,25(OH)D, DBP, ionized calciumosteocalcin, IL1 2 , and sIL6R were lower than in controls; PTH and bonespecific alkaline phosphatase levels were normal; serum carboxy and amino
ConclusionsProlonged critically ill patients were vitaminD defi cient. Increasing vitaminD supplement to the currently recom mended dose did not normalize circulating 25(OH)D or 1,25(OH) D. Furthermore, severe bone hyperresorption was asso 2 ciated with osteoblast dysfunction and aggravated with time in intensive care, independent of vitamin D supplementation.
P9 Assessmentof energy expenditure and COproduction with different enteral feeds 2 Z Rusavy, M Zourek, Z Jankovec, D Cechurova, S Lacigova Department of Medicine I, University Hospital, Plzen Alej Svobody 80, Plzen 300 00, Czech Republic Critical Care2003,7(Suppl 2):P009 (DOI 10.1186/cc1898) The aim of the study is to consider to which extent the productionResults did not differ depending on the different composition of of CO(V )and the resting energy expenditure (REE) are influnutrition in the case of adequate energy supply I. (REE= 2 CO2 enced by overfeeding and to which extent by the composition of1438 ± 264.1 kcal/24 hours,V =179.1 ± 31.6 ml/min) × III.(REE = CO2 enteral nutrition.1431 ± 342.7,V =190 ± 54.2),likewise upon overfeeding II. CO2 (REE = 1674 ± 389.6,V =218 ± 52.0) × IV.(REE =1661 ± 378.7, CO2 V =202 ± 42.3).In the highsugar (60%) diet the overfeeding CO2 increased REE (Pand V(< 0.05)P< 0.01)(I. × II.).In the high CO2 Five male and four female patients with Crohn’s disease in remislipid (60%) diet the overfeeding increased REE (Pbut not< 0.01) sion were enrolled. REE and Vwere measured using theV (III.× IV.) CO2 CO2 method of indirect calorimetry. The measurements were performed under hospitalization in the morning after 10hours fasting in fourConclusionExcessive energy supply results in higher Vand in CO2 modifications: I. high sugar (60%) in dose 1.2× REE;II. high sugarhigher REE in comparison with adequate food intake. However, the (60%) and highenergy supply (2.4× REE);III. highfat (60%) innutrition with high content of fat does not lead upon overfeeding to dose 1.2× REE;IV. highfat (60%), high energy (2.4× REE).significant increase of COproduction. The composition of the 2 Between measurements there was a time interval of 7–10days, nutritionwith appropriate energy amount does not significantly S4and the REE.influence Vwhen patients were only on home enteral nutrition. CO2
P10 Themetabolic effect of induced mild hypothermia in critically ill patients
M Bitzani, G Vassiliadou, C Iasonidou, S Tsaggalof, T Kontakiotis, D Riggos ICU, ‘G. PAPANIKOLAOU’ Hospital, Thessaloniki, Greece Critical Care2003,7(Suppl 2):P010 (DOI 10.1186/cc1899)
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Introductionkcal,± 434vs 2292± 228 kcal38°C to 36°C (2593The aim of our study was to evaluate the metabolicP= 0.056). effect of induced mild hypothermia in critically ill patients and toRewarming was followed by a gradual reverse of these effects. assess if rewarming reverses these effects. Statistics were calculated with SPSS version 10, using nonparametric Methodstests. Correlation between T, REE, VDuring a 2 year period, 12 consecutive critically ill patientswas tested by Pearand V O2 CO2 under continuous venovenous hemofiltration (CVVH), due to acuteson’s correlation coefficient. Comparison between REE, Vand V O2 CO2 renal failure, were studied prospectively. All patients were mechaniat different temperatures was performed using Student’s pairedttest. cally ventilated, nine of them were sedated but none was paralyzed. Core temperature(T) was continuously monitored through aConclusionMild hypothermia does not affect the metabolic rate in nasopharyngeal sensor, while resting energy expenditure (REE), Vcritically ill patients. Cooling in the febrile critically ill patient is fol O2 and Vwere evaluated by means of indirect calorimetry. Baselinelowed by a significant decrease in energy expenditure. This may CO2 measurements were recorded before the onset of CVVH. Serialprove beneficial, minimizing the potential for tissue hypoxia, in situ measurements were performed each timeTations of limited oxygen delivery.was decreased by 1°C. After the interruption of CVVH, measurements were also repeated serially with the increase of core temperature of 1°C.References 1. FaenzaS:Hypothermia: an adverse effect or a missing partner?Intensive Care Med1997,23:10151017. ResultsDecrease of temperature from 37°C to 35°C has no sta 2. FrankSM,et al.:Adrenergic respiratory and cardiovascular effects tistically significant influence on metabolic demands. During the of core cooling in humans.Am J Physiol1997,272:557562. reduction of temperature from 38°C to 35°C a statistically signifi 3. SesslerDI:Deliberate mild hypothermia.J Neurosurg Anesthe cant decrease in REE (2593± 228 kcalvs 2095± 618 kcal, siol1995,7:3846. Pas well as in V(= 0.041),Pwas observed. A differ= 0.051)O,4. Prakashet al.:Cardiorespiratory and metabolic effects of CO2 ence at the limits of significance was also observed in REE fromprofound hypothermia.Crit Care Med1978,6:340346. P11 Changesin lymphocyte subpopulations during enrichment of early enteral nutrition with lactic acid bacterium after major abdominal surgery 1 11 11 23 S Lüdemann, O Ahlers, A Möller, D Keh, I Kürer, N Rayes, P Neuhaus, H Gerlach 1 2 Department of Anesthesiology and Intensive Care, andDepartment of Surgery, CharitéVirchowKlinikum, 13344 Berlin, Germany; 3 Department of Anesthesiology, VivantesKlinikum Neuköln, 12313 Berlin, Germany Critical Care2003,7(Suppl 2):P011 (DOI 10.1186/cc1900) Background/aimsMajor abdominal surgery causes changes inResultsNumbers of total lymphocytes as well as Thelper (T4), lymphocyte subpopulations and impairs the immune response.Tsuppressor (T8) and naturalkillerlymphocytes decreased signif Early enteral nutrition (EEN) enriched with probiotic bacteria mayicantly in both groups. No significant differences in this parameters reduce this phenomenon and may improve the clinical course ofcould be found between the groups. However, the T4/T8 ratio this patients. The aim of this randomised, doubleblind trial was toshowed a higher increase from day1 until day8 in the verum investigate changes of lymphocyte subpopulations of patientsgroup. Simultaneously, mean expression of CD45RA on T4cells receiving EEN either enriched with lactic acid bacterium (LAB) orwas significantly lower in the verumgroup while mean expression placebo before and after major abdominal surgery.of CD45RO on T8 cells was significantly higher in this group. Patients and methodsThirtythree patients undergoing either pyloruspreserving pancreaticoduodenectomy or Whipple’s operaSummary/conclusionEnrichment of EEN with LAB seems to tion were enrolled. EEN enriched with either LAB (nno significant influence on the well known postoperativeor have= 17) placebo (n= 16)decrease of total lymphocytes and naturalkiller cells. In contrast,was supplied for a period of 5 days beginning on the day before surgery. Blood samples were taken before surgeryLAB supply seems to improve the T4/T8 ratio by mobilisation of as well as postperatively on day 1, 4 and 8. Flow cytometry analysismature T4and T8cells. Further investigations are necessary to was performed immediately.evaluate the underlying mechanisms and clinical consequences. P12 Enrichmentof early enteral nutrition with lactic acid bacterium influences the innate immune system after major abdominal surgery 1 11 12 13 3 A Möller, O Ahlers, S Lüdemann, I Kürer, N Rayes, D Keh, P Neuhaus, H Gerlach 1 2 Department of Anesthesiology and Intensive Care, andDepartment of Surgery, CharitéVirchowKlinikum, 13344 Berlin, Germany; 3 Department of Anesthesiology, VivantesKlinikum Neuköln, 12313 Berlin, Germany Critical Care2003,7(Suppl 2):P012 (DOI 10.1186/cc1901) Background/aimsReduced bacterial translocation in the gut and resulting changes inThere is strong evidence that early enteral nutrition (EEN) enriched with probiotic bacteria may improve theinnate immune response may be responsible for this phenomenon. clinical course of patients undergoing major abdominal surgery.The aim of this randomised, doubleblind trial was to investigateS5
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changes of innate immunity of patients receiving EEN eitherthe observation period. CD62Lpositive PMNs decreased while enriched with lactic acid bacterium (LAB) or placebo before andCD62Lpositive monocytes increased in both groups with signifi after major abdominal surgery.cantly lower values in the verumgroup. HLADRpositive mono cytes decreased in both groups until day1 but showed a Patients and methodsThirtythree patients undergoing either8 in patients receiving LAB.significantly lower increase until day pyloruspreserving pancreaticoduodenectomy or Whipple’s operaNumber of PMNs, monocytes, total leukocytes and CD62Lpositive tion were enrolled. EEN enriched with either LAB (nshowed no significant differences between both groups.= 17)or PMNs placebo (n= 16)was supplied for a period of 5 days beginning on the day before surgery. Blood samples were taken before surgerySummary/conclusionNumbers of PMNs, monocytes and total as well as postperatively on day 1, 4 and 8. Flow cytometry analysisleukocytes as well as CD62Lpositive PMNs showed well known was performed immediately.changes after major surgery regardless of enrichement of EEN with LAB. In contrast, LAB supply seems to impair the expression of ResultsNumber of neutrophil granulocytes (PMNs), monocytesHLADR and CD62L on monocytes. Further investigations are nec and total leukocytes increased significantly in both groups duringessary to evaluate the underlying mechanisms. P13 Highcorrelation between increased negative calorie balance and morbidity in critically ill patients D Dvir, L Gibstein, E Grozovski, I Alterman, M Shapiro, J Cohen, P Singer General Intensive Care Department, Rabin Medical Center, Beilinson Campus, petah Tikva 49100, Israel; Sackler School of Medicine, Tel Aviv University, Israel Critical Care2003,7(Suppl 2):P013 (DOI 10.1186/cc1902) 2 Accurate energy balance is difficult to assess since prescribedResultsMean body mass index was 26.9± 5.0 kg/mand mean energy intake is not always actual energy intake administered, intraAPACHE IIwas 22.7± 7.2.The bedside information system venous dextrose given as part of a fluid program is not always takenrevealed a meanIV calorie intake of 154kcal/day and reaching into account and resting energy expenditure (REE) is not usually mea370 kcal/dayin some patients. Mean cumulative balance for an sured on a daily basis. We used a bedside computerized informationoverall ICU stay of 395days was –4261kcal (range system to measure daily and cumulative energy balance in critically ill172 to –17,274 kcal).Six of 25patients had a negative calorie ventilated patients to assess its impact on patient outcome.balance >–10,000 kcal.A strong correlation (rwas found= –0.75) between negative energy balance and complication rate, but not Methods and patientsTwentyfive ventilated patients (mean agewith length of ventilation, length of ICU stay or length of hospitaliza 54.7 ± 18.4 years,19 males,six females) were prospectively foltion. Six patients died (three had a negative energy balance lowed during their ICU stay. Energy balance (REE) was measured> –10,000 kcal). daily using both indirect calorimetry (DeltatracII, DatexOhmeda, Finland) and a bedside computerized information system (iMDsoft,ConclusionWe conclude that a bedside information system pro Israel) which was able to collect data from all sources (enteral, parvides online and accurate information regarding energy balance in enteral nutrition and and IVfluids containing calories). Daily andcritically ill patients and may allow for the early detection and pre total energy balance were calculated on a continuous basis. Morvention of severe negative energy balance, which is correlated with bidity (acquired organ dysfunction, pressure sores, need forthe occurrence of significant complications (organ dysfunction and surgery) and mortality were noted.pressure sores). P14 Useof anabolic steroid therapy in critically ill ICU patients 1 2 J Pikul, MD Sharpe 1 2 Department of Clinical Nutritional Services andDepartment of Anesthesia, University of Western Ontario, London, Canada N6A5A5 Critical Care2003,7(Suppl 2):P014 (DOI 10.1186/cc1903) Critical illness leads to a loss of lean body mass (LBM) and isTable 1 associated with impaired immune function and wound healing, 2 weeks prior to ASAfter 3 doses increased infection, and poorer outcomes [1,2]. Aggressive nutri tional support can decrease net catabolic losses by only ~50%, Pre Nbalance LBMPre Nbalance LBM therefore other methods need to be examined. We initiated ana Patient ALB(g/day) (kg)ALB (g/day) (kg) bolic steroid therapy (AS) (nandrolone intramuscular injection, once weekly× threedoses) on 10critically ill patients. Criteria for 1. F0.09 +2.322.3 0.09+3.2 22.8 AS: moderate to severe malnutrition, ICU stay >14 days, tolerating 2. F0.08 –3.418.4 0.21+4.8 19.2 enteral feeds, and exhibiting poor response to nutritional support. 3. M0.11 –5.836.3 0.32+7.2 38.1 Feeds were 130–150% of measured energy expenditure and 4. M< 0.07–6.7 27.20.19 +1.827.9 protein at 2.0–2.5g/kg per day. Response was monitored by nitro 5. M0.18 –14.239.4 0.28+6.9 40.8 gen balance and LBM. 6. F0.07 –5.212.8 0.16*+5.3* 15.3* 7. M0.14 –6.8N/A 0.35+3.8 N/A 8. M< 0.07–10.2 29.10.16 +5.429.9 Eight of 10 patients exhibited a good response to AS, with attain 9. M0.15 –17.620.5 0.14–10.0 22.1 ment of positive nitrogen balance and improvement in skeletal and 10. M0.10 –19.626.8 0.14+4.6 25.8 visceral protein levels. AS may be useful as adjunctive therapy for S6malnourished, critically ill patients for protein repletion.* Data collected 6 weeks post steroid.
References 1. ChangDW, DeSanti L, Demling RH:Shock1998,10:155160. 2. FerrandoAA, SheffieldMoore M, Wolf SEet al.:Crit Care Med 2001,29:19361942.
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P15 Hypercapniaattenuates the endotoxininduced tissue metabolic acidosis in esophageal mucosa
1 21 M Ponichter, H Billert, J Jastrzebski 1 2 Clinic of Anesthesiology and Intensive Care, Center of Medical Postgraduate Education, Warsaw, Poland;Clinic of Anesthesiology and Intensive Care, Medical Academy of Poznan, Poland Critical Care2003,7(Suppl 2):P015 (DOI 10.1186/cc1904)
ObjectiveTo assess the effects of hypercapnia on the tissue meta bolic response toEscherichia coliendotoxemia in rabbits.
DesignProspective, controlled experimental study.
SettingUniversity laboratory.
SubjectsThirtysix rabbits of both sexes, anesthetized with pento barbital and ventilated mechanically (normoventilation).
InterventionsAnimals were assigned to one of four groups: a) endotoxemiccontrol group (n= 9),receiving intravenous Escherichia colimg/kg bolus) via a peripheral vein;endotoxin (20 b) hypercapniacontrol group (nreceiving exogenous carbon= 9), dioxide to achieve mild hypercapnia 60–90mmHg; c) hypercapnia treated group (n= 9),treated identically to endotoxemic controls, and additionally receiving exogenous carbon dioxide to achieve mild hypercapnia 60–90mmHg; d) control group (nreceiving= 9), neither endotoxin nor carbon dioxide.
MeasurementsWe compared hemodynamics, blood gases, WBC, rectal temperature and tonometric findings in esophageal mucosa
obtained in each group. Endotoxin injection decreased mean arterial pressure from 79± 9to 54± 17.5 mmHg,decreased bicarbonate level from 21.6± 3to 17.6± 4 mmHg,decreased WBC from 7.9± 2 to 1.9± 0.7 G/l,increased rectal temperature from 37.7± 1to 39.9 ± 1.5ºC,and caused a marked, continuous decrease in regional pH (pHi) from 7.40± 0.08to 7.12± 0.11at the end of the experi ment. Hypercapnia alone had a minimal effect on the parameters and findings. Both hypercapnia and endotoxemia had no significant effect on regional CO(PrCO ) compared with controls, indicating lack of 2 2 significant mucosal blood flow abnormalities throughout the experi ment. In the hypercapnia treated group we observed an initial decrease in regional pH (pHi) from 7.42± 0.13to 7.13± 0.08,but the value of this parameter remained stable (7.07± 0.05at the end of the experiment) and the statistical difference compared with hypercapnia controls was nonsignificant (P> 0.05).
Conclusions1. Endotoxin injection caused marked tissue acidosis without disturbing esophageal mucosal blood flow, which indicates a metabolic character of acidosis and underlines the significance of intracellular abnormalities during endotoxemia. 2.We hypothe size that hypercapnia attenuates the endotoxininduced tissue metabolic acidosis and may exert a cytoprotective effect.
P16 Bloodgases: a dreadful combination of metabolic, respiratory and lactic acidosis
1 2 A Aaron, AS Bachwani 1 2 Intensive Care Unit, Parsee General Hospital, Cumballa Hill, Mumbai 400026, India;BARC Hospital, Mumbai 400094, India Critical Care2003,7(Suppl 2):P016 (DOI 10.1186/cc1905)
IntroductionArterial blood gases (ABGs) are the immediate,Group 2.These patients came to the ICU deteriorated with easiest, most reliable and cost effective bedside method of assessmultiorgan involvement, in an unstable condition needing mechani ing an unstable patient. It portrays an array of functional reservescal support beside all medical strategies. The outcome was not from the lungs to the kidneys and the blood cells in between. Itthat good in this group. also hints at the causes of hypoxia and hypercarbia. We applied the Henderson Hasselbalch Equation (PCO= HCO× 1.5 + 8)toGroup 3.Very poor outcome from this group. Patients did not 2 3 interpret the blood gas and used it effectively to prognosticate thesurvive after this combination of metabolic, respiratory and lactic patient’s outcome.acidosis occurred. This was much in evidence in a patient who had multiorgan failure and septic shock. The PCOin this group was 2 always on the higher side then the calculated value as is in evi MethodsAll patients with acidosis on blood gas were included. Indence in sample number 3. addition, PCOwas calculated independently using the Hender 2 son Hasselbalch Equation. Patients are divided into three groupsConclusion1. The Henderson Hasselbalch Equation is very useful as shown in Table 1. Prototype ABGs of each group as shown inin the interpretation of blood gases and guides us about the sever Table 2.ity of illness and prognosis of the patient. 2. If sodabicarbonate has to be used, the equation can be used to ExplanationGroup 1.1 did not haveguide us of its effect on the patient.Patients in blood gas group any problem, responded very well to the treatment and were stable. The PCOmatches with the HCOaccording to the Henderson3. The combination of metabolic, lactic and respiratory acidosis is a 2 3 Hasselbalch Equation. In dehydrated patients, sodabicarb wasdreadful combination usually culminating in death. Commonly given to replace the loss of carbonates.patients had multiorgan dysfunction and irreversible shock.S7
Sepsis, cardiogenic shock
Matches with blood gas
104 19 14.42 29.3 30
Infections, dehydration
Ventilator, inotropes
Antibiotics, fluids
546 100 18.02 31.2 46
Matches with blood gas
205 38 21.41 33.6 40
TCO BE 2 12.2 –5 14.5 –11.4 15.2 –20.1
SO 2 98.1 98.4 97.1
PO 2 120 135.6 142.3
Dehydration, pulmonary edema, infection
HCO 3 11.2 13.6 13.4
Metabolic acidosis with lactic acidosis (n= 151)
Table 1
4. It is imperative that we adopt an aggressive approach early on in5. Tobegin with, patients presenting in group3 were more treatment of metabolic and lactic acidosis combination and shouldseverely ill and warranted an aggressive approach irrespective of not allow patients to go in to Group 3.the blood gas. P17 Lacticversus nonlactic metabolic acidosis: outcomes in critically ill patients KJ Gunnerson, M Saul, JA Kellum CRISMA Laboratory, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261, USA Critical Care2003,7(Suppl 2):P017 (DOI 10.1186/cc1906) IntroductionCritical care physicians associate lactic acidosis (LA)Ca, Mg, Phos within 24hours, and albumin any time during the with higher morbidity and mortality. Other forms of metabolic acihospitalization. When multiple data sets were available, the set dosis are generally regarded as less dangerous and any associawith the highest lactate was used. We classified patients into four tion with adverse outcomes in critically ill patients is poorlygroups: A)no metabolic acidosis, standard base excess (SBE) understood. We sought to compare differences in mortality and–2; B)lactic acidosis50% of SBE;, lactate accounted for > length of stay (LOS) between LA and other forms of metabolicC)strong ion gap (SIG) acidosis50% of, SIG accounted for > acidoses. SBE(and not LA); D)hyperchloremic acidosis, absence ofA, B, or C. MethodsIn this observational pilot study, we reviewed records of 9799 patients admitted to the ICUs at our institution betweenResultsWe identified 862 patients (8.9% of ICU admissions). Of 1 January 2001 and 30 June 2002. This cohort of patients had anthese, 546 patients (63.3%) had a metabolic acidosis. LA inpatient mortality of 14%, a hospital LOS of 12 days and an ICUoccurred in 43% of acidemic patients and was associated with a LOS of 5.8days. We selected cases on the following criteria:57% mortality. Table1 presents the unadjusted relative mortality 1) clinicians caring for each patient suspected the presence of LA;and LOS. Other forms of acidosis were collectively associated with + + 2) arterial blood gas (ABG) and lactate were measured; 3) Na, K, a37% mortality. There was no difference in ICU or hospital LOS – – Cl , and COwere drawn within 4 hours of the referenced ABG,between all groups. 2
Table 2 Group pH 1 7.25 2 7.27 3 6.96
PCO 2 25 29.1 59.4
Metabolic acidosis with lactic acidosis (n= 119)
23rd International Symposium on Intensive Care and Emergency Medicine
Septic shock, MOF
Ventilator, iInotropes
Typical case scenarioTreatment
Higher than blood gas by +4–5
Calculated PCO 2
MODS, septic shock
MODS, septic shock
n % of acidosis ICU LOS days (survivors) LOS days (survivors) Mortality (%) S8
Table 1 Group Features (%) 1 Metabolicacidosis without lactic acidosis (n= 200)
Critical CareMarch 2003 Vol 7 Suppl 2
SIG acidosis
Lactic acidosis
All cases SBE < –2
237 43 19.38 33.2 57
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Conclusionsappear to be associated with high mortality and increased ICU andIn patients suspected of having LA, LA was more commonly associated with hospital mortality than nonLA.hospital LOS. However, all forms of metabolic acidosis, even hyperchloremic, P18 Relationshipbetween platelet counts, Creactive protein and plasma fibrinolytic capacity in critically ill patients 1 12 21 1 K Zouaoui Boudjeltia, M Piagnerelli, E Carlier, S Jamart, Ph Cauchie, M Vanhaeverbeek 1 2 Experimental Medicine Laboratory, ULB 222 Unit, andDepartment of Intensive Care, A. Vésale Hospital, 6110 MontignyleTilleul, Belgium Critical Care2003,7(Suppl 2):P018 (DOI 10.1186/cc1907) BackgroundMultiple Organ Failure (MOF) complicating theResultsThe ECLT was significantly correlated with CRP (R= 0.64; sepsis remains the first cause of death in the ICU. A recent studyP< 0.001)and PC (R= –0.4;P= 0.02).The twoway ANOVA showed that vascular endothelial damage was the primary cause ofshowed that the sepsis status increased significantly the ECLT MOF in patients with thrombopenia and that humoral mediators(P= 0.023)and that platelets under 208,500 cells/µl (median of the played a major role in the development of this process [1]. Otherhistogram of PC was used as the cutoff) also increased the ECLT parameters like Cprotein reactive were also probably important via(PHowever, there was no interaction (= 0.023).P= 0.184). a direct effect on endothelial cells and increasing the secretion of IL6. In this study, we aimed to evaluate the relation between theConclusionPlatelets can protect the endothelium against several platelet counts (PC), the Creactive protein and plasma fibrinolyticforms of oxidative injuries [3]. With this study we showed that the capacity (as a marker of endothelium dysfunction) in ICU patients.decrease of the platelets count could favor the endothelium dys function and impaired fibrinolytic capacity, and this independently of sepsis. In addition, Creactive protein is not only an inflammatory MethodsWe studied blood samples of ICU patients with (n= 11) marker, but it might be involved in the endothelium damage. and without (n= 21) sepsis at the first day of admission. Fibrinolytic capacity was evaluated by the Euglobulin Clot Lysis Time (ECLT) References determined by a new method [2]. We also collected biological 1. HirokazuU,et al.:Crit Care Med2002,30:22422248. data and the SAPSII score for each patients. The correlations 2. ZouaouiBoudjeltia K,et al.:BMC Biotechnology2002,2:8. were depicted by Spearman’s test.3. VincentJL,et al.:Crit Care Med2002,30:S313S317. Table 1 Sepsis (n= 11)Nonsepsis (n= 21)Pvalue CRP (mg%)25 (17–30)6.9 (2.1–11.6)< 0.001 3 WBC (x 10cells/µ(7.7–12.9) 9.8(8–12) 0.69l) 10.5 Fibrinogen (mg%)662 (597–686)455 (333–542)< 0.001 SAPS 48(39–56) 23(15–35) 0.003 3 Platelets (x 10cells/µ(179–296) 0.17(123–227) 229l) 186 ECLT (min)987 (845–1375)599 (477–950)0.01 Data presented as median (25–75%).
P19 Drotregocinalfa (activated) inhibits degradation of cytokinemRNA in an endothelial model of inflammation M Brueckmann, HM Weiler, V Liebe, A Marx, U Hoffmann, S Lang, C Liebetrau, M Borggrefe, KK Haase, G Huhle Department of Medicine I, Faculty of Clinical Medicine Mannheim, University of Heidelberg, 68167 Mannheim, Germany Critical Care2003,7(Suppl 2):P019 (DOI 10.1186/cc1908) Backgrounddependent increase in MCP1, IL6 and IL8protein productionC (APC) pathway has beenThe activated protein suggested to be a common link between coagulation and inflam(P< 0.001for rhAPC 5µg/ml at 4–24hours) in HUVEC. Experi mation. APC may function to restore hemostasis via modulation ofments were conducted to evaluate the effect of rhAPC on mRNA cytokine expression. We investigated the effect of Drotrecogin alfadegradation and mRNA stability independently of its possible (activated) (recombinant human activated proteinC [rhAPC]) oneffects on gene transcription. After stimulation of mRNA transcrip the expression of monocyte chemoattractant protein1 (MCP1),tion by TNFalpha (0.1–1ng/ml) for 3 hours, HUVEC were treated interleukin6 (IL6) and IL8 in human umbilical vein endothelialwith actinomycinD (1µg/ml), preventing new synthesis of tran cells (HUVEC) in the presence and absence of tumor necrosisscript, in the presence or absence of rhAPC. HUVEC receiving factoralpha (TNFalpha). MCP1, IL6 and IL8 are mediators ofrhAPC contained more MCP1mRNA and IL8mRNA after 1 hour inflammation and their gene expression is controlled by the activaand up to 8 hours than controls, suggesting an inhibitory effect of tion of the transcription factor nuclear factorkappa B (NFκB). rhAPCon mRNA degradation. Electrophoretic mobility shift assays (EMSA) revealed that APC attenuated NFκB activity implying that ResultsrhAPC (2.5–20µNFg/ml) upregulated the amount of MCP1κB may not be involved in the upregulatory effect of rhAPC on mRNA and IL8mRNA and caused a timedependent and doseMCP1, IL6 and IL8 production.S9
Critical CareMarch 2003 Vol 7 Suppl 2
23rd International Symposium on Intensive Care and Emergency Medicine
ConclusionsThe ability of APC to upregulate the production of MCP1, IL6 and IL8, most likely by increasing the stability of MCP1mRNA rather than by transcriptional activation via NFκB,
identifies a novel posttranscriptional pathway, by which APC may control the local inflammatory reaction, thereby modulating the extent of endothelial injury.
P20 Genearray transcript profiling of human endothelial cells identifies pathways regulated by Drotrecogin alfa (activated)
M Brueckmann, S Lang, HM Weiler, V Liebe, U Hoffmann, M Borggrefe, KK Haase, G Huhle Department of Medicine I, Faculty of Clinical Medicine Mannheim, University of Heidelberg, 68167 Mannheim, Germany Critical Care2003,7(Suppl 2):P020 (DOI 10.1186/cc1909)
BackgroundAlthough the role of Drotrecogin alfa (activated) (recombinant human activated proteinC [rhAPC]) in modulating microvascular coagulation through the inhibition of thrombin gener ation has been well studied in experimental and clinical settings of severe sepsis, little is known about its direct antiinflammatory effects on vascular endothelial cells. To better understand the mol ecular mechanisms of action of rhAPC on endothelial cell function during sepsis we used gene array transcript profiling of messenger RNA (mRNA) from primary cultured human umbilical vein endothe lial cells (HUVEC) exposed to Drotregocin alfa (activated) in the presence of the central proinflammatory mediator tumornecrosis factoralpha (TNFalpha).
Methods and resultsThe effect of rhAPC on TNFalphaactivated HUVEC was assessed using Affymetrix microarrays. Briefly, mRNA from treated cells was isolated and converted to doublestranded copy (c)DNA, which was then used to generate biotinylated cRNA. Biotinylated cRNA was hybridized to Affymetrix oligonucleotide arrays, containing approximately 33,000 human genes. Data analy sis was performed using GeneChip 3.1 software. We found that
rhAPC reproducibly upregulated TNFalphainduced gene expres sion of the following genes: monocyte chemoattractant protein1 (MCP1), plateletderived growth factoralphachain (PDGFA), interleukin6 (IL6), transforming growth factorbeta receptorII, insulinlike growth factorbinding protein (IGFBP) and interleukin8 (IL8). rhAPC downregulated the following genes induced by TNFalpha stimulation: the secreted apoptosis related protein1 (SARP1), basic fibroblast growth factor (bFGF), lymphotoxinβ, the adhesion molecules vascular cell adhesion molecule1 (VCAM1) and intercellular adhesion molecule1 and 2 (ICAM1 and ICAM2). Results for IL6, IL8 and MCP1 were confirmed by protein mea surements in cell culture supernatants by ELISA as well as by a col orimetric assay for mRNA quantitation (Quantikine assay).
ConclusionsThe ability of rhAPC to modulate gene expression of a cluster of proinflammatory genes, genes responsible for cell adhesion and leukocyte trafficking as well as genes involved in endothelial apoptosis, provides insight into the molecular mecha nisms contributing to the efficacy of rhAPC in systemic inflamma tion and sepsis.
P21 Treatmentof adults with sepsisinduced coagulopathy and purpura fulminans with a plasmaderived protein C concentrate (Ceprotin®) 1 21 11 1 P Schellongowski, E Bauer, G Locker, M Frass, T Staudinger, P Knöbl 1 2 Department of Internal Medicine I andDepartment of Internal Medicine IV, University of Vienna, Währinger Gürtel 1820, A1090 Wien, Austria Critical Care2003,7(Suppl 2):P021 (DOI 10.1186/cc1910) Disseminated intravascular coagulation (DIC) is a severe complicaone a large intrahepatic necrosis. In five patients Ceprotin® was tion of sepsis, especially when associated with skin or organ necrogiven as a leveladjusted continuous infusion (starting with 10U/kg sis appearing as purpura fulminans. Several reports describedper hour) after an initial bolus of 100U/kg, two patients were beneficial effects of proteinC replacement in preterm neonates,treated with bolus infusions (100U/kg every 8hours). Additionally, infants, and adults with purpura fulminans. We treated seven adultheparin infusions (seven patients), freshfrozen plasma (five patients (six female, one male), median age 35years (rangepatients), antithrombin concentrates (three patients), fibrinogen 19–48 years),with DIC and purpura fulminans with a plasmaconcentrates (two patients), lowdose rtPA (two patients), platelet derived human proteinC concentrate (Ceprotin®; Baxter, Vienna,and erythrocyte transfusions, antibiotics, and hydrocortisone (four Austria). Three patients had meningococcal, three had pneumococpatients) were given. Protein C activity increased to 1.34–2.0U/ml cal, and one had pseudomonas and cytomegalyvirus infections. Atin all patients, coagulation abnormalities resolved within 1–6 days. A admission, all patients had signs of skin necrosis, severe infectiontotal of 8000–77,000U Ceprotin® were given during 1–7days. and acute illness. Coagulation assays suggested DIC in fiveOne patient died the same day from multiorgan failure, one died patients (median [range]): platelet count 19 (17–23) G/l, fibrinogen14 days after the end of Ceprotin® infusion from candida sepsis. All 60 (44–103) mg/dl,antithrombin activity 0.47 (0.25–0.76)U/ml, otherpatients survived, three needed amputations of toes, two had normotest 32(14–39)%, APTT 88 (42–160)s, Ddimerno sequels. Our data suggest that Ceprotin® can be a useful 66 (3.3–140) ng/ml;the remaining two patients were treatedhemostatic support in the treatment of adults with severe, lifethreat because of typical skin necrosis and meningococcemia alone. Initialening purpura fulminans, which would have a high mortality with protein C activity was reduced to 0.35 (0.2–0.5) U/ml. Five patientsconventional therapy alone. Controlled studies are needed to estab S10lish the value of this drug in the treatment of sepsis.had neurologic alterations, five renal failure, three respiratory failure,