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E de Jonge

Publications and source records attributed to E de Jonge.

At least 19 recordsLinked to original sources
PubMed2006

Differential effects of a perioperative hyperinsulinemic normoglycemic clamp on the neurohumoral stress response during coronary artery surgery.

BACKGROUND: Hyperglycemia in patients undergoing coronary artery bypass grafting (CABG) is associated with adverse outcome. Although insulin infusion strategies are increasingly used to improve outcome, a pathophysiological rationale is currently lacking. The present study was designed to quantify the effects of a perioperative hyperinsulinemic normoglycemic clamp on the neurohumoral stress response during CABG. METHODS: Forty-four nondiabetic patients, scheduled for elective CABG, were randomized to either a control group (n = 22) receiving standard care or to a clamp group (n = 22) receiving additionally a perioperative hyperinsulinemic (regular insulin at a fixed rate of 0.1 IU.kg(-1).h(-1)) normoglycemic (plasma glucose between 3.0 and 6.0 mmol.liter(-1)) clamp during 26 h. We measured the endocrine response of the hypothalamus-pituitary-adrenal (HPA) axis, the sympathoadrenal axis, and glucagon, as well as plasma glucose and insulin at regular intervals from the induction of anesthesia at baseline through the end of the second postoperative day (POD). RESULTS: There were no differences in clinical outcome between the groups. In the control group, hyperglycemia developed at the end of surgery and remained present until the final measurement point on POD2, whereas plasma insulin levels remained unchanged until the morning of POD1. In the intervention group, normoglycemia was well maintained during the clamp, whereas insulin levels ranged between 600 and 800 pmol.liter(-1). In both groups, plasma ACTH and cortisol increased from 6 h after discontinuation of cardiopulmonary bypass onward. However, during the clamp period, a marked reduction in the HPA axis response was found in the intervention group, as reflected by a 47% smaller increase in area under the curve in plasma ACTH (P = 0.035) and a 27% smaller increase in plasma cortisol (P = 0.002) compared with the control group. Compared with baseline, epinephrine and norepinephrine increased by the end of the clamp interval until POD2 in both groups. Surprisingly, the area under the curve of epinephrine levels was 47% higher (P = 0.026) after the clamp interval in the intervention group as compared with the control group. CONCLUSION: A hyperinsulinemic normoglycemic clamp during CABG delays and attenuates the HPA axis response during the first 18 h of the myocardial reperfusion period, whereas after the clamp, plasma epinephrine is higher. The impact of delaying cortisol responses on clinical outcome of CABG remains to be elucidated.

Adrenocorticotropic Hormone↗
PubMed2006

Short-term and long-term mortality in very elderly patients admitted to an intensive care unit.

OBJECTIVE: To report short-term and long-term mortality of very elderly ICU patients and to determine independent risk factors for short-term and long-term mortality DESIGN AND SETTING: Retrospective cohort study in the medical/surgical ICU of a tertiary university teaching hospital. PATIENTS: 578 consecutive ICU patients aged 80 years or older. RESULTS: Demographic, physiological, and laboratory values derived from the first 24h after ICU admission. ICU mortality of unplanned surgical (34.0%) and medical patients (37.7%) was higher than that of planned surgical patients (10.6%), as was post-ICU hospital mortality (26.5% and 29.7% vs. 4.4%). Mortality 12 months after hospital discharge, including ICU and hospital mortality, was 62.1% in unplanned surgical and 69.2% in medical patients vs. 21.6% in planned patients. Only median survival of planned surgical patients did not differ from survival in the age- and gender-matched general population. Independent risk factors for ICU mortality were lower Glasgow Coma Scale score, higher SAPS II score, the lowest urine output over 8 h, abnormal body temperature, low plasma bicarbonate levels, and higher oxygen fraction of inspired air. High urea concentrations and admission type were risk factors for hospital mortality, and high creatinine concentration was an independent risk factor for 12-month mortality. CONCLUSION: Mortality in very elderly patients after unplanned surgical or medical ICU admission is higher than after planned admission. The most important factors independently associated with ICU mortality were related to the severity of illness at admission. Long-term mortality was associated with renal function.

Aged↗
PubMed2005

[Admission of elderly patients to intensive care].

Elderly patients have an increased probability of dying after treatment in an intensive care unit (ICU), compared with younger patients. The risk of dying is largely determined by the admission type (patients with planned admissions have a better prognosis than those with unplanned admissions), severity of illness and functional status prior to admission. Elderly patients surviving ICU often experience a decline in functional status. No data are available on the factors that predict functional outcome. Elderly patients do not necessarily prefer life-sustaining treatment to palliative care. The willingness to undergo ICU treatment depends on the likelihood of survival and beneficial functional outcome. New prognostic models should be developed specifically to predict both survival and functional outcome in individual elderly patients after admission to ICU.

Age Factors↗
PubMed2005

Glucose, insulin and potassium applied as perioperative hyperinsulinaemic normoglycaemic clamp: effects on inflammatory response during coronary artery surgery.

BACKGROUND: The clinical benefits of glucose-insulin-potassium (GIK) and tight glycaemic control in patients undergoing coronary artery bypass grafting (CABG) may be partly explained by an anti-inflammatory effect. We applied GIK as a hyperinsulinaemic normoglycaemic clamp for >25 h and quantified its effect on systemic inflammation in patients undergoing CABG. METHODS: Data obtained in 21 non-diabetic patients with normal left ventricular function scheduled for elective coronary artery surgery, who were randomly allocated to a control or GIK group, were analysed. In GIK patients, regular insulin was infused at a fixed rate of 0.1 IU kg(-1) h(-1). The infusion rate of glucose (30%) was adjusted to maintain blood glucose levels within a target range of 4.0-5.5 mmol litre(-1). Plasma concentrations of interleukins 6, 8 and 10, C-reactive protein (CRP) and serum amyloid A (SAA) were measured on the day of surgery and on the first and second postoperative days (POD1 and POD2). RESULTS: In the GIK group hypoglycaemia (glucose <2.2 mmol litre(-1)) did not occur, whereas hyperglycemia (glucose >6.1 mmol litre(-1)) developed in 15% of all measurements. In control patients, hyperglycaemia developed in >80% of all measurements in the presence of low endogenous insulin levels. CRP and SAA levels increased in both groups, with maximum levels measured on POD2. GIK treatment significantly reduced CRP and SAA levels. Interleukin levels increased significantly in both groups following cardiopulmonary bypass, but no differences were found between the groups. CONCLUSION: Hyperinsulinaemic normoglycaemic clamp is an effective method of maintaining tight glycaemic control in patients undergoing CABG and it attenuates the systemic inflammatory response in these patients. This effect may partly contribute to the reported beneficial effect of glycaemic control in patients undergoing CABG.

Aged↗
PubMed2005

Reliability and accuracy of Sequential Organ Failure Assessment (SOFA) scoring.

OBJECTIVE: The Sequential Organ Failure Assessment (SOFA) score was developed to quantify the severity of patients' illness, based on the degree of organ dysfunction. This study aimed to evaluate the accuracy and the reliability of SOFA scoring. DESIGN: Prospective study. SETTING: Adult intensive care unit (ICU) in a tertiary academic center. SUBJECTS: Thirty randomly selected patient cases and 20 ICU physicians. MEASUREMENTS AND MAIN RESULTS: Each physician scored 15 patient cases. The intraclass correlation coefficient was .889 for the total SOFA score. The weighted kappa values were moderate (0.552) for the central nervous system, good (0.634) for the respiratory system, and almost perfect (>0.8) for the other organ systems. To assess accuracy, the physicians' scores were compared with a gold standard based on consensus of two experts. The total SOFA score was correct in 53% (n = 158) of the cases. The mean of the absolute deviations of the recorded total SOFA scores from the gold standard total SOFA scores was 0.82. Common causes of errors were inattention, calculation errors, and misinterpretation of scoring rules. CONCLUSIONS: The results of this study indicate that the reliability and the accuracy of SOFA scoring among physicians are good. We advise implementation of additional measures to further improve reliability and accuracy of SOFA scoring.

Coma↗
PubMed2005

Methods for evaluation of medical terminological systems--a literature review and a case study.

OBJECTIVES: The usability of terminological systems (TSs) strongly depends on the coverage and correctness of their content. The objective of this study was to create a literature overview of aspects related to the content of TSs and of methods for the evaluation of the content of TSs. The extent to which these methods overlap or complement each other is investigated. METHODS: We reviewed literature and composed definitions for aspects of the evaluation of the content of TSs. Of the methods described in literature three were selected: 1) Concept matching in which two samples of concepts representing a) documentation of reasons for admission in daily care practice and b) aggregation of patient groups for research, are looked up in the TS in order to assess its coverage; 2) Formal algorithmic evaluation in which reasoning on the formally represented content is used to detect inconsistencies; and 3) Expert review in which a random sample of concepts are checked for incorrect and incomplete terms and relations. These evaluation methods were applied in a case study on the locally developed TS DICE (Diagnoses for Intensive Care Evaluation). RESULTS: None of the applied methods covered all the aspects of the content of a TS. The results of concept matching differed for the two use cases (63% vs. 52% perfect matches). Expert review revealed many more errors and incompleteness than formal algorithmic evaluation. CONCLUSIONS: To evaluate the content of a TS, using a combination of evaluation methods is preferable. Different representative samples, reflecting the uses of TSs, lead to different results for concept matching. Expert review appears to be very valuable, but time consuming. Formal algorithmic evaluation has the potential to decrease the workload of human reviewers but detects only logical inconsistencies. Further research is required to exploit the potentials of formal algorithmic evaluation.

Evaluation Studies as Topic↗
PubMed2004

Recombinant nematode anticoagulant protein c2, an inhibitor of tissue factor/factor VIIa, attenuates coagulation and the interleukin-10 response in human endotoxemia.

The tissue factor-factor (F)VIIa complex (TF/FVIIa) is responsible for the initiation of blood coagulation under both physiological and pathological conditions. Recombinant nematode anticoagulant protein c2 (rNAPc2) is a potent inhibitor of TF/FVIIa, mechanistically distinct from tissue factor pathway inhibitor. The first aim of this study was to elucidate the pharmacokinetics and pharmacodynamics of a single intravenous (i.v.) dose of rNAPc2. The second aim was to study its effect on endotoxin-induced coagulation and inflammation. Initially, rNAPc2 was administered to healthy volunteers in three different doses. There were no safety concerns and the pharmacokinetics were consistent with previous studies, in which rNAPc2 was administered subcutaneously. rNAPc2 elicited a dose-dependent reduction of the endogenous thrombin potential and a selective prolongation of prothrombin time. Subsequently, the effect on endotoxin-induced coagulation and inflammation was studied. The administration of rNAPc2 completely blocked the endotoxin-induced thrombin generation, as measured by plasma prothrombin fragment F1+2. The endotoxin-induced effect on fibrinolytic parameters such as plasmin-antiplasmin complexes and plasminogen activator inhibitor type 1 was not affected by rNAPc2. The administration of rNAPc2 attenuated the endotoxin-induced rise in interleukin (IL)-10, without affecting the rise in other cytokines. In conclusion, rNAPc2 is a potent inhibitor of TF/FVIIa, which was well tolerated and could safely be used intravenously in this Phase I study in healthy male volunteers. A single i.v. dose rNAPc2 completely blocked endotoxin-induced thrombin generation without affecting the fibrinolytic response. In addition, rNAPc2 attenuated the endotoxin-induced rise in IL-10, without affecting the rises in other cytokines.

Adolescent↗
PubMed2003

[Intensive care medicine in the Netherlands, 1997-2001. I. Patient population and treatment outcome].

OBJECTIVE: To describe the patients admitted to intensive care units (ICUs) in the Netherlands between 1997-2001 and the treatment outcome. DESIGN: Descriptive. METHOD: For the years 1997-2001, prospective admission and discharge data as well as all data necessary for calculating prospective severity of illness scores (e.g. APACHE II and SAPS II) were collected for all patients that were admitted to 18 ICUs participating in the Dutch National Intensive Care Evaluation (NICE). Outcome measures were ICU mortality and hospital mortality, length of hospital and ICU admission, and standardised mortality ratio (SMR). RESULTS: Data from 55,016 admissions were registered. The median APACHE II score was 15 (P25-P75: 10-20) and the median SAPS II score was 29 (19-43). The median ICU length of admission for individual ICUs varied between 0.86 and 2.76 days. The occupied ICU capacity of individual ICUs varied between 220 and 1260 days per 100 patients admitted for non-cardiosurgical patients and between 110 and 330 days per 100 patients admitted for cardiosurgical patients. The ICU mortality and hospital mortality were 9.0% and 12.9% respectively. The mean SMR according to APACHE II was 0.95 (95% CI: 0.93-0.98). The SMR of the individual participating hospitals varied between 0.55 (95% CI: 0.37-0.80) and 1.20 (1.13-1.28). CONCLUSION: Hospital mortality for ICU-admitted patients in the NICE registration was 12.9%. For patients who could be evaluated with the APACHE II model, actual hospital mortality was lower than predicted by this model. Significant differences in length of admission, hospital mortality and SMR were found between individual hospitals.

APACHE↗
PubMed2003

[Intensive care medicine in the Netherlands, 1997-2001. II. Changes over time and differences between hospitals].

OBJECTIVE: To describe efficacy (mortality) and efficiency (length of admission) of intensive care (IC) treatment after admission due to a prior cardiothoracic operation or pneumonia, based on data from the Dutch National Intensive Care Evaluation (NICE) foundation. DESIGN: Descriptive. METHOD: Data for the period 1 January 1997-31 December 2001 were extracted from the NICE databank for patients admitted after cardiothoracic surgery and for patients admitted with pneumonia. The variables changes in time, risk factors for mortality, and differences between hospitals were analysed. RESULTS: There were 25,463 admissions to 5 hospitals following cardiothoracic surgery and 1408 admissions to 18 hospitals due to pneumonia. An increase in valve surgery was noted in the cardiothoracic surgery group: from about 10% to about 25%. In the group undergoing valve operations, there was an increase in the average age of the patients and in the number of patients with comorbidity. No significant differences in mortality between hospitals were detected. However, the length of ICU treatment differed. Hospital mortality in the pneumonia group was 33.9%. Differences between hospitals with respect to mortality (both crude mortality and severity-of-illness adjusted mortality) and length of ICU admission were found. CONCLUSION: With the NICE registration it is possible to detect differences and trends. This is a valuable tool for indicating where and how quality and efficiency in intensive care medicine can be improved.

Cardiac Surgical Procedures↗
PubMed2003

[The value of the pulmonary-artery catheter: not ruled out, but not proven either].

A number of prospective, randomized trials have recently been published on the effects of using the pulmonary artery (Swan-Ganz) catheter in the peri-operative management of high-risk patients and in the treatment of critically ill patients on the intensive-care unit. These studies show that using the pulmonary-artery catheter does not lead to increased survival. It cannot be excluded that more beneficial effects would have been found with other treatment goals, or if different populations had been studied. However, based on the present evidence from the literature, the routine use of the pulmonary-artery catheter can no longer be defended.

Catheterization, Swan-Ganz↗
PubMed2002

Prevalence of pre-cancerous lesions and cervical cancer in South Africa--a multicentre study.

OBJECTIVES: To describe the age-specific prevalence rates of cancer of the cervix in South African women presenting for screening. DESIGN: A multicentre prevalence survey in 10 geographically defined areas following a common core protocol. Services were located in existing service sites, with the exception of KwaZulu-Natal which used a mobile service. Women aged 20 years and above were eligible for inclusion. OUTCOME MEASURES: Age-specific cervical cytologically diagnosed abnormality rates according to the Bethesda classification. RESULTS: During the study 20,603 women participated. Eighty per cent of the sample had never had a Pap smear before and just over 91% had not had a Pap smear in the last 5 years. In this study population 468 women screened (2.42%) were found to have low-grade squamous intra-epithelial lesions (LSIL) and the average age of these women was 33.1 years; 366 (1.8%) had high-grade SIL (HSIL) and these women were statistically significantly older at 37.97 years of age; and 92 women (0.47%) were found to have cytologically diagnosed invasive cancer. These women were significantly older, with an average age of 51.3 years. A clear relationship was found between age and LSIL, with younger women having a high rate of LSIL which decreases with increasing age. A similar but inverse relationship between age and invasive cancer is described, with the rate being low in young women and increasing with increasing age. A clear relationship between HSIL and age is not described in these data. The adequacy rate (satisfactory and satisfactory but limited) of the slides was 95%, and just under 92% of the study sample received their results. Not all women were appropriately referred and it was not possible to assess if women referred for treatment received it. CONCLUSIONS: These data indicate that cancer of the cervix is a common disease and that, similar to other countries, it is a disease of older women. These data give some positive indicators for future screening--older women will present for screening and the majority of women received their results. However, improvements in health system functioning are needed. A uniform national cytology reporting system is required as well as clear guidelines for providers on what action to take based on cytology reports. Linkage between the site of screening and treatment centre is inadequate and requires urgent attention in order to decrease cervical cancer mortality.

Adult↗
PubMed2002

Drotrecogin alfa Eli Lilly.

Drotrecogin alfa (Xigris, recombinant activated protein C) is an anticoagulant developed and launched by Eli Lilly & Co for the treatment of sepsis [333781], [339372], [430133], [436271]. The FDA and the EMEA accepted the brand name Xigris for drotrecogin alfa in June 2001. This trade name had been proposed by Lilly in place of the previous brand name, Zovant, which was deemed unacceptable by the EMEA due to concerns that the name could be confused with hospital-based drugs [412512]. Filings for sepsis were made in the US, EU and Australia in February 2001 [398514], [447870] and in March 2001, the US FDA assigned drotrecogin alfa Priority Review status [403435]. The FDA extended the action date from July 27 to October 27, 2001 for completion of its review of the biologics license application (BLA) for drotrecogin alfa to assess further supplementary data submitted by Lilly [412512]. At the October 16, 2001 meeting (postponed from September 12), the FDA Advisory Committee on Anti-Infective Drugs split 10 to 10 over whether to recommend approval [425873], [425940]. In late October 2001, Lilly received an approvable letter from the FDA for the treatment of severe sepsis. Approval was contingent upon successful negotiation of labeling, agreement on post-approval clinical trials, and successful completion of manufacturing inspections [427301]. In November 2001, the FDA approved drotrecogin alfa for the reduction of mortality in adult patients with severe sepsis who have a high risk of death [430133]; the product was launched onto the US market days later [436271]. Following the FDA committee's split decision in October 2001, Credit Suisse First Boston, which expected mid-2002 approval but with restrictive labeling, revised its predictions from $1.265 billion in 2004 sharply downwards to $543 million [425929].

Journal Article↗
PubMed2001

Decreased circulating levels of von Willebrand factor after intravenous administration of a rapidly degradable hydroxyethyl starch (HES 200/0.5/6) in healthy human subjects.

OBJECTIVE: Impairment of haemostasis has been described with slowly degradable medium molecular weight hydroxyethyl starch (MMW-HES), whereas rapidly degradable MMW-HES is generally considered to have no important effects on blood coagulation. This study was undertaken to investigate the effects of a rapidly degradable MMW-HES plasma substitute on primary haemostasis and blood coagulation in human subjects. DESIGN: Randomised, cross-over study. SETTING: Research unit of a university hospital. PARTICIPANTS: Nine healthy, adult male volunteers. INTERVENTIONS: A 60-min intravenous infusion of 1 l HES 200/0.5/6 (HAES-steril 6%) or 4% albumin (control). MEASUREMENT AND RESULTS: The infusion of HES resulted in decreased circulating levels of von Willebrand factor antigen (from 85+/-8% to 59+/-6% after HES vs from 80+/-7% to 69+/-8% after albumin, p<0.05) and ristocetin cofactor activity (from 93+/-4 to 67+/-4% after HES vs from 79+/-5 to 75+/-5% after albumin, p<0.01). This was associated with an impairment of in vitro platelet function as determined with the PFA-100 platelet function analyser (closure time with collagen/epinephrine from 120+/-7 to 159+/-14 s after HES vs from 121+/-7 to 137+/-10 s after albumin, p<0.05; with collagen/ADP from 88+/-3 to 116+/-9 s and from 103+/-4 to 114+/-7 s after HES and albumin, respectively, p=0.01). CONCLUSIONS: The infusion of 1 l of HES 200/0.5/6 in healthy human subjects results in moderately decreased plasma levels of von Willebrand factor associated with impairment of platelet function.

Adult↗
PubMed2001

Tissue factor pathway inhibitor does not influence inflammatory pathways during human endotoxemia.

Activation of coagulation induces a proinflammatory response in in vitro and animal experiments. Inhibition of the tissue factor-dependent pathway of coagulation inhibits cytokine release and prevents death in gram-negative sepsis models in primates. This study investigated the influence of blocking the coagulation system by tissue factor pathway inhibitor (TFPI) on endotoxin-induced inflammatory responses in healthy humans. Eight men were studied in a double-blind, randomized, placebo-controlled cross-over study. They received a bolus intravenous injection of 4 ng/kg of endotoxin, followed by a 6-h continuous infusion of either TFPI (0.2 mg/kg/h after a bolus of 0.05 mg/kg) or placebo. Endotoxin induced-activation of coagulation was prevented completely by TFPI. In contrast, TFPI did not influence leukocyte activation, chemokine release, endothelial cell activation, or the acute phase response. Thus, complete prevention of coagulation activation by TFPI does not influence activation of inflammatory pathways during human endotoxemia.

Acute-Phase Reaction↗
PubMed2001

Advances in the understanding of the pathogenetic pathways of disseminated intravascular coagulation result in more insight in the clinical picture and better management strategies.

Disseminated intravascular coagulation (DIC) is a syndrome characterized by systemic intravascular activation of coagulation leading to widespread deposition of fibrin in the circulation. There is ample experimental and pathological evidence that the fibrin deposition contributes to multiple organ failure. The massive and ongoing activation of coagulation may result in depletion of platelets and coagulation factors, which may cause bleeding (consumption coagulopathy). Recent knowledge on important pathogenetic mechanisms that may lead to DIC has resulted in novel preventive and therapeutic approaches to patients with DIC. DIC is not a disease in itself but is a complication of a variety of disorders. However, the pathogenesis of DIC follows similar pathways in almost all of these situations, with a pivotal role of proinflammatory cytokines. The cornerstone of the management of DIC is the specific and vigorous treatment of the underlying disorder. Strategies aimed at the inhibition of coagulation activation may theoretically be justified and have been found to be beneficial in experimental and initial clinical studies. These strategies comprise inhibition of tissue factor-mediated activation of coagulation and restoration of physiological anticoagulant pathways by means of the administration of (activated) protein C concentrate or antithrombin concentrate.

Disseminated Intravascular Coagulation↗
PubMed2001

Regulatory role of cytokines in disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) can complicate a number of diseases. DIC in the setting of sepsis is considered to result from strong activation of the coagulation system and concurrent inhibition of fibrinolysis and other anticoagulant pathways. Cytokines have been implicated as important mediators in these hemostatic alterations. This article summarizes recent insights into which cytokines are likely to be involved in the procoagulant response to systemic infection.

Animals↗
PubMed2001

Anticoagulant factor concentrates in disseminated intravascular coagulation: rationale for use and clinical experience.

Natural inhibitors of coagulation, in other words, antithrombin (AT), the protein C system, and tissue factor pathway inhibitor (TFPI), play an important role in controlling the activation of coagulation during disseminated intravascular coagulation (DIC). Furthermore, they may not only influence coagulation but also attenuate inflammatory responses during sepsis. Low circulating levels of AT and protein C have been associated with poor outcome. Replacement therapy with AT, activated protein C (APC), and TFPI has been shown to attenuate thrombin generation and to reduce mortality in experimental sepsis models. Experience with AT and APC in patients is promising. Data from large phase III trials of AT and APC as treatment of patients with severe sepsis will soon be available. Recombinant TFPI is currently in phase II clinical trials for severe sepsis.

Antithrombins↗