Steven Vanderschueren

Thrombocytopenia and prognosis in intensive care

Objective To study the incidence and prognosis of thrombocytopenia in adult intensive care unit (ICU) patients. Design Prospective observational cohort study. Setting The medical ICU of a university hospital and the combined medical-surgical ICU of a regional hospital. Patients All patients consecutively admitted during a 5-month period. Interventions Patient surveillance and data collection. Measurements and Main Results The primary outcome measure was ICU mortality. Data of 329 patients were analyzed. Overall ICU mortality rate was 19.5%. A total of 136 patients (41.3%) had at least one platelet count <150 × 109/L. These patients had higher Multiple Organ Dysfunction Score (MODS), Simplified Acute Physiology Score (SAPS) II, and Acute Physiology and Chronic Health Evaluation (APACHE) II scores at admission, longer ICU stay (8 [4–16] days vs. 5 [2–9] days) (median [interquartile range]), and higher ICU mortality (crude odds ratio [OR], 5.0; 95% confidence interval [CI], 2.7–9.1) and hospital mortality than patients with daily platelet counts >150 × 109/L (p < .0005 for all comparisons). Bleeding incidence rose from 4.1% in nonthrombocytopenic patients to 21.4% in patients with minimal platelet counts between 101 × 109/L and 149 × 109/L (p = .0002) and to 52.6% in patients with minimal platelet counts <100 × 109/L (p < .0001). In all quartiles of admission APACHE II and SAPS II scores, a nadir platelet count <150 × 109/L was related with a substantially poorer vital prognosis. Similarly, a drop in platelet count to ≤50% of admission was associated with higher death rates (OR, 6.0; 95% CI, 3.0–12.0;p < .0001). In a logistic regression analysis with ICU mortality as the dependent variable, the occurrence of thrombocytopenia had more explanatory power than admission variables, including APACHE II, SAPS II, and MODS scores (adjusted OR, 4.2; 95% CI, 1.8–10.2). Conclusions Thrombocytopenia is common in ICUs and constitutes a simple and readily available risk marker for mortality, independent of and complementary to established severity of disease indices. Both a low nadir platelet count and a large fall of platelet count predict a poor vital outcome in adult ICU patients.

Fever of unknown origin in adults: 40 years on

Abstract.  Knockaert DC, Vanderschueren S, Blockmans D. (Gasthuisberg University Hospital, Leuven, Belgium). Fever of unknown origin in adults: 40 years on (Review). J Intern Med 2003; 253: 263–275.

Relationship between fluorodeoxyglucose uptake in the large vessels and late aortic diameter in giant cell arteritis

OBJECTIVE GCA carries an increased risk of developing thoracic aortic aneurysms. Previous work with fluorodeoxyglucose (FDG)-PET has shown that the aorta is frequently involved in this type of vasculitis. We wanted to investigate whether there is a correlation between the extent of vascular FDG uptake during the acute phase of GCA and the aortic diameter at late follow-up. METHODS All patients with biopsy-proven GCA who ever underwent an FDG-PET scan in our centre were asked to undergo a CT scan of the aorta. The diameter of the aorta was measured at six different levels (ascending aorta, aortic arch, descending aorta, abdominal suprarenal, juxtarenal and infrarenal aorta) and the volumes of the thoracic and of the abdominal aorta were calculated. RESULTS Forty-six patients agreed to participate (32 females, 14 males). A mean of 46.7 +/- 29.9 months elapsed between diagnosis and CT scan. All aortic dimensions were significantly smaller in women than in men, except for the diameter of the ascending aorta. Patients who had an increased FDG uptake in the aorta at diagnosis of GCA, had a significantly larger diameter of the ascending aorta (P = 0.025) and descending aorta (P = 0.044) and a significantly larger volume of the thoracic aorta (P = 0.029). In multivariate analysis, FDG uptake at the thoracic aorta was associated with late volume of the thoracic aorta (P = 0.039). CONCLUSION GCA-patients with increased FDG uptake in the aorta may be more prone to develop thoracic aortic dilatation than GCA patients without this sign of aortic involvement.

Medication adherence in patients with chronic non‐malignant pain: Is there a problem?

Health care providers, treating patients with chronic non‐malignant pain, often experience that medication is not as effective as expected. It is important to realize that the effectiveness of a pharmacological treatment can be influenced by the way the medication is taken. Medication adherence is a topic that gains more attention, especially in chronic conditions, because it affects treatment outcome. A systematic review of studies on medication adherence in patients with chronic non‐malignant pain was performed to gain insight in the prevalence of the problem, the impact on treatment outcome, influencing variables and interventions. Searching several electronic databases (Medline, CINAHL, Psychinfo and Cochrane), 14 relevant articles were found. The results indicate that medication non‐adherence is common in patients with chronic non‐malignant pain. Both overuse and underuse of medication occurs. However, due to the scarce literature and important methodological limitations, it is not possible to make firm conclusions concerning the impact on outcome, influencing variables and optimal intervention strategies. This review highlights some important gaps in the adherence literature in a chronic non‐malignant pain population and sets the stage for future research.

Pain during bone marrow aspiration: prevalence and prevention

The prevalence, intensity, determinants and prevention of pain during bone marrow aspiration (BMA) in adults are not well defined. In the first part of this prospective study (observational phase), 132 adult hematological patients undergoing BMA after local anesthesia scored the procedural pain by means of a visual analogue scale (VAS). Moderate to severe pain was defined as a VAS score exceeding 30 mm. Eighty-six percent reported procedural pain. The VAS score (mean+/-SEM) was 27.2+/-2.1 mm. Thirty-six percent of patients graded the pain as moderate to severe. In a linear regression analysis, VAS score correlated positively with the duration of the procedure (P=0.029) and negatively with the age of the patient (P=0.006). In the second part of the study (interventional phase), 100 patients were randomized to 50 mg tramadol or placebo, given orally at least one hour before BMA. VAS scores during aspiration were significantly lower in tramadol recipients versus placebo recipients (16.5+/-3.0 mm and 28.8+/-3.4 mm, respectively, P=0.003). Pretreatment with tramadol reduced the percentage of patients with at least moderate pain from 40% to 20% (P=0.029). Four tramadol and 3 placebo recipients reported side effects (dizziness or sedation). In conclusion, notwithstanding local anesthesia, the great majority of adult hematological patients experience transient pain during BMA that is of at least moderate intensity in over a third. Pretreatment with tramadol lowers pain intensity significantly and is well tolerated.

Thrombolytic Therapy of Peripheral Arterial Occlusion With Recombinant Staphylokinase

BACKGROUND Recombinant staphylokinase (STAR) induces fibrin-specific coronary artery recanalization in patients with evolving myocardial infarction. The present pilot study evaluates its thrombolytic efficacy, safety, fibrin specificity, and immunogenicity in patients with peripheral arterial occlusive disease. METHODS AND RESULTS Thirty patients (37 to 86 years of age) with angiographically documented thromboembolic peripheral arterial occlusion of recent origin (21 +/- 5.5 days, mean +/- SEM) were treated with heparin and intra-arterial STAR given as a 1-mg bolus followed by a 0.5-mg/h infusion in 20 patients or as a 2-mg bolus followed by a 1-mg/h infusion in 10 subsequent patients. With 7.0 +/- 0.7 mg STAR infused over 8.7 +/- 1.0 hours, recanalization was complete in 25 patients, partial in 2, and absent in 3. Two major hemorrhagic complications occurred: one fatal hemorrhagic stroke and one hypovolemic shock caused by bleeding at the angiographic puncture site. Administration of STAR did not induce fibrinogen breakdown or a significant prolongation of template bleeding time. STAR-neutralizing activity and anti-STAR IgG were low at baseline, increased markedly from the second week on, and remained elevated for several months. CONCLUSIONS Intra-arterial administration of STAR restores vessel patency in patients with peripheral arterial occlusion in the absence of fibrinogen degradation.

Recombinant Staphylokinase Variants With Altered Immunoreactivity IV: Identification of Variants With Reduced Antibody Induction but Intact Potency

BACKGROUND The thrombolytic potency and antibody induction of selected variants of recombinant staphylokinase (SakSTAR), including SakSTAR(K74) with Lys74, SakSTAR(E75) with Glu75-, SakSTAR(EER) with Glu38, Glu75, and Arg77, and SakSTAR(K74ER) with Lys74, Glu75, and Arg77 replaced by Ala, were studied. METHODS AND RESULTS In rabbits, SakSTAR(74) and SakSTAR(EER) elicited significantly less circulating neutralizing activity than SakSTAR and SakSTAR(E75) (P = .005 and P = .0002 versus SakSTAR, respectively). In baboons, SakSTAR(K74) induced significantly fewer antibodies than wild-type SakSTAR (P < .05). Intra-arterial administration in patients with peripheral arterial occlusion of SakSTAR(K74) (n = 11) or SakSTAR(K74ER) (n = 6) induced significantly fewer circulating neutralizing antibodies [median values and interquartile ranges, 20 (3.8 to 26) and 2.4 (0.2 to 59) micrograms compound neutralized/mL plasma after 3 to 4 weeks (P = .01 and P = .035 versus SakSTAR, respectively)] than SakSTAR (n = 9) [median value and interquartile range, 93 (24 to 110) micrograms compound neutralized/mL plasma]. Overt neutralizing antibody induction (> 10 micrograms compound neutralized/mL plasma) occurred in all 9 patients given wild-type SakSTAR, in 6 of the 11 SakSTAR(K74ER) patients (P = .038 versus SakSTAR), and in 2 of the 6 SakSTAR(K74ER) patients (P = .011 versus SakSTAR). CONCLUSIONS SakSTAR(K74), a variant of recombinant staphylokinase with a single substitution of Lys74 with Ala, and SakSTAR(K74), with Lys74, Glu75, and Arg77 substituted with Ala, have intact thrombolytic potencies but induce significantly less antibody formation in patients.

Recombinant Staphylokinase Variants With Altered Immunoreactivity II: Thrombolytic Properties and Antibody Induction

BACKGROUND The substitution variants K35A,E38A,K74A, E75A,R77A (SakSTAR.M38) and K74A,E75A,R77A,E80A, D82A (SakSTAR.M89) of recombinant staphylokinase (SakSTAR) with reduced antibody reactivity were assayed for thrombolytic potency and antibody induction in animal models and in patients. METHODS AND RESULTS In a 125I-fibrin-labeled pulmonary embolism model in the hamster, the doses giving 50% clot lysis in 90 minutes were 25 micrograms/kg for SakSTAR, 85 micrograms/kg for SakSTAR.M38, and 90 micrograms/kg for SakSTAR.M89. In rabbits with 125I-fibrin-labeled plasma clots incorporated into extracorporeal arteriovenous loops, lysis within 2 hours was 76 +/- 18% (mean +/- SD, n = 28) with 400 micrograms/kg SakSTAR, 53 +/- 13% (n = 8) with 1000 micrograms/kg SakSTAR.M38, and 39 +/- 13% (n = 6) with 800 micrograms/kg SakSTAR.M89. When groups of eight rabbits were immunized by intravenous administration of 0.2 to 1.0 micrograms/kg compound followed by subcutaneous injection of 0.4 mg in Freunds adjuvant at 2, 3, and 5 weeks, SakSTAR.M38 and SakSTAR.M89 elicited markedly less circulating neutralizing activity, compared with SakSTAR, when determined at 6 weeks (neutralizing 6.1 +/- 3.0 and 4.9 +/- 1.3 micrograms compound/mL plasma, respectively, versus 20 +/- 17 micrograms/mL; P = .02 and P = .01, respectively) and induced significantly less resistance to thrombolysis (residual thrombolytic potency producing 59 +/- 25% and 39 +/- 12% lysis, respectively, versus 8.5 +/- 5.7%; P = .008 and P = .006, respectively). In patients with peripheral arterial occlusion, intra-arterial administration of SakSTAR.M38 (n = 4) or SakSTAR.M89 (n = 4) induced significantly fewer circulating neutralizing antibodies (P = .03) and specific IgG (P = .01) at 2 to 3 weeks than SakSTAR (n = 8). CONCLUSIONS SakSTAR.M38 and SakSTAR.M89 induce less antibody formation and might constitute preferred agents for thrombolytic therapy in humans.

Risk Factors for Infective Endocarditis and Outcome of Patients With Staphylococcus aureus Bacteremia

OBJECTIVE To investigate the risk factors for Staphylococcus aureus infective endocarditis (SAIE) and 6-month mortality in patients with S aureus bacteremia (SAB). PATIENTS AND METHODS This study consisted of patients who were diagnosed as having nosocomial or community-acquired SAB or SAIE between June 1, 2000, and December 31, 2005. Clinical characteristics of patients with SAB were compared with those of patients with SAIE, and predictors of mortality in patients with SAB were analyzed. RESULTS The median age of the 132 randomly selected patients with SAB and the 66 patients with SAIE was 66 and 68 years, respectively. Univariable analysis showed that unknown origin of SAB, a valvular prosthesis, a pacemaker, persistent fever, and persistent bacteremia were significantly associated with SAIE. In multivariable analysis, unknown origin of SAB (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.9-9.3; P=.001), a valvular prosthesis (OR, 9.2; 95% CI, 3.2-26.2; P<.001), persistent fever (OR, 3.1; 95% CI, 1.0-9.0; P=.04), and persistent bacteremia (OR, 6.8; 95% CI, 2.3-20.2- P=.001) were independently associated with SAIE. Six- month mortality was 8% in patients with SAB vs 35% in patients with SAIE (OR, 6.5; 95% CI, 2.9- 14.8; P<.001). In univariable analysis, methicillin- resistant S aureus (OR, 7.2; 95% CI, 1.7 - 29.4; P=.005) was significantly associated with 6-month mortality in patients with SAB. CONCLUSION Unknown origin of SAB, a valvular prosthesis, persistent fever, and persistent bacteremia were independently associated with SAIE in patients with SAB. In univariable analysis, methicillin-resistant S aureus was associated with 6-month mortality in patients with SAB. S aureus infective endocarditis had a significantly higher mortality than SAB. The optimal management of SAB and SAIE deserves further study.

Management of Prosthetic Valve Infective Endocarditis

This study analyzed the profile and outcome of surgically versus medically treated patients with prosthetic valve infective endocarditis (PVE). From 2000 to 2006, 80 patients >16 years of age (median 71) with definite PVE according to modified Duke criteria were included. The medically treated group was separated into deliberately conservative and perforce conservative treatments, the latter group including patients with contraindications to a cardiosurgical intervention. The most frequent causative micro-organisms were staphylococci. Forty-six percent of patients were surgically treated, 34% had deliberately conservative treatment, and 20% had perforce conservative treatment. Six-month mortality was 29%; 27% of surgically treated patients died, 4% deliberately conservatively patients died, and 75% perforce conservatively treated patients died. Septic shock, multiorgan failure, and type of treatment were significantly associated with death in univariable analysis. Multivariable analysis revealed that type of treatment (perforce conservative) and septic shock predicted death in patients with PVE. Survival was most favorable in deliberately conservatively treated patients, including PVE due to Staphylococcus aureus. In conclusion, there remains a role for watchful waiting in patients with PVE without evidence of major complications. Moreover, patients with uncomplicated S. aureus PVE can be treated successfully without cardiac surgery. Conversely, patients with major complicated PVE should preferentially undergo surgery. Predictors of mortality in patients with PVE included septic shock and perforce conservative treatment.