E. de Jonge

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.

Sequential measurements of chemokines in urosepsis and experimental endotoxemia.

Chemokines are a superfamily of small chemotactic proteins. While increased levels of interleukin-8 have been measured in serum and urine during urinary tract infection, little is known about other chemokines in this condition. Monocyte chemoattractant protein (MCP)–1, macrophage inflammatory protein (MIP)–1α, MIP-1β and interferon-γ inducible protein (IP)–10 were measured in 30 patients with culture-proven urosepsis during a 3-day follow-up and in 11 healthy humans after intravenous injection of endotoxin (4 ng/kg). Urine and serum levels of MCP-1, MIP-1β, and IP-10, but not of MIP-1α, were elevated in patients on admission, and decreased after initiation of antibiotic treatment. Endotoxin administration to healthy subjects induced increases in plasma and urine concentrations of all four chemokines. These data indicate that clinical and experimental gram-negative infection in humans is associated with enhanced production of chemokines that act mainly on mononuclear cells and that these chemokines are at least in part locally produced.

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

Summary.  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.

Perioperative hyperinsulinaemic normoglycaemic clamp causes hypolipidaemia after coronary artery surgery

BACKGROUND Glucose-insulin-potassium (GIK) administration is advocated on the premise of preventing hyperglycaemia and hyperlipidaemia during reperfusion after cardiac interventions. Current research has focused on hyperglycaemia, largely ignoring lipids, or other substrates. The present study examines lipids and other substrates during and after on-pump coronary artery bypass grafting and how they are affected by a hyperinsulinaemic normoglycaemic clamp. METHODS Forty-four patients were randomized to a control group (n=21) or to a GIK group (n=23) receiving a hyperinsulinaemic normoglycaemic clamp during 26 h. Plasma levels of free fatty acid (FFA), total and lipoprotein (VLDL, HDL, and LDL)-triglycerides (TG), ketone bodies, and lactate were determined. RESULTS In the control group, mean FFA peaked at 0.76 (sem 0.05) mmol litre(-1) at early reperfusion and decreased to 0.3-0.5 mmol litre(-1) during the remaining part of the study. GIK decreased FFA levels to 0.38 (0.05) mmol litre(-1) at early reperfusion, and to low concentrations of 0.10 (0.01) mmol litre(-1) during the hyperinsulinaemic clamp. GIK reduced the area under the curve (AUC) for FFA by 75% and for TG by 53%. The reduction in total TG was reflected by a reduction in the VLDL (-54% AUC) and HDL (-42% AUC) fraction, but not in the LDL fraction. GIK prevented the increase in ketone bodies after reperfusion (-44 to -47% AUC), but was without effect on lactate levels. CONCLUSIONS Mild hyperlipidaemia was only observed during early reperfusion (before heparin reversal) and the hyperinsulinaemic normoglycaemic clamp actually resulted in hypolipidaemia during the largest part of reperfusion after cardiac surgery.

An evaluation of patient data management systems in dutch intensive care

Objective: To assess the agreement between the functions of seven configurations of Patient Data Management Systems (PDMS) and the Dutch specifications prepared by the users prior to use.Design: An observational descriptive study with hospital visits of seven configurations of five different PDMS systems including three commercial systems and two locally developed systems.Setting: Seven Dutch level I intensive care units in university and teaching hospitals.Measurements and results: A substantial disagreement was found between the Dutch specifications and the actual functions of the PDMS configurations tested. Between the PDMS configurations, major differences in key features, including “automated charting”, “information and care planning”, and “management information”, were observed. Automated charting is adequately supported by the three commercial systems. All configurations tested had limited functions supporting care planning. In none of the configurations tested was the required function present to support unit management with reports on resource utilisation and outcome performance. The automatic calculation of prognostic scores was either absent or incorrect. The implementation, the (continuous) configuration and the training required a substantial investment in costs and human resources.Conclusion: Today, none of the PDMSs tested satisfy the Dutch specifications. This can be explained by technical impossibilities of the systems and shortcomings in the actual configuration or in the unit organisation. The PDMS might become a valuable tool in improving the quality of ICU practice, but full implementation of these systems according to the specifications still has a long way to go.

Outcomes of intensive care unit admissions after elective cancer surgery.

BACKGROUND Postoperative care for major elective cancer surgery is frequently provided on the Intensive Care Unit (ICU). OBJECTIVE To analyze the characteristics and outcome of patients after ICU admission following elective surgery for different cancer diagnoses. METHODS We analyzed all ICU admissions following elective cancer surgery in the Netherlands collected in the National Intensive Care Evaluation registry between January 2007 and January 2012. RESULTS 28,973 patients (9.0% of all ICU admissions; 40% female) were admitted to the ICU after elective cancer surgery. Of these admissions 77% were planned; in 23% of cases the decision for ICU admission was made during or directly after surgery. The most frequent malignancies were colorectal cancer (25.6%), lung cancer (18.5%) and tumors of the central nervous system (14.3%). Mechanical ventilation was necessary in 24.8% of all patients, most frequently after surgery for esophageal (62.5%) and head and neck cancer (50.2%); 20.7% of patients were treated with vasopressors in the acute postoperative phase, in particular after surgery for esophageal cancer (41.8%). The median length of stay on the ICU was 0.9 days (interquartile ranges [IQR] 0.8-1.5); surgery for esophageal cancer was associated with the longest ICU length of stay (median 2.0 days) with the largest variation (IQR 1.0-4.8 days). ICU mortality was 1.4%; surgery for gastrointestinal cancer was associated with the highest ICU mortality (colorectal cancer 2.2%, pancreatico-cholangiocarcinoma 2.0%). CONCLUSION Elective cancer surgery represents a significant part of all ICU admissions, with a short length of stay and low mortality.

Construction of an Interface Terminology on SNOMED CT Generic Approach and Its Application in Intensive Care

OBJECTIVE To provide a generic approach for developing a domain-specific interface terminology on SNOMED CT and to apply this approach to the domain of intensive care. METHODS The process of developing an interface terminology on SNOMED CT can be regarded as six sequential phases: domain analysis, mapping from the domain concepts to SNOMED CT concepts, creating the SNOMED CT subset guided by the mapping, extending the subset with non-covered concepts, constraining the subset by removing irrelevant content, and deploying the subset in a terminology server. RESULTS The APACHE IV classification, a standard in the intensive care with 445 diagnostic categories, served as the starting point for designing the interface terminology. The majority (89.2%) of the diagnostic categories from APACHE IV could be mapped to SNOMED CT concepts and for the remaining concepts a partial match was identified. The resulting initial set of mapped concepts consisted of 404 SNOMED CT concepts. This set could be extended to 83,125 concepts if all taxonomic children of these concepts were included. Also including all concepts that are referred to in the definition of other concepts lead to a subset of 233,782 concepts. An evaluation of the interface terminology should reveal what level of detail in the subset is suitable for the intensive care domain and whether parts need further constraining. In the final phase, the interface terminology is implemented in the intensive care in a locally developed terminology server to collect the reasons for intensive care admission. CONCLUSIONS We provide a structure for the process of identifying a domain-specific interface terminology on SNOMED CT. We use this approach to design an interface terminology on SNOMED CT for the intensive care domain. This work is of value for other researchers who intend to build a domain-specific interface terminology on SNOMED CT.

Association between angiographic culprit lesion and out-of-hospital cardiac arrest in ST-elevation myocardial infarction patients

BACKGROUND Factors related to the occurrence of out-of-hospital cardiac arrest (OHCA) in ST-elevation myocardial infarction (STEMI) are still poorly understood. The current study sought to compare STEMI patients presenting with and without OHCA to identify angiographic factors related to OHCA. METHODS This multicenter registry consisted of consecutive STEMI patients, including OHCA patients with return-of-spontaneous circulation. Patients were treated with primary percutaneous coronary intervention (PCI) and therapeutic hypothermia when indicated. Outcome consisted of in-hospital neurological recovery, scored using the Cerebral Performance Categories (CPC) scale, and 1-year survival. Logistic regression was used to identify factors associated with OHCA and survival was displayed with Kaplan-Meier curves and compared using log rank tests. RESULTS In total, 224 patients presented with OHCA and 3259 without OHCA. Average age was 63.3 years and 75% of patients were male. OHCA occurred prior to ambulance arrival in 68% of patients and 48% required intubation. Culprit lesion was associated with OHCA: risk was highest for proximal left coronary lesions and lowest for right coronary lesions. Also, culprit lesion determined the risk of cardiogenic shock and sub-optimal reperfusion after PCI, which were strongly related to survival after OHCA. Neurological recovery was acceptable (CPC≤2) in 77.1% of OHCA patients and did not differ between culprit lesions. CONCLUSIONS In the present STEMI population, coronary culprit lesion was associated with the occurrence of OHCA. Moreover, culprit lesion influenced the risk of cardiogenic shock and success of reperfusion, both of which were related to prognosis of OHCA patients.

Accumulation of oral antibiotics as an adverse effect of selective decontamination of the digestive tract: a series of three cases

An 80-year-old male patient was admitted to the intensive care unit (ICU) with respiratory insufficiency caused by congestive heart failure accompanying myocardial infarction. SDD and enteral feeding was commenced on arrival at the ICU. After 18 days diagnostic bronchoscopy revealed an incomplete longitudinal tracheal compression. Because of the persistent hemodynamic and respiratory problems, withdrawal of treatment was decided upon and the patient died shortly thereafter. Post-mortem examination demonstrated a solid mass completely obstructing the esophagus around an intact gastric tube (Fig. 1). Macroscopically the mass resembled clotted SDD paste, and this was confirmed by identification of tobramycin and amphotericin B by pharmaceutical analysis.

Granulocyte Colony-Stimulating Factor Receptors on Granulocytes Are Down-Regulated after Endotoxin Administration to Healthy Humans

Granulocyte colony-stimulating factor (G-CSF) is considered an important mediator of host defense against infection, and recombinant G-CSF is administered to patients with various infections. G-CSF binds to a specific receptor that is expressed on granulocytes and monocytes. To obtain insight about the regulation of the G-CSF receptor after an acute infectious challenge, 8 healthy subjects received an intravenous injection of lipopolysaccharide (LPS; 4 ng/kg), and receptor expression was determined on blood leukocytes by fluorescence-activated cell sorter analysis, both by measurement of saturation binding of recombinant G-CSF and by use of an anti-G-CSF-receptor antibody. LPS induced a transient decrease in granulocyte, but not monocyte, G-CSF-receptor expression. In whole blood in vitro, not only LPS but also gram-positive stimuli and proinflammatory cytokines were capable of down-modulating the G-CSF receptor on granulocytes. Bacterial antigens down-regulate the G-CSF receptor at the surface of granulocytes, which may impair neutrophil functions important for antibacterial host defense.