Rob Spanjersberg

Accuracy and feasibility of point-of-care and continuous blood glucose analysis in critically ill ICU patients

IntroductionTo obtain strict glucose regulation, an accurate and feasible bedside glucometry method is essential. We evaluated three different types of point-of-care glucometry in seriously ill intensive care unit (ICU) patients. The study was performed as a single-centre, prospective, observational study in a 12-bed medical ICU of a university hospital.MethodsPatients with an expected ICU stay of more than 48 hours were included. Because the reference laboratory delivers glucose values after approximately 30 to 60 minutes, which is too slow to use in a glucose regulation protocol and for calibration of the subcutaneous continuous glucose monitoring system (CGMS) (CGMS System Gold), we first validated the ICU-based blood gas/glucose analyser ABL715 (part 1 of the study). Subsequently, part 2 was performed: after inserting (and calibrating) the subcutaneous CGMS, heparinised arterial blood samples were drawn from an arterial line every 6 hours and analysed on both the Precision PCx point-of-care meter using test strips and on the blood gas/glucose analyser ABL715. CGMS glucose data were downloaded after 24 to 72 hours. The results of the paired measurements were analysed as a scatter plot by the method of Bland and Altman and were expressed as a correlation coefficient.ResultsPart 1: Four hundred and twenty-four blood samples were drawn from 45 critically ill ICU patients. The ICU-based blood gas/glucose analyser ABL715 provided a good estimate of conventional laboratory glucose assessment: the correlation coefficient was 0.95. In the Clarke error grid, 96.8% of the paired measurements were in the clinically acceptable zones A and B. Part 2: One hundred sixty-five paired samples were drawn from 19 ICU patients. The Precision PCx point-of-care meter showed a correlation coefficient of 0.89. Ninety-eight point seven percent of measurements were within zones A and B. The correlation coefficient for the subcutaneous CGMS System Gold was 0.89. One hundred percent of measurements were within zones A and B.ConclusionThe ICU-based blood glucose analyser ABL715 is a rapid and accurate alternative for laboratory glucose determination and can serve as a standard for ICU blood glucose measurements. The Precision PCx is a good alternative, but feasibility may be limited because of the blood sample handling. The subcutaneous CGMS System Gold is promising, but real-time glucose level reporting is necessary before it can be of clinical use in the ICU. When implementing a glucose-insulin algorithm in patient care or research, one should realise that the absolute glucose level may differ systematically among various measuring methods, influencing targeted glucose levels.

Impact of digestive and oropharyngeal decontamination on the intestinal microbiota in ICU patients

PurposeSelective digestive microbial decontamination (SDD) is hypothesized to benefit patients in intensive care (ICU) by suppressing Gram-negative potential pathogens from the colon without affecting the anaerobic intestinal microbiota. The purpose of this study was to provide more insight to the effects of digestive tract and oropharyngeal decontamination on the intestinal microbiota by means of a prospective clinical trial in which faecal samples were collected from ICU patients for intestinal microbiota analysis.MethodsThe faecal samples were collected from ICU patients enrolled in a multicentre trial to study the outcome of SDD and selective oral decontamination (SOD) in comparison with standard care (SC). Fluorescent in situ hybridization (FISH) was used to analyze the faecal microbiota. The numbers of bacteria from different bacterial groups were compared between the three regimens.ResultsThe total counts of bacteria per gram faeces did not differ between regimens. The F. prausnitzii group of bacteria, representing an important group among intestinal microbiota, was significantly reduced in the SDD regimen compared to the SC and SOD. The Enterobacteriaceae were significantly suppressed during SDD compared to both SOD and SC; enterococci increased in SDD compared to both other regimens.ConclusionsThe composition of the intestinal microbiota is importantly affected by SDD. The F. prausnitzii group was significantly suppressed during SDD. This group of microbiota is a predominant producer of butyrate, the main energy source for colonocytes. Reduction of this microbiota is an important trade-off while reducing gram-negative bacteria by SDD.

Inhibition of p38 mitogen-activated protein kinase: Dose-dependent suppression of leukocyte and endothelial response after endotoxin challenge in humans

Objective We studied the activity of a single oral dose of RWJ-67657, a synthetic p38 mitogen-activated protein kinase inhibitor, in preventing dual leukocyte/endothelial activation after endotoxin infusion in healthy volunteers. Design Prospective placebo-controlled study. Setting Intensive care unit at a university medical center. Subjects Twenty-one healthy male volunteers. Interventions Endotoxin (4 ng/kg) as a 1-min infusion. According to randomization, the volunteers received placebo (n = 6) or 1400 mg (n = 4), 700 mg (n = 6), or 350 mg (n = 5) of RWJ-67657. Measurements and Main Results Neutrophil activation was investigated by analyzing the extent of membrane expression of adhesion markers by calibrated flow cytometry. Circulating intercellular adhesion molecule-1 and E-selectin were measured by enzyme-linked immunosorbent assays. The endotoxin-induced shedding of L-selectin was diminished in a dose-dependent manner (p < .0001). High-dose RWJ-67657 prevented up-regulation of the integrins CD11b (p < .01) and CD 66b (p < .01) on neutrophils. The endotoxin-induced increase in circulating intercellular adhesion molecule-1 and circulation E-selectin was almost completely prevented by high-dose RWJ-67657. Conclusion A single oral dose of RWJ-67657 prevented neutrophil and endothelial activation after endotoxin infusion.

Physicians' and nurses' opinions on selective decontamination of the digestive tract and selective oropharyngeal decontamination: a survey

IntroductionUse of selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) in intensive care patients has been controversial for years. Through regular questionnaires we determined expectations concerning SDD (effectiveness) and experience with SDD and SOD (workload and patient friendliness), as perceived by nurses and physicians.MethodsA survey was embedded in a group-randomized, controlled, cross-over multicenter study in the Netherlands in which, during three 6-month periods, SDD, SOD or standard care was used in random order. At the end of each study period, all nurses and physicians from participating intensive care units received study questionnaires.ResultsIn all, 1024 (71%) of 1450 questionnaires were returned by nurses and 253 (82%) of 307 by physicians. Expectations that SDD improved patient outcome increased from 71% and 77% of respondents after the first two study periods to 82% at the end of the study (P = 0.004), with comparable trends among nurses and physicians. Nurses considered SDD to impose a higher workload (median 5.0, on a scale from 1 (low) to 10 (high)) than SOD (median 4.0) and standard care (median 2.0). Both SDD and SOD were considered less patient friendly than standard care (medians 4.0, 4.0 and 6.0, respectively). According to physicians, SDD had a higher workload (median 5.5) than SOD (median 5.0), which in turn was higher than standard care (median 2.5). Furthermore, physicians graded patient friendliness of standard care (median 8.0) higher than that of SDD and SOD (both median 6.0).ConclusionsAlthough perceived effectiveness of SDD increased as the trial proceeded, both among physicians and nurses, SOD and SDD were, as compared to standard care, considered to increase workload and to reduce patient friendliness. Therefore, education about the importance of oral care and on the effects of SDD and SOD on patient outcomes will be important when implementing these strategies.Trial registrationISRCTN35176830.

Pharmacokinetics of cefpirome in critically ill patients with renal failure treated by continuous veno-venous hemofiltration

Objective: To study the cefpirome pharmacokinetics of patients with sepsis and multiple organ failure treated with CVVH. Design: Measurements of serum and ultrafiltrate (UF) concentrations and in vitro sensitivity testing of isolated micro-organisms. Setting: University hospital-based, single ICU. Patients: Six critically ill CVVH- dependent patients with sepsis and multiple organ dysfunction syndrome in need of antimicrobial therapy. Age range: 60–75 years; APACHE II score for severity of illness on admission: 19–30. One patient survived. Interventions: Cefpirome i. v. was started at 2 g in 30 min, then continued 1 g i. v. b. i. d. Measurements: The UF rate was 27 ± 7 ml/min on day 1 and 34 ± 2 ml/min on day 2. Serum and ultrafiltrate samples were measured by a validated high performance liquid chromatography assay. Volume of distribution: 23 · 5(SD ± 4 · 6) l. Total cefpirome clearance was 32 ± 6 · 3 ml/min; cefpirome CVVH clearance (ClCVVH): 17 ± 4.2 ml/min; mean serum half-life (t1/2): 8.8 ± 2.3 h; mass transfer on day 1: 660 ± 123 mg/12 h (33 ± 6 % of administered dose)and day 2: 642 ± 66 mg/12 h (64 ± 7 %). Estimated sieving coefficient (ClCVVH/UF rate): 64 ± 11 %. In vitro sensitivity of isolated microbes was excellent except for two non-sensitive enterococci and Candida spp. Conclusions: The sieving coefficient (64 %) indicates that a substantial fraction of the drug is not filtered; clearance by pathways other than CVVH mounted to 50 % of the total clearance and increased on day 2, indicating that the dosing schedule used is appropriate for this setting. Cefpirome appeared to be safe in these patients and effective for most of the nosocomial microbial isolates. During more than 90 % of the time, serum levels were maintained above killing concentrations for susceptible micro-organisms.

Bispectral index values and propofol concentrations at loss and return of consciousness in patients with frontal brain tumours and control patients

BACKGROUND The influence of frontal brain tumours on bispectral index (BIS) measurements and propofol requirements is unknown. The primary aim of our study was to determine whether BIS values recorded at loss and return of consciousness (LOC and ROC, respectively) differ between patients with unilateral frontal brain tumours and control patients. Secondary goals were to compare propofol requirements for LOC and to determine whether there were significant inter-hemispheric differences between BIS values in tumour and control patients. METHODS We enrolled 20 patients with a frontal brain tumour and 20 control patients. Bilateral BIS measurements were done during induction of propofol anaesthesia, during recovery of consciousness, and during a second induction of anaesthesia. The isolated-forearm test was used to determine the moments of LOC1, ROC, and LOC2. Arterial blood samples were obtained every 4 min for determination of measured propofol concentrations. RESULTS The median BIS values recorded at LOC1, ROC, and LOC2 did not differ between the groups. There were no significant inter-hemispheric differences in BIS in tumour and control patients. The median [inter-quartile range (IQR)] total propofol doses at LOC1 were 82 (75-92) and 78 (68-91) mg in tumour and control patients, respectively. The median (IQR) measured plasma propofol concentrations at LOC1 were 12 (9-14) and 13 (11-15) µg ml(-1) in the tumour and control groups, respectively. CONCLUSIONS The presence of a frontal brain tumour did not affect ipsilateral BIS values, and so need not influence the placement of unilateral BIS electrodes if BIS monitoring is used to titrate propofol anaesthesia.