Ben van der Hoven

High-volume hemofiltration improves hemodynamics of endotoxin-induced shock in the pig☆

This study was designed to assess the influence of high-volume continuous hemofiltration on the hemodynamics of endotoxin-induced shock in pigs. Eighteen anesthetized and ventilated pigs were studied for 240 minutes following the start of a 30-minute infusion of 0.5 mg/kg endotoxin. They were randomly divided into three groups: group 1 served as a control group, receiving endotoxin only; group 2 received zero balance, high-volume, venovenous hemofiltration with the removal of 6,000 mL ultrafiltrate/hr; and group 3 was used to evaluate the hemodynamic effect of the extracorporeal circuit itself. The decline in mean arterial pressure for group 2 was less than for group 1 (24 ± 7.8 mm Hg [mean ± SEM] versus 60 ± 3.4 mm Hg; P < .001) as was the drop in cardiac output (0.35 ± 0.24 L/min versus 1.53 ± 0.59 L/min; P < .01). The decline in cardiac output was more pronounced in group 3 than in group 1 (3.98 ± 0.21 L/min versus 1.53 ± 0.59 L/min; P < .01). Left ventricular stroke work decreased by 61 ± 6.8 g in group 1 versus 14 ± 2.0 g in group 2 (P < .01), while left ventricular stroke work in group 3 was lower than that in group 1 (P < .02). Right ventricular stroke work increased further in group 2 than in group 1 (16 ± 2.1 g v 3 ± 0.8 g; P < .01). The pulmonary vascular resistance, systemic vascular resistance, right atrial pressure, and pulmonary artery wedge pressure in groups 2 and 3 did not differ from those in group 1. We conclude that in this model, high-volume venovenous hemofiltration significantly improves cardiac function but does not affect pulmonary vascular resistance or systemic vascular resistance, while the use of the extracorporeal circuit adversely affects cardiac function. The effect of hemofiltration was more pronounced in this study than in others, probably because of the higher ultrafiltrate volume.

Prognostic Value of Blood Lactate Levels : Does the Clinical Diagnosis at Admission Matter?

BACKGROUND Hyperlactatemia and its reduction after admission in the intensive care unit (ICU) have been related to survival. Because it is unknown whether this equally applies to different groups of critically ill patients, we compared the prognostic value of repeated lactate levels (a) in septic patients versus patients with hemorrhage or other conditions generally associated with low-oxygen transport (LT) (b) in hemodynamically stable versus unstable patients. METHODS In this prospective observational two-center study (n = 394 patients), blood lactate levels at admission to the ICU (Lac(T0)) and the reduction of lactate levels from T = 0 to T = 12 hours (DeltaLac(T0-12)) and from T = 12 to T = 24 hours (DeltaLac(T12-24)), were related to in-hospital mortality. RESULTS Reduction of lactate was associated with a lower mortality only in the sepsis group (DeltaLac(T0-12): hazard ratio [HR] 0.34, p = 0.004 and DeltaLac(T12-24): HR 0.24, p = 0.003), but not in the LT group (DeltaLac(T0-12); HR 0.78, p = 0.52 and DeltaLac(T12-24); HR 1.30, p = 0.61). The prognostic values of Lac(T0), DeltaLac(T0-12), and DeltaLac(T12-24) were similar in hemodynamically stable and unstable patients (p = 0.43). CONCLUSIONS Regardless of the hemodynamic status, lactate reduction during the first 24 hours of ICU stay is associated with improved outcome only in septic patients, but not in patients with hemorrhage or other conditions generally associated with LT. We hypothesize that in this particular group a reduction in lactate is not associated with improved outcome due to irreversible damage at ICU admission.

Effectiveness of insertion and maintenance bundles to prevent central-line-associated bloodstream infections in critically ill patients of all ages: a systematic review and meta-analysis

BACKGROUND Central-line-associated bloodstream infections (CLABSIs) are a major problem in intensive care units (ICUs) worldwide. We aimed to quantify the effectiveness of central-line bundles (insertion or maintenance or both) to prevent these infections. METHODS We searched Embase, MEDLINE OvidSP, Web-of-Science, and Cochrane Library to identify studies reporting the implementation of central-line bundles in adult ICU, paediatric ICU (PICU), or neonatal ICU (NICU) patients. We searched for studies published between Jan 1, 1990, and June 30, 2015. For the meta-analysis, crude estimates of infections were pooled by use of a DerSimonian and Laird random effect model. The primary outcome was the number of CLABSIs per 1000 catheter-days before and after implementation. Incidence risk ratios (IRRs) were obtained by use of random-effects models. FINDINGS We initially identified 4337 records, and after excluding duplicates and those ineligible, 96 studies met the eligibility criteria, 79 of which contained sufficient information for a meta-analysis. Median CLABSIs incidence were 5·7 per 1000 catheter-days (range 1·2-46·3; IQR 3·1-9·5) on adult ICUs; 5·9 per 1000 catheter-days (range 2·6-31·1; 4·8-9·4) on PICUs; and 8·4 per 1000 catheter-days (range 2·6-24·1; 3·7-16·0) on NICUs. After implementation of central-line bundles the CLABSI incidence ranged from 0 to 19·5 per 1000 catheter-days (median 2·6, IQR 1·2-4·4) in all types of ICUs. In our meta-analysis the incidence of infections decreased significantly from median 6·4 per 1000 catheter-days (IQR 3·8-10·9) to 2·5 per 1000 catheter-days (1·4-4·8) after implementation of bundles (IRR 0·44, 95% CI 0·39-0·50, p<0·0001; I(2)=89%). INTERPRETATION Implementation of central-line bundles has the potential to reduce the incidence of CLABSIs. FUNDING None.

What to do when a competent ICU patient does not want to live anymore but is dependent on life-sustaining treatment? Experience from The Netherlands

If patients on the intensive care unit (ICU) are awake and life-sustaining treatment is suspended because of the patients’ request, because of recovering from the disease, or because independence from organ function supportive or replacement therapy outside the ICU can no longer be achieved, these patients can suffer before they inevitably die. In The Netherlands, two scenarios are possible for these patients: (1) deep palliative (terminal) sedation through ongoing administration of barbiturates or benzodiazepines before withdrawal of treatment, or (2) deliberate termination of life (euthanasia) before termination of treatment. In this article we describe two awake patients who asked for withdrawal of life-sustaining measures, but who were dependent on mechanical ventilation. We discuss the doctrine of double effect in relation to palliative sedation on the ICU. Administration of sedatives and analgesics before withdrawal of treatment is seen as normal palliative care. We conclude that the doctrine of the double effect is not applicable in this situation, and mentioning it criminalised the practice unnecessarily and wrongfully.

Enhanced Paracetamol Clearance with Molecular Adsorbents Recirculating System (MARS ) in Severe Autointoxication

time of ingestion was approximately 7 h before presentation at the emergency de-partment. Initial trauma screening with CT scan imaging showed no signs of brain hemorrhage or injury and further screen-ing excluded a cardiac diagnosis. With a Glasgow coma score of 5, being hemody-namically stable, endotracheal intubation and mechanical ventilation was indicated. According to protocol high doses of intra- We would like to report an interesting observation concerning enhanced clear-ance of paracetamol in a case of severe au-to-intoxication using a Molecular Adsor-bents Recirculating System (MARS ). This case involves a 64-year-old woman admitted to the intensive care with deep hypothermia (29.5 ° C) and loss of con-sciousness after ingestion of 50 g para-cetamol and 5 g codeine. The suspected

Immature granulocytes predict microbial infection and its adverse sequelae in the intensive care unit

BACKGROUND We evaluated the predictive value of immature granulocyte (IG) percentage in comparison with white blood cell counts (WBC) and C-reactive protein (CRP), for infection, its invasiveness, and severity in critically ill patients. METHODS In 46 consecutive patients, blood samples were collected at the day (0) of a clinical suspicion of microbial infection and at days 1 and 3 thereafter. We defined infections, bloodstream infection, and septic shock within 7 days after enrollment. RESULTS Of the 46 patients, 31 patients had infection, 15 patients developed bloodstream infection, and 13 patients septic shock. C-reactive protein and IG percentage increased with increasing invasiveness and severity of infection, from day 0 onwards. Receiver operating characteristic analysis to predict infection showed an area under the curve of 0.66 (P=.10) for WBC vs 0.74 (P=.01) for CRP and 0.73 (P=.02) for IG percentage on day 0. Comparing WBC and CRP to WBC and IG percentage results in comparable prediction of microbial infection. Comparing WBC and CRP with WBC, CRP, and IG percentage suggests an additional early value of IG percentage, when not elevated, in ruling out infection. CONCLUSION Immature granulocyte percentage is a useful marker, as CRP, to predict infection, its invasiveness, and severity, in critically ill patients. However, the IG percentage adds to WBC and CRP in the early exclusion of infection and can be obtained routinely without extra blood sampling or costs.

Noninvasive functional liver blood flow measurement: comparison between bolus dose and steady-state clearance of sorbitol in a small-rodent model

Plasma clearance of D-sorbitol, a nontoxic polyol, occurs predominantly in the liver and has been used to measure functional liver blood flow after bolus and steady- state intravenous administration. However, it is not known which of these two administration methods is superior. Therefore, plasma D-sorbitol clearance was studied in an animal model both after a bolus dose and under steady-state (SS) conditions and compared directly with liver blood flow, under normal conditions, and after the induction of endotoxin (LPS) sepsis. Adult male Wistar rats (526 +/- 38 g body wt; n = 27) were anesthetized and mechanically ventilated. Hemodynamics, hepatic arterial flow, and portal venous flow were measured. Two groups were studied, namely healthy animals that served as controls and a sepsis group that received 5 mg/kg LPS intravenously (Escherichia coli O127:B8). Each animal received either a SS infusion (0.1 mg/100 g body wt per min) or a bolus (3 mg/100 g body wt) of a 5% D-sorbitol solution intravenously in a randomized order. After the initial measurements and a 60-min pause time in between (T(1/2,sorbitol) = 9 min), a crossover was done. The hepatic clearance of D-sorbitol in the control group showed a good correlation between bolus and SS (Spearmans r = 0.7681, P = 0.0004), and both techniques correlated well with total liver blood flow (TLBF) (r = 0.7239, P = 0.0023 and r = 0.7226, P = 0.0023, respectively). Also in the sepsis group there was a good correlation between bolus and SS sorbitol clearance (r = 0.6655, P = 0.0182). In the sepsis group, only the SS clearance correlated with TLBF (r = 0.6434, P = 0.024). In conclusion, in normal and under septic conditions, hepatic clearance of D-sorbitol either by bolus or a SS infusion is comparable. In healthy animals, this also correlated well with TLBF but not in septic conditions. However, this is expected because of the changes in the liver microcirculation, shunting, and decreased hepatocyte function in sepsis.

Intestinal fatty acid binding protein as a marker for intra-abdominal pressure-related complications in patients admitted to the intensive care unit; study protocol for a prospective cohort study (I-Fabulous study)

BackgroundIntra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) have detrimental effects on all organ systems and are associated with increased morbidity and mortality in critically ill patients admitted to an intensive care unit. Intra-bladder measurement of the intra-abdominal pressure (IAP) is currently the gold standard. However, IAH is not always indicative of intestinal ischemia, which is an early and rapidly developing complication. Sensitive biomarkers for intestinal ischemia are needed to be able to intervene before damage becomes irreversible. Gut wall integrity loss, including epithelial cell disruption and tight junctions breakdown, is an early event in intestinal damage. Intestinal Fatty Acid Binding Protein (I-FABP) is excreted in urine and blood specifically from damaged intestinal epithelial cells. Claudin-3 is a specific protein which is excreted in urine following disruption of intercellular tight junctions. This study aims to investigate if I-FABP and Claudin-3 can be used as a diagnostic tool for identifying patients at risk for IAP-related complications.Methods/DesignIn a multicenter, prospective cohort study 200 adult patients admitted to the intensive care unit with at least two risk factors for IAH as defined by the World Society of the Abdominal Compartment Syndrome (WSACS) will be included. Patients in whom an intra-bladder IAP measurement is contra-indicated or impossible and patients with inflammatory bowel diseases that may affect I-FABP levels will be excluded. The IAP will be measured using an intra-bladder technique. During the subsequent 72 hours, the IAP measurement will be repeated every six hours. At these time points, a urine and serum sample will be collected for measurement of I-FABP and Claudin-3 levels. Clinical outcome of patients during their stay at the intensive care unit will be monitored using the Sequential Organ Failure Assessment (SOFA) score.DiscussionSuccessful completion of this trial will provide evidence on the eventual role of the biomarkers I-FABP and Claudin-3 in predicting the risk of IAP-associated adverse outcome. This may aid early (surgical) intervention.Trial registrationThe trial is registered at the Netherlands Trial Register (NTR4638).

Voriconazole Resistance and Mortality in Invasive Aspergillosis: A Multicenter Retrospective Cohort Study

BACKGROUND Triazole resistance is an increasing problem in invasive aspergillosis (IA). Small case series show mortality rates of 50%-100% in patients infected with a triazole-resistant Aspergillus fumigatus, but a direct comparison with triazole-susceptible IA is lacking. METHODS A 5-year retrospective cohort study (2011-2015) was conducted to compare mortality in patients with voriconazole-susceptible and voriconazole-resistant IA. Aspergillus fumigatus culture-positive patients were investigated to identify patients with proven, probable, and putative IA. Clinical characteristics, day 42 and day 90 mortality, triazole-resistance profiles, and antifungal treatments were investigated. RESULTS Of 196 patients with IA, 37 (19%) harbored a voriconazole-resistant infection. Hematological malignancy was the underlying disease in 103 (53%) patients, and 154 (79%) patients were started on voriconazole. Compared with voriconazole-susceptible cases, voriconazole resistance was associated with an increase in overall mortality of 21% on day 42 (49% vs 28%; P = .017) and 25% on day 90 (62% vs 37%; P = .0038). In non-intensive care unit patients, a 19% lower survival rate was observed in voriconazole-resistant cases at day 42 (P = .045). The mortality in patients who received appropriate initial voriconazole therapy was 24% compared with 47% in those who received inappropriate therapy (P = .016), despite switching to appropriate antifungal therapy after a median of 10 days. CONCLUSIONS Voriconazole resistance was associated with an excess overall mortality of 21% at day 42 and 25% at day 90 in patients with IA. A delay in the initiation of appropriate antifungal therapy was associated with increased overall mortality.

Flatus profuse present in the muscles: subcutaneous emphysema of the lower abdominal wall and thighs, described in 1593 by Fabricius Hildanus.

BACKGROUND Between 1598 and 1641, 600 medical and surgical observations made by the famous German surgeon Guilhelmius Fabricius Hildanus (1560-1634) were published in his Observationum et curationum chirurgicarum centuriae I-VI. METHODS Review of the extant document for evidence of infection-related cases. RESULTS One of the case reports, published as Observatio LXX in the fifth Centuria, bears the title (in translation) Of flatus, profuse present in the muscles. This case report probably is the earliest accurate description of subcutaneous emphysema of the lower abdomen and thighs secondary to a retroperitoneal abscess. CONCLUSION The presence of gas in the superficial tissues of the abdominal wall or thighs is a rare feature and can be a late sign of an otherwise-obscure intra-abdominal abscess with gas-producing bacteria. Fabricius Hildanus almost certainly was the first to document this rare feature in 1593, and judged it important enough to describe in his Centuriae.