Reducing the dosing frequency of selective digestive tract decontamination to three times daily provides effective decontamination of Gram-negative bacteria.

This study evaluated the effectiveness of selective digestive tract decontamination (SDD) application three times daily (t.i.d.) compared to the standard four times daily (q.i.d.). Retrospective equivalence (combined non-inferiority and non-superiority design) study with a before-and-after design on a tertiary ICU in which the SDD frequency was reduced from q.i.d. to t.i.d. All patients with ICU admissions ≥72h and with ≥2 surveillance cultures collected on different dates were included in this study. We compared successful decontamination of Gram-negative bacteria (GNB). Furthermore, time to decontamination, ICU-acquired GNB bacteraemia and 28-day mortality were compared between the two groups. In total 1958 ICU admissions (1236 q.i.d., 722 t.i.d). Decontamination was achieved during the first week of admission in 77% and 76% of patients receiving SDD q.i.d and t.i.d., respectively. Successful decontamination within 14 days (without consecutive acquisition of Gram-negative bacteria) was achieved in 69.3% of the admissions with q.i.d. versus 66.8% in t.i.d. SDD (p-value = 0.2519). The proportions of successful decontamination of GNB were equivalent in both groups (-0.025, 98% CI: -0.087; 0.037). There was no significant difference in time to decontamination between the two regimens (log-rank test p-value = 0.55). Incidence (episodes/1000 days) of ICU-acquired GNB bacteraemia was 0.9 in both groups, and OR for death at day 28 in the t.i.d. group compared to the q.i.d. group was 0.99 (95% confidence interval, 0.80-1.21). This study shows that a t.i.d. application regimen achieves similar outcomes to the standard q.i.d. regime, for both microbiological and clinical outcome measures.

Citrate anticoagulation for continuous venovenous hemofiltration.

OBJECTIVE: Continuous venovenous hemofiltration (CVVH) is applied in critically ill patients with acute renal failure for renal replacement. Heparins used to prevent circuit clotting may cause bleeding. Regional anticoagulation with citrate reduces bleeding, but has metabolic risks. The aim was to compare the safety and efficacy of the two. DESIGN: Randomized, nonblinded, controlled single-center trial. SETTING: General intensive care unit of a teaching hospital. PATIENTS: Adult critically ill patients needing CVVH for acute renal failure and without an increased bleeding risk. INTERVENTIONS: Regional anticoagulation with citrate or systemic anticoagulation with the low-molecular weight heparin nadroparin. MEASUREMENTS AND MAIN RESULTS: End points were adverse events necessitating discontinuation of study anticoagulant, transfusion, metabolic and clinical outcomes, and circuit survival. Of the 215 randomized patients, 200 received CVVH per protocol (97 citrate and 103 nadroparin). Adverse events required discontinuation of citrate in two patients (accumulation and clotting) of nadroparin in 20 (bleeding and thrombocytopenia) (p < 0.001). Bleeding occurred in 6 vs. 16 patients (p = 0.08). The median number of red blood cell units transfused per CVVH day was 0.27 (interquartile range, 0.0-0.63) for citrate, 0.36 (interquartile range, 0-0.83) for nadroparin (p = 0.31). Citrate conferred less metabolic alkalosis (p = 0.001) and lower plasma calcium (p < 0.001). Circuit survival was similar. Three-month mortality on intention-to-treat was 48% (citrate) and 63% (nadroparin) (p = 0.03), per protocol 45% and 62% (p = 0.02). Citrate reduced mortality in surgical patients (p = 0.007), sepsis (p = 0.01), higher Sepsis-Related Organ Failure Assessment score (p = 0.006), and lower age (p = 0.009). CONCLUSIONS: The efficacy of citrate and nadroparin anticoagulation for CVVH was similar, however, citrate was safer. Unexpectedly, citrate reduced mortality. Less bleeding could only partly explain this benefit, less clotting could not. Post hoc citrate appeared particularly beneficial after surgery, in sepsis and severe multiple organ failure, suggesting interference with inflammation.

Off hour admission to an intensivist-led ICU is not associated with increased mortality.

INTRODUCTION: Caring for the critically ill is a 24-hour-a-day responsibility, but not all resources and staff are available during off hours. We evaluated whether intensive care unit (ICU) admission during off hours affects hospital mortality. METHODS: This retrospective multicentre cohort study was carried out in three non-academic teaching hospitals in the Netherlands. All consecutive patients admitted to the three ICUs between 2004 and 2007 were included in the study, except for patients who did not fulfil APACHE II criteria (readmissions, burns, cardiac surgery, younger than 16 years, length of stay less than 8 hours). Data were collected prospectively in the ICU databases. Hospital mortality was the primary endpoint of the study. Off hours was defined as the interval between 10 pm and 8 am during weekdays and between 6 pm and 9 am during weekends. Intensivists, with no responsibilities outside the ICU, were present in the ICU during daytime and available for either consultation or assistance on site during off hours. Residents were available 24 hours a day 7 days a week in two and fellows in one of the ICUs. RESULTS: A total of 6725 patients were included in the study, 4553 (67.7%) admitted during daytime and 2172 (32.3%) admitted during off hours. Baseline characteristics of patients admitted during daytime were significantly different from those of patients admitted during off hours. Hospital mortality was 767 (16.8%) in patients admitted during daytime and 469 (21.6%) in patients admitted during off hours (P < 0.001, unadjusted odds ratio 1.36, 95%CI 1.20-1.55). Standardized mortality ratios were similar for patients admitted during off hours and patients admitted during daytime. In a logistic regression model APACHE II expected mortality, age and admission type were all significant confounders but off-hours admission was not significantly associated with a higher mortality (P = 0.121, adjusted odds ratio 1.125, 95%CI 0.969-1.306). CONCLUSIONS: The increased mortality after ICU admission during off hours is explained by a higher illness severity in patients admitted during off hours.

Influence of severity of illness, medication and selective decontamination on defecation.

OBJECTIVE: To describe the pattern of defecation in critically ill ventilated patients and the influence of selective decontamination (SDD) and other medication. DESIGN: Descriptive cohort study. SETTING: Mixed surgical-medical ICU in a university Hospital. PATIENTS: Ventilated patients with a length of stay >or=7 days taking part in a study on SDD. MEASUREMENTS: Daily registration of defecation, SOFA (sepsis-related organ failure assessment score) score, administration of dopamine, noradrenaline, morphine and other medications. RESULTS: The first defecation occurred after a mean of 6.2 days. Patients with defecation within 6[Symbol: see text]days had lower mean SOFA scores, received more cisapride and lactulose and less dopamine, noradrenaline and morphine, and had a shorter duration of mechanical ventilation and ICU stay. On 57% of the days, no stools were produced; on 31% diarrhea, and on 12%, normal stools. Patients receiving SDD had more days with normal stools and less with diarrhea. Diarrhea was preceded by the administration of lactulose in the majority of patients. CONCLUSION: Time to first defecation correlated with severity of illness, vasoactive medication, administration of morphine, cisapride and lactulose, duration of mechanical ventilation and length of stay. Diarrhea seemed at least partially iatrogenic.

Pitfalls in gastrointestinal permeability measurement in ICU patients with multiple organ failure using differential sugar absorption.

OBJECTIVE: To assess whether gastrointestinal permeability (GIP) at intensive care unit (ICU) admission, measured by differential sugar absorption, is related to severity of disease and multiple organ failure (MOF). Post hoc, to analyse the relation between the urinary sugar recovery and renal function. DESIGN: Prospective observational cohort study. SETTING: Eighteen-bed general ICU of a teaching hospital. PATIENTS: Sixty-four ventilated patients admitted with MOF. INTERVENTIONS: GIP was assessed within 24 h using cellobiose (C), sucrose (S) and mannitol (M) absorption. MEASUREMENTS AND RESULTS: Severity of disease: APACHE II and III, SAPS II and MPM II systems. Organ failure: SOFA, MODS and Goris score. The median urinary recovery of C was 0.147% (range 0.004-2.145%), of S 0.249% (0.001-3.656%) and of M 10.7% (0.6-270%). In 16 patients, M recovery was over 100% of the oral dose. They received red blood cell transfusion (RBC). In the non-transfused, the median cellobiose/mannitol (CM) ratio was 0.015 (0.0004-0.550). CM ratio was not related to severity of disease and inversely related to the SOFA score ( r=-0.30, p=0.04). Post hoc regression analysis showed that recoveries of C, S and M were positively related to urinary volume. Recoveries of C and S, but not of M, were positively related to creatinine clearance. The CM ratio corrected for diuresis, but was inversely related to creatinine clearance. CONCLUSIONS: Differential C, S and M absorption testing is unreliable after RBC transfusion, since bank blood contains mannitol. The excretion of C and S, but not of M, is limited by renal dysfunction. Differential sugar absorption is not reliable to test GIP in MOF patients, since non-permeability related factors act as confounders.

Serum neuron-specific enolase predicts outcome in post-anoxic coma: a prospective cohort study.

OBJECTIVE: The aim of this study was to investigate whether serial serum neuron-specific enolase (NSE) can be used to predict neurological prognosis in patients remaining comatose after cardiopulmonary resuscitation (CPR). DESIGN. Observational cohort study. Clinicians were blinded to NSE results. SETTING: Eighteen-bed general ICU. PATIENTS: Comatose patients admitted to the ICU after CPR. INTERVENTIONS: Serum NSE was measured at admission and daily for 5 days. MEASUREMENTS AND RESULTS: Patients received full intensive treatment until recovery or until absence of cortical response to somatosensory evoked potentials more than 48 h after CPR proved irreversible coma. Of the 110 patients included (mean GCS at ICU admission 3, range 3--9), 34 regained consciousness, five of whom died in hospital. Seventy-six patients did not regain consciousness, 72 of whom died in hospital. Serum NSE at 24 h and at 48 h after CPR was significantly higher in patients who did not regain consciousness than in patients who regained consciousness (at 24 h: median NSE 29.9 microg/l, range 1.8-250 vs 9.9 microg/l, range 4.5-21.5, P<0.001; at 48 h: median 37.8 microg/l, range 4.4-411 vs 9.5 microg/l, range 6.2-22.4, P= 0.001). No patient with a serum NSE level >25.0 microg/l at any time regained consciousness. Addition of NSE to GCS and somatosensory evoked potentials increased predictability of poor neurological outcome from 64% to 76%. CONCLUSIONS: High serum NSE levels in comatose patients at 24 h and 48 h after CPR predict a poor neurological outcome. Addition of NSE to GCS and somatosensory evoked potentials increases predictability of neurological outcome.

Hospital mortality is associated with ICU admission time.

INTRODUCTION: Previous studies have shown that patients admitted to the intensive care unit (ICU) after "office hours" are more likely to die. However these results have been challenged by numerous other studies. We therefore analysed this possible relationship between ICU admission time and in-hospital mortality in The Netherlands. METHODS: This article relates time of ICU admission to hospital mortality for all patients who were included in the Dutch national ICU registry (National Intensive Care Evaluation, NICE) from 2002 to 2008. We defined office hours as 08:00-22:00 hours during weekdays and 09:00-18:00 hours during weekend days. The weekend was defined as from Saturday 00:00 hours until Sunday 24:00 hours. We corrected hospital mortality for illness severity at admission using Acute Physiology and Chronic Health Evaluation II (APACHE II) score, reason for admission, admission type, age and gender. RESULTS: A total of 149,894 patients were included in this analysis. The relative risk (RR) for mortality outside office hours was 1.059 (1.031-1.088). Mortality varied with time but was consistently higher than expected during "off hours" and lower during office hours. There was no significant difference in mortality between different weekdays of Monday to Thursday, but mortality increased slightly on Friday (RR 1.046; 1.001-1.092). During the weekend the RR was 1.103 (1.071-1.136) in comparison with the rest of the week. CONCLUSIONS: Hospital mortality in The Netherlands appears to be increased outside office hours and during the weekends, even when corrected for illness severity at admission. However, incomplete adjustment for certain confounders might still play an important role. Further research is needed to fully explain this difference.

Erythromycin precipitation in vena femoralis: investigation of crystals found in postmortem material of an intensive care unit patient.

A case of intravenous precipitation of erythromycin is reported along with the patient history, pathologic findings, and a description of the analytical methods and results. The patient was a 75-year-old woman with a history of myocardial infarction, deep venous thrombosis, and diabetes mellitus who underwent aortic valve replacement. She developed endocarditis and recurrent episodes of urosepsis, with multiple organ failure including severe gastric retention, for which she was treated with erythromycin intravenously. She died because of refractory septic shock. Autopsy revealed aortic valve endocarditis, thrombi in the right femoral vein, arterial (nonfungal) thromboemboli in the celiac trunk, and coarse material in the right femoral vein where the tip of the central venous catheter had been located. Microscopical examination of the coarse material showed that it was birefringent crystalline material. Part of the postmortem material was analyzed in the laboratory of the department of clinical pharmacy and revealed the presence of erythromycin. Erythromycin was detected using Fourier transform infrared spectroscopy. An additional specific color test and thin-layer chromatography confirmed this finding. On the basis of the postmortem findings, patient history, and analytical-toxicologic results, we conclude that erythromycin precipitation can occur in vivo after intravenous administration in patients with impaired blood flow.

Laxation of critically ill patients with lactulose or polyethylene glycol: a two-center randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To study whether lactulose or polyethylene glycol is effective to promote defecation in critically ill patients, whether either of the two is superior, and whether the use of enteral laxatives is related to clinical outcome. DESIGN: Double-blind, placebo-controlled, randomized study. SETTING: Two tertiary intensive care units. PATIENTS: Three hundred and eight consecutive patients with multiple organ failure were included when receiving mechanical ventilation and intravenous circulatory support and when defecation did not occur on day 3 after admission. INTERVENTIONS: Thrice daily administration of lactulose, polyethylene glycol, or placebo until defecation occurred, to a maximum of 4 days. MEASUREMENTS AND MAIN RESULTS: The number of patients with defecation during the study period was 32 of 103 (31%) for placebo, 76 of 110 (69%) for lactulose, and 70 of 95 (74%) for polyethylene glycol (p = .001 for lactulose and polyethylene glycol vs. placebo). Lactulose and polyethylene glycol-treated patients produced stools after a median of 36 and 44 hrs, respectively, compared with 75 hrs for the placebo group (p = .001 for lactulose and polyethylene glycol vs. placebo). Length of stay in the intensive care unit was a median of 156 hrs for the lactulose group, 190 hrs for the polyethylene glycol group, and 196 hrs for the placebo group (p = .001). Intestinal pseudoobstruction or Ogilvie's syndrome occurred in 4.1% of patients in the placebo group, 5.5% of patients in the lactulose group, and 1.0% of patients in the polyethylene glycol group. There was no difference in hospital mortality. Administration of morphine was associated with a longer time before first defecation, except in the polyethylene glycol group. For all groups, defecation within 6 days after admission was associated with a shorter length of stay. CONCLUSIONS: Both lactulose and polyethylene glycol are more effective in promoting defecation than placebo. Patients receiving polyethylene glycol had a slightly lower incidence of acute intestinal pseudoobstruction, whereas length of stay was shorter in lactulose-treated patients. Morphine administration was associated with delayed defecation except in the polyethylene glycol-treated group. Irrespective of study medication, early defecation was associated with a shorter length of stay.