Anne Marie G. A. de Smet

Long-term propofol infusion and cardiac failure in adult head-injured patients

Five adult patients with head injuries inexplicably had fatal cardiac arrests In our neurosurgical intensive-care unit after the introduction of a sedation formulation containing an increased concentration of propofol. To examine the possible relation further, we did a retrospective cohort analysis of head-injured adults admitted to our unit between 1996 and 1999 who were sedated and mechanically ventilated. 67 patients met the inclusion criteria, of whom seven were judged to have died from propofol-infusion syndrome. The odds ratio for the occurrence of the syndrome was 1.93 (95% CI 1.12-3.32, p=0.018) for every mg/kg per h increase in mean propofol dose above 5 mg/kg per h. We suggest that propofol infusion at rates higher than 5 mg/kg per h should be discouraged for long-term sedation in the intensive-care unit.

Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial

BACKGROUND In critically ill patients, antibiotic therapy is of great importance but long duration of treatment is associated with the development of antimicrobial resistance. Procalcitonin is a marker used to guide antibacterial therapy and reduce its duration, but data about safety of this reduction are scarce. We assessed the efficacy and safety of procalcitonin-guided antibiotic treatment in patients in intensive care units (ICUs) in a health-care system with a comparatively low use of antibiotics. METHODS We did a prospective, multicentre, randomised, controlled, open-label intervention trial in 15 hospitals in the Netherlands. Critically ill patients aged at least 18 years, admitted to the ICU, and who received their first dose of antibiotics no longer than 24 h before inclusion in the study for an assumed or proven infection were eligible to participate. Patients who received antibiotics for presumed infection were randomly assigned (1:1), using a computer-generated list, and stratified (according to treatment centre, whether infection was acquired before or during ICU stay, and dependent on severity of infection [ie, sepsis, severe sepsis, or septic shock]) to receive either procalcitonin-guided or standard-of-care antibiotic discontinuation. Both patients and investigators were aware of group assignment. In the procalcitonin-guided group, a non-binding advice to discontinue antibiotics was provided if procalcitonin concentration had decreased by 80% or more of its peak value or to 0·5 μg/L or lower. In the standard-of-care group, patients were treated according to local antibiotic protocols. Primary endpoints were antibiotic daily defined doses and duration of antibiotic treatment. All analyses were done by intention to treat. Mortality analyses were completed for all patients (intention to treat) and for patients in whom antibiotics were stopped while being on the ICU (per-protocol analysis). Safety endpoints were reinstitution of antibiotics and recurrent inflammation measured by C-reactive protein concentrations and they were measured in the population adhering to the stopping rules (per-protocol analysis). The study is registered with ClinicalTrials.gov, number NCT01139489, and was completed in August, 2014. FINDINGS Between Sept 18, 2009, and July 1, 2013, 1575 of the 4507 patients assessed for eligibility were randomly assigned to the procalcitonin-guided group (761) or to standard-of-care (785). In 538 patients (71%) in the procalcitonin-guided group antibiotics were discontinued in the ICU. Median consumption of antibiotics was 7·5 daily defined doses (IQR 4·0-12·7) in the procalcitonin-guided group versus 9·3 daily defined doses (5·0-16·6) in the standard-of-care group (between-group absolute difference 2·69, 95% CI 1·26-4·12, p<0·0001). Median duration of treatment was 5 days (3-9) in the procalcitonin-guided group and 7 days (4-11) in the standard-of-care group (between-group absolute difference 1·22, 0·65-1·78, p<0·0001). Mortality at 28 days was 149 (20%) of 761 patients in the procalcitonin-guided group and 196 (25%) of 785 patients in the standard-of-care group (between-group absolute difference 5·4%, 95% CI 1·2-9·5, p=0·0122) according to the intention-to-treat analysis, and 107 (20%) of 538 patients in the procalcitonin-guided group versus 121 (27%) of 457 patients in the standard-of-care group (between-group absolute difference 6·6%, 1·3-11·9, p=0·0154) in the per-protocol analysis. 1-year mortality in the per-protocol analysis was 191 (36%) of 538 patients in the procalcitonin-guided and 196 (43%) of 457 patients in the standard-of-care groups (between-group absolute difference 7·4, 1·3-13·8, p=0·0188). INTERPRETATION Procalcitonin guidance stimulates reduction of duration of treatment and daily defined doses in critically ill patients with a presumed bacterial infection. This reduction was associated with a significant decrease in mortality. Procalcitonin concentrations might help physicians in deciding whether or not the presumed infection is truly bacterial, leading to more adequate diagnosis and treatment, the cornerstones of antibiotic stewardship. FUNDING Thermo Fisher Scientific.

Ecological effects of selective decontamination on resistant gram-negative bacterial colonization.

RATIONALE Selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD) eradicate gram-negative bacteria (GNB) from the intestinal and respiratory tract in intensive care unit (ICU) patients, but their effect on antibiotic resistance remains controversial. OBJECTIVES We quantified the effects of SDD and SOD on bacterial ecology in 13 ICUs that participated in a study, in which SDD, SOD, or standard care was used during consecutive periods of 6 months (de Smet AM, Kluytmans JA, Cooper BS, Mascini EM, Benus RF, van der Werf TS, van der Hoeven JG, Pickkers P, Bogaers-Hofman D, van der Meer NJ, et al. N Engl J Med 2009;360:20-31). METHODS Point prevalence surveys of rectal and respiratory samples were performed once monthly in all ICU patients (receiving or not receiving SOD/SDD). Effects of SDD on rectal, and of SDD/SOD on respiratory tract, carriage of GNB were determined by comparing results from consecutive point prevalence surveys during intervention (6 mo for SDD and 12 mo for SDD/SOD) with consecutive point prevalence data in the pre- and postintervention periods. MEASUREMENTS AND MAIN RESULTS During SDD, average proportions of patients with intestinal colonization with GNB resistant to either ceftazidime, tobramycin, or ciprofloxacin were 5, 7, and 7%, and increased to 15, 13, and 13% postintervention (P < 0.05). During SDD/SOD resistance levels in the respiratory tract were not more than 6% for all three antibiotics but increased gradually (for ceftazidime; P < 0.05 for trend) during intervention and to levels of 10% or more for all three antibiotics postintervention (P < 0.05). CONCLUSIONS SOD and SDD have marked effects on the bacterial ecology in an ICU, with rising ceftazidime resistance prevalence rates in the respiratory tract during intervention and a considerable rebound effect of ceftazidime resistance in the intestinal tract after discontinuation of SDD.

Comparative Evaluation of the VITEK 2, Disk Diffusion, Etest, Broth Microdilution, and Agar Dilution Susceptibility Testing Methods for Colistin in Clinical Isolates, Including Heteroresistant Enterobacter cloacae and Acinetobacter baumannii Strains

ABSTRACT Increasing antibiotic resistance in gram-negative bacteria has recently renewed interest in colistin as a therapeutic option. The increasing use of colistin necessitates the availability of rapid and reliable methods for colistin susceptibility testing. We compared seven methods of colistin susceptibility testing (disk diffusion, agar dilution on Mueller-Hinton [MH] and Isosensitest agar, Etest on MH and Isosensitest agar, broth microdilution, and VITEK 2) on 102 clinical isolates collected from patient materials during a selective digestive decontamination or selective oral decontamination trial in an intensive-care unit. Disk diffusion is an unreliable method to measure susceptibility to colistin. High error rates and low levels of reproducibility were observed in the disk diffusion test. The colistin Etest, agar dilution, and the VITEK 2 showed a high level of agreement with the broth microdilution reference method. Heteroresistance for colistin was observed in six Enterobacter cloacae isolates and in one Acinetobacter baumannii isolate. This is the first report of heteroresistance to colistin in E. cloacae isolates. Resistance to colistin in these isolates seemed to be induced upon exposure to colistin rather than being caused by stable mutations. Heteroresistant isolates could be detected in the broth microdilution, agar dilution, Etest, or disk diffusion test. The VITEK 2 displayed low sensitivity in the detection of heteroresistant subpopulations of E. cloacae. The VITEK 2 colistin susceptibility test can therefore be considered to be a reliable tool to determine susceptibility to colistin in isolates of genera that are known not to exhibit resistant subpopulations. In isolates of genera known to (occasionally) exhibit heteroresistance, an alternative susceptibility testing method capable of detecting heteroresistance should be used.

Effects of Decontamination of the Oropharynx and Intestinal Tract on Antibiotic Resistance in ICUs: A Randomized Clinical Trial

IMPORTANCE Selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) are prophylactic antibiotic regimens used in intensive care units (ICUs) and associated with improved patient outcome. Controversy exists regarding the relative effects of both measures on patient outcome and antibiotic resistance. OBJECTIVE To compare the effects of SDD and SOD, applied as unit-wide interventions, on antibiotic resistance and patient outcome. DESIGN, SETTING, AND PARTICIPANTS Pragmatic, cluster randomized crossover trial comparing 12 months of SOD with 12 months of SDD in 16 Dutch ICUs between August 1, 2009, and February 1, 2013. Patients with an expected length of ICU stay longer than 48 hours were eligible to receive the regimens, and 5881 and 6116 patients were included in the clinical outcome analysis for SOD and SDD, respectively. INTERVENTIONS Intensive care units were randomized to administer either SDD or SOD. MAIN OUTCOMES AND MEASURES Unit-wide prevalence of antibiotic-resistant gram-negative bacteria. Secondary outcomes were day-28 mortality, ICU-acquired bacteremia, and length of ICU stay. RESULTS In point-prevalence surveys, prevalences of antibiotic-resistant gram-negative bacteria in perianal swabs were significantly lower during SDD compared with SOD; for aminoglycoside resistance, average prevalence was 5.6% (95% CI, 4.6%-6.7%) during SDD and 11.8% (95% CI, 10.3%-13.2%) during SOD (P < .001). During both interventions the prevalence of rectal carriage of aminoglycoside-resistant gram-negative bacteria increased 7% per month (95% CI, 1%-13%) during SDD (P = .02) and 4% per month (95% CI, 0%-8%) during SOD (P = .046; P = .40 for difference). Day 28-mortality was 25.4% and 24.1% during SOD and SDD, respectively (adjusted odds ratio, 0.96 [95% CI, 0.88-1.06]; P = .42), and there were no statistically significant differences in other outcome parameters or between surgical and nonsurgical patients. Intensive care unit-acquired bacteremia occurred in 5.9% and 4.6% of the patients during SOD and SDD, respectively (odds ratio, 0.77 [95% CI, 0.65-0.91]; P = .002; number needed to treat, 77). CONCLUSIONS AND RELEVANCE Unit-wide application of SDD and SOD was associated with low levels of antibiotic resistance and no differences in day-28 mortality. Compared with SOD, SDD was associated with lower rectal carriage of antibiotic-resistant gram-negative bacteria and ICU-acquired bacteremia but a more pronounced gradual increase in aminoglycoside-resistant gram-negative bacteria. TRIAL REGISTRATION trialregister.nlIdentifier: NTR1780.

The role of intestinal colonization with gram-negative bacteria as a source for intensive care unit-acquired bacteremia

Objective:Selective digestive tract decontamination aims to eradicate Gram-negative bacteria in both the intestinal tract and respiratory tract and is combined with a 4-day course of intravenous cefotaxime. Selective oropharyngeal decontamination only aims to eradicate respiratory tract colonization. In a recent study, selective digestive tract decontamination and selective oropharyngeal decontamination were associated with lower day-28 mortality, when compared to standard care. Furthermore, selective digestive tract decontamination was associated with a lower incidence of intensive care unit-acquired bacteremia caused by Gram-negative bacteria. We quantified the role of intestinal tract carriage with Gram-negative bacteria and intensive care unit-acquired Gram-negative bacteremia. Design:Data from a cluster-randomized and a single-center observational study. Setting:Intensive care unit in The Netherlands. Patients:Patients with intensive care unit stay of >48 hrs that received selective digestive tract decontamination (n = 2,667), selective oropharyngeal decontamination (n = 2,166) or standard care (n = 1,945). Interventions:Selective digestive tract decontamination or selective oropharyngeal decontamination. Measurements and Main Results:Incidence densities (episodes/1000 days) of intensive care unit-acquired Gram-negative bacteremia were 4.5, 3.0, and 1.4 during standard care, selective oropharyngeal decontamination, and selective digestive tract decontamination, respectively, and the daily risk for developing intensive care unit-acquired Gram-negative bacteria bacteremia increased until days 36, 33, and 31 for selective digestive tract decontamination, standard care, and selective oropharyngeal decontamination and was always lowest during selective digestive tract decontamination. Rectal colonization with Gram-negative bacteria was present in 26% and 71% of patient days during selective digestive tract decontamination and selective oropharyngeal decontamination, respectively (p < .01). Irrespective of interventions, incidence densities of intensive care unit-acquired Gram-negative bacteremia was 4.5 during patient days with both intestinal and respiratory tract Gram-negative bacteria carriage. These incidence densities reduced with 33% (to 3.1) during days with intestinal Gram-negative bacteria carriage only and with another 45% (to 1.0) during days without Gram-negative bacteria carriage at both sites. Conclusions:Respiratory tract decolonization was associated with a 33% and intestinal tract decolonization was associated with a 45% reduction in the occurrence of intensive care unit-acquired Gram-negative bacteremia.

Cerebral hemodynamic responses to blood pressure manipulation in severely head-injured patients in the presence or absence of intracranial hypertension

The management of cerebral perfusion pressure (CPP) remains a controversial issue in the critical care of severely head-injured patients. Recently, it has been proposed that the state of cerebrovascular autoregulation should determine individual CPP targets. To find optimal perfusion pressure, we pharmacologically manipulated CPP in a range of 51 mm Hg (median; 25th–75th percentile, 48–53 mm Hg) to 108 mm Hg (102–112 mm Hg) on Days 0, 1, and 2 after severe head injury in 13 patients and studied the effects on intracranial pressure (ICP), autoregulation capacity, and brain tissue partial pressure of oxygen. Autoregulation was expressed as a static rate of regulation for 5-mm Hg CPP intervals based on middle cerebral artery flow velocity. When ICP was normal (26 occasions), there were no major changes in the measured variables when CPP was altered from a baseline level of 78 mm Hg (74–83 mm Hg), indicating that the brain was within autoregulation limits. Conversely, when intracranial hypertension was present (11 occasions), CPP reduction to less than 77 mm Hg (73–82 mm Hg) further increased ICP, decreased the static rate of regulation, and decreased brain tissue partial pressure of oxygen, whereas a CPP increase improved these variables, indicating that the brain was operating at the lower limit of autoregulation. We conclude that daily trial manipulation of arterial blood pressure over a wide range can provide information that may be used to optimize CPP management.

Does hypercarbia develop faster during laparoscopic herniorrhaphy than during laparoscopic cholecystectomy? Assessment with continuous blood gas monitoring

The use of CO2 to create and maintain a pneumoperitoneum during laparoscopic surgery may lead to hypercarbia and acidosis.CO2 is also insufflated into the preperitoneal space to create and maintain a pneumopreperitoneum for laparoscopic herniorrhaphy. This study examined the influence of CO2 pneumopreperitoneum on the development of hypercarbia and acidosis assessed with continuous intraarterial blood gas monitoring. Changes in blood gas values were measured with both continuous intraarterial and intermittent blood gas monitoring. Over a 4-mo period, blood gas values of 14 patients undergoing laparoscopic herniorrhaphy (pneumopreperitoneum) were compared with those of 13 patients undergoing laparoscopic cholecystectomy (pneumoperitoneum) in a tertiary referral center. Additionally, heart rate and blood pressure were measured during stable ventilation at constant insufflation pressure. Pneumopreperitoneum resulted in a significantly faster development of hypercarbia (P = 0.023) and acidosis (P = 0.027) than pneumoperitoneum. These results were not explained when corrected for changes in hemodynamic and ventilatory variables using analysis of covariance. We conclude that the more rapid development of hypercarbia and acidosis during pneumopreperitoneum can be explained by increased CO2 absorption through an increasing gas exchange area during the procedure and through a larger wound bed. (Anesth Analg 1995;81:1243-9)

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.

Selective decontamination of the digestive tract

Purpose of reviewThe aim of this article is to review relevant studies on the topic of selective decontamination of the digestive tract published in 2006 and 2007. Recent findingsThe only recently published randomized controlled selective decontamination of the digestive tract study failed to demonstrate a benefit of selective decontamination on survival among trauma patients. In fact, two new meta-analyses of selective decontamination of the digestive tract studies were presented: one demonstrated reduced incidences of Gram-negative bacteraemia; in the other no reduction in fungaemia was found. Although selective decontamination of the digestive tract has been associated with increased selection of methicillin-resistant Staphylococcus aureus (MRSA), transmission of MRSA was controlled in a Spanish unit when using selective decontamination in combination with topical vancomycin. Several randomized studies and one meta-analysis suggest that oropharyngeal decontamination with antiseptics is also highly effective in preventing respiratory tract infection in critically ill patients. SummaryThe evidence that selective decontamination of the digestive tract improves patient outcome in mixed ICU patients is still based upon meta-analysis and two single centre studies in MRSA-naïve settings. Larger and preferably multicentre studies are needed to confirm these observations. Further remaining questions are whether oropharyngeal decontamination alone is as effective as the full selective decontamination of the digestive tract regimen and whether selective decontamination could be applied successfully in settings with high levels of antibiotic resistance.