Background: Colorectal surgery is frequently complicated by surgical site infections (SSIs). The ... more Background: Colorectal surgery is frequently complicated by surgical site infections (SSIs). The most important consequences of SSIs are prolonged hospitalization, an increased risk of surgical reintervention and an increase in mortality. Perioperative intravenously administered antibiotic prophylaxis is the standard of care to reduce the risk of SSIs. In the last few decades, preoperative orally administered antibiotics have been suggested as additional prophylaxis to further reduce the risk of infection, but are currently not part of routine practice in most hospitals. The objective of this study is to evaluate the efficacy of a preoperative orally administered antibiotic prophylaxis (Pre-OP) in addition to intravenously administered perioperative antibiotic prophylaxis to reduce the incidence of deep SSIs and/or mortality after elective colorectal surgery. Methods/design: The PreCaution trial is designed as a multicenter, double-blind, randomized, placebo-controlled clinical trial that will be carried out in The Netherlands. Adult patients who are scheduled for elective colorectal surgery are eligible to participate. In total, 966 patients will be randomized to receive the study medication. This will either be Pre-OP, a solution that consists of tobramycin and colistin sulphate, or a placebo solution. The study medication will be administered four times daily during the 3 days prior to surgery. Perioperative intravenously administered antibiotic prophylaxis will be administered to all patients in accordance with national infection control guidelines. The primary endpoint of the study is the cumulative incidence of deep SSIs and/or mortality within 30 days after surgery. Secondary endpoints include both infectious and non-infectious complications of colorectal surgery, and will be evaluated 30 days and/or 6 months after surgery. Discussion: To date, conclusive evidence on the added value of preoperative orally administered antibiotic prophylaxis in colorectal surgery is lacking. The PreCaution trial should determine the effects of orally administered antibiotics in preventing infectious complications in elective colorectal surgery.
Introduction: Selective decontamination of the digestive tract (SDD) and selective oropharyngeal ... more Introduction: Selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) have been shown to improve intensive care unit (ICU) patients' outcomes. The aim of this study was to determine the effects of long-term use of SDD and SOD on colistin and tobramycin resistance among gram-negative bacteria. Methods: We performed a post hoc analysis of two consecutive multicentre cluster-randomised trials with crossover of interventions. SDD and SOD were alternately but continuously used during 7 years in five Dutch ICUs participating in two consecutive cluster-randomised trials. In both trials, to measure colistin and tobramycin resistance among gram-negative bacteria, rectal and respiratory samples were obtained monthly from all patients present in the ICU. Results: The prevalence of tobramycin resistance in respiratory and rectal samples decreased significantly during long-term use of SOD and SDD. (rectal samples risk ratio (RR) 0.35 (0.23 to 0.53); respiratory samples RR 0.48 (0.32 to 0.73), SDD compared to standard care). Colistin resistance in rectal and respiratory samples did not change (rectal samples RR 0.63 (0.29 to 1.38); respiratory samples RR 1.26 (0.35 to 4.57), SDD compared to standard care). Conclusions: In this study, in a setting with low antimicrobial resistance rates, the prevalence of resistance against colistin and tobramycin among gram-negative isolates did not increase during a mean of 7 years of SDD or SOD use.
Antimicrobial Resistance and Infection Control, Jun 15, 2020
Background: Surgical site infections (SSIs) are common complications after colorectal surgery. Or... more Background: Surgical site infections (SSIs) are common complications after colorectal surgery. Oral non-absorbable antibiotic prophylaxis (OAP) can be administered preoperatively to reduce the risk of SSIs. Its efficacy without simultaneous mechanical cleaning is unknown. Methods: The Precaution trial was a double-blind, placebo-controlled randomized clinical trial conducted in six Dutch hospitals. Adult patients who underwent elective colorectal surgery were randomized to receive either a three-day course of preoperative OAP with tobramycin and colistin or placebo. The primary composite endpoint was the incidence of deep SSI or mortality within 30 days after surgery. Secondary endpoints included both infectious and non-infectious complications at 30 days and six months after surgery. Results: The study was prematurely ended due to the loss of clinical equipoise. At that time, 39 patients had been randomized to active OAP and 39 to placebo, which reflected 8.1% of the initially pursued sample size. Nine (11.5%) patients developed the primary outcome, of whom four had been randomized to OAP (4/39; 10.3%) and five to placebo (5/39; 12.8%). This corresponds to a risk ratio in the intention-to-treat analysis of 0.80 (95% confidence interval (CI) 0.23-2.78). In the per-protocol analysis, the relative risk was 0.64 (95% CI 0.12-3.46).
PurposeAlthough elective surgery is generally safe, some procedures remain associated with an inc... more PurposeAlthough elective surgery is generally safe, some procedures remain associated with an increased risk of complications. Improved preoperative risk stratification and earlier recognition of these complications may ameliorate postoperative recovery and improve long-term outcomes. The perioperative longitudinal study of complications and long-term outcomes (PLUTO) cohort aims to establish a comprehensive biorepository that will facilitate research in this field. In this profile paper, we will discuss its design rationale and opportunities for future studies.ParticipantsPatients undergoing elective intermediate to high-risk non-cardiac surgery are eligible for enrolment. For the first seven postoperative days, participants are subjected to daily bedside visits by dedicated observers, who adjudicate clinical events and perform non-invasive physiological measurements (including handheld spirometry and single-channel electroencephalography). Blood samples and microbiome specimens ar...
Objectives: Prolonged emergency department to ICU waiting time may delay intensive care treatment... more Objectives: Prolonged emergency department to ICU waiting time may delay intensive care treatment, which could negatively affect patient outcomes. The aim of this study was to investigate whether emergency department to ICU time is associated with hospital mortality. Design, Setting, and Patients: We conducted a retrospective observational cohort study using data from the Dutch quality registry National Intensive Care Evaluation. Adult patients admitted to the ICU directly from the emergency department in six university hospitals, between 2009 and 2016, were included. Using a logistic regression model, we investigated the crude and adjusted (for disease severity; Acute Physiology and Chronic Health Evaluation IV probability) odds ratios of emergency department to ICU time on mortality. In addition, we assessed whether the Acute Physiology and Chronic Health Evaluation IV probability modified the effect of emergency department to ICU time on mortality. Secondary outcomes were ICU, 30...
Colorectal surgery is frequently complicated by surgical site infections (SSIs). The most importa... more Colorectal surgery is frequently complicated by surgical site infections (SSIs). The most important consequences of SSIs are prolonged hospitalization, an increased risk of surgical reintervention and an increase in mortality. Perioperative intravenously administered antibiotic prophylaxis is the standard of care to reduce the risk of SSIs. In the last few decades, preoperative orally administered antibiotics have been suggested as additional prophylaxis to further reduce the risk of infection, but are currently not part of routine practice in most hospitals. The objective of this study is to evaluate the efficacy of a preoperative orally administered antibiotic prophylaxis (Pre-OP) in addition to intravenously administered perioperative antibiotic prophylaxis to reduce the incidence of deep SSIs and/or mortality after elective colorectal surgery. The PreCaution trial is designed as a multicenter, double-blind, randomized, placebo-controlled clinical trial that will be carried out i...
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2017
Selective Digestive Decontamination (SDD) and Selective Oropharyngeal Decontamination (SOD) impro... more Selective Digestive Decontamination (SDD) and Selective Oropharyngeal Decontamination (SOD) improved ICU, hospital and 28-day survival in Intensive Care Units (ICU) with low levels of antibiotic resistance. Yet, it is unclear whether the effect differs between medical and surgical ICU patients. In an individual patient data meta-analysis we systematically searched PubMed and included all randomized controlled studies published since 2000. We performed a two-stage meta-analysis with separate logistic regression models per study and per outcome (hospital survival and ICU survival) and subsequent pooling of main and interaction effects. Six studies, all performed in countries with low levels of antibiotic resistance, yielded 16,528 hospital admissions and 17,884 ICU-admissions for complete case analysis. Compared to standard care or placebo the pooled adjusted odds ratios (aOR) for hospital mortality was 0·82 (95% Confidence Interval [CI] 0·72 - 0·93) for SDD and 0·84 (95%-CI 0·73 - 0·...
Dysnatremia is associated with adverse outcome in critically ill patients. Changes in patients or... more Dysnatremia is associated with adverse outcome in critically ill patients. Changes in patients or treatment strategies may have affected the incidence of dysnatremia over time. We investigated long-term changes in the incidence of dysnatremia and analyzed its association with mortality. Over a 21-year period (1992-2012), all serum sodium measurements were analyzed retrospectively in two university hospital ICUs, up to day 28 of ICU admission for the presence of dysnatremia. The study period was divided into five periods. All serum sodium measurements were collected from the electronic databases of both ICUs. Serum sodium was measured at the clinical chemistry departments using standard methods. All sodium measurements were categorized in the following categories: <120, 120-124, 125-129, 130-134, 135-139, 140-145, 146-150, 151-155, 156-160, >160 mmol/L. Mortality was determined at 90 days after ICU admission. In 80,571 ICU patients, 913,272 serum sodium measurements were analyz...
In critically ill patients, antibiotic therapy is of great importance but long duration of treatm... more 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. 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 (accord...
Introduction: Use of selective decontamination of the digestive tract (SDD) and selective orophar... more Introduction: Use 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. Methods: A 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. Results: In 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). Conclusions: Although 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 registration: ISRCTN35176830.
Take-down policy If you believe that this document breaches copyright please contact us providing... more Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
OBJECTIVESTo develop a scoring system model that predicts mortality within 30 days of admission o... more OBJECTIVESTo develop a scoring system model that predicts mortality within 30 days of admission of patients older than 80 years admitted to intensive care units (ICUs).DESIGNProspective cohort study.SETTINGA total of 306 ICUs from 24 European countries.PARTICIPANTSOlder adults admitted to European ICUs (N = 3730; median age = 84 years [interquartile range = 81‐87 y]; 51.8% male).MEASUREMENTSOverall, 24 variables available during ICU admission were included as potential predictive variables. Multivariable logistic regression was used to identify independent predictors of 30‐day mortality. Model sensitivity, specificity, and accuracy were evaluated with receiver operating characteristic curves.RESULTSThe 30‐day‐mortality was 1562 (41.9%). In multivariable analysis, these variables were selected as independent predictors of mortality: age, sex, ICU admission diagnosis, Clinical Frailty Scale, Sequential Organ Failure Score, invasive mechanical ventilation, and renal replacement therapy...
Respiratory pathogens like Streptococcus pneumoniae can cause severe pneumonia. Nonetheless, mech... more Respiratory pathogens like Streptococcus pneumoniae can cause severe pneumonia. Nonetheless, mechanically ventilated intensive care patients, who have a high risk of contracting pneumonia, rarely develop pneumococcal pneumonia.
Frontiers in Cellular and Infection Microbiology, 2020
Background: Virtually no studies on the dynamics of the intestinal microbiota in patients admitte... more Background: Virtually no studies on the dynamics of the intestinal microbiota in patients admitted to the intensive care unit (ICU) are published, despite the increasingly recognized important role of microbiota on human physiology. Critical care patients undergo treatments that are known to influence the microbiota. However, dynamics and extent of such changes are not yet fully understood. To address this topic, we analyzed the microbiota before, during and after planned major cardio surgery that, for the first time, allowed us to follow the microbial dynamics of critical care patients. In this prospective, observational, longitudinal, single center study, we analyzed the fecal microbiota using 16S rRNA gene sequencing. Results: Samples of 97 patients admitted between April 2015 and November 2016 were included. In 32 patients, data of all three time points (before, during and after admission) were available for analysis. We found a large intra-individual variation in composition of gut microbiota. During admission, a significant change in microbial composition occurred in most patients, with a significant increase in pathobionts combined with a decrease in strictly anaerobic gut bacteria, typically beneficial for health. A lower bacterial diversity during admission was associated with longer hospitalization. In most patients analyzed at all three time points, the change in microbiota during hospital stay reverted to the original composition post-discharge. Conclusions: Our study shows that, even with a short ICU stay, patients present a significant change in microbial composition shortly after admission. The unique longitudinal setup of this study displayed a restoration of the microbiota in most patients to baseline composition post-discharge, which demonstrated its great restorative capacity. A relative decrease in benign or even beneficial bacteria and increase of pathobionts shifts the microbial balance in the gut, which could have clinical relevance. In future studies, the microbiota of ICU patients should be considered a good target for optimisation.
Pneumonia is an infection of the lungs, where the alveoli in the affected area are filled with pu... more Pneumonia is an infection of the lungs, where the alveoli in the affected area are filled with pus and fluid. Although ventilated patients are at risk, not all ventilated patients develop pneumonia. This suggests that the sputum environment may possess antimicrobial activities. Despite the generally acknowledged importance of antimicrobial activity in protecting the human lung against infections, this has not been systematically assessed to date. Therefore, the objective of the present study was to measure antimicrobial activity in broncho-alveolar aspirate ('sputum") samples from patients in an intensive care unit (ICU) and to correlate the detected antimicrobial activity with antibiotic levels, the sputum microbiome, and the respective patients' characteristics. To this end, clinical metadata and sputum were collected from 53 mechanically ventilated ICU patients. The antimicrobial activity of sputum samples was tested against Streptococcus pneumoniae, Staphylococcus aureus and Streptococcus anginosus. Here we show that sputa collected from different patients presented a high degree of variation in antimicrobial activity, which can be partially attributed to antibiotic therapy. The sputum microbiome, although potentially capable of producing antimicrobial agents, seemed to contribute in a minor way, if any, to the antimicrobial activity of sputum. Remarkably, despite its potentially protective effect, the level of antimicrobial activity in the investigated sputa correlated inversely with patient outcome, most likely because disease severity outweighed the beneficial antimicrobial activities.
In the Simple Intensive Care Studies-I (SICS-I), we aim to unravel the value of clinical and haem... more In the Simple Intensive Care Studies-I (SICS-I), we aim to unravel the value of clinical and haemodynamic variables obtained by physical examination and critical care ultrasound (CCUS) that currently guide daily practice in critically ill patients. We intend to (1) measure all available clinical and haemodynamic variables, (2) train novices in obtaining values for advanced variables based on CCUS in the intensive care unit (ICU) and (3) create an infrastructure for a registry with the flexibility of temporarily incorporating specific (haemodynamic) research questions and variables. The overall purpose is to investigate the diagnostic and prognostic value of clinical and haemodynamic variables. The SICS-I includes all patients acutely admitted to the ICU of a tertiary teaching hospital in the Netherlands with an ICU stay expected to last beyond 24 hours. Inclusion started on 27 March 2015. On 31 December 2016, 791 eligible patients fulfilled our inclusion criteria of whom 704 were in...
Background: Colorectal surgery is frequently complicated by surgical site infections (SSIs). The ... more Background: Colorectal surgery is frequently complicated by surgical site infections (SSIs). The most important consequences of SSIs are prolonged hospitalization, an increased risk of surgical reintervention and an increase in mortality. Perioperative intravenously administered antibiotic prophylaxis is the standard of care to reduce the risk of SSIs. In the last few decades, preoperative orally administered antibiotics have been suggested as additional prophylaxis to further reduce the risk of infection, but are currently not part of routine practice in most hospitals. The objective of this study is to evaluate the efficacy of a preoperative orally administered antibiotic prophylaxis (Pre-OP) in addition to intravenously administered perioperative antibiotic prophylaxis to reduce the incidence of deep SSIs and/or mortality after elective colorectal surgery. Methods/design: The PreCaution trial is designed as a multicenter, double-blind, randomized, placebo-controlled clinical trial that will be carried out in The Netherlands. Adult patients who are scheduled for elective colorectal surgery are eligible to participate. In total, 966 patients will be randomized to receive the study medication. This will either be Pre-OP, a solution that consists of tobramycin and colistin sulphate, or a placebo solution. The study medication will be administered four times daily during the 3 days prior to surgery. Perioperative intravenously administered antibiotic prophylaxis will be administered to all patients in accordance with national infection control guidelines. The primary endpoint of the study is the cumulative incidence of deep SSIs and/or mortality within 30 days after surgery. Secondary endpoints include both infectious and non-infectious complications of colorectal surgery, and will be evaluated 30 days and/or 6 months after surgery. Discussion: To date, conclusive evidence on the added value of preoperative orally administered antibiotic prophylaxis in colorectal surgery is lacking. The PreCaution trial should determine the effects of orally administered antibiotics in preventing infectious complications in elective colorectal surgery.
Introduction: Selective decontamination of the digestive tract (SDD) and selective oropharyngeal ... more Introduction: Selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) have been shown to improve intensive care unit (ICU) patients' outcomes. The aim of this study was to determine the effects of long-term use of SDD and SOD on colistin and tobramycin resistance among gram-negative bacteria. Methods: We performed a post hoc analysis of two consecutive multicentre cluster-randomised trials with crossover of interventions. SDD and SOD were alternately but continuously used during 7 years in five Dutch ICUs participating in two consecutive cluster-randomised trials. In both trials, to measure colistin and tobramycin resistance among gram-negative bacteria, rectal and respiratory samples were obtained monthly from all patients present in the ICU. Results: The prevalence of tobramycin resistance in respiratory and rectal samples decreased significantly during long-term use of SOD and SDD. (rectal samples risk ratio (RR) 0.35 (0.23 to 0.53); respiratory samples RR 0.48 (0.32 to 0.73), SDD compared to standard care). Colistin resistance in rectal and respiratory samples did not change (rectal samples RR 0.63 (0.29 to 1.38); respiratory samples RR 1.26 (0.35 to 4.57), SDD compared to standard care). Conclusions: In this study, in a setting with low antimicrobial resistance rates, the prevalence of resistance against colistin and tobramycin among gram-negative isolates did not increase during a mean of 7 years of SDD or SOD use.
Antimicrobial Resistance and Infection Control, Jun 15, 2020
Background: Surgical site infections (SSIs) are common complications after colorectal surgery. Or... more Background: Surgical site infections (SSIs) are common complications after colorectal surgery. Oral non-absorbable antibiotic prophylaxis (OAP) can be administered preoperatively to reduce the risk of SSIs. Its efficacy without simultaneous mechanical cleaning is unknown. Methods: The Precaution trial was a double-blind, placebo-controlled randomized clinical trial conducted in six Dutch hospitals. Adult patients who underwent elective colorectal surgery were randomized to receive either a three-day course of preoperative OAP with tobramycin and colistin or placebo. The primary composite endpoint was the incidence of deep SSI or mortality within 30 days after surgery. Secondary endpoints included both infectious and non-infectious complications at 30 days and six months after surgery. Results: The study was prematurely ended due to the loss of clinical equipoise. At that time, 39 patients had been randomized to active OAP and 39 to placebo, which reflected 8.1% of the initially pursued sample size. Nine (11.5%) patients developed the primary outcome, of whom four had been randomized to OAP (4/39; 10.3%) and five to placebo (5/39; 12.8%). This corresponds to a risk ratio in the intention-to-treat analysis of 0.80 (95% confidence interval (CI) 0.23-2.78). In the per-protocol analysis, the relative risk was 0.64 (95% CI 0.12-3.46).
PurposeAlthough elective surgery is generally safe, some procedures remain associated with an inc... more PurposeAlthough elective surgery is generally safe, some procedures remain associated with an increased risk of complications. Improved preoperative risk stratification and earlier recognition of these complications may ameliorate postoperative recovery and improve long-term outcomes. The perioperative longitudinal study of complications and long-term outcomes (PLUTO) cohort aims to establish a comprehensive biorepository that will facilitate research in this field. In this profile paper, we will discuss its design rationale and opportunities for future studies.ParticipantsPatients undergoing elective intermediate to high-risk non-cardiac surgery are eligible for enrolment. For the first seven postoperative days, participants are subjected to daily bedside visits by dedicated observers, who adjudicate clinical events and perform non-invasive physiological measurements (including handheld spirometry and single-channel electroencephalography). Blood samples and microbiome specimens ar...
Objectives: Prolonged emergency department to ICU waiting time may delay intensive care treatment... more Objectives: Prolonged emergency department to ICU waiting time may delay intensive care treatment, which could negatively affect patient outcomes. The aim of this study was to investigate whether emergency department to ICU time is associated with hospital mortality. Design, Setting, and Patients: We conducted a retrospective observational cohort study using data from the Dutch quality registry National Intensive Care Evaluation. Adult patients admitted to the ICU directly from the emergency department in six university hospitals, between 2009 and 2016, were included. Using a logistic regression model, we investigated the crude and adjusted (for disease severity; Acute Physiology and Chronic Health Evaluation IV probability) odds ratios of emergency department to ICU time on mortality. In addition, we assessed whether the Acute Physiology and Chronic Health Evaluation IV probability modified the effect of emergency department to ICU time on mortality. Secondary outcomes were ICU, 30...
Colorectal surgery is frequently complicated by surgical site infections (SSIs). The most importa... more Colorectal surgery is frequently complicated by surgical site infections (SSIs). The most important consequences of SSIs are prolonged hospitalization, an increased risk of surgical reintervention and an increase in mortality. Perioperative intravenously administered antibiotic prophylaxis is the standard of care to reduce the risk of SSIs. In the last few decades, preoperative orally administered antibiotics have been suggested as additional prophylaxis to further reduce the risk of infection, but are currently not part of routine practice in most hospitals. The objective of this study is to evaluate the efficacy of a preoperative orally administered antibiotic prophylaxis (Pre-OP) in addition to intravenously administered perioperative antibiotic prophylaxis to reduce the incidence of deep SSIs and/or mortality after elective colorectal surgery. The PreCaution trial is designed as a multicenter, double-blind, randomized, placebo-controlled clinical trial that will be carried out i...
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2017
Selective Digestive Decontamination (SDD) and Selective Oropharyngeal Decontamination (SOD) impro... more Selective Digestive Decontamination (SDD) and Selective Oropharyngeal Decontamination (SOD) improved ICU, hospital and 28-day survival in Intensive Care Units (ICU) with low levels of antibiotic resistance. Yet, it is unclear whether the effect differs between medical and surgical ICU patients. In an individual patient data meta-analysis we systematically searched PubMed and included all randomized controlled studies published since 2000. We performed a two-stage meta-analysis with separate logistic regression models per study and per outcome (hospital survival and ICU survival) and subsequent pooling of main and interaction effects. Six studies, all performed in countries with low levels of antibiotic resistance, yielded 16,528 hospital admissions and 17,884 ICU-admissions for complete case analysis. Compared to standard care or placebo the pooled adjusted odds ratios (aOR) for hospital mortality was 0·82 (95% Confidence Interval [CI] 0·72 - 0·93) for SDD and 0·84 (95%-CI 0·73 - 0·...
Dysnatremia is associated with adverse outcome in critically ill patients. Changes in patients or... more Dysnatremia is associated with adverse outcome in critically ill patients. Changes in patients or treatment strategies may have affected the incidence of dysnatremia over time. We investigated long-term changes in the incidence of dysnatremia and analyzed its association with mortality. Over a 21-year period (1992-2012), all serum sodium measurements were analyzed retrospectively in two university hospital ICUs, up to day 28 of ICU admission for the presence of dysnatremia. The study period was divided into five periods. All serum sodium measurements were collected from the electronic databases of both ICUs. Serum sodium was measured at the clinical chemistry departments using standard methods. All sodium measurements were categorized in the following categories: <120, 120-124, 125-129, 130-134, 135-139, 140-145, 146-150, 151-155, 156-160, >160 mmol/L. Mortality was determined at 90 days after ICU admission. In 80,571 ICU patients, 913,272 serum sodium measurements were analyz...
In critically ill patients, antibiotic therapy is of great importance but long duration of treatm... more 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. 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 (accord...
Introduction: Use of selective decontamination of the digestive tract (SDD) and selective orophar... more Introduction: Use 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. Methods: A 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. Results: In 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). Conclusions: Although 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 registration: ISRCTN35176830.
Take-down policy If you believe that this document breaches copyright please contact us providing... more Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
OBJECTIVESTo develop a scoring system model that predicts mortality within 30 days of admission o... more OBJECTIVESTo develop a scoring system model that predicts mortality within 30 days of admission of patients older than 80 years admitted to intensive care units (ICUs).DESIGNProspective cohort study.SETTINGA total of 306 ICUs from 24 European countries.PARTICIPANTSOlder adults admitted to European ICUs (N = 3730; median age = 84 years [interquartile range = 81‐87 y]; 51.8% male).MEASUREMENTSOverall, 24 variables available during ICU admission were included as potential predictive variables. Multivariable logistic regression was used to identify independent predictors of 30‐day mortality. Model sensitivity, specificity, and accuracy were evaluated with receiver operating characteristic curves.RESULTSThe 30‐day‐mortality was 1562 (41.9%). In multivariable analysis, these variables were selected as independent predictors of mortality: age, sex, ICU admission diagnosis, Clinical Frailty Scale, Sequential Organ Failure Score, invasive mechanical ventilation, and renal replacement therapy...
Respiratory pathogens like Streptococcus pneumoniae can cause severe pneumonia. Nonetheless, mech... more Respiratory pathogens like Streptococcus pneumoniae can cause severe pneumonia. Nonetheless, mechanically ventilated intensive care patients, who have a high risk of contracting pneumonia, rarely develop pneumococcal pneumonia.
Frontiers in Cellular and Infection Microbiology, 2020
Background: Virtually no studies on the dynamics of the intestinal microbiota in patients admitte... more Background: Virtually no studies on the dynamics of the intestinal microbiota in patients admitted to the intensive care unit (ICU) are published, despite the increasingly recognized important role of microbiota on human physiology. Critical care patients undergo treatments that are known to influence the microbiota. However, dynamics and extent of such changes are not yet fully understood. To address this topic, we analyzed the microbiota before, during and after planned major cardio surgery that, for the first time, allowed us to follow the microbial dynamics of critical care patients. In this prospective, observational, longitudinal, single center study, we analyzed the fecal microbiota using 16S rRNA gene sequencing. Results: Samples of 97 patients admitted between April 2015 and November 2016 were included. In 32 patients, data of all three time points (before, during and after admission) were available for analysis. We found a large intra-individual variation in composition of gut microbiota. During admission, a significant change in microbial composition occurred in most patients, with a significant increase in pathobionts combined with a decrease in strictly anaerobic gut bacteria, typically beneficial for health. A lower bacterial diversity during admission was associated with longer hospitalization. In most patients analyzed at all three time points, the change in microbiota during hospital stay reverted to the original composition post-discharge. Conclusions: Our study shows that, even with a short ICU stay, patients present a significant change in microbial composition shortly after admission. The unique longitudinal setup of this study displayed a restoration of the microbiota in most patients to baseline composition post-discharge, which demonstrated its great restorative capacity. A relative decrease in benign or even beneficial bacteria and increase of pathobionts shifts the microbial balance in the gut, which could have clinical relevance. In future studies, the microbiota of ICU patients should be considered a good target for optimisation.
Pneumonia is an infection of the lungs, where the alveoli in the affected area are filled with pu... more Pneumonia is an infection of the lungs, where the alveoli in the affected area are filled with pus and fluid. Although ventilated patients are at risk, not all ventilated patients develop pneumonia. This suggests that the sputum environment may possess antimicrobial activities. Despite the generally acknowledged importance of antimicrobial activity in protecting the human lung against infections, this has not been systematically assessed to date. Therefore, the objective of the present study was to measure antimicrobial activity in broncho-alveolar aspirate ('sputum") samples from patients in an intensive care unit (ICU) and to correlate the detected antimicrobial activity with antibiotic levels, the sputum microbiome, and the respective patients' characteristics. To this end, clinical metadata and sputum were collected from 53 mechanically ventilated ICU patients. The antimicrobial activity of sputum samples was tested against Streptococcus pneumoniae, Staphylococcus aureus and Streptococcus anginosus. Here we show that sputa collected from different patients presented a high degree of variation in antimicrobial activity, which can be partially attributed to antibiotic therapy. The sputum microbiome, although potentially capable of producing antimicrobial agents, seemed to contribute in a minor way, if any, to the antimicrobial activity of sputum. Remarkably, despite its potentially protective effect, the level of antimicrobial activity in the investigated sputa correlated inversely with patient outcome, most likely because disease severity outweighed the beneficial antimicrobial activities.
In the Simple Intensive Care Studies-I (SICS-I), we aim to unravel the value of clinical and haem... more In the Simple Intensive Care Studies-I (SICS-I), we aim to unravel the value of clinical and haemodynamic variables obtained by physical examination and critical care ultrasound (CCUS) that currently guide daily practice in critically ill patients. We intend to (1) measure all available clinical and haemodynamic variables, (2) train novices in obtaining values for advanced variables based on CCUS in the intensive care unit (ICU) and (3) create an infrastructure for a registry with the flexibility of temporarily incorporating specific (haemodynamic) research questions and variables. The overall purpose is to investigate the diagnostic and prognostic value of clinical and haemodynamic variables. The SICS-I includes all patients acutely admitted to the ICU of a tertiary teaching hospital in the Netherlands with an ICU stay expected to last beyond 24 hours. Inclusion started on 27 March 2015. On 31 December 2016, 791 eligible patients fulfilled our inclusion criteria of whom 704 were in...
Uploads
Papers by Anne de Smet