Use of therapeutic caffeine in acute care postoperative and critical care settings: a scoping review.

BACKGROUND: Caffeine is the most utilised psychoactive drug worldwide. However, caffeine withdrawal and the therapeutic use of caffeine in intensive care and in the perioperative period have not been well summarised. Our objective was to conduct a scoping review of caffeine withdrawal and use in the intensive care unit (ICU) and postoperative patients. METHODS: PubMed, Embase, CINAHL Complete, Scopus and Web of Science were systematically searched for studies investigating the effects of caffeine withdrawal or administration in ICU patients and in the perioperative period. Areas of recent systematic review such as pain or post-dural puncture headache were not included in this review. Studies were limited to adults. RESULTS: Of 2268 articles screened, 26 were included and grouped into two themes of caffeine use in in the perioperative period and in the ICU. Caffeine withdrawal in the postoperative period increases the incidence of headache, which can be effectively treated prophylactically with perioperative caffeine. There were no studies investigating caffeine withdrawal or effect on sleep wake cycles, daytime somnolence, or delirium in the intensive care setting. Administration of caffeine results in faster emergence from sedation and anaesthesia, particularly in individuals who are at high risk of post-extubation complications. There has only been one study investigating caffeine administration to facilitate post-anaesthetic emergence in ICU. Caffeine administration appears to be safe in moderate doses in the perioperative period and in the intensive care setting. CONCLUSIONS: Although caffeine is widely used, there is a paucity of studies investigating withdrawal or therapeutic effects in patients admitted to ICU and further novel studies are a priority.

Occurrence and determinants of enterococcal bloodstream infections: a population-based study.

Background: Although enterococci are common causes of bloodstream infections (BSIs), few studies have examined their epidemiology in non-selected populations.Objective: To examine the incidence and risk factors for development of enterococcal BSI.Methods: Surveillance for incident enterococcal BSI was conducted among all residents of the western interior of British Columbia, Canada during 2011-2018.Results: The overall annual incidence was 10.0 per 100,000 and was 6.6 and 2.7 per 100,000 for E. faecalis and E. faecium, respectively. Among the overall cohort of 145 incident cases of enterococcal BSI, 22 (15.2%) were community-associated, 63 (43.5%) were healthcare associated and 60 (41.4%) were hospital-onset. Enterococcal BSI was predominantly a disease of older adults with rare cases occurring among those aged less than 40 years. Males showed significantly increased risk compared to females (14.3 vs. 5.6 per 100,000; incidence rate ratio; IRR; 2.6; 95% confidence interval; CI; 1.8-3.8; p < .0001) and this was most pronounced with advanced age. Several co-morbid illnesses were associated with increased risk (IRR; 95% CI) for development of enterococcal BSI most importantly cancer (8.8; 6.0-12.9; p < .0001), congestive heart failure (5.7; 3.1-9.7; p < .0001), diabetes mellitus (4.4; 3.0-6.3; p < .0001) and stroke (3.7; 1.9-6.5; .0001). As compared to patients with E. faecalis, patients with E. faecium BSI were more likely to be of hospital-onset, more likely to have an intra-abdominal/pelvic focus, and trended towards higher 30-day case-fatality rate.Conclusions: Enterococci are relatively common causes of BSI. Although E faecalis and E faecium share commonalities they are epidemiologically distinguishable on several criteria.

Defining microbial invasion of the bloodstream: a structured review.

Background: Microbial invasion of the bloodstream is associated with a major burden of illness. Despite its importance, there is inconsistency in utilization of terms used to define it.Objective: To characterize the contemporary use of terms to define microbial invasion of the bloodstream for surveillance and research purposes.Methods: Structured review of publications reported from 2000 to 2019.Results: The search strategy retrieved 10,095 citations of which bloodstream infection, bacteraemia and fungaemia were included in 2813, 6900 and 1054 articles, respectively. There was a tripling of the number of annual citations during the study and although bacteraemia was most frequent, there was a progressive increase in the use of the term bloodstream infection. Among the 100 reports randomly selected for detailed review, the terms bacteraemia, bloodstream infection and fungaemia were used in 57, 51 and 19 publications, respectively. Explicit definitions for bloodstream infection (26/51; 51%), bacteraemia (13/57; 23%) and fungaemia (7/19; 37%) were included in reports where these terms were used. Although nearly all (95%) of the studies indicated a positive blood culture as an inclusion criteria and/or definition, only a minority indicated means to exclude contaminants (33%) or specific attributes to support clinical significance (38%). Use of explicit definitions was more common among reports that exclusively used the term bloodstream infection as compared to bacteraemia.Conclusions: Terms have been inconsistently defined and imprecisely used to refer to microbial invasion of the bloodstream. Clinically relevant and objective definitions that are widely acceptable are needed for surveillance and research purposes.

Development and testing of a low cost simulation manikin for extracorporeal cardiopulmonary resuscitation (ECPR) using 3-dimensional printing.

BACKGROUND: There has been an explosive growth of ECPR within new and established ECMO programs worldwide with the concomitant need for simulation trainers. However, current commercially available ECMO simulation models are expensive and lack many standard cardiorespiratory resuscitative (CPR) features. OBJECTIVE: To use 3-dimensional (3D) printing to develop a training manikin for comprehensive ECPR simulation. METHODS: A standard commercially available CPR manikin with airway model was used as the base model for modification. An inexpensive 3D printer was used to print a modular plastic pelvis. A medical silicone gel incorporated silicone femoral vasculature component was manufactured with connection to a gravity fed vascular system. RESULTS: The resulting modified manikin included the modular in-house designed ECMO cannulation and vascular structures wedded to the commercially available airway and CPR components. In simulation exercise involving first responders, paramedics, and emergency and critical care physicians, the model was reported as realistic with ultrasound views, cannulation, and resuscitative components functional. The entire cost for development of the ECMO component was estimated at $2000 Australian dollars AUD, including the printer purchase and supplies. Future reuse of components is estimated to cost less than $5 AUD per simulation run. CONCLUSIONS: A novel in-house modified manikin for ECPR was developed that was cost-efficient and realistic to use from first response through to establishment of ECMO circulation.

When not to start antibiotics: avoiding antibiotic overuse in the intensive care unit.

BACKGROUND: Most intensive care unit (ICU) patients receive broad-spectrum antibiotics. While lifesaving in some, in others these treatments may be unnecessary and place patients at risk of antibiotic-associated harms. OBJECTIVES: To review the literature exploring how we diagnose infection in patients in the ICU and address the safety and utility of a 'watchful waiting' approach to antibiotic initiation with selected patients in the ICU. SOURCES: A semi-structured search of PubMed and Cochrane Library databases for articles published in English during the past 15 years was conducted. CONTENT: Distinguishing infection from non-infectious mimics in ICU patients is uniquely challenging. At present, we do not have access to a rapid point-of-care test that reliably differentiates between individuals who need antibiotics and those who do not. A small number of studies have attempted to compare early aggressive versus conservative antimicrobial strategies in the ICU. However, this body of literature is small and not robust enough to guide practice. IMPLICATIONS: This issue will not likely be resolved until there are diagnostic tests that rapidly and reliably identify the presence or absence of infection in the ICU population. In the meantime, prospective trials that identify clinical situations wherein it is safe to delay or withhold antibiotic initiation in the ICU until the presence of an infection is proven are warranted.

Culturing rate and the surveillance of bloodstream infections: a population-based assessment.

OBJECTIVES: Diagnosis of a bloodstream infection (BSI) requires a positive blood culture. However, low culturing rates will underestimate the true incidence of BSI and high rates may increase the risk of false-positive results. We sought to investigate the relationship between culturing rates and the incidence of BSI at the population level. METHODS: Population-based surveillance was conducted in the western interior of British Columbia, Canada, between 1 April 2010 and 31 March 2017. RESULTS: Among 60 243 blood culture sets drawn, 5591 isolates were obtained, of which 2303 were incident, 1929 were repeat positive and 1359 were contaminants. Overall annual rates of culturing, incident, repeat positive and contaminant isolates were 4832, 185, 155 and 109 per 100 000 population, respectively. During the 84-month study, there was an increase in the culturing rate that reached a plateau at 48 months (5403 cultures per 100 000 per year). The rate of both repeat isolates and contaminants increased linearly with an increasing culturing rate. However, the incident isolate rate reached an inflection point at a rate of approximately 5550 per 100 000 annually, at which point the increase in incident isolates per culture sample was diminished. At a culturing rate above 6123 per 100 000 per year, the number of repeat isolates exceeded that of incident isolates. CONCLUSIONS: The determined incidence of BSI will increase with increased culturing in a population. Further studies are needed to explore optimal BSI culturing rates in other populations.

Burden of community-onset bloodstream infections, Western Interior, British Columbia, Canada.

Although community-onset bloodstream infection (BSI) is recognized as a major cause of morbidity and mortality, its epidemiology has not been well defined in non-selected populations. We conducted population-based surveillance in the Interior Health West region of British Columbia, Canada in order to determine the burden associated with community-onset BSI. A total of 1088 episodes were identified for an overall annual incidence of 117·8/100 000 of which 639 (58·7%) were healthcare-associated (HA) and 449 (41·3%) were community-associated (CA) BSIs for incidences of 69·2 and 48·6/100 000, respectively. The incidence of community-onset BSI varied by age and gender and elderly males were at the highest risk. Overall 964 (88·6%) episodes resulted in hospital admission for a median length of stay of 8 days; the total days of acute hospitalization associated with community-onset BSI was 13 530 days or 1465 days/100 000 population per year. The in-hospital mortality rate was 10·6% (102/964) and this was higher for HA-BSI (72/569, 12·7%) compared to CA-BSI (30/395, 7·6%, P = 0·014) episodes. Community-onset BSI, especially HA-BSI, is associated with a major burden of illness.

Incidence, risk factors, and outcomes for Enterococcus spp. blood stream infections: a population-based study.

BACKGROUND: Enterococci are a clinically significant cause of bloodstream infections (BSI), particularly in the nosocomial setting. The purpose of this study was to characterize the incidence, risk factors for acquisition, microbiological characteristics and mortality of enterococcal BSI within the well-defined population of a large Canadian health region. METHODS: Surveillance for all episodes of enterococcal BSI occurring among residents of the Calgary Health Zone (population 1.2 million) between 2000 and 2008 was conducted using an electronic surveillance system. Clinical features, microbiology, and outcomes were obtained. RESULTS: A total of 710 incident episodes of enterococcal BSI were identified for an annual incidence of 6.9 episodes per 100,000; the incidences of E. faecalis and E. faecium BSI were 4.5, and 1.6 per 100,000, respectively. Enterococcus faecalis infections were associated with a urinary focus, genitourinary malignancy, and abnormal genitourinary anatomy. E. faecium infections were associated with a gastrointestinal focus. Resistance to ampicillin, vancomycin and ciprofloxacin was higher in E. faecium infection. The overall case fatality rate was 22.8%, and was higher for E. faecium infection. CONCLUSIONS: This is the second population-based study to assess the risk factors for enterococcal BSI and compare the characteristics of infection with E. faecalis and E. faecium. Results suggest that BSI with E. faecalis and E. faecium should be regarded as two clinically different entities with unique sets of risk factors and microbiologic characteristics.

Case fatality ratio and mortality rate trends of community-onset Staphylococcus aureus bacteraemia.

Lethal outcomes can be expressed as a case fatality ratio (CFR) or as a mortality rate per 100 000 population per year (MR). Population surveillance for community-onset methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus bacteraemia was conducted in Canada, Australia, Sweden and Denmark to evaluate 30-day CFR and MR trends between 2000 and 2008. The CFR was 20.3% (MSSA 20.2%, MRSA 22.3%) and MR was 3.4 (MSSA 3.1, MRSA 0.3) per 100 000 per year. Although MSSA CFR was stable the MSSA MR increased; MRSA CFR decreased while its MR remained low during the study. Community-onset S. aureus bacteraemia, particularly MSSA, is associated with major disease burden. This study highlights complementary information provided by evaluating both CFR and MR.

Incidence of bloodstream infection: a review of population-based studies.

Bloodstream infection (BSI) is associated with major morbidity and mortality. Population-based studies are the optimal designs to determine the occurrence of BSI. This is because in these designs all cases of BSI occurring in residents of a defined population are included, and where the population at risk is known incidence rates may be determined. Furthermore, selection bias is minimized by inclusion of all cases fulfilling the case definition. Despite the methodological advantages, there is only a small body of published literature investigating BSI at the population level. Few studies conducted since the 1970s have included all aetiologies of BSI and have reported rates between 80 and 189 per 100 000 per year with higher rates reported in more recent years. The three most common aetiologies of BSI are Escherichia coli, Staphylococcus aureus and Streptococcus pneumoniae, which occur at approximate rates of 35, 25 and 10 per 100 000 population, respectively. The incidence of BSI has been demonstrated to vary significantly among regions, and this is in part related to blood culturing rates, population demographic differences and risk factor distribution in regions. Knowledge of the incidence of BSI is important for setting healthcare and research priorities and for evaluating the effectiveness of preventative interventions.

Population-based assessment of the incidence, risk factors, and outcomes of anaerobic bloodstream infections.

BACKGROUND: Anaerobes are a relatively uncommon but important cause of bloodstream infection. However, their epidemiology has not been well defined in non-selected populations. We sought to describe the incidence of, risk factors for, and outcomes associated with anaerobic bacteremia. METHODS: Population-based surveillance for bacteremia with anaerobic microorganisms was conducted in the Calgary area (population 1.2 million) during the period from 2000 to 2008. RESULTS: A total of 904 incident cases were identified, for an overall population incidence of 8.7 per 100,000 per year; 231 (26 %) were nosocomial, 300 (33 %) were healthcare-associated community-onset, and 373 (41 %) were community-acquired. Elderly males were at the greatest risk. The most common pathogens identified were: Bacteroides fragilis group (3.6 per 100,000), Clostridium (non-perfringens) spp. (1.1 per 100,000), Peptostreptococcus spp. (0.9 per 100,000), and Clostridium perfringens (0.7 per 100,000). Non-susceptibility to metronidazole was 2 %, to clindamycin 17 %, and to penicillin 42 %. Relative to the general population, risk factors for anaerobic bloodstream infection included: male sex, increasing age, a prior diagnosis of cancer, chronic liver disease, heart disease, diabetes mellitus, stroke, inflammatory bowel disease, human immunodeficiency virus (HIV) infection, chronic obstructive pulmonary disease (COPD), and/or hemodialysis-dependent chronic renal failure (HDCRF). The 30-day mortality was 20 %. Increasing age, nosocomial acquisition, presence of malignancy, and several other co-morbid illnesses were independently associated with an increased risk of death. CONCLUSION: Anaerobic bloodstream infection is responsible for a significant burden of disease in general populations. The data herein establish the extent to which anaerobes contribute to morbidity and subsequent mortality. This information is key in developing preventative, empiric treatment and research priorities.

Population-based laboratory assessment of the burden of community-onset bloodstream infection in Victoria, Canada.

Although community-onset bloodstream infection (BSI) is recognized as a major cause of morbidity and mortality, its epidemiology has not been well defined in non-selected populations. We conducted population-based laboratory surveillance in the Victoria area, Canada during 1998-2005 in order to determine the burden associated with community-onset BSI. A total of 2785 episodes were identified for an overall annual incidence of 101·2/100,000. Males and the very young and the elderly were at highest risk. Overall 1980 (71%) episodes resulted in hospital admission for a median length of stay of 8 days; the total days of acute hospitalization associated with community-onset BSI was 28 442 days or 1034 days/100,000 population per year. The in-hospital case-fatality rate was 13%. Community-onset BSI is associated with a major burden of illness. These data support ongoing and future preventative and research efforts aimed at reducing the major impact of these infections.

The changing epidemiology of Staphylococcus aureus bloodstream infection: a multinational population-based surveillance study.

Although the epidemiology of Staphylococcus aureus bloodstream infection (BSI) has been changing, international comparisons are lacking. We sought to determine the incidence of S. aureus BSI and assess trends over time and by region. Population-based surveillance was conducted nationally in Finland and regionally in Canberra, Australia, western Sweden, and three areas in each of Canada and Denmark during 2000-2008. Incidence rates were age-standardized and gender-standardized to the EU 27-country 2007 population. During 83 million person-years of surveillance, 18,430 episodes of S. aureus BSI were identified. The overall annual incidence rate for S. aureus BSI was 26.1 per 100,000 population, and those for methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) were 24.2 and 1.9 per 100,000, respectively. Although the overall incidence of community-onset MSSA BSI (15.0 per 100,000) was relatively similar across regions, the incidence rates of hospital-onset MSSA (9.2 per 100,000), community-onset MRSA (1.0 per 100,000) and hospital-onset MRSA (0.8 per 100,000) BSI varied substantially. Whereas the overall incidence of S. aureus BSI did not increase over the study period, there was an increase in the incidence of MRSA BSI. Major changes in the occurrence of community-onset and hospital-onset MSSA and MRSA BSI occurred, but these varied significantly among regions, even within the same country. Although major changes in the epidemiology of community-onset and hospital-onset MSSA and MRSA BSIs are occurring, this multinational population-based study did not find that the overall incidence of S. aureus BSI is increasing.

Defining the epidemiology of bloodstream infections: the 'gold standard' of population-based assessment.

Bloodstream infections (BSIs) are a major cause of morbidity and mortality. Although population-based studies have been proposed as an optimal means to define their epidemiology, the merit of these designs has not been well documented. This report investigated the potential value of using population-based designs in defining the epidemiology of BSIs. Population-based BSI surveillance was conducted in Calgary, Canada (population 1.24 million) and illustrative comparisons were made between the overall and selected subgroup cohorts within five main themes. The value of population denominator data, and age and gender standardization for calculation and comparison of incidence rates were demonstrated. In addition, a number of biases including those related to differential admission rates, selected hospital admission, and referral bias were highlighted in non-population-based cohorts. Due to their comprehensive nature and intrinsic minimization of bias, population-based designs should be considered the gold standard means of defining the epidemiology of an infectious disease.

Risk factors for recurrence and death after bacteraemia: a population-based study.

Although most bacteraemic outcome studies have focused on mortality, a repeated episode(s) is another important outcome of bacteraemia. We sought to characterize patient factors and microbial species associated with recurrence and death from bacteraemia. Population-based surveillance for bacteraemia was conducted in a Canadian health region during 2000-2008. Episodes of bacteraemia were extracted and characterized. Transition intensities of both recurrence and death were estimated by separate multivariate Cox proportional hazards models. We identified 9713 patients with incident episodes of bacteraemia. Within 1 year: 892 (9.2%) had recurrent bacteraemia, 2401 (24.7%) had died without a recurrent episode and 330 (3.4%) had died after a recurrent episode. Independent risk factors for recurrence within 1 year (hazard ratio; 95% confidence interval) were: increasing Charlson comorbidity scores (score 1-2: 2.2; 1.8-2.7 and score 3+: 3.4; 2.8-4.2), origin of infection (nosocomial: 2.1; 1.8-2.6 and healthcare-associated: 2.4; 2.0-2.8), microorganism (polymicrobial: 1.5; 1.2-2.0 and fungal: 2.8; 1.9-4.2) and focus of infection (verified urogenital: 0.4; 0.3-0.6). Independent risk factors for death within 1 year included: a recurrent bacteraemic episode 3.6 (3.1-4.0), increasing age and different foci of infection. This study identifies patient groups at risk of having a recurrent episode and dying from these infections. It adds recurrent bacteraemia as an independent risk factor of death within 1 year and may help to target patients for prevention or changes in management.

Long-term mortality associated with community-onset bloodstream infection.

PURPOSE: Although bloodstream infection is widely recognized as an important cause of acute morbidity and mortality, long-term mortality outcomes are less well defined. The objective of this study was to define the early (≤28 days) and late (>28 days) mortality and assess determinants of late death following community-onset bloodstream infection. METHODS: All adult residents of the Calgary Zone who had community-onset bloodstream infections during the period 1 January 2003 and 31 December 2007 were included. The mortality outcome was assessed through to 31 December 2008. RESULTS: A total of 4,553 cases were identified, of which 2,105 (46%) were healthcare-associated and 2,448 (54%) were community-acquired. The 28-day, 90-day, and 365-day all-cause case-fatality rates were 561/4,553 (12%), 780/4,553 (17%), and 1,131 (25%), respectively. Within the first 28 days, the median time to death was 4 (interquartile range [IQR] 1-12) days, with 158 (28%) and 212 (38%) of early (≤28-day) deaths occurring by days 1 and 2, respectively. Among survivors to 28 days (n = 3,992), 570 (14%) suffered late 1-year mortality (i.e., death occurred between 29 and 365 days postinception). The most common causes of death in this cohort as listed by the vital statistics data were malignancy in 220 (39%), cardiovascular in 135 (24%), and infection-related in 37 (7%). Older age, higher Charlson score, prolonged initial admission duration, and healthcare-associated and polymicrobial infections were independently associated with late 1-year mortality. CONCLUSIONS: Community-onset bloodstream infection is associated with major early and late mortality.

Cost and outcomes of nosocomial bloodstream infections complicating major traumatic injury.

The objective of this study was to assess the incidence, outcomes, and costs of trauma-related nosocomial bloodstream infection (BSI). This was a 3:1 matched cohort study in patients with severe trauma [defined by an injury severity score (ISS)≥12] admitted to adult or paediatric regional trauma centres over a four-year period. Case patients with nosocomial BSI were matched to controls without a BSI based on predetermined criteria. Outcomes of interest included mortality, length of stay (LOS), and cost attributable to nosocomial BSI. Fifty-seven cases were identified, among whom 51 were successfully matched to three controls. The mean ISS among cases was 30.3, and Staphylococcus aureus was the most commonly isolated pathogen (27%). Being a case was accompanied by a 27% relative increase in the hospital LOS (P=0.02). The odds ratio for 30 day mortality associated with being a case was 5.8 (95% confidence interval (CI): 1.1-30.8; P=0.04). Among survivor-matched groups, being a case was associated with 53% relative increase in the geometric mean total hospital cost [$97,993 (95% CI: $70,143-136,899) for cases and $62,297 (95% CI: $52,155-74,411) for controls, P<0.0001]. This is the first study to show that nosocomial BSI complicating severe trauma is associated with a substantial increase in hospital LOS and in total hospital cost. Our data provide justification to support efforts to reduce the adverse impact of BSI in trauma victims.

Validity of ascertainment of co-morbid illness using administrative databases: a systematic review.

Co-morbid illnesses have a major influence on the epidemiology of infectious diseases. Although International Classification of Diseases (ICD) discharge codes are frequently used to evaluate the presence of co-morbidities in observational research, additional research is required about their validity. We reviewed the evidence supporting the use of routinely coded administrative data for ascertainment of co-morbid diseases with emphasis as it relates to the study of infectious diseases. A systematic Medline, Embase, and bibliographic review were conducted in order to identify and critically appraise published (1990-2008) studies comparing administrative databases with conventional chart review. Twenty-one co-morbidities commonly associated with infectious diseases risk were a priori selected for specific evaluation. Of the 21 co-morbid conditions chosen, only 19 had adequate data available for evaluation. Thirteen studies were included; only one focused on an infectious disease population. Eleven articles validated individual co-morbid conditions data in electronic administrative databases and reported a wide range of pooled sensitivity (13-82%) but overall high pooled specificity (>97%) when compared with medical chart review. Seven articles compared Charlson Co-morbidity Index scores derived from administrative data algorithms as compared with that calculated from medical record review and found that administrative data underscored the index in all articles with kappa agreement ranging from 0.30 to 0.56. The small body of literature published to date suggests that electronic administrative databases have limited validity for co-morbidity evaluation. Studies evaluating administrative database ascertainment of co-morbidities specifically in infectious diseases research are needed.