David Leasa

Incidence of and Risk Factors for Ventilator-Associated Pneumonia in Critically Ill Patients

A recent international prevalence study involving more than 1000 intensive care units indicated that pneumonia is responsible for almost half of the infections in critically ill patients in Europe [1]. Ventilator-associated pneumonia accounts for approximately 90% of infections in patients requiring assisted ventilation [2, 3]. An independent contribution to mortality conferred by ventilator-associated pneumonia was recently suggested [4, 5]. Although debate persists about the mortality attributable to ventilator-associated pneumonia among other causes of death in critically ill patients [1, 4-7], there is little doubt that ventilator-associated pneumonia causes substantial morbidity by increasing the duration of mechanical ventilation and intensive care unit stay [4, 5]. It is therefore important to understand the factors that are predictive of ventilator-associated pneumonia, to identify patients at highest risk, and to target these patients for the most effective preventive strategies as determined by randomized trials [8, 9]. Risk factors for nosocomial pneumonia have been evaluated in hospitalized elderly persons [10], heterogeneous groups of hospitalized patients breathing spontaneously or requiring assisted ventilation [11], and similar mixed populations admitted to the intensive care unit [2, 12-15]. Investigations in ventilated critically ill patients only are needed to identify independent predictors of ventilator-associated pneumonia. Most studies of risk factors for ventilator-associated pneumonia have been conducted at single institutions, and different predictors have been examined. In cohort studies using multivariable analyses [16-21], only reintubation [17, 19, 21] and antibiotic use [18, 20] were identified as risk factors in more than one report. However, a direct relation between antibiotics and pneumonia was found in one study [18], whereas an inverse relation was found in another [20]. We examined factors associated with ventilator-associated pneumonia. We explored baseline and time-dependent characteristics, including measures of illness severity, factors relating to mechanical ventilation, variables in the gastropulmonary route of infection, and drug exposure. Methods Patients We used a multicenter national database of 1200 patients who received mechanical ventilation for 48 hours or more and were enrolled from October 1992 to May 1996 in a double-blind, concealed, randomized trial of sucralfate compared with ranitidine to determine rates of ventilator-associated pneumonia and gastrointestinal bleeding [22]. Patients were followed until death, discharge, or clinical suspicion of ventilator-associated pneumonia as determined by the attending intensivist. Bronchoalveolar lavage or protected specimen brush was indicated for patients with a clinical suspicion of ventilator-associated pneumonia. A diagnosis of ventilator-associated pneumonia was considered only in patients who were receiving mechanical ventilation or who stopped receiving ventilation for less than 48 hours. In the absence of a reference standard for diagnosing pneumonia in critically ill patients [23, 24], each patients clinical, laboratory, and radiographic data were independently reviewed by one of four pairs of adjudicators blinded to treatment group. The readers in each adjudication pair decided on the presence or absence of ventilator-associated pneumonia, resolving any disagreement through discussion. Consensus was achieved on all cases. The adjudicated outcome was used for the primary analysis [177 cases]. However, each case of pneumonia was classified according to four additional definitions: 1) the bedside clinicians diagnosis [233 cases]; 2) the modified Centers for Disease Control and Prevention criteria [25], which require a new radiographic infiltrate persistent for 48 hours or more plus a body temperature greater than 38.5 C or less than 35.0 C, a leukocyte count of more than 10 cells 109/L or less than 3 cells 109/L, purulent sputum or change in character of sputum, or isolation of pathogenic bacteria from an endotracheal aspirate [211 cases]; 3) a Clinical Pulmonary Infection score of 7 or more [26] [194 cases]; or 4) a positive culture from bronchoalveolar lavage (>104 colony-forming units/mL) or protected specimen brush (<103 colony-forming units/mL) (97 cases). Statistical Analysis We expressed continuous variables as the mean (SD) or as the median and interquartile range if their distribution was skewed. We used the Student t-test to compare continuous variables and the chi-square test to compare proportions. All statistical tests were two-tailed. We performed a forward stepwise Cox proportional-hazards regression analysis to evaluate potential risk factors for ventilator-associated pneumonia. The Cox model assesses the effect of each risk factor on the hazard rate of ventilator-associated pneumonia over time, adjusted for other factors in the model and allowing for censoring because of death or discharge. The hazard function in the Cox model can be used to estimate the event rate per day over the duration of stay in the intensive care unit. Independent variables recorded at baseline included age; sex; primary diagnosis; medical or surgical status; hospital admission in the fall or winter compared with spring or summer; location before admission to the intensive care unit; treatment center; Acute Physiology and Chronic Health Evaluation II score; Acute Physiology score; Multiple Organ Dysfunction score [27]; Glasgow Coma Scale score; and chronic comorbid conditions, such as alcoholism, a smoking history of 10 or more pack-years, asthma, bronchiectasis, pulmonary fibrosis, cancer, and HIV infection; organ transplantation; and recent corticosteroid therapy or chemotherapy. Additional independent variables evaluated daily throughout the intensive care unit stay were classified as illness severity measures (daily Multiple Organ Dysfunction score and change in Multiple Organ Dysfunction score from baseline), ventilation variables (mechanical ventilation, change or reinsertion of endotracheal tube, discontinuation and reinstitution of mechanical ventilation, and tracheostomy), nutritional variables (nasoenteral nutrition, gastrostomy feeding, jejunostomy feeding, enteral nutrition through any route, central parenteral nutrition, peripheral parenteral nutrition, and insulin requirement of more than 15 U/d), witnessed aspiration, and drug exposure (stress-ulcer prophylaxis with ranitidine or sucralfate, paralytic agents, and antibiotics). The Multiple Organ Dysfunction Score combines measures of physiologic dysfunction in six domains: the cardiovascular system (heart rate x right atrial pressure/mean arterial pressure), pulmonary system (Pao 2:Fio 2 ratio), the renal system (serum creatinine concentration), the hepatic system (serum bilirubin level), the hematologic system (platelet count), and the central nervous system (Glasgow Coma Scale score) [25]. These continuous variables are constructed in 5 categories so that 0 represents normal function and 4 reflects marked physiologic derangement and is associated with a mortality rate greater than 50%. Composite scores provide a quantitative measure of global physiologic dysfunction at a discrete point in the intensive care unit stay. For individual domains, either the raw data or their score provides a measure of dysfunction in the system of interest. Variables that were associated with ventilator-associated pneumonia in the univariable analysis and had a P value less than 0.10 were entered into a multivariable regression analysis. Factors were considered significant if the P value was less than 0.05 in the multivariable analysis. We calculated risk ratios and 95% CIs for all significant predictors of ventilator-associated pneumonia in the multivariable analysis using all five definitions. We tested for all pairwise interactions between significant risk factors in the multivariable model. We also tested for interactions between predictors in the multivariable model and factors that were significant in the univariable analysis. Finally, we investigated the possibility that the effects of risk factors may vary over the duration of stay in the intensive care unit; this was done by using a nonproportional Cox model testing the interaction of each variable in the final model with time. For example, we hypothesized that the influence of antibiotics on ventilator-associated pneumonia may vary over time. Time was considered both a continuous variable and a discretized variable by using 3-day and 5-day intervals. We did not consider antibiotics administered 24 hours before the diagnosis of ventilator-associated pneumonia, so that drugs prescribed in response to early ventilator-associated pneumonia would be excluded [28]. Role of Study Sponsor Our funding sources had no role in the acquisition, analysis, or interpretation of data or in the submission of this report. Results Of the 1200 patients enrolled in this study, 186 were excluded (85 were discharged, 71 died, and 30 had pneumonia in the first 48 hours), leaving 1014 patients ventilated for 48 hours or more who were free of pneumonia at admission to the intensive care unit. Of these patients, 177 (17.5%) developed ventilator-associated pneumonia 9.0 5.9 days after admission (median, 7 days [interquartile range, 5 to 10 days]). The characteristics of patients with and without ventilator-associated pneumonia are shown in Table 1. The total duration of mechanical ventilation among patients with ventilator-associated pneumonia was 19.3 16.0 days (median, 15 days [interquartile range, 9 to 23 days]) compared with 10.2 10.5 days (median, 7 days [interquartile range, 4 to 11 days]) in other patients (P < 0.001). Among the 177 patients with ventilator-associated pneumonia, 131 (74.0%) had bronchoscopic testing with bronchoalveolar lavage or protected specimen brush. Patients in the following admitting diagnostic categories

A Comparison of Sucralfate and Ranitidine for the Prevention of Upper Gastrointestinal Bleeding in Patients Requiring Mechanical Ventilation

BACKGROUNDnCritically ill patients who require mechanical ventilation are at increased risk for gastrointestinal bleeding from stress ulcers. There are conflicting data on the effect of histamine H2-receptor antagonists and the cytoprotective agent sucralfate on rates of gastrointestinal bleeding, ventilator-associated pneumonia, and mortality.nnnMETHODSnIn a multicenter, randomized, blinded, placebo-controlled trial, we compared sucralfate with the H2-receptor antagonist ranitidine for the prevention of upper gastrointestinal bleeding in 1200 patients who required mechanical ventilation. Patients received either nasogastric sucralfate suspension (1 g every six hours) and an intravenous placebo or intravenous ranitidine (50 mg every eight hours) and a nasogastric placebo.nnnRESULTSnThe patients in the two groups had similar base-line characteristics. Clinically important gastrointestinal bleeding developed in 10 of 596 (1.7 percent) of the patients receiving ranitidine, as compared with 23 of 604 (3.8 percent) of those receiving sucralfate (relative risk, 0.44; 95 percent confidence interval, 0.21 to 0.92; P=0.02). In the ranitidine group, 114 of 596 patients (19.1 percent) had ventilator-associated pneumonia, as compared with 98 of 604 (16.2 percent) in the sucralfate group (relative risk, 1.18; 95 percent confidence interval, 0.92 to 1.51; P=0.19). There was no significant difference between the groups in mortality in the intensive care unit (ICU) (23.5 percent in the ranitidine group and 22.9 percent in the sucralfate group) or the duration of the stay in the ICU (median, nine days in both groups).nnnCONCLUSIONSnAmong critically ill patients requiring mechanical ventilation, those receiving ranitidine had a significantly lower rate of clinically important gastrointestinal bleeding than those treated with sucralfate. There were no significant differences in the rates of ventilator-associated pneumonia, the duration of the stay in the ICU, or mortality.

A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group.

BACKGROUNDnCritically ill patients who require mechanical ventilation are at increased risk for gastrointestinal bleeding from stress ulcers. There are conflicting data on the effect of histamine H2-receptor antagonists and the cytoprotective agent sucralfate on rates of gastrointestinal bleeding, ventilator-associated pneumonia, and mortality.nnnMETHODSnIn a multicenter, randomized, blinded, placebo-controlled trial, we compared sucralfate with the H2-receptor antagonist ranitidine for the prevention of upper gastrointestinal bleeding in 1200 patients who required mechanical ventilation. Patients received either nasogastric sucralfate suspension (1 g every six hours) and an intravenous placebo or intravenous ranitidine (50 mg every eight hours) and a nasogastric placebo.nnnRESULTSnThe patients in the two groups had similar base-line characteristics. Clinically important gastrointestinal bleeding developed in 10 of 596 (1.7 percent) of the patients receiving ranitidine, as compared with 23 of 604 (3.8 percent) of those receiving sucralfate (relative risk, 0.44; 95 percent confidence interval, 0.21 to 0.92; P=0.02). In the ranitidine group, 114 of 596 patients (19.1 percent) had ventilator-associated pneumonia, as compared with 98 of 604 (16.2 percent) in the sucralfate group (relative risk, 1.18; 95 percent confidence interval, 0.92 to 1.51; P=0.19). There was no significant difference between the groups in mortality in the intensive care unit (ICU) (23.5 percent in the ranitidine group and 22.9 percent in the sucralfate group) or the duration of the stay in the ICU (median, nine days in both groups).nnnCONCLUSIONSnAmong critically ill patients requiring mechanical ventilation, those receiving ranitidine had a significantly lower rate of clinically important gastrointestinal bleeding than those treated with sucralfate. There were no significant differences in the rates of ventilator-associated pneumonia, the duration of the stay in the ICU, or mortality.

Cardiopulmonary resuscitation directives on admission to intensive-care unit: an international observational study

BACKGROUNDnResuscitation directives should be a sign of patients preference. Our objective was to ascertain prevalence, predictors, and procurement pattern of cardiopulmonary resuscitation directives within 24 h of admission to the intensive-care unit (ICU).nnnMETHODSnWe enrolled 2916 patients aged 18 years and older from 15 ICUs in four countries, and recorded whether, when, and by whom their cardiopulmonary resuscitation directives were established. By polychotomous logistic regression we identified factors associated with a resuscitate or do-not-resuscitate directive.nnnFINDINGSnOf 2916 patients, 318 (11%; 95% CI 9.8-12.1) had an explicit resuscitation directive. In 159 (50%; 44.4-55.6) patients, the directive was do-not-resuscitate. Directives were established by residents for 145 (46%; 40.0-51.3) patients. Age strongly predicted do-not-resuscitate directives: for 50-64, 65-74, and 75 years and older, odds ratios were 3.4 (95% CI 1.6-7.3), 4.4 (2.2-9.2), and 8.8 (4.4-17.8), respectively. APACHE II scores greater than 20 predicted resuscitate and do-not-resuscitate directives in a similar way. An explicit directive was likely for patients admitted at night (odds ratio 1.4 [1.0-1.9] and 1.6 [1.2-2.3] for resuscitate and do-not-resuscitate, respectively) and during weekends (1.9 [1.3-2.7] and 2.2 [1.5-3.2], respectively). Inability to make a decision raised the likelihood of a do-not-resuscitate (3.7 [2.6-5.4]) than a resuscitate (1.7 [1.2-2.3]) directive (p=0.0005). Within Canada and the USA, cities differed strikingly, as did centres within cities.nnnINTERPRETATIONnCardiopulmonary resuscitation directives established within 24 h of admission to ICU are uncommon. As well as clinical factors, timing and location of admission might determine rate and nature of resuscitation directives.

Prolonged mechanical ventilation in Canadian intensive care units: A national survey

BACKGROUNDnWe sought to describe prevalence and care practices for patients experiencing prolonged mechanical ventilation (PMV), defined as ventilation for 21 or more consecutive days and medical stability.nnnMETHODSnWe provided the survey to eligible units via secure Web link to a nominated unit champion from April to November 2012. Weekly telephone and e-mail reminders were sent for 6 weeks.nnnRESULTSnResponse rate was 215 (90%) of 238 units identifying 308 patients requiring PMV on the survey day occupying 11% of all Canadian ventilator-capable beds. Most units (81%) used individualized plans for both weaning and mobilization. Weaning and mobilization protocols were available in 48% and 38% of units, respectively. Of those units with protocols, only 25% reported weaning guidance specific to PMV, and 11% reported mobilization content for PMV. Only 30% of units used specialized mobility equipment. Most units referred to speech language pathologists (88%); use of communication technology was infrequent (11%). Only 29% routinely referred to psychiatry/psychology, and 17% had formal discharge follow-up services.nnnCONCLUSIONSnProlonged mechanical ventilation patients occupied 11% of Canadian acute care ventilator bed capacity. Most units preferred an individualized approach to weaning and mobilization with considerable variation in weaning methods, protocol availability, access to specialized rehabilitation equipment, communication technology, psychiatry, and discharge follow-up.

Variation in definition of prolonged mechanical ventilation

Consistency of definitional criteria for terminology applied to describe subject cohorts receiving mechanical ventilation within ICU and post-acute care settings is important for understanding prevalence, risk stratification, effectiveness of interventions, and projections for resource allocation. Our objective was to quantify the application and definition of terms for prolonged mechanical ventilation. We conducted a scoping review of studies (all designs except single-case study) reporting a study population (adult and pediatric) using the term prolonged mechanical ventilation or a synonym. We screened 5,331 references, reviewed 539 full-text references, and excluded 120. Of the 419 studies (representing 38 countries) meeting inclusion criteria, 297 (71%) reported data on a heterogeneous subject cohort, and 66 (16%) included surgical subjects only (46 of those 66, 70% cardiac surgery). Other studies described COPD (16, 4%), trauma (22, 5%), neuromuscular (17, 4%), and sepsis (1, 0.2%) cohorts. A total of 741 terms were used to refer to the 419 study cohorts. The most common terms were: prolonged mechanical ventilation (253, 60%), admission to specialized unit (107, 26%), and long-term mechanical ventilation (79, 19%). Some authors (282, 67%) defined their cohorts based on duration of mechanical ventilation, with 154 studies (55%) using this as the sole criterion. We identified 37 different durations of ventilation ranging from 5 h to 1 y, with > 21 d being the most common (28 of 282, 7%). For studies describing a surgical cohort, minimum ventilation duration required for inclusion was ≥ 24 h for 20 of 66 studies (30%). More than half of all studies (237, 57%) did not provide a reason/rationale for definitional criteria used, with only 28 studies (7%) referring to a consensus definition. We conclude that substantial variation exists in the terminology and definitional criteria for cohorts of subjects receiving prolonged mechanical ventilation. Standardization of terminology and definitional criteria is required for study data to be maximally informative.

Cough Augmentation Techniques in the Critically Ill: A Canadian National Survey

BACKGROUND: Critically ill mechanically ventilated patients experience impaired airway clearance due to ineffective cough and impaired secretion mobilization. Cough augmentation techniques, including mechanical insufflation-exsufflation (MI-E), manually assisted cough, and lung volume recruitment, improve cough efficiency. Our objective was to describe use, indications, contraindications, interfaces, settings, complications, and barriers to use across Canada. METHODS: An e-mail survey was sent to nominated local survey champions in eligible Canadian units (ICUs, weaning centers, and intermediate care units) with 4 telephone/e-mail reminders. RESULTS: The survey response rate was 157 of 238 (66%); 78 of 157 units (50%) used cough augmentation, with 50 (64%) using MI-E, 53 (68%) using manually assisted cough, and 62 (79%) using lung volume recruitment. Secretion clearance was the most common indication (MI-E, 92%; manually assisted cough, 88%; lung volume recruitment, 76%), although the most common units (44%) used it <50% of the time. Use during weaning from invasive (MI-E, 21%; manually assisted cough, 39%; lung volume recruitment, 3%) and noninvasive ventilation (MI-E, 21%; manually assisted cough, 33%; lung volume recruitment, 21%) was infrequent. The most common diagnoses were neuromuscular disease (97%) and spinal cord injury (83%). Pneumothorax was the most frequently identified absolute contraindication for MI-E (93%) and lung volume recruitment (83%); rib fracture was most frequently identified for manually assisted cough (69%). MI-E mean inspiratory pressure was 31 cm H2O, and expiratory pressure was −32 cm H2O. Mucus plugging requiring tracheostomy inner change was the most frequent complication for MI-E (23%), chest pain for manually assisted cough (36%), and hypotension for lung volume recruitment (17%). The most commonly cited barriers were lack of expertise (70%), knowledge (65%), and resources (52%). CONCLUSIONS: We found moderate adoption of cough augmentation techniques, particularly for secretion management. Lack of expertise and knowledge are potentially modifiable barriers addressed with educational interventions.

Patterns of healthcare utilisation for respiratory complications of adults with neuromuscular disease: a population study

Our objective was to quantify health service utilisation including monitoring and treatment of respiratory complications for adults with neuromuscular disease (NMD), identifying practice variation and adherence to guideline recommendations at a population level. We conducted a population-based longitudinal cohort study (2003–2015) of adults with NMD using hospital diagnostic and health insurance billing codes within administrative health databases. We identified 185u200a586 adults with NMD. Mean age 52u2005years, 59% female. 41u200a173 (22%) went to an emergency department for respiratory complications on average 1.6 times every 3u2005years; 14u200a947 (8%) individuals were admitted to hospital 1.4 times every 3u2005years. Outpatient respiratory specialist visits occurred for 64u200a084 (35%) with four visits every 3u2005years, although substantial variation in visit frequency was found. 157u200a285 (85%) went to the emergency department (all-cause) almost 4 times every 3u2005years, 100u200a052 (54%) were admitted to hospital. Individuals with amyotrophic lateral sclerosis/motor neurone disease (ALS/MND) had more emergency department visits compared with other types of NMD (p<0.0001). One-third of adults with NMD received respiratory specialist care at a frequency recommended by professional guidelines, although substantial variation exists. Emergent healthcare utilisation was substantial, emphasising the burden of NMD on the healthcare system and urgent need to improve community and social supports, particularly for ALS/MND patients. One-third of adults with neuromuscular disease received specialist respiratory care. Emergent healthcare use was substantial, emphasising an urgent need to improve community and social supports. http://ow.ly/FluZ30leuLk

Respiratory health service utilization of children with neuromuscular disease

To quantify health service utilization including assessment, monitoring, and treatment of respiratory complications of children with neuromuscular disease (NMD), identifying practice variation and adherence to guideline recommendations at a population level.

Risk factors for gastrointestinal bleeding in critically ill patients

BACKGROUNDnThe efficacy of prophylaxis against stress ulcers in preventing gastrointestinal bleeding in critically ill patients has led to its widespread use. The side effects and cost of prophylaxis, however, necessitate targeting preventive therapy to those patients most likely to benefit.nnnMETHODSnWe conducted a prospective multicenter cohort study in which we evaluated potential risk factors for stress ulceration in patients admitted to intensive care units and documented the occurrence of clinically important gastrointestinal bleeding (defined as overt bleeding in association with hemodynamic compromise or the need for blood transfusion).nnnRESULTSnOf 2252 patients, 33 (1.5 percent; 95 percent confidence interval, 1.0 to 2.1 percent) had clinically important bleeding. Two strong independent risk factors for bleeding were identified: respiratory failure (odds ratio, 15.6) and coagulopathy (odds ratio, 4.3). Of 847 patients who had one or both of these risk factors, 31 (3.7 percent; 95 percent confidence interval, 2.5 to 5.2 percent) had clinically important bleeding. Of 1405 patients without these risk factors, 2 (0.1 percent; 95 percent confidence interval, 0.02 to 0.5 percent) had clinically important bleeding. The mortality rate was 48.5 percent in the group with bleeding and 9.1 percent in the group without bleeding (P < 0.001).nnnCONCLUSIONSnFew critically ill patients have clinically important gastrointestinal bleeding, and therefore prophylaxis against stress ulcers can be safely withheld from critically ill patients unless they have coagulopathy or require mechanical ventilation.