Using a targeted metabolomics approach to explore differences in ARDS associated with COVID-19 compared to ARDS caused by H1N1 influenza and bacterial pneumonia.

RATIONALE: Acute respiratory distress syndrome (ARDS) is a life-threatening critical care syndrome commonly associated with infections such as COVID-19, influenza, and bacterial pneumonia. Ongoing research aims to improve our understanding of ARDS, including its molecular mechanisms, individualized treatment options, and potential interventions to reduce inflammation and promote lung repair. OBJECTIVE: To map and compare metabolic phenotypes of different infectious causes of ARDS to better understand the metabolic pathways involved in the underlying pathogenesis. METHODS: We analyzed metabolic phenotypes of 3 ARDS cohorts caused by COVID-19, H1N1 influenza, and bacterial pneumonia compared to non-ARDS COVID-19-infected patients and ICU-ventilated controls. Targeted metabolomics was performed on plasma samples from a total of 150 patients using quantitative LC-MS/MS and DI-MS/MS analytical platforms. RESULTS: Distinct metabolic phenotypes were detected between different infectious causes of ARDS. There were metabolomics differences between ARDSs associated with COVID-19 and H1N1, which include metabolic pathways involving taurine and hypotaurine, pyruvate, TCA cycle metabolites, lysine, and glycerophospholipids. ARDSs associated with bacterial pneumonia and COVID-19 differed in the metabolism of D-glutamine and D-glutamate, arginine, proline, histidine, and pyruvate. The metabolic profile of COVID-19 ARDS (C19/A) patients admitted to the ICU differed from COVID-19 pneumonia (C19/P) patients who were not admitted to the ICU in metabolisms of phenylalanine, tryptophan, lysine, and tyrosine. Metabolomics analysis revealed significant differences between C19/A, H1N1/A, and PNA/A vs ICU-ventilated controls, reflecting potentially different disease mechanisms. CONCLUSION: Different metabolic phenotypes characterize ARDS associated with different viral and bacterial infections.

Compassionate End-of-Life Care: Mixed-Methods Multisite Evaluation of the 3 Wishes Project.

Background: The 3 Wishes Project (3WP) is an end-of-life program that aims to honor the dignity of dying patients by creating meaningful patient- and family-centered memories while promoting humanistic interprofessional care. Objective: To determine whether this palliative intervention could be successfully implemented-defined as demonstrating value, transferability, affordability, and sustainability-beyond the intensive care unit in which it was created. Design: Mixed-methods formative program evaluation. (ClinicalTrials.gov: NCT04147169). Setting: 4 North American intensive care units. Participants: Dying patients, their families, clinicians, hospital managers, and administrators. Intervention: Wishes from dying patients, family members, and clinicians were elicited and implemented. Measurements: Patient characteristics and processes of care; the number, type, and cost of each wish; and semistructured interviews and focus groups with family members, clinicians, and managers. Results: A total of 730 patients were enrolled, and 3407 wishes were elicited. Qualitative data were gathered from 75 family members, 72 clinicians, and 20 managers or hospital administrators. Value included intentional comforting of families as they honored the lives and legacies of their loved ones while inspiring compassionate clinical care. Factors promoting transferability included family appreciation and a collaborative intensive care unit culture committed to dignity-conserving end-of-life care. Staff participation evolved from passive support to professional agency. Program initiation required minimal investment for reusable materials; thereafter, the mean cost was $5.19 (SD, $17.14) per wish. Sustainability was demonstrated by the continuation of 3WP at each site after study completion. Limitation: This descriptive formative evaluation describes tertiary care center-specific experiences rather than aiming for generalizability to all jurisdictions. Conclusion: The 3WP is a transferrable, affordable, and sustainable program that provides value to dying patients, their families, clinicians, and institutions. Primary Funding Source: Greenwall Foundation.

Outcomes of Critically Ill Patients Who Have Serotype 5 Invasive Pneumococcal Disease.

PURPOSE: To determine whether invasive pneumococcal disease (IPD) due to serotype 5, which occurred as a local outbreak in 2006 to 2007, is associated with intensive care unit (ICU) admission, hospital mortality, or organ supports in those who are critically ill. MATERIALS AND METHODS: Retrospective review of patients who presented with IPD to 2 tertiary hospitals in Vancouver, Canada, from July 2004 to June 2007. We compared patient characteristics, interventions, and outcomes between patients who had serotype 5 and other serotypes using bivariate and multivariate analyses. RESULTS: A total of 149 patients had serotype 5 and 106 had nonserotype 5. Patients with serotype 5 were younger, had lower prevalence of comorbid diseases, and had higher rates of substance use than patients with nonserotype 5. There were no differences in chest tube placement for complications of pneumonia or in ICU admission. Frequency of necrotizing pneumonia and hospital mortality were lower in the serotype 5 group. For the 71 patients with IPD who were admitted to ICU, there was no difference in severity of illness, ICU length of stay, or ICU mortality between the groups. There was also no difference in organ supports except that the serotype 5 group was more likely to receive vasopressors. CONCLUSION: Serotype 5 in patients who have IPD is associated with no difference in ICU admission but with increased use of vasopressors and lower hospital mortality.

Adding vitamin C to hydrocortisone lacks benefit in septic shock: a historical cohort study.

PURPOSE: Sepsis has high incidence and mortality rates, particularly in the intensive care unit (ICU). Corticosteroids may improve outcomes, and vitamin C may add benefit. We aimed to assess whether vitamin C and corticosteroids improved outcomes compared with corticosteroids alone. METHODS: This historical cohort study (11 December 2016 to 21 February 2018) was conducted in the ICU of a quaternary referral hospital. Patients with an ICU admission diagnosis of sepsis or septic shock who received vitamin C and hydrocortisone within 72 hr were compared with those who received only hydrocortisone. All patients received standard sepsis care including source control, antibiotics, and fluid resuscitation. Most patients received thiamine as standard ICU care. The primary outcome was hospital mortality. Secondary outcomes included ICU mortality, ventilator-free days, vasopressor-free days, dialysis use, and duration of ICU admission. RESULTS: One hundred and forty-four patients were included in the study. The mean (standard deviation [SD]) age was 64 (15) yr; 39% were female; and the mean (SD) Acute Physiology And Chronic Health Evaluation IV score was 89 (30). Eighty-eight patients did not receive vitamin C and 52 received vitamin C. There was no observed difference in hospital mortality between the non-vitamin C (36%) and vitamin C (39%) groups (adjusted odds ratio for hospital death, 0.52; 95% confidence interval, 0.20 to 1.34; P = 0.18). There were no statistically significant differences in any secondary outcomes. CONCLUSION: In this small observational study of ICU patients with septic shock, the addition of vitamin C to hydrocortisone therapy did significantly affect hospital mortality or other measures of mortality or organ dysfunction.

RéSUMé: OBJECTIF: Le sepsis comporte une incidence et des taux de mortalité élevés, particulièrement à l'unité de soins intensifs (USI). Les corticostéroïdes pourraient améliorer les pronostics, et la vitamine C pourrait être bénéfique. Notre objectif était d'évaluer si la vitamine C et les corticostéroïdes amélioraient les devenirs par rapport à un traitement de corticostéroïdes seulement. MéTHODE: Cette étude de cohorte historique (réalisée entre le 11 décembre 2016 et le 21 février 2018) a été réalisée à l'USI d'un hôpital quaternaire. Les patients ayant un diagnostic de sepsis ou de choc septique lors de leur admission à l'USI et ayant reçu de la vitamine C et de l'hydrocortisone dans les premières 72 heures ont été comparés à ceux n'ayant reçu que de l'hydrocortisone. Tous les patients ont reçu des soins standard pour le sepsis, soit un contrôle de la source de l'infection, un traitement antibiotique et une réanimation liquidienne. La plupart des patients ont reçu de la thiamine, un traitement standard à l'USI. Le critère d'évaluation principal était la mortalité hospitalière. Les critères d'évaluation secondaires comprenaient la mortalité à l'USI, les jours sans respirateur, les jours sans vasopresseurs, le recours à la dialyse et la durée de séjour à l'USI. RéSULTATS: Cent quarante-quatre patients ont été inclus dans notre étude. L'âge moyen (écart type [ÉT]) était de 64 (15) ans; 39 % étaient de sexe féminin; et le score APACHE IV moyen (ÉT) de 89 (30). Quatre-vingt-huit patients n'ont pas reçu de vitamine C et 52 en ont reçu. Aucune différence n'a été observée en matière de mortalité hospitalière entre les groupes sans vitamine C (36 %) ou avec vitamine C (39 %) (rapport de cotes ajusté pour la mortalité hospitalière, 0,52; intervalle de confiance 95 %, 0,20 à 1,34; P = 0,18). Il n'y a eu aucune différence statistiquement significative en ce qui touchait aux critères d'évaluation secondaires. CONCLUSION: Dans cette petite étude observationnelle portant sur des patients de l'USI en choc septique, l'ajout de vitamine C à un traitement d'hydrocortisone n'a pas eu d'impact significatif sur la mortalité hospitalière ou les autres mesures de mortalité ou d'atteintes organiques.

Association of intensive care unit occupancy during admission and inpatient mortality: a retrospective cohort study.

PURPOSE: There is conflicting evidence regarding the influence of intensive care unit (ICU) occupancy at the time of admission on important patient outcomes such as mortality. The objective of this analysis was to characterize the association between ICU occupancy at the time of ICU admission and subsequent mortality. METHODS: This single-centre, retrospective cohort study included all patients admitted to the ICU at the Vancouver General Hospital between 4 January 2010 and 8 October 2017. Intensive care unit occupancy was defined as the number of ICU bed hours utilized in a day divided by the total amount of ICU bed hours available for that day. We constructed mixed-effects logistic regression models controlling for relevant covariates to assess the impact of admission occupancy quintiles on total inpatient (ICU and ward) and early (72-hr) ICU mortality. RESULTS: This analysis included 10,365 ICU admissions by 8,562 unique patients. Compared with ICU admissions in the median occupancy quintile, admissions in the highest and second highest occupancy quintile were associated with a significant increase in the odds of inpatient mortality (highest: odds ratio [OR], 1.33; 95% confidence interval [CI], 1.12 to 1.59; P value < 0.001; second highest: OR, 1.21; 95% CI, 1.02 to 1.44; P value < 0.03). No association between admission occupancy and 72-hr ICU mortality was observed. CONCLUSIONS: Admission to the ICU on days of high occupancy was associated with increased inpatient mortality, but not with increased 72-hr ICU mortality. Capacity strain on the ICU may result in significant negative consequences for patients, but further research is needed to fully characterize the complex effects of capacity strain.

Association between intensive care unit occupancy at discharge, afterhours discharges, and clinical outcomes: a historical cohort study.

PURPOSE: There is a paucity of evidence evaluating whether intensive care unit (ICU) discharge occupancy is associated with clinical outcomes. It is unknown whether increased discharge occupancy leads to greater afterhours discharges and downstream consequences. We explore the association between ICU discharge occupancy and afterhours discharges, 72-hr readmission, and 30-day mortality. METHODS: This single-centre, historical cohort study included all patients discharged from the Vancouver General Hospital ICU between 5 April 2010 and 13 September 2017. Data were obtained from the British Columbia Critical Care Database. Occupancy was defined as the number of ICU bed hours utilized divided by the available bed hours for that day. Any discharge between 22:00 and 6:59 was considered afterhours. Logistic regression models adjusting for important covariates were constructed. RESULTS: We included 8,862 ICU discharges representing 7,288 individual patients. There were 1,180 (13.3%) afterhours discharges, 408 (4.6%) 72-hr readmissions, and 574 (6.5%) 30-day post-discharge deaths. Greater discharge occupancy was associated with afterhours discharges (per 10% increase: adjusted odds ratio [aOR], 1.12; 95% confidence interval [CI], 1.03 to 1.20; P = 0.005). Discharge occupancy was not associated with 72-hr readmission (per 10% increase: aOR, 0.97; 95% CI, 0.87 to 1.09; P = 0.62) or 30-day mortality (per 10% increase: aOR, 1.05; 95% CI, 0.95 to 1.16; P = 0.32). Afterhours discharge was not associated with 72-hr readmission (aOR, 1.15; 95% CI, 0.86 to 1.54; P = 0.34) or 30-day mortality (aOR, 1.05; 95% CI, 0.82 to 1.36; P = 0.69). CONCLUSIONS: Greater ICU discharge occupancy was associated with a significant increase in afterhours discharges. Nevertheless, neither discharge occupancy nor afterhours discharge were associated with 72-hr readmission or 30-day mortality.

RéSUMé: OBJECTIF: Il n'existe que peu de données probantes évaluant si le taux d'occupation de l'unité de soins intensifs (USI) au moment du congé est associé aux devenirs cliniques. Nous ne savons pas si un taux d'occupation plus élevé au moment du congé entraîne davantage de congés pendant la nuit et si cette situation a des conséquences. Nous avons exploré l'association entre le taux d'occupation de l'USI au moment du congé et les congés donnés pendant la nuit, la réadmission dans les premières 72 h, et la mortalité à 30 jours. MéTHODE: Cette étude de cohorte historique et monocentrique a englobé tous les patients ayant reçu leur congé de l'USI de l'Hôpital général de Vancouver entre le 5 avril 2010 et le 13 septembre 2017. Les données ont été tirées de la Base de données des soins intensifs de Colombie-Britannique (British Columbia Critical Care Database). Le taux d'occupation était défini comme le nombre d'heures d'occupation de lit de l'USI utilisées divisé par le nombre d'heures d'occupation de lit disponibles pour ladite journée. Tout congé reçu entre 22 h et 6 h 59 était considéré comme survenant pendant la nuit. Des modèles de régression logistique ont été élaborés afin de tenir compte des covariables importantes. RéSULTATS: Nous avons inclus 8862 congés de l'USI, représentant 7288 patients individuels. Au total, il y a eu 1180 (13,3 %) congés donnés pendant la nuit, 408 (4,6 %) réadmissions dans les 72 h suivantes, et 574 (6,5 %) décès à 30 jours après le congé. Un taux d'occupation plus élevé au moment du congé était associé à des congés pendant la nuit (par augmentation de 10 % : rapport de cotes ajusté [RCA], 1,12; intervalle de confiance [IC] 95 %, 1,03 à 1,20; P = 0,005). Le taux d'occupation lors du congé n'a pas été associé à une réadmission dans les premières 72 h (par augmentation de 10 % : RCA, 0,97; IC 95 %, 0,87 à 1,09; P = 0,62) ou à une mortalité à 30 jours (par augmentation de 10 % : RCA, 1,05; IC 95 %, 0,95 à 1,16; P = 0,32). Les congés pendant la nuit n'ont pas été associés à une réadmission dans les 72 h suivantes (RCA, 1,15; IC 95 %, 0,86 à 1,54; P = 0,34) ou à une mortalité à 30 jours (RCA, 1,05; IC 95 %, 0,82 à 1,36; P = 0,69). CONCLUSION: Un taux d'occupation de l'USI plus élevé au moment du congé était associé à une augmentation significative des congés donnés pendant la nuit. Cependant, ni le taux d'occupation lors du congé, ni le congé donné pendant la nuit, n'étaient associés à une réadmission à 72 h ou une mortalité à 30 jours.

Development of a Provincial initiative to improve glucose control in critically ill patients.

OBJECTIVE: To describe the development, implementation and initial evaluation of an initiative to improve glucose control in critically ill patients. DESIGN: Glucose control in critically ill patients was chosen by critical care leaders as a target for improvement. This was an observational study to document changes in processes and measures of glucose control in each intensive care unit (ICU). ICU nurse educators were interviewed to document relevant changes between April 2012 and April 2016. SETTING: 16 ICUs in British Columbia, Canada. PARTICIPANTS: ICU leaders. INTERVENTION(S): A community of practice (CoP) was formed, guidelines were adopted, two learning sessions were held, and an electronic system to collect data was created. Then, each ICU introduced their own educational and process interventions. MAIN OUTCOME MEASURE(S): Average hyperglycemic index (area under the curve of serum glucose concentration versus time above the upper limit (10 mmol/l) divided by time on insulin infusion), number of hypoglycemic events (<3.5 mmol/l) divided by time on insulin infusion and standardized mortality rate (actual/predicted hospital mortality) for each 3-month period. RESULTS: Although there were some isolated points and short trends that indicated special cause variation, there were no major trends over time and no obvious association with any of the process changes for each hospital. However, the average hyperglycemic index was higher in some of the smaller hospitals than in the larger hospitals. CONCLUSIONS: In this, 4-year observation of glucose control in ICUs within a CoP, the lack of sustained improvement suggests the need for more active and durable interventions.

Implementation of Neurocritical Care Is Associated With Improved Outcomes in Traumatic Brain Injury.

Background Traditionally, the delivery of dedicated neurocritical care (NCC) occurs in distinct NCC units and is associated with improved outcomes. Institution-specific logistical challenges pose barriers to the development of distinct NCC units; therefore, we developed a consultancy NCC service coupled with the implementation of invasive multimodal neuromonitoring, within a medical-surgical intensive care unit. Our objective was to evaluate the effect of a consultancy NCC program on neurologic outcomes in severe traumatic brain injury patients. METHODS: We conducted a single-center quasi-experimental uncontrolled pre- and post-NCC study in severe traumatic brain injury patients (Glasgow Coma Scale ≤8). The NCC program includes consultation with a neurointensivist and neurosurgeon and multimodal neuromonitoring. Demographic, injury severity metrics, neurophysiologic data, and therapeutic interventions were collected. Glasgow Outcome Scale (GOS) at 6 months was the primary outcome. Multivariable ordinal logistic regression was used to model the association between NCC implementation and GOS at 6 months. RESULTS: A total of 113 patients were identified: 76 pre-NCC and 37 post-NCC. Mean age was 39 years (standard deviation [SD], 2) and 87 of 113 (77%) patients were male. Median admission motor score was 3 (interquartile ratio, 1-4). Daily mean arterial pressure was higher (95 mmHg [SD, 10]) versus (88 mmHg [SD, 10], p<0.001) and daily mean core body temperature was lower (36.6°C [SD, 0.90]) versus (37.2°C [SD, 1.0], p=0.001) post-NCC compared with pre-NCC, respectively. Multivariable regression modelling revealed the NCC program was associated with a 2.5 increased odds (odds ratios, 2.5; 95% confidence interval, 1.1-5.3; p=0.022) of improved 6-month GOS. CONCLUSIONS: Implementation of a NCC program is associated with improved 6 month GOS in severe TBI patients.

Hypoglycemia and risk of death in critically ill patients.

BACKGROUND: Whether hypoglycemia leads to death in critically ill patients is unclear. METHODS: We examined the associations between moderate and severe hypoglycemia (blood glucose, 41 to 70 mg per deciliter [2.3 to 3.9 mmol per liter] and ≤40 mg per deciliter [2.2 mmol per liter], respectively) and death among 6026 critically ill patients in intensive care units (ICUs). Patients were randomly assigned to intensive or conventional glucose control. We used Cox regression analysis with adjustment for treatment assignment and for baseline and postrandomization covariates. RESULTS: Follow-up data were available for 6026 patients: 2714 (45.0%) had moderate hypoglycemia, 2237 of whom (82.4%) were in the intensive-control group (i.e., 74.2% of the 3013 patients in the group), and 223 patients (3.7%) had severe hypoglycemia, 208 of whom (93.3%) were in the intensive-control group (i.e., 6.9% of the patients in this group). Of the 3089 patients who did not have hypoglycemia, 726 (23.5%) died, as compared with 774 of the 2714 with moderate hypoglycemia (28.5%) and 79 of the 223 with severe hypoglycemia (35.4%). The adjusted hazard ratios for death among patients with moderate or severe hypoglycemia, as compared with those without hypoglycemia, were 1.41 (95% confidence interval [CI], 1.21 to 1.62; P<0.001) and 2.10 (95% CI, 1.59 to 2.77; P<0.001), respectively. The association with death was increased among patients who had moderate hypoglycemia on more than 1 day (>1 day vs. 1 day, P=0.01), those who died from distributive (vasodilated) shock (P<0.001), and those who had severe hypoglycemia in the absence of insulin treatment (hazard ratio, 3.84; 95% CI, 2.37 to 6.23; P<0.001). CONCLUSIONS: In critically ill patients, intensive glucose control leads to moderate and severe hypoglycemia, both of which are associated with an increased risk of death. The association exhibits a dose-response relationship and is strongest for death from distributive shock. However, these data cannot prove a causal relationship. (Funded by the Australian National Health and Medical Research Council and others; NICE-SUGAR ClinicalTrials.gov number, NCT00220987.).

Intensive versus conventional glucose control in critically ill patients.

BACKGROUND: The optimal target range for blood glucose in critically ill patients remains unclear. METHODS: Within 24 hours after admission to an intensive care unit (ICU), adults who were expected to require treatment in the ICU on 3 or more consecutive days were randomly assigned to undergo either intensive glucose control, with a target blood glucose range of 81 to 108 mg per deciliter (4.5 to 6.0 mmol per liter), or conventional glucose control, with a target of 180 mg or less per deciliter (10.0 mmol or less per liter). We defined the primary end point as death from any cause within 90 days after randomization. RESULTS: Of the 6104 patients who underwent randomization, 3054 were assigned to undergo intensive control and 3050 to undergo conventional control; data with regard to the primary outcome at day 90 were available for 3010 and 3012 patients, respectively. The two groups had similar characteristics at baseline. A total of 829 patients (27.5%) in the intensive-control group and 751 (24.9%) in the conventional-control group died (odds ratio for intensive control, 1.14; 95% confidence interval, 1.02 to 1.28; P=0.02). The treatment effect did not differ significantly between operative (surgical) patients and nonoperative (medical) patients (odds ratio for death in the intensive-control group, 1.31 and 1.07, respectively; P=0.10). Severe hypoglycemia (blood glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was reported in 206 of 3016 patients (6.8%) in the intensive-control group and 15 of 3014 (0.5%) in the conventional-control group (P<0.001). There was no significant difference between the two treatment groups in the median number of days in the ICU (P=0.84) or hospital (P=0.86) or the median number of days of mechanical ventilation (P=0.56) or renal-replacement therapy (P=0.39). CONCLUSIONS: In this large, international, randomized trial, we found that intensive glucose control increased mortality among adults in the ICU: a blood glucose target of 180 mg or less per deciliter resulted in lower mortality than did a target of 81 to 108 mg per deciliter. (ClinicalTrials.gov number, NCT00220987.)

Intracranial pressure monitors in traumatic brain injury: a systematic review.

We conducted a systematic review to examine the relationship between intracranial pressure monitors (ICP) monitors and mortality in traumatic brain injury (TBI). We systematically searched for articles that met the following criteria: (1) adults patients, (2) TBI, (3) use of an ICP monitor, (4) point estimate for mortality with ICP monitoring (5) adjustment for potential confounders. Six observational studies were identified with 11,371 patients. There was marked between-study heterogeneity that precluded a pooled analysis. Patients with ICP monitors had different clinical characteristics and received more ICP targeted therapy in the ICU. Four studies found no significant relationship between ICP monitoring and survival, while the other two studies demonstrated conflicting results. Significant confounding by indication in observational studies limits the examination of isolated TBI interventions. More research should focus on interventions that affect TBI careplan systems. Further research is needed to identify which subset of severe TBI patients may benefit from ICP monitoring.

Variation in the Management of Pain, Agitation, and Delirium in Intensive Care Units in British Columbia.

BACKGROUND: Pain, agitation, and delirium are associated with negative outcomes in critically ill patients. Reducing variation in pain, agitation, and delirium management among institutions could improve care. OBJECTIVES: To define opportunities to improve pain, agitation, and delirium management in intensive care units in British Columbia, Canada. METHODS: A 13-item survey was developed to determine practices for assessing and managing pain, agitation, and delirium. Target participants were persons designated as the most informed about pain, agitation, and delirium management at each of the 30 intensive care units in British Columbia. Main measures were protocol use, assessment tool(s) used and frequency, and management approaches. RESULTS: All 30 units responded; half of them had a unit-specific pain algorithm. The Behavioral Pain Scale and the numerical rating scale were the most common tools used to assess pain. Sites reported 15 different approaches to pain management: two-thirds used a sedation assessment tool, but some relied on physician diagnoses to identify sedation. Sites reported 18 different approaches to sedation management: most included an algorithm or order set for sedation management, but the most commonly used approach was individualized management by a clinician (17% for sedation and 30% for agitation). Sites reported 22 different approaches for delirium management: more than two-thirds used a delirium measurement instrument, but some relied on physician diagnoses to identify delirium. CONCLUSION: Variation in assessment and management of pain, agitation, and delirium in British Columbia intensive care units highlights opportunities to improve care.

Identifying missed opportunities to curtail antimicrobial therapy for presumed ventilator-associated pneumonia using the clinical pulmonary infection score.

BACKGROUND: Early discontinuation of antimicrobial therapy for ventilator-associated pneumonia can reduce the emergence of antimicrobial resistance, the occurrence of adverse drug events, and the cost of therapy. Evidence suggests that discontinuation of therapy by day 3 may be appropriate for patients with a clinical pulmonary infection score of 6 or less at baseline and on day 3. OBJECTIVES: To determine the proportion of patients eligible for antimicrobial discontinuation on day 3 and day 7 of therapy and to determine the proportion of eligible patients for whom antimicrobials were discontinued within these timeframes. METHODS: A 6-month observational study was conducted from October 3, 2005, to March 31, 2006, in a 27-bed medical-surgical tertiary care intensive care unit. Clinical pharmacists attended daily rounds and prospectively identified patients for inclusion in the study. A study pharmacist retrospectively calculated clinical pulmonary infection scores. Other data were obtained from the quality-improvement database and patient health records for the intensive care unit. RESULTS: Ninety-two patients were treated for ventilator-associated pneumonia during the study period, of whom 49 were included in the analysis. At day 3, 17 (35%) of the 49 patients were eligible for early discontinuation of antimicrobial therapy, but therapy was discontinued for only 2 (12%) of these 17 patients. At day 7, 10 (32%) of 31 patients were eligible for antimicrobial discontinuation, but therapy was discontinued for only 1 (10%) of these 10 patients. CONCLUSIONS: A significant opportunity exists at the authors' institution to develop and implement an antimicrobial discontinuation policy that uses the clinical pulmonary infection score to guide antimicrobial use for patients with ventilator-associated pneumonia.

Moral distress in intensive care unit personnel is not consistently associated with adverse medication events and other adverse events.

PURPOSE: To examine the association between moral distress in ICU personnel, and medication errors and adverse events, and other adverse events. MATERIALS AND METHODS: In 13 ICUs, we measured moral distress once in all ICU staff, and incidence of five explicity-defined adverse safety events over 2 years. In 10 of the ICUs, pharmacists tabulated medication errors and adverse events during 1 day in the 2-year period. Average moral distress scores for each professional group were correlated with each safety measure. RESULTS: In the pharmacy study, there were almost no significant correlations between moral distress and measures of medication safety. However, higher moral distress in nurses was associated with more interceptions of near misses per administration error (r = 0.68, p = 0.04), and higher moral distress in physicians was associated with more incorrect measurements for medication monitoring per recommended action for monitoring (r = 0.68, p = 0.03). For the other adverse events, the only significant association was a positive association between moral distress in physicians and bleeding while on anticoagulants (OR: 1.1; 95% CI: 1.0-1.3). CONCLUSION: Moral distress in ICU personnel is generally not associated with medication errors or adverse events, or other adverse events, but it may be associated with both hyper-vigilance and distraction.

Community-acquired methicillin-resistant Staphylococcus aureus pneumonia: radiographic and computed tomography findings.

OBJECTIVE: The aim of our study was to review the radiologic findings of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) pneumonia. MATERIALS AND METHODS: The hospital infection control computer database was used to identify patients who had a CA-MRSA infection with organisms isolated from blood, bronchoalveolar lavage fluid, or pleural fluid samples. Criteria for CA-MRSA pneumonia were consolidation seen on chest radiography or computed tomography (CT), growth of MRSA from sputum and/or sterile pulmonary site, clinical complaints of cough and/or shortness of breath. Chest radiographs and CT scans for 9 patients (5 men, mean age 45 y, range 35 to 71 y) were retrospectively reviewed by 2 chest radiologists. RESULTS: The most common chest radiographic finding was consolidation, which was bilateral in 7 patients and unilateral in 2 patients. The consolidation was patchy and nonsegmental in 5 and segmental in 4 patients. Two patients had cavitation evident on the chest radiograph. The most common CT scan findings were bilateral (n=8), often symmetric (n=5) consolidation, bilateral septal lines (n=7), and multiple nodules (n=5). Cavitation was present in 5 patients, either in regions of consolidation (n=5) or in large nodules (n=3). Five patients with CA-MRSA pneumonia had rapid clinical deterioration requiring ventilatory support. Two patients died. CONCLUSIONS: CA-MRSA pneumonia is characterized by extensive bilateral consolidation and frequent cavitation and is commonly associated with rapid progression and clinical deterioration. CT is superior to radiography in demonstrating the presence of cavitation.

Purulent pericarditis in a patient with rheumatoid arthritis treated with etanercept and methotrexate.

Purulent pericarditis is rarely seen in this post-antibiotic era. We report a case of spontaneous purulent pericarditis in a patient with rheumatoid arthritis being treated with etanercept, a tumour necrosis factor-alpha (TNF-alpha) antagonist, and methotrexate, an immunosuppressant. Both are disease-modifying anti-rheumatic drugs. We discuss the pathophysiology of purulent pericarditis and the recent literature on the infectious complications of TNF-alpha antagonists.

Hyperglycemia in acutely ill emergency patients--cause or effect?

OBJECTIVES: To clarify the benefits, risks and timing of glucose control and intensive insulin therapy in several groups, specifically the neurologic, cardiac and septic populations of patients, commonly seen in the emergency department. METHODS: Electronic search of MEDLINE (1966-2005; once with PubMed and once with Ovid) and Embase (1980-2005) using the terms insulin and glucose combined with emergency medicine, intensive care, cardiology and emergency department. RESULTS: There is considerable controversy in the literature surrounding the use of strict glucose control in cardiac, neurologic and septic patients. Much of this literature is non-randomized, and the timing of therapy is poorly investigated. CONCLUSIONS: Hyperglycemia is associated with adverse outcomes in acutely ill neurologic, cardiac and septic patients, but it remains unclear whether this is a causative association. Glucose control and intensive insulin therapy may be useful in some patient subgroups; however, controlled trials of aggressive glycemic control have provided insufficient evidence to justify subjecting patients to the real risks of iatrogenic hypoglycemia. We recommend a cautious approach to the control of glucose levels in acutely ill emergency department patients, with a target glucose of below 8 to 9 mmol/L.

Novel Therapies for Myocardial Irritability following Extreme Hydroxychloroquine Toxicity.

Introduction. Hydroxychloroquine (HCQ) overdose is rare and potentially deadly when consumed in large doses. Management of severe HCQ toxicity is limited and infrequently reported. This report presents the case of a massive ingestion of HCQ. Case Report. A 23-year-old female presents following an intentional ingestion of approximately 40 g of HCQ. Within six hours after ingestion, she developed severe hemodynamic instability resulting from myocardial irritability with frequent ventricular ectopic activity leading to runs of polymorphic ventricular tachycardia (PMVT) and ventricular fibrillation (VF) requiring multiple defibrillations. Additional treatments included intravenous diazepam, epinephrine, norepinephrine, sodium bicarbonate, and magnesium sulfate. Despite the ongoing hemodynamic instability, the patient was also treated with Intralipid (ILE) and received hemodialysis. Improvements in her hemodynamics were observed after 18 hours. She survived her massive overdose of HCQ. Conclusion. HCQ poisoning is rare but serious because of its rapid progression to life-threatening symptoms. Hemodynamic support, gastric decontamination, electrolyte monitoring and replacement, and management of arrhythmias are the mainstays of treatment. The combined role of dialysis and ILE in the setting of massive HCQ overdose may improve outcomes.