Background: Following national and regional recommendations, intravenous lipid emulsion (ILE) has become established in clinical practice as a treatment for acute local anesthetic (LA) toxicity, ...although evidence of efficacy is limited to animal studies and human case reports. A collaborative lipid emulsion workgroup was therefore established by the American Academy of Clinical Toxicology to review the evidence on the effect of ILE for LA toxicity. Methods: We performed a systematic review of the literature published through 15 December 2014. Relevant articles were determined based on pre-defined inclusion and exclusion criteria. Pre-treatment experiments, pharmacokinetic studies not involving toxicity and studies that did not address antidotal use of ILE were excluded. Results: We included 113 studies and reports. Of these, 76 were human and 38 animal studies. One publication included both a human case report and an animal study. Human studies included one randomized controlled crossover trial involving 16 healthy volunteers. The subclinical LA toxicity design did not show a difference in the effects of ILE versus saline. There was one case series and 73 case reports of ILE use in the context of toxicity (83 patients) including CNS depression or agitation (n = 45, 54%), seizures (n = 49, 59%), hypotension, hypertension, EKG changes, arrhythmias (n = 39, 47%), cardiac arrest (n = 18, 22%), cardiopulmonary resuscitation, and/or requirement for endotracheal intubation and/or mechanical ventilation (n = 35, 42%). There were 81 (98%) survivors including 63 (76%) with no reported sequelae from the LA poisoning or ILE, although the presence or absence of sequelae was not reported in 15 (18%) cases. Animal studies included 29 randomized controlled studies, three observational studies, five case series, and one case report; bupivacaine was used in 29 of these reports (76%). Of 14 controlled experiments in animals, eight showed improved survival or time to return of spontaneous circulation and five no benefit of ILE versus saline or non-ILE treatments. Combining ILE with epinephrine improved survival in five of the six controlled animal experiments that studied this intervention. The studies were heterogeneous in the formulations and doses of ILE used as well as the doses of LA. The body of the literature identified by this systematic review yielded only a very low quality of evidence. Conclusion: ILE appears to be effective for reversal of cardiovascular or neurological features in some cases of LA toxicity, but there is currently no convincing evidence showing that ILE is more effective than vasopressors or to indicate which treatment should be instituted as first line therapy in severe LA toxicity.
We sought to develop and internally validate a clinical prediction model to estimate the outcome of very elderly patients 12 months after being admitted to the ICU.
Prospective, longitudinal cohort ...study.
Twenty-two Canadian ICUs.
We recruited 527 patients 80 years or older who had a medical or urgent surgical diagnosis and were admitted to an ICU for at least 24 hours.
At baseline, we completed a comprehensive geriatric assessment of enrolled patients; survival and functional status was determined 12 months later. We defined recovery from critical illness as Palliative Performance Scale score of greater than or equal to 60. We used logistic regression analysis to examine factors associated with this outcome. Of the 434 patients (82%) whose Palliative Performance Scale was known at 12 months, 50% had died and 29% (126/434) had a score of greater than or equal to 60. In the multivariable model, we found that being married, having a primary diagnosis of emergency coronary artery bypass grafting or valve replacement, and higher baseline Palliative Performance Scale were independently predictive of a 12-month Palliative Performance Scale score of greater than or equal to 60. Male sex, primary diagnosis of stroke, and higher Acute Physiology and Chronic Health Evaluation II score, Charlson comorbidity index, or clinical frailty scale were independently predictive of Palliative Performance Scale score of less than 60.
Approximately one-quarter of very old ICU patients achieve a reasonable level of function 1 year after admission. This prediction model applied to individual patients may be helpful in decision making about the utility of life support for very elderly patients who are admitted to the ICU.
Very elderly persons admitted to ICUs are at high risk of death. To document life-sustaining interventions (mechanical ventilation, vasopressors, renal replacement therapy) provided in the ICU and ...outcomes of care.
Multicenter, prospective cohort study.
ICUs of 24 Canadian hospitals.
Patients 80 years old or older admitted to the ICU.
None.
One thousand six hundred seventy-one patients were included. The average age of the cohort was 85 years (range, 80-100 yr). Median total length of stay in ICU was 4 days (interquartile range, 2-8 d) and in hospital was 17 days (interquartile range, 8-33 d). Of all patients included, 502 (30%) stayed in ICU for 7 days or more and 344 (21%) received some form of life-sustaining treatment for at least 7 days. ICU and hospital mortality were 22% and 35%, respectively. For nonsurvivors, the median time from ICU admission to death was 10 days (interquartile range, 3-20 d). Of those who died (n = 5 85), 289 (49%) died while receiving mechanical ventilation, vasopressors, or dialysis. The presence of frailty or advance directives had little impact on limiting use of life-sustaining treatments or shortening the time from admission to death.
In this multicenter study, one third of very elderly ICU patients died in hospital, many after a prolonged ICU stay while continuing to receive aggressive life-sustaining interventions. These findings raise questions about the use of critical care at the end of life for the very elderly.
Delayed cerebral ischemia (DCI) disproportionately affects poor grade aneurysmal subarachnoid hemorrhage (aSAH) patients. An unreliable neurological exam and the lack of appropriate monitoring leads ...to unrecognized DCI, which in turn is associated with severe long-term deficits and higher mortality. Near Infrared Spectroscopy (NIRS) offers simple, continuous, real time, non-invasive cerebral monitoring. It provides regional cerebral oxygen saturation (c-rSO
), which reflects the balance between cerebral oxygen consumption and supply. Reports have demonstrated a good correlation with other cerebral oxygen and blood flow monitoring, and credible cerebrovascular reactivity indices were also derived from NIRS signals. Multiple critical c-rSO
values have been reported in aSAH patients, based on various thresholds, duration, variation from baseline or cerebrovascular reactivity indices. Some were associated with vasospasm, some with DCI and others with clinical outcomes. However, the poor grade aSAH population has not been specifically studied and no randomized clinical trial has been published. The available literature does not support a specific NIRS-based intervention threshold to guide diagnostic or treatment in aSAH patients. We review herein the fundamental basic concepts behind NIRS technology, relationship of c-rSO
to other brain monitoring values and their potential clinical interpretation. We follow with a critical evaluation of the use of NIRS in the aSAH population, more specifically its ability to diagnose vasospasm, to predict DCI and its association to outcome. In summary, NIRS might offer significant potential for poor grade aSAH in the future. However, current evidence does not support its use in clinical decision-making, and proper technology evaluation is required.
Patients undergoing gastrointestinal cancer surgery often receive packed red blood cell transfusions. Understanding practice variation is critical to support efforts working toward responsible ...transfusion use. We measured the extent and importance of variation in perioperative packed red blood cell transfusion use across physicians and hospitals among gastrointestinal cancer surgery patients.
We identified patients who underwent elective gastrointestinal cancer resection between 2007 and 2019 using linked administrative health data sets in Ontario, Canada. We used funnel plots to describe variation in transfusion use, adjusted for patient case mix. Hierarchical regression models quantified patient-level, between-physician, and between-hospital variation in transfusion use with R2 measures, variance partition coefficients, and median odds ratios.
Of 59,964 included patients (median age 69 years; 43.2% female; 75.8% colorectal resections), 18.0% received perioperative packed red blood cell transfusions. Funnel plots showed variation in transfusion use among physicians and hospitals. Patient characteristics, such as age, comorbidity, and procedure type, combined to explain 12.8% of the variation. After adjusting for case mix, systematic between-physician and between-hospital differences were responsible for 2.8% and 2.1% of the variation, respectively. This translated to an approximately 30% difference in the odds of transfusion for 2 similar patients treated by distinct physicians (median odds ratio: 1.35, 95% confidence interval 1.30–1.40) and hospitals (median odds ratio: 1.30, 95% confidence interval 1.23–1.42). We observed comparable effects across procedure-type subgroups.
Transfusion provision is highly driven by patient factors. Yet the impact of the treating physician and hospital on variation relative to other factors is important and reflects opportunities to target modifiable processes of care to standardize perioperative packed red blood cell transfusion practice.
Between March and July 2009, the largest number of confirmed cases of 2009 influenza A(H1N1) infection occurred in North America.
To describe characteristics, treatment, and outcomes of critically ...ill patients in Canada with 2009 influenza A(H1N1) infection.
A prospective observational study of 168 critically ill patients with 2009 influenza A(H1N1) infection in 38 adult and pediatric intensive care units (ICUs) in Canada between April 16 and August 12, 2009.
The primary outcome measures were 28-day and 90-day mortality. Secondary outcomes included frequency and duration of mechanical ventilation and duration of ICU stay.
Critical illness occurred in 215 patients with confirmed (n = 162), probable (n = 6), or suspected (n = 47) community-acquired 2009 influenza A(H1N1) infection. Among the 168 patients with confirmed or probable 2009 influenza A(H1N1), the mean (SD) age was 32.3 (21.4) years; 113 were female (67.3%) and 50 were children (29.8%). Overall mortality among critically ill patients at 28 days was 14.3% (95% confidence interval, 9.5%-20.7%). There were 43 patients who were aboriginal Canadians (25.6%). The median time from symptom onset to hospital admission was 4 days (interquartile range IQR, 2-7 days) and from hospitalization to ICU admission was 1 day (IQR, 0-2 days). Shock and nonpulmonary acute organ dysfunction was common (Sequential Organ Failure Assessment mean SD score of 6.8 3.6 on day 1). Neuraminidase inhibitors were administered to 152 patients (90.5%). All patients were severely hypoxemic (mean SD ratio of Pao(2) to fraction of inspired oxygen Fio(2) of 147 128 mm Hg) at ICU admission. Mechanical ventilation was received by 136 patients (81.0%). The median duration of ventilation was 12 days (IQR, 6-20 days) and ICU stay was 12 days (IQR, 5-20 days). Lung rescue therapies included neuromuscular blockade (28% of patients), inhaled nitric oxide (13.7%), high-frequency oscillatory ventilation (11.9%), extracorporeal membrane oxygenation (4.2%), and prone positioning ventilation (3.0%). Overall mortality among critically ill patients at 90 days was 17.3% (95% confidence interval, 12.0%-24.0%; n = 29).
Critical illness due to 2009 influenza A(H1N1) in Canada occurred rapidly after hospital admission, often in young adults, and was associated with severe hypoxemia, multisystem organ failure, a requirement for prolonged mechanical ventilation, and the frequent use of rescue therapies.
To evaluate the efficacy and safety of heparin in patients with sepsis, septic shock, or disseminated intravascular coagulation associated with infection.
Systematic review and metaanalysis.
...Randomized controlled trials from MEDLINE, EMBASE, CENTRAL, Global Health, Scopus, Web of Science, the International Clinical Trials Registry Platform (inception to April 2014), conference proceedings, and reference lists of relevant articles.
Two reviewers independently identified and extracted trial-level data from randomized trials investigating unfractionated or low molecular heparin administered to patients with sepsis, severe sepsis, septic shock, or disseminated intravascular coagulation associated with infection. Internal validity was assessed in duplicate using the Risk of Bias tool. The strength of evidence was assessed in duplicate using Grading of Recommendations Assessment, Development, and Evaluation methodology. Our primary outcome was mortality. Safety outcomes included hemorrhage, transfusion, and thrombocytopenia.
We included nine trials enrolling 2,637 patients. Eight trials were of unclear risk of bias and one was classified as having low risk of bias. In trials comparing heparin to placebo or usual care, the risk ratio for death associated with heparin was 0.88 (95% CI, 0.77-1.00; I2 = 0%; 2,477 patients; six trials; moderate strength of evidence). In trials comparing heparin to other anticoagulants, the risk ratio for death was 1.30 (95% CI, 0.78-2.18; I2 = 0%; 160 patients; three trials; low strength of evidence). In trials comparing heparin to placebo or usual care, major hemorrhage was not statistically significantly increased (risk ratio, 0.79; 95% CI, 0.53-1.17; I2 = 0%; 2,392 patients; three trials). In one small trial of heparin compared with other anticoagulants, the risk of major hemorrhage was significantly increased (2.14; 95% CI, 1.07-4.30; 48 patients). Important secondary and safety outcomes, including minor bleeding, were sparsely reported.
Heparin in patients with sepsis, septic shock, and disseminated intravascular coagulation associated with infection may be associated with decreased mortality; however, the overall impact remains uncertain. Safety outcomes have been underreported and require further study. Increased major bleeding with heparin administration cannot be excluded. Large rigorous randomized trials are needed to evaluate more carefully the efficacy and safety of heparin in patients with sepsis, severe sepsis, and septic shock.
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