Stepwise Rostrocaudal Brainstem Anesthesia as a Complication of Local Anesthesia: A Case Report.

Iatrogenic cranial nerve palsies can rarely complicate neurosurgical, oral maxillofacial, and otolaryngological procedures. Among the most serious complications of cranial nerve palsy is upper airway obstruction, which is life threatening. We present a case of multiple cranial nerve palsies evolving rapidly in a rostrocaudal stepwise fashion after infiltration of lidocaine to repair a cerebrospinal fluid leak in a patient postoccipital craniectomy. This led to hypoxic respiratory failure requiring mechanical ventilation before resolving spontaneously. This is the first known case of accidental brainstem anesthesia secondary to lidocaine infiltration at an occipital craniectomy site and serves to caution clinicians who manage similar patients.

Experts Consensus Recommendations for the Management of Calcium Channel Blocker Poisoning in Adults.

OBJECTIVE: To provide a management approach for adults with calcium channel blocker poisoning. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: Following the Appraisal of Guidelines for Research & Evaluation II instrument, initial voting statements were constructed based on summaries outlining the evidence, risks, and benefits. DATA SYNTHESIS: We recommend 1) for asymptomatic patients, observation and consideration of decontamination following a potentially toxic calcium channel blocker ingestion (1D); 2) as first-line therapies (prioritized based on desired effect), IV calcium (1D), high-dose insulin therapy (1D-2D), and norepinephrine and/or epinephrine (1D). We also suggest dobutamine or epinephrine in the presence of cardiogenic shock (2D) and atropine in the presence of symptomatic bradycardia or conduction disturbance (2D); 3) in patients refractory to the first-line treatments, we suggest incremental doses of high-dose insulin therapy if myocardial dysfunction is present (2D), IV lipid-emulsion therapy (2D), and using a pacemaker in the presence of unstable bradycardia or high-grade arteriovenous block without significant alteration in cardiac inotropism (2D); 4) in patients with refractory shock or who are periarrest, we recommend incremental doses of high-dose insulin (1D) and IV lipid-emulsion therapy (1D) if not already tried. We suggest venoarterial extracorporeal membrane oxygenation, if available, when refractory shock has a significant cardiogenic component (2D), and using pacemaker in the presence of unstable bradycardia or high-grade arteriovenous block in the absence of myocardial dysfunction (2D) if not already tried; 5) in patients with cardiac arrest, we recommend IV calcium in addition to the standard advanced cardiac life-support (1D), lipid-emulsion therapy (1D), and we suggest venoarterial extracorporeal membrane oxygenation if available (2D). CONCLUSION: We offer recommendations for the stepwise management of calcium channel blocker toxicity. For all interventions, the level of evidence was very low.

Screening for Frailty in Canada's Health Care System: A Time for Action.

As Canada's population ages, frailty - with its increased risk of functional decline, deterioration in health status, and death - will become increasingly common. The physiology of frailty reflects its multisystem, multi-organ origins. About a quarter of Canadians over age 65 are frail, increasing to over half in those older than 85. Our health care system is organized around single-organ systems, impairing our ability to effectively treat people having multiple disorders and functional limitations. To address frailty, we must recognize when it occurs, increase awareness of its significance, develop holistic models of care, and generate better evidence for its treatment. Recognizing how frailty impacts lifespan will allow for integration of care goals into treatment options. Different settings in the Canadian health care system will require different strategies and tools to assess frailty. Given the magnitude of challenges frailty poses for the health care system as currently organized, policy changes will be essential.

Glutamine and antioxidants in the critically ill patient: a post hoc analysis of a large-scale randomized trial.

BACKGROUND: The recent large randomized controlled trial of glutamine and antioxidant supplementation suggested that high-dose glutamine is associated with increased mortality in critically ill patients with multiorgan failure. The objectives of the present analyses were to reevaluate the effect of supplementation after controlling for baseline covariates and to identify potentially important subgroup effects. MATERIALS AND METHODS: This study was a post hoc analysis of a prospective factorial 2 × 2 randomized trial conducted in 40 intensive care units in North America and Europe. In total, 1223 mechanically ventilated adult patients with multiorgan failure were randomized to receive glutamine, antioxidants, both glutamine and antioxidants, or placebo administered separate from artificial nutrition. We compared each of the 3 active treatment arms (glutamine alone, antioxidants alone, and glutamine + antioxidants) with placebo on 28-day mortality. Post hoc, treatment effects were examined within subgroups defined by baseline patient characteristics. Logistic regression was used to estimate treatment effects within subgroups after adjustment for baseline covariates and to identify treatment-by-subgroup interactions (effect modification). RESULTS: The 28-day mortality rates in the placebo, glutamine, antioxidant, and combination arms were 25%, 32%, 29%, and 33%, respectively. After adjusting for prespecified baseline covariates, the adjusted odds ratio of 28-day mortality vs placebo was 1.5 (95% confidence interval, 1.0-2.1, P = .05), 1.2 (0.8-1.8, P = .40), and 1.4 (0.9-2.0, P = .09) for glutamine, antioxidant, and glutamine plus antioxidant arms, respectively. In the post hoc subgroup analysis, both glutamine and antioxidants appeared most harmful in patients with baseline renal dysfunction. No subgroups suggested reduced mortality with supplements. CONCLUSIONS: After adjustment for baseline covariates, early provision of high-dose glutamine administered separately from artificial nutrition was not beneficial and may be associated with increased mortality in critically ill patients with multiorgan failure. For both glutamine and antioxidants, the greatest potential for harm was observed in patients with multiorgan failure that included renal dysfunction upon study enrollment.

Enhanced protein-energy provision via the enteral route feeding protocol in critically ill patients: results of a cluster randomized trial.

OBJECTIVES: To determine the effect of the enhanced protein-energy provision via the enteral route feeding protocol, combined with a nursing educational intervention on nutritional intake, compared to usual care. DESIGN: Prospective, cluster randomized trial. SETTING: Eighteen ICUs from United States and Canada with low baseline nutritional adequacy. PATIENTS: One thousand fifty-nine mechanically ventilated, critically ill patients. INTERVENTIONS: A novel feeding protocol combined with a nursing educational intervention. MEASUREMENTS AND MAIN RESULTS: The two primary efficacy outcomes were the proportion of the protein and energy prescriptions received by study patients via the enteral route over the first 12 days in the ICU. Safety outcomes were the prevalence of vomiting, witnessed aspiration, and ICU-acquired pneumonia. The proportion of prescribed protein and energy delivered by enteral nutrition was greater in the intervention sites compared to the control sites. Adjusted absolute mean difference between groups in the protein and energy increases were 14% (95% CI, 5-23%; p = 0.005) and 12% (95% CI, 5-20%; p = 0.004), respectively. The intervention sites had a similar improvement in protein and calories when appropriate parenteral nutrition was added to enteral sources. Use of the enhanced protein-energy provision via the enteral route feeding protocol was associated with a decrease in the average time from ICU admission to start of enteral nutrition compared to the control group (40.7-29.7 hr vs 33.6-35.2 hr, p = 0.10). Complication rates were no different between the two groups. CONCLUSIONS: In ICUs with low baseline nutritional adequacy, use of the enhanced protein-energy provision via the enteral route feeding protocol is safe and results in modest but statistically significant increases in protein and calorie intake.

A randomized trial of glutamine and antioxidants in critically ill patients.

BACKGROUND: Critically ill patients have considerable oxidative stress. Glutamine and antioxidant supplementation may offer therapeutic benefit, although current data are conflicting. METHODS: In this blinded 2-by-2 factorial trial, we randomly assigned 1223 critically ill adults in 40 intensive care units (ICUs) in Canada, the United States, and Europe who had multiorgan failure and were receiving mechanical ventilation to receive supplements of glutamine, antioxidants, both, or placebo. Supplements were started within 24 hours after admission to the ICU and were provided both intravenously and enterally. The primary outcome was 28-day mortality. Because of the interim-analysis plan, a P value of less than 0.044 at the final analysis was considered to indicate statistical significance. RESULTS: There was a trend toward increased mortality at 28 days among patients who received glutamine as compared with those who did not receive glutamine (32.4% vs. 27.2%; adjusted odds ratio, 1.28; 95% confidence interval [CI], 1.00 to 1.64; P=0.05). In-hospital mortality and mortality at 6 months were significantly higher among those who received glutamine than among those who did not. Glutamine had no effect on rates of organ failure or infectious complications. Antioxidants had no effect on 28-day mortality (30.8%, vs. 28.8% with no antioxidants; adjusted odds ratio, 1.09; 95% CI, 0.86 to 1.40; P=0.48) or any other secondary end point. There were no differences among the groups with respect to serious adverse events (P=0.83). CONCLUSIONS: Early provision of glutamine or antioxidants did not improve clinical outcomes, and glutamine was associated with an increase in mortality among critically ill patients with multiorgan failure. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00133978.).

The adequacy of timely empiric antibiotic therapy for ventilator-associated pneumonia: an important determinant of outcome.

OBJECTIVE: The individual impact of timeliness vs adequacy of empiric antibiotic therapy for a clinical suspicion of ventilator-associated pneumonia (CSVAP) is unknown. Accordingly, in patients with CSVAP and timely initiation of empiric antibiotic therapy, we determined the impact of inadequate therapy (IT). METHODS: Analysis of a randomized trial of CSVAP treated empirically with meropenem or meropenem plus ciprofloxacin was done. Adequate therapy (AT) was considered present if all pathogens in the index culture were sensitive to the empiric antibiotics; IT was defined as the presence of pathogens resistant to the empiric antibiotics. A priori, for Pseudomonas sp, 2 antibiotics with activity against the organisms were required for AT to be considered present. RESULTS: Of 739 patients with CSVAP, 350 had positive cultures: 313 (89.4%) had AT, and 37 (10.6%), IT. The IT group had higher intensive care unit (35.1% vs 11.8%, P = .0001) and hospital mortalities (48.7% vs 19.5%, P < .0001), increased mechanical ventilation (15.8 vs 6.8 days, P = .0005), intensive care unit stay (13.5 vs 8.4 days, P = .02), and hospital stay (42.2 vs 27.9 days, P = .04). In multivariate analysis and a separate case control analysis, the odds ratio of hospital mortality with IT was 3.05 (95% confidence interval, 1.25-7.45; P = .01) and 3.00 (95% confidence interval, 1.24-7.24; P = .01), respectively. CONCLUSION: In the context of early administration of empiric broad spectrum antibiotics for CSVAP, IT is associated with higher morbidity and mortality.

Guidelines, guidelines, guidelines: what are we to do with all of these North American guidelines?

Over the past decade, clinical guidelines for nutrition therapy in the critically ill have been developed by different North American societies. To avoid target audience confusion and uncertainty, there is a need to undergo a review of the content of these guidelines. In this review, the authors compared the grading systems, the levels of evidence used, and the content of North American nutrition clinical guidelines. The 3 clinical guidelines that met their search criteria and hence were included in the comparison are the Canadian Clinical Practice Guidelines, the American Dietetics Association's evidence-based guideline for critical illness, and the Society of Critical Care Medicine and American Society of Parenteral and Enteral Nutrition's joint guideline. Through their comparison, the authors have shown that although there are several topics where there is a similar direction of recommendation across the 3 societies/organizations, there are stark contrasts among many of the recommendations. These major differences can be attributed to the admission of different populations, lower levels of evidence or expert opinion into the guideline production process, lack of clarity in the link between the evidence and the recommendation, and lack of uniformity in the reporting of levels of evidence and grades of recommendation. The authors have identified the need for the North American nutrition organizations to harmonize the development of future nutrition guidelines in a timely way, so that they remain current and up-to-date. Furthermore, guideline users need to be aware of the dissimilarities in these guidelines before applying the recommendations to their daily practice.

Correlates of clinical failure in ventilator-associated pneumonia: insights from a large, randomized trial.

PURPOSE: Our objective was to determine clinical variables measured at baseline and day 3 that may relate to failure of resolution of ventilator-associated pneumonia (VAP). MATERIALS AND METHODS: In patients with confirmed VAP derived from a large, randomized controlled trial comparing different modalities for the diagnosis and treatment of VAP, we identified risk factors associated with clinical failure. Clinical failure was prospectively defined in this trial as death, persistence of clinical and radiographic features of infection throughout the study period requiring additional antibiotics, superinfection, or relapsing infection. We examined the relationship between VAP resolution and clinical characteristics measured both at study enrollment and at day 3. We used logistic regression to identify independent factors associated with clinical failure and conducted a sensitivity analysis focusing only on patients who met the definition for clinical failure but who nonetheless survived until day 28. RESULTS: Of 563 subjects with VAP, 179 (31.8%) were classified as clinical failures. Death was the most common reason for clinical failure. At baseline, clinical failure patients were older, more severely ill, had been on mechanical ventilation for a longer period, and had higher Clinical Pulmonary Infection Score values and lower Pao2/Fio2 ratios. By day 3, patients defined as clinical failures remained more severely ill and continued to have worse oxygenation. In multivariate analysis, 4 factors were independently associated with clinical failure: older age, duration of ventilation before enrollment, presence of neurologic disease at admission, and failure of the Pao2/Fio2 ratio to improve by day 3. Repeating this multivariable model in only surviving patients suggested that persistence of fever was the only variable associated with clinical failure. CONCLUSIONS: Clinical characteristics correlate with eventual outcomes in VAP. Failure of the Pao2/Fio2 ratio and fever to improve are independently associated with clinical failure. We suggest that clinicians follow these measures and consider integrating them in their decisions as to when to reevaluate persons with VAP who are not improving.

Randomized trial of combination versus monotherapy for the empiric treatment of suspected ventilator-associated pneumonia.

OBJECTIVE: To compare a strategy of combination therapy with a strategy of monotherapy with broad-spectrum antibiotics for suspected late ventilator-associated pneumonia. DESIGN: Randomized trial. SETTING: Twenty-eight intensive care units in Canada and the United States. PATIENTS: The study included 740 mechanically ventilated patients who developed suspected ventilator-associated pneumonia after 96 hrs in the intensive care unit. Patients known to be colonized or infected with Pseudomonas or methicillin-resistant Staphylococcus aureus or who were immunocompromised were excluded from the study. INTERVENTIONS: As initial unblinded therapy, patients were allocated to receive meropenem (1 g every 8 hrs) and ciprofloxacin (400 mg every 12 hrs) or meropenem alone. Before starting antibiotics, patients were also randomized to bronchoalveolar lavage with quantitative cultures or endotracheal aspirates. When culture results were available, physicians were encouraged to adjust antibiotics. Adequacy of antibiotics was defined as the organism present in the enrollment culture having in vitro susceptibility to one or more of the study antibiotics. MEASUREMENTS AND MAIN RESULTS: Baseline characteristics and etiologies of ventilator-associated pneumonia were similar in the two groups. There was no difference in 28-day mortality between the combination and monotherapy groups (relative risk = 1.05, 95% confidence interval 0.78-1.42, p = .74). Duration of intensive care unit and hospital stay, clinical and microbiological treatment response, emergence of antibiotic-resistant bacteria, isolation of Clostridium difficile in stool, and fungal colonization were also similar in the two groups. In a subgroup of patients who had infection due to Pseudomonas species, Acinetobacter species, and multidrug-resistant gram-negative bacilli at enrollment (n = 56), the adequacy of initial antibiotics (84.2% vs. 18.8%, p < .001) and microbiological eradication of infecting organisms (64.1% vs. 29.4%, p = .05) was higher in the combination group compared with the monotherapy group, but there were no differences in clinical outcomes. CONCLUSIONS: For critically ill patients who have suspected late ventilator-associated pneumonia and who are at low risk for difficult-to-treat gram-negative bacteria, monotherapy is associated with similar outcomes compared with combination therapy. For those patients at high risk of difficult-to-treat gram-negative bacteria, combination therapy is safe and may be associated with better microbiological and clinical outcomes.

REducing Deaths due to OXidative Stress (The REDOXS Study): Rationale and study design for a randomized trial of glutamine and antioxidant supplementation in critically-ill patients.

Critically-ill patients experience an extent of hyperinflammation, cellular immune dysfunction, oxidative stress and mitochondrial dysfunction. Supplementation with key nutrients, such as glutamine and antioxidants, is most likely to have a favourable effect on these physiological derangements, leading to an improvement in clinical outcomes. The results of two meta-analyses suggest that glutamine and antioxidants may be associated with improved survival. The purpose of the present paper is to report the background rationale and study protocol for the evaluation of the effect of high-dose glutamine and antioxidant supplementation on mortality in a large-scale randomized trial in 1200 mechanically-ventilated, critically-ill patients. Patients admitted to an intensive care unit (ICU) with clinical evidence of severe organ dysfunction will be randomized to one of four treatments in a 2 x 2 factorial design: (1) glutamine; (2) antioxidant therapy; (3) glutamine and antioxidant therapy; (4) placebo. The primary outcome for this study is 28 d mortality. The secondary outcomes are duration of stay in ICU, adjudicated diagnosis of infection, multiple organ dysfunction, duration of mechanical ventilation, length of stay in hospital and health-related quality of life at 3 and 6 months. A novel design feature is the combined use of parenteral and enteral study nutrients dissociated from the nutrition support. The therapeutic strategies tested in the randomized trial may lead to less morbidity and improved survival in critically-ill patients. The trial will be conducted in approximately twenty tertiary-care ICU in Canada and the first results are expected in 2009.