Surgery, general anesthesia, and related events have been implicated to promote cancer proliferation. We investigated the incidence of cancer within 5 years after surgery in relation to duration of anesthesia (TANESTH) and also by time with bispectral index (BIS) under 45 (TBIS<45) serving as a proxy for more profound anesthesia exposure.

Methods
New malignant diagnoses after surgery under sevoflurane anesthesia were obtained in a prospective cohort of 2972 BIS-monitored patients without any clinically diagnosed malignant disease at the time of index surgery. The risk of cancer during follow-up in relation to TANESTH and TBIS<45 was assessed by Cox regression. The cancer incidence in this surgical population was compared with the incidence in a standardized general population by calculation of standard incidence ratio.

Results
One hundred twenty-nine patients (4.3%) were assigned 136 new malignant diagnoses within 5 years after surgery. No relation between TANESTH or TBIS<45 and new malignant disease was found, nor were any significant relations obtained when other thresholds for BIS (i.e., <30, <40, and <50, respectively) were used in the calculations. The standard incidence ratio for new malignant disease was 1.37 (confidence interval, 1.15–1.62).

Conclusion
Neither duration of anesthesia nor increased cumulative time with profound sevoflurane anesthesia was associated with an increased risk for new malignant disease within 5 years after surgery in previously cancer-free patients.

Crit Care. 2010;14(2):R29

Statins reduce risk of cardiovascular events and have beneficial pleiotropic effects; both may reduce mortality in critically ill patients. We examined whether statin use was associated with risk of death in general intensive care unit (ICU) patients.

Methods
Cohort study of 12,483 critically ill patients > 45 yrs of age with a first-time admission to one of three highly specialized ICUs within the Aarhus University Hospital network, Denmark, between 2001 and 2007. Statin users were identified through population-based prescription databases. We computed cumulative mortality rates 0–30 days and 31–365 days after ICU admission and mortality rate ratios (MRRs), using Cox regression analysis controlling for potential confounding factors (demographics, use of other cardiovascular drugs, comorbidity, markers of social status, diagnosis, and surgery).

Results
1882 (14.3%) ICU patients were current statin users. Statin users had a reduced risk of death within 30 days of ICU admission [users: 22.1% vs. non-users 25.0%; adjusted MRR = 0.76 (95% confidence interval (CI): 0.69 to 0.86)]. Statin users also had a reduced risk of death within one year after admission to the ICU [users: 36.4% vs. non-users 39.9%; adjusted MRR = 0.79 (95% CI: 0.73 to 0.86)]. Reduced risk of death associated with current statin use remained robust in various subanalyses and in an analysis using propensity score matching. Former use of statins and current use of non-statin lipid-lowering drugs were not associated with reduced risk of death.

Conclusions
Preadmission statin use was associated with reduced risk of death following intensive care. The associations seen could be a pharmacological effect of statins, but unmeasured differences in characteristics of statin users and non-users cannot be entirely ruled out.

Intensive Care Med 2004;30:556–575

Hypothermia has been used for medicinal purposes since ancient times. This paper reviews the current potential clinical applications for mild hypothermia (32–35^oC).

Design and setting
Induced hypothermia is used mostly to prevent or attenuate neurological injury, and has been used to provide neuroprotection in traumatic brain injury, cardiopulmonary resuscitation, stroke, and various other disorders. The evidence for each of these applications is discussed, and the mechanisms underlying potential neuroprotective effects are reviewed. Some of this evidence comes from animal models, and a brief overview of these models and their limitations is included in this review.

Results
The duration of cooling and speed of re-warming appear to be key factors in determining whether hypothermia will be effective in preventing or mitigating neurological injury. Some other potential usages of hypothermia, such as its use in the perioperative setting and its application to mitigate cardiac injury following ischemia and reperfusion, are also discussed. Conclusions: Although induced hypothermia appears to be a highly promising treatment, it should be emphasized that it is associated with a number of potentially serious side effects, which may negate some or all of its potential benefits. Prevention and/or early treatment of these complications are the key to successful use of hypothermia in clinical practice. These side effects, as well as various physiological changes induced by cooling, are discussed in a separate review.

Chest 2007;132:1368-1378

Patients experiencing acute elevations of ammonia present to the ICU with encephalopathy, which may progress quickly to cerebral herniation. Patient survival requires immediate treatment of intracerebral hypertension and the reduction of ammonia levels. When hyperammonemia is not thought to be the result of liver failure, treatment for an occult disorder of metabolism must begin prior to the confirmation of an etiology. This article reviews ammonia metabolism, the effects of ammonia on the brain, the causes of hyperammonemia, and the diagnosis of inborn errors of metabolism in adult patients.

Sleep Medicine 2008;9:818-822

Despite the high prescription rate of benzodiazepine-like hypnotics (z-hypnotics), there is limited information on the road traffic accident risk associated with the use of these drugs. We wanted to investigate whether filling a prescription for zopiclone or zolpidem was associated with increased risk of road traffic accidents at a national population level. Nitrazepam and flunitrazepam were used as comparator drugs.

Method
All Norwegians 18–69 years (3.1 million) were followed-up from January 2004 until the end of September 2006. Information on prescriptions, road traffic accidents and emigration/death was obtained from three Norwegian population-based registries. The first week after the hypnotics had been dispensed was considered to be the exposure period. Standardized incidence ratios (SIRs) were calculated by comparing the incidence of accidents in the exposed person-time to the incidence of accidents in the unexposed person-time.

Results
During exposure, 129 accidents were registered for zopiclone, 21 for zolpidem, 27 for nitrazepam and 18 for flunitrazepam. The SIRs were (SIR for all ages and both sexes combined; 95% CI): z-hypnotics (zopiclone + zolpidem) 2.3; 2.0–2.7, nitrazepam 2.7; 1.8–3.9 and flunitrazepam 4.0; 2.4–6.4. The highest SIRs were found among the youngest users for all hypnotics.

Conclusions
This study found that users of hypnotics had a clearly increased risk of road traffic accidents. The SIR for flunitrazepam was particularly high.

Anesthesiology 2008;109:962-972

Welcome to the 2008 year in review, highlighting articles that the Editorial Board believes exemplify the mission of Anesthesiology, to advance the science and practice of perioperative, critical care, and pain medicine through the promotion of seminal discovery. Our goals are to remind you of articles that may change your clinical practice today, to help you better understand the scientific basis of current practice, and to provide glimpses into the future. We recognize how busy you are and hope these brief synopses guide you to new and relevant information.

The full-text on-line articles are a click away at our newly redesigned Web site-www.anesthesiology.org -described more fully in an editorial in this issue.1 In addition to the synopses chronicled in this review, the Anesthesiology Web site now offers new functionality, such as most viewed or most in the press, that will also help you to determine the most relevant and important content for your practice and research. Two thousand eight is the first full calendar year during which content is regularly highlighted through the American Society of Anesthesiologists Press Release office, and the press release program has met with remarkable success. Throughout the year, several news releases were picked up by more than 1,000 news outlets, including nearly all the major news media entities. As Editors, we are very excited about the public interest in research and other content published in the Journal because press interest stresses the critically important medical advances in our specialty and offers well-deserved recognition to the outstanding authors who publish with us.

This year saw the reorganization of our Table of Contents into the three major medical branches of our specialty: perioperative, critical care, and pain medicine. Although we could have organized these synopses into these three areas, we chose to provide a more clinically focused approach. As such, the first six articles address preoperative assessment; the next eight articles address intraoperative care, and the final four articles address postoperative and critical care.

JAMA 2008;300:2514-2526

Use of generic drugs, which are bioequivalent to brand-name drugs, can help contain prescription drug spending. However, there is concern among patients and physicians that brand-name drugs may be clinically superior to generic drugs.

Objectives
To summarize clinical evidence comparing generic and brand-name drugs used in cardiovascular disease and to assess the perspectives of editorialists on this issue.

Data sources
Systematic searches of peer-reviewed publications in MEDLINE, EMBASE, and International Pharmaceutical Abstracts from January 1984 to August 2008.

Study selection
Studies compared generic and brand-name cardiovascular drugs using clinical efficacy and safety end points. We separately identified editorials addressing generic substitution.

Data extraction
We extracted variables related to the study design, setting, participants, clinical end points, and funding. Methodological quality of the trials was assessed by Jadad and Newcastle-Ottawa scores, and a meta-analysis was performed to determine an aggregate effect size. For editorials, we categorized authors’ positions on generic substitution as negative, positive, or neutral.

Results
We identified 47 articles covering 9 subclasses of cardiovascular medications, of which 38 (81%) were randomized controlled trials (RCTs). Clinical equivalence was noted in 7 of 7 RCTs (100%) of β-blockers, 10 of 11 RCTs (91%) of diuretics, 5 of 7 RCTs (71%) of calcium channel blockers, 3 of 3 RCTs (100%) of antiplatelet agents, 2 of 2 RCTs (100%) of statins, 1 of 1 RCT (100%) of angiotensin-converting enzyme inhibitors, and 1 of 1 RCT (100%) of {alpha}-blockers. Among narrow therapeutic index drugs, clinical equivalence was reported in 1 of 1 RCT (100%) of class 1 antiarrhythmic agents and 5 of 5 RCTs (100%) of warfarin. Aggregate effect size (n = 837) was –0.03 (95% confidence interval, –0.15 to 0.08), indicating no evidence of superiority of brand-name to generic drugs. Among 43 editorials, 23 (53%) expressed a negative view of generic drug substitution.

Conclusions
Whereas evidence does not support the notion that brand-name drugs used in cardiovascular disease are superior to generic drugs, a substantial number of editorials counsel against the interchangeability of generic drugs.

Critical Care Medicine 2007;35:1517-1521

Smokers admitted to the intensive care unit may receive nicotine replacement therapy to prevent withdrawal. However, the safety of nicotine replacement in the critically ill has not been studied. The objective of this study was to determine the impact of nicotine replacement on the outcome of critically ill patients.

Design
Retrospective, case-control.

Setting
The medical intensive care unit of a tertiary academic hospital.

Patients
Patients who were active smokers at admission to the intensive care unit were included in the study. Those who received nicotine replacement therapy were considered as cases, and those who did not receive nicotine replacement were considered as controls.

Interventions
None.

Measurements and Main Results
For each of the 90 cases, one control smoker who did not receive nicotine replacement therapy was selected based on the severity of illness and then age. Outcome was measured by hospital mortality and 28-day intensive care unit-free days, defined as the number of days spent outside of intensive care or without mechanical ventilation by a living patient following admission to intensive care. The mean mortality rate predicted by the Acute Physiology and Chronic Health Evaluation III was 9.2% for the cases compared with 10.3% for the controls (p = .7127). The observed hospital mortality rate was 20% in the cases vs. 7% in the control group (p = .0085). When adjusted for the severity of illness and invasive mechanical ventilation, nicotine replacement therapy was independently associated with increased mortality (odds ratio, 24.6; 95% confidence interval, 3.6-167.6; p = .0011). The mean (sd) 28-day intensive care unit-free days were 20.7 (10.5) in the case group compared with 23.4 (7.1) in the control group (p = .0488).

Conclusions
Our study shows that nicotine replacement therapy is associated with increased hospital mortality in critically ill patients. However, because of the limitations of the study, a future study based on a better case-control design is warranted.

NEJM 2008;358:2787-2795

Progressive enlargement of the aortic root, leading to dissection, is the main cause of premature death in patients with Marfan’s syndrome. Recent data from mouse models of Marfan’s syndrome suggest that aortic-root enlargement is caused by excessive signaling by transforming growth factor β (TGF-β) that can be mitigated by treatment with TGF-β antagonists, including angiotensin II–receptor blockers (ARBs). We evaluated the clinical response to ARBs in pediatric patients with Marfan’s syndrome who had severe aortic-root enlargement.

Methods
We identified 18 pediatric patients with Marfan’s syndrome who had been followed during 12 to 47 months of therapy with ARBs after other medical therapy had failed to prevent progressive aortic-root enlargement. The ARB was losartan in 17 patients and irbesartan in 1 patient. We evaluated the efficacy of ARB therapy by comparing the rates of change in aortic-root diameter before and after the initiation of treatment with ARBs.

Results
The mean (±SD) rate of change in aortic-root diameter decreased significantly from 3.54±2.87 mm per year during previous medical therapy to 0.46±0.62 mm per year during ARB therapy (P<0.001). The deviation of aortic-root enlargement from normal, as expressed by the rate of change in z scores, was reduced by a mean difference of 1.47 z scores per year (95% confidence interval, 0.70 to 2.24; P<0.001) after the initiation of ARB therapy. The sinotubular junction, which is prone to dilation in Marfan’s syndrome as well, also showed a reduced rate of change in diameter during ARB therapy (P<0.05), whereas the distal ascending aorta, which does not normally become dilated in Marfan’s syndrome, was not affected by ARB therapy.

Conclusions
In a small cohort study, the use of ARB therapy in patients with Marfan’s syndrome significantly slowed the rate of progressive aortic-root dilation. These findings require confirmation in a randomized trial.

Ann Int Med 2008;148,xxx

Standard proton-pump inhibitor–based therapy for Helicobacter pylori infection fails in up to one quarter of patients. Sequential therapy may be more efficacious.

Purpose
To compare sequential therapy with standard triple therapy for H. pylori infection.

Data Sources
MEDLINE, EMBASE (1981 to October 2007), the Cochrane Central Register of Controlled Trials, and Google Scholar. PubMed and Ovid were the search engines used.

Study Selection
Randomized, controlled trials (RCTs) comparing sequential and standard triple therapies in treatment-naive patients with documented H. pylori infection.

Data Extraction
3 reviewers independently assessed trial eligibility and quality and extracted data on eradication.

Data Synthesis
The crude rates of H. pylori eradication in 10 RCTs involving 2747 patients were 93.4% (95% CI, 91.3% to 95.5%) for sequential therapy (n = 1363) and 76.9% (CI, 71.0% to 82.8%) for standard triple therapy (n = 1384) (relative risk reduction, 71% [CI, 64% to 77%]; absolute risk reduction, 16 percentage points [CI, 14 to 19 percentage points]). The median rates of adherence were 97.4% (range, 90.0% to 98.9%) for sequential therapy and 96.8% (range, 93.0% to 100%) for standard therapy. Sequential therapy appeared superior in prespecified sensitivity (subgroup) analyses stratified by trial quality; smoking status; diagnosis (ulcer disease or nonulcer dyspepsia); resistance to clarithromycin, imidazoles, or both; duration of triple therapy; and method of diagnosis. Both treatments had similar side effect profiles.

Limitations
Only 1 study was double-blinded. Most patients were from Italy. There was clear evidence of publication bias.

Conclusions
Sequential therapy appears superior to standard triple therapy for eradication of H. pylori infection. If RCTs in other countries confirm these findings, 10-day sequential therapy could become a standard treatment for H. pylori infection in treatment-naive patients.

Cardiovascular morbidity and mortality resulting from congestive heart failure are major concerns for the critical care physician. Although heart failure is commonly associated with impaired systolic function, in up to one half of cases, heart failure occurs exclusively on the basis of an impairment of diastolic function. Diastole is the summation of processes by which the heart loses its ability to generate force and shorten and returns to its precontractile state. The two principal processes responsible for diastole are relaxation and passive pressure-volume properties of the ventricle. Echocardiography provides a comprehensive, noninvasive evaluation of diastolic filling of the ventricle, myocardial relaxation, and ventricular stiffness; the information obtained by echocardiography has prognostic value and is a guide to proper therapy. This article reviews the physiology of diastole, the pathogenesis of diastolic heart failure, and the diagnosis of diastolic dysfunction, with a focus on the diagnostic utility of echocardiography and an emphasis on those areas of greatest interest to the critical care physician.

J Am Coll Cardiol, 2007; 50:187-204

The American College of Cardiology Foundation (ACCF) and the American Society of Echocardiography (ASE), together with key specialty and subspecialty societies, conducted an appropriateness review for transthoracic and transesophageal echocardiography (TTE/TEE). This review assesses the risks and benefits of TTE and/or TEE for several indications or clinical scenarios and scored them based on a scale of 1 to 9. The upper range (7 to 9) implies that the test is generally acceptable and is a reasonable approach, and the lower range (1 to 3) implies that the test is generally not acceptable and is not a reasonable approach. The midrange (4 to 6) indicates a clinical scenario for which the indication for an echocardiogram is uncertain.

The indications for this review were drawn from common applications or anticipated uses as well as current clinical practice guidelines. Use of TTE/TEE for initial evaluation of structure and function was viewed favorably, while routine repeat testing and general screening uses in certain clinical scenarios were viewed less favorably. It is anticipated that these results will have a significant impact on physician decision-making and performance, reimbursement policy, and will help guide future research.

Critical Care 2007, 11:305

Randomized clinical trials (RCTs) that stop earlier than planned because of apparent benefit often receive great attention and affect clinical practice. Their prevalence, the magnitude and plausibility of their treatment effects, and the extent to which they report information about how investigators decided to stop early are, however, unknown.

Objective
To evaluate the epidemiology and reporting quality of RCTs involving interventions stopped early for benefit.

Design
Systematic review up to November 2004 of MEDLINE, EMBASE, Current Contents, and full-text journal content databases to identify RCTs stopped early for benefit.

Study selection
Randomized clinical trials of any intervention reported as having stopped early because of results favoring the intervention. There were no exclusion criteria.

Data extraction
Twelve reviewers working independently and in duplicate abstracted data on content area and type of intervention tested, reporting of funding, type of end point driving study termination, treatment effect, length of follow-up, estimated sample size and total sample studied, role of a data and safety monitoring board in stopping the study, number of interim analyses planned and conducted, and existence and type of monitoring methods, statistical boundaries, and adjustment procedures for interim analyses and early stopping.

Data synthesis
Of 143 RCTs stopped early for benefit, the majority (92) were published in 5 high-impact medical journals. Typically, these were industry-funded drug trials in cardiology, cancer, and human immunodeficiency virus/AIDS. The proportion of all RCTs published in high-impact journals that were stopped early for benefit increased from 0.5% in 1990–1994 to 1.2% in 2000–2004 (P < .001 for trend). On average, RCTs recruited 63% (SD, 25%) of the planned sample and stopped after a median of 13 (interquartile range [IQR], 3–25) months of follow-up, 1 interim analysis, and when a median of 66 (IQR, 23–195) patients had experienced the end point driving study termination (event). The median risk ratio among truncated RCTs was 0.53 (IQR, 0.28–0.66). One hundred thirty-five (94%) of the 143 RCTs did not report at least 1 of the following: the planned sample size (n = 28), the interim analysis after which the trial was stopped (n = 45), whether a stopping rule informed the decision (n = 48), or an adjusted analysis accounting for interim monitoring and truncation (n = 129). Trials with fewer events yielded greater treatment effects (odds ratio, 28; 95% confidence interval, 11–73).

Conclusion
RCTs stopped early for benefit are becoming more common, often fail to adequately report relevant information about the decision to stop early, and show implausibly large treatment effects, particularly when the number of events is small. These findings suggest clinicians should view the results of such trials with skepticism.

Critical Care 2006, 10:167

Pneumonia (hospital-acquired and community-acquired) is commonly encountered in intensive care. Several papers recently published on this subject have shed more light on different aspects of this important topic. Hypothermia has been shown to improve post-arrest outcome, but how often do we use it? And finally, several papers have recently appeared in the journals related to the admission of the elderly to the critical care area and their outcome.

Critical Care 2006, 10:220

In the critically ill, metabolic acidosis is a common observation and, in clinical practice, the cause of this derangement is often multi-factorial. Various measures are often employed to try and characterise the aetiology of metabolic acidosis, the most popular of which is the anion gap. The purpose of the anion gap can be perceived as a means by which the physician is alerted to the presence of unmeasured anions in plasma that contribute to the observed acidosis. In many cases, the causative ion may be easily identified, such as lactate, but often the causative ion(s) remain unidentified, even after exclusion of the ‘classic’ causes. We describe here the various attempts in the literature that have been made to address this observation and highlight recent studies that reveal potential sources of such hitherto unmeasured anions.

Critical Care Medicine. 2006;34(6):1661-1667

Objective
To describe the erythropoietin pharmacokinetic profile after once-weekly epoetin alfa treatment in critically ill patients. Secondary objectives were to compare pharmacodynamic and safety profiles between active treatment and placebo in these patients.

Design
Randomized, double-blind, placebo-controlled study.

Setting
Medical, surgical, or mixed medical/surgical intensive care units.

Patients
A total of 73 anemic critically ill adults with an expected stay of >3 days and a hematocrit value of <38%.

Interventions
Patients were randomized 2:1 to epoetin alfa, 40,000 IU, administered subcutaneously once weekly (n = 48) or matching placebo (n = 25) for up to 4 wks.

Measurements and Main Results
Serum erythropoietin concentration and hematologic variables (percentage reticulocytes [RETI], hemoglobin [Hb], and total red blood cell [RBC] counts) were measured, and area under the serum concentration-time curve from time 0 to the last blood sampling time at time t (t: 120, 144, or 168 hrs) postdose (AUC0-Tlast) for these three variables was determined. Mean serum erythropoietin concentrations in placebo patients were slightly higher than typical physiologic levels of erythropoietin in healthy subjects, although not appropriate for the degree of anemia in these patients. Overall, exposure of endogenous erythropoietin in the placebo group (in terms of AUC0-Tlast) was only about 20% of exposure to exogenous erythropoietin in the epoetin alfa group. Baseline hemoglobin levels were the same in both groups (9.9 g/dL). Mean change in hemoglobin level from baseline through day 29 was 1.9 g/dL and 1.6 g/dL in the epoetin alfa and placebo groups, respectively. Mean AUC(RETI)0-Tlast was higher with epoetin alfa than with placebo and was related to the AUC of erythropoietin. There were no apparent differences in AUC(Hb)0-Tlast and AUC(RBC)0-Tlast between epoetin alfa and placebo groups, which was most likely due to bleeding and transfusion events. Epoetin alfa was safe and well tolerated, with a rate of treatment-emergent complications similar to that seen with placebo.

Conclusion
Epoetin alfa, once weekly, augmented the erythropoietic response in critically ill patients as indicated by the increased erythropoietin levels and larger AUC(RETI)0-Tlast in treated patients.

Critical Care Medicine 2006;34:1372-1377

Objective
Pump-driven extracorporeal gas exchange systems have been advocated in patients suffering from severe acute respiratory distress syndrome who are at risk for life-threatening hypoxemia and/or hypercapnia. This requires extended technical and staff support.

Design
We report retrospectively our experience with a new pumpless extracorporeal interventional lung assist (iLA) establishing an arteriovenous shunt as the driving pressure.

Setting
University hospital.

Patients
Ninety patients with acute respiratory distress syndrome.

Interventions
Interventional lung assist was inserted in 90 patients with acute respiratory distress syndrome.

Measurements and Main Results
Oxygenation improvement, carbon dioxide elimination, hemodynamic variables, and the amount of vasopressor substitution were reported before, 2 hrs after, and 24 hrs after implementation of the system. Interventional lung assist led to an acute and moderate increase in arterial oxygenation (Pao2/Fio2 ratio 2 hrs after initiation of iLA [median and interquartile range], 82 mm Hg [64-103]) compared with pre-iLA (58 mm Hg [47-78], p < .05). Oxygenation continued to improve for 24 hrs after implementation (101 mm Hg [74-142], p < .05). Hypercapnia was promptly and markedly reversed by iLA within 2 hrs (Paco2, 36 mm Hg [30-44]) in comparison with before (60 mm Hg [48-80], p < .05], which allowed a less aggressive ventilation. For hemodynamic stability, all patients received continuous norepinephrine infusion. The incidence of complications was 24.4%, mostly due to ischemia in a lower limb. Thirty-seven of 90 patients survived, creating a lower mortality rate than expected from the Sequential Organ Failure Assessment score.

Conclusions
Interventional lung assist might provide a sufficient rescue measure with easy handling properties and low cost in patients with severe acute respiratory distress syndrome and persistent hypoxia/hypercapnia.

Critical Care Medicine 2006;34:1345-1350

Objective
To determine whether treatment with corticosteroids decreases the incidence of postextubation airway obstruction in an adult intensive care unit.

Design
Clinical experiment.

Setting
Adult medical and surgical intensive care unit of a teaching hospital.

Patients
One hundred twenty-eight patients who were intubated for >24 hrs with a cuff leak volume <24% of tidal volume and met weaning criteria.

Interventions
Patients were randomized into a placebo group (control, n = 43) receiving four injections of normal saline every 6 hrs, a 4INJ group (n = 42) receiving four injections of methylprednisolone sodium succinate, or a 1INJ group (n = 42) receiving one injection of the corticosteroid followed by three injections of normal saline. Cuff volume was assessed 1 hr after each injection, and extubation was performed 1 hr after the last injection. Postextubation stridor was confirmed by examination using bronchoscopy or laryngoscopy.

Measurements and Main Results
The incidences of postextubation stridor were lower both in the 1INJ and the 4INJ groups than in the control group (11.6% and 7.1% vs. 30.2%, both p < .05), whereas there was no difference between the two treated groups (p = .46). The cuff leak volume increased after the second and fourth injection in the 4INJ group and after a second injection in the 1INJ group compared with the control group (both p < .05).

Conclusions
A reduced cuff leak volume is a reliable indicator to identify patients at high risk to develop stridor. Treatment with a single or multiple injections of methylprednisolone can effectively reduce the occurrence of postextubation stridor.

Critical Care Medicine 2006;34:1338-1343

Objective
To assess the intrarater and interrater reliability of electrocardiogram (ECG) interpretation in critically ill patients and to assess the effect of knowledge of cardiac troponin values on these reliability estimates.

Design
Prospective cohort study.

Setting
Fifteen-bed medical-surgical intensive care unit.

Patients
Consecutive adults admitted over a 2-month period.

Measurements and Results
All consecutive 12-lead ECGs were interpreted independently by two raters for the presence of myocardial ischemia or infarction and secondarily for specific ische-mic ECG abnormalities. The ECGs were first interpreted blinded to the patient’s troponin levels and reinterpreted on two separate occasions, blinded and unblinded to the troponin values. Results are reported using chance-independent agreement (phi) with associated 95% confidence intervals. For the presence of ischemia or infarction, the intrarater reliability ranged from fair to moderate (phi = 0.35 [95% confidence interval = 0.16, 0.52] and 0.59 [0.33, 0.77] for the two raters, respectively); interrater reliability was slight when blinded to troponin levels (phi = 0.18 [0.03, 0.32]) and increased to moderate when the raters were unblinded to troponin values (phi = 0.52 [0.33, 0.66], p value for the difference = .004). For specific ECG changes, the intrarater and interrater reliability were low for T-wave flattening, whereas detection of a left bundle branch block showed high reliability.

Conclusions
ECG interpretation in critically ill patients for the presence of myocardial ischemia or infarction showed moderate reliability at best; however, there was high reliability for specific ECG changes. Knowledge of the patient’s troponin values increased the reliability for all studied ECG changes and resulted in a statistically significant increase in the interrater reliability for diagnosing myocardial ischemia or infarction. Additional studies assessing the appropriate methods of diagnosing myocardial ischemia and infarction and assessing the reliability of these diagnostic tests in critically ill patients are required.

Critical Care Medicine 2006;34:1333-1337

Objective
To discuss the rationale, technique, and clinical application of the fluid challenge.

Data Source
Relevant literature from MEDLINE and authors’ personal databases.

Study Selection
Studies on fluid challenge in the acutely ill.

Data Extraction
Based largely on clinical experience and assessment of the relevant published literature, we propose that the protocol should include four variables, namely 1) the type of fluid administered, 2) the rate of fluid administration, 3) the critical end points, and 4) the safety limits.

Conclusions
A protocol for routine fluid challenge is proposed with defined rules and based on the patient’s response to the volumes infused. The technique allows for prompt correction of fluid deficits yet minimizes the risks of fluid overload.