Angioedema in the emergency department: a practical guide to differential diagnosis and management

Background

Angioedema is a common presentation in the emergency department (ED). Airway angioedema can be fatal; therefore, prompt diagnosis and correct treatment are vital.

Objective of the review

Based on the findings of two expert panels attended by international experts in angioedema and emergency medicine, this review aims to provide practical guidance on the diagnosis, differentiation, and management of histamine- and bradykinin-mediated angioedema in the ED.

Review

The most common pathophysiology underlying angioedema is mediated by histamine; however, ED staff must be alert for the less common bradykinin-mediated forms of angioedema. Crucially, bradykinin-mediated angioedema does not respond to the same treatment as histamine-mediated angioedema. Bradykinin-mediated angioedema can result from many causes, including hereditary defects in C1 esterase inhibitor (C1-INH), side effects of angiotensin-converting enzyme inhibitors (ACEis), or acquired deficiency in C1-INH. The increased use of ACEis in recent decades has resulted in more frequent encounters with ACEi-induced angioedema in the ED; however, surveys have shown that many ED staff may not know how to recognize or manage bradykinin-mediated angioedema, and hospitals may not have specific medications or protocols in place.

Conclusion

ED physicians must be aware of the different pathophysiologic pathways that lead to angioedema in order to efficiently and effectively manage these potentially fatal conditions.

     

Identification of sepsis subtypes in critically ill adults using gene expression profiling

Introduction

Sepsis is a syndromic illness that has traditionally been defined by a set of broad, highly sensitive clinical parameters. As a result, numerous distinct pathophysiologic states may meet diagnostic criteria for sepsis, leading to syndrome heterogeneity. The existence of biologically distinct sepsis subtypes may in part explain the lack of actionable evidence from clinical trials of sepsis therapies. We used microarray-based gene expression data from adult patients with sepsis in order to identify molecularly distinct sepsis subtypes.

Methods

We used partitioning around medoids (PAM) and hierarchical clustering of gene expression profiles from neutrophils taken from a cohort of septic patients in order to identify distinct subtypes. Using the medoids learned from this cohort, we then clustered a second independent cohort of septic patients, and used the resulting class labels to evaluate differences in clinical parameters, as well as the expression of relevant pharmacogenes.

Results

We identified two sepsis subtypes based on gene expression patterns. Subtype 1 was characterized by increased expression of genes involved in inflammatory and Toll receptor mediated signaling pathways, as well as a higher prevalence of severe sepsis. There were differences between subtypes in the expression of pharmacogenes related to hydrocortisone, vasopressin, norepinephrine, and drotrecogin alpha.

Conclusions

Sepsis subtypes can be identified based on different gene expression patterns. These patterns may generate hypotheses about the underlying pathophysiology of sepsis and suggest new ways of classifying septic patients both in clinical practice, and in the design of clinical trials.     

Angioedema: Etiology,Pathophysiology, Current and Emerging Therapies

Background

Angioedema (AE) is characterized by nonpitting edema of the dermis and subcutaneous layers. The most common sites of involvement are the tongue, lips, face, and throat; however, swelling can also occur in the extremities, genitalia, and viscera. Life-threatening airway swelling can also occur. AE may be allergic or nonallergic. The overall lifetime incidence of AE is reported to be as high as 15%.

Objective

This article summarizes the etiology, pathophysiology, and current treatment of several forms of nonallergic AE (including hereditary, acquired, and idiopathic AE) and focuses on angiotensin-converting enzyme inhibitor–induced angioedema (ACEi-AE), which is responsible for 30%−40% of all AE seen in United States emergency departments.

Discussion

Although the triggers, which are primary biologic mechanisms, and treatments for ACEi-AE may differ from those of the hereditary and acquired forms of AE, the clinical effects of ACEi-AE are mediated through a shared pathway, the kallikrein-kinin system. Thus, although current therapeutic options for ACEi-AE are limited, recent advances in the treatment of hereditary AE (HAE) appear promising for improving the outcomes of patients with ACEi-AE.

Conclusions

New HAE medications that correct imbalances in the kallikrein-kinin system may prove safe and efficacious in the treatment of ACEi-AE.     

Safety of cervical spine manipulation: are adverse events preventable and are manipulations being performed appropriately? A review of 134 case reports

Background

Cervical spine manipulation (CSM) is a commonly utilized intervention, but its use remains controversial.

Purpose

To retrospectively analyze all available documented case reports in the literature describing patients who had experienced severe adverse events (AEs) after receiving CSM to determine if the CSM was used appropriately, and if these types of AEs could have been prevented using sound clinical reasoning on the part of the clinician.

Data sources

PubMed and the Cumulative Index to Nursing and Allied Health were systematically searched for case reports between 1950 and 2010 of AEs following CSM.

Study selection

Case reports were included if they were peer-reviewed; published between 1950 and 2010; case reports or case series; and had CSM as an intervention. Articles were excluded if the AE occurred without CSM (e.g. spontaneous); they were systematic or literature reviews. Data extracted from each case report included: gender; age; who performed the CSM and why; presence of contraindications; the number of manipulation interventions performed; initial symptoms experienced after the CSM; and type of resultant AE.

Data synthesis

Based on the information gathered, CSMs were categorized as appropriate or inappropriate, and AEs were categorized as preventable, unpreventable, or unknown. Chi-square analysis with an alpha level of 0.05 was used to determine if there was a difference in proportion between six categories: appropriate/preventable, appropriate/unpreventable, appropriate/unknown, inappropriate/preventable, inappropriate/unpreventable, and inappropriate/unknown.

Results

One hundred thirty four cases, reported in 93 case reports, were reviewed. There was no significant difference in proportions between appropriateness and preventability, P = .46. Of the 134 cases, 60 (44.8%) were categorized as preventable, 14 (10.4%) were unpreventable and 60 (44.8%) were categorized as ‘unknown’. CSM was performed appropriately in 80.6% of cases. Death resulted in 5.2% (n = 7) of the cases, mostly caused by arterial dissection.

Limitations

There may have been discrepancies between what was reported in the cases and what actually occurred, since physicians dealing with the effects of the AE, rather than the clinician performing the CSM, published many of the cases.

Conclusions

This review showed that, if all contraindications and red flags were ruled out, there was potential for a clinician to prevent 44.8% of AEs associated with CSM. Additionally, 10.4% of the events were unpreventable, suggesting some inherent risk associated with CSM even after a thorough exam and proper clinical reasoning.     

Bradykinin-mediated angioedema: factors prompting ED visits

Objective

Bradykinin-mediated angioedema (AE) is characterized by periodic subcutaneous or submucosal swelling, with the absence of urticaria and itching. It affects the face and extremities. Attacks of abdominal pain and obstruction of the upper airways are the hallmarks of disease severity. The aim of this study was to determine the factors prompting patients to turn up at the hospital emergency department (ED) in the event of an attack.

Methods

This was a retrospective review of attacks experienced by all patients with bradykinin-mediated AE (hereditary, acquired, or drug-induced) who visited our ED between January 2002 and March 2011. Characteristics of attacks prompting ED visits and attacks when patients stayed at home were compared using logistic regression with generalized estimating equations to take into account the correlation between multiple attacks from the same patient.

Results

A total of 55 patients were included, of whom 39 had hereditary AE; 13, drug-induced AE; and 3, acquired C1 inhibitor deficiency. The median follow-up was 32 months (interquartile range, 10-99 months). The attack was severe in 324 (58%) of 559 cases. Thirty-two patients (58%) visited the ED for a total of 75 attacks. First attack and laryngeal edema were significantly associated with more frequent ED visits (odds ratio, 5.28 [95% confidence interval, 2.42-11.5] and 4.83 [1.54-15.5], respectively]. C1 inhibitor concentrate and icatibant treatment was significantly more often administered in the ED than at home (odds ratio, 4.9 [2.43-9.88] and 8.25 [2.4-28.3], respectively).

Conclusions

First attack of bradykinin AE and swelling of the larynx were significantly associated with visits to the ED.     

A Randomized Clinical Trial of Aquatic versus Land Exercise to Improve Balance, Function, and Quality of Life in Older Women with Osteoporosis

Purpose:

Despite the decreased gravitational loading that is experienced in an aquatic environment, little research has been conducted on this exercise medium for women with osteoporosis (OP). Aquatic exercise (AE) may improve function and balance, thus ultimately decreasing fall risk and the potential for hip fractures in this high-risk population.

Method:

A total of 68 women with OP, aged 60 years or older, were recruited into a randomized clinical trial evaluating the impact of AE, land exercise (LE), and no exercise (NE) on balance, functional mobility, and quality of life (QOL).

Results:

Only one balance measure (backward tandem walk) significantly improved with AE compared to LE, but this did not translate into a greater improvement in self-report function. There were no significant differences between the exercise interventions and NE, except for in ratings of global change, where participants in the AE group were three times more likely to report improvement than those in the NE group.

Conclusion:

There were no differences in balance, function, or QOL in women with OP who followed an AE or LE programme compared to those in an NE control group. However, the significant differences in backward tandem walk between the AE and LE groups and self-reported global change between the AE and NE groups warrant further investigation. Significant improvements in balance and global change suggest that AE is a viable alternative for older women with OP who have difficulty exercising on land.     

Medical students’ views on training in intellectual disabilities

OBJECTIVE

To examine undergraduate medical training in the field of intellectual disabilities (ID) from the perspective of clinical clerks.

DESIGN

Cross-sectional self-administered survey.

SETTING

Clerkship rotations at Queen’s University in Kingston, Ont, and the University of Toronto in Ontario in 2006.

PARTICIPANTS

A total of 196 upper-year undergraduate medical students (clerks).

MAIN OUTCOME MEASURES

Contact with people with ID, training in the field of ID, perceptions of current training in ID, and views on ways to improve the curriculum in the area of ID.

RESULTS

Most students (85.6%) had received some didactic and clinical training in managing patients with ID, but most of these (93.3%) believed that curriculum enhancements, especially more contact with patients with ID and more time in the curriculum for training in care of people with ID, were necessary.

CONCLUSION

This study found that the curriculum enhancements long recommended by experts in the field of ID were also desired by clinical clerks. This finding adds considerable weight to the recommendation that improvements in training in ID should be incorporated into undergraduate medical education programs.     

Does space make waste? The influence of ICU bed capacity on admission decisions

Expanded abstract

Citation

Stelfox HT, Hemmelgarn BR, Bagshaw SM, Gao S, Doig CJ, Nijssen-Jordan C, Manns B: Intensive care unit bed availability and outcomes for hospitalized patients with sudden clinical deterioration. Arch Intern Med 2012, 172:467-474.

Background

Intensive care unit (ICU) beds are a scarce resource, and admissions may require prioritization when demand exceeds supply. However, there are few empiric data on whether the availability of ICU beds influences triage and processes of care for hospitalized patients who develop sudden clinical deterioration.

Methods

Objective

The objective was to evaluate the effect of ICU bed availability on the processes and outcomes of care for hospitalized patients with sudden clinical deterioration on a hospital ward.

Design

We conducted a retrospective cohort study.

Setting

The study was conducted in three hospitals in Calgary, Alberta, Canada, with 2,040 beds and a catchment population of 1.5 million individuals.

Subjects

Hospitalized adults (n = 3,494) with a sudden clinical deterioration triggering medical emergency team (MET) activation between 1 January 2007 and 31 December 2009 participated.

Analysis

This study compared treatments and outcomes among sudden clinical deterioration patients according to the number of ICU beds available (zero, one, two, or more than two) at the time of the MET activation. The outcomes of interest were ICU admission rates (within 2 hours of MET activation), changes in the goals of care (resuscitative, medical, and comfort), and hospital mortality. All analyses were adjusted for hospital, physician, and patient factors.

Results

The cohort consisted of 3,494 patients. Reduced ICU bed availability was associated with a decreased likelihood of ICU admission within 2 hours of MET activation (P = 0.03) and with an increased likelihood of change in patient goals of care (P <0.01). Patients with sudden clinical deterioration when zero ICU beds were available were 33.0% (95% confidence interval (CI), −5.1% to57.3%) less likely to be admitted to the ICU and were 89.6% (95% CI, 24.9% to 188.0%) more likely to have their goals of care changed compared with when more than two ICU beds were available. However, hospital mortality did not vary significantly by ICU bed availability (P = 0.82).

Conclusions

For hospitalized patients with sudden clinical deterioration, ICU bed scarcity decreases the probability of ICU admission and increases the probability of initiating comfort measures on the ward but does not influence hospital mortality.     

Feasibility of an interdisciplinary program for obesity management in Canada

Objective

To assess the feasibility of a medically supervised, publicly funded interdisciplinary program for obesity management in a Canadian setting.

Design

Retrospective chart audit using electronic medical records.

Setting

Wharton Medical Clinic in Hamilton and Burlington, Ont.

Participants

A total of 2739 consenting patients attending the interdisciplinary obesity-management program at Wharton Medical Clinic.

Main outcome measures

Three- and 6-month weight changes and factors affecting weight loss.

Results

The 1085 patients attending the clinic for at least 3 months (mean [SD] of 8.1 [6.1] visits and 5.4 [4.7] months) lost a mean (SD) of 4.2 (7.1) kg or 3.5% (6.8%) of their initial body weight, with 32% and 9% of these patients attaining weight reductions of 5% or greater and 10% or greater, respectively. The 289 patients attending the clinic for 6 months or more (mean [SD] of 13.2 [9.7] visits and 10.5 [6.9] months) lost a mean (SD) of 5.4 (10.6) kg or 4.3% (9.2%) of their initial body weight, with 47% and 17% attaining reductions of 5% or greater and 10% or greater, respectively. Visit frequency was positively associated with weight loss independent of age, sex, body mass index, and treatment duration.

Conclusion

Preliminary data support the short-term effectiveness and clinical utility of this publicly funded program. Using this interdisciplinary model, approximately half of patients were able to attain clinically significant weight loss.     

Data discipline in electronic medical records: Improving smoking status documentation with a standardized intake tool and process

Objective

To evaluate the transformation in smoking status documentation after implementing a standardized intake tool as part of a primary care smoking cessation program.

Design

A before-and-after evaluation of smoking status documentation was conducted following implementation of a smoking assessment tool. To evaluate the effect of the intervention, the Canadian Primary Care Sentinel Surveillance Network was used to extract aggregate smoking data on the study cohort.

Setting

Academic primary care clinic in Kingston, Ont.

Participants

A total of 7312 primary care patients.

Interventions

As the first phase in a primary care smoking cessation program, a standardized intake tool was developed as part of a vital signs screening process.

Main outcome measures

Documented smoking status of patients before implementation of the intake tool and documented smoking status of patients in the 6 months after its implementation.

Results

Following the implementation of the standardized intake tool, there was a 55% (P < .001; 95% CI 0.53 to 0.56) increase in the proportion of patients with a completed smoking status; more than 1100 former smokers were identified and the documented smoking rate in this cohort increased from 4.4% to 16.2%.

Conclusion

This study shows that the implementation of an intake tool, integrated into existing clinical operational structures, is an effective way to standardize clinical documentation and promotes the optimization of electronic medical records.     

Clearing up the confusion: The results of two pilot studies of antipsychotics for ICU delirium

Citation #1

Girard TD, Pandharipande PP, Carson SS, Schmidt GA, Wright PE, Canonico AE, Pun BT, Thompson JL, ShintaniAK, Meltzer HY, Bernard GR, Ditt us RS, Ely EW: Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: the MIND randomized, placebo-controlled trial. Crit Care Med 2010, 38:428-437 [1].

Background

Given the lack of compelling evidence supporting the use of antipsychotics for delirium in critically ill patients and the potential adverse effects associated with these medications, placebo-controlled clinical trials are greatly needed.

Methods

Objective

To demonstrate the feasibility of a placebo-controlled trial of antipsychotics for delirium in the intensive care unit and to test the hypothesis that antipsychotics would improve days alive without delirium or coma.

Design

Randomized, double-blind, placebo-controlled trial.

Setting

Six tertiary care medical centers in the US.

Subjects

One hundred one mechanically ventilated medical and surgical intensive care unit patients.

Intervention

Patients were randomly assigned to receive haloperidol or ziprasidone or placebo every 6 hrs for up to 14 days. Twice each day, frequency of study drug administration was adjusted according to delirium status, level of sedation, and side effects.

Outcomes

The primary end point was the number of days patients were alive without delirium or coma. Secondary efficacy end points included daily delirium risk, duration of delirium, duration of coma, the number of days patients were alive and breathing without assistance during the 21-day study period (ventilator-free days), time to ICU and hospital discharge, and all-cause 21-day survival.

Results

During the 21-day study period, patients in the haloperidol group spent a similar number days alive without delirium or coma (median [inter quartile range], 14.0 [6.0-18.0] days) as did patients in the ziprasidone (15.0 [9.1-18.0] days) and placebo groups (12.5 [1.2-17.2] days; p = 0.66). No differences were found in secondary clinical outcomes, including ventilator-free days (p = .25), hospital length of stay (p = .68), and mortality (p = .81). Ten (29%) patients in the haloperidol group reported symptoms consistent with akathisia, compared with six (20%) patients in the ziprasidone group and seven (19%) patients in the placebo group (p = .60), and a global measure of extra pyramidal symptoms was similar between treatment groups (p = .46).

Conclusions

A randomized, placebo-controlled trial of antipsychotics for delirium in mechanically ventilated intensive care unit patients is feasible. Treatment with antipsychotics in this limited pilot trial did not improve the number of days alive without delirium or coma, nor did it increase adverse outcomes. Thus, a large trial is needed to determine whether use of antipsychotics for intensive care unit delirium is appropriate.

Citation #2

Devlin JW, Roberts RJ, Fong JJ, Skrobik Y, Riker RR, Hill NS, Robbins T, Garpestad E: Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multi center, randomized, double-blind, placebo-controlled pilot study. Crit Care Med 2010, 38:419-427 [2].

Background

To date, there are no published double-blind, randomized, placebo-controlled trials to establish the efficacy or safety of any antipsychotic medication in the management of delirium in the ICU.

Methods

Objective

To compare the efficacy and safety of scheduled quetiapine to placebo for the treatment of delirium in critically ill patients requiring as-needed haloperidol.

Design

Prospective, randomized, double-blind, placebo-controlled study.

Setting

Three academic medical centers in the US and Canada.

Subjects

Thirty-six adult intensive care unit patients with delirium (Intensive Care Delirium Screening Checklist score > = 4), tolerating enteral nutrition, and without a complicating neurologic condition.

Intervention

Patients were randomized to receive quetiapine 50 mg every 12 hrs or placebo. Quetiapine was increased every 24 hrs (50 to 100 to 150 to 200 m gevery 12 hrs) if more than one dose of haloperidol was given in the previous 24 hrs. Study drug was continued until the intensive care unit team discontinued it because of delirium resolution, therapy > = 10 days, or intensive care unit discharge.

Outcomes

The primary end point was time to first resolution of delirium. Secondary outcomes included duration of mechanical ventilation, ICU and hospital length of stay, hospital mortality, and discharge disposition. Measures of safety included total number of adverse and serious adverse events related to study drug, incidence of extra pyramidal symptoms, and episodes of QTc interval prolongation.

Results

Baseline characteristics were similar between the quetiapine (n = 18) and placebo (n = 18) groups. Quetiapine was associated with a shorter time to first resolution of delirium [1.0 (inter quartile range [IQR], 0.5-3.0) vs. 4.5 days (IQR, 2.0-7.0; p = .001)], a reduced duration of delirium [36 (IQR, 12-87) vs. 120 hrs (IQR, 60-195; p = .006)], and less agitation (Sedation-Agitation Scale score > = 5) [6 (IQR, 0-38) vs. 36 hrs (IQR, 11-66; p = .02)]. Whereas mortality (11% quetiapine vs. 17%) and intensive care unit length of stay (16 quetiapine vs. 16 days) were similar, subjects treated with quetiapine were more likely to be discharged home or to rehabilitation (89% quetiapine vs. 56%; p = .06). Subjects treated with quetiapine required fewer days of as-needed haloperidol [3 [(IQR, 2-4)] vs. 4 days (IQR, 3-8; p = .05)]. Whereas the incidence of QTc prolongation and extrapyramidal symptoms was similar between groups, more somnolence was observed with quetiapine (22% vs. 11%; p = .66).

Conclusions

Quetiapine added to as-needed haloperidol results in faster delirium resolution, less agitation, and a greater rate of transfer to home or rehabilitation. Future studies should evaluate the effect of quetiapine on mortality, resource utilization, post-intensive care unit cognition, and dependency after discharge in a broader group of patients.     

Does intra-aortic balloon support for myocardial infarction with cardiogenic shock improve outcome?

Expanded abstract

Citation

Thiele H, Zeymer U, Neumann FJ, Ferenc M, Olbrich HG, Hausleiter J, Richardt G, Hennersdorf M, Empen K, Fuernau G, Desch S, Eitel I, Hambrecht R, Fuhrmann J, Böhm M, Ebelt H, Schneider S, Schuler G, Werdan K; IABP-SHOCK II Trial Investigators: Intraaortic balloon support for myocardial infarction with cardiogenic shock. N Engl J Med 2012, 367:1287-1296.

Background

In the current international guidelines, intra-aortic balloon pump (IABP) counterpulsation is considered a class I treatment for acute myocardial infarction complicated by cardiogenic shock. However, evidence is based mainly on registry data, and there is a paucity of randomized clinical trials.

Methods

Objective

To test the hypothesis that IABP counterpulsation, as compared with the best available medical therapy alone, results in a reduction in mortality among patients with acute myocardial infarction complicated by cardiogenic shock for whom early revascularization is planned.

Design

Randomized, prospective, open-label, multicenter trial.

Setting

Thirty-seven centers in Germany.

Subjects

All adults had acute myocardial infarction complicated by cardiogenic shock and were expected to undergo early revascularization (by means of percutaneous coronary intervention or bypass surgery).

Intervention

After enrollment, 600 patients were randomly assigned to intra-aortic balloon counterpulsation (IABP group, 301 patients) or no IABP counterpulsation (control group, 299 patients).

Outcomes

The primary efficacy endpoint is 30-day all-cause mortality.

Results

At 30 days, 119 patients in the IABP group (39.7%) and 123 patients in the control group (41.3%) had died (relative risk with IABP, 0.96; 95% confidence interval, 0.79 to 1.17; P = 0.69). There were no significant differences in secondary endpoints or in process-of-care measures, including the time to hemodynamic stabilization, the length of stay in the intensive care unit, serum lactate levels, the dose and duration of catecholamine therapy, and renal function.

Conclusions

The use of IABP counterpulsation did not significantly reduce 30-day mortality in patients with acute myocardial infarction complicated by cardiogenic shock for whom an early revascularization strategy was planned.     

Albumin and furosemide for acute lung injury

Citation

Martin GS, Moss M, Wheeler AP, Mealer M, Morris JA, Bernard GR: A randomized, controlled trial of furosemide with or without albumin in hypoproteinemic patients with acute lung injury. Crit Care Med 2005, 33:1681–1687 [1].

Background

Hypoproteinemia is a common condition in critically ill patients, associated with the development of acute lung injury and acute respiratory distress syndrome and subsequent worse clinical outcomes. Albumin with furosemide benefits lung physiology in hypoproteinemic patients with acute lung injury/acute respiratory distress syndrome, but the independent pharmacologic effects of these drugs are unknown.

Methods

Objective

To determine the independent pharmacologic effects of albumin and furosemide in hypoproteinemic patients with acute lung injury/acute respiratory distress syndrome.

Design

Randomized, double-blinded, placebo-controlled multicentered trial.

Setting

Eleven medical, surgical, and trauma intensive care units including 190 beds within two university hospital systems.

Subjects

Forty mechanically ventilated patients with acute lung injury/acute respiratory distress syndrome, whose serum total protein concentrations were <6.0 g/dL were included. Patients were excluded for hemodynamic instability or significant renal or hepatic failure.

Intervention

Subjects were equally randomly allocated to receive furosemide with albumin or furosemide with placebo for 72 hrs, titrated to fluid loss and normalization of serum total protein concentration.

Outcomes

The primary outcome was change in oxygenation from baseline to day 1, with secondary physiologic and clinical outcomes.

Results

There were no differences in baseline characteristics of the subjects in relation to group assignment. Albumin-treated patients had greater increases in oxygenation (mean change in Pao2/Fio2: +43 vs. -24 mm Hg at 24 hrs and +49 vs. -13 mm Hg at day 3), serum total protein (1.5 vs. 0.5 g/dL at day 3), and net fluid loss (-5480 vs. -1490 mL at day 3) throughout the study period (all p < .05). Fluid bolus administration to control patients reduced net negative fluid balance; control patients more frequently developed hypotension and had fewer shock-free days, which translated to differences in organ failure at study end. Apart from more frequent hypotension in the control group, there were no adverse events. There were seven deaths in the treatment group and nine in the control group (35% vs. 45% mortality rate; p = .52).

Conclusion

The addition of albumin to furosemide therapy in hypoproteinemic patients with acute lung injury/acute respiratory distress syndrome significantly improves oxygenation, with greater net negative fluid balance and better maintenance of hemodynamic stability. Additional randomized clinical trials are necessary to examine mechanisms and determine the effect on important clinical outcomes, such as the duration of mechanical ventilation.     

Treatment of laryngeal hereditary angioedema

Background

In the emergency department, patients with laryngeal swelling and an inconclusive patient history may receive treatment for allergy-mediated angioedema. Intubation may be necessary if the patient does not respond to treatment. Because angioedema subtypes respond to different interventions, a correct diagnosis is vital.

Objectives

Review the differential diagnosis of angioedema and characteristics differentiating subtypes. Discuss therapies for angioedema subtypes. Introduce therapies for prevention and acute treatment of hereditary angioedema (HAE).

Case Report

A 10-year-old girl presented with laryngeal swelling unresponsive to diphenhydramine, methylprednisolone, and epinephrine. It was later revealed that she had a family history of HAE, was C1 inhibitor deficient, and enrolled in a clinical study of acute HAE treatment. She was given 1000 units of nanofiltered C1 inhibitor and was able to swallow within 30 min. She was prescribed routine prophylaxis with C1 inhibitor concentrate and has had no subsequent severe HAE swelling attacks.

Conclusion

This case illustrates the need for providers to consider HAE in light of available diagnostic testing and recent Food and Drug Administration approval of specific therapies for HAE.     

Early surgery for native valve infective endocarditis

Expanded abstract

Citation

Kang DH, Kim YJ, Kim SH, Sun BJ, Kim DH, Yun SC, Song JM, Choo SJ, Chung CH, Song JK, Lee JW, Sohn DW: Early surgery versus conventional treatment for infective endocarditis. N Engl J Med 2012, 366: 2466-2473.

Background

The timing and indications for surgical intervention to prevent systemic embolism in infective endocarditis (IE) remain controversial. This trial compares clinical outcomes of early surgery and conventional treatment in patients with IE.

Methods

Objective

To determine the effect of early surgery (<48 hours) to decrease the rate of death or embolic events as compared with conventional treatment for IE.

Design

Prospective randomized trial.

Setting

Two academic medical centers in Korea.

Subjects

Adult patients with left-sided, native-valve IE and a high risk of embolism.

Intervention

Valve repair or replacement with removal of vegetation within 48 hours of random assignment versus no early surgery.

Outcomes

Composite primary endpoint of in-hospital death and embolic events occurring within 6 weeks after random assignment. Secondary endpoints, at 6 months, included death from any cause, embolic events, recurrence of IE, and repeat hospitalization due to the development of congestive heart failure.

Results

Thirty-seven patients were assigned to the early-surgery group (<48 hours), whereas 39 were assigned to conventional therapy. Of the 39 randomly assigned to conventional therapy, 27 patients (77%) underwent surgery during the initial hospitalization and three during follow-up. One patient (3%) in the early-surgery group and nine (23%) in the conventional-treatment group reached the primary endpoint (hazard ratio (HR) 0.10, 95% confidence interval (CI) 0.01 to 0.82; P = 0.03). There was no significant difference in all-cause mortality at 6 months in the early-surgery and conventional-treatment groups (3% and 5%, respectively; HR 0.51, 95% CI 0.05 to 5.66; P = 0.59). The rates of the composite endpoint of death from any cause, embolic events, or recurrence of IE at 6 months were 3% in the early-surgery group and 28% in the conventional-treatment group (HR 0.08, 95% CI 0.01 to 0.65; P = 0.02).

Conclusions

Early surgery in patients with IE and large vegetations significantly reduced the composite endpoint of death from any cause and embolic events by effectively decreasing the risk of systemic embolism.     

Continuity of care is good for elderly people with diabetes: retrospective cohort study of mortality and hospitalization

Objective

To examine the relationship between continuity of family physician care and all-cause mortality and acute hospitalizations in older people with diabetes.

Design

Retrospective cohort study of administrative health databases. Continuity of family physician care for elderly patients newly diagnosed with diabetes was estimated by 3 continuity indexes using physician claims data. The relationship of continuity of family physician care to mortality and acute hospitalizations was investigated.

Setting

The province of Newfoundland and Labrador.

Participants

A total of 305 family practice patients 65 years of age or older with diabetes.

Main outcome measures

Death rate and hospitalization rate during a 3-year period.

Results

Overall, continuity of family physician care was high. In the 3 years examined, the higher-continuity group had lower rates of hospitalization (53.5% vs 68.2%) and death (8.6% vs 18.5%) than the lower-continuity group.

Conclusion

The findings suggest an association between higher continuity of family physician care and reductions in likelihood of death and hospitalizations in older people with diabetes.     

Rethinking bystander CPR for out-of-hospital cardiac arrest

Citation

SOS-KANTO study group: Cardiopulmonary resuscitation by bystanders with chest compression only (SOS-KANTO): an observational study. Lancet 2007, 369:920–926 [1].

Background

Mouth-to-mouth ventilation is a barrier to bystanders doing cardiopulmonary resuscitation (CPR), but few clinical studies have investigated the efficacy of bystander resuscitation by chest compressions without mouth-to-mouth ventilation (cardiac-only resuscitation).

Methods

Objective

To compare the effect of bystander-provided cardiac-only resuscitation to conventional CPR in adults who had out-of-hospital cardiac arrest.

Design

Prospective multicenter observational study.

Setting

58 emergency hospitals and emergency medical service units in the Kanto region of Japan.

Subjects

Patients with witnessed out-of-hospital cardiac arrest who were subsequently transported by paramedics to participating emergency hospitals. Exclusion criteria were age <18 years, further cardiac arrest after the arrival of paramedics, documented terminal illness, presence of a do-not-resuscitate order, and bystander resuscitation without documented chest compressions.

Intervention

None. On arrival at the scene, paramedics assessed the technique of bystander resuscitation, recording it as conventional CPR (chest compressions with mouth-to-mouth ventilation), cardiac-only resuscitation (chest compressions alone), or no bystander CPR. Patients were followed and revaluated 30 days after the arrest to determine neurologic status.

Outcome

The primary endpoint was favorable neurological outcome 30 days after cardiac arrest using the Glasgow-Pittsburgh cerebral-performance scale, with favorable neurological outcome defined as a category 1 (good performance) or 2 (moderate disability) on a 5-point scale.

Results

4068 adult patients who had out-of-hospital cardiac arrest witnessed by bystanders were included; 439 (11%) received cardiac-only resuscitation from bystanders, 712 (18%) conventional CPR, and 2917 (72%) received no bystander CPR. Any resuscitation attempt was associated with a higher proportion having favorable neurological outcomes than no resuscitation (5.0%vs 2.2%, p < 0.0001). Cardiac-only resuscitation resulted in a higher proportion of patients with favorable neurological outcomes than conventional CPR in patients with apnea (6.2%vs 3.1%; p = 0.0195), with shockable rhythm (19.4%vs 11.2%, p = 0.041), and with resuscitation that started within 4 min of arrest (10.1%vs 5.1%, p = 0.0221). However, there was no evidence for any benefit from the addition of mouth-to-mouth ventilation in any subgroup. The adjusted odds ratio for a favorable neurological outcome after cardiac-only resuscitation was 2.2 (95% CI 1.2–4.2) in patients who received any resuscitation from bystanders.

Conclusion

Cardiac-only resuscitation by bystanders is the preferable approach to resuscitation for adult patients with witnessed out-of-hospital cardiac arrest, especially those with apnea, shockable rhythm, or short periods of untreated arrest.     

Ultrasound in the evaluation of interstitial pneumonia

Background

The diagnostic value of thoracic ultrasonography (US) has recently increased. Skilled sonographers with experience in pulmonary medicine have demonstrated the existence of US signs of chest pathology.

Purpose

To detect US findings associated with infectious interstitial pneumonia that can be used to supplement other diagnostic tools.

Materials and methods

Over a period of 5 years (2001–2006), 55 patients were referred to our ultrasonography units for evaluation of probable viral or viral-like infections of the respiratory tract. Each patient was subjected to a work-up that included clinical examination, blood tests, pulmonary function tests, bronchoscopy, chest radiographs, high-resolution computed tomography (HRCT), and thoracic US, which was performed under blinded conditions.

Results

Based on the findings that emerged from the work-up described above, all 55 patients were diagnosed with interstitial pneumonia. Evaluation of the US scans for the signs of interstitial lung disease described by Lichtenstein revealed “comet-tail” artifacts in the anterolateral lung fields in 31 (56.36%) patients and mixed patterns consisting in increased density associated with ring-down artifacts in 24 (46.64%). Pleural involvement was also observed in 34 cases (61.82%).

Conclusions

Thoracic US appears to be a useful adjunct to clinical, laboratory and radiological studies in patients suspected of having infectious interstitial pneumonia.     

Early or late parenteral nutrition: ASPEN vs. ESPEN

Citation

Casaer MP, Mesotten D, Hermans G et al. Early versus late parenteral nutrition in critically ill adults. N Engl J Med. 2011;365: 506-517.

Background

Controversy exists about the timing of the initiation of parenteral nutrition (PN) in critically ill adults in whom caloric targets cannot be met by enteral nutrition (EN) alone.

Methods

Objective

To compare early-initiation of PN (European guidelines) with late-initiation (American and Canadian guidelines) in adults who are receiving insufficient enteral nutrition in the intensive care unit (ICU).

Design

Prospective, randomized, controlled, parallel-group, multicenter clinical trial.

Setting

Seven multidisciplinary ICUs in Belgium.

Subjects

All adults admitted to participating ICUs with a nutritional risk score of 3 or more who did not meet any exclusion criteria.

Intervention

After enrollment, 2312 patients were randomized to receive PN 48 hours after ICU admission (early-initiation) and 2328 patients were randomized to receive PN on day 8 (late-initiation group). Both groups received early EN using a standardized protocol. PN was continued until EN met 80% of calorific goals, or when oral nutrition was resumed. It was restarted if enteral or oral feeding fell below 50% of calculated calorific needs.

Outcomes

Primary end point was the duration of dependency on intensive care, defined as the number of intensive care days and time to discharge from the ICU.

Results

The median stay in the ICU was one day shorter for the late-initiation group (3 v. 4; p = 0.02). The late-initiation group had a relative increase, of 6.3%, in the likelihood of being discharged earlier, and alive, from the ICU (hazard ratio 1.06; 95% confidence interval [CI] 1.00-1,13; p = 0.04). Rates of death in the ICU and survival at 90 days were similar between the two groups. The late-initiation group, as compared to the early-initiation group, had fewer ICU infections (22.8% v. 26.2%; p = 0.008), less days of renal replacement therapy (7 days (interquartile range [IQR] 3-16) v. 10 days (IQR 5-23); p = 0.008) and fewer patients requiring more than 2 days of mechanical ventilation (36.3% v. 40.2%; p = 0.006).

Conclusions

Late-initiation of PN was associated with faster recovery and fewer complications, when compared with early-initiation.

Trial Registration

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